title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Psycho-social counselling in predictive genetic testing for cancer: the association between number of supportive sessions and client characteristics as assessed by psycho-social workers. | Given the increased demand on genetic services, it is important to identify clients who may require relatively more extensive psychosocial support. This paper describes which client characteristics, as assessed in the first psycho-social counselling session, were associated with requiring relatively more psycho-social support (> or = 3 sessions) in the process of predictive testing for cancer. The study population consisted of 244 counselees for hereditary cancer. Data were derived from an electronic data-base, used by psycho-social workers for the systematic registration of relevant details of each counselling session. Data were analysed for two respective groups: (A) patients who had a known mutation in the family and (B) patients with an as yet unknown mutation in the family. Results show that two or more psychosocial sessions were given if the information derived from the first session indicated the client to have childhood experiences with cancer (in group A), to experience the family role and/or the psychological impact as burdensome (in both groups) or to experience the social impact as burdensome (in group B). We conclude that the first assessment by a psychosocial worker already provides valuable information on the psychological support needs of patients. These findings provide insight into possible problem areas for clients dealing with predictive genetic testing. | 18,751,878 |
A pilot study of dose-dense adjuvant paclitaxel without growth factor support for women with early breast carcinoma. | Granulocyte-colony stimulating factor (G-CSF) was used in CALGB 9741 to support dose-dense sequential chemotherapy with doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) (Citron et al. J Clin Oncol 21:1431-1439, 2003). However, myelosuppression is not known to be dose or schedule limiting for paclitaxel. We therefore conducted this trial to determine the need for routine G-CSF, using the pegylated product (pG-CSF), support during the paclitaxel component of dose-dense sequential chemotherapy in women with early stage breast carcinoma (BC). Eligible patients received dose-dense chemotherapy consisting of four cycles of AC followed by four cycles of P at two week intervals. pG-CSF (Neulasta) was administered after each of four cycles of AC but was held after P. Planned enrollment was 59 pts. Of the first 15 patients, nine completed therapy without delays due to neutropenia but 6 (40%) did not, leading to implementation of the pre-specified early termination rule. Overall, 85% of P doses were successfully delivered on time. The mean treatment delay for the entire group due to neutropenia was 0.75 days. There was no significant correlation between neutropenia and prior WBC, ANC, or concurrent treatment with trastuzumab. Pts with neutropenia tended to be younger (Mean age 43.5) and have a lower BSA (1.65 m(2)). There were no febrile episodes due to omission of pG-CSF. When paclitaxel is administered in a dose-dense fashion without growth factor support brief treatment delays are common. Further study is needed to identify the minimal pG-CSF administration that will avoid treatment delays. | 18,751,888 |
Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake. | Glucose metabolism is essential for normal brain function and plays a vital role in synaptic transmission. Recent evidence suggests that ATP synthesized locally by glycolysis, particularly via glyceraldehyde 3-phosphate dehydrogenase/3-phosphoglycerate kinase, is critical for synaptic transmission. We present evidence that ATP generated by synaptic vesicle-associated pyruvate kinase is harnessed to transport glutamate into synaptic vesicles. Isolated synaptic vesicles incorporated [(3)H]glutamate in the presence of phosphoenolpyruvate (PEP) and ADP. Pyruvate kinase activators and inhibitors stimulated and reduced PEP/ADP-dependent glutamate uptake, respectively. Membrane potential was also formed in the presence of pyruvate kinase activators. "ATP-trapping" experiments using hexokinase and glucose suggest that ATP produced by vesicle-associated pyruvate kinase is more readily used than exogenously added ATP. Other neurotransmitters such as GABA, dopamine, and serotonin were also taken up into crude synaptic vesicles in a PEP/ADP-dependent manner. The possibility that ATP locally generated by glycolysis supports vesicular accumulation of neurotransmitters is discussed. | 18,751,889 |
Comparison of nitrogen narcosis and helium pressure effects on striatal amino acids: a microdialysis study in rats. | Exposure to nitrogen-oxygen mixture at high pressure induces narcosis, which can be considered as a first step toward general anaesthesia. Narcotic potencies of inert gases are attributed to their lipid solubility. Nitrogen narcosis induces cognitive and motor disturbances that occur from 0.3 MPa in man and from 1 MPa in rats. Neurochemical studies performed in rats up to 3 MPa have shown that nitrogen pressure decreases striatal dopamine release like argon, another inert gas, or nitrous oxide, an anaesthetic gas. Striatal dopamine release is under glutamatergic and other amino acid neurotransmission regulations. The aim of this work was to study the effects of nitrogen at 3 MPa on striatal amino acid levels and to compare to those of 3 MPa of helium which is not narcotic at this pressure, by using a new technique of microdialysis samples extraction under hyperbaric conditions, in freely moving rats. Amino acids were analysed by HPLC coupled to fluorimetric detection in order to appreciate glutamate, aspartate, glutamine and asparagine levels. Nitrogen-oxygen mixture exposure at 3 MPa decreased glutamate, glutamine and asparagine concentrations. In contrast, with helium-oxygen mixture, glutamate and aspartate levels were increased during the compression phase but not during the stay at maximal pressure. Comparison between nitrogen and helium highlighted the narcotic effects of nitrogen at pressure. As a matter of fact, nitrogen induces a reduction in glutamate and in other amino acids that could partly explain the decrease in striatal dopamine level as well as the motor and cognitive disturbances reported in nitrogen narcosis. | 18,751,893 |
Constitutive modeling of rate-dependent stress-strain behavior of human liver in blunt impact loading. | An understanding of the mechanical deformation behavior of the liver under high strain rate loading conditions could aid in the development of vehicle safety measures to reduce the occurrence of blunt liver injury. The purpose of this study was to develop a constitutive model of the stress-strain behavior of the human liver in blunt impact loading. Experimental stress and strain data was obtained from impact tests of 12 unembalmed human livers using a drop tower technique. A constitutive model previously developed for finite strain behavior of amorphous polymers was adapted to model the observed liver behavior. The elements of the model include a nonlinear spring in parallel with a linear spring and nonlinear dashpot. The model captures three features of liver stress-strain behavior in impact loading: (1) relatively stiff initial modulus, (2) rate-dependent yield or rollover to viscous "flow" behavior, and (3) strain hardening at large strains. Six material properties were used to define the constitutive model. This study represents a novel application of polymer mechanics concepts to understand the rate-dependent large strain behavior of human liver tissue under high strain rate loading. Applications of this research include finite element simulations of injury-producing liver or abdominal impact events. | 18,751,900 |
Microarray analysis reveals similarity between CD8+CD28- T cells from young and elderly persons, but not of CD8+CD28+ T cells. | We isolated highly purified CD8+CD28+ and CD8+CD28- T cell populations from healthy young and elderly persons for gene expression profiling using Affymetrix oligonucleotide microarrays. We demonstrate that the gene expression profile of CD8+CD28- T cells is very similar in young and elderly persons. In contrast, CD8+CD28+ in elderly differ from CD8+CD28+ in young persons. Hierarchical clustering revealed that CD8+CD28+ in elderly are located between CD8+CD28+ in young and CD8+CD28- (young and old) T cells regarding their differentiation state. Our study demonstrates a dichotomy of gene expression levels between CD8+CD28+ T cells in young and elderly persons but a similarity between CD8+CD28- T cells in young and elderly persons. As CD8+CD28+ T cells from elderly and young persons are distinct due to a different composition of the population, these results suggest that the gene expression profile does not depend on chronological age but depends on the differentiation state of the individual cell types. | 18,751,903 |
Fatty acid amide hydrolase: a gate-keeper of the endocannabinoid system. | The family of endocannabinoids contains several polyunsaturated fatty acid amides such as anandamide (AEA), but also esters such as 2-arachidonoylglycerol (2-AG). These compounds are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of Delta9-tetrahydrocannabinol (Delta9-THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA at its receptors is limited by cellular uptake, through a putative membrane transporter, followed by intracellular degradation by fatty acid amide hydrolase (FAAH). Growing evidence demonstrates that FAAH is the critical regulator of the endogenous levels of AEA, suggesting that it may serve as an attractive therapeutic target for the treatment of human disorders. In particular, FAAH inhibitors may be next generation therapeutics of potential value for the treatment of pathologies of the central nervous system, and of peripheral tissues. Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAH inhibitors, are the topic of this chapter. | 18,751,909 |
MALDI-TOF MS analysis of lipids from cells, tissues and body fluids. | Many diseases as atherosclerosis and metabolic dysfunctions are known to correlate with changes of the lipid profile of tissues and body fluids. Therefore, the importance of reliable methods of lipid analysis is obvious. Although matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) was so far primarily used for protein analysis, this method has itself proven to be very useful in lipid analysis, too. This review provides an overview of applications of MALDI-TOF MS in lipid analysis and summarizes the specific advantages and drawbacks of this modern soft-ionization method. The focus will be on the analysis of body fluids and cells as well as the diagnostic potential of the method in the lipid field. It will be shown that MALDI-TOF mass spectra can be recorded in a very short time and provide important information on the lipid as well as the fatty acyl composition of the lipids of an unknown sample. However, it will also be shown that only selected lipid classes (in particular those with quaternary ammonia groups as phosphatidylcholine) are detected if crude mixtures are analyzed as they are more sensitively detectable than other ones. This review ends with a short outlook emphasizing current methodological developments. | 18,751,926 |
Lipidomics in diagnosis of lipidoses. | A review is presented of the major clinical features of a number of glycolipidoses including Fabry, Gaucher, Tay-Sachs, metachromatic leukodystrophy as well as CeroidLipofucinosis and Sjogren-Larsson syndrome. The possibilities offered by lipidomics for diagnosis and follow-up after enzyme replacement therapy are presented from a practical perspective. The contribution of HPLC coupled with tandem mass spectrometry has considerably simplified the detection and assay of abnormal metabolites. Corresponding internal standards consisting of weighed mixtures of the stable-isotope labeled metabolites required to calibrate and quantitate lipid components of these orphan diseases standards have yet to become commercially available. A lipidomics approach has been found to compare favorably with DNA-sequence analysis for the rapid diagnosis of pre-birth syndromes resulting from these multiple gene defects. The method also seems to be suitable for screening applications in terms of a high throughput combined with a low rate of false diagnoses based on the wide differences in metabolite concentrations found in affected patients as compared with normal subjects. The practical advantages of handling samples for lipidomic diagnoses as compared to enzyme assay are presented for application to diagnosis during pregnancy. | 18,751,927 |
Laparoscopic cholecystectomy in patients with a history of gastrectomy. | Previous gastrectomy has been considered a relative contraindication to laparoscopic cholecystectomy (LC). The aim of this study was to evaluate the safety and efficacy of LC in patients with a history of gastrectomy. From a database of 1 104 consecutive patients with symptomatic gallstone disease, who underwent LC between April 1992 and January 2007, 51 (4.6%) had undergone previous gastrectomy: for gastric cancer (n = 36) or gastroduodenal ulcer (n = 15). We compared the operative time, blood loss, conversion rate, morbidity rate, diet resumption, and postoperative hospital stay between patients with, and those without, a history of gastrectomy. The incidence of common bile duct stones was significantly higher (33.3% vs 8.6%, P < 0.001) and operative time was significantly longer (111.2 min vs 77.9 min, P < 0.001) in the patients with a history of gastrectomy. There was no significant difference in operative time between the first-half and second-half periods. Conversion to an open cholecystectomy was required in two patients. There was no significant difference between the two groups in blood loss, conversion rate, morbidity rate, diet resumption, or postoperative hospital stay. Laparoscopic cholecystectomy is a safe and effective treatment for symptomatic gallstone disease in patients with a history of gastrectomy, although previous gastrectomy is associated with an increased need for adhesiolysis and a longer operative time. | 18,751,943 |
The rapid growth of intraluminal tumor metastases at the intestinal wall sites damaged by obstructive colitis due to sigmoid colon cancer: report of a case. | A 53-year-old woman who was traveling in Australia was admitted to a local hospital with pyrexia and diarrhea. Megacolon was diagnosed from an X-ray and an emergency operation was performed. However, the cause of megacolon was not clear, and the attempted operation ended in a simple laparotomy. Sigmoid cancer was found 3 weeks after the first operation and a colostomy was performed at the ascending colon. After the second operation, she returned to Japan and was thereafter admitted to our hospital. Total colonoscopy before the third surgery (sigmoidectomy) revealed erosive mucosa but no tumor. The damaged mucosa in the proximal colon (compatible with a diagnosis of obstructive colitis) was found during a sigmoidectomy. Watery diarrhea and melena persisted after the third operation. Colonoscopy showed disseminated tumor nodules at the proximal colon of the anastomosis at 37 days after the third surgery. Finally, a subtotal colectomy and jejunal pouch reconstruction were carried out. The exfoliated malignant cells from the sigmoid colon appeared to form micrometastases in the mucosal sites damaged by obstructive colitis. In conclusion, in a case of obstructive colitis due to cancer, we must consider the possibility that the tumor may spread to damaged mucosal sites and grow intraluminally. | 18,751,956 |
[Diffuse abdominal pain and eosinophilia]. | Eosinophilic gastroenteritis is a rare clinical condition of unknown aetiology and heterogenic etiopathology. Important differential diagnoses are intestinal parasitic infections, hypereosinophilic syndrome, malignancies such as lymphoma and allergic diseases. The diagnosis can be made in most cases by patient history, routine laboratory testing and endoscopic biopsies or paracentesis. Patients with only mild diarrhea can be treated with antidiarrheal medications. More symptomatic patients are usually treated with corticosteroids. | 18,751,963 |
Prospective dosimetry with 99mTc-MDP in metabolic radiotherapy of bone metastases with 153Sm-EDTMP. | On the basis of the encouraging results achieved in several clinical trials and its proven therapeutic efficacy, (153)Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP) has become widely used to palliate pain from bone metastases. The results reported in the literature have led the product suppliers (QUADRAMET, Schering) to suggest administering a fixed activity per kilogram (37 MBq/kg). However, considering the observed extreme inter-patient variability of skeletal uptake of (153)Sm-EDTMP, a real therapy optimization would require the individualization of the activity to be administered on a dosimetric basis. This should be planned taking into account the generally accepted 2-Gy dose constraint to the haematopoietic red marrow, the critical organ in palliative treatments with beta-emitting, bone-seeking radiopharmaceuticals. Seven to 14 days before treatment with (153)Sm-EDTMP, 44 patients underwent (99m)Tc-methylene diphosphonate (MDP) total-body bone scan with two scans (the first within 10 min of injection, the second after 6 h). The percentage bone uptake (Tc(%)) was evaluated as the ratio between total counts at 6 h, adjusted for decay, and total counts at the first scan. Tc(%) was then compared to Sm(%) similarly derived from 10-min and 24-h whole-body scans. Tc(%) and Sm(%) were compared both with and without Brenner's method for soft tissue uptake. The correlation between Tc(%) and Sm(%) was R (2) = 0.81 and R (2) = 0.88 with and without soft tissue correction, respectively. The difference between their average values was statistically significant (Sm(%) = 64.3 +/- 15.2, Tc(%) = 56.2 +/- 16.0; p = 0.017) with soft tissue correction, while was not statistically significant (Sm(%) = 68.2 +/- 15.5, Tc(%) = 66.9 +/- 14.0; p = 0.670) without soft tissue correction. The rate of retention of (99m)Tc-MDP in bone provides a reliable estimate of the (153)Sm-EDTMP rate of retention. The proposed method can be usefully adopted for prospective dosimetry seeing its extreme simplicity, and it requires no special investment in terms of human or instrumental resources. This allows an optimization of administered (153)Sm-EDTMP activity. | 18,751,975 |
Non-operative diagnosis--effect on repeat-operation rates in the UK breast screening programme. | Non-operative diagnosis rates in the UK breast screening programme have improved dramatically from 48.8% in 1994/95 (only nine units achieved the then minimum standard of 70%) to 94% in 2005/06 (only seven units failed to achieve the target of 90%). Preoperative and operative history of all 120,550 women diagnosed with screen-detected breast cancer in the UK between April 1994 and March 2006 was derived from different national databases. In 2005/06, 2,790 (17.8%) of the 15,688 women having surgery needed two or more operations. In 2001/02 (non-operative diagnosis rate 87%), the re-operation rate was 23.8% (2,377 of 9,969). Extrapolation backwards to 1994/95 (non-operative diagnosis rate 48.8%) suggests a re-operation rate of 62%. Analysis over the 4 years from April 2002 (n=34,198) demonstrates that 4,089 (12%) women with a correct non-operative diagnosis of invasive disease required additional surgery compared to 1,166 (48%) of women who were under-staged (diagnosed as non-invasive based on core biopsy, but actually suffering from invasive disease). Failure to achieve a non-operative diagnosis of invasive disease (n=1,542) or non-invasive disease (n=2,247) resulted in re-operation rates of 65 and 43% respectively. Given the impact of not having a diagnosis pre-operatively, or of under-staging invasive carcinoma, it seems timely to introduce more sophisticated standards. | 18,751,983 |
Genome-wide distribution of ancestry in Mexican Americans. | Migrations to the new world brought together individuals from Europe, Africa and the Americans. Inter-mating between these migrant and indigenous populations led to the subsequent formation of new admixed populations, such as African and Latino Americans. These unprecedented events brought together genomes that had evolved independently on different continents for tens of thousands of years and presented new environmental challenges for the indigenous and migrant populations, as well as their offspring. These circumstances provided novel opportunities for natural selection to occur that could be reflected in deviations at specific locations from the genome-wide ancestry distribution. Here we present an analysis examining European, Native American and African ancestry based on 284 microsatellite markers in a study of Mexican Americans from the Family Blood Pressure Program. We identified two genomic regions where there was a significant decrement in African ancestry (at 2p25.1, p < 10(-8) and 9p24.1, p < 2 x 10(-5)) and one region with a significant increase in European ancestry (at 1p33, p < 2 x 10(-5)). These locations may harbor genes that have been subjected to natural selection after the ancestral mixing giving rise to Mexicans. | 18,752,003 |
Identification of novel gene expression in healing fracture callus tissue by DNA microarray. | Fracture healing requires controlled expression of thousands of genes. Only a small fraction of these genes have been isolated and fewer yet have been shown to play a direct role in fracture healing. The purpose of this study was threefold: (1) to develop a reproducible open femur model of fracture healing that produces consistent fracture calluses for subsequent RNA extraction, (2) to use this model to determine temporal expression patterns of known and unknown genes using DNA microarray expression profiling, and (3) to identify and validate novel gene expression in fracture healing. In the initial arm of the study, a total of 56 wild-type C57BL/6 mice were used. An open, stabilized diaphyseal femur fracture was created. Animals were killed at 1, 5, 7, 10, 14, 21, and 35 days after surgery and the femurs were harvested for analysis. At each time point, fractures were radiographed and sectioned for histologic analyses. Tissue from fracture callus at all stages following fracture yielded reproducibly large amounts of mRNA. Expression profiling revealed that genes cluster by function in a manner similar to the histologic stages of fracture healing. Based on the expression profiling of fracture tissue, temporal expression patterns of several genes known to be involved in fracture healing were verified. Novel expression of multiple genes in fracture callous tissue was also revealed including leptin and leptin receptor. In order to test whether leptin signaling is required for fracture repair, mice deficient in leptin or its receptor were fractured using the same model. Fracture calluses of mice deficient in both leptin or leptin receptor are larger than wild-type mice fractures, likely due to a delay in mineralization, revealing a previously unrecognized role of leptin signaling in fracture healing. This novel model of murine fracture repair is useful in examining both global changes in gene expression as well as individual signaling pathways, which can be used to identify specific molecular mechanisms of fracture healing. | 18,752,025 |
Staphylococcal cassette chromosome mec (SCCmec) characterization and panton-valentine leukocidin gene occurrence for methicillin-resistant Staphylococcus aureus in Turkey, from 2003 to 2006. | Methicillin-resistant Staphylococcus aureus (MRSA) cause serious community-acquired and nosocomial diseases all over the world. We determined the SCCmec types and occurrence of the PVL gene by using TaqMan real-time PCR method, and correlated these with phenotypic antibiotic susceptibility patterns for MRSA strains collected from Gulhane Military Medical Academy Hospital (GMMAH) during 4 years study period. To our knowledge, this is the first report from Turkey of molecular SCCmec typing analysis of MRSA stains. A total of 385 clinical MRSA isolates collected in the clinical and Microbiology Laboratory at GMMAH between 2003 and 2006 were included in the study. Overall, SCCmec types-I, II, III, IV, V, nontypeable and PVL occurrence were detected in 11 (2.8%), 3 (0.8%), 316 (82.1%), 20 (5.1%), 20 (5.1%), 15 (3.9%) and 5 (1.3%) isolates, respectively. A total of 330 (85.5%) were SCCmec-I/II/III and 40 (10.3%) were SCCmec IV/V. SCCmec-I/II/III isolates were recovered more from patients with serious infections in surgical departments especially those with intensive care units than the SCCmec-IV/V isolates (chi(2) = 13.560, P < 0.001). SCCmec-I/II/III MRSA strains were predominantly recovered from blood stream (53.0%, P = 0.014), while SCCmec-IV/V strains were predominately isolated from skin and soft tissue and abscess (55.0%, P < 0.001). The PVL gene was detected in 10.0% of SCCmec-IV/V isolates in contrast to 0.3% in SCCmec-I/II/III (chi(2) = 25.164, P < 0.001). SCCmec-I/II/III MRSA strains were more resistant to clindamycin (chi(2) = 5.078, P = 0.024), amoxicillin-clavulanate (chi(2) = 84.912, P < 0.001), erythromycin (chi(2) = 4.651, P = 0.031), gentamicin (chi(2) = 24.869, P < 0.001), and rifampin (chi(2) = 18.878, P < 0.001) than SCCmec-IV/V MRSA strains. This data indicates that SCCmec-III MRSA strains that do not carry the PVL gene are the predominant MRSA strains in our hospital setting in Ankara, capital of Turkey and that SCCmec-I/II/III MRSA strains may cause serious infections in surgical departments especially those with intensive care units. | 18,752,036 |
Inhibitor of DNA binding-1 overexpression in prostate cancer: relevance to tumor differentiation. | Inhibitor of DNA binding-1 (Id1) is a dominant-negative regulator of basic helix-loop-helix transcription factor, which control malignant cell behaviors in several types of carcinomas. This study aimed to find the relationship between Id1 expression and some clinical parameters. Paraffin-embedded tissue specimens from two normal human prostates, 12 benign prostatic hyperplasia (BPH), 43 prostate cancers(PCa) were detected by immunofluorescence assay. Prostatectomy samples from 11 BPH and 28 PCa were used for real time RT-PCR. The relationship between Id1 staining and several patient's clinical parameters, including Gleason grade, PSA, clinical stage, and size of tumor, was further analyzed. Significant up-regulated Id1 protein was shown in prostate cancer specimens, while only weak expression in some BPH samples (5/12). Analyzed by image software, the mean proportion of Id1 positive staining remarkably increased with the increasing of Gleason grade in prostate cancer specimens (r = 0.9967, P < 0.01). Id1 expression was not significantly associated with PSA, TNM stage or tumor size. Furthermore, the average mRNA of prostate cancer was 3.09 times of BPH. This study confirms that Id1 protein and mRNA are over expressed in prostate cancer tissues. Overexpression of Id1 protein correlates with tumor tissue differentiation. We propose that Id1 over expression can be used in the analysis of the progression of prostate cancer. | 18,752,043 |
Mass spectrometric quantification of amino acid oxidation products identifies oxidative mechanisms of diabetic end-organ damage. | Diabetes mellitus is increasingly prevalent worldwide. Diabetic individuals are at markedly increased risk for premature death due to cardiovascular disease. Furthermore, substantial morbidity results from microvascular complications which include retinopathy, nephropathy, and neuropathy. Clinical studies involving diabetic patients have suggested that degree of diabetic hyperglycemia correlates with risk of complications. Recent evidence implicates a central role for oxidative stress and vascular inflammation in all forms of insulin resistance, obesity, diabetes and its complications. Although, glucose promotes glycoxidation reactions in vitro and products of glycoxidation and lipoxidation are elevated in plasma and tissue in diabetics, the exact relationships among hyperglycemia, the diabetic state, and oxidative stress are not well-understood. Using a combination of in vitro and in vivo experiments, we have identified amino acid oxidation markers that serve as molecular fingerprints of specific oxidative pathways. Quantification of these products utilizing highly sensitive and specific gas chromatography/mass spectrometry in animal models of diabetic complications and in humans has provided insights in oxidative pathways that result in diabetic complications. Our studies strongly support the hypothesis that unique oxidants are generated in the microenvironment of tissues vulnerable to diabetic damage. Potential therapies interrupting these reactive pathways in target tissue are likely to be beneficial in preventing diabetic complications. | 18,752,069 |
[Up-date on the treatment of serious fungal infections]. | In recent years, there has been an exponential increase in the incidence of severe fungal infections with elevated morbidity-mortality. An attempt is currently being made to obtain faster and more reliable diagnostic tests for a certainty diagnosis and to be able to use clinical criteria to identify patients who could be candidates to receive early antifungal treatment and thus be able to improve the prognosis. For the purposes of this article, we reviewed the indexed literature for the last 15 years. We used different key words: invasive fungal infection (IFI), invasive aspergillosis, candidemia, and candidiasis, emerging fungi, prophylaxis and antifungal treatment (empiric, directed and pre-emptive treatment). The approach to antifungal treatment is also undergoing significant changes. These go from the appearance of new molecules, new generations of other already known ones and also changes in the more <<traditional>> approach in its use. This article is structured on the use slope of antifungal agents in non-neutropenic critical patients from their prophylaxis, empiric treatment, aimed towards new strategies (pre-emptive treatment or early therapy or combined use of antifungal agents). Furthermore, an attempt is being made to obtain simple scores to indicate their early onset in patients with high risk of IFI. The combination of rapid identification of patients with risk (scores), faster diagnostic methods and finally more effective antifungal treatment with the providing of new antifungal agents and/or strategies will be essential to try to decrease the elevated morbidity-mortality in severe patients. | 18,752,076 |
Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. | Sunitinib is a multitargeted tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST), and undergoing evaluation for other malignancy. Hypertension is one of its major side effects with a substantial variation in the reported incidences among clinical studies. We here performed a systematic review and meta-analysis of published clinical trials to determine its overall risk. Relevant studies were searched and identified in MEDLINE (OVID 1966 to July, 2007), Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2007. Eligible studies were prospective clinical trials that had described events of hypertension for patients who received single agent sunitinib. The incidence of hypertension and relative risk (RR) were calculated using the random-effects or the fixed-effects model. A total of 4,999 patients with RCC and other malignancies from 13 clinical trials were included for analysis. Among patients receiving sunitinib, the incidence of all-grade and high-grade hypertensions were 21.6% (95% CI: 18.7-24.8%) and 6.8% (95% CI: 5.3-8.8%) respectively. The risk may vary with tumor type and the dosing schedule of sunitinib. Sunitinib was associated with a significantly increased risk of high-grade hypertension (RR=22.72, 95% CI: 4.48 to 115.29, p<0.001) and renal dysfunction (RR: 1.36, 95% CI: 1.20 to 1.54, p<0.001) in comparison with controls. There is a significant risk of developing hypertension and renal dysfunction among patients receiving sunitinib. Adequate monitoring and treatment of hypertension is recommended. | 18,752,081 |
The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis. | Amyotrophic lateral sclerosis is increasingly recognized to be a complex multisystems disorder both at the level of its pathobiology and in the breadth of non-motor manifestations that can accompany it. Paramount among these are disorders of frontotemporal function which can be associated with syndromes of behavioural, cognitive or executive dysfunction or manifest as a frontotemporal dementia (FTD). While these may occur in isolation and precede the development of motor deficits, more commonly they insidiously onset following the initial neuromuscular dysfunction. The earliest clinical manifestation is a loss of verbal fluency, disproportionate to impairments in oromotor control. There is good correlation between the presence of a syndrome of frontotemporal dysfunction and alterations in brain structure or function as identified with a wide variety of neuroimaging techniques and which reflect a frontotemporal lobar degeneration (FTLD). Although the cause(s) of this process remain to be defined, as with the clinical heterogeneity, there is likely to be significant biochemical heterogeneity. This includes alterations in tau protein metabolism which are present in a proportion of familial and sporadic ALS cases, as well as the western Pacific variant, and recently described alterations in the metabolism of the TAR DNA binding protein 43 (TDP-43). | 18,752,088 |
Barriers in the help-seeking process: a multiple-case study of early-onset dysthymia in Sweden. | The aim of this study was to investigate barriers to diagnosis and adequate treatment of patients with early-onset dysthymia by studying how understandings of illness by patients and providers have evolved and how treatments have been negotiated over time. A theory-testing and explorative multiple-case study design was used with developmental cognitive theory as framework. Data pertaining 10 non-remission dysthymic patients were analyzed using five sources: 1) case records, 2) interviews, 3) self-report questionnaires, 4) observations, and 5) life-charting, eliciting life events, course and treatments. The analysis comprised qualitative content analysis and a coding scheme of knowledge structures. Barriers could be explained by misunderstandings as patients mainly expressed illness in concrete, perceptually bound knowledge structures and providers focused on one aspect, instead of on the complexity of concurrent aspects. Another barrier, associated to comorbid personality disorder, was a core pattern of concealing due to fear of rejection and mistrust. Other barriers were connected to providers' attitudes and contextual factors such as access problems and lack of follow-up. A theoretical model that involves patients' understanding of illness in preoperational thinking and providers' cognitive errors can explain communication barriers. Means of shared understanding and treatment planning are suggested. Future treatment research could elucidate the impact of the core belief of rejection with associated strategy of concealing by assessing these variables as predictors and as targets for change. | 18,752,107 |
The relationship between alexithymia and salivary cortisol levels in somatoform disorders. | The purpose of this study was to investigate cortisol levels as a function of the hypothalamic-pituitary-adrenal axis (HPA) in relation to alexithymia in patients with somatoform disorders (SFD). Diurnal salivary cortisol was sampled in 32 patients with SFD who also underwent a psychiatric examination and filled in questionnaires (Toronto Alexithymia Scale, TAS scale; Screening for Somatoform Symptoms, SOMS scale; Hamilton Depression Scale, HAMD). The mean TAS total score in the sample was 55.6+/-9.6, 32% of patients being classified as alexithymic on the basis of their TAS scores. Depression scores were moderate (HAMD=13.2, Beck Depression Inventory, BDI=16.5). The patients' alexithymia scores (TAS scale "Difficulty identifying feelings") correlated significantly positively with their somatization scale scores (Symptom Checklist-90 Revised, SCL-90-R); r=0.3438 (P<0.05) and their scores on the Global Severity Index (GSI) on the SCL-90-R; r=0.781 (P<0.01). Regression analysis was performed with cortisol variables as the dependent variables. Cortisol levels [measured by the area under the curve-ground (AUC-G), area under the curve-increase (AUC-I) and morning cortisol (MCS)] were best predicted in a multiple linear regression model by lower depressive scores (HAMD) and more psychopathological symptoms (SCL-90-R). No significant correlations were found between the patients' alexithymia scores (TAS) and cortisol levels. The healthy control group (n=25) demonstrated significantly higher cortisol levels than did the patients with SFD; in both tests P<0.001 for AUC-G and AUC-I. However, the two groups did not differ in terms of their mean morning cortisol levels (P>0.05). The results suggest that pre-existing hypocortisolism might possibly be associated with SFD. | 18,752,108 |
SOCS-3 is associated with vascular invasion and overall survival in hepatocellular carcinoma. | Alteration of the suppressor of cytokine signalling-3 (SOCS-3) has been observed in certain human cancers. However, the clinical role of this short-lived protein in hepatocellular carcinoma (HCC) is not well established. Therefore, we aimed to explore the potential role of SOCS-3 proteins in HCC. Paraffin embedded sections from 87 HCC patients were included in this study. The expression patterns of SOCS-3 proteins were analysed using immunohistochemistry and the results were correlated with clinicopathological characteristics and overall survival of the HCC patients. The SOCS-3 expression of HCC lesions and the adjacent non-tumourous liver tissues was significantly correlated (p = 0.035), while the SOCS-3 expression in HCC lesions was significantly and positively correlated with vascular invasion and histological grading (p = 0.034 and 0.032, respectively). The Kaplan-Meier survival curve showed that the HCC patients with high SOCS-3 expression were associated with a poor overall survival rate in the HCC subgroup with positive vascular invasion (p = 0.014). Furthermore, a multivariate Cox regression model showed that SOCS-3 expression was also a significant determinant of the overall survival for HCC (p = 0.006). Our results indicate that altered SOCS-3 expression is associated with the overall survival in a subset of HCC patients with positive vascular invasion. Constitutive and altered SOCS-3 expression may have potential roles in a subset of HCC patients. | 18,752,121 |
Pattern and spectrum of morphology referrals in breast pathology consultation. | We aimed to identify common reasons for second opinion breast pathology referrals at the Pathology Department, Singapore General Hospital, focusing on queries and diagnostic issues raised by referring clinicians and pathologists. Request forms for breast pathology consultations were retrieved from a specialist's correspondence files consisting of pathologists' referrals, and from centralised laboratory records, comprising clinician-initiated referrals. Clinical and histomorphological queries raised by the referrals were collated. Of 299 cases evaluated, clinician-initiated referrals (n = 137, 46%) included requests for review of overall histopathology to confirm carcinoma subtype (n = 47), grade (n = 2), size (n = 4), lymphovascular invasion (n = 1) and confirm hormonal receptor and c-erbB-2 assays (n = 33). Also required were: comparison of recurrent with previous lesions (n = 8); settling discrepant diagnoses between two or more prior pathology reports (n = 4); verification of microinvasion (n = 6), in situ carcinomas (n = 6) or atypical ductal hyperplasias (n = 4); delineation of benign (n = 8) and spindle cell lesions (n = 3); to establish a breast origin of metastatic lesions (n = 5); and distinction of carcinoma from lymphoma (n = 2). Pathologist-initiated referrals (n = 162, 54%) sought arbitration between borderline proliferative lesions (n = 46) and papillary lesions (n = 34); verification of microinvasion (n = 23), stromal lesions (n = 16), and carcinoma subtype (n = 13), especially if the patient was young (n = 5); clarification of metaplastic changes (n = 4) and lobular neoplasia (n = 8); and comparison of fibroepithelial lesions (n = 11). Clinicians sought a second opinion mainly to verify histological diagnoses and report important pathological details for staging and confirmation of hormonal receptor and c-erbB-2 status prior to therapy. Borderline breast lesions are worrisome for both clinicians and pathologists in view of implications for management. | 18,752,122 |
Paget's osteosarcoma and post-radiation osteosarcoma: secondary osteosarcoma at Middlemore Hospital, New Zealand. | To review the clinical and histological features of our cases of Paget's osteosarcoma and post-radiation osteosarcoma. A search through the files of the New Zealand Bone and Soft Tissue Tumour Registry was performed, patients were identified and the relevant details were collated. Thirty-one cases of Paget's osteosarcoma and eight cases of post-radiation osteosarcoma were identified. Patients with Paget's osteosarcoma were aged between 48 and 67 years, predominantly female, and axial and appendicular skeleton were equally affected. The outcome was known in 29 cases, with a median survival of 7.25 months and 5 year overall survival of 10%. Patients with post-radiation osteosarcoma were aged between 17 and 68 years, equally male or female, and axial and appendicular skeleton were equally affected. Index lesions included benign or malignant osseous and non-osseous conditions. The average age at diagnosis of the index lesion was 30.1 years and the average latent period was 13.5 years. The outcome was known in all eight cases, with a median survival of 33 months and 5 year overall survival of 38%. Paget's osteosarcoma and post-radiation osteosarcoma are examples of secondary osteosarcoma. The former affects elderly patients, and has a poor prognosis and response to treatment. The later affects a wide age group, and has a prognosis and response to treatment comparable with primary osteosarcoma. | 18,752,128 |
Are positive surgical margins in radical prostatectomy specimens an independent prognostic marker? | A positive surgical margin (PSM) is considered an adverse prognostic indicator in patients undergoing radical prostatectomy (RP). However, there are discrepancies among studies concerning the effect of PSM on prognosis. In addition, the significance of PSM location and extent is uncertain. The aim of this study was to examine the impact of surgical margin status on serum prostate-specific antigen (sPSA) relapse in men consecutively receiving RP in a non-screened population. In total, 219 prostatectomy specimens were examined microscopically. The mean follow-up time was 62 months (range 6-121 months). Tumour grade (Gleason score), pathological tumour stage and tumour involvement of the surgical margins were recorded. The 71 specimens with one or more PSM were re-examined with regard to location, number of locations and total linear extent of PSM. Kaplan-Meier plots and Cox proportional hazards regression were used in the univariate analyses. Multivariate analyses controlling for the known preoperative sPSA, pathological stage and Gleason score were also performed, using Cox proportional hazards regression. In the univariate analyses, PSM without regard to location, PSM at the anterior prostate or at the apex, PSM at three or more locations and linear extent of PSM > or =6mm were associated with a statistically significant higher hazard ratio of PSA relapse. However, none of these variables remained statistically significant when controlling for the known risk factors. In this non-screened prostate cancer population PSM status (linear extent, location and number of locations) had an impact on postoperative sPSA recurrence. In multivariate analyses PSM showed a strong trend (p approximately 0.06) towards having an independent statistically significant negative influence on the risk of PSA relapse following RP. | 18,752,153 |
Hazardous use of gamma hydroxybutyrate: driving under the influence. | Focus group discussions elicited descriptive experiences of driving under the influence of gamma hydroxybutyrate (GHB), and uncovered motivations that led participants to decide whether to get behind the wheel after ingesting this illegal psychoactive substance. Of the 51 current and past users interviewed, average age 31.1 +/- 7.7 years, 40% were female. All were recruited from the San Francisco Bay Area, in 2004. Factors making users vulnerable to adverse complications of driving while under the influence of GHB are also examined. Study limitations were noted. Implications for various law enforcement agencies and health professionals are derived from the data. | 18,752,156 |
Alkyl-functionalized oxide-free silicon nanoparticles: synthesis and optical properties. | Highly monodisperse silicon nanoparticles (1.57 +/- 0.21 nm) are synthesized with a covalently attached alkyl monolayer on a gram scale. Infrared spectroscopy shows that these silicon nanoparticles contain only a few oxygen atoms per nanoparticle. XPS spectra clearly show the presence of unoxidized Si and attached alkyl chains. Owing to the relatively efficient synthesis (yields approximately 100-fold higher than of those previously reported) the molar extinction coefficient epsilon can be measured: epsilon(max) = 1.7 x 10(-4) M(-1)cm(-1), only a factor of 4 lower than that of CdS and CdSe nanoparticles of that size. The quantum yield of emission ranges from 0.12 (C(10)H(21)-capping) to 0.23 (C(16)H(33)-capping). UV/Vis absorption and emission spectroscopy show clear vibrational progressions (974 +/- 14 cm(-1); up to five vibrational bands visible at room temperature), resembling bulk SiC phonons, which support the monodispersity observed by TEM. This was also confirmed by time-resolved fluorescence anisotropy measurements, which display a strictly monoexponential decay that can only be indicative of monodisperse, ball-shaped nanoparticles. | 18,752,208 |
Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors. | Plasmepsins (Plm) II (EC number: 3.4.23.39) and IV (EC number: 3.4.23.B14) are aspartic proteases present in the food vacuole of the malaria parasite Plasmodium falciparum and are involved in host hemoglobin degradation. Based on our established efficient synthetic sequence, a series of inhibitors for Plm II and IV has been synthesized bearing a 2,3,4,7-tetrahydro-1H-azepine scaffold as the core structural element. During the computational design cycle, thorough investigations were carried out in order to find a reasonable theoretical binding mode for Plm II and IV. The conformation of Plm II in the crystal structure (PDB code: 1LF2) provides a good starting geometry for our virtual screening approach. In contrast, the only available co-crystal structure for Plm IV of P. falciparum (PDB code: 1LS5) appears inappropriate for inhibitor design. Therefore, a homology model was constructed based on the Plm II 1LF2 structure. A combinatorial docking run using FlexX(c) suggested compounds which, after synthesis, turned out to exhibit affinities in the sub-micromolar range. The observed structure-activity relationships of the synthesized compounds confirm the assumed binding mode for Plm II and IV. The best-binding inhibitors designed for Plm II and IV are devoid of any inhibitory potency against human cathepsin D (EC number: 3.4.23.5). | 18,752,222 |
Intracellular uptake and inhibitory activity of aromatic fluorinated amino acids in human breast cancer cells. | Nonproteinogenic amino acids that either occur naturally or are synthesized chemically are becoming important tools in modern drug discovery. In this context, fluorinated amino acids have great potential in the development of novel pharmaceuticals and drugs. To assess whether different fluorinated aromatic amino acid analogues of phenylalanine, tyrosine, and tryptophan are potentially interesting as therapeutic drugs, we examined their cytostatic and cytotoxic effects on the growth of the human breast cancer cell line MCF-7. Of all the tested analogues L-4-fluorotryptophan, L-6-fluorotryptophan and L-p-fluorophenylalanine effectively and irreversibly inhibited cell growth with IC(50) values in the low micromolar range (3-15 microM). Additionally, using L-4-[14C]fluorotryptophan, and L-6-[14C]fluorotryptophan, we discovered that the cellular uptake of these fluorinated amino acids occurs through active transport with a 70-fold excess of intracellular over extracellular concentrations. We identified system L as the responsible amino acid transporter. Our findings fully support the idea that fluorinated aromatic amino acid analogues are promising chemotherapeutics with the potential for use in combination with classical cancer therapy, and as new cytotoxic drugs for certain tumor types such as melanoma. | 18,752,223 |
Thiocarbamate-linked peptides by chemoselective peptide ligation. | Peptide chemical ligation chemistries, which allow the chemoselective coupling of unprotected peptide fragments, are useful tools for synthesizing native polypeptides or unnatural peptide-based macromolecules. We show here that the phenylthiocarbonyl group can be easily introduced into peptides on alpha or epsilon amino groups using phenylthiochloroformate and standard solid-phase method. It reacts chemoselectively with cysteinyl peptides to give an alkylthiocarbamate bond. S,N-shift of the alkylaminocarbonyl group from the Cys side chain to the alpha-amino group did not occur. The method was used for linking two peptide chains through their N-termini, for the synthesis of a cyclic peptide or for the synthesis of di- or tetravalent multiple antigenic peptides (MAPs). Thiocarbamate ligation is thus complementary to thioether, thioester or disulfide ligation methods. | 18,752,254 |
Dose-escalation designs in oncology: ADEPT and the CRM. | The ADEPT software package is not a statistical method in its own right as implied by Gerke and Siedentop (Statist. Med. 2008; DOI: 10.1002/sim.3037). ADEPT implements two-parameter CRM models as described in O'Quigley et al. (Biometrics 1990; 46(1):33-48). All of the basic ideas (use of a two-parameter logistic model, use of a two-dimensional prior for the unknown slope and intercept parameters, sequential estimation and subsequent patient allocation based on minimization of some loss function, flexibility to use cohorts instead of one by one inclusion) are strictly identical. The only, and quite trivial, difference arises in the setting of the prior. O'Quigley et al. (Biometrics 1990; 46(1):33-48) used priors having an analytic expression whereas Whitehead and Brunier (Statist. Med. 1995; 14:33-48) use pseudo-data to play the role of the prior. The question of interest is whether two-parameter CRM works as well, or better, than the one-parameter CRM recommended in O'Quigley et al. (Biometrics 1990; 46(1):33-48). Gerke and Siedentop argue that it does. The published literature suggests otherwise. The conclusions of Gerke and Siedentop stem from three highly particular, and somewhat contrived, situations. Unlike one-parameter CRM (Biometrika 1996; 83:395-405; J. Statist. Plann. Inference 2006; 136:1765-1780; Biometrika 2005; 92:863-873), no statistical properties appear to have been studied for two-parameter CRM. In particular, for two-parameter CRM, the parameter estimates are inconsistent. This ought to be a source of major concern to those proposing its use. Worse still, for finite samples the behavior of estimates can be quite wild despite having incorporated the kind of dampening priors discussed by Gerke and Siedentop. An example in which we illustrate this behavior describes a single patient included at level 1 of 6 levels and experiencing a dose limiting toxicity. The subsequent recommendation is to experiment at level 6! Such problematic behavior is not common. Even so, we show that the allocation behavior of two-parameter CRM is very much less stable than that of one-parameter CRM. | 18,752,259 |
A cremophor-free formulation for tanespimycin (17-AAG) using PEO-b-PDLLA micelles: characterization and pharmacokinetics in rats. | Tanespimycin (17-allylamino-17-demethoxygeldanamycin or 17-AAG) is a promising heat shock protein 90 inhibitor currently undergoing clinical trials for the treatment of cancer. Despite its selective mechanism of action on cancer cells, 17-AAG faces challenging issues due to its poor aqueous solubility, requiring formulation with Cremophor EL (CrEL) or ethanol (EtOH). Therefore, a CrEL-free formulation of 17-AAG was prepared using amphiphilic diblock micelles of poly(ethylene oxide)-b-poly(D,L-lactide) (PEO-b-PDLLA). Dynamic light scattering revealed PEO-b-PDLLA (12:6 kDa) micelles with average sizes of 257 nm and critical micelle concentrations of 350 nM, solubilizing up to 1.5 mg/mL of 17-AAG. The area under the curve (AUC) of PEO-b-PDLLA micelles was 1.3-fold that of the standard formulation. The renal clearance (CL(renal)) increased and the hepatic clearance (CL(hepatic)) decreased with the micelle formulation, as compared to the standard vehicle. The micellar formulation showed a 1.3-fold increase in the half-life (t(1/2)) of the drug in serum and 1.2-fold increase in t(1/2) of urine. As expected, because it circulated longer in the blood, we also observed a 1.7-fold increase in the volume of distribution (V(d)) with this micelle formulation compared to the standard formulation. Overall, the new formulation of 17-AAG in PEO-b-PDLLA (12:6 kDa) micelles resulted in a favorable 150-fold increase in solubility over 17-AAG alone, while retaining similar properties to the standard formulation. Our data indicates that the nanocarrier system can retain the pharmacokinetic disposition of 17-AAG without the need for toxic agents such as CrEL and EtOH. | 18,752,263 |
A fast, fully automated cell segmentation algorithm for high-throughput and high-content screening. | High-throughput, high-content screening (HT-HCS) of large compound libraries for drug discovery imposes new constraints on image analysis algorithms. Time and robustness are paramount while accuracy is intrinsically statistical. In this article, a fast and fully automated algorithm for cell segmentation is proposed. The algorithm is based on a strong attachment to the data that provide robustness and have been validated on the HT-HCS of large compound libraries and different biological assays. We present the algorithm and its performance, a description of its advantages and limitations, and a discussion of its range of application. | 18,752,283 |
Determination of tenatoprazole enantiomers and their enantioselective pharmacokinetics in rats. | The enantioselective pharmacokinetics of tenatoprazole were studied in Wistar rats after the administration of a single oral dose of rac-tenatoprazole. Serial plasma samples were collected; and the pharmacokinetic behavior of each enantiomer was characterized using a sequential achiral and chiral liquid chromatographic method. Tenatoprazole was extracted from a small aliquot of plasma (100 microl) by one-step extraction using hexane-dichloromethane-isopropanol (20:10:1, v/v/v) as extract solvent. Plasma drug concentration-time data were analyzed for each enantiomer by using a noncompartmental method. The AUC(0-infinity) and C(max) values of (+)-tenatoprazole were significantly greater than those of (-)-tenatoprazole (P < 0.001). The mean AUC(0-infinity) value of (+)-tenatoprazole was 7.5 times greater than that of (-)-tenatoprazole after oral administration of rac-tenatoprazole to rats at a dose of 5 mg/kg. There are also significant differences in t(1/2) and CL/F (P < 0.01 and P < 0.001, respectively) values between enantiomers. This study suggests that the pharmacokinetics of tenatoprazole are enantioselective in rats. | 18,752,288 |
Pair distribution function X-ray analysis explains dissolution characteristics of felodipine melt extrusion products. | Solid solutions of felodipine with EUDRAGIT E and EUDRAGIT E/NE were shown to dramatically increase the dissolution rate of felodipine in biorelevant media. Of the two polymer systems, extrudates containing 5% EUDRAGIT NE showed a faster dissolution rate and less recrystallization (no precipitation within 2 h). Although differential scanning calorimetry (DSC) and conventional X-ray powder diffraction (XRPD) were able to verify the amorphous state of the drug after melt extrusion, it was not possible to differentiate the two extrudate compositions further with these methods. We then applied pair distribution function (PDF) analysis to investigate extrudates. It was possible to more closely characterize the solid state of the amorphous extrudates in terms of local structural order: PDF analysis revealed that addition of minor amounts of EUDRAGIT NE to the main component EUDRAGIT E during extrusion changed the local structure of EUDRAGIT E in a nonadditive way. We conclude that local ordering can be important to the release characteristics of extrudates, even when the components are present in the amorphous state. | 18,752,290 |
Attenuation of TCDD-induced oxidative stress by 670 nm photobiomodulation in developmental chicken kidney. | 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent developmental teratogen inducing oxidative stress and sublethal changes in multiple organs, provokes developmental renal injuries. In this study, we investigated TCDD-induced biochemical changes and the therapeutic efficacy of photobiomodulation (670 nm; 4 J/cm(2)) on oxidative stress in chicken kidneys during development. Eggs were injected once prior to incubation with TCDD (2 pg/g or 200 pg/g) or sunflower oil vehicle control. Half of the eggs in each dose group were then treated with red light once per day through embryonic day 20 (E20). Upon hatching at E21, the kidneys were collected and assayed for glutathione peroxidase, glutathione reductase, catalase, superoxide dimutase, and glutathione-S-transferase activities, as well as reduced glutathione and ATP levels, and lipid peroxidation. TCDD exposure alone suppressed the activity of the antioxidant enzymes, increased lipid peroxidation, and depleted available ATP. The biochemical indicators of oxidative and energy stress in the kidney were reversed by daily phototherapy, restoring ATP and glutathione contents and increasing antioxidant enzyme activities to control levels. Photobiomodulation also normalized the level of lipid peroxidation increased by TCDD exposure. The results of this study suggest that 670 nm photobiomodulation may be useful as a noninvasive treatment for renal injury resulting from chemically induced cellular oxidative and energy stress. | 18,752,309 |
Prolonged survival of patients with lung adenocarcinoma expressing XAGE-1b and HLA class I antigens. | XAGE-1b is a cancer/testis antigen that has been shown to be expressed at a significant frequency and to be immunogenic in non-small cell lung cancer (NSCLC). In the present study, we investigated correlations between XAGE-1b expression and NSCLC patient survival. XAGE-1b expression was examined immunohistochemically using USO9-13, an anti-XAGE-1b monoclonal antibody, in 121 NSCLCs (83 adenocarcinomas and 38 other histological types). XAGE-1b expression was observed in 27 (32.5%) adenocarcinoma specimens. In the other histological types, positive staining was observed in only 1 specimen. HLA class I expression in these samples was assessed previously. XAGE-1b expression had no correlation with overall survival. However, both XAGE-1b and HLA class I expression correlated with prolonged survival (P = 0.019). Moreover, expression of XAGE-1b combined with down-regulated HLA class I expression correlated with poor survival (P = 0.01). The density of cancer nest-infiltrating CD8+ T-cells in tumors expressing both XAGE-1b and HLA class I was higher than that in other groups. The findings suggest that XAGE-1b and HLA class I expression elicited a CD8+ T-cell response against minimal residual disease after surgery and resulted in prolonged survival of NSCLC patients. | 18,752,338 |
[Effect of endothelin-1 on tumor arteries in patients with colorectal cancer]. | Endothelin-1 is an endothelium-derived vasoconstrictor peptide whose plasma levels are increased in patients with colorectal cancer, and which may be involved in tumor blood flow regulation. To study whether response to this peptide is altered in tumor arteries, mesenteric arteries supplying blood flow to colorectal tumors, and mesenteric arteries far from said tumors were obtained from 13 patients undergoing colectomy; mesenteric arteries were also obtained from patients with diverticulitis (n = 4) or inflammatory bowel disease (n = 3). Arteries were prepared for isometric tension recording in an organ bath, and in this preparation it was found that endothelin-1 induced contraction in all three types of arteries, but that sensitivity to this peptide was greater in arteries supplying blood flow to the tumor than in arteries far from the tumor or arteries from patients without cancer. These results suggest that endothelin-1 may regulate blood flow to colorectal tumors by inducing a greater contraction in tumor-supplying arteries than in non-tumor arteries. | 18,752,360 |
Safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia. | To evaluate the safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia (HIT). Retrospective cohort study. University-affiliated hospital. Thirty-seven adults with a diagnosis or history of HIT who were treated with bivalirudin between January 1, 2004, and March 31, 2007. Patients had a mean +/- SD age of 50 +/- 16 years and weighed 80 +/- 20 kg; 62% were male, 73% were Caucasian, and 95% were treated in the intensive care unit. Patients were divided into three renal function groups for assessment of bivalirudin dosing requirements: creatinine clearance (Cl(cr)) greater than 60 ml/minute (12 patients, group 1); Cl(cr) 30-60 ml/minute (11 patients, group 2); and Cl(cr) lower than 30 ml/minute or receiving continuous renal replacement therapy ([RRT] 14 patients, group 3). Except for renal function, baseline demographic characteristics were similar among groups. A total of 19 (51%) of the 37 patients achieved goal activated partial thromboplastin time (aPTT) with initial mean +/- SD bivalirudin doses of 0.14 +/- 0.04 (median 0.15), 0.1 +/- 0.07 (median 0.08), and 0.05 +/- 0.05 (median 0.05) mg/kg/hour in groups 1, 2, and 3, respectively. Doses remained similar over the study period and were 0.13 +/- 0.04 (median 0.15), 0.1 +/- 0.06 (median 0.1), and 0.04 +/- 0.02 (median 0.03) mg/kg/hour for groups 1, 2, and 3, respectively. The mean +/- SD aPTT value after achieving goal range was 64 +/- 9 seconds (all patients). Bivalirudin dosing requirements correlated with Cl(cr) (r(2) = 0.37, p<0.0001). Therapy duration was a mean +/- SD of 11 +/- 13 days (median 7 days). Systemic thrombosis and bleeding while receiving bivalirudin were also evaluated. Thrombosis occurred in one patient; clinically significant bleeding occurred in two patients. Bivalirudin dosing requirements correlated with renal function; therefore, dosage reduction is required in patients with moderate or severe renal dysfunction. Starting bivalirudin at 0.15 mg/kg/hour in patients with Cl(cr) greater than 60 ml/minute, 0.08-0.1 mg/kg/hour in patients with Cl(cr) 30-60 ml/minute, and 0.03-0.05 mg/kg/hour in patients with Cl(cr) below 30 ml/minute or receiving continuous RRT is effective at achieving goal aPTT values in most patients. | 18,752,382 |
Research in women and special populations. | The American College of Clinical Pharmacy charged a Task Force on Research in Special Populations to review, update, and broaden its 1993 White Paper on Women as Research Subjects. Participants of the task force included pharmacy clinicians and investigators in the field. This resulting White Paper, Research in Women and Special Populations, discusses the current concepts regarding the conduct of research in women, as well as in special populations such as children, elderly, minorities, cognitively impaired, and other vulnerable populations (e.g., prisoners and refugees). For each specific population, the barriers to research participation, current guidelines and regulations, and available recommendations to address these barriers are discussed. The participation in research by these populations requires addressing special social and ethical challenges. Clinical pharmacy researchers should be cognizant of these guidelines and be an advocate for the inclusion and the rights of women and special populations in research participation. | 18,752,392 |
Socioeconomic disparities affect prefrontal function in children. | Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of prefrontal function. However, the influence of socioeconomic disparity on direct measures of neural activity is unknown. Here, we provide electrophysiological evidence indicating that prefrontal function is altered in LSES children. We found that prefrontal-dependent electrophysiological measures of attention were reduced in LSES compared to high SES (HSES) children in a pattern similar to that observed in patients with lateral prefrontal cortex (PFC) damage. These findings provide neurophysiological evidence that social inequalities are associated with alterations in PFC function in LSES children. There are a number of factors associated with LSES rearing conditions that may have contributed to these results such as greater levels of stress and lack of access to cognitively stimulating materials and experiences. Targeting specific prefrontal processes affected by socioeconomic disparity could be helpful in developing intervention programs for LSES children. | 18,752,394 |
Dissociation of frontal and medial temporal lobe activity in maintenance and binding of sequentially presented paired associates. | Substructures of the prefrontal cortex (PFC) and the medial-temporal lobe are critical for associating objects presented over time. Previous studies showing frontal and medial-temporal involvement in associative encoding have not addressed the response specificity of these regions to different aspects of the task, which include instructions to associate and binding of stimuli. This study used a novel paradigm to temporally separate these two components of the task by sequential presentation of individual images with or without associative instruction; fMRI was used to investigate the temporal involvement of the PFC and the parahippocampal cortex in encoding each component. Although both regions showed an enhanced response to the second stimulus of a pair, only the PFC had increased activation during the delay preceding a stimulus when associative instruction was given. These findings present new evidence that prefrontal and medial-temporal regions provide distinct temporal contributions during associative memory formation. | 18,752,401 |
All numbers are not equal: an electrophysiological investigation of small and large number representations. | Behavioral and brain imaging research indicates that human infants, humans adults, and many nonhuman animals represent large nonsymbolic numbers approximately, discriminating between sets with a ratio limit on accuracy. Some behavioral evidence, especially with human infants, suggests that these representations differ from representations of small numbers of objects. To investigate neural signatures of this distinction, event-related potentials were recorded as adult humans passively viewed the sequential presentation of dot arrays in an adaptation paradigm. In two studies, subjects viewed successive arrays of a single number of dots interspersed with test arrays presenting the same or a different number; numerical range (small numerical quantities 1-3 vs. large numerical quantities 8-24) and ratio difference varied across blocks as continuous variables were controlled. An early-evoked component (N1), observed over widespread posterior scalp locations, was modulated by absolute number with small, but not large, number arrays. In contrast, a later component (P2p), observed over the same scalp locations, was modulated by the ratio difference between arrays for large, but not small, numbers. Despite many years of experience with symbolic systems that apply equally to all numbers, adults spontaneously process small and large numbers differently. They appear to treat small-number arrays as individual objects to be tracked through space and time, and large-number arrays as cardinal values to be compared and manipulated. | 18,752,403 |
When time shapes behavior: fMRI evidence of brain correlates of temporal monitoring. | Time processing may shape behavior in several ways, although the underlying neural correlates are still poorly understood. When preparatory intervals between stimuli vary randomly in a block, for instance, responses are faster as the interval gets longer. This effect, known as variable foreperiod (FP) effect, has been attributed to a process monitoring the conditional probability of stimulus occurrence as the interval increases. Previous evidence points to the right dorsolateral prefrontal cortex (DLPFC) as a possible node for this time-monitoring process. The present study addresses this hypothesis with functional magnetic resonance imaging (fMRI). Block-design fMRI was used on 14 young participants while they performed a visual discrimination task with fixed and variable preparatory intervals (FPs) of 1 and 3 sec. In the variable versus fixed FP contrast, the right DLPFC and a visual area were more activated in the subgroup of participants who showed a reliable variable FP effect than in another subgroup who did not show that effect. Only the activation in the right DLPFC was supported by a significant interaction between FP condition (variable vs. fixed) and group. This finding may reflect possible differences in the strategy adopted by the two subgroups of participants while performing the task. Although results suggest that many brain areas may be involved in preparation over time, the role of the right DLPFC is critical to observe the strategically mediated behavioral effects in the variable FP paradigm. | 18,752,413 |
Immune mechanisms in thyroid eye disease. | Thyroid eye disease (TED) is an inflammatory condition of the orbit closely associated with Graves' disease. During the course of TED, fibrosis can develop around the extraocular muscles, and excess extracellular matrix and fat accumulates in the periorbital space. This dramatic remodeling results in protrusion of the eye, also known as exophthalmos. Current treatments are sometimes effective in alleviating the symptoms of the disease, but there remains a demand for treatments that prevent or reverse the pathological alterations of orbital tissues. Such treatments may become available as a result of research aimed at understanding the mechanism by which Graves' disease leads to specific remodeling of orbital tissues. Recent findings have uncovered the importance of intercellular communication between autoreactive T cells and orbital fibroblasts. When orbital fibroblasts are activated, possibly by Graves' disease-related autoantibodies, they release T cell chemoattractants, initiating an interaction in which these cells activate each other. These interactions ultimately result in fibroblasts expressing extracellular matrix molecules, proliferating and differentiating into myofibroblasts or lipofibroblasts. Although the mechanisms underlying these processes are not completely understood, several currently available therapeutic strategies might interrupt the signaling between B and T cells and fibroblasts, thereby treating the clinical manifestations of TED. | 18,752,427 |
Decreasing listeriosis mortality in the United States, 1990-2005. | Listeria monocytogenes is among the most virulent foodborne pathogens, with 20% of clinical infections resulting in death. To explore listeriosis-associated mortality in the United States and to evaluate prevention efforts, we reviewed vital records over a 16-year period to assess demographic, temporal, and seasonal trends. Nonperinatal listeriosis-associated deaths from 1990 through 2005 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates. Poisson regression was used to model time trends, and logistic regression was used to identify comorbid conditions associated with listeriosis on the death record. Of the 37,267,946 deaths occurring in the United States during the 16-year study period, 1178 included listeriosis on the death record. Listeriosis-related mortality rates decreased annually by 10.74% from 1990 through 1996 and by 4.26% from 1996 through 2005. Seasonal trends show a distinct peak in mortality from July through October. After adjustment for age, sex, and race/ethnicity, listeriosis was positively associated with human immunodeficiency virus (HIV) infection (odds ratio, 4.19; 95% confidence interval, 3.06-5.73), lymphoid and hematopoietic cancers (odds ratio, 5.27; 95% confidence interval, 4.47-6.22), and liver disease (odds ratio, 2.05; 95% confidence interval, 1.54-2.73) on the death record. Nonperinatal listeriosis-associated deaths in the United States have decreased, paralleling a decreasing trend in incidence. Strict monitoring of food manufacturing processes, as well as improved treatment for HIV infection, may have played influential roles in preventing human infections. Health care providers should be aware of seasonal listeriosis patterns, as well as conditions predisposing individuals to severe infection and death due to L. monocytogenes infection, to guide strategies for disease management and prevention. | 18,752,441 |
Preferential protection of Borrelia burgdorferi sensu stricto by a Salp15 homologue in Ixodes ricinus saliva. | Ixodes ticks are the main vectors for Borrelia burgdorferi sensu lato. In the United States, B. burgdorferi is the sole causative agent of Lyme borreliosis and is transmitted by Ixodes scapularis. In Europe, 3 Borrelia species-B. burgdorferi, B. garinii, and B. afzelii-are prevalent, which are transmitted by Ixodes ricinus. The I. scapularis salivary protein Salp15 has been shown to bind to B. burgdorferi outer surface protein (Osp) C, protecting the spirochete from antibody-mediated killing. We recently identified a Salp15 homologue in I. ricinus, Salp15 Iric-1. Here, we have demonstrated, by solid-phase overlays, enzyme-linked immunosorbent assay, and surface plasmon resonance, that Salp15 Iric-1 binds to B. burgdorferi OspC. Importantly, this binding protected the spirochete from antibody-mediated killing in vitro and in vivo; immune mice rechallenged with B. burgdorferi preincubated with Salp15 Iric-1 displayed significantly higher Borrelia numbers and more severe carditis, compared with control mice. Furthermore, Salp15 Iric-1 was capable of binding to OspC from B. garinii and B. afzelii, but these Borrelia species were not protected from antibody-mediated killing. Salp15 Iric-1 interacts with all European Borrelia species but differentially protects B. burgdorferi from antibody-mediated killing, putatively giving this Borrelia species a survival advantage in nature. | 18,752,445 |
p.Ala546 > Asp and p.Arg555 > Trp mutations of TGFBI gene and their clinical manifestations in two large Chinese families with granular corneal dystrophy type I. | The aim of this study was to conduct clinical, genetic, and molecular analysis of Chinese patients with granular corneal dystrophy type I (CDGG1). Two large unrelated Chinese families with CDGG1 were clinically and genetically evaluated. Molecular genetic analysis was performed on DNA extracted from peripheral blood. Exons 4, 11, 12, and 14 of the human transforming growth factor beta-induced gene (TGFBI, formerly designated BIGH3) were amplified by PCR, scanned for mutations using the single-strand conformation polymorphism method, and the mutations identified by nucleotide sequencing. One family segregated the p.Ala546 > Asp mutation, and the other family had a p.Arg555 > Trp mutation. These missense mutations were not found in 53 unrelated, healthy individuals analyzed as controls. Clinical and genetic evaluations revealed the variable severity, symmetry, and age of onset in visual impairment in these families for different mutations. Penetrance of visual impairment in these families was 100% and 75%, respectively. This study confirms that the p.Arg555 > Trp mutation is a frequent cause of CDGG1, and that the p.Ala546 > Asp mutation is also associated with this disease. | 18,752,451 |
Effect of cyclosporin A and tacrolimus on sister chromatid exchange frequency in renal transplant patients. | Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients. | 18,752,452 |
Novel TFAP2B mutation in nonsyndromic patent ductus arteriosus. | Mutations in the gene encoding the TFAP2B transcription factor can cause Char syndrome with cardiac, craniofacial, and hand abnormalities. However, TFAP2B mutations result in great phenotypic variability, which is believed to reflect different expression patterns of tissue-specific TFAP2 coactivators. We investigated a consanguineous family with isolated patent ductus arteriosus (PDA) for mutations in TFAP2B. Our study suggests that a novel splicing mutation in TFAP2B can cause isolated PDA without other clinical features. | 18,752,453 |
Fluorescence microscopy as a tool for in situ life detection. | The identification of extant and, in some cases, extinct bacterial life is most convincingly and efficiently performed with modern high-resolution microscopy. Epifluorescence microscopy of microbial autofluorescence or in conjunction with fluorescent dyes is among the most useful of these techniques. We explored fluorescent labeling and imaging of bacteria in rock and soil in the context of in situ life detection for planetary exploration. The goals were two-fold: to target non-Earth-centric biosignatures with the greatest possible sensitivity and to develop labeling procedures amenable to robotic implementation with technologies that are currently space qualified. A wide panel of commercially available dyes that target specific biosignature molecules was screened, and those with desirable properties (i.e., minimal binding to minerals, strong autofluorescence contrast, no need for wash steps) were identified. We also explored the potential of semiconductor quantum dots (QDs) as bacterial and space probes. A specific instrument for space implementation is suggested and discussed. | 18,752,456 |
Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. | Active hexose correlated compound (AHCC) is a fermented mushroom extract that is promoted for immune support. This review focuses on results from in vivo studies evaluating the effects of AHCC supplementation on survival and the immune response to a variety of infectious agents, including influenza virus, avian influenza virus, Klebsiella pneumoniae, Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Supplementation with AHCC appears to modulate immunity and increase survival in response to acute infection and warrants further investigation. | 18,752,476 |
TNF/IL-1/NIK/NF-kappa B transduction pathway: a comparative study in normal and pathological human prostate (benign hyperplasia and carcinoma). | Tumour necrosis factor (TNF)-alpha induces death or cell proliferation by activation of nuclear factor (NF)-kappaB, also activated by interleukin (IL)-1 alpha. The aim was to investigate upstream and downstream components of NIK transduction pathway in normal (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC). Immunohistochemistry and Western blotting were performed. In NP, the cytoplasm of epithelial cells was intensely immunoreactive to IL-1 receptor-associated kinase (IRAK), TNF receptor-associated factor (TRAF)-6, NF-kappaB inducing kinase (NIK), I kappa kappa alpha/beta, I kappaB alpha and p-I kappaB; weakly to NF-kappaB-p50; and negative to NF-kappaB-p65. BPH samples were intensely immunoreactive to IRAK, TRAF-6, NIK, I kappa kappa alpha/beta, I kappaB alpha, p-I kappaB; weakly to NF-kappaB-p50 and NF-kappaB-p65. Whereas low-grade PIN showed intermediate results between NP and BPH, results in high-grade PIN were similar to those found in PC (low Gleason). In PC, immunoreactivity was intense for IRAK, TRAF-6, NIK, I kappa kappa alpha/beta (increasing with Gleason), I kappaB alpha, p-I kappaB (decreasing with Gleason); weak for NF-kappaB-p50 and NF-kappaB-p65 (decreasing with Gleason). Nuclear NF-kappaB was observed in PC. NF-kappaB enhances cell proliferation, but also ATF-2 or Elk-1. Since IL-1 and TNF-alpha are related to inflammation and their immunoexpression increases in PC, inhibition of these cytokines might be a possible target for PC treatment, because they decrease the activity of all transduction pathway members that activate transcription factors such as NF-kappaB, Elk-1 or ATF-2. | 18,752,500 |
Gender-related differences in cataract surgery outcome: a 5-year follow-up. | A prospective, longitudinal, population-based cohort study was performed to analyse gender-related differences in subjective and objective visual function 5 years after cataract surgery. All patients (n = 810) who underwent cataract surgery during a 1-year period (1997-98) at Norrlands University Hospital in Umeå, Sweden, were studied with visual acuity (VA) data and questionnaires (VF-14) before and after surgery, as well as 5 years later. Five hundred and thirty patients (177 men, 353 women) answered the questionnaire, constituting 90% (530/590) of the survivors. Four hundred and sixty-seven (156 men, 311 women) also underwent an eye examination. The women were significantly older (P = 0.009) and were more often operated on both eyes (P = 0.005). Before surgery and postoperatively, the women had a significantly lower age- and VA-adjusted VF-14 score (P = 0.000 and P = 0.036, respectively). This difference was not significant 5 years after surgery (P = 0.16). Five years after surgery, a significantly larger proportion of women had a decline of more than 0.1 logarithm of the minimum angle of resolution of the better-seeing eye (P = 0.013). There were no significant gender-related differences in the operated eye. Female cataract surgery patients assess their visual function worse than males after adjustment for age and VA preoperatively and postoperatively. These differences were not significant 5 years after surgery although the men had better best-corrected visual acuity (BCVA) of their better eye. It is important to be aware of gender-related differences in perception when performing questionnaire-based outcome studies. | 18,752,528 |
Ultrasound biomicroscopy of zonular anatomy in clinically unilateral exfoliation syndrome. | To evaluate the ability of ultrasound biomicroscopy (UBM) to detect abnormalities in the zonular apparatus in unaffected eyes of patients with clinically unilateral exfoliation syndrome (XFS) using a standardized grading system. The affected and unaffected eyes of 17 patients with clinically unilateral XFS and 17 eyes of 17 control subjects underwent UBM. Radial sections detailing the lens and zonules at 12:00, 1:30, 3:00, 4:30, 6:00, 7:30, 9:00 and 10:30 clock hours were obtained. The images were graded by a masked, experienced UBM observer using a standardized scoring system based on the zonular appearance (0, none; 1 and 2, uneven or disrupted zonules with or without patchy deposits; 3, diffuse granulation, thick zonules or both; 4, total zonular disruption). Affected meridians were compared by the Friedman test, while distributions of unaffected and affected eyes were compared using the Student t-test. In the control group, 15/17 eyes showed normal zonules; the remaining two eyes showed grade 1 changes in some meridians. The mean grade score was 0.33 [standard deviation (SD) 0.84]. Eyes with XFS had a higher score than control eyes, with a mean score of 14.35 (SD 7.14, P < 0.001, Student t-test). In clinically unaffected fellow eyes, the mean score was 10.53 (SD 7.44), and was less than that of XFS eyes (P = 0.008, Student t-test). Twelve XFS eyes (71%) and six unaffected fellow eyes (35%) had grade 3 or 4 in at least one meridian (P = 0.07, Friedman test). Bilateral zonular involvement is present in subjects with clinically unilateral XFS. These zonular changes may be extensive in fellow eyes without clinically evident exfoliation material. UBM assessment of zonular status in fellow eyes prior to cataract extraction may aid in surgical planning. | 18,752,530 |
Erroneous automated optical platelet counts in 1-hour post-transfusion blood samples. | Thrombocytopenic patients with acute leukemia may show high post-transfusion count increments that significantly exceed the number of transfused platelets. This study demonstrates that the automated hematology analyzer Sysmex XE-2100 reports erroneously high optical platelet counts when the blood sample contains particles in the size range of platelets or smaller. Thrombocytopenic or low-normal whole blood samples were spiked with 1 mum latex beads (n = 14) to mimic contaminants under controlled conditions. Optical and impedance measurements of spiked and control samples with the Sysmex XE-2100 were compared with the Advia 120 and the manual counts. The added beads unexpectedly increased the automated optical platelet counts in the Sysmex XE-2100 and, to a lesser extent, the Advia 120 (Wilcoxon signed ranks test, P < 0.05), while the beads were not included in the impedance or the manual microscopic platelet counts. Differential interference contrast microscopy was used to investigate samples from platelet concentrates for transfusion. Platelet concentrates (32/128) were identified as possible sources for particles that were microscopically distinct from platelets but would be included in the automated optical count. Transfusion of platelet concentrates containing contaminating particles can lead to unexpectedly high post-transfusion platelet counts and misdiagnosis of thrombocytopenic patients. | 18,752,538 |
Clinical experiences of solid pseudopapillary tumors of the pancreas in China. | To discuss the clinical experiences of solid pseudopapillary tumors (SPTs) of the pancreas by summarizing clinical information of patients with this disease in China. Chinese literature concerning SPTs of the pancreas published between January 1996 and October 2006 were retrospectively reviewed and analyzed. A total of 390 cases had been reported, among which 47 were men, with a female to male ratio of 7.30:1. Mean age of the patients was 25.3 years old, more than 50 per cent were between 10 and 24 years. The mean diameter of the tumor was 8.4 cm (range, 2 cm-25 cm). There was no significant difference in patient age and tumor size between male and female. Major clinical presentations included abdominal pain or discomfort, and palpable abdominal masses, however, nearly one third of all patients were asymptomatic. The rate of pre-operative misdiagnosis was rather high. Those who tested positive to metastases or invasions, 14.4% of the patients were diagnosed as malignant SPTs. Sex, age, symptoms, tumor size and tumor markers were not significant clinical factors to predict SPTs with malignant potential. Surgical procedures mainly included pancreatoduodenectomy, distal pancreatectomy and local resection. Three patients developed local recurrence, and one patient developed hepatic metastasis, all within four years after tumor resection. Five patients with malignant SPTs died due to tumor progression within 25 months after surgery. Surgical resection is the most effective means for curing this rare tumor. Despite metastasis, a good satisfactory effect could be achieved by surgical debulking. At least 4-yearly follow-up is mandatory for all patients undergoing surgical resection. | 18,752,561 |
Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis. | Adverse pregnancy outcomes have been related to environmental and/or genetic factors. Of interest are genes associated with the clotting system as any perturbation in the balance of thrombotic and thrombolytic cascades could affect the placental circulation and hence the viability of the developing fetus. Several previous reports using relatively small numbers of cases and controls have suggested that there is a relationship between poor pregnancy outcomes and two polymorphisms, one in the factor V gene, the 1691G to A change (rs6025) located on chromosome 1q23 (factor V Leiden, FVL), and the other in the prothrombin gene, 20210G to A change (rs1799963) on chromosome 11p11-q12 (PT). These results, however, are conflicting. We genotyped 6755 mother/infant pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether maternal or fetal FVL or PT, either alone or in combination, are associated with fetal growth restriction (FGR) or pre-eclampsia (PE). We also added the present results to previous cohort studies using meta-analysis. Smoking, primiparity and lower body mass index (BMI) were all associated with FGR, but neither maternal nor fetal FVL or PT, singly or in combination, were associated with FGR in the ALSPAC cohort. Meta-analysis confirmed the lack of association between maternal FVL and FGR with a pooled odds ratio (OR) of 1.15 [95% confidence interval (CI) 0.95-1.39]. High BMI, primiparity, diabetes and chronic hypertension were all associated with pre-eclampsia. Combining ALSPAC results with previous studies in ameta-analysis indicated that maternal FVL is significantly associated with pre-eclampsia, with a pooled OR of 1.49 (95% CI 1.13-1.96). Neither maternal nor fetal FVL or PT, singly or in combination, are associated with FGR; this contradicts previous case-control studies and meta-analyses based on these studies. In a meta-analysis of all published cohort studies to date, maternal FVL appears to increase the risk of pre-eclampsia by almost 50%. This result is robust, homogeneous and does not appear to be affected by publication bias. | 18,752,569 |
Adhesive receptors, extracellular proteins and myosin IIA orchestrate proplatelet formation by human megakaryocytes. | Megakaryocytes release platelets from the tips of cytoplasmic extensions, called proplatelets. In humans, the regulation of this process is still poorly characterized. To analyse the regulation of proplatelet formation by megakaryocyte adhesion to extracellular adhesive proteins through different membrane receptors. Human megakaryocytes were obtained by differentiation of cord blood-derived CD34(+) cells, and proplatelet formation was evaluated by phase contrast and fluorescence microscopy. We found that human megakaryocytes extended proplatelets in a time-dependent manner. Adhesion to fibrinogen, fibronectin or von Willebrand factor (VWF) anticipated the development of proplatelets, but dramatically limited both amplitude and duration of the process. Type I, but not type III or type IV, collagen totally suppressed proplatelet extension, and this effect was overcome by the myosin IIA antagonist blebbistatin. Integrin alphaIIbbeta3 was essential for megakaryocyte spreading on fibrinogen or VWF, but was not required for proplatelet formation. In contrast, proplatelet formation was prevented by blockade of GPIb-IX-V, or upon cleavage of GPIbalpha by the metalloproteinase mocarhagin. Membrane-associated VWF was detected exclusively on proplatelet-forming megakaryocytes, but not on round mature cells that do not extend proplatelets. Our findings show that proplatelet formation in human megakaryocytes undergoes a complex spatio-temporal regulation orchestrated by adhesive proteins, GPIb-IX-V and myosin IIA. | 18,752,571 |
Bispecific targeting of thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 by a heterodimer diabody. | Thrombin activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) play important roles in fibrinolysis. Both reduce plasmin generation, but they exert their antifibrinolytic effects via different mechanisms. This study reports the cloning and characterization of a heterodimer diabody that inhibits TAFI and PAI-1 simultaneously. The diabody was derived from two inhibiting monoclonal antibodies, i.e. MA-33H1F7, an anti-PAI-1 antibody that induces non-inhibitory substrate behavior of PAI-1, and MA-T12D11, an anti-TAFI antibody that inhibits activation of TAFI by the thrombin-thrombomodulin complex. A single-chain variable fragment (scFv) was derived from MA-T12D11 that displayed slightly reduced binding and inhibitory properties as compared to MA-T12D11. Characterization of the diabody revealed a similar affinity for TAFI and PAI-1 as that of the parental antibodies. Furthermore, the inhibitory properties of MA-33H1F7 and MA-T12D11 were fully preserved in the diabody format. In platelet-free plasma (PFP) clots, addition of the diabody had a stronger effect in shortening lysis times than either MA-T12D11 or MA-33H1F7. A similar reduction in clot lysis time was observed in platelet-rich plasma (PRP) clots. The same effect on clot lysis times in PFP and PRP was also achieved by the combined addition of MA-T12D11 and MA-33H1F7. The lysis rate of human model thrombi, made from whole blood, was approximately doubled after addition of the diabody. Moreover, this effect was significantly better than after the combined addition of the individual antibodies. These observations demonstrate that simultaneous inhibition of TAFI and PAI-1 results in faster lysis of the formed thrombus. | 18,752,580 |
Interaction of the active metabolite of prasugrel, R-138727, with cysteine 97 and cysteine 175 of the human P2Y12 receptor. | The P2Y(12) receptor plays a crucial role in platelet aggregation and is the target of platelet aggregation inhibitors, including the thienopyridine compound prasugrel. The present study analyzed the effects of R-138727 (2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid), the active metabolite of prasugrel, on recombinant wild-type and mutant human P2Y(12) receptors in order to identify the molecular site of action of R-138727. The function of wild-type and mutant P2Y(12) receptors stably expressed in Chinese hamster ovary cells was assessed by measuring the 2-methylthio-ADP-mediated inhibition of forskolin-stimulated cellular cAMP production. In cells expressing wild-type receptors, R-138727 potently inhibited receptor function with a half-maximal concentration below 1 microm. The mode of action was irreversible. The same effect of R-138727 was observed in cells expressing Cys17Ala/Cys270Ala constructs. In contrast, in cells expressing either a Cys97Ala construct or a Cys175Ala construct, R-138727 failed to inhibit the response to the agonist. When cells expressing wild-type receptors were pretreated with the P2 receptor antagonists ATP or suramin, no effect of R-138727 was observed. Similar experiments with N-acetylcysteine 10 microm showed no interference of N-acetylcysteine with R-138727. The experiments demonstrate a potent and irreversible action of R-138727 at the recombinant human P2Y(12) receptor. The data suggest that R-138727 interacts with cysteine 97 (upper portion of the predicted third transmembrane region) and cysteine 175 (second extracellular loop) of the receptor, which are likely to form a disulfide bridge in native receptors. Moreover, the data also suggest that this site of action of R-138727 is close to the ligand-binding site of the receptor. | 18,752,581 |
Polymorphisms in the kappa casein (CSN3) gene in horse and comparative analysis of its promoter and coding region. | The major parts of the coding region and promoter of the equine kappa casein (CSN3) gene were sequenced and compared among several species. Four SNPs were identified in the CSN3 gene: two in exon 1 and two in exon 4. The SNPs were genotyped in six Slovenian horse breeds using RFLP and two different PCR-based methods. The highest variation in genotype frequencies was found in the Slovenian cold-blood breed. The SNPs in exon 4 may cause a change in the amino acid sequence and may alter chemical/functional properties of the protein. Using horse-specific primers, we obtained 400 bp of exon 4 sequence from zebra and donkey. Two SNPs within the zebra exon 4 sequence were discovered; both presumably caused amino acid substitutions. Within the equine promoter sequence, 15 SNPs were found and 12 of them could be involved in the gain/loss of potential transcription factor (TF) binding sites. Using a comparative genomics approach, we obtained 1482 bp of the promoter sequence from zebra and donkey. Sequence alignment revealed highly conserved blocks of promoter sequence among nine species (sheep, goat, cow, zebra, donkey, horse, chimp, macaque and human) and clustered these species in three distinct groups. Consensus binding sites for TFs STAT5, C/EBP, NF1 and STAT6, previously demonstrated to be associated with expression, were located within conserved regions. Four promoter regions were tested for specific binding of TFs using electrophoretic mobility shift assays. Predicted binding sites for C/EBP and NF1 were confirmed and one conserved region was specifically detected by a yet-uncharacterized TF. | 18,752,583 |
Titrated low-dose vaginal and/or oral misoprostol to induce labour for prelabour membrane rupture: a randomised trial. | To evaluate the clinical effectiveness and safety of titrated low-dose misoprostol for induction of labour (IOL) in the presence of prelabour rupture of membranes (PROM). Randomised controlled trial. Maternity units in the UK (9) and Egypt (1). Women >34 weeks of gestation with PROM, singleton viable fetus and no previous caesarean section. Subjects randomised to IOL with a titrated low-dose misoprostol regimen (oral except if unfavourable cervix, where initial dose vaginal) or a standard induction method, namely vaginal dinoprostone followed by intravenous oxytocin if the cervix was unfavourable or intravenous oxytocin alone if the cervix was favourable. Primary outcome measures were caesarean section and failure to achieve vaginal delivery within 24 hours. Analysis was by intention to treat. The trial did not achieve the planned sample size of 1890 due to failure in obtaining external funding. Seven hundred and fifty-eight women were randomised (375 misoprostol and 383 standard). There were less caesarean section (14 versus 18%, relative risk [RR] 0.79; 95% CI 0.57-1.09) and less women who failed to achieve vaginal delivery within 24 hours in the misoprostol group (24 versus 31%, RR 0.79; 95% CI 0.63-1.00), but the differences were not statistically significant. Subgroup analysis showed that with unfavourable cervix, misoprostol may be more effective than vaginal dinoprostone. There was no difference in hyperstimulation syndrome. There were more maternal adverse effects with misoprostol, but no significant differences in maternal and neonatal complications. Titrated low-dose misoprostol may be a reasonable alternative for IOL in the presence of PROM, particularly in women with an unfavourable cervix. Safety and rare serious adverse events could not be evaluated in a trial of this size. | 18,752,586 |
On the adaptive accuracy of directional asymmetry in insect wing size. | Subtle left-right biases are often observed in organisms with an overall bilateral symmetry. The evolutionary significance of these directional asymmetries remains uncertain, however, and scenarios of both developmental constraints and adaptation have been suggested. Reviewing the literature on asymmetry in insect wings, we analyze patterns of directional asymmetry in wing size to evaluate the possible adaptive significance of this character. We found that directional asymmetry in wing size is widespread among insects, with left- and right-biased asymmetries commonly observed. The direction of the asymmetry does not appear to be evolutionarily conserved above the species level. Overall, we argue that the very small magnitude of directional asymmetry, 0.7% of the wing size on average, associated with an extremely imprecise expression, precludes directional asymmetry from playing any major adaptive role. | 18,752,614 |
An evolutionary expressed sequence tag analysis of Drosophila spermatheca genes. | This study investigates genes enriched for expression in the spermatheca, the long-term sperm storage organ (SSO) of female Drosophila. SSO genes are likely to play an important role in processes of sexual selection such as sperm competition and cryptic female choice. Although there is keen interest in the mechanisms of sexual selection at the molecular level, very little is known about the female genes that are involved. In the present study, a high proportion of genes enriched for expression in the spermatheca are evolving rapidly. Most of the rapidly evolving genes are proteases and genes of unknown function that could play a specialized role in the spermatheca. A high percentage of the rapidly evolving genes have secretion signals and thus could encode proteins that directly interact with ejaculate proteins and coevolve with them. In addition to identifying rapidly evolving genes, the present study documents categories of genes that could play a role in spermatheca function such as storing, maintaining, and utilizing sperm. In general, candidate genes discovered in this study could play a key role in sperm competition, cryptic female choice of sperm, and sexually antagonistic coevolution, and ultimately speciation. | 18,752,616 |
Allelopathic growth inhibition by the toxic, bloom-forming cyanobacterium Planktothrix rubescens. | Blooms of freshwater cyanobacteria are typically accompanied by an important decrease in phytoplankton biodiversity in the water bodies where they occur. This study examines the potential production of growth-inhibiting substances by the toxic, bloom-forming cyanobacterium Planktothrix rubescens, following the observation of physical segregation between this and another cyanobacterium during previously performed mixed-culture competition experiments. Inhibition assays examining the growth of target strains exposed to donor culture filtrates showed that the growth of Planktothrix agardhii TCC 83-2, P. agardhii PMC 75.02 and Mougeotia gracillima TCC 50-2 was significantly inhibited in the presence of culture filtrate from P. rubescens TCC 29-1, isolated from Lake Bourget, France. Filtrates from P. rubescens TCC 69-6 and P. rubescens TCC 69-7, isolated from Lakes Nantua and Paladru (France), respectively, did not, however, inhibit the growth of P. agardhii TCC 83-2. This brief exploration of the allelopathic activity of P. rubescens suggests that it may potentially inhibit coexisting competitors as well as phytoplankton isolated from other freshwater ecosystems, and that this capacity may vary among different strains of Planktothrix. The potential importance of this phenomenon in pelagic competition dynamics is discussed. | 18,752,621 |
Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobule. | Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in multiple cognitive domains. Its pathological hallmarks include senile plaques and neurofibrillary tangles. Mild cognitive impairment (MCI) is the earliest detectable stage of AD with limited symptomology and no dementia. The yearly conversion rate of patients from MCI to AD is 10-15%, although conversion back to normal is possible in a small percentage. Early diagnosis of AD is important in an attempt to intervene or slow the advancement of the disease. Early AD (EAD) is a stage following MCI and characterized by full-blown dementia; however, information involving EAD is limited. Oxidative stress is well-established in MCI and AD, including protein oxidation. Protein nitration also is an important oxidative modification observed in MCI and AD, and proteomic analysis from our laboratory identified nitrated proteins in both MCI and AD. Therefore, in the current study, a proteomics approach was used to identify nitrated brain proteins in the inferior parietal lobule from four subjects with EAD. Eight proteins were found to be significantly nitrated in EAD: peroxiredoxin 2, triose phosphate isomerase, glutamate dehydrogenase, neuropolypeptide h3, phosphoglycerate mutase1, H(+)- transporting ATPase, alpha-enolase and fructose-1,6-bisphosphate aldolase. Many of these proteins are also nitrated in MCI and late-stage AD, making this study the first to our knowledge to link nitrated proteins in all stages of AD. These results are discussed in terms of potential involvement in the progression of this dementing disorder. | 18,752,637 |
A post-mortem survey on end-of-life decisions using a representative sample of death certificates in Flanders, Belgium: research protocol. | Reliable studies of the incidence and characteristics of medical end-of-life decisions with a certain or possible life shortening effect (ELDs) are indispensable for an evidence-based medical and societal debate on this issue. This article presents the protocol drafted for the 2007 ELD Study in Flanders, Belgium, and outlines how the main aims and challenges of the study (i.e. making reliable incidence estimates of end-of-life decisions, even rare ones, and describing their characteristics; allowing comparability with past ELD studies; guaranteeing strict anonymity given the sensitive nature of the research topic; and attaining a sufficient response rate) are addressed in a post-mortem survey using a representative sample of death certificates. Reliable incidence estimates are achievable by using large at random samples of death certificates of deceased persons in Flanders (aged one year or older). This entails the cooperation of the appropriate administrative authorities. To further ensure the reliability of the estimates and descriptions, especially of less prevalent end-of-life decisions (e.g. euthanasia), a stratified sample is drawn. A questionnaire is sent out to the certifying physician of each death sampled. The questionnaire, tested thoroughly and avoiding emotionally charged terms is based largely on questions that have been validated in previous national and European ELD studies. Anonymity of both patient and physician is guaranteed through a rigorous procedure, involving a lawyer as intermediary between responding physicians and researchers. To increase response we follow the Total Design Method (TDM) with a maximum of three follow-up mailings. Also, a non-response survey is conducted to gain insight into the reasons for lack of response. The protocol of the 2007 ELD Study in Flanders, Belgium, is appropriate for achieving the objectives of the study; as past studies in Belgium, the Netherlands, and other European countries have shown, strictly anonymous and thorough surveys among physicians using a large, stratified, and representative death certificate sample are most suitable in nationwide studies of incidence and characteristics of end-of-life decisions. There are however also some limitations to the study design. | 18,752,659 |
Osteoid osteoma of a metacarpal bone: a case report and review of the literature. | Osteoid osteoma is a benign tumor of the growing skeleton. It presents with pain, which is usually worse at night. The radiographic features consist of a central oval or round nidus surrounded first by a radiolucent area followed by another area of sclerotic bone. In the hand, osteoid osteoma is more commonly located in the phalanges and carpal bones. The metacarpals are the least common sites for osteoid osteoma. We present a case of an osteoid osteoma of the left third metacarpal bone in a 36-year-old woman. The clinical and radiographic findings along with the surgical management of the lesion are presented. The pain disappeared immediately after the operation. At the 2-year follow-up, the patient was pain-free and there was no evidence of recurrence. Physicians should be aware of the unusual presence and the atypical clinical presentation of this benign lesion in the metacarpal bones of the hand. | 18,752,665 |
Identification and correction of abnormal, incomplete and mispredicted proteins in public databases. | Despite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases. Since the majority of incomplete, abnormal or mispredicted entries are not annotated as such, these errors seriously affect the reliability of these databases. Here we describe the MisPred approach that may provide an efficient means for the quality control of databases. The current version of the MisPred approach uses five distinct routines for identifying abnormal, incomplete or mispredicted entries based on the principle that a sequence is likely to be incorrect if some of its features conflict with our current knowledge about protein-coding genes and proteins: (i) conflict between the predicted subcellular localization of proteins and the absence of the corresponding sequence signals; (ii) presence of extracellular and cytoplasmic domains and the absence of transmembrane segments; (iii) co-occurrence of extracellular and nuclear domains; (iv) violation of domain integrity; (v) chimeras encoded by two or more genes located on different chromosomes. Analyses of predicted EnsEMBL protein sequences of nine deuterostome (Homo sapiens, Mus musculus, Rattus norvegicus, Monodelphis domestica, Gallus gallus, Xenopus tropicalis, Fugu rubripes, Danio rerio and Ciona intestinalis) and two protostome species (Caenorhabditis elegans and Drosophila melanogaster) have revealed that the absence of expected signal peptides and violation of domain integrity account for the majority of mispredictions. Analyses of sequences predicted by NCBI's GNOMON annotation pipeline show that the rates of mispredictions are comparable to those of EnsEMBL. Interestingly, even the manually curated UniProtKB/Swiss-Prot dataset is contaminated with mispredicted or abnormal proteins, although to a much lesser extent than UniProtKB/TrEMBL or the EnsEMBL or GNOMON-predicted entries. MisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors. We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases. | 18,752,676 |
A cross-sectional study to determine the seroprevalence of bluetongue virus serotype 8 in sheep and goats in 2006 and 2007 in the Netherlands. | In August 2006 a major epidemic of bluetongue virus serotype 8 (BTV8) started off in North-West Europe. In the course of 2007 it became evident that BTV8 had survived the winter in North-West Europe, re-emerged and spread exponentially. Recently, the European Union decided to start vaccination against BTV8. In order to improve the understanding of the epidemiological situation, it was necessary to execute a cross-sectional serological study at the end of the BT vector season. Cattle were the target species for cross-sectional serological studies in Europe at the end of 2006 and 2007. However, there was no information on the BTV8-seroprevalence in sheep and goats. On the basis of our cross-sectional study, the estimated seroprevalence of BTV8-exposed locations in the Netherlands in 2006 was 0% for goats (95% confidence interval: 0 - 5.6%) and 7.0% for sheep (95% confidence interval: 3.5 - 12.9%). The estimated seroprevalence of BTV-8 exposed locations in 2007 was 47% for goats (95% confidence interval: 36 - 58%) and 70% for sheep (95% confidence interval: 63 - 76%). There was a wide range in within-location seroprevalence in locations with goats and sheep (1 - 100%). A gradient in seroprevalence was seen, with the highest level of seroprevalence in the southern Netherlands, the area where the epidemic started in 2006, and a decreasing seroprevalence when going in a northern direction. There is a much higher estimated seroprevalence of locations with goats exposed to BTV8 than can be inferred from the rather low number of reported clinical outbreaks in goats. This is probably due to the fact that clinical signs in infected goats are far less obvious than in sheep. The wide range in within-location seroprevalence observed means that the proportion of animals protected in 2008 by a natural infection in 2006 and/or 2007 can differ highly between flocks. This should be taken into account when vaccinating animals. | 18,752,681 |
Executive dysfunction correlates with impaired functional status in older adults with varying degrees of cognitive impairment. | Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment. 89 individuals (mean age 73.8 years) were recruited at a memory clinic in São Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 31) and mild Alzheimer's disease (AD, n = 26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R). Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r =-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs. | 18,752,698 |
Phylogenetic analysis of Trypanosoma vivax supports the separation of South American/West African from East African isolates and a new T. vivax-like genotype infecting a nyala antelope from Mozambique. | In this study, we addressed the phylogenetic and taxonomic relationships of Trypanosoma vivax and related trypanosomes nested in the subgenus Duttonella through combined morphological and phylogeographical analyses. We previously demonstrated that the clade T. vivax harbours a homogeneous clade comprising West African/South American isolates and the heterogeneous East African isolates. Herein we characterized a trypanosome isolated from a nyala antelope (Tragelaphus angasi) wild-caught in Mozambique (East Africa) and diagnosed as T. vivax-like based on biological, morphological and molecular data. Phylogenetic relationships, phylogeographical patterns and estimates of genetic divergence were based on SSU and ITS rDNA sequences of T. vivax from Brazil and Venezuela (South America), Nigeria (West Africa), and from T. vivax-like trypanosomes from Mozambique, Kenya and Tanzania (East Africa). Despite being well-supported within the T. vivax clade, the nyala trypanosome was highly divergent from all other T. vivax and T. vivax-like trypanosomes, even those from East Africa. Considering its host origin, morphological features, behaviour in experimentally infected goats, phylogenetic placement, and genetic divergence this isolate represents a new genotype of trypanosome closely phylogenetically related to T. vivax. This study corroborated the high complexity and the existence of distinct genotypes yet undescribed within the subgenus Duttonella. | 18,752,705 |
Anti-VSG antibodies induce an increase in Trypanosoma evansi intracellular Ca2+ concentration. | Trypanosoma evansi and Trypanosoma vivax have shown a very high immunological cross-reactivity. Anti-T. vivax antibodies were used to monitor changes in the T. evansi intracellular Ca2+ concentration ([Ca2+]i) by fluorometric ratio imaging from single parasites. A short-time exposure of T. evansi parasites to sera from T. vivax-infected bovines induced an increase in [Ca2+]i, which generated their complete lysis. The parasite [Ca2+]i boost was reduced but not eliminated in the absence of extracellular Ca2+ or following serum decomplementation. Decomplemented anti-T. evansi VSG antibodies also produced an increase in the parasite [Ca2+]i, in the presence of extracellular Ca2+. Furthermore, this Ca2+ signal was reduced following blockage with Ni2+ or in the absence of extracellular Ca2+, suggesting that this response was a combination of an influx of Ca2+ throughout membrane channels and a release of this ion from intracellular stores. The observed Ca2+ signal was specific since (i) it was completely eliminated following pre-incubation of the anti-VSG antibodies with the purified soluble VSG, and (ii) affinity-purified anti-VSG antibodies also generated an increase in [Ca2+]i by measurements on single cells or parasite populations. We also showed that an increase of the T. evansi [Ca2+]i by the calcium A-23187 ionophore led to VSG release from the parasite surface. In addition, in vivo immunofluorescence labelling revealed that anti-VSG antibodies induced the formation of raft patches of VSG on the parasite surface. This is the first study to identify a ligand that is coupled to calcium flux in salivarian trypanosomes. | 18,752,709 |
Cardiac resynchronization therapy: application of imaging to optimize patient selection and assess response. | Cardiac resynchronization therapy (CRT) has been shown to be effective for advanced heart failure and discoordinate wall motion, although the nonresponse rate for patients meeting standard CRT criteria remains about 30%. Although electrical delay (wide QRS) is commonly used to select candidates, recent data show that direct measures of mechanical dyssynchrony rather than surrogate -electrical measurements improve the identification of potential responders. This observation has stimulated the pursuit of imaging-based methods for characterizing dyssynchrony. Echocardiographic techniques have played a major role in this regard, but their accuracy and reliability have recently been scrutinized in multicenter clinical trials. This has shifted attention toward newer advanced echo methods and cardiac magnetic resonance imaging (CMR). Although CMR has a number of advantages over echocardiography for the assessment of dyssynchrony, these methods are relatively underdeveloped and not used widely clinically. This paper highlights imaging modalities for assessing wall motion and various methods for integrating the output from these complex imaging-based datasets into simple indices of dyssynchrony. Further, we investigate the role of imaging not only to improve selection of CRT responders but also to define CRT response. | 18,752,761 |
In-capillary derivatization and capillary electrophoresis separation of amino acid neurotransmitters from brain microdialysis samples. | A new in-capillary derivatization method with naphtalene-2,3-dicarboxyaldehyde (NDA)/CN(-) has been developed for capillary electrophoresis with laser-induced fluorescence detection of brain microdialysate amino acids. Samples are sandwiched between two plugs of reagent mixture at the capillary inlet and subsequently separated. Highest derivatization yields are obtained by using a reagent to sample plug length ratio equal to 4, performing a first electrophoretic mixing followed by a zero potential amplification step before applying the separation voltage and using a NaCN to NDA concentration ratio equal to 1. This new single-step methodology allows the analysis of amino acid neurotransmitters in rat brain microdialysis samples. | 18,752,800 |
Development of cultural strategies of attention in North American and Japanese children. | Recent studies suggest that North American adults exhibit a focused strategy of attention that emphasizes focal information about objects, whereas Japanese adults exhibit a divided strategy of attention that emphasizes contextual information about objects. The current study investigated whether 4- and 5-, 6- to 8-, and 9- to 13-year-old North American and Japanese children exhibit these divergent attention strategies. Two experiments suggest that those older than 6 years of age exhibit measurable cultural differences in attention, whereas 4- to 6-year-olds do not. We suggest that sociocognitive development and socialization experiences that occur around 5 to 7 years of age may foster the development of cultural strategies of attention. | 18,752,808 |
Model approach for estimating potato pesticide bioconcentration factor. | We presented a model that estimates the bioconcentration factor (BCF) of pesticides in potatoes supposing that the pesticide in the soil solution is absorbed by the potato by passive diffusion, following Fick's second law. The pesticides in the model are nonionic organic substances, traditionally used in potato crops that degrade in the soil according to a first-order kinetic equation. This presents an expression that relates BCF with the pesticide elimination rate by the potato, with the pesticide accumulation rate within the potato, with the rate of growth of the potato and with the pesticide degradation rate in the soil. BCF was estimated supposing steady state equilibrium of the quotient between the pesticide concentration in the potato and the pesticide concentration in the soil solution. It is suggested that a negative correlation exists between the pesticide BCF and the soil sorption partition coefficient. The model was built based on the work of Trapp et al. [Trapp, S., Cammarano, A., Capri, E., Reichenberg, F., Mayer, P., 2007. Diffusion of PAH in potato and carrot slices and application for a potato model. Environ. Sci. Technol. 41 (9), 3103-3108], in which an expression to calculate the diffusivity of persistent organic substances in potatoes is presented. The model consists in adding to the expression of Trapp et al. [Trapp, S., Cammarano, A., Capri, E., Reichenberg, F., Mayer, P., 2007. Diffusion of PAH in potato and carrot slices and application for a potato model. Environ. Sci. Technol. 41 (9), 3103-3108] the hypothesis that the pesticide degrades in the soil. The value of BCF suggests which pesticides should be monitored in potatoes. | 18,752,828 |
Innovative PCDD/F-containing gas stream generating system applied in catalytic decomposition of gaseous dioxins over V2O5-WO3/TiO2-based catalysts. | Development of effective PCDD/F (polychlorinated dibenzo-p-dioxin and dibenzofuran) control technologies is essential for environmental engineers and researchers. In this study, a PCDD/F-containing gas stream generating system was developed to investigate the efficiency and effectiveness of innovative PCDD/F control technologies. The system designed and constructed can stably generate the gas stream with the PCDD/F concentration ranging from 1.0 to 100ng TEQ Nm(-3) while reproducibility test indicates that the PCDD/F recovery efficiencies are between 93% and 112%. This new PCDD/F-containing gas stream generating device is first applied in the investigation of the catalytic PCDD/F control technology. The catalytic decomposition of PCDD/Fs was evaluated with two types of commercial V(2)O(5)-WO(3)/TiO(2)-based catalysts (catalyst A and catalyst B) at controlled temperature, water vapor content, and space velocity. 84% and 91% PCDD/F destruction efficiencies are achieved with catalysts A and B, respectively, at 280 degrees C with the space velocity of 5000h(-1). The results also indicate that the presence of water vapor inhibits PCDD/F decomposition due to its competition with PCDD/F molecules for adsorption on the active vanadia sites for both catalysts. In addition, this study combined integral reaction and Mars-Van Krevelen model to calculate the activation energies of OCDD and OCDF decomposition. The activation energies of OCDD and OCDF decomposition via catalysis are calculated as 24.8kJmol(-1) and 25.2kJmol(-1), respectively. | 18,752,829 |
The extent of active processing of a long-duration stimulus modulates the scalp-recorded sustained potential. | A long-duration stimulus will elicit a negative sustained potential (SP) that is maximum in amplitude over fronto-central areas of the scalp. This study examines how the duration of active attentional processing of the stimulus might also elicit a nonsensory contingent negative variation (CNV) that overlaps and summates to the SP. Subjects were presented with either a low- or high-pitched 1.4s duration stimulus. In different conditions, a 20 ms gap occurred either 300 or 1300 ms after stimulus onset in half the stimuli. The subject's task was to button press upon detection of the gap in the low-pitched stimulus. The subject was not required to respond to the gap occurring in the high-pitched tone. In a separate Ignore condition, subjects ignored all stimuli and read a book. In the Ignore condition, a SP was apparent to the long-duration stimuli. In the Attend condition, a large amplitude slow wave, probably the CNV, overlapped and summated with the SP. The extent of the overlapping CNV was dependent on whether the gap occurred early or late. The CNV was not apparent following presentation of the high-pitched tone, when the gap did not need to be detected. Consistent with previous studies, a SP was thus elicited even when active processing of the stimulus was not required. The morphology of the scalp-recorded SP was, nevertheless, much modified by an overlapping and summating CNV, depending on the extent to which active processing of the long-duration stimulus was required. | 18,752,881 |
Risk for excessive alcohol use and drinking-related problems in college student athletes. | There is compelling evidence that college student athletes engage in frequent episodes of heavy drinking and are prone to negative consequences resulting from such use. This study sought to identify risk and protective factors associated with student-athlete drinking and determine if student-athlete risk factors differed from those of non-athletes. Athletes compared to non-athletes reported more exaggerated perceptions of peer heavy drinking and lower sensation seeking and coping and enhancement motives for drinking, suggesting a risk profile distinct from non-athletes. In the overall sample, higher sensation seeking, overestimation of peer heavy drinking, non-use of protective behaviors while drinking, and higher enhancement and coping drinking motives were associated with greater frequency of heavy episodic drinking and more negative drinking consequences. In athletes compared to non-athletes, sensation seeking was more strongly associated with heavy episodic drinking and drinking to cope was more strongly associated with negative alcohol-related consequences. Overall, the results suggest that already proven brief intervention strategies, with minor adaptations related to the roles of sensation seeking and drinking to cope, may be helpful for student athletes. | 18,752,900 |
The catechol-O-methyltransferase (COMT) gene polymorphism and prevalence of uterine fibroids. | To assess the possible association between the catechol-O-methyltransferase (COMT) polymorphism and uterine fibroids in Brazilian women. Case-control study. Department of Gynecology; teaching hospital. One hundred twenty-four premenopausal women with fibroids, and 193 postmenopausal controls not presenting the disease. The subjects were classified as white or non-white (black and mulatto), and COMT genotypes were determined. DNA was extracted from the uterus of cases and from peripheral blood of controls and submitted to polymerase chain reaction (PCR) and agarose gel electrophoresis. The presence of the COMT polymorphism was recorded for all patients, and the frequency and distribution among cases and controls were compared according to race. Binomial log regression models were used to estimate odds-ratios (OR) for uterine volumes of <290 cm(3) (small fibroids) vs. those >290 cm(3) (large fibroids). Potential confounding variables (age, race and parity) were added to the model. Genotypes positive for the COMT polymorphism (heterozygous or mutant homozygous) were found in 45% of white and 28.9% of non-white women (p = .013) and the polymorphic allele frequencies in these groups were 27.2% and 16.3%, respectively (p = .006). However, there were no clear differences between patients and controls within the white subgroup with regard to the presence of COMT polymorphism-containing genotypes (41.5% vs. 46.0%, respectively) (p = .60), or for the polymorphic allele frequency (26.8% vs. 27.3%, respectively) (p = .92). For non-white women, there were also no differences between cases and controls for the frequency of polymorphic genotypes (28.9% vs. 28.9%, respectively) (p = .995), or for the polymorphic allele frequency (17.8 vs. 14.5, respectively) (p = .565). Estimated OR for small or large fibroids in association with the polymorphic allele revealed a positive association between the allele with lower activity and large fibroids (vs. small) (OR = 3.3; 95% confidence interval [CI] = 1.31-8.46). The adjusted OR was 4.35 (95% confidence interval [CI] = 1.58-11.9). The catechol-O-methyltransferase polymorphism is a risk factor for the development of large uterine fibroids in Brazilian women suffering from fibroids. | 18,752,908 |
Effects of biotin deficiency on embryonic development in mice. | The purpose of this investigation was to determine the effects of biotin deficiency on maternal metabolism and embryonic development in pregnant mouse dams. The pregnant mice were randomly assigned to one of three dietary groups and given a biotin-deficient diet, biotin-supplemented diet, or biotin-control diet during gestation. On days of gestation (dgs) 0, 4, 8, 12, and 16, organic acids including 3-hydroxyisovaleric acid in urine were discovered by high-performance liquid chromatography, and the biotin level in the serum and urine was determined by a bioassay. On dg 18, fetuses were examined for morphologic development. In the biotin-deficient group, biotin excretion in urine decreased on dg 4 and was subsequently below the lower limit, whereas the urinary concentration of 3-hydroxyisovaleric acid increased after dg 12. In contrast, the biotin concentration in urine significantly increased on dgs 4, 8 and 12 in the biotin-supplemented group, but decreased on dg 16 in the biotin-supplemented and biotin-control groups. The urinary excretion of pyruvic acid in the biotin-deficient group was significantly higher than that in the biotin-supplemented group throughout the entire gestation. These concentrations in urine significantly increased on dg 16 compared with dg 0. The inhibition of embryonic development and external malformations such as cleft palate (100%), micrognathia (100%), and micromelia (91.4%) were also detected in biotin-deficient fetuses. These findings indicated that, as the requirement of biotin increases during gestation and/or embryonic development, a large amount of biotin is necessary for maintaining normal reproductive performance during the late stage of gestation. | 18,752,930 |
Curcumin attenuates the organ dysfunction caused by endotoxemia in the rat. | Curcumin has antioxidant, antitumor, and anti-inflammatory properties. However, it remains unknown whether curcumin has any protective effects on sepsis. The purpose of this study was to demonstrate whether curcumin prevents organ dysfunction in animals with sepsis. Rats were randomized into four groups. The control group (group I, n = 7) did not receive any treatment. The curcumin group (group II, n = 10) only received 1.2 g/kg of curcumin. Escherichia coli were injected into the remaining groups intraperitoneally after general anesthesia. Five hours after injection, 12 rats received placebo (group III), and 10 rats received 1.2 g/kg of curcumin (group IV) for 7 d. All rats were sacrificed on postsepsis day 8 and a midline laparotomy was performed. Livers, kidneys, and small bowels were excised for evaluation of the degree of inflammation and tissue alterations histopathologically. In the liver, widespread hydropic degeneration of hepatocytes were seen in the sepsis group. There was no hydropic degeneration of hepatocytes and no portal inflammation in the sepsis/curcumin group. With respect to the small bowel, the sepsis group showed edema and prominent intraepithelial infiltration of neutrophil leucocytes and plasma cells. Inflammation and hyperemia in the lamina propria in the sepsis/curcumin group were less than those in the sepsis group. With respect to the kidneys, the sepsis group showed severe acute tubular necrosis that was more restricted in the sepsis/curcumin group than in the sepsis group. Curcumin reduced organ dysfunction in rats with experimentally formed sepsis. We propose that curcumin may be useful in the therapy of organ dysfunction due to sepsis, shock, and other diseases associated with local or systemic inflammation. | 18,752,929 |
Comparative performance and microbial diversity of hyperthermophilic and thermophilic co-digestion of kitchen garbage and excess sludge. | The objective of this study was to evaluate the performance characteristics of a hyperthermophilic digester system that consists of an acidogenic reactor operated at hyperthermophilic (70 degrees C) conditions in series with a methane reactor operated at mesophilic (35 degrees C), thermophilic (55 degrees C), and hyperthermophilic (65 degrees C) conditions. Lab-scale reactors were operated continuously, and were fed with co-substrates composed of artificial kitchen garbage (TS 9.8%) and excess sludge (TS 0.5%) at the volumetric ratio of 20:80. In the acidification step, COD solubilization was in the range of 22-46% at 70 degrees C, while it was 21-29% at 55 degrees C. The average protein solubilization was 44% at 70 degrees C. The double bond fatty acid removal ratio at 70 degrees C was much higher than at 55 degrees C. These results suggested that the optimal operation conditions for the acidogenic fermenter were about 3.1 days of HRT and 4 days of SRT at 70 degrees C. Methane conversion efficiency and the VS removal percentage in the methanogenic step following acidification was around 65% and 64% on average at 55 degrees C, respectively. The optimal operational conditions for this system are acidogenesis performed at 70 degrees C and methanogenesis at 55 degrees C. The key microbes determined in the hyperthermophilic acidification step were Anaerobic thermophile IC-BH at 6.4 days of HRT and Thermoanaerobacter thermohydrosulfuricus DSM 567 at 2.4 days of HRT. These results indicated that the hyperthermophilic system provides considerable advantages in treating co-substrates containing high concentrations of proteins, lipids, and nonbiodegradable solid matter. | 18,752,938 |
Discovery of novel series of benzoic acid derivatives containing biphenyl ether moiety as potent and selective human beta(3)-adrenergic receptor agonists: Part IV. | Identification and SAR study of novel series of beta(3)-AR agonists with benzoic acid are described. Conversion of ether linkage position of phenoxybenzoic acid derivative 2b led to compound 7b with moderate beta(3)-AR activity. Further modification in right, center and left parts of compound 7b was investigated to improve the beta(3)-AR potency and selectivity. Compounds 7g and 7k, with the bulky aliphatic-substituted group at 2-position of benzoic acid moiety, were identified as potent and selective beta(3)-AR agonists. In addition, in vivo efficacy of compounds 7g and 7k was exhibited on dog OAB model. | 18,752,946 |
Mobilizations of the asymptomatic cervical spine can reduce signs of shoulder dysfunction in adults. | Generalized shoulder pain is a common problem that is difficult to treat and frequently recurrent. The asymptomatic cervical spine must be ruled out as a cause of any shoulder pain, as it can have a similar presentation to an isolated shoulder disorder. Previous studies have shown that lateral cervical glide mobilizations to the asymptomatic cervical spine at C5/6 can affect peripheral pain, but none have examined shoulder pain. A randomized, blinded, placebo-controlled, cross-over trial was used to examine the immediate effects of cervical lateral glide mobilizations on pain intensity and shoulder abduction painful arc in subjects with shoulder pain. Twenty-one subjects received interventions of both cervical mobilization and placebo over two sessions. Pain intensity using a visual analog scale (VAS) and painful arc were assessed prior to and following application of cervical mobilization or placebo intervention. Evaluation of cervical mobilization revealed the shoulder abduction painful arc (12.5 degrees +/-15.6 degrees, p=0.002) and shoulder pain intensity (1.3+/-1.1cm, p<0.001) were significantly decreased. The results of this study suggest that any immediate change in shoulder pain or active shoulder range of motion following cervical mobilizations indicate that treatment directed toward the asymptomatic cervical spine may expedite recovery. | 18,752,983 |
Anticipatory postural control following fatigue of postural and focal muscles. | To investigate the effect of fatigue of postural and focal muscles on anticipatory postural adjustments (APAs). Nine healthy adults performed rapid bilateral arm raising movements before and after isometric hamstring (postural) and deltoid (focal/prime mover) muscle fatigue. Muscle force and peak acceleration of the arm movements were recorded to assess the presence of fatigue. Ground reaction forces, EMG activity of trunk and leg muscles and center of pressure (COP) displacements were recorded and quantified within the time intervals typical of APAs. Early APA onset was seen in erector spinae and semitendinosus muscles post-deltoid fatigue. Anticipatory EMG integrals were reduced in the semitendinosus muscle post-hamstring fatigue, and were increased in the gastrocnemius muscle post-deltoid fatigue. No changes in COP displacement were observed following fatigue of both muscle groups. A common pattern of APA adaptations seen following fatigue of either muscle groups along with no changes observed in COP displacements emphasizes the efficiency of the CNS in maintaining dynamic postural stability in the presence of fatigue. The outcome of the study is important for better understanding of the effect of muscular fatigue on feedforward mechanisms of postural control with possible implications for the elderly and individuals with neurological disorders. | 18,752,990 |
Sleep patterns among rural Chinese twin adolescents. | To examine sleep patterns and influencing factors (age, gender, Tanner Stage, weekday vs. weekend, and pre-sleep activity) among rural Chinese adolescents. This is a prospective study among 621 adolescents aged 11-20 years (341 males) using both a questionnaire and sleep diary to obtain bedtime, wake-up time, sleep latency, and total sleep time (TST). The median TST was 8.6h on weekdays and 9.4h on weekends. Despite absence of late night social pressure and computers, a U-shaped TST pattern was observed across age and Tanner Stage, with a nadir around age 15-16 years or Tanner IV. Bedtimes became progressively later with age and Tanner Stage, while wake-up time was considerably earlier for school students or up to Tanner IV. Later wake-up times and longer TST on weekends were seen in school students, but not in non-school adolescents (>17 years). Pre-sleep activity, like reading or studying, was related to later bedtime, earlier wake-up time, and shorter TST in both genders. Age, Tanner Stage, and pre-sleep activity affected sleep patterns in this sample of rural Chinese adolescents. Later bedtime coupled with earlier wake-up time associated with academic demand appear to be important contributors to sleep loss among school students. | 18,752,997 |
Periodic leg movements in RLS patients as compared to controls: Are there differences beyond the PLM index? | To characterize periodic leg movements (PLM) and their association with sleep disturbances in drug-free patients with restless legs syndrome (RLS) and healthy subjects without sleep complaints. Polysomnographic recordings of 95 patients with idiopathic RLS and 31 age-matched controls were compared, and correlation analysis between sleep efficiency and PLM variables was performed. All patients and controls were free of medication for 10 days prior to polysomnography. PLM measures revealed a significantly longer mean duration of single PLM during wakefulness and non rapid eye movement (NREM) sleep in RLS patients as compared to controls. PLM indices were higher in RLS patients than in controls during all sleep stages, but not during wakefulness and slow wave sleep. A significantly higher number of PLM sequences was found in RLS patients than in controls. In RLS patients decreased sleep efficiency was associated with a higher number and a shorter duration of PLM sequences. The mean duration of single PLM might be an appropriate parameter to discriminate between healthy subjects with PLM and patients with RLS. High numbers of PLM sequences of short duration might be an indicator for the decreased sleep quality in RLS patients. | 18,753,004 |
A finite element study on the effects of disorder in cellular structures. | The susceptibility to deformation localization of simple cubic arrangements of struts, which are a simple approximation of the micro-architecture in cancellous bone, is analyzed. The coherence between structural disorder and the tendency towards deformation localization is investigated and its relevance from a biological point of view is discussed. A systematic study on the spatial deformation distribution of regular and disordered open cell structures is carried out. To this end, finite element models are employed which account for elastic-plastic bulk material and large strain theory, and a methodology for the estimation of the degree of deformation localization is introduced. | 18,753,022 |
[Effect of maternal BDE-209 exposure on the expression of GAP-43 and BDNF in the hippocampus of the offspring rats]. | To evaluate the effect of prenatal and lactational exposure to brominated diphenyl ethers-209 (BDE-209) on the expression of growth associated protein-43 (GAP-43) and brain-derived neurotrophic factors (BDNF) in the hippocampus of the offspring rats. Peanut oil suspensions of commercial BDE-209 were administered daily at doses of 100, 300, 600, and 1200 mg/kg by oral gavage in pregnant Wistar rats (groups A, B, C, and D, respectively). The control group (E) only received peanut oil of an equivalent volume. The hippocampus was isolated from 10 offspring rats in each group to determine the expression of GAP-43 and BDNF using immunohistochemistry. The GAP-43 in the BDE-209-treated groups were lower than that of the control group, and decreased with the increase of the dose of BDE-209 exposure. The groups C and D (P=0.013, P=0.000), but not the groups A and B (P=0.177, P=0.093), showed significant difference from the control group in GAP-43 expression. The positive expression of BDNF in the hippocampus was decreased as the exposure dose to BDE-209 increased, and significant differences were found between the groups B, C, D and the control group (P=0.033, P=0.005, P=0.001, respectively), but not between group A and the control group (P=0.066). Maternal BDE-209 exposure can decrease the expression of GAP-43 and BDNF in the hippocampus of offspring rats, which may affect the axonal plasticity and regeneration of the neurons. | 18,753,049 |
[Effects of ruthenium red on body temperature in rats with lipopolysaccharide-induced fever]. | To observe the effect of ruthenium red (RR) on the body temperature of rats with lipopolysaccharide (LPS)-induced fever and investigate the possible mechanism. Rat models of fever were established with lipopolysaccharide and the effects of RR at different doses were observed on the body temperature of the rats and the content of TRPV4 in the hypothalamus. Compared with those in LPS group, the rats with LPS-induced fever receiving RR treatment showed a dose-dependent lowering of the body temperature. The rats with RR treatment had lower body temperature than those with saline injection. The content of TRPV4 in the saline group was significantly higher than that in RR+LPS and RR group. RR inhibits LPS-induced fever in rats and regulates the hypothalamal expression of TRPV4 channels, which may participate in the maintenance of normal body temperature. | 18,753,064 |
[Effect of peptide YY on subcutaneous transplantation tumor of human hepatoma in nude mice]. | To investigate the effects of peptide YY (PYY) on subcutaneous transplantation tumor of human hepatoma in nude mice and preliminarily explore the mechanisms. HepG2 human hepatic carcinoma cells were injected into nude mice subcutaneously, and the resultant tumor were taken and prepared into small tissue blocks. The tissue blocks were implanted subcutaneously into nude mice to establish mouse models bearing human hepatoma. Thirty-two such mouse models were assigned equally into 4 groups to receive subcutaneous PYY injection at a high or low dose, intraperitoneal injection of floxuridine (positive control group), or subcutaneous normal saline injection (negative control group). The general condition of the tumor-bearing mice and the growth of the tumors were observed. Compared with the negative control group, the high- and low-dose PYY groups showed reduced gross tumor volume, lowered serum AFP, tumor weight, and cAMP content in the tumor tissue (P<0.05). PYY can inhibit the growth of subcutaneous hepatoma in nude mice, which might be associated with the reduction of cAMP content in the tumors following PYY treatment. | 18,753,082 |
[Construction of a three-dimensional mandible model containing teeth based on the Virtual Chinese Human data]. | To construct a three-dimensional (3D) model of the mandible containing the teeth based on the Virtual Chinese Human Data. From the previously established Virtual Chinese Human Dataset, 280 consecutive images containing the mandibular region were taken as a source data for reconstruction of the 3D mandible model. The Photoshop software was adopted for 2D image processing, and a special medical reconstruction software was used for the 3D reconstruction of the mandible model, followed by software-based smoothing and rendering of the model. A 3D model of the mandible was successfully reconstructed, which allows a clear 3D observation of the anatomy of the mandible. | 18,753,084 |
Metabolic effects of 2 days of strict bed rest. | To examine the possibility of whether 2 days of strict hospitalized bed rest would alter the metabolic profile (including insulin resistance as calculated by the quantitative insulin sensitivity check index or QUICKI) in both normal subjects and patients with type 2 diabetes in comparison with 2 days of normal activity. The design of this pilot study was a randomized, crossover protocol that evaluated the effects of strict bed rest versus normal activity in 5 healthy normal subjects and 5 healthy patients with type 2 diabetes. All study participants completed a screening visit for assessment of baseline health. All 10 study subjects completed the protocol without adverse events. Fasting plasma glucose, insulin, and C-peptide levels as well as several known risk factors for atherosclerosis were unchanged in both the subjects without diabetes and the patients with type 2 diabetes after 2 days of hospitalized bed rest. Insulin resistance demonstrated no significant change during the 48 hours of bed rest when compared with the mean value at baseline. This study demonstrates that 48 hours of bed rest has no significant effect on insulin resistance or standard metabolic variables in normal subjects and patients with type 2 diabetes. Therefore, achieving good glucose control in patients hospitalized for a period of 2 days or less does not necessitate early ambulation to prevent an increase in insulin resistance. | 18,753,098 |
Treatment of altered body composition in HIV-associated lipodystrophy: comparison of rosiglitazone, pravastatin, and recombinant human growth hormone. | Treatment options for HIV-associated lipodystrophy syndrome (HALS) remain limited. The objective of this randomized open-label study was to compare three emerging therapies, rosiglitazone, pravastatin, and growth hormone alone and together, in men and women with HALS. Sixty-four subjects received daily rosiglitazone (4 mg, n = 14), pravastatin (40 mg, n = 11), or rosiglitazone plus pravastatin (n = 13) for 48 weeks or recombinant human growth hormone (rhGH; Serostim 2 mg, 12 weeks, n = 13) alone or combined with rosiglitazone (n = 13). Primary endpoint was body composition change by dual X-ray absorptiometry (DXA) and computed tomography (CT). Rosiglitazone resulted in slow accrual of limb fat detected by DXA (+444 +/- 186 g; p < .05) but not CT. Pravastatin had no consistent significant effects on body composition, although it reduced total and LDL cholesterol. Negative interactions were observed between pravastatin and rosiglitazone. rhGH reduced abdominal fat by CT (-31 +/- 15 cm2, 26%; p < .05) and DXA (-1597 +/- 383 g, 27%; p < .05) and increased trunk and limb lean mass (+10% and +12%, respectively). However, effects largely disappeared within 12 weeks post treatment. rhGH alone impaired insulin sensitivity but not when combined with rosiglitazone. Prolonged rosiglitazone treatment slowly improves lipoatrophy. rhGH rapidly and selectively reduces visceral fat, although effects are short-lived; co-administered rosiglitazone abrogates rhGH-related insulin resistance. | 18,753,120 |
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