title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Mild systemic inflammation has a neuroprotective effect after stroke in rats. | Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia. To test this hypothesis, marginal periodontitis was induced by ligatures on the second maxillary molars in BB/LL Wistar rats for 3 weeks. Two weeks after periodontitis initiation, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery. After a survival time of 7 days after ischemia, rats were killed and bone loss was determined on the buccal and palatinal surfaces of the defleshed jaw. In addition, markers of systemic inflammation were determined in a different group of laboratory animals at 14 days after the onset of periodontitis. The infarct size and markers of the inflammatory reaction in the brain were determined by immunohistochemistry. We found: (i) rats with ligatures exhibited significantly more periodontal bone loss than the control rats; (ii) the development of periodontitis was associated with an elevated gene expression for several markers of systemic inflammation (interleukin-10, transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-1beta and interferon gamma; (iii) rats with periodontitis and a mild systemic inflammation had a significantly reduced infarct volume and a significant reduction in the number of brain macrophages in the infarcted area. In conclusion we found that mild systemic inflammation elicited prior to stroke onset may have a neuroprotective effect in rats by reducing the infarct volume and tissue destruction by brain macrophages. | 18,991,656 |
Clinical potential of minocycline for schizophrenia. | Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestorative or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to various clinical trials. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline as an open-label adjunct to antipsychotic medication to patients with schizophrenia. The results of this trial suggested that minocycline might be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating schizophrenia. The present review summarizes the available data supporting the clinical testing of minocycline for patients with schizophrenia. In addition, we extend our discussion to the potential applications of minocycline for combining this treatment with cellular and molecular therapy. | 18,991,666 |
Cardiac metabolism in diabetes mellitus. | Diabetes mellitus is one of the most common chronic illnesses throughout the world. Diabetic cardiomyopathy is a specific syndrome, consisting of cardiomegaly, left ventricular dysfunction, electrical remodeling of the ventricle, and symptoms of congestive heart failure, that is seen in diabetic patients in the absence of other predisposing factors. Many researchers have suggested that inhibition of the renin-angiotensin-aldosterone system and the sympathetic nervous system may exert a therapeutic effect in individuals with diabetic cardiomyopathy. Indeed, angiotensin II and aldosterone blockade may be effective, partly because aldosterone blockade down-regulates Na(+)/H(+) exchanger 1 activity. Further study of the alterations in ion channel physiology in the context of diabetic cardiomyocytes may be of benefit. | 18,991,669 |
Imaging of tumor hypoxia to predict treatment sensitivity. | Non-invasive detection of tumor hypoxia using radiolabeled 2-nitroimidazoles has been a major effort during the last two decades. Recent years have witnessed the introduction of several new compounds which are chemically related to [(18)F]fluoromisonidazole (FMISO) but show slight but distinct differences in biodistribution and metabolic clearance. Although [(18)F]FMISO has shown clinical potential it suffers from suboptimal oxygen dependent tissue contrast and newer agents seek to improve this essential feature. The limited data on other interesting tracers keeps the investigators busy at demonstrating the potential advantages over [(18)F]FMISO while efforts should start to concentrate on proving the clinical significance of such techniques in the form of outcome data from image-guided therapy modification. We review here our experiences with two hypoxia-avid agents [(18)F]fluoroerythronitromidazole (FETNIM) and [(18)F] 2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) and focus on the similarities and differences of these two tracers in comparison to other radiolabeled 2-nitroimidazoles. It is recognized that only [(18)F]FMISO has thus far shown clinical utility and newer tracers need to be tested against this circumstance. | 18,991,711 |
PET imaging of steroid receptor expression in breast and prostate cancer. | The vast majority of breast and prostate cancers express specific receptors for steroid hormones, which play a pivotal role in tumor progression. Because of the efficacy of endocrine therapy combined with its relatively mild side-effects, this intervention has nowadays become the treatment of choice for patients with advanced breast and prostate cancer, provided that their tumors express hormone receptors. However, in case of breast cancer it is well known that part of the patients have hormone receptor-negative tumors at diagnosis, whereas other patients have discordant receptor expression across lesions. In addition, receptor expression can change during therapy and result in resistance to this therapy. Besides several lines of hormonal treatments, also other strategies to affect the hormone receptors are currently under investigation, namely histone deacetylases (HDAC) and heat shock protein (HSP) inhibitors. Knowledge of the actual receptor status can support optimal treatment decision-making and the evaluation of new drugs. Positron emission tomography (PET) is a non-invasive nuclear imaging technique that allows monitoring and quantification of hormone receptor expression across lesions throughout the body. Several PET tracers have been developed for imaging of the most relevant hormone receptors in breast and prostate cancer: i.e. the estrogen, progesterone and androgen receptors. Some of these PET tracers have been successfully applied in early clinical studies. This review will give an overview of the current status of PET imaging of hormone receptors in breast and prostate cancer. | 18,991,716 |
Synthesis of chiral 3-methyl- and 3-methyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline and prevention of MPP+ -induced cytotoxicity. | The chemical structure of selegiline, a commercially available drug for Parkinson's disease (PD), resembles that of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endogenous parkinsonism-inducing compound. In the present study, we evaluated the direct cytotoxicity of (R)- and (S)-3-methyl-TIQ (3-MeTIQ) and (R)- and (S)-3-methyl-N-propargyl-TIQ (3-Me-N-propargyl-TIQ), as selegiline-mimetic TIQ derivatives, and their ability to prevent 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced cell death. Synthesis of optically-pure 3-MeTIQs was achieved via the super acid-induced cyclization of chiral N-benzyl-N-[1-methyl-2-(phenylsulfinyl)ethyl]formamide using a Pummerer-type cyclization reaction as the key step in producing excellent yields. Subsequent N-propargylation of chiral 3-MeTIQs using propynylbromide gave the corresponding 3-Me-N-propargyl-TIQs. In our in vitro experiments, the direct cytotoxicity of chiral 3-MeTIQs and 3-Me-N-propargyl-TIQs was almost identical, with no relationship to optical chirality except for (S)-3-Me-N-propargyl-TIQ, which had significantly weaker direct cytotoxicity than the other 3-MeTIQ derivatives. However, the decreased viability of PC12 cells induced by treatment with MPP(+) was accelerated by the coexistence of 3-MeTIQs and inhibited by 3-Me-N-propargyl-TIQs without any participation of the stereochemistry at the 3-position. These results suggest that the N-propargyl group is necessary for protection of cells against the toxicity of MPP(+). Furthermore, the stereochemistry of the 3-position appears to partially participate in the direct cytotoxicity of 3-Me-N-propargyl-TIQs. | 18,991,736 |
2-Arylbenzimidazoles as antiviral and antiproliferative agents. Part 1. | Being involved in an anti-Flaviviridae Project, and because of the role played by benzimidazole derivatives as promising inhibitors of the HCV helicase and RNA polymerase, as well as of the Zn finger transcription factor, we synthesized a new series of 2-arylbenzimidazoles and evaluated them for antiviral activity, as well as for antiproliferative activity. Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae). Compounds 15, 28 and 29 resulted moderately active only against Yellow Fever Virus (a Flavivirus) (range 6-27 microM), whereas none of the title benzimidazoles showed any antiviral activity at concentrations not cytotoxic for the resting cell monolayers. Compounds were also tested for antiproliferative activity against a panel of exponentially growing cell lines derived from human haematological and solid tumors. Several new benzimidazoles turned out active. Among them, compound 27 was the most potent against human haematologic and solid tumor cells and turned out to be as potent as Etoposide and more potent than 6-mercaptopurine (6-MP), used as reference antitumor agents. | 18,991,746 |
Therapeutic targeting of g-protein coupled receptor-mediated epidermal growth factor receptor transactivation in human glioma brain tumors. | The epidermal growth factor receptor (EGFR) is the main tyrosine kinase receptor dysregulated or overexpressed in brain cancer types and its expression is directly correlated with tumor malignancy and unfavorable prognosis. Recently, the availability of endogenous EGFR ligands has been reported to be also regulated indirectly by the activation of several G-protein-coupled receptors (GPCRs) in many cancer cell types. This EGFR transactivation mechanism requires the initial activation of a GPCR that in turn induces the cleavage of membrane-bound EGFR ligands precursors via the involvement of the family of disintegrin and metalloproteases (ADAMs). The discovery of ADAMs in this transactivation mechanism led to the development of small molecule inhibitors. In this minireview we describe the expression of GPCR, ADAMs and EGFR ligands in human glioma brain tumors and the characteristics of small molecule ADAMs inhibitors. The addition of ADAM inhibitors to our pharmacological arsenal could enhance the outcome of combination therapies when using EGFR inhibitors against human brain tumors. | 18,991,757 |
Structural fragments in protein model refinement. | We survey a method that uses patterns of residue packing in known protein structures to refine structural models. The method can be used to refine models that include only one coordinate point per residue (C(alpha)) and is not dependent on homology. We demonstrate that the method improves both decoy and CASP7 target models. | 18,991,773 |
[Effect of strict glycemic control on clinical state and course of the disease in patients with chronic heart failure and type II diabetes mellitus. Results of the REMBO "rational effective multicomponent therapy in the struggle against diabetes mellitus in patients with congestive heart failure" study]. | With the aim to investigate influence of glycemic control on clinical state and course of disease, renal function, and neurohormonal profile of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM) we studied 81 patients with NYHA functional class (FC) II - III CHF, left ventricular ejection fraction (LVEF) 45% and type 2 DM. As a result of randomization 2 groups were formed - active with achievement of target levels of glycemia (n=41) and usual treatment (n=40). Retrospective analysis in dependence of efficacy of sugar lowering therapy was also conducted. Group 1 (n=18) comprised patients with achieved 1% lowering of glycated hemoglobin (HbA1 ), group 2 (n=26) - patients with bA1c lowering < 1%, group 3 (n=31) - patients with increase of HbA1 . Total duration of the investigation for the first analysis was 12, for the second - 6 months. Control examination was carried out at baseline, after 6 and 12 months of investigation and included assessment of clinico-functional status, glomerular filtration rate, neurohormonal profile (brain natriuretic peptide, noradrenalin, and angiotensin II). The state of carbohydrate metabolism was assessed with the help of determination of the level of HbA1c and oral glucose tolerance test. Absence of dynamics of glycemia in active and nonactive groups, in the active group improvement of clinico-functional status, quality of life, and parameters of remodeling was noted. Complementary retrospective analysis revealed improvement of functional status, renal function, and lowering of RAAS activity at 1% lowering of HbA1 and achievement of its target values. With this it was shown that betterment of functional possibilities ensued at lowering of HbA1c level not less than by 0.8%. Thus necessity and efficacy of strict glycemic control of DM in patients with CHF was proved. | 18,991,816 |
[Efficacy of the use of a sour milk product enriched with phytosterols in diet therapy of patients with cardiovascular diseases]. | We studied effect of antiatherogenic diet with inclusion of a sour milk product Danacor enriched with phytosterols on clinical and biochemical parameters of patients with cardiovascular diseases. Results of the study showed that antiatherogenic diet with phytosterols facilitated improvement of clinical status, anthropometric parameters, and lipid spectrum of blood. | 18,991,820 |
[Possibility of optimization of hypertension control in operators of trains on the basis of automatic system of pre-work examination]. | We have investigated possibility of the use of automatic systems for controlling arterial pressure in a specific occupational group - train\'s operators. This method is based on measurement and analysis of parameters of arterial pressure and pulse during pre-work (pre-haul) medical examinations of train\'s operators with subsequent entering of these results in computer data base. It allows to realize detection and registration of all operators with hypertension. The data obtained also show that the use of automated system of pre-work examination facilitates lowering of blood pressure levels. | 18,991,833 |
[Identification of pacemaker cells from atrial natriuretic peptide expressing embryonic stem cells]. | At present there exists a limited understanding of mechanisms of differentiation and specialization of cardiac conduction system in mammals. For characterization of its development and differentiation on early stages we used as experimental model murine embryonic stem cells expressing enhanced green fluorescent protein (eGFP) under transcriptional control of human atrial natriuretic peptide (ANP) as promoter. Cardiac nature of ANP-eGFP was confirmed by immuno staining with antibodies to troponin I and a-actinin. In ANP- eGFP expressing embryonic stem cells it is possible to distinguish subpopulation of spindle-shaped pacemaker cells capable to higher frequency of spontaneous contractions, velocity of activation and amplitude compared with those of triangular and polygonal atrial-like cardiomyocytes. These results show that expression of ANP-eGFP cells allows to identify pacemaker cells among embryonic stem cells by their morphological and electrophysiological properties. | 18,991,834 |
Association study of the calcineurin A gamma subunit gene (PPP3CC) and methamphetamine-use disorder in a Japanese population. | Several lines of evidence from animal and genetic analyses showed that the calcineurin A gamma subunit gene (PPP3CC) plays an important role in the pathogenesis of schizophrenia. Moreover, a recent large Japanese case-control study confirmed the genetic association of PPP3CC with schizophrenia. The symptoms of methamphetamine (MAP)-induced psychosis are similar to those of schizophrenia, suggesting that PPP3CC is an attractive candidate gene not only for schizophrenia, but also for METH-related disorders. In this study, we carried out a genetic association study of PPP3CC with MAP-use disorder in a Japanese population. We selected five haplotype-tagging SNPs from the aforementioned replication study and genotyped 393 samples (MAP abuse, 128; control, 265). We could not detect a significant association of all tagging SNPs with each condition. In conclusion, our data suggest that PPP3CC does not elevate the risk of MAP-use disorder in the Japanese population. | 18,991,849 |
Methamphetamine-induced early increase of IL-6 and TNF-alpha mRNA expression in the mouse brain. | The mechanisms by which methamphetamine (METH) causes neurotoxicity are not well understood. Recent studies have suggested that METH-induced neuropathology may result from a multicellular response in which glial cells play a prominent role, and so it is plausible to suggest that cytokines may participate in the toxic effects of METH. Therefore, in the present work we evaluated the effect of an acute administration of METH (30 mg/kg in a single intraperitoneal injection) on the interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA expression levels in the hippocampus, frontal cortex, and striatum of mice. We observed that METH did not induce changes in the IL-1beta mRNA expression levels in both hippocampus and striatum, with immeasurable levels in the frontal cortex. Regarding IL-6, METH induced an increase in the expression levels of this cytokine in the hippocampus and striatum, 1 h and 30 min post injection, respectively. In the frontal cortex, the increase in IL-6 mRNA levels was more significant and remained high even after 2 h. Moreover, the expression levels of TNF-alpha were increased in both hippocampus and frontal cortex 30 min post METH administration, with immeasurable levels in the striatum. We conclude that the pro-inflammatory cytokines IL-6 and TNF-alpha rapidly increase after METH administration, providing a new insight for understanding the effect of this drug of abuse in the brain. | 18,991,854 |
Analysis of single, purified inclusions as a novel approach to understand methamphetamine neurotoxicity. | A variety of neurodegenerative diseases leading to movement disorders such as Parkinson's disease (PD) are characterized by neuronal inclusions. Despite evidence of the presence of these intrusions, these intracellular bodies have been poorly investigated because of the technical limits of reproducing them in experimental models and the difficulties in isolating these ultrastuctures. Here, we describe a simple method for the isolation of single, purified inclusion bodies using immunomagnetic separation. We profited from the high number and maturation stage of inclusions produced in vitro by methamphetamine (METH) in cultured PC12 cells; in fact, this experimental condition is highly reproducible and has a limited number of experimental variables, while it is predictive of what is described in vivo in dopamine neurons. | 18,991,863 |
Influence of chronic exercise on the amphetamine-induced dopamine release and neurodegeneration in the striatum of the rat. | The aim of this study was to verify the effect of chronic exercise on the striatal dopamine (DA) outflow induced by low and high single doses of amphetamine (AMPH), and verify the existence of an exercise protective role on neurodegeneration. Adult male Sprague-Dawley rats were randomly separated into six groups: chronic exercise, saline; chronic exercise, 5 mg kg(-1) AMPH; chronic exercise, 30 mg kg(-1) AMPH; without exercise, saline; without exercise, 5 mg kg(-1) AMPH; without exercise, 30 mg kg(-1) AMPH. Chronic exercise consisted of an 8-week running program on a treadmill, with increasing intensity. Animals were anesthetized, placed into a stereotaxic frame and an intracerebral guide cannula implanted into the caudate-putamen. When indicated, microdialysis was performed. Dialysate samples were collected during 30-min intervals for 6 h, before and after the intraperitonial administration of AMPH or saline solution. HPLC with electrochemical detection was used to quantify DA. Chronic exercise did not significantly change the extracellular DA basal values. Regarding the maximal DA levels in the dialysates, in the rats treated with 5 mg kg(-1) AMPH, there was no significant difference between groups with and without chronic exercise; on the contrary, in animals treated with 30 mg kg(-1) AMPH, the DA release was lower in the group with chronic exercise. Moreover, the maintenance of higher levels of DA along time in the training group suggests a diminished reuptake of DA. By using the Fluoro-Jade C staining technique, we did not find neuronal death in any of the groups. In conclusion, these results suggest that chronic exercise leads to a diminished release and reuptake of DA after administration of a high dose of AMPH, whereas neither chronic exercise nor AMPH seems to induce neurodegeneration. | 18,991,868 |
Methamphetamine changes NMDA and AMPA glutamate receptor subunit levels in the rat striatum and frontal cortex. | Methamphetamine (METH) is a powerful psychostimulant whose noxious effects depend largely on the pattern of abuse. METH-induced glutamate release may overactivate N-methyl-d-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (NMDAR and AMPAR, respectively) causing excitotoxicity. In the brain, these receptors are also known for their essential role in mediating memory consolidation. Therefore, we assessed glial fibrillary acidic protein (GFAP) expression as a marker for astrogliosis and neurodegeneration by using Fluoro-Jade C (F-J C) staining. Moreover, we investigated the effect of two METH regimens on NMDAR NR1 and NR2A and on AMPAR GluR2 subunit expression in the rat striatum and frontal cortex 24 h after drug treatment. Adult Sprague-Dawley rats were injected subcutaneously (s.c.) on six consecutive days with saline (control and acute groups) or with an increasing dose of METH (10, 15, 15, 20, 20, 25 mg/kg/day; ED group). On the seventh day, both METH groups were given a "bolus" of 30 mg/kg METH, whereas controls received saline. We evaluated the expression levels of GFAP by both Western blot and immunohistochemical assays and concluded that there was no difference from control levels. In addition, neither drug regimen resulted in neurodegeneration within 24 h of last METH administration. In the frontal cortex of the acute group, NR1 expression level was decreased, and both NR2A and GluR2 were increased. Also, in the striatum of the acute group, the expression level of GluR2 was significantly increased, and both GluR2 and NR2A levels were augmented in the striatum of the ED group. Taken together, these results suggest a protective mechanism by decreasing permeability and/or functionality of AMPAR and NMDAR to counteract METH-induced glutamate overflow in the brain. Moreover, these results may explain, in part, the mnemonic deficits and psychotic behavior associated with METH abuse. | 18,991,869 |
Crucial role of acetaldehyde in alcohol activation of the mesolimbic dopamine system. | Ethyl alcohol (EtOH), the main psychoactive ingredient of alcoholic drinks, is widely considered responsible for alcohol abuse and alcoholism through its positive motivational properties, which depend, at least partially, on the activation of the mesolimbic dopaminergic system. On the other hand, acetaldehyde (ACD), EtOH's first metabolite, has been classically considered aversive and useful in the pharmacologic therapy of alcoholics. Here we show that EtOH-derived ACD is necessary for EtOH-induced place preference, a preclinical test with high predictive validity for reward liability. We also found that ACD is essential for EtOH-increased microdialysate dopamine (DA) levels in the nucleus accumbens (NAcc), and that this effect is mimicked by ACD administration to the intraventral tegmental area (VTA). Furthermore, in vitro, ACD enhances VTA DA neuronal firing. Coherently, EtOH-stimulating properties on DA neurons are prevented by pharmacologic blockade of local catalase: the main metabolic step for biotransformation of EtOH into ACD in the central nervous system. These results provide in vivo and in vitro evidence for a key role of ACD in EtOH motivational properties and its activation of the mesolimbic DA system. Additionally, these observations suggest that ACD, by increasing VTA DA neuronal activity, would oppose its well-known peripherally originating aversive properties. These findings could help in devising new effective pharmacologic therapies in alcoholism. | 18,991,876 |
Defining "neuroinflammation". | Neuroinflammation is a hot topic in contemporary neuroscience. A relatively new open-access journal, the Journal of Neuroinflammation, focuses on this field. As another example, abstracts to the 2007 Annual Meeting of the Society for Neuroscience could be submitted in several subcategories of neuroinflammation, a strong signal of growth in this research area. While it is becoming clear that activation of microglia and astroglia and the attendant expression of proinflammatory cytokines and chemokines often are associated with disease-, trauma-, and toxicant-induced damage to the CNS, it is by no means clear that a cause-and-effect relationship exists between the presence of a neuroinflammatory process and neural damage. We have explored this issue with two models of dopaminergic neurotoxicity. We used a single low-dose regimen of MPTP or METH, a paradigm that causes selective degeneration of striatal dopaminergic nerve terminals without affecting the cell body in the substantia nigra. Both compounds increased the expression of the microglia-associated factors, Il-1alpha, Il6, Ccl2, and Tnf-alpha, and also elicited morphologic evidence of microglial activation prior to induction of astrogliosis. Pharmacologic antagonism of MPTP and METH neurotoxicity prevented these proinflammatory responses, findings suggestive of a link between neuroinflammation and the observed neurotoxic outcomes. Nevertheless, when we used minocycline to suppress the expression of all these mediators, with the exception of Tnf-alpha, we failed to see neuroprotection. Likewise, when we examined the effects of MPTP or METH in transgenic mice lacking Il6, Ccl2, or Tnfr1/2 genes, deficiency of either Il6 or Ccl2 did not alter neurotoxicity, whereas deficiency in Tnfr1/2 was neuroprotective. Although these observations pointed to a role of the proinflammatory cytokine, TNF-alpha, in the neurotoxic effects of MPTP and METH, other observations did not support this supposition. For example, activation of NF-kappaB or induction of iNOS, known components of inflammatory responses and free radical formation, were not observed. Moreover, immunosuppressive regimens of glucocorticoids failed to suppress TNF-alpha or attenuate neurotoxicity. Taken together, our observations suggest that MPTP and METH neurotoxicity are associated with the elaboration of a "neuroinflammatory" response, yet this response lacks key features of inflammation and, with the exception of TNF-alpha, neurotoxicity appears to be the cause rather than the consequence of proinflammatory signals. | 18,991,877 |
Screening for marijuana and cocaine abuse by immunoanalysis and gas chromatography. | Drug abuse among college students is characterized by lower academic performance and long-term negative consequences. Screening to detect students at high risk of consuming drugs is of primary importance to insure early identification and appropriate levels of care. As a result, this study aimed to determine the current or past use of drug abuse through a questionnaire applied to a student population at the Universidad Autónoma del Estado de Morelos. The results were confirmed by immunoanalysis and gas chromatography of urine. We interviewed 181 students aged 15 to 21 (gender was not considered in this study), and urine samples were collected for analytical analysis. For detection of metabolites Delta9-THCA-A and benzoylecgonine from marijuana and cocaine, respectively, a homogenous enzymatic inmmunoanalysis was used; subsequent samples were analyzed by a mass spectrometer with quadrupole detector. Seven samples of the total (181) did not completely fit the inclusion criteria and were eliminated. The results showed 0.50% and 1.16% positive samples for benzoylecgonine and Delta9-THCA-A, respectively. These results are not different from those of the National Questionnaire on Addiction. We can establish a program for detecting drug consumption in our students. This kind of study is important in order to implement programs that can help us to decrease the abuse of drugs in our college population. | 18,991,889 |
Functional expression of brain neuronal CB2 cannabinoid receptors are involved in the effects of drugs of abuse and in depression. | Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2-Rs) in healthy brains, but CB2-R expression has been demonstrated in rat microglial cells and other brain-associated cells during inflammation. Thus, neuronal expression of CB2-Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of the CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances, including opiates, cocaine, and ethanol, in rodents. Here we demonstrate that a high incidence of Q63R but not H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated after exposure to stressors and administration of abused drugs. Mice that developed an alcohol preference had reduced CB2 gene expression, and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 antisense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. Using electron microscopy we report the subcellular localization of CB2-Rs that are mainly on postsynaptic elements in rodent brain. Our data demonstrate the functional expression of CB2-Rs in the brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuroimmunocannabinoid activity. | 18,991,891 |
Asia's changing role in global climate change. | Asia's role in global climate change has evolved significantly from the time when the Kyoto Protocol was being negotiated. Emissions of carbon dioxide, the principal greenhouse gas, from energy use in Asian countries now exceed those from the European Union or North America. Three of the top five emitters-China, India, and Japan, are Asian countries. Any meaningful global effort to address global climate change requires the active cooperation of these and other large Asian countries, if it is to succeed. Issues of equity between countries, within countries, and between generations, need to be tackled. Some quantitative current and historic data to illustrate the difficulties involved are provided, and one approach to making progress is suggested. | 18,991,898 |
Children's environmental health: intergenerational equity in action--a civil society perspective. | Since World War II, approximately 80,000 new commercial synthetic chemicals have been released into the environment, with approximately 1500 new chemicals released annually. Most of these have not been adequately tested for their impacts on human health or their particular impacts on children and the developing fetus. Yet, children are exposed to hazardous chemicals through residues in their food, indoor and outdoor air pollution, and through household products and contaminated house dust. Many of these synthetic chemicals are persistent and bio-accumulative, remaining in the human body long after exposure. Developing fetuses acquire toxic chemicals that have bioaccumulated in the mother's body and readily cross the placental barrier. Babies are now born with many man-made chemicals in their small bodies. Newborns take in more through breast milk or formula. There are no tests to assess the combined impacts of the "chemical soup" to which children are exposed. WHO, UNICEF, and UNEP have reported a growing number of children's health impacts caused by exposure to hazardous chemicals, including asthma, birth defects, hypospadias, behavioral disorders, learning disabilities, autism, cancer, dysfunctional immune systems, neurological impairments, and reproductive disorders. WHO states that approximately 3 million children under the age of five die every year due to environmental hazards, and this is not limited to developing countries. All children, both in the developing and developed world are affected by exposure to hazardous chemicals. In 2004, the European Union's Ministerial Conference on Children's Environmental Health identified air pollution, unsafe water conditions, and lead exposure as the main culprits in the death and disabling of children in Europe. The conference found that by reducing exposure to hazardous chemicals, the lives of many children could be saved. The key issues in children's environmental health and potential policy and management remedies are examined from both national (Australian) and international perspectives. | 18,991,917 |
Domestic fuels, indoor air pollution, and children's health. | Reliance on solid biomass fuel for cooking and heating exposes many children of developing countries to high levels of indoor air pollution. This study investigates the association between household use of biomass fuels for cooking and prevalence of respiratory symptoms and diseases among children in rural India. The air-quality parameters (CO, CO(2), NO, NO(2), SO(2), O(3), suspended particulate matter (SPM), including temperature and relative humidity) were investigated using a YES-Plus multigas air-quality monitor for gaseous and Kimoto handy samplers (HS-7) for TSPM. Seven hundred fifty households and 1505 children were selected for this study. A questionnaire developed on the pattern of the the International Study of Asthma and Allergies in Childhood (ISAAC) and the International Union Against Tuberculosis and Lung Disease (IUATLD) with some modifications were used for evaluation of respiratory health. The lung function parameters, namely, PEF, FVC, FEV(1), FEF, and SVC were examined on an electronic Spiro Meter (Maestro Medline Ltd.). Logistic regression was used to estimate the odds of suffering from respiratory infections among children from households using biomass fuels relative to children from households using liquified petroleum gas (LPG), after controlling for potentially confounding factors. The study suggests that exposure to cooking smoke from biomass combustion is significantly associated with decline in lung function and prevalence of doctor-diagnosed asthma (OR = 2.20; 95% CI: 1.16, 4.19) and other respiratory diseases. | 18,991,919 |
Zinc toxicity among galvanization workers in the iron and steel industry. | Galvanization is the process of coating steel or cast iron pieces with zinc, allowing complete protection against corrosion. The ultimate goal of this work was to assess the effect of occupational exposure to zinc in the galvanization process on different metals in the human body and to detect the association between zinc exposure and its effect on the respiratory system. This study was conducted in 111 subjects in one of the major companies in the iron and steel industry. There were 61 subjects (workers) who were involved in the galvanization process. Fifty adult men were chosen as a matched reference group from other departments of the company. All workers were interviewed using a special questionnaire on occupational history and chest diseases. Ventilatory functions and chest X rays were assessed in all examined workers. Also, complete blood counts were performed, and serum zinc, iron, copper, calcium, and magnesium levels were tested. This study illustrated the relation between zinc exposure in the galvanization process and high zinc levels among exposed workers, which was associated with a high prevalence rate of metal fume fever (MFF) and low blood copper and calcium levels. There was no statistically significant difference between the exposed and control groups with regards to the magnesium level. No long-term effect of metals exposure was detected on ventilatory functions or chest X rays among the exposed workers. | 18,991,923 |
Contents and occurrence of cadmium in the coals from Guizhou province, China. | Eleven raw coal samples were collected from Liuzhi, Suicheng, Zunyi, Xingren, Xingyi, and Anlong districts in Guizhou Province, Southwest China. The content of cadmium (Cd) in coal was determined using inductively coupled plasma mass-spectrometry (ICP-MS). Cd contents ranged from 0.146 to 2.74 ppm (whole coal basis), with an average of 1.09 ppm. In comparison with the arithmetic means of Cd in Chinese coal (0.25 ppm), this is much higher. In order to find its occurrence in coal, float-sink analysis and a coal flotation test by progressive release were conducted on two raw coal samples. The content of the Cd and ash yield of the flotation products were determined. The organic matter was removed by low-temperature ashing (LTA). X-ray diffraction (XRD) was used to differentiate the main, minor, and trace minerals in the LTA from different flotation subproducts. Quartz, kaolinite, pyrite, and calcite were found to dominate the mineral matters, with a proportion of anatase, muscovite, and illite. Then quantitative analysis of minerals in LTA was conducted using material analysis using diffraction (MAUD) based on the Rietveld refinement method. Results show that Cd has a strong association with kaolinite. | 18,991,925 |
The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents. | To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong. | 18,991,931 |
Solid-waste management practices of households in Manila, Philippines. | The experiences and practices of household waste management of people in a barangay (village) in Manila, Philippines are documented. The data were gathered through an interview with household members using open-ended questions. Interviews were also conducted with garbage collectors as well as scavengers. Results showed that the households generated an average of 3.2 kg of solid waste per day, or 0.50 kg/capita/day. The types of wastes commonly generated are food/kitchen wastes, papers, PET bottles, metals, and cans, boxes/cartons, glass bottles, cellophane/plastics, and yard/garden wastes. The respondents segregate their wastes into PET bottles, glass bottles, and other waste (mixed wastes). No respondents perform composting. It is worth noting, however, that burning of waste is not done by the respondents. The households rely on garbage collection by the government. Collection is done twice daily, except Sundays, and household members bring their garbage when the garbage truck arrives. However, there are those who dump their garbage in nondesignated pick-up points, usually in a corner of the street. The dumped garbage becomes a breeding ground for disease-causing organisms. Some household respondents said that it is possible that the dumping in certain areas caused the dengue fever suffered by some of their family members. Mothers and household helpers are responsible for household waste management. Scavengers generally look for recyclable items in the dumped garbage. All of them said that it is their only source of income, which is generally not enough for their meals. They are also aware that their work affects their health. Most of the respondents said that garbage collection and disposal is the responsibility of the government. The results of the study showed that RA 9003, also known as the Ecological Solid Waste Management Act of 2000, is not fully implemented in Metro Manila. | 18,991,942 |
Protein kinases and addiction. | Although drugs of abuse have different chemical structures and interact with different protein targets, all appear to usurp common neuronal systems that regulate reward and motivation. Addiction is a complex disease that is thought to involve drug-induced changes in synaptic plasticity due to alterations in cell signaling, gene transcription, and protein synthesis. Recent evidence suggests that drugs of abuse interact with and change a common network of signaling pathways that include a subset of specific protein kinases. The best studied of these kinases are reviewed here and include extracellular signal-regulated kinase, cAMP-dependent protein kinase, cyclin-dependent protein kinase 5, protein kinase C, calcium/calmodulin-dependent protein kinase II, and Fyn tyrosine kinase. These kinases have been implicated in various aspects of drug addiction including acute drug effects, drug self-administration, withdrawal, reinforcement, sensitization, and tolerance. Identifying protein kinase substrates and signaling pathways that contribute to the addicted state may provide novel approaches for new pharmacotherapies to treat drug addiction. | 18,991,950 |
Implication of activated astrocytes in the development of drug dependence: differences between methamphetamine and morphine. | Astrocytes are a subpopulation of glial cells that directly affect neuronal function. This review focuses on the potential functional roles of astrocytes in the development of behavioral sensitization and rewarding effects induced by chronic treatment with drugs of abuse. In vitro treatment of cortical neuron/glia cocultures with either methamphetamine or morphine caused activation of astrocytes via protein kinase C (PKC). Purified cortical astrocytes were markedly activated by methamphetamine, whereas morphine had no such effect. Methamphetamine, but not morphine, caused a long-lasting astrocytic activation in cortical neuron/glia cocultures. Morphine-induced behavioral sensitization, assessed as hyperlocomotion, was reversed by 2 months of withdrawal from intermittent morphine administration, whereas behavioral sensitization to methamphetamine-induced hyperlocomotion was maintained even after 2 months of withdrawal. In vivo treatment with methamphetamine, which was associated with behavioral sensitization, caused PKC-dependent astrocytic activation in the mouse cingulate cortex and nucleus accumbens. Furthermore, the glial modulator propentofylline dramatically diminished the activation of astrocytes and the rewarding effect induced by methamphetamine and morphine. On the other hand, intra-nucleus accumbens and intra-cingulate cortex administration of astrocyte-conditioned medium aggravated the development of rewarding effects induced by methamphetamine and morphine. Furthermore, astrocyte-conditioned medium, but not methamphetamine itself, clearly induced differentiation of neural stem cells into astrocytes. These findings provide direct evidence that astrocytes may, at least in part, contribute to the development of the rewarding effects induced by drugs of abuse in the nucleus accumbens and cingulate cortex. | 18,991,953 |
ADHD and smoking: from genes to brain to behavior. | Attention-deficit/hyperactivity disorder (ADHD) and tobacco smoking are among the most common and costly psychiatric and behavioral problems. The rates of co-occurrence of these two common problems are larger than expected by chance. Despite progress in identifying the neural and genetic substrates of each, the mechanisms underlying the high rates of comorbidity between ADHD and smoking remain largely unknown. We propose that ADHD and smoking involve dysregulation of dopaminergic and nicotinic-acetylcholinergic circuits and that these aberrations are likely to arise, at least in part, from genetic variations. This review describes an integrative model of the ADHD-smoking comorbidity, with an emphasis on shared neuropharmacological mechanisms. We first describe the prevalence of smoking among ADHD patients. We then describe how ADHD influences stages of smoking behavior (e.g., initiation, maintenance, and relapse). We review common potential genetic substrates of ADHD and smoking, focusing on genes that regulate monoaminergic neurotransmission. We review the behavioral and neuropharmacological bases of smoking and ADHD, focusing on the modulatory roles of nicotine on attention and behavioral control. Finally, we discuss the implications of this model for prevention and clinical outcomes. | 18,991,955 |
Predicting treatment outcome in stimulant dependence. | The purpose of this review is to highlight some of the issues that need to be addressed to optimally use functional neuroimaging as a clinical tool to predict outcomes in substance use disorders. First, the importance of recognizing the clinical heterogeneity of the substance use disorders population is highlighted. We also emphasize that empirical and theoretical analyses support the idea that the courses of substance use disorders are relatively independent of the types of substance being used. Second, various approaches to the measurement and characterization of the longitudinal courses of substance use disorders are summarized. Third, predictors of outcomes are reviewed and their limitations are discussed. Within this context, we describe aspects of our work that focus on using functional magnetic resonance imaging to predict outcomes. Fourth, we discuss future directions, critical experiments, and the utility of functional neuroimaging as a clinical tool. | 18,991,963 |
Quality of life in young people with cystic fibrosis: effects of hospitalization, age and gender, and differences in parent/child perceptions. | The Cystic Fibrosis Questionnaire-Revised version (CFQ-R) was used to evaluate age/gender effects on quality of life (QOL) in Australian young people with cystic fibrosis (CF) who were inpatients/outpatients aged 6-18 years. Parent/child agreement was also examined. The CFQ-R was completed by 18 outpatients, and 15 inpatients at admission for an acute pulmonary exacerbation to a tertiary hospital, Brisbane, Australia, as well as by parents of those aged 6-13 years. Inpatients scored significantly lower than outpatients for the CFQ-R domains 'emotional state', 'social', 'body image' and 'respiratory symptoms'. Young people aged 6-13 years scored significantly better than those aged 14-18 years for 'emotional state', 'body image' and 'treatment burden'. Women perceived less 'treatment burden' than did men. Young people aged 6-13 years perceived less 'treatment burden' than did their parents. A significant interaction occurred between child/parent report and gender for 'emotional state' and 'eating disturbances'. The CFQ-R found differences between inpatients and outpatients and between younger and older paediatric patients with CF, and between parent and child perceptions of QOL. | 18,991,968 |
The interaction of sexually and naturally selected traits in the adaptive radiations of cichlid fishes. | The question of how genetic variation translates into organismal diversity has puzzled biologists for decades. Despite recent advances in evolutionary and developmental genetics, the mechanisms that underlie adaptation, diversification and evolutionary innovation remain largely unknown. The exceptionally diverse species flocks of cichlid fishes are textbook examples of adaptive radiation and explosive speciation and emerge as powerful model systems to study the genetic basis of animal diversification. East Africa's hundreds of endemic cichlid species are akin to a natural mutagenesis screen and differ greatly not only in ecologically relevant (hence naturally selected) characters such as mouth morphology and body shape, but also in sexually selected traits such as coloration. One of the most fascinating aspects of cichlid evolution is the frequent occurrence of evolutionary parallelisms, which has led to the question whether selection alone is sufficient to produce these parallel morphologies, or whether a developmental or genetic bias has influenced the direction of diversification. Here, I review fitness-relevant traits that could be responsible for the cichlids' evolutionary success and assess whether these were shaped by sexual or natural selection. I then focus on the interaction and the relative importance of sexual vs. natural selection in cichlid evolution. Finally, I discuss what is currently known about the genes underlying the morphogenesis of adaptively relevant traits and highlight the importance of the forthcoming cichlid genomes in the quest of the genetic basis of diversification in this group. | 18,992,003 |
Evaluation of reproductive functions in male adolescents following renal transplantation. | The aim of this study was to analyze the semen variables and hormone profiles in kidney transplanted male adolescents. Eight post-pubertal male patients who underwent successful renal tx during the peripubertal period and who had ESRD during childhood were enrolled in the study. Patients who underwent tx before 14 yr old (group I) and patients who underwent tx after 14 yr old (group II) were evaluated separately. Semen was collected and analyzed. Serum levels of LH, FSH, and testosterone were measured and found to be normal in all patients except one. The mean age at the diagnosis of CKD was six yr and 13 yr in groups I and II, respectively. The mean age at the time of tx was 12 yr in the first and 17.8 yr in the second group. The patients in group I had received prednisone, cyclosporine A and azathioprine with a longer duration of time compared with patients in group II. Sperm counts (15.5 +/- 15.7 vs. 82.3 +/- 64.2 millions/mL) and sperm motilities (37.8 +/- 30.9 vs. 57.8 +/- 22.1%) were lower in group I than group II. Only one patient in group II had normal sperm parameters and azospermia was observed in one patient from group I. We conclude that the earlier onset and the longer duration of uremia, the more impairment of reproductive function. Also, it seems that duration of exposure to corticosteroids or cyclosporine combined with azathioprine contribute to sperm dysfunction in peripubertal transplanted boys. | 18,992,046 |
Neonates with severe infantile hepatic hemangioendothelioma: limitations of liver transplantation. | IHHE as the most common vascular tumor of the liver in infancy can present with acute postnatal liver and congestive heart failure. LTx may be a lifesaving option, but can be complicated by extrahepatic involvement and bleeding complications, especially in neonates. Here we discuss the benefit of LTx in cases of acute postnatal deterioration and massive extent of the hepatic tumor. Three infants with IHHE were transplanted at our institution between 2005 and 2007. Two were neonates with acute postnatal decompensation and progressive liver and heart failure within days. Treatment with steroids and chemotherapy was ineffective; resection surgery and interventional treatment were not considered appropriate. LTx was performed at the age of 7 and 24 days, respectively. An additional infant with a bilobar tumor that evolved more slowly was transplanted on day-of-life 56. Patients 1 and 2 had to be resuscitated during the LTx procedure because of massive bleeding and both died during the procedure. Patient 3 had a complicated post-operative course but is doing well one-yr post-LTx. Neonates with extended hepatic and extrahepatic involvement of IHHE should be evaluated carefully prior to LTx. Whenever possible, alternative interventional treatment options should be considered. | 18,992,050 |
Calcineurin-inhibitor free immunosuppression with mycophenolate mofetil and corticosteroids in paediatric renal transplantation improves renal allograft function without increasing acute rejection. | The aim of this study was to determine whether CNIs can be safely withdrawn in paediatric patients with declining renal allograft function receiving MMF and corticosteroids for long-term immunosuppression following renal transplantation. We performed a retrospective review of paediatric renal transplant recipients who received MMF with corticosteroids at least three months after transplantation with or without CNI in a single centre. Thirty-eight children (71% male), mean age 7.2 +/- 3.7 yr received MMF and corticosteroids, with 29 (76%) receiving a CNI. Mean follow-up was 59.2 +/- 42 months post-MMF commencement and 109 +/- 98.8 months post-transplantation. Patient and renal allograft survival were 100% and 94%, respectively. There was a significant improvement in eGFR after MMF introduction both in children on a CNI and those where the CNI was withdrawn, with stabilisation of eGFR after two yr. There was no significant difference in the number of acute rejection episodes prior to or following introduction of MMF between the groups. MMF in combination with corticosteroids is a safe and effective immunosuppressive regimen in paediatric renal transplantation. Complete withdrawal of CNIs after conversion to MMF should be considered in all patients, to preserve renal function as evidenced by improved eGFR. | 18,992,054 |
Separation of phasic arousal and expectancy effects in a speeded reaction time task via fMRI. | Sixteen neurologically normal volunteers performed a 2-choice speeded reaction time (RT) task in which the imperative was the change in color of a clock hand. During trial blocks with low temporal uncertainty (good clock condition), this imperative stimulus occurred at a fixed location (e.g., 2:00). In the bad clock condition, the clock was unpredictive of imperative onset. On half of both good and bad clock trials, a task-irrelevant, cutaneous accessory stimulus accompanied the imperative. The speeding of reactions by the accessory was associated with activation primarily in and near the supramarginal gyrus of the parietal lobe. Contrasts of good- versus bad-clock conditions revealed activation in a variety of perceptual, motor, and executive control regions. Apart from interactions within the cerebellum and left anterior insula, there was little overlap between structures influenced by the arousal and expectancy manipulations. | 18,992,072 |
Comparative study between slow freezing and vitrification of mouse embryos using different cryoprotectants. | The objective of this study was to evaluate the effects of different cryoprotectants and different cryopreservation protocols on the development of mouse eight-cell embryos. Mouse eight-cell embryos were cryopreserved by using propylene glycerol (PROH), ethylene glycerol (EG), dimethyl sulfoxide (DMSO) or glycerol (G) as cryoprotectant with slow-freezing or Vit-Master vitrification protocol. After thawing, the survival rate, blastocyst formation rate and blastocyst hatching rate of the embryos were compared. When the mouse eight-cell embryos were cryopreserved by the slow-freezing, the survival rate, the blastocyst formation rate and the blastocyst hatching rate of the embryos with PROH were significantly higher than those of DMSO and G (p < 0.05, respectively), but not significantly different among those of DMSO, G and EG (p > 0.05, respectively), and not significantly different between those of PROH and EG (p > 0.05, respectively). When the mouse eight-cell embryos were cryopreserved by Vit-Master vitrification, the survival rate, the blastocyst formation rate and the blastocyst hatching rate of the embryos with EG were significantly higher than those of PROH, DMSO and G (p < 0.05, respectively). Yet, there were no significant differences among those of PROH, DMSO and G (p > 0.05, respectively). In conclusion, PROH was the optimal cryoprotectant for the cryopreservation of mouse eight-cell embryos by slow-freezing protocol. EG was the optimal cryoprotectant for the cryopresevation of mouse eight-cell embryos by Vit-Master vitrification protocol, which may be commonly used in clinical and laboratory practice. | 18,992,080 |
Single-layer centrifugation through colloid positively modifies the sperm subpopulation structure of frozen-thawed stallion spermatozoa. | The present study attempted to select the subpopulation of stallion spermatozoa that best survived a conventional freezing and thawing procedure, using centrifugation of post-thawed semen samples through a single layer of a glycidoxypropyltrimethoxysilane-coated silica colloid with a species-specific formulation (Androcoll-E). After freezing and thawing, four sperm subpopulations were identified, listed as FT1 to FT4. While subpopulations FT1 and FT2 were characterized by low sperm velocity, high velocities characterized the ones called FT3 and FT4. The single-layer centrifugation (SLC)-handled sperm sample was enriched in subpopulation FT3, reaching a proportion of 82.6% of the present spermatozoa, in contrast with the non-filtered control post-thawed semen, where this sperm subpopulation only accounted for 16.3% of the total. It is concluded that in the equine industry, the SLC is a practical, easy-to-perform approach to improve the quality of equine frozen-thawed semen samples. | 18,992,085 |
Expression of occludin in testis and epididymis of wild rabbits, Lepus sinensis coreanus. | Tight junctions (TJs) in inter-Sertoli junctional areas and epididymal epithelia build up the blood-testis barrier (BTB) and the blood-epididymal barrier (BEB), respectively. In this study, the expression of occludin, an integral member of the TJs, was examined in testis and different regions of epididymis of Lepus sinensis coreanus, an Korean wild rabbit species. In testis, intense occludin immunoreactivity was found in the basally located inter-Sertoli junctional area together with diffused immunoreactivity of occludin in the cytoplasm of Sertoli cells. It can be suggested that occludin is one of the robust elements of BTB in seminiferous tubules of rabbit testis. In proximal and distal caput epididymis, occludin immunoreactivity was found in the lateral as well as apical contacts of epithelial cells. In corpus epididymis, intense occludin immunoreactivity was found in the basolateral as well as apical contacts of epithelial cells together with cytoplasmic signal. In cauda epididymis, occludin immunoreactivity in luminal epithelia was relatively strong but largely found in the cytoplasm. This suggests that intriguing regulatory mechanisms differentially recruit occludin to the TJ in the different regions of epididymal epithelia. The differences in the subcellular localization as well as expression levels of occludin among the epididymal segments may reflect differential paracellular permeability of epithelia along the epididymal tubules and be correlated with sperm maturation in rabbit. In Western blot, a major form of occludin was MW 62 kDa together with small fragments of MW 34-39 kDa in testis and epididymis, suggesting the peptide cleavage of occludin. This is the first report on the molecular nature of TJs in a wild rabbit testis and epididymis. | 18,992,101 |
Effects of hydrogen peroxide (H2O2) on fresh and cryopreserved buffalo sperm functions during incubation at 37 degrees C in vitro. | The magnitude of damage to buffalo spermatozoa during incubation with different levels of H2O2 was assessed. A total number of 24 ejaculates from four Murrah buffalo bulls were analysed in the study. Each ejaculate was split into two parts (part I and II). Part I was extended in Tris-egg yolk-citrate extender (20% egg yolk:7% glycerol), equilibrated (4 h at 5 degrees C) and cryopreserved in 0.5-ml French straws and stored in liquid nitrogen. The other part was utilized for fresh semen studies. The sperm in fresh, equilibrated and frozen-thawed semen was separated by centrifugation (1500 g; 15 min) and were washed with sperm TALP. The sperm cells were re-suspended in incubation TALP at the rate of 10(8) sperm cells per millilitre and incubated with 0, 10, 25, and 50 microm H2O2 per ml at 37 degrees C. Sperm motility, viability and intact acrosome percentages were assessed at 15-min intervals up to 60 min of incubation. Lipid peroxidation levels of sperm were assessed at 0 and 60 min of incubation. The results of the experiment revealed that sperm motility decreased drastically during incubation with H2O2. Among the different levels of H2O2, the 50-microm H2O2-incorporated group had significantly (p<0.05) higher malonaldehyde (MDA) level than the other groups. In the 50-microm H2O2-incorporated group, the MDA levels in fresh, equilibrated and frozen-thawed semen after incubation for 60 min were 961.6+/-12.7, 991.8+/-10.3 and 1234.9+/-9.6 nm per 10(9) spermatozoa respectively. An inverse relationship was observed between sperm motility, viability, intact acrosome percentages and concentration of H2O2 and duration of incubation. The decrease in sperm functions with duration of incubation and concentration of H2O2 was significantly (p<0.05) higher in frozen-thawed than fresh and equilibrated spermatozoa. | 18,992,123 |
Exploring valid reference genes for gene expression studies in Brachypodium distachyon by real-time PCR. | The wild grass species Brachypodium distachyon (Brachypodium hereafter) is emerging as a new model system for grass crop genomics research and biofuel grass biology. A draft nuclear genome sequence is expected to be publicly available in the near future; an explosion of gene expression studies will undoubtedly follow. Therefore, stable reference genes are necessary to normalize the gene expression data. A systematic exploration of suitable reference genes in Brachypodium is presented here. Nine reference gene candidates were chosen, and their gene sequences were obtained from the Brachypodium expressed sequence tag (EST) databases. Their expression levels were examined by quantitative real-time PCR (qRT-PCR) using 21 different Brachypodium plant samples, including those from different plant tissues and grown under various growth conditions. Effects of plant growth hormones were also visualized in the assays. The expression stability of the candidate genes was evaluated using two analysis software packages, geNorm and NormFinder. In conclusion, the ubiquitin-conjugating enzyme 18 gene (UBC18) was validated as a suitable reference gene across all the plant samples examined. While the expression of the polyubiquitin genes (Ubi4 and Ubi10) was most stable in different plant tissues and growth hormone-treated plant samples, the expression of the S-adenosylmethionine decarboxylase gene (SamDC) ranked was most stable in plants grown under various environmental stresses. This study identified the reference genes that are most suitable for normalizing the gene expression data in Brachypodium. These reference genes will be particularly useful when stress-responsive genes are analyzed in order to produce transgenic plants that exhibit enhanced stress resistance. | 18,992,143 |
Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression. | Previous results showed that over-expression of the WTH3 gene in MDR cells reduced MDR1 gene expression and converted their resistance to sensitivity to various anticancer drugs. In addition, the WTH3 gene promoter was hypermethylated in the MCF7/AdrR cell line and primary drug resistant breast cancer epithelial cells. WTH3 was also found to be directly targeted and up regulated by the p53 gene. Furthermore, over expression of the WTH3 gene promoted the apoptotic phenotype in various host cells. To further confirm WTH3's drug resistant related characteristics, we recently employed the small hairpin RNA (shRNA) strategy to knockdown its expression in HEK293 cells. In addition, since the WTH3 promoter's p53-binding site was located in a CpG island that was targeted by methylation, we were interested in testing the possible effect this epigenetic modification had on the p53 transcription factor relative to WTH3 expression. To do so, the in vitro methylation method was utilized to examine the p53 transgene's influence on either the methylated or non-methylated WTH3 promoter. The results generated from the gene knockdown strategy showed that reduction of WTH3 expression increased MDR1 expression and elevated resistance to Doxorubicin as compared to the original control cells. Data produced from the methylation studies demonstrated that DNA methylation adversely affected the positive impact of p53 on WTH3 promoter activity. Taken together, our studies provided further evidence that WTH3 played an important role in MDR development and revealed one of its transcription regulatory mechanisms, DNA methylation, which antagonized p53's positive impact on WTH3 expression. | 18,992,151 |
Isolated vertebral fractures give elevated serum protein S-100B levels. | Serum protein S-100B determinations have been widely proposed in the past as markers of traumatic brain injury and used as a predictor of injury severity and outcome. The purpose of this prospective observational case series was therefore to determine S-100B serum levels in patients with isolated injuries to the back. Between 1 February and 1 May 2008, serum samples for S-100B analysis were obtained within 1 hour of injury from 285 trauma patients. All patients with a head injury, polytrauma, and intoxicated patients were excluded to select isolated injuries to the spine. 19 patients with isolated injury of the back were included. Serum samples for S-100B analysis and CT spine were obtained within 1 hours of injury. CT scans showed vertebral fractures in 12 of the 19 patients (63%). All patients with fractures had elevated S-100B levels. Amongst the remaining 7 patients without a fracture, only one patient with a severe spinal contusion had an S-100B concentration above the reference limit. The mean S-100B value of the group with fractures was more than 4 times higher than in the group without fractures (0.385 vs 0.087 microg/L, p = 0.0097). Our data, although limited due to a very small sample size, suggest that S-100B serum levels might be useful for the diagnosis of acute vertebral body and spinal cord injury with a high negative predictive power. According to the literature, the highest levels of serum S-100B are found when large bones are fractured. If a large prospective study confirms our findings, determining the S-100B level may contribute to more selective use of CT and MRI in spinal trauma. | 18,992,158 |
Cooperation between gatekeepers in sickness insurance - the perspective of social insurance officers. A qualitative study. | Objective was to describe variations in how social insurance officers conceive the cooperation with the health care in their daily work with sick leave. Fifteen social insurance officers (SIOs) working with administration of sickness benefits were interviewed. They were purposefully recruited to represent different parts of the social insurance office organization, different ages, gender, education, and work experience. The interviews were audio-recorded, transcribed verbatim and analyzed using phenomenographic approach. 11 women and 4 men, aged 25-65, with a work experience ranging from 1-40 years were interviewed. Three descriptive categories embracing eleven subcategories emerged: 1) Communication channels included three subcategories; to obtain medical opinions, to hold meetings with actors involved, to experience support functions; 2) Organizational conditions included five subcategories; to experience lack of time, to experience problems of availability, to experience lack of continuity, to experience unclear responsibility, to experience ongoing change; 3) Attitudes included three subcategories; to conceive the attitudes of the physicians, to conceive the attitudes of the patients, to conceive the attitudes of the SIOs. Personal communication was described as crucial to ensure a more efficient working process. The personal contact was obstructed mainly by issues related to work load, lack of continuity, and reorganisations. By enhancing and enabling personal contact between SIOs and health care professionals, the waiting times for the sick-listed might be shortened, resulting in shorter periods of sick-leave. Issues around collaboration and communication between gatekeepers need to be recognized in the ongoing work with new guidelines and education in insurance medicine. | 18,992,160 |
Predictors of gastrointestinal lesions on endoscopy in iron deficiency anemia without gastrointestinal symptoms. | Iron deficiency anaemia (IDA) due to occult gastrointestinal (GI) blood loss usually remains unnoticed until patient become symptomatic. There is sparse data in IDA patients without gastrointestinal symptoms. This study was designed to find out the frequency and predictors of endoscopic lesions in IDA without gastrointestinal symptoms. Cross-sectional study performed on a convenience sample of consecutive subjects. Ninety five consecutive patients with laboratory based diagnosis of IDA having no gastrointestinal symptoms were interviewed and their clinical and biochemical variables were recorded. All the study patients underwent esophago-gastroduodenoscopy (EGD) and colonoscopy. Endoscopic findings were documented as presence/absence of bleeding related lesion and presence/absence of cause of IDA. Multiple logistic regressions were performed to identify variables significantly related to outcome variables. Possible cause of anaemia was found in 71% and bleeding related lesions were found in 53% of patients. Upper gastrointestinal tract lesions were found in 41% of patients with bleeding related lesions. On multivariable logistic regression; advancing age, low mean corpuscular volume (MCV<or=60 fl), and positive fecal occult blood test were predictive factors for bleeding related GI lesions and cause of IDA CONCLUSION: Clinical and Biochemical markers can predict gastrointestinal lesions on endoscopy in IDA patients without gastrointestinal symptoms. High proportion of upper gastrointestinal involvement warrants EGD as initial endoscopic procedure however, this needs validation by further studies. | 18,992,171 |
Between-year variation and spatial dynamics of Cryptosporidium spp. and Giardia spp. infections in naturally infected rodent populations. | Prevalence and abundance of Cryptosporidium spp. and Giardia spp. infections were studied over the 8-year period in 3 species of rodents in N.E. Poland (bank vole Myodes glareolus-1523; yellow-necked mouse Apodemus flavicollis- 638; common vole Microtus arvalis- 419). Prevalence was 53.8, 28.1 and 62.3% respectively for Cryptosporidium spp. and 58.3, 24.4 and 74.2% respectively for Giardia spp. Prevalence and abundance of infection varied markedly across 8 years of the study with 1998 and 2002 being years of higher prevalence and abundance, following changes in the densities of host species. The distribution of intestinal protozoa in forest rodents did not vary in the 3 isolated sites during the 4-year study. In the case of Cryptosporidium, fewer older animals carried infection and infections of the oldest bank and common voles were relatively milder. In the case of Giardia in yellow-necked mice, infections were more common in older age classes (2 and 3). The two species showed significant co-occurrence and in animals carrying both species there was a strong significant positive correlation between abundance of infection with each. These data are discussed in relation to the parasite genotypes identified in this region and in respect of the role of various ecological factors in shaping of intestinal protozoa communities. | 18,992,178 |
A population of serum deprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells. | The bone marrow represents an easy accessible source of adult stem cells suitable for various cell based therapies. Several studies in recent years suggested the existence of pluripotent stem cells within bone marrow stem cells (BMSC) expressing marker proteins of both embryonic and tissue committed stem cells. These subpopulations were referred to as MAPC, MIAMI and VSEL-cells. Here we describe SD-BMSC (serumdeprivation-induced BMSC) which are induced as a distinct subpopulation after complete serumdeprivation. SD-BMSC are generated from small-sized nestin-positive BMSC (S-BMSC) organized as round-shaped cells in the top layer of BMSC-cultures. The generation of SD-BMSC is caused by a selective proliferation of S-BMSC and accompanied by changes in both morphology and gene expression. SD-BMSC up-regulate not only markers typical for neural stem cells like nestin and GFAP, but also proteins characteristic for embryonic cells like Oct4 and SOX2. We hypothesize, that SD-BMSC like MAPC, MIAMI and VSEL-cells represent derivatives from a single pluripotent stem cell fraction within BMSC exhibiting characteristics of embryonic and tissue committed stem cells. The complete removal of serum might offer a simple way to specifically enrich this fraction of pluripotent embryonic like stem cells in BMSC cultures. | 18,992,240 |
Acute internalization of gap junctions in vascular endothelial cells in response to inflammatory mediator-induced G-protein coupled receptor activation. | During the inflammatory response, activation of G-protein coupled receptors (GPCRs) by inflammatory mediators rapidly leads to inhibition of gap junction intercellular communication (GJIC); however, the steps that lead to this inhibition are not known. Combining high-resolution fluorescence microscopy and functional assays, we found that activation of the GPCRs PAR-1 and ET(A/B) by their natural inflammatory mediator agonists, thrombin and endothelin-1, resulted in rapid and acute internalization of gap junctions (GJs) that coincided with the inhibition of GJIC followed by increased vascular permeability. The endocytosis protein clathrin and the scaffold protein ZO-1 appeared to be involved in GJ internalization, and ZO-1 was partially displaced from GJs during the internalization process. These findings demonstrate that GJ internalization is an efficient mechanism for modulating GJIC in inflammatory response. | 18,992,245 |
Automated 5-D analysis of cell migration and interaction in the thymic cortex from time-lapse sequences of 3-D multi-channel multi-photon images. | This paper presents automated methods to quantify dynamic phenomena such as cell-cell interactions and cell migration patterns from time-lapse series of multi-channel three-dimensional image stacks of living specimens. Various 5-dimensional (x, y, z, t, lambda) images containing dendritic cells (DC), and T-cells or thymocytes in the developing mouse thymic cortex and lymph node were acquired by two-photon laser scanning microscopy (TPLSM). The cells were delineated automatically using a mean-shift clustering algorithm. This enables morphological measurements to be computed. A robust multiple-hypothesis tracking algorithm was used to track thymocytes (the DC were stationary). The tracking data enable dynamic measurements to be computed, including migratory patterns of thymocytes, and duration of thymocyte-DC contacts. Software was developed for efficient inspection, corrective editing, and validation of the automated analysis results. Our software-generated results agreed with manually generated measurements to within 8%. | 18,992,251 |
Crystal structure of the resuscitation-promoting factor (DeltaDUF)RpfB from M. tuberculosis. | Mycobacterium tuberculosis is able to establish a non-replicating state and survive in an intracellular habitat for years. Resuscitation of dormant M. tuberculosis bacteria is promoted by resuscitation-promoting factors (Rpfs), which are secreted from slowly replicating bacteria close to dormant bacteria. Here we report the crystal structure of a truncated form of RpfB (residues 194-362), the sole indispensable Rpf of the five Rpfs encoded in this bacterium genome. The structure, denoted as (DeltaDUF)RpfB, exhibits a comma-like shape formed by a lysozyme-like globular catalytic domain and an elongated G5 domain, which is widespread among cell surface binding proteins. The G5 domain, whose structure was previously uncharacterised, presents some peculiar features. The basic structural motif of this domain, which represents the tail of the comma-like structure, is a novel super-secondary-structure element, made of two beta-sheets interconnected by a pseudo-triple helix. This intricate organisation leads to the exposure of several backbone hydrogen-bond donors/acceptors. Mutagenesis analyses and solution studies indicate that this protein construct as well as the full-length form are elongated monomeric proteins. Although (DeltaDUF)RpfB does not self-associate, the exposure of structural elements (backbone H-bond donors/acceptors and hydrophobic side chains) that are usually buried in globular proteins is typically associated with adhesive properties. This suggests that the RpfB G5 domain has a cell-wall adhesive function, which allows the catalytic domain to be properly oriented for the cleavage reaction. Interestingly, sequence comparisons indicate that these structural features are also shared by G5 domains involved in biofilm formation. | 18,992,255 |
Crystallographic analysis of a sex-specific enhancer element: sequence-dependent DNA structure, hydration, and dynamics. | The crystal structure of a sex-specific enhancer element is described at a resolution of 1.6 A. This 16-bp site, designated Dsx(A), functions in the regulation of a genetic switch between male and female patterns of gene expression in Drosophila melanogaster. Related sites are broadly conserved in metazoans, including in the human genome. This enhancer element is unusually rich in general regulatory sequences related to DNA recognition by multiple classes of eukaryotic transcription factors, including the DM motifs, homeodomain, and high mobility group box. Whereas free DNA is often crystallized as an A-form double helix, Dsx(A) was crystallized as B-DNA and thus provides a model for the prebound conformation of diverse regulatory DNA complexes. Sequence-dependent conformational properties that extend features of shorter B-DNA fragments with respect to double helical parameters, groove widths, hydration, and binding of divalent metal ions are observed. The structure also exhibits a sequence-dependent pattern of isotropic thermal B-factors, suggesting possible variation in the local flexibility of the DNA backbone. Such fluctuations are in accord with structural variability observed in prior B-DNA structures. We speculate that sites of intrinsic flexibility within a DNA control element provide hinges for its protein-directed reorganization in a transcriptional preinitiation complex. | 18,992,257 |
Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways. | Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes to explore associations with microsatellite instability (MSI), CpG Island methylator phenotype (CIMP), mutations of p53 in exons 5 through 8, and mutations in codons 12 and 13 of Ki-ras. Insulin-related genes were associated with CIMP-positive and MSI tumors, with the strongest associations among aspirin users. The Fok1 vitamin D receptor (VDR) polymorphism was associated with CIMP-positive/Ki-ras-mutated tumors; the Poly A and CDX2 VDR polymorphisms were associated only with Ki-ras-mutated tumors. NAT2 was associated with CIMP-positive/Ki-ras-mutated tumors but not with MSI tumors. The TCF7L2 rs7903146 polymorphism was associated with p53 mutated tumors. Most associations varied by recent aspirin/NSAID use: IL6 rs1800796 and rs1800795 polymorphisms were associated inversely with tumor mutations in the presence of aspirin/NSAIDs; POMC significantly reduced risk of Ki-ras-mutated tumors when aspirin/NSAIDs were not used; the TCF7L2 rs7903146 was associated with reduced risk of Ki-ras-mutated tumors in the presence of aspirin and increased risk in the absence of aspirin. These data, although exploratory, identify specific tumor subsets that may be associated with specific exposures/polymorphism combinations. The important modifying effects of aspirin/NSAIDs on associations with genetic polymorphisms reinforce the underlying role of inflammation in the etiology of colon cancer. | 18,992,263 |
Development of an asymmetric PCR-ELISA typing method for citrus tristeza virus based on the coat protein gene. | The coat protein gene of isolates of citrus tristeza virus (CTV) from 20 citrus-producing regions around the world was amplified by RT-PCR, TA cloned, and characterized by SSCP. Haplotypes that produced different patterns within each geographic region were sequenced and a database of 153 accessions of CTV was assembled. Phylogenetic analysis revealed the existence of seven well-defined clusters (Coefficient of differentiation 0.78). An asymmetric PCR-ELISA typing (APET) assay was developed in the frame of this clustering pattern using a set of eight hybridisation probes. The membership of any unknown haplotype is determined by comparing its pattern of reaction against the whole set of probes and not, as previously done in hybridisation assays, in an all-or-nothing basis. Interpretation of the results is objective and done through a visual basic application that compares the rates of hydrolysis of the ELISA substrate of an assayed isolate to a matrix of rates of hydrolysis obtained from standard haplotypes. This assay was validated and showed a better ability to resolve haplotypes than other assays to which it was compared experimentally. It may be automated to the same extent as any ELISA. | 18,992,281 |
Stimulus intensity dependence of cerebral blood volume changes in left frontal lobe by low-frequency rTMS to right frontal lobe: A near-infrared spectroscopy study. | Repetitive transcranial magnetic stimulation (rTMS) has recently been widely employed for the investigation of brain function and treatment of psychiatric and neurological disorders. Although high and low stimulation frequencies are assumed to activate and deactivate brain function, respectively, the optimal parameters of rTMS for treatment of depression have been determined only on the basis of their clinical efficacy. In this study, we administered a 60-s low-frequency rTMS of three grades low intensities over the right dorsolateral prefrontal cortex (DLPFC) in 10 healthy volunteers, and monitored functional changes of the contralateral DLPFC by near-infrared spectroscopy (NIRS) during and immediately after rTMS. Obtained results demonstrated significant [oxy-Hb] decreases during rTMS, and significant differences in the time courses of [oxy-Hb] changes among three stimulus intensities, that is, [oxy-Hb] decreases were most prominent during the latter half of the stimulation and the first 30s of poststimulation only at 15mm condition (58% intensity). These results suggest that monitoring of brain functional changes due to rTMS using NIRS is useful for elucidating the brain mechanisms underlying the clinical effects of rTMS, and the effects of rTMS over contralateral DLPFC are obtained if the stimulus intensities are more than one-half of the motor thresholds. | 18,992,287 |
Lipid compounds of the umbilical cord vein and their alterations in preeclampsia. | The lipid composition of vascular walls changes during development, ageing and pathological processes. Preeclampsia is the most common pregnancy-associated pathological syndrome. It is accompanied by significant remodelling of the extracellular matrix, both in the umbilical cord vessels and in the surrounding Wharton's jelly. Lipids of the umbilical cord have not been extensively studied. Here we evaluate the lipid composition of the umbilical cord vein and its alteration in preeclampsia. Thin layer chromatography and high-performance liquid chromatography were employed for these analyses. It was found that the umbilical cord vein wall, as with most human tissues, contains free fatty acids, mono-, di- and triacylglycerols, free cholesterol and its esters. The characteristic feature is the presence of high amounts of monounsaturated fatty acids, mainly myristoleic acid (C14:1) and oleic acid (C18:1), and polyunsaturated fatty acids, including eicosapentaenoic acid (C20:5) and docosahexaenoic acid (C22:6), which are rather minor lipid components of most human tissues. They exist both in a free form and in a form of acylglycerols and cholesterol esters. Preeclampsia is associated with an increase in the accumulation of free fatty acids, acylglycerols and cholesterol esters in the umbilical cord vein wall, with a proportional reduction in unsaturated fatty acid contents in all the investigated lipid fractions. Total amount of myristoleate was similar to control values. It is suggested that stimulation of lipolysis in maternal tissues increases supply of free fatty acids to foetal blood and promotes the accumulation fatty acids and their esters in some foetal vascular walls. | 18,992,302 |
In vitro and in vivo characteristics of prochlorperazine oral disintegrating film. | Oral disintegrating film containing prochlorperazine, a dopamine D(2) receptor antagonist with anti-emetic property, was newly developed using microcrystalline cellulose, polyethlene glycol and hydroxypropylmethyl cellulose as the base materials. The uniformity of dosage units of the preparation was acceptable according to the criteria of JP15 or USP27. The film showed an excellent stability at least for 8 weeks when stored at 40 degrees C and 75% in humidity. The dissolution test revealed a rapid disintegration property, in which most of prochlorperazine dissolved within 2 min after insertion into the medium. Subsequently, rats were used to compare pharmacokinetic properties of the film preparation applied topically into the oral cavity with those of oral administration of prochlorperazine solution. None of the parameters, including T(max), C(max), area under curves, clearance and steady-state distribution volume was significantly different between oral disintegrating film and oral solution. These findings suggest that the present prochlorperazine-containing oral film is potentially useful to control emesis induced by anti-cancer agents or opioid analgesics in patients who limit the oral intake. | 18,992,311 |
Imaging neurodegeneration in Parkinson's disease. | Neuroimaging techniques have evolved over the past several years giving us unprecedented information about the degenerative process in Parkinson's disease (PD) and other movement disorders. Functional imaging approaches such as positron emission tomography (PET) and single photon emission computerised tomography (SPECT) have been successfully employed to detect dopaminergic dysfunction in PD, even while at a preclinical stage, and to demonstrate the effects of therapies on function of intact dopaminergic neurons within the affected striatum. PET and SPECT can also monitor PD progression as reflected by changes in brain levodopa and glucose metabolism and dopamine transporter binding. Structural imaging approaches include magnetic resonance imaging (MRI) and transcranial sonography (TCS). Recent advances in voxel-based morphometry and diffusion-weighted MRI have provided exciting potential applications for the differential diagnosis of parkinsonian syndromes. Substantia nigra hyperechogenicity, detected with TCS, may provide a marker of susceptibility to PD, probably reflecting disturbances of iron metabolism, but does not appear to correlate well with disease severity or change with disease progression. In the future novel radiotracers may help us assess the involvement of non-dopaminergic brain pathways in the pathology of both motor and non-motor complications in PD. | 18,992,326 |
Alternative splicing and disease. | Almost all protein-coding genes are spliced and their majority is alternatively spliced. Alternative splicing is a key element in eukaryotic gene expression that increases the coding capacity of the human genome and an increasing number of examples illustrates that the selection of wrong splice sites causes human disease. A fine-tuned balance of factors regulates splice site selection. Here, we discuss well-studied examples that show how a disturbance of this balance can cause human disease. The rapidly emerging knowledge of splicing regulation now allows the development of treatment options. | 18,992,329 |
Sexual and seasonal plasticity in the emission of social electric signals. Behavioral approach and neural bases. | Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in addition to locomotor displays. Gymnotiformes can modulate the EOD rate to produce signals that participate in different behaviors. We studied the reproductive behavior of Brachyhypopomus pinnicaudatus both in the wild and laboratory settings. During the breeding season, fish produce sexually dimorphic social electric signals (SES): males emit three types of chirps (distinguished by their duration and internal structure), and accelerations, whereas females interrupt their EOD. Since these SES imply EOD frequency modulations, the pacemaker nucleus (PN) is involved in their generation and constitutes the main target organ to explore seasonal and sexual plasticity of the CNS. The PN has two types of neurons, pacemakers and relays, which receive modulatory inputs from pre-pacemaker structures. These neurons show an anisotropic rostro-caudal and dorso-ventral distribution that is paralleled by different field potential waveforms in distinct portions of the PN. In vivo glutamate injections in different areas of the PN provoke different kinds of EOD rate modulations. Ventral injections produce chirp-like responses in breeding males and EOD interruptions in breeding females, whereas dorsal injections provoke EOD frequency rises in both sexes. In the non-breeding season, males and females respond with interruptions when stimulated ventrally and frequency rises when injected dorsally. Our results show that changes of glutamate effects in the PN could explain the seasonal and sexual differences in the generation of SES. By means of behavioral recordings both in the wild and in laboratory settings, and by electrophysiological and pharmacological experiments, we have identified sexual and seasonal plasticity of the CNS and explored its underlying mechanisms. | 18,992,332 |
Altered pharmacology and GABA-A receptor subunit expression in dorsal midline thalamic neurons in limbic epilepsy. | The mediodorsal (MD) and paraventricular (PV) thalamic nuclei play a significant role in limbic epilepsy, and previous reports have shown changes in GABA-A receptor (GABAAR) mediated synaptic function. In this study, we examined changes in the pharmacology of GABAergic drugs and the expression of the GABAAR subunits in the MD and PV neurons in epilepsy. We observed nucleus specific changes in the sensitivity of sIPSCs to zolpidem and phenobarbital in MD and PV neurons from epileptic animals. In contrast, the magnitude of change in electrically evoked response (eIPSC) to zolpidem and phenobarbital were uniformly diminished in both MD and PV neurons in epilepsy. Immunohistochemical studies revealed that in epilepsy, there was a reduction in GAD65 expression and NeuN positive neurons in the MD neurons. Also, there was a decrease in immunoreactivity of the alpha1 and beta2/3 subunit of GABAARs, but not the gamma2 of the GABAAR in both MD and PV in epilepsy. These findings demonstrate significant alterations in the pharmacology of GABA and GABAARs in a key region for seizure generation, which may have implications for the physiology and pharmacology of limbic epilepsy. | 18,992,345 |
Cytolocalization of the class V chitin synthase in the yeast, hyphal and sclerotic morphotypes of Wangiella (Exophiala) dermatitidis. | Wangiella (Exophiala) dermatitidis is a polymorphic fungus that produces polarized yeast and hyphae, as well as a number of non-polarized sclerotic morphotypes. The phenotypic malleability of this agent of human phaeohyphomycosis allows detailed study of its biology, virulence and the regulatory mechanisms responsible for the transitions among the morphotypes. Our prior studies have demonstrated the existence of seven chitin synthase structural genes in W. dermatitidis, each of which encodes an isoenzyme of a different class. Among them, the class V chitin synthase (WdChs5p) is most unique in terms of protein structure, because it has an N-terminal myosin motor-like domain with a P-loop (MMD) fused to its C-terminal chitin synthase catalytic domain (CSCD). However, the exact role played by WdChs5p in the different morphotypes remains undefined beyond the knowledge that it is the only single chitin synthase required for sustained cell growth at 37 degrees C and consequently virulence. This report describes the expression in Escherichia coli of a 12kDa polypeptide (WdMyo12p) of WdChs5p, which was used to raise in rabbits a polyclonal antibody that recognized exclusively its MMD region. Results from the use of the antibody in immunocytolocalization studies supported our previous findings that WdChs5p is critically important at infection temperatures for maintaining the cell wall integrity of developing yeast buds, elongating tips of hyphae, and random sites of expansion in sclerotic forms. The results also suggested that WdChs5p localizes to the regions of cell wall growth in an actin-dependent fashion. | 18,992,354 |
Pre-B cell colony-enhancing factor in lower vertebrates: first evidence of this cytokine being involved in antioxidant activity by reconstruction of a novel NAD salvage pathway in E. coli. | The pre-B cell colony-enhancing factor identified in mammals is an important cytokine involved in multiple functions, such as immunoregulation, cellular proliferation and differentiation. However, little is known about its existence and function in lower vertebrates; therefore, we investigated the characterization, expression and especially the biofunction of this factor in Tetraodon nigroviridis, a model organism of lower vertebrates. We focus on the question of whether the pre-B cell colony-enhancing factor of lower vertebrates contributes to the NAD mediated antioxidant activity by its involvement in the biosynthesis of NAD through pyridine nucleotide cycles. Experimental data demonstrated that by transforming fish pre-B cell colony-enhancing factor into Escherichia coli cells, the amounts of NAD and NADP significantly increased, and cellular antioxidant activity greatly improved. This is the first report about vertebrate pre-B cell colony-enhancing factor acting as a nicotinamide phosphoribosyltransferase to reconstruct a pyridine nucleotide cycle III pathway in E. coli and playing an important role in antioxidant stress by up-regulation of NAD biosynthesis. We hope that our observations may enrich the study of pre-B cell colony-enhancing factor, and contribute to a better understanding of the molecular and functional evolution of the pre-B cell colony-enhancing factor family in both lower vertebrates and mammals as a whole. | 18,992,361 |
Deletion 2p25.2: a cryptic chromosome abnormality in a patient with autism and mental retardation detected using aCGH. | We describe a 7-year-old patient with autism, moderate mental retardation, secondary microcephaly, agenesis of right optic nerve, and dysmorphic features carrying a de novo cryptic deletion of chromosome 2p25.2, detected by aCGH. Pure monosomies of 2p are very rare, and are usually observed as part of more complex aberrations involving other chromosomes. To the best of our knowledge, this is the first case presenting with a severe clinical phenotype and a de novo pure deletion of 2p25.2. The phenotypic effects of this rearrangement and the role of SOX11 gene, removed in our case, are herein discussed. | 18,992,374 |
Funding of drugs: do vaccines warrant a different approach? | Vaccines have features that require special consideration when assessing their cost-effectiveness. These features are related to herd immunity, quality-of-life losses in young children, parental care and work loss, time preference, uncertainty, eradication, macroeconomics, and tiered pricing. Advisory committees on public funding for vaccines, or for pharmaceuticals in general, should be knowledgable about these special features. We discuss key issues and difficulties in decision making for vaccines against rotavirus, human papillomavirus, varicella-zoster virus, influenza virus, and Streptococcus pneumoniae. We argue that guidelines for economic evaluation should be reconsidered generally to recommend (1) modelling options for the assessment of interventions against infectious diseases; (2) a wider perspective to account for impacts on third parties, if relevant; (3) a wider scope of costs than health-care system costs alone, if appropriate; and (4) alternative discounting techniques to explore social time preference over long periods. | 18,992,409 |
Carotid artery entrapment by the hyoid bone. | We report a patient with a transient ischemic attack presumably caused by an entrapment of the internal carotid artery by the hyoid bone and without a significant carotid artery stenosis. The patient was operated on, with a release of the right internal and external carotid artery and resection of the right greater cornu of the hyoid bone. One year after treatment, the patient has not experienced any further neurologic symptoms, and a color duplex scan showed no stenosis of the right carotid artery. The hyoid bone is a potential cause of damage to the carotid vessels, depending on the individual's anatomy. Provocative maneuvers can be performed in patients with cerebrovascular symptoms who are not demonstrated to have significant anatomic stenosis with carotid imaging. | 18,992,420 |
Surgical management of renal tumors: a historical perspective. | The modern era of renal surgery began on August 2, 1869 when the first planned nephrectomy on a living human being was performed. Eighteen years later in 1887, the first partial nephrectomy to remove a renal tumor was performed. Both total and partial nephrectomy have become the hallmark surgical procedures used today to treat renal tumors, and their conception and evolution represent two of the most important advances in medicine and surgery. Surgery for kidney cancer continues to evolve. This article traces the history of surgical management for renal tumors. | 18,992,608 |
Predictors of smoking relapse in women with cardiovascular disease in a 30-month study: extended analysis. | To identify predictors of long-term cessation after intervention for woman hospitalized with cardiovascular diseases (CVD). A randomized clinical trial (RCT) with a 30-month follow-up was conducted, recruiting 277 woman smokers with CVD from 10 hospitals. The intervention consisted of inpatient and outpatient counseling on smoking cessation and pharmacological protocol. Psychophysiological factors and time since quitting associated with relapse in the literature were assessed in our prediction model. The nine independent variables for smoking relapse included time since quitting, group assignment, the interaction between time and group assignment, serious quit attempts and five and psychophysiological factors. Lower self-efficacy at baseline was a significant predictor of relapse (OR = 0.98, 95%CI = 0.97,0.99). Another predictor was the interaction between time and group assignment and the finding showed that for the usual care group, increase in time since quitting provided a significant protective factor (OR = 0.69, 95%CI = 0.60,0.79). Cessation programs should include content on self-efficacy to help prevent relapse. The interaction between time and group warrants further investigation for its prediction for relapse. | 18,992,629 |
Embryonal rhabdomyosarcoma with a novel t(2;6)(p23;p21.1). | Chromosomal translocations are infrequently encountered in embryonal rhabdomyosarcoma (E-RMS). Here, we present a case of an infant with a chest wall E-RMS in which t(2;6)(p23;p21.1) was detected. Despite the involvement of the 2p23 locus in the translocation, the tumor did not express ALK. The t(2;6)(p23;p21.1) is a novel finding in E-RMS that may provide insight into the pathogenesis of this relatively frequent childhood tumor. | 18,992,640 |
MLL rearrangement with t(6;11)(q15;q23) as a sole abnormality in a patient with de novo acute myeloid leukemia: conventional cytogenetics, FISH, and multicolor FISH analyses for detection of rare MLL-related chromosome abnormalities. | We report a rare case of acute myeloid leukemia (AML) with t(6;11)(q15;q23) in a 50-year-old female showing a poor prognosis. Bone marrow biopsy revealed markedly hypercellular marrow with infiltrates of myeloblasts, consistent with AML-M2 morphology. The karyotype of this patient was 46,XX,t(6;11)(q15;q23) in all analyzed cells, and the results of fluorescence in situ hybridization (FISH) and multi-color FISH analysis confirmed this unique MLL rearrangement as a sole abnormality. To our knowledge, t(6;11)(q13 approximately q15;q23) is the most rare type of MLL rearrangement involving the long arm of chromosome 6. Only two cases with t(6;11)(q13;q23) and three cases with t(6;11)(q15;q23) have been reported, but detailed clinical or laboratory data were not available. From this report, it is apparent that in a cytogenetic laboratory, the accurate detection of a rare type of MLL rearrangement is very important in the differential diagnosis, prompt treatment, and prediction of prognosis of leukemias. | 18,992,643 |
Soluble and membranous vascular endothelial growth factor receptor-1 in pregnancies complicated by pre-eclampsia. | Vascular endothelial growth factor receptor-1 (VEGFR-1) is essential for the normal development and function of the placenta. Defective placental vasculogenesis and trophoblast function may lead to pre-eclampsia, a pregnancy-specific syndrome of hypertension and proteinuria. In order to study the association of VEGFR-1 with the development of pre-eclampsia, a cross-sectional study was carried out to evaluate the concentration of soluble VEGFR-1 (sVEGFR-1) in 360 serum samples and to analyze the expression of membranous VEGFR-1 in 40 placental samples of normal and pre-eclamptic pregnant women. Serum and placental samples at different gestational ages were collected from the Department of Obstetrics and Gynaecology, VMMC and Safdarjang Hospital, New Delhi. The serum levels of sVEGFR-1 and the expression of membranous VEGFR-1 were estimated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The serum levels of sVEGFR-1 were seen to be positively increased (p=0.0001) in patients with pre-eclampsia at different gestational intervals as compared to the healthy pregnant women they were matched with. However, receiver operating characteristic (ROC) curve analysis showed a higher sensitivity (89.17%) and specificity (90.0%) in early onset (< or =34 weeks) in contrast with the late-onset (>34 weeks) pre-eclamptic group. Also, significant up-regulation of membranous VEGFR-1 immunoreactivity was observed in all placental cells (syncytiotrophoblast, cytotrophoblast, endothelial cells and Hofbauer cells) of pre-eclamptic groups in both < or =34 weeks (p=0.0001) and >34 weeks (p=0.0001) as compared to the normal group. Elevated sVEGFR-1 serum levels and up-regulated membranous VEGFR-1 expression in placenta denote abnormality in VEGF-mediated function in all placental cells, and thus may contribute to etiopathogenesis of pre-eclampsia. Nevertheless, this study also shows the possible diagnostic utility of sVEGFR-1 as a sensitive and specific biomarker for the early onset (< or =34 weeks) of pre-eclampsia. | 18,992,679 |
An historical perspective of early Italian air medical transport. | The early times of aviation medicine were dominated by military actions and needs. This article describes the pioneering era of Italian air medical transport during the period between World War I and early World War II. | 18,992,688 |
Quality improvement in long term care: the psychotropic assessment tool (PAT). | There are already a substantial number of individuals with dementia in long-term care. Many nursing home patients have difficult behaviors and are currently managed with psychotropic medications. Medications for behavior need to be titrated and monitored over time for efficacy and safety, and subsequently tapered if ineffective. Some of these medications are not without risk, and that risk-benefit ratio should be discussed and documented with the family. Currently, we are not aware of any quality improvement process that has been developed in long-term care to address these issues. To describe the process of a novel quality improvement intervention that was designed to improve documentation in the medical record and interdisciplinary communication of the usefulness and possible side effects of psychotropic agents used in the management of difficult behaviors for dementia. Retrospective review of the chart and quality improvement records in a long-term care facility. An academic long-term care facility that specializes in dementia care in St. Louis, MO. The quality improvement team created a process and a form named the Psychotropic Assessment Tool (PAT) to document current behavioral symptoms of the residents; determine whether the resident was on psychotropic agents; identify whether agents had been initiated, titrated, and/or tapered if appropriate; and whether there were any side effects related to the behavioral medications. A letter was created and provided to the surrogate decision maker that described the risk-benefit ratio of the use of antipsychotic agents when these drugs were prescribed. Recommendations from the quality improvement team were provided to the primary care physician. After 1 year of this process, we reviewed the medical charts and quality improvement PAT forms of all residents. We documented the use of psychotropic agents before and after initiating the PAT process, the presence of current behavioral symptoms, the presence of possible side effects, and the recommendations of the interdisciplinary team that met after the monthly quality improvement meetings. A total of 110 patients were included in this study, which reviewed psychotropic drug use between July 2005 and July 2006. The mean age of the residents was 83.8 +/- 7.5 years. All residents had a diagnosis of dementia. Mean MMSE score was 13.5 +/- 7.3. The prevalence of potential problems that could have been associated with psychotropic drug use was not insignificant and included falls (45%), weight loss (16%), weight gain (7%), dizziness (9%), and sedation (5%). However, behaviors that might warrant psychotropic drug use were not uncommon and included active depression (12%), anxiety (24%), hallucinations (11%), disruptive behavior (21%) and delusions (21%). The percentage of residents on antipsychotics changed from 26.5% pre-PAT process to 25.2% post-PAT process; those on anxiolytics changed from 6.0% to 4.0%. There was a change in hypnotics from 2.6% to 3.4%. Antidepressant usage remained the same at 55%. The PAT CHAT discussion resulted in recommendation of medication changes in 25% of residents. The initiation of this quality improvement process using the PAT led to improved chart documentation and interdisciplinary communication between the team, primary care physicians, and families. Further studies are needed to determine whether this process can impact use of psychotropic agents, improve quality of life, decrease adverse drug events, and/or reduce medical-legal risk. | 18,992,701 |
Ischemic tolerance following low dose NMDA involves modulation of cellular stress proteins. | Mild NMDA receptor activation is correlated with neuroprotection in models of cerebral ischemia. Neuroprotection with NMDA manifests as a form of ischemic tolerance and involves the induction of cellular stress systems sensitive to disturbances in cellular calcium homeostasis. Unilateral micro-injection of 10, 160 and 320 microM NMDA into the prefrontal cortex of a rat 30 min prior to permanent occlusion of the middle cerebral artery (MCAO) significantly reduced the area of infarct observed after 4 h of ischemia. The highest dose of NMDA (320 microM) prevented the propagation of ischemic damage through a direct toxicity on neuronal tissue adjacent to the injection site as demonstrated in thionin-stained sections. As a result, the degree of ischemia-induced damage was similar to that measured in rats pretreated with the low dose of NMDA (10 microM). Expression of heat shock protein (HSP) 70 and glucose-regulated protein (GRP) 94 in cortical samples taken from the region of infarct following MCAO was significantly reduced in rats pretreated with 10 microM NMDA compared to saline-injected control rats and rats pretreated with higher doses of NMDA. Furthermore, 10 microM NMDA did not appear to influence expression of m-calpain or GRP78, however, higher doses of NMDA did significantly induce expression of both proteins as assessed by Western blotting. In summary, our data demonstrate an in vivo rodent model of ischemic tolerance in which 30 min of neuronal preconditioning with 10 microM NMDA confers protection against a 4 h period of MCAO-induced ischemia. This effect may involve modulation of cellular stress signals, in particular HSP70 and GRP94. | 18,992,720 |
Tie2Cre-mediated inactivation of plexinD1 results in congenital heart, vascular and skeletal defects. | PlexinD1 is a membrane-bound receptor that mediates signals derived from class 3 secreted semaphorins. Although semaphorin signaling in axon guidance in the nervous system has been extensively studied, functions outside the nervous system including important roles in vascular patterning have also been demonstrated. Inactivation of plexinD1 leads to neo-natal lethality, structural defects of the cardiac outflow tract, peripheral vascular abnormalities, and axial skeletal morphogenesis defects. PlexinD1 is expressed by vascular endothelial cells, but additional domains of expression have also been demonstrated including in lymphocytes, osteoblasts, neural crest and the central nervous system. Hence, the cell-type specific functions of plexinD1 have remained unclear. Here, we describe the results of tissue-specific gene inactivation of plexinD1 in Tie2 expressing precursors, which recapitulates the null phenotype with respect to congenital heart, vascular, and skeletal abnormalities resulting in neonatal lethality. Interestingly, these mutants also have myocardial defects not previously reported. In addition, we demonstrate functions for plexinD1 in post-natal retinal vasculogenesis and adult angiogenesis through the use of inducible cre-mediated deletion. These results demonstrate an important role for PlexinD1 in embryonic and adult vasculature. | 18,992,737 |
Role for protein geranylgeranylation in adult T-cell leukemia cell survival. | Adult T-cell leukemia (ATL) is a fatal lymphoproliferative disease that develops in human T-cell leukemia virus type I (HTLV-I)-infected individuals. Despite the accumulating knowledge of the molecular biology of HTLV-I-infected cells, effective therapeutic strategies remain to be established. Recent reports showed that the hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitor statins have anti-proliferative and apoptotic effects on certain tumor cells through inhibition of protein prenylation. Here, we report that statins hinder the survival of ATL cells and induce apoptotic cell death. Inhibition of protein geranylgeranylation is responsible for these effects, since simultaneous treatment with isoprenoid precursors, geranylgeranyl pyrophosphate or farnesyl pyrophosphate, but not a cholesterol precursor squalene, restored the viability of ATL cells. Simvastatin inhibited geranylgeranylation of small GTPases Rab5B and Rac1 in ATL cells, and a geranylgeranyl transferase inhibitor GGTI-298 reduced ATL cell viability more efficiently than a farnesyl transferase inhibitor FTI-277. These results not only unveil an important role for protein geranylgeranylation in ATL cell survival, but also implicate therapeutic potentials of statins in the treatment of ATL. | 18,992,741 |
RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. | IL-17-producing CD4(+) T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)gamma, which regulates Th17 differentiation, in chronic intestinal inflammation. Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)-, IL-17F-, IL-22-, and RORgamma-deficient CD4(+)CD25(-) T cells in RAG1-null mice. Adoptive transfer of IL-17A-, IL-17F-, or IL-22-deficient T lymphocytes into RAG1-null mice caused severe colitis that was indistinguishable from that caused by wild-type cells. In contrast, transfer of RORgamma-null T cells failed to increase mucosal IL-17 cytokine levels and did not induce colitis. Treatment with IL-17A was able to restore colitis after transfer of RORgamma-null T cells, indicating a crucial role for Th17 cells in pathogenesis. Treatment of RAG1 mice that received IL-17F-null (but not wild-type) T cells with a neutralizing anti-IL-17A antibody significantly suppressed disease, indicating redundant biological effects of IL-17A and IL-17F. We have identified a crucial role of RORgamma-expressing Th17 cells in chronic intestinal inflammation. RORgamma controls IL-17A and IL-17F production, and these cytokines have a redundant but highly pathogenic role in gut inflammation. Reagents that target RORgamma or a combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis. | 18,992,745 |
Androgens and bone. | Testosterone is the major gonadal sex steroid produced by the testes in men. Testosterone is also produced in smaller amounts by the ovaries in women. The adrenal glands produce the weaker androgens dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. These androgens collectively affect skeletal homeostasis throughout life in both men and women, particularly at puberty and during adult life. Because testosterone can be metabolized to estradiol by the aromatase enzyme, there has been controversy as to which gonadal sex steroid has the greater skeletal effect. The current evidence suggests that estradiol plays a greater role in maintenance of skeletal health than testosterone, but that androgens also have direct beneficial effects on bone. Supraphysiological levels of testosterone likely have similar effects on bone as lower levels via direct interaction with androgen receptors, as well as effects mediated by estrogen receptors after aromatization to estradiol. Whether high doses of synthetic, non-aromatizable androgens may, in fact, be detrimental to bone due to suppression of endogenous testosterone (and estrogen) levels is a potential concern that warrants further study. | 18,992,761 |
Corticotropin releasing factor influences aggression and monoamines: modulation of attacks and retreats. | Salmonids establish social hierarchies as a result of aggressive social interactions. The establishment of dominant or subordinate status is strongly linked to neuroendocrine responses mediated through the stress axis. In this study, we tested the effects of introcerebroventricular (icv) corticotropin releasing factor (CRF) on the behavioral outcome, plasma cortisol and monoamine function in trout subjected to a socially aggressive encounter. Rainbow trout were treated with an icv injection of artificial cerebrospinal fluid (aCSF), 500 or 2000 ng ovine CRF, or not injected. Fish were allowed to interact with a similarly sized conspecific for 15 min. Following the behavioral interaction, plasma cortisol and central monoamine concentrations were analyzed. Trout treated with CRF were victorious in approximately 66% of the aggressive encounters against aCSF-treated opponents. Trout injected with CRF exhibited a reduction in the total number of attacks and decreased latency to attack. When trout were divided into winners and losers, only victorious CRF-treated fish exhibited a reduced latency to attack and fewer retreats. Social stress increased cortisol levels in both winners and losers of aggressive interaction. This effect was enhanced with the additional stress incurred from icv injection of aCSF. However, icv CRF in addition to social stress decreased plasma cortisol in both winners and losers. While aggression stimulated significant changes in serotonergic and dopaminergic activity, the magnitude and direction were dependent on limbic brain region, CRF dose, and outcome of social aggression. With broad effects on aggressive behavior, anxiety, stress responsiveness, and central monoaminergic activity, CRF plays an important role in modulating the behavioral components of social interaction. | 18,992,791 |
Involvement of cytochrome P450-mediated metabolism in tienilic acid hepatotoxicity in rats. | Tienilic acid is reported to be converted into electrophilic metabolites by cytochrome P450 (CYP) in vitro. In vivo, however, the metabolites have not been detected and their effect on liver function is unknown. We previously demonstrated that tienilic acid decreased the GSH level and upregulated genes responsive to oxidative/electrophilic stresses, such as heme oxygenase-1 (Ho-1), glutamate-cysteine ligase modifier subunit (Gclm) and NAD(P)H dehydrogenase quinone 1 (Nqo1), in rat liver, as well as inducing hepatotoxicity by co-treatment with the glutathione biosynthesis inhibitor l-buthionine-(S,R)-sulfoximine (BSO). In this study, for the first time, we identified a glutathione-tienilic acid adduct, a stable conjugate of putative electrophilic metabolites with glutathione (GSH), in the bile of rats given a single oral dose of tienilic acid (300mg/kg). Furthermore, a tienilic acid-induced decrease in the GSH level and upregulation of Ho-1, Gclm and Nqo1 were completely blocked by pretreatment with the CYP inhibitor 1-aminobenzotriazole (ABT, 66mg/kg, i.p.). The increase in the serum ALT level and hepatocyte necrosis resulting from the combined dosing of BSO and tienilic acid was prevented by ABT, despite a low hepatic GSH level. These findings suggest that the electrophilic metabolites of tienilic acid produced by CYP induce electrophilic/oxidative stresses in the rat liver and this contributes to the hepatotoxicity of tienilic acid under impaired GSH biosynthesis. | 18,992,796 |
Engineering natural products using combinatorial biosynthesis and biocatalysis. | Many biologically active natural products are produced by the host organisms using dedicated biosynthetic pathways. The programming rules of these pathways may be rationally manipulated through combinatorial biosynthesis to produce natural products that contain structural variations or enhanced pharmacological properties. Furthermore, these pathways contain enzymes that can be harvested as powerful biocatalysts for the synthesis of both new drugs and existing blockbuster therapeutics. This review will highlight recent advances in exploring natural product biosynthetic pathways for new compounds, novel enzymes and useful biocatalysts. | 18,992,814 |
CR3 complement receptor: cloning and characterization in rainbow trout. | The beta 2 integrin CR3 is a leukocyte adhesion heterodimeric glycoprotein which functions both as receptor for iC3b and in several cell-cell and cell-substrate adhesion interactions. In order to elucidate the molecular evolution of the CR3 receptor, here we report the cloning and characterization of its beta2 (CD18) and aM (CD11b) subunits in rainbow trout (Oncorhynchus mykiss). The predicted polypeptide sequences of trout CD18 and CD11b-like exhibit 50, 49, or 61% and 25, 25, or 30% identity with human, mouse, and zebrafish orthologs, respectively. The 'domain' architecture of trout CD18 and CD11b-like subunits retains several characteristics of the mammalian ortholog proteins, such as cysteine-rich regions, N-linked glycosylation sites and several proposed domains and signal sequences (von Willebrand factor type A, Integrin alpha, Integrin B tail, EGF, and Transmembrane domain). The tissue expression profiles of trout CR3 subunits diverge from those of mammalian counterparts, showing the kidney as the main source of the trout CD18 and CD11b-like mRNA transcripts. This is the first report of cloning and characterization of the CR3 receptor in low vertebrates. | 18,992,821 |
Plant antigens cross-react with rat polyclonal antibodies against KLH-conjugated peptides. | Keyhole limpet hemocyanin (KLH)-conjugated peptides are routinely used to raise polyclonal antibodies for biochemical or immunolocalization studies. Rats are suitable for producing antisera against plant antigens as they often lack non-specific response towards plant materials. We attempted to obtain rat antisera against peptides derived from several plant proteins. However, most antisera recognized the same background KLH-related plant antigen (KRAP) in Arabidopsis and tobacco. We characterized KRAP with respect to size and cellular localization and examined possible antigen-specific reasons for the failure of most immunizations. We also found no reports of successful use of rat anti-KLH-peptide antibodies in plant studies. We thus believe that the rat-KLH:peptide system is poorly suited for production of antibodies, especially against plant antigens, and should be used with caution, if at all. | 18,992,832 |
Effect of hypoxic treatment on bone marrow cells that are able to migrate to the injured liver. | Restricted numbers and poor regenerative properties limit the use of adult stem cells. We tested the effect of hypoxic treatment as a method by which to increase cell migration. Bone marrow cells (BMCs) were cultured under oxygen saturations of 0.1, 3, and 20% for 24h. After hypoxic treatment, BMCs of apoptotic fraction were decreased. The expression of CXCR4 was noticeably increased in the hypoxia-treated BMCs and their migration in response to SDF-1alpha was enhanced compared with cells cultured under normoxic condition. Hypoxic BMCs had a higher degree of engraftment to the CCl(4)-injured liver than the normoxic cells. Hypoxic treatment of BMCs may have merits in decreasing apoptosis of those cells as well as in enhancing cellular migration to SDF-1alpha, the chemokine which binds to BMCs expressed CXCR4 and to the injured tissue, such as CCl(4) damaged liver. | 18,992,833 |
Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis. | Osteoporosis, a highly heritable disease, is characterized mainly by low bone-mineral density (BMD), poor bone geometry, and/or osteoporotic fractures (OF). Copy-number variation (CNV) has been shown to be associated with complex human diseases. The contribution of CNV to osteoporosis has not been determined yet. We conducted case-control genome-wide CNV analyses, using the Affymetrix 500K Array Set, in 700 elderly Chinese individuals comprising 350 cases with homogeneous hip OF and 350 matched controls. We constructed a genomic map containing 727 CNV regions in Chinese individuals. We found that CNV 4q13.2 was strongly associated with OF (p = 2.0 x 10(-4), Bonferroni-corrected p = 0.02, odds ratio = 1.73). Validation experiments using PCR and electrophoresis, as well as real-time PCR, further identified a deletion variant of UGT2B17 in CNV 4q13.2. Importantly, the association between CNV of UGT2B17 and OF was successfully replicated in an independent Chinese sample containing 399 cases with hip OF and 400 controls. We further examined this CNV's relevance to major risk factors for OF (i.e., hip BMD and femoral-neck bone geometry) in both Chinese (689 subjects) and white (1000 subjects) samples and found consistently significant results (p = 5.0 x 10(-4) -0.021). Because UGT2B17 encodes an enzyme catabolizing steroid hormones, we measured the concentrations of serum testosterone and estradiol for 236 young Chinese males and assessed their UGT2B17 copy number. Subjects without UGT2B17 had significantly higher concentrations of testosterone and estradiol. Our findings suggest the important contribution of CNV of UGT2B17 to the pathogenesis of osteoporosis. | 18,992,858 |
Development and validation of a solid-phase extraction and gas chromatography-tandem mass spectrometry method for the determination of isopropyl-9H-thioxanthen-9-one in carton packaged milk. | A simple and efficient method for the determination of isopropyl-9H-thioxanten-9-one (ITX) in different fat content milk samples and baby milk samples stored in packaged cartons was developed and validated. Samples were extracted using solid-phase extraction (SPE) and analysed by gas chromatography-tandem mass spectrometry operated in selected reaction monitoring mode (SRM). Validation was carried out in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision and trueness. LOD and LOQ values in the low microg/L were achieved, whereas linearity was established within 0.5-500 microg/L range. Good precision was obtained both in terms of intra-day repeatability and inter-day precision on two concentration levels (RSD% lower than 2%). Good percentage recoveries were obtained (92.0-102.0%) even in the presence of high amount of fat. Finally, the developed method was successfully applied to analyse a number of commercial milk samples with different fat content and baby milk samples. | 18,992,884 |
Improved conjugation and purification strategies for the preparation of protein-polysaccharide conjugates. | A glycoconjugate constituted by the Streptococcus pneumoniae serotype 14 capsular polysaccharide (CPS14) and bovine serum albumin (BSA) was prepared, and the unique properties of Sephadex LH-20 were used to separate the conjugate from the unconjugated material. The strength of this approach consists in its capacity to produce pure polysaccharide-protein conjugate in good yield and free from unconjugated material, a common residual contaminant of this type of immunobiologicals. The CPS14-BSA conjugate prepared via an improved 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP)-activation technique was characterized chemically and its immunogenicity was evaluated in mice. The purified conjugate, unlike the corresponding polysaccharide, produced a T-cell-dependent response in this species. | 18,992,885 |
Phase inversion of the Pickering emulsions stabilized by plate-shaped clay particles. | We investigated the phase inversion of Pickering emulsions stabilized by plate-shaped clay particles. Addition of water induced a phase inversion from a water-in-oil (W/O) emulsion to an oil-in-water (O/W) emulsion when the amount of the oil phase exceeded a limiting amount of oil absorption to solid particles. On the other hand, a phase inversion from a powdery state to an O/W emulsion state through an oil-separated state is observed when the amount of an oil phase is less than the limiting amount of the oil absorption. Interestingly, the oil separated is re-dispersed as emulsion droplets into the O/W emulsion phase. This type of phase inversion, which is a feature of the Pickering emulsions stabilized by the clay particles, is caused by a change in the aggregate structures of particles. | 18,992,900 |
Ependymoma of the sella turcica: a variant of pituicytoma. | A broad spectrum of neoplasms affects the sellar region. Among these, gliomas are rare, most being tumors of pituicytes such as granular cell tumor and pituicytoma. Only 4 ependymomas of the human sellar region have been reported to date and all have had classic histologic features. Herein, we describe the clinicopathologic features of a sellar, low-grade ependymoma with unusual histology, but classic ultrastructural features, occurring in an elderly patient and thus expanding the spectrum of reported cases. The literature is reviewed and concepts of histogenesis are explored, particularly an origin in "ependymal pituicytes." The concept that sellar ependymoma is pituicyte-derived is explored. | 18,992,914 |
Removal mechanisms for endocrine disrupting compounds (EDCs) in wastewater treatment - physical means, biodegradation, and chemical advanced oxidation: a review. | Endocrine disrupting compounds (EDCs) are pollutants with estrogenic or androgenic activity at very low concentrations and are emerging as a major concern for water quality. Within the past few decades, more and more target chemicals were monitored as the source of estrogenic or androgenic activity in wastewater, and great endeavors have been done on the removal of EDCs in wastewater. This article reviewed removal of EDCs from three aspects, that is, physical means, biodegradation, and chemical advanced oxidation (CAO). | 18,992,918 |
The dynamics of protein and metal metabolism in acclimated and Cd-exposed freshwater crabs (Potamonautes warreni). | Climatic and man-made impacts induced dynamic molecular responses in the South African freshwater crab, Potamonautes warreni. Adult crabs exhibited MT-like protein, binding Cd (0.02micromolg(-1) wet mass+/-0.02), Cu (0.326micromolg(-1) wet mass+/-0.15), and Zn (0.534micromolg(-1) wet mass+/-0.20). The native protein binding Cd, Cu, and Zn showed a respective molecular mass (M) of 9.10kDa+/-1.74, 8.95kDa+/-1.66, and 9.32kDa+/-0.93. With exposure to 0.2mgCd(2+)l(-1) for up to 21 days in 50% of these crabs approximately 90% of Cd was bound to the MT-like protein component (8.54kDa+/-1.64), coinciding with a Zn-bound MT-like component (8.2kDa+/-1.54). Less than 10% were bound in the high M protein component, suggesting a protective function of the protein. In the remaining crabs metals were bound to protein (6.8kDa) with a predominant Cu-binding component. | 18,992,941 |
Tributyltin-binding protein type 1 has a distinctive lipocalin-like structure and is involved in the excretion of tributyltin in Japanese flounder, Paralichthys olivaceus. | Tributyltin-binding protein type 1 (TBT-bp1) is a newly discovered protein that binds with TBT in the blood of the Japanese flounder, Paralichthys olivaceus. We determined the genomic sequence of TBT-bp1 and found that this protein has a conserved exon-intron structure that is common to the lipocalin protein family. The secondary and tertiary structures of TBT-bp1, predicted from amino acid sequence, included at least two alpha-helices and eight beta-sheets that are conserved in all lipocalins and form a barrel structure that may bind with ligands. Analysis of the gene structure, secondary structure, and tertiary structure demonstrated that TBT-bp1 could be classified as a lipocalin. A homology search revealed the presence of TBT-bp1-like proteins in eight species of teleost. When flounder were injected intraperitoneally with TBT-d27 at 11.6mug/fish, TBT-d27 was detected in the blood and in the skin mucus. The concentration of TBT-d27 in mucus was approximately 1/100 of that in the serum. Western blotting analysis revealed that TBT-bp1 was present in the skin mucus. These results suggest that TBT-bp1 in Japanese flounder binds with TBT and is excreted from the body via the mucus. | 18,992,946 |
Autophagy and aging: keeping that old broom working. | Autophagy, a highly conserved mechanism of quality control inside cells, is essential for the maintenance of cellular homeostasis and for the orchestration of an efficient cellular response to stress. The decrease in autophagic activity observed in almost all cells and tissues as organisms age was proposed to contribute to different aspects of the aging phenotype and to the aggravation of detrimental age-related diseases. The recent advances in our understanding of the molecular mechanisms underlying autophagy and the identification of the subset of genes involved in this process has enabled the use of genetic manipulations to start testing this hypothesis. Here, I review the recent genetic evidence in support of tight connections between autophagy, health span and aging. | 18,992,957 |
Allergic patch test reactions associated with cosmetics: retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2004. | Allergy to cosmetics is common. We sought to characterize patients with positive patch test reactions associated with a cosmetic source, to identify common allergens; and to explore gender and occupational associations. We performed a retrospective, cross-sectional analysis. Of 6621 female and 3440 male patients, 1582 female (23.8%) and 611 of male (17.8%) patients had at least one allergic patch test reaction associated with a cosmetic source. Of "allergic" patients (>1 allergic reaction, n = 6815), females were 1.21 times more likely to have an allergic reaction associated with a cosmetic source than were male patients (p < .0001, 95% confidence interval [CI] 1.12-1.31). Within the "cosmetic allergic" group (n = 2243), head and neck involvement was significantly higher in female than in male patients (49.3% vs 23.7%, p < .0001). One hundred twenty-five patients had occupationally related allergic reactions associated with a cosmetic. This study is limited by its cross-sectional, retrospective design. Of all patients studied, 21.8% had an allergic reaction associated with a cosmetic. Site of dermatitis, cosmetic categories, and specific allergens differed somewhat by gender. | 18,992,965 |
Avoidance response of Enchytraeus albidus in relation to carbendazim ageing. | In this study, avoidance response of Enchytraeus albidus to LUFA 2.2 soil contaminated with pesticide carbendazim was investigated. The aim was to clarify minimal test duration and temporal changes in avoidance response due to contamination ageing. Firstly, the concentration causing 50% avoidance (EC(50)) was determined as 7.6 mg/kg. Then, test duration needed to reach this value (ET(50)=approximately 18 h) was identified. Finally, the capability of E. albidus avoidance test to reflect the changes of pollutant bioavailability was tested. The soil was spiked with carbendazim at the EC(50) concentration 1, 14, or 28 days before the test started and avoidance effects of fresh versus aged contamination were compared. The results indicated that enchytraeids preferred soil contaminated for 28 days prior to assay where carbendazim was probably less bioavailable than in freshly spiked soil. Our results open an interesting research area of potential use of avoidance tests for contaminant bioavailability assessment. | 18,992,976 |
Reliability of pulse palpation by healthcare personnel to diagnose paediatric cardiac arrest. | To determine the reliability of pulse palpation to diagnose paediatric cardiac arrest. With all cardiovascular information obscured, 209 doctors and nurses (rescuers) were requested once each to determine if a pulse was present in 1 of 16 infants and children (average age 1.8 years, range 1 week-13 years) provided with non-pulsatile circulation with veno-arterial extracorporeal membrane oxygenation or left ventricular assistance for cardiac arrest or failure. Rescuers did not know the stage of recovery of the heart and did not if a true pulse was present or absent. Rescuer decisions "pulse absent" or "pulse present" were compared with concurred decisions of investigators and bedside nurse who knew cardiovascular data and had unlimited time to palpate pulses. Rescuer pulse palpation accuracy was 78% (95% CI 70-82), sensitivity 0.86 (95% CI 0.77-0.90) and specificity 0.64 (95% CI 0.53-0.74). When investigators diagnosed cardiac arrest pulse pressure was 6+/-5mmHg (range 0-20) compared with 9+/-8mmHg (range 0-29) with rescuers (p=0.0004). With pulse pressure zero, rescuer accuracy was 89% and sensitivity 0.89. Sixty per cent of rescuers chose a brachial pulse, 33% a femoral pulse with respective accuracies of 78% and 77%, sensitivities 0.86 and 0.85 and specificities 0.67 and 0.56. Pulse palpation is unreliable to diagnose paediatric cardiac arrest. Rescuers misdiagnose on 22% of occasions and which may lead them to withhold external cardiac compression on 14% of occasions when needed and on 36% to give it when not needed. Brachial palpation is slightly more reliable than femoral palpation. | 18,992,985 |
Arsenic, lead and nickel accumulation in Rubus ulmifolius growing in contaminated soil in Portugal. | This work investigates the potential of Rubus ulmifolius, indigenous to a metal contaminated site--Esteiro de Estarreja--for phytoremediation purposes. The site has a long history of metal contamination. The accumulation of lead (Pb), arsenic (As) and nickel (Ni) in different sections--roots, stems and leaves - of the plant was assessed and compared to the levels of those metals in the soil and in the available fraction. The distribution of metals throughout the area was quite heterogeneous, presenting levels of As, Pb and Ni of up to 3078, 1400 and 135 mg kg(-1), respectively, and the metal content in the sections of R. ulmifolius collected in the banks of the stream varied among sites of collection. Levels of metals were higher in the plant roots: As levels (mgkg(-1)) ranged from 277 to 1721 in the roots, 30 to 110 in the stems, and 60 to 265 in the leaves; Pb concentrations (mgkg(-1)) ranged from 248 to 1178 in the roots, 35 to 133 in the stems, and 25 to 149 in the leaves; and Ni (mgkg(-1)) ranged from 48 to 151 in the roots. Significant correlations were found between the total levels of Pb and As in the soil and the levels in the roots of the plant; further correlations between total and available levels in the soil and metals in other plant tissues were generally found as non-significant. According to the metal accumulation patterns of R. ulmifolius, this species seems to be valuable for application in phytostabilisation strategies. | 18,992,988 |
[Lepromatous leprosy revealed by a swollen hands syndrome]. | Osteoarticular pathology in leprosy is common and described at all stages, but rarely as the most evident clinical manifestation. We report a case of borderline lepromatous leprosy with initial and disabling hands edema. The swollen hands syndrome is probably due to chronic Mycobacterium leprae tenosynovitis. | 18,993,001 |
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