title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Environmentally friendly slow release formulations of alachlor based on clay-phosphatidylcholine. | A new clay-liposome complex was developed for reducing leaching of herbicides and contamination of groundwater. The liposomes were composed of the neutral and Environmental Protection Agency approved phospholipid phosphatidylcholine (PC). Adsorption of PC liposomes on the clay mineral montmorillonite could exceed the cation exchange capacity of the clay, and was well simulated by the Langmuir equation. X-ray diffraction results for 6 mM PC and 1.6 g/L clay (3 day incubation) yielded a basal spacing of 7.49 nm, which was interpreted as the formation of a supported planar bilayer on montmorillonite platelets. Fluorescence methods demonstrated structural changes which reflected adsorption of PC followed by loss of vesicle integrity as measured by the penetration of dithionite into the internal monolayer of fluorescently labeled liposomes, resulting in a decrease in fluorescence intensity to 18% of initial after 4 h. Energy transfer was demonstrated after 1 h from labeled liposomes to montmorillonite labeled by an acceptor. The neutral herbicide alachlor adsorbed on the liposome-clay complex, yielding a formulation of up to 40% active ingredient, and 1.6-fold reduction in herbicide release in comparison to the commercial formulation. Hence, the PC-montmorillonite complex can form a basis for environmentally friendly formulations of herbicides, which would yield reduced leaching. | 18,754,508 |
Event related potentials in hypothyroidism. | Central nervous system (CNS) dysfunction is an important consequence of thyroid hormone deficiency Several studies using objective behavioral measures reported that cognition is impaired in patients with hypothyroidism. The aim of the present study is to evaluate objectively the functional changes in the nervous system and possible cognitive effects of hypothyroidism by using event related potentials (ERP) in order to determine the frequencies of these changes in patients with hypothyroidism. Forty-two patients (3 males, 39 females) (mean age: 40 +/- 11) with newly diagnosed primary hypothyroidism were included in the study. In all patients the cause of hypothyroidism were chronic autoimmune thyroiditis. None of them had received thyroid hormone as a replacement therapy. In hypothyroid group both N2 and P300 latencies from FZ, CZ, PZ electrode positions were prolonged relative to controls and the differences were statistically significant; respectively (N200: P < 0.003, 0.003, 0.002--P300: P < 0.008, 0.02, 0.001) N100 and P200latencies from FZ, CZ, PZ electrode positions did not differed significantly from those of normal controls; respectively. (p < 0.140, 0.195, 0.153--p < 0.400, 0.185, 0.766) Latency and amplitudes of P300 did not correlated with FT3, FT4 or neither with TSH values in the patient group. We believe like other's that with the aid of this technique we are able to detect early effect on central information processing compatible with a reduction of processing resources and increased effort necessary for a given task in hypothyroid individuals. | 18,754,529 |
Evaluation of pupil mobility in patients with myasthenia gravis. | The aim of this study is to investigate the effect of Myasthenia Gravis (MG) on the Central Nervous System (CNS) and/or the smooth muscles of the iris through pupillometry. Sixteen recently diagnosed Myasthenic and sixteen non-Myasthenic subjects of matching age and gender underwent a pupillometric study of the effects of single flash stimuli of 24.6 candelas/m2 intensity and 20 msec duration. A significant decrease in Amplitude (p < 0.001), Maximum Constriction Velocity (p < 0.001) and especially Maximum Constriction Acceleration with a perfect discrimination ability (AUC= 1, p < 0.001). was observed in the Myasthenic compared to the non-Myasthenic subjects. In contrast, no significant difference was observed in Baseline Pupil Radius (R1) and 3.5 secs Percentage Recovery-Redilatation (R%) (p = 0.051 and p = 0.517, respectively). Of the parameters that are studied, R1 and R% are governed mainly by the action of the Sympathetic Nervous System (SNS) and the rest by the Parasympathetic Nervous System (ParNS), through Acetylcholine. The analysis of these parameters demonstrates that the SNS remains unaltered while the ParNS may be affected in MG. This post-synaptic cholinergic receptors' deficit may be central, within the CNS, or peripheral, related to the Neuromuscular Junction of the iris' sphincter. | 18,754,530 |
[Modern treatment concepts of anaphylactic reactions]. | Anaphylactic reactions are induced by the liberation of different inflammatory mediators. The symptoms are determined by the type, quantity and relation of these mediators and by the individual predisposition. In general, these symptoms can be detected on the skin, the lungs, the cardiovascular system, and the gastrointestinal tract. The early treatment of circulatory and pulmonary disturbances is a decisive factor for the prognosis of the patient. The severity of symptoms is graded from 1 to 4. An adequate therapy has to be started immediately according to the severity of the symptoms in a step-wise approach. Initially, common procedures like an interruption of the allergen exposition, oxygen supply and intravenous ports are essential. A few substances have been established for a specific drug therapy, such as catecholamines (epinephrine, dopamine, noradrenaline), histamine-antagonists, glucocorticoids, theophyllin and drugs for volume replacement. Intravenous administration of calcium is not recommended. | 18,754,569 |
Multicomponent, one-pot sequential synthesis of 1,3,5- and 1,3,5,5-substituted barbiturates. | Carbodiimides and malonic acid monoethylesters readily react to afford N-acylurea derivatives that could be cyclized in situ by addition of a suitable base. This process represents a general and straightforward one-pot sequential synthesis of 1,3,5-trisubstituted barbiturates in very mild conditions (organic solvent/2 N NaOH aqueous solution, 20 degrees C). Performing the reaction in the presence of an electrophile resulted in the formation of fully substituted (namely, 1,3,5,5-tetrasubstituted) barbiturates through a three-component one-pot sequential process. The latter, however, occurred only with highly reactive electrophiles, such as benzyl and, in some instances, allyl halides. In order to expand the scope of the process, we sought to develop a general method for the C-alkylation of 1,3,5-trisubstituted barbiturates. We found that C-alkylation occurred upon treatment of 1,3,5-trisubstituted barbiturates with an alkyl halide in CH3CN at 120 degrees C in the presence of anhydrous K2CO3 affording the target 1,3,5,5-tetrasubstituted barbiturates in good yields. The multicomponent process was accomplished by combining the three steps in a one-pot sequential fashion, i.e., the condensation of carbodiimides with malonic acid monoethylesters, the cyclization of the resulting N-acylureas, and the C-alkylation of the resulting 1,3,5-substituted barbiturates. A detailed study of the influence of the structure of the reactants on the reaction outcome and mechanism is presented. By selective N'-deprotection of 1,3,5,5-tetrasubstituted barbiturates, the corresponding 1,5,5-trisubstituted barbiturates were also prepared. | 18,754,580 |
Activation of H2 by phosphinoboranes R2PB(C6F5)2. | Phosphinoboranes that combine bulky electron-rich phosphides and electron deficient B(C6F5)2 fragments produce monomeric phosphinoboranes that undergo facile addition of H2 to give the phosphine-borane adducts (R2PH)(HBR'2). This finding in combination with DFT calculations shed light on the uptake of H2 across a group 13-group 15 bond, a critical requirement for the development of recyclable H2 storage materials. | 18,754,584 |
Tailored magnetic nanoparticles for direct and sensitive detection of biomolecules in biological samples. | We developed nanoparticles with tailored magnetic properties for direct and sensitive detection of biomolecules in biological samples in a single step. Thermally blocked nanoparticles obtained by thermal hydrolysis, functionalized with specific ligands, are mixed with sample solutions, and the variation of the magnetic relaxation due to surface binding is used to detect the presence of biomolecules. The binding significantly increases the hydrodynamic volume of nanoparticles, thus changing their Brownian relaxation frequency which is measured by a specifically developed AC susceptometer. The system was tested for the presence of Brucella antibodies, a dangerous pathogen causing brucellosis with severe effects both on humans and animals, in serum samples from infected cows and the surface of the nanoparticles was functionalized with lipopolysaccharides (LPS) from Brucella abortus. The hydrodynamic volume of LPS-functionalized particles increased by 25-35% as a result of the binding of the antibodies, measured by changes in the susceptibility in an alternating magnetic field. The method has shown high sensitivity, with detection limit of 0.05 microg x mL(-1) of antibody in the biological samples without any pretreatment. This magnetic-based assay is very sensitive, cost-efficient, and versatile, giving a direct indication whether the animal is infected or not, making it suitable for point-of-care applications. The functionalization of tailored magnetic nanoparticles can be modified to suit numerous homogeneous assays for a wide range of applications. | 18,754,596 |
Reduction of an eta2-iminoacyl ligand to eta2-iminium enabled by adjacent carbon monoxide ligand replacement with a variable electron donor alkyne ligand in a cationic Tungsten(II) bis(acetylacetonate) complex. | Cationic iminoacyl-carbonyl tungsten complexes of the type [W(CO) (eta (2)-MeNCR)(acac) 2] (+) (acac = acetylacetonate; R = Ph ( 1a), Me ( 1b)) easily undergo thermal substitution of CO with two-electron donors to yield [W(L)(eta (2)-MeNCR)(acac) 2] (+) (L = tert-butylisonitrile [R = Ph ( 2a), Me ( 2b)], 2,6-dimethylphenylisonitrile [R = Me ( 2c)], triphenylphosphine [R = Ph ( 3a), Me ( 3c)], and tricyclohexylphosphine [R = Ph ( 3b)]). Tricyclohexylphosphine complex 3b exhibits rapid, reversible phosphine ligand exchange at room temperature on the NMR time scale. Photolytic replacement of carbon monoxide with either phenylacetylene or 2-butyne occurs efficiently to form [W(eta (2)-alkyne)(eta (2)-MeNCR)(acac) 2] (+) complexes ( 5a- d) with a variable electron donor eta (2)-alkyne paired with the eta (2)-iminoacyl ligand in the W(II) coordination sphere. PMe 3 adds to 1a or 5b to form [W(L)(eta (2)-MeNC(PMe 3)Ph)(acac) 2] (+) [L = CO ( 4), MeCCMe ( 6)] via nucleophilic attack at the iminoacyl carbon. Addition of Na[HB(OMe) 3] to 5b yields W(eta (2)-MeCCMe)(eta (2)-MeNCHPh)(acac) 2, 8, which exhibits alkyne rotation on the NMR time scale. Addition of MeOTf to 8 places a second methyl group on the nitrogen atom to form an unusual cationic eta (2)-iminium complex [W(eta (2)-MeCCMe)(eta (2)-Me 2NCHPh)(acac) 2][OTf] ( 9[OTf], OTf = SO 3CF 3). X-ray structures of 2,6-dimethylphenylisonitrile complex 2c[BAr' 4 ], tricyclohexylphosphine complex 3b[BAr' 4 ], and phenylacetylene complex 5a[BAr' 4 ] confirm replacement of CO by these ligands in the [W(L)(eta (2)-MeNCR)(acac) 2] (+) products. X-ray structures of alkyne-imine complexes 6[BAr' 4 ] and 8 show products resulting from nucleophilic addition at the iminoacyl carbon, and the X-ray structure of 9[BAr' 4 ] reflects methylation at the imine nitrogen to form a rare eta (2)-iminium ligand. | 18,754,617 |
Electrodissolution of inorganic ions/DNA multilayer film for tunable DNA release. | A layer-by-layer film composed of DNA and inorganic zirconium ion (Zr(4+)) was fabricated on the surface of gold thin film, and an electric field triggered disintegration of the multilayer film was studied by using electrochemical surface plasmon resonance (EC-SPR). EC-SPR results demonstrated that the film was disassembled upon the application of an electric field and the disassembly rate varied with the applied potential, leading to the controlled release of DNA. The electrodissolution could be switched off by removing the electric potential and reactivated by reapplying the potential. By incorporating plasmid DNA (pDNA) in to this controlled release system, the multilayer film could sustain the consecutive release of pDNA electrochemically. The released pDNA retained its integrity and transfection activity, and expressed enhanced green fluorescent protein (EGFP) after being transfected into HEK 293 cells. The electrochemical systems, with advantages of miniaturization, surface-tailoring, safety, simplicity, convenience, automation, low-cost, and free of immune reactions, made the electrical route a very attractive gene-delivery alternative. | 18,754,640 |
Coordination-tuned single-molecule-magnet behavior of TbIII-CuII dinuclear systems. | Tb (III)-Cu (II)-based single-molecule magnet (SMM) and non-SMM were synthesized to investigate the relationship between magnetic anisotropy and the symmetry of the ligand field by the reaction of [TbCu( o-vanilate) 2(NO 3) 3] with methoxypropylamine (MeOC 3H 6NH 2, 1) or ethoxyethylamine (EtOC 2H 4NH 2, 2). In both complexes, Tb (III) ions have a bicapped square-antiprism coordination geometry. When the Tb (III) ion is in a less symmetrical ligand field, it has an easy-axis anisotropy and shows SMM behavior, whereas when it is in a more symmetrical environment, it has an easy-plane anisotropy and exhibits non-SMM behavior. | 18,754,656 |
pH-induced conformational change of the influenza M2 protein C-terminal domain. | The M2 protein from influenza A is a pH-activated proton channel that plays an essential role in the viral life cycle and serves as a drug target. Using spin labeling EPR spectroscopy, we studied a 38-residue M2 peptide spanning the transmembrane region and its C-terminal extension. We obtained residue-specific environmental parameters under both high- and low-pH conditions for nine consecutive C-terminal sites. The region forms a membrane surface helix at both high and low pH, although the arrangement of the monomers within the tetramer changes with pH. Both electrophysiology and EPR data point to a critical role for residue Lys 49. | 18,754,675 |
Effects of heavy metals on riverine benthic macroinvertebrate assemblages with reference to potential food availability for drift-feeding fishes. | We examined the influence of heavy metal pollution from an abandoned mine on benthic macroinvertebrates, at population and community levels, and the potential amount of food available for drift-feeding fish in northern Japanese streams. We studied multiple polluted and unpolluted sites with similar longitudinal positions to avoid problems caused by upstream-downstream comparisons. The ranges of zinc, copper, cadmium, and lead concentrations among the study sites were 5 to 812 microg/L, less than 0.12 to 5.2 microg/L, less than 0.0026 to 4.9 microg/L, and 0.1 to 18.6 microg/L, respectively. The abundance of several populations and community metrics showed a significant negative response to heavy metal pollution. Mayfly diversity and abundance was relatively sensitive to heavy metal pollution. In addition, the biomass of groups of macroinvertebrate taxa that are highly available for salmonids were significantly reduced at metal-polluted sites; this decrease in the most highly available group was noticeable (99% at the heavily polluted upper sites and 69% at the moderately polluted lower sites in spring). These results suggest that we should consider the indirect effect of pollution on food availability for the conservation of fish populations that depend on drifting macroinvertebrates. | 18,754,701 |
Novel oncolytic agent GLV-1h68 is effective against malignant pleural mesothelioma. | Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carrying transgenes encoding Renilla luciferase, green fluorescent protein (both inserted at the F14.5L locus), beta-galactosidase (inserted at the J2R locus, which encodes thymidine kinase), and beta-glucuronidase (at the A56R locus, which encodes hemagglutinin). This virus was tested in six human MPM cell lines (MSTO-211H, VAMT, JMN, H-2373, H-2452, and H-2052). GLV-1h68 successfully infected all cell lines. For the most sensitive line, MSTO-211H, expression of green fluorescent protein (GFP) started within 4 hr with increasing intensity over time until nearly 100% of cells expressed GFP at 24 hr. All cell lines were sensitive to killing by GLV-1h68, with the degree of sensitivity predictable by infectivity assay. Even the most resistant cell line exhibited 44 +/- 3.8% cell survival by day 7 when infected at a multiplicity of infection of 1.0. Viral proliferation assays demonstrated 2-to 4-fold logarithmic replication of GLV-1h68 in the cell lines tested. In an orthotopic model, GLV-1h68 effectively prevented development of cachexia and tumor-related morbidity, reduced tumor burden, and cured MPM in both early and late treatment groups. GLV-1h68 was successfully used to treat MPM in vitro and in an orthotopic model (in vivo). These promising results warrant clinical investigation of GLV-1h68 as a novel agent in the treatment of MPM. | 18,754,710 |
Delivery of insulin to the buccal mucosa utilizing the RapidMist system. | The burgeoning number of people with diabetes mellitus is a global problem. Simple but effective treatment with minimal side effects will be required to reduce the risk for macro- and micro-vascular complications. A big part of this goal can be achieved by the ready administration of insulin with or without other medications. The RapidMist drug delivery system places human recombinant insulin in a liquid formulation so as to be delivered to the buccal mucosa with an asthma-like device. As with nitroglycerin, the insulin PK-PD is very fast, thus affording flexibility. Serial data show clinical efficacy in Type 1 and Type 2 diabetes with at least non-inferiority to regular insulin. | 18,754,753 |
The influence of carbon sources on recombinant-human- growth-hormone production by Pichia pastoris is dependent on phenotype: a comparison of Muts and Mut+ strains. | The influence of carbon sources on rhGH (recombinant human growth hormone) production by two Pichia pastoris strains having different methanol utilization phenotypes (P. pastoris-hGH-Mut(+) and P. pastoris-hGH-Mut(s)) was investigated using batch bioreactors. The effect of methanol concentration (C(MeOH)) in defined and complex media, and further glycerol/methanol mixed defined media, was analysed systematically over a wide range. With methanol as the sole carbon source, strain Mut(s) grew only slightly, whereas with Mut(+), a cell concentration (C(X)) of 6.0 g of dry cells/dm(3) was obtained and an rhGH concentration (C(rhGH)) of 0.032 g/dm(3) was produced. In complex medium without glycerol at a C(MeOH) of 2% (v/v), a C(rhGH) of 0.16 g of rhGH/dm(3) was produced by Mut(s), a value 3-fold higher than that produced by Mut(+), despite the fact that the C(X) of Mut(+) (6.1 g/dm(3)) was 2-fold higher than that of Mut(s) (3.0 g/dm(3)). In a glycerol/methanol mixed defined medium, methanol consumption began when glycerol was totally depleted, indicating that glycerol is a repressor of the AOX1 (alcohol oxidase-1 gene) promoter. With strain Mut(s) at a glycerol concentration (C(Gly)) of 30 g/dm(3) and a C(MeOH) of 1% (v/v), the C(rhGH) produced was 0.11 g/dm(3), whereas, with the Mut(+) strain, a C(rhGH) of 0.06 g/dm(3) was obtained at a C(Gly) of 30 g/dm(3) and a C(MeOH) of 4%. As methanol is not consumed by Mut(s) strain effectively and the presence of methanol in the fermentation broth triggers induction of the AOX1 promoter, our results encourage the use of the Mut(s) strain for rhGH production. In addition to rhGH production, the specific cell growth rates, specific methanol and/or glycerol utilization rates and maintenance coefficients in methanol- and glycerol-based defined media were determined. With a methanol-based defined medium and using the Mut(+) strain, a higher specific growth rate (mu) of approx. 0.14 h(-1) was observed during the exponential cell growth phase at a C(MeOH) of <or=2.0%. When glycerol was used as a sole carbon source, both phenotypes showed similar cell-growth and glycerol-utilization rates. The results of the present study should enable one to optimize the expression of other therapeutic proteins by P. pastoris. | 18,754,757 |
Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in Taiwan. | This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case-control study. Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1-6.5, P = 0.02) was associated with female SDICH. This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan. | 18,754,764 |
Altered frontostriatal coupling in pre-manifest Huntington's disease: effects of increasing cognitive load. | Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington's disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals. Sixteen healthy controls and sixteen pre-HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load-dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. In pre-HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre-HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre-HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. These findings suggest that early prefrontal connectivity abnormalities in pre-HD individuals are modulated by cognitive demand. | 18,754,766 |
ATP stimulates MDM2-mediated inhibition of the DNA-binding function of E2F1. | Murine double minute 2 (MDM2) protein exhibits many diverse biochemical functions on the tumour suppressor protein p53, including transcriptional suppression and E3 ubiquitin ligase activity. However, more recent data have shown that MDM2 can exhibit ATP-dependent molecular chaperone activity and directly mediate folding of the p53 tetramer. Analysing the ATP-dependent function of MDM2 will provide novel insights into the evolution and function of the protein. We have established a system to analyse the molecular chaperone function of MDM2 on another of its target proteins, the transcription factor E2F1. In the absence of ATP, MDM2 was able to catalyse inhibition of the DNA-binding function of E2F1. However, the inhibition of E2F1 by MDM2 was stimulated by ATP, and mutation of the ATP-binding domain of MDM2 (K454A) prevented the ATP-stimulated inhibition of E2F1. Further, ATP stabilized the binding of E2F1 to MDM2 using conditions under which ATP destabilized the MDM2:p53 complex. However, the ATP-binding mutant of MDM2 was as active as an E3 ubiquitin ligase on E2F1 and p53, highlighting a specific function for the ATP-binding domain of MDM2 in altering substrate protein folding. Antibodies to three distinct domains of MDM2 neutralized its activity, showing that inhibition of E2F1 is MDM2-dependent and that multiple domains of MDM2 are involved in E2F1 inhibition. Dimethylsulfoxide, which reduces protein unfolding, also prevented E2F1 inhibition by MDM2. These data support a role for the ATP-binding domain in altering the protein-protein interaction function of MDM2. | 18,754,770 |
MicroRNAs--micro in size but macro in function. | MicroRNAs (miRNAs) are endogenous small RNAs that can regulate target mRNAs by binding to their 3'-UTRs. A single miRNA can regulate many mRNA targets, and several miRNAs can regulate a single mRNA. These have been reported to be involved in a variety of functions, including developmental transitions, neuronal patterning, apoptosis, adipogenesis metabolism and hematopoiesis in different organisms. Many oncogenes and tumor suppressor genes are regulated by miRNAs. Studies conducted in the past few years have demonstrated the possible association between miRNAs and several human malignancies and infectious diseases. In this article, we have focused on the mechanism of miRNA biogenesis and the role of miRNAs in human health and disease. | 18,754,771 |
Submembraneous microtubule cytoskeleton: interaction of TRPP2 with the cell cytoskeleton. | TRPP2, also called polycystin-2, the gene product of PKD2, is a membrane protein defective in 10-15% of cases of autosomal dominant polycystic kidney disease. Mutations in PKD2 are also associated with extrarenal disorders, such as hepatic cystogenesis and cardiovascular abnormalities. TRPP2 is a Ca-permeable nonselective cation channel present in the endoplasmic reticulum and plasma membrane, as well as in cilia of renal epithelial and embryonic nodal cells, in which it likely forms part of a flow sensor. Recent studies have identified a number of TRPP2-interacting proteins, of which many are cytoskeletal components. Work from our and other laboratories indicates that cytoskeletal partner proteins seem to play important, albeit highly complex, roles in the regulation of TRPP2 expression, localization and channel function. This minireview covers current knowledge about cytoskeletal interactions with TRPP2, and suggests that mutations in proteins of the TRPP2-cytoskeleton complex may be implicated in the pathogenesis of autosomal dominant polycystic kidney disease. | 18,754,774 |
Submembraneous microtubule cytoskeleton: regulation of microtubule assembly by heterotrimeric Gproteins. | Heterotrimeric Gproteins participate in signal transduction by transferring signals from cell surface receptors to intracellular effector molecules. Gproteins also interact with microtubules and participate in microtubule-dependent centrosome/chromosome movement during cell division, as well as neuronal differentiation. In recent years, significant progress has been made in our understanding of the biochemical/functional interactions between Gprotein subunits (alpha and betagamma) and microtubules, and the molecular details emerging from these studies suggest that alpha and betagamma subunits of Gproteins interact with tubulin/microtubules to regulate the assembly/dynamics of microtubules, providing a novel mechanism for hormone- or neurotransmitter-induced rapid remodeling of cytoskeleton, regulation of the mitotic spindle for centrosome/chromosome movements in cell division, and neuronal differentiation in which structural plasticity mediated by microtubules is important for appropriate synaptic connections and signal transmission. | 18,754,776 |
Mycoplasma penetrans under nutritional stress: influence on lipid and lipoprotein profiles and on the binding to and invasion of HeLa cells. | By serial passages through media containing decreasing concentrations of horse serum, the sterol-requiring Mycoplasma penetrans strain HF-2 was adapted to grow in a serum-free medium supplemented with bovine serum albumin, cholesterol and free fatty acids. Chemical analysis of membrane preparations obtained from the native and adapted strains revealed two major differences. (1) The polar lipid fraction of the native strain contains, in addition to the de novo-synthesized phospholipids, exogenous lipids incorporated unchanged from the growth medium, whereas exogenous lipids were not detected in the adapted strain. (2) Protein analyses of the native and adapted strains showed that upon adaptation, the 42-kDa membrane lipoprotein, one of the two major lipoproteins of this organism, was missing. Studies on the adhesion to, and invasion of HeLa cells by the native and adapted strains revealed that whereas the adherence to HeLa cells of the adapted strain was almost the same as that of the native strain, the invasiveness of the adapted strain into HeLa cells was very low or nonexistent. | 18,754,786 |
Mutation in a gene encoding anti-sigma factor in A. brasilense confers tolerance to elevated temperature, antibacterial peptide and PEG-200 via carotenoid synthesis. | Azospirillum brasilense Sp7 has been shown to overproduce carotenoids if the anti-sigma factor (anti-sigma(E))-encoding gene is inactivated. The anti-sigma mutant (Car-1) of A. brasilense Sp7 was more tolerant to the stresses generated by elevated temperature (40 degrees C), PEG-200 (30 mg mL(-1)) and the antibacterial agent Polymyxin-B (PMB, 25 microg mL(-1)) but not to elevated salinity (15 mg mL(-1)). Inhibition of carotenoid synthesis by diphenylamine inhibited the ability of the mutant to tolerate all the three stresses. Out of the four stress agents, only elevated temperature and salinity induced the rpoE promoter and increased the carotenoid content in Sp7 as well as in the Car-1 mutant. Comparison of the membrane permeability of the parent and the mutant by a PMB-N-phenyl-1-naphthylamine coupled assay showed that the presence of carotenoids in the mutant reduced the permeability of their membranes. Our study indicates that the carotenoid synthesis, which is under the control of extracytoplasmic function sigma factor (sigma(E)) in A. brasilense Sp7, plays a positive role in tolerating elevated temperature, the antibacterial peptide and PEG-200. | 18,754,787 |
Impact of oleic acid (cis-9-octadecenoic acid) on bacterial viability and biofilm production in Staphylococcus aureus. | Staphylococcus aureus is responsible for a broad variety of chronic infections. Most S. aureus clinical isolates show the capacity to adhere to abiotic surfaces and to develop biofilms. Because S. aureus growing in a biofilm is highly refractory to treatment, inhibition of biofilm formation represents a major therapeutic objective. We evaluated the effects of oleic acid on primary adhesion and biofilm production in eight genotypically different S. aureus strains as well as in the biofilm-negative Staphylococcus carnosus strain TM300. Oleic acid inhibited primary adhesion but increased biofilm production in every S. aureus strain tested. Staphylococcus aureus strain UAMS-1 was then selected as a model organism for studying the mechanisms triggered by oleic acid on the formation of a biofilm in vitro. Oleic acid inhibited the primary adhesion of UAMS-1 dose dependently with an IC(50) around 0.016%. The adherent bacterial population decreased proportionally with increasing concentrations of oleic acid whereas an opposite effect was observed on the planktonic population. Overall, the total bacterial counts remained stable. Macroscopic detachments and clumps were visible from the adherent bacterial population. In the presence of oleic acid, the expression of sigB, a gene potentially involved in bacterial survival through an effect on fatty acid composition, was not induced. Our results suggest a natural protective effect of oleic acid against primary adhesion. | 18,754,790 |
Identification and characterization of a Jem1p ortholog of Candida albicans: dissection of Jem1p functions in karyogamy and protein quality control in Saccharomyces cerevisiae. | Jem1p of yeast Saccharomyces cerevisiae is a J-domain containing co-chaperone (J protein) in the endoplasmic reticulum (ER) lumen. Jem1p is required for nuclear fusion during mating (karyogamy) and functions together with another J protein, Scj1p, in protein folding and quality control in the ER as a partner for the ER Hsp70 (BiP/Kar2p). Candida albicans has a gene encoding a homolog of S. cerevisiae Jem1p, CaJem1p. CaJem1p localized in the ER when expressed in S. cerevisiae, and expression of CaJem1p from a single-copy plasmid suppressed the temperature sensitive growth and the ER quality control defect of the jem1Deltascj1Delta mutant, indicating that CaJem1p is functional in S. cerevisiae. However, CaJem1p suppressed the karyogamy defect of the jem1Deltamutant only when it was over-expressed from a multicopy plasmid. Domain-swapping experiments showed that this was due to the difference between the N-terminal domains of ScJem1p and CaJem1p. The N-terminal domain of ScJem1p is essential for its function and interacts with Nep98p, a component of the spindle pole body involved in karyogamy. Since the interaction of CaJem1p with Nep98p is weaker than that of ScJem1p, the Nep98p-ScJem1p interaction is likely important for promoting karyogamy in S. cerevisiae. | 18,754,794 |
The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D-deficient HIV-1-infected patients. | The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients. Twenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D(3) (1,25(OH)2D3), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D(3) [25(OH)D(3)], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks. After 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D3 and 1,25(OH)2D3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides. The effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of > or =2000 IU are necessary to achieve 1,25(OH)2D3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials. | 18,754,805 |
TRP-ML1 functions as a lysosomal NAADP-sensitive Ca2+ release channel in coronary arterial myocytes. | Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent intracellular Ca(2+) signalling second messenger, but the mechanism of NAADP-induced Ca(2+) release is still poorly understood. The present study tested the hypothesis that NAADP induces Ca(2+) release from the lysosomal store via a TRP-ML1 (transient receptor potential-mucolipin 1)-mediated Ca(2+) release channel in coronary arterial myocytes (CAMs). RT-PCR and Western blot analyses demonstrated that TRP-ML1 was present in CAMs, and fluorescence resonance energy transfer (FRET) detection revealed that the TRP-ML1 was closely associated with some lysosomal proteins in these CAMs. ET-1, a well-known NAADP stimulator, was found to induce a local Ca(2+) burst from lysosomes followed by a global Ca(2+) release. This lysosome-associated Ca(2+) release was significantly inhibited in the TRP-ML1 siRNA pre-treated CAMs by 46.8 +/- 12.6% in the local Ca(2+) burst and 73.3 +/- 14.9% in the global Ca(2+) wave. In the reconstituted lysosomal channels from CAMs, NAADP activated Ca(2+) release channels at concentrations of 1-1000 nM, but neither activators (1 microM IP(3), 5 microM Rya) nor blockers (100 microM 2-APB, 50 microM Rya) of sarcoplasmic reticulum (SR) Ca(2+) release channels had effect on the channel activity. Moreover, TRP-ML1 gene silencing reduced this NAADP-sensitive Ca(2+) release channel activity in lysosomes by 71.5 +/- 18.5%. Immunoprecipitation or blockade of TRP-ML1 by anti-TRP-ML1 antibodies almost abolished NAADP-induced activation of lysosomal Ca(2+) channels (to 14.0 +/- 4.4% of control). These results for the first time provide direct evidence that an NAADP-sensitive Ca(2+) release channel is characteristic of TRP-ML1 channels. | 18,754,814 |
Psychometric testing of the SF-36 Taiwan version on older stroke patients. | To assess the psychometric properties of the SF-36 Taiwan version on a sample of older stroke patients in Taiwan. The Medical Outcomes Study Short Form-36 (SF-36) has proven to be a valid and reliable instrument in evaluating outcomes among stroke patients in western countries; however, less is known regarding its value for Asian stroke patients. A descriptive correlational study design was used to explore the reliability and validity of the SF-36 Taiwan version. Older stroke patients (n = 87) from a medical centre in northern Taiwan were interviewed at the end of the first and sixth months after hospital discharge. Items on each subscale of the SF-36 Taiwan version had similar standard deviations, supporting the scaling assumption of equal-item variance in measuring the same concept. Correlations between items and their subscale were generally >or=0.70 with a few being 0.50 or 0.60. Cronbach's alpha coefficients were >0.70 for almost all subscales, supporting internal consistency. At both the first and sixth months after discharge, participants had lower scores, especially on the physical- and social function-related scales, than the norm for older people. At both times, patients with physical dependence had lower scores across subscales than those without physical dependence, supporting construct validity. The SF-36 Taiwan version demonstrated good reliability and validity when applied to stroke patients at either a transitional or stable time point after hospital discharge. However, the SF-36 Taiwan version has a potential to underestimate changes in certain domains due to floor or ceiling effects. Health care providers who deal with Taiwanese/Chinese stroke patients can use the SF-36 Taiwan version to assess health outcomes at either a transitional or a stable time point after hospital discharge. | 18,754,817 |
Long-term non-invasive positive airway pressure ventilation in infants. | To evaluate the clinical application of long-term non-invasive ventilation (NIV) in infants with life-threatening ventilatory failure with regard to: diagnosis, age at initiation, indication for and duration of treatment, clinical outcome and mortality and adverse effects. The medical records of 18 infants treated in a home setting during a 7-year period were reviewed. The criteria for ventilatory support were: (a) transcutaneous partial pressures of carbon dioxide (TcPCO(2)) >6.5 kPa and oxygen (TcPO(2)) < 8.5 kPa and (b) decreased cough ability and/or recurrent chest infections. The median age at initiation was 4 months (range 1-12). NIV was initiated because of hypoventilation in 12 infants and because of reduced cough ability and/or recurrent infections in six infants. Tracheotomy was eventually needed in two infants. The median duration of treatment was 24 months (range 1-84). NIV produced significant improvements, with median TcPCO(2) falling from 9.9 to 6.1 kPa, and median TcPO(2) rising from 9.8 to 11.1 kPa. NIV can be successfully and safely used in infants with prolonged life-threatening ventilatory failure, potentially avoiding intubation and tracheotomy. | 18,754,825 |
Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions. | Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population. We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates. Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens-Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found. Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs. | 18,754,840 |
Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects. | The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects. An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration. Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration-time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2. This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians. | 18,754,843 |
Red ginseng for treating erectile dysfunction: a systematic review. | Korean red ginseng (unskinned Panax ginseng before it is steamed or otherwise heated and subsequently dried) is one of the most widely used herbal remedies. This systematic review evaluates the current evidence for the effectiveness of red ginseng for treating erectile dysfunction. Systematic searches were conducted on 20 electronic databases without language restrictions. Hand-searches included conference proceedings and our files. All randomized clinical studies (RCT) of red ginseng as a treatment of erectile dysfunction were considered for inclusion. Methodological quality was assessed using the Jadad score. Seven RCTs met all the inclusion criteria. Their methodological quality was low on average. Six of the included RCTs compared the therapeutic efficacy of red ginseng with placebo. The meta-analysis of these data showed a significant effect (n = 349, risk ratio, 2.40; 95% CI of 1.65, 3.51, p < 0.00001, heterogeneity: tau(2) = 0.05, chi(2) = 6.42, p = 0.27, I(2) = 22%). Subgroup analyses also showed beneficial effects of red ginseng in psychogenic erectile dysfunction (n = 135, risk ratio, 2.05; 95% CI of 1.33, 3.16, p = 0.001, heterogeneity: chi(2) = 0.08, p = 0.96, I(2) = 0%). Collectively these RCTs provide suggestive evidence for the effectiveness of red ginseng in the treatment of erectile dysfunction. However, the total number of RCTs included in the analysis, the total sample size and the methodological quality of the primary studies were too low to draw definitive conclusions. Thus more rigorous studies are necessary. | 18,754,850 |
Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma. | The epidermal growth factor receptor (EGFR)-RAS-RAF-mitogen-activated protein kinase signaling cascade is an important pathway in cancer development and recent reports show that EGFR and its downstream signaling molecules are mutated in a number of cancers. We have analyzed 91 Japanese head and neck squamous cell carcinomas (HNSCC) and 12 HNSCC cell lines for mutations in EGFR, ErbB2, and K-ras. Exons encoding the hot-spot regions in the tyrosine kinase domain of both EGFR (exons 18, 19, and 21) and ErbB2 (exons 18-23), as well as exons 1 and 2 of K-ras were amplified by polymerase chain reaction and sequenced directly. EGFR expression was also analyzed in 65 HNSCC patients using immunohistochemistry. Only one silent mutation, C836T, was found in exon 21 of EGFR in the UT-SCC-16A cell line and its corresponding metastasic cell line UT-SCC-16B. No other mutation was found in EGFR, ErbB2, or K-ras. All tumors showed EGFR expression. In 21 (32%) tumors, EGFR was expressed weakly (+1). In 27 (42%) tumors it was expressed (+2) moderately, and in 17 (26%) tumors high expression (+3) was detected. Overexpression (+2, +3) was found in 44 tumors (68%). A worse tumor differentiation and a positive nodal stage were significantly associated with EGFR overexpression (P = 0.02, P = 0.032, respectively). Similar to patients from western ethnicity, mutations are absent or rare in Japanese HNSCC. Protein overexpression rather than mutation might be responsible for activation of the EGFR pathway in HNSCC. | 18,754,871 |
Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages. | Attention has recently focused on the critical role of inflammatory responses in the tumor stroma that provide favorable conditions for cancer-cell growth and invasion/metastasis. In particular, macrophages recruited into the tumor stroma and activated, known as tumor-associated macrophages, are suggested to promote tumorigenesis. In this study, we examined the effect of a decrease in the number of monocytes/macrophages in peripheral blood and the tumor stroma on the development of bone and muscle metastases by lung cancer cells. Treatment with clodronate encapsulated by liposomes (Cl(2)MDP-LIP) has been developed for the depletion of monocytes/macrophages in an animal model. Subcutaneous administration of Cl(2)MDP-LIP markedly reduced the number of monocytes in peripheral blood, resulting in efficient suppression of both bone metastasis and muscle metastasis when lung cancer HARA-B cells were injected into the left cardiac ventricle of mice. Treatment with Cl(2)MDP-LIP significantly reduced the number of macrophages in tumors and the number of osteoclasts in bone marrow, as well as peripheral monocytes in mice harboring lung cancer cells. In contrast, treatment with an osteoclast-targeting antibiotic, reveromycin A, inhibited bone metastasis by lung cancer cells, but not muscle metastasis. The survival of human macrophages in culture was found to be specifically blocked by Cl(2)MDP-LIP, but not by reveromycin A. Cl(2)MDP-LIP thus exerted antimetastatic effects in both bone and muscle whereas reveromycin A did so only in bone. Liposome-encapsulated bisphosphonate may modulate metastasis through decreasing the number of monocytes/macrophages in both peripheral blood and the tumor stroma, suggesting that tumor-associated macrophages might be suitable targets for antimetastatic therapy. | 18,754,872 |
Up-regulation of matrix metalloproteinase-3 in the dorsal root ganglion of rats with paclitaxel-induced neuropathy. | Paclitaxel-induced painful peripheral neuropathy is a major dose-limiting factor. Recently, it has been reported that macrophages accumulated in the dorsal root ganglion of paclitaxel-treated rats, and their activation is suggested to contribute to generation and development of the neuropathy. However, the mechanism for macrophage activation is still unknown. In this study, to explore candidate genes involved in the mechanism for macrophage activation in the dorsal root ganglion of paclitaxel-treated rats, we developed model rats for paclitaxel-induced neuropathic pain and performed a microarray assay to analyze the changes of gene expressions in the dorsal root ganglion. Among the genes with changed expression levels, we focused on matrix metalloproteinase-3 (MMP-3, stromelysin-1) and CD163, a macrophage marker. By reverse transcription-polymerase chain reaction, the expression levels of MMP-3 and CD163 were markedly up-regulated in paclitaxel-treated dorsal root ganglion. As a result of immunohistochemical study, large ganglion neurons, but neither Schwann cells nor macrophages, predominantly expressed MMP-3. This MMP-3 up-regulation occurred prior to macrophage accumulation in the dorsal root ganglion. In addition, recombinant MMP-3 led to the activation of RAW264 macrophages in vitro. Taken together, the up-regulation of MMP-3 and following macrophage activation caused in the dorsal root ganglion might be a significant event to trigger a series of reactions developing paclitaxel-induced peripheral neuropathic pain. | 18,754,875 |
Compound muscle action potentials in newborn infants with spina bifida. | The aim of this study was to investigate the relationship between compound muscle action potentials (CMAPs) and neurological impairment in newborn infants with spina bifida. Thirty-one newborn infants (17 males, 14 females, mean gestational age 39 wks [SD 2]; mean birthweight 3336 g [SD 496]) with spina bifida were investigated at a median age of 2 days (range 1-18 d). Motor and sensory impairment and muscle stretch reflexes were assessed and neuroimaging was performed. CMAPs were recorded from the tibialis anterior muscle and the gastrocnemius muscle after percutaneous electrical nerve stimulation. CMAPs were obtained in almost all infants. The area under the curve of the CMAP (CMAP-area) was associated with motor and sensory impairment and with the presence of muscle stretch reflexes, but not with the morphological level of the spinal anomaly. These associations were stronger for the gastrocnemius muscle than for the tibialis anterior muscle. In conclusion, the CMAP-area correlates with neurological impairment in neonatal spina bifida and provides an estimate of residual motor neuron function in affected spinal segments. The assessment of CMAPs after percutaneous electrical nerve stimulation is recommended as an additional instrument to the clinical neurological examination and imaging studies. | 18,754,922 |
Hydatid cyst of the right ventricle in early pregnancy. | Although hydatic cyst disease rarely involves myocardium and endocardium, cardiac echinococcosis, a potentially life-threatening condition, should be managed promptly. We report a case of right ventricle hydatid cyst detected after syncopal attack in a pregnant woman by using echocardiography. | 18,754,937 |
Success of a lactation education program on NICU nurses' knowledge and attitudes. | To test an educational intervention designed to improve lactation knowledge, attitudes, and beliefs of NICU nurses and to improve their intentions to provide mothers with lactation support. Quasi-experimental, time-series pretest/posttest. NICU of a Midwestern, free-standing, tertiary-care children's hospital. Convenience sample of 64 NICU nurses and 2 separate convenience samples of mothers of infants hospitalized in the NICU (n=19 and 13, respectively). Nurses were measured on study outcomes at multiple time points, beginning with 2 weeks before and ending at 3 months after attendance to a 4-hour educational program. Mothers were sampled before and 3 months after the intervention. Nurses' lactation knowledge, attitudes, beliefs, and intentions to support lactation and mothers' perceptions of lactation support in the NICU. Findings suggest that this educational intervention was effective for improving NICU nurses' lactation knowledge and attitudes, and that these improvements were maintained over time. Further, the supportive atmosphere for lactation in this NICU significantly improved following the implementation of the educational intervention for nurses. Intermittent, short educational programs which include practical how-to's and motivational encouragement for staff may provide the empowerment nurses need in order to be supportive of lactation. | 18,754,981 |
Perineal trauma and postpartum perineal morbidity in Asian and non-Asian primiparous women giving birth in Australia. | To describe the postpartum perineal morbidity of primiparous women who had a vaginal birth and compare outcomes between Asian and non-Asian women in the first 2 days following the birth and at 6 and 12 weeks postpartum. Data from a randomized clinical trial of a perineal management technique (perineal warm packs) were used to address the study objective. Two maternity hospitals in Sydney, Australia. Primiparous women who had a vaginal birth in the trial were included (n=697). One third of the women were identified as "Asian." Compared with non-Asian women, Asian women were significantly more likely to have an episiotomy; require perineal suturing; sustain a third- or fourth-degree perineal tear; and report their perineal pain as being moderate to severe on day 1 following the birth. Asian women were less likely to give birth in an upright position or to resume sexual intercourse by 6 or 12 weeks following the birth. More research is needed into methods that could reduce the high rates of perineal trauma experienced by Asian women, and midwives need to be able to offer appropriate support for Asian women. | 18,754,983 |
Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus--a systematic review. | Caesarean section before labor or before ruptured membranes ("elective caesarean section", or ECS) has been introduced as an intervention for preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Currently, no evidence that ECS versus vaginal delivery reduces the rate of MTCT of HBV has been generally provided. The aim of this review is to assess, from randomized control trails (RCTs), the efficacy and safety of ECS versus vaginal delivery in preventing mother-to-child HBV transmission. We searched Cochrane Pregnancy and Childbirth Group's Trials Register (January, 2008), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2008, issue 1), PubMed (1950 to 2008), EMBASE (1974 to 2008), Chinese Biomedical Literature Database (CBM) (1975 to 2008), China National Knowledge Infrastructure (CNKI) (1979 to 2008), VIP database (1989 to 2008), as well as reference lists of relevant studies. Finally, four randomized trails involving 789 people were included. Based on meta-analysis, There was strong evidence that ECS versus vaginal delivery could effectively reduce the rate of MTCT of HBV (ECS: 10.5%; vaginal delivery: 28.0%). The difference between the two groups (ECS versus vaginal delivery) had statistical significance (RR 0.41, 95% CI 0.28 to 0.60, P < 0.000001). No data regarding maternal morbidity or infant morbidity according to mode of delivery were available. ECS appears to be effective in preventing MTCT of HBV and no postpartum morbidity (PPM) was reported. However, the conclusions of this review must be considered with great caution due to high risk of bias in each included study (graded C). | 18,755,018 |
Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration. | This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle. | 18,755,028 |
FERN - a Java framework for stochastic simulation and evaluation of reaction networks. | Stochastic simulation can be used to illustrate the development of biological systems over time and the stochastic nature of these processes. Currently available programs for stochastic simulation, however, are limited in that they either a) do not provide the most efficient simulation algorithms and are difficult to extend, b) cannot be easily integrated into other applications or c) do not allow to monitor and intervene during the simulation process in an easy and intuitive way. Thus, in order to use stochastic simulation in innovative high-level modeling and analysis approaches more flexible tools are necessary. In this article, we present FERN (Framework for Evaluation of Reaction Networks), a Java framework for the efficient simulation of chemical reaction networks. FERN is subdivided into three layers for network representation, simulation and visualization of the simulation results each of which can be easily extended. It provides efficient and accurate state-of-the-art stochastic simulation algorithms for well-mixed chemical systems and a powerful observer system, which makes it possible to track and control the simulation progress on every level. To illustrate how FERN can be easily integrated into other systems biology applications, plugins to Cytoscape and CellDesigner are included. These plugins make it possible to run simulations and to observe the simulation progress in a reaction network in real-time from within the Cytoscape or CellDesigner environment. FERN addresses shortcomings of currently available stochastic simulation programs in several ways. First, it provides a broad range of efficient and accurate algorithms both for exact and approximate stochastic simulation and a simple interface for extending to new algorithms. FERN's implementations are considerably faster than the C implementations of gillespie2 or the Java implementations of ISBJava. Second, it can be used in a straightforward way both as a stand-alone program and within new systems biology applications. Finally, complex scenarios requiring intervention during the simulation progress can be modelled easily with FERN. | 18,755,046 |
Effects of ascorbic acid, phytic acid and tannic acid on iron bioavailability from reconstituted ferritin measured by an in vitro digestion-Caco-2 cell model. | The effects of ascorbic acid (AA), phytate and tannic acid (TA) on Fe bioavailability from Fe supplied as reconstituted ferritin were compared with FeSO4 using an in vitro digestion-Caco-2 cell model. Horse spleen apoferritin was chemically reconstituted into an animal-type ferritin (HSF) and a plant-type ferritin (P-HSF) according to the typical ratios of Fe:P found in these molecules. In the presence of AA (Fe:AA molar ratio of 1:20), significantly more Fe was absorbed from FeSO4 (about 303 %), HSF (about 454 %) and P-HSF (about 371 %) when compared with ferrous sulfate or ferritin without AA. Phytic acid (PA; Fe:PA molar ratio of 1:20) significantly reduced Fe bioavailability from FeSO4 (about 86 %), HSF (about 82 %) and P-HSF (about 93 %) relative to FeSO4 and the ferritin controls. Treatment with TA (Fe:TA molar ratio of 1:1) significantly decreased Fe bioavailability (about 97 %) from both FeSO4 and the ferritin samples. AA was able to partially reverse the negative effect of PA (Fe:PA:AA molar ratio of 1:20:20) on Fe bioavailability but did not reverse the inhibiting effect of TA (Fe:TA:AA molar ratio of 1:1:20) on Fe bioavailability from ferritin and FeSO4. Overall, there were no significant differences in bioavailable Fe between P-HSF, HSF or FeSO4. Furthermore, the addition of AA (a known promoter) or the inhibitors, PA and TA, or both, did not result in significant differences in bioavailable Fe from ferritin relative to FeSO4. The results suggest that Fe in the reconstituted ferritin molecule is easily released during in vitro digestion and interacts with known promoters and inhibitors. | 18,755,051 |
Mutation spectra induced by 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide in the supF gene of human XP-A fibroblasts. | 1-Nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide are oxidative metabolites that are responsible for the mutagenicity of 1-nitropyrene. In this study, the mutation spectra induced by oxidative metabolites in human cells were determined using a shuttle vector assay. The mutation frequencies induced by 1-nitropyrene 9,10-oxide were 2-3 times higher than those induced by 1-nitropyrene 4,5-oxide. The base substitutions induced by 1-nitropyrene 4,5-oxide were G --> A transitions, G --> C transversions, and G --> T transversions. In the case of 1-nitropyrene 9,10-oxide, G --> A transitions, G --> T transversions, A --> G transitions and G --> C transversions were observed. Most base substitution mutations induced by oxidative metabolites occurred at the guanine sites in the supF gene. These sequence-specific hot spots were commonly identified as 5'-GA sequences for both metabolites. On the other hand, the sequence-specific hot spots at the adenine sites were identified as 5'-CAC sequences for 1-nitropyrene 9,10-oxide. These results suggest that the oxidative metabolites of 1-nitropyrene induce sequence-specific DNA mutations at the guanine and adenine sites at high frequency. | 18,755,077 |
[Assessment criteria for public policies on obesity: the view of Spanish stakeholders]. | To explore the criteria used to assess public policy initiatives on obesity in Spain by the main stakeholders. Multicriteria mapping was performed within the framework of the European PorGrow Project "Policy options for responding to obesity" through a structured interview with 21 stakeholders, who were leaders in the public and private sectors in Spain in the area of food and physical exercise. Qualitative and quantitative information was included in the analysis. The interviewees justified their positions for or against the various policy options with criteria that were weighted by their relative importance and documented with quotations and nuggets from the interviewees' discourse. We identified 93 criteria for policy selection in the 21 interviewees. The most frequent criteria and those perceived as most important were efficacy (n = 18), social benefits (n = 17) and social acceptability (n = 14). The economic impact on individuals and the public sector was not considered important by the interviewees. The economic impact on the commercial sector was not included by any of the participants. The criterion most highly valued by public sector stakeholders was societal benefits while that most valued by private sector stakeholders was efficacy. Spain is in the initial stages of developing public policy on obesity and, as yet, there are no winners and losers among those concerned, which may explain why economic costs seem to be relatively unimportant for the stake-holders, opening a window of opportunity for the development of regulatory policies. | 18,755,081 |
[Detection of a hepatitis A outbreak in Ceuta (Spain) through a microbiological surveillance system]. | The Public Health Department of Ceuta informed the Spanish National Epidemiology Center of an increase in hepatitis A cases detected by the microbiological surveillance system. We conducted a study to confirm the outbreak and to initiate control measures. A descriptive study and a case-control study were performed. A standardized telephone questionnaire was used to collect information on demographic characteristics, symptoms, and risk factors. Nineteen cases of hepatitis A were identified. Univariate analysis revealed an association between infection and eating raw vegetables (OR = 9.3; 95%CI: 1.5-57.6) or razor-shell (OR = 55; 95%CI: 4.3-703.4). In the logistic regression model, only razor-shell consumption remained a significant risk factor (OR = 36.1; 95%CI: 2.45-530.4). None of the 3 inspected restaurants had public health authorization or records of food purchase histories. We confirmed a hepatitis A outbreak associated with consumption of contaminated razor-shell in homes and restaurants. The microbiological surveillance system was the main means of detecting this outbreak. | 18,755,092 |
[Vitamin D deficiency in women of reproductive age]. | To determine the level of hypovitaminosis D in adult healthy women attended in primary care and their associated factors. Cross-sectional, descriptive study. A neighbourhood of Barcelona, Spain, with a socially deprived population with a high percentage of immigrants, and urban factors which meant that they lived with hardly any sunlight. Women between 15-50 years seen between February and March 2005. Primary: residence time (years), skin phototype, sun exposure, vitamin D deficiency pain type, calcium, vitamin D consumed, and measurement of serum 25-hydroxyvitamin D (25[OH]D) or calcidiol and parathyroid hormone (PTH) if (25[OH]D) was <10 ng/mL; 94 women were included. Mean age: 33 years (SD, 7.8); 62.8% immigrants (mean years of residence, 11.5). Mean (25[OH]D), 14.0 ng/mL (95% CI, 12.5-15.5). Skin phototype V-VI was associated with low levels of (25[OH]D) (P=.001). None of the women stated that they consumed the recommended amount of vitamin D and only 46% the recommended amount of calcium. Sun exposure of >4 hours/week: 37%. Sixteen percent had musculo-skeletal pain. No relationship was found between vitamin D levels and immigration. All the women had (25[OH]D) levels of <40 mg/mL, 47.9% had insufficient (25[OH]D), 10-20 ng/mL, and 37.2% were deficient: pound10 mg/mL. PTH was within the normal range. All the women had low levels of vitamin D, more than a third of these, deficient. No relationship with immigration was found. A relationship was established between skin phototype V-VI and (25[OH]D) deficiency. None of the cases consumed the recommended amounts of vitamin D. | 18,755,099 |
[Three-dimensional echocardiography: preliminary experience in congenital cardiac disease]. | Anatomical comprehension of congenital cardiac diseases by 2D echocardiography is occasionally very difficult. 3D echocardiography provides a more spatial anatomical information avoiding the need of two-dimensional reconstruction. Of the 271 cases studied 80 were foetal and 191 patients. In all cases, 2D and 3D echocardiography was performed (Sonos 7500 with matrix probe). Four modes of 3D imaging were used. 3D echocardiography gave an accurate description of the size, form and wedges of septals defects. In atrioventricular septal defects and mitral anomalies, 3D echocardiography was useful for the assessment of dynamic valve morphology and mechanisms of regurgitation. In foetal screening the segmentary heart study was carried out from a single acoustic window. 3D real time echocardiography is a feasible, easy and rapid technique. It provides anatomical and functional details needed for an accurate comprehension of congenital cardiac diseases. In foetal screening, it provides an easier segmentary analysis of the entire foetal heart. | 18,755,119 |
RXR agonists inhibit oxidative stress-induced apoptosis in H9c2 rat ventricular cells. | Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. We examined its role in regulating oxidative stress-induced apoptosis in H9c2 rat ventricular cells. We showed for the first time that functional RXR protein was downregulated by hydrogen peroxide (H2O2) in H9c2 cardiomyocytes. Natural and synthetic agonists of RXR, 9-cis-RA, and LGD1069 respectively, prevented H2O2-triggered apoptosis, and this anti-apoptotic effect was inhibited by the RXR antagonist HX531. Further investigation into the protective mechanisms of RXR demonstrated that H2O2-induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and caspase-3 activation were all significantly attenuated by pretreatment with RXR agonists. Furthermore, this protection was associated with a reduction in intracellular reactive oxygen species and an upregulation in catalase activity. Thus, these data indicate that pharmacological activation of RXR exerts protective effects against H2O2-induced apoptosis in H9c2 rat ventricular cells through antioxidant and mitochondria-protective mechanisms. | 18,755,147 |
Regulation of hormone-sensitive lipase expression by saturated fatty acids and hormones in bovine mammary epithelial cells. | Hormone-sensitive lipase was firstly identified as an epinephrine-induced lipase in adipocyte. HSL mRNA was detected by RT-PCR in cloned bovine mammary epithelial cells (bMEC) and bovine lactating mammary gland. Saturated fatty acids (stearate and palmitate), but not unsaturated fatty acids (oleate and linoleate) induced up-regulation of HSL mRNA in a time- and concentration-dependent manner in bMEC. Treatment with insulin (5-10 ng/ml), dexamethasone (50-250 nM) or GH (50 ng/ml) induced down-regulation of HSL. These results suggest that HSL was regulated by fatty acids and some hormones in mammary epithelial cells and thereby play an important role of lipid and energy metabolism. | 18,755,148 |
Superoxide modifies AMPA receptors and voltage-gated K+ channels of mouse hippocampal neurons. | Lucifer Yellow CH (LY), a fluorescent membrane-impermeable cell-marker dye, has been routinely loaded into cells through recording electrodes to visualize these cells after electrophysiological investigation. Recently we showed that LY produced superoxide when LY was exposed to light at ordinary intensities for microscopy, and that the resultant superoxide retarded the inactivation of voltage-gated Na+ channels even in the dark. Here, we show that superoxide produced by exposure to light prolongs the duration of action potentials, and increases the magnitude of outward rectifier K+ currents and inward rectifier K+ currents in cultured mouse hippocampal neurons. Superoxide also increases the current response of AMPA receptors, but has no effect on that of kainate and NMDA receptors, GABA(A) receptors, high-voltage activated Ca2+ channels of the hippocampal neurons, nor on 5HT3 receptors of N1E-115 cells. These superoxide effects are irreversible. The addition of superoxide dismutase, an enzyme that selectively decomposes superoxide, to LY-loaded recording electrodes reverses the superoxide effects, but addition of heat-inactivated superoxide dismutase fails to reverse the effects. The application of dithiothreitol, a free radical scavenger, to a bathing solution also reverses the superoxide effects. This shows that superoxide rather selectively modifies ion channels. The effects of exogenous and endogenous superoxide on the superoxide-susceptible channels are discussed. | 18,755,163 |
Appetite regulatory mechanisms and food intake in mice are sensitive to mismatch in diets between pregnancy and postnatal periods. | Human and animal studies suggest that obesity in adulthood may have its origins partly during prenatal development. One of the underlying causes of obesity is the perturbation of hypothalamic mechanisms controlling appetite. We determined mRNA levels of genes that regulate appetite, namely neuropeptide Y (NPY), pro-opiomelanocortin (POMC) and the leptin receptor isoform Ob-Rb, in the hypothalamus of adult mouse offspring from pregnant dams fed a protein-restricted diet, and examined whether mismatched post-weaning high-fat diet altered further expression of these gene transcripts. Pregnant MF1 mice were fed either normal protein (C, 18% casein) or protein-restricted (PR, 9% casein) diet throughout pregnancy. Weaned offspring were fed to adulthood a high-fat (HF; 45% kcal fat) or standard chow (21% kcal fat) diet to generate the C/HF, C/C, PR/HF and PR/C groups. Food intake and body weight were monitored during this period. Hypothalamic tissues were collected at 16 weeks of age for analysis of gene expression by real time RT-PCR. All HF-fed offspring were observed to be heavier vs. C groups regardless of the maternal diet during pregnancy. In the PR/HF males, but not in females, daily energy intake was reduced by 20% vs. the PR/C group (p<0.001). In PR/HF males, hypothalamic mRNA levels were lower vs. the PR/C group for NPY (p<0.001) and Ob-Rb (p<0.05). POMC levels were similar in all groups. In females, mRNA levels for these transcripts were similar in all groups. Our results suggest that adaptive changes during prenatal development in response to maternal dietary manipulation may have long-term sex-specific consequences on the regulation of appetite and metabolism following post-weaning exposure to an energy-rich nutritional environment. | 18,755,169 |
Sample preparation for liquid chromatography-tandem mass spectrometry using functionalized ferromagnetic micro-particles. | To study the applicability of functionalized ferromagnetic micro-particles in the sample preparation for quantification of small molecules by LC-MS/MS. A representative analyte (itraconazole) was extracted from plasma samples using small quantities of C18-modified ferromagnetic micro-particles. 125 microg of functionalized micro-particles was sufficient to extract the target analyte from 10 microL of plasma with a recovery rate of approximately 100%; linearity (r>0.99) and reproducibility (inter-assay CV< or =7%) of quantitative results was found. C18-functionalized ferromagnetic particles can be used to efficiently extract small molecule analytes from complex biological matrices for quantitative analyses using LC-MS/MS. | 18,755,176 |
Proteasome inhibition compromises direct retention of cytochrome P450 2C2 in the endoplasmic reticulum. | To determine whether protein degradation plays a role in the endoplasmic reticulum (ER) retention of cytochromes P450, the effects of proteasomal inhibitors on the expression and distribution of green fluorescent protein chimeras of CYP2C2 and related proteins was examined. In transfected cells, expression levels of chimeras of full-length CYP2C2 and its cytosolic domain, but not its N-terminal transmembrane sequence, were increased by proteasomal inhibition. Redistribution of all three chimeras from the reticular ER into a perinuclear compartment and, in a subset of cells, also to the cell surface was observed after proteasomal inhibition. Redistribution was blocked by the microtubular inhibitor, nocodazole, suggesting that redistribution to the cell surface followed the conventional vesicular transport pathway. Similar redistributions were detected for BAP31, a CYP2C2 binding chaperone; CYP2E1 and CYP3A4, which are also degraded by the proteasomal pathway; and for cytochrome P450 reductase, which does not undergo proteasomal degradation; but not for the ER membrane proteins, sec61 and calnexin. Redistribution does not result from saturation of an ER retention "receptor" since in some cases protein levels were unaffected. Proteasomal inhibition may, therefore, alter ER retention by affecting a protein critical for ER retention, either directly, or indirectly by affecting the composition of the ER membranes. | 18,755,184 |
Reciprocal regulation of 12- and 15-lipoxygenases by UV-irradiation in human keratinocytes. | The 12/15-lipoxygenase (12/15-LOX) pathways of arachidonate metabolism have been implicated in the pathogenesis of psoriasis. Since UV photo-therapy is a commonly used technique for inhibiting cell proliferation and inflammation in skin diseases, we hypothesized that UV-irradiation may affect 12/15-LOX expression which might regulate cell proliferation. In this study, we showed that UV-irradiation suppressed 12-LOX expression, whereas up-regulated 15-LOX expression. Treatment with the 15-LOX metabolites sufficiently suppressed insulin-like growth factor II-induced 12-LOX expression and blocked cell cycle progression. On the basis of our findings, we think that the 15-LOX metabolites may inhibit epidermal hyperplasia in psoriasis by regulating 12-LOX expression. | 18,755,188 |
Increased expression, but not postsynaptic localisation, of ionotropic glutamate receptors during the late-phase of long-term potentiation in the dentate gyrus in vivo. | Long-term potentiation (LTP) is extensively studied as a cellular mechanism of information storage in the brain. The induction and early expression mechanisms of LTP depend on activation and rapid modulation of ionotropic glutamate receptors. However, the mechanisms that underlie maintenance of LTP over the course of days or longer are poorly understood. Here, we have investigated the overall expression of AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively), as well as their levels at the synaptic surface membrane and in the postsynaptic density (PSD), in the dentate gyrus at 48h following the induction of LTP at perforant path synapses in awake rats. We found a high-frequency stimulation-dependent increase in the overall levels of AMPAR subunits GluA1 and GluA2, but not GluA3 in the dentate gyrus. The increases in GluA1 and GluA2 levels were partially NMDAR-dependent, but were not found in biochemically isolated synaptic surface membrane or PSD fractions. In contrast, we found that the core NMDAR subunit, GluN1, increased in the synaptic surface-membrane fraction but it also was not targeted to the PSD. The GluA1 and GluA2 expression and the surface localisation of GluN1 returned to baseline levels by 2 weeks post-LTP induction. These data suggest that the late-phase LTP is not mediated by an overt increase in the AMPAR content of perforant path synapses. The increase in surface expression NMDARs may influence thresholds for future plasticity events. | 18,755,203 |
Maternal and developmental toxicity study of sodium azide in rats. | Sodium azide (NaN(3)) is being proposed for use as an active ingredient to control a broad spectrum of soil borne pathogens including insects, weeds, nematodes, fungi, and bacteria. The purpose of this study was to determine the maternal and developmental toxicity of NaN(3) in rats. Sperm-positive Sprague-Dawley rats were treated with NaN(3) via oral gavage once daily from Gestation Day (GD) 6 through 19 at respective dose levels of 0, 1, 5, and 17.5mg/kg/day. From GD 10-12, the high-dose was reduced to 10mg/kg/day due to maternal mortality. Cesarean section was performed on GD 20 and implantation and resorptions sites, live and dead fetuses were counted. Fetuses were weighed, sexed externally and processed for gross external, visceral and skeletal examinations. A high rate of maternal mortality; reduced gestation body weight, gestation body weight changes and food consumption; decreased corrected body weight and corrected weight gain were observed at 17.5/10mg/kg/day. Fetal weight was also reduced at 17.5/10mg/kg/day. There were no maternal deaths, clinical signs or body weight effects that were considered related to NaN(3) at 1 and 5mg/kg/day. No increase in the incidence of malformations and variations were observed at any of the doses evaluated. Based on the results of this study, the No Observed Adverse Effect Level (NOAEL) and the Lowest Observed Adverse Effect Level (LOAEL) for maternal and developmental toxicity of NaN(3) in rats were considered to be 5 and 17.5/10mg/kg/day, respectively. | 18,755,233 |
Immunomodulatory effect of DDT (bis[4-chlorophenyl]-1,1,1-trichloroethane) on complement system and macrophages. | DDT (bis[4-chlorophenyl]-1,1,1-trichloroethane) is responsible for many immuno-dysregulatory functions in exposed animals, but data particularly on complement system and macrophages are limited. In this study we have shown that DDT activates the complement system through the alternative pathway in the absence of any pathogen. A significant (p<0.05) increase in C3b, C3d and C3a generation, and decline in complement hemolytic activity was observed in insecticide exposed sera. The uncontrolled complement consumption reduces the lytic activity of the complement, which enhances the susceptibility to pyogenic infection if the exposure to DDT remains unabated. Further, DDT induced the significant (p<0.05) production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in macrophages and thus contributes inflammatory reactions, cytokine imbalance and immune-dysregulation. These molecular changes in macrophages lead to structural aberrations like heterochromatin condensation, loss of pseudopodia, cytoplasmic vacuolization, DNA fragmentation and hypodiploid nuclei as seen in our study, suggesting apoptosis. However, in presence lipopolysaccharide, DDT induced significant (p<0.05) suppression of TNF-alpha and NO generation, suggestive of impairment of macrophage microbiocidal effects. This study concludes that the functional and structural derangements of macrophages in association with uncontrolled and excessive complement consumption by DDT are perhaps one of the major mechanisms contributing to the immunosuppressive effects of insecticide. | 18,755,234 |
Cytotoxicity effects induced by Zearalenone metabolites, alpha Zearalenol and beta Zearalenol, on cultured Vero cells. | Zearalenone (Zen) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium. It has been implicated in several mycotoxicosis in farm animals and in humans. The major metabolites of this mycotoxin in various species are alpha and beta Zearalenol. In vivo, Zen is mainly reduced to these alcoholic metabolites which cause reproductive tract disorders and impaired fertility due to their estrogenic activities. In this study, we examined the cytotoxicity of alpha and beta Zearalenol in cultured cells. For this purpose, the MTT assay was carried out and the influence of alpha and beta Zearalenol on protein and DNA syntheses was assessed. To evaluate the cell stress caused by these two metabolites, oxidative stress measured by MDA induction and stress protein induction (Hsp 70, Hsp 27) were tested. Results showed that alpha and beta Zearalenol were metabolites that caused cytotoxicity by inhibiting cell viability, protein and DNA syntheses and inducing oxidative damage and over-expression of stress proteins. However, the Zen metabolites exhibited lower toxicity than Zen, with beta zearalenol being the more active of the two metabolites. | 18,755,238 |
Beneficial effect of autologous transplantation of bone marrow stromal cells and endothelial progenitor cells on cerebral ischemia in rabbits. | We tested the therapeutic effect of autologous transplanted bone marrow stromal cells (BMSCs) and endothelial progenitor cells (EPCs) on cerebral ischemia in rabbits. Rabbit permanent middle cerebral artery occlusion (MCAO) models were intravenously injected with ex vivo expanded autologous BMSCs (n = 8), EPCs (n = 8), or phosphate-buffered saline (n = 6). 14 days after the transplantation, both infusion groups witnessed a functional improvement, a decrease in the number of apoptotic cells and an increase in the microvessel density in the ischemic boundary area, as compared to vehicle-treated control group. The EPCs treated group also exhibited a diminished infarct area in comparison with the control group. Moreover, immunohistochemistry revealed that few transplanted BMSCs expressed markers for astrocytes (GFAP+) and neurons (NeuN+), and most of EPCs were capable of binding to UEA-1 lectin and were incorporated into capillaries. Our data suggest that both BMSCs and EPCs, despite differences in their action mechanism, can be functional cytoreagents for treatment of cerebral ischemia in rabbits. | 18,755,241 |
The role of muscarinic receptor subtypes in acetylcholine release from urinary bladder obtained from muscarinic receptor knockout mouse. | We investigated the subtype of prejunctional muscarinic receptors associated with inhibition of acetylcholine (ACh) released from the mouse bladder. We measured endogenous ACh release in the bladder obtained from the wild-type mice and muscarinic 1-5 (M1-M5) receptor knockout (KO) mice. Electrical field stimulation increased ACh release in all bladder preparations obtained from wild-type and M1-M5 receptor KO mice. The amount of ACh released from M1-M3 and M5 receptor KO mice was equal to that in the wild-type mice. In contrast, the amount of electrical field stimulation-induced ACh release in M4 receptor KO mice was significantly larger than that in the wild-type mice, but the extent of increase was small. Atropine increased electrical field stimulation-induced ACh release to levels found in wild-type mice in all M1-M5 receptor KO mice. In M2/M4 receptor double KO mice, the amount of electrical field stimulation-induced ACh release was equivalent to that in the M4 receptor KO mice. The cholinergic component of electrical field stimulation-induced contraction (in the presence of alpha,beta-methylene ATP) in the detrusor of M4 receptor KO mice was no different from that in the detrusor of wild-type mice. M4 receptor immunoreactivity was located between smooth muscle cells, colocalized with choline acetyltransferase immunoreactivity. These results indicate that the prejunctional inhibitory muscarinic receptors are of the M4 and non-M2 receptor subtypes. The nature of the non-M2 receptors remains unknown. | 18,755,247 |
Cytosine arabinoside treatment impairs the remote spatial memory function and induces dendritic retraction in the anterior cingulate cortex of rats. | Clinical studies on cancer patients have revealed that chemotherapy is associated with long-term cognitive impairment. In the present study, we used a rat model to evaluate the effects of the anticancer drug cytosine arabinoside (Ara-C) on spatial learning, memory, and the dendritic morphology of neurons in the anterior cingulate cortex (ACC) and hippocampus. The drug was observed to induce deficits in the long-term spatial memory function but not in the spatial learning and recent memory, as was assessed by performing the Morris water maze test. In the Ara-C treated rats, retraction of the apical dendrites was noted in the neurons in the ACC but not in the pyramidal neurons in the hippocampal region CA1. Our in vivo adult rat model of neurotoxicity provides data on the long-term cognitive and cellular morphometric alterations in the frontal lobes induced by Ara-C treatment. Retraction of the apical dendrites of the pyramidal neurons in the ACC may contribute to the remote spatial memory impairment induced by Ara-C treatment. | 18,755,251 |
Optimization of ibuprofen gel formulations using experimental design technique for enhanced transdermal penetration. | The aims of this study were to develop a transdermal gel formulation for ibuprofen using experimental design techniques and to evaluate its pharmacokinetic properties. The three factors chosen for factorial design were the concentrations of drug, polyoxyethylene(5)cetyl/oleyl ether and ethanol and the levels of each factor were low, medium and high. Skin permeation rates and lag times of ibuprofen were evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The permeation rate of ibuprofen significantly increased in proportion to the drug concentration, but significantly decreased in proportion to POE(5)cetyl/oleyl ether concentration. Ethanol concentration was inversely proportional to the lag time. The pharmacokinetic properties of the optimized formulation were compared with those of two marketed products in rats. The relative bioavailability of ibuprofen gel compared to the two marketed products was 228.8% and 181.0%. In conclusion, a transdermal ibuprofen gel was formulated successfully using the technique of experimental design and these results helped in finding the optimum formulation for transdermal drug release. | 18,755,258 |
Assessing TF regulatory relationships of divergently transcribed genes. | Ambiguously located transcription factor (TF) binding sites may introduce a large number of potentially erroneous regulatory associations into models of transcriptional regulatory networks. We have used a two-step expression similarity strategy to distinguish between likely and unlikely regulatory associations for TFs located between divergently transcribed genes in the yeast genome. Most regulatory associations of divergently transcribed genes could be assigned to either high-confidence (HC) or low-confidence (LC) groups. In support of our result, we found that most of the previously characterized regulatory associations reported in the literature fell into the HC group rather than the LC group. Moreover, genomic distance analysis showed that TF binding sites tend to be located in relative proximity to the gene that is most likely to be regulated by this TF. Finally, removal of low-confidence (i.e., most probably erroneous) regulatory associations from the transcriptional regulatory network barely affected its basic architecture. | 18,755,263 |
Activation of the maternal immune system alters cerebellar development in the offspring. | A common pathological finding in autism is a localized deficit in Purkinje cells (PCs). Cerebellar abnormalities have also been reported in schizophrenia. Using a mouse model that exploits a known risk factor for these disorders, maternal infection, we asked if the offspring of pregnant mice given a mid-gestation respiratory infection have cerebellar pathology resembling that seen in these disorders. We also tested the effects of maternal immune activation in the absence of virus by injection of the synthetic dsRNA, poly(I:C). We infected pregnant mice with influenza on embryonic day 9.5 (E9.5), or injected poly(I:C) i.p. on E12.5, and assessed the linear density of PCs in the cerebellum of adult or postnatal day 11 (P11) offspring. To study granule cell migration, we also injected BrdU on P11. Adult offspring of influenza- or poly(I:C)-exposed mice display a localized deficit in PCs in lobule VII of the cerebellum, as do P11 offspring. Coincident with this are heterotopic PCs, as well as delayed migration of granule cells in lobules VI and VII. The cerebellar pathology observed in the offspring of influenza- or poly(I:C)-exposed mice is strikingly similar to that observed in autism. The poly(I:C) findings indicate that deficits are likely caused by the activation of the maternal immune system. Finally, our data suggest that cerebellar abnormalities occur during embryonic development, and may be an early deficit in autism and schizophrenia. | 18,755,264 |
mRNA expression changes of slit proteins following peripheral nerve injury in the rat model. | Slit family of proteins is one of the repulsive axonal guidance cues, and it also plays an important role in neuronal migration and branching through the interaction with roundabout receptors. The function and role of Slit family proteins during peripheral nerve regeneration are still unknown. We examined the expressions of Slits 1-3 mRNAs in the facial nerve nuclei after facial nerve transection by in situ hybridization, using Sprague-Dawley rats. Slit 1 mRNA was weakly expressed in the facial motoneurons, and its expression increased from day 5 to day 28 after transection, with the peak on day 14 after axotomy. Slits 2 and 3 mRNAs were expressed in the motoneurons of the facial nerve before injury, but the expression of Slit 2 mRNA was down-regulated from day 1 to day 7 after axotomy, with the peak on the first day after injury. Slit 3 mRNA expression in the axotomized side remained unchanged throughout the examination period. Slits 1 and 2 mRNA expression returned to the normal level on day 56 postoperatively. The difference in expression pattern of Slit family mRNA in the neurons during peripheral nerve regeneration suggests that it plays a different role in axonal regeneration after axotomy of peripheral nerves. | 18,755,265 |
Electron crystallography of proteins in membranes. | Electron crystallography has played a vital role in advancing our understanding of proteins in membranes since the 'fluid mosaic model' was proposed in 1972. It is now an established technique to reveal the structures of proteins in their natural bilayer environment and makes possible the study of biological mechanisms through freeze-trapping of transitional states. Thus, images and diffraction patterns of well-ordered, planar and tubular protein-lipid crystals are yielding atomic models, which tell us how the proteins in situ are designed and carry out their membrane-specific tasks. Recent methodological advances and the inclusion of tomographic and cryo-sectioning techniques are enabling detailed information to be obtained from increasingly smaller and more disordered membrane assemblies, extending the potential of this approach. | 18,755,273 |
High concentrations of phenylalanine stimulate peroxisome proliferator-activated receptor gamma: implications for the pathophysiology of phenylketonuria. | If left untreated, the common inherited metabolic disorder phenylketonuria (PKU) presents with mental retardation and reduced brain weight. The underlying molecular reasons for these deficits are unknown so far. Using human neuroblastoma cells as a model for normal human neuroblasts, elevated phenylalanine concentrations suppressed proliferation of these cells in culture. Furthermore, microarray and functional assays of these cells revealed that both phenylalanine and the known PPARgamma agonist rosiglitazone regulated the same set of genes causing subsequently similar changes in the functional assays. The lowered brain weight of PKU patients may thus be the result of reduced neuroblast proliferation caused by phenylalanine-induced stimulation of PPARgamma receptors. The observation that high concentrations of small substrates can activate receptors may serve as a new paradigm for other metabolic diseases and provides a new approach for the treatment of these disorders by application of specific receptor antagonists. | 18,755,275 |
Layer specific tracing of corticocortical and thalamocortical connectivity in the rodent using manganese enhanced MRI. | Information about layer specific connections in the brain comes mainly from classical neuronal tracers that rely on histology. Manganese Enhanced MRI (MEMRI) has mapped connectivity along a number of brain pathways in several animal models. It is not clear at what level of specificity neuronal connectivity measured using MEMRI tracing can resolve. The goal of this work was to determine if neural tracing using MEMRI could distinguish layer inputs of major pathways of the cortex. To accomplish this, tracing was performed between hemispheres of the somatosensory (S1) cortex and between the thalamus and S1 cortex. T(1) mapping and T(1) weighted pulse sequences detected layer specific tracing after local injection of MnCl(2). Approximately 12 h following injections into S1 cortex, maximal T(1) reductions were observed at 0.6+/-0.07 and 1.1+/-0.12 mm from the brain surface in the contralateral S1. These distances correspond to the positions of layer 3 and 5 consistent with the known callosal inputs along this pathway. Four to six hours following injection of MnCl(2) into the thalamus there were maximal T(1) reductions between 0.7+/-0.08 and 0.8+/-0.08 mm from the surface of the brain, which corresponds to layer 4. This is consistent with terminations of the known thalamocortical projections. In order to observe the first synapse projection, it was critical to perform MRI at the right time after injections to detect layer specificity with MEMRI. At later time points, tracing through the cortical network led to more uniform contrast throughout the cortex due to its complex neuronal connections. These results are consistent with well established neuronal pathways within the somatosensory cortex and demonstrate that layer specific somatosensory connections can be detected in vivo using MEMRI. | 18,755,280 |
Genetic polymorphism of Algerian Leishmania infantum strains revealed by multilocus microsatellite analysis. | The present study applies multilocus microsatellite typing (MLMT) for studying the polymorphism among 55 strains of Leishmania infantum from Algeria. These strains from different Algerian foci representing different zymodemes, hosts and clinical forms were analysed using 14 microsatellite markers. All 55 strains had individual MLMT profiles and no relationship was observed between them and different host or geographical origins. Three populations of Algerian L. infantum were identified by a Bayesian clustering approach implemented in STRUCTURE software and supported by genetic distance analysis. Two populations, A and B, consisted mainly of strains belonging to zymodeme MON-1, and the third population, C, mainly of MON-24 strains isolated from cutaneous leishmaniasis cases. Interestingly, a small group of strains appeared as a mixture of different populations and might be putative hybrids. Genetic migration was noticed among the two MON-1 populations, A and B, as well as between populations A and C. Due to its high discriminatory power MLMT could be also successfully applied for differentiating relapses or re-infection for patients suffering from multiple episodes of visceral leishmaniasis. | 18,755,285 |
Use of single cell gel electrophoresis assays for the detection of DNA-protective effects of dietary factors in humans: recent results and trends. | This article summarises the results of human dietary intervention trials employing the comet assay (single cell gel electrophoresis, SCGE), which have been published in the last few years (i.e., between 2005 and 2008) and describes new trends and developments as well as current problems concerning the design of intervention trials and the interpretation of the results. Most new studies were carried out with complex plant derived foods and juices; only a few were conducted with individual food constituents. With specific vegetables, for example with water cress and Brussels sprouts, potent antioxidant effects were observed; also coffee caused a protective effect and it is notable that it was more effective than consumption of a diet containing increased levels of fruits and vegetables. Interesting recent developments include the development of protocols which enable us to monitor protection towards genotoxic chemicals contained in the human diet, and it was shown in preliminary studies that alterations of the activities of drug metabolising enzymes by dietary factors lead to altered sensitivity of lymphocytes against DNA damage caused by certain dietary carcinogens. Another novel approach is the development of methods to monitor the effects of dietary factors on DNA repair. The development of protocols for experiments with exfoliated buccal cells is another potentially valuable innovation. The adequate experimental design of SCGE trials is still a matter of debate and the evaluation of the available data shows that there is an urgent need to develop guidelines concerning the number of participants, sampling periods, duration of trials, use of placebos, and definition of adequate run-in and wash-out phases. Recent studies showed that the results of dietary studies could be biased by factors such as age, sex, body mass index and life style habits and by seasonal effects. Another still unsolved problem is the interpretation of the results of SCGE trials in regard to potential beneficial health effects. The use of -omics techniques may contribute to provide mechanistic explanations in addition to conventional approaches (such as enzyme measurements). Information on health effects of dietary factors and on prevention of diseases related to DNA damage can also be obtained in experiments with animals, using SCGE to detect decreases in DNA damage in inner organs. | 18,755,290 |
Expression of genes involved in sumoylation in the Drosophila germline. | Post-translational modification of proteins by the covalent addition of small ubiquitin-related modifier (SUMO) proteins has been reported to regulate a wide range of cellular processes. However, the spatiotemporal expression pattern of genes encoding the sumoylation machinery during development is largely unknown. Here, we report the expression of five sumoylation genes, Uba2, Aos1, smt3, Ulp1, and lesswright (lwr), in the Drosophila germline. Transcripts from all five genes were detected throughout the early embryo by whole-mount in situ hybridization, while they were predominantly expressed in the germline progenitors, or pole cells, in late stage embryos. These genes were also expressed in the germline during oogenesis and spermatogenesis. Finally, we found that SUMO protein was enriched in the nuclei of pole cells and gametogenic cells. Given that a large fraction of SUMO substrates are nuclear proteins, these data suggest that sumoylation is highly active in the germline. Our data provide a basis for understanding how sumoylation regulates germline development. | 18,755,298 |
Nutritional issues in long-term care. | Because long-term care residents often have chronic illnesses and complex care regimens, nutritional issues are common in these populations. Furthermore, management is complicated because some residents are terminally ill and under palliative care treatment plans that allow for dehydration and low oral intake. As a result, the medical management of nutrition is complex and challenging for medical providers caring for residents of nursing homes, assisted living facilities, and other long-term care settings. Quality nutritional practice in long-term care involves careful assessment of barriers to adequate nutrition; reduction of risk factors; attention to specialized diets, food presentation, and supplements, when appropriate; awareness of the importance of psychosocial and environmental issues; and consideration of the role of medication both as a cause and a therapeutic adjunct. Optimal practice at a facility level would involve a systematic approach to applying the best evidence-based approaches, with a focus on individualizing each resident's nutritional management. | 18,755,420 |
Audience response systems: technology to engage learners. | An audience response system (ARS) provides a means of infusing interaction into a traditional didactic lecture format, enhancing student attention and learning. It can be used in a variety of ways, with both large and small audiences, to evaluate participants' knowledge, attitudes, and opinions or to verify student attendance at a lecture. The technology of ARS has markedly improved over the years, resulting in systems that are less costly and easier to use. Commercial systems that can be rented or purchased as well as local systems that can be downloaded free via the Internet are available. In this essay, the author reviews the components of an ARS, the history of ARS, educational outcomes related to ARS use, the benefits and limitations of ARS, tips for using an ARS, and current developments in ARS. | 18,755,440 |
South African farm workers' interpretation of risk assessment data expressed as pictograms on pesticide labels. | Pesticide companies and regulators in developing countries use the United Nations Food and Agricultural Organization (FAO) recommended pictograms on pesticide labels to communicate risk information based on toxicological and environmental risk assessment data. The pesticide label not only is often the only access people have to pesticide risk information, but also in many countries is a legally binding document. As a result of the crucial role pesticide labels play in protecting health and the environment and as a legal instrument, pictograms are used to overcome literacy challenges in transmitting pesticide risk information. Yet, this risk communication tool is often prone to misinterpretations of the risk information which results in hazardous exposures to pesticides for farm workers and end-users generally. In this paper, results are presented from a study with 115 farm workers on commercial vineyards in the Western Cape, South Africa, assessing their interpretations of 10 commonly used pictograms. A standardized questionnaire based on four commonly used pesticide labels was administered. Overall, 50% or more of the study farm workers had misleading, incorrect and critically confused interpretations of the label pictograms. Interpretations often reflected farm workers' social and cultural frames of reference rather than the technically intended risk information. For example, the pictogram indicating a pesticide's toxicity requires boots must be worn, evoked interpretations of "dangerous to pedestrians" and "don't walk through pesticides". Furthermore, there was a gender variation in pictogram comprehension whereby males generally had more correct interpretations than females. This is a result both of a lack of training for women who are assumed to not work with pesticides, as well as a lack of pictograms relevant for female exposures. These findings challenge the viability of the United Nations current initiative to globally harmonize pictograms used on all chemical labels under the new Globally Harmonized System for the Classification and Labelling of Chemicals (GHS). Particularly as the GHS pictograms were not piloted prior to adoption of the system and represent complex risk assessment data such as chronic hazards. Public health and pesticide policy, backed by relevant research, need to address developing applicable and effective pesticide risk communication tools, particularly for developing country populations. Merely providing risk assessment derived information in a pictogram does not ensure that an end-user will interpret the message as intended and be able to make risk decisions which mitigate risks from exposures to pesticides or chemicals in general. | 18,755,451 |
Measurement of nicotine in household dust. | An analytical method of measuring nicotine in house dust was optimized and associations among three secondhand smoking exposure markers were evaluated, i.e., nicotine concentrations of both house dust and indoor air, and the self-reported number of cigarettes smoked daily in a household. We obtained seven house dust samples from self-reported nonsmoking homes and 30 samples from smoking homes along with the information on indoor air nicotine concentrations and the number of cigarettes smoked daily from an asthma cohort study conducted by the Johns Hopkins Center for Childhood Asthma in the Urban Environment. House dust nicotine was analyzed by isotope dilution gas chromatography-mass spectrometry (GC/MS). Using our optimized method, the median concentration of nicotine in the dust of self-reported nonsmoking homes was 11.7 ng/mg while that of smoking homes was 43.4 ng/mg. We found a substantially positive association (r=0.67, P<0.0001) between house dust nicotine concentrations and the numbers of cigarettes smoked daily. Optimized analytical methods showed a feasibility to detect nicotine in house dust. Our results indicated that the measurement of nicotine in house dust can be used potentially as a marker of longer term SHS exposure. | 18,755,452 |
Behavioral therapy for urinary incontinence in India. | To ascertain the prevalence of urinary incontinence in a sample of women from northern India, and the impact of behavioral therapy to treat its occurrence and severity. A randomized controlled trial conducted from 2005-2006 to test the null hypothesis that behavioral therapy would not have an effect on urinary incontinence. Following a prevalence study, a total of 198 women with urinary incontinence were randomized into 2 groups: an intervention group (behavioral therapy) and a control group (no therapy). The prevalence of urinary incontinence was 11.6%. After an 8-month follow-up period, 41 women (52.5%) in the intervention group had become continent, and severity had shifted from severe to mild in 19 women (24.4%). In contrast, 11 women (12.8%) in the control group had become continent. In the intervention group, mean daytime voiding frequency decreased from 9.56 to 7.64, mean nighttime voiding frequency decreased from 1.45 to 0.69, and mean episodes of urine leakage decreased from 1.97 to 0.23. Behavioral therapy was effective in treating urinary incontinence, particularly in women with mild and moderate incontinence. | 18,755,458 |
Neuromuscular neutral zones response to cyclic lumbar flexion. | The in vivo lumbar spine of the anaesthetized feline was subjected to passive cyclic anterior flexion-extension at 0.25 Hz and 40 N peak load for cumulative 60 min duration. Displacement (or displacement neuromuscular neutral zones-DNNZ) and tension (or tension neuromuscular neutral zones-TNNZ) at which reflexive EMG activity from the multifidi muscles was initiated and terminated were recorded, for single-test cycles, before and for 7h after cyclic loading. Displacement and tension NNZs increased significantly after loading. The displacement NNZs decreased exponentially to near baseline by the 7th hour of rest. The tension NNZs, however, decreased to below the baseline by the 2nd to 3rd hour after loading and continued decreasing into the 7th hour. Peak EMG significantly decreased (49-57%) to below the baseline immediately after loading and then exponentially increased, exceeding the baseline by the 2nd to 3rd hour and reaching 33-59% above baseline by the 7th hour. EMG median frequency decreased after loading and then exceeded the baseline after the 3rd hour, indicating initial de-recruitment, followed by recruitment of new motor units. These findings suggest that the lumbar spine was exposed to instability for 2-3h after cyclic loading, due to concurrent laxity of the viscoelastic tissues and deficient muscular activity. A delayed neuromuscular compensation mechanism was found to exist, triggering the musculature significantly earlier and at higher magnitude than baseline, while the viscoelastic tissues were still lax. Thus, it is suggested that prolonged cyclic loading may compromise lumbar stability during the immediate 2-3h post-loading, increasing the risk of injury. | 18,755,463 |
Interferon gamma is not required for recurrent herpetic stromal keratitis. | The role that interferon-gamma (IFNgamma) plays during herpetic stromal keratitis (HSK) has not been definitively determined. In primary HSK most reports suggest that IFNgamma may help control viral replication and contribute to corneal pathology. However, its role in recurrent HSK has not been directly addressed. The present study addresses its role in recurrent HSK by comparing HSK in latently infected normal and IFNgamma gene knockout (GKO) on the C57BL/6 background. We initially evaluated HSK following primary infection and observed that GKO mice had higher tear film virus titers, but virtually identical ocular disease as normal mice. In contrast, following reactivation of latent virus, GKO mice had a greater incidence and severity of opacity, neovascularization, and blepharitis. Interestingly, the incidence of reactivation after UV-B exposure was equivalent in GKO and normal mice, but virus shedding was increased in the GKO groups. We also observed diminished delayed-type hypersensitivity responses in GKO mice, as expected. These data indicate that IFNgamma is important for the control of virus replication in both primary and recurrent ocular HSV infection in C57BL/6 mice. The enhanced recurrent disease seen in GKO mice may be the result of increased viral titers and persistence in these mice which act to prolong the stimulation of an inflammatory response. | 18,755,490 |
Animal models of anxiety: do I need multiple tests? | The combination of cutting-edge molecular technology and high-throughput phenotyping tools will not bring the expected contribution to the pre-clinical study of anxiety if not paralleled by an increase in our capacity to interpret behavioral data. Here, previous views about the multidimensional nature of emotional behaviors will be expanded and the psychological meaning and behavioral overlaps of widely used anxiety tests such as the open field, elevated plus maze and light-dark box will be discussed. It is proposed here that short-term, intra-individual variations in emotionality, although normally overlooked, constitute an important factor in the study of anxiety and can lead to unreliable estimates of the similarities between tests. The physical integration of different current tests in one single apparatus, in such a way that the emotional status of an animal becomes assessable through a series of distinct tasks, could contribute to increase reliability, rapidity and comprehensiveness in behavioral testing. | 18,755,516 |
The use of scoring rubrics to determine clinical performance in the operating suite. | This research evolved out of the need to examine the validity and inter-rater reliability of a set of performance-based scoring rubrics designed to measure competencies within the operating suite. Both holistic and analytical rubrics were developed aligned to the ACORN Standard [Australian College of Operating Room Nurses Standard NR4, 2004. ACORN Competency Standards for Perioperative Nurses: Standard NR4: The Instrument Nurse in the Perioperative Environment. Australian College of Operating Room Nurses Ltd, Adelaide] and underpinned by the Dreyfus model (1981). Three video clips that captured varying performance of nurses performing as instrument nurses in the operating suite were recorded and used as prompts by expert raters, who judged the performance using the rubrics. The study found that the holistic rubrics led to more consistent judgments than the analytical rubrics, yet the latter provided more diagnostic information for intervention purposes. Despite less consistency, the Analytical Observation Form had sufficient construct validity to satisfy the requirements of criterion referencing as determined by the Item Separation Index (Rasch, 1960), including high internal consistency and greater inter-rater reliability when average ratings were used. The study was an empirical investigation of the use of concomitant Analytical and Holistic Rubrics to determine various levels of performance in the operating suite including inter-rater reliability. The methodology chosen was theoretically sound and sufficiently flexible to be used to develop other competencies within the operating suite. | 18,755,529 |
Acaricidal activity of limonene, limonene oxide and beta-amino alcohol derivatives on Rhipicephalus (Boophilus) microplus. | Limonene, limonene oxide and eight beta-amino alcohol derivatives obtained by synthesis were investigated for the effect on egg hatchability and mortality rates of newly hatched larvae of the cattle tick Rhipicephalus (Boophilus) microplus. At the doses between 10 microg/ml and 2.5 microg/ml all the compounds were highly lethal to the larvae and some of them showed activity at lower concentrations. The effect on the eggs hatchability was observed in all the treatments. | 18,755,549 |
Bolstering confidence in obesity prevention and treatment counseling for resident and community pediatricians. | To assess whether equipping resident pediatricians and community pediatricians with both training and practical tools improves their perceived confidence, ease, and frequency of obesity-related counseling to patients. In 2005-2006, resident pediatricians (n = 49) and community pediatricians (n = 18) received training regarding three evidence-based obesity prevention/treatment tools and responded to pre- and post-intervention questionnaires. We analyzed changes in reported mean confidence, ease, and frequency of dietary, physical activity, and weight status counseling. Baseline scores of confidence, ease, and frequency of counseling were higher in community pediatricians than residents. Mean scores increased significantly in the combined group, among residents only, and trended towards improvement in the community pediatricians following the intervention. Means for "control" questions were unchanged. Training and tools for residents and community pediatricians improved their confidence, ease, and frequency of obesity-related counseling. This study demonstrates that when feasible and appropriate tools and training were provided through a simple intervention, physicians gained confidence and ease and increased their counseling frequency. The results here suggest that widespread implementation of such educational interventions for community practitioners and practitioners in training could change the way physicians counsel patients to prevent the often frustrating problem of childhood obesity. | 18,755,567 |
Design and synthesis of fluorescent SGLT2 inhibitors. | The design and synthesis of the first fluorophore-conjugated SGLT2 inhibitors is described. The mode of linking the fluorophore to the SGLT2 pharmacophore was found to be crucial in achieving optimum potency. Superior potency to phlorizin was provided by examples containing TAMRA, BODIPY, Cy3B and NBD fluorophores. | 18,755,586 |
Discovery of thieno[2,3-c]pyridines as potent COT inhibitors. | Evaluation of hit chemotypes from high throughput screening identified a novel series of 2,4-disubstituted thieno[2,3-c]pyridines as COT kinase inhibitors. Structural modifications exploring SAR at the 2- and 4-positions resulting in inhibitors with improved enzyme potency and cellular activity are disclosed. | 18,755,587 |
Structure-guided design of substituted aza-benzimidazoles as potent hypoxia inducible factor-1alpha prolyl hydroxylase-2 inhibitors. | We report the structure-based design and synthesis of a novel series of aza-benzimidazoles as PHD2 inhibitors. These efforts resulted in compound 22, which displayed highly potent inhibition of PHD2 function in vitro. | 18,755,588 |
[Interests of applied anthropology to oncology]. | From now on the introduction of social and human sciences studies in the field of oncology has not always been conclusive. This article aims to analyze the bounds that border the meeting and the understanding between physicians, patients and anthropologists. It also treats the problems due to the introduction of applied anthropology in the field of oncology and points up the interests and practical contributions that this disciplinary bring and could bring. | 18,755,645 |
Methane emissions by alpine plant communities in the Qinghai-Tibet Plateau. | For the first time to our knowledge, we report here methane emissions by plant communities in alpine ecosystems in the Qinghai-Tibet Plateau. This has been achieved through long-term field observations from June 2003 to July 2006 using a closed chamber technique. Strong methane emission at the rate of 26.2+/-1.2 and 7.8+/-1.1microg CH4 m-2h-1 was observed for a grass community in a Kobresia humilis meadow and a Potentilla fruticosa meadow, respectively. A shrub community in the Potentilla meadow consumed atmospheric methane at the rate of 5.8+/-1.3microg CH4 m-2h-1 on a regional basis; plants from alpine meadows contribute at least 0.13Tg CH4 yr-1 in the Tibetan Plateau. This finding has important implications with regard to the regional methane budget and species-level difference should be considered when assessing methane emissions by plants. | 18,755,657 |
Moving with the beat: heart rate and visceral temperature of free-swimming and feeding bluefin tuna. | Owing to the inherent difficulties of studying bluefin tuna, nothing is known of the cardiovascular function of free-swimming fish. Here, we surgically implanted newly designed data loggers into the visceral cavity of juvenile southern bluefin tuna (Thunnus maccoyii) to measure changes in the heart rate (fH) and visceral temperature (TV) during a two-week feeding regime in sea pens at Port Lincoln, Australia. Fish ranged in body mass from 10 to 21 kg, and water temperature remained at 18-19 degrees C. Pre-feeding fH typically ranged from 20 to 50 beats min(-1). Each feeding bout (meal sizes 2-7% of tuna body mass) was characterized by increased levels of activity and fH (up to 130 beats min(-1)), and a decrease in TV from approximately 20 to 18 degrees C as cold sardines were consumed. The feeding bout was promptly followed by a rapid increase in TV, which signified the beginning of the heat increment of feeding (HIF). The time interval between meal consumption and the completion of HIF ranged from 10 to 24 hours and was strongly correlated with ration size. Although fH generally decreased after its peak during the feeding bout, it remained elevated during the digestive period and returned to routine levels on a similar, but slightly earlier, temporal scale to TV. These data imply a large contribution of fH to the increase in circulatory oxygen transport that is required for digestion. Furthermore, these data oppose the contention that maximum fH is exceptional in bluefin tuna compared with other fishes, and so it is likely that enhanced cardiac stroke volume and blood oxygen carrying capacity are the principal factors allowing superior rates of circulatory oxygen transport in tuna. | 18,755,679 |
Iron-mediated aggregation and a localized structural change characterize ferritin from a mutant light chain polypeptide that causes neurodegeneration. | Nucleotide insertions in the ferritin light chain (FTL) polypeptide gene cause hereditary ferritinopathy, a neurodegenerative disease characterized by abnormal accumulation of ferritin and iron in the central nervous system. Here we describe for the first time the protein structure and iron storage function of the FTL mutant p.Phe167SerfsX26 (MT-FTL), which has a C terminus altered in sequence and extended in length. MT-FTL polypeptides assembled spontaneously into soluble, spherical 24-mers that were ultrastructurally indistinguishable from those of the wild type. Far-UV CD showed a decrease in alpha-helical content, and 8-anilino-1-naphthalenesulfonate fluorescence revealed the appearance of hydrophobic binding sites. Near-UV CD and proteolysis studies suggested little or no structural alteration outside of the C-terminal region. In contrast to wild type, MT-FTL homopolymers precipitated at much lower iron loading, had a diminished capacity to incorporate iron, and were less thermostable. However, precipitation was significantly reversed by addition of iron chelators both in vitro and in vivo. Our results reveal substantial protein conformational changes localized at the 4-fold pore of MT-FTL homopolymers and imply that the C terminus of the MT-FTL polypeptide plays an important role in ferritin solubility, stability, and iron management. We propose that the protrusion of some portion of the C terminus above the spherical shell allows it to cross-link with other mutant polypeptides through iron bridging, leading to enhanced mutant precipitation by iron. Our data suggest that hereditary ferritinopathy pathogenesis is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates. | 18,755,684 |
Promoting the formation of an active synthetase/tRNA complex by a nonspecific tRNA-binding domain. | Previous studies showed that valyl-tRNA synthetase of Saccharomyces cerevisiae contains an N-terminal polypeptide extension of 97 residues, which is absent from its bacterial relatives, but is conserved in its mammalian homologues. We showed herein that this appended domain and its human counterpart are both nonspecific tRNA-binding domains (K(d) approximately 0.5 microm). Deletion of the appended domain from the yeast enzyme severely impaired its tRNA binding, aminoacylation, and complementation activities. This N-domain-deleted yeast valyl-tRNA synthetase mutant could be rescued by fusion of the equivalent domain from its human homologue. Moreover, fusion of the N-domain of the yeast enzyme or its human counterpart to Escherichia coli glutaminyl-tRNA synthetase enabled the otherwise "inactive" prokaryotic enzyme to function as a yeast enzyme in vivo. Different from the native yeast enzyme, which showed different affinities toward mixed tRNA populations, the fusion enzyme exhibited similar binding affinities for all yeast tRNAs. These results not only underscore the significance of nonspecific tRNA binding in aminoacylation, but also provide insights into the mechanism of the formation of aminoacyl-tRNAs. | 18,755,686 |
Vibrio cholerae O1 from Accra, Ghana carrying a class 2 integron and the SXT element. | Vibrio cholerae O1 from a 2006 outbreak in Accra were commonly resistant to multiple antimicrobials and, in particular, to trimethoprim/sulfamethoxazole, drugs commonly used in the treatment of cholera. We sought to determine the genetic basis for trimethoprim/sulfamethoxazole resistance in outbreak isolates. Twenty-seven isolates from the outbreak were screened by PCR and sequencing for class 1 and 2 integrons and for the SXT element. Twenty-one of the 27 isolates examined, all from the Accra metropolitan area, carried both SXT, an integrated chromosomal element, and a class 2 integron bearing dfrA1, sat and aadA1 cassettes. All these isolates had identical random amplification of polymorphic DNA profiles and two of them also carried a class 1 integron. Most strains characterized carried multiple elements conferring resistance to trimethoprim. This suggests that trimethoprim/sulfamethoxazole should not be used empirically in cholera treatment. | 18,755,696 |
Tissues from routine pathology archives are suitable for microRNA analyses by quantitative PCR. | MicroRNAs have recently taken centre stage as short non-coding RNAs that regulate mRNA expression. To assess the feasibility of using microRNA techniques on routinely processed tissues, the accessibility of two representative microRNAs was examined by real-time quantitative PCR in 86 human formalin-fixed paraffin-embedded (FFPE) samples from liver, breast, bone marrow, lymphatic tissues and colon. Murine liver was used to analyse the influence of fixation time and different fixatives. High-quality microRNA was successfully extracted from routinely processed formalin-fixed tissues, resembling PCR amplification results from snap-frozen material analysed in parallel. While fixation time did not affect microRNA accessibility, non-buffered formalin or fixative supplements such as glutaraldehyde influenced PCR results. Storage of human tissues for up to 7 years did not cause a significant deterioration of microRNA. However, microRNA quality in human archival material following routine processing 10-20 years ago was decreased. Oxidation by ambient air during storage and fixation in non-buffered formalin is a possible reason for loss of microRNA quality. The assessment of microRNAs in readily obtained formalin-fixed paraffin-embedded samples is a highly promising tool in molecular pathology when similarly treated samples are analysed. Therefore, microRNA analyses will gain wider acceptance as an adjunct to morphological tissue assessment in routine pathology and retrospective studies. | 18,755,714 |
Failure of first-line eradication treatment significantly increases prevalence of antimicrobial-resistant Helicobacter pylori clinical isolates. | Helicobacter pylori infection is a major health problem worldwide, and effective eradication of the infection is mandatory. The efficacy of recommended eradication regimens is approximately 70%. To avoid treatment failure and the consequent development of secondary resistance(s), it is important to choose the most appropriate first-line treatment regimen. This choice should also be made based on the knowledge of the antimicrobial resistance peculiar to a given geographical area. We evaluated the prevalence of antimicrobial-resistant H pylori strains isolated from naive patients and from patients with previous unsuccessful treatments. This study examined 109 H pylori-infected subjects (Group 1) who had never received an eradication treatment and 104 H pylori-infected subjects (Group 2) who had failed one or more eradication treatments. Resistance to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MET) and levofloxacin (LEV) was determined using the epsilometer test. The significance of differences was evaluated by the chi2 test. The prevalence of antimicrobial resistance was 0% versus 3.1% to AMO, 0% versus 2% to TET, 27% versus 41.3% to MET (p<0.05), 18% versus 45.8% to CLA (p<0.05) and 3% versus 14.6% to LEV (p<0.05) in Group 1 vs Group 2, respectively. In Group 2, there was an increased prevalence of H pylori strains resistant to multiple antimicrobials. This study confirms the high prevalence of H pylori strains resistant to CLA and MET, and indicates that unsuccessful treatments significantly increase resistance. Choosing eradication regimens other than standard triple therapy as a first-line therapy should be advisable in areas with high primary antimicrobial resistance prevalence. | 18,755,715 |
Abatement by naringin of lomefloxacin-induced genomic instability in mice. | Lomefloxacin is a difluorinated quinolone antibacterial drug. It is widely used against infectious diseases including meningitis, those of the genitourinary and upper respiratory tracts, and skin infections. Lomefloxacin, like other fluoroquinolones, is mutagenic and the formation of reactive oxygen species appears to be responsible for this genomic instability. The anti-mutagenic effects of naringin, a grapefruit flavonone, against lomefloxacin-induced genomic instability in vivo were evaluated in mouse bone marrow cells by chromosomal aberration and micronucleus (MN) assays. Naringin was neither genotoxic nor cytotoxic in mice at doses equivalent to 5 or 50 mg/kg. Pre-treatment of mice with naringin significantly reduced lomefloxacin-induced chromosomal aberrations and the MN formation in bone marrow. The protective effect of naringin was found to be stronger at the higher dose, indicating the dose-dependent effect of naringin. Lomefloxacin induced marked biochemical alterations characteristic of oxidative stress, including enhanced lipid peroxidation and reduction in the reduced glutathione level. Prior administration of naringin ahead of lomefloxacin challenge ameliorated these biochemical markers. It is concluded that naringin has a protective role in the abatement of lomefloxacin-induced genomic instability that resides, at least in part, in its anti-radical effects. Thus, naringin might be a good alternative to reduce genotoxic risks associated with lomefloxacin therapy. | 18,755,759 |
Exposure to antipsychotics and risk of stroke: self controlled case series study. | To investigate the association between use of typical and atypical antipsychotic drugs and incidence of stroke in patients with and without dementia. Self controlled case series. UK based electronic primary care records in the general practice research database (GPRD). All patients registered in the database with a recorded incident stroke and at least one prescription for any antipsychotic drug before the end of 2002: 6790 eligible participants were identified and included in the final analysis. Rate ratio for stroke in periods of time exposed to antipsychotics compared with unexposed periods. Use of any antipsychotic drug was associated with a rate ratio for stroke of 1.73 (95% confidence interval 1.60 to 1.87): 1.69 (1.55 to 1.84) for typical antipsychotics and 2.32 (1.73 to 3.10) for atypical antipsychotics. In patients receiving any antipsychotic drug, the rate ratios were 3.50 (2.97 to 4.12) for those with dementia and 1.41 (1.29 to 1.55) for those without dementia. All antipsychotics are associated with an increased risk of stroke, and the risk might be higher in patients receiving atypical antipsychotics than those receiving typical antipsychotics. People with dementia seem to be at a higher risk of an associated stroke than people without dementia and use of antipsychotics should, when possible, be avoided in these patients. | 18,755,769 |
In vivo birthdating by BAPTISM reveals that trigeminal sensory neuron diversity depends on early neurogenesis. | Among sensory systems, the somatic sense is exceptional in its ability to detect a wide range of chemical, mechanical and thermal stimuli. How this sensory diversity is established during development remains largely elusive. We devised a method (BAPTISM) that uses the photoconvertible fluorescent protein Kaede to simultaneously analyze birthdate and cell fate in live zebrafish embryos. We found that trigeminal sensory ganglia are formed from early-born and late-born neurons. Early-born neurons give rise to multiple classes of sensory neurons that express different ion channels. By contrast, late-born neurons are restricted in their fate and do not form chemosensory neurons expressing the ion channel TrpA1b. Accordingly, larvae lacking early-born neurons do not respond to the TrpA1b agonist allyl isothiocyanate. These results indicate that the multimodal specification and function of trigeminal sensory ganglia depends on the timing of neurogenesis. | 18,755,773 |
Genes associated with membrane-initiated signaling of estrogen and energy homeostasis. | During the reproductive cycle, fluctuations in circulating estrogens affect multiple homeostatic systems controlled by hypothalamic neurons. Two of these neuronal populations are arcuate proopiomelanocortin and neuropeptide Y neurons, which control energy homeostasis and feeding. Estradiol modulates these neurons either through the classical estrogen receptors (ERs) to control gene transcription or through a G protein-coupled receptor (mER) activating multiple signaling pathways. To differentiate between these two divergent ER-mediated mechanisms and their effects on homeostasis, female guinea pigs were ovariectomized and treated systemically with vehicle, estradiol benzoate (EB) or STX, a selective mER agonist, for 4 wk, starting 7 d after ovariectomy. Individual body weights were measured after each injection day for 28 d, at which time the animals were euthanized, and the arcuate nucleus was microdissected. As predicted, the body weight gain was significantly lower for EB-treated females after d 5 and for STX-treated females after d 12 compared with vehicle-treated females. Total arcuate RNA was extracted from all groups, but only the vehicle and STX-treated samples were prepared for gene microarray analysis using a custom guinea pig gene microarray. In the arcuate nucleus, 241 identified genes were significantly regulated by STX, several of which were confirmed by quantitative real-time PCR and compared with EB-treated groups. The lower weight gain of EB-treated and STX-treated females suggests that estradiol controls energy homeostasis through both ERalpha and mER-mediated mechanisms. Genes regulated by STX indicate that not only does it control neuronal excitability but also alters gene transcription via signal transduction cascades initiated from mER activation. | 18,755,790 |
Modulation of Runx2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer. | The transcription factors Runx2 and estrogen receptor-alpha (ERalpha) are involved in numerous normal and disease processes, including postmenopausal osteoporosis and breast cancer. Using indirect immunofluorescence microscopy and pull-down techniques, we found them to colocalize and form complexes in a ligand-dependent manner. Estradiol-bound ERalpha strongly interacted with Runx2 directly through its DNA-binding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2's amino acids 417-514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ERalpha's DNA-binding domain. As a consequence of the interaction, Runx2's transcriptional activation activity was strongly repressed, as shown by reporter assays in COS7 cells, breast cancer cells, and late-stage MC3T3-E1 osteoblast cultures. Metaanalysis of gene expression in 779 breast cancer biopsies indicated negative correlation between the expression of ERalpha and Runx2 target genes. Selective ER modulators (SERM) induced ERalpha-Runx2 interactions but led to various functional outcomes. The regulation of Runx2 by ERalpha may play key roles in osteoblast and breast epithelial cell growth and differentiation; hence, modulation of Runx2 by native and synthetic ERalpha ligands offers new avenues in selective ER modulator evaluation and development. | 18,755,791 |
Transcriptome response of enterocytes to dietary lipids: impact on cell architecture, signaling, and metabolism genes. | Intestine contributes to lipid homeostasis through the absorption of dietary lipids, which reach the apical pole of enterocytes as micelles. The present study aimed to identify the specific impact of these dietary lipid-containing micelles on gene expression in enterocytes. We analyzed, by microarray, the modulation of gene expression in Caco-2/TC7 cells in response to different lipid supply conditions that reproduced either the permanent presence of albumin-bound lipids at the basal pole of enterocytes or the physiological delivery, at the apical pole, of lipid micelles, which differ in their composition during the interprandial (IPM) or the postprandial (PPM) state. These different conditions led to distinct gene expression profiles. We observed that, contrary to lipids supplied at the basal pole, apical lipid micelles modulated a large number of genes. Moreover, compared with the apical supply of IPM, PPM specifically impacted 46 genes from three major cell function categories: signal transduction, lipid metabolism, and cell adhesion/architecture. Results from this first large-scale analysis underline the importance of the mode and polarity of lipid delivery on enterocyte gene expression. They demonstrate specific and coordinated transcriptional effects of dietary lipid-containing micelles that could impact the structure and polarization of enterocytes and their functions in nutrient transfer. | 18,755,805 |
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