Effect of the Organochlorine Pesticide Endosulfan on GnRH and Gonadotrope Cell Populations in Fish Larvae

Endocrine-disrupting chemicals can influence the hypothalamus-pituitary-gonad axis and possibly affect reproduction in vertebrates. We analyzed the effect of 30-day endosulfan (ES) exposure in sexually undifferentiated larvae of the cichlid fish Cichlasoma dimerus. The number, area, mean cytoplasmic and nuclear diameter, and mean cytoplasmic optical density of gonadotropin-releasing hormone (GnRH) I, II, and III immunoreactive (ir-) neurons and β follicle-stimulating hormone (βFSH) ir-cells were measured. Animals exposed to the highest ES concentration (0.1?μg/l) showed a decrease in GnRH I nucleus/cytoplasm area ratio upon exposure. Nuclear area and mean nuclear diameter of βFSH ir-cells was higher in ES treated fish. βFSH nucleus/cytoplasm area ratio was high in exposed animals, and animals exposed to 0.1?μg/l ES showed smaller mean cytoplasmic optical density. These findings suggest that ES affects GnRH I and βFSH protein synthesis/release. However, these responses seem to be insufficient to affect gonadal differentiation at this stage of development.     

Reference intervals and percentiles for carotid‐femoral pulse wave velocity in a healthy population aged between 9 and 87 years

There is little information regarding age‐related reference intervals (RIs) of carotid‐femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year‐to‐year percentile curves and body‐height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9–87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age‐related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age‐specific (year‐to‐year) percentile curves that were defined using the standard normal distribution. Age‐specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height‐related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years.     

Membrane activity of an amphiphilic alpha-helical membrane-proximal cytoplasmic domain of the MoMuLV envelope glycoprotein

In the Moloney murine leukemia virus (MoMuLV) envelope glycoprotein (Env) we identified a membrane-proximal cytoplasmic domain (residues 598-616) that facilitates the Env incorporation into virions and Env-mediated fusion [Rozenberg, Y., Conner, J., Aguilar-Carreno, H., Chakraborti, S., Dimiter, D.S., Anderson, W.F., 2008. Viral entry: membrane-proximal cytoplasmic domain of MoMuLV envelope tail facilitates fusion. In the same issue. (accompanying paper)]. By biophysical methods (CD, EPR) a corresponding peptide (membrane-proximal peptide, 598-616) was demonstrated to form a membrane-parallel amphiphilic alpha-helix in the presence of membranes. Electrophysiological studies with planar bilayers and liposomes indicate that the membrane-proximal peptide is membrane destabilizing. This peptide and the fusion peptide from the MoMuLV transmembrane (TM) ectodomain were tested for their effect on the bilayer for hexagonal phase transition temperature of dipalmitoleoylphosphatidylethanolamine (T(H)). Importantly, the external fusion peptide and the internal membrane-proximal peptides of MoMuLV env exert opposite effects on membrane curvature. The fusion peptide lowers T(H) while the membrane proximal peptide raises it. These effects on T(H) correlate with the ability of these peptides to induce lipid mixing in large unilamellar vesicles composed of dioleoylphosphatidylethanolamine: dioleoylphosphatidylcholine:cholesterol (1:1:1 mol). When added externally to preformed liposomes, the N-terminal fusion peptide promotes lipid mixing while the cytoplasmic membrane-proximal peptide inhibits this effect. These finding indicate a possible mechanism by which the membrane-proximal domain in MoMuLV Env may affect the formation of membrane fusion intermediates.     

Reduced elastic mismatch achieved by interposing vein cuff in expanded polytetrafluoroethylene femoral bypass decreases intimal hyperplasia

BACKGROUND: Wall shear stress, arterial wall elasticity, and intimal hyperplasia are related. The aim of this study was to investigate the in vitro mechanical properties of ovine femoral arteries, jugular veins, and expanded polytetrafluoroethylene conduits, and to evaluate postoperative intimal hyperplasia. METHODS: Arterial, venous, and ePTFE mechanical properties were studied in a circulating loop at isobaric systemic pressures. Histological studies of intimal hyperplasia in ePTFE-bypassed femoral arteries with and without Miller cuffs were performed at the 40th and 120th day. RESULTS: The incremental elastic modulus of veins was significantly higher than that of femoral arteries (P < 0.05), but significantly lower than that of ePTFE graft conduits (P < 0.05). Intimal hyperplasia was significantly less in Miller-cuff-bypassed arteries both at the 40th and 120th day (P < 0.01). CONCLUSIONS: The Miller cuff acts as a mechanical adapter enhancing wall shear stress and the elastic matching between ePTFE and the native artery, resulting in an early decrease of intimal hyperplasia.     

Interaction between gonadal steroids and neuroimmune system in acute experimental autoimmune encephalomyelitis (EAE) in Wistar rats

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS mediated by autoreactive T lymphocytes directed against myelin antigens. Since neuroendocrine-immune dysfunction appears to contribute to the pathogenesis of autoimmune diseases, the present work was designed to study the effect of changes in the endocrine system on the development of acute EAE and the immune response against myelin basic protein (MBP). Intact and sham males and intact female Wistar rats showed the most severe clinical symptoms (acute period) 12-14 days post-inoculation (dpi). Then, they began gradually to recover, regaining the total ability to walk by 15-17 dpi. Male Wistar rats with altered levels of gonadal hormones by surgical castration showed an onset of the symptoms retarded 2-3 days with respect to the other EAE groups, showing neuropathological symptoms up to 27-28 dpi, and remaining with lower body weight even at 40 dpi. The castrated animals exhibited a specific delay in MBP-stimulated DTH reactivity that correlates with the delay in the onset of the clinical symptoms. Also significant lymphocyte proliferation to MBP was still present at 35 dpi that was absent in the sham group. The distribution of the IgG subclasses indicated that at 35 dpi castrated animals have a higher IgG2b/IgG1 ratio (35.1) in comparison to that presented by sham rats (4.8). Considering that at this time the castrated animals were not completely recuperated, these results could indicate an ongoing inflammatory immune response associated with Th1 activity in these animals. Also castrated animals developed antibodies to a diversity of MBP epitopes in comparison to sham rats, which presented a dominance of antibodies to MBP peptide p96-128. These results indicate that sex hormones levels regulate cell-mediated immunity and the specificity of anti-MBP antibodies related to the induction and development of acute EAE.