Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane damage of Leydig cells in adult male mouse

Permethrin, a popular synthetic pyrethroid insecticide used to control noxious insects in agriculture, forestry, households, horticulture, and public health throughout the world, poses risks of environmental exposure. Here we evaluate the reproductive toxicity of cis-permethrin in adult male ICR mice that were orally administered cis-permethrin (0, 35, or 70 mg/kg d) for 6 wk. Caudal epididymal sperm count and sperm motility in the treated groups were statistically reduced in a dose-dependent manner. Testicular testosterone production and plasma testosterone concentration were significantly and dose-dependently decreased with an increase in LH, and a significant regression was observed between testosterone levels and cis-permethrin residues in individual mice testes after exposure. However, no significant changes were observed in body weight, reproductive organ absolute and relative weights, sperm morphology, and plasma FSH concentration after cis-permethrin treatment. Moreover, cis-permethrin exposure significantly diminished the testicular mitochondrial mRNA expression levels of peripheral benzodiazepine receptor (PBR), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc) and enzyme and protein expression levels of StAR and P450scc. At the electron microscopic level, mitochondrial membrane damage was found in Leydig cells of the exposed mouse testis. Our results suggest that the insecticide permethrin may cause mitochondrial membrane impairment in Leydig cells and disrupt testosterone biosynthesis by diminishing the delivery of cholesterol into the mitochondria and decreasing the conversion of cholesterol to pregnenolone in the cells, thus reducing subsequent testosterone production.     

Stereotactic navigation in oral and maxillofacial surgery

Navigation is an adjunct to existing surgical procedures. It is potentially useful in any procedure where it is possible to make a three-dimensional surgical plan from computed tomography (CT) or magnetic resonance imaging (MRI) data, but is not easy to translate this plan into surgical reality because of absolute limitations of access or lack of anatomical landmarks.     

Quercetin protects embryonic chicken spermatogonial cells from oxidative damage intoxicated with 3-methyl-4-nitrophenol in primary culture

Diesel exhaust particles (DEP) are considered to be one of the most important air pollutants. In this study, the protective effect of quercetin, an antioxidant flavonoid, on oxidative damage of testicular cells was studied by analysis of the intracellular antioxidant system of embryonic chickens after treatment with 3-methyl-4-nitrophenol (PNMC) derived from DEP. Testicular cells from 18-day-old embryos were cultured in serum-free McCoys’5A medium and challenged with PNMC (10⁻⁷ to 10⁻⁵ M) alone or in combinations with quercetin (1.0 μg/ml) for 48 h. Results showed that exposure to PNMC (10⁻⁵ M) induced condensed nuclei and vacuolated cytoplasm, a decrease in testicular cell viability and spermatogonial cell number. Exposure to PNMC induced lipid peroxidation by an elevation of thiobarbituric acid reactive substances as well as decreasing glutathione peroxidation activity and superoxide dismutase activity. However, simultaneous supplementation with quercetin restored these parameters to the similar levels as the control. PNMC is therefore concluded to have induced the oxidative stress of the spermatogonial cells, which can be attenuated by combined quercetin treatment. Our results support the therapeutic use of quercetin in the prevention or treatment of the reproductive toxicity by environmental toxicant PNMC.     

Elevated matrix metalloproteinase-9 and degradation of perineuronal nets in cerebrocortical multiple sclerosis plaques

Matrix metalloproteinases (MMPs) degrade extracellular matrix; MMP activity, particularly of MMP-9, is elevated in the white matter in multiple sclerosis (MS) patients. The cerebral cortical extracellular matrix includes perineuronal nets (PNs) that surround parvalbumin-positive neurons (PV-positive neurons) and are important for their function. We measured active and total MMP-9 levels in postmortem homogenates of demyelinated and nondemyelinated cerebral cortical regions from 9MS and 7 control cases and assessed Wisteria floribunda agglutin (WFA)-positive PNs in paraffin sections from 15 MS and 6 controls and PV-positive neurons in sections from 26 MS and 6 controls. Active MMP-9 levels were higher in demyelinated than in nondemyelinated or control cortex (p < 0.05). The area fraction positive for WFA was lower in demyelinated than nondemyelinated MS or control cortex; the latter difference was significant (p < 0.05). Most PV-positive neurons in demyelinated but not intact cortex lackeda PN, and some showed perikaryal phosphorylated neurofilament protein accumulation. Loss of WFA-labeled PNs was not associated with reduced PV-positive neurons numbers. Thus, elevated MMP-9 in cortical plaques is associated with loss of PNs; PV-positive neurons are preserved but show abnormal neurofilament accumulations. Matrix metalloproteinase-mediated degradation of PNs in cortical plaques may, therefore, contribute to neuronal dysfunction and degeneration in MS patients.     

A life-threatening complication of the arterial tourniquet in Timothy syndrome

An infant with Timothy syndrome, a congenital syndrome resulting in a long QT interval and high risk of death in childhood, is presented along with his perioperative management. Characteristic life-threatening arrhythmias thought to be caused by excess sympathetic stimulation secondary to an arterial tourniquet are described.     

Indomethacin inhibits the secretion of inhibin and oestradiol-17 beta stimulated by pregnant mare serum gonadotrophin in the immature female rat.

The involvement of prostaglandins (PGs) in the regulation of inhibin and oestradiol-17 beta secretion from the ovary was studied by determining the effects of indomethacin and/or pregnant mare serum gonadotrophin (PMSG) on the levels of ovarian hormones in immature female rats. An increase in serum and ovarian levels of inhibin and oestradiol-17 beta was observed with a reciprocal reduction in serum follicle-stimulating hormone (FSH) levels from within 26 to 50 h after a single injection of 5 IU PMSG (s.c.) when the rats were 26 days of age. Administration of indomethacin to suppress PGs synthesis, simultaneously with PMSG, resulted in a substantial reduction in the levels of ovarian PGF2 alpha and serum inhibin and oestradiol-17 beta, which were both enhanced by PMSG treatment, 24 h after treatment with drugs. Indomethacin also reduced the basal serum level of inhibin. In the indomethacin-treated animals, the serum level of FSH was significantly increased regardless of the treatment with PMSG, indicating that the negative feedback regulation between FSH and inhibin is operating in these animals. These results demonstrate the inhibitory effects of indomethacin on PMSG-enhanced inhibin and oestradiol-17 beta production, suggesting that PGs play a regulatory role in the secretion of inhibin and oestradiol-17 beta from the gonadotrophin-stimulated ovary.