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.     

Lactational state modifies alcohol pharmacokinetics in women

BACKGROUND: Given the physiological adaptations of the digestive system during lactation, the present study tested the hypothesis that lactation alters alcohol pharmacokinetics. METHODS: Lactating women who were exclusively breastfeeding a 2- to 5-month-old infant and 2 control groups of nonlactating women were studied. The first control group consisted of women who were exclusively formula-feeding similarly aged infants, whereas the other consisted of women who had never given birth. A within-subjects design study was conducted such that women drank a 0.4 g/kg dose of alcohol following a 12-hour overnight fast during one test session (fasted condition) or 60 minutes after consuming a standard breakfast during the other (fed condition). Blood alcohol concentration (BAC) levels and mood states were obtained at fixed intervals before and after alcohol consumption. RESULTS: Under both conditions, the resultant BAC levels at each time point were significantly lower and the area under the blood alcohol time curve were significantly smaller in lactating women when compared with the 2 groups of nonlactating women. That such changes were due to lactation per se and not due to recent parturient events was suggested by the finding that alcohol pharmacokinetics of nonlactating mothers, who were tested at a similar time postpartum, were no different from women who had never given birth. Despite lower BAC levels in lactating mothers, there were no significant differences among the 3 groups of women in the stimulant effects of alcohol. However, lactating women did differ in the sedative effects of alcohol when compared with nulliparous but not formula-feeding mothers. That is, both groups of parous women felt sedated for shorter periods of time when compared with nulliparous women. CONCLUSIONS: The systemic availability of alcohol was diminished during lactation. However, the reduced availability of alcohol in lactating women did not result in corresponding changes in the subjective effects of alcohol.     

Enhanced markers of oxidative stress, altered antioxidants and NADPH-oxidase activation in brains from Fragile X mental retardation 1-deficient mice, a pathological model for Fragile X syndrome

Fragile X syndrome is the most common form of inherited mental retardation in humans. It originates from the loss of expression of the Fragile X mental retardation 1 (FMR1) gene, which results in the absence of the Fragile X mental retardation protein. However, the biochemical mechanisms involved in the pathological phenotype are mostly unknown. The availability of the FMR1-knockout mouse model offers an excellent model system in which to study the biochemical alterations related to brain abnormalities in the syndrome. We show for the first time that brains from Fmr1-knockout mice, a validated model for the syndrome, display higher levels of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase activation, lipid peroxidation and protein oxidation than brains from wild-type mice. Furthermore, the antioxidant system is deficient in Fmr1-knockout mice, as shown by altered levels of components of the glutathione system. FMR1-knockout mice lacking Fragile X mental retardation protein were compared with congenic FVB129 wild-type controls. Our results support the hypothesis that the lack of Fragile X mental retardation protein function leads to a moderate increase of the oxidative stress status in the brain that may contribute to the pathophysiology of the Fragile X syndrome.     

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models

PURPOSE: Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. MATERIALS AND METHODS: In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. RESULTS: Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. CONCLUSIONS: Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.     

Sevoflurane breakdown produces flammable concentrations of hydrogen

BACKGROUND: Fires, explosions, and extreme heat production may occur when sevoflurane reacts with desiccated barium hydroxide lime. The identity of the flammable gas has not previously been published, although carbon monoxide, methanol, formaldehyde, and methyl formate have been identified in low quantities. METHODS: The authors reacted sevoflurane with excess desiccated barium hydroxide lime or soda lime at 55 degrees, 100 degrees, 200 degrees, 300 degrees, and 400 degrees C. Formaldehyde, methanol, sodium formate, and hexafluoroisopropanol were reacted with barium hydroxide lime at 300 degrees or 400 degrees C. The authors measured hydrogen production by gas chromatography with a thermal conductivity detector and calculated the molar yield of hydrogen produced. RESULTS: Up to 3 moles of hydrogen were produced per mole of sevoflurane degraded. Each mole of formaldehyde produced up to 2 moles of hydrogen at 400 degrees C. Formate and hexafluoroisopropanol produced up to 1 mole of hydrogen each at 400 degrees C. More than 2 moles of hydrogen were produced by methanol at 400 degrees C. Soda lime and barium hydroxide lime produced similar amounts of hydrogen from sevoflurane above 200 degrees C, but barium hydroxide lime produced more than soda lime at lower temperatures. The temperature above which large amounts of hydrogen were produced seemed to be 300 degrees C. CONCLUSIONS: Up to 3 moles of hydrogen are produced by the chemical reaction of sevoflurane with heated, desiccated absorbent. The high yield, ease of ignition, and low tissue solubility of hydrogen make it the most likely fuel in anesthesia machine fires due to the reaction of sevoflurane with desiccated absorbent.     

The endothelium modulates the arterial wall mechanical response to intra-aortic balloon counterpulsation: in vivo studies

Intra-aortic balloon pump (IABP) benefits could depend on variations in the cardiovascular biomechanical properties associated with blood flow-induced endothelium-dependent changes. However, if IABP results in changes in the peripheral artery biomechanics and if the endothelium plays a role in these potential changes remains unknown. The aim of this study is to characterize acute IABP effects on peripheral artery biomechanics in control and acute heart failure (AHF) states and the role of the endothelium in IABP effects on peripheral artery biomechanics. Pressure and diameter were recorded in sheep (n= 7) iliac arteries (IAs), before and during 1:2 IABP, during four states: (i) control with intact IA; (ii) AHF with intact IA; (iii) control with de-endothelialized (DE) (mechanical rubbing) IA; and (iv) AHF with DE IA. Arterial distensibility, elastic modulus, and conduit function (CF) (1/characteristic impedance) were calculated. The results of this study include: (i) during control conditions, IABP resulted in intact IA dilatation, stiffness reduction, and CF increase; (ii) AHF induction determined a reduction in intact IA diameter and CF, and a stiffness increase. These changes reverted during IABP; (iii) the increase in IA stiffness observed after DE remained unchanged during IABP; (iv) in DE IA, AHF did not result in diameter or stiffness changes; and (v) IABP during AHF did not associate changes in diameter or stiffness in the DE IA. In conclusion, during control and AHF states, IABP results in IA dilatation and stiffness reduction. The integrity of the endothelial layer would be critical for the IABP-associated changes in IA biomechanics.