Lyn Batia

Magnesium sulfate effectively reduces blood pressure in an animal model of preeclampsia

Objective. We tested the ability of magnesium sulfate to reduce hypertension and neonatal growth retardation in an animal model of preeclampsia. Study design. On day 17 of pregnancy, osmotic minipumps were inserted subcutaneously to continuously deliver either vehicle (saline control group), or N-nitro-l-arginine methyl ester (L-NAME) (50 mg/kg/day), or L-NAME (50 mg/kg/day) in combination with magnesium sulfate (60 mg/kg/day). Prior to insertion, blood pressure and heart rate were monitored with a pneumatic tail cuff device. Blood pressure measurements were repeated on days 18, 20, and 21 of pregnancy. Blood was obtained on days 17 and 21, along with urine, to assess magnesium levels and degree of proteinuria. Pups were weighed and measured at 48 hours postpartum. Results. Rats receiving L-NAME developed hypertension within 24 hours of implantation (108 ± 3.9 vs. 123 ± 3.4 mmHg, p < 0.05). Magnesium sulfate, given along with L-NAME did not prevent mean blood pressure from increasing, but reduced it by day 21 compared to L-NAME given alone (107 ± 3.4 vs. 122 ± 8.7 mmHg, respectively, p < 0.05). Magnesium sulfate reduced neonatal growth retardation by improving the weight of the pups compared to pups from maternal rats given L-NAME alone (6.1 ± 0.1 vs. 5.2 ± 0.3 grams, respectively, p < 0.05). Conclusion. Maternal magnesium sulfate reduces blood pressure and increases neonatal size compared to L-NAME without magnesium. These findings support a beneficial effect of magnesium in preeclampsia.

Stimulation of murine intestinal secretion by daily genistein injections: gender-dependent differences.

Background/Aims: The effect of daily injections with genistein (naturally occurring phytoestrogen) on intestinal chloride (Cl-) secretion was measured with Ussing chamber short circuit current (Isc, µA/cm2), in C57BL/6J male and female mice, using 600 mg/kg genistein/day (600G), 300 mg/kg genistein/day (300G), 150 mg/kg genistein/day (150G) or genistein-free vehicle control (0G) for 1- or 2-weeks. Methods and Results: Injecting with 600G elicited significant increases in basal Isc in females after 1-week (ñ70 µA/cm2, n=15, p < 0.05) and in males after 2-weeks (ñ80 µA/cm2, n=5, p < 0.05) compared to their 0G counterparts. Chloride-free ringer significantly reduced basal Isc by 65% in 600G males and 72% in 600G females, suggesting that Cl- was the major anion comprising the genistein-stimulated secretion. The forskolin-stimulated (10 µM) Isc was significantly inhibited by the CFTR chloride channel inhibitors, glibenclamide (500 µM) and CFTRinh-172 (100 µM) in 600G males and females, suggesting some contribution by genistein-dependent CFTR-mediated Cl- secretion. We found no associated changes in intestinal morphology, nor change in total CFTR protein with 600G. There was a 5% increase in apical/subapical ratio in 600G males compared to controls (no change in females). Conclusion: These data suggest that male and female mice both exhibit increased Cl- secretion with 600G, however, the mechanisms mediating this are gender-dependent.

Genistein Induces Estrogen-Like Effects in Ovariectomized Rats but Fails to Increase Cardiac GLUT4 and Oxidative Stress

This study aimed to determine whether a 2-week genistein treatment induced estrogen-like effects in ovariectomized (OVX) Sprague-Dawley rats, after 2 weeks of subcutaneous genistein injections (250 mg/kg of body weight/day). Uterine weight, uterine-to-body weight ratio, femur weight, and femur-to-body weight ratio were all significantly increased with genistein in OVX rats. Body weight was significantly decreased with genistein in OVX rats. Genistein had no effect on the weights of heart, heart-to-body ratio, and fat pad but significantly decreased heart rate and pulse pressure. Genistein had no effect on cardiac GLUT4 protein, oxidative stress, plasma glucose, nonesterified fatty acids, or low-density lipoprotein levels; however, plasma insulin levels were significantly increased. Our results show that a 2-week genistein treatment produced favorable estrogen-like effects on some physical and physiological characteristics in OVX rats. However, based on our experimental conditions, the effects of genistein were not associated with changes in cardiac GLUT4 or oxidative stress.

Effect of gestational ethanol exposure on parvalbumin and calretinin expressing hippocampal neurons in a chick model of fetal alcohol syndrome

Fetal alcohol syndrome (FAS), a condition occurring in some children of mothers who have consumed alcohol during pregnancy, is characterized by physical deformities and learning and memory deficits. The chick hippocampus, whose functions are controlled by interneurons expressing calcium-binding proteins parvalbumin (PV) and calretinin (CR), is involved in learning and memory mechanisms. Effects on growth and development and hippocampal morphology were studied in chick embryos exposed to 5% and 10% ethanol volume/volume (vol/vol) for 2 or 8 days of gestation. There was a significant dose-dependent reduction (P<.05) in body weight and mean number per section of PV and CR expressing hippocampal neurons in ethanol-exposed chicks, without alterations in neuronal nuclear size or hippocampal volume, compared appropriate controls. Moreover, when chicks exposed to 5% ethanol for 2 and 8 days of gestation were compared, no significant differences were found in body parameters or neuronal counts. Similarly, exposure to 10% ethanol did not induce any significant changes in chicks exposed for 2 or 8 gestational days. Thus, these results suggest that gestational ethanol exposure induces a reduction in the mean number per section of PV and CR expressing hippocampal neurons, and could be a possible mechanism responsible for learning and memory disorders in FAS.