Effect of prolonged use of injectable hormonal contraceptives on blood pressure and body weight

The study was undertaken to determine the effect of prolonged use of injectable hormonal contraceptive on blood pressure and body weight in young women. Two hundred volunteers were selected for the purpose. Of them, one hundred and forty were taking injectable hormonal contraceptive, DMPA for 3 to 5 years uninterruptedly. Rest forty subjects served as control using no contraceptive steroid. Blood pressure, systolic as well as diastolic, was measured by sphygmomanometer. Body weight was measured by weighing machine. It was observed that there were insignificant (P>0.05) elevations of systolic and diastolic blood pressure from DMPA use. But body weight of the experimental subjects was significantly (P <0.05) increased in comparison to that of the control.     

Observed hand cleanliness and other measures of handwashing behavior in rural Bangladesh

Background  

We analyzed data from the baseline assessment of a large intervention project to describe typical handwashing practices in rural Bangladesh, and compare measures of hand cleanliness with household characteristics.     

In vivo study on the roles of cytochrome P450 enzymes for metabolism of 3,4-methylenedioxymethamphetamine (Ecstasy) in rats

Some major metabolic pathways of 3,4-methylenedioxymethamphetamine (MDMA) have been shown to be dependent on cytochrome P450 (CYP) isozymes by in vitro studies. The aim of this study was to clarify the roles of these CYP enzymes for in vivo metabolism of MDMA with respect to two pathways using rats: N-demethylation of MDMA to 3,4-methylenedioxyamphetamine (MDA) and O-demethylenation of MDMA to 3,4-dihydroxymethamphetamine (HHMA)followed by O-methylation to 4-hydroxy-3-methoxymethamphetamine (HMMA). Rats were pretreated with phenobarbital (PB, 80 mg/kg i.p.) or β-naphthoflavone (BNF, 80 mg/kg i.p.) once a day for 3 days before administration of MDMA (10 mg/kg i.p.). Metabolic changes were monitored by measuring the urinary excretion of MDMA and its metabolites. Twenty-four hours after MDMA administration, MDA in rat urine was significantly decreased by 43% and 70%, and HMMA was significantly increased by 33% and 64% in urine samples from PB-pretreated and BNF-pretreated rats, respectively, as compared with the control values. Testosterone 6β-hydroxylase (CYP3A), pentoxyresorufin O-dealkylase (CYP2B1), ethoxyresorufin O-deethylase (CYP1A1), and methoxyresorufin O-demethylase (CYP1A2) activities were increased 2–6 fold in both PB-pretreated and BNF-pretreated rat liver microsomes sampled at 24 h after MDMA administration as compared with the control values. These results suggest that PB-induced and BNF-induced CYP enzymes have inhibitory effects on N-demethylation of MDMA to MDA in vivo in rats. If HHMA is the precursor of HMMA in rats, there is a possibility that the O-demethylenation of MDMA to HHMA is increased by the induced CYP enzymes. The decreased urinary concentration of MDMA and very low percent recoveries of MDA, HMMA, and (4-hydroxy-3-methoxyphenyl)acetone (HMPA) in the inducer-pretreated groups suggest that other metabolic pathways of MDMA exist and are activated under the present experimental conditions.     

Effects of Nicotine on Bone Mass, Turnover, and Strength in Adult Female Rats

This study investigated the effects of nicotine, the chemical responsible for tobacco addiction, on bone and on serum mineral and calcitropic hormone levels in adult, female rats to help resolve a current controversy regarding the impact of nicotine on bone health. Seven-month-old rats received either saline (n = 12), low-dose nicotine (4.5 mg/kg/day, n = 2), or high-dose nicotine (6.0 mg/kg/day, n = 12) administered subcutaneously via osmotic minipumps for 3 months. Blood, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy for determination of serum mineral and hormonal concentrations, bone density (femora and vertebrae), bone turnover (tibiae), and bone strength (femora). The presence of nicotine in serum (111 +/- 7 and 137 +/- 10 ng/ml for the low- and high-dose nicotine groups, respectively) confirmed successful delivery of the drug via osmotic minipumps. Nicotine-induced treatment differences were not detected in serum calcium, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D. However, serum phosphorus and parathyroid hormone (PTH) were higher in rats treated with high-dose nicotine, and serum calcitonin was lower in rats treated with both high- and low-dose nicotine than in control rats. Nicotine treatment had no effect on tibial cancellous or cortical bone turnover or femoral bone mineral content (BMC) and density (BMD). Femoral ultimate load and vertebral BMC were lower in rats treated with high-dose nicotine than in control rats. We conclude that nicotine at serum concentrations 2.5-fold greater than the average in smokers has limited detrimental effects on bone in normal, healthy female rats.     

High incidence of false positives by a latex agglutination test for the diagnosis of Clostridium difficile associated colitis in compromised patients

Detection of Clostridium difficile cytotoxin using cell culture assays for the diagnosis of antibiotic-associated colitis has been used for over a decade. Because the methodology is time consuming and cumbersome, a recently introduced commercial latex agglutination (LA) kit has attracted much attention. We compared the sensitivity and specificity of this method with the cytotoxic assay (CTA) using diarrheal stools from 652 patients at a referral tertiary care center. Specimens from 71 (10.9%) patients were found positive with CTA and 98 (15%) by LA. Of these, 67 stools were positive by both methods. Four specimens showed cytotoxicity but were negative by LA. Of the 31 patient specimens that were positive by LA but negative by CTA, 22 were obtained from leukemic bone marrow transplant and four from renal transplant patients [corrected]. Sixteen of these patients had Giardia lamblia (four), Salmonella enteritidis (three), Blastocystis hominis (five), Rotavirus (two), and Shigella boydii (two) in their stools [corrected]. No significant organisms were found in the rest of the LA-positive and CTA-negative specimens.     

Protective effect of a novel,potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis

OBJECTIVE: To determine whether activation of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS) contributes to mortality rate, myocardial dysfunction, and cardiovascular collapse in a porcine model of sepsis induced by implantation of an infected clot. DESIGN: Prospective, random animal study. SETTING: Research laboratory at Rush Presbyterian St. Luke's Medical Center. SUBJECTS: Twenty pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure, sonomicrometer crystals in the left ventricle to measure short axis diameter, an ultrasonic flow meter to measure cardiac output, and catheters in the pulmonary artery and aorta to measure blood pressures and collect samples. INTERVENTIONS: By using a randomized study design, we administered either the novel potent PARS inhibitor PJ34 (10 mg/kg for 1 hr, 2 mg x kg(-1) x hr(-1) for 96 hrs) or vehicle to pigs immediately before intraperitoneal implantation of Escherichia coli 0111.B4 (2.3 +/- 0.1 x 10(10) colony-forming units/kg)-laden fibrin clots to produce peritonitis and bacteremia. MEASUREMENTS AND MAIN RESULTS: In vehicle-treated pigs, 12% survival was recorded at 24 hrs, whereas 83% and 66% survival was recorded in the PJ34-treated animals at 24 and 96 hrs, respectively (p <.05). PJ34 treatment attenuated bacteremia-induced increases in systemic and pulmonary vascular resistances. In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha. PJ34 treatment significantly attenuated this cytokine response. The formation of peroxynitrite and the activation of PARS were confirmed in hearts and lungs of the septic pigs by the immunohistochemical detection of nitrotyrosine and poly(ADP-ribose), respectively. Inhibition of PARS with PJ34 abolished poly(ADP-ribose) formation in septic animals. CONCLUSIONS: Treatment with a potent PARS inhibitor improved survival and cardiovascular status and attenuated an important mediator component of the inflammatory response in a lethal porcine model of sepsis.