Species- and sex-specific variations in binding of ochratoxin A by renal proteins in vitro

The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and induces renal fibrosis in pigs. Furthermore, OTA has been associated with the development of renal tumors and nephropathies in humans. Large species- and sex-differences are observed in sensitivity toward OTA-mediated toxicity and carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the reasons for the observed species- and sex-specificities are known. This paper investigated variations in OTA handling viz binding to renal proteins which could possibly explain the observed differences in OTA susceptibility in vivo and in vitro. The results obtained via a modification of a standard receptor-binding assay demonstrated the presence of at least one homogeneous binding component in renal cortical homogenates from pig, mouse, rat and humans. This component was shown to bind OTA in a specific and saturable manner. A range of compounds selected for their affinity for steroid receptors and/or for various known organic anion transporters were employed in a competition assay to answer the question whether this homogenous OTA binding component represents a steroid-like receptor component or one of the known organic anion transporters of the kidney. Although many of the compounds were able to compete with OTA for protein-binding, the competition patterns displayed a distinct species specificity and did not correspond to the competition patterns associated with presently known organic anion transporters of the kidney in the mouse, rat or human. The data thus suggests the presence of a new organic anion transporter or more likely, a cytosolic binding component of unknown function with high affinity and capacity for OTA binding in humans, rats, mice and possibly pigs.     

Routine gallbladder screening not necessary in patients undergoing laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Management of the gallbladder in patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) is controversial. We reviewed our experience in patients undergoing LRYGBP without routine gallbladder screening. METHODS: The data of 644 patients who underwent LRYGBP at our institution were analyzed. Preoperative ultrasonography was routinely obtained early in our series and selectively thereafter in patients with suspected symptomatic biliary disease. Cholecystectomy at LRYGBP was performed in symptomatic patients with positive ultrasound findings. Postoperatively, patients with intact gallbladders were prescribed ursodiol for 6 months. RESULTS: Of the 644 patients, 155 (24%) had history of cholecystectomy. A total of 104 patients underwent preoperative ultrasonography. Of the 104 patients, 20 had positive ultrasound findings and symptoms consistent with biliary disease and underwent concomitant cholecystectomy. Twelve patients had positive ultrasound findings and no biliary symptoms and did not undergo cholecystectomy. At a mean follow-up of 26.4 months, only 1 (8.3%) of the 12 patients had required cholecystectomy. Of the 104 patients, 72 had negative ultrasound findings. At a mean follow-up of 21.2 months, 5 of them (6.9%) had required cholecystectomy. The remaining 385 patients did not undergo any gallbladder screening. At a mean follow-up of 14 months, 32 (8.3%) of 385 patients had required cholecystectomy. Compliance with ursodiol for >4 months was only 39%. A time-to-event analysis did not reveal a significant difference in the cholecystectomy rate between asymptomatic patients with preoperative gallbladder screening and patients with no screening. CONCLUSION: Omission of gallbladder screening in asymptomatic patients undergoing LRYGBP is a reasonable approach that spares the patient a potentially unnecessary procedure with all its associated risks.     

The prevalence of airways hyperresponsiveness in members of an exercise training facility.

Athletes have a high prevalence (11-50%) of exercise-induced asthma, which may be caused by the hyperventilation accompanying repetitive bouts of strenuous exercise. We hypothesized that recreational exercisers would display a similar trend. Eucapnic voluntary hyperventilation (EVH) bronchoprovocation (breathing 21% O2, 5% CO2, and 74% N2 at 60% of MVV for 5 minutes) was performed to determine the prevalence of airways hyperresponsiveness (AHR) in adults (n=212, 146 males, mean +/- standard deviation, age 32 +/- 10 years) who exercised regularly (10 +/- 10 years, 31 +/- 28% of their lives): none had a previous diagnosis of asthma. AHR was defined by at least a 10%, 20%, or 25% decline in FEV1, FEF(25-75), or PEFR, respectively, by spirometry at 1, 5, 10, and 15 minutes post-EVH. Forty-one of 212 (19%) tested positive for AHR: 20 of 41 (49%) were positive by FEV1, 28 of 41 (68%) by FEF(25-75), and 27 of 41 (66%) by PEFR. Comparing responders with nonresponders: pre-EVH lung function was equivalent, except for FEV1, which was reduced (p<0.05) in responders (96 +/- 13 vs. 102 +/- 12% predicted). Mean maximal negative deflections for responders were: for FEV1, -17 +/- 7%; FEF(25-75), -31 +/- 10%; PEFR, -38 +/- 11%. Ranges of decline for responders were: FEV1, -10 to -33%; FEF(25-75), -20 to -59%; PEFR, -25- to -70%. We conclude that in these regular exercisers, the prevalence of AHR is high and comparable with some athletic populations.     

“Classical” neuroendocrine peptide hormones produced by cells of the immune system

Cells of the immune system are shown to produce peptide hormones whose production was once thought to be restricted to neuroendocrine tissue. Interestingly, in some cases, very specific stimuli elicit the production of one species of neuropeptide hormone. In other instances, it appears that some peptide hormones are constitutively produced. In either situation, the various immunocyte-derived hormones have biological activity in endocrinological assays. In the present report, a review of the various neuroendocrine hormones produced by cells of the immune system is discussed.     

Lorazepam versus diazepam for the treatment of status epilepticus

A retrospective study was performed to compare intravenous lorazepam and intravenous diazepam in the treatment of status epilepticus. Forty-five episodes of status epilepticus in children between the ages of 2 weeks and 18 years were reviewed. Lorazepam and diazepam proved similar in efficacy of seizure control and incidence of adverse effects. The dose of lorazepam required to control status epilepticus ranged from 0.03 to 0.22 mg/kg with a mean of 0.11 mg/kg (S.D. = 0.05 mg/kg). Among children treated with lorazepam, only children younger than 2 years of age had respiratory depression which required intubation.