Effects of different types of diet and sodium saccharin on proliferation at the limiting ridge of the rat forestomach

Sodium saccharin, at high doses in the diet, has been reported to cause hyperplasia of the forestomach (squamous portion of stomach), at the limiting ridge in F344 rats, in addition to its potential to induce proliferative effects on the urinary bladder epithelium. We have characterized this hyperplasia of the squamous epithelium of the forestomach at the limiting ridge in F344 and Sprague-Dawley rats given various doses of sodium saccharin for 4 to 95 wk. With increasing doses of sodium saccharin, the limiting ridge of the forestomach showed dose-related morphological changes: basal-cell hyperplasia, early papillary hyperplasia with basal-cell hyperplasia and papillary hyperplasia. Calcium saccharin in Prolab diet caused hyperplasia of the forestomach at the limiting ridge, similar to that caused by sodium saccharin. The severity of hyperplasia was influenced by the type of diet and by the strain of rats. AIN-76A diet without added sodium saccharin caused basal-cell hyperplasia in F344 rats, whereas Prolab, Purina and NIH-07 diets without added sodium saccharin had little or no effect on the forestomach. The effect of AIN-76A diet alone persisted through 95 wk of feeding without any evidence of tumour formation. In Sprague-Dawley rats, which appeared more sensitive to effects on the forestomach than F344 rats, Prolab 3200 and Purina diets without sodium saccharin caused basal-cell hyperplasia in more than half of the treated rats. The forestomach hyperplasia associated with AIN-76A or saccharin administration appears to be mild, limited in extent to the limiting ridge, and not associated with carcinogenesis.     

Canine, but not rat bladder contracts to serotonin via activation of 5HT2 receptors

Serotonin is a biogenic amine that can exert multiple effects on smooth muscle, including smooth muscle of the genitourinary tract; effects that may be species dependent. The present study using isolated tissues documents potent contractile responses to serotonin in canine bladder smooth muscle. Contractile responses to serotonin in canine bladder could be mimicked by alpha-methyl serotonin, a selective 5HT2 receptor agonist. In fact, although alpha-methyl serotonin was slightly less potent as a contractile agonist relative to serotonin, the contractile response to alpha-methyl serotonin was more persistent as evidenced by a greater recovery time to resting force following washout. In contrast, the 5HT1A receptor agonist, 8-OH-DPAT and the 5HT3 selective agonist, 2-methyl serotonin, did not markedly contract canine bladder. These data establish that contractile responses to serotonin in the canine bladder are mediated by activation of 5HT2 receptors. We further demonstrated that the 5HT2 receptor antagonist, LY53857, potently inhibited the contractile response to both serotonin and alpha-methyl serotonin in the canine bladder consistent with agonist activation of 5HT2 receptors. In contrast to the potent response to serotonin observed in the canine bladder, rat bladder preparations did not markedly contract in response to serotonin, alpha-methyl serotonin, 8-OH-DPAT, or 2-methyl serotonin. Thus, these studies reinforce the marked species variability in responsiveness to serotonin and indicate that contraction to serotonin in the canine bladder is mediated by activation of the 5HT2 receptor.     

Peripheral retinal neovascularization and rubeosis iridis after a bilateral circular buckling operation

This report describes a young high-myopic patient who developed rubeosis iridis with peripheral retinal neovascularization one year after a circular buckling operation. Subsequently, vitreous bleeding and exudation led to traction retinal detachment which was treated successfully by anterior vitrectomy and cryopexy. It is suggested that this case represents a mild form of anterior-segment ischemia, combined with peripheral retinal ischemia.     

Magnetization transfer effects in MR-detected multiple sclerosis lesions: comparison with gadolinium-enhanced spin-echo images and nonenhanced T1-weighted images.

PURPOSETo define the relationship between magnetization transfer and blood-brain-barrier breakdown in multiple sclerosis lesions using gadolinium enhancement as an index of the latter.METHODSTwo hundred twenty lesions (high-signal abnormalities on T2-weighted images) in 35 multiple sclerosis patients were studied with gadolinium-enhanced spin-echo imaging and magnetization transfer. Lesions were divided into groups having nodular or uniform enhancement, ring enhancement, or no enhancement after gadolinium administration. For 133 lesions, T1-weighted images without contrast enhancement were also analyzed. These lesions were categorized as isointense or hypointense based on their appearance on the unenhanced T1-weighted images.RESULTSThere was no difference between the magnetization transfer ratio (MTR) of lesions as a function of enhancement. MTR of hypointense lesions on unenhanced T1-weighted images was, however, lower than the MTR of isointense lesions.CONCLUSIONWe speculate that diminished MTR may reflect diminished myelin content and that hypointensity on T1-weighted images corresponds to demyelination. Central regions of ring-enhancing lesions had a lower MTR than the periphery, suggesting that demyelination in multiple sclerosis lesions occurs centrifugally. In addition, the short-repetition-time pulse sequence seems useful in the evaluation of myelin loss in patients with multiple sclerosis.     

Physical status score and trends in anesthetic complications

Since deaths due to anesthesia have now become rare, emphasis in quality assurance of anesthetic care must focus on morbidity rather than only on mortality. To facilitate comparisons of outcomes, data from a large anesthesia follow-up program (N = 112,000 anesthetics) were used to evaluate the usefulness of the American Society of Anesthesiologists' Physical Status score (PS) as an independent predictor of nonfatal adverse anesthetic complications. For each patient, the anesthesiologist filled out a form containing information about the patient, the anesthetic, the operative procedure, and outcomes in the operating and recovery rooms. Postoperative complications were assessed by a designated anesthesia follow-up nurse. We calculated the PS-specific complication rate by dividing the number of complications to patients in each PS category by the number of anesthetics given to patients in the same category. We found that PS-specific complication rates increased with increasing PS scores for most complications sought. For intraoperative and recovery room complications, the PS-specific rates increased from 1978-80 and 1981-83 as compared to 1975-77. However, there was no increase over time in the rate of postoperative major complications. After adjusting for patient, anesthesia, and surgery-related variables by multiple logistic regression, the relative odds of having an intraoperative or postoperative major complication were increased for patients classified PS2, PS3 and PS4 & 5 as compared to PS1. However, those in higher PS categories were less likely to have a recovery room complication than PS1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related alterations of NMDA-receptor properties in the mouse forebrain: partial restoration by chronic phosphatidylserine treatment.

The effect of aging on the properties of N-methyl-D-aspartate (NMDA) receptors in the forebrain of female NMRI mice was investigated using the antagonist [3H]MK-801 as radioligand. Compared to young (3 months) mice, aged (20 months) mice showed changes of the properties of the NMDA receptor at three different levels: (1) the density was reduced by about 35%; (2) the efficacy of L-glutamate and glycine for stimulating specific [3H]MK-801 binding was enhanced, probably because more NMDA receptor-associated ion channels are closed under baseline conditions in the aged brain; (3) the affinity of L-glutamate and glycine to its binding sites at the NMDA receptor complex was also enhanced. Chronic treatment of aged mice with phosphatidylserine (20 mg/kg, i.p., once daily) for three weeks completely normalized enhanced efficacy and affinity of L-glutamate and glycine and elevated NMDA receptor density by approximately 25%. These findings are consistent with the assumptions that deficits of the NMDA receptor are one of the mechanisms of age-related cognitive impairment and that the beneficial effects of phosphatidylserine treatment on cognitive deficits of aged individuals might be partially due to the effects of this drug on age-related NMDA receptor deficits.     

Limited lists and the purchase of pharmaceutical products by government agencies in the RSA

The use of a limited list to restrict the range and type of medication used by medical institutions that operate under the auspices of the provincial authorities has been mooted as one possible method of cost containment. This study discusses the implementation of such measures in other countries and then quantifies the cost savings that might be obtained in the South African case. The possible savings are somewhat offset by other costs such a measure would introduce.