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.     

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.     

Biological Markers of Breast Cancer: A Review

This review of biological markers of breast carcinoma has summarized a fairly representative series of studies pertaining to endocrine, carcinoembryonic, tissue-associated, serologic, biochemical, and specific tumor markers, with attention to some of the contributions from genetic engineering techniques applied to this research area. It is meant to be a helpful review with two purposes: those involved in research or clinical studies of breast cancer may wish to use this review as a basis for adding additional references in each category and to refer to the references provided for further study, thought, and synthesis of the data, perhaps to stimulate new Associations between pertinent facts; those involved in the general scientific or clinical fields may wish to use it as an overview of biological markers pertaining to a particular form of cancer and perhaps this review will permit faster, more easily asscessible synthesis of data, and a better understanding of a variety of parameters which are Associated with breast cancer diseases.     

Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion

Serum zinc levels and urinary zinc excretion were compared in 15 patients with essential hypertension taking chronically a combination of hydrochlorothiazide and amiloride as monotherapy, eight patients maintained with hydrochlorothiazide alone, and eight control subjects. Serum zinc values were statistically comparable in all three groups. However, urinary zinc excretion was abnormally elevated in the two patient groups. In the dosage used, amiloride did not have a zinc-sparing effect.