Effects of 17 beta-estradiol on serum hormone concentrations and estrous cycle in female Crl:CD BR rats: effects on parental and first generation rats

It has been proposed that short-term activation of the hypothalamo-pituitary adrenal axis, with a consequent increase in the secretion of cortisol, amy disrupt the endocrine events prior to ovulation and thereby impair reproduction in females. We investigated this concept in gilts in which oestrus was detected by introduction to boars, where intense physical contact is possible, or by applying pressure to the back of gilts (back-pressure test) during fence-line exposure to boars, where intense physical contact is prohibited. We expected that there would be a greater release of cortisol and that reproduction would be inhibited in gilts introduced to boars compared to gilts in which the back-pressure test was used. As expected, introduction of gilts to boars resulted in a significant transient increase in plasma concentrations of cortisol while there was no significant effect of using the back-pressure test on plasma cortisol. Nevertheless, introduction of gilts to boars did not impair reproduction and there was no effect of method of detecting oestrus on duration of oestrus, sexual receptivity, fertility or fecundity. The length of the oestrous cycle was decreased and ovulation rate increased in gilts that were introduced to boars compared to gilts that underwent the back-pressure test, indicating that introduction of gilts to boars may have stimulated these aspects of reproduction. These stimulatory effects may have been due to an increased exposure of gilts to sexual behaviour and stimuli from boars when introduced to boars and/or to stimulatory effects of the hypothalamo-pituitary adrenal axis on some aspects of reproduction.     

Increased bile acid pool inhibits cholesterol 7 alpha-hydroxylase in cholesterol-fed rabbits

BACKGROUND & AIMS: Cholesterol feeding unexpectedly inhibits cholesterol 7 alpha-hydroxylase in rabbits. The aim of this study was to explore the mechanism. METHODS: Twenty male New Zealand white rabbits were fed regular chow with and without 2% cholesterol for 10 days followed by 7 days of bile drainage. The activities of hepatic cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase that control bile acid synthesis in classic and alternative pathways were related to the size and composition of bile acid pool. RESULTS: After feeding cholesterol, plasma and hepatic cholesterol concentrations increased, the bile acid pool doubled (from 254 +/- 44 to 533 +/- 51 mg; P < 0.001), cholesterol 7 alpha-hydroxylase activity decreased 68% (P < 0.01), but sterol 27-hydroxylase activity increased 66% (P < 0.05) with increased cholic acid synthesis (P < 0.01). Bile drainage in the cholesterol-fed rabbits depleted the bile acid pool and stimulated down-regulated cholesterol 7 alpha-hydroxylase activity 11.4-fold (P < 0.001), although hepatic cholesterol remained elevated. Hepatic sterol 27-hydroxylase activity was unaffected. CONCLUSIONS: Feeding cholesterol increased hepatic cholesterol and stimulated sterol 27-hydroxylase and alternative bile acid synthesis, which expanded the bile acid pool and inhibited cholesterol 7 alpha-hydroxylase in rabbits. In distinction, hepatic sterol 27-hydroxylase was insensitive to changes in the bile acid pool.     

Social physique anxiety in postmenopausal women

Social physique anxiety (SPA), the degree to which individuals become anxious when others observe their bodies, is an important concept for postmenopausal women because it may be directly related to their physical activity behavior. Women with high levels of social physique anxiety may not participate in health-enhancing physical activity. Therefore, the main purpose of this study was to examine SPA in postmenopausal women relative to leisure time physical activity (LTPA, activities such as exercise, recreation, and sports). Other factors, such as percent body fat, body fat distribution, age, and hormone replacement therapy status were also examined for their relationship to SPA. Women who expended < or = 500 kcal.wk-1 in LTPA had significantly higher SPA than women who expended > or = 2,000 kcal.wk-1, independent of percent body fat. Women with more than 37.5% body fat had significantly higher SPA than those with less than 37.5% body fat. Women with upper BFD (waist-to-hip ratio or WHR > 0.85) had higher SPA than women with lower BFD (WHR < 0.75). There were no differences in SPA relative to age or HRT status. It appears that a sedentary lifestyle, high percent body fat, and upper body fat distribution are associated with increased SPA in postmenopausal women, thus health promotion professionals should be aware of these concerns when developing physical activity interventions for postmenopausal women.     

Upper extremity nerve lesions (diagnosis, indications, surgical techniques)

OBJECTIVE: Revision and questioning of orthodox principles regarding the conduction of nerve impulse. DESIGN: Retrospective study with clinical analysis of results. SITE: Hospital das Clinicas (HCFMSP), public university institution with research programs and tertiary attention to health. GROUP MEMBERS: Author and a team of residents and trainees. OPERATION: Direct suture of nervous stumps utilizing auxiliary technical procedures:- joint-flexion, nerve transposition, tendon transplants, bone shortening. MEASUREMENT: Clinical evaluation and objective tests for tactile and stereognostic function recovery (Weber Test). RESULTS: Variable, depending on preoperative conditions:- type of lesion, time elapsed since injury. CONCLUSIONS: Neurorrhaphy should be the procedure of choice even for long term lesions, although the expected results may be less favourable. Periodical evaluation from 24 hs. postoperative, checking for early undefined signals of nervous function recovery. Association of specific drugs for chemical biophysics of the nerve.     

Pharmacological characterization of N-methyl-D-aspartate receptors in spinal cord of rats with a chronic peripheral mononeuropathy

N-Methyl-D-aspartate (NMDA) receptor antagonists, acting in the spinal cord, are analgesic. However, the clinical utility of these antagonists is diminished by their adverse effects on cognition and behavior. To facilitate the development of spinal cord-selective NMDA receptor antagonists, we characterized ligand interactions at NMDA receptors in spinal cord of normal rats and rats with a chronic peripheral neuropathy. NMDA receptors in spinal cord were distinguished from those in cerebral cortex on the basis of differences in the potencies of competitive and noncompetitive antagonists and on the basis of differences in their response to spermidine. D(-)-2-Amino-5-phosphonopentanoic acid (AP-5) and (+)-(1-hydroxy-3-aminopyrrolidine-2-one) (HA-966) were more potent in inhibiting NMDA-dependent [3H]TCP binding in spinal cord while, conversely, MK-801 was more potent in inhibiting [3H]TCP binding to NMDA receptors in cerebral cortex. Spermidine increased [3H]TCP binding to NMDA receptors in cerebral cortex (39+/-8%) but not spinal cord (2+/-1%). Based on these properties, NMDA receptors in spinal cord more closely resembled those in cerebellum than those in cerebral cortex. Generation of a chronic neuropathy had no effect on the density of NMDA receptors in lumbar spinal cord. There were also no major changes in the potencies of competitive antagonists or channel blocking ligands, although there was a trend for kynurenic acid and D-CPP to be more potent in the spinal cords of neuropathic animals. These findings indicate that, in both normal and neuropathic pain states, NMDA receptors in spinal cord can be distinguished pharmacologically from those in cerebral cortex. These findings underscore the feasibility of developing spinal cord-selective NMDA receptor antagonists as novel analgesics.     

Phase I and pharmacologic study of penclomedine, a novel alkylating agent, in patients with solid tumors

PURPOSE: To determine the maximum-tolerated dose (MTD), principal toxicities, and pharmacologic behavior of penclomedine, a novel alkylating agent. PATIENTS AND METHODS: Penclomedine (45 to 550 mg/ m2/d every 3 weeks) was administered as a 1- or 3-hour intravenous (IV) infusion for 5 consecutive days to patients with solid tumors. RESULTS: On a 1-hour dosing schedule, ataxia, vertigo, nystagmus, and a motor aphasia were the principal toxicities of penclomedine. These neurologic effects were dose-related, and evolved from complaints of somnolence and dizziness, to more pronounced signs and symptoms of cerebellar dysfunction. Up to and including doses of 415 mg/m2, these effects were well tolerated and resolved within 2 hours posttreatment. In contrast, both patients treated at the 550-mg/m2 dose level experienced a dose-limiting constellation of perinfusional aphasia and vertigo, with either ataxia of over 2 weeks' duration or recurrent dizziness. Prolongation of the infusion duration to 3 hours at this dose level resulted in less neurotoxicity; however, delayed trilineage hematologic toxicity precluded timely administration on this schedule. A statistically significant relationship was demonstrated between the development of ataxia and maximum plasma concentrations of penclomedine. CONCLUSION: Neurotoxicity was the dose-limiting toxicity (DLT) of penclomedine administered as a 1-hour infusion daily for 5 days every 3 weeks, and the recommended dose for further evaluations was 415 mg/m2. The nature of the principal toxicities and the lack of any detectible antitumor activity indicate that phase II evaluations of penclomedine on this administration schedule should be focused on specific disease settings, such as breast cancer and intracerebral tumors, in which antitumor activity has been demonstrated.     

Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding

Previous studies have shown that integrin alpha chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin alpha4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the alpha4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/ or antibodies. Furthermore, alpha4 tail deletion also significantly decreased the membrane diffusivity of alpha4beta1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon alpha4 tail deletion. Together, these results suggest that alpha4 tail deletion exposes the beta1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside-out signaling mechanisms for beta1 integrins.     

Oral ranitidine as prophylaxis for gastric stress ulcers in intensive care unit patients: serum concentrations and cost comparisons

During the period 1985 to 1989 foetal chromosomal analysis was performed in 121 of 318 pregnant women with foetal malformations detected by ultrasound. There were six failures. The percentage of foetuses karyotyped for developmental disorders increased from 13% in 1985 to 62% in 1989. An abnormal chromosomal pattern was found in 28 (24%) of the foetus. The pregnancy was terminated in 86% of cases with abnormal karyotype. The corresponding number in the group with normal chromosomes was 51%. The authors discuss the malformations leading to karyotyping, the methods used for karyotyping, the results of these tests and the consequences for the pregnancies.     

A curvilinear trend in naming errors as a function of early vocabulary growth

This research examines changes in word retrieval and naming during a developmental period in which there is a substantial increase in productive vocabulary. That increase generally occurs when children have between 50 to 150 words in productive vocabulary. We examined children's naming errors in two studies for what these errors could tell us about the emerging lexicon. The method we used for eliciting spontaneous naming was picture book reading by the parent. In Experiment 1, 12 children were followed longitudinally at three-week intervals from 15 to 22 months. Parent diaries were used as a measure of vocabulary growth. Experiment 2 used a cross-sectional design to compare the naming errors of 60 children assigned to one of three vocabulary ranges. Measures of vocabulary size were based on the MacArthur Communicative Development Inventory. In both experiments we found a sharp increase in naming errors in the picture book task that was coincident with sudden changes in productive vocabulary. These naming errors were often perseverative in nature and appear to reflect interference in the retrieval process from previously retrieved words. The results suggest that these errors in naming are a consequence of changes in lexical processing that occur with rapid growth of productive vocabulary and concurrent increased rates of speaking.