Effects of cigarette smoking and age on the maturation of human oocytes

We investigated whether cigarette smoking, measured by follicular fluid concentrations of cotinine (a major metabolite of nicotine), affects the maturity of oocytes from women undergoing in-vitro fertilization (IVF) and embryo transfer. In 234 women, follicular fluid samples were assessed for cotinine and their 2020 oocytes were assessed for maturity stage. Data on individual proportions of oocytes which were mature (OM) and were fertilized (OF) were analysed by regression in relation to age and follicular fluid cotinine. OF gave an independent assessment of oocyte maturity. Both age and follicular fluid cotinine entered the OM and OF regressions and were significant. The age-adjusted regression coefficients for log cotinine were positive; greater cotinine concentrations usually accompanied greater OM and OF. The cotinine effect on OM was positive in younger women, but it became negative (decreased OM with increasing cotinine concentrations) in older women (> or = 40 years). We further found in older women an average reduction of approximately 50% in the number of mature oocytes; this reduced number was lower than the number of embryos usually transferred. Smoking can reduce the number of mature oocytes even further, therefore risking a negative IVF-embryo transfer outcome. This may be the reason why the negative effects of smoking become clinically detectable in older women.     

Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes

Although hyperketonemia and/or altered growth hormone secretion caused by diabetes have been implicated in enhanced CYP2E1, 2B, 3A and 4A expression, the effect of insulin on hepatic P450 expression, in the absence of associated metabolic/hormonal alterations, remains unknown. Primary cultured rat hepatocytes have been shown (Zangar et al., Drug Metab. Dispos., 23:681, 1995) to express stable and inducible CYP2E1 mRNA and protein levels, and provide an excellent system for mechanistic examination of the effect of insulin on CYP2E1, 2B, 3A and 4A expression. Maintaining primary rat hepatocytes in culture in the absence of insulin for 48, 72, or 96 h increased CYP2E1 mRNA levels 5-, 11-, and 4-fold, respectively, relative to cells maintained in the presence of the standard concentration of 1 microM insulin. In contrast, CYP2B mRNA levels increased only approximately 2-fold in the absence of insulin, when compared with the presence of 1 microM insulin. CYP2E1 and 2B protein levels were increased 6.7- and 3.8-fold, respectively, in cells cultured for 96 h in the absence of insulin as compared with those cultured in medium containing 1 microM insulin. Concentration-response studies revealed that decreasing the concentration of insulin below 10 nM (i.e. 1 nM, 0.1 nM, no insulin) increased CYP2E1 mRNA levels 4-, 7-, and 11-fold, respectively. In contrast, no such concentration-dependence was observed for CYP2B mRNA expression. As CYP3A and 4A expression is also elevated in diabetic rats, the effects of insulin on these P450s was also examined. CYP3A mRNA levels were unaltered and CYP4A mRNA levels were decreased marginally (approximately 50%) by the absence of insulin relative to levels in cells cultured in the presence of 1 microM insulin over 96 h in culture. The results of this study provide evidence that insulin itself, in the absence of other diabetes-induced metabolic or hormonal alterations, affects CYP2E1 and 2B, but not CYP3A or 4A, expression in primary cultured rat hepatocytes. Furthermore, CYP2E1 expression is differentially regulated by insulin relative to CYP2B, 3A or 4A. This study also demonstrates that decreasing the concentration of insulin in the culture medium provides a method by which CYP2E1 levels can be increased in primary cultured hepatocytes to facilitate mechanistic studies on the regulation of CYP2E1 expression.     

Influence of Threshold Stress on the Estimation of the Weibull Statistics

The influence of threshold stress on the estimation of the Weibull statistics is discussed in terms of the Akaike information criterion. Numerical simulations show that, if sample data are limited in number and threshold stress is not too large, the two-parameter Weibull distribution is still a preferred choice. For example, the fit of strength data of glass and ceramics to the two- and three-parameter Weibull distributions is compared.     

Alterations in reflex function contributing to syncope: orthostatic hypotension, carotid sinus hypersensitivity and drug-induced dysfunction

Orthostatic hypotension and related neurologic symptoms are frequently encountered in clinical practice. The maintenance of appropriate blood pressure and heart rate responses upon assuming the upright posture are dependent upon: 1. intact mechanical (venous valves) mechanisms, 2. functioning arterial and cardiopulmonary baroreceptors, 3. normal peripheral neural pathways, 4. normal central neural integration, and 5. appropriate neurohormonal secretion. Dysfunction at one or more of these loci may facilitate the occurrence of orthostatic hypotension and syncope. In general, the mechanisms of orthostatic hypotension may be divided into three categories. In the first category, processes interfere with normal compensatory responses to upright posture. Examples of this mechanism include age related autonomic changes, diabetic neuropathy and central nervous system disease such as Shy-Drager syndrome. The second principal mechanism involves overwhelming otherwise normal reflexes by an intense orthostatic stimulus. An obvious example of this mechanism is syncope related to hemorrhage. A final category of orthostatic hypotension relates to interference with reflex responses by drugs that may limit vasoconstriction, heart rate or cardiac output adjustments or exaggerate venous pooling. These are commonly used medications such as vasodilators, beta-adrenergic blockers and nitrates. The treatment of orthostatic hypotension revolves around the recognition of underlying causes or contributing factors amenable to correction or avoidance. Other helpful treatment options include nocturnal head-up tilting and mineralocorticoids, both of which help to expand blood volume. Many other therapeutic agents have been tried in small and selected patient populations, often with disappointing results. While many of the drugs available (phenylephrine, ephedrine, tyramine, dihydroergotamine) can improve upright blood pressure, side effects are common, and supine hypertension is problematic in many patients. Interventions of this type should be carefully initiated in a monitored setting. The carotid sinus is an important component of a neural control system responsible for heart rate and blood pressure homeostasis. Excessive heart rate and blood pressure responses to distortion of the carotid sinus are the basis for the carotid sinus syndrome (CSS). Patients with CSS tend to be elderly males and local pathology in the neck is frequently involved. Atherosclerotic coronary artery disease and hypertension are important clinical correlates. Two major categories of carotid sinus hypersensitivity (CSH) are recognized: cardioinhibitory and vasodepressor. Cardioinhibitory CSH is the most common, and in its purest form consists of sinus bradycardia or arrest, asystole or AV block during carotid sinus massage. This vagally-mediated response is eliminated by atropine. Cardiac pacing is nearly universally successful in preventing severe symptoms.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of dietary fiber in the etiology of non-insulin-dependent diabetes mellitus. The San Luis Valley Diabetes Study

Accuracy of patient positioning and dose delivery in mantle field irradiations was investigated on 29 patients treated between August 1990 and December 1991. Patients were treated in two different centers, University Hospital St. Rafa?l in Leuven and Institut Gustave Roussy in Villejuif, where different techniques and procedures were used. Measurements were performed on 341 portal films and entrance doses were measured in 518 treatment set-ups. The impact of systematic errors occurring during treatment preparation and day-to-day variations on the accuracy of treatment execution were separately analysed. Daily reproducibility, defined as the deviation from the respective mean measured value for a treatment was demonstrated to be good for both the treated volume and the delivered dose and no difference between the two techniques was shown. Comparing the successive portal films of individual patients (reproducibility of a treatment, once it has started), only small day-to-day variations are found: the SD is 3.4 mm for craniocaudal movements and 2.6 mm for lateral movements. For dose delivery very narrow distributions are obtained with SDs of, respectively, 1.5% and 1.85% for the Leuven and the Villejuif group. This suggests that the position of the patient, which is often thought as the critical point in this complex set-up can be done in a very accurate way, regardless of the position used. To assess the global accuracy of the treatment, the actually treated volume and delivered dose were compared with the planned values. Apart from reproducibility this also takes into account the whole preparatory procedure between planning and the start of the therapy (first session).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCl

Cardio-pulmonary function was measured in male broilers reared on diets formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE group). A snare placed around the right pulmonary artery permitted acute shunting of the entire cardiac output (CO) through the left pulmonary artery, resulting in sustained increases in blood flow (BF) through the left lung in both groups. The unilateral increase in BF was accompanied by sustained increases in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL group. However, following initial transient increases in PAP and PVR in the ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus PAP, in spite of the ongoing elevation of BF through the left lung. The capacity of the pulmonary vasculature in the ARGININE group to accommodate an increased BF at a normal PAP accounts for the previously reported lower incidence of pulmonary hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both groups after tightening the pulmonary artery snare, in spite of a compensatory increase in the respiratory rate. The gradual return of PVR and PAP to presnare levels in the ARGININE group did not eliminate the concurrent ventilation-perfusion mismatch caused by the increased rate of BF through the left lung. Tightening the pulmonary artery snare caused mean systemic arterial pressure (MAP) to drop from control levels of approximately 98 mm Hg to sustained hypotensive levels of approximately 65 mm Hg in both groups. This systemic hypotension was caused by decreases in CO and total peripheral resistance (TPR). The reduction in CO were caused by reduction in stroke volume (SV) rather than heart rate (HR), suggesting that acutely tightening the pulmonary artery snare increased PVR sufficiently to impede left ventricular filling. Accordingly, the maximum increment in PAP attainable by the right ventricle during acute increases in PVR apparently was inadequate to propel the entire CO through the pulmonary vasculature, setting the stage for the congestive right-sided pooling of blood routinely associated with PHS in broilers.     

Rail-to-rail amplifier input stage with constant g/sub m/ and commonmode elimination

A new scheme for achieving rail-to-rail input to an amplifier is introduced. Constant g/sub m/ and common mode removal is obtained by using a single input differential pair and tunable DC level shifters via multiple input floating gate transistors. The feedback circuitry basically fixes the common mode of the amplifier, resulting in consistent and stable operation for rail-to-rail inputs and a high common mode rejection ratio.     

Does Physiological Blood Glucose Control Require an Adaptive Control Strategy?

To test the hypothesis that only an adaptive algorithm would guarantee optimal feedback control of glycemia in insulin-dependent diabetes, fasting chronically diabetic dogs at rest were subjected to short-term artificial beta cell treatment. Insulin was applied intravenously and an oral glucose load was given during the experiment. Employing the same dosing algorithm, three different control strategies were employed in a random order on different days: adaptive control (minimum variance controller, Test A), fixed command control using on-line parameter estimates (Test B), and fixed command control using off-line individually optimized dosage constants (Test C). Comparison was made to nondiabetic control animals. The glycemic profiles were entirely normal in Test A and C, but were distinctly elevated in Test B. The peripheral hyperinsulinaemia could, however, not be avoided by adaptive control. It is concluded that the restoration of physiological blood glucose control in insulin-dependent diabetes requires dosage parameters which are either continually adapted to the actual situation (adaptive control) or are optimized to meet the individual's needs. In the latter case, fixed command control may be employed. Peripheral hyperinsulinaemia cannot be avoided as long as insulin is administered by a posthepatic route.     

Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin

Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells. BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin.