Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, lleum, and lung of the guinea pig

The effects of feeding diest containing either cholesterol (0.24% w/w) or cholestyramine (2.5% w/w) and of fasting on sterol synthesis in the liver, ileum, and lung of both male and female guinea pigs have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into total digitoninpredipitable sterols. Cholesterol feeding significantly decreased (P less than 0.05) sterol synthesis in the liver, ileum, and lung of the males and in the ileum of females. Cholestyramine feeding stimulated the rate of hepatic sterol synthesis 13-fold but did not significantly affect sterologenesis in the ileum. Sterol synthesis in the lung was significantly increased (P less than 0.05) but to a much lesser extent than in the liver. Fatty acid synthesis in the liver, ileum, and lung was not significantly affected by either cholesterol or cholestyramine feeding. In guinea pigs fasted for 24 hr, sterol synthesis was inhibited in all three tissues, the most pronounced effect occurring in the liver. Only in the lung was fatty acid synthesis significantly decreased (P less than 0.001) by fasting. Cholesterol feeding resulted in increased concentrations of cholesterol in the plasma and liver. Cholestyramine feeding reduced plasma cholesterol concentration by 81% in females and by 64% in males. However, it did not significantly change the tissue cholesterol concentrations. Fasting resulted in a significant increase (P less than 0.05) in plasma cholesterol concentration but did not effect the concentration of cholesterol in the tissues. It was concluded that in the normal guinea pig, the feedback inhibition produced by both cholesterol and also possibly by bile acids suppresses sterol synthesis in the liver to very low rates compared to those in the small intestine, where sterologenesis is not only less sensitive to the cholesterol negative feedback system than that in the liver, but also is not subject to regulation by the bile acid negative feedback system.     

Perforation of diverticulum of terminal ileum presenting as acute appendicitis

Two cases of perforated diverticula of the terminal ileum are presented with a discussion of the literature. Primary resection is the treatment of choice. Asymptomatic diverticula discovered on routine contrast studies should not be managed surgically.     

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin, including quality control parameters

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 < = or 2.0 micrograms/ml).     

The CTFA Evaluation of Alternatives Program: an evaluation of in vitro alternatives to the Draize primary eye irritation test. (Phase III) surfactant-based formulations

The CTFA Evaluation of Alternatives Program is an evaluation of the relationship between data from the Draize primary eye irritation test and comparable data from a selection of promising in vitro eye irritation tests. In Phase III, data from the Draize test and 41 in vitro endpoints on 25 representative surfactant-based personal care formulations were compared. As in Phase I and Phase II, regression modelling of the relationship between maximum average Draize score (MAS) and in vitro endpoint was the primary approach adopted for evaluating in vitro assay performance. The degree of confidence in prediction of MAS for a given in vitro endpoint is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curve. Prediction intervals reflect not only the error attributed to the model but also the material-specific components of variation in both the Draize and the in vitro assays. Among the in vitro assays selected for regression modeling in Phase III, the relationship between MAS and in vitro score was relatively well defined. The prediction bounds on MAS were most narrow for materials at the lower or upper end of the effective irritation range (MAS = 0-45), where variability in MAS was smallest. This, the confidence with which the MAS of surfactant-based formulations is predicted is greatest when MAS approaches zero or when MAS approaches 45 (no comment is made on prediction of MAS > 45 since extrapolation beyond the range of observed data is not possible). No single in vitro endpoint was found to exhibit relative superiority with regard to prediction of MAS. Variability associated with Draize test outcome (e.g. in MAS values) must be considered in any future comparisons of in vivo and in vitro test results if the purpose is to predict in vivo response using in vitro data.     

Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha

This study determined effects of follicle stimulating hormone (FSH) alone and in combination with tumour necrosis factor (TNF), on granulosa cells from small (5-10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal phases of the cycle and during periods of acyclicity. Granulosa cells were collected from ovaries of premenopausal women undergoing oophorectomy. The cells were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and 96 h after culture and progesterone, oestradiol and cAMP in media were measured by radioimmunoassays. FSH stimulated the accumulation of oestradiol from granulosa cells of small follicles during the follicular and luteal phases but not during acyclicity; and TNF reduced oestradiol accumulation in the presence of FSH. Interestingly, in granulosa cells from small follicles, progesterone and cAMP secretion increased in response to FSH and neither was affected by TNF. Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in granulosa cells from small follicles. FSH stimulated oestradiol production by granulosa cells of large follicles obtained only during the follicular phase of the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells obtained from large follicles during the luteal phase and during acyclicity did not accumulate oestradiol in response to FSH. However, FSH increased progesterone and cAMP secretion by granulosa cells obtained from large follicles during the follicular and luteal phases. During the luteal phase alone, TNF in combination with FSH increased progesterone accumulation above that of FSH alone. FSH did not increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained from large follicles during acyclicity. Thus, FSH increases progesterone, oestradiol and cAMP secretion by granulosa cells of small follicles during the follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol secretion specifically in those cells. In large follicles, FSH-stimulated granulosa cell secretion of oestradiol is limited to the follicular phase and this effect can be inhibited by TNF. In addition, when granulosa cells of large follicles do not increase oestradiol secretion in response to FSH, TNF stimulates progesterone secretion.