Endocrine and reproductive function in ewes exposed to the organochlorine pesticides lindane or pentachlorophenol

The effects of lindane (LIN, gamma-hexachlorocyclohexane) and pentachlorophenol (PCP) on reproduction and general endocrine function were examined in breeding ewes as a model for wild and domestic ungulates, which may be exposed to low levels of pesticides that are potential endocrine-disrupting chemicals. Ewes (n = 13/group) were fed either a control untreated diet (CON), or a diet treated with LIN (1 mg/kg/d) or PCP (1 mg/kg/d) during the 5 wk prior to mating and throughout pregnancy and lactation. Mating response, ovulation rate, follicle and corpus luteum size, gestation length, pregnancy rate, lambing rate, and lamb birth weight were recorded. After weaning, 6 ewes from each group were bled at 15-min intervals for 8 h during the day and night and for 1 h before and 5 h after i.v. administration of gonadotropin-releasing hormone, thyroid-stimulating hormone (TSH), and adrenocorticotropin, to measure serum concentrations of luteinizing hormone, follicle-stimulating hormone, thyroxine (T4), and cortisol. Ewes were then killed and endocrine tissues examined histologically. Pregnancy rate as a result of matings taking place at the synchronized estrus was significantly decreased by the lindane treatment However, PCP and lindane did not markedly affect any other aspect of reproductive function studied. In PCP-treated ewes, serum concentrations of T4 were significantly reduced compared to control ewes during the day and night; however, the T4 response to TSH was not altered by PCP treatment. No other measured endocrine parameters were consistently affected by lindane or PCP. Thyroid follicle size was significantly increased in the LIN and PCP ewes compared to the control ewes. Low serum concentrations of T4 in the PCP ewes may have resulted in increased TSH secretion and increased thyroid follicle size. In conclusion, although pesticide treatments had no serious adverse effects on reproductive function in breeding ewes, PCP reduced T4 concentration, which in the long term could influence reproductive and general performance.     

Inhibitory effect of leptin on the rat ovary during the ovulatory process

The aims of this study were to investigate the negative action of leptin on some intraovarian ovulatory mediators during the ovulatory process and to assess whether leptin is able to alter the expression of its ovarian receptors. Immature rats primed with gonadotrophins were used to induce ovulation. Serum leptin concentration was diminished 4 h after human chorionic gonadotrophin (hCG) administration, whereas the ovarian expression of leptin receptors, measured by western blot, was increased by the gonadotrophin treatment. Serum progesterone level, ovulation rate and ovarian prostaglandin E (PGE) content were reduced in rats primed with equine chorionic gonadotrophin (eCG)/hCG and treated with acute doses of leptin (five doses of 5 mug each). These inhibitory effects were confirmed by in vitro studies, where the presence of leptin reduced the concentrations of progesterone, PGE and nitrites in the media of both ovarian explants and preovulatory follicle cultures. We also investigated whether these negative effects were mediated by changes in the expression of the ovarian leptin receptors. Since leptin treatment did not alter the expression of ovarian leptin receptor, the inhibitory effect of leptin on the ovulatory process may not be mediated by changes in the expression of its receptors at ovarian level, at least at the concentrations assayed. In summary, the ovulatory process was significantly inhibited in response to an acute treatment with leptin, and this effect may be due, at least in part, to the direct or indirect impairment of some ovarian factors, such as prostaglandins and nitric oxide.     

On Self-growing Modeling for Curves

This paper presents a novel curve modeling method based on controlling rules of the shaping technique.The method describes the curve based on steplength and turning angle,and the characteristics of the curve near a point.Then it introduces the process to extract ″growing-rules″ for 2D and 3D curves described by familiar analytical expressions and curvature-torsion expressions.Examples of self-growing modeling for familiar analytical curves are presented.New curves are obtained by designing the grow-rules;co...     

The prevalence of insulin resistance and other cardiovascular disease risk factors in healthy elderly southwestern Nigerians

A derivative of coumarin, 8-nitro-7-hydroxycoumarin (8-NO2-7-OHC), was synthesised, purified and characterised. The cytostatic and cytotoxic nature of this compound was determined using both human and animal cell lines grown in vitro for 96 h in the presence of drug (0-500 microM, equivalent to 0-104 microg/ml). 8-NO2-7-OHC was shown to be cytotoxic to three cell lines, but cytostatic to all cell lines tested. With K562 and HL-60 cells, cell death was found to occur by apoptosis. This cytotoxic effect was found to be irreversible, with cell death continuing to occur following a 96 h recovery period. The cytostatic effects were found to be irreversible in four of the five cell lines tested. 8-NO2-7-OHC demonstrated its cytostatic effects within 24 or 48 h, while its cytotoxic effects appeared more gradually. The IC50 of 8-NO2-7-OHC was 475-880 microM, depending on the cell line tested. It was shown to exert its cytostatic effect through an alteration of cell cycle. It also inhibited DNA synthesis. The toxicity of 8-NO2-7-OHC does not appear to be mediated through the multi-drug resistance (MDR) protein since it caused significant cytostatic and cytotoxic effects to CHrC5 cells, which have an increased expression of this protein. This compound was shown to be non-mutagenic in a standard Ames test, both with or without a mammalian enzyme activation system. The applications and mode of actions of coumarins are discussed.     

Influence of ionizing radiation on proliferation, c-myc expression and the induction of apoptotic cell death in two breast tumour cell lines differing in p53 status

PURPOSE: To determine the capacity of ionizing radiation to inhibit proliferation, to suppress c-myc expression and to induce apoptotic cell death in the p53 wild-type MCF-7 cell line and the p53 mutated MDA-MB231 cell line. MATERIALS AND METHODS: Growth inhibition and cell killing were determined by cell number and trypan blue exclusion. Apoptosis was assessed through cell morphology and fluorescent end-labelling. c-myc expression was monitored by Northern blotting. RESULTS: Inhibition of cell proliferation by ionizing radiation was similar in both cell lines. MDA-MB231 cells accumulated in G2 while MCF-7 cells accumulated in both the G1 and G2 phases of the cell cycle after irradiation. There was no evidence of apoptosis in either cell line. In MCF-7 cells, growth inhibition correlated closely with an early dose-dependent suppression of c-myc expression; in MDA-MB231 cells, there was no correspondence between growth inhibition and a transient, dose-independent reduction in c-myc message. CONCLUSIONS: These findings suggest that in the absence of classical apoptotic cell death, radiosensitivity is not predictably related to the p53 status of the cell. While both p53 and c-myc may be linked to the DNA damage response pathway, neither p53 nor c-myc are essential for growth arrest in response to ionizing radiation.     

Potent 2''-amino-, and 2''-fluoro-2''-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor

BACKGROUND: Results of in vitro studies have documented colonic absorption of lactose in the newborn. A stable isotope model was developed for assessing the entry rate of intact lactose into the portal circulation in newborn piglets. METHODS: In experiment 1, unlabeled and [D-1-(13C)]-lactose were infused into two separate mesenteric veins, and in experiment 2, labeled lactose was infused into a mesenteric vein and unlabeled lactose was infused into the colon. The 13C-enrichment of plasma lactose was assessed by high performance liquid chromatography gas chromatography combined with mass spectrometry. RESULTS: The isotopic estimate of the mesenteric venous infusion rate of lactose was 91% of the theoretical. In the second experiment 13% of the unlabeled lactose infused into the colon reached the portal circulation. CONCLUSIONS: The current study provides the first, direct, in vivo confirmation of colon absorption of intact lactose. The tracer model could be used to evaluate intestinal or colonic absorption of other organic compounds not endogenously synthesized, including vitamins or drugs.     

Structural alterations in synaptosomal membrane-associated proteins and lipids by transient middle cerebral artery occlusion in the cat

We have previously reported that ischemia reperfusion injury results from free radical generation following transient global ischemia, and that this radical induced damage is evident in the synaptosomal membrane of the gerbil. [Hall et al, (1995) Neuroscience 64: 81-89]. In the present study we have extended these observations to transient focal ischemia in the cat. We prepared synaptosomal membranes from frontal, parietal-temporal, and occipital regions of the cat cerebral cortex with reperfusion times of 1 and 3 hours following 1 hour right middle cerebral artery occlusion. The membranes were selectively labeled with protein and lipid specific paramagnetic spin labels and analyzed using electron paramagnetic resonance spectrometry. There were significant motional changes of both the protein and lipid specific spin labels in the parietal-temporal and occipital regions with 1 hour reperfusion; but, both parameters returned to control values by 3 hours reperfusion. No significant changes were observed in the normally perfused frontal pole at either reperfusion time. These results support the argument that free radicals play a critical role in cell damage at early reperfusion times following ischemia.