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Biomedical subjects

D Crook

Publications and source records attributed to D Crook.

At least 109 records · Page 6Linked to original sources
PubMed1989

Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives.

1. Azole antifungal agents such as ketoconazole act by inhibiting cytochrome P-450 mediated sterol synthesis in the fungal cell membrane and thus have the potential to interfere with mammalian steroidogenesis. Fluconazole is a novel orally-effective antifungal triazole which has been reported to have more specific effects on the cytochrome P-450 enzymes involved in fungal sterol synthesis. 2. Due to the potential value of systemic antifungal agents in the treatment of infections commonly occurring in women, we assessed the effect of oral fluconazole on the metabolic profile of 18 healthy premenopausal women, 10 of whom were taking combined oral contraceptives (OC). Each woman acted as her own control, being studied both before and 21-28 days after fluconazole therapy (50 mg daily), in the luteal phase of consecutive menstrual cycles. 3. The endocrinological profile included measurement of serum oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) concentrations, short tetracosactrin adrenal stimulation test and thyroid function tests. Carbohydrate metabolism was investigated by means of an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations. Serum lipids, lipoproteins and apolipoproteins were analysed on samples taken after an overnight fast. 4. Minor biochemical changes associated with fluconazole treatment included increases in serum thyroxine and testosterone concentrations (but not in women taking OC as well as fluconazole) and in insulin and apolipoprotein B levels (but only in women taking OC as well as fluconazole). In general, these changes were small and of no clinical significance with the values remaining within the laboratory normal range. There were no adverse side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Zoladex versus danazol in the treatment of pelvic endometriosis: effects on plasma lipid risk factors.

Plasma lipid risk markers for coronary heart disease (CHD) are influenced by sex steroid concentrations. Therapies that alter sex hormone levels have the potential to affect CHD risk. Zoladex had no effect on plasma lipids, but increased high density lipoprotein (HDL) subfraction 3, a lipoprotein of uncertain clinical significance. Danazol increased low density lipoprotein and decreased HDL concentrations to give a lipid profile associated with increased risk of CHD.

Buserelin↗
PubMed1989

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy.

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.

Adult↗
PubMed1988

Oral contraceptives and coronary heart disease: modulation of glucose tolerance and plasma lipid risk factors by progestins.

Widespread use of oral contraceptive formulations by women throughout their reproductive life has given rise to concerns about the effects of oral contraceptives on risk factors for coronary heart disease. Oral contraceptive-induced changes in both carbohydrate and lipoprotein risk factors may contribute to an increased risk of coronary heart disease. Carbohydrate and lipoprotein risk factors for coronary heart disease are reviewed, and oral contraceptive-induced changes in carbohydrate and lipoprotein metabolism, which may lead to altered risk status for coronary heart disease, are discussed. The importance of methodology in evaluating the results of studies assessing such oral contraceptive-induced changes is stressed. The role of progestins in influencing coronary heart disease risk factors is surveyed, and differences among progestins commonly used in oral contraceptive formulations are discussed. In addition, the effect of various combination oral contraceptives on risk factor status is outlined. Finally, the implications of available evidence for the selection of progestins for oral contraceptive formulations of the future are discussed. Current data indicate that medium- and low-fixed-dose oral contraceptive formulations containing estrogen/norethindrone acetate have less metabolic impact than do comparable levonorgestrel-containing formulations, including multiphasic formulations. Triphasic formulations may have less effect on coronary heart disease risk factors, although data are not yet conclusive. Novel progestins such as desogestrel may also have lesser effects on metabolic functions, but the reduced androgenicity of such compounds may expose women to an increased risk of estrogen-induced hypertriglyceridemia.

Cholesterol, HDL↗
PubMed1988

Investigation of hypertriglyceridemia in small for gestational age fetuses.

Plasma triglyceride, nonesterified fatty acid (NEFA), glycerol, insulin and blood glucose concentrations were measured in 32 small for gestational age (SGA) and 54 appropriate for gestational age fetuses. Although the values of plasma NEFA and glycerol concentrations were not different in the two groups, some SGA fetuses were hypertriglyceridemic, hypoglycemic and hypoinsulinemic. These findings suggest that hypertriglyceridemia in hypoxemic SGA fetuses is not due to lipolysis, nor to increased triglyceride synthesis, but rather to impaired utilization of circulating triglycerides.

Blood Glucose↗
PubMed1987

Drug promotion.

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Drug Industry↗
PubMed1987

Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions.

We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men the age-related increase in low-density lipoprotein (LDL) concentrations diminishes beyond 50 years of age, whereas in women the rate of increase remains unchanged. Studies of the effects of gonadectomy are of doubtful relevance in assessing the roles of sex hormones in CHD, and have not been performed with sufficient rigor to provide definitive conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

An alternative procedure for incorporating radiolabelled cholesteryl ester into human plasma lipoproteins in vitro.

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 degrees C in human serum (d greater than 1.215) that had been prelabelled with [4-14C]cholesteryl oleate or [1,2-3H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. . pmol-1 (46 d.p.m. . ng-1) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction.

Carbon Radioisotopes↗
PubMed1980

Serum bile acid concentration in some experimental liver lesions of rat.

The usefulness of measuring serum bile acid concentrations by RIA in a number of acute experimental liver injuries of rats was assessed by comparing the concentrations with the results of some of the routinely employed methods of examining hepatotoxic changes. Centrilobular liver cell injury produced by CCl4 revealed leakage of GPT and GDH and to a lesser extent AP; along with minimal increase in serum bile acid levels. Serum bilirubin concentration remained unchanged. Surgical bile duct ligation resulted in marked rises in AP, GPT and GDH and total bilirubin levels and levels of serum bile acids. Intravenous injection of MnSO4 induced focal necrosis of liver and bile canalivular dilation associated with elevated GDH and GPT concentrations. AP and bilirubin levels were unchanged. Bile acid levels were raised among female rats. 2,4-Xylidine induced hepatotoxicity revealed bile duct hyperplasia, liver cell enlargement, liver cell necrosis, biliary canalicular dilation and proliferation of endoplasmic reticulum. GDH and GPT levels were raised along with bile acid concentrations. This study suggested that assay of bile acid concentration is a sensitive indicator of several acute hepatic injuries.

Alanine Transaminase↗
PubMed1980

Reversible suppression of spermiogenesis in beagle dogs following overdosage with the narcotic analgesic cogazocine lactate.

Acute single overdosage (1.0 mg/kg, i.m.) with the novel benzmorphan narcotic analgesic agent Cogazocine lactate lowered serum LH and testosterone concentrations of Beagle dogs. The effect was rapidly reversible and persisted for less than 24 h after drug administration. Repeated administration (1.0 mg/kg, i.m.) induced reversible suppression of spermatid maturation with subsequent effects on semen characteristics. Examination of circulating LH and testosterone concentrations, together with pituitary and prostate morphology, suggested that the changes were due to inhibition of LH release. It is probable that the underlying mechanism is an exaggerated pharmacological response to repeated overdosage, common to many potent narcotic analgesic agents.

Analgesics, Opioid↗
PubMed1980

Quantitative aspects of spermatogenesis in rats and dogs after repeated hexachlorophene treatment.

Hexachlorophene was administered orally, at subneurotoxic doses, to rats (5 mg/kg/day) and dogs (3 mg/kg/day) for 9 weeks: some of the rats and dogs were observed for a further 13 weeks. The serum concentrations of pituitary gonadotrophin and testosterone were unaffected in either species. No changes were induced in the testicular dimensions or semen characteristics of dogs and no macroscopic post mortem abnormalities, organ weight differences or lesions detectable by conventional light microscopy were found in their testes, pituitaries or secondary sex organs. A transient reduction in the number of germ cells counted in cross-sections of seminiferous tubules was seen in rats after 4 weeks treatment. After 9 weeks treatment, reduced spermatogonial counts were recorded in canine seminiferous tubules; in other respects spermatogenesis was proceeding normally. No delayed effects were apparent in eith species. It is concluded that repeated administration of hexachlorophene at subneurotoxic levels did not induce significant impairment of spermatogenesis in rats or dogs.

Animals↗
PubMed1980

Effects of morphine sulphate on pituitary-testicular morphology of rats.

Morphine sulphate was administered, buy s.c. injection, to male rats at 50 mg/kg/day for up to 9 weeks. Control rats were given s.c. injections of sterile water. Serum luteinising hormone (LH) and testosterone concentrations and the weight and morphology of testes, pituitary glands and secondary sex organs were examined after 4 and 9 weeks' morphine treatment and also 13 weeks after dosing stopped. Treatment with morphine decreased serum LH and testosterone concentrations and reduced secondary sex organ weights. Differential staining techniques revealed modified secretory activity of pituitary gonadotrophic cells. All stages of spermatogenesis were found in testicular sections, but quantitative reductions in spermatogenic cell populations were found among morphine-treated rats. All the observed effects were reversed within 13 weeks of drug withdrawal. These findings are discussed in relation to existing knowledge of the hormonal control of spermatogenesis in rats.

Animals↗
PubMed1979

Canine pituitary-testicular function in relation to toxicity testing.

The physiological onset and establishment of adult pituitary-testicular function has been characterised for Beagle dogs. Testicular measurements, circulating prolactin, luteinising hormone and testosterone concentrations, semen analyses and the histological appearance of testicular biopsies, suggest that male Beagles attain sexual maturity between 35 and 41 weeks of age. The assessment of testicular toxicity is discussed and attention drawn to possible approaches for investigating primary mechanisms of toxic action on the canine testis. Expected values for testicular size, hormone levels and semen characteristics are reported.

Aging↗
PubMed1977

Comparison of effects of aspirin and indomethacin on human platelet prostaglandin synthetase.

Human platelets were incubated in vitro with either aspirin or indomethacin and the prostaglandin synthetase activity of the resultant microsomal fraction from each incubation measured using a radiometric technique. Whereas aspirin produced a dose-related inhibition of the enzyme, indomethacin produced little or no inhibition over the same concentration range (10(-6) mol/l--10(-3) mol/l). Furthermore, administration of aspirin (600 mg) to volunteers produced a highly significant, prolonged inhibition of platelet microsomal prostaglandin synthetase whereas no inhibition was found with indomethacin (50 mg). As indomethacin is considerably more potent than aspirin as an inhibitor of human platelet prostaglandin synthetase in vitro, the results suggest a fundamental difference in the nature of the inhibition produced by each drug, aspirin being an essentially irreversible inhibitor whereas the inhibition produced by indomethacin is reversible. Studies with [3H-acetyl] aspirin have confirmed previous findings (Roth and Majerus, 1975) that aspirin produces an irreversible acetylation of a particulate fraction protein from human platelets.

Aspirin↗
PubMed1976

Prostaglandin synthetase activity from human rheumatoid synovial microsomes. Effect of 'aspirin-like' drug therapy.

Using a radiometric technique, prostaglandin synthetase activity was measured in vitro in the microsomal fraction of 19 synovial tissues taken from 17 rheumatoid arthritis patients. The enzyme was inhibited in vitro by low concentrations of several 'aspirin-like' drugs, though paracetamol and salicylic acid were virtually inactive. While the synthetase preparations from patients receiving indomethacin, ibuprofen, or naproxen therapy exhibited considerable activity in vitro, we were unable to show any activity in preparations from patients taking aspirin, even in low doses. These findings suggest that in vivo aspirin may be unique in being an irreversible inhibitor of the enzyme, compared with other 'aspirin-like' drugs.

Adult↗