The influence of norethisterone oenanthate on ovarian function

The experiences acquired using a new dilutor in the serological field are dealt with here. The versatile dilutor is particularly adapted to the execution of two-fold dilutions. Among the many possible techniques, the relatives to ASLO, THPA and serum-agglutinins are thoroughly described.     

Estradiol inhibits LDL oxidation: do the progestins medroxyprogesterone acetate and norethisterone acetate influence this effect?

Estrogen replacement therapy in postmenopausal women must be combined with progestin to avoid endometrial cancer. However, progestin addition could antagonize cardioprotective effects of estradiol. Therefore we investigated the effect of the two most commonly used progestins--medroxyprogesterone acetate (progesterone-derivative) and norethisterone acetate (nortestosterone-derivate)--alone and in combination with 17 beta-estradiol on copper-mediated oxidation of low density lipoprotein (LDL). Whereas 17 beta-estradiol alone inhibited the onset of LDL oxidation at the concentrations 0.5, 1.0, 5 and 10 microM, the progestins alone did not demonstrate any significant effect. In the estrogen-progestin combinations of 0.5 microM 17 beta-estradiol with 0.5, 1.0, 5 and 10 microM progestin, respectively, the estradiol effect was not changed. These results suggest that medroxyprogesterone acetate as well as norethisterone acetate do not counteract the beneficial effect of 17 beta-estradiol on LDL oxidation when used in hormone replacement therapy.     

The effect of injectable norethisterone oenanthate on ovarian hormones in Thai women

The ovarian hormones, progesterone and estradiol, as well as norethisterone concentrations were studied in 15 subjects receiving a single intramuscular injection of norethisterone oenanthate. Three treatment groups were studied. The 5 subjects of group A had no additional treatment, the 5 subjects of group B received ethynylestradiol and the 5 subjects of group C received combined ethynylestradiol and norgestrel orally. Additional treatment was for 5 consecutive days 6 weeks after the injection. Blood samples were obtained weekly for 12 weeks post-treatment. All subjects showed a similar pattern of norethisterone concentrations with a range of 3.5-19.5 ng/ml 1 week after injection, declining to levels of less than 0.02 ng/ml at the end of treatment period. Progesterone concentrations of greater than 4 ng/ml indicated that ovulation had occurred in 2 subjects of group A, 5 subjects of group B and 2 subjects of group C during the study period. Serum estradiol concentrations reached pre-ovulatory levels (greater than 200 pg/ml) in 4,3 and 2 subjects of group A,B and C, respectively, during the treatment period. With the other subjects, serum estradiol showed lesser increases. Among the 15 Thai women in the study, the median time of ovulation was 11 weeks, with the earliest occurring at 6 weeks. Three women receiving NET-OEN and no other treatment had ovulated by 6 weeks. Thai women in this study appear to be more resistant to the antiovulatory effect of NET-OEN as compared to women in other published studies.     

Hemodynamic effects of transdermal estradiol alone and combined with norethisterone acetate

Of various vital dyes used to assess schistosomula viability, toluidine blue enabled differential counting of the schistosomula on microscope slides but not in culture wells, whereas methylene blue could be added directly to the schistosomula suspension in culture wells of microtiter plates. Toluidine blue uptake by dead parasites was very fast. It mostly also partially stained damaged but not dead organisms. Its main disadvantage was rapid, nonspecific staining of live schistosomula, requiring prompt counting of a preparation and additional reliance on motility for assessment of viability. Methylene blue staining of dead worms was slower, but it did not stain the live worms until about 1 h after dye application, enabling its addition to a series of preparations for consecutive counting. It did not always stain flattened, dead schistosomula or it stained them an uncontrasting pale blue. This dye remarkably induced movement in seemingly inert and probably damaged worms, thus enabling determination of viability even following poor staining or a lack of staining.     

Propranolol effect on plasma glucose, free fatty acid, insulin, and growth hormone in Graves' disease

A 3-hr glucose tolerance test was performed in 12 thyrotoxic patients before and after propranolol treatment for 30 days (120 mg/day). Plasma glucose, free fatty acid, insulin, and growth hormone levels were determined on each test and compared to each other and against nine clinically healthy volunteers. In eight thyrotoxic patients (subgroup A) an improvement in carbohydrate tolerance was observed after propranolol treatment, along with a fall in the previously elevated fasting FFA; no change in plasma insulin levels was observed. Plasma growth hormone levels were higher than normal both before and after propranolol; however, a 46% glucose-induced suppression was seen in both instances. In the other four patients (subgroup B) (who had had a marked and rapid weight loss) a deterioration of the previously normal glucosnificant changes in insulin levels. Elevated fasting plasma free fatty acids remained so despite propranolol treatment. Plasma growth hormone was higher than normal before and after propranolol; a late suppression (at 120 min) and no suppression at all were seen, respectively. After propranolol treatment, subgroup B had higher plasma free fatty acid than subgroup A in the fasting state and at 30 and 180 min. It is proposed that the improvement or deterioration in carbohydrate tolerance after propranolol treatment might be related to whether or not a satisfactory propranolol-induced lipolytic blockade is achieved, leading to a decrease in plasma free fatty acid levels, improved insulin sensitivity, and better peripheral glucose utilization. Therefore, a uniform dose of propranolol will not always be sufficient to obtain adequate lipolytic blockade, particularly if the thyrotoxic patient has had a marked and rapid weight loss.     

The effects of long-term, moderate intensity, intermittent exercise on aerobic capacity, body composition, blood lipids, insulin and glucose in overweight females

OBJECTIVE: To test the hypotheses that the accumulation of 30 min of moderate intensity, intermittent exercise, 5d/week-1, for 32 weeks, will increase aerobic capacity, alter body composition and improve blood lipids, insulin and glucose. Secondly, to identify individuals who may respond to moderate intensity, intermittent exercise. SUBJECTS: Thirteen sedentary, moderately obese females, aged 43 +/- 11 (y), body mass index (BMI) 32.7 +/- 7.7 (kg/M2), body fat 40.6 +/- 8.8 (%), VO2max 24.0 +/- 4.6 (ml/kg-1/min-1). MEASUREMENTS: Aerobic capacity, body composition, blood lipids, fasting insulin and glucose, energy intake. RESULTS: Group data showed no significant changes for aerobic capacity, body composition, blood lipids, insulin or glucose. However, 7 of the 13 subjects increased aerobic capacity, lost fat weight and improved insulin. Adherence to the exercise regimen was excellent with 82.6 +/- 10.0% of the exercise completed. CONCLUSIONS: Moderate intensity, intermittent exercise for a total of 30 min, 5d/week,-1 for 32 weeks duration, was not a sufficient stimulus to significantly increase aerobic capacity, and alter weight, body composition or improve blood lipids, insulin or glucose for the entire group. However, those subjects who increased aerobic capacity and decreased fat weight were significantly older, had lower maximal aerobic capacity and greater body fat at baseline compared to the six subjects who did not increase aerobic capacity and decrease fat weight. For both groups, moderate intensity, intermittent exercise showed excellent adherence and this may be a useful model for future research studies.     

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 beta-estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary.     

Comparison of the effects of growth hormone and insulin-like growth factor I on substrate oxidation and on insulin sensitivity in growth hormone-deficient humans

Insulin-like growth factor-I (IGF-I) is considered to be the mediator of the growth-promoting effects of growth hormone (GH). The metabolic effects of these two hormones, however, are different. Whereas GH treatment leads to elevated insulin and glucose levels, reduced insulin sensitivity, and impaired glucose tolerance, IGF-I treatment leads to reduced insulin and GH levels and enhanced insulin sensitivity. IGF-I may, therefore, not only be the mediator of the growth-promoting effects of GH but also a modulator of the effects of GH on insulin action and glucose metabolism. To study the influence of GH and IGF-I on substrate metabolism and insulin sensitivity (assessed by euglycemic, hyperinsulinemic clamping combined with indirect calorimetry and glucose tracer infusion), we have treated eight GH-deficient adults with GH (2 IU/m2 daily subcutaneously [s.c.]), IGF-I (10 micrograms/kg.h s.c.), or both hormones together for 7 d, respectively, and compared the effects of these treatment regimens with a control phase. Our findings suggest that (a) both GH and IGF-I promote lipolysis and lipid oxidation, albeit by different mechanisms; (b) treatment with either hormone is followed by enhanced energy expenditure and reduced protein oxidation; and (c) IGF-I reverses the insulin resistance induced by GH.     

Postprandial glucose, insulin, free fatty acid and growth hormone responses in children consuming all the day's protein in one meal

BLOOD GLUCOSE, INSULIN (IRI), growth hormone, and plasma free fatty acids (FFA) were determined in six children consuming a diet of uneven distribution of protein relative to energy (study period). Preprandial and postprandial samples surrounding the 8 AM protein-free feeding and the 3 PM feeding containing all the day's protein were compared with values obtained in the same children similarly sampled while consuming an isonitrogenous isoenergetic diet of even protein distribution (control period). After the 8 AM feeding during the study period there was a mean maximal rise of blood glucose at 30 min of 51 mg/dl compared with a rise of 16 mg/dl during the control period. Glucose remained significantly elevated above fasting values at 120 min during the study but not the control period. IRI response after the 8 AM feeding was significantly greater and suppression of FFA was more marked during the study than during the control period. Glucose concentration 30 min after the 3 PM feeding was significantly lower during the study period than during the control period. A peak value occurred at 60 min during the study period which was equal to the 30 min peak control value. Despite the slower elevation of blood glucose during the study period, IRI rose at 30 min, possibly related to a larger influx of amino acids from the protein-containing meal. FFA rose at 30 and 60 min and were then suppressed by the slowly rising blood glucose. Growth hormone after both meals while consuming both diets was variable but considered normal. The qualitative changes in glucose-IRI-FFA responses were for the most part attributable to differences in the test meals and suggested little long-term adaptation to the uneven protein distribution diet.     

Plasma insulin and growth hormone during antarctic residence

A 50-year-old female developed a swelling in the epigastrium which later ruptured to form a sinus. A diagnosis of primary cutaneous cryptococcosis was made with the help of histopathology and microbiological studies. Treatment with amphotericin-B and 5-flucytosine gave a good therapeutic response and the sinus healed within 2 months.     

The influence of norethisterone acetate on urinary urodilatin excretion in postmenopausal women

Malignant hyperthermia developed in two Landrace x Large White pigs, 75 and 105 minutes after the induction of anaesthesia with halothane. Rapid treatment and discontinuation of halothane anaesthesia were unable to reverse the condition in the first case but were successful in the second. The delayed onset of malignant hyperthermia after delivery of halothane is unusual and for successful treatment careful monitoring and rapid and aggressive therapy are needed.     

The effect of recombinant human growth hormone on regulation of growth hormone secretion and blood glucose in insulin-dependent diabetes

The type 1 copper in Pseudomonas aeruginosa azurin was studied by electron paramagnetic resonance (EPR) spectroscopy at low microwave frequencies. Partially resolved ligand hyperfine structure was observed in the perpendicular region of the spectra at both S-band (2.4 GHz) and L-band (1.1 GHz). A trial and error method, requiring several hundred simulations, has been used to simulate the low frequency EPR data and yield an optimum value of 30 MHz for ACUx, more than one half that previously reported. The fit between the simulated and experimental data is sensitive to changes in the Euler angles and, in particular, to the angle alpha which rotates the Cu A-tensor about the z-axis. Thus, the A- and g-tensors for copper in P. aeruginosa azurin do not appear to be coincident. A value for the Euler angle beta of at least 10 degrees does not disturb the fit between the simulated and experimental data. These studies demonstrate the advantage of evaluating EPR parameters from simulations at more than one frequency, especially at low frequencies where ligand superhyperfine structure may be resolved for type 1 copper.     

Effect of insulin on farnesyltransferase. Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor

We have previously demonstrated that insulin activates farnesyltransferase (FTase) and augments the amounts of farnesylated p21 (Goalstone, M. L., and Draznin, B. (1996) J. Biol. Chem. 271, 27585-27589). We postulated that this aspect of insulin action might explain the "priming effect" of insulin on the cellular response to other growth factors. In the present study, we show the specificity of the effect of insulin on FTase. Insulin, but not insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF), stimulated the phosphorylation of the alpha-subunit of FTase and the amounts of farnesylated p21. Even though all four growth factors utilized the Ras pathway to stimulate DNA synthesis, only insulin used this pathway to influence FTase. Insulin failed to stimulate FTase in cells expressing the chimeric insulin/IGF-1 receptor and in cells derived from the insulin receptor knock-out animals. Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, alpha-hydroxyfarnesylphosphonic acid. We conclude that the effect of insulin on FTase is specific, requires the presence of an intact insulin receptor, and serves as a conduit for the "priming" influence of insulin on the nuclear effects of other growth factors.     

Effects of fasting on insulin binding, glucose transport, and glucose oxidation in isolated rat adipocytes: relationships between insulin receptors and insulin action

Insulin binding, glucose transport, and glucose oxidation were studied in isolated adipocytes obtained from fasting rats. Fasting led to an increase in the overall binding affinity for insulin, while the number of receptor sites per cell remained constant. Glucose oxidation was markedly attenuated during fasting. Basal rates of oxidation decreased by about 50%, while insulin-stimulated rates decreased 6 to 10-fold. Glucose transport was assessed by measuring initial uptake rate of 2-deoxy-glucose. Fasting led to a 40-50% decrease in the apparent maximal transport capacity (Vmax) of 2-deoxy-glucose uptake with no change in apparent Km. A progressive decrease in basal and insulin-stimulated rates of 2-deoxy-glucose uptake was seen from 24-72 h of starvation and a significant correlation (r=0.85, P less than 0.001) existed between basal and maximal insulin-stimulated uptake rates in individual animals. When 2-deoxy-glucose uptake was plotted as a function of insulin bound, due to the decrease in maximal uptake capacity, cells from fasting animals took up less hexose for any amount of insulin bound. When the insulin bound was plotted as a function of the percent insulin effect on uptake, control cells and cells from 24-h-fasted rats gave comparable results, while cells from 48- and 72-h-fasted animals still took up less hexose for any amount of bound insulin. The effects of fasting on 3-O-methyl glucose uptake were comparable to the 2-deoxy-glucose data. In conclusion: (a) insulin binding is increased during fasting due to an increased overall binding affinity with no change in receptor number; (b) glucose oxidation is severely impaired during fasting; (c) 2-deoxy-glucose uptake decreases with fasting due to a decrease in maximal transport capacity (Vmax) with no change in Km; (d) the decrease in glucose oxidation is much greater than the decrease in glucose transport, indicating impaired intracellular oxidative metabolism; and (e) coupling between insulin receptors and the glucose transport system is normal after 24 h of fasting but is impaired at 48 and 72 h.