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1.
Chronic oestrogen treatment augments adenohypophyseal weight and the thyroxine-binding capacity of adenohypophyseal proteins in rats. Since these reactions are both inhibited by ergocornine and ergoline derivatives (as well as by the thyroid hormones, testosterone, anti-oestrogens and antiandrogens), and are potentiation by perphenazine and the dopaminergic neurone blocker Pimozide, the peroral effectiveness of various other substances presumed to act in the region of the dopaminergic or serotoninergic neurones of the hypothalamus was tested. L-DOPA (10 mg/rat/day) did not modify the adenohypophyseal reaction, either alone or combined with the DOPA-decarboxylate inhibitor Ro-4-4602 (1 mg/rat/day). alpha-Methyl-DOPA (10 mg/rat/day), apomorphine (3 mg/rat/day), haloperidol (0.2 mg/rat/day), pyridoxine (20 mg/rat/day) and cyproheptadine (1 mg/rat/day) were likewise ineffective.  相似文献   

2.
Studies of embryo-fetal development in rats were conducted with two 5-lipoxygenase inhibitors. SB-202235 (1,000 mg/kg/day) or SB-210661 (50, 100, or 500 mg/kg/day) was administered orally by gavage to female rats on days 6-17 postcoitus (pc) or days 7-16 pc. SB-202235 (1,000 mg/kg/day) and SB-210661 (100 mg/kg/day) reduced maternal body weight gain for the treatment period by 16% and 21%, respectively, relative to controls. SB-202235 (1,000 mg/kg/day) or SB-210661 (50 or 100 mg/kg/day), did not affect numbers of resorptions, dead or live fetuses/litter, but 500 mg/kg/day of SB-210661 caused 100% embryo lethality. SB-202235 (1,000 mg/kg/day) and SB-210661 (50 and 100 mg/kg/day) reduced fetal body weight by 15-30% and produced extensive cardiovascular malformations, as well as diaphragmatic hernias. SB-210661 also caused thymic abnormalities and cryptorchidism. Cardiovascular defects included abnormalities in aorticopulmonary septation, the aortic arch, pulmonary trunk, and ventricular septal defects are discussed relative to comparable human syndromes of cardiovascular malformation.  相似文献   

3.
The effect of propranolol was studied in a double-blind crossover trial in 24 carefully selected hypertensive outpatients. Each patient received propranolol 60 mg/day, 120 mg/day, 240 mg/day, and placebo for four weeks each according to a randomised sequence. Propranolol 60 mg/day was no better than placebo in reducing blood pressure. The effects of propranolol 120 mg/day and 240 mg/day were not significantly different. Both doses reduced lying blood pressure by about 20/10 mm Hg from an initial level of 173/104 mm Hg. No difference was detected between the effects of the different doses of propranolol and placebo on weight or on the occurrence of adverse reactions.  相似文献   

4.
Swimming activity of the obligatory air-breathing fish Ophiocephalus striatus reared in cylindrical aquaria on different rations (0–43.3 mg/g/day) increased from 58 m/day for the starving group to 439 m/day for the group fed a maximum ration. Swimming speed also increased from 2.4 cm/sec in the former group to 5.2 cm/sec in the latter group. Owing to sustained swimming activity and the consequent fatigue, the test individuals 'hung' to the surface for a definite interval. Duration of surface 'hanging' increased from 3.2 h/day to 15.8 h/day with decreasing ration. The group receiving 25.5 mg/g/day converted most efficiently (28%). The maintenance energy cost is equivalent to 10 mg/g/day and dry substance equivalent to 5 or 12 mg/g/day was expended on the sustained swimming activity by the fish receiving the optimum (25 mg/g/day) or the maximum (43 mg/g/day) ration.  相似文献   

5.
Cimetidine, a substituted imidazole, is an inhibitor of hepatic cytochrome P-450-mediated drug metabolism in rats and humans. We investigated the effect of cimetidine on phenobarbital induction of hepatic microsomal aminopyrine N-demethylase activity in the rat. Phenobarbital induction of aminopyrine N-demethylase was log-linear in the range of 1-6 mg/kg/day and the ED50 was approximately 3 mg/kg/day. Cimetidine 75 mg/kg (four times a day) attenuated the induction of aminopyrine N-demethylase activity by 58% in low dose (3 mg/kg/day) but not in high dose (40 mg/kg/day) phenobarbital treated rats. This result could not be explained by residual inhibition of enzyme activity by cimetidine and suggests that cimetidine affects the induction of hepatic cytochrome P-450 by low dose phenobarbital.  相似文献   

6.
OBJECTIVE: To describe the effect of CoQ10 (added to either a fibrate, or PUFA or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. DESIGN: Open, sequential, comparative intervention study. SETTING: Specialised centres for dyslipidemia management. SUBJECTS: 15 subjects (mean age: 45.1 +/- 12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. INTERVENTIONS: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day + fenofibrate 200 mg/day, PUFA 3000 mg/day + CoQ10 150 mg/day, fenofibrate 200 mg/day + CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day + PUFA 3000 mg/day + CoQ10 150 mg/day. RESULTS: CoQ10 supplementation improved, in the control group, systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and gamma-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. CONCLUSION: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone.  相似文献   

7.
On a restricted food supply of Tubifex tubifex (2h/day) the fish consumed only 69.5 mg dry food/g live fish/day and grew only to 25.6 mg live body weight by the 30th day of it's age, while those fed ad libitum consumed 94.7 mg/g/day and attained a body weight of 125.9 mg live weight by the 30th day. Conversion efficiency (K1) averaged to 8.3% in the former and 14.1% in the latter series, throughout the 30 day experimental period.Feeding rate of the test series fed individually and at ad libitum, decreased from 780 mg dry food/g dry fish/day for a fish weighing 4 mg dry weight to 180 mg/g/ day for one weighing 41 mg, exhibiting a log-log relationship to the body weight (Y = 2.20140–0.5639 X). Growth rate also decreased as a log-log function with increasing body weight (Y = 1.2309–0.4384 X).  相似文献   

8.
Linagliptin (TRADJENTA?) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3-4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67-89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (-16.5% to -20.3%; P<0.01) or 30 mg/kg/day (-14.5% to -26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic-hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected by the insulin sensitizing effect of linagliptin. Long-term linagliptin treatment reduced liver fat content in animals with diet-induced hepatic steatosis and insulin resistance, and may account for improved insulin sensitivity.  相似文献   

9.
Monod's equation adequately described aerobic biodegradation rates of benzene and toluene by the microbial population of a sandy aquifer when these compounds were initially present at concentrations lower than 100 mg/l each. Concentrations higher than 100 mg/l were inhibitory, and no benzene or toluene degradation was observed when these compounds were initially present at 250 mg/l each. The Monod coefficients were calculated as k = 8.3 g-benzene/g-cells/day and Ks = 12.2 mg/l for benzene, and k = 9.9 g-toluene/g-cells/day and Ks = 17.4 mg/l for toluene. Specific first-order coefficients would be 0.68 l/mg.day for benzene and 0.57 l.mg.day for toluene.  相似文献   

10.
Studies on energy transformation in the freshwater snail Pila globosa   总被引:1,自引:0,他引:1  
The effects of eleven chosen feeding levels ranging from 0 to 198 mg damp dry (plant) Ceratophyllum/g live snail/day on the absorption, conversion and metabolism of the snail Pila globosa (of 1 -9 g body weight) have been studied. Absorption rates increased from 3-0 to 21-0 mg dry food/g live snail/day in snails fed 3-4-28-8 mg dry food/g live snail/day. In these snails, absorption efficiency decreased from 87.5 to 73.0%. Conversion rates increased from 0-3 mg/g/day for snails receiving 23-4 mg/g/day to 2-7 mg/g/day for those fed maximum amounts, and the efficiency (K2) also increased from 1-9% to 130%. When compared to other gastropods, Pila globosa appears to be a poor convertor. During 30 days' starvation, the test individuals lost 4.4 mg dry body substance/g/day i.e. the maintenance cost was 14-7 cal/g live snail/day. The SDA increased by four times for those feeding on maximum rations in comparison to those receiving about 5 mg/g/day, i.e. the energy cost for converting food was increased four times.  相似文献   

11.
Cerebrotendinous xanthomatosis (CTX) is a rare inherited lipid storage disease caused by a defect in bile acid synthesis in which cholesterol and its product cholestanol are deposited in neurological and vascular tissue. Therapy with chenodeoxycholic acid but not with the 7 beta-epimeric ursodeoxycholic acid is usually successful. In an untreated patient, total and low density lipoprotein (LDL) cholesterol were found to be low (134 +/- 11 and 78 +/- 8 mg/dl, respectively). The production rate (PR) and fractional catabolic rate (FCR) of very low density (VLDL) apolipoprotein B (apoB) were, however, both markedly increased (34.7 mg/kg per day and 13.7 pools/day, respectively vs. 15.1 +/- 5.0 mg/kg per day and 6.2 +/- 3.8 pools/day in controls) while the PR and FCR of LDL apoB were moderately elevated (16.3 mg/kg per day and 0.65 pools/day, respectively vs. 12.9 +/- 1.2 mg/kg per day and 0.52 +/- 0.10 pools/day in controls). After 1 month of 750 mg/day of chenodeoxycholic acid, the FCR and PR of both VLDL and LDL apoB became normal while total plasma cholesterol increased significantly to 145 +/- 18 mg/dl. In a second patient who had been receiving 750 mg/day of chenodeoxycholic acid for 6 months lipoprotein kinetics were normal. These parameters did not change when the subject was switched to 750 mg/day ursodeoxycholic acid. We postulate that cholesterol biosynthesis in CTX is derepressed by a diminished hepatic pool of chenodeoxycholic acid and that the elevated secretion of apoB is a response to the increased rate of cholesterol production.  相似文献   

12.
A Ortega  M Puig  J L Domingo 《Teratology》1991,44(4):379-384
1-beta-D-Arabinofuranosylcytosine (Ara-C), an effective drug for the treatment of leukemia and breast cancer, was evaluated for developmental toxicity in pregnant Swiss mice. Ara-C was administered by intraperitoneal injection on gestational days 6-15 at doses of 0, 0.5, 2, and 8 mg/kg/day. Maternal observations included clinical signs, body weight change, food consumption, and gross evaluation of organs and uterine contents at necropsy (day 18). Live fetuses were examined for external, visceral, and skeletal alterations. Maternal toxicity was observed at 2 and 8 mg/kg/day, as evidenced by a significant decrease in body weight gain and food consumption during the treatment period. Significantly increased early and late resorptions and reduced number of live fetuses per liter as well as decreased fetal body weight were observed at 8 mg/kg/day. At 2 mg/kg/day, the incidence of cleft palate, renoureteral agenesis or hypoplasia, and poly- or oligodactyly was significantly increased, whereas fetal weight was reduced at 0.5 mg/kg/day. Thus, the developmental no-observed-adverse-effect-level (NOAEL) of Ara-C in the pregnant mouse is lower than 0.5 mg/kg/day, while the NOAEL for maternal toxicity is 0.5 mg/kg/day. We believe that exposure to this agent ought to be avoided during organogenesis.  相似文献   

13.
The effect of a low dose of methyldopa combined with (a) a non-selective and (b) a selective beta-adrenoceptor antagonist was studied in a double-blind crossover trial in 24 carefully selected patients with moderate hypertension (mean initial lying blood pressure 189/117 mm Hg). Each patient received methyldopa 750 mg/day, propranolol 240 mg/day, practolol 600 mg/day, methyldopa 750 mg/day combined with propranolol 240 mg/day, methyldopa 750 mg/day combined with practolol 600 mg/day, and placebo for four weeks each according to a random sequence. After four weeks of therapy the most effective treatment, methyldopa combined with propranolol, reduced lying and standing blood pressures by 36-5/21-4 mm Hg and 44-7/25 mm Hg respectively. Thic combination had similar effects to those of the combination of methyldopa with the cardioselective agent practolol except that it reduced lying diastolic pressure further. The combination was more effective than either treatment alone. No significant differences were found between the effects of propranolol, practolol, or methyldopa at the doses used.  相似文献   

14.
D-fenfluramine, an anorectic agent in rats and man, was administered daily at doses 1.25, 2.5, 5 or 10 mg/kg/day for 10 days, and sacrificed 6 days later. Hypothalamic serotonin (5-HT) levels were unchanged in rats receiving 1.25-5 mg/kg/day of d-fenfluramine but reduced by 22% (p less than 0.01) at the highest drug dose (10 mg/kg/day); hypothalamic 5-hydroxyindole acetic acid (5-HIAA) levels were reduced by 15% (p less than 0.05) or 28% (p less than 0.01) in rats receiving 5 or 10 mg/kg/day of the drug, respectively. Hypothalamic slices prepared from rats which were previously treated with any of the drug doses spontaneously released endogenous 5-HT at rates that did not differ from those of vehicle-treated rats. 5-HT released with electrical field-stimulation was unaffected by prior d-fenfluramine treatment at doses of 1.25-5 mg/kg/day, and was reduced by 20% (p less than 0.05) from slices prepared from rats which received 10 mg/kg/day. 5-HIAA efflux was also attenuated by the highest drug dose. These data indicate that chronic administration to rats of customary anorectic doses of d-fenfluramine (i.e. 0.06-1.25 mg/kg) fail to cause long-lasting reductions in brain 5-HT release.  相似文献   

15.
The rates of mobile cholesterol turnover processes were measured by the isotopic equilibrium method in normocholesterolemic (SW) and hypercholesterolemic homozygote (RICO) rats fed a semi-synthetic base diet containing 0.05% cholesterol. When the absorption rate is similar in SW and RICO rats, the internal secretion rate is 60% higher in RICO (25.3 mg/day) than in SW (16.2 mg/day). This increase is compensated by an increase in fecal excretion (RICO: 5 mg/day; SW: 3.8 mg/day), urinary excretion (RICO: 1.7 mg/day; SW: 1.1 mg/day) and above all the transformation of cholesterol into bile acids (RICO: 24.2 mg/day; SW: 15.3 mg/day). The fact that 70 minutes after [14C]acetate administration, the only variations obtained in RICO compared to SW rats are a doubled sterol radioactivity in the small intestine and a tripled one in the liver suggests that the increase in internal secretion of the RICO rat has both an intestinal and hepatic origin. This cholesterogenic stimulation in RICO rats takes place in the jejunum as well as in the ileum and in the crypt cells as well as in the villosities. It is concomitant with a doubled cholesterolemia, a doubled intestinal, caecal and colon bile acid pool and a 20% increase in the enterocyte protein content.  相似文献   

16.
Using diets with a mounting egg albumin and mutton protein concentration, the authors determined the optimum physiological doses, which are identical with the maximum of linearity of the given parameters, from changes in body nitrogen, body weight and body water. The regression equations of the lines from these parameters were used to determine the minimum physiological doses for newly weaned rats. The optimum and minimum physiological doses of the amino acids in the relevant dietary proteins were also determined by analysing the source for its nitrogen content and other components and for the amino acid spectrum. The optimum dose of egg albumin protein for newly weaned rats was 1.69 g/day (on a 15% protein diet) and of mutton protein 2.56 g/day (on a 12.5% protein diet), with daily amounts of 60 mg methionine, 93 mg phenylalanine, 112 mg valine and 60 mg tyrosine for both proteins. The minimum doses of egg albumin and mutton protein, determined from changes in body nitrogen were 282 mg and 213 mg/day respectively [methionine 10.4 (4.7) mg/day, phenylalanine 16.1 (7.5) mg/day, valine 19.1 (9.2) mg/day and tyrosine 9.8 (5.2) mg/day)].  相似文献   

17.
Isotopic methods for the measurement of dietary cholesterol absorption were compared with the lymph cholesterol balance procedure in filarial chyluria patients. After a single intravenous injection of radioactive cholesterol, absorption was found to be 746 +/- 136 mg/day by method I, which is based upon the fecal endogenous neutral steroid mass measurement, and 471 +/- 135 mg/day by the simultaneously measured lymph/plasma ratio of cholesterol specific activity (dpm/mg). The corresponding value, determined as the difference between lymph cholesterol transport on a cholesterol-containing diet (1500 mg) and on a cholesterol-free diet, was 622 mg/day. When radioactive cholesterol (1487 mg/day) was fed daily to a second patient, absorption determined by isotopic fecal recovery (353 mg/day) matched that obtained by the lymph balance procedure (326 mg/day). Transudation of plasma cholesterol into the intestinal lymph, estimated by the single intravenous injection of radioactive beta-sitosterol, was independent of both the luminal content of plant sterols and the absorption of dietary cholesterol. The absorption of endogenous cholesterol was calculated by: 1) subtracting the cholesterol originating from plasma (transudation) together with the absorbed dietary cholesterol found in lymph from the total mass of cholesterol transported in lymph, and 2) the lymph balance method, i.e., after interrupting the endogenous cholesterol mucosal uptake by beta-sitosterol feeding (9 g/day) while on a cholesterol-free diet. Endogenous cholesterol was preferentially absorbed compared to dietary cholesterol, but there was no competition for absorption. The major portion of dietary cholesterol found in lymph was esterified, but esterification was not a prerequisite for absorption.  相似文献   

18.
The ability of the Alcaligenes faecalis 2 strain to utilize acrylamide and acrylic acid upon cultivation with these compounds as the only sources of carbon and energy has been investigated. Complete utilization of the acrylic acid present in the medium at concentrations below 0.113 g/L was observed by cultivation day 5, at a concentration of 0.225 g/L by day 7, and at a concentration of 0.45 g/L by day 17. Complete utilization of the acrylamide present in the medium at concentrations below 0.4 g/L was observed by day 5, at a concentration of 0.9 g/L by day 7, and at a concentration of 1.8 g/L by day 20. Importantly, bacterial growth did not start before complete transformation of acrylamide into acrylic acid. The rate of acrylamide transformation by growing bacteria and a cell suspension in the stationary growth phase amounted to 12.5 mg/L h at a cell concentration of 610 mg/L and 300 mg/L h, at a concentration of 1500 mg/L. A. faecalis 2 cells immobilized on BVV-22 basalt fibers and Carbopon-B-aktiv at concentrations of 3000 and 800 mg dry cells/L, respectively, transformed acrylamide at a rate of 1200 mg/L h.  相似文献   

19.
Rats given gentamicin chronically become resistant to its nephrotoxic effects. To further explore this adaptation to nephrotoxicity, we gave male rats gentamicin 40 mg/kg/day for 12 days, then 80 mg/kg/day for 24 days. We then challenged them with 110 mg/kg/day of gentamicin for 9 days. Spermine was given 16 mg/kg/day for 42 days, then gentamicin challenge at 60 mg/kg/day for 9 days. Gossypol was given at 6 mg/kg/day for 19 days, then gentamicin at 60 mg/kg/day for 21 days. A fourth group of rats (controls) received 0.5 ml saline daily for 42 days and then received gentamicin 60 mg/kg/day for 9 days. Urine N-acetyl-beta-glucosaminidase (NAG) was measured 3 times weekly and serum creatinine was measured 5 times during the study. Each drug-treated rat increased its urine NAG from baseline values. After a period of drug administration, all NAG values returned to the predrug values. Then all animals were given gentamicin daily. NAG values increased 20-fold in the animals previously treated with saline but did not rise in the other groups. The serum creatinine frequently but not always changed in parallel with the NAG values. These observations indicate that adaptation to these nephrotoxic substances occurs and that cross-resistance to gentamicin is produced by spermine and gossypol.  相似文献   

20.
Grape proanthocyanidins (GPCs) are a family of naturally derived polyphenols that have aroused interest in the poultry industry due to their versatile role in animal health. This study was conducted to investigate the potential benefits and appropriate dosages of GPCs on growth performance, jejunum morphology, plasma antioxidant capacity and the biochemical indices of broiler chicks. A total of 280 newly hatched male Cobb 500 broiler chicks were randomly allocated into four treatments of seven replicates each, and were fed a wheat–soybean meal-type diet with or without (control group), 7.5, 15 or 30 mg/kg of GPCs. Results show that dietary GPCs decrease the feed conversion ratio and average daily gain from day 21 to day 42, increase breast muscle yield by day 42 and improve jejunum morphology between day 21 and day 42. Chicks fed 7.5 and 15 mg/kg of GPCs show increased breast muscle yield and exhibit improved jejunum morphologies than birds in the control group. Dietary GPCs fed at a level of 15 mg/kg markedly increased total superoxide dismutase (T-SOD) activity between day 21 and day 42, whereas a supplement of GPCs at 7.5 mg/kg significantly increased T-SOD activity and decreased lipid peroxidation malondialdehyde content by day 42. A supplement of 30 mg/kg of GPCs has no effect on antioxidant status but adversely affects the blood biochemical indices, as evidenced by increased creatinine content, increased alkaline phosphatase by day 21 and increased alanine aminotransferase by day 42 in plasma. GPC levels caused quadratic effect on growth, jejunum morphology and plasma antioxidant capacity. The predicted optimal GPC levels for best plasma antioxidant capacity at 42 days was 13 to 15 mg/kg, for best feed efficiency during grower phase was 16 mg/kg, for best jejunum morphology at 42 days was 17 mg/kg. In conclusion, GPCs (fed at a level of 13 to 17 mg/kg) have the potential to be a promising feed additive for broiler chicks.  相似文献   

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