The effect of pindolol on carbohydrate and fat metabolism in diabetes mellitus

Twenty-seven diabetic patients, nine treated with insulin, nine treated with tolbutamid, and nine placed on diet, were given either pindolol or placebo 5 mg, three times daily during a 6-week period. The following 6-week period those receiving pindolol in the first 6 weeks received placebo and vice versa. Pindolol had no influence on the concentration of blood glucose, free fatty acids, triglycerides, or total cholesterol. The effect of pindolol on carbohydrate and fat metabolism appears to be of no clinical relevance in diabetic patients receiving their usual therapy.     

The effect of oral ritodrine on maternal and fetal carbohydrate metabolism

The reported growth-promoting effects of the beta-sympathomimetic compound, ritodrine, have been investigated. The carbohydrate tolerance of eight pregnant women was found to be unaffected by treatment with oral ritodrine over a ten-week period. A further observation that the carbohydrate metabolism of the newborn infants of these women was within normal limits tends to discount possibility that any growth-promoting action ritodrine may have on the fetus is mediated through a diabetogenic effect on the mother.     

The effect of taurine on the carbohydrate metabolism of diabetic animals]

A study was made of a new antidiabetic preparation--taurin in various methods of its administration to rats and rabbits with alloxan and ditisone model of diabetes. A short-term restoration of carbohydrate metabolism was seen after intraperitoneal and intravenous injection in a dose of 200 mg/kg. Oral use of aqueous taurin solution in the same dose failed to produce the desirable result. Microcapsulated taurin with acetylcellulose in the capacity of a filler given per os in a dose of 300 mg/kg restored to the normal glycogen content in the liver and leukocytes, blood and urine sugar level, and the insulin-like activity of blood plasma. Taurin (in a concentration of 3 mg/ml) possessed an insulinogenic action in experiments on fragments of the pancreas isolated from diabetia animals.     

The effect of stevioside on glucose metabolism in rat

This study was conducted to determine the effect of stevioside (SVS) on glucose metabolism. The experiments were performed in male Wistar rats treated with SVS either by intravenous infusion or feeding. SVS infusion (150 mg/mL) was carried out in doses of 0.67, 1.00, and 1.33 mL.kg-1 body weight.h-1. The plasma glucose level significantly increased both during and after SVS infusion, whereas it was not affected by SVS feeding (13.3 mL.kg-1 body weight). The glucose turnover rate (GTR) of [14C(U)]glucose and [3(-3)H]glucose was not significantly different between control and SVS infusion animals. Percent glucose carbon recycling and glucose clearance were reduced from 28.7 +/- 1.3 to 23.0 +/- 1.6% (p < 0.05) and from 6.46 +/- 0.34 to 4.99 +/- 0.20 mL.min-1.kg-1 body weight (p < 0.01), respectively. The plasma insulin level did not change, whereas the plasma glucose level significantly increased from 120.3 +/- 5.9 to 176.8 +/- 10.8 mg% (p < 0.01) during SVS infusion. Animals pretreated with angiotensin II and arginine vasopressin showed no significant effect, while animals pretreated with prazosin had an attenuated hyperglycemic effect of SVS infusion. Pretreatment with indomethacin or N omega-nitro-L-arginine methyl ester (L-NAME) alleviated the plasma glucose level during the second period of SVS infusion. Pretreatment with the combination infusion of indomethacin and L-NAME reduced the plasma glucose level from 117.0 +/- 1.8 to 109.0 +/- 1.7 mg% (p < 0.001), and normalized the plasma glucose level in the second period of SVS infusion. Insulin infusion inhibited the hyperglycemic effect of SVS infusion. The present results show that the elevation of the plasma glucose level during SVS infusion is not due to the reduction of the insulin level. It is probably the effect of SVS on glucose transport across the cell. Insulin response to a high plasma glucose level is suppressed during SVS infusion. Several interactions among norepinephrine, prostaglandin, and nitric oxide are involved in modulating the hyperglycemia during SVS infusion.     

Effect of immobilization on skeletal muscle nicotinic cholinergic receptors in the rat

The effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]alpha-bungarotoxin ([3H]alpha-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.     

Acute effect of ascorbic acid infusion on carbohydrate tolerance

Large doses (1 to 2g/3 hr) of ascorbic acid were administered intravenously to normal weight and obese, nondiabetic subjects. Glucose tolerance and fasting plasma glucose levels were unaffected, despite a 3- to 8-fold rise in plasma concentrations of the vitamin. Infusion of ascorbic acid did not alter fasting serum insulin levels in normal subjects, but was associated with lower concentrations of hormone during an intravenous glucose tolerance test. Plasma glucose, serum insulin, growth hormone, and glucagon levels in obese subjects remained unchanged during the ascorbic acid infusion.     

The effect of propionyl L-carnitine on skeletal muscle metabolism in renal failure

The effect of propionyl L-carnitine on skeletal muscle metabolism in chronic renal failure. Carnitine deficiency, resulting in defective oxidative ATP synthesis, has been implicated in the myopathy of chronic renal failure. Using 31P magnetic resonance spectroscopy we examined calf muscle metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g.p.o. daily. Resting phosphocreatine/ATP (4.41 +/- 0.20 [SEM]) decreased to normal control levels on PLC (3.98 +/- 0.14; controls 4.00 +/- 0.06). In contrast, there was no effect of PLC on aerobic and anaerobic metabolism of muscle during or following 2-10 min exercise. The maximal calculated oxidative capacity (Qmax) remained below normal (28 +/- 3 mM/min before and 24 +/- 3 mM/min after PLC; controls 49 +/- 3 mM/min). Qmax correlated positively with hemoglobin concentration ([Hb]) after PLC (p < 0.03). Oxidative capacity assessed by phosphocreatine recovery T significantly improved with PLC administration (0.93 +/- 0.1 to 0.74 +/- 0.08 min) in those patients (n = 6) with [Hb] > 10 g/dl. [Hb] was rate limiting to oxidative metabolism in recovery from exercise but only following treatment with PLC. Patients with anemia or those subjects who use relatively more non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative metabolism did not normalize on PLC suggesting that anemia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.     

The effect of biotin supplementation on ascorbic acid metabolism in chickens

The objective of the paper was to show the effect of supplementation of biotin (vitamin H) on vitamin C synthesis in chickens. A significant vitamin C increase was observed in kidneys, adrenal glands, liver, glandular stomach, jejunum wall, caecum wall and in blood plasma. A clear increase in the level of D-glucuronic acid was observed in adrenal glands, jejunum wall, and caecum wall. The activity of L-gulono-gamma-oxidase enzyme clearly increased in adrenal glands, jejunum wall and in stomach. The increase in vitamin C synthesis was found in adrenal glands, jejunum, caecum wall and stomach, but accumulation of vitamin C took place in liver and kidneys. The data imply that the supplementation of biotin accelerates vitamin C synthesis in chickens. Biotin, increasing vitamin C level in the organism, indirectly affects all the processes taking place with the participation of vitamin C.     

The effect of promethazine hydrochloride on bilirubin metabolism in the rat

The effect of 21 days of promethazine-HC1 administration on hepatic bilirubin metabolism and transport was studied in adult rats. A significant increase in mean cumulative hepatic bilirubin uptake (84.5 +/- 7.6 (SE) mug/100 g/min in controls vs. 110.0 +/- 4.3 in treated rats), mean hepatic glucuronide conjugation (1,330 +/- 86 (SE) mug bilirubin conjugated/g liver/40 min in controls vs. 1.713 +/- 61 in treated rats), and mean maximal hepatic excretion (47.2 +/- 4.9 (SE) mug/100 g/min vs. 63.5 +/- 2.7) was observed in treated animals. Mean total liver weight and total hepatic protein also increased significantly. These observations suggest that promethazine is an inducer of protein and enzyme synthesis in rat liver and is capable of significantly stimulating the three major steps in hepatic disposal of bilirubin.     

The effect of under- and overnutrition on essential fatty acid metabolism in childhood

Intermittent catheterisation is suitable for a range of patients and has a high level of patient satisfaction. Careful education is required to minimise the risk of complications and nurses should be aware of the various types of catheter available.     

The effect of allopurinol on interstitial purine metabolism and tissue damage in skeletal muscle I-R injury

The causes and manners of death in medico-legal cases from a five-year period were examined. Alcoholics died more often of combined alcohol/drug intoxication and of carbon monoxide poisoning. They had a lower frequency of heart diseases, and there was no support for the existence of an alcoholic heart muscle disease. Lobar pneumonia was only found in alcoholics. There were, as expected, higher frequencies of the known alcohol-related diseases such as hepatic coma, bleeding oesophageal varices and alcohol intoxication. An observed higher frequency of death before the age of 35 could be attributed to alcohol-related diseases. The manners of death showed surprisingly small differences, as the main finding was a higher frequency of alcoholics with undeterminable manner of death.     

The metabolism of 22:5(-6) and of docosahexaenoic acid [22:6(-3)] compared in rat hepatocytes

BACKGROUND: Between January 1985 and June 1995, more than 1800 consecutive patients underwent implantation of a new permanent cardiac pacemaker at our institution. Thirty-six patients (0.02%) had 45 reinterventions for infected pacemaker systems. METHODS: in group A, 24 of 27 patients received simultaneous implantation of a new pacemaker. One had reimplantation of the same pacemaker in the same pocket, and two did not require reimplantation. The leads were retained in 19 (70%) of the patients. In group B, nine patients underwent cardiopulmonary bypass or pursestring surgery for removal of an infected pacemaker; a new epicardial pacemaker system was simultaneously implanted in seven patients. RESULTS: Identification of an infectious agent failed in 17 patients (47%), and Staphylococci were found in 15 patients (42%). The time from pacemaker implantation to onset of infection ranged from 1 month to 11 years (mean 31 months; median 19 months) and the time from onset of infection to surgical treatment from 1 month to 7 years (mean 7 months; median 2 months). The mean follow-up time is 74 months (range, 1 month to 10 years; median 5 years). There were 9 reoperations in 3 patients (16%) of group A for recurrent infection of their retained leads ultimately necessitating the use of open cardiac surgery. There was no early death; six patients died late due to unrelated causes. CONCLUSIONS: Complete removal of all pacemaker leads is recommended; open heart surgery with the use of cardiopulmonary bypass is indicated in selected cases and is effective and safe.     

Age-related abnormalities in regulation of the ryanodine receptor in rat fast-twitch muscle

MPB64, a secretory protein of Mycobacterium bovis BCG Tokyo, was isolated from a culture filtrate of the bacteria in Sauton synthetic medium harvested on day 8. The protein was isolated by five steps; (i) concentration of the culture filtrate by cutting the molecules smaller than 5 kDa with the Millipore Pellicon Cassette system, (ii) affinity separation by a Phenyl Sepharose CL-4B column, (iii) separation with a DEAE-Sepharose CL-6B column with 3 M urea, (iv) separation with a Sephacryl S200HR column, and (v) separation with a DEAE-Sepharose column without urea. MPB64 in each fraction was determined by comparing the band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with that of standard MPB64. The specificity of isolated MPB64 was tested by immunoblotting with anti-MPB64 antibody. The potency of isolated MPB64 in eliciting skin reaction in the BCG-sensitized guinea pigs was the same to that of standard MPB64. The method described herein is an improved one for isolating MPB64 from a large volume of culture filtrate of M. bovis BCG Tokyo. The technique should be applicable to isolation of other mycobacterial secretory proteins.     

The effect of lactic acid bacteria on intestinal metabolism and metabolic profile in gnotobiotic pigs

The effect of inoculation of Lactobacillus casei on selected parameters of metabolic profile and intestinal metabolism of gnotobiotic piglets was investigated during the first three weeks of their life. The experiment was carried out on 8 germ-free piglets. The experimental group was inoculated once a day with the Lactobacillus casei subsp. casei strain. The inoculum contained 1 x 10(8) microorganisms in 1 ml. The control group of piglets received no inoculum. Lactobacillus casei colonized jejunum and ileum in the numbers from 5.63 to 6.06 log 10 cm-2 and their numbers in the jejunal and ileal contents were in the range 8.38-9.87 log 10.ml-1. The daily consumption of milk by the inoculated animals was significantly higher (p < 0.001). The average weight of inoculated piglets at the end of the period investigated was higher by 29.7%. Lactobacillus casei affected several parameters investigated. Piglets inoculated with lactobacilli showed significantly lower (p < 0.05-0.01) values of pH of the jejunal content, numbers of erythrocytes, values of haematocrit, urea, glucose, total lipids, cholesterol and calcium in the serum and significantly higher values (p < 0.05-0.01) of lactic acid in the jejunal content. The values of phagocytic activity and the index of phagocytic activity in the piglets of the experimental group were two to three-fold higher in comparison with those detected in the control group. The application of Lactobacillus casei affected positively the growth of gnotobiotic piglets, their intestinal metabolism, the level of cholesterol in the serum and phagocytic activity.     

The relative effect of dietary fats and carbohydrates on lipid metabolism in the albino rat

This study is concerned with the effect of two carbohydrates, cane-sugar and corn starch, at four different levels in the presence of two dietary fats, on the serum and the tissue lipids (cholesterol, phospholipid and fatty acid patterns). Keeping the dietary fats (coconut safflower seed oil) at 20% level, diets containing (a) startch (54%) + cane sugar (0%), (b) starch (44%) + cane sugar 10%), (c) starch (10%) + cane sugar (44%) and (d) only cane sugar (54%) were administered to rats for 8 weeks. The lipid levels were determined at the end of the feeding period. The beneficial effect of the unsaturated fat in lowering the serum cholesterol level is nullified by an excess of cane sugar in the diet. In liver, there is an increase of 40-50% of cholesterol, as the cane sugar level in the diet is raised, irrespective of the type of dietary fat. The fatty acid pattern of the serum and tissue lipids is influenced by dietary fats as well as carbohydrates.     

Prolonged exposure to halothane and associated changes in carbohydrate metabolism in rat muscles in vivo

Halothane, an anesthetic presently used in animal experimentation, is reported to stimulate glycogen breakdown in isolated preparations of rat skeletal muscles, suggesting that it may not be a suitable anesthetic for the study of glycogen metabolism in rats in vivo. The purpose of this study was to establish whether prolonged exposure to halothane in rats in vivo is associated with accelerated glycogenolysis. Exposure of rats to halothane for up to 1 h was not accompanied by either any change in the levels of glycogen or increase in activity ratios of glycogen phosphorylase in muscles, irrespective of their fiber compositions. In marked contrast, the levels of lactate, inorganic phosphate, glucose 1-phosphate, glucose 6-phosphate, fructose 1,6-bisphosphate, and fructose 2, 6-bisphosphate changed progressively during anesthesia. Accordingly, the interpretation of muscle metabolite levels must be performed with caution in experiments involving prolonged exposure to halothane. Overall, our findings indicate that the reported halothane-mediated stimulation of glycogen breakdown in vitro is likely to be an artifact and that halothane is a suitable anesthetic for experiments concerned with glycogen metabolism in rats.     

The effects of norgestrel on carbohydrate and lipid metabolism over one year

Carbohydrate and lipid metabolism were studied with the use of a three-hour oral glucose tolerance test in 71 women before and after one year of daily oral norgestrel, 0.075 mg., treatment. There was no significant change in weight or fasting plasma triglyceride and cholesterol levels. There was a significant elevation of both the blood glucose and plasma insulin levels after one year of treatment. This was true for both the fasting and the glucose-stimulated values. Whereas all of the individual glucose tolerance curves at the pretreatment control test were normal by selection, 15.5 per cent of the curves were borderline abnormal to abnormal at the one-year test. The significance of these metabolic alterations is discussed.     

Effect of carbohydrate restriction on lipoprotein abnormalities in maturity-onset diabetes mellitus

Hyperlipoproteinemia occurs commonly in diabetics and may contribute to early atherosclerosis in these patients. The effect of dietary carbohydrate restriction on lipid abnormalities has been examined in 42 newly diagnosed maturity-onset diabetics, in whom plasma lipoproteins were measured before treatment was started and at regular intervals during ten months of dietary therapy. Twenty-four patients (57%) had abnormal lipids when diabetes was first diagnosed. Nine were classed as Type II and 15 as Type IV hyperlipoproteinemia. Plasma lipids reverted to normal in half these patients after dietary treatment for one month. Only 8 diabetics (19%) showed persistent lipid abnormality after ten months' treatment: all had been unable to diet satisfactorily as judged by persisting obesity and hyperglycemia. The common lipoprotein abnormalities of maturity-onset diabetes can usually be returned to normal by the simplest possible carbohydrate-restricted diet, if patients adhere to this. Specialized and complex diets or lipid-lowering drugs are unncessary in the majority of patients.     

Pharmacology of the nicotinic acetylcholine receptor from fetal rat muscle expressed in Xenopus oocytes

BACKGROUND: Firefly luciferase is a 62 kDa protein that catalyzes the production of light. In the presence of MgATP and molecular oxygen, the enzyme oxidizes its substrate, firefly luciferin, emitting yellow-green light. The reaction proceeds through activation of the substrate to form an adenylate intermediate. Firefly luciferase shows extensive sequence homology with a number of enzymes that utilize ATP in adenylation reactions. RESULTS: We have determined the crystal structure of firefly luciferase at 2.0 A resolution. The protein is folded into two compact domains. The large N-terminal domain consists of a beta-barrel and two beta-sheets. The sheets are flanked by alpha-helices to form an alphabetaalphabetaalpha five-layered structure. The C-terminal portion of the molecule forms a distinct domain, which is separated from the N-terminal domain by a wide cleft. CONCLUSIONS: Firefly luciferase is the first member of a superfamily of homologous enzymes, which includes acyl-coenzyme A ligases and peptide synthetases, to have its structure characterized. The residues conserved within the superfamily are located on the surfaces of the two domains on either side of the cleft, but are too far apart to interact simultaneously with the substrates. This suggests that the two domains will close in the course of the reaction. Firefly luciferase has a novel structural framework for catalyzing adenylate-forming reactions.     

The effect of inhibitors of arachidonic acid metabolism on proliferation and death of tumor cells

We describe a distinctive tissue artifact that results from the use of biopsy bags for processing small impressionable pieces of tissue. In its fully developed form, the artifact produces a tic-tac-toe pattern, while in less pronounced cases it may produce elongated oval spaces in the tissue or a serrated contour at the periphery of the tissue. The artifact was observed in 60% of endometrial specimens, 55% of endocervical curettings, and sporadically in other small specimens. In the endometrial and endocervical specimens, the artifact was focal and did not interfere with the diagnosis. In occasional small lung and prostate specimens, there was focally significant distortion that potentially could compromise the diagnosis.