Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HEXOSAMINES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2000

Overexpression of glutamine:fructose-6-phosphate amidotransferase in rat-1 fibroblasts enhances glucose-mediated glycogen accumulation via suppression of glycogen phosphorylase activity.

The hexosamine biosynthesis pathway (HBP) mediates many of the adverse effects of excess glucose. We have shown previously that glucose down-regulates basal and insulin-stimulated glycogen synthase (GS) activity. Overexpression of the rate-limiting enzyme in the HBP, glutamine:fructose-6-phosphate amidotransferase (GFA), mimics these effects of high glucose and renders the cells more sensitive to glucose. Here we examine the role of the HBP in regulating cellular glycogen content. Glycogen content and glycogen phosphorylase (GP) activity were determined in Rat-1 fibroblasts that overexpress GFA. In both GFA and controls there was a dose-dependent increase in glycogen content (approximately 8-fold) in cells cultured in increasing glucose concentrations (1-20 mM). There was a shift to the left in the glucose dose-response curve for glycogen content in GFA cells (ED50 for glycogen content = 5.80+/-1.05 vs. 8.84+/-0.87 mM glucose, GFA vs. control). Inhibition of GFA reduced glycogen content by 28.4% in controls cultured in 20 mM glucose. In a dose-dependent manner, glucose resulted in a more than 35% decrease in GP activity in controls. GP activity in GFA cells was suppressed compared with that in controls, and there was no glucose-induced down-regulation of GP activity. Glucosamine and uridine mimicked the effects of glucose on glycogen content and GP activity. However, chronic overexpression of GFA is a unique model of hexosamine excess, as culturing control cells in low dose glucosamine (0.1-0.25 mM) did not suppress GP activity and did not eliminate the glucose-mediated down-regulation of GP activity. We conclude that increased flux through the HBP results in enhanced glycogen accumulation due to suppression of GP activity. These results demonstrate that the HBP is an important regulator of cellular glucose metabolism and supports its role as a cellular glucose/satiety sensor.

Animals↗
PubMed1983

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. II. Inhibitory effects of carboxamide-methylated L chain from human serum IgG on various ulcer models and its inhibition mechanism.

In view of the strong inhibitory effects of the carboxamide-methylated L chain (Fr. I-L) from human IgG on gastric ulceration and juice secretion, we carried out various experiments to clarify the mechanism of its action and obtained the following results. Fr. I-L inhibited the gastric ulceration induced by phenylbutazone or aspirin in rats, but no appreciable effect was observed on stress or acetic acid ulceration. The distribution of 14C-labelled Fr. I-L increased particularly in the stomach mucous membrane of rats after the intravenous or intraperitoneal administration. The hexosamine content in the gastric mucous membrane, reduced by the treatment with phenylbutazone, aspirin or pylorus-ligation, was recovered by the administration of Fr. I-L to an intact level. The high total of hexosamine levels found in the gastric juice after aspirin treatment or pylorus-ligation were decreased by the injection of Fr. I-L or cimetidine. The histochemical observation revealed that the concomitant administration of Fr. I-L with phenylbutazone or aspirin prevented the abolishment of Hematoxylin-Eosin, Periodic Acid Schiff and Alcian Blue staining polysaccharides from the stomach epithelial cells.

Animals↗
PubMed1983

Inhibitory effects of unsaturated fatty acids of trans-2-C10:1 to trans-2-C16:1 several C18:n and C20:n on gastric secretion and experimental ulceration in rats.

Among various unsaturated fatty acids which were examined in this experiment, trans-2-tridecenoic acid was found to be a potent inhibitor on gastric secretion in rats (i.p. or i.d.). Therefore, the effects of trans-2-tridecenoic acid on several experimental ulcerations in rats were examined. At the dose of 10 mg/kg, trans-2-tridecenoic acid significantly decreased the ulcer index in pylorus-ligated rats; aspirin-, phenylbutazone-, histamine- and stress-induced ulcerations were also significantly inhibited at the dose of 25 mg/kg. Finally, effects of trans-2-tridecenoic acid on hexosamine and sialic acid contents in the gastric mucous were examined. In intact or phenylbutazone-induced ulcerated rats, trans-2-tridecenoic acid increased the sialic acid levels in the gastric mucous at the dose of 25 mg/kg. The decreased hexosamine content in the gastric mucous by phenylbutazone treatment was recovered by the administration of trans-2-tridecenoic acid.

Animals↗
PubMed1989

[Pharmacological study on Agkistrodon blomhoffii blomhoffii BOIE. I. Effect of the 50% ethanolic extract on experimental gastric ulceration].

Anti-ulcerogenic activities of a 50% ethanolic extract [( M]) from whole body of Agkistrodon blomhoffii blomhoffii BOIE were investigated in rats. [M] at oral doses of 250-500 mg/kg was found to show a prophylactic effect on the water-immersion stress- and ethanol-induced ulcer and a remedial effect on acetic acid-induced ulcer, but not Shay-ulcer in pylorus-ligated rats and indomethacin-induced ulcer. [M] increased the gastric mucosal blood flow in intact rats and improved the decrease of the blood flow in acetic acid-induced ulcer rats. [M] inhibited the decrease in content of hexosamine of gastric mucosa in rats treated with acetic acid. These results suggest that [M] have a prophylactic effect on ulcerogenics, and an anti-ulcer effect by the increase and/or maintenance of gastric mucosal blood flow and hexosamine, but further investigations are required to understand the mechanism involved.

Animals↗
PubMed1978

Strain differences in aspirin-induced gastric ulceration in rats.

We found that there are strain differences in aspirin-induced ulceration in pylorus-ligated rats; the ulcer indices varied, from high to low, in the following order: Donryu greater than Sprague-Dawley greater than Wistar. Several experiments including analysis of gastric contents or ionic flux, determination of serum aspirin esterase activity, absorption of aspirin from the stomach, prothrombin time and hexosamine content in gastric mucosa and juice were performed to elucidate the origin of the differences. A significantly higher acid output in Donryu rats, and higher hexosamine content in the gastric mucosa of Wistar rats were noted. However, it appears unlikely that these factors only contribute to the marked strain difference in aspirin-induced ulcers. The possible different sensitivity of gastric mucosal cell itself to aspirin must be considered.

Animals↗
PubMed1979

Studies on the mechanism of action of cetraxate [4'-(2-carboxyethyl)phenyl trans-4-aminomethyl cyclohexanecarboxylate hydrochloride], a new anti-ulcer agent.

To elucidate mechanisms involved in the anti-ulcer action of cetraxate, the effects of this agent on the ulcer index (UI), fibrinolytic activity (FA) and contents of several connective tissue components in ulcer tissue were examined using aspirin- and acetic acid ulcers in rats. In aspirin ulcer, cetraxate (100 and 300 mg/kg p.o.), like tranexamic acid (500 mg/kg p.o.), epsilon-aminocaproic acid (500 mg/kg p.o.) and gefarnate (200 mg/kg p.o.), inhibited both the UI and FA. However, aluminum sucrose sulfate (1000 mg/kg p.o.) was effective only against the UI and L-glutamine (500 mg/kg p.o.) failed to inhibit both parameters. In acetic acid ulcer, following oral, daily X either 5 or 8 administrations, cetraxate (200 and 300 mg/kg), gefarnate (200 mg/kg), aluminum sucrose sulfate (1000 mg/kg) and L-glutamine (500 mg/kg) were effective on both the UI and FA. Tranexamic acid (500 mg/kg) and epsilon-aminocaproic acid (500 mg/kg) were ineffective on the UI, although both agents inhibited FA. In acetic acid ulcer, cetraxate induced increases in hexosamine and uronic acid, that is, acid mucopolysaccharides (AMPS), especially chondroitin sulfate A and -C, whereas L-glutamine and aluminum sucrose sulfate resulted in increases in hexosamine and sialic acid, that is, glycoproteins. From these results, cetraxate may mainly accelerate the ulcer healing by increasing AMPS in ulcer tissue. Moreover, the local anti-FA property of this agent may be also beneficial in treating bleeding ulcers.

Acetates↗
PubMed1994

Cytoprotective effect of NC-1300-O-3 against gastric lesions induced by necrotizing agents in rats.

The cytoprotective effect of NC-1300-O-3 and its mechanism of action were investigated. NC-1300-O-3 at doses of 3 and 10 mg/kg, p.o. significantly prevented the formation of gastric lesions by HCl.ethanol in rats, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-O-3 and necrotizing agents in the stomach, which is considered to be related to the development of cytoprotection, was not observed. A preventive effect of NC-1300-O-3 against gastric lesions was observed at the same dose even when gastric secretion was completely inhibited by pretreatment with omeprazole. This suggests that the cytoprotective effect of NC-1300-O-3 is an action on the gastric mucosa independent of its antisecretory effect. The cytoprotective effect of NC-1300-O-3 was not affected by pretreatment with indomethacin but was partly decreased by N-ethylmaleimide pretreatment, suggesting the participation of endogenous sulfhydryl compounds in the action of NC-1300-O-3. This compound dose-dependently increased the hexosamine content in the gastric lumen in rats at a dose range of 3-30 mg/kg, p.o. and slightly inhibited a reduction in surface mucus and mucosal hexosamine content caused by necrotizing agents. Moreover, NC-1300-O-3 at doses of 10 and 30 mg/kg, p.o. significantly inhibited the increased gastric vascular permeability caused by alcohol treatment; and at 30 mg/kg, p.o., it inhibited the reduction in potential difference caused by aspirin in rats. These actions were suggested to contribute to the cytoprotective effect of NC-1300-O-3.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Castration-induced hyperactivity of seminal vesicle in the catfish Clarias batrachus: a case of paradox and blockade by antiandrogen (cyproterone acetate) treatment.

Castration of the catfish Clarias batrachus in late preparatory-early prespawning phase (April-May) caused time-dependent stimulatory effect on morphology, weight, and in the concentrations of biochemical correlates, such as total proteins, fructose, hexosamines and sialic acid in the seminal vesicle (SV). The peak changes were noticed on week 4 of castration. The hyperactivity was related to augmented production of testosterone by the SV of castrates with the levels significantly high from week 3 onwards. As a result, serum testosterone level fluctuated with a significant decrease in the first and fifth weeks, a significant increase in the third week, and no significant difference in the second and fourth weeks. Serum E2 level decreased significantly throughout. Cyproterone acetate treatment (CA; 1 mg/fish daily for 21 days) from the second day of castration decreased the size and weight of the SV and the concentrations of total proteins, hexosamines, fructose and sialic acid. The antiandrogen treatment did not alter serum testosterone level but the E2 level was significantly decreased. It is concluded that the hypersecretory activity of the SV in castrates is a sequel to local synthesis and action of testosterone and the effect could be prevented by CA by blocking androgen actions.

Androgen Antagonists↗
PubMed1975

Biochemical study of fibrosis in the rat liver in biliary obstruction.

In an attempt to study the collagen formation in the liver occurring in association with obstructive jaundice, the authors carried out an experiment with liver slices from common bile duct-ligated rats. Hepatic collagen was fractionated into the neutral soluble, acid soluble and insoluble fractions, and the hydroxyproline synthesis rate of each fraction was measured using 14C-proline. Determination was also made for hexosamine content in the same liver tissue. The hydroxyproline content of hepatic collagen increased as biliary obstruction was prolonged, particularly from the 4th week, which is the transitional period of liver histology into biliary cirrhosis. The hexosamine content of hepatic collagen showed a similar tendency. The neutral soluble, acid soluble and insoluble collagen fractions all increased as biliary obstruction was prolonged. The collagenosynthetic activity of the neutral soluble fraction, attained a peak in 1 to 2 weeks of biliary obstruction, which indicates that collagen fibers are formed actively in the early stage of jaundice, although there is only a slight increase in the absolute amount of fibers developed then. Serum monoamine oxidase level tended to be parallel to collagenosynthetic activity but not to collagen content.

Animals↗
PubMed1991

Initial pathophysiological changes in chronic pancreatitis induced by pancreatic ductular obstruction model.

An experimental chronic pancreatitis model was made in five dogs with chronic pancreatic fistula by injection of microspheres into the peripheral pancreatic duct. Sequential changes of pancreatic exocrine and endocrine functions with morphology were studied. Significant decreases in volume bicarbonate output and amylase output were detected in each sample collected separately on secretin and secretin cerulean stimulation. While the viscosity of pancreatic juice was significantly increased with a concomitant increase in hexosamine concentration, chronic pancreatitis was demonstrated morphologically. These results suggest that concentrated pancreatic juice caused by a decrease in volume and an increase in viscosity of pancreatic juice with a concomitant increase in hexosamine concentration brings about the progression of chronic pancreatitis in this experimental model.

Amylases↗
PubMed1992

N-(F-18)-fluoroacetyl-D-glucosamine: a new positron labeled pharmaceutical for cancer study.

In order to evaluate the role of hexosamine metabolism in tumor tissue, we studied the biodistribution of N-(F-18)-fluoroacetyl-D-glucosamine (FAGlu) in male Donryu rats bearing poorly differentiated hepatomas (AH109A and AH272). Compare with the former result of the high tumor uptake of FAGlu in C3H/He mice bearing well differentiated spontaneous hepatoma, the tumor uptakes of FAGlu in these tumors showed the lower values. This suggested that spontaneous hepatoma maintained a high activity of glucosamine metabolism, while poorly differentiated hepatoma had little activity. Metabolism of glucosamine in tumor tissue may be another marker for characterizing tumors. We also discuss the tissue distribution of new F-18 labeled hexosamines, N-(F-18)-fluoroacetyl-D-mannosamine and N-(F-18)-fluoroacetyl-D-galactosamine in tumor bearing rats.

Acetylgalactosamine↗
PubMed2002

Hyperglycemia inhibits capacitative calcium entry and hypertrophy in neonatal cardiomyocytes.

Hyperglycemia alters cardiac function and often leads to diabetic cardiomyopathy as cardiomyocyte apoptosis causes a hypertrophied heart to deteriorate to dilation and failure. Paradoxically, many short-term animal models of hyperglycemia protect against ischemia-induced damage, including apoptosis, by limiting Ca(2+) overload. We have determined that, like nonexcitable cells, both neonatal and adult cardiomyocytes respond to depletion of sarcoplasmic/endoplasmic reticulum Ca(2+) stores with an influx of extracellular Ca(2+) through channels distinct from voltage-gated Ca(2+) channels, a process termed capacitative Ca(2+) entry (CCE). Here, we demonstrate that in neonatal rat cardiomyocytes, hyperglycemia decreased CCE induced by angiotensin II or the Ca(2+)ATPase inhibitor thapsigargin. Hyperglycemia also significantly blunted Ca(2+)-dependent hypertrophic responses by approximately 60%, as well as the Ca(2+)-sensitive nuclear translocation of a chimeric protein bearing the nuclear localization signal of a nuclear factor of activated T-cells transcription factor. The attenuation of CCE by hyperglycemia was prevented by azaserine, an inhibitor of hexosamine biosynthesis, and partially by inhibitors of oxidative stress. This complements previous work showing that increasing hexosamine metabolites in neonatal cardiomyocytes also inhibited CCE. The inhibition of CCE by hyperglycemia thus provides a likely explanation for the transition to diabetic cardiomyopathy as well as to the protection afforded to injury after ischemia/reperfusion in diabetic models.

Animals↗
PubMed1989

Changes in levels of mucosal glycoprotein on cysteamine-induced duodenal ulcers in rats.

Duodenal ulcers were induced in rats by cysteamine administration. Time-course changes in duodenal hexosamine, blood flow and intragastric pH were measured, as well as changes in the susceptibility of Brunner's glands to concanavalin A (Con A) staining. Hexosamine contents in the duodenum decreased significantly at 5 and 24 h. In the control group, Brunner's glands were stained brown using Con A staining. One day after cysteamine administration, the extent of Con A staining markedly decreased. At 3 and 7 days, gland susceptibility to staining was essentially the same as that of the control group.

Animals↗
PubMed1990

The effects of testosterone propionate and methenolone enanthate on the healing of humeral osteotomies in the Wistar rat.

A randomized blind prospective study was carried out to determine if an anabolic androgenic steroid with a high anabolic/androgenic ratio, Group A, (1/0.05) methenolone enanthate (me), compared to an anabolic/androgenic agent with a low anabolic/androgenic ratio, Group B, (1.0/1.0) testosterone propionate (tp), compared to a control, Group C, cottonseed oil (co), affected midhumeral osteotomy healing in 100 two-month-old female Wistar rats. The rats received 4 mg/kg me, 4 mg/kg te, and equal volumes of co weekly. The rats were sacrificed at 2, 4, and 6 weeks. The entire humerus with the healing osteotomy was carefully dissected until all soft tissue attachments were stripped. The healing callus was then subjected to (1) biochemical analysis (hexosamine, hydroxyproline, and calcium), (2) biomechanical testing (progressive distraction of the callus at 1 mm/min on an electrohydraulic materials test system, model 1331, Instron Corp, Canton, MA, and (3) histology. Results of the biochemical testing demonstrated that the percentage of calcium in the healing callus at 2 weeks in group B (tp) was 7.3 +/- 1.0, and this value was greater than that in group C (co), 4.8 +/- 1.6 (p greater than .01), and greater than that in group A (me), 5.6 +/- 0.6 (p greater than .01). At 4 weeks, the percentage of calcium in the callus in group B (tp) was 6.8 +/- 1.9, in group A (me) 7.3 +/- 3.7, and these values were both greater than that in group C (co), 3.9 +/- 2.2 (p greater than .02 and .01, respectively). At 6 weeks the percentage of calcium in the callus in group B (tp) was 11.7 +/- 3.9 and in group A (me) 12.7 +/- 3.9, and again these values were both greater than that in group C (co), 6.7 +/- 2.6 (p greater than .02 and .01, respectively). The remainder of the biochemical analysis, hexosamine and hydroxyproline content, did not show a statistical difference in groups A, B, and C at 2, 4, and 6 weeks. The biomechanical studies and histology also failed to show statistical differences between the three groups at 2, 4, and 6 weeks. The conclusion of this study is that an agent with a low androgenic activity does not increase calcium callus concentrations early in the course of fracture healing compared to an agent with higher androgenic activity. As healing progresses, both agents increase the concentration of calcium in osteotomy healing. The clinical significance of this study is that agents with low androgenic activities favorably influence osteotomy healing and may be clinically useful because they lack unwanted virilizing activity.

Animals↗
PubMed1981

Further studies of angiopathic serum factor in perinephritic hypertensive dogs.

The serum of perinephritic hypertensive dogs causes waterlogging and increased sodium (Na) content of rabbit aorta explants in tissue culture. In the present study, we investigated the role of tissue glycosaminoglycans in the pathogenesis of these changes. The effect of ouabain and prostaglandin F2 alpha on the composition of rabbit aorta explants in tissue culture was studied to determine if they produced alterations that were similar to those produced by the serum of hypertensive dogs. Rabbit aortic media explants were cultured in tissue culture medium supplemented (15-20%) with serum obtained from 12 dogs during a pre-hypertension control period and after induction of one-kidney, one-wrapped hypertension. After 3 weeks of culture, the explants were harvested, and their Na, potassium (K) and hexosamine content was measured. Compared to the composition of explants cultured in pre-hypertension control serum, the water and Na content of explants cultured in the serum of hypertensive dogs was increased (p less than 0.02, and p less than 0.01). There were no differences in the K and hexosamine content of explants cultured in the two sera. There was a dose-dependent increase in the NA content and a reduction in the K content of explants cultured in the presence of ouabain (5 X 10-8 to 5 X 10-7 M) and PGF2 alpha (1 microgram/ml). The findings of this study provide further evidence for angiopathic serum factor(s) in perinephritic hypertensive dogs. The excess Na of explants cultured in the serum of hypertensive dogs does not appear to be bound to glycosaminoglycans, The accumulation of excess Na is not due to an ouabain-like mechanism.

Animals↗
PubMed1979

The healing of experimental fractures by compression osteosynthesis. II. Morphometric and chemical analysis.

The effects of rigid plate fixation on the structure and chemical composition of bones during healing of experimental fractures were studied by morphometric and chemical analysis at intervals of 3 to 24 weeks after attachment of six-hole AO plates to osteotomized rabbit tibiae. After fracture union gradual porotic transformation could be observed from 9 weeks onwards, with rapid excavation and breakdown of the cortical wall. During the study over 24 weeks the degree of porosity increased from 9.0 +/- 4.8 per cent to 37.5 +/- 10.2 per cent (P less than 0.001). This osteoporosis was accompanied by formation of new subperiosteal bone. The changes in the tubular bone led to a progressive increase in overall diameter and in the area occupied by the medullary cavity throughout the experiment. In the osteotomy area increased values were found for the content of hexosamines and the ratio of hexosamines to hydroxyproline at 3 weeks, indicating formation of connective tissue in the fracture area. Later on, no chemical signs of callus formation could be detected. In spite of the slight increase in the content by hydroxyproline, reflecting the formation of new bone subperiosteally, the chemical composition of the unresorbed cortical bone remained unchanged.

Animals↗
PubMed1979

Glycosaminoglycan metabolism of the medial meniscus, the medial collateral ligament and the hip joint capsule in experimental osteoarthritis caused by immobilization of the rabbit knee.

A study was made of glycosaminoglycan metabolism in experimental osteoarthritis caused by immobilization of the rabbit knee in extension. Samples from the medial meniscus, the medial collateral ligament of the knee and the hip joint capsule were obtained and analysed after 2, 6, 10, 17, 30 and 87 days of immobilization, samples from the mobile limb serving as controls. The tissue concentrations of glycosaminoglycans were determined from measurements of hexosamine and uronic acid after prior papain proteolysis and subsequent purification. The uptake of 35S-sulphate (DPM/microgram hexosamine) was used as an indicator of the synthesis rate of sulphated glycosaminoglycans. In both early and advanced immobilization osteoarthritis, the synthesis rate and the content of glycosaminoglycans were increased in all tissues.

Animals↗
PubMed1981

Biochemical changes in bone grafts stabilized with rigid plates. I. Cancellous grafts.

The effect of rigid plate fixation on the chemical composition of cancellous interposition grafts was studied in rabbit-fibular bones. The concentrations of hexosamines and, to a lesser degree, of hydroxyproline and nitrogen, were high in the graft for the first 6 weeks, decreased from weeks 6 to 12, but remained higher than the corresponding values for the controls throughout the experiment (52 weeks). The ratio of hexosamines to hydroxyproline was highest for the graft at 3 weeks, indicating formation of cartilage and osteoid. The initially low calcium concentration of the graft increased by 35 per cent from weeks 1 to 6, decreased from weeks 6 to 12, and remained below normal thereafter in comparison with corresponding values for the cortical host bone. The ratio of calcium to hydroxyproline increased throughout the experiment, reflecting maturation of the graft to lamellar bone. Thus, biochemically the early incorporation of rigidly fixed cancellous interposition grafts resembles the healing of unimmobilized fractures by callus formation.

Animals↗