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PubMed1989

Evaluation of the gastric antiulcerogenic effects of Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats.

Antiulcerogenic activities of three plant drugs were studied against aspirin-induced gastric ulcers in rats. In addition, their effects on output of gastric acid and pepsin and hexosamine concentrations in gastric fluid were recorded in ulcerated and non-ulcerated rats. Solanum nigrum (aerial parts) powder and its methanolic extract decreased the ulcer index significantly. The activity may be due to inhibition of acid and pepsin secretions and/or their in vitro ability to bind these. Brassica oleracea (leaf) powder did not affect the ulcer index significantly but its aqueous extract lowered the index and increased hexosamine levels, suggesting gastric mucosal protection. Ocimum basilicum (aerial parts) powder and its aqueous and methanolic extracts decreased the index. Moreover, the acid output was decreased by its methanolic extract while hexosamine secretion was enhanced. This suggests that its antiulcerogenic effect is due to decreases of acid and pepsin outputs which enhance gastric mucosal strength. The reference drug gefarnate decreased the ulcer index by increasing the hexosamine level only. Cimetidine inhibited the acid production but did not decrease the ulcer index.

Animals↗
PubMed1982

Connective tissue aging in the human hypophysis-gonadal system.

The basic issue in our project was to quantify the age-process in the human hypophysis-gonadal system. Of the many aspects of aging, we estimated, using human autopsy material, the content of desoxyribonucleic acid (DNA), of hydroxyproline, of hexosamines and of uronic acids in the hypophysis, testis, and ovary. The respective organs were weighed and homogenised in acid-buffer solution after which, for each of the parameters, 1.0 ml of homogenate was extracted and processed: DNA-estimation according to modified Dische/Seibert (1929) method; hydroxy-proline according to Stegemann and Stalder (1967); hexosamines and uronic acids according to Gatt and Berman (1966) and Blumenkrantz and Asboe-Hansen (1973) respectively. All values obtained were expressed in micrograms/ml of homogenate. The age investigated ranged from a few days old to 99 years. The DNA-curves for the hypophysis initially showed a decline till about the third decade of life and then remained almost constant with a significant decline up to the senile age. The DNA-curves for the testis and ovary demonstrated a sharp decline initially till the third decade of life, after which the curves remained constant, but showed reduction during higher age. Similar pattern of distribution was also observed for hexosamines, and uronic acids: after the initial decline of uronic acids in the human hypophysis and testis during the first three decades of life and nearly constant values thereafter, hexosamines, together with the uronic acids show minimal decrease in content during the senile period. Contents od hydroxyproline significantly increased in testis, ovary and hypophysis with aging. This biochemically proven age-fibrosis in the human gonads corresponds to the morphologically observed vascular and interstitial sclerosis in the testis and the ovary and may partly help to explain the declined sensitivity of these target organs to hypophyseal stimulation during the aging period.

Adolescent↗
PubMed1983

Induction and morphogenesis of chlamydospores in an agerminative variant of Candida albicans.

A strain of Candida albicans that did not form germ tubes was endowed with a pronounced ability for massive production of chlamydospores under appropriate environmental conditions. Development of chlamydospores was induced by N-acetyl hexosamines, especially N-acetyl-D-glucosamine, and this induction did not depend on non-specific utilization of N-acetyl hexosamines as metabolic sources nor did it correlate with induction of germ-tube formation. Formation of chlamydospores in N-acetyl hexosamine-agar medium occurs through a multiplication stage (10-12 h) consisting of a few cycles of budding leading to short, "pseudo-hypha-like" structures, followed by progressive differentiation of most cells into young chlamydospores (16-18 h) which go to complete maturation in 36-48 h. There were marked differences in chlamydospore formation among different strains of C. albicans but, when induced, the morphology and kinetics of sporulation were identical in all strains. This study shows that chlamydospore formation is not necessarily associated with the mycelial phase and suggests that N-acetyl hexosamines may induce sporulation by controlling endogenous metabolism rather than through products of their own metabolism.

Acetylgalactosamine↗
PubMed1988

Mucin in gall bladder bile of gall stone patients: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid.

The concentration of hexosamine, a marker for mucin, was determined and related to the degree of cholesterol saturation and to the occurrence of cholesterol crystals in gall bladder bile of gall stone patients (n = 40) and gall stone free subjects (n = 25). Ten of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and eight with ursodeoxycholic acid (UDCA) three to four weeks before cholecystectomy. The hexosamine content was significantly higher in gall stone patients (137 (19) ng/ml, mean (SE) than in gall stone free subjects (83 (9) ng/ml, p less than 0.02). Treatment with CDCA or UDCA decreased cholesterol saturation, but did not significantly affect the hexosamine concentration. There was no difference in hexosamine concentration between gall stone patients with and without cholesterol crystals. The results do not support the hypothesis that the degree of cholesterol saturation is important for the mucin content of gall bladder bile in man. Neither do the data indicate that the formation and occurrence of cholesterol crystals in gall bladder bile from gall stone patients is caused by an increased concentration of mucin. As the studies were conducted on patients who had already had gall stones for several years, however, an effect of mucin in the very early stage of gall stone formation cannot be completely excluded.

Adult↗
PubMed2000

Role of vascular endothelial growth factor in portal hypertensive gastropathy.

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. METHOD: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(-)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. RESULTS: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(-)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(-)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(-)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. CONCLUSION: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.

Adult↗
PubMed1996

Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance.

The hexosamine biosynthetic pathway has been hypothesized to be involved in mediating some of the toxic effects of hyperglycemia. Glutamine:fructose-6-phosphate amidotransferase (GFA), the first and rate limiting enzyme of the hexosamine biosynthetic pathway, was overexpressed in skeletal muscle and adipose tissue of transgenic mice. A 2.4-fold increase of GFA activity in muscle of the transgenic mice led to weight-dependent hyperinsulinemia in random-fed mice. The hyperinsulinemic-euglycemic clamp technique confirmed that transgenic mice develop insulin resistance, with a glucose disposal rate of 68.5 +/- 3.5 compared with 129.4 +/- 9.4 mg/kg per min (P < 0.001) for littermate controls. The decrease in the glucose disposal rate of the transgenic mice is accompanied by decreased protein but not mRNA levels of the insulin-stimulated glucose transporter (GLUT4). These data support the hypothesis that excessive flux through the hexosamine biosynthesis pathway mediates adverse regulatory and metabolic effects of hyperglycemia, specifically insulin resistance of glucose disposal. These mice can serve as a model system to study the mechanism for the regulation of glucose homeostasis by hexosamines.

Adipose Tissue↗
PubMed1984

Antiulcer activity of clotiazepam in rats.

Effect of the anti-anxiety drug clotiazepam on the experimental gastric ulceration induced by restraint and water-immersion stress or aspirin was studied in rats. Clotiazepam prevented the development of each gastric ulcer. From the effect of clotiazepam on aspirin-induced ulceration, we presumed that clotiazepam should have some other antiulcer mechanism in addition to its action on the central nervous system. There was an appreciable correlation between the decrease in the hexosamine level of gastric tissue and associated ulceration. After treatment with aspirin, the hexosamine level was abruptly reduced and was maintained at a low level for several hours. In the clotiazepam -pretreated group, the hexosamine level reduced by aspirin was progressively restored to the intact level. By histological examination with periodic acid-Schiff (PAS)/alcian-blue (AB) staining, clotiazepam increased the amount of gastric mucopolysaccharides decreased by aspirin. Clotiazepam did not affect gastric secretion in pylorus-ligated rats. Atropine and cimetidine inhibited ulceration induced by stress or aspirin and gastric secretion, but did not affect the hexosamine level reduced by aspirin. These results indicate that the antiulcer efficacy of clotiazepam may be attributed to its action not only on the central nervous system, but also on the mucus in gastric mucosa.

Animals↗
PubMed1977

Connective tissue constituents of the fowl. Effects of exogenous estrogen.

The levels of connective tissue constituents (hexosamine, hexuronic acid, hexose and hydroxyproline) and the composition of isolated mucopolysaccharide-peptide complexes were determined in some organs and tissue of male and female fowl treated and not treated with estradiol-17beta. Most of the changes occurred in the male. Estrogen administration brought statistically significant increases in the contents of hexosamine and hexuronic acid in the cartilage of the male and of hexose in the spleen of both males and females. It also increased the hydroxyproline in the testis and in the cartilage of the male. Estrogen decreased the content of hexosamine in the combs of both males and females, and in the wattle of the female, of hexuronic acid, hexose and hydroxyproline in the liver of the male, and hydroxyproline in the breast muscle of the male. Hexosamine, sialic acid, lipid and protein contents of blood sera of estrogenized birds were substantially higher than that of the controls. Gas liquid chromatography of the lipids of the tissues indicated that estrogen administration brought about an increase in the proportion of the unsaturated fraction to the total fatty acid content.

Animals↗
PubMedDate not supplied

[Glycoproteins in rat blood serum and tissues and thiamine saturation of the body].

In blood serum and tissues of rats with alimentary and antimetabolic thiamin deficiencies content of glycoproteins was determined. The alimentary B1-avitaminosis caused a decrease in content of ceruloplasmin, hexosamines and sialic acids in blood serum and also of hexosamines in liver tissue and aorta. In dificiency of thiamin, caused by a single administration of hydroxythiamin, content of hexosamines and sialic acids were decreased in liver, pancreas and heart; in blood serum content of ceruloplasmin was decreased but that of glycoproteins was increased. Thiamin increased content of glycoproteins and sialic acids in blood serum and the content of sialic acids in liver tissue, but it decreased content of hexosamines in liver and pancreas. Content of the metabolites studied in animals, maintained on avitaminous diet, was normalized by means of repeated administration of thiamin during four weeks.

Animals↗
PubMed1986

Glycosaminoglycan production by bovine aortic endothelial cells cultured in sulfate-depleted medium.

Bovine aortic endothelial cells were cultured in medium containing [3H]glucosamine and concentrations of [35S]sulfate ranging from 0.01 to 0.31 mM. While the amount of [3H]hexosamine incorporated into chondroitin sulfate and heparan sulfate was constant, decreasing concentrations of sulfate resulted in lower [35S]sulfate incorporation. Sulfate concentrations greater than 0.11 mM were required for maximal [35S]sulfate incorporation. Chondroitin sulfate was particularly affected so that the sulfate to hexosamine ratio in [3H]chondroitin [35S]sulfate dropped considerably more than the sulfate to hexosamine ratio in [3H] heparan [35S]sulfate. Sulfate concentration had no effect on the ratio of chondroitin 4-sulfate to chondroitin 6-sulfate. The ratios of sulfate to hexosamine in cell-associated glycosaminoglycans were essentially identical with the ratios in media glycosaminoglycans at all sulfate concentrations. DEAE-cellulose chromatography confirmed that sulfation of chondroitin sulfate was particularly sensitive to low sulfate concentrations. While cells incubated in medium containing 0.31 mM sulfate produced chondroitin sulfate which eluted later than heparan sulfate, cells incubated in medium containing less than 0.04 mM sulfate produced chondroitin sulfate which eluted before heparan sulfate and near hyaluronic acid, indicating that many chains were essentially unsulfated. At intermediate concentrations of sulfate, chondroitin sulfate was found in very broad elution patterns suggesting that most did not fit an "all or nothing" mechanism. Heparan sulfate produced at low concentrations of sulfate eluted with narrower elution patterns than chondroitin sulfate, and there was no indication of any "all or nothing" sulfation.

Animals↗
PubMed1972

Rabbit muscle gangliosides.

Four ganglioside fractions were isolated from rabbit muscle: one hematoside and three hexosamine-containing species. They were analyzed for hexoses, hexosamine, sialic acid, fatty acids, and long-chain base content. The molar ratios of sphingosine-hexose-hexosamine-sialic acid were: for hematoside, 1:2:0:1; for the disialogangliosides, 1:3:1:2; and for trisialoganglioside, 1:3:1:3. The carbohydrates were studied by thin-layer and paper chromatography. The hexoses were glucose and galactose; the hexosamine was N-acetylgalactosamine and the sialic acid was N-acetylneuraminic acid. Fatty acids and long-chain bases were analyzed by gas-liquid chromatography. The fatty acid composition was similar in all of the four gangliosides. The most abundant fatty acids were 16:0 and 18:0, but significant amounts of 16:1, 18:1, 20:0, and 22:0 were also found. Hydroxy fatty acids were not detected. In all of the muscle gangliosides the main long-chain bases were C(18)-sphingenine and C(20)-sphingenine. In hematoside there were also measurable amounts of C(18)-sphinganine and C(20)-sphinganine, whereas in the major gangliosides only traces of C(18)-sphinganine were detected.

Animals↗
PubMedDate not supplied

[Connective tissue of rats under prolonged hypokinesia and in the recovery period].

Changes in the content of collagen (with respect to hydroxyproline), total aminopolysaccharides (with respect to hexosamines), and acid glycosaminoglycanes (with respect to hexuronic acids) in the skin and tendons of xuronic acids) in the skin and tendons of 102 white rats (including 46 controls) were determined on the 15, 30 and 90th hypokinetic days and on the 15, 30 and 90th days of posthypokinesia recovery. The hydroxyproline content in the skin and tendons did not change. The content of hexosamines and hexuronic acid decreased in tendons on hypokinetic days 15 and 90 and in the skin on day 15. The content of hexosamines in the skin increased on day 90. The content of hexosamines and hexuronic acids in the skin and tendons increased on recovery day 15 and remained unaltered on day 90.

Aging↗
PubMed1993

Effects of short-term cast immobilization on equine articular cartilage.

Hexosamine concentration (an index of proteoglycan content), DNA content (an index of cellularity), and [35S]sulfate incorporation (an index of proteoglycan synthesis) of articular cartilage were measured in biopsy specimens from medial proximal sesamoid bone, medial condyle of the third metacarpal bone, and proximal dorsal rim of the proximal phalanx in both metacarpophalangeal joints of 6 adult horses. One limb was then placed in a fiberglass cast that extended down from the proximal portion of the metacarpus and enclosed the hoof; the other limb was not casted. After 30 days of stall confinement, additional specimens were taken from the medial proximal sesamoid bone, medial condyle of the third metacarpal bone, midproximal portion of the proximal phalanx, distal portion of the proximal phalanx, and proximal portion of the middle phalanx of both limbs for comparison. Immobilization resulted in an apparent decrease in the hexosamine content of the cartilage when the 30-day immobilized vs 30-day mobilized specimens were analyzed. This decrease was accentuated by opposing trends in the 2 limbs. The immobilized cartilage tended to lose hexosamine, whereas the mobilized limb tended to gain hexosamine during the 30-day period; a similar trend also was seen with [35S] incorporation, but this trend was not statistically significant. The largest change was a significant increase in glycosaminoglycan synthesis in the mobilized limb, compared with little change in the immobilized joint cartilage. We concluded that contralateral limbs are unsuitable for controls in immobilization studies because of their biological response to increased weight bearing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The pathophysiological characteristics of bile from patients with gallstones: the role of prostaglandins and mucin in gallstone formation.

Bile was obtained from 82 patients with various biliary tract diseases and concentrations of prostagloandins, leukotriens, mucin, and a number of lithogenic components were measured in order to evaluate the role of these substances in the pathogenesis of gallstone formation. The characteristics of bile in cases of cholesterol gallstones included high concentrations of prostaglandins and hexosamine and a high cholesterol saturation index. Prostaglandin E2 and prostaglandin F2 alpha concentrations in bile were correlated with hexosamine concentration, and prostaglandins and hexosamine were found to be actively synthesized and secreted in the gallbladder. Prostaglandins E2 and F2 alpha may therefore stimulate mucin secretion in the gallbladder with supersaturated bile. The characteristics of bile in cases of calcium bilirubinate gallstones included a high detection rate for bacteria, high beta-glucuronidase activity, a high percentage of unconjugated bilirubin, a low cholesterol saturation index and high concentrations of prostaglandins and hexosamine. Moreover, the synthesis and secretion of prostaglandins in the biliary tract were accelerated in cases of infected bile. Thus, hypersecretion of mucin, stimulated by prostaglandins, my participate in the onset and development of biliary tract infection or in the formation of calcium bilirubinate gallstones. Regarding the role of prostaglandins and mucin, the hypotheses for gallstone formation previously reported by many authors are supported by the clinical data obtained in the current study.

Bile↗
PubMed1983

Glycosaminoglycans: their distribution and potential vasoactive action in the nonpregnant and pregnant ovine uterus.

The effects of direct uterine artery infusions of glucosamine-hydrochloric acid, dextrose, and mannitol were evaluated in ewes that had undergone oophorectomy. Glucosamine-hydrochloric acid caused a prompt dose-related increase in uterine blood flow which approximated uterine blood flow rates induced by estradiol. Infusions of dextrose caused similar but transient vasodilatation, whereas infusions of mannitol had no effect. The glycosaminoglycans content of endometrium, myometrium, and caruncles/cotyledons (placentomes) was measured in nonpregnant and early pregnant ewes between 19 and 45 days' gestation. In endometrium and myometrium, total hexosamine levels were similar in nonpregnant and pregnant ewes. In the placentomes, total hexosamine levels increased steadily after 20 to 25 days' gestation. The hyaluronic acid fraction of total glycosaminoglycans hexosamine increased similarly and paralleled the total hexosamine levels. Galactosamine levels were unchanged in all tissues. It is postulated that a function of Wharton's jelly may be to provide the mechanism for shunting of uterine blood flow to the ovine placentomes.

Animals↗
PubMed2001

Comparative studies on metal biosorption by two strains of Cladosporium cladosporioides.

Two strains of a fungus, Cladosporium cladosporioides 1 and C. cladosporioides 2 showed different metal biosorption properties. Strain 1 showed preferential sorption of gold and silver, while strain 2 could bind metals such as copper and cadmium in addition to gold and silver. Strain 1 had a cell-wall hexosamine content of 0.1%. X-ray photoelectron spectroscopy (XPS) and Fourier transform infra-red spectroscopy (FTIR) analyses indicated that nitrogen was not involved in metal biosorption by the strain. In strain 2 the cell-wall hexosamine content was 150 times that of strain 1. These results indicated that hexosamine was responsible for non-specific metal binding while cell-wall polymers other than hexosamines had a role in conferring selectivity in precious-metal binding.

Absorption↗
PubMed2000

Thyroidectomy modulates rat prostatic monosaccharides.

Earlier studies have shown that thyroid hormones play an important role in glycoprotein metabolism in the prostate. In this paper, hypothyroidism induced changes in prostatic glycoprotein-associated monosaccharides and fructose concentrations were studied in 30-day-old peripubertal rats. Hypothyroidism was induced by total surgical thyroidectomy and confirmed by radioimmunoassay (RIA) of thyroid hormones and thyroid stimulating hormone (TSH). Animals were killed after 30 and 60 days post-thyroidectomy. To test the direct effect of thyroid hormones on prostatic monosaccharides, prostatic tissue was incubated for 24 h at 37 degrees C with 25, 50 or 100 ng/mL T3. Ventral prostatic hexosamines and sialic acid concentrations were significantly decreased in hypothyroid rats aged 30 and 60 days, whereas fucose concentration was increased at 30 days but decreased at 60 days in hypothyroid rats. In the case of the dorsolateral prostate, hypothyroidism enhanced the concentration of hexosamines but caused a decrease in levels of fucose, sialic acid and fructose, irrespective of the duration of hypothyroidism. Concentrations of fucose, fructose and hexosamines in the anterior prostate were decreased and sialic acid concentration was increased in 60-day hypothyroid rats. In in vitro studies, the concentrations of fucose, sialic acid and hexosamines were significantly increased in all three prostatic lobes irrespective of the T3 dose with which they had been incubated. A consistent increase in fructose concentration was observed in anterior and dorsolateral prostates when incubated with different doses of T3 stimulation. It is concluded that the influence of hypothyroidism on prostatic monosaccharides seems to be specific for each sugar in different lobes of the prostate. These results clearly show that thyroid hormones differentially regulate prostatic glycoprotein metabolism.

Animals↗
PubMed2006

Glycosylation mediates up-regulation of a potent antiangiogenic and proatherogenic protein, thrombospondin-1, by glucose in vascular smooth muscle cells.

Accelerated development of atherosclerotic lesions remains the most frequent and dangerous complication of diabetes, accounting for 80% of deaths among diabetics. However, our understanding of the pathways mediating glucose-induced gene expression in vascular cells remains controversial and incomplete. We have identified an intracellular metabolic pathway activated by high glucose in human aortic smooth muscle cells that mediates up-regulation of thrombospondin-1 (TSP-1). TSP-1 is a potent antiangiogenic and proatherogenic protein that may represent an important link between diabetes and vascular complications. Using different glucose analogs and metabolites sharing distinct, limited metabolic steps with glucose, we demonstrated that activation of TSP-1 transcription is mediated by the hexosamine pathway of glucose catabolism, possibly resulting in modulation of the activity of nuclear proteins activity through their glycosylation. Specific inhibitors of glutamine: fructose 6-phosphate amidotransferase (GFAT), an enzyme controlling the hexosamine pathway, as well as direct inhibitors of protein glycosylation efficiently inhibited TSP-1 transcription and the activity of a TSP-1 promoter-reporter construct stimulated by high glucose. Overexpression of recombinant GFAT resulted in increased TSP-1 levels. Pharmacological inhibition of GFAT or protein glycosylation inhibited increased proliferation of human aortic smooth muscle cells caused by glucose. We have demonstrated that the hexosamine metabolic pathway mediates up-regulation of TSP-1 by high glucose. Our results suggest that the hexosamine pathway and intracellular glycosylation may control important steps in initiation and development of atherosclerotic lesions.

Angiogenesis Inhibitors↗