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Effect of teprenone on portal hypertensive gastric mucosa.

Teprenone (geranylgeranylacetone) is a gastric mucosal protective drug used clinically in Japan for treatment of gastric ulcers and gastritis. Its effect on portal hypertensive (PHT) gastric mucosa which has impaired defensive mechanisms is not known. In 20 PHT and 20 sham-operated rats, we studied the effects of teprenone or placebo on: (1) portal pressure; (2) gastric pH; (3) gastric mucosal blood flow using laser doppler flowmetry, and (4) hexosamine content in gastric mucosa. The gastric mucosal blood flow was significantly higher in the PHT + teprenone group than in the PHT + placebo group (463 +/- 75 and 381 +/- 82 perfusion units, respectively; p < 0.05). The hexosamine content was significantly lower in PHT rats than in sham-operated controls (12.6 +/- 2.3 vs. 14.3 +/- 2.2 micrograms/mg, respectively). Teprenone treatment significantly increased the gastric mucosal hexosamine concentration in both sham-operated and PHT rats (17.2 +/- 3.1 and 15.6 +/- 3.6 micrograms/mg, respectively). These effects of teprenone, combined with its known prostaglandin-stimulating action, suggest a potential role for this agent in the treatment of PHT gastric mucosal abnormalities.

Animals↗

Glutamine:fructose-6-phosphate amidotransferase activity in cultured human skeletal muscle cells: relationship to glucose disposal rate in control and non-insulin-dependent diabetes mellitus subjects and regulation by glucose and insulin.

We examined the activity of the rate-limiting enzyme for hexosamine biosynthesis, glutamine:fructose-6-phosphate amidotransferase (GFA) in human skeletal muscle cultures (HSMC), from 17 nondiabetic control and 13 subjects with non-insulin-dependent diabetes. GFA activity was assayed from HSMC treated with low (5 mM) or high (20 mM) glucose and low (22 pM) or high (30 microM) concentrations of insulin. In control subjects GFA activity decreased with increasing glucose disposal rate (r = -0.68, P < 0.025). In contrast, a positive correlation existed between GFA and glucose disposal in the diabetics (r = 0.86, P < 0.005). Increased GFA activity was also correlated with body mass index in controls but not diabetics. GFA activity was significantly stimulated by high glucose (22%), high insulin (43%), and their combination (61%). GFA activity and its regulation by glucose and insulin were not significantly different in diabetic HSMC. We conclude that glucose and insulin regulate GFA activity in skeletal muscle. More importantly, our results are consistent with a regulatory role for the hexosamine pathway in human glucose homeostasis. This relationship between hexosamine biosynthesis and the regulation of glucose metabolism is altered in non-insulin-dependent diabetes.

Adult↗

Exacerbation of acetic acid ulcer induced by non-steroidal anti-inflammatory drugs in rats.

The influences of non-steroidal anti-inflammatory drugs (NSAID) on acetic acid ulcer were examined in rats. NSAID used in this study were aspirin (ASP, 200 mg/kg), indomethacin (IND, 2 mg/kg) and phenylbutazone (PHE, 100 mg/kg). These NSAID were administered consecutively for 5 days once a day at the early stage of the ulcer. Eleven days after the ulceration, suppression of the healing was observed in rats treated with all of the NSAID. In the rats treated with either ASP or IND, a delay of healing was observed not only 11 days after ulceration, but also 16 days after ulceration. The ulcer index in rats treated with either ASP or IND 16 days after ulceration was greater than that at 11 days after ulceration. Further studies were performed regarding the progressive change of mucosal hexosamine content, gastric secretion and gastric emptying during the healing process of the ulcer. It was found that the increase of hexosamine plays an important role in the healing of the ulcer and that a durable fall in hexosamine content was related to the remarkable exacerbation of ulcer induced by either ASP or IND. Hypersecretion, back diffusion of hydrogen ion or a delay of gastric emptying cannot be regarded as a cause of the exacerbation of the ulcer.

Acetates↗

Acute radiation effects on saliva composition in rats with different vitamin A levels in serum.

Irradiation of the head and neck often causes loss of salivary gland function which may lead to severe oral discomfort. The effects of a single dose of 25 Gy given to rats with different serum levels of vitamin A were studied. The salivary secretion rate as well as concentrations of protein, hexosamine, amylase and electrolytes, and the activities of two antibacterial glycoproteins were measured. At an adequate level of vitamin A in the diet, irradiation significantly reduced whole saliva secretion rate, and decreased the concentration of salivary sodium, calcium and hexosamine as well as the activity of a glycoprotein agglutinating a serotype c strain of S. mutans. Peroxidase, amylase and potassium were not significantly affected. The reductions seen at an adequate level of vitamin A were not reduced by supplementation of excess dietary retinol. The damage caused by irradiation was enhanced by vitamin A deficiency as seen in the reduced protein and hexosamine concentrations.

Animals↗

Effect of jianpiyiwei capsule on gastric precancerous lesions in rats.

AIM: To evaluate the therapeutic effect of compound Chinese drugs, Jianpiyiwei capsule (JPYW) on gastric precancerous lesions in rats and to explore its mechanism of action. METHODS: Model of gastric precancerous lesions was constructed in male Wistar rats: a metal spring was inserted and fixed through pyloric sphincter. One week after recovery, each rat was given 50-60 degrees hot paste containing 150 g/L NaCl 2 mL orally, twice a week for 15 weeks. Then 10 normal and 11 model rats were anaesthetized, after the measurement of gastric mucosa blood flow (GMBF), the rats were killed and the mucosal hexosamines and malonic dialdehyde (MDA) were measured. The morphological changes of gastric mucosa were observed macroscopically and microscopically, and by an automatic imaging analysis system. Other rats were treated with JPYW 1.5 g/kg.d(-1) or 4.5 g/kg.d(-1), or distilled water as negative control respectively (n=10 in each group). After 12 weeks, all the rats were examined as above. RESULTS: The gastric mucosa of model rats showed chronic atrophic gastritis with dysplasia and intestinal metaplasia (IM), GMBF and hexosamine content were reduced significantly and MDA was increased as compared to the normal group (P<0.01). After 12 weeks treatment, the pathological changes of the negative control group became worsened, while in JPYW treated groups the changes were modified with significant increase of GMBF and reduction of MDA, although the hexosamine concentration increased only mildly. CONCLUSION: JPYW increases GMBF and reduces MDA content in gastric mucosa and has therapeutic effects on gastric precancerous lesions.

Animals↗

Comparison of blood protein levels between diabetic and non-diabetic patients with retinopathy.

OBJECTIVE: To compare serum protein levels between diabetic and non-diabetic patients with retinopathy. STUDY DESIGN: Comparative study. PLACE AND DURATION: Ziauddin Medical University and Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from 2000 to 2002. PATIENTS AND METHODS: Sixty patients were selected. Among them, 21 were diabetic patients without any clinical evidence of chronic diabetic complications; 20 were diabetic patients with retinopathy and 19 were non-diabetic patients with retinopathy. Twenty-one apparently normal, age, gender and weight-matched control subjects were also inducted. All these patients were selected on clinical grounds. Blood values, fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, glycosylated plasma protein, hexosamine, sialic acid and total serum proteins were determined and compared. RESULTS: Fasting plasma glucose was high in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine concentrations. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with retinopathy and diabetic patients without any complications. These values were not different in diabetic patients with retinopathy and diabetic patients without chronic complications as compared with control subjects. Alpha-1 and alpha-2 globulins were significantly increased in diabetic patients with retinopathy, diabetic patients without complications and non-diabetic patients with retinopathy as compared with control subjects. Beta globulin was significantly increased in diabetic patients with retinopathy as compared with non-diabetic patients with retinopathy, diabetic patients without complication and control subjects. Gamma globulin was significantly decreased in diabetic and non-diabetic patients with retinopathy. CONCLUSION: Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with and without complications but these parameters remained within normal limits in non-diabetic patients with retinopathy. The decrease in gamma globulins may be associated with a retinopathy.

Blood Proteins↗

[Regulative effects pentagastrin and somatostatin on growth of human gastric cancer cells in vitro].

In order to observe the regulative effects of pentagastrin (PG) and somatostatin (SS) on the growth of two human gastric cancer cell lines (HGC803 and HGC823) in vitro, we observed the effects of PG and SS on proliferation of human gastric cancer cells by means of MTT. The contents such as gastrin, insulin, and glucagon were determined by radioimmunoassay (RIA), and the hexosamine content was determined by Neuhaus' method. The results showed that the growth of the two human gastric cancer cell lines were obviously promoted by PG. On the contrary, the growth and secretion of gastrin and glucagon were inhibited by SS. In addition, the hexosamine content of human gastric cancer cells was significantly increased by PG (7.58 +/- 0.66 versus 4.20 +/- 0.39 pg/cell, (P < 0.05). But the hexosamine content was decreased by SS (2.62 +/- 0.29 versus 4.20 +/- 0.39 pg/cell, P < 0.05). These findings indicate that the growth of gastric cancer cells is regulated by PG and SS, nevertheless a host of problems need to be elucidated.

Cell Division↗

Effects of administration of testosterone on some biochemical correlates in seminal vesicle of Heteropneustes fossilis (Bloch) during preparatory phase: a study correlating changes in plasma testosterone level and testis activity.

In the catfish H. fossilis, administration of testosterone (0.25, 0.5, 1 and 2 micrograms/g body weight for 20 days) during mid-preparatory phase (March) increased plasma testosterone, gonadosomatic index, seminal vesicle-somatic index and concentrations of total proteins, fructose and hexosamines in seminal vesicle (SV) and testis in a dose-related manner. In the lowest dosage (0.25 microgram) group, only the hexosamine and SV protein levels were significantly high. Glucose level decreased in a dose-related manner, the decrease being not significant in the 0.25 microgram group. The results indicate that testosterone stimulates SV and testicular secretions of total proteins, hexosamines and fructose in catfish. Decrease in glucose content suggests its conversion into fructose under testosterone stimulation.

Animals↗

[Biochemical studies of the temporomandibular ligament in dogs].

The purpose of this investigation was to determine the biochemical composition of the normal adult dog's temporomandibular ligament (TML) along its ligament (TML) along its length. Water content and hexosamine concentration as an index of glycosaminoglycan content and collagen concentration were quantified; and the results compared statistically with anatomically identified TML segments. The TML contained lower water content and higher collagen, hexosamine concentration than capsule (P less than 0.05). All the contents of these components in different locations along the ligament were not significantly different, with the exception that on the insertion site of the temporal eminence the concentration of the hexosamine was less than that in other areas (P less than 0.05). This study provided useful data for the analysis of TML functions and its mechanical properties.

Animals↗

The effects of menadione, ethyl biscoumacetate, and sodium salicylate on the metabolism of mucopolysaccharides in the aortic wall and liver of rats.

In rats with hyper- and hypovitaminosis the contents were determined of acid mucopolysaccharides (MPS) on the basis of contents of hexuronic acids; the total contents of biopolymers containing hexosamines (acid MPS, glycoproteins), on the basis of contents of hexosamines in the aortic wall and in the liver; and the activity of glutamine-fructose-6-phosphate aminotransferase (GPAT; EC 2.6.1.16) in the liver. Menadione-induced K hypervitaminosis was accompanied by moderate elevations of indicators of MPS metabolism. Protracted administration of ethyl biscoumacetate or sodium salicylate lowered the contents of acid MPS and of biopolymers containing hexosamines in the aortic wall and in the liver. Simultaneously, the GPAT activity in the liver markedly decreased.

Animals↗

Changes in glycosylated proteins in diabetic and non-diabetic patients with and without cardiovascular complications.

The objective of this study was to find the changes in glycoprotein composition in both diabetic and non-diabetic patients with and without cardiovascular complications. The study was carried out in Ziauddin Medical University Karachi, Pakistan. Eighty-three patients and control subjects were selected. Among them twenty-one were diabetic patients without any clinical evidence of chronic diabetic complications, twenty-one were diabetic patients with cardiovascular complications, twenty were non-diabetic patients with cardiovascular complications and twenty-one apparently normal, age, sex and weight matched control subjects were investigated. All these patients were selected on clinical grounds from National Institute of Cardiovascular Disease, Karachi. Fasting plasma glucose was increased in all diabetic patients and correlated significantly with and without cardiovascular complications. Fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein and its fractions were increased in diabetic patients with and without cardiovascular complications. Fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid and hexosamine were not different in diabetic patients with cardiovascular complications and diabetic patients without chronic complications as compared with control subjects. In conclusion, fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum proteins and its fractions were increased in diabetic patients with and without complications, but these parameters remained within normal limits in non-diabetic patients with cardiovascular complications.

Blood Glucose↗

Proteoglycan synthesis and content in articular cartilage and cartilage repair tissue in horses.

Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.

Animals↗

Gastric mucosal protection during restraint stress in rats: alteration in gastric adherent mucus and dissolved mucus in gastric secretion.

In order to assess the role of gastric mucus glycoproteins in the protection of gastric mucosa against stress ulceration, albino rats were subjected to restraint stress for 20 h, at the end of which the visible mucus adhering to the gastric mucosa, and the components of non-dialysable mucosubstances --sialic acid, hexoses, fucose and hexosamines were estimated in the gastric secretion. The molar ratio between the carbohydrate components of the dissolved mucus were also calculated. Restraint stress was found to reduce the gastric adherent mucus in oxyntic and pyloric gland areas, to decrease the concentration of sialic acid and hexosamines in gastric secretion and to increase the ratios of hexoses to hexosamines, and fucose to sialic acid. It was concluded that the gastric adherent mucus plays an important role in protecting the gastric mucosa against ulceration, and that this protective force breaks down during restraint stress, as indicated by reduced gastric adherent mucus and a low level of carbohydrate components in the gastric secretion.

Animals↗

Combined biochemical and clinical investigation of chemonucleolysis failures.

To attempt to understand the etiology of failures of chemonucleolysis, biochemical analyses were performed on intervertebral disk material to determine if the enzyme had actually digested the nucleus pulposus proteoglycans. This information was then correlated with the clinical laboratory data to see if a pattern evolved for the failures. Nine chymopapain treated disks, 6 untreated herniated disks and 6 lumbar disks from scoliotic patients were obtained at surgery. The results indicated that 6 out of 9 patients treated with chymopapain had a marked reduction in the proteoglycan (hexosamine) content of their disk compared to the untreated controls. There was a significant inverse correlation of intrinsic lysosomal enzymes and hexosamine content in those cases where the chymopapain failed to destroy the proteoglycan. The other 3 patients, however, had hexosamine levels virtually identical to those disks not treated with chymopapain. The clinical evaluation, consisting of preoperative myelograms, diskograms, the surgeon's observations at laminectomy and evaluation of the postoperative regimen did not explain the failures. This study suggests that the chymopapain failures are not the result of inactivity of the enzyme or failure to digest the nuclear material in at least 6 of the 9 cases. However, there were 3 patients where either the enzyme was not reaching the nuclear material or it was inactive.

Chymopapain↗

[Studies on defensive factors of experimental ulcers (2). Increasing action of aceglutamide aluminum on defensive factors in acetic acid ulcers of rats (author's transl)].

Severe ulcers were produced in rats by injections of 20% acetic acid in a volume of 0.05 ml into the subserosal layer of two portions in the corpus, and the effects of aceglutamide aluminum on hexosamine, sialic acid, uronic acid and hydroxyproline contents of the mucosa and stroma in the ulcerated regions were compared with the effects of L-glutamine. When aceglutamide aluminum (1,000 mg/kg x 2/day) was orally administered for 4 consecutive days beginning the day of the operation, this drug inhibited the ulcer index and the perforations in ulcerated regions by 18 and 66%, respectively. In addition, the drug remarkably increased the total amounts (microgram/ulcer areas/rat) of hexosamine, sialic acid, and uronic acid in the mucosa of ulcerated regions. It was notable than with the sialic acid contents, an increase in the concentration (microgram/100 mg dry tissue) was also observed. On the other hand, in the stroma of ulcerated regions, the contents of those components containing hydroxyproline were little affected by this drug. Following daily oral administration for 14 consecutive days, aceglutamide aluminum (1,000 mg/kg x 2/day) brought about more potent effects than those following the 4 days administrations, and this drug showed a 37% inhibition of the ulcer index and a complete inhibition of the perforations. Moreover, the drug pronouncedly increased both total amounts and concentrations of hexosamine, sialic acid, and uronic acid in the mucosa in the ulcerated portions. Of these components, the increment of the sialic acid content was the greatest. In the stroma of ulcerated portions, total amounts and concentrations of those components containing hydroxyproline were significantly increased by this drug, although the increase in the stroma were less than those in the mucosa. These effects of aceglutamide aluminum were far more potent than those of L-glutamine at the same dose. From the above results, aceglutamide aluminum may accelerate ulcer repair by potentiating defensive factors through the increases of components forming the mucus and granuloma in ulcerated tissues.

Acetates↗

Association of glycosaminoglycan depletion and degradative enzyme activity in scoliosis.

Although several theories have been advanced about etiology of idiopathic scoliosis, the pathogenesis still remains unknown. One study detected a decrease in the glycosaminoglycan content of the nucleus pulposus in idiopathic scoliosis, and it was theorized that this represented increased degradation. The present study was designed to investigate degradative enzyme activity in scoliotic intervertebral disks. Twenty-three disks from 5 patients with idiopathic scoliosis and 18 disks from 3 patients with scoliosis resulting from myelomeningocele were obtained at surgery (Dwyer procedure). Five disks were obtained during 2 postmortem examinations. Analyses of hydroxyproline, hexosamine and acid phosphatase were performed separately on the annulus and nucleus of each disk. Hexosamine was decreased in idiopathic scoliotic nuclei versus controls (p less than 0.001) by approximately 25%. Hydroxyproline was proportionately increased (p less than 0.05). Similar changes of a greater magnitude were seen when comparing myelomeningoceles to controls. In both types of scoliosis, acid phosphatase was elevated in nuclear and annular tissue. Acid phosphatase activity and hexosamine varied inversely in the nucleus. Finding similar biochemical patterns in idiopathic and neurovascular scoliosis raises the possibility that these changes may be secondary.

Acid Phosphatase↗

[Investigation of damage of the gastric mucosal barrier by Helicobacter pylori].

Damage of the gastric mucosal barrier by Helicobacter pylori (Hp) has been investigated with estimation of antral mucosal hexosamine and phospholipid, and the degree of pathologic changes to be also evoluted in 100 cases of chronic superficial gastritis. There are 42% of 50 cases of Hp positive patients with active gastric lesions, and significantly high than 50 cases of Hp negative patients (8%). The mean value of antral mucosal hexosamine is 30.33 mg/g in Hp positive group, while in Hp negative group, the mean value is 36.98 mg/g (P < 0.005). The mean value of antral mucosal phospholipid is 31.96 mg/g in Hp positive. While in Hp negative is 36.49 mg/g (P < 0.05). So, estimation of mucosal hexosamine and phospholipid can be represent the degree of damage of gastric mucosal barrier. Hp should be considered as causative agent to break down the gastric mucosal barrier.

Gastric Mucosa↗

Cumulus expansion during in vitro maturation of bovine oocytes: relationship with intracellular glutathione level and its role on subsequent embryo development.

Glutamine (GLN) is a metabolic precursor for hexosamine synthesis and its inclusion in culture medium has been reported to improve cumulus expansion. Glutamine and cysteine share the same transport system. Excess external GLN may act as a competitive inhibitor for the uptake of cysteine and stimulate loss of cellular cysteine, interfering this with GSH synthesis. Experiments were designed to evaluate the effect of 1-3 mM GLN during in vitro maturation (IVM) on bovine-cumulus expansion, intracellular GSH levels in both oocytes and cumulus cells, and subsequent embryo development up to blastocyst stage. Also, GSH content was measured in 6- to 8-cell embryos and a possible relationship between cumulus expansion and GSH synthesis was studied. Intact cumulus cell-oocyte complexes were incubated for 24 hr and cumulus expansion was measured by a computerized image-digitizing system either before or after IVM. IVM/IVF bovine oocytes were cultured up to 6- to 8-cell stage embryos for assessment of GSH content or for 8 days up to blastocyst stage for embryo development. The measurement of total GSH content was performed by an enzymatic method in oocytes, cumulus cells and 6- to 8-cell embryos. The maximal expansion was achieved by addition of 2 mM GLN without affecting GSH levels, in both oocytes and cumulus cells. At 3 mM, the degree of cumulus expansion was lower and the GSH levels decreased. The addition of 2 mM GLN improves cleavage and blastocyst rates, whereas no differences were found between O, 1, and 3 mM GLN. Moreover, the GSH content in 6- to 8-cell embryos was similar at any GLN concentrations. In order to study the relationship between GSH and cumulus expansion: 6-diazo-5-oxo-1-norleucine (DON), an inhibitor of hexosamine synthesis, or buthionine sulfoximide (BSO), an inhibitor of GSH synthesis, either alone or with GLN was added to IVM medium. GSH level was not affected by the presence of DON. However, the degree of cumulus expansion was reduced in the presence of BSO. In conclusion, bovine oocytes matured in the presence of 2 mM GLN improve their capacity for subsequent embryo development. Nevertheless, GSH level was altered when GLN was added to IVM medium at a high concentration with a reduction in the degree of cumulus expansion. This study provides evidence that optimal cumulus expansion in vitro is partially dependent on hexosamine production and intracellular GSH content.

Animals↗