Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We observed the influence of recombinant growth hormone (rGH) on protein metabolism during sepsis and found its mechanisms. Cecal ligation and puncture were choosen to duplicate the severe infection model. Animals of therapy group received rGH 1 U/kg/d after CLP operation, while sepsis group received normal saline. rGH accelerated regaining of the positive nitrogen equilibrium, improved plasma albumin level. rGH accelerated the recovery of intestinal mucosa glutaminase activity, preserved the normal structure of intestinal mucosa, reduced the portal venous endotoxin level and venous TNF level. rGH improved the albumin synthesis of isolated hepatocytes, and inhibited the expression of albumin mRNA level during severe infection. We conelude that rGH preserves the normal structure and function of intestinal mucosa during sepsis, and reduces gut origin hypermetabolism reactions. Moreover, rGH improves the synthesis of protein.
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PMID:[Influence of recombinant growth hormone on protein metabolism during severe infection: an animal experiment]. 1037 88

The liver shows net glutamine uptake after a protein-containing meal, during uncontrolled diabetes, sepsis and short-term starvation, but changes to net release during long-term starvation and metabolic acidosis. Some studies report a small net release of glutamate by the liver. The differential expression of glutamine synthetase (perivenous) and glutaminase (periportal) within the liver indicates that glutamine is used for urea synthesis in periportal cells, whereas glutamine synthesis serves to detoxify any residual ammonia in perivenous cells. Experiments in vivo suggest that changes in net hepatic glutamine balance are due predominantly to regulation of glutaminase activity, with the flux through glutamine synthetase being relatively constant.
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PMID:Glutamine and glutamate metabolism across the liver sinusoid. 1073 66

Expression of high activities of both glutamine synthetase and glutaminase allows the liver to play a major role in the regulation of glutamine homeostasis. The liver shows net glutamine output in metabolic acidosis, in prolonged starvation and animals bearing tumors, net glutamine uptake in the postabsorptive state, on consuming high protein diets, and in uncontrolled diabetes or sepsis. Liver glutamine synthetase is expressed only in a small population of perivenous cells that allows it to salvage any ammonia not incorporated into urea in periportal cells. Hepatic glutaminase is a unique isozyme found only in periportal liver parenchymal cells where it provides glutamate and ammonia for the urea cycle. Control of hepatic glutamine metabolism occurs almost exclusively through changes in the activity of glutaminase, with no change in glutamine synthetase flux.
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PMID:Hepatic glutamine metabolism. 1193 40

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to alpha-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue. Our aim here is to review on some amino acids with high functional priority such as glutamine and to define their effective activity in human health and pathologies.
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PMID:II. Glutamine and glutamate. 1248 81

In order to study the effect of total parenteral nutrition (TPN) with or without glutamine supplementation in septic rats, septic Wistar albino rats were randomly assigned to receive 0.23 g of nitrogen and 113 kJ (100 g BW)(-1) per day in the form of amino acids with (group 2) or without (group 1) glutamine supplementation or 10% (w/v) glucose only (group 3). After 4 days of TPN treatments, rats receiving glutamine-supplemented TPN had a cumulative nitrogen balance of -24.4 +/- 3.3 mg N, which was significantly (P < 0.001) better compared to other TPN-treated groups. Septic rats of group 2 survived sepsis significantly (P < 0.001) better than those in groups 1 and 3. Glutamine-supplemented TPN treatment resulted in significant increases in jejunal weight (P < 0.001), DNA and protein contents (P < 0.001), villous height (P < 0.001) and crypt depth (P < 0.001) when compared with septic rats of group 1. Septic rats of group 2 extracted and metabolised glutamine by the small bowel at higher rates (P < 0.001) than that observed in septic rats of group 1. Increases in jejunal glutaminase (38.2%, P < 0.001) and decreases in glutamine synthetase (41.7%, P < 0.001) activities were observed in response to glutamine-supplemented TPN treatment. It is concluded that the administration of glutamine-supplemented TPN is beneficial to the small bowel of septic rats.
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PMID:Effect of glutamine-supplemented total parenteral nutrition on the small bowel of septic rats. 1683 99

Berberine was reported to protect against the intestinal injury and improve the survival rate in sepsis, and glutamine deficiency was considered to be correlated with mortality in sepsis. We found that berberine pretreatment ameliorated lipopolysaccharide-induced direct intestinal injury and mucosal hypoplasia and attenuated impairments of intestinal glutamine transport and glutaminase activity, B(0)AT1 mRNA and protein expressions, and glutaminase protein expression. These findings showed the first time that berberine pretreatment could improve intestinal recovery and attenuate the impairment of glutamine transport and glutaminase activity in rat sepsis. This might be one of the mechanisms for the beneficial effect of berberine on sepsis.
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PMID:Berberine attenuates lipopolysaccharide-induced impairments of intestinal glutamine transport and glutaminase activity in rat. 2107 32

Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization.
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PMID:Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. 2579 80


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