Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.
 ...
PMID:Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions. 9 98

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.
 ...
PMID:Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation. 65 52

The catabolism of glucose and amino acids has been studied in the normal, the fasted, and the fasted septic dog. The fasted septic dog oxidized more glucose and alanine, and had more gluconeogenesis from alanine and the five tritiated amino acids--glutamate, threonine, phenylalanine, leucine, and valine--as compared to the normal and equally fasted dog. Thus the total body protein catabolic state was characterized in biochemical terms. In contrast, following glucose infusion, the fasted septic animal responded much like the fasted animal in terms of decreased animo acid gluconeogenesis and decreased plasma concentrations of amino acids, fats and fat products, but considerably increased the oxidation of alanine. The increased alanine oxidation appeared to be primarily related to increased tissue clearance and increased plasma concentration. There was some suggestive evidence for enhanced oxidation of the tritiated amino acids including leucine and valine during glucose infusion. The protein catabolic state secondary to this sort of sepsis in dogs only on per os fluid support appears to be best characterized as a glucose catabolic state with alanine being oxidized directly. Such states are known to be ones of enhanced metabolic rate secondary to enhanced synthetic processes generally. This is probably related to enhanced sympathetic nervous system release of glucagon with insulin being normally responsive to glucose because of a normal plasma epinephrine.
 ...
PMID:Turnover of amino acids in sepsis and starvation: Effect of glucose infusion. 125 26

The sequential changes in plasma free amino acid concentration were analyzed and compared in burned patients with sepsis (n = 12) and without sepsis (n = 19). After burn injury, phenylalanine, methionine, lysine, and the Phe/Tyr ratio were significantly increased in two groups (P < 0.05-0.01). Threonine, serine, histidine, arginine, proline and BCAA/AAA ratio were significantly decreased in two groups (P < 0.05-0.001). The Phel Tyr ratio in patients with sepsis was much higher than that in patients without sepsis on postburn days 14 and 21 (P < 0.05), while the BCAA/AAA ratio in patients with sepsis was much lower than that in patients without sepsis on postburn day 14 (P < 0.01). The level of proline in patients with sepsis was much higher than that in patients without sepsis on postburn days 3 and 7 (P < 0.05). It is suggested that these results, in collaboration with other clinical and laboratory findings, may be helpful in foretelling the probable development of sepsis in patients with major burns.
 ...
PMID:[Changes in plasma free amino acid concentration in burned patients with sepsis]. 130 55

Amino acid fund has been studied during complex therapy of 25 patients with sepsis. In 15 patients complex therapy included detoxicating hemosorption (3-5 sessions), in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions). Complex therapy employing hemosorption led to a decrease in serine plasma level. Changes in the amino acid fund of the whole blood were insignificant. Leucine, isoleucine, threonine and phenylalanine blood levels were significantly increased. The introduction of ultraviolet blood irradiation into complex therapy of patients reduced traumatic effect of sorption detoxication on blood cells and enhanced detoxicating effect.
 ...
PMID:[Changes in the amino acid spectrum of the blood in patients with sepsis in the process of complex intensive therapy]. 176 53

Bacteriological and clinical studies on cefodizime (CDZM, THR-221), a new cephem developed by Hoechst AG and Roussel Uclaf, were carried out and the results are summarized below: 1. Against Gram-positive bacteria, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, antibacterial activities of CDZM were similar to those of cefotaxime (CTX), cefazolin, cefotiam and piperacillin. Against Escherichia coli, Klebsiella pneumoniae and Serratia sp., antibacterial activities of CDZM were similar to that of CTX, and superior to those of other tested antibiotics. Especially against Haemophilus influenzae and Branhamella catarrhalis, it showed an excellent antibacterial activity. 2. Although the clinical efficacy was poor in 1 patient with sepsis caused by Salmonella marcescens and in another with cervical lymphadenitis, in 5 patients with upper respiratory tract infection, 4 patients with bronchitis, 6 patients with bronchopneumonia, 18 patients with pneumonia, 5 patients with urinary tract infection and 1 patient with enteritis, the clinical efficacy was excellent or good and the efficacy rate was 95.1% (39/41) including excellent efficacies in 25 cases. 3. Bacteriologically, all identified causative bacteria were eradicated except for 1 case of Salmonella sp., thus the eradication rate was 97.4% (38/39). Especially S. pneumoniae in 10 cases, H. influenzae in 12 cases and B. catarrhalis in 3 cases were eradicated totally. 4. Adverse reactions were studied in 46 cases, and digestive symptoms were observed in 9 cases (diarrhea 5 cases, loose stools 4 cases). Eruption and vascular pain were observed in 1 case each. As digestive symptoms in 9 cases were mild, the treatment were not suspended. In laboratory test values, elevation of GOT, elevation of GPT, elevation of bilirubin, and eosinophilia were observed in 1 case each. Influences on blood coagulation parameters were studied. No change was observed between the beginning and the end of the treatment. From above results, we have concluded that CDZM is a useful and safe antibiotic in pediatrics, administered at a daily dose of 20 mg/kg divided into 3 or 4 doses and administered intravenously.
 ...
PMID:[Bacteriological and clinical studies of cefodizime in pediatrics]. 188 Sep 19

Concentrations of amino acids in the plasma of 13 neonatal foals with septicemia were compared with the concentrations of amino acids in the plasma of 13 age-matched neonatal foals without septicemia. Analysis of the results revealed significantly lower concentrations of arginine, citrulline, isoleucine, proline, threonine, and valine in the plasma of foals with septicemia. The ratio of the plasma concentrations of the branched chain amino acids (isoleucine, leucine, and valine) to the aromatic amino acids (phenylalanine and tyrosine), was also significantly lower in the foals with septicemia. In addition, the concentrations of alanine, glycine, and phenylalanine were significantly higher in the plasma of foals with septicemia. Therefore, neonatal foals with septicemia had significant differences in the concentrations of several amino acids in their plasma, compared with concentrations from healthy foals. These differences were compatible with protein calorie inadequacy and may be related to an alteration in the intake, production, use, or clearance of amino acids from the plasma pool in sepsis.
 ...
PMID:Concentrations of amino acids in the plasma of neonatal foals with septicemia. 190 45

Amino acid fund was studied during intensive therapy of 25 patients with sepsis. In 15 patients complex therapy involved detoxicating hemosorption (3-5 sessions) and in 10 patients hemosorption was supplemented by ultraviolet blood irradiation (5-10 sessions). Complex therapy with hemosorption led to a decrease in plasma serine content. The amino acid fund of the whole blood changed insignificantly. There was a significant increase in leucine, isoleucine, threonine and phenylalanine levels. The introduction of ultraviolet blood irradiation into complex therapy of patients decreases a traumatic effect of sorption detoxication on blood cells and potentiates detoxicating effect.
 ...
PMID:[Changes in the amino acid spectrum pf the blood in patients with sepsis undergoing complex intensive therapy]. 207 30

The effect of sterile inflammation and chronic sepsis on the plasma and hepatic free amino acid concentrations was determined. Relative to control animals, only minor alterations in the plasma amino acid concentrations were observed in sterile inflammation and sepsis. In liver, concentrations of alanine, serine, threonine, asparagine, proline, and glycine were significantly increased to the same extent in sterile inflammation and sepsis, while hepatic glutamine concentrations were significantly decreased. Compared with sterile inflammation, the branched-chain amino acid concentrations were depressed in the liver of septic animals. Following administration of dichloroacetate, hepatic alanine concentrations were significantly reduced more than threefold in each of the conditions examined; in contrast, significant increases in hepatic concentrations of threonine, glycine, glutamine, glutamate, histidine, and proline were observed. Also following administration of dichloroacetate, the branched-chain amino acid concentrations were all significantly elevated in each of the conditions examined, and plasma alanine concentrations were significantly decreased, while those of glutamine and glycine were significantly increased. These results demonstrate that there is a disassociation between the plasma and hepatic concentration of free amino acids in sterile inflammation and sepsis. Furthermore, the results demonstrate that some of the alterations in hepatic amino acid metabolism may be reversed pharmacologically by dichloroacetate.
 ...
PMID:Effect of dichloroacetate on plasma and hepatic amino acids in sterile inflammation and sepsis. 267 41

Human peripheral adherent cells from splenectomized subjects, human spleen cells and mouse spleen cells were tested for IL-1 production in vitro in presence or absence of synthetic tuftsin (Thr-Lys-Pro-Arg). Application of synthetic tuftsin to peripheral blood adherent cells from normal donors as well as from splenectomized subjects induces IL-1 production. In splenectomized subjects the extent of induction was more evident than in controls. In human splenic cells tuftsin stimulates IL-1 production without KLH or LPS. In mouse spleen cells tuftsin alone did not stimulate the IL-1 secretion. However, addition of tuftsin to mouse spleen cells incubated with KLH augmented significantly the IL-1 secretion. As removal of the spleen leads to tuftsin deficiency, our present findings may perhaps explain the fulminant nature of the postplenectomy sepsis and some immune disturbances described in the postplenectomy state.
 ...
PMID:Tuftsin stimulates IL-1 production by human mononuclear cells, human spleen cells and mouse spleen cells in vitro. 278 82


1 2 3 4 5 6 Next >>