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)

To understand the molecular mechanisms responsible for the sepsis-induced enhanced glucose uptake, we have examined the levels of GLUT4 and GLUT1 mRNA and protein in the adipose tissue of septic animals. Rats were challenged with a nonlethal septic insult where euglycemia was maintained and hexose uptake in adipose tissue was markedly elevated. Northern blot analysis of total RNA isolated from epididymal fat pads indicated differential regulation of the mRNA content for the two transporters: GLUT1 mRNA was increased 2.6 to 4.6-fold, while GLUT4 mRNA was decreased by 2.5 to 2.9-fold. Despite the difference in mRNA levels, both GLUT1 and GLUT4 protein were down regulated in plasma membranes (40% and 25%, respectively) and microsomal membranes (42% and 25%, respectively) of the septic animals. The increased glucose uptake cannot be explained by the membrane content of GLUT1 and GLUT4 protein. Thus, during hypermetabolic sepsis, increased glucose utilization by adipose tissue is dependent on alternative processes.
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PMID:Differential regulation of glucose transporter gene expression in adipose tissue or septic rats. 155 May 51

Hepatic dysfunction is a frequent finding in sepsis and peritonitis. In the present study, hepatic function in experimental peritonitis in the rat was determined by measuring serum levels of bilirubin, alkaline phosphatase (ALP), glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), together with antipyrine (AP) clearance as a determinant of microsomal function. Peritonitis was induced by intraperitoneal injection of 3 x 10(8) colony-forming units of E. coli together with either 1.0 ml bile or saline. E. coli + bile peritonitis rats had significantly elevated levels of bilirubin, ALP, GOT and GPT as compared with both controls and rats with peritonitis induced by E. coli alone. The derangements gradually increased with time over the 10-hour period studied. In contrast, no reduction of AP clearance was observed in the peritonitis models. On the contrary, AP clearance was enhanced at 10 hours after induction of peritonitis by E. coli alone. In conclusion, hepatic dysfunction as revealed by routine laboratory tests is seen early in experimental peritonitis in the rat, but this is not accompanied by a reduced AP clearance rate.
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PMID:Effect of bile on liver function tests in experimental E. coli peritonitis in the rat. 176 53

Autoimmune thyroiditis in infancy is a very rare condition. Only 1 case has been reported previously. In the present patient an acquired primary hypothyroidism with high titers of thyroid microsomal antibodies was diagnosed at the age of 7 months. The patient died at 9 months of age in a sepsis-like condition. Autopsy revealed an atrophic thyroiditis. The more severe and complex clinical picture of autoimmune thyroiditis in infancy compared to that later in childhood is discussed.
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PMID:Atrophic, autoimmune thyroiditis in infancy. A case report. 279 73

Na+-K+-ATPase, Ca2+-ATPase and Mg2+-ATPase activities of erythrocyte membrane, microsomal fractions of rectus muscle, and liver were measured colorimetrically in the biopsy specimens of 14 control, 7 uncomplicated trauma (group 2), and 14 severe trauma or septic patients (groups 3-A and 3-B). In erythrocytes, these three ATPase activities in group 2 were not significantly changed but sepsis of both the acute (group 3-A) and ongoing type (group 3-B) decreased all of the ATPase activities. In muscle, there was a significant loss of three ATPase activities in the acute insult of severe trauma or sepsis (group 3-A), while Na+-K+-ATPase and Mg2+-ATPase activities were not significantly changed in ongoing, severe trauma (group 3-B). In the liver, a tendency for all three ATPase activities to decrease is noted in the severe traumatic group. However, a statistical difference between the control and severe traumatic group showed only for Na+-K+ ATPase and Mg2+-ATPase in group 3-A and Ca2+-ATPase in group 3-B. Correlation coefficients between erythrocyte, muscle, and liver for three ATPase activities are between 0.4 and 0.5. The mechanism which alters ATPase activity remains unknown in this study, but it may account for the variation in traumatic insult, in hemodynamic and hormone changes, and in tissue energy stores.
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PMID:Alterations of Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase activities in erythrocyte, muscle, and liver of traumatic and septic patients. 304 Feb 90

The hypothesis was tested that several metabolic and functional alterations associated with endotoxicosis and sepsis could be due to a Ca overload of liver and heart in rats. Male rats were given intravenously E. coli endotoxin (ET) or rendered septic by cecal ligation and puncture. At various intervals after ET injection and 16-18 h after the onset of peritonitis the animals were sacrificed and the liver and heart sampled for assay of the total Ca content. Also, livers of saline- or ET-treated rats were perfused in vitro to study several aspects of Ca movements as affected by phenylephrine infusion. Livers, were also fractionated to study the subcellular distribution of Ca. ET treatment produced a slight, but significant increase in total hepatic Ca content (12.6% at 4 h and 7.7% at 24 h after ET injection). Sepsis did not affect this parameter in either liver or heart. ET also produced a decrease of Ca content in the microsomal fraction of liver, while sepsis was associated with an elevated Ca content of liver mitochondria. Perfused livers of saline-treated rats responded to phenylephrine by accumulating Ca, while the perfused organs of ET-treated rats did not display such a response to agonist infusion. We conclude that impairment of intracellular Ca homeostasis--under the conditions studied--consists of a slight Ca overload in endotoxicosis, associated with discrete alterations of Ca fluxes and compartmentalization within the cell both in endotoxicosis and sepsis.
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PMID:Calcium content in liver and heart and its intracellular distribution in liver during endotoxicosis and sepsis in rats. 332 66

Despite substantial progress in handling the acute phase after thermal injury, severely burned patients still succumb to systemic sepsis as a consequence of a compromised defence system. It is likely that autotoxic mechanisms play an important role in the aetiology of the impaired host defence. One of the primary target systems of autotoxic cell damage is the liver. In the present work oxidative alterations in the microsomal compartment of liver cells have been investigated. It was found that thermal burns are associated with extensive oxidation of polyunsaturated fatty acids which can be antagonized by antioxidants such as silibinin.
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PMID:Changes in the pattern of microsomal fatty acids in rat liver after thermal injury and therapeutic intervention. 337 May 12

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
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PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

The frequency of gram-negative infections and endotoxemia in the perinatal period prompted an investigation of the effects of endotoxin (Escherichia coli 026B6) on hepatic drug metabolism. Gravid female rats given injections IP with different dosages of lipopolysaccharide during late pregnancy resulted in significant depression of the liver microsomal cytochrome P-450 dependent monooxygenase activities. The acute administration of endotoxin to mothers (1.4 mg/kg on seventh day after parturition) significantly decreased the hepatic activity of aminopyrine demethylase and contents of cytochrome P-450 of suckling neonates and mothers. However, chronic administration of endotoxin (0.2 mg/kg/day for 7 days) to lactating mothers did not alter neonatal enzyme activities. When neonates themselves were given injections of endotoxin (1.0 mg/kg) at 7, 16, and 27 days of age, a significant reduction in levels of mixed function oxidase enzymes was observed. These observations suggest that the ability of mothers and neonates to metabolize drugs is significantly decreased upon exposure to endotoxin, and this demands careful evaluation of drug disposition studies in gram-negative sepsis.
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PMID:Gram-negative endotoxin administration decreases hepatic drug-metabolizing enzymes during development in rats. 699 41

The utilisation of assays for TSH with improved sensitivity has revealed that abnormal TSH results are frequently observed in patients with nonthyroidal illnesses, such as trauma, renal diseases, liver diseases or sepsis. The aim of this study was to investigate the prevalence of abnormal TSH concentrations, using a sensitive immunometric assay, in patients with type 2 (non-insulin-dependent) diabetes mellitus. The study population consisted of 290 type 2 diabetics, 159 females and 131 males aged 40 to 93 years (mean 60.6 +/- 11.9 years), hospitalised because of poor diabetic control or recent-onset diabetes (mean HbA1c value = 9.6 +/- 2.2%). All patients with TSH values outside the normal range (0.45 to 3.66 mlU/l) had FT4 assay and thyroid microsomal autoantibody assay performed on the same specimen of serum. Abnormal TSH concentrations were detected in 91 patients (31.4%). Subclinical hypothyroidism (high TSH, normal FT4) was most common (48.3%), followed by subclinical hyperthyroidism (low TSH, normal FT4) (24.2%) and by definite hypothyroidism (high TSH, low FT4) (23.1%). Definite hyperthyroidism (low TSH, raised FT4) was found in 4 patients (4.4%). None of the patients with low TSH values had increased FT3 concentrations. The prevalence of abnormal thyroid function test results was significantly higher in the female than in the male patients (40.9% vs. 19.8%, p < 0.0005) and in the insulin-treated patients than in those receiving oral hypoglycaemic agents (OHA) (37.3% vs. 23.1%, p < 0.02). Thirty patients with abnormal thyroid function test results (33.0%) had evidence of thyroid autoimmunity (titre of thyroid microsomal autoantibodies > 250 IU/l). Five thyroid microsomal antibody-negative patients had non-autoimmune thyroid diseases, 7 had nonthyroidal illnesses other than diabetes mellitus and 4 were receiving drugs known to affect the hypothalamic-pituitary-thyroid axis. Twenty-seven thyroid microsomal auto-antibody-negative patients with abnormal TSH values (17 with subclinical hypothyroidism and 10 with subclinical hyperthyroidism), who were not receiving drugs known to affect TSH secretion and were free of diseases other than diabetes mellitus, were retested after two months of adequate treatment of diabetes with OHA or insulin. TSH concentrations decreased in all but one patient with initial subclinical hypothyroidism and increased in all patients with initial subclinical hyperthyroidism. These changes were coupled with a significant fall of glycated haemoglobin values. In view of the transient changes in TSH secretion, we suggest that the diagnosis of thyroid dysfunction in type 2 diabetics should be delayed until improvement of the metabolic status.
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PMID:Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. 764 93

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with the length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers. Livers were harvested at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions prepared. Cytochrome P450 concentration was determined by assay and P450 activity was determined by the metabolism of ethoxyresorufin and ethoxycoumarin. Lipid peroxidation was estimated by measuring malondialdehyde content. Septic rats showed decreases in P450 levels and activity, which worsened with duration of sepsis. These decreases were partially lessened by hyperoxia. Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant. This study suggests that while MFO content and activity decrease with sepsis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance.
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PMID:Mixed-function oxidase activity in sepsis. 853 82


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