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)

Three type I diabetic patients nonresponsive to subcutaneous insulin were implanted with a subcutaneous peritoneal access device. In these patients, multiple subcutaneous injections had been unable to prevent recurrent hospital admissions for diabetic ketoacidosis. The patients were responsive to intravenous insulin but had limited accessible peripheral veins. Complications of thrombosis and/or septicemia from permanent central venous catheters prevented the long-term use of this route. The peritoneal access device was implanted subcutaneously adjacent to the umbilicus with its insulin delivery catheter terminating in the peritoneal space. Transcutaneous injection of insulin into the subcutaneous access port resulted in the same quantity of insulin entering the peritoneal space. Using a mixture of regular and protamine zinc insulin in a ration of 1:1 resulted in acute increases in plasma free insulin concentration with meals and a declining background level postprandially. All peritoneal access devices have been functioning well for at least 2 mo and in one of the implanted diabetic subjects, it has been in continuous use for 5 mo with no evidence of peritonitis or resistance to peritoneal insulin. These results suggest that a subcutaneous peritoneal access device may provide an alterative insulin delivery route for patients who are nonresponsive to subcutaneous insulin injections.
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PMID:Subcutaneous peritoneal access device for type I diabetic patients nonresponsive to subcutaneous insulin. 715 35

Previous studies have demonstrated that the administration of the cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF)(20 micrograms/kg) to rats in a fasting state can produce many and perhaps most of the metabolic alterations found in patients with sepsis and injury. The purposes of the present study were 1) to define the metabolic effects of IL-1 and TNF during a fed state provided by continuous intravenous feeding for 20 h and 2) to characterize the unique effects of IL-1 among the overall response to cytokines by using IL-1 receptor antagonist (IL-1RA; 5 mg/kg). The effects were also explored during the endotoxemic condition induced by infusion of 200 micrograms/kg of endotoxin into rats. The results showed that during feeding IL-1 is responsible for the increase in glucose flux and plasma insulin, the development of insulin resistance, and plasma zinc depression during condition mimicking sepsis and injury, similar to effects observed in the fasting state. The changes in energy expenditure have a more complex mechanism. The results also suggested that certain host responses to cytokines or endotoxin, particularly related to protein metabolism, differed between the fed and fasting states. These data may have a special clinical relevance for the insulin-resistant state that develops during severe infection, since using IL-1RA in conjunction with nutritional therapy may offer additional advantages in the treatment of these severe metabolic disorders.
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PMID:Differential effects of interleukin-1 receptor antagonist in cytokine- and endotoxin-treated rats. 786 1

Group B streptococci (GBS) are important pathogens in neonatal sepsis, pneumonia, and meningitis. The ability of GBS to invade the collagen-rich amniotic membrane of the placenta has been shown in vitro. In the presence of GBS, the collagen fibrils of the amnion appear disordered, suggesting a role for GBS in premature rupture of membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Sephadex G-200 column chromatography, and gelatin zymograms were used in this study to characterize cell-associated collagenolytic activities of GBS. The synthetic peptide 2-furanacryloyl-Leu-Gly-Pro-Ala (FALGPA), which mimics the primary structure of collagen, was degraded by GBS USF704, a clinical isolate from the placenta of a septic newborn. Cells of GBS USF704 (9 x 10(7) CFU/ml) hydrolyzed 902 nmol of FALGPA over a 24-h period. As reported for zinc metalloenzymes such as collagenase, the hydrolysis of FALGPA by GBS was inhibited by addition of EDTA or 1,10-phenanthroline. Boiling of the cells resulted in loss of activity, while higher activity was observed with crude GBS cell lysates (hydrolysis of 970 nmol of FALGPA in 1.5 h). Antiserum raised against collagenase from Clostridium histolyticum was found to cross-react with cell-associated proteins produced by GBS and to inhibit GBS FALGPA hydrolysis. Twenty-five additional GBS clinical isolates were screened and found to have various levels of FALGPA hydrolytic activity. These observations suggest a cell-associated collagenolytic activity by GBS which may be involved in premature rupture of membranes and neonatal disease.
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PMID:Cell-associated collagenolytic activity by group B streptococci. 796 Jan 47

We have cloned a full length complementary DNA (cDNA) of the porcine tumor necrosis factor alpha (pTNF-alpha) gene and expressed it in porcine and murine cells. Total RNA obtained from lipopolysaccharide (LPS) stimulated porcine peripheral blood mononuclear cells was reverse transcribed with a specific antisense pTNF-alpha primer to generate a single stranded cDNA which was subsequently amplified by the polymerase chain reaction utilizing an additional pTNF-alpha specific sense primer. The resulting double stranded cDNA was introduced into the pBMGNeo expression vector and transfected by electroporation in porcine (PK(15)) and murine (L929) cell lines. TNF-alpha bioactivity was detected in the supernatant of the transfected cells using a standard L929 bioassay or a PK(15) bioassay. The activity was zinc inducible as expected for a gene controlled by a metallothionein promoter. The bioactivity was not lowered by an anti-mouse TNF-alpha antiserum neutralizing murine, but not human TNF-alpha and a broad immunoreactive band of 17-19 kD was detected using an anti-mouse TNF-alpha serum suitable for immunoblotting. This newly developed tool will allow us to investigate the role of TNF-alpha in pathogenesis of viral infections and gram-negative sepsis.
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PMID:Cloning and expression in mammalian cells of porcine tumor necrosis factor alpha: examination of biological properties. 825 38

Serum zinc and copper concentrations were measured by flame atomic absorption spectroscopy in 34 patients between 1 and 3 weeks after thermal injury. Mean (range) admission burn surface area was 29.8% (10% to 79%), and mean (range) serum zinc and copper concentrations within the first postburn week were 0.59 (0.2 to 1.5) and 0.74 (0.1 to 1.6) mg/L, respectively. Serum copper concentration was inversely correlated with burn surface area (r = -0.611, p < 0.01), whereas serum zinc concentration showed no such association. In the first postburn week hypocupremia (< 0.7 mg/L) was found in 15 of 32 (48%) of patients and hypozincemia (< 0.7 mg/L) in 21 of 32 (68%). Serum copper concentrations in patients with less than 15% burns remained within normal limits throughout the study period, but hypozincemia was found in patients irrespective of burn surface area. Long-term monitoring of two patients with 79% and 70% burns showed initial hypocupremia and hypozincemia. Hypocupremia only resolved in the patient with 79% burns when skin healing was almost complete 75 days after burns. Postburn hypozincemia was found to be very variable and not associated with either serum albumin concentration or periods of clinical sepsis. Because major burn injuries are associated with hypocupremia, serial monitoring is recommended with appropriate copper supplementation.
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PMID:Serum copper and zinc concentrations in patients with burns in relation to burn surface area. 853 18

Anastomotic leakage remains the most important cause of morbidity and mortality in digestive surgery. Despite the development of new surgical techniques and devices, intestinal anastomose continue to be complicated by leakage even in the best and most experienced of hands. One may explain the persistence of anastomotic leakage in spite of these technical advances on the basis of the dynamic effect that multiple factors (shock, peritoneal sepsis, inadequate intestinal preparation, advanced age, malignancy, malnutrition, coagulopathy, steroid dependence, uremia, radiation therapy, diabetes, perforation, anemia, fecal soiling and deficiency of vitamin C, iron and zinc) have on the healing of an anastomosis. Awareness of these factors and proper precautions by the surgeon can make a high-risk anastomosis less prone to leakage. Collagen is the essential material for composing an anastomosis and the basis of a good surgical suture. Recognition an correction of factors that compromise collagen synthesis, should be the goal of the surgeon. Over the years, numerous anastomotic techniques have been proposed, but the search for the ideal technical anastomosis goes on. Traditional inverting methods ignore the basic principle of accurately opposing clean-cut tissues, and temporary clamping of the gut and crushing of mucosal tissue by intraluminal sutures may damage the microcirculation. Submucosa should always be included in the formation of an anastomosis because it is the strongest intestinal layer and because the collagen has its origin and its synthesis just in submucosa. Monofilament sutures may be more desirable for anastomosis. Staple sutures have minimum tissue reaction. Single layer extramucosal technique has many of the attributes of an ideal intestinal anastomosis. Single interrupted and continuous sutures are not opposite and both give satisfactory results.
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PMID:[Sutures in digestive surgery]. 869 52

Elevated zinc serum concentrations have been shown to restore impaired immune response. Therefore, pharmacologic zinc supplementation has been used to improve immune function, particularly in intensive care patients. In these patients, Gramnegative sepsis, the symptoms of which are predominantly caused by LPS-induced release of monokines, represents a serious problem. We have recently shown that zinc enhances induction of TNF-alpha and IL-1 beta in cultures of PBMC by LPS. By fluorescence polarization and infrared spectroscopic measurements we found that zinc addition leads to decreased fluidity of the hydrocarbon chains of LPS. Experiments at different temperatures showed that the less fluid gel (beta) phase of LPS is more effective in cytokine induction than the more fluid liquid-crystalline (alpha) phase. Our studies suggest that the synergistic effect of zinc on monokine induction by LPS is caused by direct interaction of zinc with LPS altering the fluidity of the hydrocarbon chains. Although this effect is zinc specific, other divalent ions, like cobalt and nickel, with a complex structure and size comparable to those of zinc also enhance LPS-induced monokine secretion but to a much lesser extent. Our data indicate that the zinc level represents a relevant clinical parameter in the treatment of Gram-negative infection. This reveals potential risks in the therapeutic application of zinc.
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PMID:Zinc enhances lipopolysaccharide-induced monokine secretion by alteration of fluidity state of lipopolysaccharide. 881 25

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.
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PMID:Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia. 893 27

The acute phase response (APR) that follows injury or infection is characterized by a decrease in serum zinc concentrations, which we hypothesized benefits the host. Additionally, we proposed that preventing this decline by supplementing zinc would result in an exaggerated APR as indicated by elevated temperatures, increased serum cytokine concentrations, interleukin 6 and the acute phase protein (ceruloplasmin). A prospective, randomized, double-blinded, clinical trial was conducted. Patients on home parenteral nutrition with a diagnosis of catheter sepsis and patients with a diagnosis of pancreatitis, also on total parenteral nutrition (TPN), were recruited for the study. Following enrollment, block randomization was used to assign patients to receive 0 mg (n = 23) or 30 mg (n = 21) of zinc per day for the first 3 d of TPN. Blood samples for measurement of serum zinc, copper, ceruloplasmin and interleukin-6 were obtained upon enrollment and on d 1 through 3 of TPN. The highest temperatures reported on these days in the medical record were also recorded. Repeated measures ANOVA was used to determine differences in the primary outcome variables over time. No significant differences between groups were observed in serum interleukin-6 or ceruloplasmin concentrations. A significantly higher (P = 0.035) temperature was observed in the zinc-supplemented group compared with the control group on d 3 of parenteral nutrition. We conclude that parenteral zinc supplementation in patients experiencing a mild APR resulted in an exaggerated APR as evidenced by a significantly higher febrile response.
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PMID:Parenteral zinc supplementation in adult humans during the acute phase response increases the febrile response. 904 May 47

As with most liver diseases, the symptoms of hepatitis in dogs are nearly always aspecific: the dogs eat less, are apathetic, sometimes have polyuria/polydipsia, and sometimes have diarrhoea. Hepatoencephalopathy and ascites only occur with these symptoms in very advanced stages of chronic hepatitis. Only a part of the dogs have jaundice. Because of these aspecific symptoms, the diagnosis hepatitis is often not taken into consideration, even though the presence of a liver disease can be easily detected by measuring plasma concentrations of alkaline phosphatase and bile acids, one or both of which are elevated. The diagnosis is confirmed by histological examination of a liver biopsy sample. The most common forms of hepatitis are non-specific reactive hepatitis, acute hepatitis, and chronic hepatitis. Non-specific reactive hepatitis is a reaction against endotoxin as a result of sepsis or an increased gastrointestinal absorption. Treatment is directed to the primary process. Leptospirosis also causes non-specific reactive hepatitis, but then renal insufficiency is the most prominent feature. The diagnosis is made not on the basis of a liver biopsy but on the basis of increased IgM titres against Leptospira. Immediate treatment with antibiotics and infusions at the first signs (jaundice and uraemia) can save the animal's life. Acute hepatitis can develop as a result of infection, toxins, or liver hypoxia. There is no specific treatment, but adequate recovery often occurs with supportive treatment. Corticosteroids are contraindicated. Chronic hepatitis, which can lead to cirrhosis, is the most common form of hepatitis. It is an autoimmune inflammatory reaction that is usually caused by a virus infection but sometimes by poisoning (intoxication). Long treatment with prednisolone or azathioprine is usually successful, but early recognition of the disease increases the likelihood of success. Nowadays, chronic hepatitis due to hepatic copper accumulation in Beddlington terriers can be detected by DNA tests. Such tests make it possible to distinguish between carriers and non-carriers. Affected animals can be kept symptom-free by life-long treatment with zinc gluconate or penicillamine.
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PMID:[Hepatitis in dogs; a review]. 958 48


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