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)

A novel copper-binding protein was identified in the liver supernatant (100,000 x g) of Indian childhood cirrhosis (ICC), purified to apparent homogeneity and characterized [corrected]. Purified major copper-binding protein (MCuBP) is solely responsible for binding about 35% of the total supernatant copper. Elution profile of ICC liver supernatant on Sephadex G-75 column chromatography showed three peaks. About 60% of the total supernatant copper was resolved in peak II, whereas zinc content was insignificant in this peak. But peak II was almost missing in a gel elution profile of control liver supernatant. The control group included cases of various liver diseases viz. neonatal hepatitis, septicemia, and mixed nodular cirrhosis. Copper-binding proteins of peak II further purified on ion-exchange chromatography and elution profile showed that peak II was a MCuBP with high copper-binding capacity (10 g atoms/mol of native protein). SDS-PAGE of this protein also revealed the existence of a single band with molecular mass of about 50 kD. UV spectra of MCuBP showed the maximal absorbance at 254 nm. Unlike the classical metallothionein, the amino acid composition of MCuBP revealed the presence of aromatic amino acids and higher content of glutamic acid and aspartic acid followed by glycine and serine. The ratio (0.3) of basic amino acids to acidic amino acids strongly indicates that it is an acidic protein. The cysteine content in this protein was insignificant, which further corroborates the possibility that the acidic amino acids might be prominent candidates for binding copper. Thus, the 50-kD MCuBP apparently makes a major contribution to the total copper-binding activity in ICC liver cytosol and may play a significant role in hepatic intracellular copper accumulation.
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PMID:Identification of a novel copper-binding protein from the liver of Indian childhood cirrhosis: purification and physicochemical characterization [corrected]. 980 48

In contrast with the full-term infant, the skin of the preterm neonate is structurally and functionally immature, especially birth occurred before 30 weeks gestation. The inefficiency of the epidermal barrier may result in dehydration, thermal instability and toxic reactions from percutaneous absorption of topically applied agents. An increased risk for bacteremia and sepsis exist because of the easily injured skin, combined with compromised immunity. The present article summarizes the consequences of this skin immaturity and the different means to avoid them. We shall also describe 2 pathologies more frequent in premature infants: sclerema neonatorum and acquired zinc deficiency.
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PMID:[Dermatological particularities and pathologies of premature infants]. 1060 18

Acrodermatitis enteropathica is characterized by eczematous and scaly plaques on the face, scalp, acral, and anogenital regions. In addition to typical lesions, unusual prominent vesiculobullous lesions are also described. We report a full-term, 9-month-old boy who has acrodermatitis enteropathica and Pseudomonas sepsis. In this patient there were clinical findings of sepsis and eczematous vesiculobullous lesions on the periorificial and acral areas. Serum zinc level was extremely low. Pseudomonas aeruginosa was identified in cultures of blood and fluid which was aspirated from the bullous lesions. After oral zinc sulfate and intravenous antibiotic treatment his condition improved within 2 weeks.
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PMID:Acrodermatitis enteropathica with Pseudomonas aeruginosa sepsis. 1063 41

1. The ulcerogenesis of gastric haemorrhagic damage during sepsis is unclear. The present study first proposes that gastric haemorrhagic ulcer is modulated by mucosal glutathione, histamine and oxyradicals in lipopolysaccharide (LPS)-induced sepsis in rats. The protective effects of several drugs on the ulcerogenic parameters also were evaluated. 2. Male specific pyrogen-free Wistar rats were deprived of food for 24 h. For the induction of sepsis, intravenous LPS (0, 1, 3 or 10 mg/kg in 1 mL sterilized normal saline) was challenged to rats 12 h after withdrawal of food. Rat stomachs were vagotomized, followed by irrigation for 3 h with normal saline or a physiological acid solution containing 100 mmol/L HCI and 54 mmol/L NaCl. 3. The aggravation of gastric ulcerogenic parameters, such as gastric acid back-diffusion, luminal haemoglobin content, mucosal lipid peroxide production, histamine concentration, as well as lowered concentrations of defensive substances, including mucosal glutathione, were dependent on the doses of LPS used for challenge. A high correlation was observed between mucosal histamine release and lipid peroxide production in LPS rats. 4. The ulcerogenic parameters obtained in LPS (3 mg/kg, i.v.) rats were potently attenuated by diamine oxidase, ketotifen and zinc sulphate. 5. Several oxyradical scavengers, including glutathione, dimethylsulphoxide and allopurinol, also were effective in inhibiting haemorrhagic ulcer. 6. In conclusion, gastric mucosal histamine release and oxyradical generation play pivotal roles in the formation of haemorrhagic ulcers in septic rats.
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PMID:Importance of histamine, glutathione and oxyradicals in modulating gastric haemorrhagic ulcer in septic rats. 1077 30

Aeromonas hydrophila is an opportunistic pathogen and the leading cause of fatal hemorrhagic septicemia in rainbow trout. A gene encoding an elastolytic activity, ahyB, was cloned from Aeromonas hydrophila AG2 into pUC18 and expressed in Escherichia coli and in the nonproteolytic species Aeromonas salmonicida subsp. masoucida. Nucleotide sequence analysis of the ahyB gene revealed an open reading frame of 1,764 nucleotides with coding capacity for a 588-amino-acid protein with a molecular weight of 62,728. The first 13 N-terminal amino acids of the purified protease completely match those deduced from DNA sequence starting at AAG (Lys-184). This finding indicated that AhyB is synthesized as a preproprotein with a 19-amino-acid signal peptide, a 164-amino-acid N-terminal propeptide, and a 405-amino-acid intermediate which is further processed into a mature protease and a C-terminal propeptide. The protease hydrolyzed casein and elastin and showed a high sequence similarity to other metalloproteases, especially with the mature form of the Pseudomonas aeruginosa elastase (52% identity), Helicobacter pylori zinc metalloprotease (61% identity), or proteases from several species of Vibrio (52 to 53% identity). The gene ahyB was insertionally inactivated, and the construct was used to create an isogenic ahyB mutant of A. hydrophila. These first reports of a defined mutation in an extracellular protease of A. hydrophila demonstrate an important role in pathogenesis.
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PMID:A major secreted elastase is essential for pathogenicity of Aeromonas hydrophila. 1081 68

Reactive oxygen species are strongly implicated in diaphragmatic dysfunction during sepsis. We investigated whether the heme oxygenase (HO) pathway, which is a powerful protective cellular system, protects the diaphragm against oxidative stress and contractile failure during sepsis. A basal expression of both the inducible and constitutive HO protein isoforms (HO-1 and HO-2, respectively) was found in the diaphragm. Enhanced HO-1 expression in diaphragmatic myocytes was observed 24 h after Escherichia coli endotoxin (lipopolysaccharide, LPS) inoculation and remained elevated for at least 96 h. Enhanced HO-1 expression was also observed in the rectus abdominis and soleus muscles and in the left ventricular myocardium of endotoxemic animals. Diaphragmatic HO-2 expression was not modified by endotoxin. Diaphragmatic HO activity exhibited a biphasic time course characterized by a transient decrease during the first 12 h followed by a significant increase at 24 h, corresponding to HO-1 induction. Diaphragmatic force was significantly reduced 24 h after LPS, concomitantly with muscular oxidative stress. Administation of an inhibitor of heme oxygenase activity, zinc protoporphyrin IX (ZnPP-IX), further impaired muscular oxidative stress and contractile failure. By contrast, increased levels of HO-1 expression obtained by pretreatment of rats with hemin, a powerful inducer of HO-1, completely prevented LPS-mediated diaphragmatic oxidative stress and contractile failure. This protective effect was reversed by ZnPP-IX. These results show an important protective role for the HO pathway against sepsis-induced diaphragmatic dysfunction, which could be related to its antioxidant properties.
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PMID:Protective role of heme oxygenases against endotoxin-induced diaphragmatic dysfunction in rats. 1125 35

This is a report of a 54-year-old schizophrenic patient with a 15-year history of ingesting metal objects (pica). He presented with severe anemia (hemoglobin of 3 g/dl and hematocrit of 8.3%) and leukopenia (white blood count of 1,300/mm3). Work-up revealed copper deficiency (copper level of <0.05 microg/ml) and elevated zinc levels (280 microg/ml). The zinc toxicity was produced by the zinc content in the coins ingested by the patient over a period of many years. He was initially treated with -acetylcysteine and sodium bicarbonate followed by intravenous copper sulfate. He was also placed on Adolph's meat tenderizer and pancreatin thrice a day orally to loosen the massive amount of metallic objects including coins in his bowel and allow them to pass out in his feces. He was also continued on oral copper sulfate. His copper levels began to rise and reached a maximum of 0.72 microg/ml, and his zinc level fell to 153 microg/ml. However, as he refused surgery to remove the metal objects from his bowel and continued to ingest more coins, there was continued absorption of zinc, which later overcame the efforts to reduce the zinc level and increase copper levels in his blood. He finally succumbed to sepsis and multiorgan failure. Autopsy revealed a coin mass in the stomach weighing 1,870 grams in addition to a sigmoid volvulus caused by another coin bezoar in the colon.
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PMID:Case report of sideroblastic anemia caused by ingestion of coins. 1142 Dec 92

Electron transfer from iron or copper ions to oxygen is an important example of cellular free radical initiation. Oxygen derived free radicals have been implicated as mediators of cellular injury in several model systems. To evaluate the importance of iron, copper and zinc levels on lipid peroxidation in peritonitis, we measured peritoneum malondialdehyde (MDA) as a marker of lipid peroxidation, zinc, copper, and iron levels during an animal model of intraperitoneal sepsis. Additionally the effects of the free radical scavenger alpha-tocopherol administration was studied. The peritoneum MDA, iron, copper and zinc levels were increased after induction of peritonitis with Escherichia Coli. The treatment with alpha-tocopherol was decreased the peritoneum MDA, iron and copper levels significantly, except the zinc level (p < 0.001, p < 0.001, p < 0.001, respectively). Additionally the alpha-tocopherol treatment for three days prior to injection of E.Coli more decreased MDA, copper and iron levels than that of the treatment with alpha-tocopherol at the time of injection of E. Coli (p < 0.001, p < 0.001, p<0.001, respectively). Our results indicated that copper, iron and zinc had important effects on peroxidation events in E. Coli induced peritonitis, and alpha-tocopherol treatment can improve the oxidant status.
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PMID:Trace element levels in the experimental peritonitis. 1178 75

A sepsis model induced by cecal ligation and puncture was used to study the role of endogenous carbon monoxide in hypotension pathogenesis of rats during septic shock. After administration of zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG),an inhibitor of heme oxygenase (HO),blood pressure (BP),HO activity and carbon monoxide (CO) release from vascular muscle tissue were measured. The results showed that BP of sepsis rats, including systolic and diastolic arterial BP, decreased significantly while HO activity and CO content were significantly increased. In contrast, after administration of ZnDPBG, BP of sepsis rats was significantly increased while the HO activity and CO production were significantly decreased. These findings suggest that HO activity and CO release within vascular musculature are increased during septic shock; inhibition of HO may elevate BP of rats during septic shock through a decrease of endogenous CO production. It is concluded that endogenous CO derived from vascular muscle cells plays an important role in regulating vascular tone, and the up-regulation of HO activity followed by subsequent CO production contributes to hypotension pathogenesis during septic shock.
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PMID:Role of endogenous carbon monoxide in the pathogenesis of hypotension during septic shock. 1197 67

Pentoxifylline, a methylxanthine derivative and nonspecific type 4 phosphodiesterase inhibitor, has been used to improve survival of animals with sepsis and to attenuate lung injury in acute lung inflammation. The purpose of this study was to examine whether pentoxifylline would inhibit the expression of inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), and thereby decrease the pathophysiology of acute porcine pleuropneumonia. E. coli lipopolysaccharide (LPS) and bacterial extracts of A. pleuropneumoniae--induced elevations in TNF mRNA which were fully abrogated by addition of pentoxifylline in both alveolar macrophage and neutrophil cultures. A 30% reduction in the level of LPS-induced interleukin (IL)-1beta mRNA levels also was achieved in macrophages. Pentoxifylline did not affect either IL-1alpha or IL-8 expression in vitro. Pentoxifylline therapy in vivo significantly reduced the number of band neutrophils in swine but did not reduce the pathology associated with pleuropneumonia, including changes in serum zinc, iron, or haptoglobin. Neither did it alter TNF, IL-1, IL-6, or IL-8 expression. Measurement of pentoxifylline and its metabolites in pig sera suggested that efficacious doses of pentoxifylline were probably not achieved in vivo. However, subcutaneous doses of pentoxifylline higher than 25 mg/kg produced transient diarrhea, vomiting, and tremors. These results suggest that pentoxifylline is an effective pharmacological tool for the dissection of cytokine regulation in vitro, but inhibitory concentrations may not be achievable for in vivo pharmacological use in swine.
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PMID:Effects of pentoxifylline on inflammatory cytokine expression and acute pleuropneumonia in swine. 1199 42


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