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

The subcellular mechanisms responsible for myocardial depression during sepsis remain unclear. Recent data suggest a role for impaired energy generation and utilization, resulting in altered contractile function. Here, we studied the energetic and mechanical properties of skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia. Thirty-six hours after lipopolysaccharide (LPS) injection (in the presence of altered myocardial contractility), mitochondrial respiration, coupling between oxidation and phosphorylation, and creatine kinase function were similar in preparations from endotoxemic (LPS) and control animals. The maximal Ca2+-activated force was similar in LPS and control preparations. However, the Ca2+ concentration corresponding to half-maximal force (pCa50, where pCa = -log10[Ca2+]) was 5.55 +/- 0.01 (n = 11) in LPS fibers versus 5.61 +/- 0.01 (n = 10) in control fibers (p < 0.01). Both protein kinase A (PKA) and alkaline phosphatase treatment led to the disappearance in the difference between control and LPS pCa50 values. Incubation of control fibers with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) did not change the Ca2+ sensitivity after subsequent skinning, whereas isoproterenol decreased pCa50 from 5.62 +/- 0.01 to 5.55 +/- 0.01 (p < 0.01). These data suggest that during sepsis, cardiac mitochondrial and creatine kinase systems remain unaltered, whereas protein phosphorylation decreases myofibrillar Ca2+ sensitivity and may contribute to the depression of cardiac contractility.
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PMID:Phosphorylation-dependent alteration in myofilament ca2+ sensitivity but normal mitochondrial function in septic heart. 1117 7

Sepsis-associated cholestasis should always be considered as part of the differential diagnosis of jaundice in the hospitalized or critically ill patient. The development of a disproportionate elevation of serum bilirubin in comparison with serum alkaline phosphatase and serum aminotransferases should be considered an early warning sign of an underlying infection, even in the absence of fever, leukocytosis, or other signs or symptoms. Prompt recognition and appropriate medical and surgical intervention may reduce morbidity and mortality.
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PMID:Sepsis and cholestasis. 1129 Dec 34

A newborn girl with hemorrhagic purpura, suspected neonatal sepsis, and pale and dry skin was lethargic with remarkable hepatosplenomegaly, convergent strabismus, severe anemia, and elevated alkaline phosphatase activity. Radiographs showed a generalized increase in bone density, small medullary cavities, sclerosis of the skull and vertebrae, transverse wavy stripes of sclerotic bone in the metaphyses, and bone-in-bone appearance in phalanges of hands and feet. On this basis, she was diagnosed with malignant infantile osteopetrosis. On the first day of life, the infant was given a blood transfusion and vitamin K (1 mg intravenously [iv]). Corticosteroid therapy was started with prednisone (2 mg/kg per day). She showed marked improvement of symptoms. On the 26th day and 42nd day of life, she received additional blood transfusions. On the 49th day, the patient was discharged and corticosteroid therapy was continued at a regimen of 5 mg/day. Subsequent blood sample analyses revealed normal values for age. At 1 year of life, a bone marrow sample showed normal white and red cell lineages. X-ray confirmed attenuation of the bone sclerosis; therefore, bone marrow transplantation (BMT) was not implemented. At the age of 1.5 years, prednisone therapy was discontinued gradually and withdrawn before the age of 2 years. Subsequent follow-up showed normalization of all radiological and hematologic parameters. At present, the patient is 3 years old and appears healthy with apparently complete regression of the disease.
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PMID:Apparent cure of a newborn with malignant osteopetrosis using prednisone therapy. 1176 Aug 52

Lipopolysaccharide (LPS) may cause sepsis when it enters the blood circulation. The toxic moiety of LPS is the well-preserved lipid A part. Lipid A contains two phosphate groups attached to diglucosamine, which are crucial for the many biological activities of LPS. In previous studies we found that alkaline phosphatase (AP) was able to dephosphorylate LPS. To test whether LPS-dephosphorylation can be used for intervention during sepsis, we investigated the effects of Salmonella minnesota Re 595 LPS and its dephosphorylated counterpart monophosphoryl lipid A (MPLA) on macrophage activation in vivo and in vitro. Exposure of RAW264.7 cells to LPS induced high levels of tumor necrosis factor (TNFalpha) and nitric oxide (NO), whereas MPLA elicited no response. LPS in vivo induced a significant rise in TNFalpha levels in mice and an enhanced inflammatory cell influx in the lung, whereas MPLA did not. Having shown the relevance of this particular phosphate group of LPS, we subsequently explored the LPS-dephosphorylating ability of AP in different tissues, and the effect of AP administration in mice challenged with LPS. Histochemical data show that AP dephosphorylated native LPS in all tissues examined, whereas MPLA was not dephosphorylated. When mice received AP immediately after the LPS challenge, the survival rate was 100%, over 57% in the control group. We conclude that the enzymatic removal of phosphate groups from LPS by AP represents a crucial detoxification reaction, which may provide a new strategy to treat LPS-induced diseases like sepsis.
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PMID:Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. 1246 66

Neonatal sepsis is very common in preterm infants, and severe morbidity during the neonatal period is a major cause of osteopenia of prematurity. We examined the effect of neonatal sepsis on bone turnover markers in premature infants. Twenty-four premature infants participated in the study. Ten of the premature infants developed sepsis during their hospitalization in the neonatal intensive care unit (mean gestational age [GA] 27.3 +/- 0.4 weeks; mean birth weight [BW] 898 +/- 82 g). Fourteen infants who did not develop sepsis served as controls (GA: 26.8 +/- 0.8 weeks, BW: 892 +/- 66 g). Blood samples for bone turnover markers were collected during the initial sepsis workup, and at the end of the first week of treatment, and were compared to the corresponding weekly changes in bone markers in the controls. In addition, samples were collected at the end of the 10th week of life to determine long-term effects of sepsis on bone turnover. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of circulating carboxy terminal cross-links telopeptide of type I collagen (ICTP). There were no significant differences in the weekly changes of all bone turnover markers in premature infants who developed or did not develop sepsis. No significant differences were found in bone turnover markers at the age of 10 weeks between the groups. Neonatal sepsis in premature infants was not associated with biochemical evidence of reduced bone turnover.
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PMID:The effect of neonatal sepsis on bone turnover in very-low birth weight premature infants. 1270 67

In this study the possibility to deliver the acid-sensitive enzyme alkaline phosphatase (AP) from calf intestine (CIAP) to the intestinal system by oral administration was investigated. Tablets were prepared and in vitro evaluated. Final proof of concept studies were performed in rats. This acid labile enzyme is potentially useful in the treatment of sepsis, a serious condition during which endotoxins can migrate into the blood stream. The CIAP was freeze-dried with inulin and subsequently compacted into round biconvex tablets with a diameter of 4mm and a weight of 25-30 mg per tablet. The tablets were coated with an enteric coating in order to ensure their survival in the stomach. In vitro evaluation of tablets containing alkaline phosphatase from bovine intestine (BIAP) was the first step in the development. It was found that tablets without enteric coating dissolved rapidly in 0.10 M HCl with total loss of enzymatic activity of the alkaline phosphatase. Tablets that were coated were stable for at least 2 h in 0.10 M HCl, but dissolved rapidly when the pH was increased to 6.8. Furthermore, it was shown that the enzymatic activity of the released BIAP was fully preserved. The in vivo test clearly showed that the oral administration of enteric coated tablets resulted in the release of enzymatically active CIAP in the intestinal lumen of rats. The location of the enhanced enzymatic activity of AP in the intestines varied with the time that had passed between the administration of the tablets and the sacrificing of the rats. Also, the level of enzymatic activity increased with an increasing number of tablets that were administered.
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PMID:Investigations into the stabilisation of drugs by sugar glasses: II. Delivery of an inulin-stabilised alkaline phosphatase in the intestinal lumen via the oral route. 1271 Nov 82

Acute acalculous cholecystitis (AAC) is marked by a very high mortality rate but its relative rarity makes its features obscure to many physicians. This often contributes to a delayed diagnosis. In this study, we review one center's experience, examine the clinical features of the disorder, and describe the progression of pathological events that culminate in AAC. We performed a 10-year retrospective review of cases of AAC reported at our institution between 1988 and 1998. Fifteen cases of AAC were identified from this period, during which 5804 cardiovascular operations were performed. The mortality rate was 46.6%. Multiple organ failure was present in 12 of the 15 cases, and 9 of the patients were over 60 years of age. Prolonged hypotension occurred in 13 patients, and fever in all 15. Nine cases of gangrenous gallbladder occurred. Gram-negative septicemia was present in 12. Visceral arterial hypoperfusion was frequently evident at operation or necropsy. Thirteen patients showed clinical jaundice, a disproportionate elevation of the alkaline phosphatase, or both. Heart failure was found in 9 patients. Open cholecystectomy was most often the definitive intervention. Arterial hypoperfusion of the gut and or sepsis appear central to the pathogenesis of AAC in our series. Gallbladder inflammation and cholestasis result and bacterial invasion of the organ ensues, culminating in AAC, frequently with gangrene. A model of the pathogenesis of AAC is discussed.
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PMID:Acute acalculous cholecystitis associated with systemic sepsis and visceral arterial hypoperfusion: a case series and review of pathophysiology. 1462 41

Retransplantation for recurrent hepatitis C virus (HCV) has been evaluated in small series. In this study, patients undergoing transplantation for HCV-related cirrhosis with subsequent retransplantation more than 90 days for recurrent HCV (proven by pathologic examination of the explant and exclusion of other factors) were prospectively followed. This group was compared with a simultaneous cohort without HCV infection undergoing retransplantation more than 90 days after primary transplantation. Forty-two patients underwent retransplantation for recurrent HCV with a median survival of 12.9 +/- 6.7 months after retransplantation. Twenty patients (48%) were dead at 6 months, and 13 (65%) of these deaths were due to sepsis. On univariate analysis, creatinine level greater than or equal to 3 mg/dL, platelet count less than 100000/microL, prothrombin time (PT) greater than or equal to 16 seconds, alkaline phosphatase level less than or equal to 240 U/L, gamma-glutamyltransferase level less than or equal to 130 U/L, and donor age of 60 years or greater all correlated significantly with shorter survival after retransplantation. PT and donor age were predictors of survival on multivariate analysis. Patients undergoing retransplantation for recurrent HCV had a significantly shorter median survival than the 55 patients undergoing retransplantation for other chronic reasons of graft loss (75.6 +/- 17.7 months). In conclusion, median survival after liver retransplantation for recurrent HCV is significantly shorter than after retransplantation for other causes of late graft loss. Most deaths occur in the first 6 months and are due to sepsis. Candidates for retransplantation with a preoperative PT less than 16 seconds and those receiving grafts from donors younger than 60 years can expect a significantly longer median survival after retransplantation.
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PMID:Results of retransplantation for recurrent hepatitis C. 1464 54

Sepsis-associated cholestasis should always be considered as part of the differential diagnosis of jaundice in the hospitalized or critically ill patient. The development of a disproportionate elevation of serum bilirubin in comparison with serum alkaline phosphatase and serum aminotransferases should be considered an early warning sign of an underlying infection, even in the absence of fever,leukocytosis, or other signs or symptoms. Prompt recognition and appropriate medical and surgical intervention may reduce morbidity and mortality.
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PMID:Sepsis and cholestasis. 1506 95

In this retrospective study, we describe 14 cats diagnosed with hepatic abscesses. The objective of the study was to report the clinical signs, physical examination findings, clinicopathologic findings, and outcomes in affected cats. These findings were then compared with those previously reported in dogs and humans. Clinical signs were vague and included anorexia, lethargy, and weight loss. Only 23% of cats had fever, whereas 31% were hypothermic. Increases in serum activities of alanine aminotransferase and alkaline phosphatase were found in 45 and 18%, respectively, of the 11 cats that had laboratory work performed. Abdominal ultrasound examinations were performed in 7 cats, and abnormalities were found in 71% of them. Four cats had solitary abscesses, all of which were located in the right liver lobes. The other 10 cats had multifocal small abscesses or microabscesses, and all of these cats had clinical signs suggestive of sepsis. Cytologic evaluation of samples obtained by abdominocentesis indicated septic inflammation in 67% of cats in which peritoneal fluid was analyzed. Hepatic abscess cultures yielded polymicrobial growth in 66% of the cats: Escherichia coli was the most commonly cultured organism. Overall mortality rate was 79%. All survivors underwent exploratory laparotomy for partial hepatectomy to resect the abscess followed by medical management. Hepatic abscesses should be considered in cats with signs consistent with sepsis. More routine use of ultrasonography may aid in earlier diagnosis of hepatic abscesses, potentially improving prognosis and outcome.
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PMID:Hepatic abscesses in cats: 14 cases (1985-2002). 1518 14


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