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)

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve clinical outcome in a number of inflammatory diseases including burns and sepsis. One mechanism contributing to the anti-inflammatory effect is the incorporation of n-3 PUFAs into membrane phospholipids which decreases macrophage eicosanoid production. We hypothesize that an additional mechanism for their effects is an alteration of membrane signal transduction that decreases macrophage responsiveness to inflammatory stimuli. Kupffer cells, the fixed macrophages of the liver, were obtained from rats pair fed diets for 6 weeks with 15% of calories supplied as menhaden (high n-3), corn (control), or safflower (high n-6) oils. The effects of the dietary oils on Kupffer cell membrane signal transduction and eicosanoid production were assessed by measuring inositol phospholipid (PI) metabolism, intracellular calcium responses, and prostaglandin E2 (PGE2) production to the inflammatory signals endotoxin (LPS) and platelet activating factor (PAF). The menhaden oil diet resulted in significant incorporation of n-3 PUFAs into total cellular PUFAs compared to corn and safflower oil. (total n-3 PUFAs, 28.1% menhaden vs 2.1% corn vs 1.2% safflower, P less than 0.03). This incorporation altered signal transduction of PAF as both PI turnover (65% +/- 10% of corn oil) and calcium response (0.6-fold vs 5.0-fold for corn oil) were significantly reduced in the menhaden oil group. (P less than 0.05) The menhaden oil diet also reduced significantly PGE2 production in response to PAF and LPS (corn, 348 +/- 23 pg/ml; menhaden, 48 +/- 6 pg/ml, P less than 0.01). We conclude that, in addition to modulating eicosanoid production, n-3 PUFAs can also alter macrophage membrane signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of Kupffer cell membrane phospholipid function by n-3 polyunsaturated fatty acids. 254 Dec 81

The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis.
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PMID:Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats. 258 48

Hypercalcemic crisis represents a medical emergency. If conservative treatment is ineffective, low calcium bath or zero calcium bath hemodialysis are good alternatives. We report 4 patients treated with calcium free acetate hemodialysis because of hypercalcemic crisis due to breast cancer, hepatocellular carcinoma, cirrhosis of the liver and immobilisation with hydrochlorothiazids' medication. Following 3 h of hemodialysis, serum calcium concentrations fell from a mean value of 3.96 (range 3.53-4.46) mmol/l to 2.71 (2.28-3.12) mmol/l. In 2 patients rapid clinical improvement was achieved and in one oliguric patient diuresis started spontaneously during hemodialysis. One patient died from gram-negative sepsis. In 3 cases the subsequent conservative treatment was sufficient to maintain serum calcium levels within the normal range. Together with the previously reported cases (5 patients treated by hemodialysis with low dialysate calcium and 3 patients by hemodialysis with calcium free dialysate) our experience indicates that hemodialysis is an effective and safe therapy for hypercalcemic crisis.
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PMID:Calcium free hemodialysis: an effective therapy in hypercalcemic crisis--report of 4 cases. 260 Feb 93

It is well known that patients who undergo surgical operations have a high risk of infection and sepsis. One explanation for this high risk may be a depression of neutrophil functions at the postoperative period. In the present study, the effects of surgical stresses on neutrophil functions were studied in ten patients who underwent general anesthesia and major surgery. The neutrophil functions especially focused on were the producing capacities of 5-lipoxygenase metabolites of arachidonic acid such as Leukotriene B4 (LTB4), LTC4, LTD4, 6-trans-LTB4, and w-oxidation products of LTB4. Neutrophils were stimulated with calcium-ionophore A23187 (2x10(-5) M) in the presence of arachidonic acid (5x10(-5) M) for 5 minutes at 37 degrees C. The arachidonic acid metabolites were extracted by methanol. After centrifugation, the supernatant of the mixture was concentrated and applied to a C-18 column on reversed phase high performance liquid chromatography (RP-HPLC) system, monitoring the absorbance at 280 nm. In all cases, the LTB4 production significantly increased postoperatively with an increment of 6-trans-LTB4 and w-oxidation products of LTB4. The LTC4 production, by contrast, significantly decreased postoperatively. LTD4 production was observed at neither pre nor postoperative periods. The total amount of LTA4 metabolites at the postoperative period, including LTB4, LTC4, and 6-trans-LTB4, increased 1.2 times compared with that at preoperative period. This indicates the possibility of the alteration of the neutrophil metabolism in 5-lipoxygenase cascade, the increment of LTA4 generation and the change of LTA4 metabolism from LTC4 synthesis to LTB4 generating pathway.
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PMID:Neutrophil producing capacity of 5-lipoxygenase metabolites of arachidonic acid after major surgery. 260 90

Recently, the association of granulocytic fragments on blood smear with leukoerythroblastosis in sepsis has been identified in nine patients. Granulocytic fragments were identified by both light and electron microscopy as well as cytochemistry. Leukoerythroblastosis is a poorly defined, uncommon syndrome with leukocytosis, left shift, and nucleated red blood cells (nRBCs) disproportionate to the degree of anemia, which may be associated with leukemia or neoplasia in the bone marrow, acute infection, hemolysis, myelofibrosis, or miscellaneous causes. Here a subgroup with high white blood cells (WBC) and acute infection was studied. The corrected WBC for nine patients was 40 x 10(9) per L with 33 nRBC per 100 WBC; serum C3 and C4 levels before and after the development of leukoerythroblastosis were 0.6 +/- 2 g per L; 0.18 +/- 0.04 g per L pre-leukoerythroblastosis and 0.7 +/- 0.46 g per L; 0.30 +/- 0.27 g per L post-leukoerythroblastosis, respectively, in four patients. The platelet count, prothrombin time (PT), and activated partial prothrombin time (aPTT) were 133 x 10(9) per L, 24.4 sec., and 53.5 sec., respectively, for nine patients. Multiphasic chemistries at the time of leukoerythroblastosis were measured in five patients; abnormal values included calcium of 2.0 +/- 0.4 mmol per L, creatinine of 336 +/- 130 mumol per L, total protein of 45 +/- 17 g per L, albumin of 27 +/- 11 g per L, total bilirubin of 421 +/- 362 mumol per L, uric acid of 499 +/- 264 mumol per L, triglycerides of 4.9 +/- 3.7 mmol per L, and alkaline phosphatase of 3.5 +/- 1.0 mu kat per L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical values, complement levels, and hemostatic data in septic leukoerythroblastosis. 260 78

All patients with chronic renal failure have secondary hyperparathyroidism shown by elevated serum parathormone. Medical and surgical treatment is involves the use of phosphate binders, one alpha and increased frequency of dialysis. Surgery is indicated when medical treatment fails to control the Ca2+ PO4(2-) levels that activate renal osteodystrophy. High alkaline phosphatase and Ca2+ above 2.7 mmol/l are indications for surgery. Careful preoperative preparation and postoperative control minimise complications of haemorrhage, sepsis, tetany and cardiac arrhythmias. Long-term complications are hypoparathyroidism and recurrent hyperparathyroidism. Shortened dialysis periods may lead to increased parathyroid complications.
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PMID:Surgical treatment of secondary and tertiary hyperparathyroidism. 267 38

Myocardial function in sepsis and endotoxin shock is reviewed. Clinical, whole animal, and isolated tissue studies are compared to answer the question whether sepsis and/or endotoxin directly damage the myocardium. Myocardial performance is considered relative to control of preload, afterload, and heart rate. Despite the fact that these vary widely in different studies, there is overwhelming evidence that myocardial performance is depressed in both sepsis and endotoxin shock. The depression is dose related, occurs early after large doses of endotoxin but may follow a hyperdynamic phase in sepsis or after low doses of endotoxin. Endotoxin itself does not appear to be the depressant factor; the final depressant substance(s) is unknown. Calcium transport by the sarcoplasmic reticulum is depressed. This defect is more prominent in the endocardium than in the epicardium. Myocardial adenosinetriphosphatase (ATPase) and norepinephrine stores may be depleted. The septic myocardium has an increased dependence on sympathetic nerve stimulation. There is little evidence that the cause of the myocardial depression is an inadequate coronary blood flow.
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PMID:Myocardial function in sepsis and endotoxin shock. 269 Jun 45

Oxidative metabolism of polymorphonuclear leukocytes (PMNs) in uremic patients is enhanced due to unknown serum or plasma factor(s) which are removed during hemodialysis. Respiratory burst activity is diminished in both PMA-stimulated and unstimulated states compared to healthy controls. Hemodialysis treatment normalizes stimulated hydrogen peroxide production and decreases unstimulated hydrogen peroxide production. Several authors found that resting and stimulated chemiluminescence (CL) during hemodialysis correlate with complement activation, whereas other authors describe the development of CL using dialyzer membranes with only mild anaphylatoxin formation. Alterations in PMN carbohydrate metabolism in uremic patients improve during HD. These alterations may be responsible for disturbances in phagocytosis. Degranulation during HD also occurs in the absence of complement activation. Calcium channel blockers decrease activation of PMNs when dialyzers with only little anaphylatoxin formation are used. Acute renal failure and sepsis induce activation of PMNs. Hemodialysis with membranes made of cuprophan leads to further activation of these PMNs and may contribute to granulocyte dysfunction.
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PMID:Metabolic response of neutrophils to uremia and dialysis. 269 99

Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle. The results suggest that calcium uptake and content in skeletal muscle are increased during sepsis and that high calcium concentrations in vitro stimulate nonmyofibrillar protein breakdown. Muscles from septic animals may be more sensitive to the effect of calcium in vitro than muscles from nonseptic rats. Whether increased calcium uptake and content in skeletal muscle is partly responsible for accelerated muscle proteolysis during sepsis remains to be determined.
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PMID:Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: results from a preliminary study. 274 Sep 90

To determine the prevalence and clinical consequences of hypocalcemia in pediatric intensive care unit patients, we prospectively studied calcium homeostasis in 145 of these patients. The total serum calcium concentration was measured in all patients. The serum ionized calcium concentration was measured in blood samples collected from those 71 (49%) patients who had low total serum calcium values (less than 8.5 mg/dl (2.12 mmol/L). Of the 71 patients, 26 (36.6%) had ionized hypocalcemia. Therefore the prevalence of ionized hypocalcemia was at least 17.9% (26/145). Death occurred in 8 (31%) of 26 patients with ionized hypocalcemia versus 3 (2.5%) of 119 patients with normocalcemia (p less than 0.0001). However, the severity of illness score was higher (p less than 0.05) in the children with ionized hypocalcemia than in normocalcemic children (mean Therapeutic Intervention Scoring System score 33 +/- 17 vs 22 +/- 11, respectively). More of the children with ionized hypocalcemia had sepsis (p = 0.0299) and they required the administration of vasopressor agents more often (p = 0.0002) than their normocalcemic counterparts. Of the 26 patients with ionized hypocalcemia, 17 (65.4%) had biochemical evidence of either absolute or relative hypoparathyroidism, determined by means of an immunoradiometric assay that measures only biologically active parathyroid hormone. We conclude the following: (1) ionized hypocalcemia is common in severely ill children. (2) Patients with ionized hypocalcemia have a higher mortality rate than those with normocalcemia; however, because the former are more severely ill, no causality is apparent or suggested. (3) Functional hypoparathyroidism may occur in critically ill children.
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PMID:Hypocalcemia in critically ill children. 278 63


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