Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immobilization-related hypercalcaemia is an uncommon but important condition being associated not infrequently with both urolithiasis and osteoporosis. In this study 5 patients who had been immobilized for a mean of 3 months and had a mean adjusted serum calcium of 3.15 mmol/l were treated with doses of intravenous pamidronate ranging between 10 mg and 45 mg. All patients became normocalcaemic by day 3. Patients 1-3 mobilized shortly after treatment and remained normocalcaemic. In those patients who continued to be immobile hypercalcaemia recurred after an interval of several weeks. Retreatment with pamidronate again resulted in normocalcaemia. No side effects were noted with treatment. All of the patients studied had increased rates of bone resorption as shown by elevated urinary hydroxyproline/creatinine ratios (median:range) of 0.101:0.045-0.180 (normal less than 0.033) and elevated calcium/creatinine ratios of 2.50:0.69-3.63 (normal less than 0.50). None of the patients in this study had any of the usual risk factors for developing immobilization-related hypercalcaemia though all 5 patients had problems with significant sepsis which we postulate may have lead to cytokine release which in turn contributed to the development of hypercalcaemia. We conclude that pamidronate (at doses as low as 10 mg) is safe and effective in immobilization-related hypercalcaemia and suggest that sepsis should be added to the list of risk factors for development of this syndrome.
 ...
PMID:Immobilization-related hypercalcaemia--a possible novel mechanism and response to pamidronate. 226 2

From January 1976 through December 1988 we encountered ninety nine cases of intrahepatic stones. Eight of them were complicated with postoperative bile duct strictures which were formed on cholangiojejunostomy in 5 cases, cholangioduodenostomy, hepatic hilum and common hepatic duct in 1 case, respectively. Six cases of them are anastomotic strictures. The stones were mainly composed of bilirubin calcium. We guessed that the bile duct stricture resulted from cholangiojejunostomy without Roux-en-Y in 1 case and anastomotic insufficiency in 5 cases. Intrahepatic stones were removed by percutaneous transhepatic cholangioscopy (PTCS), and the treatment for the stricture was cholangiojejunostomy in 1 case and the dilatation by PTCS in 5 cases, including 3 endoprostheses by pig-tail silicone catheter and 2 internal-external biliary drainage. Two patients who did not undergo cholangioscopic dilatation died of sepsis due to cholangitis. Three of 5 patients who underwent endoscopic dilatation by PTCS could return to social life without recurrence of gallstones. In other two cases an endoprosthetic catheter was removed by PTCS because of dislodgement or obstruction of the catheter after confirming anastomotic strictures had improved. Authors recommended that PTCS should be applied for postoperative bile duct stricture complicated with intrahepatic stone.
 ...
PMID:[A study on postoperative bile duct stricture with intrahepatic stones]. 227 19

Ionized Ca (Ca2+) is essential for maintaining physiologic functioning in the cardiovascular system (CVS). Sepsis affects the CVS by several mechanisms and is associated with decreased serum Ca2+. The pharmacodynamic response of the CVS to serum Ca2+ alteration was compared in acutely septic and nonseptic dogs at serum Ca2+ levels of 50%, 100%, 150% and 200% of normal baseline values. Serum Ca2+ alterations caused similar changes in both groups, although finite differences existed between septic and nonseptic subjects. Ca manipulation produced limited differences in the response of mean arterial pressure, cardiac output, left ventricular dP/dtmax, systemic (SVR) and pulmonary (PVR) vascular resistance between septic and nonseptic subjects. PVR and SVR demonstrated opposite responses during hypocalcemia; PVR was lower than baseline in both groups, whereas SVR was higher at the 50% level. No difference was evident for total oxygen consumption (VO2) or heart rate. In view of the limited differences in response and the failure to improve systemic VO2, serum Ca2+ supplementation does not afford any additional benefit in this experimental model of acute sepsis.
 ...
PMID:Pharmacodynamic response to ionized calcium during acute sepsis. 237 5

Kupffer cell control of hepatocyte protein synthesis may be an important mechanism involved in the regulation of normal liver function and may be one mechanism responsible for the alterations in liver function seen during sepsis. The present series of in vitro experiments compare the response to various inflammatory stimuli of hepatocytes cocultured with Kupffer cells with that of hepatocytes cultured alone. In the absence of inflammatory stimuli, Kupffer cells stimulated hepatocyte protein synthesis. Lipopolysaccharide or gentamicin-killed Escherichia coli triggered Kupffer cell-mediated inhibition of cocultured hepatocyte protein synthesis but had no effect on protein synthesis of hepatocytes cultured alone. Phorbol myristate acetate, muramyl dipeptide, and calcium ionophore had no effect on hepatocytes cultured alone but resulted in a loss of Kupffer cell-mediated stimulation of cocultured hepatocyte protein synthesis without inhibition. Addition of dexamethasone to cocultures prevented the Kupffer cell-mediated inhibition of hepatocyte protein synthesis triggered by lipopolysaccharide, but did not block Kupffer cell-mediated stimulation in the absence of lipopolysaccharide. The data suggest that Kupffer cells can stimulate and inhibit hepatocyte protein synthesis by independent mechanisms. Kupffer cells may be important regulators of hepatocellular function in health and disease.
 ...
PMID:Evidence that rat Kupffer cells stimulate and inhibit hepatocyte protein synthesis in vitro by different mechanisms. 249 43

Neutrophils can be "primed" for an enhanced respiratory burst by lipopolysaccharide (LPS) in concentrations measurable in patients with septic shock. Leukotriene B4 (LTB4) is the primary eicosanoid product of neutrophils and is felt to be a mediator of host defense and inflammation. We investigated the in vitro effects of LPS on neutrophil production of LTB4 and the omega-oxidation metabolites of LTB4. Incubation of neutrophils with LPS in concentrations ranging from 0.01 to 100 ng/ml did not result in production of LTB4 or metabolites in the absence of a second stimulus. Priming neutrophils with LPS and then stimulating with opsonized zymosan, phorbol-myristate-acetate or a low concentration of the calcium ionophore A23187 resulted in enhanced production of LTB4. LPS priming of neutrophils occurred in a concentration dependent manner. LPS did not result in LTB4 production in response to the chemoattractant peptide FMLP. LPS priming of neutrophils had no effect on cytosolic calcium concentrations of resting or zymosan-stimulated cells. These results suggest that LPS might effect host defense and tissue injury by potentiating the effect of other stimulants on neutrophil production of LTB4. This LPS induced enhancement may represent an important pathogenetic pathway in patients with gram negative sepsis.
 ...
PMID:Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4. 253 52

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)
 ...
PMID:Modulation of Kupffer cell membrane phospholipid function by n-3 polyunsaturated fatty acids. 254 Dec 81

Because of the improvement resuscitation techniques have shown since the 1960s and because of the development of the out-of-hospital medical care, a cardiac arrest is no longer synonymous with death in every case. However the cardiac arrest resuscitation is only relevant if its adverse consequences can be limited. That is mainly the neurological after-effects and the cellular anoxia. Therefore, the "Service d'Aide Medicale Urgente" (SAMU) of Lyon has been concentrating its research aiming at: (a) Shortening the duration of cardiopulmonary resuscitation to limit the cerebral anoxia. (b) Analysing and treating some of the causes responsible for the aggravation of anoxia. On the basis of several studies in Lyon, here are some suggestions: (1) The use of high doses of epinephrine that unables a better percentage of primary recoveries (47.5% vs. 39%) (P less than 0.05) and secondary recoveries (21.3% vs. 14.8%) (P less than 0.01) without modifying the qualitative survival at long term. (On the basis of: 5 mg intravenous bolus repeated every 3 min in case of asystole instead of 1 mg every 5 min as it is usually recommended). (2) The choice of a peripheral intravenous line instead of a central intravenous line each time it is possible for the administration of drugs since it is as efficient as the second one. (40.7% vs. 33.4%) (P:NS). (3) The alkalinisation of the prolonged cardiac arrest in order to keep the acid-base balance. Most of the survivors show a pH equal or superior to the normal standard. (On the basis of 1 mmol/kg of sodium bicarbonate if the cardiac arrest lasts for more than 10 min). (4) The abolition of the dextrose solution as maintaining infusion the patients who are in a "coma depasse" (brain death) after the resuscitation have an average glycemia superior to the survivors without after-effects. (19.7 vs. 14.8 mmol/l) (P less than 0.05). (5) The monitoring at once at the hospital of the intra-cranial pressure. It reveals the frequency of high pression at an early stage (superior to 15 mmHg in 51.1% of the cases) and the absence of favourable evolution in case of high intracranial pressure. At the moment the absence of consequences on the ICR of a calcium entry blocker (Nimodipine) is being studied. The first results do not seem to show any improvement of the cerebral survival. (6) The prophylactic treatment of septicemia with intestinal origin since they occur frequently and prove to be fatal.
 ...
PMID:Out-of-hospital cardiac arrest: the teaching of experience at the SAMU of Lyon. 255 Oct 23

Coculture of endothelial and smooth muscle cells was used to study effects of endotoxin on depolarization-induced Ca2+ transients in fura-2-loaded individual smooth muscle cells. Although endotoxin did not modify the response of cultured smooth muscle cells to depolarization, endotoxin resulted in an attenuation of cytosolic Ca2+ (Cai2+) transients in response to K+ depolarization and failure of KCl-induced contractions in smooth muscle cells when they were cocultured with endothelial cells. The observed endothelial modulation of smooth muscle responses was not accomplished via gap junctions. The possible role of free radical species secreted by endothelial cells in conditioning of smooth muscle responses to depolarization was supported by the results of three sets of experiments: 1) endothelial cells did respond to endotoxin with oxidative burst, 2) pretreatment of cocultured cells with catalase prevented endotoxin-induced downregulation of Ca2+ transients, and 3) in isolated smooth muscle cells, the addition of hydrogen peroxide virtually abolished depolarization-induced Ca2+ transients. Hence vascular endothelium stimulated by endotoxin generates reduced oxygen intermediates, which in turn downregulate depolarization-induced Cai2+ transients in smooth muscle cells. This phenomenon may contribute to the development of hypotension in septicemia.
 ...
PMID:Role of endothelium in endotoxin blockade of voltage-sensitive Ca2+ channels in smooth muscle cells. 255 35

In patients with septicemia and septic shock the contact phase of blood coagulation is activated. It has been suggested that polymorphonuclear leukocytes (PMN) are directly activated by purified plasma kallikrein. This has been recently questioned because granulocytic elastase release induced by recalcification of normal and prekallikrein-deficient plasma was similar. We studied the interaction of different preparations of purified human plasma kallikrein with PMN. Cytosolic calcium shifts were measured with the quin2 method, PMN aggregation was assayed in an aggregometer, and superoxide production was quantitated as superoxide dismutase inhibitable cytochrome c reduction in a continuous assay. No increase of cytosolic free calcium was found during at least 5 min after adding 10 micrograms/ml plasma kallikrein to PMN. Similarly, highly purified plasma kallikrein from two different sources did not induce PMN aggregation at all, nor did it stimulate superoxide production. However, sequential exposure of PMN to plasma kallikrein and formylpeptide increased the superoxide production compared to stimulation with formylpeptide alone. This phenomenon which is called priming was observed at plasma kallikrein concentrations greater than or equal to 7 micrograms/ml. The active site of the molecule was required for the priming, because plasma prekallikrein, active site-inactivated plasma kallikrein, and soybean trypsin inhibitor treated kallikrein did not prime PMN. This indicates that the contact activation system may play a role in host defence against bacterial infection.
 ...
PMID:Purified human plasma kallikrein does not stimulate but primes neutrophils for superoxide production. 255 88

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.
 ...
PMID:Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats. 258 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>