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

Single daily injections of recombinant human interleukin-1 alpha (IL-1 alpha) or interleukin-1 beta (IL-1 beta) were given for 1-3 days to normal mice, and blood ionized calcium concentrations were measured before and at various times after each injection. Mean blood calcium levels fell significantly in both groups of animals 3 h after the first IL-1 injections and returned to pretreatment values at 5 h. However, at 24 and 48 h mean values were significantly higher than those in saline-heated controls. Despite this progressive underlying increase in mean blood ionized calcium concentrations, blood calcium concentrations also fell significantly 3 h after the second and third IL-1 injections. The transient decrease in blood calcium was prevented by treatment with indomethacin and, thus, appears to be prostaglandin mediated. Hypocalcemia was not observed after single bolus injections of tumor necrosis factor-alpha or -beta (lymphotoxin). These findings suggest that IL-1 is a potential mediator of the hypocalcemia that occurs in up to 40% of patients with bacteremic sepsis and severe tissue injury and is associated with an increased mortality rate.
 ...
PMID:Bolus injections of recombinant human interleukin-1 cause transient hypocalcemia in normal mice. 279 8

A depression in aortic contractility has been previously demonstrated in rat intraperitoneal sepsis and during endotoxemia. In this study, we determined whether the mobilization of extracellular calcium (using 45Ca) and the release of intracellular calcium are altered in septic rat aorta when compared to sham-operated controls. The concentration of protein kinase C was also determined by using [3H] phorbol-12,13-dibutyrate (PDBu). We found that calcium influx was unaltered under basal conditions but that the ability of norepinephrine (NE) to augment influx was significantly depressed (P less than .05; [control vs. septic, 572 +/- 54 [SE] vs. 428 +/- 30 mumol Ca2+/kg dry wt. aorta]). Calcium influx stimulated by high K+ was unchanged in aortae between control and septic animals. In the presence of NE, calcium efflux (an indirect measurement of intracellular calcium release) was significantly diminished (P less than .001) in aortae from septic rats. The concentration of aortic protein kinase C as assessed by PDBu binding sites was unaltered in septic rats when compared with controls. In conclusion, we found that during sepsis alpha 1-adrenergic receptor activation of both calcium influx and efflux by NE is decreased; these alterations could be related to the depressed aortic contractility observed in sepsis.
 ...
PMID:Alterations in bidirectional transmembrane calcium flux occur without changes in protein kinase C levels in rat aorta during sepsis. 283 8

Myocardial sarcoplasmic reticulum (SR) plays a critical role in the regulation of the cytosolic calcium fluctuations that occur during the cardiac cycle. One function of the SR is to lower the calcium concentration so that myocardial relaxation and thus ventricular filling can occur. The aim of the present study was to determine if hyperdynamic sepsis induced a decrease in the capacity of SR to take up calcium. This defect would result in decreased ventricular filling and thus decreased cardiac output, as has previously been shown in isolated perfused working hearts removed from septic rats. Therefore, rats were anesthetized with ether, and sepsis was induced by the injection of an aliquot of a fecal homogenate into the peritoneal cavity. Control animals either underwent surgery and received an aliquot of sterilized fecal inoculum (sham) or were untreated (no surgery). On day 2 after surgery, animals were anesthetized with pentobarbital, and hearts were removed, weighted, and SR isolated. The rate of uptake of 45Ca2+ by SR from septic rats was not depressed compared to controls but in fact was elevated. Maximum 45Ca2+ accumulated by the SR and Ca2+-stimulated ATPase activity were similar in SR from control and septic hearts. These results suggest that the contractile dysfunction noted in the myocardium in early sepsis is probably not due to inadequate SR removal of Ca2+ during diastole.
 ...
PMID:Calcium uptake by sarcoplasmic reticulum isolated from hearts of septic rats. 297 70

Our results reviewed here may be summarized as follows: 1. Continuous endotoxemia significantly interferes with Ca2+-dependent information flow in the liver. 2. The subcellular sites where these molecular lesions can be localized include: a.) the plasma membrane-there are effects at the level of alpha 1-adrenergic and vasopressin binding, and also in the coupling of receptor activation to inositol lipid metabolism in terms of PIP2 degradation and resynthesis b.) the endoplasmic reticulum in terms of Ca2+ release and PI synthesis. Another one of the sequelae of Ca2+-associated receptor activation, namely, cytosolic ionized Ca2+ concentration is also affected. 3. Finally, in addition to seeing the impact of acute or continuous endotoxemia at the level of receptor activation and signal generation, we can also document alterations in the expression of physiologic function subserved by these Ca2+- and inositol lipid-associated signaling processes--i.e. in glycogen phosphorylase activity-being consistent with the above described changes. In conclusion, we state that a causal link is shown between receptor binding, agonist-induced phosphoinositide hydrolysis, intracellular Ca2+ mobilization and activation of phosphorylase a in the liver, suggesting that these alterations may underlie some of the metabolic consequences of chronic sepsis.
 ...
PMID:Perturbation of transmembrane signaling mechanisms in acute and chronic endotoxemia. 303 27

Hypocalcemia is common in critically ill patients with sepsis; however, its etiology remains unclear. We have previously reported that hypocalcemia occurs in approximately 20% of patients with gram-negative septicemia. Based upon this finding, we evaluated the effect of endotoxin on calcium homeostasis in laboratory animals. We report here that endotoxin produces a dose-related decrease in circulating ionized calcium levels and impairs calcium mobilization during ethylenebis (oxyethylenenitrilo)-tetraacetic acid infusion. We conclude that endotoxin or its products can cause ionized hypocalcemia during sepsis by impairing calcium mobilization.
 ...
PMID:Endotoxin-induced hypocalcemia results in defective calcium mobilization in rats. 313 Oct 36

As many UK renal units commence more patients on CAPD than hemodialysis (HD) as the first mode of therapy a retrospective study of long-term CAPD (greater than 4 years continuous CAPD) was performed in 4 centers with substantial CAPD programs. One hundred and seventy-seven patients (103M, 74F) started CAPD before December, 1981. There was no difference in primary renal disease. Age was significantly greater in 2 units (51.9 +/- 11.7 and 53.2 +/- 12.1 vs 40.6 +/- 16.2 and 42.5 +/- 14.6 years, p less than 0.05) and correlates with pre-CAPD activity scores (Scale 3-0). After 4 years: 34 patients (19.2%) remained on CAPD: the proportion was similar in all centers. Sixty-five percent of patients were alive but 54% transferred to HD mainly due to peritonitis (overall 2.0 episodes/intercenter variation p less than 0.001). Fourty-four patients were transplanted. Significant increases occurred in hemoglobin, albumin, calcium and creatinine; a decrease in activity score (2.4 +/- 0.7 to 1.5 +/- 0.9, p less than 0.005); no change in weight, BP, urea or bone disease. Thirty-eight patients died, mainly cardiac (14) or sepsis (11). Using Cox's method of analysis significant risk multipliers were age (2.07 per decade), male sex (2.18), frequency of peritonitis (1.36), activity score less than 2 (4.45) and amyloidosis (12.45). Despite differing techniques in different centers CAPD offered a satisfactory mode of therapy for many patients; peritonitis was the main reason for transfer to HD and several significant factors were identified.
 ...
PMID:Long-term CAPD--some U.K. experience. 318 May 35

Inositol trisphosphate-dependent Ca2+ release was measured in saponin-permeabilized hepatocytes isolated from acutely (2 mg/100 g body wt iv) or chronically (0.1 mg X 100 g body wt-1 X 24 h-1 for 30 h) endotoxin-treated (ET, Escherichia coli) rats or from animals rendered septic by cecal ligation and puncture. A decrease of this parameter was observed in acutely ET-treated rats (52%, P less than 0.01) and after 30 h of continuous ET infusion (33%, P less than 0.01). Sepsis was associated with an elevated Ca2+ release (34%, P less than 0.01) as compared with the sham-operated animals. We conclude that during endotoxicosis and sepsis alterations of intracellular Ca homeostasis take place, reaching sites beyond the level of the plasma membrane. Such alterations could account in part for metabolic and functional changes associated with these pathologic states. In addition, ET treatment provides the first known intervention resulting in the modulation of inositol trisphosphate-dependent Ca2+ release.
 ...
PMID:IP3-dependent Ca2+ release in permeabilized hepatocytes of endotoxemic and septic rats. 330 64

The hypothesis was tested that several metabolic and functional alterations associated with endotoxicosis and sepsis could be due to a Ca overload of liver and heart in rats. Male rats were given intravenously E. coli endotoxin (ET) or rendered septic by cecal ligation and puncture. At various intervals after ET injection and 16-18 h after the onset of peritonitis the animals were sacrificed and the liver and heart sampled for assay of the total Ca content. Also, livers of saline- or ET-treated rats were perfused in vitro to study several aspects of Ca movements as affected by phenylephrine infusion. Livers, were also fractionated to study the subcellular distribution of Ca. ET treatment produced a slight, but significant increase in total hepatic Ca content (12.6% at 4 h and 7.7% at 24 h after ET injection). Sepsis did not affect this parameter in either liver or heart. ET also produced a decrease of Ca content in the microsomal fraction of liver, while sepsis was associated with an elevated Ca content of liver mitochondria. Perfused livers of saline-treated rats responded to phenylephrine by accumulating Ca, while the perfused organs of ET-treated rats did not display such a response to agonist infusion. We conclude that impairment of intracellular Ca homeostasis--under the conditions studied--consists of a slight Ca overload in endotoxicosis, associated with discrete alterations of Ca fluxes and compartmentalization within the cell both in endotoxicosis and sepsis.
Cell Calcium 1987 Oct
PMID:Calcium content in liver and heart and its intracellular distribution in liver during endotoxicosis and sepsis in rats. 332 66

Systemic acidosis has a negative inotropic effect on myocardial function, which in the intact animal, is counteracted by the activation of the sympathoadrenal system. Although there are extensive animal data in this field, human studies quantifying the influence of systemic acidosis on myocardial function in various disease states is lacking. In patients with hypocalcemia, a single infusion of calcium does not sustain increased calcium levels, and the hemodynamic improvement is only transient. Hemodynamic changes in septic shock are complex, and there are convincing data documenting myocardial dysfunction in sepsis. There is a need for elucidating the biochemical characteristics of the myocardial depressant factor (or factors).
 ...
PMID:Effects of acid base disturbance, septic shock, and calcium and phosphorous abnormalities on cardiovascular function. 333 22

The incidence and the clinical implications of hypocalcemia were evaluated in acutely ill patients admitted to the Medical Intensive Care Unit of the Detroit Receiving Hospital. Total and ionized calcium levels were prospectively evaluated upon admission for all patients over a three-month interval. A high proportion of patients (62 of 88, 70 percent) were found to have decreased levels of both total and ionized calcium. Known causes of hypocalcemia could be identified in only 28 patients (45 percent). These included hypomagnesemia (17, 28 percent), renal insufficiency (five, 8 percent), alkalosis (four, 6 percent), and acute pancreatitis (two, 3 percent). In the remaining 34 patients (55 percent), no readily identifiable cause could be found. These 34 patients had a lower mean albumin level than did the 23 normocalcemic patients (p less than 0.01), but there were no differences in age, pH, serum creatinine, magnesium, or phosphate between the two groups. Serum albumin correlated directly with ionized calcium levels (n = 82, r = 0.33, p less than 0.01), as well as with total calcium levels (n = 76, r = 0.70, p less than 0.01). There was a strong association between sepsis and hypocalcemia. Patients who survived the hospitalization had higher mean ionized calcium, total calcium, and albumin values than did nonsurvivors, but there were no differences in age, serum creatinine, magnesium, and phosphate between the two groups. The mortality of the hypocalcemic patients (44 percent) was significantly greater (p less than 0.05) than the mortality of the normocalcemic patients (17 percent). These findings suggest that hypocalcemia is a very common abnormality in acutely ill patients and is associated with a poor prognosis.
 ...
PMID:Prevalence and clinical implications of hypocalcemia in acutely ill patients in a medical intensive care setting. 340 50


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