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)

Septicemia, a common complication in chronic dialysis patients, may be an important factor in erythropoietin (EPO) hyporesponsiveness, because it is a form of inflammation. The quantitative impact of septicemia on EPO requirements has not been studied. The purpose of this study was to analyze patterns of EPO use and levels of anemia among patients who had ESRD and were hospitalized with septicemia. Using United States Renal Data System data, septicemia admissions were identified in patients with first ESRD service from 1996 to 2001. Mean EPO dosage and hematocrit (Hct) level were analyzed from 2 mo before until 3 mo after admission and compared with patients who were hospitalized with acute myocardial infarction (AMI) and patients with no hospitalizations. A total of 4640 hospitalized patients were included in the analysis: 3975 for septicemia and 665 for AMI. In both groups, mean Hct declined significantly in the month of admission and increased in the second month after admission. At all time points, both groups had significantly lower Hct levels compared with the nonhospitalized group. Mean EPO dosage increased, most rapidly in the month after admission. EPO use was highest in the septicemia group. Hospitalization with septicemia is associated with worsening anemia and increasing EPO use. This also was observed for patients who were hospitalized with AMI, suggesting that acute intercurrent illness plays an important role in EPO hyporesponsiveness. Strategies to prevent septicemia are important not only to decrease clinical morbidity but also to conserve EPO usage and thus contain the costs of care for this complex patient population.
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PMID:Septicemia in patients with ESRD is associated with decreased hematocrit and increased use of erythropoietin. 1769 52

It is well known that iron is pro-oxidant. Chronic kidney disease (CKD) is a pro-oxidant state, and intravenous administration of iron is frequently used to correct anemia. On one hand, there is little doubt that iron causes oxidative stress. On the other, it is far from clear whether oxidative stress, so generated, leads to poor clinical outcomes. Iron has benefits that may be independent of the correction of anemia. Furthermore, concerns surround the use of high doses of erythropoietin in causing excess heart failure and death in patients with CKD. Thus, it would be prudent if iron were to continue to be used judiciously in patients who require erythropoietin. Iron, given orally, would be the preferred first-line agent in patients not on hemodialysis. In patients with sepsis, intravenous treatment with iron should be avoided, because, in animal experiments, intravenous administration of iron can compound the inflammatory response and increase mortality. Clinical trials are needed to ascertain the risk and benefits of the intravenous administration of iron in patients with CKD.
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PMID:Iron, oxidative stress, and clinical outcomes. 1803 Apr 98

Simple, sensitive and specific predictors of mortality in the critically ill remain elusive goals, and brain natriuretic peptide and venous lactate are the subjects of recent studies. The role of vasopressin in sepsis continues to be the focus of much research interest. Dose ranging studies, potential adverse effects, and selective V1 agonists are discussed below in recent trials. Finally the use of erythropoietin in the critically ill continues to be studied but many continue to urge caution for widespread use outside of clinical trials.
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PMID:Recently published papers: predictors, pressors and poietins. 1819 Jul 27

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants, with a mortality rate of 10-50%. It is uncommon in term infants and in premature infants who have not yet been fed. Most commonly NEC develops suddenly in a preterm infant who was otherwise well, with initial symptoms of abdominal distention, bilious or bloody emesis or gastric aspirates, hematochezia, and pneumatosis intestinalis, and sometimes progresses quickly to include bowel perforation, acidosis, shock, and death. Trigger factors (i.e. perinatal hypoxia, mild infection or formula feeding) cause focal mild intestinal mucosal injury. In the presence of proliferation of commensal bacteria, local breakdown of mucosal barrier may cause entry of bacterial products (e.g. lipopolysaccharides, platelet-activating factor). Endothelial platelet-activating factor and/or tumor necrotizing factor and/or direct stimulating effects of polymorphonuclear leukocytes cause proinflammatory cascade and focal necrosis, which increase the entry of large amounts of bacterial toxins, and then severe NEC, sepsis, and shock develop. Therapies for the prevention of NEC that appear to have some benefit are breastfeeding and antenatal steroids, and probably probiotics. Enteral immunoglobulin, polyunsaturated fatty acids, and arginine or glutamine supplementation are therapies for the prevention of NEC that do not appear to be of benefit. Enteral erythropoietin and enteral granulocyte colony-stimulating factor are promising novel therapies. Treatment options are limited to gut rest, parenteral nutrition, broad-spectrum antibiotics, and surgical interventions for enteral perforation. Two commonly used methods for NEC with intestinal perforation are laparotomy or primary peritoneal drainage ("patch, drain and wait"); however, the preferred method is controversial.
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PMID:What next in necrotizing enterocolitis? 1836 84

The management of severe anemia in patients who do not accept heterologous blood transfusion for religious reasons presents many different challenges both at the level of treatment strategy and ethics. Recently, new interventional treatment strategies have become available, including human and bovine hemoglobin substitutes and high-dose recombinant human erythropoietin. We present the successful management of two Jehovah's Witnesses patients with severe, life-threatening anemia caused by chronic renal failure and exacerbated by sepsis.
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PMID:[Severe, life-threatening renal anemia treatment in patients who do not accept heterologous blood transfusion for religious reasons--case report]. 1840 59

Hepcidin is a small protein comprised of 25 amino acids, synthesized in the liver. It was first described in 2001 as a component of the innate immunity due to its antimicrobial activity. Soon after, hepcidin was recognized as a key component in iron homeostasis, involved in maladies of iron overload or iron deficiency. Hepcidin acts by binding to the transmembrane protein ferroportin, in charge of exporting iron from cells. Upon binding to ferroportin, the latter is internalized into cytoplasmic lysosomes and is hydrolyzed, thus iron is accumulating in cells, and hypoferremia ensues. In hereditary and juvenile types of hemochromatosis, iron overload could be partially due to the down-regulation of hepcidin by the mutated genes HFE and HJV. In ferroportin disease, hepcidin synthesis is not inhibited, yet cells are still overloaded with iron due to mutations in ferroportin, preventing the binding of hepcidin and iron export from cell to the blood. Hepcidin has also been implicated in the scenario related to as "anemia of inflammation". In this condition significant hypoferremia develops as a result of acute sepsis, but also in wake of infections, chronic inflammation, rheumatic diseases and in certain malignancies. Such scarcity of iron leads to anemia that may not be corrected by erythropoietin treatment, and hepcidin synthesis in such anemic state is dramatically elevated. Future therapeutic approach may attempt administering synthetic hepcidin, or its antagonists, to correct states of iron overload or scarcity.
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PMID:[Hepcidin--the discovery of a small protein with a pivotal role in iron homeostasis]. 1848 71

Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P < 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.
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PMID:Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha. 1849 5

The mortality rate for end-stage renal disease patients is six times higher than in the general population. Hemodialysis central venous catheter (CVC) utilization has increased by 50% between 1998 and 2004 and data from the United States Renal Data System suggest that 81% of the patients initiate hemodialysis through a CVC. There is evidence that the two observations are linked in both an obvious way (catheter-related sepsis) as well as in a less obvious manner-chronic inflammation. Inflammation is highly prevalent in chronic hemodialysis (CHD) patients and is consistently associated with poor outcomes. Some of the most important consequences of inflammation in CHD include, but are not limited to, cardiovascular disease, uremic protein-energy wasting, erythropoietin hyporesponsiveness, and increased hospitalization and death rates. Use of CVC has been long suspected to play a role in the inflammatory response in CHD patients. Recent studies have shown that the presence of CVCs is associated with higher levels of C-reactive protein (CRP), lower serum albumin values, and lower hemoglobin values. Furthermore, there are data showing that CRP levels decrease following CVC removal. Accordingly, avoidance of CVC represents an effective strategy to limit the inflammatory response in CHD patients and potentially prevent its devastating consequences.
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PMID:Hemodialysis central venous catheters as a source of inflammation and its implications. 1857 35

Anemia is a well recognized complication of chronic renal failure (CRF). Although the use of erythropoietin (EPO) in the treatment of anemia in patients on dialysis is well established, its use in pre-dialysis patients is less well recognized. The preferred route of administration of EPO in pre-dialysis patients is subcutaneous and it is indicated in any patient with CRF who is symptomatic of anemia. Studies have shown that EPO is effective in correcting anemia in these patients with a considerable improvement in quality-of-life scores. There have been no deleterious effects on blood pressure or rate of decline of renal function. However, these two indices should be monitored closely. Common causes of treatment failure include iron deficiency, blood loss and occult sepsis. The available evidence indicates that EPO therapy is safe and effective in the treatment of anemia in pre-dialysis patients.
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PMID:Use of Erythropoietin in the Correction of Anemia in Pre-dialysis Patients. 1858 39

Eryptosis, the suicidal death of erythrocytes, is characterised by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognised by macrophages, which engulf and degrade the affected cells. Reported triggers of eryptosis include osmotic shock, oxidative stress, energy depletion, ceramide, prostaglandin E(2), platelet activating factor, hemolysin, listeriolysin, paclitaxel, chlorpromazine, cyclosporine, methylglyoxal, amyloid peptides, anandamide, Bay-5884, curcumin, valinomycin, aluminium, mercury, lead and copper. Diseases associated with accelerated eryptosis include sepsis, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency, hemolytic uremic syndrome and Wilsons disease. Eryptosis may be inhibited by erythropoietin, adenosine, catecholamines, nitric oxide (NO) and activation of G-kinase. Most triggers of eryptosis except oxidative stress are effective without activation of caspases. Their signalling involves formation of prostaglandin E(2) with subsequent activation of cation channels and Ca2+ entry and/or release of platelet activating factor (PAF) with subsequent activation of sphingomyelinase and formation of ceramide. Ca2+ and ceramide stimulate scrambling of the cell membrane. Ca2+ further activates Ca2+-sensitive K+ channels leading to cellular KCl loss and cell shrinkage and stimulates the protease calpain resulting in degradation of the cytoskeleton. Eryptosis allows defective erythrocytes to escape hemolysis. On the other hand, excessive eryptosis favours the development of anemia. Thus, a delicate balance between proeryptotic and antieryptotic mechanisms is required to maintain an adequate number of circulating erythrocytes and yet avoid noneryptotic death of injured erythrocytes.
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PMID:Erythrocyte programmed cell death. 1872 Apr 18


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