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)

Diastolic heart failure is an underestimated pathology with a high risk of acute decompensation during the perioperative period. This article reviews the epidemiology, risk factors, pathophysiology, and treatment of diastolic heart failure. Although frequently underestimated, diastolic heart failure is a common pathology. Diastolic heart failure involves heart failure with preserved left ventricular (LV) function, and LV diastolic dysfunction may account for acute heart failure occurring in critical care situations. Hypertensive crisis, sepsis, and myocardial ischaemia are frequently associated with acute diastolic heart failure. Symptomatic treatment focuses on the reduction in pulmonary congestion and the improvement in LV filling. Specific treatment is actually lacking, but encouraging data are emerging concerning the use of renin-angiotensin-aldosterone axis blockers, nitric oxide donors, or, very recently, new agents specifically targeting actin-myosin cross-bridges.
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PMID:Diastolic heart failure in anaesthesia and critical care. 1746 92

Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for the formation of inflammatory prostanoids such as prostaglandins and thromboxane. Its role in the pathophysiology of inflammatory states like sepsis is increasingly recognized. Recently, we demonstrated that sepsis upregulates the endotoxin receptor Toll-like receptor 4 (TLR4) in rat kidney. Because Cox-2 is one of the downstream products of TLR4 activation, we hypothesized that sepsis-induced changes in renal Cox-2 expression are TLR4 dependent. Indeed, we show that in Sprague-Dawley rats, cecal ligation and puncture (a sepsis model) increases Cox-2 expression in cortical and medullary thick ascending loops (cTAL and mTAL, respectively) as well as inner medullary collecting ducts. These are all sites of increased TLR4 expression during sepsis. To determine the actual dependence on TLR4, we measured Cox-2 expression in wild-type and mutant mice which harbor a TLR4 gene deletion (TLR4-/-). In wild-type mice, sepsis increased Cox-2 expression in proximal tubules, cTAL, and mTAL. In contrast, septic TLR4-/- mice showed no significant increase in cTAL or mTAL Cox-2 expression. Furthermore, renin was absent from juxtaglomerular cells of TLR4-/- mice. We conclude that the dependence of sepsis-induced renal Cox-2 expression on TLR4 is tubule specific. The TLR4-dependent Cox-2 expression is mostly restricted to cortical and medullary thick ascending loops of Henle that characteristically express and secrete Tamm-Horsfall protein.
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PMID:Sepsis induces an increase in thick ascending limb Cox-2 that is TLR4 dependent. 1763 95

Sepsis-related acute kidney injury (AKI) is the leading cause of AKI in intensive care units. Endotoxin is a primary initiator of inflammatory and hemodynamic consequences of sepsis and is associated with experimental AKI. The present study was undertaken to further examine the role of the endothelium, specifically prostacyclin (PGI(2)), in the pathogenesis of endotoxemia-related AKI. A low dose of endotoxin (LPS, 1 mg/kg) in wild-type (WT) mice was associated with stable glomerular filtration rate (GFR) (164.0 +/- 16.7 vs. 173.3 +/- 6.7 microl/min, P = not significant) as urinary excretion of 6-keto-PGF(1alpha), the major metabolite of PGI(2), increased. When cyclooxygenase inhibition with indomethacin abolished this rise in 6-keto-PGF(1alpha), the same low dose of LPS significantly decreased GFR (110.7 +/- 12.1 vs. 173.3 +/- 6.7 microl/min, P < 0.05). The same dose of indomethacin did not alter GFR in WT mice. To further study the role of PGI(2) in endotoxemia, renal-specific PGI synthase (PGIs) transgenic (Tg) mice were developed that had increased PGIs expression only in the kidney and increased urinary 6-keto-PGF(1alpha). These Tg mice, however, demonstrated endotoxemia-related AKI with low-dose LPS (1 mg/kg) (GFR: 12.6 +/- 3.9 vs. 196.5 +/- 21.0 microl/min P < 0.01), which did not alter GFR in WT mice (164.0 +/- 16.7 vs. 173.3 +/- 6.7 microl/min, P = not significant). An elevation in renal cAMP, however, suggested an activation of the PGI(2)-cAMP-renin system in these Tg mice. Moreover, angiotensin-converting enzyme inhibition afforded protection against endotoxin-related AKI in these Tg mice. Thus endothelial PGIs-mediated PGI(2), as previously shown with endothelial nitric oxide synthase-mediated nitric oxide, contributes to renal protection against endotoxemia-related AKI. This effect may be overridden by excessive activation of the renin-angiotensin system in renal-specific PGIs Tg mice.
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PMID:Prostacyclin in endotoxemia-induced acute kidney injury: cyclooxygenase inhibition and renal prostacyclin synthase transgenic mice. 1765 70

Sepsis is associated with an activation of the renin-angiotensin system and causes acute kidney injury. The aim was to examine the effects of a low, nondepressor dose of the selective angiotensin II type 1 receptor antagonist candesartan on renal hemodynamics and function in endotoxemic rats. Endotoxemia was induced in Sprague-Dawley rats by a dose of LPS (Escherichia coli O127:B8; 7.5 mg kg(-1), i.p.). At 16 h after endotoxin administration, renal clearance experiments were performed in thiobutabarbital anesthetized rats. Study groups (1) sham-saline, (2) LPS-saline, and (3) LPS-candesartan received isotonic saline or candesartan (10 microg kg(-1), i.v.) after baseline measurements. Kidney function, renal blood flow (RBF), and cortical and outer medullary perfusion (laser-Doppler flowmetry) and oxygen tension (P(O2); Clark-type microelectrodes) were analyzed during 2 h after drug administration. At baseline, endotoxemic rats showed an approximately 50% reduction in glomerular filtration rate and RBF (P < 0.05), a decline in cortical and outer medullary perfusion, and Po2 (P < 0.05), but no significant alterations in MAP compared with saline-injected controls. Candesartan treatment significantly improved RBF (+40% +/- 6% vs. baseline), cortical perfusion (+18% +/- 3% vs. baseline), and cortical (+19% +/- 7% vs. baseline) and outer medullary (+22% +/- 10% vs. baseline) P(O2) in endotoxemic rats (P < 0.05 vs. LPS-saline). Candesartan did not significantly influence MAP or glomerular filtration rate, whereas filtration fraction was reduced by 27% +/- 5% vs. baseline (P < 0.05 vs. LPS-saline). In conclusion, candesartan, in a dose that did not significantly decrease MAP, caused renal vasodilation and markedly improved RBF and intrarenal P(O2) in endotoxemic rats. These findings suggest renoprotective effects of candesartan in sepsis.
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PMID:Low-dose candesartan improves renal blood flow and kidney oxygen tension in rats with endotoxin-induced acute kidney dysfunction. 1809 74

Hyperprostaglandin E syndrome (HPS) is the antenatal variant of Bartter syndrome and characterized by polyhydramnios and preterm delivery in the antenatal period and salt-wasting, isosthenuric or hyposthenuric polyuria, hypercalciuria and nephrocalcinosis in the postnatal period. We report a one-month-old infant with HPS with a 15-year-old sister with Bartter syndrome. The infant's birth weight was 2750 g and she had severe dehydration on the 2nd day of life. She had hypercalcemia, hyponatremia, hypokalemia, metabolic alkalosis and elevated plasma renin and aldosterone levels. We instituted indomethacin therapy accompanied by steroid therapy for hypercalcemia. However, the patient developed abdominal distention on the 30th day, which was due to diffuse pneumatosis in sigmoid colon revealed by a subsequent surgical intervention. Following surgery, the patient developed fever, electrolyte abnormalities and subsequently sepsis. The patient died due to sepsis 10 days after surgery. We conclude that indomethacin and steroid therapy must be used cautiously in infants with HPS.
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PMID:Hyperprostaglandin E syndrome: use of indomethacin and steroid, and death due to necrotizing enterocolitis and sepsis. 1901 56

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presented to an emergency department (ED), and it is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. For diagnosing CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in elderly population, and in patients with renal dysfunction. They might have also a prognostic value. Studies demonstrated that the use of BNP or NT-proBNP in dyspneic patients early in the ED reduced the time to discharge, total treatment cost. BNP and NT-proBNP should be available in every ED 24 hours a day, because literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients.Etiologic diagnosis of febrile patients who present to an ED is complex and sometimes difficult. However, new evidence showed that there are interventions (including early appropriate antibiotics), which could reduce mortality rate in patients with sepsis. For diagnosing sepsis, procalcitonin (PCT) is more accurate than C-reactive protein. Thus, because of its excellent specificity and positive predictive value, an elevated PCT concentration (higher than 0.5 ng/mL) indicates ongoing and potentially severe systemic infection, which needs early antibiotics (e.g. meningitis). In lower respiratory tract infections, CAP or COPD exacerbation, PCT guidance reduced total antibiotic exposure and/or antibiotic treatment duration.
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PMID:Useulness of B Natriuretic Peptides and Procalcitonin in Emergency Medicine. 1957 5

Natriuretic peptides play a central role in cardiovascular, endocrine, and renal homeostasis and can be considered physiologic antagonists to the renin-angiotensin-aldosterone system. ANP and BNP in the circulation are derived primarily from the myocardium, whereas CNP is mainly derived from endothelial cells and the central nervous system. Increased ventricular and atrial diastolic wall stretch augment synthesis and release of BNP and NT-proBNP from cardiomyocytes, and is the principal stimulus controlling BNP production. Circulating BNP and NT-proBNP levels are increased in heart failure in proportion to disease severity, but elevated levels may also be observed in other cardiac and noncardiac disease states, including cardiac arrhythmias, ventricular hypertrophy, myocardial ischemia, pulmonary embolism, acute and chronic cor pulmonale, renal failure, anemia, hyperthyroidism, and sepsis. Fully automated analyses of both BNP and NT-proBNP can be rapidly performed on large hospital-based platforms as well as on small point-of-care devices.
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PMID:Natriuretic peptides: physiologic and analytic considerations. 1963 Nov 73

Sepsis causes impaired vascular reactivity, hypotension and acute renal failure. The ability of the Escherichia coli endotoxin (lipopolysaccharide [LPS]) to impair agonist-induced contractility in mesangial cells, which contributes to LPS-induced renal dysfunction, was evaluated. Agonist-induced intracellular calcium ([Ca(2+)]i) mobilization was analyzed using angiotensin II (AngII). The effect of LPS on the levels of the renin-angiotensin system (RAS) components and the roles of vasodilatation-inducing molecules including AT2 receptor (AT2R) and nitric oxide (NO) in the cell reactivity were also evaluated. Confluent human mesangial cells (HMCs) were stimulated with LPS (0111-B4, 100 microg/mL). AngII-induced [Ca(2+)]i mobilization was measured by fluorometric analysis using Fura-2AM in the absence and presence of an AT2R antagonist (PD123319). The mRNA and protein levels for angiotensinogen, renin, angiotensin-converting enzyme, AT1R and AT2R were analyzed by realtime reverse transcriptase-polymerase chain reaction and Western blot, respectively. NO production was measured by the chemiluminescence method in the culture media after 24, 48 and 72 h of LPS incubation. After 24 h, LPS-stimulated HMCs displayed lower basal [Ca(2+)]i and an impaired response to AngII-induced rise in [Ca(2+)]i. LPS significantly increased AT2R levels, but did not cause significant alterations of RAS components. PD123319 restored both basal and AngII-induced [Ca(2+)]i peak, suggesting an involvement of AT2R in these responses. The expected increase in NO production was significant only after 72 h of LPS incubation and it was unaffected by PD123319. Results showed that LPS reduced the reactivity of HMCs to AngII and suggest that the vasodilatation induced by AT2R is a potential mediator of this response through a pathway independent of NO.
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PMID:Escherichia coli lipopolysaccharide impairs the calcium signaling pathway in mesangial cells: role of angiotensin II receptors. 2051 80

A 3-year-old girl presented to the emergency department with seizures, low-grade fever and vomiting. She had tachycardia and a slow capillary refill. Blood pressure could not be measured. Because of suspected sepsis and/or meningo-encephalitis, broad spectrum antibiotics and antiviral medication were given together, along with volume expansion and anticonvulsive therapy. A few hours later, after a second seizure, the blood pressure was extremely high (156/116 mm Hg). The girl was treated with anticonvulsants and intravenous antihypertensive agents. MRI of the brain showed signs of posterior reversible encephalopathy syndrome. Cultures of blood and cerebrospinal fluid remained sterile. Further investigation into the cause of the malignant hypertension revealed hypokalemia, metabolic alkalosis and extremely high plasma renin activity, caused by a rare renal abnormality: bilateral renal segmental hypoplasia or Ask-Upmark kidneys.
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PMID:A 3-year old girl with seizures, hypokalemia and metabolic alkalosis. 2279 82

The critically ill subjects are represented by a heterogeneous group of patients suffering from a life-threatening event of different origin, e.g. trauma, cardiopulmonary failure, surgery or sepsis. The majority of these patients are dependent on the artificial lung ventilation, which means a life-saving chance for them. However, the artificial lung ventilation may trigger ventilation-associated lung injury (VALI). The mechanical ventilation at higher volumes (volutrauma) and pressure (barotrauma) can cause histological changes in the lungs including impairments in the gap and adherens junctions and desmosomes. The injured lung epithelium may lead to an impairment of the surfactant production and function, and this may not only contribute to the pathophysiology of VALI but also to acute respiratory distress syndrome. Other components of VALI are atelectrauma and toxic effects of the oxygen. Collectively, all these effects may result in a lung inflammation associated with a subsequent profibrotic changes, endothelial dysfunction, and activation of the local and systemic endocrine responses such as the renin-angiotensin system (RAS). The present review is aimed to describe some of the pathophysiologic aspects of VALI providing a basis for novel therapeutic strategies in the critically ill patients.
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PMID:The role of endocrine mechanisms in ventilator-associated lung injury in critically ill patients. 2280 8


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