Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents that attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.
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PMID:Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence. 217 54

To establish the potential value of quantitative tests of liver function following orthotopic liver transplantation (OLT), a total of 100 determinations of caffeine clearance (CafCl) and galactose elimination capacity (GEC) were made in ten OLT recipients early in the post-operative course (days 2, 4, 6, 8 and 12) and later when clinically stable (3-12 months). Values were compared with a reference range in six normal volunteers in whom it was shown that the standard doses of caffeine (125 mg) and galactose (0.5 g per kg body weight) could be given together without interference. In orthotopic liver transplantation recipients initial GEC and CafCl measurements showed no correlation with peri-operative blood loss, donor ischaemia time, initial bile flow or survival. Throughout the early post-operative period, there were wide inter- and intra-individual variations in both CafCl (17-fold range from 0.16 to 2.7 ml.min-1.kg-1) and GEC (2.4-fold range from 5.1 to 12 mg.min-1.kg-1), but the only correlation of test values with standard liver function tests results was between GEC and gamma-glutamyltranspeptidase. However, GEC values fell by 19% during periods of acute rejection and there was an inverse correlation of GEC with white cell count probably related to sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Use of quantitative liver function tests--caffeine clearance and galactose elimination capacity--after orthotopic liver transplantation. 233 84

Changes in Ca2+-induced Ca2+ release in cardiac sarcoplasmic reticulum (SR) during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The 45Ca2+ release studies show that the amount of Ca2+ released from the passively and the actively loaded SR vesicles was unaffected during the early sepsis (9 h after CLP), but it was significantly decreased during the late phase (18 h after CLP) of sepsis. The [3H]ryanodine binding assays reveal that the Bmax for ryanodine binding was unaffected during the early phase, but was decreased by 32.1% during the late phase of sepsis. The affinity of ryanodine receptor for Ca2+ remained unchanged during sepsis. ATP, AMP-PCP, and caffeine stimulated binding, while MgCl2 and ruthenium red inhibited [3H]ryanodine binding in control, early sepsis, and late sepsis groups. The EC50 and IC50 values for these regulators were unaffected during the progression of sepsis. Digestion of control SR with phospholipase A2 decreased [3H]ryanodine binding and the decrease was reversible by the addition of phosphatidylcholine (PC), phosphatidylethanolamine (PE), or phosphatidylserine (PS). Addition of PC, PE, or PS to the SR isolated from septic rats stimulated [3H]ryanodine binding. These data demonstrate that Ca2+-induced Ca2+ release from cardiac SR remained relatively unaffected during the early phase, but was significantly impaired during the late phase of sepsis. The sepsis-induced impairment in SR Ca2+ release is a result of a quantitative reduction in the number of Ca2+ release channels. Furthermore, the reduction is associated with a mechanism involving a modification of membrane lipid profile in response to certain stimuli such as activation of phospholipase A2.
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PMID:Impairment of the ryanodine-sensitive calcium release channels in the cardiac sarcoplasmic reticulum and its underlying mechanism during the hypodynamic phase of sepsis. 1144 13

Using the 125-day baboon model of long-term bronchopulmonary dysplasia, we hypothesized that early use of nasal continuous positive airway pressure (nCPAP), a noninvasive ventilatory method, combined with prophylactic surfactant therapy would permit continuation of alveolar and vascular development in the lung. Retrospective human studies have shown that infants treated with nCPAP spend less time on mechanical ventilation and thereby sustain less volutrauma. After delivery by cesarean section at 125 days (term, 185 days), the infants received two doses of surfactant (Curosurf) and daily caffeine citrate. Weaning from low-volume positive pressure ventilation to nCPAP was attempted at 24 hours of age. Serial physiological parameters were recorded. Lung histopathology and morphometric measurements of nCPAP animals were done after necropsy at 28 days and data were compared with 125- and 156-day gestational controls. Documented episodes of clinical sepsis and pneumonia at postmortem examination were absent. nCPAP lungs showed enlarged thin-walled air spaces with minimal fibroproliferation and scattered secondary crests. Internal surface area and surface-to-volume ratio dimensions were similar to those of 156-day gestational control lungs, the intrauterine developmental control. nCPAP is an effective noninvasive ventilatory technique that minimizes lung injury in baboons at risk of developing bronchopulmonary dysplasia.
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PMID:Treatment of immature baboons for 28 days with early nasal continuous positive airway pressure. 1496 19

The purpose of the study was to propose recommendations for endotracheal intubation and respiratory support in newborn and in infants. The recommendations for endotracheal intubation are preceeded by a short history of intubation, basic anatomy of the upper airway in infants and children and the most common methods of airway control. The main indications for intubation are airway protection and control of the airway. Such circumstances may be: general anaesthesia, congenital malformations and diseases of the upper airway, mechanical ventilation, perinatal resuscitation and various forms of acute respiratory distress. Endotracheal intubation is strongly recommended during general anaesthesia in infants, complete and almost complete obstruction of the upper airway (grade A). Intubation is also necessary when bag-mask ventilation is ineffective, and when external chest compressions are being delivered. The position of the tube must be confirmed by a capnometer or a disposable CO(2) sensor (Class A, LOE 1a and 1b). Endotracheal intubation and mechanical ventilation should be considered in cases of frequent, caffeine and nCPAP-resistant apnoeic episodes, in the ARDS and progressive ventilatory failure in sepsis. (Class B).
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PMID:[Indications for endotracheal intubation]. 1947 Oct 55

Human skeletal muscles contain the largest single pool of K+ in the body (2600 mmol, 46 times the total K+ content of the extracellular space). Intense exercise may double arterial plasma K+ in one min. This is because of excitation-induced release of K+ from the working muscle cells via K+ channels. This hyperkalemia is rapidly corrected by reaccumulation of K+ into the muscle cells via Na+,K+ pumps, often leading to hypokalemia. Hyperkalemia may also arise from muscle cell damage, excessive oral or intravenous administration of K+, acidosis, renal failure, depolarization of muscle cells with succinyl choline, activation of K+ channels by fluoride poisoning, hyperkalemic periodic paralysis, malignant hyperthermia, inhibition of the Na+,K+ pumps by digitalis glycosides or treatment with nonselective beta blockers. Hyperkalemia may cause arrhythmia and can be treated with beta2 agonists, insulin or hemodialysis. Hypokalemia may be induced by the stimulation of the Na+,K+ pumps in skeletal muscles seen postexercise, or by catecholamines, beta2 agonists, pheochromocytoma, theophylline, caffeine or insulin, by sepsis, myocardial infarction, trauma, burns and heart failure. Rare causes are hypokalemic periodic paralysis, inhibition of K+ channels by barium, chloroquine or barbiturates. Hypokalemia often reflects dietary K+ deficiency, alkalosis, renal or gastrointestinal loss of K+. Hypokalemia is more likely to cause arrhythmia than hyperkalemia and can be treated by oral or intravenous administration of K+ under frequent control of electrocardiogram and plasma K+. Because of their size and high contents of K+, Na+,K+ pumps and K+ channels, the skeletal muscles play a central role in the acute, from min-to-min ongoing regulation of plasma K+. This is decisive for the maintenance of muscle contractility and heart function.
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PMID:Hormonal and pharmacological modification of plasma potassium homeostasis. 2061 71

Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in preterm neonates are associated with significant mortality and morbidity, including long-term neurodevelopmental impairment and socioeconomic burden. Safe and effective drugs for the prevention and treatment of these conditions are urgently needed. Pentoxifylline, a synthetic theobromine derivative, is a non-steroidal immunomodulating agent with unique hemorrheologic effects which has been used in a range of infectious, vascular, and inflammatory conditions in adults and children. The unique properties of pentoxifylline explain its potential benefits in preterm neonates with sepsis, NEC, and CLD, conditions characterized by activation of the inflammatory cytokine cascade, free radical toxicity, and impaired microcirculation. Pentoxifylline has anti-inflammatory properties resulting from inhibition of erythrocyte phosphodiesterase. It lowers blood viscosity and improves microcirculation and tissue perfusion. As a phosphodiesterase inhibitor, pentoxifylline downregulates pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Methylxanthines, including caffeine, theophylline, and theobromine are relatively non-toxic drugs; of these, theobromine is the least toxic. Pentoxifylline-related significant adverse events are thus very rare. Unlike other methylxanthines, pentoxifylline does not have significant cardiac and bronchodilating effects at therapeutic doses. Although it is contraindicated in adults with recent cerebral hemorrhage due to its effect on platelets, red blood cells, and plasma fibrinogen levels, no significant adverse effects including thrombocytopenia and bleeding have been reported in critically ill preterm neonates with sepsis or NEC after treatment with pentoxifylline. Based on data from pilot randomized trials and observational studies, our systematic review suggests that pentoxifylline may reduce mortality and/or morbidity in preterm neonates with sepsis, NEC, and CLD. Results of experimental studies also indicate that pentoxifylline may potentially be beneficial in meconium aspiration syndrome and hypoxic ischemic encephalopathy. Given the substantial burden of sepsis, NEC, and CLD in high-risk preterm neonates, and the findings of this systematic review, pentoxifylline needs to be evaluated urgently as a preventative and therapeutic agent for these conditions in randomized controlled trials that can detect minimal clinically significant effect sizes. Further clinical and experimental studies are also necessary to evaluate whether pentoxifylline is safe and effective in meconium aspiration syndrome and hypoxic ischemic encephalopathy.
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PMID:Pentoxifylline in preterm neonates: a systematic review. 2079 59

Premature infants have immature respiratory control that predisposes them to apnoea, haemoglobin oxygen desaturation and bradycardia. Apnoeas are loosely classified, according to the presence or absence of respiratory effort, into central, obstructive or mixed. There are a variety of conditions, in the perioperative period, that predispose an infant to apnoea, including: central nervous system (CNS) lesions, infections and sepsis, ambient temperature fluctuations, cardiac abnormalities, metabolic derangements, anaemia, upper airway structural abnormalities, necrotising enterocolitis, drug administration (including opiates and general anaesthetics) and possibly gastro-oesophageal reflux. Various monitoring techniques are discussed; the mainstay are pulse oximetry and abdominal-pressure transduction. There is some evidence of both short- and long-term complications of repeated apnoeas in the neonatal period, but the causal relationship is difficult to establish. Continuous positive airway pressure and caffeine therapy (up to 10 mg kg(-1)) are the most common treatments of neonatal apnoea. The less soluble volatile agents and regional anaesthetic techniques (without concurrent sedation) are associated with a lower incident of postoperative apnoea.
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PMID:Neonatal apnoea. 2103 10

Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors.
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PMID:Structural changes of the heart during severe sepsis or septic shock. 2230 6

Preterm infants are often considered too unstable to be fed enterally so they are exposed to complications related to a prolonged enteral fasting. Our study aims to compare feeding tolerance of adequate for gestational age (AGA) versus small for gestational age (SGA) infants and to evaluate which perinatal factors affect feeding tolerance (measured as time to achieve full enteral feeding, FEF). Inborn infants with a gestational age (GA) less than 32 weeks, born from January 2006 to December 2010, were eligible for this study. We enrolled 310 infants. The time to FEF was longer for SGA infants than for AGA, while a longer GA was associated to a reduced time to FEF. A beneficial effect was observed for antenatal steroids, while Apgar score below 7, the administration of inotrops or caffeine, the occurrence of sepsis or NEC and the presence of PDA were associated to a longer time to FEF. When evaluated jointly with a multivariate analysis, GA (p < 0.0001), antenatal steroids prophylaxis (p = 0.002), SGA (p < 0.0001) and occurrence of NEC (p = 0.0002) proved to have independent prognostic impact on the time to FEF. Feeding tolerance is better as GA increases, and worsen in SGA infants. Antenatal betamethasone is effective in reducing the time to FEF in both AGA and SGA.
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PMID:Feeding tolerance of preterm infants appropriate for gestational age (AGA) as compared to those small for gestational age (SGA). 2313 Nov 36


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