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)

Physiological respiratory and hormonal changes occurring during pregnancy result in increased oxygen consumption related to fetal growth. The increase in the maternal basal metabolism leads to hyperventilation and increased cardiac output. This explains why pathological respiratory or cardiovascular conditions existing prior to pregnancy can rapidly worsen during the course of the pregnancy. However, even if no cardiorespiratory disease exists prior to pregnancy, an inhalation lung disease, pre-eclampsia or sepsis can lead to pulmonary edema due to the increased plasma volume in the pregnant woman. These different pathological situations as well as infectious lung diseases are discussed here. We examine the evolution of respiratory function during the course of labor, delivery and the post-partum period. In addition, pregnancy also has an effect on chronic respiratory disease, particularly asthma.
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PMID:[Development of acute and chronic respiratory diseases during pregnancy]. 1063 1

Our objectives were to evaluate the frequency of air leaks (AL) from the respiratory tract (pneumothorax, pneumomediastinum, pneumoperitoneum, subcutaneous emphysema) in critically ill children on mechanical ventilation (MV) for severe respiratory diseases, and to examine whether AL could be correlated with specific clinical events or ventilator settings. The study constitutes a retrospective cohort of 80 consecutive critically ill children receiving MV for severe respiratory diseases between 1986 and 1993. Patients (mean age 2.9 +/- 0.6 years, 49 males and 31 females), were admitted to the Pediatric Intensive Care Unit (PICU) with acute respiratory syndrome (ARDS) (27%), asthma (15%), bronchiolitis (10%), pneumonia (21%), pulmonary congenital diseases (9%), or foreign body aspiration (18%). Patients were divided into two groups; those with AL (n=22) and those without air-leaks (non-AL) (n = 58). Air leaks developed in 22 of 80 patients or in 27.5%. Survival was significantly lower in the AL group, compared to the non-AL group (41% vs. 76%, P < 0.01). The odds ratio that a patient with multiple organ system failure (MOSF) or infection would develop AL was 2.96 and 2.19, respectively. Candida and Pseudomonas species were recovered with significantly higher frequency in the AL group compared with the non-AL group (P < 0.025). There was a strong positive correlation between the incidence of AL and high ventilatory pressures (PIP 36 vs. 29.7 cm H(2)O, P < 0.001), or large tidal volumes (V(T) 12 vs. 9 mL/kg, P < 0.05), suggesting that large volumes might elicit injury to the pulmonary epithelium. Multiple logistic regression analysis showed that only V(T) was independently associated with the development of AL in children with primary severe respiratory disease (r(2) = -0.38, P = 0.01). In conclusion, MV will produce AL, particularly when high peak airway pressures (barotrauma) or large tidal volumes (volotrauma) are delivered by the ventilator. Sepsis, MOSF, and lung superinfection with Pseudomonas or Candida species may be also important factors in the development of AL in critically ill children.
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PMID:Air leaks from the respiratory tract in mechanically ventilated children with severe respiratory disease. 1063 3

Pathological increases in vascular leakage lead to edema and swelling, causing serious problems in brain tumors, in diabetic retinopathy, after strokes, during sepsis and also in inflammatory conditions such as rheumatoid arthritis and asthma. Although many agents and disease processes increase vascular leakage, no known agent specifically makes vessels resistant to leaking. Vascular endothelial growth factor (VEGF) and the angiopoietins function together during vascular development, with VEGF acting early during vessel formation, and angiopoietin-1 acting later during vessel remodeling, maturation and stabilization. Although VEGF was initially called vascular permeability factor, there has been less focus on its permeability actions and more effort devoted to its involvement in vessel growth and applications in ischemia and cancer. Recent transgenic approaches have confirmed the profound permeability effects of VEGF (refs. 12-14), and have shown that transgenic angiopoietin-1 acts reciprocally as an anti-permeability factor when provided chronically during vessel formation, although it also profoundly affects vascular morphology when thus delivered. To be useful clinically, angiopoietin-1 would have to inhibit leakage when acutely administered to adult vessels, and this action would have to be uncoupled from its profound angiogenic capabilities. Here we show that acute administration of angiopoietin-1 does indeed protect adult vasculature from leaking, countering the potentially lethal actions of VEGF and inflammatory agents.
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PMID:Angiopoietin-1 protects the adult vasculature against plasma leakage. 1074 56

Based on the essential involvement of NF-kappaB in immune and inflammatory responses and its apoptosis-rescue function in normal and malignant cells, inhibitors of this transcription factor are potential therapeutics for the treatment of a wide range of diseases, from bronchial asthma to cancer. Yet, given the essential function of NF-kappaB in the embryonic liver, it is important to determine its necessity in the liver beyond embryogenesis. NF-kappaB is normally retained in the cytoplasm by its inhibitor IkappaB, which is eliminated upon cell stimulation through phosphorylation-dependent ubiquitin degradation. Here, we directed a degradation-resistant IkappaBalpha transgene to mouse hepatocytes in an inducible manner and showed substantial tissue specificity using various means, including a new method for live-animal imaging. Transgene expression resulted in obstruction of NF-kappaB activation, yet produced no signs of liver dysfunction, even when implemented over 15 months. However, the transgene-expressing mice were very vulnerable both to a severe immune challenge and to a systemic bacterial infection. Despite having intact immunocytes and inflammatory cells, these mice were unable to clear Listeria monocytogenes from the liver and succumbed to sepsis. These findings indicate the essential function of the hepatocyte through NF-kappaB activation in certain systemic infections, possibly by coordinating innate immunity in the liver.
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PMID:High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-kappaB activation. 1080 15

Studies investigating the role of bradykinin in disease states such as hypertension, sepsis, and asthma have been confounded by difficulties in measuring the concentration of this short-lived peptide. The purpose of this study was to determine a stable metabolite of bradykinin in the systemic circulation of humans. Bradykinin (containing trace concentrations of [(3)H]bradykinin) was administered i.v. into three human volunteers in increasing amounts up to a maintenance rate of 200 ng/kg/min until a total dose of 1 mg was given. Metabolic products were purified and identified by HPLC and by electrospray ionization mass spectrometry. Infused bradykinin was rapidly degraded, such that no exogenous bradykinin was detected in venous plasma sampled during infusion. BK1-5 (Arg-Pro-Pro-Gly-Phe), the 1-to-5 amino acid fragment of bradykinin, was identified as a major stable plasma metabolite of bradykinin. Plasma concentrations of BK1-5 correlated with dose of bradykinin infused and concentrations at the end of bradykinin infusion were 1510 to 4600 fmol/ml of blood. BK1-5 was cleared from blood with a terminal half-life of 86 to 101 min. Thus, in humans, bradykinin is rapidly degraded in vivo to BK1-5, a stable metabolite. Measurement of this metabolite could provide a tool to assess pathophysiologic and pharmacologic alterations in systemic bradykinin generation associated with human disease.
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PMID:Metabolism of bradykinin In vivo in humans: identification of BK1-5 as a stable plasma peptide metabolite. 1087 21

Although hypophosphatemia is relatively uncommon, it may be seen in anywhere from 20% to 80% of patients who present to the ED with alcoholic emergencies, diabetic ketoacidosis (DKA), and sepsis. Severe hypophosphatemia, as defined by a serum level below 1.0 mg/dL, may cause acute respiratory failure, myocardial depression, or seizures. Because hypophosphatemia is not as often treated by ED physicians, becoming familiar with a single intravenous phosphate solution and specific guidelines for phosphate repletion are essential. One mL of the most commonly available phosphate solution (K2PO4) contains 4.4 meq of potassium and 3 mmol (93 mgs) of phosphate. Administering K2PO4 at a rate of 1 mL per hour is almost always a very safe and appropriate treatment for hypophosphatemia. This article provides guidelines for phosphate therapy in hypophosphatemic ED patients including those in DKA, those presenting with alcohol-related complaints including alcoholic ketoacidosis and patients with acute exacerbation of asthma and chronic obstructive pulmonary disease.
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PMID:Hypophosphatemia in the emergency department therapeutics. 1091 39

The molecular mechanism of the participation of carnosine in the functioning of soluble guanylate cyclase is discussed. It is shown that carnosine inhibits the activation of soluble guanylate cyclase by sodium nitroprusside and a derivative of furoxan--1,2,5-oxadiazolo-trioxide (an NO donor). However, carnosine has no effect on stimulation of the enzyme by a structural analog of the latter compound, a furazan derivative (1,2,5-oxadiazolo-dioxide) that is not an NO donor; nor was carnosine involved in the enzyme activation by protoporphyrin IX, whose stimulatory effect is not associated with the guanylate cyclase heme. The inhibition by carnosine of guanylate cyclase activation by an NO donor is due to the interaction of carnosine with heme iron with subsequent formation of a chelate complex. It was first demonstrated that carnosine is a selective inhibitor of NO-dependent activation of guanylate cyclase and may be used for suppression of activity of the intracellular signaling system NO-soluble guanylate cyclase-cGMP, whose sharp increase is observed in malignant tumors, sepsis, septic shock, asthma, and migraine.
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PMID:Carnosine as a regulator of soluble guanylate cyclase. 1095 Oct 96

Listeria monocytogenes causes sepsis and meningitis in immunocompromised hosts and a devastating maternal/fetal infection in pregnant women. In recent years a more benign gastroenteritis in normal hosts has been described. Listeria has been increasingly identified as a food-borne pathogen, and large-scale contamination of processed foods with resulting outbreaks has occurred in recent years, possibly as a result of consolidation of the food industry. Experimental listeriosis in mice has proven to be an extraordinarily useful model for analyzing cell-mediated immune host defenses. Contrary to original concepts, we found that neutrophils, not macrophages, are the prime effectors during early infection. CD8+ T cells are then responsible for lysing infected hepatocytes through perforin-related (early primary and secondary infection) or Fas-L/Fas mechanism (late primary). Of interest, non-classical MHC class Ib restricted recognition mechanisms exist early, whereas MHC class Ia mechanisms can be detected throughout infection.
Allergy Asthma Proc
PMID:An updated model of cell-mediated immunity--listeriosis: clinical and research aspects. 1095 86

The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction of the smooth muscle walls in bronchioles and pulmonary arteries and aggregation of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively. The cells that express these receptors in the lung have not been thoroughly investigated, nor has their expression been examined during inflammation. Accordingly, C3aR and C5aR expression in normal human and murine lung was determined in this study by immunohistochemistry and in situ hybridization. In addition, the expression of these receptors was delineated in mice subjected to LPS- and OVA-induced models of inflammation. Under noninflamed conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expression increased significantly on both bronchial epithelial and smooth muscle cells in mice treated with LPS; however, in the OVA-challenged animals only the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in mice treated with LPS, but was not elevated in either cell type in the OVA-challenged mice. These results demonstrate the expression of C3aR and C5aR by cells endogenous to the lung, and, given the participation of bronchial epithelial and smooth muscle cells in the pathology of diseases such as sepsis and asthma, the data suggest a role for these receptors during lung inflammation.
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PMID:Expression of the complement anaphylatoxin C3a and C5a receptors on bronchial epithelial and smooth muscle cells in models of sepsis and asthma. 1116 Feb 52

In recent years a plethora of data has accumulated directing toward an important role of polypeptides C3a and C5a and its degradation product C5adesArg, summarized as anaphylatoxins (ATs), in microbial host defense and immune regulation. The ATs exert their various biologic functions by interacting with specific C3a- and C5a-receptors present on cells of myeloid origin, epithelial cells, smooth muscle cells as well as on activated B- and T-cells. Activation of AT receptors mediates signal transduction pathways triggering a variety of proinflammatory events. However, by interacting with the cytokine- and chemokine network C3a and C5a exhibit also anti-inflammatory properties. In this review the focus is on the pathogenetic role of the ATs in sepsis, immune complex disease, delayed type hypersensitivity and asthma. Discussed are data from animal models in which the ATs are blocked by specific C3a or C5a inhibitors or from mice with genetic deletions of the specific receptors of either C3a or C5a/C5adesArg.
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PMID:Anaphylatoxins and infectious and non-infectious inflammatory diseases. 1153 79


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