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)

C5L2 is an enigmatic serpentine receptor that is co-expressed with the C5a receptor on many cells including polymorphonuclear neutrophils. The apparent absence of coupling of C5L2 with G proteins suggests that this receptor may modulate the biological activity of C5a, perhaps by acting as a decoy receptor. Alternatively, C5L2 may affect C5a function through formation of a heteromeric complex with the C5aR, or it may utilize a G protein-independent signaling pathway. Here we show that in mice bearing a targeted deletion of C5L2, the biological activity of C5a/C5a(desArg) is enhanced both in vivo and in vitro. The biological role of C5L2 thus appears to be limiting to the pro-inflammatory response to the anaphylatoxin. Accordingly, up-regulation of C5L2 may be of benefit in inflammatory states driven by C5a, including sepsis, asthma, cystic fibrosis, and chronic obstructive lung disease.
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PMID:An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. 1620 43

The Toll-like receptor (TLR) family regulates both innate and adaptive immune responses. Given its broad effect on immunity, the function of TLRs in various human diseases has been investigated largely by comparing the incidence of disease among persons with different polymorphisms in the genes that participate in TLR signaling. These studies demonstrate that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis, and asthma. These findings have resulted in new opportunities to study the pathogenesis of disease, identify subpopulations at greater risk of disease, and, potentially, identify novel therapeutic approaches.
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PMID:Polymorphisms of the Toll-like receptors and human disease. 1623 38

The cytokine macrophage migration inhibitory factor (MIF) is a constitutive element of the host antimicrobial defenses and stress response that promotes proinflammatory function of the innate and acquired immune systems. MIF plays an important role in the pathogenesis of acute and chronic inflammatory or autoimmune disorders, such as sepsis, acute respiratory distress syndrome, asthma, rheumatoid arthritis, and inflammatory bowel diseases. Polymorphisms of the human MIF gene (that is, guanine-to-cytosine transition at position -173 or CATT-tetranucleotide repeat at position -794) have been associated with increased susceptibility to or severity of juvenile idiopathic and adult rheumatoid arthritis, ulcerative colitis, atopy, or sarcoidosis. Whether these MIF polymorphisms affect the susceptibility to and outcome of sepsis has not yet been examined. Analyses of MIF genotypes in patients with sepsis may help to classify patients into risk categories and to identify those patients who may benefit from anti-MIF therapeutic strategies.
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PMID:Macrophage migration inhibitory factor: gene polymorphisms and susceptibility to inflammatory diseases. 1623 55

Undesired activation of the complement system, a part of the immune system, is a major pathogenic factor contributing to various diseases, such as ischemia-reperfusion injury, sepsis, asthma, allergic reactions, rheumatoid arthritis, Alzheimer's disease, myasthenia, multiple sclerosis and others. The history of the development of complement system inhibitors, preventing its destructive action on the body, represents the evolution of the main methods of drug design. This review illustrates the main approaches of drug design, ranging from screening and modification of natural products to structure-based ligand design, on the basis of complement inhibitors' creation. The current status of the field of complement inhibitors is also discussed.
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PMID:Drug design using the example of the complement system inhibitors' development. 1625 76

Peripheral blood CD16 (Fc receptor for immunoglobulin G III)-positive monocytes have been shown to expand in different pathological conditions, such as cancer, asthma, sepsis, human immunodeficiency virus infection, and AIDS progression, but data in leishmaniasis are lacking. We found that cutaneous leishmaniasis patients (n = 15) displayed a significant increase in the percentage (3.5 vs. 10.1) as well as mean fluorescent intensity (13.5 vs. 29.2) of ex vivo CD16 expression in monocytes as compared with healthy controls. We observed a significant positive correlation between the percentage of ex vivo CD16+ monocytes and lesion size (P = 0.0052, r = 0.75) or active transforming growth factor-beta plasma levels (P = 0.0017, r = 0.78). In addition, two patients with nonhealing lesions during a 3-year follow-up had high (9.1-19.4%) CD16 levels at diagnosis. Our data suggest a deleterious role for CD16 in human leishmaniasis, as well as its possible use as a marker for disease severity and/or adverse disease outcome.
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PMID:CD16+ monocytes in human cutaneous leishmaniasis: increased ex vivo levels and correlation with clinical data. 1628 34

The role of suspected or confirmed neonatal sepsis in modifying the risk of atopic disease during childhood was assessed. Children with early-onset neonatal sepsis were identified from a cohort of neonates, hospitalized between 1990 and 1995. Of 196 individuals, 140 were recruited (71.4%). Pre- and postnatal history was ascertained from neonatal medical records. Based on clinical symptoms and a positive blood culture or at least three of initially defined laboratory or bacteriological criteria, they were stratified in either confirmed neonatal sepsis (CS) or suspected sepsis (SS) group. A control group (C) comprised children who were never hospitalized during infancy (n = 696). Primary end-point was the development of atopic dermatitis, bronchial asthma or allergic rhinitis during childhood (mean age 8.4 yr, range 5.7-12.4). CS and SS children had a higher prevalence of atopic dermatitis (CS 15.7%, SS 21.4%) compared with controls (C 5.2%, p < 0.001). Similarly, children with SS (7.1%), but not with CS (4.3%) had significantly more often a doctor's diagnosis of bronchial asthma compared to controls (1.9%, p = 0.02). No difference in the prevalence of allergic rhinitis was observed (CS 4.3%, SS 10%, C 8.3%). After adjusting for parental history of atopic disease and demographic factors, no significant difference for the risk to develop atopic dermatitis, asthma or allergic rhinitis among the groups was calculated in children with normal birth weight (>2500 g). Our data failed to show a possible link between hospital admission with SS and development of atopic disease.
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PMID:Hospital admission with neonatal sepsis and development of atopic disease: Is there a link? 1634 83

A 92-year-old man with a history of bronchial asthma and allergic rhinitis received antibiotics for sepsis by methicillin-resistant Staphylococcus aureus and multidrug-resistant Enterococcus gallinarum. During the antibiotics treatment, skin eruptions, liver dysfunction, and hypereosinophilia developed, followed by dyspnea, congestive heart failure, electrocardiographic abnormalities, and diffuse mild myocardial hypokinesis. After the discontinuation of the antibiotics and the administration of steroid, skin eruptions, liver dysfunction, and hypereosinophilia improved parallel with the improvement of the congestive heart failure. Vancomycin hydrochloride and teicoplanin were suspected as the causative drugs on the basis of the treatment course. Although congestive heart failure is rare in the case of drug-induced hypereosinophilia, it is one of life-threatening complications. We describe herein a case of congestive heart failure associated with hypereosinophilia developed during antibiotics treatment, successfully treated with steroid after the discontinuation of the causative drug.
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PMID:[Case of congestive heart failure associated with hypereosinophilia developed during antibiotics treatment]. 1640 68

Platelet Activating Factor (PAF) is a D-glycerol derived phosopholipid which is a potent endogenous mediator of inflammation. PAF is synthesized and released by a variety of cell types and elicits its biological activity by interacting with specific G-protein coupled receptors found on platelets, neutrophils, and other inflammatory cells. The physiological consequences of the interaction on PAF with its receptor include an increase in vascular permeability, hypotension, bronchoconstriction, and platelet and neutrophil aggregation. These biological effects are consistent with the concept that PAF is involved in a number of inflammatory diseases such as septic shock and asthma (Arimura A., 1998). Given the potent pathophysiological effects of PAF, a great deal of effort has been focused on the discovery of agents which block the action of PAF at its receptor. Within the past 10 years, a wide range of structures have been identified as PAF antagonists. These include not only PAF analogs, but also antagonists derived form natural product as well as non-lipid synthetic compounds. Several theories have been proposed to unify these diverse structural classes, but sophisticated molecular models of the receptor have not been widely employed (Braquet P., 1987). The discovery of new PAF antagonists has relied heavily on traditional medicinal chemistry approaches. A number of PAF antagonists have advanced to clinical evaluation. While several early compounds demonstrated efficacy in animal models of asthma they have failed to provide benefit for this condition in man. The current generation of potent antagonists are being evaluated as therapies for sepsis, pancreatitis and other disorders (Braquet C., 1991).
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PMID:Platelet Activating Factor antagonists. 1641 13

Platelet-activating factor (PAF) is a potent lipid mediator that has been implicated in asthma, sepsis, acute lung injury and ischemia/reperfusion injury. Its actions in the lungs include vasoconstriction, bronchoconstriction, and edema formation. Despite the fact that PAF exerts these actions within minutes, they are mediated by other lipid mediators, in particular eicosanoids generated by cyclooxygenase and lipoxygenase enzymes and sphingolipids generated by acid sphingomyelinase.We will discuss the mechanisms of the PAF-induced pressor responses that are triggered by thromboxane A(2) and leukotrienes, as well the PAF-induced increase in vascular permeability that is mediated by prostaglandin E(2) (PGE(2)) and ceramide.
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PMID:Mechanisms of platelet-activating factor (PAF)-mediated responses in the lung. 1641 1

Toxic neutrophils exhibit a variety of nuclear and cytoplasmic abnormalities in Romanowsky-stained blood smears, and are associated with inflammation and infection. The purpose of the retrospective study reported here was to investigate the association of toxic neutrophils with clinicopathologic characteristics, diseases, and prognosis in cats. Cats with toxic neutrophils (n = 150) were compared with negative-control cats (n = 150). Statistical analyses included Fisher exact, independent t-, nonparametric Mann-Whitney, and chi-squared tests. Cats with toxic neutrophils had significantly (P < .05) higher prevalence of fever, icterus, vomiting, diarrhea, depression, dehydration, weakness, and cachexia, as well as leukocytosis, neutrophilia, left shift, neutropenia, anemia, hypokalemia, and hypocalcemia. The prevalence of shock, sepsis, panleukopenia, peritonitis, pneumonia, and upper respiratory tract diseases was significantly higher among these cats, as were infectious (viral and bacterial) and metabolic disorders. Control cats had a significantly higher prevalence of feline asthma, as well as allergic, idiopathic, and vascular disorders. Hospitalization duration and treatment cost were significantly (P < .001) higher in cats with toxic neutrophils. In 53 and 47% of the cats with toxic neutrophils, the leukocyte and neutrophil counts were normal, respectively, whereas in 43%, both abnormalities and left shift were absent, and toxic neutrophils were the only hematologic evidence of inflammation or infection. In conclusion, toxic neutrophils were found to be associated with certain clinicopathologic abnormalities, and when present, may aid in the diagnosis, as well as the assessment of hospitalization duration and cost. The evaluation of blood smears for toxic neutrophils provided useful clinical information.
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PMID:Toxic neutrophils in cats: clinical and clinicopathologic features, and disease prevalence and outcome--a retrospective case control study. 1649 19


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