Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the paucity of known self lipid-reactive ligands for NKT cells, interactions among distinct NKT cell subsets as well as immune consequences following recognition of self glycolipids have not previously been investigated. Here we examined cellular interactions and subsequent immune regulatory mechanism following recognition of sulfatide, a self-glycolipid ligand for a subset of CD1d-restricted type II NKT cells. Using glycolipid/CD1d tetramers and cytokine responses, we showed that activation of sulfatide-reactive type II NKT cells and plasmacytoid DCs caused IL-12- and MIP-2-dependent recruitment of type I, or invariant, NKT (iNKT) cells into mouse livers. These recruited iNKT cells were anergic and prevented concanavalin A-induced (ConA-induced) hepatitis by specifically blocking effector pathways, including the cytokine burst and neutrophil recruitment that follow ConA injection. Hepatic DCs from IL-12(+/+) mice, but not IL-12(-/-) mice, adoptively transferred anergy in recipients; thus, IL-12 secretion by DCs enables them to induce anergy in iNKT cells. Our data reveal what we believe to be a novel mechanism in which interactions among type II NKT cells and hepatic DCs result in regulation of iNKT cell activity that can be exploited for intervention in inflammatory diseases, including autoimmunity and asthma.
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PMID:Type II NKT cell-mediated anergy induction in type I NKT cells prevents inflammatory liver disease. 1764 82

The era of interferon (IFN) administration in the treatment of patients with chronic viral hepatitis creates an essential turning point for therapy of these diseases. Incessant progress of the new, more efficient and lower side effects of interferon causes decrease in treatment withdrawal. The side effects like myalgia, nausea, fatigue and loss of appetite, usually with good reaction for symptomatic treatment and intensity of the symptoms decreases during treatment continuation. Due to strong immuno-modulatory activities and long-lasting therapy, autoimmune diseases are observed in some cases. Therefore treatment process should be carefully and trifle monitored especially in autoantibodies appearance aspect. To the most common interferon mediated autoimmune diseases belong thyroiditis, autoimmune hepatitis and thrombocytopenia. Interstitial pneumonitis, systemic lupus erythematosus, type I diabetes mellitus, asthma and sarcoidosis exacerbation as well as glomerular diseases are observed rarely. In our paper we discus an issue of autoimmune diseases induction phenomena caused by interferon therapy administrated in the treatment of chronic viral hepatitis.
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PMID:[Interferon therapy in chronic viral hepatitis; an autoimmunity dilemma]. 1794 66

Corticosteroids have been used extensively since cortisone was first synthesized in the 1950s. Glucocorticoids are derived from cortisone and are used in treatments for inflammation, dermatitis, allergic reactions, asthma, hepatitis, lupus erythematosus, nausea, vomiting and inflammatory bowel diseases. In the setting of palliative care, glucocorticoids have many uses, including many symptoms of malignancy, nausea, vomiting, depression, fatigue, anorexia and cachexia.
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PMID:Role of corticosteroids in palliative care. 1803 21

This article presents a case report of a 41-year-old male firefighter with cholecystitis and a history of mildly elevated alanine aminotransferase. Liver biopsy showed periodic acid Schiff-positive, diastase-resistant periportal globules. Retrospective review of clinical data revealed progressive lung function decline despite absent pulmonary symptoms and normal pulmonary function testing. The following disorders should be considered in any patient with elevated transaminases without an apparent etiology: viral hepatitides, medication toxicity, autoimmune hepatitis, alcohol-induced hepatic injury, and alpha-1-antitrypsin deficiency.
Allergy Asthma Proc
PMID:Liver enzyme elevation and normal pulmonary function in an adult with a declining forced expiratory volume in 1 second. 1853 93

YM-58483/BTP2 is a blocker of store-operated Ca2+ entry (SOCE), which regulates the activation of non-excitable cells such as lymphocytes. YM-58483 has been reported to inhibit cytokine production and proliferation in T cells, and to be useful as a probable medicinal candidate for treatment of bronchial asthma. The present study investigated the pharmacological profile and therapeutic potential of YM-58483 in relation to cell-mediated immune responses. In the mouse graft-versus-host disease (GVHD) model, YM-58483 (1-30 mg/kg, p.o.) and cyclosporine A (1-30 mg/kg, p.o.) inhibited donor anti-host cytotoxic T lymphocyte (CTL) activity and IFN-gamma production, and also reduced the number of donor T cells, especially donor CD8+ T cells, in the spleen. YM-58483 and cyclosporine A inhibited T cell proliferation in a one-way mixed lymphocyte reaction (MLR) with IC50 values of 330 and 12.7 nM, respectively. Additionally, YM-58483 (1-10 mg/kg, p.o.) and cyclosporine A (2, 10 mg/kg, p.o.) inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) response. These results suggest that the inhibition of SOCE leads to the prevention of antigen-induced T cell responses, which participate in autoimmune diseases such as autoimmune hepatitis and rheumatoid arthritis.
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PMID:Characterization of YM-58483/BTP2, a novel store-operated Ca2+ entry blocker, on T cell-mediated immune responses in vivo. 1879 56

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.
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PMID:Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro. 1882 13

Picroliv, an iridoid glycoside derived from the plant Picrorhiza kurroa, is used traditionally to treat fever, asthma, hepatitis, and other inflammatory conditions. However, the exact mechanism of its therapeutic action is still unknown. Because nuclear factor-kappaB (NF-kappaB) activation plays a major role in inflammation and carcinogenesis, we postulated that picroliv must interfere with this pathway by inhibiting the activation of NF-kappaB-mediated signal cascade. Electrophoretic mobility shift assay showed that pretreatment with picroliv abrogated tumor necrosis factor (TNF)-induced activation of NF-kappaB. The glycoside also inhibited NF-kappaB activated by carcinogenic and inflammatory agents, such as cigarette smoke condensate, phorbol 12-myristate 13-acetate, okadaic acid, hydrogen peroxide, lipopolysaccharide, and epidermal growth factor. When examined for the mechanism of action, we found that picroliv inhibited activation of IkappaBalpha kinase, leading to inhibition of phosphorylation and degradation of IkappaBalpha. It also inhibited phosphorylation and nuclear translocation of p65. Further studies revealed that picroliv directly inhibits the binding of p65 to DNA, which was reversed by the treatment with reducing agents, suggesting a role for a cysteine residue in interaction with picroliv. Mutation of Cys(38) in p65 to serine abolished this effect of picroliv. NF-kappaB inhibition by picroliv leads to suppression of NF-kappaB-regulated proteins, including those linked with cell survival (inhibitor of apoptosis protein 1, Bcl-2, Bcl-xL, survivin, and TNF receptor-associated factor 2), proliferation (cyclin D1 and cyclooxygenase-2), angiogenesis (vascular endothelial growth factor), and invasion (intercellular adhesion molecule-1 and matrix metalloproteinase-9). Suppression of these proteins enhanced apoptosis induced by TNF. Overall, our results show that picroliv inhibits the NF-kappaB activation pathway, which may explain its anti-inflammatory and anticarcinogenic effects.
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PMID:Modification of cysteine residue in p65 subunit of nuclear factor-kappaB (NF-kappaB) by picroliv suppresses NF-kappaB-regulated gene products and potentiates apoptosis. 3018 11

At The Aesthetic Meeting 2002 of the American Society for Aesthetic Plastic Surgery, the Aesthetic Surgery Education and Research Foundation/Plastic Surgery Educational Foundation (ASERF/PSEF) Emerging Trends Task Force and Innovative Procedures Committee requested an update on zafirlukast (Accolate; AstraZeneca Pharmaceuticals, Wilmington, DE) and montelukast (Singulair; Merck & Co, West Point, PA) - what they are and how they work. These two asthma medications were reported to possibly treat and prevent capsular contracture after breast augmentation. On further analysis of postmarketing complications associated with zafirlukast based on information obtained through the Freedom of Information Act, it was discovered that between November 1, 1997, and October 31, 2002, 66 cases of hepatitis or liver failure in asthma patients occurred after a normal dose (13 of these 66 patients were taking no other medication). Two patients required liver transplants. Twenty-three deaths were reported (8 of these 23 patients were taking no other medication); 12 of these deaths followed liver failure. It should be noted that the Adverse Event Reporting System contains a disclaimer saying, "The reports have not been scientifically or otherwise verified as to a cause-and-effect relationship and cannot be used to estimate the incidence of adverse drug reactions." Many physicians entered the specific code to indicate zafirlukast as the "primary suspect" in the adverse event. Merck & Co reported no postmarketing cases of hepatitis or liver failure associated with montelukast. This article summarizes the proposed logic behind using these two asthma medications for the prevention and treatment of breast implant capsular contracture. (Aesthetic Surg J 2003;23:98-102.).
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PMID:Investigation of accolate and singulair for treatment of capsular contracture yields safety concerns. 1933 61

The family of mammalian chitinases includes members both with and without glycohydrolase enzymatic activity against chitin, a polymer of N-acetylglucosamine. Chitin is the structural component of fungi, crustaceans, insects and parasitic nematodes, but is completely absent in mammals. Exposure to antigens containing chitin- or chitin-like structures sometimes induces strong T helper type-I responses in mammals, which may be associated with the induction of mammalian chitinases. Chitinase 3-like-1 (CHI3L1), a member of the mammalian chitinase family, is induced specifically during the course of inflammation in such disorders as inflammatory bowel disease, hepatitis and asthma. In addition, CHI3L1 is expressed and secreted by several types of solid tumors including glioblastoma, colon cancer, breast cancer and malignant melanoma. Although the exact function of CHI3L1 in inflammation and cancer is still largely unknown, CHI3L1 plays a pivotal role in exacerbating the inflammatory processes and in promoting angiogenesis and remodeling of the extracellular matrix. CHI3L1 may be highly involved in the chronic engagement of inflammation which potentiates development of epithelial tumorigenesis presumably by activating the mitogen-activated protein kinase and the protein kinase B signaling pathways. Anti-CHI3L1 antibodies or pan-chitinase inhibitors may have the potential to suppress CHI3L1-mediated chronic inflammation and the subsequent carcinogenic change in epithelial cells.
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PMID:Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells. 1990 31

Little is known about the general healthcare needs of detainees in police custody. The aims of this study were to: determine the level of general health issues, diseases and/or pathology for detainees in police custody, and to determine how well those general health issues, diseases and/or pathology are being managed. This was done by a detailed analysis of healthcare issues of a cohort of detainees and reviewing intended and prescribed medication needs with current medication availability. In August 2007, a prospective detailed, anonymised, structured questionnaire survey was undertaken of 201 detainees in police custody in London, UK. Of these 83.6% consented to participate in the study. 85.1% of subjects were male; mean age was 33.9 years; 70.8% had English as a first language; 13.7% were of no fixed abode; 70.2% were registered with a general practitioner (primary care physician); 25% were already in contact with other healthcare teams; 7.1% had previously been sectioned under the Mental Health Act 1983; 16.7% had previously intentionally self-injured; 33.9% were dependent on heroin, 33.9% on crack cocaine; 25% on alcohol, 16.6% on benzodiazepines and 63.1% on cigarettes. 56% of subjects had active medical conditions; of those with active medical conditions 74% were prescribed medication for those medical conditions; only 3/70 had their medication available. 28/70 were not taking medication regularly, and many were not taking it at all. Three subjects who had deep vein thromboses were not taking their prescribed anticoagulants and six subjects with severe mental health issues were not taking their anti-psychotic medication. Mental health issues and depression predominated, but there was a very large range of mixed diseases and pathology. Asthma, epilepsy, diabetes, deep vein thrombosis, pulmonary embolism, hepatitis, and hypertension were all represented. The study has achieved its aims and has also shown that--in part because of the chaotic lifestyle of many detainees--appropriate care was not being rendered, thereby, putting both detainee, and potentially others coming into contact with them, at risk.
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PMID:Healthcare issues of detainees in police custody in London, UK. 2008 45


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