Chronic active

Hematologic diseases autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, pernicous anemia Kidney disease Goodpasture syndrom, lipoid nephroses, minimal change glomerulonephritis Diseases of the gastrointestinal tract autoimmune chronic active hepatitis, autoimmune atrophic gastritis, Crohn s disease, ulcerative colitis... 

Therapeutic efficacy of adoptively transferred cytotoxic T lymphocytes (CTL) has been demonstrated in clinical trials for cytomegalovirns (CMV)-associated disease (Walter et al. 1995), for EBV-associated lymphoma (Rooney et al. 1995) and nasopharyngeal carcinoma (Comoli et al. 2005) as well as for chronically active EBV infection (Savoldo et al. 2002). 

CAH Chronic active hepatitis CALLA Common lymphoblastic leukaemia antigen CALX Conjunctival associated lymphoid tissue CaM Calmodulin cAMP Cyclic adenosine monophosphate also knomt as adenosine 3, 5 -phosphate CAM CeU adhesion molecule CAP57 Cationic protein from neutrophils CAT Catalase CatG Cathepsin G... 

CAH Chronic active hepatitis DCC Direct-current cardioversion... 

Ben Yahia M, Mavier P, Metreau JM, et al. Chronic active hepatitis and cirrhosis induced by wild germander. 3 cases. Gastroenterol Clini Biol 17(12) 959—962, 1993. 

Thomas JO, Ribelin WE, Woodward JR, Deeds F (1967) The chronic activity of diphenyl-amine for dogs. Toxicol Appl Pharmacol 11 184—194... 

Elevated ET-1 in SCA patients, even in the steady state, may play an important role in the dehydration of sickle erythrocytes and the resulting enhanced intra-erythrocytic HbS polymerization. Indeed, it has been shown that ET-1 activates Ca2+- gated K+ channels in mouse erythrocytes [34]. ET-1, as a pro-inflammatory agonist, has been shown to induce the production of inflammatory cytokines by monocytes. One of the cytokines, namely TNFa enhances the adherence of sickle erythrocytes to vascular endothelium [35]. In addition, endothehns upregulate the expression of endothelial adhesion molecules such as ICAM-l, VCAM-1 and E-se-lectin, which participate in the recruitment of white cells to the site of inflammation. The overall conclusions that can be drawn from these data is that ET-1 plays a critical role in the vasospasm and inflammation that result in VOC. The major effect of HU in ameliorating the clinical symptoms of SCA likely results from its ability to inhibit the chronically activated ET-1 expression in SCA patients. 

A number of early in vitro studies demonstrated a considerable role of free radicals in liver injury (see, for example, Proceedings of International Meeting on Free Radicals in Liver Injury [341]). Later on, it was shown that chronic inflammation in the liver-induced oxidative DNA damage stimulated chronic active hepatitis and increased the risk of hepatocarcinogenesis [342,343]. Farinati et al. [344] showed that 8-OHdG content increased in circulating leukocytes of patients with chronic hepatitis C virus (HCV) infection. DNA oxidative damage is supposedly an early event of HCV-related hepatitis. The formation of isoprostanes in the liver of carbon tetrachloride-treated rats can be suppressed by the administration of vitamin E [345],... 

At least three distinct forms of the IP3-R have been identified, and these share an overall amino acid homology of 60-80%. Type I predominates in the cerebellum and has been most extensively studied. It is the largest of the 3 forms of the receptor and, unlike type II and III receptors, the gene possesses a 120 nucleotide insert. Type II IP3-Rs are found mainly in non-neural tissues, whereas type III receptors occur in both neural and non-neural tissues. In response to chronic activation, IP3-Rs are degraded via the ubiquitin-proteasome pathway [14] (see also Ch. 2). 

Liver biopsies for pathologic classification as chronic persistent hepatitis, chronic active hepatitis, or cirrhosis. 

Approximately 11% of patients with ulcerative colitis have hepatobiliary complications including fatty liver, pericholangitis, chronic active hepatitis, cirrhosis, sclerosing cholangitis, cholangiocarcinoma, and gallstones. 

Therefore, T-cells participate in bone loss during inflammation or when T-cells are chronically activated (rheumatoid arthritis, periodontitis, infections, bone prothesis) and recently have been implicated in postmenopausal bone loss (Cenci et al. 2000,2003 Roggia et al. 2001). 

Herzog, D. et al, Study of immune reactivity of minocycline-induced chronic active hepatitis. Dig. Dis. Sci., 42, 1100, 1997. 

Mascheretti, S., Hampe, J., Kuhbacher, T, et al. (2002) Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn s disease treated with infliximab. Pharmacogenomics J. 2, 127-136. 

There is evidence that stressful conditions decrease the effectiveness of the immune system the loss of a job, a divorce or a bereavement increases the risk of development of cancer. This is due to impairment of the process of immune surveillance carried out by the neutrophils and other immune cells. They kill tumour cells that are migrating from a primary tumour to establish another tumour in a different tissue. The impairment may be due to chronic activation of the sympathetic system, which increases the... 

Antipsychotic activity Many at5 ical neuroleptics (e.g. amperozide and risperidone) are 5-HT2 receptor antagonists. In animals, 5-HT3 antagonists have profiles similar to chronically active neuroleptics... 

Several types of immunosuppression have also been tried. Azathioprine alone was found to have no effect on PBC [82], but additional benificial effects were found in combination with ursodeoxychohc add and corticosteroids [78]. Cyclosporin showed some success, espe-dally in corticosteroid-resistant autoimmune hepatitis [83], but its use is generally considerably hmited by severe side-effects. Corticosteroids were effective in the management of several types of autoimmune chronic active hepatitis [84,85] and in the management of acute al-cohohc hepatitis [86]. Their use, however, has to be brief hi order to minimize side-effects. In the treatment of PBC, corticosteroids alone were found to be toxic and had only limited efficacy [77]. 

The events described above demonstrate the complexity and fine balance between various processes resulting in either resolution or enhancement of inflammation. Failure to control one or more of these, and possibly other presently unknown, regulatory mechanisms may lead to chronic activation of the immune system resulting in chronic inflammatory diseases. 

Hepatitis Corticosteroids may be harmful in chronic active hepatitis positive for hepatitis B surface antigen. 

Hepatic function impairment Fenofibrate is associated with significant increases in serum transaminases (AST or ALT). Increases to more than 3 times the upper limit of normal (ULN) occurred. Hepatocellular, chronic active and cholestatic hepatitis associated with fenofibrate therapy have been reported after exposures of weeks to several years. 

Helicobacter pylori H. pylori is found in approximately 100% of chronic active antral gastritis cases, 90% to 95% of duodenal ulcer patients, and 50% to 80% of gastric ulcer patients. The treatment of documented H. pylori infection in patients with confirmed peptic ulcer on first presentation or recurrence has been recommended by the National Institutes for Health in a 1994 Consensus Conference. Once H. py/on eradication has been achieved, reinfection rates are less than 0.5% per year, and ulcer recurrence rates are dramatically reduced. 

Hepatic reactions Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. 

Hepatic Cholestatic jaundice, chronic active hepatitis, hepatic necrosis, hepatic reactions, hepatitis (rare). 

Rat 13 wk Resp 0.11 (alveolar macrophage 0.2 (chronic active Benson et al. 

F (minimal to mild chronic active inflammation and alveolar epithelial hyperplasia)... 

Numerous studies in animals have investigated the respiratory effects of nickel exposure. Intermittent exposure (6 hours/day, 5 days/week) of rats and mice for 16 days or 13 weeks resulted in chronic active inflammation in the lungs, fibrosis, macrophage hyperplasia, interstitial infiltrates, and increased lung weight following exposure to 0.06 mg nickel/m as nickel sulfate, 0.11 mg nickelM as nickel subsulfide, and 0.4 mg nickel/m as nickel oxide (Benson et al. 1987, 1988, 1989 Durmick et al. 

In an intermediate-duration inhalation study of nickel sulfate in rats (Dunnick et al. 1989 NTP 1996c), alveolar macrophage hyperplasia was observed at all concentrations (0, 0.03, 0.06, 0.11, 0.22, and 0.44 mg nickel/m ), and chronic active inflammation of the lungs and olfactory epithelial atrophy were noted at 0.6 mg/m. Macrophage hyperplasia tends to be an inconsistent or perhaps reversible effect that showed an increase after 7 months of exposure but not at 2 years in the chronic study. In addition to being a minimal or reversible effect, alveolar macrophage hyperplasia can be attributed to the physical stimulus of particulate treatment and is not necessarily speciflc for nickel. Therefore use of 0.03 mg/m as a LOAEL for macrophage hyperplasia to derive an intermediate MRL is questionable. Because the NOAEL identified in the chronic study (0.03 mg/m ) is at the level of a minimal LOAEL in the intermediate-duration study, the chronic MRL should be protective of both chronic- and intermediate-duration exposures. 

In this profile, a chronic-duration inhalation MRL of 2x lO " mg nickel/m has been derived based on a NOAEL of 0.03 mg nickel/m as nickel sulfate that was identified in a 2-year study of nickel sulfate in rats (NTP 1996c). Chronic active inflammation of the lungs was observed at 0.06 mg nickel/m. The inflammation was described as follows multifocal, minimal-to-mild accumulations of macrophages, and neutrophils and cell debris within alveolar spaces. The prevalence of lung fibrosis was also significantly increased at 0.06 mg nickel/m This chronic-duration inhalation MRL should also be protective of intermediate-duration exposure. 

Body weights of female rats were 6-9% lower than controls during the second year. Hematology examinations completed at a 15 month interim sacrifice showed no effects. The only treatment-related changes noted were in the respiratory tract. Minimal to mild chronic active inflammation was observed at all concentrations at the 7 month interim sacrifice, but only at the two higher concentrations at two years. The inflammation was described as multifocal, minimal to mild accumulations of macrophages, neutrophils and cell debris within alveolar spaces. Fibrosis was observed in 2/54, 6/53, 35/53 and 43/53 male rats, and 8/52, 7/53, 45/53, and 49/53 female rats at 0, 0.03, 0.06, and 0.11 mg/m, respectively. Hyperplasia of the bronchial lymph nodes and atrophy of the olfactory epithelium were observed at the high dose. 

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