Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (Cmax) averaged 15.9 micrograms/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t1/2) was 6 to 7 hours. There were no apparent differences in Cmax, the time at which Cmax occurred (tmax), area under the serum concentration/time curve (AUC0-24), or t1/2 between groups of young men (n = 20), elderly men (n = 24), and elderly men with osteoarthritis (n = 20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in Cmax, tmax, AUC0-24 or t1/2 between groups of normal subjects (n = 10) and patients with mild-to-moderate renal impairment (n = 10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p less than 0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter tmax in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.
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PMID:Profile of etodolac: pharmacokinetic evaluation in special populations. 252 81

We investigated the association of non-insulin-dependent (Type 2) diabetes mellitus and depression symptoms in a representative community-dwelling elderly population independently of other conditions such as gender, age, status, disability, cognitive impairment and a number of chronic medical conditions such as chronic obstructive lung disease, degenerative joint disease, heart disease, cirrhosis of the liver, cholelithiasis, peptic ulcer and kidney stones. A total of 1339 elderly subjects living in southern Italy were randomly selected from electoral rolls and evaluated. All subjects were tested by the Geriatric Depression Scale to detect depression, the Mini-Mental State Examination to study cognitive function and the Activity Daily Living Index to evaluate disability. Non-insulin-dependent diabetes mellitus affected 14.7% of our sample. Depression was more prevalent in women over 75 years of age than in younger women (15.9 vs 8.1%, p < 0.001). In multiple linear regression analysis, diabetes mellitus was found to be significantly associated with depression independently of age, gender, loneliness, cognitive impairment, chronic obstructive lung disease, degenerative joint disease, heart diseases, cancer, kidney disease, cirrhosis of the liver and cholelithiasis. It is concluded that non-insulin-dependent diabetes mellitus is significantly associated with depression in the elderly, which may have clinical implications for the achievement of sufficient blood glucose control.
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PMID:Non-insulin-dependent diabetes mellitus is associated with a greater prevalence of depression in the elderly. The Osservatorio Geriatrico of Campania Region Group. 889 92

The numbers of elderly people in sub-Saharan Africa are growing rapidly with increasing life expectancy while at the same time the proportions of children in the populations are declining. The number of people 80 years and above increased tenfold in large parts of Africa since the 1950's, and the number of widows is growing fast. All this has several implications, including erosion of the social support by extended families and a dramatic change in the disease pattern. There will be increasing rates of cancer, liver cirrhosis, kidney failure, eye disease, osteoarthrosis, diabetes, mental illness and chronic degenerative illnesses such as cardiovascular disease. Multiple illness and permanent disability will become more common. African health care systems are ill-prepared for this transition, and social security for the elderly need to be improved in the coming years. Local and regional research into morbidity and well-being is important for policy formulation. The situation of different categories of chronically sick needs to be investigated. Improved health in childhood and middle age will probably be followed by improved health in old age, and this may offset the burden on the health care system of the growing number of elderly.
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PMID:Health and the elderly in developing countries with special reference to sub-Saharan Africa. 952 43

Diacerein is a drug for the treatment of patients with osteoarthritis. This drug is administered orally as 50 mg twice daily. Diacerein is entirely converted into rhein before reaching the systemic circulation. Rhein itself is either eliminated by the renal route (20%) or conjugated in the liver to rhein glucuronide (60%) and rhein sulfate (20%); these metabolites are mainly eliminated by the kidney. The pharmacokinetics characteristics of diacerein are about the same in young healthy volunteers and elderly people with normal renal function, both after a single dose (50 mg) or repeated doses (25 to 75 mg twice daily). Rhein kinetics after single oral doses of diacerein are linear in the range 50 to 200 mg. However, rhein kinetics are time-dependent, since the nonrenal clearance decreases with repeated doses. This results in a moderate increase in maximum plasma concentration, area under the plasma concentration-time curve and elimination half-life. Nevertheless, the steady-state is reached by the third administration and the mean elimination half-life is then around 7 to 8 hours. Taking diacerein with a standard meal delays systemic absorption, but is associated with a 25% increase in the amount absorbed. Mild-to-severe (Child Pugh's grade B to C) liver cirrhosis does not change the kinetics of diacerein, whereas mild-to-severe renal insufficiency (creatinine clearance < 2.4 L/h) is followed by accumulation of rhein which justifies a 50% reduction of the standard daily dosage. Rhein is highly bound to plasma proteins (about 99%), but this binding is not saturable so that no drug interactions are likely to occur, in contrast to those widely reported with nonsteroidal anti-inflammatory drugs. Except for moderate and transient digestive disturbances (soft stools, diarrhoea), diacerein is well tolerated and seems neither responsible for gastrointestinal bleeding nor for renal, liver or haematological toxicity.
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PMID:Clinical pharmacokinetics of diacerein. 983 88

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of many conditions including rheumatoid arthritis, osteoarthritis, gouty arthritis, the joint and muscle discomfort associated with systemic lupus erythematosus, and other musculoskeletal disorders. Yet, their benefits, which are believed to be a result of their ability to inhibit cyclooxygenase-2 (COX-2), are accompanied by considerable toxicity. NSAIDs' untoward effects are attributed to their inhibition of the constitutively expressed enzyme cyclooxygenase-1 (COX-1), with attendant suppression of the synthesis of prostanoids, substances that mediate key homeostatic functions. Side effects include suppression of hemostasis through inhibition of platelet aggregation, adverse effects in patients with heart failure and cirrhosis, and those with certain renal diseases, as well as complicating antihypertensive therapies involving diuretics or beta-adrenoceptor blockade. Perhaps most importantly, NSAIDs disrupt the gastrointestinal mucosal-protective and acid-limiting properties of prostaglandins, frequently leading to upper gastrointestinal erosions and ulceration, with possible subsequent hemorrhage and perforation. These complications can be reduced through identification of patients at risk, with circumspect use of NSAIDs, careful functional monitoring, and, in the case of gastrointestinal toxicity, co-administration of such agents as misoprostol or omeprazole. However, these strategies introduce complexity into the treatment paradigm. Moreover, side effects and adverse events may be significantly reduced through the use of COX-2-specific inhibitors, new agents that alleviate pain and inflammation without the liability for adverse events caused by COX-1 inhibition.
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PMID:Gastrointestinal effects of nonsteroidal anti-inflammatory therapy. 1039 Jan 23

Elevated levels of CHI3L1 (chitinase-3-like protein 1) are associated with disorders exhibiting increased connective tissue turnover, such as rheumatoid arthritis, osteoarthritis, scleroderma, and cirrhosis of the liver. This secreted protein is not synthesized in young healthy cartilage, but is produced in cartilage from old donors or patients with osteoarthritis. The molecular processes governing the induction of CHI3L1 are currently unknown. To elucidate the molecular events involved in CHI3L1 synthesis, we investigated two models of articular chondrocytes: neonatal rat chondrocytes, which do not express CHI3L1, and human chondrocytes, which express CHI3L1 constitutively. In neonatal rat chondrocytes, the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 potently induced steady-state levels of CHI3L1 mRNA and protein secretion. Treatment of chondrocytes with TNF-alpha for as little as 1 h was sufficient for sustained induction up to 72 h afterward. Using inhibitors selective for the major signaling pathways implicated in mediating the effects of TNF-alpha and interleukin-1, only inhibition of NF-kappaB activation was effective in curtailing cytokine-induced expression, including after removal of the cytokine, indicating that induction and continued production of CHI3L1 are controlled mainly by this transcription factor. Inhibition of NF-kappaB signaling also abolished constitutive expression by human chondrocytes. Thus, induction and continued secretion of CHI3L1 in chondrocytes require sustained activation of NF-kappaB. Selective induction of CHI3L1 by cytokines acting through NF-kappaB coupled with the known restriction of the catabolic responses by CHI3L1 in response to these inflammatory cytokines represents a key regulatory feedback process in controlling connective tissue turnover.
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PMID:Inflammatory cytokines induce production of CHI3L1 by articular chondrocytes. 1623 40

A 51-year-old Caucasian female presented with asymmetric arthritis and a positive rheumatoid factor. She was initially treated for rheumatoid arthritis. However, she had features such as abnormal liver function tests and osteoarthritis in an unusual location, the metacarpophalangeal joint. Further workup revealed that the patient had active hepatitis C and hereditary hemochromatosis. Phlebotomy treatment initiation seemed to be associated with improvement in joint symptoms but, more importantly, may have prevented future risk of cirrhosis and hepatocellular cancer. Treatment for the hepatitis C may also be needed. Clinicians should look for underlying systemic illnesses leading to atypical inflammatory arthritis.
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PMID:Atypical arthritis due to combined hereditary hemochromatosis and active hepatitis C. 1843 Oct 93

Though medical consequences of war attract attention, the health consequences of the prisoner-of-war (POW) experience are poorly researched and appreciated. The imprisonment of Allied military personnel by the Japanese during the World War II provides an especially dramatic POW scenario in terms of deprivation, malnutrition and exposure to tropical diseases. Though predominantly British, these POWs also included troops from Australia, Holland and North America. Imprisonment took place in various locations in Southeast Asia and the Far East for a 3.5-year period between 1942 and 1945. Nutritional deficiency syndromes, dysentery, malaria, tropical ulcers and cholera were major health problems; and supplies of drugs and medical equipment were scarce. There have been limited mortality studies on ex-Far East prisoners (FEPOWs) since repatriation, but these suggest an early (up to 10 years post-release) excess mortality due to tuberculosis, suicides and cirrhosis (probably related to hepatitis B exposure during imprisonment). In terms of morbidity, the commonest has been a psychiatric syndrome which would now be recognized as post-traumatic stress disorder--present in at least one-third of FEPOWs and frequently presenting decades later. Peptic ulceration, osteoarthritis and hearing impairment also appear to occur more frequently. In addition, certain tropical diseases have persisted in these survivors--notably infections with the nematode worm Strongyloides stercoralis. Studies 30 years or more after release have shown overall infection rates of 15%. Chronic strongyloidiasis of this type frequently causes a linear urticarial 'larva currens' rash, but can potentially lead to fatal hyperinfection if immunity is suppressed. Finally, about 5% of FEPOW survivors have chronic nutritional neuropathic syndromes--usually optic atrophy or sensory peripheral neuropathy (often painful). The World War II FEPOW experience was a unique, though often tragic, accidental experiment into the longer term effects of under nutrition and untreated exotic disease. Investigation of the survivors has provided unique insights into the medical outcome of deprivation in tropical environments.
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PMID:Consequences of captivity: health effects of far East imprisonment in World War II. 1924 47

Human Glyco_18 domain-containing proteins constitute a family of chitinases and chitinase-like proteins. Chitotriosidase and AMCase are true enzymes which hydrolyse chitin and have a C-terminal chitin-binding domain. YKL-40, YKL-39, SI-CLP and murine YM1/2 proteins possess solely Glyco_18 domain and do not have the hydrolytic activity. The major sources of Glyco_18 containing proteins are macrophages, neutrophils, epithelial cells, chondrocytes, synovial cells, and cancer cells. Both macrophages and neutrophils use the regulated secretory mechanism for the release of Glyco_18 containing proteins. Glyco_18 containing proteins are established biomarkers for human diseases. Chitotriosidase is overproduced by lipid-laden macrophages and is a major marker for the inherited lysosomal storage Gaucher disease. AMCase and murine lectin YM1 are upregulated in Th2-environment, and enzymatic activity of AMCase contributes to asthma pathogenesis. YKL proteins act as soluble mediators for the cell proliferation and migration, and are also involved in rheumatoid arthritis, inflammatory bowel disease, hepatic fibrosis and cirrhosis. Chitotriosidase and YKL-40 reflect the macrophage activation in atherosclerotic plaques. Serum level of YKL-40 is a diagnostic and prognostic marker for numerous types of solid tumors. YKL-39 is a marker for the activation of chondrocytes and the progression of the osteoarthritis in human. Recently identified SI-CLP is upregulated by Th2 cytokine IL-4 as well as by glucocorticoids. This unique feature of SI-CLP makes it an attractive candidate for the examination of individual sensitivity of patients to glucocorticoid treatment and prediction of side effects of glucocorticoid therapy. Human chitinases and chitinase-like proteins are found in tissues and circulation, and can be detected by non-invasive technologies.
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PMID:Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. 1966 98

Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.
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PMID:Matrix metalloproteinases involvement in pathologic conditions. 2049 35


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