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)

Endothelins are powerful vasoconstrictor agents produced by endothelial cells and identified by Yanagisawa et al. in 1988. Two types of receptors for endothelins have been identified: ET(A) receptors are located on smooth muscle cells of the vascular wall and are responsible for endothelin-induced vasoconstriction while ET(B) receptors are located on endothelial cells and induce these cells to release NO and prostacyclin. Moreover, these peptides not only cause a potent and prolonged vasoconstriction but are also known to enhance cell proliferation and to stimulate extracellular matrix accumulation. High levels of plasma or tissue endothelins have been found in patients with heart failure, diabetes, stroke, primary pulmonary hypertension, liver cirrhosis and other diseases. Given these effects of endothelins, blocking their receptors might be a new way to reduce blood pressure and to treat other illnesses. Accordingly, many endothelin antagonists have been developed and evaluated in animals and humans. Enrasentan is a mixed ET(A) and ET(B) receptor antagonist with a higher affinity for ET(A) receptors, although it cannot be considered a selective antagonist. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan has been added to conventional treatment in patients with heart failure (NYHA Class 2-3) and no addictive effect of the drug has been observed. This is in contrast with results obtained in animal models and still has not been explained. In conclusion, many possible clinical applications can be suggested for this drug, but further studies are necessary to better evaluate its therapeutic efficacy.
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PMID:Enrasentan, an antagonist of endothelin receptors. 1259 14

Alcohol abuse is the third leading preventable cause of death in the United States. Because binge and heavy drinking increase the risk for cirrhosis, cancer, heart disease, stroke, injury, and depression, public health efforts have focused on reducing these patterns of alcohol use. The Council of State and Territorial Epidemiologists, the Association of State and Territorial Chronic Disease Program Directors, and CDC developed Indicators for Chronic Disease Surveillance, which provides a standard set of measures for alcohol surveillance. The New Hampshire Department of Health and Human Services used these measures to facilitate statewide trend analysis of alcohol use among adolescents and adults. This report summarizes the results of that analysis, which indicated that, in 2003, a total of 30.6% of adolescents reported binge drinking. In 2001, a total of 15.8% of adults reported binge drinking, and 6.3% reported heavy drinking. Interventions are needed to prevent adolescent drinking and to reduce excessive alcohol use among adults.
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PMID:Alcohol use among adolescents and adults--New Hampshire, 1991-2003. 1500 78

Brain metastases from hepatocarcinoma are exceptional and only a few cases have been reported in the literature, mainly from Far-Eastern countries. Clinical diagnosis in asymptomatic patients with preserved liver function is difficult and usually late. In some cases, cerebral metastasis is the initial manifestation of HCC and patients may develop intracerebral hemorrage and have a stroke-like presentation. We report on the first Italian case of cerebral metastases from multifocal hepatocellular carcinoma in an asymptomatic HbsAg negative patient with unknown HCV related chronic hepatitis and no evidence of liver cirrhosis. For many years he had a mild liver enzyme elevation and the presence of multiple misinterpreted hypoechogenic hepatic lesions. The hepatic tumor spread to the lungs and the brain and the patient developed two major episodes of intracranial hemorrage. He had two nodular lesions in the brain and alpha-fetoprotein levels were more than 10,000 ng/ml. He died from neurologic causes, without major signs of liver failure.
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PMID:Intracranial hemorrage due to brain metastases in an Italian HCV patient with hepatocellular carcinoma. 1505 9

A 54-year-old man was found dead in the driver's seat of his vehicle on a winter's day. Investigations of the vehicle revealed that the engine was running, and the car heater was left on with the maximum temperature and velocity. The body was found excessively sweating. Rectal temperature of the body was 43 degrees C at 10 h post mortem. In autopsy, several superficial skin burns were observed on the face, the shoulders and the legs. The lungs were heavily congested and hemorrhagic. The liver showed typical alcohol-induced micronodular cirrhosis. The alcohol concentrations were 0.17% in the blood of both the left and the right heart, 0.17% in the femoral-vein blood, 0.21% in the bladder urine and 0.34% in the gastric contents. A reconstruction experiment demonstrated that the temperature inside the vehicle rose rapidly and reached 50-58 degrees C in 3 h. Animal experiments showed that the temperature threshold for rats to succumb to heat was between 40 and 45 degrees C. This case shows that heat stroke in a vehicle can occur in adults with chronic diseases or alcoholism, such as in this particular case, even in the winter.
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PMID:Death as a result of heat stroke in a vehicle: an adult case in winter confirmed with reconstruction and animal experiments. 1533 16

This article covers in vitro, in vivo, and human data on the positive effect of vitamin K2 on osteoporosis. Data is available on vitamin K2 for osteoporosis caused by a number of conditions, including postmenopausal osteoporosis, Parkinson's disease, biliary cirrhosis, stroke, and drug-induced osteoporosis. The activity of vitamin K2 involves both an increase in the bone-building process and a separate decrease in the bone-loss process. Vitamin K2 exerts a more powerful influence on bone than vitamin K1, and should be considered for prevention or treatment in those conditions known to contribute to osteoporosis.
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PMID:Vitamin K2 in bone metabolism and osteoporosis. 1577 60

The aim of the study was to analyze the etiology, the factors for progression of chronic renal failure to end-stage-renal disease (ESRD), and the influence of ESRD on the survival rate among a cohort of 59 heart transplant patients (HTP) referred for the management of chronic renal failure (CRF). At the time of the first nephrology consultation (6 +/- 4.25 years after cardiac transplantation) the mean creatininemia was 261.5 +/- 99 micromol/L and mean creatinine clearance (Cockcroft formula) was 32 +/- 15 mL/min. The cause of CRF were calcineurin inhibitor toxicity in 38.9% of patients, vascular events in 15.2%, hemolytic uremic syndrome in 5%, membranous glomerulopathy in 3.3%, diabetes in two patients, focal/segmental glomerulosclerosis in 3.3%, renal hypoplasia in 1.7%, and unknown in 27%. Evolution to ESRD occurred in 38.9% of patients: 17 patients started hemodialysis, three peritoneal dialysis, and two received a preemptive kidney transplantation. Creatininemia (micromol/L) at the time of nephrology referral was 229.2 +/- 72.6 versus 315.8 +/- 113.4 (P < .001) and creatinine clearance (mL/min) was 34.9 +/- 15.1 versus 27.3 +/- 13.7 (P = .049) for patients with CRF versus ESRD, respectively. Both proteinuria (g/24 hours) of 1 +/- 2.2 versus 2.3 +/- 1.8 (P = .02) and tobacco use in 35.1% versus 54.4% (P = .045) were significantly associated with progression of CRF, while age at the time of heart transplantation, cause of cardiac failure and renal failure, high blood pressure, type 2 diabetes, dyslipidemia, alcoholism, cirrhosis, and cerebral vascular accident were not. Death occurred in 18 HTP: 50% of patients with ESRD and 18.5% of patients with CRF-a 2.6 relative risk of of death in HTP patients with ESRD compared with HTP with CRF only (P < .01).
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PMID:Chronic renal failure and end-stage renal disease are associated with a high rate of mortality after heart transplantation. 1584 18

Etidronate is an oral bisphosphonate compound that is known to reduce bone resorption through the inhibition of osteoclastic activity. The efficacy of etidronate for involutional (postmenopausal and senile) and glucocorticoid-induced osteoporosis, as well as that for other skeletal diseases, was reviewed in Japanese patients. Cyclical etidronate treatment (200 mg or 400mg/day for 2 weeks about every 3 months) increases the lumbar bone mineral density (BMD) in patients with involutional osteoporosis and prevents incident vertebral fractures in patients with glucocorticoid-induced osteoporosis. The losses of the lumbar BMD in patients with liver cirrhosis and the metacarpal BMD in hemiplegic patients after stroke are prevented, and the lumbar BMD is possibly increased, preventing fragile fractures in adult patients with osteogenesis imperfecta type I. Furthermore, proximal bone resorption around the femoral stem is reduced and some complications may be prevented in patients who undergo cementless total hip arthroplasty. Oral etidronate treatment may also help to transiently relieve metastatic cancer bone pain followed by a decrease in abnormally raised bone resorption in patients with painful bone metastases from primary cancer sites, such as the lung, breast and prostate. Thus, oral etidronate treatment is suggested to be efficacious for osteoporosis, as well as other skeletal diseases associated with increased bone resorption, in Japanese patients. Randomized controlled trials needed to be conducted on a large number of patients to confirm these effects.
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PMID:Efficacy of oral etidronate for skeletal diseases in Japan. 1598 1

Despite the recent introduction of a number of new compounds, there has of late been a cooling of interest by pharmaceutical companies in the development of centrally-active, selective kappa opioid agonists for therapeutic purposes. This is reflected in the discontinuation of a number of clinical trials, for reasons that are often not completely clear to outside observers. Spiradoline and enadoline have apparently been abandoned as potential analgesics because they induce dose-limiting central side-effects (i.e., dysphoria) in models of post-surgical pain. The development of niravoline as an aquaretic for the treatment of cirrhosis with ascites and other hyponatraemic disorders has also been halted. Enadoline may yet find some application against ischaemic stroke and severe head injury, presumably in comatose patients in whom psychiatric side-effects are taken to be immaterial, while apadoline and TRK 820 remain in Phase II clinical testing against cancer pain. The peripherally-selective kappa agonists, asimadoline, and the atypical compound, fedotozine, are well-tolerated in man. Results of Phase III trials of fedotozine against irritable bowel syndrome and dyspepsia have, however, ultimately been disappointing, whereas asimadoline is currently in Phase II clinical trials against pain of rheumatic and osteoarthritic origin. The results of these trials are eagerly awaited.
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PMID:Novel developments with selective, non-peptidic kappa-opioid receptor agonists. 1598 6

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.
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PMID:Hepatic steatosis and vascular disease. 1623 88

Motor dysfunction is an important clinical finding in patients with liver cirrhosis and mild forms of hepatic encephalopathy. The mechanisms and clinical appearance of motor impairment in patients with liver cirrhosis are not completely understood. We studied fine motor control in forty four patients with advanced liver cirrhosis (excluding those with hepatic encephalopathy grade II) and 48 healthy controls using a kinematic analysis of standardized handwriting tests. We analysed parameters of velocity, the ability to coordinate and the level of automatisation of handwriting movements. Furthermore, we studied the association between impairment of handwriting and clinical neuro-psychiatric symptoms. As compared with control subjects, patients showed a statistically significant reduction of movement peak velocity in all handwriting tasks as well as a substantial increase of number of velocity inversions per stroke. Using a z-score based assessment we found impairment of handwriting in fourteen out of forty four patients (31.8 %). The deterioration of handwriting was associated with clinical symptoms of motor dysfunction, such as bradykinesia, adiadochokinesia, dysmetria of upper extremities and gait ataxia. This is the first study that quantitatively investigates impairment of handwriting in patients with liver cirrhosis. Our findings suggest the application of kinematic analysis of handwriting for diagnostics of motor dysfunction in patients with mild forms of hepatic encephalopathy.
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PMID:Motor dysfunction in patients with liver cirrhosis: impairment of handwriting. 1624 13


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