Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 70 alcoholic patients the amount of collagen in the space of Disse was compared, using an electron microscopic graded score, to the height of the intrahepatic pressure. A highly significant correlation was found between the amount of collagen and intrahepatic pressure in the group as a whole (r = 0.84; p < 10(-6)), as well as in subgroups of 30 alcoholic patients with normal livers or steatosis (r = 0.83; p < 10(-6)), 9 patients with alcoholic hepatitis (r = 0.81; p < 0.01), and 31 with cirrhosis (r = 0.86; p < 10(-6)). A nonparametric correlational analysis for the complete group also showed a significant relationship (rho = 0.85; p < 10(-6)) between collagen scores and intrahepatic pressure. In 60 patients hepatocyte surface area was measured in the biopsies. In these, hepatocyte surface area significantly correlated with intrahepatic pressure (r = 0.68; p < 10(-7)). No correlation was found between intrahepatic pressure and fat, alcoholic hyalin, or terminal hepatic vein sclerosis. Only with necrosis (r = 0.38; p < 0.001) and inflammation (r = 0.29; p < 0.05) was there a significant relationship with intrahepatic pressure. Chronic ethanol administration for 4 wk in liquid diets to young Wistar rats produced a 50% hepatomegaly due to an increase in hepatocyte size. Intrahepatic pressure in the rats receiving alcohol (19.3 +/- 2.3 mmHg) was significantly higher than in the controls on sucrose (10.4 +/- 0.9 mmHg) (p < 0.01). A highly significant correlation was found between hepatocyte surface area and intrahepatic pressure (r = 0.70; p < 0.005). There was no increase in collagen in the Disse space in these animals. Therefore, hepatomegaly in the absence of an increase in collagen in the Disse space may result in increased intrahepatic pressure. These studies may indicate a sequence of events: hepatomegaly, portal hypertension, and collagenization in the Disse space, which could occur in alcoholic liver disease.
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PMID:Correlation of intrahepatic pressure with collagen in the Disse space and hepatomegaly in humans and in the rat. 745 Apr 45

The purpose of this study was to determine whether long-term ethanol consumption affects the long-term regeneration of the liver after partial hepatectomy and to study whether the metabolic demands imposed on the liver by the regenerative process accentuate liver damage produced in the liver by ethanol. Animals fed alcohol (35% of total calories) in liquid diets over time were partially hepatectomized (68% removal) and then were given ethanol-containing diets until complete liver restitution. They were studied at 24 hr and at 7 and 14 days. At these times, prior and continued ethanol administration did not result in changes in total DNA restituted, percent of cells undergoing mitosis, or incorporation of 3H-thymidine into DNA as determined chemically and by autoradiography. After partial hepatectomy, ethanol-fed animals showed a reduction in both DNA and proteins per gram of liver. However, these effects were the result of the hepatomegaly induced by ethanol and were also observed in sham-operated animals fed the diets containing ethanol. An apparent decrease in percent restitution of live weight was observed at 24 hr after hepatectomy in the ethanol-fed animals. However, this was caused by a marked increase in hepatocyte size in the controls, which matched the already enlarged hepatocytes in the ethanol-fed animals. Partial hepatectomy was found to transiently increase the lipid content of the livers in control animals. In ethanol-fed animals partial hepatectomy resulted in markedly fatty livers, as observed both histologically and chemically, which exceeded these abnormalities in alcohol-fed sham-operated rats. In conclusion, long-term ethanol consumption prior to partial hepatectomy and continuous ethanol consumption after the operation did not affect negatively the complete restitution of the liver when compared with controls.
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PMID:Long-term ethanol administration and short- and long-term liver regeneration after partial hepatectomy. 745 93

Bacterin of Propionibacterium acnes (Corynebacterium parvum), its cellular fractions (lipids, fractions obtained by mechanical disruption and differential centrifugation, by phenol-water and pyridine extractions), and a polysaccharide from culture filtrate were prepared and tested in mice. The activation of RES by splenomegaly and hepatomegaly, prevention of listerial infection, prevention of the lethal effect of sarcoma 180, and depression of liver microsomal cytochrome P-450 were employed. The bacterin was effective in all tests. Lipid-free cells were less active, in particular in the activation of RES and in the listerial infection model. Fractions prepared by the disruption and differential centrifugation lost their activity in all tests along with a decrease in molecular weight. Lipids extracted by ethanol caused pronounced splenomegaly and decreased the cytochrome P-450 content. The residue left after the phenol-water extraction was very active, its delipidation did not destroy the activity. Pyridine extraction provided a completely inactive extract, but a very active residue. The possibility of reducing the complexity of bacterin while preserving immunomodulatory effect is demonstrated.
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PMID:The influence of Propionibacterium acnes (Corynebacterium parvum) fractions on immune response in vivo. 772 4

Protein accumulation in liver cells contributes to alcohol-induced hepatomegaly and is the result of an ethanol-elicited deceleration of protein catabolism (Alcohol Clin Exp Res 13:49, 1989). Because lysosomes are active in the degradation of most hepatic proteins, the present studies were conducted to determine whether ethanol administration altered the proteolytic activities of partially purified hepatic lysosomes. Rats were fed liquid diets containing either ethanol (36% of calories) or isocaloric maltodextrin for periods of 2-34 days. Prior to death, all animals were injected with [3H]leucine to label hepatic proteins. Rats subjected to even brief periods of ethanol feeding (2-8 days) exhibited significant hepatomegaly and hepatic protein accumulation compared with pair-fed control animals. Crude liver homogenates and isolated lysosomal-mitochondrial and cytosolic subfractions were incubated at 37 degrees C, and the acid-soluble radioactivity generated during incubation was measured as an index of proteolysis. At neutral pH, in vitro protein breakdown in incubated liver homogenates and subcellular fractions from control and ethanol-fed rats did not differ significantly. The extent of protein hydrolysis increased when samples were incubated at pH 5.5, which approximates the pH optimum for catalysis by lysosomal acid proteases. Under the latter conditions, partially purified lysosomes from control animals had 2-fold higher levels of proteolysis than corresponding fractions from ethanol-fed rats. The difference in proteolytic capacity appeared to be related to a lower latency and a higher degree of fragility of lysosomes from ethanol-fed rats at the acidic pH.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1994 Jun
PMID:Ethanol administration alters the proteolytic activity of hepatic lysosomes. 794 51

Alcoholic hepatitis is a precirrhotic lesion; it develops in only a minority of chronic alcohol abusers even after decades of abuse. The clinical spectrum of disease varies from asymptomatic hepatomegaly to florid hepatocellular failure with gastrointestinal bleeding and hepatic encephalopathy. Corresponding variation is observed both in morbidity and mortality. The majority of individuals with mild to moderate alcoholic hepatitis improve significantly following abstinence from alcohol and the provision of a diet sufficient to meet their nutritional requirements; their long-term outcome is determined largely by their ability to maintain abstinence from alcohol. Individuals with severe alcoholic hepatitis require intensive nutritional support and vigorous management of the complications of their liver injury; their outcome is generally poor. A small, carefully selected subgroup of these very sick patients may benefit, at least in the short-term, from treatment with corticosteroids; the place of orthotopic hepatic transplantation, in this patient group, is still the subject of debate. No other treatment modalities have been shown to confer benefit consistently. A number of new therapeutic approaches have been proposed and need to be explored.
Alcohol Alcohol 1996 Mar
PMID:The treatment of alcoholic hepatitis. 873 7

Cardiomyopathy is a consistent feature of diabetic myocardium as well as in prolonged alcohol consumption. Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes. The present study compares the effectiveness of the calcium channel blocker nifedipine (dihydropyridine-type) with verapamil (phenylalkylamine-type) in reversing myocardial dysfunction and diminishing the negative inotropic effect of ethanol on diabetic rat myocardium. Wistar rats were made diabetic with streptozotocin (55 mg/kg, i.v.) and isolated electrically stimulated papillary muscles were studied under isometric conditions in the absence and presence of clinically relevant concentrations of ethanol (80-240 mg/dl, i e., 17.4-52.1 mM). Subgroups of diabetic and normal animals received daily injections of verapamil or nifedipine 2 weeks after induction of diabetes for 8 weeks. Untreated diabetic animals exhibited hyperglycemia, hyperlipidemia, reduced growth, cardiomegaly, and hepatomegaly. Compared to verapamil chronic nifedipine treatment normalized or reversed the effects of diabetes on myocardial mechanical function. The negative inotropic effect of ethanol was attenuated only in muscles from verapamil-treated diabetic animals. Thus, chronic nifedipine treatment may be more effective than verapamil in reducing hyperglycemia, attenuating both cardiac and liver enlargement, and restoring myocardial mechanical function, in experimental diabetes. However, chronic verapamil therapy is more effective in diminishing the negative inotropic effect of ethanol on diabetic myocardium. These findings may have clinical significance among diabetic patients who consume alcoholic beverages while receiving long-term calcium blocker therapy.
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PMID:Differential effects of chronic calcium channel blocker treatment on the inotropic response of diabetic rat myocardium to acute ethanol exposure. 876 17

The direct toxic effect of alcohol and its metabolite acetaldehyde has been demonstrated both in laboratory animals and in humans. Alterations in the mitochondrial ultrastructure and the dilatation of the sarcoplasmatic reticulum have been shown after an acute infusion of alcohol in the heart. These changes correlate with decreased mitochondrial function, defects in protein synthesis and the occurrence of arrhythmias. The risk of developing alcoholic cardiomyopathy is related to both the mean daily alcohol intake and the duration of drinking, but there is much individual susceptibility to the toxic effect of alcohol. Most patients, in whom alcoholic cardiomyopathy develops, have been drinking over 80 g/d for more than 5 years. The clinical diagnosis of alcoholic cardiomyopathy reflects the coexistence of global myocardial dysfunction in a heavy drinker in whom no other cause for myocardial disease was found. In studies focussing on alcoholic cardiomyopathy the surprising histologic findings in endomyocardial biopsy in about 30% of all cases was myocarditis with a lymphocytic infiltrate in association with myocyte degeneration or focal necrosis. In myocarditis, the network of microtubules and intermediate filaments is also disrupted by the inflammatory reaction which involves resident cells (myocytes, fibroblasts, endothel cells) and systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. After all, in patients with alcohol abuse and myocarditis the immune functioning appears to be compromised. Several studies suggest that heavy drinking alters both lymphocyte and granulocyte production and function. Alcohol consumption per se might harm the immune system. Furthermore, the myocardial damage due to alcohol consumption could initiate autoreactive mechanisms comparable to those in viral or idiopathic myocarditis. Patients with alcohol abuse and myocarditis have a poor prognosis: signs of biventricular failure including tachycardia, hepatomegaly, and peripheral and lung edema are observed. These symptoms are as nonspecific as are various echocardiographic and electrocardiographic changes such as atrial and ventricular arrhythmias which may be associated both with myocarditis, alcoholic cardiomyopathy and acute effects of drinking without hemodynamic alterations. For the management of patients with alcohol abuse the prevention of further alcohol intake is mandatory to reverse the myocardial damage and the unfavorable predisposition for infection. Specific treatment of myocarditis is the second important option, and treatment of heart failure by reducing the size of the dilated heart and alleviating the signs and symptoms of heart failure is a logical third step.
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PMID:[Alcohol and myocarditis]. 880 5

1. Two separate cases of acute occupational poisoning following exposure to vapours of a fire extinguishing liquid are described. Analytical, clinical, pathological and toxicological data leave little doubt that toxicity was due, in both cases, to inhalation of carbon tetrachloride present at high concentrations ( > 15% and 78% by weight, respectively) in the fire extinguishing liquid. 2. Both subjects were admitted to hospital, 4 and 8 days after exposure, respectively, and developed severe hepato-nephrotoxicity with hepatomegaly, increased values of serum transaminases, blood urea nitrogen (BUN), creatinine, gamma-glutamyl-transpeptidase (gamma-GT), bilirubin and uric acid and, finally, anuria. They recovered in about three to four weeks, after several haemodialytic sessions. 3. Interestingly, in both cases the other workers exposed under the same conditions and for the same period of time as the two patients showed no signs or symptoms of toxicity. The reason for the observed different susceptibility to CCl4 is attributable to an abnormally high ethanol abuse by the two workers, as reported in the clinical records and confirmed by their relatives and colleagues (120 and 250 g per day, respectively). Daily ethanol intake by the coworkers was less than 50 g for all subjects. 4. Although the potentiating effect of ethanol on the toxicity of CCl4 is well known in experimental animals, as a result of cytochrome P-450 induction, direct evidence in humans reported in the literature so far was limited by the lack of information, in all published reports, on the presence or absence of effects in non-alcoholic exposed "controls', when these were present.
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PMID:Potentiation of occupational carbon tetrachloride toxicity by ethanol abuse. 884 18

Acute ethanol exposure depresses cardiac electromechanical function, whereas chronic ethanol consumption leads to the development of a specific myopathic state. Chronic hypertension and aging have similar effects in the impairment of myocardial function. However, little is known about the effects of ethanol on cardiac mechanical function in hypertension. We studied the effect of age on baseline mechanical properties and the inotropic response to clinically relevant concentrations of ethanol (18 to 71 mmol/L) using papillary muscles from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 10 and 25 weeks of age. Mechanical parameters measured were peak tension developed, time to peak tension, time to 90% relaxation, and maximal velocities of tension development and tension decline. SHR exhibited elevated systolic pressure and body weight as well as cardiomegaly and hepatomegaly at 10 and 25 weeks of age. Baseline mechanical properties were similar in SHR and WKY muscles at 10 weeks, whereas at 25 weeks, SHR muscles developed less tension, and both maximal velocities of tension development and tension decline were markedly depressed. Ethanol exposure produced concentration-dependent negative inotropic effects in both groups at both ages. Ethanol (> 18 nmol/L) decreased peak tension developed in both groups at 10 weeks, although higher concentrations were required at 25 weeks. The negative inotropic effect of ethanol resulted in the shortening of time to 90% relaxation in both groups at 10 weeks and was associated with a slowing of maximal velocities of both tension development and tension decline. The results suggest that aging depresses baseline mechanical properties when coupled with hypertension. In addition, the magnitude of the negative inotropic effect of ethanol was attenuated in both groups at 25 weeks of age.
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PMID:Influence of age on the inotropic response to acute ethanol exposure in spontaneously hypertensive rats. 890 37

Chronic ethanol consumption induces hepatocellular retention of nascent proteins leading to hepatomegaly. While the molecular mechanisms behind this impairment are undefined, it has been predicted that protein retention results from a disruption of vesicle-mediated secretory processes. Small GTP-binding proteins (rab proteins) have recently been implicated in the regulation of vesicular trafficking in eukaryotic cells. Our objectives were to identify intracellular sites of ethanol-induced protein retention and to determine whether the distribution of secretory rab proteins was altered by ethanol. Transport of hepatic proteins along the secretory pathway in livers from control and ethanol-fed rats was analyzed using subcellular fractionation and immunoprecipitation in the context of in vivo pulse-chase experiments. We show that pre-Golgi and Golgi compartments, as well as secretory vesicles, are sites of ethanol-induced retention of nascent soluble and transmembrane secretory proteins. These results are supported by immunofluorescence localization of hepatic proteins on liver sections. Further, immunoblot analyses of hepatic subcellular fractions from ethanol-damaged livers indicate a dramatic reduction in the association of rab2 with a Golgi compartment as compared with controls. In contrast, rab6 and alpha-mannosidase II, Golgi marker proteins, appear unchanged. These studies provide a detailed analysis of the intracellular site of ethanol-induced protein retention in the hepatocyte and lend novel insight into a potential mechanism behind this impairment. The effects of ethanol exposure on rab proteins and Golgi function are discussed.
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PMID:Ethanol-induced retention of nascent proteins in rat hepatocytes is accompanied by altered distribution of the small GTP-binding protein rab2. 890 35


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