Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.Liver Cirrhosis, Alcoholic: FIBROSIS of the hepatic parenchyma due to chronic excess ALCOHOL DRINKING.Liver Cirrhosis, Experimental: Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.Liver Cirrhosis, Biliary: FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.Liver Neoplasms: Tumors or cancer of the LIVER.Liver Diseases: Pathological processes of the LIVER.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Liver Function Tests: Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions.Hypertension, Portal: Abnormal increase of resistance to blood flow within the hepatic PORTAL SYSTEM, frequently seen in LIVER CIRRHOSIS and conditions with obstruction of the PORTAL VEIN.Ascites: Accumulation or retention of free fluid within the peritoneal cavity.Hepatic Encephalopathy: A syndrome characterized by central nervous system dysfunction in association with LIVER FAILURE, including portal-systemic shunts. Clinical features include lethargy and CONFUSION (frequently progressing to COMA); ASTERIXIS; NYSTAGMUS, PATHOLOGIC; brisk oculovestibular reflexes; decorticate and decerebrate posturing; MUSCLE SPASTICITY; and bilateral extensor plantar reflexes (see REFLEX, BABINSKI). ELECTROENCEPHALOGRAPHY may demonstrate triphasic waves. (From Adams et al., Principles of Neurology, 6th ed, pp1117-20; Plum & Posner, Diagnosis of Stupor and Coma, 3rd ed, p222-5)Esophageal and Gastric Varices: Dilated blood vessels in the ESOPHAGUS or GASTRIC FUNDUS that shunt blood from the portal circulation (PORTAL SYSTEM) to the systemic venous circulation. Often they are observed in individuals with portal hypertension (HYPERTENSION, PORTAL).Fatty Liver: Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.Hepatitis, Chronic: INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.Liver Regeneration: Repair or renewal of hepatic tissue.Carbon Tetrachloride: A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)Hepatitis: INFLAMMATION of the LIVER.Liver Circulation: The circulation of BLOOD through the LIVER.Thioacetamide: A crystalline compound used as a laboratory reagent in place of HYDROGEN SULFIDE. It is a potent hepatocarcinogen.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein.Portal System: A system of vessels in which blood, after passing through one capillary bed, is conveyed through a second set of capillaries before it returns to the systemic circulation. It pertains especially to the hepatic portal system.Liver Diseases, Alcoholic: Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.Hepatitis C, Chronic: INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.Gastrointestinal Hemorrhage: Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.alpha-Fetoproteins: The first alpha-globulins to appear in mammalian sera during FETAL DEVELOPMENT and the dominant serum proteins in early embryonic life.Portal Pressure: The venous pressure measured in the PORTAL VEIN.Drug-Induced Liver Injury: A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.Hepatitis, Viral, Human: INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D).Mitochondria, Liver: Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)Hepatitis B: INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.Hydrothorax: A collection of watery fluid in the pleural cavity. (Dorland, 27th ed)Hepatectomy: Excision of all or part of the liver. (Dorland, 28th ed)Alanine Transaminase: An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 22.214.171.124.Hepatitis B, Chronic: INFLAMMATION of the LIVER in humans caused by HEPATITIS B VIRUS lasting six months or more. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.Hepatitis C: INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.Paracentesis: A procedure in which fluid is withdrawn from a body cavity or organ via a trocar and cannula, needle, or other hollow instrument.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Hepatorenal Syndrome: Functional KIDNEY FAILURE in patients with liver disease, usually LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL), and in the absence of intrinsic renal disease or kidney abnormality. It is characterized by intense renal vasculature constriction, reduced renal blood flow, OLIGURIA, and sodium retention.End Stage Liver Disease: Final stage of a liver disease when the liver failure is irreversible and LIVER TRANSPLANTATION is needed.Liver Failure, Acute: A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.Hepacivirus: A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery.Hepatic Veins: Veins which drain the liver.Liver Neoplasms, Experimental: Experimentally induced tumors of the LIVER.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Liver Abscess: Solitary or multiple collections of PUS within the liver as a result of infection by bacteria, protozoa, or other agents.Hepatitis, Alcoholic: INFLAMMATION of the LIVER due to ALCOHOL ABUSE. It is characterized by NECROSIS of HEPATOCYTES, infiltration by NEUTROPHILS, and deposit of MALLORY BODIES. Depending on its severity, the inflammatory lesion may be reversible or progress to LIVER CIRRHOSIS.Bilirubin: A bile pigment that is a degradation product of HEME.Hepatitis B virus: The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum.Hepatitis, Autoimmune: A chronic self-perpetuating hepatocellular INFLAMMATION of unknown cause, usually with HYPERGAMMAGLOBULINEMIA and serum AUTOANTIBODIES.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Liver Extracts: Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia.Bile Ducts: The channels that collect and transport the bile secretion from the BILE CANALICULI, the smallest branch of the BILIARY TRACT in the LIVER, through the bile ductules, the bile ducts out the liver, and to the GALLBLADDER for storage.Liver Failure: Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Carbon Tetrachloride PoisoningTime Factors: Elements of limited time intervals, contributing to particular results or situations.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.Pancreatitis, Alcoholic: Acute or chronic INFLAMMATION of the PANCREAS due to excessive ALCOHOL DRINKING. Alcoholic pancreatitis usually presents as an acute episode but it is a chronic progressive disease in alcoholics.Cholestasis: Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).Hepatopulmonary Syndrome: A syndrome characterized by the clinical triad of advanced chronic liver disease, pulmonary vascular dilatations, and reduced arterial oxygenation (HYPOXEMIA) in the absence of intrinsic cardiopulmonary disease. This syndrome is common in the patients with LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL).Portasystemic Shunt, Transjugular Intrahepatic: A type of surgical portasystemic shunt to reduce portal hypertension with associated complications of esophageal varices and ascites. It is performed percutaneously through the jugular vein and involves the creation of an intrahepatic shunt between the hepatic vein and portal vein. The channel is maintained by a metallic stent. The procedure can be performed in patients who have failed sclerotherapy and is an additional option to the surgical techniques of portocaval, mesocaval, and splenorenal shunts. It takes one to three hours to perform. (JAMA 1995;273(23):1824-30)Elasticity Imaging Techniques: Non-invasive imaging methods based on the mechanical response of an object to a vibrational or impulsive force. It is used for determining the viscoelastic properties of tissue, and thereby differentiating soft from hard inclusions in tissue such as microcalcifications, and some cancer lesions. Most techniques use ultrasound to create the images - eliciting the response with an ultrasonic radiation force and/or recording displacements of the tissue by Doppler ultrasonography.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Melena: The black, tarry, foul-smelling FECES that contain degraded blood.Platelet Count: The number of PLATELETS per unit volume in a sample of venous BLOOD.Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Lypressin: The porcine antidiuretic hormone (VASOPRESSINS). It is a cyclic nonapeptide that differs from ARG-VASOPRESSIN by one amino acid, containing a LYSINE at residue 8 instead of an ARGININE. Lys-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.Venous Pressure: The blood pressure in the VEINS. It is usually measured to assess the filling PRESSURE to the HEART VENTRICLE.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Portasystemic Shunt, Surgical: Surgical venous shunt between the portal and systemic circulation to effect decompression of the portal circulation. It is performed primarily in the treatment of bleeding esophageal varices resulting from portal hypertension. Types of shunt include portacaval, splenorenal, mesocaval, splenocaval, left gastric-caval (coronary-caval), portarenal, umbilicorenal, and umbilicocaval.Antiviral Agents: Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Aspartate Aminotransferases: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 126.96.36.199.ROC Curve: A graphic means for assessing the ability of a screening test to discriminate between healthy and diseased persons; may also be used in other studies, e.g., distinguishing stimuli responses as to a faint stimuli or nonstimuli.Cholagogues and Choleretics: Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).Hepatic Stellate Cells: Perisinusoidal cells of the liver, located in the space of Disse between HEPATOCYTES and sinusoidal endothelial cells.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Amino Acids, Branched-Chain: Amino acids which have a branched carbon chain.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum.Prothrombin Time: Clotting time of PLASMA recalcified in the presence of excess TISSUE THROMBOPLASTIN. Factors measured are FIBRINOGEN; PROTHROMBIN; FACTOR V; FACTOR VII; and FACTOR X. It is used for monitoring anticoagulant therapy with COUMARINS.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Hepatitis B Surface Antigens: Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Hepatomegaly: Enlargement of the liver.Ligation: Application of a ligature to tie a vessel or strangulate a part.Splenectomy: Surgical procedure involving either partial or entire removal of the spleen.Serum Albumin: A major protein in the BLOOD. It is important in maintaining the colloidal osmotic pressure and transporting large organic molecules.Sclerotherapy: Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels.Bile Ducts, Intrahepatic: Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Peritonitis: INFLAMMATION of the PERITONEUM lining the ABDOMINAL CAVITY as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the PERITONEAL CAVITY via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the ABDOMINAL CAVITY itself through RUPTURE or ABSCESS of intra-abdominal organs.TaiwanSensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Common Bile Duct: The largest bile duct. It is formed by the junction of the CYSTIC DUCT and the COMMON HEPATIC DUCT.Tomography, X-Ray Computed: Tomography using x-ray transmission and a computer algorithm to reconstruct the image.Bacterial Translocation: The passage of viable bacteria from the GASTROINTESTINAL TRACT to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the INTESTINAL MUCOSA resulting in increased intestinal permeability. Bacterial translocation from the lung to the circulation is also possible and sometimes accompanies MECHANICAL VENTILATION.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Alcoholism: A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)gamma-Glutamyltransferase: An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Kupffer Cells: Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells.Egypt: A country in northern Africa, bordering the Mediterranean Sea, between Libya and the Gaza Strip, and the Red Sea north of Sudan, and includes the Asian Sinai Peninsula Its capital is Cairo.Indocyanine Green: A tricarbocyanine dye that is used diagnostically in liver function tests and to determine blood volume and cardiac output.Liver, Artificial: Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Liver Glycogen: Glycogen stored in the liver. (Dorland, 28th ed)Hemochromatosis: A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)Cholestasis, Intrahepatic: Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).HemosiderinKorea: Former kingdom, located on Korea Peninsula between Sea of Japan and Yellow Sea on east coast of Asia. In 1948, the kingdom ceased and two independent countries were formed, divided by the 38th parallel.Living Donors: Non-cadaveric providers of organs for transplant to related or non-related recipients.Albumins: Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.Jaundice: A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.Fasciolidae: A family of flukes of the class Trematoda occurring primarily in the liver of animals and man. There are six genera: Fasciola, Fasciolopsis, Fascioloides, Tenuifasciola, Parafasciolopsis, and Protofasciola. The adult form of Fasciolopsis occurs in the intestines of pigs and man.Hyperammonemia: Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Portography: Examination of the portal circulation by the use of X-ray films after injection of radiopaque material.Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.Splanchnic Circulation: The circulation of blood through the BLOOD VESSELS supplying the abdominal VISCERA.Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Hematemesis: Vomiting of blood that is either fresh bright red, or older "coffee-ground" in character. It generally indicates bleeding of the UPPER GASTROINTESTINAL TRACT.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.RomaniaRhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.Cholangiocarcinoma: A malignant tumor arising from the epithelium of the BILE DUCTS.Recurrence: The return of a sign, symptom, or disease after a remission.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Portacaval Shunt, Surgical: Surgical portasystemic shunt between the portal vein and inferior vena cava.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Alcohol Drinking: Behaviors associated with the ingesting of alcoholic beverages, including social drinking.Spleen: An encapsulated lymphatic organ through which venous blood filters.Splenomegaly: Enlargement of the spleen.Statistics, Nonparametric: A class of statistical methods applicable to a large set of probability distributions used to test for correlation, location, independence, etc. In most nonparametric statistical tests, the original scores or observations are replaced by another variable containing less information. An important class of nonparametric tests employs the ordinal properties of the data. Another class of tests uses information about whether an observation is above or below some fixed value such as the median, and a third class is based on the frequency of the occurrence of runs in the data. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1284; Corsini, Concise Encyclopedia of Psychology, 1987, p764-5)Chi-Square Distribution: A distribution in which a variable is distributed like the sum of the squares of any given independent random variable, each of which has a normal distribution with mean of zero and variance of one. The chi-square test is a statistical test based on comparison of a test statistic to a chi-square distribution. The oldest of these tests are used to detect whether two or more population distributions differ from one another.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Focal Nodular Hyperplasia: Solitary or multiple benign hepatic vascular tumors, usually occurring in women of 20-50 years of age. The nodule, poorly encapsulated, consists of a central stellate fibrous scar and normal liver elements such as HEPATOCYTES, small BILE DUCTS, and KUPFFER CELLS among the intervening fibrous septa. The pale colored central scar represents large blood vessels with hyperplastic fibromuscular layer and narrowing lumen.Kinetics: The rate dynamics in chemical or physical systems.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Iron Overload: An excessive accumulation of iron in the body due to a greater than normal absorption of iron from the gastrointestinal tract or from parenteral injection. This may arise from idiopathic hemochromatosis, excessive iron intake, chronic alcoholism, certain types of refractory anemia, or transfusional hemosiderosis. (From Churchill's Illustrated Medical Dictionary, 1989)Diethylnitrosamine: A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties.Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Ribavirin: A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.Organ Size: The measurement of an organ in volume, mass, or heaviness.Hepatitis D, Chronic: INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS in conjunction with HEPATITIS B VIRUS and lasting six months or more.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Cholangitis, Sclerosing: Chronic inflammatory disease of the BILIARY TRACT. It is characterized by fibrosis and hardening of the intrahepatic and extrahepatic biliary ductal systems leading to bile duct strictures, CHOLESTASIS, and eventual BILIARY CIRRHOSIS.Chemoembolization, Therapeutic: Administration of antineoplastic agents together with an embolizing vehicle. This allows slow release of the agent as well as obstruction of the blood supply to the neoplasm.Cholangitis: Inflammation of the biliary ductal system (BILE DUCTS); intrahepatic, extrahepatic, or both.Incidence: The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.Cytochrome P-450 CYP2E1: An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.Malnutrition: An imbalanced nutritional status resulted from insufficient intake of nutrients to meet normal physiological requirement.
Mir-652 microRNA precursor family: In molecular biology mir-652 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, with expression levels of miRNAs and respective target mRNAs negatively correlated.Metastatic liver disease: A liver metastasis is a malignant tumor in the liver that has spread from another organ affected by cancer. The liver is a common site for metastatic disease because of its rich, dual blood supply (the liver receives blood via the hepatic artery and portal vein).American Association for the Study of Liver Diseases: The American Association for the Study of Liver Diseases (AASLD) is the leading organization of scientists and health care professionals committed to preventing and curing liver disease. AASLD was founded in 1950 by a small group of leading liver specialists (including Hans Popper, Leon Schiff, Fred Hoffbauer, Cecil Watson, Jesse Bollman, and Sheila Sherlock, to name a few) to bring together those who had contributed to the field of hepatology.Liver sinusoid: A liver sinusoid is a type of sinusoidal blood vessel (with fenestrated, discontinuous endothelium) that serves as a location for the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.SIU SOM Histology GIJean Emond: Jean C. Emond is the current Thomas S.Fibrolamellar hepatocellular carcinomaLiver biopsyPortal hypertensionHepatic encephalopathyGastric varicesFatty liverSilicon tetrachlorideMicrosome: In cell biology, microsomes are vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.Pylephlebitis: Pylephlebitis (also called pyelophlebitis and infective suppurative thrombosis of the portal vein) is an uncommon thrombophlebitis of the portal vein or any of its branches (ie a portal vein thrombosis) that is caused by infection. It is usually a complication of intraabdominal sepsis, most often following diverticulitis, perforated appendicitis, or peritonitis.Portal-visceral hypothesisFibroTest: FibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy.Glasgow-Blatchford score: The Glasgow-Blatchford bleeding score (GBS) is a screening tool to assess the likelihood that a patient with an acute upper gastrointestinal bleeding (UGIB) will need to have medical intervention such as a blood transfusion or endoscopic intervention. The tool may be able to identify patients who do not need to be admitted to hospital after a UGIB.Alpha-fetoprotein: Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the AFP gene. The AFP gene is located on the q arm of chromosome 4 (4q25).Hepatitis B immune globulinHydrothoraxAlanine transaminase: Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALAT) and was formerly called serum glutamate-pyruvate transaminase (SGPT) or serum glutamic-pyruvic transaminase (SGPT).NitazoxanideList of people with hepatitis C: The infectious disease hepatitis C is caused by the hepatitis C virus (HCV), which affects the liver and is transmitted by blood-to-blood contact, or by exposure to another person's infected blood. The infection is often asymptomatic, but chronic infection can cause inflammation of the liver (chronic hepatitis).ParacentesisAscitesUnited Kingdom Model for End-Stage Liver Disease: The United Kingdom Model for End-Stage Liver Disease or UKELD is a medical scoring system used to predict the prognosis of patients with chronic liver disease. It is used in the United Kingdom to help determine the need for liver transplantation.King's College Criteria: The King's College Criteria or the King's College Hospital criteria were devised in 1989 to determine if there were any early indices of poor prognosis in patients with acute liver failure. Acute liver failure is defined as the onset of encephalopathy (altered mental status) or coagulopathy (altered bleeding tendencies) within 26 weeks of a patient diagnosed with liver disease.Canine hepacivirus: Canine hepacivirus is a single strand RNA virus of the genus Hepacivirus.Kapoor A, Simmonds P, Gerold G, Qaisar N, Jain K, Henriquez JA, Firth C, Hirschberg DL, Rice CM, Shields S, Lipkin WI (2011) Characterization of a canine homolog of hepatitis C virus.Splenic vein: The splenic vein (formerly the lienal vein) is a blood vessel that drains blood from the spleen, the stomach fundus and part of the pancreas. It is part of the hepatic portal system.Liver abscessAlcoholic hepatitisBilirubinHepatitis B virus precore mutant: A precore mutant is a variety of hepatitis B virus that does not produce hepatitis B virus e antigen (HBeAg). These mutants are important because infections caused by these viruses are difficult to treat, and can cause infections of prolonged duration and with a higher risk of liver cirrhosis.Autoimmune hepatitisCholangiocyte: Cholangiocytes are the epithelial cells of the bile duct. They are cuboidal epithelium in the small interlobular bile ducts, but become columnar and mucus secreting in larger bile ducts approaching the porta hepatis and the extrahepatic ducts.Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingNested case-control study: A nested case control (NCC) study is a variation of a case-control study in which only a subset of controls from the cohort are compared to the incident cases. In a case-cohort study, all incident cases in the cohort are compared to a random subset of participants who do not develop the disease of interest.Hepatopulmonary syndrome: In medicine, hepatopulmonary syndrome is a syndrome of shortness of breath and hypoxemia (low oxygen levels in the blood of the arteries) caused by vasodilation (broadening of the blood vessels) in the lungs of patients with liver disease. Dyspnea and hypoxemia are worse in the upright position (which is called platypnea and orthodeoxia, respectively).Transjugular intrahepatic portosystemic shuntBiomarkers of aging: Biomarkers of aging are biomarkers that better predict functional capacity at a later age than chronological age. Stated another way, biomarkers of aging would give the true "biological age", which may be different from the chronological age.Elpis Melena: Elpis Melena (1818–1899, born as Marie Espérance von Schwartz) was an Anglo-German writer who published under the name of Elpis Melena.Gross examinationQRISK: QRISK2 (the most recent version of QRISK) is a prediction algorithm for cardiovascular disease (CVD) that uses traditional risk factors (age, systolic blood pressure, smoking status and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with body mass index, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.TerlipressinBrain biopsyAntiviral drug: Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses.Tumor progression: Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells.Non-communicable disease: Non-communicable disease (NCD) is a medical condition or disease that is non-infectious or non-transmissible. NCDs can refer to chronic diseases which last for long periods of time and progress slowly.TransaminaseLeucineProthrombin time: The prothrombin time (PT) — along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) — are assays evaluating the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "PT/INR".ExbivirumabMature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.HepatosplenomegalyOverwhelming post-splenectomy infection: An overwhelming post-splenectomy infection (OPSI) is a rare but rapidly fatal infection occurring in individuals following removal of the spleen. The infections are typically characterized by either meningitis or sepsis, and are caused by encapsulated organisms including Streptococcus pneumoniae.Bisalbuminemia: Bisalbuminemia is the, sometimes inherited, condition of having two types of serum albumin that differ in mobility during electrophoresis. It can be seen in densitometry as a bifid mountain where albumin has 2 heads.Sclerotherapy
(1/499) Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation.
Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects. (+info)
(2/499) Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat.
We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCATbeta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis. In rats that received a single application of AdCATbeta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated. All AdCATbeta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCATbeta-TR-untreated rats died of liver dysfunction. The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearly in a persistent fibrosis model that prevention of fibrosis by anti-TGF-beta intervention could be therapeutically useful. (+info)
(3/499) Comparison of two aquaretic drugs (niravoline and OPC-31260) in cirrhotic rats with ascites and water retention.
kappa-Opioid receptor agonists (niravoline) or nonpeptide antidiuretic hormone (ADH) V2 receptor antagonists (OPC-31260) possess aquaretic activity in cirrhosis; however, there is no information concerning the effects induced by the chronic administration of these drugs under this condition. To compare the renal and hormonal effects induced by the long-term oral administration of niravoline, OPC-31260, or vehicle, urine volume, urinary osmolality, sodium excretion, and urinary excretion of aldosterone (ALD) and ADH were measured in basal conditions and for 10 days after the daily oral administration of niravoline, OPC-31260, or vehicle to cirrhotic rats with ascites and water retention. Creatinine clearance, serum osmolality, ADH mRNA expression, and systemic hemodynamics were also measured at the end of the study. Niravoline increased water excretion, peripheral resistance, serum osmolality, and sodium excretion and reduced creatinine clearance, ALD and ADH excretion, and mRNA expression of ADH. OPC-31260 also increased water metabolism and sodium excretion and reduced urinary ALD, although the aquaretic effect was only evident during the first 2 days, and no effects on serum osmolality, renal filtration, and systemic hemodynamics were observed. Therefore, both agents have aquaretic efficacy, but the beneficial therapeutic effects of the long-term oral administration of niravoline are more consistent than those of OPC-31260 in cirrhotic rats with ascites and water retention. (+info)
(4/499) TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis.
Transforming growth factor-beta1 (TGF-beta1) is a powerful stimulus for collagen formation in vitro. To determine the in vivo effects of TGF-beta1 on liver fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C-reactive protein (CRP)/TGF-beta1] consisting of the cDNA coding for an activated form of TGF-beta1 under the control of the regulatory elements of the inducible human CRP gene promoter. Two transgenic lines were generated with liver-specific overexpression of mature TGF-beta1. After induction of the acute phase response (15 h) with lipopolysaccharide (100 microgram ip), plasma TGF-beta1 levels reached >600 ng/ml in transgenic animals, which is >100 times above normal plasma levels. Basal plasma levels of uninduced transgenic animals were about two to five times above normal. As a consequence of hepatic TGF-beta1 expression, we could demonstrate marked transient upregulation of procollagen I and procollagen III mRNA in the liver 15 h after the peak of TGF-beta1 expression. Liver histology after repeated induction of transgene expression showed an activation of hepatic stellate cells in both transgenic lines. The fibrotic process was characterized by perisinusoidal deposition of collagen in a linear pattern. This transgenic mouse model gives in vivo evidence for the important role of TGF-beta1 in stellate cell activation and liver fibrogenesis. Due to the ability to control the level of TGF-beta1 expression, this model allows the study of the regulation and kinetics of collagen synthesis and fibrolysis as well as the degree of reversibility of liver fibrosis. The CRP/TGF-beta1 transgenic mouse model may finally serve as a model for the testing of antifibrogenic agents. (+info)
(5/499) Vascular properties of isoflurane: comparison between normal and cirrhotic rats.
Isoflurane is known to dilate blood vessels and to modulate nitric oxide production. Because cirrhosis is characterized by over production of endothelial nitric oxide, isoflurane-induced vasodilatation may be altered in this situation. We have compared the vasodilator effects of isoflurane in normal rats and rats with secondary biliary cirrhosis. Aortic rings (intact or endothelium denuded) from normal and cirrhotic rats were suspended in HEPES solution and preconstricted with KCl 40 mmol litre-1. Isoflurane dose-dependently relaxed vessels in both groups. Maximal relaxation was comparable between normal and cirrhotic rats in intact (mean 80 (SEM 4) vs 81 (6)%; ns) and in denuded (100 (4) vs 95 (5)%; ns) vessels. Intact vessels relaxed more than denuded vessels in both groups (100 (4) vs 80 (4)% (P = 0.0008) in normal rats and 95 (5) vs 80 (6)% (P = 0.0008) in cirrhotic rats). We conclude that cirrhosis did not modify isoflurane-induced vasodilatation and that the modulator effect of endothelium was conserved. (+info)
(6/499) Hepatic artery flow and propranolol metabolism in perfused cirrhotic rat liver.
The oxygen limitation theory states that capillarization of the sinusoidal endothelium in cirrhosis impairs hepatocellular oxygen uptake manifesting as a reduction in oxygen-dependent enzyme activity including phase 1 drug metabolism. The hepatic artery supplies highly oxygenated blood to the liver. Therefore, we tested whether augmentation of hepatic arterial blood flow could improve hepatic oxygenation and function in cirrhosis. Rats were treated with carbon tetrachloride and phenobarbitone to induce hepatic cirrhosis or fibrosis. We used a bivascular rat liver perfusion model to examine the effects of increased hepatic artery flow on propranolol clearance and oxygen consumption. Each liver was perfused at three hepatic artery flow rates, 1 to 3, 4 to 6, and 7 to 9 ml/min with a constant portal venous flow of 7 to 9 ml/min. Increasing the hepatic artery flow led to improvement in propranolol clearance in control (n = 7, P <.001), fibrotic (n = 8, P <.001), and cirrhotic (n = 6, P <.001) livers. Intrinsic clearance of propranolol increased only in the cirrhotic livers (P =.01), indicating an improvement in enzyme activity. Regression analysis indicated that this improvement was mediated by change in oxygen delivery alone (P =.001). The results confirm that propranolol metabolizing enzyme activity in cirrhosis can be improved by increasing oxygen delivery by increasing hepatic arterial blood flow. These findings suggest that increasing hepatic arterial blood flow may be an important therapeutic strategy for improving global liver function in cirrhosis. (+info)
(7/499) Role of Pneumolysin's complement-activating activity during pneumococcal bacteremia in cirrhotic rats.
We investigated the role of pneumolysin's complement-activating activity during Streptococcus pneumoniae bacteremia in a hypocomplementemic, cirrhotic host. Isogenic mutant pneumococcal strains, in which pneumolysin was expressed from a plasmid, were used. These strains included H+C+, expressing wild-type pneumolysin with both cytolytic and complement-activating activity; PLY-, carrying the plasmid without the pneumolysin gene; and, H+C-, expressing pneumolysin with cytolytic activity only. In control rats, intravenous infection with 2.0 x 10(7) CFU of H+C+ per ml of blood resulted in a decrease in bacteremia of 3.5 log units by 18 h postinfection and 55% mortality. By contrast, cirrhotic rats infected similarly with the H+C+ strain demonstrated a 0.2-log-unit increase in bacteremia by 18 h postinfection and 100% mortality. Both control and cirrhotic rats cleared the PLY- strain more effectively from their bloodstreams by 18 h postinfection (6.2 and 5. 6 log unit decreases, respectively). Infection with the PLY- strain also resulted in low mortality (0 and 14%, respectively) for control and cirrhotic rats. When infected with the H+C- strain (without complement-activating activity), both groups cleared the organism from their bloodstreams nearly as well as they did the PLY- strain. Furthermore, the mortality rate for control and cirrhotic rats was identical after infection with the H+C- strain. These studies suggest that pneumolysin production contributes to decreased pneumococcal clearance from the bloodstream and higher mortality in both control and cirrhotic rats. However, pneumolysin's complement-activating activity may uniquely enhance pneumococcal virulence in the hypocomplementemic, cirrhotic host. (+info)
(8/499) Dihydropyrimidine dehydrogenase activity and fluorouracil pharmacokinetics with liver damage induced by bile duct ligation in rats.
Hepatic metabolism is the main determinant in the pharmacokinetics of 5-fluorouracil (5-FU). Its disposition might be affected with liver dysfunction. In the present study, the influence of liver damage induced by bile duct ligation on dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme in 5-FU catabolism, CYP2B, and 5-FU pharmacokinetics were compared in male Sprague-Dawley rats. After 3 weeks of the ligation in two different groups of animals for in vitro and pharmacokinetic experiments, significant increases in serum bilirubin level and spleen weight were found in both groups. No significant differences were noted in bilirubin level or spleen weight of the bile duct ligation group between the two experiment groups. In the in vitro experiment, DPD activity and protein levels determined by Western blot analysis in the bile duct ligation group were slightly but significantly greater than those of a sham-operated group, whereas CYP2B activity and protein level were significantly reduced. These findings were supported by mRNA levels of CYP2B and DPD. When 40 mg/kg 5-FU was administered i.v. in the pharmacokinetic experiment, no significant differences in pharmacokinetic parameters were found between the bile duct ligation and sham-operated groups. These results suggested that DPD activity and protein level were maintained and that 5-FU pharmacokinetics was not altered in the presence of liver damage accompanied by a significant reduction in CYP2B activity and protein level, supporting previous clinical studies showing that mild to moderate liver dysfunction does not affect 5-FU disposition. (+info)