Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine transcarbamoylase (OTC) deficiency is the most common hereditary urea cycle disorder. It is an X-linked recessive disorder that usually presents with encephalopathy and hyperammonaemia. We report a 14-month-old female carrier of OTC deficiency, who presented with a history of intermittent vomiting for 5 weeks and irritability and lethargy for 1 week. She was found to be in acute liver failure, with elevated transaminases, coagulopathy and a consistently low urea. Identifying an OTC mutation and ruling out other possible causes of acute hepatic failure confirmed the diagnosis. She was placed on low-protein diet supplemented with essential amino acids, and her liver enzymes, hyperammonaemia and coagulopathy corrected. Three other female patients have been reported with OTC deficiency presenting with severe cryptogenic hepatitis; our patient is unique in that the presentation of her disease was dominated by acute liver failure on a back ground of normal growth and development, no liver enlargement, and mild hyperammonaemia. OTC deficiency should be considered in the differential diagnosis of infants presenting with acute hepatocellular dysfunction, especially in females.
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PMID:Ornithine transcarbamoylase deficiency presenting with acute liver failure. 1680 8

We prospectively studied the evolution of HBsAg antibody (HBsAb) after primary vaccination (four doses; Engerix B, 40 pg i.m at 0, one, two and six months) in 29 patients who were seronegative (HBsAb <10 IU/L), had not been previously vaccinated and were on hemodialysis. Their mean age was 45.58 +/- 10.98 years, and the hemodialysis duration ranged from 1-21 years. In addition, we assessed dialysis adequacy for all cases on four different occasions beside the estimation of predialysis serum albumin, serum ferritin, C-reactive protein (CRP), transferrin saturation ratio (TSAT), body mass index (BMI) and subjective global assessment (SGA). We measured anti-HBs titer eight weeks after the fourth dose. Our results showed that two patients (6.90%) were nonresponders (HBsAb <10 IU/L) after the completion of vaccination. One patient (3.45%) was a weak responder (10-100 IU/L). Strikingly, 26 patients (89.65%) showed good antibody response (>100 IU/L). HBsAb titers showed no significant correlation with age, duration of HD therapy, serum albumin, CRP, TSAT level, BMI or SGA scores (p > 0.05). Responders to primary vaccination had significantly higher levels of urea reduction ratio (%) and Kt/V compared to nonresponders (63.61 +/- 6.97% and 1.25 +/- 0.15 vs. 52.0 +/- 2.10% and 0.92 +/- 0.13, respectively, P < 0.05). In conclusion, this was a preliminary study showing a very high response to hepatitis-B vaccination among hemodialysis patients that neither correlated with age, systemic inflammation nor nutritional status. Efficient hemodialysis was associated with good response to hepatitis-B vaccine.
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PMID:Antibody level after hepatitis-B vaccination in hemodialysis patients: impact of dialysis adequacy, chronic inflammation, local endemicity and nutritional status. 1722 40

Several studies have investigated the role of neutrophils during endotoxin-mediated liver injury, yet the precise mechanism for endotoxin-mediated hepatic neutrophil transmigration is unknown. The primary objective of this study was to establish a reliable lipopolysaccharide (LPS)-mediated necro-hepatitis model to investigate the mechanisms of hepatic neutrophil infiltration following LPS administration. Male Sprague Dawley rats were administered a single (5 or 10 mg kg(-1), i.v.) or repeated injection of LPS (10 mg kg(-1), i.v., 24 h apart) with appropriate controls (i.v. saline) and were killed at various time points following LPS injection. Significant hematologic changes included neutrophilia, elevation of the neutrophil to lymphocyte ratio and toxic changes in neutrophils. Biochemical changes were observed in several liver (aspartate aminotransferase AST, gamma glutamyl transferase GGT) and kidney (blood urea nitrogen BUN) associated parameters generally at the earliest time points. Histopathology revealed a time-dependent neutrophil and mononuclear infiltration around the periportal areas in the single dose study and multifocal midzonal coagulative necrosis in the repeated dose study. The neutrophil adhesion molecule, CD 11b was up-regulated in single and repeat dose studies. Based on these studies, a reliable LPS-mediated hepatitis model with necrosis was developed by intravenous administration of LPS in a repeat dose fashion. Midzonal hepatic necrosis, peripheral neutrophilia, hepatic neutrophil infiltration and up-regulation of CD11b were the most significant and consistent markers of LPS mediated effects in this model.
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PMID:Characterization of a lipopolysaccharide mediated neutrophilic hepatitis model in Sprague Dawley rats. 1737 Feb 40

2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT-exposed humans, notable toxic manifestations have included aplastic anaemia, toxic hepatitis, cataracts, hepatomegaly and liver cancer. Therefore, it is important to develop protection measures and to monitor workers involved in the clean-up of ammunition sites. Haemoglobin (Hb) adducts of TNT, 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT), and the urine metabolites of TNT, 4ADNT and 2ADNT were found in 22-50% of the exposed workers, but not in the control group. The exposed workers were wearing protective equipment. The levels of erythrocytes, haemoglobin, creatinine, serum glutamic pyruvic transaminase and lymphocyte levels were significantly lower in the exposed workers than in the non-exposed workers. The levels of blood urea and reticulocytes were significantly higher in the exposed workers than in the non-exposed workers. Headache (26%), mucous membrane irritation (16%), sick leave (18%), lassitude (8%), anxiety (6%), shortness of breath (3%), nausea (5%) and allergic reactions (8%) were reported by the exposed workers. In a further analysis the U-4ADNT levels and the Hb-adduct levels were compared to the blood parameter and the health effects. The blood parameters were not significantly different between the U-4ADNT positive and U-4ADNT-negative group. Headache, mucous membrane irritation, sick leave, lassitude, anxiety, shortness of breath and allergic reactions were statistically not different between the two groups. Also in the workers with Hb-4ADNT adducts no significant negative changes were seen in regards to the changes of the blood parameters or the health effects. According to the results of the present study, it appears that the blood parameter changes and the health effects are more influenced by other factors than by the internal exposure to TNT.
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PMID:Biomonitoring of workers cleaning up ammunition waste sites. 1785 74

This work analyzes the prevalence of TTV DNA in peripheral blood cells from patients with hepatic alterations and healthy blood donors and measures levels of sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in certain randomly selected patients. DNA samples from 111 individuals were evaluated. They were divided into two groups, "A" (study) and "B" (control), including 54 patients with liver enzyme alterations (ALT/AST) presenting non-B-non-C hepatitis and 57 blood donors, respectively. TTV DNA was determined by nested PCR. Certain products of the second-round PCR were sequenced. Serum biochemical assay was performed and disclosed TTV in 31.48% (17/54) of patients in group A and 5.26% (3/57) in the control group B. TTV prevalence was significantly higher in patients with liver disease than in healthy donors. In group A, sodium, potassium, urea, creatinine, phosphatase alkaline, total and direct bilirubin, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were analyzed in certain randomly selected patients and no significant difference in biochemical levels (p>0.05) was found when TTV infected and noninfected individuals were compared. Knowledge related to TTV has rapidly increased, but many fundamental aspects remain unclear. This led us to question the role of TTV and doubt remains as to whether or not it is just a commensal virus. Further studies are necessary to confirm and extend these findings.
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PMID:Detection of TTV in peripheral blood cells from patients with altered ALT and AST levels. 1862 84

Bacterial L-asparaginases are enzymes that catalyze the hydrolysis of l-asparagine to aspartic acid. For the past 30 years, these enzymes have been used as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Their intrinsic low-rate glutaminase activity, however, causes serious side-effects, including neurotoxicity, hepatitis, coagulopathy, and other dysfunctions. Erwinia carotovora asparaginase shows decreased glutaminase activity, so it is believed to have fewer side-effects in leukemia therapy. To gain detailed insights into the properties of E. carotovora asparaginase, combined crystallographic, thermal stability and cytotoxic experiments were performed. The crystal structure of E. carotovoral-asparaginase in the presence of L-Asp was determined at 2.5 A resolution and refined to an R cryst of 19.2 (R free = 26.6%) with good stereochemistry. Cytotoxicity measurements revealed that E. carotovora asparaginase is 30 times less toxic than the Escherichia coli enzyme against human leukemia cell lines. Moreover, denaturing experiments showed that E. carotovora asparaginase has decreased thermodynamic stability as compared to the E. coli enzyme and is rapidly inactivated in the presence of urea. On the basis of these results, we propose that E. carotovora asparaginase has limited potential as an antileukemic drug, despite its promising low glutaminase activity. Our analysis may be applicable to the therapeutic evaluation of other asparaginases as well.
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PMID:Structural and functional insights into Erwinia carotovora L-asparaginase. 1864 44

Rabbit hemorrhagic disease virus (RHDV) induced viral fulminant hepatitis in adult rabbits. We investigated the damage of renal function and electrolyte balance in experimentally infected rabbit by measuring the related serum parameters to elucidate the pathogenesis of RHDV as an index for medical treatment. Nineteen New Zealand White rabbits, ten females and nine males, were each intramuscularly inoculated with 0.5 ml 50% rabbit lethal dose (RLD(50)) rabbit hemorrhagic disease virus. Blood samples were collected at 0 hr post inoculation (HPI) and every 6 hr from 18 HPI repeatedly through 66 HPI. After virus inoculation, serum blood urea nitrogen (BUN), creatinine (CREA) and sodium (Na(+)) were elevated to a highly significant level (p<0.0001), whereas serum potassium (K(+)) was moderately elevated to a significant level (p<0.05). Hypoglycemia developed highly significantly (p<0.0001). Serum chloride ion (Cl(-)) was the only parameter which did not change significantly (p=0.077). No significant sexual difference was observed among these parameters. Renal insufficiency progressed from 36 hr, as indicated by the increases in BUN and CREA; significant changes in electrolytes resulting in the increased osmolality of extracellular fluid that induced flow disturbance which consequently destroy the homeostasis in cells. Therefore, the later impairments in renal function and electrolyte balance might be an important threat for rabbits which might have survived from acute fulminant hepatitis in RHD.
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PMID:Impairment of renal function and electrolyte balance in rabbit hemorrhagic disease. 1884 Sep 70

The effects of lactic acid bacteria-fermented soybean extract (Biofermentics; BF) on experimental models of hepatic and renal disorders were investigated in vivo and in vitro. In rat, hepatitis induced by feeding of deoxycholic acid (DCA, 0.5 wt/wt, n = 6) or intraperitoneal injection of d-galactosamine (GMN, 500 mg/body wt, n = 6), the increase in serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were inhibited significantly (P < 0.05) by feeding a diet containing 5% dried BF. Moreover, the BF-administered rat group showed lower concentrations of blood urea nitrogen and a larger amount of urine as compared with values in the control group. Pretreatment of primary cell cultures of rat hepatic and renal cells with BF prior to exposure to dichromate (K(2)Cr(2)O(7)) resulted in a marked decrease of dichromate-induced cytotoxicity as evaluated by the leakage of lactate dehydrogenase The levels of dichromate-induced lipid peroxidation, as monitored by malondialdehyde formation, were also reduced by pretreatment of hepatocytes with BF. These results suggest that BF may play a role in hepatic and renal disorders, and may be useful for maintaining health in humans as well.
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PMID:Improvement of Experimentally Induced Hepatic and Renal Disorders in Rats using Lactic Acid Bacteria-fermented Soybean Extract (BiofermenticsTM). 1895 65

Recombinant human erythropoietin (rHuEPO) has been successfully and safely used to treat anemia in patients with end stage renal disease (ESRD). The safety profile of rHuEPO had been considered to be excellent with possible exception of hypertension and increased risk of dialysis access thrombosis. Recently, antibody-mediated pure red cell aplasia associated with administration of rHuEPO has been identified as a cause of major concern; we aimed to detect and evaluate the presence of anti-EPO antibodies in patients with ESRD on regular dialysis who are using rHuEPO. Serum anti-EPO antibodies were detected by enzyme-linked immunosorbant assay technique in a total of 90 patients who are currently on regular hemodialysis and using rHuEPO alpha subcutaneously for more than 6 months. All patients were subjected to full history taking and clinical examination. Complete blood count, reticulocytes count, serum creatinine, blood urea, serum albumin, serum ferritin, and hepatitis markers were performed for all patients. Our results showed that 35 patients (38.9%) had the anti-EPO antibodies in their blood, while 55 patients (61.1%) did not have the circulating antibodies. The mean hemoglobin (Hb) level was significantly lower in the antibody positive group (8.8 g/dl +/- 1.35) than in the antibody negative group (9.42 g/dl +/- 1.32) (P = 0.000). The reticulocytes count was also significantly much lower in the patients who had anti-EPO antibodies with mean of (1.99 +/- 1.14) vs. (3.15 +/- 0.89) in the antibody negative (P = 0.000). The dose of EPO administrated in both studied groups was insignificantly different. The incidence of anti-EPO antibodies is high in ESRD patients on maintenance hemodialysis. Its presence is associated with increased incidence of anemia possibly due to immune-mediated inhibition of erythropoiesis as evidenced by reticulocytopenia.
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PMID:Detection of circulating antierythropoietin antibodies in patients with end stage renal disease on regular hemodialysis. 1970 35

It has been reported that an active aloe polysaccharide isolated from Aloe barbadensis Miller exerted various pharmacological effects, such as anti-inflammatory, wound healing, anti-hepatitis, anti-gastric ulcer, and anti-tumorigenicity in animals. Adverse health effects of aloe are of concern in humans. Therefore, this study was conducted to investigate a tolerable upper intake level (UL) of active aloe or a maximal allowable daily intake (ADImax) of active aloe based on 4-wk oral toxicity investigation in ICR mice. An active aloe was daily administered to male and female ICR mice for 4 wk at different dose levels (0, 120, 600, 3000, or 15,000 mg/kg body weight [bw]). All animals were sacrificed at the end of the experiment and changes of body weight, food consumption, organ weights, and hematological and biochemical parameters were recorded. In this study, no changes in clinical signs, urinalysis, or hematological or biochemical analysis were observed. In females, a dose-dependent quantitative decrease in albumin (ALB) levels was observed, but it was not significant, due to wide interindividual variations. A significant decrease in male kidney weight was observed from the 120-mg/kg to the 15,000-mg/kg bw treatment groups, and blood urea nitrogen (BUN) levels were also quantitatively lower. A dose-dependent reduction in the body weight of females was also observed, which might be related to less food consumption. Based on the reduced kidney weights in males, the lowest-observed-adverse-effect level (LOAEL) of an active aloe was estimated to be 120 mg/kg bw in male ICR mice, and the UL or ADImax was 0.4 mg/kg bw/d [(120 mg/kg bw/d)/(100 for safety factor) x (3 for modifying factor)], or 24 mg for a 60-kg adult (24 mg x 200 = 4.8 g of aloe gel/d/adult), assuming that consumers utilize active aloe for a month. Data showed that an active aloe did not induce any remarkable subacute toxic effects, but decreased male kidney weights, which requires further investigation.
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PMID:Estimation of tolerable upper intake level (UL) of active aloe. 2007 18


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