Alanine Aminotransaminase Activity Research Articles

Modulation of antioxidant activities, markers of hepatic and renal dysfunctions in alloxan-induced diabetic rats by Combretum dolichopetalum

Diabetes mellitus is a metabolic dysfunction of insulin secretion exhibiting hyperglycemia with abnormalities in protein, fat and carbohydrate metabolism. The present study aimed to investigate the effect of Combretum dolichopetalum (CD) on hepatic parameters, renal indices and antioxidant markers of alloxan-induced diabetic rats. Twenty (20) male rats were used, and they were divided into four groups of five rats each. Group 1- Normal control received distilled water (non-diabetic control); Group 2- Diabetic control received distilled water; Group 3 and Group 4 are Diabetic rats treated with 200 mg/kg and 400 mg/kg of CD extract. There were significant decreases in the final body weights of Group 2 compared with Group 1 and an elevation of the body weights of Groups 3 and 4 compared with Group 2. There were significant increases in the blood glucose concentration of Group 2 compared with Group 1 and a reduction in blood glucose concentration of Groups 3 and 4 compared with Group 2. There were increases in the alanine amino transaminase (ALT), alkaline phosphatase (ALP) activities and serum total and conjugated bilirubin levels of Groups 2 and 3 compared with Group 1, but a reduction in the ALP, ALT activities and total bilirubin in Group 4. There was an elevation in the superoxide dismutase (SOD) the activity of Group 4. There were reductions in catalase activities and no change in the renal indices. The study showed ameliorating potentials on hyperglycemia, hepatoprotective activity and antioxidation effects.

Adjunctive systemic antibiotic effect on periodontal state, salivary enzyme activity, and glycemia imbalance in type-2 diabetics after non-surgical periodontal management

ABSTRACT Aim: The current study aimed at analyzing the effect of non-surgical periodontal treatment accompanied by systemic antibiotics on salivary enzyme activities, periodontal parameters, and glycemic control in type−2 diabetic (T2D) patients with chronic periodontitis. Methods: The study included 125 type−2 diabetic patients with chronic periodontitis who had good glycemic control (T2Dc), 125 type−2 diabetics who had bad glycemic control (T2Dpc). The 125 T2Dpc were divided randomly into two groups. The first one enrolled 63 T2Dpc and received a non-surgical periodontal treatment (T2Dpc + NST). The second group enrolled 62 T2Dpc and received the non-surgical treatment accompanied by systemic antibiotics (T2Dpc+NST+A). HbA1c, periodontal indices, and salivary enzyme activities were assessed for all groups. The Glycated hemoglobin (HbA1c) was assessed. The Salivary alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) activities were measured. Results: The T2Dpc were characterized by the highest probing depth (PPD) and clinical attachment loss (CAL) periodontal scores, as well as ALP, AST, and ALT enzymatic activities. However, BOP did not differ significantly between T2Dc and T2Dpc. Whereas the rest of clinical parameters PI, GI, and OHI-S did not significantly differ between groups. The Pearson’s analysis revealed three correlations between ALP-PPD, ALP-CAL, and ALP-BOP (bleeding on probing) in both T2Dc and T2Dpc (P < 0.05). Interestingly, a significant decrease in periodontal indices, salivary enzyme activities, and HbA1c was recorded in T2Dpc+NST+A group. Conclusion: The increase in ALP, AST, and ALT activities reflects the impact of uncontrolled T2D on periodontal tissue alteration. The ALP activity increase was associated with the severity of periodontal status in diabetic patients. In comparison to non-surgical treatment alone, the adjunct use of systemic antibiotics improves periodontal state, enzyme activity, and glycemic control.

Docking-Based Virtual Screening Ascertaining β-Sitosterol-Induced Alterations in the Helicoverpa armigera Hübner Gut Enzymes

Present investigation attempts to study binding of β-sitosterol with Helicoverpa armigera midgut enzymes; alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP); through docking-based virtual screening. Extraction of the protein sequence of the enzymes revealed a respective linear chain of 535, 522 and 430 amino acids for ALP, ALT and AST. The binding energy for ALT-ligand complex was lowest as compared to the AST and ALP-docked complexes. The ALT-docked complex had ligand efficiency of (-) 0.32 with an inhibition constant of 104.01, more hydrogen bonds and hydrophobic interactions leading to a more stable complex. However, unfavored bumps in AST and ALP complexes may have led to comparatively unstable complexes. The dietary β-sitosterol exhibits differential binding with midgut enzymes of H. armigera larvae. The strong binding of β-sitosterol with ALT indicates the highest inhibition of ALT activity due to the activity-stability trade-off. The enzymes, AST and ALP exhibited relatively higher activity as a resultant of lesser stabilization of the β-sitosterol-enzyme complex. In silico studies have indicated that β-sitosterol can be used an effective control agent against H. armigera.

Haemato-biochemical and ionic regulatory responses of the hybrid catfish, Heteroclarias, to sublethal concentrations of palm oil mill effluents

BackgroundPollution arising from the noxiousness of palm oil mill effluent (POME) has become a serious threat to aquatic biotas. However, a paucity of information exists on fish response to POME-mediated oxidative stress, lipid peroxidation, haemato-biochemical, enzymatic and ionic changes. This study, therefore, evaluates the effects of 28-day exposure of Heteroclarias, a hybrid catfish, to POME. Juvenile Heteroclarias (n = 350, average weight: 11.90 ± 0.70 g and average length: 9.04 ± 0.71 cm) were exposed to sublethal concentrations (0-control, 4.00, 8.00 and 12.00 mg/l) of POME to determine its effects on red blood cells (RBC), haemoglobin (HB), packed cell volume (PCV), white blood cells (WBC), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC) and mean cell volume (MCV). The activities of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), lactate dehydrogenase (LDH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA), calcium (Ca+), potassium (K+), magnesium (Mg2+) and sodium (Na+) ions were also assayed in the gill and liver.ResultsExposure to POME caused significant (p < 0.05) concentration-dependent decrease in RBC, HB, PCV, MCV, MCH and MCHC values, whereas a significant (p < 0.05) concentration-dependent increase in WBC was observed in POME-exposed fish compared to the control. ALT, AST, LDH, GPx, SOD and CAT activities in the gill and liver significantly (p < 0.05) increased in a concentration-dependent manner. MDA level significantly (p < 0.05) increased in the gill relative to control, while in the liver it was insignificantly different. Both tissues exhibited an increase in Ca+, K+, Mg2+ and Na+ levels at the highest toxicant concentration with a rise of 77.93, 38.46, 109.54 and 41.99% recorded for the electrolytes in the gill and 79.17, 26.92, 55.48 and 38.78% in the liver above the control value, respectively. The levels of all the electrolytes except K+ were higher in the gill than the liver and were in the order: Na+ > K+ > Mg+ > Ca2+ in both tissues.ConclusionsThese results may be used as a suitable tool for pollution assessment and policy formulation to mitigate the discharge of untreated POME into aquatic ecosystems and their impacts on resident organisms.

Diminished Activity of Larval Midgut Transaminases and Phosphatases in Helicoverpa armigera Hübner (Lepidoptera) Induced by Dietary Stem Extracts of Thevetia neriifolia

Helicoverpa armigera Hubner (Noctuidae) is a common crop pest causing extensive loss of crop yields despite several efforts and diverse measures taken. As utilization of synthetic pesticides in the fields have caused ecological disturbances and lethal effects on humans and organisms; present studies explore Thevetia neriifolia (Apocynaceae), a widely used ornamental plant, against H. armigera as an alternate control measure. The study investigates the dietary effects of hexane and methanol extracts of T. neriifolia stems (HSE, MSE) on the activity of midgut enzymes of H. armigera, the alterations in which could hamper its growth and development. Different concentrations of the stem extracts, ranging from 0.001% to 0.02%, were incorporated in the diet of early IV instars of H. armigera. Effect of each extract was assessed by estimating the activity of four midgut enzymes; alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), acid phosphatase (ACP) and alkaline phosphatase (ALP) of cotton boll worm. Investigations showed that dietary stem extracts resulted in significant and dose-dependent reduced activity of all the enzymes. The percent inhibition of the enzymatic activity was higher with dietary MSE of T. neriifolia as compared to the hexane stem extract. Also, the enzyme inhibition effects of extracts were more pronounced on phosphatases in comparison to transaminases. Larval feeding with T. neriifolia MSE diminished ALT activity by 26.95% to 49.79% and AST activity by 11.02% to 56.53%, whereas the ACP and ALP activity decreased by 44.65% to 87.61% and 21.97% to 85.97%, respectively. On the other hand, HSE inhibited ALT activity by 29.43% to 41.67% and AST activity by just 2.72% to 47.08%. However, a respective reduction of 14.58% to 78.44% and 32.73% to 78.07% was noticed in ACP and ALP activity with dietary HSE. The GC-MS analysis of the stem hexane and methanol extracts of T. neriifolia reveals the presence of 39 and 30 phyto-chemicals, respectively. Investigations showed the possible use of T. neriifolia extracts as a growth regulatory agent against H. armigera. Identification and isolation of bioactive compounds require further investigations.

Time – Course of Sodium Arsenate Induced Hepatotoxicity and Nephrotoxicity in Male Wistar Rats

Arsenic exposure has been implicated by several epidemiological studies as an important metalloid that is currently poisoning millions of people globally. In order to investigate the time – course of arsenic exposure on hepatic and renal toxicity, male albino rats (n=45) were exposed to arsenic (100 ppm, 150 ppm and 200 ppm) for 4, 8 and 12 weeks as sodium arsenate in their drinking water. Control animals (n=15) received distilled water for the same period after which blood and vital organs were removed from the animals and analyzed for alanine amino transaminase (ALT), aspartate amino transaminase (AST) gamma amino transaminase (γGT), alkaline phosphatase (ALP), creatinine and urea spectrophotometrically. Histological changes in hepatocytes was also examined. Before the commencement of arsenic exposure, five animals were sacrificed to obtain baseline data. Significant elevation in plasma ALT, AST, γGT and alkaline phosphatase activities characterized the effect of the arsenical at all doses and time interval relative to the controls. Plasma levels of creatinine and urea were also elevated at all-time intervals in the arsenic group. In most of the cases observed, the elevated level of these biochemical marker in circulation are time – and dose – dose dependent. Hepatic histopathology reveals degeneration of cytoplasmic contents, evidence of necrosis, collapse of central vein, cytoplasmic inclusion and enlarged hepatic sinusoids in arsenic – exposed groups. These findings suggest that different dose regimens of sodium arsenate at different time interval caused degenerative changes in hepatic and renal tissues in rats in dose – and time – dependent fashion. Keywords: Arsenic, Time – course, Hepatotoxicity, Nephrotoxicity DOI: 10.7176/JNSR/9-4-09

Protective effect of benzethonium chloride on diethylnitrosamine-induced hepatocellular carcinoma

This study aims to evaluate the protective effect of Benzethonium Chloride (BZC) on- diethylnitrosamine (DEN)‑induced hepatocellular carcinoma. Thirty-two male albino rats were used (eight animal per group). The hepatocarcinogenesis was induced in male Wistar albino rats by DEN (20 mg/kg b.w, orally (five times per week for 6 weeks). The treatment group rats received a similar dosage as above then injected with benzethonium chloride (5 mg/ kg b.w i.p.) for 4 weeks. Blood samples for serum parameters were collected or determination of biochemical markers such as alanine amino transaminase (ALT), aspartate amino transaminase (AST), alkaline phosphatase (ALP), and total bilirubin, albumin and total protein. Also, liver tissues were taken for histopathological investigation. The obtained result revealed that treatment with benzethonium chloride significantly reduced DEN-induced elevation of ALT, AST and ALP activities and total bilirubin concentration. However, significant increase in the serum albumin and total protein concentration were observed in benzethonium chloride-treated rats as compared with DEN‑treated group. The obtained results suggest that benzethonium chloride possesses chemopreventive activity against DEN‑induced liver cancer.

Effects of Lycii fructus Water Extracts of Serum Enzymes Activities on Renin and Aldosterone Hormone in Aluminum Fed Rats

This study was designed to investigate the effects of Korean Lycii fructus water extract in Al (Aluminum) administered rats. Forty-eight male Sprague-Dawley rats were divided into six groups: Control group, water extract group with 3% Lycii fructus, 1000 and 2000 ppm of Al groups, and 1000 and 2000 ppm of Al with 3% Lycii fructus water extract group. The Al content of rat tissue in the Al administered group was lower than that in rat tissue in the Al with 3% Lycii fructus water extract group. Plasma levels of renin and aldosterone activity was higher in the Al administration group, compared with the 3% Lycii fructus water extract group and Al administered group. Aspartate amino transaminase and alanine amino transaminase activities were elevated in the Al administered group and lower in the 3% Lycii fructus water extract group. Lactate dehydrogenase was lower in the 3% Lycii fructus water extract Al group than in the Al group. Choline acetyltransferase was higher in the 3% Lycii fructus water extract Al group than in the Al group.

Early detection of paracetamol toxicity using circulating liver microRNA and markers of cell necrosis

Paracetamol (acetaminophen) overdose is a common medical emergency. The decision to treat with acetylcysteine is predominately based on the dose of drug ingested and a timed blood paracetamol concentration. These risk markers are used because most patients present to hospital soon after overdose, before hepatotoxicity can be excluded using current biomarkers such as serum alanine aminotransaminase activity (ALT). To improve patient stratification, sensitive liver-specific and mechanism-based biomarkers are in development [1–3]. In a recent study we demonstrated that the liver-enriched microRNA, miR-122, and the necrosis marker proteins high-mobility group box 1 (HMGB1) and keratin-18 (K18) identified hepatotoxicity on hospital admission with areas under their respective receiver operator curves >90% and negative predictive values >95% [1]. Here we present a case that demonstrates their potential utility. A 25-year-old man attended the Royal Infirmary of Edinburgh 4.5 h after a single Co-codamol overdose (60–70 tablets, total 30–35 g paracetamol/480–560 mg codeine). Blood was drawn 4.5 h after overdose and the paracetamol concentration was 107 mg l−1 (Table 1). The patient was deemed at low risk of hepatotoxicity applying the criteria that were standard UK practice at that time [4] and, therefore, the paracetamol concentration was interpreted using the ‘200-line’ on the UK paracetamol treatment nomogram (line starting at 200 mg l−1 at 4 h post-ingestion). According to the UK guidance used at the time of presentation, acetylcysteine treatment was not indicated and the patient was discharged after psychiatric review. The patient returned to hospital 43 h after overdose because he had been vomiting and felt lethargic. Repeat blood tests (43 h post-overdose) demonstrated hepatotoxicity with coagulopathy (Table 1). The patient was immediately treated with intravenous acetylcysteine and recovered fully. Table 1 Blood results from first presentation to hospital (4.5 h after overdose) and second presentation (43 h after overdose). For miR-122, HMGB1 and K18 the upper limit of normal (ULN) is the upper limit of 95% prediction interval based on the ... Retrospectively, biomarkers were measured (by a researcher blind to the patient's data) in the patient's first presentation sample (taken 4.5 h after overdose) and hepatotoxicity was unambiguously reported (Table 1). MiR-122 is a liver-enriched microRNA that is released into the circulation following paracetamol-induced hepatotoxicity. Both rodent and human studies demonstrate it is elevated early, when ALT is still normal [1, 3, 5]. At 4.5 h after overdose in this patient, miR-122 was elevated 50-fold above the upper limit of normal (ULN). HMGB1 and K18 are proteins released by necrotic cells that are elevated in the circulation of rodents and humans with paracetamol toxicity [2, 6]. In this patient they both reported toxicity on first hospital presentation (approximately 8-fold above ULN). At the time of first presentation to hospital, the UK guidelines were correctly applied and the patient was not treated. This misclassification may reflect the patient having increased susceptibility to hepatotoxicity, the time of overdose being earlier than reported, drug absorption being delayed by codeine or a second overdose after first discharge from hospital. However, had the new biomarkers been available toxicity would have been identified at first presentation. Since this case, the UK guidelines have changed and a single ‘100-line’ (line starting at 100 mg l−1 at 4 h post-ingestion) is used for treatment decisions in all patients, meaning this case would now be correctly classified as needing treatment. However, this lowering of the treatment threshold is likely to result in increased hospital bed occupancy and overall financial cost, for only marginal benefits [7]. Adoption of these biomarkers into clinical practice could target treatment to patients at elevated risk of hepatotoxicity. In North America, Australia and New Zealand, where a ‘150-line’ is used (line starting at 150 mg l−1 at 4 h post-ingestion), this patient would still not be treated. This case report demonstrates the potential of new blood biomarkers for hospital front door stratification. This may improve patient identification for trials of new management pathways, facilitate earlier, safe, patient discharge and/or identify the rare patient with hepatotoxicity missed by current biomarkers.

L-ascorbic acid- and L-ascorbic acid 2-glucoside accelerate in vivo liver regeneration and lower serum alanine aminotransaminase activity in 70% partially hepatectomized rats.

The effects of L-ascorbic acid and its stable analogue L-ascorbic acid 2-glucoside on the restoration of liver mass and recovery of liver function after 70% partial hepatectomy (PH), were compared with other natural vitamin C analogues in rats in vivo. L-Ascorbic acid (100 mg/kg/d, intraperitoneally (i.p.))- and L-ascorbic acid 2-glucoside (50 mg/kg/d, i.p.)-treated rats showed an approximately 1.3-fold increase in the ratio of liver weight (LW) to body weight (BW), when compared to saline (as control)-, L-dehydroascorbic acid (150 mg/kg/d, i.p.)- and D-isoascorbic acid (150 mg/kg/d, i.p.)-administrated rats on day 3 after PH. Accordingly, 5-bromo-2-deoxyuridine-labeling index in the regenerating liver was significantly higher in L-ascorbic acid- and L-ascorbic acid 2-glucoside-treated rats compared with saline-, L-dehydroascorbic acid and D-isoascorbic acid-treated rats on day 1. In control rats, liver-related serum alanine aminotransferase (ALT) activity was rapidly elevated on day 1, and then decreased to near pre-operative levels on day 5 following PH. L-Ascorbic acid and L-ascorbic acid 2-glucoside significantly lowered the serum ALT on day 1 after PH compared with saline-, L-dehydroascorbic acid- and D-isoascorbic acid-administered rats. These results demonstrate that L-ascorbic acid and L-ascorbic acid 2-glucoside significantly promote the regeneration of liver mass and function with full recovery after liver injury.

English

&nbsp; Interest on non-conventional sources of energy in animal feeding has increased in recent time but these new ingredients still await an adequate nutritional evaluation. Milled dried cassava peel and caged layers&rsquo; manure mixed in ratio 4:1(w/w), fermented for 7 and 14 days separately and screened for microbial load were used to replace maize in weaner rabbit diets designated as A (0% inclusion of the mixture), B (25%), C (50%), D (75%), E (100%) for 7 days fermentation and F (25%), G (50%), H (75%) and I (100%) for 14 days in a 2 &times; 4 factorial experiment. Fifty-four weaner rabbits, weighing 620 &plusmn; 0.23 g at 7 weeks were randomized into 9 treatments of 3 replicates each (one male and one female rabbit per replicate) and fed for 56 days. Fermentation duration significantly increased (p&lt;0.05) crude protein and decreased crude fibre content in the fermented mixture of cassava peel and caged layers&rsquo; manure (FCPCLM). Weaner rabbits fed diets A, B and F recorded higher (p&lt;0.05) feed intake than others. Body weight gain, feed conversion ratio and protein efficiency ratio were higher (p&lt;0.05) for rabbits fed diets B and F. Packed cell volume, haemoglobin, and red blood cell counts of rabbits on diets A, B and F were higher (p&lt;0.05) than others. Mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration were also influenced (p&lt;0.05). Aspartate amino transaminase and alanine amino transaminase activities of rabbits fed diets B and F were similar and decreased (p&lt;0.05) as dietary inclusion of FCPCLM increased. Maize can be optimally replaced at 25% in the diet of weaner rabbits by FCPCLM fermented either at 7 or 14 days without adverse effect on their growth performance. &nbsp; Key word:&nbsp;Alternative source, cereal, energy, microbial load.

The Protective Effects of Aqueous Extracts of Wild-Growing and Fermented Royal Sun Mushroom, Agaricus brasiliensis S. Wasser et al. (Higher Basidiomycetes), in CCl4-Induced Oxidative Damage in Rats

Culinary-medicinal Royal Sun mushroom, Agaricus brasiliensis (AbS), has traditionally been used for the prevention of a range of diseases, including cancer, hepatitis, atherosclerosis, hypercholesterolemia, diabetes, and dermatitis. The hepatoprotective effect of the fermented mushroom of A. brasiliensis (FMAE) and wild-growing A. brasiliensis (WMAE) were studied in this paper. An in vivo study of carbon tetrachloride (CCl4)-induced antioxidant activity in 2-month-old rats was conducted by examining the levels of activities of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) and the antioxidant enzymes, including glutathione peroxidase (GSHPx) and catalase (CAT). Rats were divided into four groups, each containing six rats. The first group served as a control group. The second group was the CCl4 group. Group I and group II were treated orally with distilled water for 14 days respectively. Group III and Group IV were treated orally by WMAE and FMAE at oral doses of 50 mg/kg-day, respectively. Both WMAE and FMAE could reduce CCl4-induced toxicity, particularly hepatotoxicity, by suppressing ALT and AST activities, and increasing antioxidant enzyme activity. The studies demonstrate that both the fermented and wild-growing A. brasiliensis could protect the liver against CCl4-induced oxidative damage in rats.

Prevalence Of Hepatitis B And C Virus Amongst Blood Donors And Abnormal Alt Activities In Blood Donors In Nigeria

The present study was designed to investigate incidences of both Hepatitis B and C Virus and serum activity of alanine aminotransaminase (ALT) amongst professional blood donors. For this study, 100 professional blood donors participated. Using blood samples collected from each donor, screening for HBV and HCV were performed by qualitative detection of serum anti-HBV and anti-HCV while the serum activity of ALT was also determined in 56 of the participants. 7% of the participating blood donors were sero-positive for Hepatitis B surface antigen (HbsAg), 3% for HCV and 2% had co-morbidity for both HBV and HCV. In addition, amongst the participants that had ALT activity > 24.0 iu/l, 5(27.7%) were HBV sero-positive out of which 2(11.1%) had co-morbidity for HBV and HCV infections. The prevalent rates of HBV and HCV amongst professional blood donors call for concern. Transfusion of blood or blood products in this area is still largely a source of transmission of these viruses. The possible use of raised ALT activities in areas where HCV screening is not available to disqualify donors from donating blood still lacks the ability to rule out 1% of donors with HCV. The present study thus concludes that HBV and HCV co-morbidity is a real problem amongst blood donors in Nigeria and may limit availability of Blood for transfusion. Implications of these bindings are discussed. Keywords: hepatitis B and C, ALT, Blood, donors. Journal of Biomedical Investigation Vol. 4 (2) 2006 pp. 32-36

Vitamin B6 intakes and status of mechanically ventilated critically ill patients in Taiwan.

To assess vitamin B6 intake and status of critically ill patients. The relationship between vitamin B6 status indicators and the severity of illness and outcome in these patients was also examined. Prospective clinical study. The study was performed at the Taichung Veteran General Hospital, in the central part of Taiwan. Ninety-four patients in the intensive care unit (ICU) entered the study and 46 patients successfully completed this study. No intervention. Vitamin B6 intake was recorded for 14 days. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and urinary 4-pyridoxic acid (4-PA)) and indirect measures (erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient). The severity of illness (APACHE II score), the length of ventilation dependency, and the length of ICU and hospital stay were recorded. Patients had an adequate mean vitamin B6 intake (16.26+/-19.39 mg) during the 14 day study. Mean vitamin B6 intake was significantly higher on day 14 than on day 1 (P<0.001). However, plasma PLP and PL concentrations significantly decreased at the 14th day after admission (P<0.05). Erythrocyte alanine aminotransaminase activity coefficient and EAST-AC did not change significantly. Urinary 4-PA significantly increased at the 14th day (P<0.001). No significant relationships were found between APACHE II scores and clinical outcomes (the length of ICU and hospital stay, the length of ventilation dependency) of patients, vitamin B6 intake or status indicators. Critically ill patients received nutritional support in the ICU, and had sufficient mean vitamin B6 intake and adequate vitamin B6 status. Therefore, the severity of illness and the results should not be affected by vitamin B6 status. However, we have noted that plasma PLP and PL concentrations significantly decreased while vitamin B6 intake significantly increased on day 14. Critical clinical conditions and complex metabolism in the critically ill may account for the reduction of plasma PLP and PL. Since vitamin B6 deficiency causes profound effects on immune system function, dietary or supplemented vitamin B6 intake is suggested for hospitalized patients.

Suppression of cytochrome P450 gene expression in the livers of mice with concanavalin A-induced hepatitis

Cytochrome P450 (CYP) gene expression in the livers of mice with concanavalin A-induced hepatitis was examined. Treatment of mice with concanavalin A (10 mg/kg, i.v.) elevated plasma alanine aminotransaminase activity. In normal liver, CYP1A2, 3A and 2E1 mRNAs were expressed, and concanavalin A treatment differentially suppressed the expression of these CYP genes. Gadolinium chloride (40 mg/kg, i.p.) treatment, which inhibited the concanavalin A-induced elevation of plasma alanine aminotransferase activity without affecting concanavalin A-induced cytokine expression, counteracted the concanavalin A-induced suppression of CYP gene expression in the liver. Kupffer cell function or hepatic injury might contribute to the concanavalin A-induced suppression of CYP gene expression.

Nucleotide Sequence of Precore Region of Hepatitis B Virus DNA in HBsAg-positive Carriers in Malaysia

As most published studies on precore mutants have been carried out on isolates from patients with liver diseases, and it is unclear whether HBsAg carriers with viraemia in the absence of HBeAg are also generally infected by such mutants, it was decided to sequence the precore region in some HBV-DNA isolated from HBsAg-positive carriers. Precore sequences of HBV-DNA from 43 HBsAg carriers in Malaysia were studied. Three HBV subtypes were identified according to the nucleotide sequence of the precore region. Most of the carriers were found to be infected by the subtype adr. Mutations were detected in the precore regions. The most common conserved mutation was a silent mutation involving conversion from T to C (CCT to CCC) at position 1858 at codon 15 (proline). It was found that 4/43 (9.3%) had a mutation at the penultimate codon where TGG was changed to TAG. All 4 isolates with the TAG mutation had nt T at position 1858. Of the 4 carriers who were infected by these mutant viruses, 2 were coinfected with the wild type, 1 was infected only by a variant with the mutation at position 1896, while another was infected by a variant with mutations at positions 1896 and 1899. Three of the 4 were anti-HBe positive while 1 was HBeAg positive. Alanine aminotransaminase activities in all 4 carriers were normal. This study therefore demonstrated that variants with stop codons at the penultimate codon could be found in asymptomatic carriers in Malaysia.

One sample antipyrine clearance after 90% partial hepatectomy in the rat.

Antipyrine clearance was estimated by a one-sample saliva technique before and after 90% partial hepatectomy in nine rats. For comparison, the hepatic contents of cytochrome P450 and serum alanine amino transaminase activity were determined in vitro. Antipyrine clearance and hepatic cytochrome P450 were reduced according to the reduction in liver weight following hepatectomy. During hepatic regeneration, antipyrine clearance and liver weight increase identically, whereas total cytochrome P450 recovered more slowly, being 71% of initial values at the time when antipyrine clearance and liver weight had recovered. Serum alanine amino transferase activity increased 10-20 times 24 h after hepatectomy, and normalized after 52 h. The hepatic glutathione content per gram liver weight was unchanged during the regeneration, suggesting intact detoxification during hepatic regeneration. This study demonstrates that, although the assessment requires some time, and that a value cannot be attached to a fixed time-point, the one-sample antipyrine saliva clearance is a quantitative in vivo estimate of "functional hepatic mass". The test can easily be applied in animal studies where such a measure is requested.