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Background: While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA. Methods: Genome-wide association study (GWAS) summary data for SA (finnb-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis. Results: The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: P = 0.013; ALT: P = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT (P > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: P = 0.128; ALT: P = 0.899). Conclusion: The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA. [ABSTRACT FROM AUTHOR]

Background: The most serious respiratory consequences of coronavirus disease (COVID-19) include the common cold, coagulopathy, multiorgan failure, and death. It can also harm essential organs, including the kidney, liver, gastrointestinal tract, lungs, and brain system. Objective: The study's objectives were to investigate the impact of COVID-19 infection on liver damage by analyzing a range of indicators such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, C-reactive protein (CRP), and d-dimer protein. Materials and Methods: To achieve the study's goal, blood samples were collected from a group of patients (both males and females), and a series of serological tests were performed, including immunological testing and measurements of CRP, d-dimer, and liver function. Results: In this study of 80 patients (age range between 17 and 70 years), the female-to-male ratio in both groups was 20:20. The difference in CRP level between study groups was statistically significant (P ≤ 0.001). The d-dimer level (ng/mL) in patients with infected COVID was significantly higher (P ≤ 0.001) than in the control group, while there was no statistically significant variation in blood liver enzymes between infected and noninfected COVID groups. According to statistical analysis, there is no discernible gender difference between groups of noninfected people and infected patients. Conclusion: The study findings indicate that there are no significant differences between infected males and females when compared to the comparison group; however, there are distinct variances in CRP and d-dimer levels in the infected group. The results of liver function tests and enzyme measurements revealed no significant changes between the infected and healthy groups. [ABSTRACT FROM AUTHOR]

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are important liver enzymes in clinical settings. Their levels are known to be elevated in individuals with underlying liver diseases and those consuming hepatotoxic drugs. Serum ALT and AST levels are crucial for diagnosing and assessing liver diseases. Serum ALT is considered the most reliable and specific candidate as a disease biomarker for liver diseases. ALT and AST levels are routinely analyzed in high-risk individuals for the bioanalysis of both liver function and complications associated with drug-induced liver injury. Typically, ALT and AST require blood sampling, serum separation, and testing. Traditional methods require expensive or sophisticated equipment and trained specialists, which is often time-consuming. Therefore, developing countries have limited or no access to these methods. To address the above issues, we hypothesize that low-cost biosensing methods (paper-based assays) can be applied to the analysis of ALT and AST levels in biological fluids. The paper-based biodetection technique can semi-quantitatively measure ALT and AST from capillary finger sticks, and it will pave the way for the development of an inexpensive and rapid alternative method for the early detection and diagnosis of liver diseases. This method is expected to significantly reduce the economic burden and aid routine clinical analysis in both developed and underdeveloped countries. The development of low-cost testing platforms and their diagnostic utility will be extremely beneficial in helping millions of patients with liver disorders. [ABSTRACT FROM AUTHOR]

Abnormal levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in human serum are the most sensitive indicator of hepatocellular damage. Because liver-related health problems are directly linked to elevated levels of ALT and AST, it is important to develop accurate and rapid methods to detect these enzymes for the early diagnosis of liver disease and prevention of long-term liver damage. Several analytical methods have been developed for the detection of ALT and AST. However, these methods are based on complex mechanisms and require bulky instruments and laboratories, making them unsuitable for point-of-care application or in-house testing. Lateral flow assay (LFA)-based biosensors, on the other hand, provide rapid, accurate, and reliable results, are easy to operate, and are affordable for low-income populations. However, due to the storage, stability, batch-to-batch variations, and error margins, antibody-based LFAs are considered unaffordable for field applications. In this hypothesis, we propose the selection of aptamers with high affinity and specificity for the liver biomarkers ALT and AST to build an efficient LFA device for point-of-care applications. Though the aptamer-based LFA would be semiquantitative for ALT and AST, it would be an inexpensive option for the early detection and diagnosis of liver disease. Aptamer-based LFA is anticipated to minimize the economic burden. It can also be used for routine liver function tests regardless of the economic situation in each country. By developing a low-cost testing platform, millions of patients suffering from liver disease can be saved. [ABSTRACT FROM AUTHOR]

The De Ritis ratio (DRR), the ratio of serum levels of aspartate aminotransferase/alanine aminotransferase, has been reported to be a valuable biomarker in risk stratification for many liver and non-liver diseases. This study aimed to explore whether the inclusion of DRR at the date of intensive care unit (ICU) admission or days after ICU admission improves the predictive performance of various prognosis prediction models. This study reviewed 888 adult trauma patients (74 deaths and 814 survivors) in the trauma registered database between 1 January 2009, and 31 December 2020. Medical information with AST and ALT levels and derived DRR at the date of ICU admission (1st DRR) and 3–7 day after ICU admission (2nd DRR) was retrieved. Logistic regression was used to build new probability models for mortality prediction using additional DRR variables in various mortality prediction models. There was no significant difference in the 1st DRR between the death and survival patients; however, there was a significantly higher 2nd DRR in the death patients than the survival patients. This study showed that the inclusion of the additional DRR variable, measured 3–7 days after ICU admission, significantly increased the prediction performance in all studied prognosis prediction models. [ABSTRACT FROM AUTHOR]

The De Ritis ratio is widely used to differentiate various causes of liver disease and serves as an independent prognostic predictor for different malignancies and non-malignant illnesses. This retrospective study aimed to identify the association between the De Ritis ratio on admission and mortality outcomes in adult thoracoabdominal trauma patients. A total of 2248 hospitalized adult trauma patients with thoracoabdominal injury, defined as an abbreviated injury scale (AIS) score ≥ 1 in the thoracic and abdominal regions, between 1 January 2009, and 31 December 2019, were included. They were categorized into three tertile groups according to the De Ritis ratio. A 1:1 propensity score-matched study group was established to attenuate the confounding effect of patient characteristics on the mortality outcome assessment. The AST levels of the tertile 1, 2, and 3 groups were 115.8 ± 174.9, 115.7 ± 262.0, and 140.5 ± 209.7 U/L, respectively. Patients in the tertile 3 group had a significantly higher level of AST than those in the tertile 1 group (p = 0.032). In addition, patients in the tertile 1 group had a significantly higher level of ALT than those in the tertile 2 and 3 groups (115.9 ± 158.1 U/L vs. 74.5 ± 107.0 U/L and 61.9 ± 86.0 U/L, p < 0.001). The increased De Ritis ratio in trauma patients with thoracoabdominal injuries was mainly attributed to elevated AST levels. The propensity score-matched patient cohorts revealed that the patients in the tertile 3 group presented a 3.89-fold higher risk of mortality than the patients in the tertile 2 group. In contrast, the patients in the tertile 1 group did not have a significantly different mortality rate than those in the tertile 2 group. This study suggests that a De Ritis ratio > 1.64 may be a useful biomarker to identify patients with a higher risk for mortality. [ABSTRACT FROM AUTHOR]

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Background: Hepatitis B is acute or chronic liver inflammation caused by hepatitis B viral and can progress to hepatic chirrosis or liver cancer. Chronic hepatitis B has a high risk for liver fibrosis. Chronic inflammation and liver fibrosis are interrelated processes. This study aimed to determine the differences in T-regulator cells, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) between chronic hepatitis B patients with and without liver fibrosis. Method: This study used a cross-sectional method for patients diagnosed with chronic hepatitis B in the Inpatient and Outpatient Department of the Internal Medicine Department DR. M. Djamil Padang and other hospitals in Padang city for 6 months. Samples were selected by consecutive sampling according to inclusion and exclusion criteria. Liver fibrosis is identified by fibroscan. Data were analyzed by SPSS 21.0. Results: thirty-two patients were diagnosed with chronic hepatitis B and 50% had liver fibrosis. The levels of T-regulator cells in chronic hepatitis B patients without liver fibrosis were 2.08% and liver fibrosis 2.25%, but this difference was not statistically significant (p > 0.05). Mean ALT levels in the group without fibrosis were 19 IU/L (7IU/L-71IU/L) and liver fibrosis 61 IU/L (13IU/L-625IU/L). The mean AST level in the group without fibrosis were 15.5 IU/L (10IU/L-32IU/L) and liver fibrosis 35.5 IU/L (10IU/L-476IU/L). The difference between ALT and AST in the two groups was significant (p <0.05). Hepatitis B patients with liver fibrosis had higher ALT and AST levels than without fibrosis. Conclusion: There were differences levels of T-regulator cells in the two groups, but it was not statistically significant. ALT and AST levels were higher in the liver fibrosis group and statistically significant. [ABSTRACT FROM AUTHOR]

The study designed for the toxic role of cadmium chloride on the liver of mice from both a physiological and histological aspects. The animals were treated with a dose of 5 mg/kg of body weight for 30 days. And the protective role of Brassica nigra seed extract against cadmium chloride toxicity. This pilot study was conducted on 20 adult white rats divided into 4 equivalent groups including the control group: Animals in this group received a dosed of distilled water for 30 days. The placebo group was treated with cadmium chloride at a dose of 5 mg/kg of body weight for 30 days and returned as an infected control group. While in the third group, animals treated with cadmium chloride were dosed with Brassica nigra seed extract at a dose of 200 mg/kg of body weight for 30 days. The fourth group was dosed with Brassica nigra seed extract at a dose of 200 mg/kg of body weight for 30 days. After 30 days, liver enzymes including aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were measured by spectrophotometric method. In addition to making tissue sections of the liver. The treatment of rats led to a significant increase (P≤0.05) in liver enzymes compared with the control group. It also led to histopathology in the liver tissue, while the Brassica nigra seed extract acted as a protective role against the toxicity of cadmium chloride. [ABSTRACT FROM AUTHOR]

B- Thalassemia major is characterized by highly faulty hemoglobin A Synthesis together with enhanced hemoglobin F manufacturing impaired red blood cell manufacturing and enhanced hemolysis of faulty red blood cells. β-Thalassaemia is discovered in Arab nations, particularly in Mediterranean nations, Saudi Arabia, Jordan, Syria and Yemen. Considered Bthalassemia the most prevalent monogenic disorder in the globe, affecting both sexes equally and placing patients and families at risk a serious health and financial burden. And both iron overload and chronic anemia in patients with b-thalassemia could explain tubular dysfunction and for liver fibrosis in transfusion-dependent thalassemia. This study aimed to study some biochemical variables of Thalassemia patients, where the effect of thalassemia on liver function and kidney function was studied. This study included 60 patients from (15 to 25) years of age of both sexes. The results were compared with (30) healthy subjects. We note in this study that most of the patients with thalassemia suffer from liver disease and malfunction in the functioning of the kidney because of the process of repeated blood transfusion where, we note there are significant differences when compared to healthy. A significant increase in the serum levels of AST, ALT and ALP was found in thalassaemia patients found significant alteration in liver functions of thalassemia patients. These patients may experience both tubular and glomerular dysfunction urea, creatinine and uric acid compared with healthy control. From this study, we can conclude that beta-thalassemia disease affects liver function and kidney function. [ABSTRACT FROM AUTHOR]

Background and aims: l-carnitine supplementation is proposed to reduce liver enzymes levels; however, previous findings were equivocal. The current systematic review and meta-analysis of randomized controlled clinical trials (RCTs) were performed to assess the effect of l-carnitine supplementation on serum levels of enzymes mainly produced by liver [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGTP)]. Methods: Online databases as well as the reference lists of relevant studies were searched from inception up to June 2019. The risk of bias in individual studies was assessed using Cochrane Collaboration's tool. Data were pooled using the random-effects model and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Results: In total, 18 RCTs (1161 participants) met the eligibility criteria. l-carnitine supplementation dose ranged from 500 to 4000 mg/day. l-carnitine supplementation significantly reduced serum ALT (MD = − 8.65 IU/L, 95% CI − 13.40, − 3.90), AST (MD = − 8.52 IU/L, 95% CI − 12.16, − 4.89), and GGTP (MD = − 8.80 IU/L, 95% CI − 13.67, − 3.92) levels. The subgroup analysis showed that l-carnitine might be more effective in reducing the enzymes when supplemented in higher doses (≥ 2000 mg/day), for longer durations (> 12 weeks), and among patients with liver diseases. The meta-evidence was graded as "moderate" for ALT and AST, and "low" for GGTP according to NutriGrade scoring system. Conclusion: l-carnitine supplementation significantly improves circulating ALT, AST and GGTP levels; therefore, it might positively affect liver function, especially among patients with liver diseases. Further high-quality RCTs are recommended to confirm our results. [ABSTRACT FROM AUTHOR]

Background: COVID-19, caused by SARS-CoV-2 virus, is a novel disease that has not been previously identified. The disease may result in multiple organ impairment leading to death. Liver is also affected by this viral infection. This study aimed to investigate the association of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with mortality rate in these patients. Method: This is a retrospective cohort study of COVID-19 patients admitted in Fatmawati General Hospital during a period of March-April, 2020. Diagnosis of COVID-19 was established from real time polymerase chain reaction (RT PCR). Association of AST and ALT levels with mortality was analyzed by using SPSS® version 16.0. Results: Forty-two patients were diagnosed as confirmed case of CO VID-19, 52.3% of them were male. Mean age was 54.6 ± 12 years. Median (IQR) value of AST and ALT levels were 55(48) U/L and 39(40) U/L, respectively AST and ALT w-as elevated in 71.4% and 42.9%, respectively. Increased levels of AST and ALT < 2 times above the upper normal limit (UNL), >2 times ULN, and > 5 times ULN were found in 33.3% and 21.4%; 38.1% and 21.4%; 4.8% and 4.8%, respectively. Mortality was recorded in 45.1% of these confirmed cases, 50% occurred within 2 days of hospitalization. Higher mean value of AST is associated with an increased mortality risk (101 ± 147 U/L to. 82.78 ± 173 U/L; p 0.032). Sub-analysis identified that abnormal AST >2 times above UNL has a higher mortality proportion compared with AST < 2 times UNL and normal AST levels (62.5% vs. 50% vs. 16.7%; p 0.05). Mean value of ALT is not associated with mortality (p 0.479). Further sub-analysis found that in patients who succumbed to the disease, abnormal levels of AST and ALT is related to the time of death during hospitalization despite being statistically not significant. Conclusion: Mortality rate of COVID-19 in hospitalized patients remains high. Increased AST levels was significantly associated with higher mortality rate. Thisfinding merit further investigation by incorporating larger sample size to discern the role of these factors' contribution to mortality in COVID-19. [ABSTRACT FROM AUTHOR]

The most important task in animal husbandry is the identification and use of the biological capabilities of the animal organism in the production of cost-effective types of products. One way to solve this problem in sheep breeding is to find ways to increase the wool and meat productivity of sheep using biochemical blood parameters. The study of interior indicators in conjunction with productivity, as one of the forms of indirect selection, can accelerate the rate of selection due to early prediction of the genetic potential of highly productive animals. The theoretical justification for this relationship is the pleiotropic effect of genes, the heterozygosity of the body and the law of correlation. [ABSTRACT FROM AUTHOR]

Context Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent and underdiagnosed comorbidity of many chronic diseases that is associated with altered intestinal bacterial communities. This association has prompted research into alternative treatments aimed at modulating intestinal microbiota. Given the novelty of these treatments, scarce evidence regarding their effectiveness in clinical populations exists. Objective This meta-analysis sought to systemically review and quantitatively synthesize evidence on prebiotic, probiotic, and synbiotic therapies for patients with NAFLD in randomized controlled trials. Data sources PRISMA guidelines ensured transparent reporting of evidence. PICOS criteria defined the research question for the systematic review. A systematic keyword search in PubMed and EMBASE identified 25 studies: 9 assessed prebiotic, 11 assessed probiotic, and 7 assessed symbiotic therapies for a total of 1309 patients. Data extraction Basic population characteristics, the primary variables of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (utilized for NAFLD diagnosis), and the secondary variables of body mass index (BMI), gamma-glutamyl transferase (γ-GT), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceridges (TAG) were extracted. Pooled effect sizes of these variables were calculated by meta-analysis. No publication bias was identified using Begg's and Egger's tests or Cochrane bias assessment tool. Results Meta-analysis indicated that microbial therapies significantly reduced BMI (−0.37 kg/m2; 95% confidence interval [CI], −0.46 to −0.28; P < 0.001), hepatic enzymes (ALT, −6.9 U/L [95%CI, −9.4 to −4.3]; AST, −4.6 U/L [95%CI, −6.6 to −2.7]; γ-GT, −7.9 U/L [95%CI, −11.4 to −4.4]; P < 0.001), serum cholesterol (−10.1 mg/dL 95%CI, −13.6 to −6.6; P < 0.001), LDL-c (−4.5 mg/dL; 95%CI, −8.9 to −0.17; P < 0.001), and TAG (−10.1 mg/dL; 95%CI, −18.0 to −2.3; P < 0.001), but not inflammation (TNF-α, −2.0 ng/mL; [95%CI, −4.7 to 0.61]; CRP, −0.74 mg/L [95%CI, −1.9 to 0.37]). Subgroup analysis by treatment category indicated similar effects of prebiotics and probiotics on BMI and liver enzymes but not total cholesterol, HDL-c, and LDL-c. Conclusion This meta-analysis supports the potential use of microbial therapies in the treatment of NAFLD and sheds light on their potential mode of action. Further research into these treatments should consider the limitations of biomarkers currently used for the diagnosis and progression of NAFLD, in addition to the inherent challenges of personalized microbial-based therapies. [ABSTRACT FROM AUTHOR]

Background: Approximately 3% of the world population is infected with hepatitis C virus (HCV). Protein of hepatitis C virus modulates apoptosis and steatosis, liver cell injury, activates liver stellate cells and liverfibrosis. Hepatitis C virus infection will cause injury to the hepatocytes. This injury to the hepatocyte will activate liver stellate cells. Stellate cells have a huge role in the development of liverfibrosis. The objective of this study is to evaluate the difference of active CD38+ liver stellate cells in 'various degree offibrosis as 'well as its relation with aspartate transaminase (AST), alanine transaminase (ALT), and quantitative amount of hepatitis C virus ribonucleic acid (HCV RNA) in chronic hepatitis C. Method: This study was a cross sectional study performed in 32 patients with chronic hepatitis C who had undergone liver USG, did not suffer from hepatoma, had undergone liver biopsy. Paraffin block of patients' liver tissue was further stained using haematoxylin and eosin technique to identify the metavir degree which is categorized into mild-moderate or severe degree. Special staining is performed to evaluate liver stellate cells that were then counted in averagely infivefields of view. Results: In this study, we found significant difference in the amount of CD38+ stellate liver cells between severe and mild-moderatefibrosis (p < 0.001), there was no association between CD38+ stellate liver cells with AST (p = 0.2) or ALT (p = 0.7), and there was association between CD38+ stellate liver cells with quantitative HCVRNA (r = -0.372). Conclusion: Total amount of CD38+ stellate liver cells in severefibrosis was higher compared to the total amount ofCD38+ liver stellate cells in mild-moderatefibrosis. There was no association between the 'value of AST, ALT, and quantitative HCV RNA with the number of CD38+ stellate liver cells. [ABSTRACT FROM AUTHOR]

Compared to data on adolescents and adults, limited research has been conducted on biological correlates among young children with possible psychological difficulties, especially in Asian countries. By focusing on various peripheral biochemical indicators, we investigated potential biological correlates of psychological states in a community sample of Taiwanese school children aged 6-10 years. In total, 307 students (159 obese children and 148 normal-weight children) were selected from first- and fourth-grade school children in eight elementary schools in the Taipei metropolitan area in 2009. These children underwent a comprehensive health examination, including a physical examination, blood sample analysis, and questionnaire administration in a hospital. Differences in anthropometric and serum biochemical readings were compared between children with average and worse levels on each of the five psychological domains. We found that interleukin (IL)-1β [ β = 1.29, 95 % confidence interval ( CI) 0.50-2.09], IL-10 ( β = 1.61, 95 % CI <0.01-3.24), fasting blood glucose ( β = 0.08, 95 % CI 0.01-0.15), homocysteine ( β = 0.63, 95 % CI 0.09-1.18), and aspartate transaminase (AST) ( β = 0.15, 95 % CI <0.01-0.31) were significantly positively associated with anxiety. In addition, IL-1β, insulin, AST, and alanine aminotransaminase (ALT) were significantly positively associated with depression. Anger and disruptive behaviors were also related to specific biological correlates. Specific biological correlates, including AST/ALT, cardiovascular disease-related variables, and specific cytokines, were linked to particular psychological states among young children in this Asian population. These might provide a route for better understanding the biological aspects of children's mental health and might contribute to research on diagnostic or predictive biomarkers for psychiatric diseases in young children. [ABSTRACT FROM AUTHOR]

Abstract: Coexisting morbidities in CVID include bronchiectasis, autoimmunity and malignancies. The incidence of autoimmune disease in CVID patients may approach 20% of cases. The most common autoimmune disease found in CVID patients is autoimmune cytopenia, but rheumatoid arthritis, lupus, and now primary biliary cirrhosis have also been reported. The coexistence of immunodeficiency and autoimmunity appears paradoxical, since one represents a hypoimmune state and the other a hyperimmune state. However, this paradox may not actually be all that implausible due to the complex nature of immune cells, signaling pathways and their interactions. The cellular alterations in combined variable immunodeficiency include a range of T and B cell abnormalities. Selective immune derangements found in CVID include a downregulation of regulatory T cells (Treg cells), accelerated T cell apoptosis, abnormal cytokine production secondary to cytokine gene polymorphisms and increased autoreactive B cell production. The impact of these abnormalities on T and B cell interaction may not only explain the immunodeficiency but also the development of autoimmunity in select groups of patients with CVID. The variability in the clinical manifestations of CVID as a result of this immune interaction suggests that CVID is not one disease but many. This is important because it follows that the treatment of CVID may not always be the same, but may need to be directed specifically towards each individual patient. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Hugan Qingzhi tablet (HQT), a lipid- lowering traditional Chinese medicine formula, has been used for the prevention and treatment of nonalcoholic fatty liver (NAFLD). Aim of the study: This study was realized to evaluate the effects of HQT-medicated serum on hepatic steatosis using in vitro experiments with cells and explore the relevant mechanisms with method of serum pharmacology. Materials and methods: A model of hepatic steatosis in the L02 and HepG2 cells was induced by free fatty acid (FFA). The components in the HQT-medicated serum were assayed by high-performance liquid chromatography. Intracellular lipid droplets were detected by Oil Red O staining, and their ultrastructure was examined by transmission electron microscope. The biochemical parameters, including triglyceride (TG), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total antioxidant capacity (T-AOC), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH), were measured with commercial kits. Furthermore, the expression of adiponectin, AMP-activated protein kinase (AMPK) phosphorylation, sterol regulatory element-binding protein 1 (SREBP-1), peroxisome proliferator activated receptor-? (PPAR?), carnitine palmitoyltransferase 1 (CPT-1), and acetyl-CoA oxidase 1 (ACOX1) was analyzed by Western blot and/or quantitative reverse transcription–polymerase chain reaction (qRT–PCR). Results: Moderate- and high-dose HQT-medicated serum reduced (P<0.05 or P<0.01) the accumulation of lipid droplets and the cellular TG content in L02 and HepG2 cells. They caused significant reductions (P<0.01) in LDH, AST, ALT and MDA and significant increase (P<0.05 or P<0.01) in T-AOC in the culture medium. They also caused increase (P<0.05 or P<0.01) in GSH level and SOD activity in FFA-induced steatotic L02 and HepG2 cells. Furthermore, moderate- and high-dose HQT-medicated serum enhanced (P<0.01) adiponectin expression in a concentration-dependent manner and increased (P<0.05 or P<0.01) the phosphorylation of AMPK and the expression of PPAR?, CPT-1, and ACOX1, and reduced (P<0.05 or P<0.01) the expression of SREBP-1. Conclusion: The results suggested that HQT-medicated serum exerts a preventive effect against hepatic steatosis, and the potential mechanism might be activation of AMPK and PPAR? pathways. [Copyright &y& Elsevier]

Background & Aims: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. Methods: Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score (‘NASH score’). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort (‘NASH liver fat score’). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45–74years) to estimate the population prevalence of NASH. Results: The final ‘NASH Score’ model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for ‘NASH liver fat score’ were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using ‘NASH liver fat score’ and ‘NASH Score’, the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2–6.8%) using ‘NASH liver fat score’ and 3.6% (0.2–7.7%) using ‘NASH Score’. Conclusions: The population prevalence of NASH in 45–74year old Finnish subjects is ∼5%. [Copyright &y& Elsevier]

Objectives: The objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial. Background: pmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial. Methods: Between January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared. Results: Neither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p < 0.001) in minor adverse events (32 vs. 7), quantity of blood transfused, duration of the procedure, median hospital stay, median intensive care unit stay, median hospitalization cost, and median blood loss. During a median follow-up of 2 years, the left ventricular end-diastolic dimension of both groups returned to normal and there was no difference in closure rate, adverse events, and complications between groups. Conclusions: Transcatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799) [Copyright &y& Elsevier]

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of hepatic injury in the world. One of the most important therapeutic strategies for this disease is modulating insulin resistance and oxidative stress. In this study, we investigated the hypothesis that supplementation with cinnamon exerts an insulin sensitizer effect in patients with NAFLD. In a double-blind, placebo-controlled trial with two parallel groups, fifty patients with NAFLD were randomized to receive daily supplementation with either two capsules of cinnamon (each capsule contain 750 mg cinnamon) or 2 placebo capsules, daily for 12 weeks. During the intervention, all patients were given advice on how to implement a balanced diet and physical activity into their daily lives. In the treatment group (P < .05), significant decreases in HOMA (Homeostatic Model Assessment) index, FBS (fasting blood glucose), total cholesterol, triglyceride, ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma glutamine transpeptidase), and high-sensitivity C-reactive protein were seen, but there was no significant change in serum high-density lipoproteins levels (P = .122). In both groups, low-density lipoproteins decreased significantly (P < .05). In conclusion, the study suggests that taking 1500 mg cinnamon daily may be effective in improving NAFLD characteristics. [Copyright &y& Elsevier]

Highlights: [•] Safety study of CLNA in pig. [•] No change of body composition and biochemistry parameters. [•] Perturbation of PUFA balance in tissues. [Copyright &y& Elsevier]

Highlights: [•] PFOA altered the profiles of circulating miRNAs in mice. [•] PFOA increased level of two liver enriched miRNAs in serum, miR-122 and miR-192. [•] miRNAs with level changed in serum altered in mice livers too after PFOA exposure. [•] miR-28-5p, 32-5p, 122-5p, 192-5p, and 26b-5p may be biomarkers for PFOA exposure. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This cross-sectional study tested the hypothesis that treatment with the combination of Ezetimibe/Simvastatin (Vytorin) leads to broader changes in the expression levels of immunomodulatory genes as compared to Simvastatin monotherapy. Methods: Illumina's GenomeStudio gene expression module was used to compare gene profiles of Vytorin and Simvastatin in the peripheral blood mononuclear cells of 20 hypercholesterolemic subjects. Results: The characteristics of the immunomodulatory genes, which were altered by Vytorin, differed from those genes which were altered by Simvastatin. Vytorin mostly altered the expression levels of genes related to inflammation/oxidative stress; it downregulated the NF-KappaB and upregulated the expression of anti-inflammatory cytokine, IL-10, and anti-oxidant enzymes, GPX1 and SOD2, but also upregulated the expression levels of genes involved in cellular activation, adhesion, and coagulation cascade, including VWF, F7, PF4, PF4V1 SELP, ITGB3, ITGB5. Simvastatin mostly altered the expression levels of genes related to cellular apoptosis/proliferation. It upregulated the expression levels of apoptosis-related genes APAF1, BAX, IER3, and CSF1R, and downregulated the expression levels of genes related to cellular proliferation, including PTN and CD69. Treatment with Vytorin combination therapy modulated lipid profile and serum levels of the C-reactive protein more effectively, than treatment with Simvastatin monotherapy. Conclusion: The nature of the pleiotropic effects may play a role in Vytorin's and Simvastatin's clinical efficacies. [Copyright &y& Elsevier]

Abstract: Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-l-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-l-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation. [Copyright &y& Elsevier]

Abstract: Ibandronate is a widely used bisphosphonate with no previously well documented hepatotoxicity. We report the first case of ibandronate-related hepatotoxicity and, to our knowledge, the first case of immune-mediated drug-induced liver injury (DILI) related to bisphosphonates. [Copyright &y& Elsevier]

Abstract: Background: Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). Methods: A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis. Results: The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48–0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49–0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56–0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53–0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. Conclusions: The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. [Copyright &y& Elsevier]

Background & Aims: Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD. Methods: Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D. Results: Severe deficiency in 25(OH)D (<10ng/ml) was significantly associated with higher aspartate aminotransferase levels (p =1.00×10−3), increased hepatic venous pressure gradient (p =5.80×10−6), MELD (p =2.50×10−4), and Child-Pugh scores (p =8.50×10−7). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18–3.84, p =0.013) and mortality (HR=4.33, 95% CI=1.47–12.78, p =7.94×10−3) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p =3.00×10−3), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p =0.04). Conclusions: Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Liangxue Huayu Recipe (LHR) as a classical prescription is clinically employed to treat liver diseases in traditional Chinese medicine. Aim of study: In this study, we attempt to show that LHR attenuates hepatocyte apoptosis and hepatic injury induced by lipopolysaccharide (LPS) and d-galactosamine (GalN) in rats. The present study was also designed to examine whether LHR had the protective effects on d-GalN and tumor necrosis factor-α (TNF-α)-treated human L02 hepatocytes and its possible association with the mitochondrial pathway. Materials and methods: LHR is composed of three traditional Chinese medicines: Herba Rehmannia, Rhubarb and Radix Paeoniae Rubra. LHR at 541, 1082 and 2164mg/kg was orally administered to model and normal rats for 7 days. The effects of LHR on serum levels of liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were measured. Hepatocyte apoptosis in vivo was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) method. Apoptosis in vitro and related morphological changes of human L02 hepatocytes were determined by high content screening (HCS) assay. The expression levels of Bcl-2, Bax and cytochrome c were detected by Western-blot analysis in L02 cells. In addition, the activities of caspase-3 and caspase-9 were tested by enzyme-linked immunosorbent detector. Results: It revealed that LHR pretreatment effectively ameliorated the GalN/LPS-induced elevation of serum ALT and AST levels, and attenuated hepatocyte apoptosis in the rat model characterized by the addition of GalN/LPS. In subsequent experiments in vitro, LHR also attenuated GalN/TNF-α-induced apoptosis in human L02 hepatocytes. Furthermore, LHR improved the mitochondrial function, inhibited the upregulation of Bax/Bcl-2 protein ratio, decreased the release of cytochrome c from the mitochondria into the cytosol, as well as inhibited caspase-3 and caspase-9 activation in this cell model. Conclusions: These results indicate that LHR is effective in attenuating hepatocyte apoptosis both in vivo and in vitro, and this effect is partly mediated through the activation of the mitochondrial pathway and subsequent regulation of particular pro-apoptotic gene expression. [Copyright &y& Elsevier]

Highlights: [•] We investigated the subchronic toxicity of meat derived from transgenic cattle. [•] Transgenic cattle meat is similar to the conventional in nutritional composition. [•] Meat from transgenic cattle is as safe to eat as the conventional for food consumption. [Copyright &y& Elsevier]

Abstract: Apoaequorin, a calcium-binding protein originally isolated from jellyfish is available commercially as a dietary supplement. The objective of the present study was to investigate potential adverse effects, if any, of Apoaequorin, a recombinant protein preparation, in rats following subchronic administration. For this study, Sprague–Dawley (Hsd:SD®) rats (10/sex/group) were administered via oral gavage 0 (control), 92.6, 462.9, and 926.0mg/kg body weight (bw)/day of Apoaequorin preparation, for 90days. The corresponding amount of Apoaequorin protein was 0, 66.7, 333.3 and 666.7mg/kg bw/day, respectively. Administration of the Apoaequorin preparation did not result in any mortality. There were no clinical or ophthalmological signs, body weight, body weight gain, food consumption, food efficiency, clinical pathology or histopathological changes attributable to administration of Apoaequorin. Any changes noted were incidental and in agreement with those historically observed in the age and strain of rats used in this study. Based on the results of this study, the No Observed-Adverse-Effect Level (NOAEL) for Apoaequorin was determined as 666.7mg/kg bw/day, the highest dose tested. [Copyright &y& Elsevier]

Abstract: This study addressed the effect of indole-3-carbinol (I3C) supplementation on hepatic steatosis in mice fed a high-fat diet (HFD) and clarified the underlying mechanism. Male C57BL/6N mice were divided into three groups: those who received a normal diet, those fed with HFD and those fed with 0.1% I3C-supplemented diet (I3CD). In the present study, an HFD supplemented with 0.1% I3C significantly decreased body and liver weight as well as plasma and hepatic lipid levels. The activation of the silent mating type information regulation 2 homolog 1 (SIRT1)–AMP-activated protein kinase (AMPK) signaling system by I3C correlated with decreased mRNA levels of sterol regulatory element-binding protein-1c-regulated lipogenic enzymes. In addition, I3C significantly reversed HFD-induced up-regulation of ER stress-mediated signaling molecules in the liver, which may have contributed to the protective effects of I3C against hepatic steatosis. Furthermore, HFD-induced up-regulations of inflammatory genes such as tumor necrosis factor α and interleukin 6 were significantly reversed by dietary I3C supplementation. Our study suggests that the protective action of I3C against hepatic steatosis is mediated, at least in part, through the up-regulation of a SIRT1–AMPK signaling system in the livers of HFD-fed mice. Further investigations revealed that alleviation of the ER stress response represented a critical mechanism underlying the beneficial effects of I3C on hepatic steatosis. [Copyright &y& Elsevier]

Abstract: Unhealthy eating behaviors increase the risk of metabolic diseases, but the underlying mechanisms are not fully elucidated. Because inflammation contributes to the pathogenesis of metabolic diseases, it is important to understand the effects of unhealthy eating on the inflammatory state. The objective of our present study was to address the effects of a fasting–refeeding regime, a model of irregular eating, on the hepatic inflammatory responses in mouse. The animals were fasted for 48 h and then refed either a standard or low-carbohydrate/high-fat diet. Inflammatory gene expression in the liver was then sequentially measured for the first 17 h after initiation of refeeding. To assess the roles of dietary carbohydrates and toll-like receptor 2 (TLR2) in the refeeding-induced inflammatory changes, gene expression levels in mice refed only carbohydrates (α-corn starch and sucrose) at different doses and in TLR2-deficient mice refed a standard diet were also analyzed. Refeeding with a standard diet increased the liver expression of Tlr2, proinflammatory mediators (Cxcl10, Cxcl1, Cxcl2, Icam-1) and negative regulators of TLR-signaling (A20 and Atf3). These increases were attenuated in mice refed a low-carbohydrate/high-fat diet. Refeeding only α-corn starch and sucrose also increased the expression of these inflammatory pathway genes depending on the doses. TLR2 deficiency significantly attenuated the refeeding-induced increase in the liver expression of Cxcl10, Cxcl1, Icam-1 and A20. These findings suggest that an irregular eating behavior can elicit a liver inflammatory response, which is at least partly mediated by TLR2, and that dietary carbohydrates play critical roles in this process. [Copyright &y& Elsevier]

High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses ( N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h 60 %) and AST in both sexes (total h 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age. [ABSTRACT FROM AUTHOR]

Abstract: Glucose oxidase (β-d-glucose:oxygen 1-oxidoreductase; EC 1.1.2.3.4) is used in the food and beverage industry as a preservative and stabilizer and is commonly derived from the fungus Aspergillus niger. Although the safety of glucose oxidase preparations from A. niger is well-established, the use of preparations derived from other fungal species is of interest; however, an assessment of their safety is warranted. Here, we report on the safety of a glucose oxidase preparation derived from the fungus Penicillium chrysogenum (designated as PGO) for commercial use in food processing, as well as an ingredient in food. In a repeated dose 90-day oral toxicity study conducted in rats, PGO was without compound-related adverse effects at doses of up to 15,600U/kg body weight/day, equivalent to 193mg total organic solids/kg body weight/day. In addition, PGO was non-genotoxic in a series of genotoxicity tests, including a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and a combined in vivo mammalian erythrocyte micronucleus test and comet assay. The results of these studies support the safe use of PGO in food for human consumption. [Copyright &y& Elsevier]

Abstract: Quantitating hepatic steatosis is important in many liver diseases and liver transplantation. Since steatosis estimation by pathologists has inherent intra- and inter-observer variability, we compared and contrasted computerized techniques with magnetic resonance imaging measurements, pathologist visual scoring, and clinical parameters. Computerized methods applied to whole slide images included a commercial positive pixel count algorithm and a custom algorithm programmed at our institution. For all liver samples (n =59), including pediatric, adult, frozen section, and permanent specimens, statistically significant correlations were observed between pathology, radiology, and each image analysis modality (r =0.75–0.97, p <0.0001), with the strongest correlations in the pediatric cohort. Statistically significant relationships were observed between each method and with body mass index (r =0.37–0.56, p from <0.0001 to <0.05) and with albumin (r =0.55–0.64, p <0.05) but not with alanine aminotransferase or aspartate aminotransferase. Although pathologist assessments correlated (r =0.64–0.86, 0.92–0.97, and 0.78–0.91 for microvesicular, macrovesicular, and overall steatosis, respectively), the absolute values of hepatic steatosis visual assessment were susceptible to intra- and inter-observer variability, particularly for microvesicular steatosis. Image analysis, pathologist assessments, radiology measurements, and several clinical parameters all showed correlations in this study, providing evidence for the utility of each method in different clinical and research settings. [Copyright &y& Elsevier]

Highlights: [•] Chronic metribuzin exposure through diet induced rat undernutrition. [•] Chronic metribuzin exposure has adverse effects on rat organ functions even at low doses. [•] Metribuzin resulted in increased oxidative stress leading to physiological impairment in rat organs. [•] The nutritional management appears of the first importance in chronic metribuzin exposure at low doses. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to examine the association between patterns of past and current alcohol consumption and elevations in serum hepatic enzymes among a nationally representative sample of adults in the United States. Methods: We estimated the age-adjusted prevalence of elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) among 8993 adults aged 20years or older who participated in the 2005–2008 National Health and Nutrition Examination Survey (NHANES). We produced prevalence ratios by using patterns of alcohol consumption as a predictor; elevations in serum ALT, AST, and GGT were used as an outcome variable while adjusting for covariates in multivariate regression models. Results: The age-adjusted prevalence of elevated serum ALT, AST, and GGT in adults was 9.7%, 16.0%, and 8.6%, respectively. Male excessive current drinkers had 50%–71% and 75%–314% increased likelihoods of having elevated serum AST and GGT, respectively; female excessive drinkers with a history of consuming 5 or more drinks almost daily had a 226% increased likelihood of having elevated serum GGT, when compared to their respective counterparts who were lifetime abstainers. Conclusions: The results of this study indicate that elevations in serum hepatic enzymes, especially AST and GGT, are common in adults who are excessive current drinkers. There is evidence to suggest that excessive current drinkers with a history of protracted drinking are especially vulnerable to potential liver injury. These findings lend further support to the early identification of excessive drinkers who may have an increased risk for alcohol-related morbidity and mortality in health care settings. [Copyright &y& Elsevier]

Abstract: The in vivo hepatoprotective effects of Rhoicissus tridentata subsp. cuneifolia, a traditional Zulu medicinal plant, against carbon tetrachloride-induced acute liver injury in rats were investigated. A group of male Sprague–Dawley rats were divided into three subgroups. Two subgroups were injected with carbon tetrachloride (CCl4) and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with R. tridentata extract by stomach tube. The subgroup that received olive oil was sacrificed after 2 h. Groups of rats from the other two subgroups were sacrificed at 24, 48 and 72 h after the respective treatments. The variables investigated were the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (ASP) and glucose-6-phosphatase (G-6-Pase). In addition lipid peroxide (LPO) levels of liver homogenates as well as liver microsomal fractions were determined as malondialdehyde (MDA) levels. CCl4 intoxication resulted in significant increases (P <0.05) in all the variables investigated except G-6-Pase which was significantly decreased (P <0.05). The administration of R. tridentata extracts after CCl4 intoxication resulted in significantly reduced (P <0.05) concentrations of ALT and ASP as well as the levels of LPO whereas the concentrations of G-6-Pase were significantly increased (P <0.05). From the results obtained during the present study it could be concluded that R. tridentata has components that have hepatoprotective effects. [Copyright &y& Elsevier]

The objective of this study was to investigate the effect of ascorbic acid (AA) on the in vitro cytotoxicity of cypermethrin (CM), and on glutathione (GSH) metabolism in rat hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage were measured, as indicators of hepatic damage, at 1, 15 and 30 min of exposure to CM. Glutathione and the activities of glutathione-S-transferase (GST) and gamma glutamyl transpeptidase (γ-GT) were also measured. CM hepatotoxicity increased in a time and dose-dependent manner. In the presence of 30 μm CM, ALT and AST also increased 49 and 130% (P<0.05), respectively, indicating metabolic hepatocyte damage. AA (1 mm) was capable to preserve 100% of cell integrity and modulated ALT and AST. Furthermore, CM induced a 27% reduction in the endogenous antioxidant GSH, and increased 203% GST and 283% γ-GT (P<0.05), indicating an oxidative insult. The presence of AA showed chemopreventive capacity against CM, recovering 60% of GSH and a 54% decrease in γ-GT activity. These results suggest that AA in a 1:33 (CM:AA) ratio can modulate up to 90% of the damage caused to the cells by CM. It also demonstrates that AA can act as a primary antioxidant and hepatoprotector in rat hepatocytes. [Copyright &y& Elsevier]

Consensus among clinical chemists has dictated a change in reference temperature for enzyme catalytic concentrations from 30 to 37 °C. Consequently, International Federation of Clinical Chemistry (IFCC) reference procedures have been redefined at the latter temperature. Acceptance in practice of these new procedures requires well-established reference values and clinical decision limits, but the establishment of reference values is complex. Therefore, as a provisional approach and to facilitate early application of the new IFCC procedures, we report our experience gained with them in the transfer of values from the consensus methods used hitherto in Germany to the new procedures. The preliminary upper reference limits were determined for catalytic activity concentrations of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), γ-glutamyltransferase (γ-GT) and lactate dehydrogenase (LDH) in human sera. Since enzyme measurements are almost always made on sera from non-ambulant subjects, we have used hospital patients aged 17 years and older as the subjects of our study. The catalytic activity concentrations obtained by measurements with the German consensus methods for the respective enzyme were chosen in combination with additional enzymes of similar diagnostic relevance to classify patients'' samples as part of the respective reference collective. Measurements for the determination of the upper reference limits were performed manually by use of the primary reference procedures at the measurement temperature 37 °C according to IFCC, and also by employing mechanized measurements adapted to the reference procedures. The upper reference limits were calculated as the 97.5th percentile of the reference collectives and determined separately for women and men: ALT: 34 U/l (female) and 45 U/l (male); AST: 31 U/l (female) and 35 U/l (male); CK: 145 U/l (female) and 171 U/l (male); γ-GT: 38 U/l (female) and 55 U/l (male); LDH: 247 U/l (female) and 248 U/l (male). [Copyright &y& Elsevier]