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Early diagnosis of dementia including Alzheimer's disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (NCs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

Objectives: Animal experiments indicate that exposure to particulate matter (PM) can induce hepatotoxic effects but epidemiological evidence is scarce. We aimed to investigate the associations between long-term exposure to PM air pollution and liver enzymes, which are biomarkers widely used for liver function assessment., Methods: A cross-sectional analysis was performed among 351 852 adult participants (mean age: 40.1 years) who participated in a standard medical screening programme in Taiwan. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) levels were measured. A satellite-based spatio-temporal model was used to estimate the concentrations of ambient fine particles (PM with an aerodynamic diameter ≤2.5 µm, PM 2.5 ) at each participant's address. Linear and logistic regression models were used to investigate the associations between PM 2.5 and the liver enzymes with adjustment for a wide range of potential confounders., Results: After adjustment for confounders, every 10 µg/m 3 increment in 2-year average PM 2.5 concentration was associated with 0.02%(95% CI: -0.04% to 0.08%), 0.61% (95% CI: 0.51% to 0.70%) and 1.60% (95% CI: 1.50% to 1.70%) increases in AST, ALT and GGT levels, respectively. Consistently, the odds ratios of having elevated liver enzymes (>40 IU/L) per 10 µg/m 3 PM 2.5 increment were 1.06 (95% CI: 1.04 to 1.09), 1.09 (95% CI: 1.07 to 1.10) and 1.09 (95% CI: 1.07 to 1.11) for AST, ALT and GGT, respectively., Conclusions: Long-term exposure to PM 2.5 was associated with increased levels of liver enzymes, especially ALT and GGT. More studies are needed to confirm our findings and to elucidate the underlying mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and objectives : The pathophysiology of tethered cord syndrome (TCS) in children is not well elucidated. An inelastic filum terminale (FT) is the main factor underlying the stretching of the spinal cord in TCS. Our study aimed to investigate the expression of glutathione-S-transferase (GST) in children and fetal FT samples in order to understand the relationship between this enzyme expression and the development of TCS. Materials and Methods: FT samples were obtained from ten children with TCS (Group 1) and histological and immunohistochemical examinations were performed. For comparison, FT samples from fifteen normal human fetuses (Group 2) were also analyzed using the same techniques. Statistical comparison was made using a Chi-square test. Results: Positive GST-sigma expression was detected in eight (80%) of 10 samples in Group 1. The positive GST-sigma expression was less frequent in nine (60%) of 15 samples from Group 2. No statistically significant difference was detected between the two groups ( p = 0.197). Conclusions: Decreased FT elasticity in TCS may be associated with increased GST expression in FT. More prospective studies are needed to clarify the mechanism of the GST-TCS relationship in children., Competing Interests: The authors declare no conflicts of interest.

Objective: Our study aimed to compare the predictive value of waist-to-height ratio (WHtR) for hyperuricemia with body mass index (BMI) and waist circumference (WC)., Methods: This is a cross-sectional study of 9,206 South China residents (male/female: 4,433/4,773) aged 18-89 years recruited during years 2009-2010 and 2014-2015. Anthropometric measurements, serum uric acid, blood pressure, and plasma glucose, lipid, lipoprotein, and transferase levels were measured. Receiver operating characteristic (ROC) curve and logistic regression analyses were applied to evaluate the predictive values of anthropometric indices for hyperuricemia., Results: The prevalence of hyperuricemia increased significantly with higher quartiles of WHtR in both genders. The best cutoff points of WHtR to predict hyperuricemia are 0.52 for men and 0.49 for women and differed between different BMI and WC stratums. Although there was no significant difference between the area under the ROC curves, subjects in the top quartile of WHtR were at a highest risk of hyperuricemia (p for linear trend <0.001) and the adjusted ORs of WHtR (2.24-2.77 in men and 2.66-4.95 in women) were higher than those of BMI or WC in the multivariable regression model., Conclusions: WHtR was an independent and better predictor of hyperuricemia compared with BMI and WC., (© 2019 S. Karger AG, Basel.)

Background/aim: Diabetes mellitus (DM) is a major health problem worldwide. Cinnamic acid (CA) and its derivatives are synthesized in plants and increasing attention has been given to them in recent years due to the high number of beneficial health properties attributed to their consumption. The aim of this study was to investigate the effects of CA on streptozotocin-induced diabetes in Wistar albino rats. Materials and methods: DNA damage was evaluated in the blood, liver, and kidney cells of rats by the alkaline comet assay. Oxidative stress parameters such as catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase activities and 8-hydroxy-2-deoxyguanosine, total glutathione, and malondialdehyde levels; biochemical parameters including insulin, total bilirubin, and BCA protein levels; hepatic enzyme levels such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase; and lipid profile parameters including high-density lipoprotein, low-density lipoprotein, total cholesterol, and triglyceride levels were also evaluated. Results: DM caused genotoxic damage and alterations in lipid profiles, oxidative stress parameters, and hepatic enzymes levels. CA treatment ameliorated these effects. Conclusion: It seems that CA might have a role in the prevention of the complications of diabetes.

We investigated how the natural course of occult hepatitis B virus (HBV) infection (OBI) may evolve during HIV co-infection and long term HBV-active HAART. From a cohort of 181 HIV infected patients who were consecutively recruited over a 5 year period, 28 HBV co-infected patients with sequential sera (n = 98) were identified. Iterative HBV serology and viral loads were determined before and during treatment. The viral HBsAg gene was then serially amplified, directly sequenced, and molecularly characterized. Persistent detection of anti-HBs did not result in a modification to the clinical course of OBI. In contrast, reactivation of chronic HBV infection, hepatic enzymatic flares and cases of HBV reinfection were evident among anti-HBs negative OBI patients, and this was a notable finding. Of the 14 chronic HBV infected patients, eight progressed to persistent OBI after initiation of HBV-active HAART, increasing the number of patients with OBI in the study. Long term HBV-active HAART was not found to have a notable impact on low level viremia during OBI. While the HBsAg gene sequences isolated from chronic HBV infection were genetically stable over time, OBI-associated variants (sP111R, sT127P, sY161F) were neither stable nor predominant during the course of infection. This study is the first of its kind from South Africa to show the occurrence of hepatic enzymatic flares, HBV reactivation, and reinfection in HAART-exposed HIV co-infected patients with OBI. Among the cases studied, there was further evidence that OBI-associated variants may not play a significant role in the pathogenesis of OBI., (© 2017 Wiley Periodicals, Inc.)

Alcohol dependence (AD) leads to altered innate and adaptive immune responses, and frequently co-occurs with inflammation. Therefore, inflammatory cytokines potentially play a crucial role in the development of alcohol-related illnesses. This study evaluated changes in plasma cytokine concentrations, liver function, cravings, depression severity, and cognitive function in male patients with AD, during the course of an alcohol-detoxification program. A total of 78 male patients with AD were recruited for a conservative detoxification program; and cytokine levels, depressive score, and cognitive impairment applying the Trail Making Test (TMT) were evaluated during early withdrawal (baseline) and after 4 weeks of abstinence from alcohol. Healthy volunteers (86 males) were also recruited as controls. Inflammatory cytokine expression in all participants was assessed by multiplex magnetic bead assay. AD patients during early withdrawal demonstrated higher cytokine levels than the healthy controls (P≤0.001 for all cytokines). However, the levels of cytokine expression were significantly lower after 4 weeks of abstinence from alcohol (P≤0.001, except for IL-1β and IL-5). Higher liver function marker levels, depressive severity, and TMT times were observed in patients at the beginning of the detoxification program than in healthy controls. Fortunately, these functions significantly ameliorated after 4 weeks of abstinence. (P≤0.001). Levels of circulating cytokines, liver function, and cognitive function may markers of alcohol use disorder., (Copyright © 2016. Published by Elsevier Ltd.)

Objectives: The aim of this study has been to investigate serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide (DMF)., Material and Methods: Seventy-two workers and 72 healthy controls participated in the study. All subjects underwent complete physical examinations and abdominal ultrasound examination. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and c-glutamyl transpeptidase (c-GT) were determined by an auto-chemistry analyzer. The data of airborne concentrations of DMF was obtained from the local Center of Disease Control and Prevention. The level of urine N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) was measured by means of high-performance liquid chromatography., Results: Time weighted average (TWA) concentration of the DMF in workplace was 18.6 (range: 9.8-36.2) mg/m 3 . The concentration of the AMCC in workers' urine was 28.32 (range: 1.8-58.6) mg/l and 9 workers' AMCC exceeded the biological exposure index (40 mg/l). Thirty-one workers reported gastrointestinal symptoms (abdominal pain, nausea, anorexia) and 10 workers reported headache, dizziness and/or palpitation in the exposed group. Serum analysis revealed that both the mean of serum activities of liver enzymes (ALT, AST and c-GT) and the percentage of workers with abnormal liver function were significantly higher in the exposed group as compared to the controls., Conclusions: Dimethylformamide can cause liver damage even if air concentration is in the sub-threshold limit value (sub-TLV) level. The protection of skin contact against the exposure to the DMF might be a critical issue as far as the occupational health is concerned., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: In any calf rearing system it is desirable to obtain healthy animals, and reduce morbidity, mortality, and economic losses. Bovine syndesmochorial placentation prevents the direct transfer of bovine immunoglobulins to the fetus, and calves are born hypogammaglobulinemic. These calves therefore require colostrum immediately after birth. Colostrum is rich in immunoglobulins (Ig) and its consumption results in the transfer of passive immunity to calves. The Ig absorption occurs within the first 12 h after birth. Immunoglobulin Y (IgY), derived from chicken egg yolk, has been used in the prevention and control of diseases affecting calves because it is very similar in structure and function to immunoglobulin G (IgG). In the current study, we sought to establish whether administration routes of colostrum supplemented with avian IgY affected passive immunity in calves., Results: No significant differences were observed with respect to route of administration for colostrum. However, we did observe some differences in certain interactions between the various treatments. Calves fed colostrum containing egg yolk had higher levels of TP, ALB, and IgG, along with increased GGT activity., Conclusions: Our results suggest that supplementing colostrum with egg yolk has a beneficial effect when given to calves, regardless of administration route.

Based on a review of the literature, reference intervals for water buffalo (Bubalus bubalis) serum biochemistry and haematology have not previously been published. The current study was done to establish reference intervals for water buffalo heifers. The International Federation of Clinical Chemistry stated that at least 120 values are necessary to obtain reliable estimates for reference intervals. A total number of 127 clinically healthy buffalo heifers (1-2 years old) were included in the study. Animals were examined at buffalo farms that belong to Assiut Governorate, Egypt. Three types of samples were collected: serum samples for biochemical analysis, whole blood samples for haematological analysis and faecal samples for parasitological examination. Animals that fitted the inclusion criteria were included in the study. Biochemical analysis included serum total proteins, albumin, total globulins, alpha, beta and gamma globulin levels, and aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, creatine phosphokinase and lactate dehydrogenase activity. In addition to the above, serum creatinine, urea, total bilirubin, direct bilirubin, indirect bilirubin, sodium, potassium, chloride, magnesium, calcium, phosphorus, copper, zinc, iron, triglycerides, high density lipoprotein, low density lipoprotein, very low density lipoprotein, glucose levels and 20 haematological variables were measured. The 95.0% reference intervals were calculated by removing the upper and lower 2.5% of the interval for each serum biochemical constituent to give the 2.5 and 97.5 percentiles. Confidence intervals were calculated for each reference limit. Reference intervals from the current study were compared with established values for cows. The current study is as far as could be determined the first that establishes reference intervals for the serum biochemical and haematological parameters in water buffalo heifers.

Few or no studies have measured the effect of short- and long-term exposure to industrial leachate. Mature male Wistar strain albino rats (175-220 g) underwent sub-chronic exposure to leachate from the Elewi Odo municipal battery recycling site (EOMABRL) via oral administration for a period of 60 days at different doses (20%, 40%, 60%, 80%, and 100%) per kilogram of body weight to evaluate the toxic effects of the leachate on male reproductive function using steroidogenic enzymes and biomarkers of prostate damage. Control groups were treated equally but were given distilled water instead of the leachate. After the treatment periods, results showed that the treatment induced systemic toxicity at the doses tested by causing a significant (p<0.05) loss in absolute body weight and decline in growth rate. There was a marked significant decrease (p<0.05) in testicular activities of Δ(5)-3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase. Conversely, the activity of prostatic acid phosphatase, a key marker enzyme for prostrate damage was significantly (p<0.05) elevated in the treated rats. Similarly, the administration of EOMABRL significantly (p<0.05) exacerbated the activity of total acid phosphatase with concomitant increase in the activity of prostatic alkaline phosphatase. These findings conclude that exposure to leachate from a battery recycling site induces sub-chronic testicular toxicity by inhibiting key steroidogenic enzymes and activating key markers linked with prostate damage/cancer in rats.

Objectives: Bisphenol A (BPA) is widely used in epoxy resins in China. There are few reports on the adverse health effects of occupational exposure to BPA. This study examined associations between urinary BPA concentrations in workers and laboratory parameters for health status., Methods: Spot urine checks at the end shift on Friday were used for cross-sectional analysis of BPA concentrations, and blood or urinary markers of liver function, glucose homeostasis, thyroid function and cardiovascular diseases were measured. The 28 participants were workers in two semiautomatic epoxy resin factories., Results: The average urinary BPA concentration was 55.73±5.48 ng/ml (geometric mean ± geometric SD) (range 5.56-1934.85 ng/ml). After adjusting for urine creatinine (Cr), it was 31.96±4.42 μg/g Cr (geometric mean ± geometric SD) (range 4.61-1253.69 μg/g Cr). BPA feeding operators showed the highest concentrations, over 10 times those of the crushing and packing and office workers. Higher BPA concentrations were associated with clinically abnormal concentrations of FT3, FT4, TT3, TT4, thyroid-stimulating hormone, glutamic-oxaloacetic transaminase and γ-glutamyl transferase. Workers with higher BPA concentrations showed higher FT3 concentrations (linear trend: p<0.001). Bivariate correlation tests for laboratory analytes within normal limits showed FT3 to be positively associated with logged BPA concentrations, r=0.57, p=0.002. FT4 was positively associated with lactate dehydrogenase, r=0.45, p=0.020, and insulin was positively associated with thyroid-stimulating hormone with r=0.57, p=0.009., Conclusions: Higher occupational BPA exposure, reflected in urinary concentrations of BPA, may be associated with thyroid hormone disruption.

We investigated the toxic effect of nevirapine (NVP; Viramune(®)), an antiretroviral drug, on the liver, kidney and testis of Wistar rats. Twenty-one rats were assigned into 3 groups of 7 animals each. The first group served as control, and the second and third groups received NVP at 18 and 36 mg/kg body weight, respectively. Clinical signs of toxicity were not observed in the animals. NVP at both doses did not significantly (p > 0.05) alter the body weight gain, relative weights of kidney and testis, serum protein, urea, creatinine and alkaline phosphatase levels of the animals. However, NVP2 significantly (p < 0.05) increased the relative weight of liver, level of serum total bilirubin and activities of γ-glutamyl transferase, alanine and aspartate aminotransferases. NVP administration caused a dose-dependent, significant (p < 0.05) elevation of lipid peroxidation measured as malondialdehyde (MDA) content in the liver, kidney and testis of the rats. Hepatic, renal and testicular MDA were increased by 107%, 80% and 163%, respectively, in NVP2-treated rats. Elevation in MDA was accompanied by a significant (p < 0.05) decrease in the activities of hepatic, renal and testicular superoxide dismutase and catalase. NVP2 caused 43% and 32% decrease in spermatozoa motility and live/dead sperm count, respectively, and 94% increase in total sperm abnormalities. Histopathological findings showed that NVP2 caused degeneration of seminiferous tubules in testis, and severe necrosis in liver slides. NVP induced oxidative stress with corresponding decrease in antioxidant status of the rats. The changes in sperm parameters and, elevation of liver marker enzymes suggest an interference of NVP2 with these organs.

The aim of the current study was to elucidate the effect of Kupffer cells inhibition on hepatic injury induced by chronic cholestasis. Sprague-Dawley rats underwent bile duct ligation (BDL) or sham operation and were treated with either saline solution or gadolinium chloride (GdCl(3), a specific Kupffer cell inhibitor, 20 mg/kg i.p. daily). Serum and liver samples were collected after 28 days. Direct and total bilirubin concentrations and serum enzyme activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT) increased following BDL (p < 0.01). On the contrary to bilirubin concentrations and AST activity, GdCl(3) partially prevented the elevation in ALP, ALT and GGT enzyme activities (p < 0.05). GdCl(3) alleviated lipid peroxidation (reflected by malondialdehyde [MDA] concentration) and increased the activities of antioxidant enzymes (i.e. catalase and glutathione peroxidase) in liver samples after BDL (p < 0.05). Fibrosis, ductular proliferation and portal inflammation were also scored in liver samples. Among morphological changes appeared following BDL (i.e. marked fibrosis, portal inflammation and ductular proliferation); only ductular proliferation was not alleviated by GdCl(3). Therefore, Kupffer cells inhibition has beneficial effects against the development of hepatic injury induced by chronic cholestasis.

The toxicity of many heavy metals is due to their ability to cause oxidative damage to tissues. Lead is one of the most important metals that pollute the natural environment due to man's impact The aim of this study is to investigate the potential protective effect of epicatechin alone or combined with lycopene against toxicity of lead in male rats. Five groups of rats were involved in this study; the first was control while the other four injected with lead acetate (100 mg/kg BW) subcutaneous for 2 weeks. On the other hand, the third, fourth and fifth groups were injected with epicatechin, lycopene or epicatechin + lycopene, respectively. Results obtained showed that, the combined treatment (epicatechin + lycopene) exert its effects (100%) against toxic effects against lead by lowering the liver enzymes alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyle transferase (GGT) activities and decrease lipid peroixdation (MDA) and enhances the superoxide dismutase (SOD) activity. The high-density lipoprotein cholesterol (HDL-c) level was significantly decreased and low-density lipoprotein cholesterol (LDL-c) level was statistically significantly increased in lead-injected rats as compared with control group. The combined treatment with epicatechin and lycopene justify these levels to nearly normal values. The erythrocyte level of total glutathione was decreased in lead-injected rats as compared with control group (p < 0.001). The combined effect is significantly higher than individual treatment lycopene alone or epicatechin. A negative correlation was found between the blood lead and SOD (r = -0.6) and glutathione (r = -0.81) while a positive correlation with MDA level (r = 0.7).

In parenteral nutrition (PN), essential fatty acids are provided by soy oil-based fat emulsions, which may exert adverse effects on the immune system and lipid peroxidation. Olive oil -based fat emulsions have been said to prevent these undesired effects. This study compares effects of olive oil - and soy oil -based fat emulsions in 22 patients who underwent abdominal surgery for cancer. The first group (n = 10) received soy oil -based fat emulsion; the second group (n = 10) received olive oil -based fat emulsion. Body temperature, body mass index, (BMI) and biochemical variables were measured on days 0 and 7. There were no differences between the groups with regard to BMI or temperature. On day 7, the first group (compared with day 0) had significant increases in plasma alkaline phosphatase (81.70 ± 16.03 vs 117.60 ± 11.1), γ-glutamyl transferase (39.90 ± 15.40 vs 137.70 ± 24.09), and mean body temperature (36.72°C ± 0.14°C vs 37.20°C ± 0.17°C) (P < .01). Second group had increases in alkaline phosphatase (85.80 ± 13.46 vs 147.20 ± 34.17), γ-glutamyl transferase (48.40 ± 12.86 vs 129.40 ± 42.03), total protein (5.14 ± 0.19 vs 6.06 ± 0.49), and albumin (2.62 ± 0.14 vs 3.00 ± 0.18) (P < .05). Changes in thiobutyric acid levels were not statistically significant in either group. In postoperative cancer patients, olive oil-based fat emulsion had similar effects on BMI, body temperature, biochemical values, and thiobutyric acid levels as soy oil-based fat emulsions.

Experimental thyrotoxicosis in rats is accompanied by the increase of serum alanine aminotransferase (AlA), aspartate aminotransferase (AsA), creatine kinase-MB (CK-MB) activities and content of primary products of lipid peroxidation--conjugated dienes--in liver, heart and blood. This suggests impairments in these organs accompanying free radical processes intensification. Administration of melatonin decreased AlA, AsA and CK-MB activities and CD level decreased. Thyrotoxicosis increased catalase activity in liver, heart and blood. Exogenous melatonin decreased specific activity ofcatalase in blood and in heart in comparison with animals subjected to hyperthyroidism. However, some increase of catalase specific activity (approximately 15%) was observed in liver. alpha-Tocopherol content, raising in rat tissues in thyrotoxicosis development conditions, decreased after melatonin treatment. Thus, exogenous melatonin is capable to reduce lipid peroxidation intensity at thyrotoxicosis and to act as an adoptogen, regulating free radical homeostasis.

Study Objective: To examine the separate associations of leg length, a biomarker of prepubertal exposures and growth, and trunk length with adult levels of liver enzymes: alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), aspartate transaminase (AST) and alkaline phosphatase (ALP)., Methods: A cross-sectional analysis of baseline data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years., Results: Leg length was inversely associated with age-adjusted levels of ALT, GGT and ALP. These associations remained when controlling for childhood and adulthood social class, physical activity, smoking, alcohol consumption, waist-to-hip ratio and trunk length. Trunk length was positively associated with ALT and inversely associated with ALP and the associations remained when adjusting for covariables., Conclusions: Adult liver function is affected by early life environmental exposures as reflected in leg length, and this may suggest common childhood influences on liver development and adult risk of diabetes and coronary heart disease. Further studies with detailed measures of early life exposures relevant to leg length would be valuable in identifying any specific exposures contributing to adult liver function and cardiovascular disease.

Background: Biliary atresia (BA) is one of the most common causes of neonatal cholestasis. Stem-cell factor (SCF) has been implicated in the development of fibrosis in various diseases. The objective of the present study was to examine the significant role of SCF in BA., Methods: Fifty-seven pediatric patients with BA after Kasai operation and 30 healthy children were recruited. The mean ages of BA patients and controls were 6.1 +/- 0.6 years and 6.1 +/- 0.7 years, respectively. The patients were categorized into two groups according to their serum levels of total bilirubin (TBil < 2 mg/dL, no jaundice vs TBil > or = 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 100 vs ALT > or = 100 U/L). The serum SCF levels were determined on commercially available enzyme-linked immunosorbent assay., Results: The mean serum SCF level of the BA children was higher than that of normal controls (748.3 +/- 17.9 pg/mL vs 582.2 +/- 17.3 pg/mL; P < 0.001). Subsequent analysis demonstrated that the BA patients with serum ALT > or = 100 U/L had significantly greater levels of serum SCF compared to those with serum ALT < 100 U/L (796.5 +/- 22.6 pg/mL vs 694.7 +/- 25.0 pg/mL, respectively; P = 0.002). In addition, serum SCF levels were significantly elevated in the patients with portal hypertension (PH) compared with those without PH (810.0 +/- 18.8 pg/mL vs 634.1 +/- 20.1 pg/mL, P < 0.001)., Conclusion: The current study showed that BA patients had higher serum SCF levels compared with controls. The significant elevation in SCF levels is associated with the presence of PH and the degree of hepatic injury. These findings suggest that SCF may play a part in the pathogenesis of hepatic fibrosis in BA patients after Kasai procedure.

Trans-fatty acid intake is associated with an increased risk of CHD and diabetes. The effects of single trans-fatty acid isomers are largely unexplored. The present study examined the effects of a 6-week supplementation with two trans-18 : 1 isomers (trans-11 and trans-12) in human subjects on immune cells, several inflammatory and immunological biomarkers (for example, IL, TNFalpha, C-reactive protein, adiponectin, intercellular adhesion molecule-1, prostacyclin, phagocytic process). Following a 2-week adaptation period without supplements, the test group (n 12) received vaccenic acid (trans-11-18:1) and trans-12-18 : 1 in equal amounts (6.0 g/d) for 6 weeks. The control group (n 12) consumed an oil without trans-fatty acids and conjugated linoleic acids (CLA). Samples were collected at the end of both periods. Trans-11- and trans-12-18 : 1 were significantly increased in cellular lipids. The endogenous synthesis of cis-9, trans-11-CLA from trans-11-18 : 1 was demonstrated via increased CLA in cellular lipids of the test group. Generally, trans-isomer supplementation did not affect either inflammatory biomarkers (for example, IL-6, IL-8, TNFalpha) or immune function (for example, phagocytosis) during the present study. The dietary supplementation of trans-11- and trans-12-18 : 1 (6 g/d) and their accumulation in leucocytes had no effects on biomarkers of inflammation and immune function. However, because of the limited data on the safety of trans-fatty acid intake and effects of individual trans isomers on human health (for example, trans-9-18 : 1, trans-10-18 : 1) at present, it is prudent to reduce trans-fat intake in general.

Propolis, a natural beehive product has been known for centuries for a variety of beneficial traditional medicinal properties. The present study was conducted to ascertain the antineoplastic potential of propolis along with paclitaxel against experimental mammary carcinogenesis. Female Sprague Dawley rats at 55 days of age were treated with dimethylbenz(a)anthracene to induce breast cancer. Paclitaxel at a dose of 33 mg/kg body mass intraperitoneally and propolis 50 mg/kg body weight orally was administered to the experimental animals, immediately after the carcinogen treatment and continued until the termination of the study. At the end of the treatment activities of phase I and II xenobiotic metabolizing enzymes and liver marker enzymes were measured. A significant increase in carcinogen activating enzymes, cytochrome P(450), cytochrome b(5) and NADPH cytochrome C reductase with concomitant decrease in phase II enzymes, glutathione transferase and UDP-glucuronyl transferase were observed in animals with mammary cancer. Furthermore there was a significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase and 5' nucleotidase. Propolis treatment caused the activity of these enzymes return to almost normal control levels, indicating the protective effect of propolis against dimethyl benz(a) anthracene induced carcinogenesis. On the basis of the observed results propolis can be considered a promising chemotherapeutic agent and can be administered as an adjuvant with paclitaxel chemotherapy.

Aim: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation,at 14 and 40 d after ligation when portal pressure is spontaneously normalized., Methods: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 d after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia,plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected,were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded., Results: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished., Conclusion: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility.Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.

Objective: Occupational exposure typical of an oil refinery may alter liver function among the workers. Thus, the objective of the study was to identify risk factors for liver enzyme abnormalities among oil refinery workers., Methods: The workers at an oil refinery in Northeastern Brazil underwent routine annual medical examination from 1982 to 1998. This case-control study investigated all the 150 cases of individuals with simultaneous gamma-glutamyltransferase and alanine aminotransferase abnormalities of at least 10% above reference levels. As controls, 150 workers without any liver enzyme or bilirubin abnormalities since starting to work there were selected. Odds ratios and the respective 95% confidence intervals were calculated from logistic regression models., Results: In all the production sectors, the risk of liver enzyme abnormalities was significantly higher than in the administrative sector (OR=5.7; 95% CI: 1.7-18.4), even when the effects of alcohol, obesity and medical history of hepatitis were controlled for. During the period from 1992 to 1994, 88 out of the 89 cases occurred among workers from the various production sectors., Conclusions: Occupational exposure plays an important role in causing liver enzyme abnormalities among oil refinery workers. This is in addition to the specifically biological and/or behavioral risk factors such as obesity and alcohol consumption.

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P <.05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P <.05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P <.05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

A complex of biochemical parameters of hepatic functions was analyzed in 170 patients with chronic opisthorchiasis and in 90 apparently healthy dwellers from a region wherein opisthorchiasis is endemic. The activity of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, and choline esterase and the serum concentrations of bilirubin, cholesterol, and glucose were studied. A correlation analysis indicated that prolonged Opisthorchis invasion rearranged the system of interactions of the biochemical parameters of the functions of the liver and pancreas. The auxiliary ("local") standards obtained from a study of a group of apparently healthy dwellers from an opisthorchiasis-endemic region may be use to consider the results of individual examinations of patients with chronic opisthorchiasis in order to correct the processes of treatment and rehabilitation.

Objective: The present work was designed to study the effects of the two main isomers of conjugated linoleic acid (CLA), cis-9,trans-11 and trans-10,cis-12, on liver composition and hepatic fatty acid oxidation in hamsters., Methods: Animals were divided into three groups that were fed atherogenic diets supplemented with 0.5% linoleic acid, cis-9,trans-11 CLA, or trans-10,cis-12 CLA for 6 wk. Liver lipids, protein, water and DNA contents, and histologic structure were analyzed. Hepatic carnitine palmitoyltransferase-I and acyl coenzyme A oxidase activities were assessed. Triacylglycerol concentration, and aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities were evaluated in serum. CLA isomer contents were analyzed by gas chromatography in hepatic triacylglycerols. Peroxisome proliferator-activated receptor-alpha mRNA was determined by reverse transcriptase polymerase chain reaction., Results: Trans-10,cis-12 CLA led to significantly greater weight, lower levels of triacylglycerol, cholesterol, and phospholipid, and larger total cell number in liver. Carnitine palmitoyltransferase-I and acyl coenzyme A oxidase activities were significantly increased by this isomer. No changes were induced by cis-9,trans-11 CLA. Trans-10,cis-12 CLA was recovered in significantly lower proportions than cis-9,trans-11 in liver triacylglycerols. Histopathologic analysis showed no abnormalities. No significant differences in serum aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities or in hepatic mRNA peroxisome proliferator-activated receptor-alpha expression were found among the three experimental groups., Conclusions: These results suggest that the addition of 0.5% of these CLA isomers to the diet do not induce toxic effects in liver after 6 wk of feeding. Intake of trans-10,cis-12 isomer but not of cis-9,trans-11 CLA increases liver fatty acid oxidation. This effect leads to decreased hepatic and serum triacylglycerols.

Ampulla cardiomyopathy is named after the echocardiographic abnormalities occurring in this condition, characterized by extensive akinesis (ballooning ) of the apical region with hypercontraction of the basal segment of the ventricle. We describe 3 young female anorexia nervosa patients showing evidence of this cardiac complication after hypoglycemia. One case was complicated by echocardiographically confirmed ampulla cardiomyopathy while the other 2 patients showed increases in myocardial enzymes and transient electrocardiographic abnormalities consistent with this complication. The precipitating event for all three patients was hypoglycemic coma, and this is the first case report in which this factor lead to the complication of ampulla cardiomyopathy in anorexia nervosa patients.

Histological changes and alterations in biophysical and biochemical parameters in liver of gamma-irradiate rats have been investigated. The gamma-irradiation of the whole body of rats with a single dose of 1 Gy did not cause any impairments of beam structure of rat liver, but resulted in the lymphocytic infiltrations of portal tracts which were not accompanied by formation of spotty areas of necrosis in adjacent areas of lever parenchyma. gamma-Irradiation stimulated proliferation of the hepatocytes and induced time-dependent mitochondrial structure lesions. Post-irradiation changes in cell cytoplasm appeared as disordering in reticulum-endothelial system, among them enlarging and fragmentation of its cisterns, cytoplasmic vacuolization, enhancement of the number of lysosomes and of the lipid inclusion contents. These facts revealed the mobilization of the additional energy resources for recovery of metabolic processes in rat liver. Post-irradiation increase of the level of the hepatocyte membrane lipid peroxidation products preceded liver morphological alterations. The membrane lipid microviscosity decreased in 1 and 3 days after irradiation. As a result of damages of hepatocyte membrane, the activity of the alanin- and asparagin-aminotransferases in blood serum increased 6 hours after. We can conclude that the whole body single gamma-irradiation with a dose of 1 Gy leads to the reversible but significant damages to the rat liver cell membrane structures. These damages might be the reason of radiation-induced liver morphological alterations.

Chitotriosidase is a chitinase that is massively expressed by lipid-laden tissue macrophages in man. Its enzymatic activity is markedly elevated in serum of patients suffering from lysosomal lipid storage disorders, sarcoidosis, thalassemia, and visceral Leishmaniasis. Monitoring of serum chitotriosidase activity in Gaucher disease patients during progression and therapeutic correction of their disease is useful to obtain insight in changes in body burden on pathological macrophages. However, accurate quantification of chitotriosidase levels by enzyme assay is complicated by apparent substrate inhibition, which prohibits the use of saturating substrate concentrations. We have therefore studied the catalytic features of chitotriosidase in more detail. It is demonstrated that the inhibition of enzyme activity at excess substrate concentration can be fully explained by transglycosylation of substrate molecules. The potential physiological consequences of the ability of chitotriosidase to hydrolyze as well as transglycosylate are discussed. The novel insight in transglycosidase activity of chitotriosidase has led to the design of a new substrate molecule, 4-methylumbelliferyl-(4-deoxy)chitobiose. With this substrate, which is no acceptor for transglycosylation, chitotriosidase shows normal Michaelis-Menten kinetics, resulting in major improvements in sensitivity and reproducibility of enzymatic activity measurements. The novel convenient chitotriosidase enzyme assay should facilitate the accurate monitoring of Gaucher disease patients receiving costly enzyme replacement therapy.

Purpose: To assess MR imaging findings and clinical manifestations of diffuse-type hepatocellular carcinoma (HCC)., Materials and Methods: We retrospectively reviewed our experience with diffuse HCC from November 1994 to October 2001. MR imaging findings and clinical features were assessed., Results: Twenty-two consecutive patients with diffuse-type HCC (19 men and three women, age range 16-80 years [mean, 52 years]) were identified in a review of liver MR studies. This represented 13% of all patients with HCC imaged during this time period. Diffuse HCC showed a permeative, infiltrative pattern with ill-defined borders and no evidence of convex margination in all cases. At least 50% of the liver volume was involved with tumor. Diffuse-type HCC showed hypointensity in 15 patients, mixed intensity in three, and isointensity in four on T1-weighted images; heterogeneous hyperintensity in 16 patients; and homogeneous hyperintensity in six on T2-weighted MR images. Diffuse-type HCC showed patchy enhancement in 12 patients, miliary enhancement in nine, and minimal enhancement in one on postcontrast early-phase images, and showed heterogeneous wash-out in all patients on postcontrast late-phase images. Proximal portal venous tumor thrombosis was seen in all patients. Serum alpha-fetoprotein (AFP) value was elevated (>10 ng/mL) in 14 of 18 patients, and 13 showed a value greater than 500 ng/mL. The four patients who did not have elevated AFP had tumors which were indistinguishable from those in patients with elevated AFP; they also did not have a distinctive clinical history., Conclusion: Diffuse-type HCC was typically seen as an extensive, heterogeneous permeative hepatic tumor, with portal venous tumor thrombosis on MR images in all cases. Early enhancement, observed as patchy in 12 and miliary in nine of 22 patients, was a distinctive imaging feature. Elevated serum AFP value was a common finding; however, 22% had normal values., (Copyright 2003 Wiley-Liss, Inc.)

Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GTP), lactate dehydrogenase (LDH), urea nitrogen (BUN), uric acid (UA) and creatinine (CRE) levels were examined in 183 people (98 males and 85 females aged 10 to 68 years) living in Terai region in Nepal. The mean values of serum components examined did not differ by sex in the age group of 10-14 years. The mean values of serum AST, ALT and gamma-GTP levels differed significantly between the sexes (P<0.01). The all physical measurements and serum parameters observed correlated well in males, but a few of them correlated in females. The AST-ALT, AST-gamma-GTP, ALT-CRE and BUN-CRE correlated well in both sexes. The UA correlated with ALT and gamma-GTP, CRE with gamma-GTP, LDH and UA in males, while only AST-LDH and gamma-GTP-BUN correlated in females. The levels of most of the serum components examined in this study were within normal ranges for Japanese and others. However, it seemed to be necessary to improve their living conditions as these serum components are related to hepatic or renal function and the infectious diseases.

A study on thalassemia intermedia and major patients in Jakarta was initiated to obtain a comprehensive picture of metabolic dysregulation, iron overload, oxidative stress, and cell damage. Data are presented from a group of 14 transfusion-dependent patients in an age range of 11-25 years (T) and another group of 9 frequently transfused (for at least 15 years) patients aged 17-30 years (L). A third group comprised 6 patients (aged 7 to 14 years) who had not yet obtained transfusions (N). The 21 controls (C) were voluntary students without diagnosis or clinical signs of thalassemia up to 30 years of age. The study was approved by the Ethical Clearance Board of the Medical Faculty and all blood samples from controls and patients were obtained on fully informed consent. Levels of antioxidants (vitamins A, C, E and beta-carotene) and reactive thiols are considerably decreased in transfused patients, whereas signs of iron overload and cell damage are increased (serum iron, ferritin, transferrin saturation, SGOT, SGPT, gamma-GT, bilirubin). Results can be summarized that non-transfused thalassemia intermedia patients exert slight signs of oxidative stress, and increased hemoglobin degradation but no significant indication of tissue or cell damage. This picture differs considerably from transfusion-dependent thalassemia major patients: highly significant decrease in antioxidants and thiols and tremendous iron overload and cell damage. The picture is even worsened in long-term transfused patients. Iron chelation after transfusion is not sufficient in Indonesia, because it is normally (with few exceptions) applied only once together with transfusion. Hence, one major reason of the bad condition of transfusion-dependent thalassemia patients in Indonesia appears to be frequent transfusions (on the average one per month) and insufficient chelation of one treatment per month together with transfusion.

A potential influence of idraparinux--a synthetic analogue of the pentasaccharide sequence in heparins--on plasma liver enzyme levels was analysed in 37 patients suffering from deep vein thrombosis and participating in the PERSIST trial. Plasma gamma-glutamyl-transferase, aspartate aminotransferase and alanine aminotransferase were determined prior to enoxaparin treatment (screening), prior to randomization (baseline) and once weekly during the 12-week treatment period. Patients were initially treated with weight-adjusted enoxaparin for 4-7 days and then randomized to either idraparinux (2.5, 5, 7.5 or 10 mg) or warfarin. Gamma-glutamyl-transferase was significantly increased after administration of enoxaparin at the baseline visit (P = 0.004) and in week 2 (P = 0.009) to return to screening levels in week 3 for the remaining study period (all P > 0.05). Aspartate aminotransferase (P = 0.001) and alanine aminotransferase (P < 0.001) were significantly increased at the baseline visit and returned to screening values at week 2 for the remaining study period (all P > 0.05). There was no significant difference between the mean values of plasma liver enzymes of the four idraparinux groups and the warfarin group in all 13 measurements. We concluded that idraparinux in contrast to enoxaparin does not increase plasma liver enzymes significantly., (Copyright 2003 Lippincott Williams & Wilkins)

Background: Heart transplantation is an established tool for the treatment of terminal heart failure. Hyperlipidemia is a common problem following heart transplantation and has been implicated as an additional risk factor in the development of transplant coronary artery disease (TxCAD). Therefore, heart recipients are commonly treated with inhibitors of cholesterol synthesis (HMG-CoA reductase inhibitors). However, these patients have an increased risk of developing rhabdomyolysis due to elevated concentrations of HMG-CoA reductase inhibitors under co-administration with the immunosuppressive cyclosporin A (CsA)., Aim of the Study: Aim of our study was to obtain pharmacokinetic data on pravastatin whilst monitoring the safety and efficiency of the lipid lowering therapy in heart-transplant recipients under immunosuppression with CsA and to compare these data to those of a healthy control group., Subjects, Materials and Methods: Eleven patients (30.2 +/- 12.3 months after transplantation) receiving immunosuppressive therapy consisting of cyclosporin A, prednisone and azathioprine with LDL cholesterol (LDL-C) concentrations exceeding 3.9 mmol/l and 8 control subjects were included into the study. In addition to the immunosuppressive therapy, the patients received a daily dose of 40 mg/day pravastatin for the first 8 days which was then reduced to 10 mg/day administered until Day 29. Blood was sampled for pharmacokinetic profiling (maximum concentration of the drug (Cmax), time to reach Cmax (tmax), area under the concentration vs. time curve (AUC(0-24h)), elimination half-life time (tcl)) and measurement of the parameters of clinical chemistry on Days 1, 8 and 29. The control group received a single dose of 60 mg pravastatin and the values of Cmax and AUC(0-24h) were normalized for a dose of 10 mg., Results: Pravastatin 40 mg/day for 1 week in the patient group caused a significant reduction in total cholesterol (C) and LDL-C from 8.11 +/- 1.20 mmol/l and 5.88 +/- 1.15 mmol/l to 6.91 +/- 1.01 mmol/l and 4.72 +/- 1.05 mmol/l, respectively (p = 0.005 and p = 0.003). Triglycerides and HDL cholesterol (HDL-C) concentrations did not change significantly. Mean values for Cmax of pravastatin were 384.2 ng/ml, 392.0 ng/ml and 115.1 ng/ml in patients on Days 1, 8 and 29, respectively. After normalization for a dose of 10 mg, the corresponding values of C(max-DN10mg) and Cmax were 96.0 ng/ml, 98.0 ng/ml and 115.1 ng/ml on study Days 1, 8 and 29. These values were 7-8 times higher than the normalized value of C(max-DN10mg) for the control group (13.7 ng/ml). The corresponding values of AUC(0-24h) were 1228.2 ng/ml x h, 1214.1 ng/ml x h and 345.9 ng/ml x h in the patient group on study Days 1, 8 and 29 as well as 157.5 ng/ml x h in the control group prior to normalization. After normalization for a dose of 10 mg, the values of AUC(0-24h-DN10mg) in the patient group were approximately 12 times higher than those of the control group. However, no significant differences between the 2 groups were observed in tmax and tcl. Within the patient group, no significant increase in Cmax or AUC was found on Day 1 to Day 8. The results of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) showed also no significant increase during the observation period., Conclusion: Heart-transplant recipients treated with the HMG-CoA reductase inhibitor pravastatin generally show higher plasma concentrations of this drug than control subjects. However, our data suggest that the HMG-CoA reductase inhibitor pravastatin can be used effectively in these patients receiving the immunosuppressive cyclosporin A. The pharmacokinetic data obtained indicate that there is no significant cumulation of the drug following multiple dosages in spite of increased drug concentrations after a single oral dosage.

Background: open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion., Objective: to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair., Method: forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured., Results: WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017)., Conclusion: multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation., (Copyright 2002 Elsevier Science Ltd.)

Objective: To evaluate in a prospective study whether patients with polymyalgia rheumatica (PMR) and patients with rheumatoid arthritis (RA) with PMR-like onset show distinctive clinical and laboratory features., Methods: A cohort of 116 consecutive patients with bilateral girdle pain for at least one month and raised erythrocyte sedimentation rate (ESR) was studied and followed up for 12 months. Laboratory tests included determination of ESR, IgM rheumatoid factor, haemoglobin, white blood cell count, platelet count, percentage of CD8 lymphocytes, serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutamyltransferase concentrations., Results: At first examination, RA was diagnosed in 22/116 (19%) patients and PMR in 94 (81%) patients. During the follow up period, 19 additional patients developed RA, and the diagnosis of PMR was confirmed in 65 (56%) patients at the end of the study. Of the clinical and laboratory features, only the presence of peripheral synovitis could differentiate patients who will develop RA from those with "true" PMR, but the positive predictive value of this feature was poor., Conclusion: At present, there are no clinical or routine laboratory features allowing early differentiation between PMR and RA with PMR-like onset.

The transmembrane distribution of phospholipids plays an important regulatory role in human erythrocytes. Membrane-bound translocase enzymes maintain an asymmetric phospholipid distribution across the membrane monolayers by promoting transmembrane diffusion or flip-flop. Mechanistic understanding of the flip-flop process is weak at the molecular level. Recently, we discovered that amide and sulfonamide derivatives of tris(aminoethyl)amine facilitate phospholipid flip-flop across vesicle membranes; that is, they act as low molecular weight, synthetic translocases. In this report, NMR evidence is provided that suggests that the synthetic translocases work by forming a hydrogen-bonded complex with the phosphocholine headgroup which decreases headgroup polarity and promotes diffusion across the lipophilic interior of the membrane. Also cell morphology and fluorescence probe methods are used to show that these synthetic translocases facilitate phosphatidylcholine flip-flop across erythrocyte membranes. Addition of a small amount of dilauroylphosphatidylcholine to erythrocytes produces echinocyte morphology which takes days to revert back to the original discocyte shape. The rate of return is significantly accelerated by the presence of the synthetic translocases. The synthetic translocases facilitate inward-translocation (flip) of the fluorescent phosphatidylcholine probe, 1-palmitoyl-2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl]aminohexanoyl)-sn-glycero-3-phosphocholine (PC-NBD).

Objectives: The aim of the present study was to examine postoperative serum levels of cardiac enzymes after transmyocardial laser treatment (TML) and to evaluate any associations between this release, postoperative cardiac events and change in ejection fraction after 3 months' follow-up., Design: Forty-nine patients with angina pectoris Canadian Cardiovascular Society Angina Score Class III & IV refractory to medical therapy and untreatable by coronary artery bypass or percutaneous transluminal angioplasty treated with CO2 laser were included. Inclusion criteria were age less than 75 years, left ventricular ejection fraction greater than or equal to 30% and myocardial regions with reversible ischemia. Serum levels of aspartate aminotranspherase (ASAT), alanine aminotranspherase (ALAT) and MB-isoenzymes of creatine kinase (CK-MB) were followed during the first 72 h after surgery. Ejection fractions were estimated by multiple-gated acquisition ventriculography at inclusion and 3 months postoperatively., Results: A significant increase in serum markers of myocardial necrosis was observed 8 h after surgery. A subsequent increase from 8 to 24 h after surgery was associated with the presence of postoperative cardiac adverse events. An inverse correlation was found between peak level of cardiac enzymes and change in ejection fraction from baseline to 3 months' follow-up., Conclusions: TML with CO2 laser is followed by a significant increase in serum levels of cardiac enzymes after 8 h. Further significant increases are associated with cardiac adverse events postoperatively. Peak enzyme values are inversely correlated with change in ejection fraction from baseline to 3 months' follow-up.

Unlabelled: We evaluated whether hepatic abnormalities represent a specific feature in girls with Turner syndrome (TS) or whether they are related to an increased susceptibility to hormonal therapies and/or other factors. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase were monitored in 70 patients with TS for a mean period of 7.6+/-4.2 years. An increase in serum liver enzymes was observed in 14 out of 70 girls (20%) at a mean age of 12.7 years; it was present at entry before hormonal therapy in 3 girls and developed thereafter during the follow up in the other 11. The increase in serum liver enzymes was never observed before the age of 7 years. In the majority of cases (10/14) it was drug related: in 50% the liver abnormalities were transient and self-limiting, in the remaining cases they required interruption of hormonal therapy. Hepatotoxicity was more frequently observed in girls treated with oestrogens or oxandrolone than in those treated with growth hormone. In a small number of cases, liver disease was either auto-immunity-related (2/14), or cryptogenic (1/14) with a benign and self-limiting course. Obesity was a frequent finding, but it played a likely pivotal role only in one patient., Conclusion: Hepatic abnormalities are relatively frequent in Turner syndrome and surveillance of liver function should be included in the management of these patients independent of initiation of hormonal treatment.

In previously published studies ursodeoxycholic acid (UDCA) showed beneficial effect on the course of chronic hepatitis. We investigated the effect of UDCA on the course of acute viral hepatitis in a prospective double-blind study. Seventy-eight consecutive patients were randomly assigned either to the UDCA group or to placebo. At 12 months of follow-up 76 patients were available for the final assessment. The analysis of all cases and of the patients with hepatitis B (n = 59) showed a comparable rate of decline of the alanine aminotransferase and other liver function tests in the treatment group and in the placebo group. However, the elevation of alanine aminotransferase persisted more frequently in the placebo group (all cases, p = 0.05; hepatitis B group, p = 0.03). Persistence of the hepatitis B virus infection, measured by the presence of hepatitis B early antigen and hepatitis B virus DNA (polymerase chain reaction and hybridization) at 12 months of follow-up, was observed in I of 33 patients in the UDCA group and in 6 of 25 patients in the placebo group (p = 0.02). Gallstones detected by entry ultrasound dissolved in four of eight cases in the UDCA group and in none of six in the placebo group. We conclude that UDCA has a beneficial effect on the course of the acute viral hepatitis. It may enhance the clearance of the hepatitis B virus and thus prevent the development of chronic hepatitis.

Background and Objectives: In several populations, including the Japanese, the frequency of the A2B phenotype is significantly higher than expected based on the A2 phenotype frequency. To understand the genetic basis of this 'excess' of A2B, we examined ABO alleles in individuals with A2-related phenotypes., Materials and Methods: ABO alleles were identified by means of polymerase chain reaction single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses., Results: The frequencies of A2-related alleles (*A105, *A106, *A107, *A111 and *R101) were clearly different between the A2 and A2B phenotypes. In particular, a putative recombinant allele, *R101, was uncommon in the A2 but common in the A2B phenotype individuals. This allele was also detected in 4 of 401 (1%) unrelated A1 phenotype (AO genotype) individuals., Conclusion: *R101 is presumably expressed as phenotype A1 in *R101/*O heterozygous individuals, but as phenotype A2 in *R101/*B heterozygotes, thus giving rise to a high A2B phenotype frequency.

Experimental liver cirrhosis was produced by administration of thioacetamide. Cirrhotic animals were divided into two groups: one group was given zinc sulphate and the second kept as cirrhotic control. Zinc-treated animals showed a restoration of normal hepatic and plasma zinc and copper levels. Similarly, plasma levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl aminotransferase, and total bilirubin decreased significantly. Light microscopic studies showed that most of the hepatocytes appeared normal in zinc-treated as compared with untreated cirrhotic animals. The amount of fibrin, reticulin, and collagen, which was high in the cirrhotic livers, decreased following zinc treatment. Staining with periodic acid Schiff's reagent showed the ability of hepatocytes to store glycogen after zinc treatment. These results revealed that zinc may have some beneficial effect in the treatment of liver cirrhosis.

The effect of endotoxin administration on gentamicin pharmacokinetics in young adult (2-3 months) and old (22-24 months) rats was studied. Gentamicin (3 mg/kg, iv) was administered 24 hours after an endotoxin challenge (5 mg/kg, ip). Some blood biochemical parameters, viz. urea, AST, GGT activities in addition to PCV and Hb concentration and creatinine clearance were also measured. In young animals, endotoxin caused prolongation in gentamicin half life (t1/2), increased area under the plasma concentration-time curve (AUC) and reduced total body clearance (ClB) and volume of distribution (Vd). Endotoxin effects in the old rats were qualitatively similar to those induced in the young but were more pronounced. They included more than 10 fold increase in the t1/2 and AUC. In addition, a rising early phase in gentamicin plasma concentration was noticed in old rats treated with endotoxin which was, probably, due to an early redistribution process of gentamicin. The results indicate that aging and endotoxin, individually, can significantly alter gentamicin pharmacokinetics in the rat. These alterations were exacerbated when endotoxemia was induced in old rats.

Background/aims: In recent years, Gadolinium chloride (GdCl3), a rare earth metal, has frequently been used to study the role and function of Kupffer cells under physiological and pathological conditions. This study was performed to elucidate the consequences of GdCl3-induced Kupffer cell blockade for hepatic microcirculation, hepatocellular function and integrity., Methods/results: Using intravital fluorescence microscopy, we studied the hepatic microcirculation of rats pretreated with either GdCl3 (n = 12; 10 mg/kg; 1 ml i.v. for 2 d) or saline (n = 9; 1 ml). The GdCl3-treated animals revealed a significantly lower phagocytic activity of Kupffer cells when compared to controls. Concomitantly, GdCl3-treatment resulted in a pronounced rise of serum cytokine activity (tumor necrosis factor-alpha; interleukin-6). The hepatic microvascular perfusion was characterized by a moderate increase in the number of non-perfused sinusoids accompanied by a reduction of bile flow. In addition, GdCl3-treatment caused a slight increase in liver enzyme activity (< 200 U/l) (aspartate aminotransferase and alanine aminotransferase) with no substantial parenchymal tissue injury (light microscopy). The groups did not differ in concentrations of circulating endotoxin (GdCl3-treatment: 0.044 +/- 0.042 ng/ml; controls: 0.052 +/- 0.014 ng/ml)., Conclusions: We conclude that hepatic alterations following Kupffer cell blockade with GdCl3 may possibly be the consequence of cytokine release as a response to the phagocytic challenge of GdCl3-aggregates. If used for Kupffer cell blockade, the hepatic alterations following GdCl3-treatment described in the present study should be taken into consideration.

Obesity has been identified as a risk factor for liver disease in a number of cross-sectional studies. We investigated the association of biochemical livers tests (BLTs) among male employees of The Dow Chemical Company who had participated in two consecutive health surveillance examinations. The activity of three liver enzymes-alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transferase were used as measures of liver injury. Body mass index was strongly associated with increased enzyme activity in both examinations. Alcohol consumption was similarly associated with higher BLT results. Body mass index remained significantly associated with each BLT after controlling for alcohol consumption, race, and age. When changes in BLTs were investigated over time, the employees who gained weight showed a significant increase in alanine aminotransferase activity compared with those who did not gain weight.

Objective: To investigate whether, in the absence of galactosemia, relatively high intestinal lactase activity or low activity of an enzyme involved in galactose catabolism reduces fertility, as it does in the presence of galactosemia., Design: Retrospective cohort study., Setting: Healthy women selected from the community., Patients: Fifty-three married women., Intervention: Urinary galactose after an oral lactose challenge (a measure of intestinal lactase activity), erythrocyte galactose-1-phosphate uridyltransferase (transferase) activity, and transferase polymorphisms by isoelectric focusing., Main Outcome Measure: Pregnancy rate (number of pregnancies divided by number of months at risk) in the 12 months after stopping use of birth control to become pregnant., Results: Relatively high urinary galactose was not related to a decreased rate of pregnancy during the first 12 months (> or = 24.6 compared with < or = 14.3 mg: relative risk [RR] = 1.9; 95% confidence interval [CI] = 0.86 to 4.0). Relatively high transferase activity was not related to an increased rate of pregnancy (> or = 19.5 compared with < or = 17.2 mumol/h per g hemoglobin: RR = 1.1; 95% CI = 0.56 to 2.4). Low-activity transferase polymorphisms were not related to a decreased rate (RR = 1.2; 95% CI = 0.58 to 2.5)., Conclusion: Our study does not support the hypothesis that the biologic variation in galactose metabolism that exists in the general population influences infertility.

Polyenoylphosphatidylcholine (PPC: 100 or 300 mg kg-1 b.w., by gastric intubation for 30 days) produced a clearcut protection of the liver of rats treated with alloxan (150 mg kg-1 b.w., i.p.). The liver of rats treated with alloxan was characterized by hydropic dystrophy and lymphocytic infiltrations. Treatment with alloxan increased serum gamma-GT and ALAT activities. The liver structure of rats treated with PPC did not differ from the liver of control animals. PPC normalized the biochemical abnormalities caused by the diabetes. The number of pancreatic islets and beta/alpha cell ratio decreased in the diabetic rats. A number of beta-cells in this group did not contain granules. PPC prevented the decrease in the number of islets and the beta/alpha cell ratio in the pancreas of the diabetic rats. The intensity of staining of beta-cell granules in the pancreas of PPC-treated rats had a position intermediate between the control and diabetic groups. Alloxan increased the blood glucose content where treatment with PPC decreased this. The results suggest that PPC acts as a cytoprotector in the liver and pancreas of rats with experimental diabetes induced by alloxan.

Ten clinically healthy green iguanas (Iguana iguana) imported from South America were examined, and haematological and biochemical measurements were made on samples of blood. This paper describes the methods of blood sampling, handling and laboratory analysis, and presents the results as a set of normal blood ranges for the green iguana.

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.

Investigations performed in 96 patients with diabetes mellitus and acute biliary pathology (phlegmonous cholecystitis, mechanic jaundice) have found the relationships between plasma lypoperoxidation, degree of hepatodepression and kind of inflammation in the gall bladder. The level of glycemia and degree of transferasemia (cytolytic syndrome) are not reliable criteria of acute hepatic insufficiency and pyoinflammatory process in the biliary tracts. The choice of the complex of membrane-stabilizing drugs should be based on the severity and pattern of endotoxicosis.