Long-term exposure to ambient fine particulate matter and liver enzymes in adults: a cross-sectional study in Taiwan.

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, PM2.5) at each participant's address. Linear and logistic regression models were used to investigate the associations between PM2.5 and the liver enzymes with adjustment for a wide range of potential confounders. RESULTS: After adjustment for confounders, every 10 µg/m3 increment in 2-year average PM2.5 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/m3 PM2.5 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 PM2.5 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.

Waist-to-Height Ratio Is a Better Predictor of Hyperuricemia than Body Mass Index and Waist Circumference in Chinese.

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.

Expression of Sigma-Class Glutathione-S-Transferase in Fetal and Pediatric Filum Terminale Samples: A Comparative Study.

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.

Evolution of the serologic and virologic course of occult HBV infection in therapy experienced HIV co-infected patients.

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.

Biochemical parameters in the blood of Holstein calves given immunoglobulin Y-supplemented colostrums.

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.

Exposure to leachate from municipal battery recycling site: implication as key inhibitor of steroidogenic enzymes and risk factor of prostate damage in rats.

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)-3ß-hydroxysteroid dehydrogenase and 17ß-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.

High urinary bisphenol A concentrations in workers and possible laboratory abnormalities.

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.

Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer's disease.

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.

Reduced catechol-O-methyltransferase activity in red blood cells of women with primary affective disorder.

Red blood cell catechol-O-methyltransferase, histamine-N-methyltransferase, and a methanol-forming enzyme were examined in a number of subjects with mental diseases. Catechol-O-methyltransferase activity was significantly reduced in female subjects with primary affective disorder (depression) as compared to normal women and men, men with primary affective disorder, and schizophrenic men and women. In depressed women, histamine-N-methyltransferase activity was elevated and the methanol-forming enzyme was unchanged.

Substrate stabilization: genetically controlled reciprocal relationship of two human enzymes.

5-Phosphoribosyl-l-pyrophosphate, a substrate shared by adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase, accumulates in human erythrocytes lacking hypoxanthine-guanine phosphoribosyltransferase. 5-Phosphoribosyl-l-pyrophosphate added to purified adenine phosphoribosyltransferase stabilizes it against heat inactivation. The increased activity of adenine phosphoribosyltransferase seen in erythrocytes deficient in hypoxanthine-guanine phosphoribosyltransferase may result from substrate stabilization of this enzyme in vivo.

Lesch-Nyhan syndrome: altered kinetic properties of mutant enzyme.

Hypoxanthine-guanine phosphoribosyltransferase is virtually inactive in erythrocytes from patients with the classical Lesch-Nyhan syndrome. In one such patient, activity of this enzyme ranged from 8 to 34 percent of normal in erythrocytes when assayed with a very high concentration of magnesium 5-phosphoribosyl-1-pyrophosphate. In addition, the mutant enzyme exhibited sigmoidal kinetics with this substrate as well as an increased Michaelis constant for both guanine and hypoxanthine. These findings provide the first evidence for genetic heterogeneity within the group of patients with the Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome: preventive control by prenatal diagnosis.

The Lesch-Nyhan syndrome was detected in a fetus at a time sufficiently early to allow termination of the pregnancy. The feasibility of a preventive program for control of a severe sex-linked neurological disease through prenatal diagnosis is thus demonstrated.

The associations between height components (leg and trunk length) and adult levels of liver enzymes.

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.

Effects of cinnamic acid on complications of diabetes

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.

Inosinic acid dehydrogenase activity in the Lesch-Nyhan syndrome.

Inosinic acid dehydrogenase was evaluated in normal subjects and in patients with the Lesch-Nyhan syndrome. A significant difference in activity was found between erythrocytes derived from normal controls (1.21+/-0.47 pmoles/hr per mg protein) and from 15 patients with the Lesch-Nyhan syndrome (6.72+/-6.23 pmoles/hr per mg protein). However, no difference in activity was demonstrable in muscle or leukocytes derived from normal and Lesch-Nyhan patients. The increased activity of inosinic acid dehydrogenase in erythrocytes from patients with the Lesch-Nyhan syndrome is due to stabilization of the enzyme in vivo as well as the absence of an inhibitor which is present in erythrocytes from normal subjects.

Glycosyltransferases in human blood. II. Study of serum galactosyltransferase and N-acetylgalactosaminyltransferase in patients with liver diseases.

Serum galactosyltransferase activity was found to be elevated in patients with alcoholic and other liver disorders but remained at a normal level in patients with a variety of nonhepatic diseases. The properties of the galactosyltransferase in patients with liver disease were compared with those of the enzyme in the serum of normal subjects. The possible presence of inhibitors or activators in the serum was examined. Results indicated that in patients with liver disease, the rise in the serum galactosyltransferase was due to an increase in the level of the enzyme present in normal serum and not due to the appearance of a new enzyme. In the cases examined, the level of the enzyme increased with the deterioration of liver function and declined in a patient recovering from acute alcoholic hepatitis. Another glycosyltransferase, an N-acetylgalactosaminyltransferase, was not elevated in the serum of liver disease patients and, unlike the galactosyltransferase, was not detected in normal liver. The results suggest that the serum galactosyltransferase originates from the liver and that an abnormal rise in the level of this enzyme in serum is due to hepatocellular damage.

Hypoxanthine-guanine phosphoribosyltransferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome.

The Lesch-Nyhan syndrome is characterized clinically by choreoathetosis, spasticity, selfmutilation, and mental and growth retardation. Biochemically, there is a striking reduction of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in affected individuals. We have examined erythrocytes from 14 patients with the Lesch-Nyhan syndrome for the presence of hypoxanthine-guanine phosphoribosyltransferase activity and enzyme protein. In contrast to the usual finding of no detectable hypoxanthine-guanine phosphoribosyltransferase activity, we have found low levels (0.002-0.79 nmoles/mg protein per hr) of hypoxanthine-guanine phosphoribosyltransferase activity in erythrocyte lysates from five of these patients. In three of the five patients, hypoxanthine-guanine phosphoribosyltransferase activity appeared to be substantially more labile in vivo than normal using erythrocytes which had been separated according to their density (age). Immunochemical studies using a monospecific antiserum prepared from a homogeneous preparation of normal human erythrocyte hypoxanthine-guanine phosphoribosyltransferase revealed immunoreactive protein (CRM) in hemolysate from all 14 patients with the Lesch-Nyhan syndrome. The immunoreactive protein from each patient gave a reaction of complete identity with normal erythrocyte hypoxanthine-guanine phosphoribosyltransferase and was present in quantities equal to those observed in normal erythrocytes. In addition, a constant amount of CRM was found in erythrocytes of increasing density (age) from patients with the Lesch-Nyhan syndrome despite the decreasing hypoxanthine-guanine phosphoribosyltransferase activity. These studies confirm previous data which indicate that the mutations leading to the Lesch-Nyhan syndrome are usually, if not always on the structural gene coding for hypoxanthine-guanine phosphoribosyltransferase. In addition, although the mutant proteins appear to be present in normal amounts, they are often very labile in vivo with respect to enzymatic activity. These observations suggest that therapy directed at stabilization or activation of enzyme activity in vivo may be of potential benefit.

Relationship of nervous tissue transketolase to the neuropathy in chronic uremia.

Patients with chronic uremia develop neurologic defects which are similar to the demyelinating lesions seen in thiamine deficiency. The present study describes inhibitory effects of uremic material on nervous tissue transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway which has been reported to have functional importance in the metabolism of myelinated nervous structures. Transketolase activity (TKA) of normal human brain and spinal cord was measured by the conversion of ribose-5-phosphate (R5P) to sedoheptulose-7-phosphate (S7P). TKA was significantly inhibited by plasma, cerebrospinal fluid and low molecular weight dialysate fractions obtained from patients with uremic neuropathy, but not by samples from normal subjects. The specific effect on transketolase by uremic material was established by showing suppressed formation of S7P from R5P also in the presence of excess cofactor thiamine pyrophosphate and of the other substrate xylulose-5-phosphate. Uremic plasma likewise inhibited a partially purified transketolase preparation from bakers' yeast.31 of 35 chronic uremic patients with inhibition values between 10 and 84% before or during the early phase of intermittent hemodialysis had evidence of neuropathy. Data of clinical grading of the neurologic deficits and values of motor nerve conduction velocity revealed a correlation between the extent of uremic neuropathy and the degree of nervous tissue transketolase inhibition. Hemodialysis markedly reduced the inhibitory effects of the patients' plasma and the data indicate that uremic patients who received effective long-term dialysis treatment show a parallel decline of transketolase inhibition and uremic neuropathy.The findings demonstrate that in patients with chronic renal failure, low molecular weight factors accumulate and inhibit nervous tissue transketolase. This biochemical defect-uncorrectable by thiamine but reversible by dialysis-may interfere with the metabolism of myelin-supporting cells, and/or of the axonal metabolism of medullated structures, and may thus contribute to the degeneration of myelinated nerves seen with uremic neuropathy.

Mechanism of allopurinol-mediated increase in enzyme activity in man.

Allopurinol therapy in man interferes with pyrimidine biosynthesis de novo by inhibition of one or both of the two enzymes, orotate phosphoribosyltransferase (OPRT) and orotidylic decarboxylase (ODC), responsible for the conversion of orotic acid to uridine-5'-monophosphate. Inhibition of this pathway in vivo is followed in 1-3 wk by an increase in the activity of both of these enzymes in erythrocytes and of ODC in circulating leukocytes. This drug-mediated increase in enzyme activity in erythrocytes could not be attributed to enzyme stabilization or induction in vivo but appeared to be due to enzyme "activation." "Activation" of the OPRT enzyme was directly demonstrated in erythrocytes studied in vitro after incubation with oxipurinol, and to a lesser extent, with allopurinol. No evidence for "activation" of the ODC enzyme was demonstrated in vitro. This response to allopurinol therapy provides an excellent model for examining the mechanism of increased enzyme activity in response to drug administration.

Differential cytokine levels between early withdrawal and remission states in patients with alcohol dependence.

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-1ß 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.