Assessment of the relationship between serum uric acid levels and liver enzymes activity in Bangladeshi adults.

Serum uric acid (SUA) level has been suggested to be associated with cardiovascular disease, diabetes and metabolic syndrome. However, little is known about the relationship between SUA and liver enzymes activity in the general population. The present study aimed to assess the relationship between SUA and serum liver enzymes in an adult population in Bangladesh. In this cross-sectional study, a total of 410 blood samples were collected from apparently healthy adults aged > 18 years. SUA, liver enzymes, lipid profile and other biochemical markers were measured in the collected samples by using standard methods. Multinomial logistic regression model was used to assess the relationship between SUA and elevated levels of liver enzymes among the participants. Overall, the prevalence of hyperuricemia was 30.1% with 32.2% in male and 18.6% in female participants. About 33% of the participants had at least one or more elevated levels of liver enzymes. The mean level of SUA was significantly higher in males (389.3 ± 96.9 µmol/L) than in the female (290.4 ± 89.8 µmol/L) subjects (p < 0.001). There was a significant difference in the mean levels of serum ALT and GGT between the male (34.5 ± 16.0 U/L and 26.7 ± 19.5 U/L, respectively) and female (25.0 ± 13.0 U/L and 19.5 ± 13.2 U/L, respectively) participants (p < 0.001 and p < 0.01, respectively). An increasing trend was observed in the mean levels of serum ALT and GGT across the SUA quartile groups (p < 0.001 and p < 0.01, respectively). SUA showed a positive and significant correlation with serum ALT (p < 0.001) and GGT (p < 0.01). In further statistical analysis after adjustment for potential confounders, SUA showed an independent and significant association with serum ALT and GGT in all regression models. In conclusion, SUA was strongly associated with serum levels of ALT and GGT after adjustment for potential confounders. More prospective studies are needed to clarify the complex relationship between SUA and liver enzymes in the general population.

Assessment of Right-Sided Heart Failure in Patients with Dilated Cardiomyopathy using Magnetic Resonance Relaxometry of the Liver.

In non-ischemic dilated cardiomyopathy (DC) patients at risk of developing right heart failure (RHF), early depiction of congestive heart failure (CHF) is pivotal to inform about the hemodynamic status and tailor medical therapy. We hypothesized increased liver relaxation times measured at routine cardiovascular magnetic resonance (CMR), reflecting passive hepatic congestion, may be a valuable imaging biomarker to depict congestive heart failure. The study cohort consisted of DC patients with LV dysfunction (i.e., ejection fraction <35%) with (n = 48) and without (n = 46) right ventricular dysfunction (RVD), defined as a right ventricular ejection fraction <35%, and >45%, respectively, and a control group (n = 40). Native T1, T2, and extracellular volume (ECV) liver values were measured on routinely acquired cardiac maps. DC+RVD patients had higher C-reactive protein, troponin I and NT-pro BNP values, and worse LV functional parameters than DC-RVD patients (all p <0.001). T1, T2 and ECV Liver values were significantly higher in DC+RVD compared to DC-RVD patients and controls, that is, T1: 675 ± 88 ms verses 538 ± 39 ms and 540 ± 34 ms; T2: 54± 8 ms versus 45 ± 5 ms and 46 ± 4 ms; ECV: 36 ± 7% versus 29 ± 4% and 30 ± 3% (all p <0.001). Gamma-glutamyltranspeptidase (GGT) correlated moderately but significantly with native T1 (r2 = 0.34), T2 (r2 = 0.27), and ECV liver (r2 = 0.23) (all p <0.001). Using right atrial (RA) pressure, as surrogate measure of RHF (i.e., RA pressure >5 mm Hg), native T1 liver yielded at ROC analysis the highest area under the curve (0.906), significantly higher than ECV liver (0.813), GGT (0.806), T2 liver (0.797), total bilirubin (0.737) and alkaline phosphatase (0.561)(p = 0.04). A T1 value of 617 ms yielded a sensitivity of 79.5% and specificity of 91.0% to depict RHF. Excellent intra-/inter-observer agreement was found for assessment of native T1/T2/ECV liver values. In conclusion, in DC patients, assessment of liver relaxation times acquired on a cardiovascular magnetic resonance exam, may provide valuable information with regard to the presence of RHF.

Effects of Estrogen Therapies on Outcomes in Turner Syndrome: Assessment of Induction of Puberty and Adult Estrogen Use.

CONTEXT: Turner syndrome (TS) is often associated with delayed puberty. To induce puberty, estrogen is administered in incremental doses at an age determined by age of presentation. After puberty, various types of maintenance estrogen replacement therapy (ERT) are used. OBJECTIVE: We sought associations between age of induction of puberty and type of ERT on adult health outcomes. DESIGN: Health surveillance data included blood profiles, bone density, and blood pressure. We assessed interactions between these data and age at first estrogen exposure in women with primary amenorrhea. We also assessed these data according to ERT subgroups [combined oral contraceptive pill (OCP), oral estrogen (OE), and transdermal estradiol (TE)] using data from each of 6679 clinic visits, controlling for age, body mass index, and height. SETTING: Adult TS clinic at University College London Hospital. PATIENTS: Of 799 women with TS, 624 had primary amenorrhea and 599 had accurate maintenance ERT data. MAIN OUTCOME MEASURES: Parameters of health surveillance derived from clinical guidelines. RESULTS: Estrogen start age was negatively correlated with adult bone density (spine: r = -0.20 and hip: r = -0.022; P ≤ 0.001). OCP users had higher blood pressure and an adverse lipid profile compared with other ERT subgroups. TE was associated with elevated liver enzymes and hemoglobin A1c compared with OE (P ≤ 0.01). CONCLUSIONS: An earlier age of induction of puberty may be beneficial for adult bone density. Given the high prevalence of hypertension in TS, the use of OCP for ERT should be limited. OE may be a benefit for steatohepatitis.

Assessment of ATP8B1 Deficiency in Pediatric Patients With Cholestasis Using Peripheral Blood Monocyte-Derived Macrophages.

Progressive familial intrahepatic cholestasis type 1 (PFIC1), a rare inherited recessive disease resulting from a genetic deficiency in ATP8B1, progresses to liver failure. Because of the difficulty of discriminating PFIC1 from other subtypes of PFIC based on its clinical and histological features and genome sequencing, an alternative method for diagnosing PFIC1 is desirable. Herein, we analyzed human peripheral blood monocyte-derived macrophages (HMDM) and found predominant expression of ATP8B1 in interleukin-10 (IL-10)-induced M2c, a subset of alternatively activated macrophages. SiRNA-mediated depletion of ATP8B1 in IL-10-treated HMDM markedly suppressed the expression of M2c-related surface markers and increased the side scatter (SSC) of M2c, likely via impairment of the IL-10/STAT3 signal transduction pathway. These phenotypic features were confirmed in IL-10-treated HMDM from four PFIC1 patients with disease-causing mutations in both alleles, but not in those from four patients with other subtypes of PFIC. This method identified three PFIC1 patients in a group of PFIC patients undiagnosed by genome sequencing, an identical diagnostic outcome to that achieved by analysis of liver specimens and in vitro mutagenesis studies. In conclusion, ATP8B1 deficiency caused incomplete polarization of HMDM into M2c. Phenotypic analysis of M2c helps to identify PFIC1 patients with no apparent disease-causing mutations in ATP8B1.

Evaluation of eLIFT for Non-invasive Assessment of Liver fibrosis and Cirrhosis in Patients with Chronic Hepatitis B Virus Infection.

Recently, the easy Liver Fibrosis Test (eLIFT), a sum of points attributed to age, gender, gamma-glutamyl transpeptidase, aspartate transaminase, platelets, and prothrombin time, was developed for diagnosing advanced fibrosis and cirrhosis in chronic liver disease. We aimed to evaluate the performance of eLIFT to predict liver fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). Histologic and laboratory data of 747 CHB patients were analyzed. The performance of eLIFT for diagnosing liver fibrosis and cirrhosis was compared with that of aspartate transaminase to platelet ratio index (APRI) and fibrosis index based on the 4 factors (FIB-4). To predict advanced fibrosis, the AUROC of eLIFT was comparable with that of APRI (0.66 vs 0.71, p = 0.095) and FIB-4 (0.66 vs 0.67, p = 0.612). To predict severe fibrosis, the AUROC of eLIFT was lower than that of APRI (0.65 vs 0.83, p < 0.001) and FIB-4 (0.65 vs 0.82, p < 0.001). To predict cirrhosis, the AUROC of eLIFT was also lower than that of APRI (0.64 vs 0.85, p = 0.001) and FIB-4 (0.64 vs 0.76, p = 0.033). The eLIFT is not a good non-invasive test for the diagnosis of liver fibrosis and cirrhosis in CHB patients.

Intestinal gas and liver steatosis: a casual association? A prospective multicentre assessment.

BACKGROUND & AIMS: Excessive intestinal gas and liver steatosis are frequent sonographic findings. Both of these appear to be caused by variations of the gut microflora. We assessed the relationship between ultrasonographic detection of intestinal gas and liver steatosis. METHODS: This study included 204 consecutive patients (99 male; mean age 53.0 ± 15.6 years), who underwent ultrasonography for abdominal complaints or follow-up of benign lesions. Body mass index, biochemical liver markers, sonographic presence of liver steatosis and/or degree of intestinal gas interfering with the examination were collected. Both sonographic findings were assessed based on standardized criteria. The association between liver steatosis and intestinal gas was evaluated by means of univariate and multivariate analyses. RESULTS: Eighty (39.2%) of patients showed moderate to large amounts of gas preventing an accurate evaluation of the liver or pancreas and 90 (44.1%) had liver steatosis. A significant correlation between the degree of intestinal gas and liver steatosis both in obese (r=.603; P<.001) and in nonobese patients (r=.555; P<.001) was found. Univariate analysis showed that intestinal gas, body mass index, aspartate transaminase, alanine transaminase, gamma-GT, age and sex were predictors of liver steatosis; only intestinal gas (OR 7.4; 95% CI 3.4-16.1) and body mass index (OR; 1.4, 95% CI 1.2-1.5), however, were independent predictors at multivariate analysis. The presence of excessive gas was also significantly correlated with liver steatosis coupled with elevated ALT (P = .001). CONCLUSION: This study shows a significant correlation between excessive intestinal gas and liver steatosis. The reasons of this finding and its clinical implications remain to be defined.

[Effectiveness of clinical pathway for treatment of advanced schistosomiasis hepatic fibrosis].

Objective To assess the effectiveness of the clinical pathway for the treatment of advanced schistosomiasis hepatic fibrosis. Methods The duration of hospital stay, gross hospitalization expense, individual-paid expense, interior diameter of portal vein, levels of four serum hepatic fibrosis-related parameters (PIIIP, CIV, HA, and LN), and activities of ALT, AST and γ-GT were assessed and compared between the advanced schistosomiasis patients receiving the clinical pathway and ones receiving non-clinical pathway. Results There were 142 advanced schistosomiasis patients with hepatic fibrosis receiving the clinical pathway of anti-hepatic fibrosis. Compared with the patients receiving non-clinical pathway, the gross hospitalization expenses reduced by 11.2% (t = 6.310, P < 0.05), and the individual-paid expenses reduced by 16.1% (t = 4.326, P < 0.05). The mean HA level was twice higher than the normal range, with a positive rising from 70.4% to 83.1%, and the abnormal rates of CIV and γ-GT were 64.1% and 28.9% respectively. Conclusions The clinical pathway can drastically reduce the treatment expenses in advanced schistosomiasis patients with hepatic fibrosis. However, the patients have a trend towards the persistent disease progression. Therefore, the researches of more effective therapeutic methods for advanced schistosomiasis hepatic fibrosis are urgently needed.

Assessment of enzyme measurement procedures in China through a trueness verification program.

BACKGROUND: Since 2003, the National Center for Clinical Laboratories (NCCL) has organized a network of reference laboratories and several survey programs to improve standardization in China. METHODS: We analyzed the 2015 trueness verification program to assess the status of enzyme measurement standardization. Commutable serum-based materials were prepared and sent to 10 reference laboratories to assign target values for 2 enzymes (alanine aminotransferase-pyridoxal phosphate [ALT-pp] and γ-glutamyltransferase [GGT]) using IFCC reference measurement procedures. RESULTS: Analytical performance was assessed for compliance to 3 indexes: trueness (bias), imprecision (CV), and accuracy (total error). Of the 250 participating laboratories, about half (≥124) used heterogeneous systems. More laboratories met the tolerance limit of imprecision than of trueness or accuracy. Except at the lowest concentration, the CV pass rates were >90% for the 2 enzymes. The optimal performance criterion derived from biological variation yielded pass rates for total error (ALT 77%, GGT 80%) that were higher than for bias (ALT 63%, GGT 73%). CONCLUSIONS: PT/EQA results for commutable samples can be used to assess trueness against reference measurement procedures. Despite global and national standardization programs, bias remains a critical limitation of current enzyme measurement procedures in China.

Ethanol metabolites: their role in the assessment of alcohol intake.

BACKGROUND: Alcohol-related disorders are common, expensive in their course, and often underdiagnosed. To facilitate early diagnosis and therapy of alcohol-related disorders and to prevent later complications, questionnaires and biomarkers are useful. METHODS: Indirect state markers like gamma-glutamyl-transpeptidase, mean corpuscular volume, and carbohydrate deficient transferrin are influenced by age, gender, various substances, and nonalcohol-related illnesses, and do not cover the entire timeline for alcohol consumption. Ethanol (EtOH) metabolites, such as ethyl glucuronide, ethyl sulfate, phosphatidylethanol, and fatty acid ethyl esters have gained enormous interest in the last decades as they are detectable after EtOH intake. RESULTS: For each biomarker, pharmacological characteristics, detection methods in different body tissues, sensitivity/specificity values, cutoff values, time frames of detection, and general limitations are presented. Another focus of the review is the use of the markers in special clinical and forensic samples. CONCLUSIONS: Depending on the biological material used for analysis, ethanol metabolites can be applied in different settings such as assessment of alcohol intake, screening, prevention, diagnosis, and therapy of alcohol use disorders.

Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study.

BACKGROUND: Observational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people. METHODS: An instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak. RESULTS: In men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis. CONCLUSION: In Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations.

Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain.

Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [(13) N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [(13) N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [(13) N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [(13) N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [(15) O]H2 O. The reduction of [(13) N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [(13) N]ammonia may enable measurement of GS activity in the living brain.

Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population.

AIMS: Fatty liver disease, especially non-alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance. METHODS: We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow-up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ-glutamyltransferase, waist circumference and BMI. RESULTS: During a 4-year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index-positive) than in the group with a fatty liver index < 20 (fatty liver index-negative) after adjusting for various confounding variables including homeostasis model assessment of insulin resistance. Odds ratios were significant regardless of the insulin resistance status at baseline. CONCLUSIONS: Our results suggest that fatty liver index as a simple surrogate indicator of hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance.

Rapid colorimetric determination of reduced and oxidized glutathione using an end point coupled enzymatic assay.

A simple and rapid colorimetric coupled enzymatic assay for the determination of glutathione is described. The proposed method is based on the specific reaction catalyzed by γ-glutamyltransferase, which transfers the γ-glutamyl moiety from glutahione to an acceptor, with the formation of the γ-glutamyl derivative of the acceptor and cysteinylglycine. The latter dipeptide is a substrate of leucyl aminopeptidase, which hydrolyzes cysteinylglycine to glycine and cysteine that can be easily measured spectrophotometrically. The proposed method was used to measure the content of glutathione in acid extracts of bovine lens, to follow the NADPH-dependent reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH) catalyzed by the enzyme glutathione reductase and to determine the glutathione content in human astrocytoma ADF cells subjected to oxidative stress. The results obtained showed that the method can be suitably used for the determination of GSH and GSSG in different biological samples and to monitor tissue or cell redox status under different conditions. It is also applicable for following reactions involving GSH and/or GSSG.

Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction.

A double-blind parallel group comparison design clinical study was conducted in Japanese patients with mild to moderate erectile dysfunction to investigate the efficacy of a supplement containing Pycnogenol® and L-arginine. Subjects were instructed to take a supplement (Pycnogenol® 60 mg/day, L-arginine 690 mg/day and aspartic acid 552 mg/day) or an identical placebo for 8 weeks, and the results were assessed using the five-item erectile domain (IIEF-5) of the International Index of Erectile Function. Additionally, blood biochemistry, urinalysis and salivary testosterone were measured. Eight weeks of supplement intake improved the total score of the IIEF-5. In particular, a marked improvement was observed in 'hardness of erection' and 'satisfaction with sexual intercourse'. A decrease in blood pressure, aspartate transaminase and γ-glutamyl transpeptidase (γ-GTP), and a slight increase in salivary testosterone were observed in the supplement group. No adverse reactions were observed during the study period. In conclusion, Pycnogenol® in combination with L-arginine as a dietary supplement is effective and safe in Japanese patients with mild to moderate erectile dysfunction.

Pesticide risk assessment: A study on inhalation and dermal exposure to 2,4-D and paraquat among Malaysian paddy farmers.

A cross-section analytical study was conducted to evaluate the risk of pesticide exposure to those applying the Class II pesticides 2,4-D and paraquat in the paddy-growing areas of Kerian, Perak, Malaysia. It investigated the influence of weather on exposure as well as documented health problems commonly related to pesticide exposure. Potential inhalation and dermal exposure for 140 paddy farmers (handlers of pesticides) were assessed. Results showed that while temperature and humidity affected exposure, windspeed had the strongest impact on pesticide exposure via inhalation. However, the degree of exposure to both herbicides via inhalation was below the permissible exposure limits set by United States National Institute of Occupational Safety and Health (NIOSH). Dermal Exposure Assessment Method (DREAM) readings showed that dermal exposure with manual spraying ranged from moderate to high. With motorized sprayers, however, the level of dermal exposure ranged from low to moderate. Dermal exposure was significantly negatively correlated with the usage of protective clothing. Various types of deleterious health effects were detected among users of manual knapsack sprayers. Long-term spraying activities were positively correlated with increasing levels of the gamma-glutamyl transpeptidase (GGT) liver enzyme. The type of spraying equipment, usage of proper protective clothing and adherence to correct spraying practices were found to be the most important factors influencing the degree of pesticide exposure among those applying pesticides.

Assessment of urinary γ-glutamyltransferase and alkaline phosphatase for diagnosis of diabetic nephropathy.

BACKGROUND: Urinary biomarkers of tubular damage can be useful for early diagnosis of diabetic nephropathy. Thus, the aim of this study was to test the diagnostic accuracy of the urinary excretion of γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) for diagnosis of diabetic nephropathy (DN). METHODS: Fasting glucose, fructosamine, serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum albumin, and urinary albumin, creatinine, GGT and ALP were assessed in 74 type 2 diabetic patients without nephropathy and 38 type 2 diabetic patients with nephropathy. RESULTS: Urinary GGT and ALP were threefold higher in type 2 diabetic patients with nephropathy. Significant correlations were observed between urinary albumin and GGT (r=0.439, P<0.001) and urinary albumin and ALP (r=0.305, P<0.01). Areas under the curve for GGT and ALP were 0.7696 (P<0.001) and 0.7233 (P<0.001), respectively. At a cut-off value of 72U/g creatinine, GGT demonstrated a sensitivity of 96.0% and a specificity of 52.6%. At a cut-off value of 20U/g creatinine, ALP demonstrated a sensitivity and specificity of 83.8% and 36.8%, respectively. CONCLUSIONS: Urinary GGT and ALP have potential value in the diagnosis of nephropathy in type 2 diabetic patients, but GGT has a slightly higher ability to discriminate nephropathy than ALP.

Effective use of FibroTest to generate decision trees in hepatitis C.

AIM: To assess the usefulness of FibroTest to forecast scores by constructing decision trees in patients with chronic hepatitis C. METHODS: We used the C4.5 classification algorithm to construct decision trees with data from 261 patients with chronic hepatitis C without a liver biopsy. The FibroTest attributes of age, gender, bilirubin, apolipoprotein, haptoglobin, alpha2 macroglobulin, and gamma-glutamyl transpeptidase were used as predictors, and the FibroTest score as the target. For testing, a 10-fold cross validation was used. RESULTS: The overall classification error was 14.9% (accuracy 85.1%). FibroTest's cases with true scores of F0 and F4 were classified with very high accuracy (18/20 for F0, 9/9 for F0-1 and 92/96 for F4) and the largest confusion centered on F3. The algorithm produced a set of compound rules out of the ten classification trees and was used to classify the 261 patients. The rules for the classification of patients in F0 and F4 were effective in more than 75% of the cases in which they were tested. CONCLUSION: The recognition of clinical subgroups should help to enhance our ability to assess differences in fibrosis scores in clinical studies and improve our understanding of fibrosis progression.

Socioeconomic status, antioxidant micronutrients, and correlates of oxidative damage: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: To examine whether socioeconomic status (SES) (education, occupation, income), is associated both cross sectionally and prospectively with circulating concentrations of a) two correlates of oxidative damage, F(2)-isoprostanes (F(2)-IsoPs) and gamma-glutamyltransferase (GGT); and b) antioxidant nutrients (ascorbic acid and carotenoids). We also examine whether the proposed associations are mediated by smoking, alcohol consumption, and depression. Risk for chronic disease increases with decreasing SES. One pathway by which low SES might influence disease risk is by promoting oxidative stress. METHODS: Data from 1278 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the association of SES with oxidation correlates and antioxidant nutrients. Education, occupation, health behaviors, and body mass index (BMI) were assessed during Years 0, 10, and 15 of the study; income and depression were evaluated at Years 10 and 15. F(2)-isoprostanes were measured at Year 15, gamma-glutamyltransferase (GGT) at Years 0 and 10, carotenoids at Years 0 and 15, and ascorbic acid at Years 10 and 15. RESULTS: Cross sectionally, oxidation correlates decreased and antioxidant nutrients increased with increasing SES, estimated in several ways, independent of age, sex, race, and BMI. Prospectively, lower Year 0 education and occupation predicted greater increases in GGT and greater decreases in carotenoids over 10 to 15 years. Prospective associations of Year 0 SES with Year 15 carotenoids were independent of Year 15 SES. Smoking, drinking, and depression symptoms partially mediated these effects. CONCLUSIONS: Circulating oxidation correlates increase and antioxidant nutrients decrease with decreasing SES, both cross sectionally and prospectively.

Assessment of a new cell culture perfusion apparatus for in vitro chronic toxicity testing. Part 2: toxicological evaluation.

The goal of replacement, refinement and reduction of animal testing is critically dependent on the development and assessment of novel in vitro methodologies and the further development of existing methodologies. Here, we evaluated the use of a modified perfusion cell culture apparatus for application to chronic in vitro nephrotoxicity testing using DMSO, SDS, paracetamol and cyclosporine A as test compounds. Renal epithelial monolayers were cultured on microporous growth supports and exposed to test compounds under static or perfusion conditions. Alamar Blue reduction, gamma-glutamyl transpeptidase activity (GGT), lactate dehydrogenase activity (LDH) and remnant protein were used to assay cell toxicity. There was no significant difference in IC(50) values between static and perfusion cultures up to 72 hours exposure. However, the perfusion system allowed continuous real-time monitoring of plasma membrane damage, which gives important information of time, duration and scale of toxicity. The complexity of the system restrains its use to low-throughput analysis. However, the real and theoretical advantages of this and similar systems merit further investigations.

Assessment of copper status in epileptic patients treated with anticonvulsant drugs by measuring the specific oxidase activity of ceruloplasmin.

Significant increases in serum levels and decreases in hair copper levels have been previously described in epileptic patients treated with anticonvulsant drugs. A condition not directly related to copper nutriture, such as chronic treatment with these drugs, could increase the serum concentrations of copper and ceruloplasmin and would mask a possible copper deficiency produced by drug-increased biliary copper excretion. Serum immunoreactive ceruloplasmin concentration and its oxidase activity were determined in 90 adult epileptic patients treated with phenobarbital (n=60), phenytoin (n=70), carbamazepine (n=33) and valproic acid (n=8). The levels of ceruloplasmin and oxidase activity were significantly higher (P<0.001) than in an age and gender-matched control group (n=49). The significant correlations (P<0.01) between ceruloplasmin and the urinary excretion of D-glucaric acid, serum gamma-glutamyltransferase (GGT) and drug score in the patients group, would suggest that phenobarbital-type enzyme-inducing agents may increase the hepatic synthesis of ceruloplasmin. In 11 patients with a beta-globulin migrating GGT isoform (GGT3), a sensitive marker of cholestasis, the levels of ceruloplasmin, oxidase activity and total GGT activity were significantly higher (P<0.05) than in the group of 79 patients without the GGT3 isoform; consequently, in some cases a drug-induced cholestasis may also contribute to the increase of serum copper and ceruloplasmin. The values obtained for the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) suggest that in the most of the cases, chronic administration of phenobarbital, phenytoin, carbamazepine or valproic acid, does not produce marginal or moderate copper deficiency.