Serum paraoxonase-3 concentration is associated with the severity of hepatic impairment in patients with chronic liver disease

Objectives

Research on paraoxonase-3 (PON3) has been hampered by the lack of methods for measurement. This is a pilot study aimed at exploring whether chronic liver impairment is associated with changes in serum PON3 concentrations, and to know whether this measurement may provide useful information to investigate this derangement.

Design and methods

We studied 110 patients with chronic liver disease (21 minimal changes, 79 chronic hepatitis, 10 cirrhosis) and 356 healthy volunteers. Serum PON3 concentration was determined by ELISA using polyclonal antibodies generated against a synthetic peptide with a sequence specific to PON3.

Results

Serum PON3 concentrations were increased in patients with chronic hepatitis or cirrhosis and showed significant direct correlations with the degree of periportal abnormalities including fibrosis, and with serum FAS (a marker of antiapoptosis) concentrations.

Conclusion

These results suggest that PON3 may play a hepatoprotective role against histological alterations and hepatic cell apoptosis leading to liver disease.     

Cardiac manifestations of parasitic infections part 3: pericardial and miscellaneous cardiopulmonary manifestations

This is part three of a three-part series discussing parasites of the heart. In this section, we present an overview on parasitic diseases involving predominantly the pericardium and other miscellaneous cardiopulmonary manifestations such as some pulmonary hypertension syndromes and endomyocardial fibrosis.     

Role of Protein Kinase-C in Thymocyte Apoptosis Induced by Irradiation

The role of protein kinase C in radiation-induced death of thymocytes was studied. For this purpose murine thymocytes were irradiated and incubated for 6 h at 37°C and afterwards the fraction of fragmented DNA was measured. Results indicate that radiation-induced DNA fragmentation can be prevented by adding the protein kinase C inhibitor H-7 or staurosporine to the thymocytes during incubation time. Incubation of irradiated cells with HA-1004, an inhibitor of cAMP-dependent protein kinase, with a minor effect on protein kinase C did not affect the DNA fragmentation induced by irradiation. Incubation of cells with phorboldibutyrate gave a dose-dependent induction of DNA fragmentation. This effect can be inhibited by staurosporine. These results suggest that radiation-induced DNA fragmentation is an active cellular process in which protein kinase C plays an important role.     

Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation

OBJECTIVE: To investigate the association between the Trp64Arg beta3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. DESIGN AND SUBJECT: Cross-sectional study in 1063 (476 men and 587 women) randomly selected from this population (aged: 18-68 years). MEASUREMENTS: Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism. RESULTS: Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060). We found gender-specific associations between the Trp64Arg mutation and obesity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 +/- 3.81 vs. 26.34 +/- 3.57 kg m-2, P=0.049) and total cholesterol (5.85 +/- 1.45 vs. 5.28 +/- 1.06 mmol L-1; P=0.011) compared with wild-type individuals. Logistic regression analysis, revealed that the risk of overweight was two times higher in male carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fasting glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables. For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men and women. However, after adjustment for covariates, these associations only remained statistically significant (P < 0.02) in women. Moreover, in women, a statistically significant interaction (P=0.026) between the LPL and the ADRB3 gene loci in determining BMI was found. Thus, the Arg64 allele was associated with a higher BMI only in H+/H+ women. CONCLUSIONS: The Trp64Arg mutation was associated with BMI and lipids in men. In women, an additional gene-gene interaction with the LPL-HindIII polymorphism may explain the results.     

Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal staging in lung cancer

OBJECTIVE:

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive diagnostic test with a high diagnostic yield for suspicious central pulmonary lesions and for mediastinal lymph node staging. The main objective of this study was to describe the diagnostic yield of EBUS-TBNA for mediastinal lymph node staging in patients with suspected lung cancer.

METHODS:

Prospective study of patients undergoing EBUS-TBNA for diagnosis. Patients ≥ 18 years of age were recruited between July of 2010 and August of 2013. We recorded demographic variables, radiological characteristics provided by axial CT of the chest, location of the lesion in the mediastinum as per the International Association for the Study of Lung Cancer classification, and definitive diagnostic result (EBUS with a diagnostic biopsy or a definitive diagnostic method).

RESULTS:

Our analysis included 354 biopsies, from 145 patients. Of those 145 patients, 54.48% were male. The mean age was 63.75 years. The mean lymph node size was 15.03 mm, and 90 lymph nodes were smaller than 10.0 mm. The EBUS-TBNA method showed a sensitivity of 91.17%, a specificity of 100.0%, and a negative predictive value of 92.9%. The most common histological diagnosis was adenocarcinoma.

CONCLUSIONS:

EBUS-TBNA is a diagnostic tool that yields satisfactory results in the staging of neoplastic mediastinal lesions.     

Environmental factors modulate the effect of the APOE genetic polymorphism on plasma lipid concentrations: ecogenetic studies in a Mediterranean Spanish population

To investigate APOE gene--environment interaction effects on plasma lipid concentrations, we conducted a cross-sectional study in a Mediterranean Spanish population consisting of 396 men and 513 women aged 18 to 66 years. The frequency of the epsilon 4 variant was 0.071 (95% confidence interval 0.059, 0.082), confirming the lower frequency of this allele in Southern Europe. In general, the carriers of the epsilon 2 variant had lower concentrations (P <.05) of total and low-density lipoprotein cholesterol (LDL-C), carriers of the epsilon 3 variant had intermediate concentrations, and carriers of the epsilon 4 variant had higher concentrations (P <.05) in both sexes, even after multivariate adjustment for age, body mass index, alcohol consumption, tobacco smoking, physical activity, marital status, and education. However, when the homogeneity of allelic effects according to environmental factors was tested, significant interaction terms were found. In women, an important interaction between alcohol consumption and the APOE polymorphism in determining LDL-C concentrations was found (P <.003). LDL-C concentrations in female drinkers with the epsilon 2 variant were significantly lower (P <.014) than in nondrinkers with the epsilon 2 variant. Likewise, in female drinkers with the epsilon 4 variant, LDL-C concentrations were also significantly (P <.010) lower than in nondrinkers with the epsilon 4 variant. Moreover, in female drinkers, LDL-C concentrations did not differ between carriers of the epsilon 4 and the epsilon 3 variants, and in nondrinkers, LDL-C concentrations did not differ between carriers of the epsilon 2 and the epsilon 3 variants. We also found a statistically significant interaction effect (P <.001) between the APOE polymorphism and physical activity in determining high-density lipoprotein cholesterol concentrations in men. Our results indicate that environmental factors are important modulators of the effect of the APOE polymorphism on plasma lipid concentrations.