N-acetyltransferase 2 single-nucleotide polymorphisms and risk of gastric carcinoma

OBJECTIVE: To explore whether an association exists between the NAT2 genotype and the risk of developing gastric cancer.METHODS. Ninety-nine patients with gastric adenocarcinoma and 258 healthy subjects were analysed for single-nucleotide polymorphisms at the NAT2 gene locus, which give rise to gene variants known to be associated with slow-acetylation status.RESULTS: The functional NAT2*4 (wild-type) allele is over-represented among patients (40.4% of all allelic variants) compared with control subjects [25.8%, odds ratio (OR) 1.95, 95% confidence interval (CI) 1.36, 2.8]. According to the NAT2 genotype, 69 patients (69.9%) and 119 healthy subjects (46%) were classified as rapid acetylators (OR 2.69, 95% CI 1.6, 4.54).CONCLUSIONS: Our results, which need independent confirmation, suggest that individuals with NAT2 genotypes leading to high levels of NAT2 enzyme activity are at increased risk of developing gastric carcinoma.     

Biochemical characterization of rhinovirus RNA-dependent RNA polymerase

Human rhinoviruses (HRV) represent the single most important causative agent of the common cold. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) designated 3D polymerase that is required for replication of the HRV RNA genome. We have expressed and purified recombinant HRV-16 3D polymerase to near homogeneity from Escherichia coli transformed with an expression plasmid containing the full-length 460 amino acid HRV-16 3D sequence with a methionine at the N-terminus and a glycine-serine linker followed by a 6-histidine affinity tag at the C-terminus. The purified recombinant protein has rifampicin-resistant activity in a poly(A)-dependent poly(U) polymerase assay while corresponding fractions similarly purified from E. coli transformed with an expression plasmid without the HRV-16 3D sequence showed no activity. The optimal conditions for temperature, pH, divalent cations Mg(2+) and Mn(2+), and KCl were determined. The recombinant protein has RNA polymerase activity on homopolymeric templates poly(A) and poly(C) and heteropolymeric RNA templates primed with either RNA or DNA oligonucleotide primers or self-primed by a copy-back mechanism. A unique, secondary structureless heteropolymeric RNA template that is an efficient substrate was developed to facilitate kinetic characterizations of the enzyme. In the presence of Mg(2+), the enzyme displayed strong base and sugar specificity. However, when Mg(2+) was replaced by Mn(2+) specificity for ribonucleotides was lost, utilization of deoxynucleotides became possible and primer-independent activity was observed on the poly(C) template. Zn(2+) was found to inhibit HRV-16 3D polymerase with an IC(50) as low as 0.6 microM by a mechanism distinct from the magnesium ion stimulation. The activity of this 6His-tagged HRV-16 3D polymerase was compared with that of a recombinant HRV-16 3D polymerase expressed without the 6His-tag and was found to be identical. The availability of recombinant rhinovirus RdRp in a purified form will facilitate the structure-function analysis of this enzyme as well as the identification of specific inhibitors to the rhinovirus 3D polymerase that have therapeutic value in the treatment of the common cold.     

Pi*S and Pi*Z alpha 1 antitrypsin polymorphism and the risk for asbestosis in occupational exposure to asbestos

The effect of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) on gallium arsenide (GaAs) induced liver damage was studied. The oral feeding rat model was used in this study. The animals were exposed to 10 mg/kg GaAs, orally, once daily, 5 days a week for 24 weeks and treated thereafter with single oral daily dose of either 0.3 mmol/kg DMSA or MiADMSA for two course of 5 days treatment. The animals were sacrificed thereafter. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substance (TBARS). Liver damage was assessed by number of biochemical variables and by light microscopy. The activity of superoxide dismutase (SOD) and delta-aminolevulinic acid dehydratase (ALAD) beside reduced glutathione (GSH) concentration was measured in blood. Exposure to GaAs produced a significant reduction in GSH while, increased the oxidized glutathione (GSSG) concentration. Hepatic glutathione peroxidase (GPx) and catalase activity increased significantly while level of serum transaminase increased moderately. Gallium arsenide exposure also produced marked hepatic histopathological lesions. Overall, treatment with MiADMSA proved to be better than DMSA in the mobilization of arsenic and in the turnover of some of the above mentioned GaAs sensitive biochemical alterations. Histopathological lesions also, responded more favorably to chelation treatment with MiADMSA than DMSA.     

Mediterranean diet and reduction in the risk of a first acute myocardial infarction: an operational healthy dietary score

Summary. Background: Although an important secondary prevention trial reported an impressive protection by a Mediterranean dietary pattern on reinfarction and cardiovascular death, scarce direct epidemiologic evidence is currently available regarding the role of the Mediterranean diet in the aetiology of coronary heart disease. Aims: The aim of the study was to quantify the risk reduction of incident myocardial infarction provided by a Mediterranean dietary pattern. Methods: We included 342 subjects (171 patients who suffered their first acute myocardial infarction and 171 matched controls) in a case-control study. A validated semi-quantitative food frequency questionnaire (136 items) was used. We defined an a priori Mediterranean dietary pattern. We assessed six food items that we considered protective: 1) olive oil, 2) fiber, 3) fruits, 4)vegetables, 5) fish and 6) alcohol. For each of these six dietary factors, we calculated the distribution according to quintiles within the study and assigned each participant a score of 1 to 5 corresponding to the quintile of intake, with 1 representing the lowest and 5 representing the highest quintile. We also estimated the quintiles of two other elements assumed to be associated with a higher risk: 7) meat/meat products and 8) some items with high glycaemic load (white bread, pasta and rice). For these two elements we inversely ranked the score, with 1 representing the highest and 5 representing the lowest quintile. Finally, we summed up the eight quintile values for each participant. A second score (post hoc pattern) was built using only a single cut-off point for these eight elements. The cut-off points for each element in this post hoc pattern were decided according to the dose-response relationships between the consumption of each food item and the risk of myocardial infarction observed in the analyses that used quintiles of each food item. Results: For both patterns, we found that the higher the score, the lower the odds ratio of myocardial infarction. A significant linear trend was apparent after adjustment for the main cardiovascular risk factors. For each additional point in the a priori Mediterranean pattern (observed range: 9–38) the odds ratio (95 % confidence intervals) was 0.92 (0.86–0.98). This estimate was 0.55 (0.42–0.73) when we used the post hoc pattern (range: 0–8). Conclusions: Our data support the hypothesis that a Mediterranean diet (that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products) can be an effective measure for reducing the risk of myocardial infarction. However, our results support the exclusion of refined cereals with a high glycaemic load as healthy elements of this pattern. Received: 24 January 2002, Accepted: 13 May 2002     

Burden of illness in irritable bowel syndrome comparing Rome I and Rome II criteria

OBJECTIVES: To evaluate the burden of illness in irritable bowel syndrome (IBS), in terms of resource utilisation (direct and indirect) and health-related quality of life (HR-QOL), in individuals with IBS who meet Rome I and Rome II criteria. METHODS: A cross-sectional study, carried out by personal interview, on a representative sample (n = 2000) of the Spanish population. Individuals with suspected IBS were identified via a screening question and subsequently given an epidemiological questionnaire to complete. The questionnaire collected information on IBS symptoms, resource utilisation, and HR-QOL [Medical Outcomes Study 36-item Short Form (SF-36)]. RESULTS: Sixty-five individuals met Rome II criteria for IBS, while 146 individuals met exclusively Rome I criteria. Of Rome II individuals, 67.7% had consulted some type of healthcare professional in the previous 12 months, compared with only 41.8% of those individuals meeting exclusively Rome I criteria (p vs 17.1%); 'drug consumption' (70.8 vs 45.2%); and 'reduced performance in main activity' (60 vs 27.4%). Compared with the general population, the study sample reported significantly worse HR-QOL scores in four dimensions of the SF-36 ('bodily pain', 'vitality', 'social functioning' and 'role-emotional'. Additionally, individuals meeting Rome II criteria reported worse HR-QOL scores than those individuals meeting exclusively Rome I criteria, especially in the 'bodily pain' and 'general health' dimensions. CONCLUSIONS: The burden of illness in IBS is important and correlated to the diagnostic criteria employed. Individuals who met Rome II criteria reported a higher level of resource utilisation and worse HR-QOL than individuals meeting exclusively Rome I criteria.