HLA-subtypes B*27 and ankylosing spondylitis features comments on Fellahi’s article “Are early onset of disease and uveitis affected by HLA- subtypes B*27 in ankylosing spondylitis?”

Clinical Rheumatology -     

Serum androgens and prostate cancer among 643 cases and 643 controls in the European Prospective Investigation into Cancer and Nutrition

We examined the hypothesis that serum concentrations of circulating androgens and sex hormone binding globulin (SHBG) are associated with risk for prostate cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of androstenedione, testosterone, androstanediol glucuronide and SHBG were measured in serum samples for 643 prostate cancer cases and 643 matched control participants, and concentrations of free testosterone were calculated. Conditional logistic regression models were used to calculate odds ratios for risk of prostate cancer in relation to the serum concentration of each hormone. After adjustment for potential confounders, there was no significant association with overall risk for prostate cancer for serum total or free testosterone concentrations (highest versus the lowest thirds: OR, 1.02; 95% CI, 0.73-1.41 and OR, 1.07, 95% CI, 0.74-1.55, respectively) or for other androgens or SHBG. Subgroup analyses showed significant heterogeneity for androstenedione by cancer stage, with a significant inverse association of androstenedione concentration and risk for advanced prostate cancer. There were also weak positive associations between free testosterone concentration and risk for total prostate cancer among younger men and risk for high-grade disease. In summary, in this large nested case-control study, concentrations of circulating androgens or SHBG were not strongly associated with risk for total prostate cancer. However, our findings are compatible with a positive association of free testosterone with risk in younger men and possible heterogeneity in the association with androstenedione concentration by stage of disease; these findings warrant further investigation.     

Physical activity and endometrial cancer risk: a review of the current evidence,biologic mechanisms and the quality of physical activity assessment methods

Objectives To (1) determine the nature of the association between physical activity and endometrial cancer risk; (2) assess the contribution of variation in the quality of physical activity measurement to inconsistencies in study results; and (3) review the biologic mechanisms that might mediate possible effects of physical activity on risk. Methods We reviewed and summarized all published epidemiologic studies examining physical activity and endometrial cancer risk, and evidence relating to possible biologic mechanisms. We assigned each study a quality score for physical activity measurement. Results Fourteen of the 18 studies showed a convincing or possible protective effect of physical activity on endometrial cancer risk, with an average relative risk reduction of around 30%. A dose–response relation was observed in 7 of 13 studies. The quality score was not related to the observed strength of association or the presence of a dose–response relation. There was epidemiologic and biologic evidence that vigorous activity, as well as light and moderate intensity activities, such as housework, gardening or walking for transportation, may reduce risk. Conclusions Physical activity probably has a protective role in endometrial cancer development. More epidemiologic and biologic evidence is needed to make conclusive recommendations on optimal types, characteristics or time periods of physical activity. Financial support: Anne Cust is supported by a PhD scholarship (UPA) from the University of Sydney and a Research Scholar Award from the Cancer Institute NSW, Australia. Christine Friedenreich is supported by a Canadian Institutes for Health Research New Investigator Award and an Alberta Heritage Foundation for Medical Research Health Scholar Award. Bruce Armstrong’s research is supported by a University of Sydney Medical Foundation Program Grant.     

Liver electrolysis: pH can reliably monitor the extent of hepatic ablation in pigs

Electrolysis is a method of tissue ablation that creates chemical species and a pH gradient in response to direct current. Initial studies of electrolysis in animal models and humans have shown that it is a safe, predictable and effective process for destroying normal and tumour-bearing liver in a linear, dose-dependent manner. Presently, the amount of current that is applied (in coulombs) has to be calculated using historical data, with inherent inaccuracy. The present study tested whether pH could be used as a real-time monitor in order to predict more accurately the extent of necrosis. A total of 70 electrolytic lesions were created in 14 pigs, with pH monitoring of the lesion edge. The normal range of pH values was 6.5-8.7. A pH of less than 6 (at the anode) or more than 9 (at the cathode) reflected total cellular necrosis. When a pH value was recorded between 6.0 and 6.5 at the anode or between 8.7 and 9.0 at the cathode, the presence of necrosis was variable. In conclusion, during electrolytic ablation, pH measurement can monitor the extent of the induced necrosis.     

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC)

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.     

Effect of lead exposure on dopaminergic transmission in the rat brain

Lead is a neurotoxicant with known behavioral and neurochemical effects. In this study we attempted to relate the behavioral effects of lead to neurotransmission. Oral administration of 1000 ppm of lead acetate to young rats for 30 days caused a reduction in locomotor activity and stereotypic exploratory behavior during a 20 min testing period. This locomotor hypoactivity induced by lead was accompanied by a reduction in stereotypic behavior (sniffing, lickings, biting and grooming). These outcomes suggested that lead might interfere with catecholaminergic and particularly dopaminergic neurotransmission. Therefore, we examined the effect of the lead acetate on the uptake of dopamine in striatal synaptosomal preparations. The collected data showed a clear inhibition of the uptake of 3H-DA with an IC50 of 3.5 x 10(-5)M. This inhibition of the uptake of dopamine suggests that the behavioral effects of lead may be involved in dopaminergic neurotransmission.     

Effect of E670G Polymorphism in PCSK9 Gene on the Risk and Severity of Coronary Heart Disease and Ischemic Stroke in a Tunisian Cohort

The association of E670G (rs505151) polymorphism in PCSK9 gene with an increased risk of coronary artery disease (CAD) and ischemic stroke (IS) was reported in previous studies. We investigated the effect of the E670G (rs505151) on the risk of CAD and IS in a Tunisian cohort. Genotyping of the PCSK9 E670G was performed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) and then confirmed by direct sequencing. The frequency of the 670G allele was significantly higher in the CAD than in the no-CAD subgroup (0.132 vs. 0.068, p?=?0.030). As expected, the incidence of E670G was significantly important in IS subgroup than control group (0.122 vs. 0.073, p?=?0.032). Furthermore in CAD patients, the 670G carriers showed significantly increased plasma total cholesterol and LDL-cholesterol levels compared to E670 carriers (6.78 [6.47–7.00] vs. 4.92 [4.02–5.46] mmol/l, p?<?0.0001 and 4.60 [4.00–5.04] vs. 3.00 [2.22–3.70] mmol/l p?=?0.001, respectively). The risk and severity of CAD were significantly increased in 670G carriers between no-CAD subgroup and CAD patients presenting a stenosis ≥50 % in two or three major coronary arteries (0.068 vs. 0.198, p?=?0.001, OR?=?3.39 [1.55–7.37]). The E670G polymorphism of the PCSK9 gene is mainly associated with a increased risk and severity of CAD and IS in Tunisian cohort.