Effect of ENPP1/PC-1-K121Q and PPARgamma-Pro12Ala polymorphisms on the genetic susceptibility to T2D in the Tunisian population

Diabetes mellitus is the most common chronic metabolic disease. The raising diabetes epidemic is unfolding as an interaction between several environmental factors and a genetic predisposition. The aim of the current study was to evaluate the role of the PPARγ-Pro12Ala and ENPP1-K121Q polymorphisms on type 2 diabetes (T2D) risk in a case–control study in the Tunisian population. To assess for any association of ENPP1-K121Q and PPARγ-Pro12Ala polymorphisms with T2D risk, we analysed the genotypic and allelic distributions of each variant in the studied cohort. Our results support that the genetic variation at ENPP1-K121Q predisposes to T2D in the Tunisian population after adjustment on gender, age and BMI status (OR = 1.55, 95%CI [1.11–2.16], p = 0.007).Conversely, the PPARγ-Pro12Ala variant seems not to have a significant effect on T2D risk in our Tunisian cohort. However, the minor A-allele would convey protection against overweight in the Tunisian population. In fact, the over weighted subjects showed a significantly lower frequency of A-allele than lean controls (OR = 0.49, 95%CI [0.25–0.97], p = 0.02). In conclusion, our findings support the hypothesis that ENPP1-121Q is involved in the genetic susceptibility of T2D in the Tunisian population, while the PPARγ-12Ala allele may confer protection against overweight.     

Histopathological findings in appendectomy specimens: a study of 24,697 cases

Purpose

Appendicitis is by far the commonest major emergency general surgical operation. Histopathological examination of the appendix is routinely performed.

Methods

This study is a retrospective analysis of 24,697 appendectomies performed from January 2003 to December 2011. Pathological reports were analyzed for the following parameters: age, gender, and pathological diagnosis.

Results

Appendectomy specimens represent 17 % of all pathological reports. Acute appendicitis was present in 19,637 (79.5 %) patients. The perforation rate was 6.3 % and was significantly higher in adult patients. The negative appendectomy rate was 15 % and was significantly higher in female and adult patients. The incidence of negative appendectomies had clearly decreased over the 9-year period distribution. Incidental unexpected pathological diagnoses were noted in 226 (0.9 %) appendectomy specimens. Neoplastic lesions were present in 171 cases (0.7 %); they include carcinoid, adenocarcinoma, and mucinous neoplasms.

Conclusions

Routine pathological examination of appendectomy specimens is expensive. With advances in technology and imaging modalities, the diagnosis of acute appendicitis has improved, with a subsequent significant reduction in negative appendectomy. There are still a number of unusual diagnoses found in appendicectomy specimens supporting the continued use of routine histology.     

Skeletal phenotype/genotype in progressive pseudorheumatoid chondrodysplasia

Clinical Rheumatology - Axial and extra-axial deceleration in function and progressive joint pain with subsequent development of antalgic gait associated with swellings, and stiffness of the joints...     

Dynamics of the Toxin Cylindrospermopsin and the Cyanobacterium Chrysosporum (Aphanizomenon) ovalisporum in a Mediterranean Eutrophic Reservoir

Chrysosporum ovalisporum is a cylindrospermopsin toxin producing cyanobacterium that was reported in several lakes and reservoirs. Its growth dynamics and toxin distribution in field remain largely undocumented. Chrysosporum ovalisporum was reported in 2009 in Karaoun Reservoir, Lebanon. We investigated the factors controlling the occurrence of this cyanobacterium and vertical distribution of cylindrospermopsin in Karaoun Reservoir. We conducted bi-weekly sampling campaigns between May 2012 and August 2013. Results showed that Chrysosporum ovalisporum is an ecologically plastic species that was observed in all seasons. Unlike the high temperatures, above 26 °C, which is associated with blooms of Chrysosporum ovalisporum in Lakes Kinneret (Israel), Lisimachia and Trichonis (Greece) and Arcos Reservoir (Spain), Chrysosporum ovalisporum in Karaoun Reservoir bloomed in October 2012 at a water temperature of 22 °C during weak stratification. Cylindrospermopsin was detected in almost all water samples even when Chrysosporum ovalisporum was not detected. Chrysosporum ovalisporum biovolumes and cylindrospermopsin concentrations were not correlated (n = 31, r² = −0.05). Cylindrospermopsin reached a maximum concentration of 1.7 µg L⁻¹. The vertical profiles of toxin concentrations suggested its possible degradation or sedimentation resulting in its disappearance from the water column. The field growth conditions of Chrysosporum ovalisporum in this study revealed that it can bloom at the subsurface water temperature of 22 °C increasing the risk of its development and expansion in lakes located in temperate climate regions.     

Prognostic value of coronary CT angiography

Coronary computed tomography angiography (CTA) is a highly accurate noninvasive test that is increasingly used in symptomatic patients primarily for the diagnosis of coronary artery disease (CAD). Beyond its proven accuracy, data have now clearly demonstrated the incremental prognostic information available from coronary CTA related to the presence, extent, and severity of obstructive and nonobstructive CAD across a variety of clinical settings and patient populations. Current evidence supports the use of coronary CTA not only for the diagnosis of CAD in appropriately selected symptomatic patients but also to further refine their cardiovascular risk assessment following testing.     

Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?

Liver transplantation (LTx) is the best treatment for hepatocellular carcinoma (HCC), but should be offered only to selected patients. The usual procedure is to transplant only for small and unilobular tumors. The aim of this paper is to verify whether the actual indication criteria are still justified. The details of 121 patients with HCC who were submitted to LTx from 1985 to 2000 were analyzed. Age, gender, liver disease, Child class, alpha-fetoprotein (AFP) level, presence of tumor capsule, vascular invasion, size and number of nodules, histological grade, and pTNM were considered. The 5- and 10-year actuarial survival rates were 61.7% and 53.1%. Freedom from recurrence was 85.9% and 85.9%, respectively. At univariate analysis, size, presence of capsule, AFP levels, vascular invasion, grade, pTNM, transarterial chemoembolization (TACE), Child class, and age were all significantly related to survival and/or cancer recurrence. Presence of capsule, AFP levels, and viral cirrhosis were independent variables in Cox's analysis for survival, whereas histological grade, AFP levels, and vascular invasion were significant independent variables for recurrence. In conclusion, a strict selection should be made to optimize graft allocation while size and multifocality should probably no longer be considered a contraindication for LTx. Histological grade, AFP levels, and vascular invasion, as indicator of tumor behavior, more likely reflect the risk of recurrence.     

No effect of CYP450 and P-glycoprotein on hydroxyurea in vitro metabolism

Our objectives were (1) to study the HU metabolism via human cytochromes and (2) to test if HU is a substrate of P-gp. HU metabolism was investigated by determining the appearance of urea and HU decreasing upon incubation with human liver microsomes. Quantification was determined using HPLC coupled with UV-detection at 449 nm. Our method was linear between 5 and 1000 μ m , precise (coefficients of variation ranging from 1.7 to 9.9%), accurate (97.7–103.9%). The limit of quantification was 7 μ m . The ATPase activity of human P-gp membranes was determined by measuring inorganic phosphate liberation. HU and urea measurements in microsomes were not different between 0 and 60 min whatever HU concentration used from 30 to 300 μ m . The presence of NADPH in the medium has no effect on HU and urea measurements. In the absence of verapamil, the ATPase activity was unaffected by HU at concentrations of 10, 30, 100 and 300 μ m . HU is unlikely to cause clinically relevant drug interactions with the substrates of these enzymes/transporters. However, it will be necessary to validate these in vitro data in patients with sickle cell anemia to evaluate the impact of genetic polymorphisms of these enzymes in a black population.