Expression and activity of the cytochrome P450 2E1 in patients with nonalcoholic steatosis and steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver (NAFL) have a different prognosis and should be dealt with differently. The pathogenesis of NASH implicates the overexpression of cytochrome P450 2E1 (CYP2E1). We investigated whether the noninvasive determination of CYP2E1 activity could replace a liver biopsy in order to differentiate NASH from NAFL. METHOD: Forty patients referred for suspicion of NASH underwent liver biopsy. In these patients, CYP2E1 activity was determined noninvasively by the 6-hydroxychlorzoxazone/chlorzoxazone (CHZ) ratio (CHZ test). Expression of CYP2E1 on liver slides was assessed by immunohistochemistry, and immunostaining for smooth muscle actin was used to assess the activation of hepatic stellate cells (HSC). RESULTS: Thirty patients with NASH were compared with 10 subjects with NAFL. No statistically significant difference could be identified for the clinical and biochemical parameters between the two groups. In the histology, steatosis was more important in NASH than in NAFL (P<0.0001). There was no difference either in the activity (CHZ test) or in the expression of CYP2E1 (immunohistochemistry) between patients with NASH and patients with NAFL. The degree of HSC activation was also comparable between the two groups. A positive and significant correlation was found between the activity of CYP2E1 and body mass index (P<0.001) as well as with the degree of steatosis (P=0.008). CONCLUSION: For patients suspected to have NASH, noninvasive tests including the determination of the CYP2E1 activity are unable to distinguish them from patients with steatosis.     

Important Treatment Gaps in Vascular Protection for the Elderly After Type 2 Diabetes Therapy Initiation

Background

Canadian practice guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) for vascular protection in individuals with diabetes who are at high risk of cardiovascular events, including those ≥ 65 years. We estimated the proportion of elderly persons who initiated an ACEI or an ARB in the year after beginning oral antidiabetes (OAD) treatment, and we identified factors associated with this initiation.

Methods

Using the Quebec Health Insurance Board (RAMQ) databases, we conducted a population-based cohort study of individuals ≥ 65 years recently prescribed an OAD. We excluded those who were already taking an ACEI or ARB. Factors associated with ACEI or ARB initiation were identified using multivariate logistic regression.

Results

Among 43,700 individuals, 13,621 (31.2%) initiated an ACEI or ARB in the year after beginning OAD. Individuals were more likely to begin an ACEI or an ARB if they initially received both metformin and a sulfonylurea, lived in a rural region, began OAD treatment between 2001 and 2006, were hospitalized, or had ≥ 22 medical visits in the year before OAD initiation. Individuals ≥ 75 years, those who were prescribed an OAD by a general practitioner, initially received a sulfonylurea, or received ≥ 4 different medications in the year before OAD initiation were less likely to begin an ACEI or ARB.

Conclusions

In the elderly not already taking ACEIs or ARBs, a low proportion of those undertaking OAD treatment are prescribed the recommended cardioprotection of an ACEI or ARB in the following year. Interventions are needed to close this treatment gap.     

Bone mineral density of young boy soccer players at different pubertal stages: relationships with hormonal concentration

ObjectivesTo examine the effects of soccer in relation with the hormonal concentration, on the bone mass of young Tunisian players at different pubertal stages.MethodsTwo groups of 152 young boys (age: 13.3 ± 0.9 years) participated in this study: (1) 91 soccer players, and (2) 61 non-athletic boys used as control subjects. The bone mineral density (BMD) and the bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DXA). Pubertal stages were assessed, and serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone (GH) and the total testosterone were measured.ResultsThe BMD and BMC for whole body, lumbar spine, femoral neck, pelvis and lower limbs were higher in soccer players than in controls (p < 0.001). In early puberty, the soccer players also exhibited significantly greater BMD and BMC in the whole body and in weight-bearing bones compared with the controls (p < 0.001). However, there was no intersubject variability due to puberty in either BMD or BMC. The pubescent soccer players had significantly higher hormonal concentrations of IGF-1 and IGFBP-3 than their counterpart controls (p < 0.05). Moreover, the whole body BMD was significantly (p < 0.001) correlated with GH, IGF-1 and IGFBP-3 but not with the testosterone concentrations.ConclusionThe soccer participation of boys is generally associated with the improvement of their bone mass which is mainly marked at early and late puberty. The relationships between somatotropic axis hormones and BMD of the players may be linked to the parallel development of these two parameters during puberty.     

Competition between the replication initiator DnaA and the sequestration factor SeqA for binding to the hemimethylated chromosomal origin of E. coli in vitro

BACKGROUND: Following replication initiation, the replication origin (oriC) in Escherichia coli enters a hemimethylated state at Dam methylation sites which are recognized by the SeqA protein. SeqA binds preferentially to hemimethylated GATC sequences of DNA in vitro. SeqA is essential for the synchronous initiation of chromosome replication from oriC copies in vivo. RESULTS: We show that: (i) purified SeqA binds AT-rich and 13-mers regions and two DnaA boxes, R1 and M, of hemimethylated oriC. (ii) SeqA inhibits the in vitro replication of a hemimethylated oriC plasmid more efficiently than the fully methylated, (iii) SeqA inhibits competitive binding of DnaA protein to the regions of the hemimethylated oriC plasmid, explaining the mechanism of its inhibitory effect. The inhibition of DnaA binding by SeqA also occurs efficiently on a small hemimethylated oriC fragment containing both R1 and M DnaA boxes, but not the 13-mer region. CONCLUSIONS: SeqA binds strongly the long region from the AT-rich region to the M DnaA box of the hemimethylated oriC DNA and releases DnaA molecules from the long region.     

Primary leiomyosarcoma of the inferior vena cava: Is vascular reconstruction always necessary?

Both MRI and CT scan can determine tumor size and its extension. PLV have a poor prognosis if surgical resection cannot be achieved. We recommend no reconstruction for type II PLV if venous contact is less than 180° or where the implantation base does not exceed one third of the vena cava.     

Leptin and Leptin receptor polymorphisms,plasma Leptin levels and obesity in Tunisian volunteers

Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Leptin (LEP). The aim this study was to investigate the prevalence of single nucleotide polymorphisms in LEP gene (LEP 3′UTR A/C, ?2548 G/A) and LEPR (K109R and Q223R) and their association with Leptin level and obesity. We recruited 169 non‐obese (body mass index [BMI] = 24.51‐3.69 kg/m²) and 160 obese (BMI = 36‐4.78 kg/m²) patients. Genotyping was performed using polymerase chain reaction‐restriction fragment length polymorphism, BMI was calculated, and Leptin level was measured by ELISA. Statistical analyses were performed by spss 19.0. According to LEP 3′UTR A/C polymorphism, AC and CC genotype carriers had higher Leptin levels than AA genotype carriers, respectively, 31[0.05‐148.8] (P = .008) vs 41[0.05‐111.6] (P = .003). The K109R polymorphism was associated with obesity (P = .025) and seems to significantly decrease the LEP levels (P < .001). Concerning LEP G2548A polymorphism, our results showed that the OR of obesity associated with 2548 AA/GG was 1.87[1.106‐2.78] P = .028 vs 1.41[1.035‐1.85] P = .045 for 223AA/GG polymorphism. In our haplotype analysis, one haplotype seems to be the more protective and one other seems to be the highest risk to obesity. LEP 3′UTR A/C and LEPR K109R polymorphisms were associated with Leptin level and obesity.