Alcohol Use and Associated Environmental Factors Among Middle and High School Students in Sfax (Tunisia)

Our objective was to investigate the prevalence and the environmental determinants of alcohol use among students in the region of Sfax in Tunisia. We carried out a cross-sectional study among 315 middle and high school students. We used the Alcohol Use Disorders Identification Test (AUDIT) to identify risky alcohol consumption, and we used the Parenting Styles and Dimensions Questionnaire (PSDQ) to assess the students’ perceptions of their parents’ parenting styles. The results show that 19.7% reported drinking alcohol at least once in their lifetime. Among them, 21% scored as dependent alcohol users, according to the AUDIT. Those who drank alcohol at least once were more likely to have parents with a permissive parenting style (p < 0.001; Cramer’s V = 0.287), and a father (p < 0.001; Cramer’s V = 0.258), a mother (p = 0.025; Cramer’s V = 0.158), or a friend (p < 0.001; Cramer’s V = 0.341) who drinks. Students perceiving their parents’ parenting style as permissive had the highest AUDIT score (p = 0.005; partial η² = 0.132). The authoritarian style score was significantly higher for students who were current alcohol users (p = 0.028; Cohen’s d = 0.57). Our study highlights the influence of peers, family drinking, and parenting styles on alcohol use among middle and high school students. Therefore, particular attention should be given to students that are at risk of having the abovementioned environmental determinants of alcohol use. And, prevention strategies should involve parents, as well as enhanced guidance and counseling for these students.

     

Identification of the translocation t(15;17) in acute myeloid leukemia (AML) initially classified as FAB M1: case report and review of the literature

We report a case of a patient aged about 53 years, who initially presented with hematological disorders (WBC: 44000/mm3, Hb: 11g/dl, Pit: 127000/mm3) without tumoral syndrome. The Wright-Giemsa stained bone marrow and peripheral blood smears showed a population of blast cells characterized by cells with high N/C and strongly basophilic cytoplasm without granules. The nuclei were predominantly round. Nuclear chromatin was fine and contained small nucleoli. Cytochemisty was positive for peroxidase activity. Immunophenotyping showed myeloid typical markers of granulocytic lineage (MP0+, CD13+, CD33+, CD117+, CD34-). The karyotype revealed the expression of t(15;17) chromosomal translocation. The diagnosis of acute myeloid leukaemia (AML) was then evoked initially. The cytological features corresponded closely to the M1 subtype as defined in the FAB classification. The patient was treated with induction therapy according to the 7/3 protocol. One month later, he was discharged from hospital on hematological and cytogenetic remission. He died at home because of a heart attack. From the biological findings the patient was retrospectively diagnosed as having promyelocytic leukemia (hyperbasophilic form).     

Efficacy and Safety of Liposomal Clarithromycin and Its Effect on Pseudomonas aeruginosa Virulence Factors

We investigated the efficacy and safety of liposomal clarithromycin formulations with different surface charges against clinical isolates of Pseudomonas aeruginosa from the lungs of cystic fibrosis (CF) patients. The liposomal clarithromycin formulations were prepared by the dehydration-rehydration method, and their sizes were measured using the dynamic-light-scattering technique. Encapsulation efficiency was determined by microbiological assay, and the stabilities of the formulations in biological fluid were evaluated for a period of 48 h. The MICs and minimum bactericidal concentrations (MBCs) of free and liposomal formulations were determined with P. aeruginosa strains isolated from CF patients. Liposomal clarithromycin activity against biofilm-forming P. aeruginosa was compared to that of free antibiotic using the Calgary Biofilm Device (CBD). The effects of subinhibitory concentrations of free and liposomal clarithromycin on bacterial virulence factors and motility on agar were investigated on clinical isolates of P. aeruginosa. The cytotoxicities of the liposome preparations and free drug were evaluated on a pulmonary epithelial cell line (A549). The average diameter of the formulations was >222 nm, with encapsulation efficiencies ranging from 5.7% to 30.4%. The liposomes retained more than 70% of their drug content during the 48-h time period. The highly resistant strains of P. aeruginosa became susceptible to liposome-encapsulated clarithromycin (MIC, 256 mg/liter versus 8 mg/liter; P < 0.001). Liposomal clarithromycin reduced the bacterial growth within the biofilm by 3 to 4 log units (P < 0.001), significantly attenuated virulence factor production, and reduced bacterial twitching, swarming, and swimming motilities. The clarithromycin-entrapped liposomes were less cytotoxic than the free drug (P < 0.001). These data indicate that our novel formulations could be a useful strategy to enhance the efficacy of clarithromycin against resistant P. aeruginosa strains that commonly affect individuals with cystic fibrosis.     

Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians

Purpose

A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans.

Methods

To investigate the possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on APOL1 (n = 4) and MYH9 (n = 5) genes.

Results

We observed significantly strong associations with previously reported APOL1 variants rs73885319 and rs60910145, and their two-allele “G1” haplotype (P < 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the MYH9 variants or haplotypes after accounting for multiple testing in our sample.

Conclusions

In conclusion, APOL1 risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on APOL1/MYH9 variants may lead to screening programs, which could lead to earlier detection and interventions for non-diabetic kidney disease.     

Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

The goal of this work was to develop an in silico model that allows predicting segmental-dependent permeability throughout the small intestine (SI). In vivo permeability of 11 model drugs in 3 SI segments (jejunum, mid-SI, ileum) was studied in rats, creating a data set that reflects the conditions throughout the SI. Then, a predictive model was developed, combining physicochemical drug properties influencing the underlying mechanism of passive permeability: Log p, polar surface area, M_W, H-bond count, and Log f_u, with microenvironmental SI conditions. Excellent correlation was evident between the predicted and experimental data (R² = 0.914), with similar predictability in each SI segment. Log p and Log f_u were identified as the major determinants of permeability, with similar contribution. Total H-bond count was also a significant determinant, followed by polar surface area and M_W. Leaving out any of the model parameters decreased its predictability. The model was validated against 5 external drugs, with excellent predictability. Notably, the model was able to predict the segmental-dependent permeability of all drugs showing this trend experimentally. Model predictability was better in the high-permeability versus low-permeability range. Overall, our approach of constructing a straightforward in silico model allowed reliable predictions of segmental-dependent intestinal permeability, providing new insights into relative effects of drug-related factors and gastrointestinal environment on permeability.     

The expression of thyrotropin receptor in the brain

The regulation of the thyroid gland by TSH is mediated by a heterotrimeric G protein-coupled receptor. Nonthyroid effects of TSH have been reported, and expression of its receptor has been described in adipocytes and lymphocytes. We have previously reported the existence of specific and saturable binding sites of TSH and specific TSH effects in primary cultured rat brain astroglial cells. We now report expression of the TSH receptor gene in these cells; the coding sequence of the corresponding complementary DNA is identical to that previously established in thyroid. Using specific antisense RNA probe, expression of this gene was detected in some isolated or clustered glial fibrillary acidic protein-positive primary cultured cells by in situ hybridization. With this technique, we further detected TSH receptor messenger RNA (mRNA) expression in rat brain cryoslices in both neuronal cells and astrocytes. Its presence predominated in neuron-rich areas (pyriform and postcingulate cortex, hippocampus, and hypothalamic nuclei) and was mostly colocalized with neuron-specific enolase. In astrocytes, this mRNA was detected in the ependymal cell layer and the subependymal zone, and several isolated cells were also found in the brain parenchyma. We also detected TSH receptor mRNA and protein in primary cultured human astrocytes. The protein was detected as well in both rat and human brain cryoslices. Together, these findings clearly demonstrate the expression of the TSH receptor gene in the brain in both neuronal cells and astrocytes.     

Intravenous 64-multi-detector row CT-cholangiography of porcine livers: a feasibility study with definition of the temporal window for optimal bile duct delineation

Background/purpose

To assess the feasibility of intravenous 64-multi-detector row computed tomography (CT)-cholangiography of porcine livers with definition of the temporal window for optimal bile duct delineation.

Methods

Six healthy Landrace pigs, each weighing 28.97 ± 2.99 kg, underwent 64-multi-detector row CT-cholangiography. Each pig was infused with 50 ml of meglumine iotroxate continuously over a period of 20 min and, starting with the initiation of the infusion, 18 consecutive CT scans of the abdomen at 2-min intervals were acquired. All series were evaluated for bile duct visualization scores and maximum bile duct diameters as primary study goals and bile duct attenuation and liver enhancement as secondary study goals.

Results

Of the 16 analyzed biliary tract segments, maximum bile duct visualization scores ranged between 4.00 ± 0.00 and 2.83 ± 1.47. Time to maximum bile duct visualization scores ranged between 10 and 34 min. Average bile duct visualization scores for the 10- to 34-min interval ranged between 3.99 ± 0.05 and 2.78 ± 0.10. Maximum bile duct diameters ranged between 6.47 ± 1.05 and 2.65 ± 2.23 mm. Time to maximum bile duct diameters ranged between 24 and 34 min. Average bile duct diameters for the 10- to 34-min interval ranged between 6.00 ± 0.38 and 2.40 ± 0.13 mm.

Conclusions

Intravenous 64-multi-detector row CT-cholangiography of non-diseased porcine liver is feasible, with the best bile duct delineation acquired between 10 and 34 min after initiation of the contrast agent infusion.     

First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma

Thalidomide-dexamethasone therapy was given in patients (<61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (> or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.