Fermeture percutanée des communications interventriculaires congénitales par la prothèse Amplatzer Duct OccluderII: données préliminaire d’une étude Tunisienne monocentrique

Introduction . Percutaneous closure of congenital ventricular septal defects (VSDs) represents a promising alternative to surgery with lower rate of complications and shorter hospital stay. Its main limitation is the choice of the appropriate device for each type of defect. Aim. To report the experience of the service of cardiology (Sahloul hospital, Sousse, Tunisia) in percutaneous closure of congenital VSDs with Amplatzer Duct Occluder II (ADOII). Methods. This was a retrospective, monocentric study, conducted from January 2013 to December 2017. The study included patients treated by percutaneous closure of congenital VSDs with the ADOII device. Results. Twelve patients (6 boys; 6 girls) were included. The mean±SD of patients’ age and weight were 65±41 months and 23±10 kg, respectively. VSDs were peri-membranous (n=9) and muscular (n=3), and defects were restrictive (n=11) and non-restrictive (n=1). The mean (minimum-maximum) size of VSDs was 4.72 (3-6) mm. Eleven ADOII prostheses were successfully implanted. One failure procedure was noted with migration of the device into the pulmonary artery. A second child with perimembranous defect developed transient atrioventricular block. No deaths occurred. Conclusion. The present early experience shows that percutaneous closure with ADOII device of perimembranous and trabecular VSDs is safe and effective.     

IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by Th2 cells. It down-regulates the proinflammatory response and modulates hepatic fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell response and has many antiviral properties. Data concerning the Th-1/Th-2 balance in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity. Our results showed that spontaneous IL-10 was undetectable in patients with CH-C, HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The presence of IL-12p40 was associated with HCV level of viremia and serum AST. Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40 was unrelated to liver histology or fibrosis. We concluded that in the Egyptian patients an augmentation of IL-12p40 and a suppression of IL-10 are both found. Whether this pattern is related to HCV genotype 4, or to the presence of schistosomiasis would need to be further investigated.     

Low-Frequency Electrical Stimulation Attenuates Muscle Atrophy in CKD—A Potential Treatment Strategy

Effective therapeutic strategies to treat CKD-induced muscle atrophy are urgently needed. Low-frequency electrical stimulation (LFES) may be effective in preventing muscle atrophy, because LFES is an acupuncture technique that mimics resistance exercise by inducing muscle contraction. To test this hypothesis, we treated 5/6-nephrectomized mice (CKD mice) and control mice with LFES for 15 days. LFES prevented soleus and extensor digitorum longus muscle weight loss and loss of hind-limb muscle grip in CKD mice. LFES countered the CKD-induced decline in the IGF-1 signaling pathway and led to increases in markers of protein synthesis and myogenesis and improvement in muscle protein metabolism. In control mice, we observed an acute response phase immediately after LFES, during which the expression of inflammatory cytokines (IFN-γ and IL-6) increased. Expression of the M1 macrophage marker IL-1β also increased acutely, but expression of the M2 marker arginase-1 increased 2 days after initiation of LFES, paralleling the change in IGF-1. In muscle cross-sections of LFES-treated mice, arginase-1 colocalized with IGF-1. Additionally, expression of microRNA-1 and -206, which inhibits IGF-1 translation, decreased in the acute response phase after LFES and increased at a later phase. We conclude that LFES ameliorates CKD-induced skeletal muscle atrophy by upregulation of the IGF-1 signaling pathway, which improves protein metabolism and promotes myogenesis. The upregulation of IGF-1 may be mediated by decreased expression of microRNA-1 and -206 and/or activation of M2 macrophages.     

Effect of Rehabilitation Program on Endocrinological Parameters in Patients with COPD and in Healthy Subjects

Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation and endocrinological disturbance. The aim of this study is to analyze the effect of rehabilitation program on the balance of anabolic versus catabolic hormone in patients with COPD and in healthy subjects. Methods: Nineteen patients with COPD and 16 age-matched healthy subjects undertooked exercise training 3 days/week for 8 weeks. Before and after the training program the concentration of growth hormone (GH), Insulin-Like Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 3 (IGF-BP3), testosterone and cortisol in serum were determined. The exercise measurements included a 6-Minute Walking Test (6MWT). Results: After 8 weeks, there was no significant change in lung function in patients with COPD and healthy subjects. Growth hormone, Insulin-like Growth Factor-1 and Insulin-like Growth Factor-Binding Protein 3 increased significantly after rehabilitation training (p < 0.01). The rehabilitation program improves the testosterone/cortisol ratio (T/C ratio) in both groups. There is a significant improvement in the 6-Minute Walking distance (6MWD) in both groups (p < 0.01). Dyspnea and heart rate at rest and at the peak of the 6-Minute Walking Test (6MWT) decreased significantly after training program (p < 0.01). Conclusion: Pulmonary rehabilitation induces an improvement of the anabolic process and reduces proteine distruction by the modifications in endocrinological factors regulating skeletal muscle in patients with COPD.     

Renal impairment in children with posterior urethral valves

Background

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment.

Methods

We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011.

Results

The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p?=?0.024), nadir serum creatinine (p?<?0.001), and last known serum creatinine level (p?=?0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p?=?0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation.

Conclusions

Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.     

Evaluation of Spironolactone Solid Dispersions Prepared by Co-Spray Drying With Soluplus® and Polyvinylpyrrolidone and Influence of Tableting on Drug Release

Solid dispersions of spironolactone with Soluplus^® and polyvinylpyrrolidone were prepared by spray drying according to a mixture experimental design and evaluated for moisture content, particle size, drug solubility, crystallinity (powder X-ray diffraction and differential scanning calorimetry), and physicochemical interactions (Fourier-transform infrared spectroscopy, Raman). In vitro dissolution was evaluated for the spray dried product itself and after compression into tablets, and prediction models were derived using multiple linear regression analysis. The spray dried products consisted of amorphous drug, indicated by the absence of crystalline powder X-ray diffraction peaks. Amorphization and interactions impacted changes in the Fourier-transform infrared spectroscopy spectra in the ranges 2900-3000 cm^?1 (C-H) and 1600-1800 cm^?1 (C=O) and caused merging at 1690 cm^?1 (C=O of lactone) and 1670 cm^?1 (C=O of thioacetyl group). In the Raman spectra, amorphization and interactions resulted in disappearance of peak at 1690 cm^?1 (C=O) and merging of peaks at 582 and 600 cm^?1 (C-S). Hydrogen bonding between the thioacetyl group of the drug with the hydroxyl groups of Soluplus^® caused marked suppression of the peak at 1190 cm^?1 (R-C(=O)-S vibration). Amorphization and interactions resulted in improved solubility and dissolution which was greatest for drug/Soluplus^® ratio 1:4 and was also demonstrated in the corresponding tablets.