Design, Formulation, and Characterization of Valsartan Nanoethosomes for Improving Their Bioavailability

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and subjected to in vitro drug release studies, ex vivo test, and in vivo studies to assess the effectiveness of ethosomal formulation in enhancing the bioavailability of VLT as a poorly soluble drug and in controlling its release from the transdermal gel dosage form. The acquired results are as follows: Dependent responses were particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized VLT-ETHs had a nanometric diameter (45.8 ± 0.5 nm), a negative surface charge (−51.4 ± 6.3 mV), and a high drug encapsulation (94.24 ± 0.2). The prepared VLT ethosomal gel (VLT-ethogel) showed a high peak plasma concentration and enhanced bioavailability in rats compared with the oral solution of valsartan presented in the higher AUC (0–∞). The AUC (0–∞) with oral treatment was 7.0 ± 2.94 (μg.h/mL), but the AUC (0–∞) with topical application of the VAL nanoethosomal gel was 137.2 ± 49.88 (μg.h/mL), providing the sustained release pattern of VLT from the tested ethosomal gel

Simulation and validation of arbitrary ordered VSCP-PLLs using event-driven macromodeling

International audienc

Clinical, ultrasonographic and endocrine predictors of ovarian response to clomiphene citrate in normogonadotropic anovulatory infertility

Objective: To identify screening characteristics involved in the prediction of anovulation after clomiphene citrate (CC) medication. Design: Prospective follow-up study Setting: Infertility Clinic, University Department of Obstetrics and Gynecology and Department of Medical Biochemistry, Faculty of Medicine, Alexandria. Materials and Methods: 60 patients presenting with oligomenorrhea or amenorrhea and infertility. Clinical, ultrasonographic and endocrine screening took place before initiation of CC medication. Endocrine screening included serum assays for LH, FSH, fasting insulin, glucose, leptin, inhibin B, testosterone and androstenedione. Results: 22 patients (36.6% of the total group) did not ovulate. Age, body mass index (BMI), ovarian volume, Doppler indices of ovarian stromal blood vessels, the LH/FSH ratio serum insulin, leptin, inhibin-B, testosterone and androstenedione differed significantly between CC responders and non-responders. However, forward stepwise multivariate analyses revealed a final prediction model for CC resistant anovulation including BMI, serum insulin and androstenedione. Conclusions: Data suggest that obesity, hyperinsulinaemia and hyper- androgenaemia are crucial factors involved in ovarian dysfunction that prevent response to CC

Extracellular cystine influences human preadipocyte differentiation and correlates with fat mass in healthy adults

Abstract Plasma cysteine is associated with human obesity, but it is unknown whether this is mediated by reduced, disulfide (cystine and mixed-disulfides) or protein-bound (bCys) fractions. We investigated which cysteine fractions are associated with adiposity in vivo and if a relevant fraction influences human adipogenesis in vitro. In the current study, plasma cysteine fractions were correlated with body fat mass in 35 adults. Strong positive correlations with fat mass were observed for cystine and mixed disulfides ( r  ≥ 0.61, P  < 0.001), but not the quantitatively major form, bCys. Primary human preadipocytes were differentiated in media containing cystine concentrations varying from 10–50 μM, a range similar to that in plasma. Increasing extracellular cystine (10–50 μM) enhanced mRNA expression of PPARG2 (to sixfold ) , PPARG1 , PLIN1 , SCD1 and CDO1 ( P  = 0.042– < 0.001). Adipocyte lipid accumulation and lipid-droplet size showed dose-dependent increases from lowest to highest cystine concentrations ( P  < 0.001), and the malonedialdehyde/total antioxidant capacity increased, suggesting increased oxidative stress. In conclusion, increased cystine concentrations, within the physiological range, are positively associated with both fat mass in healthy adults and human adipogenic differentiation in vitro. The potential role of cystine as a modifiable factor regulating human adipocyte turnover and metabolism deserves further study