Preparation and characterization of co-processed starch/MCC/chitin hydrophilic polymers onto magnesium silicate

It was aimed to investigate the compressibility, compactibility, powder flow and tablet disintegration of a new excipient comprising magnesium (Mg) silicate co-processed (5%–85% w/w) onto chitin, microcrystalline cellulose (MCC) and starch as the hydrophilic polymers of interest. Initially, the mechanism of tablet disintegration was studied by measuring water infiltration rate, moisture sorption, swelling capacity and hydration ability. Moreover, the powders compression behavior was carried out by applying Kawakita model of compression analysis in addition to porosity and radial tensile strength measurements. In vitro drug release of compacts made of 400?mg ibuprofen and 300?mg of the hydrophilic polymers containing 30% w/w Mg silicate co-precipitate was investigated in phosphate buffer (pH 7.8). This work demonstrated that the incorporation of Mg silicate to the hydrophilic polymers lead to the improvement of powder flowability, compactibility, stability (with regard to storage conditions), compacts crushing strength, and disintegration time in addition to faster drug release. The overall findings are practically advantageous in the context of finding a low cost and multifunctional co-processed excipient of natural origins.     

Syzygium aromaticum ethanol extract reduces AlCl_3-induced neurotoxicity in mice brain through regulation of amyloid precursor protein and oxidative stress gene expression

Objective: To investigate the neuroprotective effects of Syzygium aromaticum(S.aromaticum)extract(500 mg/kg) on AlCl_3(300 mg/kg)-induced mouse model of oxidative stress and neurotoxicity.Methods: An ethanolic extract of S.aromaticum seeds was prepared and the active compounds were identified using nuclear magnetic resonance spectroscopy.BALB/c mice were divided into five groups(negative control, AlCl_3-treated, self-recovery, AlCl_3 + S.aromaticum, S.aromaticum only; n=10) and treated with AlCl_3 and S.aromaticum extract.Expression of oxidative markers [Superoxide dismutase 1(SOD1) and peroxiredoxin 6(Prdx6)] and amyloid precursor protein(APP) in the hippocampus and cortex was evaluated via PCR.Histopathological assessment was performed to investigate the extent of neurodegeneration.Results: It was observed that AlCl_3 exposure increased the expression of APP770 while simultaneously down regulated the expression of APP695.AlCl_3 also induced a significant decrease(P0.05) and an increase(P0.05) in the expression level of SOD1 and Prdx6, respectively.A substantial decrease substantial(P0.05) in the density of Nissl substance was also observed in cortex of the mice treated with AlCl_3.Interestingly, treatment with S.aromaticum extract normalized the alterations in the expression level of SOD1, Prdx6 and APPisoforms and improved the neuronal structural damage.Conclusions: The results showed that S.aromaticum is a promising antioxidant and a neuroprotective agent.     

17q12-21 and asthma: interactions with early-life environmental exposures

Background17q12-21 polymorphisms are associated with asthma presence and severity across different populations.ObjectiveTo extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures.MethodsWe included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry.ResultsWe found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation.ConclusionOur results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies.     

Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women

The present meta-analysis examines randomized trials of third-generation aromatase inhibitors (AIs) as alternatives to tamoxifen in three treatment settings: monotherapy, sequenced therapy and extended therapy. Eleven randomized controlled trials (RCTs) were chosen based on their similarity in terms of study design and included 34,070 post-menopausal women who had undergone surgery for estrogen-sensitive early breast cancer. DFS was significantly improved by AI monotherapy (Hazard Ratio (HR): 0.89, p = 0.001), sequenced therapy (HR: 0.7, p < 0.00001) and extended therapy (HR: 0.62, p < 0.00001). All of the patients benefited significantly from sequenced therapy (HR: 0.81, p = 0.003), and hormone receptor-positive patients benefited from AI monotherapy (HR = 0.92, p = 0.046) with respect to OS. AI monotherapy conferred significantly lower risks for thromboembolic events (OR = 0.61; p < 0.001) and endometrial cancer (OR = 0.26; p < 0.001) compared with tamoxifen monotherapy; however, there was a greater risk of cardiovascular events (OR = 1.20; p = 0.030). Sequenced therapy was also superior in terms of endometrial cancer but was inferior with respect to fractures, thromboembolic and cardiovascular events.