Effect of dimethyl-beta-cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in rats

The aim of this article is to prepare and characterize inhalable dry powders of recombinant human growth hormone (rhGH), and assess their efficacy for systemic delivery of the protein in rats. The powders were prepared by spray drying using dimethyl-beta-cyclodextrin (DMbetaCD) at different molar ratios in the initial feeds. Size exclusive chromatography was performed in order to determine protecting effect of DMbetaCD on the rhGH aggregation during spray drying. By increasing the concentration of DMbetaCD, rhGH aggregation was decreased from 9.67 (in the absence of DMbetaCD) to 0.84% (using DMbetaCD at 1000 molar ratio in the spray solution). The aerosol performance of the spray dried (SD) powders was evaluated using Andersen cascade impactor. Fine particle fraction values of 53.49%, 33.40%, and 23.23% were obtained using DMbetaCD at 10, 100, and 1000 molar ratio, respectively. In vivo studies showed the absolute bioavailability of 25.38%, 76.52%, and 63.97% after intratracheal insufflation of the powders produced after spray drying of the solutions containing DMbetaCD at 10, 100, and 1000 molar ratio, respectively in rat. In conclusion, appropriate cyclodextrin concentration was achieved considering the protein aggregation and aerosol performance of the SD powders and the systemic absorption following administration through the rat lung.     

Systolic and diastolic blood pressure percentiles by age and gender in Northeastern Iran

Hypertension (HTN) is a major risk factor for coronary artery disease. Its frequency is increasing globally. The aim of our study was to evaluate the reference range of blood pressure (BP) in the Iranian population stratified for age and gender. A total of 1449 subjects without diabetes, CVD, dyslipidemia, HTN history and with a normal BMI (18.5 ≤ BMI<25) were recruited in the present study. Participants were enrolled from the Mashhad stroke and heart atherosclerotic disorder study. Anthropometric indices and demographic data were collected by two health care specialists. A quantile regression model was used to estimate the expected systolic BP (SBP) and diastolic BP (DBP) at specific ages. A P-value of <.05 was considered significant for all analyses. All statistical analyses were performed using R (version 3.4.1) and SPSS software. The population included more men than women (51.6% vs. 48.4%). The mean and standard deviation of age in men (47.5 ± 8.4) was 2 years higher than women (45.63 ± 7.9; P < .001). SBP and DBP were higher in men than women (P < .001). By using a quantile regression model, we concluded that the 5th to 90th percentile of SBP in men, aged 30–69 years, ranged from 95 to 148.08 mm Hg and in women ranged from 86.66 to 140 mm Hg. The 5th to 90th percentile of DBP in men, aged 30–69 years, ranged from 60 to 91.66 mm Hg and in women ranged from 60 to 91.22 mm Hg. We have, for the first time, established the BP percentiles (1st, 5th, 10th, 50th, 90th, 95th, 99th) in an Iranian population stratified by age and gender. These data suggest that a local program for health promotion is necessary for the early identification of HTN in adults aged ≥30 years.     

Patient-Specific Multiscale Modeling of the Assisted Bidirectional Glenn

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Serum HDL cholesterol uptake capacity in subjects from the MASHAD cohort study: Its value in determining the risk of cardiovascular endpoints

BackgroundThe efficiency of high‐density lipoprotein (HDL) to efflux cholesterol contributes to the reverse cholesterol transport (RCT) pathway as one of HDL’s proposed functions and depends on the ability of HDL to uptake cholesterol. We aimed to investigate cholesterol uptake capacity (CUC) by a newly developed assay in samples from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorders) cohort study.MethodThe study population comprised 153 individuals developed CVD diagnosed by a specialist cardiologist, over 6 years of follow‐up, and 350 subjects without CVD. We used a modified CUC method to evaluate the functionality of HDL in serum samples.ResultThe CUC assay was highly reproducible with values for inter‐ and intra‐assay variation of 13.07 and 6.65, respectively. The mean serum CUC was significantly lower in the CVD group compared to control (p = 0.01). Although, there were no significant differences in serum HDL‐C between the groups and there was no significantly association with risk of progressive CVD. Multivariate logistic regression analysis showed that there was a significantly negative association between CUC and risk of CVD after adjustment for confounding parameters (OR = 0.57, 95% CI = 0.38–0.87, p = 0.009). The CUC was also inversely and independently associated with the risk of CVD event using Cox proportional hazards models analysis (HR = 0.62; 95% CI = 0.41–0.94, p = 0.02). We determined the optimum cutoff value of 1.7 a.u for CUC in the population. Furthermore, the CUC value was important in determining the CVD risk stratification derived from data mining analysis.ConclusionsReduced HDL functionality, as measured by CUC, appears to predict CVD in population sample from north‐eastern Iran.     

Interaction between the genetic variant of rs696217-ghrelin and food intake and obesity and dyslipidemia

In this study, we aimed to investigate the relationship between the genetic variant of rs696217-ghrelin and fasted lipid profile, indices of obesity, and environmental parameters. Amplification refractory mutation system-polymerase chain reaction (ARMs-PCR) was used for genotyping 1118 individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The interaction between the presence of the genetic variant of rs696217-ghrelin and nutritional intake and other major determinants of obesity and lipid profile was examined in the MASHAD study population. Individuals with the TT genotype at the locus had the lowest prevalence of obesity compared to other genotypes among the individuals. No significant relationship was found between the two groups regarding the lipid profile and TT genotype. Furthermore, no significant association was found between dietary intake and the genetic variant of rs696217-ghrelin in the population under study. Individuals with a TT or GT genotype appear to be at a higher risk of obesity, compared to those with a GG genotype. The results of the current study revealed a significant association between the genetic variant of rs696217-ghrelin and obesity; however, this gene did not correlate with the risk factors of cardiovascular diseases and dyslipidemia in the Iranian population.     

Alterations in Lipid Profile,Zinc and Copper Levels and Superoxide Dismutase Activities in Normal Pregnancy and Preeclampsia

Background

Increased oxidative stress (OS) and lipid peroxidation may be involved in the pathogenesis of preeclampsia (PE). We conducted a case-control study to evaluate the levels of plasma lipids and trace elements as well as activity of superoxide dismutase (SOD) in PE.