Comparative evaluation of anthropometric measures to predict cardiovascular risk factors in Tehranian adult women

OBJECTIVE: To compare the ability of waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict cardiovascular risk factors in an urban adult population of Tehranian women. DESIGN: Population-based cross-sectional study. SETTING: Tehran, the capital of Iran. SUBJECTS: This study was conducted on 5073 women aged 18-74 years, participants of the Tehran Lipid and Glucose Study. Demographic data were collected. Anthropometric indices were measured according to standard protocols. Cut-off points of BMI, WC, WHR and WHtR were considered as 25 kg m(-2), 80 cm, 0.8 and 0.5, respectively. Blood pressure was measured and hypertension was defined based on the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Biochemical analyses were conducted on fasting blood samples. Diabetes was defined as fasting plasma glucose > or = 126 mg dl(-1) or 2-hour plasma glucose > or = 200 mg dl(-1) and dyslipidaemia based on the third report of the National Cholesterol Education Program Expert Panel. The presence of 'at least one risk factor' from the three major cardiovascular risk factors (hypertension, dyslipidaemia and diabetes) was also evaluated. RESULTS: Mean (+/-standard deviation) age of women was 39.9+/-14.6 years; mean BMI, WC, WHR and WHtR were 27.1+/-1.5 kg m(-2), 86.5+/-13.5 cm and 0.83+/-0.08 and 0.55+/-0.08, respectively. Of the four anthropometric measures, WC had the highest sensitivity and specificity to identify subjects with risk factors in both the 18-39 year and the 40-74 year age categories. WC was seen to have a higher percentage of correct prediction than BMI, WHR and WHtR. CONCLUSION: It is concluded that WC is the best screening measure for cardiovascular risk factors, compared with BMI, WHR and WHtR, in Tehranian adult women.     

Effects of Peptone Supplementation in Different Culture Media on Growth,Metabolic Pathway and Productivity of CHO DG44 Cells; a New Insight into Amino Acid Profiles

Background:

The optimization of bioprocess conditions towards improved growth profile and productivity yield is considered of great importance in biopharmaceutical manufacturing. Peptones as efficient sources of nutrients have been studied for their effect on media development; however, their role on metabolic pathway is not well understood.

Methods:

In the present study, the effect of different concentration of peptones on a recombinant Chinese hamster ovary (CHO) cell line grown in three serum-free suspension cultures was determined. Six peptones of different origins and available amino acid profiles were investigated regarding their impact on cell growth, productivity, and metabolic pathways changes.

Results:

In optimized feeding strategies, increases of 136% and 159% in volumetric productivity (for a low-nutrient culture media) and 55% (for a high-nutrient culture media) were achieved. Furthermore, particular sources of peptones with specific amino acid profile developed preferential results for each different culture medium. Two peptones, SoyA2SC and SoyE-110, were the only hydrolysates that showed production improvement in all three media. Casein Peptone plus Tryptone N1 and SoyA3SC showed different improved results based on their implemented concentration for each individual basal medium.

Conclusion:

The amino acid profile of peptones may provide clues to identify the most effective feeding strategies for recombinant CHO cells.Key Words: CHO cells, Culture media, Peptones, Recombinant proteins     

Woodchuck Hepatitis Virus Post-Transcriptional Regulation Element (WPRE) Promotes Anti-CD19 BiTE Expression in Expi293 Cells

Background:Bispecific antibodies represent an important class of mAbs, with great therapeutic potentials due to their ability to target simultaneously two distinct epitopes. The generation of functional bispecific antibodies with the highest possible yields is particularly critical for the production of these compounds on industrial scales. Anti- CD3 × CD19 bsAb is a bispecific T-cell engager (BiTE) currently used for treating ALL. Herein, we have tried to optimize the expression level of this antibody in mammalian hosts. Methods:WPRE sequence was incorporated at the 3’ end of the expression cassette. This modification resulted in a notable about two-fold increase in the expression of the bsAb in the Expi293 cell line. Results & Conclusion:Follow-up flow cytometry analysis demonstrated the binding properties of the produced antibody at acceptable levels, and in vitro bioactivity assays showed that this product is potent enough for targeting and destroying CD19-positive cells. Our findings show that WPRE enhances the expression of this type of bispecific mAbs in HEK-293 family cell lines. This approach can be used in biopharma industry for the mass production of anti-CD3 × CD19 bispecific antibody. Key Words: Acute lymphoblastic leukemia, Bispecific antibodies, Monoclonal antibody     

Identification of Sequence Variation in the Apolipoprotein A2 Gene and Their Relationship with Serum High-Density Lipoprotein Cholesterol Levels

Background:

Apolipoprotein A2 (APOA2) is the second major apolipoprotein of the high-density lipoprotein cholesterol (HDL-C). The study aim was to identify APOA2 gene variation in individuals within two extreme tails of HDL-C levels and its relationship with HDL-C level.

Methods:

This cross-sectional survey was conducted on participants from Tehran Glucose and Lipid Study (TLGS) at Research Institute for Endocrine Sciences, Tehran, Iran from April 2012 to February 2013. In total, 79 individuals with extreme low HDL-C levels (≤5^th percentile for age and gender) and 63 individuals with extreme high HDL-C levels (≥95^th percentile for age and gender) were selected. Variants were identified using DNA amplification and direct sequencing.

Results:

Screen of all exons and the core promoter region of APOA2 gene identified nine single nucleotide substitutions and one microsatellite; five of which were known and four were new variants. Of these nine variants, two were common tag single nucleotide polymorphisms (SNPs) and seven were rare SNPs. Both exonic substitutions were missense mutations and caused an amino acid change. There was a significant association between the new missense mutation (variant Chr.1:16119226, Ala98Pro) and HDL-C level.

Conclusion:

None of two common tag SNPs of rs6413453 and rs5082 contributes to the HDL-C trait in Iranian population, but a new missense mutation in APOA2 in our population has a significant association with HDL-C.     

Dietary diversity score and cardiovascular risk factors in Tehranian adults

AIM: To evaluate the relationship between dietary diversity score (DDS) and cardiovascular risk factors in Tehranian adults. METHODS: In this population-based cross-sectional study, a representative sample of 581 subjects (295 males and 286 females) aged over 18 years, residents of Tehran, participated. Hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein cholesterol were defined according to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program. Diabetes was defined as fasting plasma glucose concentration > or = 126 mg dl(-1) or 2-h post challenge glucose concentration > or = 200 mg dl(-1). Hypertension was defined on the basis of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Dietary diversity was defined according to the Diet Quality Index revised. RESULTS: Mean (+/- standard deviation) DDS was 6.15 +/- 1.02. The probability of having diabetes (odds ratio (OR) among quartiles: 1.45, 1.26, 1.11 and 1.00, respectively; P for trend = 0.04) and hypertriglyceridaemia (OR = 1.41, 1.23, 1.05 and 1.00, respectively; P for trend=0.04) decreased with increasing quartile of the diversity score for whole grains. The probability of having obesity (OR among quartiles: 1.39, 1.06, 1.03 and 1.00, respectively; P for trend = 0.03), hypercholesterolaemia (OR = 1.46, 1.28, 1.11 and 1.00, respectively; P for trend = 0.03), hypertension (OR = 1.32, 1.17, 1.13 and 1.00, respectively; P for trend = 0.03) and high low-density lipoprotein cholesterol (LDL-C) (OR = 1.25, 1.12, 1.07 and 1.00, respectively; P for trend = 0.04) decreased with increasing quartile of the diversity score for vegetables. The probability of having hypercholesterolaemia, high LDL-C, hypertension and diabetes decreased with quartile of the DDS. But the probability of being obese increased with quartile of the DDS (P for trend = 0.03). CONCLUSION: DDS was inversely associated with cardiovascular risk factors in this cross-sectional study. Increased diversity scores of diets, to increase the variety score for vegetables, may be emphasised in programmes attempting to bring about changes in lifestyle.     

Association of Lecithin Cholesterol Acyltransferase rs5923 Polymorphism in Iranian Individuals with Extremely Low High-Density Lipoprotein Cholesterol: Tehran Lipid and Glucose Study

Background:

The serum concentration of high-density lipoprotein cholesterol (HDL-C) is one of the important heritable risk factors for cardiovascular disease and is a target for therapeutic intervention. In this study, we aimed to evaluate the effects of lecithin cholesterol acyltransferase (LCAT) gene polymorphism rs5923 on LCAT enzyme activity and serum HDL-C concentration.

Methods:

The study population was selected from consecutive individuals with HDL-C ≤ 5^th percentile (n = 73) and extremely high HDL-C ≥ 95^th percentile (n = 57) who had participated in the Tehran Lipid and Glucose Study. The rs5923 polymorphism was genotyped using direct sequencing. LCAT activity was measured by fluorometric assay kit, and lipid concentrations were measured using the enzymatic colorimetric method.

Results:

The genotype frequencies were significantly different between the high HDL-C group (CC 94.7%, CT 5.3%) and the low HDL-C group (CC 83.6%, CT 16.4%) (P = 0.048). The T-allele frequencies in subjects with low and high HDL-C were 0.082 and 0.026, respectively (P = 0.16). The association of the single-nucleotide polymorphism rs5923 with low HDL-C was not statistically significant after adjustment for age, sex, and BMI (odd ratio = 2.65, 95% confidence interval = 0.32-21.5, P = 0.36, regression logistic analysis). Also, the effects of LCAT enzyme activity did not depend on the HDL-C level (P = 0.24).

Conclusion:

rs5923 polymorphism is not associated with low HDL-C levels in Iranian population. Key Words: Polymorphism, Single nucleotide, Lipoproteins