Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

Background

Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited.

Methods

We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987–1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates.

Results

During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12–1.32) for glycolithocholate sulfate and 1.22 (1.10–1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes.

Conclusion

We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted.     

Tomato bushy stunt virus (TBSV) infecting Lycopersicon esculentum

Tomato bushy stunt virus (TBSV) was detected in tomato crop (Lycopersicon esculentum) in Egypt with characteristic mosaic leaf deformation, stunting, and bushy growth symptoms. TBSV infection was confirmed serologically by ELISA and calculated incidence was 25.5%. Basic physicochemical properties of a purified TBSV Egh isolate were identical to known properties of tombusviruses of isometric 30-nm diameter particles, 41-kDa coat protein and the genome of approximately 4800 nt. This is the first TBSV isolate reported in Egypt. Cloning and partial sequencing of the isolate showed that it is more closely related to TBSV-P and TBSV-Ch than TBSV-Nf and TBSV-S strains of the virus. However, it is distinct from the above strains and could be a new strain of the virus which further confirms the genetic diversity of tombusviruses.     

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Chitosan–Sodium Lauryl Sulfate Nanoparticles as a Carrier System for the In Vivo Delivery of Oral Insulin

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.KEY WORDS: chitosan, insulin, nanoparticles, oral delivery system, sodium lauryl sulfate     

Effects of high temperature on reproduction

The significance of seasonal fluctuations in the components of the reproductive cycle is complex. In mammals, high environmental temperature may cause delayed puberty, delayed onset of sexual season, irregularity in cycle length, duration of estrus, ovulation rate, frequency of anovulatory estrus,morphological abnormalities in ova, fetal size and semen characteristics. High temperatures, in birds, may affect rate of egg laying, egg weight, shell quality, fertility, size of blastoderm and hatchability. Animals have developed effective thermoregulatory mechanisms for the testis. The effects of extremes of temperatures on reproduction vary with the species,breed, age, stage of reproductive cycle,period of temperature exposure, nature of temperature fluctuation and altitude. Effects of low temperature on reproduction have been little studied.

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Zusammenfassung Die Bedeutung von jahreszeitlichen Schwankungen der Komponenten im Fortpflanzungszyklus ist komplex. Bei SÄugetieren kann hohe Temperatur eine verspÄtere PubertÄt bewirken, spÄten Beginn der Brunst, UnregelmÄssigkeiten in der ZykluslÄnge,Oestrusdauer, Ovulationsrate und HÄufigkeit von anovulatorischen Oestrus, morphologische AbnormalitÄten der Eier, der Fötengrösse und des Samens.Bei Vögeln können hohe Temperaturen die LegetÄtigkeit, Eigewicht, SchalenqualitÄt, Fruchtbarkeit, Grösse des Blastoderms und Ausbrütbarkeit beeinflussen. Tiere haben wirksame thermoregulatorische Mechanismen für die Hoden entwickelt.Die Einflüsse von Temperaturextremen auf die Fortpflanzung variiert mit der Tierart, Zucht, Alter,Stadium im Fortpflanzungszyklus, Temperatureinwirkungszeit, Art der Temperaturschwankungen und Höhe. Die Bedeutung niedriger Temperatur für die Fortpflanzung ist noch wenig untersucht.

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Resume L'importance des fluctuations saisonnières sur le cycle de reproduction est complexe. Chez les mammifères, une température élevée peut causer un retard de la puberté et du rut des irrégularités de la durée du cycle et de l'oestrus ainsi que de la fréquence des ovulations; les cycles anovulatoires, les anomalies morphologiques de l'oeuf, de la semence et les variations de la grandeur fétale sont plus frequents. Chez les oiseaux les hautes températures peuvent influencer la ponte, le poids de l'oeuf, la qualité de la coquille, la fertilité, la grandeur de blastoderme et la tendance à couver. Les animaux ont développé des mécanismes thermorégulateurs efficaces pour les testicules. Les influences des extrÊmes de température sur la reproduction varient avec l'espèce, la race, l'âge,le stade du cycle de reproduction, la nature et la durée des différences de température et l'altitude. L'influence des basses températures sur la reproduction n'a pas encore été bien étudiée.

     

Use of Hydrocyclones for Mammalian Cell Retention: Separation Efficiency and Cell Viability (Part 1)

A hydrocyclone with a volume of 2.56 cm³ was studied as a potential cell retention device for mammalian cell cultures (6 L volume). For the feasible operation range (0.9 to 1.6 L/min flow corresponding to pressure drops of 0.4 to 1.3 bar) the hydrocyclone was characterized with regard to flow split (underflow‐to‐overflow ratio) and flow ratio (underflow to supply). Cultures of BHK and HeLa cells (with low cell concentrations) were applied to measure separation efficiency and cell viability for a hydrocyclone operation period of 3 min corresponding to a cell suspension throughput of 2.7 to 4.8 L. Cell separation efficiencies ranged from 0.77 to 0.97 and cell viability was not affected except for BHK cells in the overflow at the highest pressure drop (1.3 bar). As the overflow is commonly used for product harvest and cells are discarded, the application of the hydrocyclone has no detrimental effect on the reactor perfusion system. The results indicate that only cells passing from the primary vortex downwards into the inner secondary vortex and from there upwards could be damaged. Evidence for this hypothesis is obtained from operating the hydrocyclone with closed overflow (only centrifugal forces acting) for a period of 3 h. In these studies no significant effect on cell viability could be detected for HeLa and CHO cells. Hence, the results indicate that the hydrocyclone can be appropriately used for cell retention and separation in perfusion cultures. Application at higher pressures is recommended whereby separation efficiencies of 0.97 without any loss in viability can be achieved.     

P wave indices, obesity, and the metabolic syndrome: the atherosclerosis risk in communities study

Atrial fibrillation and obesity are increasing in prevalence and are interrelated epidemics. There has been limited assessment of how obesity and the metabolic syndrome impact P wave indices, established electrocardiographic predictors of atrial fibrillation. We conducted a cross-sectional analysis to determine the association of obesity and the components of the metabolic syndrome with P wave indices in the population-based Atherosclerosis Risk in Communities (ARIC) study. Analyses were adjusted for demographic, anthropometric and clinical variables, and cardiovascular diseases and risk factors. Following relevant exclusions, 14,433 subjects were included (55% women and 24.7% black). In multivariable analyses, we identified significant, progressive increases in PR interval, P wave maximum duration, and P wave terminal force with BMI 25-30 kg/m(2) and BMI ≥30 kg/m(2) compared to the reference group <25 kg/m(2) (P < 0.0001 for trend for all P wave indices). These effects were present in both blacks and whites. Presence of metabolic syndrome was also associated with longer P wave indices. When components of the metabolic syndrome were examined separately, hypertension resulted in significant (P < 0.001) augmentation of the three P wave indices. Similarly, waist circumference was associated with greater P wave maximum duration in both races (P < 0.001). We concluded that P wave indices are significantly associated with obesity and particularly with hypertension and waist circumference. P wave indices may comprise intermediate markers, independent of age and cardiovascular risk, of the pathway linking obesity and with the risk of atrial fibrillation (AF).     

Simultaneous determination of inosine, hypoxanthine, xanthine, and uric acid and the effect of metal chelators

We describe a sensitive, reproducible method for the simultaneous determination of the ATP catabolites inosine, hypoxanthine, xanthine, and uric acid in biological samples and organ perfusate using reverse-phase chromatography and multiwavelength detection at 254, 270, and 292 nm. Sample preparation includes precipitating proteins with perchloric acid, neutralizing the sample, passing the supernatant over a polyethyleneimine column, and analyzing the collected fractions by high-performance liquid chromatography. Addition of metal chelators to the perchloric acid resulted in increased values for xanthine, hypoxanthine, and uric acid. The method was sensitive (limit of detection, 0.08 nmol on column; S/N = 4) and linear over the range 0.5-30 microM. Precision and accuracy of the method were evaluated for lung tissue and lung perfusate. Coefficients of variation ranged from 2.8 to 6.1% for perfusate and from 1.7 to 12.6% for tissue. Recoveries for all compounds exceeded 90%. We applied this method to rat lung tissue, lung perfusate, and rat and human blood. Advantages of this method are simultaneous quantitation with excellent sensitivity of all compounds, simplified peak identification by using multiwavelength detection, and improved accuracy by preventing loss of compounds with metal chelators.     

Detoxification of aflatoxin B1 by acidogenous yoghurt

Serial concentrations of aflatoxin B₁ ranged from 200 to 1000 p.p.b. were assayed for detoxification by acidogenous yoghurt. Thin-layer chromatography analysis revealed a complete transformation of 800 p.p.b. of aflatoxin B₁ to a new fluorescing compound corresponding to aflatoxin B_2a which is referred as hydroxydihydroaflatoxin B₁. Partial conversion was present in yoghurt sample containing 1000 p.p.b. Toxicity test on chickens, confirmed Ciegler findings.