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- Myocytes Oxygenation and High Energy Phosphate Levels during Hypoxia. [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e101317.
Decrease of ambient oxygen level has been used in myocytes culture experiments in examining the responsiveness to stress secondary to hypoxia. However, none of these studies measure the myocytes oxygenation levels resulting in ambiguity as to whether there is insufficient oxygen delivery. This study examined the hypothesis that at a basal myocardial work state, adequate myocyte oxygenation would be maintained until extremely low arterial pO2 levels were reached. Myocyte pO2 values in normal dogs were calculated from the myocardial deoxymyoglobin (Mb- δ) levels using 1H-spectroscopy (MRS) and were normalized to Mb-δ obtained after complete LAD occlusion. During Protocol 1 (n = 6), Mb-δ was measured during sequential reductions of the oxygen fraction of inspired gas (FIO2) from 40, 21, 15, 10, and 5%, while in protocol 2 (n = 10) Mb-δ was measured at FIO2 of 3%. Protocol 3 (n = 9) evaluated time course of Mb-δ during prolonged exposure to FIO2 of 5%. Myocardial blood flow (MBF) was measured with microspheres and high energy phosphate (HEP) levels were determined with 31P-MRS. MVO2 progressively increased in response to the progressive reduction of FIO2 that is accompanied by increased LV pressure, heart rate, and MBF. Mb-δ was undetectable during FIO2 values of 21, 15, 10, and 5%. However, FIO2 of 3% or prolonged exposure to FIO2 of 5% caused progressive increases of Mb-δ which were associated with decreases of PCr, ATP and the PCr/ATP ratio, as well as increases of inorganic phosphate. The intracellular PO2 values for 20% reductions of PCr and ATP were approximately 7.4 and 1.9 mmHg, respectively. These data demonstrate that in the in vivo system over a wide range of FIO2 and arterial pO2 levels, the myocyte pO2 values remain well above the Km value with respect to cytochrome oxidase, and oxygen availability does not limit mitochondrial oxidative phosphorylation at 5% FIO2.
- Using response variation to develop more effective, personalized behavioral medicine?: evidence from the Resist Diabetes study. [Journal Article]
- Transl Behav Med 2014 Sep; 4(3):333-8.
Health behavior interventions have achieved some notable outcomes through generally higher dose interventions with intensive initial phases and long-term, faded contact maintenance phases with attention to mean changes and adherence rates. Interventions may be improved by shifting attention to the very large response variation that is typical for such protocols as exercise with non-, low, moderate, and high responders and even those who show adverse responses. Data from the Resist Diabetes study, which included adults (N = 159, ages 50-69 years) with prediabetes who were overweight or obese (BMI 25-39.9 kg/m(2)) and previously inactive, are presented. The data show a typical pattern of wide variation for changes on a 2-h oral glucose tolerance test (OGTT), defined by blood glucose concentration measured after 2 h following ingestion of 75 g of glucose, lean body mass, fat mass, strength, and blood pressure to the same resistance training protocol within a highly supervised phase and where adherence was high. A personalized behavioral medicine approach could focus on such individual patterns of response variation to tailor and alter additional intervention components, the staging of maintenance interventions, and then determining how to most effectively, and systematically, translate this adaptive intervention approach into practice to potentially achieve more optimal clinical outcomes.
- A Genetic Variant in the Seed Region of Mir-4513 Shows Pleiotropic Effects on Lipid and Glucose Homeostasis, Blood Pressure and Coronary Artery Disease. [JOURNAL ARTICLE]
- Hum Mutat 2014 Sep 25.
MicroRNAs (miRNA) play a crucial role in the regulation of diverse biological processes by post-transcriptional modulation of gene expression. Genetic polymorphisms in miRNA-related genes can potentially contribute to a wide range of phenotypes. The effect of such variants on cardiometabolic diseases has not yet been defined. We systematically investigated the association of genetic variants in the seed regions of miRNAs with cardiometabolic phenotypes, using the thus far largest genome wide association studies on 17 cardiometabolic traits/diseases. We found that rs2168518:G>A, a seed region variant of miR-4513, associates with fasting glucose, LDL-cholesterol and total cholesterol, systolic and diastolic blood pressure and risk of coronary artery disease. We experimentally showed that miR-4513 expression is significantly reduced in presence of the rs2168518 mutant allele. We sought to identify miR-4513 target genes that may mediate these associations and revealed five genes (PCSK1, BNC2, MTMR3, ANK3 and GOSR2) through which these effects might be taking place. Using luciferase reporter assays we validated GOSR2 as a target of miR-4513 and further demonstrated that the miRNA mediated regulation of this gene is changed by rs2168518. Our findings indicate a pleiotropic effect of miR-4513 on cardiometabolic phenotypes and may improve our understanding of the pathophysiology of cardiometabolic diseases. This article is protected by copyright. All rights reserved.
- Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension. [JOURNAL ARTICLE]
- J Hypertens 2014 Sep 24.
Nonadherence to drug therapy poses a significant problem in the treatment of patients with presumed resistant hypertension. It has been shown that therapeutic drug monitoring (TDM) is a useful tool for detecting nonadherence and identifying barriers to treatment adherence, leading to effective blood pressure (BP) control. However, the cost-effectiveness of TDM in the management of resistant hypertension has not been investigated.A Markov model was used to evaluate life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios in resistant hypertension patients receiving either TDM optimized therapy or standard best medical therapy. The model ran from the age of 30 to 100 years or death, using a cycle length of 1 year. Efficacy of TDM was modeled by reducing risk of hypertension-related morbidity and mortality. Cost analyses were performed from a payer's perspective. Deterministic and probabilistic sensitivity analyses were conducted.In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of &OV0556;3854 and &OV0556;3922, respectively. Given a willingness-to-pay threshold of &OV0556;35 000 per QALY gained, the probability of TDM being cost-effective was 95% or more in all age groups from 30 to 90 years. Results were influenced mostly by the frequency of TDM testing, the rate of nonresponders to TDM, and the magnitude of effect of TDM on BP.Therapeutic drug monitoring presents a potential cost-effective healthcare intervention in patients diagnosed with resistant hypertension. Importantly, this finding is valid for a wide range of patients, independent of sex and age.
- The Wuhan-Zhuhai (WHZH) cohort study of environmental air particulate matter and the pathogenesis of cardiopulmonary diseases: study design, methods and baseline characteristics of the cohort. [JOURNAL ARTICLE]
- BMC Public Health 2014 Sep 24; 14(1):994.
Particulate air pollution has been recognized to be associated with a wide range of adverse health effects, including increased mortality, morbidity, exacerbation of respiratory conditions. However, earlier physiological or pathological changes or long-term bodies' reaction to air pollutants have not been studied in depth in China. The Wuhan-Zhuhai (WHZH) cohort study is designed to investigate the association between air pollutants exposure and physiological or pathological reactions on respiratory and cardiovascular system.The cohort is a community-based prospective study that includes 4812 individuals aged 18-80 years. The collections of data were conducted from April to May 2011 in Wuhan city and in May 2012 in Zhuhai city. At baseline, data on demographic and socioeconomic information, occupational history, family disease history, lifestyle, cooking mode, daily travel mode, physical activity and living condition have been collected by questionnaires. Participants underwent an extensive physical examination, including anthropometry, spirometry, electrocardiography, and measurements of blood pressure, heart rate, exhaled nitric oxide and carbon monoxide. Potential conditions in the lung, heart, liver, spleen, and skin were synchronously performed. In addition, samples of morning urine, fasting blood serum and plasma were collected during physical health examination. DNA were extracted and were stored at -80[degree sign]C. Environment concentrations of particulate matter and chemicals were determined for 15 days in each of four seasons. Participants are followed for physiological or pathological changes or incidence of cardiopulmonary diseases every 3 years.The results obtained in WHZH cohort study may increase a better understanding of the relationship between particulate air pollution and its components and possible health damages. And the potential mechanisms underlying the development of cardiopulmonary diseases has implications for the development of prevention and treatment strategies.
- Contribution of Impaired Renal Function to Cardiovascular Risk Prediction Models in Renal Transplant Recipients. [JOURNAL ARTICLE]
- Clin Transplant 2014 Sep 24.
The Framingham Risk Score ( FRS ) and Cardiovascular Risk Calculator for Renal Transplant Recipients ( CRCRTR - MACE ) quantify cardiovascular risk in renal transplant recipients ( RTR ). In contrast to the FRS , the CRCRTR - MACE includes serum creatinine as a variable in the risk prediction equation. Objective: To determine the influence of impaired renal function on performances of the two equations. METHODS: A chart review of 270 RTR transplanted from 1979-2012. High-risk was defined at scores ≥20%. Standard statistical analyses included multivariate analysis ( MVA ), stepwise analysis, and odds ratio to estimate contributions of risk factors. RESULTS: Mean transplant duration was 9.51±6.65 years. Mean eGFR was 59.19±28.26ml/min/1.73m (2) . FRS and CRCRTR-MACE scores of least 20% were present in 9.3% and 24.8%, respectively, while 7.2% and 11.2% of RTR with eGFR ≥60ml/min/1.73m (2) , were high-risk, respectively. Mean age, blood pressure, TC:HDL ratio, smoking and diabetes were evenly distributed in patients with varying eGFR . FRS scores remained similar at wide eGFR range (≤30ml/min/1.73m (2) to ≥90ml/min/1.73m (2) ), while CRCRTR-MACE scores significantly increased as eGFR decreased. CONCLUSIONS: CRCRTR - MACE identified more patients at high cardiovascular risk, even in those with more favorable renal function, suggesting a fundamental difference between the two calculators beyond renal function. This article is protected by copyright. All rights reserved.
- Genome Wide Association Study in Chinese Identifies Novel Loci for Blood Pressure and Hypertension. [JOURNAL ARTICLE]
- Hum Mol Genet 2014 Sep 23.
Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWAS) in European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWAS of blood pressure and hypertension in 11816 subjects followed by replication studies including 69146 additional individuals. We identified genome-wide significant (P<5.0 ¡Á 10(-8)) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13 L) and a newly discovered variant near SLC4A7. We also replicated fourteen previously reported loci, eight (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2 and JAG1) at genome-wide significance, and six (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5 and TBX3) at a suggestive level of P=1.81 ¡Á 10(-3) to 5.16 ¡Á 10(-8). These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.
- Prevalence and correlates of chronic kidney disease among civil servants in Bayelsa state, Nigeria. [JOURNAL ARTICLE]
- Niger J Clin Pract 2014 September-October; 17(5):602-607.
Introduction: Chronic kidney disease (CKD) has become a public health problem with rising incidence and prevalence world-wide. Despite the fact that Sub-Saharan Africa, including Nigeria appears to be badly hit by this epidemic, there is a paucity of data on CKD prevalence in these regions and where data exists, they are mostly hospital-based. Objectives: The present study was carried out to determine the prevalence and correlates of CKD in an urban civil service population in Bayelsa State, Nigeria. Materials and Methods: A total of 179 civil servants in the Bayelsa State secretariat were screened for CKD during the World Kidney Day on March 2012. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m 2 body surface area and/or proteinuria. Socio-demographic data was obtained using interviewer-administered semi-structured questionnaire while anthropometric measurements were taken. Blood pressure (BP), urinalysis, serum urea and creatinine were also assessed. Results: The prevalence of CKD in the study was 7.8%. Age >50 years was associated with CKD in univariate analysis but none of age, gender, body mass index, BP or hyperglycemia independently predicted it. Conclusion: The prevalence of CKD among Nigerian civil servants was fairly high and was associated with advancing age. Routine screening for CKD in this population is recommended.
- Why Patients Know More About Cars than PAD. [JOURNAL ARTICLE]
- Circulation 2014 Sep 19.
Americans who are interested in purchasing a motor vehicle often investigate automobile manufacturers, car models, and even competitive pricing using the World Wide Web. When one uses an Internet search engine to investigate Toyota, the largest automobile manufacturer in the World, there are over 93,000,000 results. Virtually every possible question one would have about a Toyota vehicle is discoverable before ever visiting a local Toyota dealership. One would anticipate that physicians have a similar luxury. A patient presents with exertional discomfort in the calf that promptly resolves with rest. The patient struggles with her diet, is 30 pounds overweight, is on several medications for her high cholesterol and high blood pressure, and has been told that she has "pre-diabetes". With the continued comparisons between Toyota LEAN mechanics and healthcare, patients likely anticipate that a physician would enter this history in a search engine and uncover the diagnosis. In fact, it is anticipated that many healthcare systems will use this type of ediagnostic strategy for many disorders in the not too distant future.
- Effects of established blood pressure loci on blood pressure values and hypertension risk in an Algerian population sample. [JOURNAL ARTICLE]
- J Hum Hypertens 2014 Sep 18.
Genome-wide association studies and subsequent replication studies have pinpointed 29 genetic variants associated with blood pressure (BP). None of these studies included North African populations. We therefore looked at whether or not these genetic variants modulated BP and hypertension (HTN) risk in an Algerian population sample. Twenty-nine single-nucleotide polymorphisms (SNPs) were genotyped in a representative sample of 787 subjects from the InSulino-résistance à ORan (ISOR) study (378 men and 409 women aged between 30 and 64 years and recruited from within the city of Oran, Algeria). Genetic variants were considered both individually and when combined as genetic predisposition scores (GPSs) for systolic BP (SBP), diastolic BP (DBP) and HTN risk. The SNPs in CYP1A1-ULK3, HFE and SH2B3 were significantly associated with BP and/or HTN. The SBP-GPS, DBP-GPS and HTN-GPS were associated with higher levels of DBP (+0.24 mm Hg P=0.05, +0.23 mm Hg P=0.05 and +0.26 mm Hg P=0.03, respectively). Moreover, the three GPSs tended to be associated with a 6% higher risk of HTN. Our study is the first to show that some of the BP loci validated in subjects of European descent were associated (either individually or when combined as GPSs) with BP traits and/or the HTN risk in an Algerian population, but to a lesser extent than in European populations. Although larger studies and meta-analyses of North African populations are needed to confirm the present results, our data contribute to a better understanding of genetic susceptibility to HTN.Journal of Human Hypertension advance online publication, 18 September 2014; doi:10.1038/jhh.2014.81.