Body mass index and change in blood pressure over a 7-year period in older Mexican Americans

Obesity and hypertension are major public health concerns in the US. We examined the relationship between body mass index (BMI) and blood pressure in older Mexican Americans using data from the Hispanic Established Population for the Epidemiological Study of the Elderly (EPESE), a longitudinal study of Mexican Americans aged 65 and over residing in the southwestern US. The study sample was 2404 older Mexican American adults with a mean age of 72.6 years of age at baseline (1993–4). Both systolic and diastolic blood pressures were higher in subjects with high BMI categories. The rate of change in systolic blood pressure and diastolic blood pressure were −0.11 mm Hg and −0.32 mm Hg per year over a 7-year period, respectively. The rate of decline in systolic and diastolic blood pressure over a 7-year period was greater in subjects with BMI categories of 25–<30 kg/m² and 30–<35 kg/m² as compared with those subjects with in the lowest and in the highest BMI categories. Hypertension is one of the most prevalent medical conditions affecting older adults. Understanding possible modifiable risk factors that may play a role in the management of hypertension will be beneficial.     

Asymmetric Cell–Matrix and Biomechanical Abnormalities in Elastin Insufficiency Induced Aortopathy

Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln ^+/? ) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln ^+/? ) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln ^+/? aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln ^+/? aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln ^+/? ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure–function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.     

Investigation of phthalate release from tracheal tubes

Phthalates are chemicals used extensively in the manufacture of plastics for their desirable physical characteristics. In addition to enhancing the performance of plastics, phthalates have a number of undesirable effects, principally endocrine disruptor effects, that may have adverse effects on reproductive development and functioning. As a result, they have been banned from the manufacture of children's toys. Despite this, they continue to be used in the manufacture of medical devices, including anaesthetic equipment. This study aimed to assess phthalate release from five brands of tracheal tube. Using gas chromatography–mass spectrometry, we analysed phthalate concentrations from samples of ultra pure water in which tracheal tubes had been submerged. Phthalate concentration increased from 6.7 to 149 μg.l^?1 over a period of 4.8 days. Phthalate release from anaesthetic equipment has not previously been documented over short time periods and raises the possibility of iatrogenic endocrine disruption with routine anaesthesia.     

Metformin in cancer: translational challenges

The anti-diabetic drug metformin is rapidly emerging as a potential anti-cancer agent. Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle. Epidemiological studies have consistently associated metformin use with decreased cancer incidence and cancer-related mortality. Furthermore, numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to an explosion of interest in evaluating this agent in human cancer. The effects of metformin on circulating insulin levels indicate a potential efficacy towards cancers associated with hyperinsulinaemia; however, metformin may also directly inhibit tumour growth. In this review, we describe the mechanism of action of metformin and summarise the epidemiological, clinical and preclinical evidence supporting a role for metformin in the treatment of cancer. In addition, the challenges associated with translating preclinical results into therapeutic benefit in the clinical setting will be discussed.     

Mental Disorders and Cigarette Use among Adults in the United States

Background: The goal of this study was to determine the association between mental disorders and cigarette consumption and nicotine dependence. Methods: Data were drawn from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a nationally representative survey of adults (N = 43,093) aged 18 and older. Relationships between specific anxiety disorders, mood disorders, nondependent cigarette use, nicotine dependence among the whole sample, and nicotine dependence among cigarette users were examined. Results: After adjusting for demographics and comorbid mental disorders, generalized anxiety disorder (OR = 1.16 (1.29-1.51)), specific phobia (OR = 1.35 (1.21-1.51)), panic disorder (PD) (OR = 1.90 (1.62-2.23)), major depression (MDD) (OR = 1.31 (1.16-1.48)), and bipolar disorder (OR = 1.30 (1.09-1.54)) were associated with increased likelihood of nondependent cigarette use. Specific phobia (OR = 1.69 (1.49-1.91)), PD (OR = 1.82 (1.50-2.21)), MDD (OR = 1.59 (1.38-1.84)), and bipolar disorder (OR = 1.71 (1.39-2.09)) were associated with increased odds of nicotine dependence among the whole sample; social phobia (OR = 1.69 (1.19-2.40)), specific phobia (OR = 1.69 (1.43-2.01)), MDD (OR = 1.65 (1.34-2.02)), and bipolar disorder (OR = 2.38 (1.74-3.24)) were associated with increased risk of nicotine dependence among cigarette users. Conclusions: Specific anxiety disorders and mood disorders were uniquely associated with nondependent cigarette use, nicotine dependence among the whole sample, and the risk of nicotine dependence among cigarette users in the United States. Findings suggest that demographic differences, comorbid mood, anxiety, substance, and personality disorders all contributed to previously observed associations between mental disorders and nicotine dependence, explaining these links in some but not all cases. (Am J Addict 2012;21:416-423).     

Factors associated with poor glycemic control in older Mexican American diabetics aged 75 years and older

ObjectiveThis study examines the prevalence and correlates of poor glycemic control in Mexican Americans aged 75 years and older with diabetes.MethodsData are from the 5^th wave (2004-05) of the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE). A total of 2,069 Mexican Americans aged 75 and over were interviewed. Six hundred eighty nine subjects (33.5%) reported having been diagnosed with diabetes and 209 (30.3%) subjects agreed to a blood test of their HbA₁c level.ResultsOf the 209 diabetic subjects with an HbA₁c test, 73 (34.9%) had good glycemic control (HbA₁c < 7%) and 136 (65.1%) had poor glycemic control (HbA₁c > 7%). Bivariate analysis revealed that subjects with poor control had longer disease duration, had lower education, used the glucometer more frequently, and had more diabetes-complications when compared to those in the good glycemic control group. Multivariable logistic regression analysis found the following factors associated with poor glycemic control: < 8 years of education, foreign-born, smoking, obesity, longer disease duration, daily glucometer use, and having macro-complications.DiscussionPrevalence of poor glycemic control is very high in this population with very high and rising prevalence of diabetes. Further studies are needed to explore the effect of these and other characteristics on glycemic control among older Mexican Americans and to develop appropriate interventions to improve diabetes outcomes and increase life-expectancy.     

Retinoic Acid-related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema

Rationale: The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. Objectives: To determine the role of Rora in smoke-induced emphysema. Methods: Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Measurements and Main Results: Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Conclusions: Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer.     

Potassium Depolarization and Raised Calcium Induces α-Synuclein Aggregates

α-Synuclein is the key aggregating protein in Parkinson’s disease (PD), which is characterized by cytoplasmic protein inclusion bodies, termed Lewy bodies, thought to increase longevity of the host neuron by sequestering toxic soluble α-synuclein oligomers. Previous post-mortem studies have shown relative sparing of neurons in PD that are positive for the Ca²⁺ buffering protein, calbindin, and recent cell culture and in vitro studies have shown that α-synuclein aggregation can be induced by Ca²⁺. We hypothesized that depolarization with potassium resulting in raised Ca²⁺ in a PD cell culture model will lead to the formation of α-synuclein protein aggregates and that the intracellular Ca²⁺ buffer, BAPTA-AM, may suppress their formation. Live cell fluorescence microscopy was performed to monitor changes in intracellular free calcium in HEK293T, SH-SY5Y neuroblastoma or stably transfected HEK293T/α-synuclein cells. Raised intracellular free Ca²⁺ was consistently observed in cells treated with KCl, but not controls. Immunohistochemistry analysis on cells 48–72 h after K⁺ treatment revealed two subsets of cells with either large (>2 μm), perinuclear α-synuclein aggregates or multiple smaller (<2 μm), cytoplasmic accumulations. Cells pre-treated with varying concentrations of trimethadione (TMO), a calcium channel blocker, showed suppression of the Ca²⁺ transient following KCl treatment and no α-synuclein aggregates at TMO concentrations >5 μM. Quantitative analysis revealed a significant increase in the number of cells bearing α-synuclein cytoplasmic inclusions in both HEK293T/α-synuclein and SHSY-5Y cells when transient intracellular raised Ca²⁺ was induced (p = 0.001). BAPTA-AM pre-loading significantly suppressed α-synuclein aggregates (p = 0.001) and the intracellular free Ca²⁺ transient. This study indicates that raised intracellular Ca²⁺ mediated by K⁺ depolarization can lead to α-synuclein aggregation.