Association between the adrenoreceptor β2 gene and pediatric asthma severity – a study of the PACMAN cohort

"Pharmacogenetics of Asthma medication in Children: Medication with Anti-Inflammatory effects" (PACMAN) is an observational retrospective pharmacy-based study carried out in 2009, in the Netherlands, aiming to investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes. Data on respiratory symptoms and medication use, including medication type and amount, was collected from pharmaceutical records of asthmatic children and data on the children’s sex, age, genetic traits, and ethnicity. We aimed to assess the association between asthma severity and the Arg16Glu polymorphism of the β2 adrenoreceptor gene (ADRB2). This gene is expressed in bronchial muscle cells, which is involved in the physiological response of the airway response and has been associated with clinical drug response and asthma exacerbations. We used the PACMAN data and considered the dispensing of oral corticosteroid prescriptions as a proxy of the disease severity since corticoids are commonly used in uncontrolled asthmatic states (exacerbations). We considered two different genetic models – additive and genotypic, which can be translated for analysis purposes into a numeric format, corresponding to the number of copies of the minor allele, and categorical (each genotype representing a category), respectively. We used models of the class of the Generalized Linear Mixed Models for count data with excess of zeros, namely zero-inflated and hurdle models, considering a Negative Binomial distribution to account for overdispersion. Both models included the polymorphism in the zero and count components and were adjusted for children’s baseline characteristics. In both approaches to deal with the excess of zeros, a significant effect of the polymorphism was found only in the binary component of the models. In the count component, only sex and age showed a significant effect. This points towards the existence of an effect of the polymorphism in the presence of asthma exacerbations, with not shown effect in the frequency of OCS prescription.This work is partially financed by national funds through FCT – Fundação para a Ciência e a Tecnologia under the project UIDB/00006/2020.info:eu-repo/semantics/publishedVersio

Cardiac venous arterialization in acute myocardial infarction: how great is the benefit?

Cardiac venous arterialization has been proposed as an alternative approach for myocardial revascularization in ischaemic heart disease. It is based on using the cardiac venous system to transport arterial blood from a systemic artery to infarcted myocardial areas. Our goal was to evaluate its benefit in reducing acute myocardial infarct size and its effects on cardiac performance. In a group of pigs, the left internal mammary artery was anastomosed to the left anterior descending vein; this vein was ligated proximally. The left anterior descending coronary artery was also occluded. Over 5 days, several diagnostic procedures were used to characterize and measure the extent of myocardial infarct, namely ECG, echocardiography, cardiac biomarkers and histopathology. Data were compared with those from a control group of pigs, which were submitted to ligation of only the left anterior descending coronary artery. In the experimental group, echocardiography revealed that the ejection fraction and thickness of the ventricular walls remained unchanged 4 days after surgery, in contrast to the major alterations in the control group. In fact, the ejection fraction in the control group decreased by 21% (P 0.2). This study reveals that selective cardiac venous arterialization can nourish the myocardium and is able to reduce infarct size by more than 50%, while protecting cardiac performance. We believe, therefore, that further investigation should be carried out into this technique in order for it to be considered as an option in coronary surgery

Moderate exercise training provides left ventricular tolerance to acute pressure overload

Moreira-Goncalves D, Henriques-Coelho T, Fonseca H, Ferreira RM, Amado F, Leite-Moreira A, Duarte JA. Moderate exercise training provides left ventricular tolerance to acute pressure overload. Am J Physiol Heart Circ Physiol 300: H1044-H1052, 2011. First published December 24, 2010; doi: 10.1152/ajpheart.01008.2010.-The present study evaluated the impact of moderate exercise training on the cardiac tolerance to acute pressure overload. Male Wistar rats were randomly submitted to exercise training or sedentary lifestyle for 14 wk. At the end of this period, the animals were anaesthetized, mechanically ventilated, and submitted to hemodynamic evaluation with biventricular tip pressure manometers. Acute pressure overload was induced by banding the descending aorta to induce a 60% increase of peak systolic left ventricular pressure during 120 min. This resulted in the following experimental groups: 1) sedentary without banding (SED + Sham), 2) sedentary with banding (SED + Band), and 3) exercise trained with banding (EX + Band). In response to aortic banding, SED + Band animals could not sustain the 60% increase of peak systolic pressure for 120 min, even with additional narrowing of the banding. This was accompanied by a reduction of dP/dt(max) and dP/dt(min) and a prolongation of the time constant tau, indicating impaired systolic and diastolic function. This impairment was not observed in EX + Band (P < 0.05 vs. SED + Band). Additionally, compared with SED + Band, EX + Band presented less myocardial damage, exhibited attenuated protein expression of active caspase-3 and NF-kappa B (P < 0.016), and showed less protein carbonylation and nitration (P < 0.05). These findings support our hypothesis that exercise training has a protective role in the modulation of the early cardiac response to pressure overload

Current management of patients with severe acute peripartum cardiomyopathy: practical guidance from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy

No abstract available

Оценка морфофункциональных параметров миокарда у пациентов с ишемической болезнью сердца на фоне первичного манифестного гипотиреоза

Aim. To evaluate the morphological and functional parameters of the myocardium in patients with coronary artery disease (CAD) and concurrent overt primary hypothyroidism, as well as to identify possible relationships between these parameters and levels of thyroid hormones.Methods. 344 patients with CAD who had verified classes 1-3 stable angina pectoris using the clinical guidelines were recruited in a study [6]. 100 patients with CAD and concurrent primary hypothyroidism were enrolled in the study group. 244 patients with CAD were enrolled in the comparison group. Severity of stenosis in one- and/ or two- and/or three-vessel disease were measured in all patients. A comparative assessment of biochemical parameters and echocardiography was performed. A single-stage cross-sectional comparative analysis of the studied parameters was performed. The presence of any relationships of thyroid hormones with morphological and functional parameters of the myocardium were determined. The correlation analysis reported the relationships between diastolic dysfunction, left ventricular ejection fraction and thyroid-stimulating hormone levels in patients with CAD and concurrent hypothyroidism.Results. Statistically significant differences in lipid profile, glucose levels, glycated hemoglobin, and glomerular filtration rate were found. Three-vessel disease prevailed in both groups, but the prevalence of three-vessel disease was higher in the study group (CAD and hypothyroidism) than in the comparison group (p&lt;0.01). Echocardiography assessment reported the differences in the levels of E/a (p = 0.02), E/E` (p = 0.001), and LVEF (p = 0.001) between the study groups.Conclusion. Patients with coronary artery disease and concurrent overt primary hypothyroidism demonstrated worse dyslipidemia parameters, glycemic indicators and impaired glomerular filtration rate. Three-vessel disease prevailed among patients enrolled in the study. The relationship between TSH and myocardial morphological and functional parameters was determined. Obtained data can be used for assessing the prognosis in this group of patients.Цель. Оценить морфофункциональные параметры миокарда пациентов с ишемической болезнью сердца (ИБС) на фоне первичного манифестного гипотиреоза, а также выявить возможную взаимосвязь параметров и уровней концентрации гормонов щитовидной железы.Материалы и методы. В анализе приняли участие 344 пациента с ИБС: стабильной стенокардией I–III функционального класса, диагностированной на основании коронароангиографии. В исследуемую группу вошли 100 пациентов с ИБС на фоне первичного гипотиреоза, в группу сравнения ‒ 244 пациента с ИБС. Регистрировались нарушения (стеноз) в одной – трех коронарных артериях с указанием степени стеноза. Проведена сравнительная оценка биохимических показателей и эхокардиографии. Выполнен одномоментный поперечный сравнительный анализ исследуемых параметров.Результаты. Получены статистически значимые различия в показателях липидограммы: общий холестерин в исследуемой группе составил 232,08 (177; 405) против 177,9 (101; 316) мг/дл в группе сравнения (р&lt;0,0001); триглицериды: 148,1 (50; 330) против 103,5 (31; 713) мг/дл (р&lt;0,0001); липопротеиды низкой плотности: 161,01 (110; 303) против 114,3 (45; 246) мг/дл (р&lt;0,0001); липопротеиды очень низкой плотности: 29,3 (10; 66) против 20,3 (6; 142) мг/дл (р&lt;0,0001); коэффициент атерогенности: 5,8 (3; 14) и 4,1 (2; 12) (р&lt;0,0001) соответственно. Обнаружены статистически значимые различия в уровнях глюкозы: 185,7 (82; 292) ммоль/л в исследуемой группе и 160,7 (83; 207) ммоль/л в группе сравнения (р&lt;0,0001); гликированного гемоглобина: 6,3 (5,2; 11,8) и 5,4 (5,1; 8,9) % (р&lt;0,0001); скорости клубочковой фильтрации: 88,7 (76; 102,7) и 95,8 (89,2; 105,7) мл/мин (р&lt;0,0001) соответственно. В обеих группах преобладало трехсосудистое поражение, однако в исследуемой группе (ИБС и гипотиреоз) количество случаев с трехсосудистым поражением коронарного русла выше в сравнении с группой пациентов только с ИБС: 60,6 и 33,6% соответственно (р&lt;0,01). При оценке параметров эхокардиографии между исследуемыми группами выявлены различия в уровнях E/a: 1,5±0,5 (0,8; 2,2) в исследуемой группе против 1,2±0,4 (0,5; 1,6) в группе сравнения (р = 0,02); Е/Е: 10,4±4 (4; 20) против 8,6±2,5 (4; 12) (р = 0,001); фракции выброса левого желудочка: 50,9±9,6 (40; 68) против 58,6±9,9 (48,7; 68,5) соответственно (р = 0,001).Заключение. У пациентов с ИБС на фоне первичного манифестного гипотиреоза выявлены статистически значимо худшие показатели дислипидемии, гликемического статуса, снижение фильтрационной функции почек. Также отмечено преобладание трехсосудистого поражения коронарных артерий. Определена взаимосвязь тиреотропного гормона и морфофункциональных показателей миокарда, что может быть использовано в оценке прогноза данной группы больных

Lower Free Triiodothyronine Levels Within the Reference Range Are Associated with Higher Cardiovascular Mortality: an Analysis of the NHANES

Thyroid hormones play a central role in cardiovascular homeostasis. Lower free triiodothyronine (FT3) levels have been associated with worse prognosis in several conditions. However, contrary to thyrotropin (TSH) and free thyroxine (FT4), the role of FT3 in morbidity and mortality in the general population remains uncertain. Our objective was to evaluate the association between within the normal range FT3 levels and mortality in the general population.info:eu-repo/semantics/publishedVersio