Myocardial Response to Biomechanical Stress

Biomechanical stress of the myocardium is the situation resulting from hypoxia, hypertension, and other forms of myocardial injury, that invariably lead to increased demands for cardiac work and/or loss of functional myocardium. As a consequence of biomechanical stress a number of responses develop involving all the myocardial cells, namely cardiomyocytes. As a result some myocardial phenotypic changes develop that are initially compensatory (i.e., hypertrophy) but which may mediate the eventual decline in myocardial function that occurs with the transition from hypertrophy to failure in conditions of persistent stress (i.e., apoptosis and fibrosis). This review focuses on the steps involved in the response of the myocardium to biomechanical stress and highlights the most recent developments in the molecular mechanisms involved in the development of heart failure

Fatores de risco para a transmissao vertical do HIV-1 e a influencia da terapia antirretroviral (ARV) no desfecho gestacional

In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.Na ausência de intervenção, as taxas de transmissão vertical do HIV podem variar de 15-45%. Com a inserção dos antirretrovirais durante a gestação e a escolha da via de parto estas taxas chegam a menos de 2%. No entanto o uso de ARV na gestação tem gerado várias duvidas quanto aos efeitos adversos causados ao desfecho gestacional e ao neonato. Este estudo objetiva analisar os fatores de risco da transmissão vertical do HIV-1 em gestantes soropositivas atendidas na cidade do Rio Grande e a influência do uso do ARV no desfecho gestacional. Entre as 262 gestantes estudadas a taxa de transmissão vertical do HIV encontrada foi de 3,8%. Em relação à TV, foi observado menor risco de transmissão quando esta havia feito uso de antirretrovirais e o pré-natal era realizado no serviço de referência. Entretanto, o uso de ARV não influenciou negativamente o desfecho gestacional. No entanto, o inicio do pré-natal após o primeiro trimestre teve influencia sobre o baixo peso ao nascer, assim como a realização de menos de seis consultas aumentou o risco de prematuridade. Portanto, os fatores de risco analisados neste estudo parecem estar relacionados à realização não adequada do pré-natal e ao comportamento materno

Dignity models in healthcare.A review of the literature

Errasti-Ibarrondo, M.B., Carvajal-Valcarcel, A., Martinez-Garcia, M., Arantzamendi-Solabarrieta, M., "Dignity models in healthcare.A review of the literature", Tipo de participación: Póster del congreso: 8th World research congress of the european association for palliative care, celebrado en Lérida, del 5 al 7 de junio de 2014

The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus

Background: Patients with type 2 diabetes mellitus (T2DM) present subclinical left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions. Our aim was to analyze whether the activity of circulating DPP4 is associated with echocardiographically defined LVD in asymptomatic patients with T2DM. Methods: In this cross-sectional study, we examined 83 T2DM patients with no coronary or valve heart disease and 59 age and gender-matched non-diabetic subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme-linked immunosorbent assay. LV function was assessed by two-dimensional echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound measurements. Differences in means were assessed by t-tests and one-way ANOVA. Associations were assessed by adjusted multiple linear regression and logistic regression analyses. Results: DPP4a was increased in T2DM patients as compared with non-diabetic subjects (5855 ± 1632 vs 5208 ± 957 pmol/min/mL, p < 0.05). Clinical characteristics and echocardiographic parameters assessing LV morphology were similar across DPP4a tertiles in T2DM patients. However, prevalence of LVD progressively increased across incremental DPP4a tertiles (13%, 39% and 71%, all p < 0.001). Multivariate regression analysis confirmed the independent associations of DPP4a with LVD in T2DM patients (p < 0.05). Similarly, multiple logistic regression analysis showed that an increase of 100 pmol/min/min plasma DPP4a was independently associated with an increased frequency of LVD with an adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001). Conclusions: An excessive activity of circulating DPP4 is independently associated with subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that DPP4 may be involved in the mechanisms of LVD in T2DM

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Cell therapy and delivery strategies for spinal cord injury

Spinal cord injury (SCI) is a complex neuropathological condition that represents a major challenge for clinicians and scientists due to patient's functional dysfunction and paralysis. Several treatments have been proposed including biological factors, drugs and cells administered in various ways. Stem cells arise as good candidates to treat SCI since they are known to secrete neurotrophic factors, improving neuroregeneration, but also due to their role in modulating the inflammatory process, favoring a pro-regenerative status. There are several types of cells that have been tested to treat SCI in experimental and clinical studies, but we still face many unanswered questions; one of them is the type of cells that can offer the best benefits and, also the ideal dose and administration routes. This review aimed to summarize recent research on cell treatment, focusing on current delivery strategies for SCI therapy and their effects in tissue repair and regeneration

Dignity models in healthcare.A review of the literature

Errasti-Ibarrondo, M.B., Carvajal-Valcarcel, A., Martinez-Garcia, M., Arantzamendi-Solabarrieta, M., "Dignity models in healthcare.A review of the literature", Tipo de participación: Póster del congreso: 8th World research congress of the european association for palliative care, celebrado en Lérida, del 5 al 7 de junio de 2014

Mechanisms of increased susceptibility to angiotensin II-induced apoptosis in ventricular cardiomyocytes of spontaneously hypertensive rats

Previous findings have shown that hypotensive doses of losartan prevent the excess of apoptosis present in the hypertrophied left ventricle of adult spontaneously hypertensive rats (SHR). This study was designed to determine whether angiotensin II facilitates apoptosis in cardiomyocytes of adult SHR. Primary cultures of ventricular cardiomyocytes from 30-week-old normotensive Wistar-Kyoto rats (WKY) and SHR with left ventricular hypertrophy were exposed to 10(-)(9) mol/L angiotensin II for 24 hours. Apoptotic cells were assessed by terminal deoxynucleotidyl transferase assay and confirmed by Annexin V detection. The expression of Bax-alpha, Bcl-2, p53, and caspase-3 proteins was assessed by Western blot assays. The expression of BAX gene was assessed by Northern blot. Angiotensin II increased (P<0.01) cardiomyocyte apoptosis, and this effect was higher (P<0.001) in SHR cells than in WKY cells. Whereas losartan (10(-7) mol/L) blocked the apoptotic effect of the octapeptide in cells from the two strains of rats, PD123319 (10(-7) mol/L) inhibited angiotensin II-mediated apoptosis only in SHR cells. Angiotensin II stimulated (P<0.01) Bax-alpha protein, and this effect was higher (P<0.01) in SHR cells than in WKY cells. Angiotensin II did not modify Bcl-2, p53, and BAX mRNA in cells from the two strains of rats. Angiotensin II induced a similar increase (P<0.05) in the ratio caspase-3/procaspase-3 (an index of caspase-3 activation) in cardiomyocytes from the two strains of rats. The present in vitro results indicate that SHR cardiomyocytes exhibit enhanced susceptibility to angiotensin II-induced apoptosis. Ligand binding to angiotensin II type 1 and type 2 receptors leading to changes in posttranscriptional processing of Bax-alpha and accumulation of this proapoptotic protein may be involved in the abnormal response of SHR cardiomyocytes. These data support a role for angiotensin II in apoptosis observed in the left ventricle of these rats

The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus

Background: Patients with type 2 diabetes mellitus (T2DM) present subclinical left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions. Our aim was to analyze whether the activity of circulating DPP4 is associated with echocardiographically defined LVD in asymptomatic patients with T2DM. Methods: In this cross-sectional study, we examined 83 T2DM patients with no coronary or valve heart disease and 59 age and gender-matched non-diabetic subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme-linked immunosorbent assay. LV function was assessed by two-dimensional echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound measurements. Differences in means were assessed by t-tests and one-way ANOVA. Associations were assessed by adjusted multiple linear regression and logistic regression analyses. Results: DPP4a was increased in T2DM patients as compared with non-diabetic subjects (5855 ± 1632 vs 5208 ± 957 pmol/min/mL, p < 0.05). Clinical characteristics and echocardiographic parameters assessing LV morphology were similar across DPP4a tertiles in T2DM patients. However, prevalence of LVD progressively increased across incremental DPP4a tertiles (13%, 39% and 71%, all p < 0.001). Multivariate regression analysis confirmed the independent associations of DPP4a with LVD in T2DM patients (p < 0.05). Similarly, multiple logistic regression analysis showed that an increase of 100 pmol/min/min plasma DPP4a was independently associated with an increased frequency of LVD with an adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001). Conclusions: An excessive activity of circulating DPP4 is independently associated with subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that DPP4 may be involved in the mechanisms of LVD in T2DM