Fisiopatogenia da hipertensão arterial

The increased peripheral resistance is considered the major cause of primary hypertension. The functional and structural factors responsible for the resistance vascular changes in hypertension are reviewed. The most important functional mechanisms acting on the resistance vessels are represented by pressor (neurogenic, angiotensin, vasopressin, endotelin, etc) and depressor. (NO, prostacyclin, atrial natriuretic peptide etc) factors. The increased activity of the vascular effector cells depends on complex influences ascribed to an imbalance of production between the pressor and depressor factors. The structural mechanism is represented by an increase in the media/lumen ration of the resistance vessels. The reduction in lumen can be produced by growth of the wall into the lumen (hypertrophy) or by a rearrangement of the amount of material around the smaller lumen (remodeling). Finally, the importance of genetic predisposition in hypertension and of genetic defects, presently analysed by powefull molecular biology methods were reviewed.Na hipertensão primária, ou essencial, a elevação da resistência periférica é a principal responsável pelo aumento da pressão arterial. Isso ocorre pela redução do calibre das arteríolas determinada pela combinação, em grau variado, de fatores funcionais e fatores estruturais. A vasoconstrição pode ser causada pela produção excessiva de fatores pressores (angiotensina, vasopressina, endotelina e sistema nervoso simpático etc), ou pela deficiência dos fatores depressores (óxido nítrico, prostaciclina e peptídio natriurético atrial). O componente estrutural é, geralmente, representado pela hipertrofia da camada média que passa a ocupar parte do espaço intravascular. Importante ressaltar que os fatores que, ativamente, contraem ou dilatam os vasos têm, também, efeitos tróficos sobre a camada muscular, estimulando ou inibindo o seu espessamento. A redução da luz das arteríolas pode resultar, igualmente, de “remodelagem”, quando ocorre redução tanto do diâmetro interno como externo, sem modificações da massa. O componente genético é responsável pela produção dos complexos fatores pressores e depressores que regulam a pressão arterial. Também, ele é o responsável pela susceptibilidade individual aos fatores ambientais (sal e estresse, por exemplo), que sobrecarregam o sistema e podem gerar o desequilíbrio causador da hipertensão

High-resolution synchrotron-based X-ray microtomography as a tool to unveil the three-dimensional neuronal architecture of the brain

The assessment of neuronal number, spatial organization and connectivity is fundamental for a complete understanding of brain function. However, the evaluation of the three-dimensional (3D) brain cytoarchitecture at cellular resolution persists as a great challenge in the field of neuroscience. In this context, X-ray microtomography has shown to be a valuable non-destructive tool for imaging a broad range of samples, from dense materials to soft biological specimens, arisen as a new method for deciphering the cytoarchitecture and connectivity of the brain. In this work we present a method for imaging whole neurons in the brain, combining synchrotron-based X-ray microtomography with the Golgi-Cox mercury-based impregnation protocol. In contrast to optical 3D techniques, the approach shown here does neither require tissue slicing or clearing, and allows the investigation of several cells within a 3D region of the brain

Planning, implementing, and running a multicentre preterm birth study with biobank resources in Brazil : the preterm SAMBA study

Background. Our aim was to describe the steps in planning, implementing, and running a multicentre cohort study of maternal and perinatal health using a high-quality biobank comprised of maternal serum, plasma, and hair samples collected from five sites in Brazil.The Preterm SAMBA study, conducted by the Brazilian Network for Studies on Reproductive and Perinatal Health, was an innovative approach used to identify women at higher risk for preterm birth. It is also of great importance in the study of other maternal and perinatal complications in the context of Brazil, which is a middle-income country. Methods. We described phases of planning, implementing, and running the Preterm SAMBA study, a multicentre Brazilian cohort study of low-risk nulliparous pregnant women, to validate a set of metabolite biomarkers for preterm birth identified in an external cohort. Procedures and strategies used to plan, implement, and maintain this multicentre preterm birth study are described in detail. Barriers and experience cited in the current narrative are not usually discussed in the scientific literature or published study protocols. Results. Several barriers and strategies were identified in different phases of the Preterm SAMBA study at different levels of the study framework (steering committee; coordinating and local centres). Strategies implemented and resources used in the study are a legacy of the Brazilian Network, aimed at training collaborators in such complex settings. Conclusion. The Brazilian Network for Studies on Reproductive and Perinatal Health has gained some experience in conducting a multicentre cohort study using a resourceful biobank which may be helpful to other research groups and maternal/perinatal health networks that plan on employing a similar approach to a similar background

Immediate response of myocardium to pressure overload includes transient regulation of genes associated with mitochondrial bioenergetics and calcium availability

Ventricular hypertrophy is one of the major myocardial responses to pressure overload (PO). Most studies on early myocardial response focus on the days or even weeks after induction of hypertrophic stimuli. Since mechanotransduction pathways are immediately activated in hearts undergoing increased work load, it is reasonable to infer that the myocardial gene program may be regulated in the first few hours. In the present study, we monitored the expression of some genes previously described in the context of myocardial hypertrophic growth by using the Northern blot technique, to estimate the mRNA content of selected genes in rat myocardium for the periods 1, 3, 6, 12 and 48 h after PO stimuli. Results revealed an immediate switch in the expression of genes encoding alpha and beta isoforms of myosin heavy chain, and up-regulation of the cardiac isoform of alpha actin. We also detected transitory gene regulation as the increase in mitochondrial cytochrome c oxidase 1 gene expression, parallel to down-regulation of genes encoding sarco(endo)plasmic reticulum Ca+2 ATPase and sodium-calcium exchanger. Taken together, these results indicate that initial myocardial responses to increased work load include alterations in the contractile properties of sarcomeres and transitory adjustment of mitochondrial bioenergetics and calcium availability

Compounds Derived From 4--anilinequinazolines With Adenosine-kiase Inhibitor Properties.

Nuevos compuestos derivados de 4-anilinoquinazolinas con propiedad inibidora de adenosina-cinases. EL presente invento presenta compuestos que son inhibidores de adenosina-cinases. Es proporcionado un proces de proteger tejidos y 6rganos como coraz6n, cerebra y rifiones alcanzados por isquemia y tratar insuficiencia cardiaca, infarto del miocardia, arritmias, hipertensi6n arterial, ateroesclerosis, re-estenosis de arteria coronaria tras Ia angioplastia, insuficiencia renal cr6nica, accidente cerebrovascular, enfermedades inflamatorias cr6nicas (ej. artritis reumatoide). Tambien proporcionado es el efecto inhibidor de adenosina-cinases de compuestos derivados de quinazolinas previamente conocidos como inhibidores reversibles de tiroxina-cinases de Ia familia de receptores del factor de crecimiento epidermico (EGFR).MXPA06009987 (A)C07D239/94A61K31/517A61K31/00MX2006PA09987C07D239/94A61K31/517A61K31/0

Atividade colinesterásica no plasma e em eritrócitos de pacientes com as formas cardíaca e indeterminada da doença de Chagas

A atividade colinesterásica foi determinada no plasma e em eritrócitos de 10 indivíduos normais e em 26 pacientes chagásicos crônicos, sendo 6 com insuficiência cardíaca congestiva compensada, 10 com cardiopatia sem insuficiência cardíaca congestiva e 10 com a forma indeterminada. Os valores enzimáticos encontrados foram (média ±sd): 2196 ± 442 UI/L no plasma e 19,4 ± 3,3 Ul/g Hb em eritrócitos do grupo controla; 2291 ± 317 UI/L no plasma e 19,2 ±3,7 Ul/g Hb em eritrócitos dos chagásicos com insuficiência cardíaca congestiva compensada; 2445 ± 357 UI/L no plasma e 18,3 + 3,0 Ul/g Hb em eritrócitos dos cardiopatas chagásicos sem insuficiência cardíaca congestiva; 2006 ± 327 UI/L no plasma e 17,8 ± 3,1 Ul/g Hb em eritrócitos de chagásicos com a forma indeterminada. Nossos dados mostram que o comprometimento neuronal que ocorre nos cardiopatas chagásicos crônicos não é suficiente para levar a alterações significativas (p > 0,05) das atividades colinesterásicas no plasma e em eritrócitos

Atividade colinesterásica no plasma e em eritrócitos de pacientes com as formas cardíaca e indeterminada da doença de Chagas

A atividade colinesterásica foi determinada no plasma e em eritrócitos de 10 indivíduos normais e em 26 pacientes chagásicos crônicos, sendo 6 com insuficiência cardíaca congestiva compensada, 10 com cardiopatia sem insuficiência cardíaca congestiva e 10 com a forma indeterminada. Os valores enzimáticos encontrados foram (média ±sd): 2196 ± 442 UI/L no plasma e 19,4 ± 3,3 Ul/g Hb em eritrócitos do grupo controla; 2291 ± 317 UI/L no plasma e 19,2 ±3,7 Ul/g Hb em eritrócitos dos chagásicos com insuficiência cardíaca congestiva compensada; 2445 ± 357 UI/L no plasma e 18,3 + 3,0 Ul/g Hb em eritrócitos dos cardiopatas chagásicos sem insuficiência cardíaca congestiva; 2006 ± 327 UI/L no plasma e 17,8 ± 3,1 Ul/g Hb em eritrócitos de chagásicos com a forma indeterminada. Nossos dados mostram que o comprometimento neuronal que ocorre nos cardiopatas chagásicos crônicos não é suficiente para levar a alterações significativas (p > 0,05) das atividades colinesterásicas no plasma e em eritrócitos.Cholinesterase activity was measured in the plasma and erythrocytes from 10 healthy individuals and 26 chronic chagasic patients. The chronic chagasic patients were distributed in 3 groups: 6 chagasic patients with compensated heart failure; 10 chagasic patients with cardiopathy but without heart failure; and 10 chagasic patients with the indeterminateform. The enzymatic levels achieved in plasma and erythrocytes were. respectively: 2,196 ± 442 UI/L and 19.4 ± 3.3 Ul/g Hb from Controls; 2,291 ±317 UI/L and 19.2 ±3.7 Ul/g Hb from chagasic patients with compensated heart failure; 2,445 ±357 UI/L and 18.3 ± 3.0 Ul/g Hb from chagasic patients with cardiopathy but without heart failure and 2,006 ± 327 UI/L and 17.8 ± 3.1 Ul/g Hb from chagasic patients with the indeterminate form. Our data show that neuronal injury in the chronic cardiopathy is not sufficient to promote significant alterations (p > 0,05) in the cholinesterase activity in the plasma and erythrocytes