Biochemical and Molecular Aspects of Vascular Adrenergic Regulation of Blood Pressure in the Elderly

Hypertension, orthostatic hypotension, arterial insufficiency, and atherosclerosis are common disorders in the elderly that lead to significant morbidity and mortality. One common factor to these conditions is an age-related decline in vascular beta-adrenergic receptor-mediated function and subsequent cAMP generation. Presently, there is no single cellular factor that can explain this age-related decline, and thus, the primary cause of this homeostatic imbalance is yet to be identified. However, the etiology is clearly associated with an age-related change in the ability of beta-adrenergic receptor to respond to agonist at the cellular level in the vasculature. This paper will review what is presently understood regarding the molecular and biochemical basis of age-impaired beta-adrenergic receptor-mediated signaling. A fundamental understanding of why β-AR-mediated vasorelaxation is impaired with age will provide new insights and innovative strategies for the management of multiple clinical disorders

p21 is decreased in polycystic kidney disease and leads to increased epithelial cell cycle progression: roscovitine augments p21 levels.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease with few treatment options other than renal replacement therapy. p21, a cyclin kinase inhibitor which has pleiotropic effects on the cell cycle, in many cases acts to suppress cell cycle progression and to prevent apoptosis. Because defects in cell cycle arrest and apoptosis of renal tubular epithelial cells occur in PKD, and in light of earlier reports that polycystin-1 upregulates p21 and that the cyclin-dependent kinase inhibitor roscovitine arrests progression in a mouse model, we asked whether (1) p21 deficiency might underlie ADPKD and (2) the mechanism of the salutary roscovitine effect on PKD involves p21.Methodsp21 levels in human and animal tissue samples as well as cell lines were examined by immunoblotting and/or immunohistochemisty. Apoptosis was assessed by PARP cleavage. p21 expression was attenuated in a renal tubular epithelial cell line by antisense methods, and proliferation in response to p21 attenuation and to roscovitine was assessed by the MTT assay.ResultsWe show that p21 is decreased in human as well as a non-transgenic rat model of ADPKD. In addition, hepatocyte growth factor, which induces transition from a cystic to a tubular phenotype, increases p21 levels. Furthermore, attenuation of p21 results in augmentation of cell cycle transit in vitro. Thus, levels of p21 are inversely correlated with renal tubular epithelial cell proliferation. Roscovitine, which has been shown to arrest progression in a murine model of PKD, increases p21 levels and decreases renal tubular epithelial cell proliferation, with no affect on apoptosis.ConclusionThe novelty of our study is the demonstration in vivo in humans and rat models of a decrement of p21 in cystic kidneys as compared to non-cystic kidneys. Validation of a potential pathogenetic model of increased cyst formation due to enhanced epithelial proliferation and apoptosis mediated by p21 suggests a mechanism for the salutary effect of roscovitine in ADPKD and supports further investigation of p21 as a target for future therapy

A Descoberta da Morte e Mundo Homérico

A insistência com que os historiadores da filosofia apresentam o mundo grego a partir do naturalismo jônio, com breves referências ao pensamento helênico anterior, leva-nos algumas vêzes a aceitar a ordem natural como a primeira sugestão para um pensamento racional, nela procurando a própria origem da noção de devir

INFRAESTRUTURA VERDE NO CONTEXTO DA INFRAESTRUTURA AMBIENTAL URBANA E DA GESTÃO DO MEIO AMBIENTE

The increasing quantity of research about the green infrastructure concept in Brazil and some performed concrete experiments reflect the need for progress on issues related to its integration in the context of environmental infrastructure necessary for large urban agencies and environmental land management. The intense range of solutions proposed by this concept presents interfaces with many other urban infrastructures and especially with different scales and actors of land management.Thus, this article intends to contribute to this debate by presenting a preliminary approach on the nature of the environmental management of urbanized areas and where the locus of those actions, connected to the concept of green infrastructure, will be. Concomitantly to this target, it will be presented the initial formulation of a concept of urban environmental management¹, which seeks to comprise the sphere of management of all structures that establish the use and consumption of natural resources in a more effective way, i.e., either relating to the ground, as well as to water and vegetation. _____________________¹ Urban environmental management meaning the urbanization of the territory, including rural and intra-urban areas, so that the whole sphere of municipal action and those which should expand to the state sphere, especially in cases of large urbanized regions, i.e., the case of metropolitan regions. It involves the insertion of the territory context used by the city, which extrapolates, partially, the limits of its urban areas and its municipal boundaries.O crescente número de pesquisas acerca do conceito de infraestrutura verde no Brasil e de algumas experiências concretas realizadas já reflete a necessidade de se avançar nas questões referentes à sua inserção no contexto da infraestrutura ambiental necessária aos grandes organismos urbanos e da gestão ambiental do território. A intensa gama de soluções propostas por esse conceito apresenta interfaces com muitas outras infraestruturas urbanas e, sobretudo, com diferentes escalas e atores da gestão do território.Neste sentido, este artigo pretende contribuir para essa reflexão, apresentando uma abordagem preliminar sobre a natureza da gestão ambiental do território urbanizado e onde estará o lócus das ações vinculadas ao conceito de infraestrutura verde. Concomitante a esse objetivo, apresenta-se a formulação inicial de um conceito de gestão ambiental urbana¹, o qual busca abranger a esfera de gestão de todas as estruturas que estabelecem o uso e o consumo dos recursos naturais de forma mais direta, ou seja, tanto em relação ao solo, como à água e à vegetação. ________________¹ Gestão ambiental urbana com o sentido da urbanização do território, incluindo as áreas rurais e intra-urbanas, assim, toda a esfera de ação municipal e naquilo que deverá se expandir para a estadual, em especial nos casos das grandes regiões urbanizadas, ou seja, o caso das regiões metropolitanas. Trata-se de inserir o contexto do território utilizado pela cidade, que extrapola, em parte, os limites de suas áreas urbanas e dos seus limites municipais

Análise estratégica do relevo e planejamento territorial urbano: compartimentos ambientais estruturantes na macrometrópole de São Paulo

The great urban spreading occurred in metropolitan areas worldwide, still in intense movement of urban expansion on old rural areas, evidenced that the environmental problems, which most affect the territories nowadays, are the result of intensive urbanization processes. In this sense, the decision about where and how to occupy a territorial area must pass through a different analysis on the topography, not anymore as just as static and passive element, which conforms to the several urban uses requested for a strategic approach linked to the urban territorial and environmental planning. By highlighting the main lines and environmental structuring compartments of a landscape under the topographic aspect and the processes of its geomorphologic form, it is possible to better glimpse the relationships urban processes and imposed infrastructures establish with these strategic landscape portions, which allow to define ways of use and land occupancy more suitable to urban and natural processes, aiming the selection of the main topographic sectors designated to environmental services for preservation of spaces of natural processes occurrence.O grande espalhamento urbano ocorrido nas regiões metropolitanas mundiais, ainda em intenso movimento de expansão urbana sobre antigos territórios rurais, colocou em evidência que os problemas ambientais que mais impactam os territórios, hoje, são os decorrentes dos processos de urbanização intensiva. Nesse sentido, a decisão sobre onde e como ocupar um território deve perpassar uma outra análise sobre o relevo, não mais apenas como um elemento estático e passivo, que se amolda aos diversos usos urbanos solicitados, mas com uma abordagem estratégica vinculada ao planejamento territorial e ambiental urbano. Ao destacar as principais linhas e compartimentos ambientais estruturantes de uma paisagem, sob o aspecto do relevo e dos processos de sua esculturação, pode-se entrever melhor as relações que os processos urbanos e suas infraestruturas impostas estabelecem com essas porções estratégicas da paisagem, podendo direcionar, assim, formas de uso e de ocupação do relevo mais condizentes com os processos urbanos e naturais, objetivando a eleição dos principais setores do relevo destinados aos serviços ambientais da preservação dos espaços de ocorrência dos processos naturais

Duplex–assisted internal carotid artery balloon angioplasty and stent placement: A novel approach to minimize or eliminate the use of contrast material

BackgroundCarotid artery balloon angioplasty and stenting (CBAS) is emerging as an acceptable alternative to carotid endarterectomy in selected high-risk patients. Conversely, patients with pre-existing renal impairment, diabetes, or both may be harmed by the nephrotoxic contrast agents required during CBAS. We attempted to limit or eliminate the use of contrast material during CBAS.MethodsEighteen patients with severe carotid stenoses (>70%) underwent CBAS at our institution over the last 12 months with duplex scan-assisted CBAS. Of these, 12 were primary procedures, and 6 were performed for carotid re-stenosis. Fourteen patients (78%) were neurologically asymptomatic. The average age of these patients was 75 ± 11 years (range, 44–92 years). Hypertension, chronic renal insufficiency (serum creatinine level ≥1.5 mg/dL), coronary artery disease, diabetes, and smoking were present in 89%, 67%, 59%, 33%, and 28% of patients, respectively. Preoperative duplex carotid mapping was performed in all cases. All procedures were performed with patients under local anesthesia and light sedation.ResultsAn ATL HDI 5000 scanner with the SonoCT feature was used. The common femoral artery was cannulated with a single-entry needle under direct ultrasound visualization. Fluoroscopy was used to assist passage of the guidewire into the aorta and the common carotid artery. In only four cases (22%) was an aortic arch angiogram obtained. Selective catheterization of the internal and external carotid arteries was performed under ultrasound guidance. The distal cerebral protection device (17 cases) was placed under fluoroscopic guidance. Balloon width and length were chosen according to ultrasound measurements. Balloon and stent deployment were successfully achieved with ultrasound guidance alone in all cases. Appropriate stent apposition and resolution of the stenosis was confirmed by duplex scanning in all cases. Five patients (28%) were noted to have low (<100 mL/min) internal carotid artery volume flow after stent deployment (range, 20–88 mL/min; mean ± SD, 50 ± 25 mL/min). The internal carotid artery volume flow increased immediately after Filterwire retrieval in all cases and ranged from 136 to 400 mL/min (mean, 245 ± 107 mL/min). This increase was statistically significant (P < .02). No ipsilateral strokes or deaths occurred during follow-up from 1 to 12 months (mean follow-up, 5 months).ConclusionsDuplex scan-assisted CBAS is feasible and may reduce the need for intra-arterial contrast injection in selected patients deemed at high risk for renal failure from nephrotoxic contrast material. Additional advantages include direct visualization of the puncture site, precise position of the balloon and stent, and B-mode and hemodynamic confirmation of the adequacy of the technique

Modelling the early mass-ejection in jet driven protostellar outflows. Lessons from Cep E

We have used the axisymmetric chemo-hydrodynamical code WALKIMYA-2D to numerically model and reproduce the physical and CO emission properties of the jet-driven outflow from the intermediate-mass protostar Cep E, which was observed at $\sim 800$au resolution in the CO $J=2\to 1$ line with the IRAM interferometer. Our simulations take into account the observational constraints available on the physical structure of the protostellar envelope to provide constraints on the dynamics of the inner protostellar environment from the study of the outflow/jet propagation away from the launch region. WALKIMYA-2D successfully reproduces the main qualitative and quantitative features of the Cep E outflow and the jet kinematics, naturally accounting for their time variability. Signatures of internal shocks are detected as knots along the jet. In the early times of the ejection process, the young emitted knots interact with the dense circumstellar envelope through high-velocity, dissociative shocks, which strongly decrease the CO gas abundance in the jet. As time proceeds, the knots propagate more smoothly through the envelope and dissociative shocks disappear after $\sim 10^3$ yr. The distribution of CO abundance along the jet shows that the latter bears memory of the early dissociative phase in the course of its propagation. Analysis of the velocity field shows that the jet material mainly consists of gas entrained from the circumstellar envelope and accelerated away from the protostar at $700$ au scale. As a result, the overall jet mass loss rate appears higher than the actual mass ejection rate by a factor $\sim 3$. Numerical modeling of the Cep E jet-driven outflow and comparison with the CO observations have allowed us to peer into the outflow formation mechanism with unprecedented detail and to retrieve the history of the mass-loss events that have shaped the outflow

Perceptions towards aqua-based exercise among older adults with osteoarthritis who have discontinued participation in this exercise mode

Aim: This study aimed to investigate reasons for ceasing participation in aqua-based exercise among older adults with osteoarthritis (OA). Methods: Eleven adults over 60 years of age with OA participated in one of two focus groups, during which they discussed barriers to aqua-based exercise and the potential benefits of this exercise mode. Each focus group was audiotaped, transcribed and then analysed using the general inductive thematic approach. The investigators reached a consensus on all coding categories and then identified themes. Results: Key barriers identified were: a lack of suitable classes; insufficient instructor knowledge, which often led to increased pain; cold water and the changing facilities. Key perceived benefits included increased physical ability in water and social interaction. Conclusions: A greater understanding of reasons for ceasing participation in aqua-based exercise among older adults with OA may help facilitate development of suitable exercise programs that minimise barriers for this group