Early stroke case-fatality rates in three hospital registries in the Northeast and Southeast of Brazil

Few studies have addressed early cerebrovascular lethality in Brazil. Objective: To evaluate 10 and 28-day stroke case-fatality rates in three hospitals in three Brazilian cities. Methods: We described the stroke registries in Sao Paulo, Joao Pessoa, and Natal. Results: Out of a total of 962 first-ever events (mean age, 68.1 years-old; 53% men), 83.6% (804 cases) were classified as ischemic and 16.4% (158) as hemorrhagic stroke. Overall, the case-fatality rates and 95% confidence intervals (95% CI) for hemorrhagic stroke events were higher than for ischemic events, both at 10 (12.3%; 95% CI 7.2-17.4 versus 7.0%; 95% CI 5.3-8.8) and at 28 days (19.8%; 95% CI 13.6-26.0 versus 11.1%; 95% CI 8.9-13.3). Conclusions: We did not find any substantial differences in early case-fatality rates according to stroke subtypes, when comparing the three centers.

EVIDENCE-BASED PRACTICES PUBLISHED IN BRAZIL: IDENTIFICATION AND ANALYSIS STUDIES ABOUT HUMAN HEALTH PREVENTION

Integrative review of Brazilian studies about evidence-based practices (EBP) about prevention in human health, published in Web of Science/JCR journals, between October 2010 and April 2011. The aim was to identify the specialties that most accomplished these studies, their foci and methodological approaches. Based on inclusion criteria, 84 studies were selected, mainly published in public health journals, focusing on primary care and also addressing clinical issues and different specialties. Prevention foci and methodological approaches also varied, with a predominance of systematic reviews without meta-analysis. The results indicate that there is no single way to conceptualize and practice EBP in the field of prevention, and that its application may not only serve to obtain indisputable evidence to equip intervention actions. This endless knowledge area is under construction, with a view to the analysis and further understanding of health phenomena.

AN EFFICIENT HPLC-UV METHOD FOR THE QUANTITATIVE DETERMINATION OF CEFADROXIL IN HUMAN PLASMA AND ITS APPLICATION IN PHARMACOKINETIC STUDIES

Cefadroxil is a semi-synthetic first-generation oral cephalosporin used in the treatment of mild to moderate infections of the respiratory and urinary tracts, skin and soft tissue infections. In this work a simple, rapid, economic and sensitive HPLC-UV method is described for the quantitative determination of cefadroxil in human plasma samples using lamivudine as internal standard. Sample pre-treatment was accomplished through protein precipitation with acetonitrile and chromatographic separation was performed with a mobile phase consisting of a mixture of sodium dihydrogen phosphate monohydrate solution, methanol and acetonitrile in the ratio of 90:8:2 (v/v/v) at a flow rate of 1.0mL/min. The proposed method is linear between 0.4 to 40.0 mu g/mL and its average recovery is 102.21% for cefadroxil and 97.94% for lamivudine. The method is simple, sensitive, reproducible, less time consuming for determination of cefadroxil in human plasma. The method can therefore be recommended for pharmacokinetics studies, including bioavailability and bioequivalence studies.

Toward Global Standards for Comparator Pharmaceutical Products: Case Studies of Amoxicillin, Metronidazole, and Zidovudine in the Americas

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running

Abstract Background The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1α. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1α protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid) metabolism. Methods Two groups of male Wistar rats (2 Mo of age, 188.82 ± 2.77 g BW) were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1α protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations. Results Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean ± SE) of 4.102 ± 0.747 km/day and consumed significantly more food as compared to sedentary controls (P < 0.001) in order to meet their increased caloric requirement. Mean plasma insulin (P < 0.001) and FFA (P < 0.006) concentrations were lower in the exercise-trained rats as compared to sedentary controls. Mean steady state plasma insulin (SSPI) and glucose (SSPG) concentrations were not significantly different in sedentary control rats as compared to exercise-trained animals. Plantaris PGC-1α protein expression increased significantly from a 1.11 ± 0.12 in the sedentary rats to 1.74 ± 0.09 in exercising rats (P < 0.001). However, exercise had no effect on PGC-1α protein content in either soleus muscle or liver tissue. These results indicate that exercise training selectively up regulates the PGC-1α protein expression in high-oxidative fast skeletal muscle type such as plantaris muscle. Conclusion These data suggest that PGC-1α most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity) and lowering of circulating FFA levels.

Suicide rates and income in São Paulo and Brazil: a temporal and spatial epidemiologic analysis from 1996 to 2008

Abstract Background In a classical study, Durkheim noted a direct relation between suicide rates and wealth in the XIX century France. Since that time, several studies have verified this relationship. It is known that suicide rates are associated with income, although the direction of this association varies worldwide. Brazil presents a heterogeneous distribution of income and suicide across its territory; however, evaluation for an association between these variables has shown mixed results. We aimed to evaluate the relationship between suicide rates and income in Brazil, State of São Paulo (SP), and City of SP, considering geographical area and temporal trends. Methods Data were extracted from the National and State official statistics departments. Three socioeconomic areas were considered according to income, from the wealthiest (area 1) to the poorest (area 3). We also considered three regions: country-wide (27 Brazilian States and 558 Brazilian micro-regions), state-wide (645 counties of SP State), and city-wide (96 districts of SP city). Relative risks (RR) were calculated among areas 1, 2, and 3 for all regions, in a cross-sectional approach. Then, we used Joinpoint analysis to explore the temporal trends of suicide rates and SaTScan to investigate geographical clusters of high/low suicide rates across the territory. Results Suicide rates in Brazil, the State of SP, and the city of SP were 6.2, 6.6, and 5.4 per 100,000, respectively. Taking suicide rates of the poorest area (3) as reference, the RR for the wealthiest area was 1.64, 0.88, and 1.65 for Brazil, State of SP, and city of SP, respectively (p for trend <0.05 for all analyses). Spatial cluster of high suicide rates were identified at Brazilian southern (RR = 2.37), state of SP western (RR = 1.32), and city of SP central (RR = 1.65) regions. A direct association between income and suicide were found for Brazil (OR = 2.59) and the city of SP (OR = 1.07), and an inverse association for the state of SP (OR = 0.49). Conclusions Temporospatial analyses revealed higher suicide rates in wealthier areas in Brazil and the city of SP and in poorer areas in the State of SP. We further discuss the role of socioeconomic characteristics for explaining these discrepancies and the importance of our findings in public health policies. Similar studies in other Brazilian States and developing countries are warranted.

A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy

Background Calstabins 1 and 2 bind to Ryanodine receptors regulating muscle excitation-contraction coupling. Mutations in Ryanodine receptors affecting their interaction with calstabins lead to different cardiac pathologies. Animal studies suggest the involvement of calstabins with dilated cardiomyopathy. Results We tested the hypothesis that calstabins mutations may cause dilated cardiomyopathy in humans screening 186 patients with idiopathic dilated cardiomyopathy for genetic alterations in calstabins 1 and 2 genes (FKBP12 and FKBP12.6). No missense variant was found. Five no-coding variations were found but not related to the disease. Conclusions These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases.

Involvement of the atrial natriuretic peptide in cardiovascular pathophysiology and its relationship with exercise

In this minireview we describe the involvement of the atrial natriuretic peptide (ANP) in cardiovascular pathophysiology and exercise. The ANP has a broad homeostatic role and exerts complex effects on the cardio-circulatory hemodynamics, it is produced by the left atrium and has a key role in regulating sodium and water balance in mammals and humans. The dominant stimulus for its release is atrial wall tension, commonly caused by exercise. The ANP is involved in the process of lipolysis through a cGMP signaling pathway and, as a consequence, reducing blood pressure by decreasing the sensitivity of vascular smooth muscle to the action of vasoconstrictors and regulate fluid balance. The increase of this hormone is associated with better survival in patients with chronic heart failure (CHF). This minireview provides new evidence based on recent studies related to the beneficial effects of exercise in patients with cardiovascular disease, focusing on the ANP.

Sanguineous normothermic, intermittent cardioplegia, effects on hypertrophic myocardium: morphometric, metabolic and ultrastructural studies in rabbits hearts

OBJECTIVES: The present investigation aimed to study the protective effect of intermittent normothermic cardioplegia in rabbit's hypertrophic hearts. METHODS: The parameters chosen were 1) the ratio heart weight / body weight, 2) the myocardial glycogen levels, 3) ultrastructural changes of light and electron microscopy, and 4) mitochondrial respiration. RESULTS: 1) The experimental model, coarctation of the aorta induced left ventricular hypertrophy; 2) the temporal evolution of the glycogen levels in hypertrophic myocardium demonstrates that there is a significant decrease; 3) It was observed a time-dependent trend of higher oxygen consumption values in the hypertrophic group; 4) there was a significant time-dependent decrease in the respiratory coefficient rate in the hypertrophic group; 5) the stoichiometries values of the ADP: O2 revealed the downward trend of the values of the hypertrophic group; 6) It was possible to observe damaged mitochondria from hypertrophic myocardium emphasizing the large heterogeneity of data. CONCLUSION: The acquisition of biochemical data, especially the increase in speed of glycogen breakdown, when anatomical changes are not detected, represents an important result even when considering all the difficulties inherent in the process of translating experimental results into clinical practice. With regard to the adopted methods, it is clear that morphometric methods are less specific. Otherwise, the biochemical data allow detecting alterations of glycogen concentrations and mitochondria respiration before the morphometric alterations should be detected

Velocity structure and seismic anisotropy in the crust and upper mantle from Receiver Function analysis: three case studies in Italy

The research for this PhD project consisted in the application of the RFs analysis technique to different data-sets of teleseismic events recorded at temporary and permanent stations located in three distinct study regions: Colli Albani area, Northern Apennines and Southern Apennines. We found some velocity models to interpret the structures in these regions, which possess very different geologic and tectonics characteristics and therefore offer interesting case study to face. In the Colli Albani some of the features evidenced in the RFs are shared by all the analyzed stations: the Moho is almost flat and is located at about 23 km depth, and the presence of a relatively shallow limestone layer is a stable feature; contrariwise there are features which vary from station to station, indicating local complexities. Three seismic stations, close to the central part of the former volcanic edifice, display relevant anisotropic signatures­­­ with symmetry axes consistent with the emplacement of the magmatic chamber. Two further anisotropic layers are present at greater depth, in the lower crust and the upper mantle, respectively, with symmetry axes directions related to the evolution of the volcano complex. In Northern Apennines we defined the isotropic structure of the area, finding the depth of the Tyrrhenian (almost 25 km and flat) and Adriatic (40 km and dipping underneath the Apennines crests) Mohos. We determined a zone in which the two Mohos overlap, and identified an anisotropic body in between, involved in the subduction and going down with the Adiratic Moho. We interpreted the downgoing anisotropic layer as generated by post-subduction delamination of the top-slab layer, probably made of metamorphosed crustal rocks caught in the subduction channel and buoyantly rising toward the surface. In the Southern Apennines, we found the Moho depth for 16 seismic stations, and highlighted the presence of an anisotropic layer underneath each station, at about 15-20 km below the whole study area. The moho displays a dome-like geometry, as it is shallow (29 km) in the central part of the study area, whereas it deepens peripherally (down to 45 km); the symmetry axes of anisotropic layer, interpreted as a layer separating the upper and the lower crust, show a moho-related pattern, indicated by the foliation of the layer which is parallel to the Moho trend. Moreover, due to the exceptional seismic event occurred on April 6th next to L’Aquila town, we determined the Vs model for two station located next to the epicenter. An extremely high velocity body is found underneath AQU station at 4-10 km depth, reaching Vs of about 4 km/s, while this body is lacking underneath FAGN station. We compared the presence of this body with other recent works and found an anti-correlation between the high Vs body, the max slip patches and earthquakes distribution. The nature of this body is speculative since such high velocities are consistent with deep crust or upper mantle, but can be interpreted as a as high strength barrier of which the high Vs is a typical connotation.

Simulation studies of correlation functions and relaxation in polymeric systems

We investigate the statics and dynamics of a glassy,non-entangled, short bead-spring polymer melt with moleculardynamics simulations. Temperature ranges from slightlyabove the mode-coupling critical temperature to the liquidregime where features of a glassy liquid are absent. Ouraim is to work out the polymer specific effects on therelaxation and particle correlation. We find the intra-chain static structure unaffected bytemperature, it depends only on the distance of monomersalong the backbone. In contrast, the distinct inter-chainstructure shows pronounced site-dependence effects at thelength-scales of the chain and the nearest neighbordistance. There, we also find the strongest temperaturedependence which drives the glass transition. Both the siteaveraged coupling of the monomer and center of mass (CM) andthe CM-CM coupling are weak and presumably not responsiblefor a peak in the coherent relaxation time at the chain'slength scale. Chains rather emerge as soft, easilyinterpenetrating objects. Three particle correlations arewell reproduced by the convolution approximation with theexception of model dependent deviations. In the spatially heterogeneous dynamics of our system weidentify highly mobile monomers which tend to follow eachother in one-dimensional paths forming ``strings''. Thesestrings have an exponential length distribution and aregenerally short compared to the chain length. Thus, arelaxation mechanism in which neighboring mobile monomersmove along the backbone of the chain seems unlikely.However, the correlation of bonded neighbors is enhanced. When liquids are confined between two surfaces in relativesliding motion kinetic friction is observed. We study ageneric model setup by molecular dynamics simulations for awide range of sliding speeds, temperatures, loads, andlubricant coverings for simple and molecular fluids. Instabilities in the particle trajectories are identified asthe origin of kinetic friction. They lead to high particlevelocities of fluid atoms which are gradually dissipatedresulting in a friction force. In commensurate systemsfluid atoms follow continuous trajectories for sub-monolayercoverings and consequently, friction vanishes at low slidingspeeds. For incommensurate systems the velocity probabilitydistribution exhibits approximately exponential tails. Weconnect this velocity distribution to the kinetic frictionforce which reaches a constant value at low sliding speeds. This approach agrees well with the friction obtaineddirectly from simulations and explains Amontons' law on themicroscopic level. Molecular bonds in commensurate systemslead to incommensurate behavior, but do not change thequalitative behavior of incommensurate systems. However,crossed chains form stable load bearing asperities whichstrongly increase friction.

Characterization of vascular wall progenitor cells and their role in therapeutic angiogenesis and Monckeberg's sclerosis

Recently, the existence of a capillary-rich vasculogenic zone has been identified in adult human arteries between the tunica media and adventitia; in this area it has been postulated that Mesenchymal Stem Cells (MSCs) may be present amidst the endothelial progenitors and hematopoietic stem cells. This hypothesis is supported by several studies claiming to have found the in vivo reservoir of MSCs in post-natal vessels and by the presence of ectopic tissues in the pathological artery wall. We demonstrated that the existence of multipotent progenitors is not restricted to microvasculature; vascular wall resident MSCs (VW-MSCs) have been isolated from multidistrict human large and middle size vessels (aortic arch, thoracic aorta and femoral artery) harvested from healthy multiorgan donors. Each VW-MSC population shows characteristics of embryonic-like stem cells and exhibits angiogenic, adipogenic, chondrogenic and leiomyogenic potential but less propensity to osteogenic ifferentiation. Human vascular progenitor cells are also able to engraft, differentiate into mature endothelial cells and support muscle function when injected in a murine model of hind limb ischemia. Conversely, VW-MSCs isolated from calcified femoral arteries display a good response to osteogenic commitment letting us to suppose that VW-MSCs could have an important role in the onset of vascular pathologies such as Mönckeberg sclerosis. Taken together these results show two opposite roles of vascular progenitor cells and underline the importance of establishing their in vivo pathological and regenerative potential to better understand pathological events and promote different therapeutic strategies in cardiovascular research and clinical applications.

The coupling between electron transfer and Protein/Solvent Dynamics in Photosynthetic Reaction Centers: Spectroscopic Studies in Amorphous Matrices

We investigated at the molecular level protein/solvent interactions and their relevance in protein function through the use of amorphous matrices at room temperature. As a model protein, we used the bacterial photosynthetic reaction center (RC) of Rhodobacter sphaeroides, a pigment protein complex which catalyzes the light-induced charge separation initiating the conversion of solar into chemical energy. The thermal fluctuations of the RC and its dielectric conformational relaxation following photoexcitation have been probed by analyzing the recombination kinetics of the primary charge-separated (P+QA-) state, using time resolved optical and EPR spectroscopies. We have shown that the RC dynamics coupled to this electron transfer process can be progressively inhibited at room temperature by decreasing the water content of RC films or of RC-trehalose glassy matrices. Extensive dehydration of the amorphous matrices inhibits RC relaxation and interconversion among conformational substates to an extent comparable to that attained at cryogenic temperatures in water-glycerol samples. An isopiestic method has been developed to finely tune the hydration level of the system. We have combined FTIR spectral analysis of the combination and association bands of residual water with differential light-minus-dark FTIR and high-field EPR spectroscopy to gain information on thermodynamics of water sorption, and on structure/dynamics of the residual water molecules, of protein residues and of RC cofactors. The following main conclusions were reached: (i) the RC dynamics is slaved to that of the hydration shell; (ii) in dehydrated trehalose glasses inhibition of protein dynamics is most likely mediated by residual water molecules simultaneously bound to protein residues and sugar molecules at the protein-matrix interface; (iii) the local environment of cofactors is not involved in the conformational dynamics which stabilizes the P+QA-; (iv) this conformational relaxation appears to be rather delocalized over several aminoacidic residues as well as water molecules weakly hydrogen-bonded to the RC.

Effects of Resources Exploitation on Water Quality: case studies in Salt Water Intrusion and Acid Mine Drainage

Throughout the world, pressures on water resources are increasing, mainly as a result of human activity. Because of their accessibility, groundwater and surface water are the most used reservoirs. The evaluation of the water quality requires the identification of the interconnections among the water reservoirs, natural landscape features, human activities and aquatic health. This study focuses on the estimation of the water pollution linked to two different environmental issues: salt water intrusion and acid mine drainage related to the exploitation of natural resources. Effects of salt water intrusion occurring in the shallow aquifer north of Ravenna (Italy) was analysed through the study of ion- exchange occurring in the area and its variance throughout the year, applying a depth-specific sampling method. In the study area were identified ion exchange, calcite and dolomite precipitation, and gypsum dissolution and sulphate reduction as the main processes controlling the groundwater composition. High concentrations of arsenic detected only at specific depth indicate its connexion with the organic matter. Acid mine drainage effects related to the tin extraction in the Bolivian Altiplano was studied, on water and sediment matrix. Water contamination results strictly dependent on the seasonal variation, on pH and redox conditions. During the dry season the strong evaporation and scarce water flow lead to low pH values, high concentrations of heavy metals in surface waters and precipitation of secondary minerals along the river, which could be released in oxidizing conditions as demonstrated through the sequential extraction analysis. The increase of the water flow during the wet season lead to an increase of pH values and a decrease in heavy metal concentrations, due to dilution effect and, as e.g. for the iron, to precipitation.