A stepwise approach to stroke surveillance in Brazil: the EMMA (Estudo de Mortalidade e Morbidade do Acidente Vascular Cerebral) study

Background Stroke mortality rates in Brazil are the highest in the Americas. Deaths from cerebrovascular disease surpass coronary heart disease. Aim To verify stroke mortality rates and morbidity in an area of Sao Paulo, Brazil, using the World Health Organization Stepwise Approach to Stroke Surveillance. Methods We used the World Health Organization Stepwise Approach to Stroke Surveillance structure of stroke surveillance. The hospital-based data comprised fatal and nonfatal stroke (Step 1). We gathered stroke-related mortality data in the community using World Health Organization questionnaires (Step 2). The questionnaire determining stroke prevalence was activated door to door in a family-health-programme neighbourhood (Step 3). Results A total of 682 patients 18 years and above, including 472 incident cases, presented with cerebrovascular disease and were enrolled in Step 1 during April-May 2009. Cerebral infarction (84 center dot 3%) and first-ever stroke (85 center dot 2%) were the most frequent. In Step 2, 256 deaths from stroke were identified during 2006-2007. Forty-four per cent of deaths were classified as unspecified stroke, 1/3 as ischaemic stroke, and 1/4 due to haemorrhagic subtype. In Step 3, 577 subjects over 35 years old were evaluated at home, and 244 cases of stroke survival were diagnosed via a questionnaire, validated by a board-certified neurologist. The population demographic characteristics were similar in the three steps, except in terms of age and gender. Conclusion By including data from all settings, World Health Organization stroke surveillance can provide data to help plan future resources that meet the needs of the public-health system.

Modulation of human cardiac function through 4 beta-adrenoceptor populations

In human heart there is now evidence for the involvement of four beta-adrenoceptor populations, three identical to the recombinant beta(1)-, beta(2)- and beta(3)-adrenoceptors, and a fourth as yet uncloned putative beta-adrenoceptor population, which we designate provisionally as the cardiac putative beta(4)-adrenoceptor. This review described novel features of beta-adrenoceptors as modulators of cardiac systolic and diastolic function. We also discuss evidence for modulation by unoccupied beta(1)- and beta(2)-adrenoceptors. Human cardiac and recombinant beta(1)- and beta(2)-adrenoceptors are both mainly coupled to adenylyl cyclase through Gs protein, the latter more tightly than the former. Activation of both human beta(1)- and beta(2)-adrenoceptors not only increases cardiac force during systole but also hastens relaxation through cyclic AMP-dependent phosphorylation of phospholamban and troponin I, thereby facilitating diastolic function. Furthermore, both beta(1) and beta(2)-adrenoceptors can mediate experimental arrhythmias in human cardiac preparations elicited by noradrenaline and adrenaline. Human ventricular beta(3)-adrenoceptors appear to be coupled to a pertussis toxin-sensitive protein (Gi?). beta(3)-Adrenoceptor-selective agonists shorten the action potential and cause cardiodepression, suggesting direct coupling of a Gi protein to a K+ channel. In a variety of species, including man, cardiac putative beta(4)-adrenoceptors mediate cardiostimulant effects of non-conventional partial agonists, i.e. high affinity beta(1)- and beta(2)-adrenoceptor blockers that cause agonist effects at concentrations considerably higher than those that block these receptors. Putative beta(4)-adrenoceptors appear to be coupled positively to a cyclic AMP-dependent cascade and can undergo some desensitisation.

Meta-analysis of the association of 4 angiotensinogen polymorphisms with essential hypertension - A role beyond M235T?

Angiotensinogen (AGT) gene polymorphisms have been linked to increased risk of hypertension, but the data remain controversial. In this study we review the most commonly investigated polymorphisms at the AGT locus (other than M235T) and provide summary estimates regarding their association with essential hypertension, while addressing heterogeneity, as well as publication biases. Data on 26 818 subjects from 46 studies for the 4 most-studied AGT variants (T174M in exon 2 and 3 promoter variants: A-6G, A-20C, and G-217A) were meta-analyzed. Statistically significant associations with hypertension were identified for the T174M ( odds ratio [OR]: 1.19; 95% CI: 1.07 to 1.33; P = 0.002) and G-217A (OR: 1.37; 95% CI: 1.17 to 1.59; P = 0.00006) polymorphisms. A dual but consistent effect was observed for the -20C allele, which was associated with a decreased risk of hypertension in populations of mixed and European ancestries (OR: 0.64; 95% CI: 0.44 to 0.92; P = 0.02 and OR: 0.77; 95% CI: 0.65 to 0.91; P = 0.003, respectively), but with a 24% increase in the odds of hypertension in Asian subjects (OR: 1.24; 95% CI: 1.04 to 1.48; P = 0.02). No association of the A-6G variant with hypertension was detected. Current studies support the notion that single variants at the AGT might modulate the risk of hypertension but indicate caution in interpreting these results because of the putative presence of publication bias and gene-environment interactions.

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR

Aneas I, Rodrigues MV, Pauletti BA, Silva GJ, Carmona R, Cardoso L, Kwitek AE, Jacob HJ, Soler JM, Krieger JE. Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR. Physiol Genomics 37: 52-57, 2009. First published January 6, 2009; doi: 10.1152/physiolgenomics.90299.2008. - To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13 - 29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. On high salt intake (1% NaCl in drinking water for 2 wk), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17, and 19 mmHg, respectively), but not the QTL on chromosome 4. Thus these four QTLs affected BP phenotypes differently: 1) in the presence of high salt intake (chromosome 16), 2) only associated with normal salt intake (chromosome 4), and 3) regardless of salt intake (chromosome 2c and 2a). Moreover, salt sensitivity was abrogated in congenics SHR. BN2a and SHR. BN16. Finally, we provide evidence for the influence of genetic background on the expression of the mapped QTLs individually or as a group. Collectively, these data reveal previously unsuspected nuances of the physiological roles of each of the four mapped BP QTLs in the SHR under basal and/or salt loading conditions unforeseen by the analysis of the F2 cross.

Kinetics of elimination and distribution in blood and liver of biocompatible ferrofluids based on Fe(3)O(4) nanoparticles: An EPR and XRF study

In this study, we evaluated the biodistribution and the elimination kinetics of a biocompatible magnetic fluid, Endorem (TM), based on dextrancoated Fe(3)O(4) nanoparticles endovenously injected into Winstar rats. The iron content in blood and liver samples was recorded using electron paramagnetic resonance (EPR) and X-ray fluorescence (XRF) techniques. The EPR line intensity at g=2.1 was found to be proportional to the concentration of magnetic nanoparticles and the best temperature for spectra acquisition was 298 K. Both EPR and XRF analysis indicated that the maximum concentration of iron in the liver occurred 95 min after the ferrofluid administration. The half-life of the magnetic nanoparticles (MNP) in the blood was (11.6 +/- 0.6) min measured by EPR and (12.6 +/- 0.6) min determined by XRF. These results indicate that both EPR and XRF are very useful and appropriate techniques for the study of kinetics of ferrofluid elimination and biodistribution after its administration into the organism. (c) 2007 Elsevier B.V. All rights reserved.

Characterization of the Biocompatible Magnetic Colloid on the Basis of Fe(3)O(4) Nanoparticles Coated with Dextran, Used as Contrast Agent in Magnetic Resonance Imaging

The magnetic resonance imaging contrast agent, the so-called Endorem (TM) colloidal suspension on the basis of superparamagnetic iron oxide nanoparticles (mean diameter of 5.5 nm) coated with dextran, were characterized on the basis of several measurement techniques to determine the parameters of their most important physical and chemical properties. It is assumed that each nanoparticle is consisted of Fe(3)O(4) monodomain and it was observed that its oxidation to gamma-Fe(2)O(3) occurs at 253.1 degrees C. The Mossbauer spectroscopy have shown a superparamagnetic behavior of the magnetic nanoparticles. The Magnetic Resonance results show an increase of the relaxation times T(1), T(2), and T(2)* with decreasing concentration of iron oxide nanoparticles. The relaxation effects of SPIONs contrast agents are influenced by their local concentration as well as the applied field strength and the environment in which these agents interact with surrounding protons. The proton relaxation rates presented a linear behavior with concentration. The measured values of thermooptic coefficient partial derivative n/partial derivative T, thermal conductivity K, optical birefringence Delta n(0), nonlinear refractive index n(2), nonlinear absorption beta` and third-order nonlinear susceptibility vertical bar chi((3))vertical bar are also reported.

Insulin-like growth factor-1 and 17 beta-estradiol down-regulate prostate apoptosis response-4 expression in MCF-7 breast cancer cells

The PKC apoptosis WTI regulator gene, also named prostate apoptosis response-4 (PAR-4), encodes a pro-apoptotic protein that sensitizes cells to numerous apoptotic stimuli. Insulin-like growth factor-1 (IGF-1) and 17 beta-estradiol (E2), two important factors for breast cancer development and progression, have been shown to down-regulate PAR-4 expression and inhibit apoptosis induced by PAR-4 in neuronal cells. In this study, we sought to investigate the mechanisms of regulation of PAR-4 gene expression in MCF-7 cells treated with E2 or IGF-1. E2 (10 nM) and IGF-1 (12.5 nM) each down-regulated PAR-4 expression in MCF-7 cells after 24 h of treatment. The effect of E2 was dependent on ER activation, as demonstrated by an increase in PAR-4 expression when cells were pretreated for 1 h with 1 mu M ICI-182,780 (ICI) before receiving E2 plus ICI. The effect of IGF-1 was abolished by pre-treatment for 1 h with 30 mu M LY294002 (a specific PI3-K inhibitor), and significantly inhibited by 30 mu M SB202190 (a specific p38MAPK inhibitor). We also demonstrated that E2 acts synergistically with IGF-1, resulting in greater down-regulation of PAR-4 mRNA expression compared with E2 or IGF-1 alone. Our results show for the first time that E2 and IGF-1 inhibit PAR-4 gene expression in MCF-7 cells, suggesting that this down-regulation may provide a selective advantage for breast cancer cell survival.

Magnetic characterization by SQUID and FMR of a biocompatible ferrofluid based on Fe(3)O(4)

Biocompatible superparamagnetic iron oxide nanoparticles of magnetite coated with dextran were magnetically characterized using the techniques of SQUID (superconducting quantum interference device) magnetometry and ferromagnetic resonance (FMR). The SQUID magnetometry characterization was performed by isothermal measurements under applied magnetic field using the methods of zero-field-cooling (ZFC) and field-cooling (FC). The magnetic behavior of the nanoparticles indicated their superparamagnetic nature and it was assumed that they consisted exclusively of monodomains. The transition to a blocked state was observed at the temperature T(B) = (43 +/- 1) K for frozen ferrofluid and at (52 +/- 1) K for the lyophilized ferrofluid samples. The FMR analysis showed that the derivative peak-to-peak linewidth (Delta H(PP)), gyromagnetic factor (g), number of spins (N(S)), and spin-spin relaxation time (T(2)) were strongly dependent on both temperature and super-exchange interaction. This information is important for possible nanotechnological applications, mainly those which are strongly dependent on the magnetic parameters.

Preaortic Iliac Confluence (Marsupial Vena Cava): Report of 4 Cases

Congenital anomalies of the inferior vena cava (IVC) call represent a difficult for abdominal surgeries, and the radiologist must be aware even of the less common of these anatomical variations. Preaortic iliac venous confluence, also known as marsupial vena cava, is a rare congenital anomaly of the development of the IVC in which the IVC or the left common iliac vein is located anterior to the aortic bifurcation or the right common iliac artery. We report 4 cases of marsupial vena cava detected on multidetector computed tomography examinations in asymptomatic patients and discuss that this congenital anomaly can be recognized more frequently with the use of this new technique based on thinner images.

Proposal for the interaction of non-conventional partial agonists and catecholamines with the 'putative beta(4)-adrenoceptor' in mammalian heart

1. Evidence for a 'putative beta(4)-adrenoceptor' originated over 20 years ago when cardiostimulant effects were observed to nonconventional partial agonists, These agonists were originally described as beta(1)- and beta(2)-adrenoceptor antagonists; however, they cause cardiostimulant effects at much higher concentrations than those required to block beta(1)- and beta(2)-adrenoceptors. Cardiostimulant effects of non-conventional partial agonists have been observed in mouse, rat, guinea-pig, cat, ferret and human heart tissues, 2. The receptor is expressed in several heart regions, including the sinoatrial node, atrium and ventricle, 3. The receptor is resistant to blockade by most antagonists that possess high affinity for beta(1)- and beta(2)- adrenoceptors, but is blocked with moderate affinity by (-)-bupranolol and CGP 20712A. 4. The receptor is pharmacologically distinct from the beta(3)-adrenoceptor. Micromolar concentrations of beta(3)-adrenoceptor agonists have no agonist or blocking activity, The receptor is also resistant to blockade by a beta(3)-adrenoceptor-selective antagonist. 5. The receptor mediates increases in cAMP levels and cAMP-dependent protein kinase (PK) A activity in cardiac tissues. Phosphodiesterase inhibition potentiates the positive chronotropic and inotropic effects of non-conventional partial agonists. 6. The receptor mediates hastening of atrial and ventricular relaxation, which is consistent with involvement of a cAMP-dependent pathway. 7. The non-conventional partial agonist (-)-[H-3]-CGP 12177A labels the cardiac putative beta(4)-adrenoceptor, Non-conventional partial agonists compete for binding with affinities that are closely similar to their agonist potencies, Catecholamines compete for binding in a stereoselective manner with a rank order of affinity of (-)-R0363 > (-)-isoprenaline > (-)-noradrenaline greater than or equal to (-)-adrenaline much greater than (-)-isoprenaline, suggesting that catecholamines can interact with the receptor. 8. The putative beta(4)-adrenoceptor appears to be coupled to the G(s)-adenylyl cyclase system, which could serve as a guide to its future cloning, Activation of the receptor may plausibly improve diastolic function but could also mediate arrhythmias.

Comparative analysis of the expression of cytokeratins (1,10,14,16,4), involucrin, filaggrin and e-cadherin in plane warts and epidermodysplasia verruciformis plane wart-type lesions

Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis with susceptibility to human papillomavirus (HPV) infection, and high risk of skin cancer considered a model of viral oncogenesis. Methods: Fifteen cases of EV plane wart (PW)-type lesions (EV) and 14 cases of PW in healthy individuals were subjected to immunohistochemical technique for cytokeratins (K) 1, 10, 14, 16, 4, involucrin, filaggrin and e-cadherin. Results: K1/10 showed retarded or negative expression in EV, being substituted by K14. Expression of K14 occurred in the basal and suprabasal layers in both groups, but in EV, its expression was observed up to the more superficial layers. Both groups showed positivity for K16 and K4, involucrin expression in lower levels of the spinous layer and unaltered filaggrin expression. E-cadherin expression was diminished at the koilocytotic foci of both lesions, more superficially in EV. Conclusion: Infection by HPV may alter the differentiation status of the epidermis, leading to a major expression of K14, delayed or absent expression of K1/10 and earlier involucrin expression, especially in EV. It also stimulates the expression of K16 and K4. Filaggrin expression is not altered, and e-cadherin is diminished in superficial koilocytotic cells` foci in EV.

Potential GABAB receptor antagonists .9. The synthesis of 3-amino-3-(4-chlorophenyl)propanoic acid, 2-amino-2-(4-chlorophenyl)ethylphosphonic acid and 2-amino-2-(4-chlorophenyl)ethanesulfonic acid

This paper describes the synthesis of 3-amino-3-(4-chlorophenyl)propanoic acid and the corresponding phosphonic and sulfonic acids, lower homologues of baclofen, phaclofen and saclofen respectively. The chlorinated acids were all weak specific antagonists of GABA at the GABAB receptor, with the sulfonic acid (pA(2) 4.0) being stronger than the phosphonic acid (pA(2) 3.8) and carboxylic acid (pA(2) 3.5).

Polymorphisms in Alcohol Metabolizing Genes and the Risk of Head and Neck Cancer in a Brazilian Population

Aims: The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC. Methods: A hospital-based case-control study was conducted in Sao Paulo, Brazil. We here investigated ADH1C Ile(350)Val, ADH1B Arg(48)His, ADH1B Arg(370)Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital. Results: Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg(48)His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21-0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20-0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13-0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg(48)His who consume alcohol > 30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21-16.11). Conclusions: The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is < 30.655 g/L/day.

Translation to Portuguese and Validation of the Douleur Neuropathique 4 Questionnaire

The Douleur Neuropathique 4 (DN4) questionnaire was developed by the French Neuropathic Pain Group and is a simple and objective tool, with the ability to distinguish nociceptive from neuropathic pain. The purpose of this work was to validate the DN4 questionnaire in the Portuguese language in order to allow its use in clinical and research settings. A double-blind, accuracy study was conducted, consisting of translation, back-translation, literal evaluation, semantic equivalence, and communication with the target population. The Portuguese version of the questionnaire was applied in a sample of 101 patients with neuropathic (N = 42) or nociceptive pain (N = 59), ranked according to medical diagnosis. The reproducibility, reliability and validity of the instrument were analyzed, and showed a high diagnostic power for this version of the DN4 questionnaire. The Portuguese version of the DN4 questionnaire presented good validity and reliability, allowing it to identify neuropathic pain and neuropathic characteristics of mixed pain syndromes. Perspective: This article presents the first validated neuropathic pain questionnaire in the Portuguese language and represents a useful tool in the assessment of neuropathic pain both in the clinical setting and in population-based studies. The sensible and quick format of this instrument are key factors that will contribute to its widespread use, permitting a true recognition of patients with neuropathic pain. (C) 2010 by the American Pain Society

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.