Veritatis Splendor e Evangelium Vitae (1993-1995): arcabouços do pontificado de João Paulo II

Pós-graduação em História - FCLAS

Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros

As mucopolissacaridoses (MPS) são doenças genéticas raras causadas pela deficiência de enzimas lisossômicas específicas que afetam o catabolismo de glicosaminoglicanos (GAG). O acúmulo de GAG em vários órgãos e tecidos nos pacientes afetados pelas MPS resulta em uma série de sinais e sintomas, integrantes de um quadro clínico multissistêmico que compromete ossos e articulações, vias respiratórias, sistema cardiovascular e muitos outros órgãos e tecidos, incluindo, em alguns casos, as funções cognitivas. Já foram identificados 11 defeitos enzimáticos que causam sete tipos diferentes de MPS. Antes do advento de terapias dirigidas para a restauração da atividade da enzima deficiente, o tratamento das MPS tinha como principal foco a prevenção e o cuidado das complicações, aspecto ainda bastante importante no manejo desses pacientes. Na década de 80 foi proposto o tratamento das MPS com transplante de medula óssea/transplante de células tronco hematopoiéticas (TMO/TCTH) e na década de 90 começou o desenvolvimento da Terapia de Reposição Enzimática (TRE), que se tornou uma realidade aprovada para uso clínico nas MPS I, II e VI na primeira década do século 21. Os autores deste trabalho têm a convicção de que um melhor futuro para os pacientes afetados pelas MPS depende da identificação, compreensão e manejo adequado das manifestações multissistêmicas dessas doenças, incluindo medidas de suporte (que devem fazer parte da assistência multidisciplinar regular destes pacientes) e terapias específicas. Embora a inibição da síntese de GAG e o resgate da atividade enzimática com moléculas pequenas também possam vir a ter um papel no manejo das MPS, o grande avanço disponível no momento é a TRE intravenosa. A TRE permitiu modificar radicalmente o panorama do tratamento das mucopolissacaridoses I, II e VI na última década, sendo que ainda pode estender seus benefícios em breve para a MPS IV A (cuja TRE já está em desenvolvimento clínico), com perspectivas para o tratamento da MPS III A e do déficit cognitivo na MPS II através de administração da enzima diretamente no sistema nervoso central (SNC). Um grande número de centros brasileiros, incluindo serviços de todas as regiões do país, já têm experiência com TRE para MPS I, II e VI. Essa experiência foi adquirida não só com o tratamento de pacientes como também com a participação de alguns grupos em ensaios clínicos envolvendo TRE para essas condições. Somados os três tipos de MPS, mais de 250 pacientes já foram tratados com TRE em nosso país. A experiência dos profissionais brasileiros, somada aos dados disponíveis na literatura internacional, permitiu elaborar este documento, produzido com o objetivo de reunir e harmonizar as informações disponíveis sobre o tratamento destas doenças graves e progressivas, mas que, felizmente, são hoje tratáveis, uma realidade que traz novas perspectivas para os pacientes brasileiros afetados por essas condições.

Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

Ensino de ciências e matemática II: temas sobre formação de conceitos

Pós-graduação em Educação para a Ciência - FC

Estudo comparativo de dois programas de computador (Dolphin Imaging e Nemotec) versus o método manual utilizados para análises cefalométricas de pacientes com deformidade dento-facial padrão II

A-Nperp, Pg-Nperp e mandibular plane). Thirty patients (male or female), with age varying from 19 to 48 years old were analyzed. All patients were diagnosted with mandibular retrognathism and submitted to bilateral sagital mandibular advancement. All tracings were performed in lateral cephalometric radiographs obtained one week before surgery. The intraclass correlation coefficient analysis (ICC), the t test adjusted for Tukey-Kramer test and Schuirmann test were applied. The results showed that the manual tracings and Nemotec® tracing had excellent reliabilities for all measures (ICC > 0.98). The Dolphin Imaging® showed low reliability in anterior facial height (value of ICC = 0.70), Co-A (value of ICC = 0.47) and Co-Gn (ICC value = 0.49). In A-Nperp, Pg-Nperp, Mandibular plan, SNA and SNB there were no differences between the 3 tracings (p > 0.05), for the anterior facial height measures differences were found between the Dolphin Imaging® and Nemotec® tracings, but no differences were observed as compared to the manual tracing (p > 0.05), in Co-A and Co-Gn measures t Dolphin Imaging® presented a significantly lower mean than the other methods (p > 0.05). The manual tracings were equivalent in 6 of 8 measures (A-Nperp, Pg-Nperp, md Plan, SNA, SNB and Co-A), there was no equivalence between the methods in the anterior facial height and Co-Gn measures (p < 0.01). The Dolphin Imaging® method was not equivalent in any of the 8 measures. It was concluded that in the manual tracing only the Co- Gn, Pg-Nperp and SNB measures confirmed the diagnosis of mandibular retrognathism, and the Nemotec® software showed better results than the Dolphin Imaging® software.

Phase II clinical study of an association for the treatment of interstitial cystitis (CYSTEX)

Painful bladder syndrome associated with interstitial cystitis (PBS/IC) is a clinical condition characterized pelvic pain, urinary urgency, and urinary frequency. In this study, 22 patients were assigned to make two visits over a three weeks period. The patients were randomly, double-blinded assigned in two groups. The first group received Cystex® capsules. The second group received placebo capsules. Two capsules were taken three times a day away from meals. The change from baseline in the O’Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and intensity of pain and urgency have been chosen as secondary outcome parameters. Mood as well as physical and sexual activity were rated by 10 questions on a scale 0 to 6. The ratings were analyzed and the average for each patient in both groups Cystex® and placebo was determined as the quality of life index. For the primary outcome there was a statistically significant difference between the groups. Mean symptom score-sum decreased from 28.4 to 20.5 in the Cystex® group compared with 29.5 to 26.8 in the placebo group (p<0.05). For the secondary end points, pain and urgency intensity improved statistically significantly in the Cystex® group compared with the placebo group (p<0.05). The frequency and functional bladder capacity improved to greater degree in the Cystex® group. The differences were statistically significant for comparison of frequency (p<0.05) and not for functional bladder capacity (p>0.05). In our study, Cystex® enhanced quality of life over the placebo showing a statistically significant. This trial have shown that the efficacy and safety of therapy with Cystex® in the treatment of interstitial cystitis and is an alternative for patients suffering from this pathology. Therefore, it can be concluded that the composition of Cystex®, increased the quality of life in treated patients.

Stress analysis in oral obturator prostheses, part II: photoelastic imaging

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Thermal study in solid state of Zn(II)-diclofenac complex: Behavior kinetic of dehydration, transition phase and thermal decomposition

The dehydration, thermal decomposition and transition phase stage of Zn(II)-diclofenac compoundwere studied by simultaneous TG-DTA and DSC techniques. The TG and DSC curves of this compoundwere obtained with the mass of sample of 2 and 5 mg. Additionally, DSC curves were carried out inopened and closed a-alumina pans under static and nitrogen atmosphere. The DTA and DSC curves showthat this compound possesses exothermic transition phase between 170-180 ºC, which it is irreversible(monotropic reaction). The kinetics study of this transition phase stage was evaluated by DSC undernon-isothermal conditions. The obtained data were evaluated with the isoconversional method, where thevalues of activation energy (Ea/kJmol-1) was plotted in function of the conversion degree (a). The resultsshow that due to mass sample, different activation energies were obtained. From these curves a tendencycan be seen where the plots maintain the same profile for closed lids and almost run parallel to each other.

Detecção da tolerância de diferentes espécies de capim-colchão a herbicidas inibidores do fotossistema II utilizando a técnica da fluorescência

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cone-beam evaluation of pharyngeal airway space in class I, II, and III patients

The purpose of this study is to make a 3-dimensional (3-D) evaluation of the pharyngeal airway space (PAS) in patients with class I, II, and III malocclusion. Sixty patients were evaluated. The patients were divided in 3 groups according to their occlusion classification. The volume and area of PAS were evaluated using the software Dolphin 3-D Imaging in the preoperative period for orthognathic surgery. PAS volume and area were influenced by different patterns of malocclusion. The mean volume and area for class III patients were statistically bigger than for classes I and II patients (P < .001). There was also a significant difference for volume values between class I and II patients, being the bigger volume for the class I patients (P < .05). It was possible to conclude that the class III patients presented a bigger PAS compared with classes I and II patients.

Ruthenium(II) complexes with 2-(diphenylphosphinomethyl)aniline

2-(Diphenylphosphinomethyl)aniline. H2L1, reacts with [RuCl2(PPh3)(3)] to yield the monomeric complexes [RuCl2(H2L1)(PPh3)(CH3CN)], [RuCl2(H2L1)(2)]and the chloro-bridged dimer [(H2L1)(PPh3)Ru(mu-Cl)(2)Ru(PPh3) (H2L1)] depending on the conditions applied. Exclusively the monochelate [RuCl2 (H2L1)(dmso)(2)] is formed during reactions of H2L1 with [RuCl2(dmso)(4)]. H2L1 acts as a neutral, bidentate ligand in all complexes. The products are studied spectroscopically and by X-ray diffraction. (C) 2012 Elsevier Ltd. All rights reserved.

Behavioral and EEG effects of GABAergic manipulation of the nigro-tectal pathway in the Wistar audiogenic rat (WAR) strain II: An EEG wavelet analysis and retrograde neuronal tracer approach

The role of the substantia nigra pars reticulata (SNPr) and superior colliculus (SC) network in rat strains susceptible to audiogenic seizures still remain underexplored in epileptology. In a previous study from our laboratory, the GABAergic drugs bicuculline (BIC) and muscimol (MUS) were microinjected into the deep layers of either the anterior SC (aSC) or the posterior SC (pSC) in animals of the Wistar audiogenic rat (WAR) strain submitted to acoustic stimulation, in which simultaneous electroencephalographic (EEG) recording of the aSC, pSC, SNPr and striatum was performed. Only MUS microinjected into the pSC blocked audiogenic seizures. In the present study, we expanded upon these previous results using the retrograde tracer Fluorogold (FG) microinjected into the aSC and pSC in conjunction with quantitative EEG analysis (wavelet transform), in the search for mechanisms associated with the susceptibility of this inbred strain to acoustic stimulation. Our hypothesis was that the WAR strain would have different connectivity between specific subareas of the superior colliculus and the SNPr when compared with resistant Wistar animals and that these connections would lead to altered behavior of this network during audiogenic seizures. Wavelet analysis showed that the only treatment with an anticonvulsant effect was MUS microinjected into the pSC region, and this treatment induced a sustained oscillation in the theta band only in the SNPr and in the pSC. These data suggest that in WAR animals, there are at least two subcortical loops and that the one involved in audiogenic seizure susceptibility appears to be the pSC-SNPr circuit. We also found that WARs presented an increase in the number of FG + projections from the posterior SNPr to both the aSC and pSC (primarily to the pSC), with both acting as proconvulsant nuclei when compared with Wistar rats. We concluded that these two different subcortical loops within the basal ganglia are probably a consequence of the WAR genetic background. (C) 2012 Elsevier Inc. All rights reserved.

CD44(+)/CD24(-) cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), antihuman CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumorinitiating cells in stage I and II breast cancer.

Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.