Estudo morfo-funcional, bioquímico e imunohistoquíco do aparelho respiratório em ratos expostos à fumaça do cigarro e ao álcool

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

BACKGROUND Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated.OBJECTIVE This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells.METHODS Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure.RESULTS The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life.CONCLUSIONS Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

Proposta de um protocolo de terapia celular para o tratamento da doença pulmonar obstrutiva crônica

The main feature of pulmonary emphysema is airflow obstruction resulting from the destruction of the alveolar walls distal to the terminal bronchioles. Existing clinical approaches have improved and extended the quality of life of emphysema patients. However, no treatment currently exists that can change the disease course and cure the patient. The different therapeutic approaches that are available aim to increase survival and/or enhance the quality of life of emphysema patients. In this context, cell therapy is a promising therapeutic approach with great potential for degenerative pulmonary diseases. In this protocol proposition, all patients will be submitted to laboratory tests, such as evaluation of heart and lung function and routine examinations. Stem cells will be harvested by means of 10 punctures on each anterior iliac crest, collecting a total volume of 200 mL bone marrow. After preparation, separation, counting and labeling (optional) of the mononuclear cells, the patients will receive an intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This article proposes a rational and safe clinical cellular therapy protocol which has the potential for developing new projects and can serve as a methodological reference for formulating clinical application protocols related to the use of cellular therapy in COPD. This study protocol was submitted and approved by the Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). (c) 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Associação do treinamento resistido e aeróbico em pacientes com doença pulmonar crônica

Introduction: The pulmonary rehabilitation (PR) is composed of aerobic and resisted exercises that improve the functional capacity to the exercise, life quality and decrease respiratory symptoms in subjects with chronic pulmonary disease. Objective: Assess the effects of a combined PR program in the cardiorespiratory function and peripheral muscle strength in subjects with chronic pulmonary disease. Method: Patients with chronic pulmonary disease were submitted to the PR program, which was developed on 24 sessions of 60 minutes (three times per week). The program was composed of aerobic exercises (two times per week) and resisted exercises (once a week). Before and after the PR the patients were submitted to manovacuometry in order to measure the maximum inspiratory pressure (MIP) and the maximum expiratory pressure (MEP), ventilometry, peek expiratory flow (PEF), six minute walking test (6MWT) and one maximum repetition (1RM). The data are presented in absolute frequency, percentage and mean±standard deviation. The t Student test was used to compare data before and after the PR and the ANOVA test to compare before, after and predicted distances in the 6MWT (p<0.05). Results: Seven patients were part of this study, 85.70% of women, 71.40% with pulmonary emphysema diagnosis. The mean age was 69.43±5.59 years old, the height was 1.61±0.07 m, the mean weight was 66.20±8.40 kg and the body mass index mean was 25.50±2.48 kg/m². From the variables assessed, the MEP increased from 79.71±13.69 to 84.42±12.83 cmH2O (p=0,03), the PEF increase from 255.71±66.3 to 320.00±93.63 l/min (p=0,03) and the distance in the 6MWT from 415.28±47.90 to 483,79±79,77 m (p=0,02). The load in the 1RM test in the reverse peck deck exercise (before - - 17.10±8.10kg; after – 210.40±9.00kg), knee in leg extension machine (before – 17.10±9.50kg; after – 26.40±13.10kg) and hip extensors (right before – 48.60±22.10kg; after – 62.90±19.30kg; and left before – 46.40±20.10kg; after – 62.10±18.20kg) increased significantly (p<0,05). Conclusion: After the PR program there was improvement in the expiratory muscular strength, in the lower limbs strength and in the functional capacity. Besides that, there was a reduction in the airflow obstruction of the subjects with chronic pulmonary disease.

Animal models in chronic obstructive pulmonary disease-an overview

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction resultant from an augmented inflammatory response of the respiratory tract to noxious particles and gases. Previous reports present a number of different hypotheses about the etiology and pathophysiology of COPD. The generating mechanisms of the disease are subject of much speculation, and a series of questions and controversies among experts still remain. In this context, several experimental models have been proposed in order to broaden the knowledge on the pathophysiological characteristics of the disease, as well as the search for new therapeutic approaches for acute or chronically injured lung tissue. This review aims to present the main experimental models of COPD, more specifically emphysema, as well as to describe the main characteristics, advantages, disadvantages, possibilities of application, and potential contribution of each of these models for the knowledge on the pathophysiological aspects and to test new treatment options for obstructive lung diseases.

Two-stage rumenostomy in buffaloes

Background: Rumenostomy may be performed for therapeutic and digestibility research purposes in bovines, small ruminants and camelids. Several studies requires romenostomy in buffaloes in order to sample ruminal content for laboratorial assays. However, complications and outcome of rumenostomy was poorly studied in buffaloes. Therefore, the aim of the current study was to describe a two-stage rumenostomy technique in buffaloes, focused on intra and post-operative period.Materials, Methods & Results: Nine Murrah buffaloes were submitted to a 36-h and 12-h of food and water fastening. The animals were given acepromazine and maintained in standing position. Flank local anesthesia was carried out. A circular skin incision was carried out in the center of the left flank, followed by divulsion of the external and internal obliques and transversus abdominus muscles, and incision of the peritoneum. Subsequently, a segment of the dorsal aspect of the rumen was grasped and pulled through the flank incision. The rumen was attached to the peritoneum and skin incision margins in four points (dorsal, ventral, cranial and caudal). Additional simple interrupted sutures attaching the rumen serosa to the skin were applied subsequently. Four additional interrupted horizontal mattress sutures were applied equidistantly, taking bites only in the skin and rumen serosa. Following 12 h, the second stage was carried out. The buffaloes were prepared and restrained as performed for the first stage. A circular flap was excised from the exteriorized rumen and the silicone romenostomy cannula was placed. Clinical parameters, postoperative recovery, weight and behavioral pain scale were assessed. Positioning and anesthesia regimen were adequate for the achievement of the procedure. However, two animals fell in the restraint chute during the first surgical stage. Mild ischemia of the exteriorized rumen segment was observed on the second surgical stage, which resulted in less hemorrhage and enhanced cannula positioning. Complete cicatrization and permanent adhesion of the rumen to the skin were achieved. No ruminal leakage to the abdominal cavity occurred. No signs of pain were reported. There were few cases of laxity of the romenostomy opening leading to drop of cannula, myiasis on the margin of the stoma site and few cases of mild ruminal content leakage on the long-term assessment.Discussion: Restraint in standing position was considered adequate, although lateral recumbence constitutes another option. However, higher risk of contamination and technical difficulties in placing the cannulas are expected if lateral recumbence is considered. In other trials using acepromazine, no accidental recumbence occurred. Xylazine was also indicated for chemical restraint of buffaloes. It is known that flexible cannulas provide better anatomic adjustment and adaptation as well as being effective for sampling ruminal content, as seen in the current study. Ruminal leakage is one of the most frequent complications of romenostomy, which may affect animal's welfare. The animals in the current study presented no variations on the body score, even though on those presenting cannula loosening or ruminal content leakage. Moreover, no significant changes of the ruminal content parameters were noticed. Myiasis was also reported following ruminal surgical interventions, which were mainly attributed to extensive breeding. Loss of the cannula, subcutaneous emphysema and suture dehiscence are common complications of romenostomy. Nonetheless, none of those complications were found on the current study. Thus, romenostomy was feasible and efficient for sampling and performing assays of the ruminal content in buffaloes.

Implicações da disponibilidade de espaço no confinamento de bovinos de corte

Pós-graduação em Zootecnia - FCAV

Respiratory immunohistochemical study in rats exposed to cigarette smoke and alcohol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relação entre poluição do ar e internações hospitalares por doenças respiratórias e cardiovascular em uma cidade do interior do Estado de São Paulo

Pós-graduação em Fisioterapia - FCT