Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema

Coordena����o de Aperfei��oamento de Pessoal de N��vel Superior (CAPES)

Cell Therapy with Bone Marrow Mononuclear Cells in Elastase-Induced Pulmonary Emphysema

Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p & 0. 05) were observed among the groups treated with BMMC and evaluated after 7, 14 and 21 days. Analysis of the mean linear intercept (Lm) values for the different groups allowed to observe that the group treated with BMMC and evaluated after 21 days showed the most significant result. The group that received no treatment showed a statistically significant difference when compared to other groups, except the group treated and evaluated after 21 days, evidencing the efficacy of cell therapy with BMMC in pulmonary emphysema. �� 2012 Springer Science+Business Media New York.

High intensity exercise training worsens alveolar destruction in pulmonary emphysema rats

OBJECTIVE: Investigation of standard intensities of physical exercise is important to better comprehend and develop rehabilitation programs for emphysema. We aimed to evaluate the effects of different intensities (moderate and high-intensity) of physical exercise on the development of a protease-induced (papain intratracheal instillation) emphysema in rats. METHODS: Male Wistar rats were randomly separated into ���ve groups that received intratracheal instillation of papain solution or vehicle: (i) papain high intensity exercise, (ii) papain moderate exercise, (iii) saline high intensity exercise, (iv) saline sedentary and (v) papain sedentary. Forty days after intratracheal instillation, the exercise groups were submitted to an exercise-training protocol on a treadmill during 10 weeks, 5 days/week, at 0.9 km/h (Papain and saline high exercise), or at 0.6 km/h (papain moderate exercise).We measured respiratory system elastance and resistance, the collagen ���ber lung parenchyma, and the pulmonary mean linear intercept. RESULTS: All animal groups that received papain instillation presented higher alveolar wall destruction compared to animals that received only saline solution. The papain high intensity exercise group presented higher values of mean linear intercept compared to emphysema groups that were trained at a moderate intensity or not submitted to exercise. CONCLUSION: High intensity exercise training worsened alveolar destruction in an experimental model of emphysema in rats when compared to moderate intensity exercise, or to no exercise.

Zirconia-based dental crown to support a removable partial denture: a three-dimensional finite element analysis using contact elements and micro-CT data

Veneer fracture is the most common complication in zirconia-based restorations. The aim of this study was to evaluate the mechanical behavior of a zirconia-based crown in a lower canine tooth supporting removable partial denture (RPD) prosthesis, varying the bond quality of the veneer/coping interface. Microtomography (��CT) data of an extracted left lower canine were used to build the finite element model (M) varying the core material (gold core - MAu; zirconia core - MZi) and the quality of the veneer/core interface (complete bonded - MZi; incomplete bonded - MZi-NL). The incomplete bonding condition was only applied for zirconia coping by using contact elements (Target/Contact) with 0.3 frictional coefficients. Stress fields were obtained using Ansys Workbench 10.0. The loading condition (L = 1 N) was vertically applied at the base of the RPD prosthesis metallic support towards the dental apex. Maximum principal (��max) and von Mises equivalent (��vM) stresses were obtained. The ��max (MPa) for the bonded condition was similar between gold and zirconia cores (MAu, 0.42; MZi, 0.40). The incomplete bonded condition (MZi-NL) raised ��max in the veneer up to 800% (3.23 MPa) in contrast to the bonded condition. The peak of ��vM increased up to 270% in the MZi-NL. The incomplete bond condition increasing the stress in the veneer/zirconia interface.

Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances

Conselho Nacional de Desenvolvimento Cient��fico e Tecnol��gico (CNPq)

Recovery of pulmonary structure and exercise capacity by treatment with granulocyte-colony stimulating factor (G-CSF) in a mouse model of emphysema

Emphysema is a chronic obstructive pulmonary disease characterized abnormal dilatation of alveolar spaces, which impairs alveolar gas exchange, compromising the physical capacity of a patient due to airflow limitations. Here we tested the effects of G-CSF administration in pulmonary tissue and exercise capacity in emphysematous mice. C57Bl/6 female mice were treated with elastase intratracheally to induce emphysema. Their exercise capacities were evaluated in a treadmill. Lung histological sections were prepared to evaluate mean linear intercept measurement. Emphysematous mice were treated with G-CSF (3 cycles of 200����g/kg/day for 5 consecutive days, with 7-day intervals) or saline and submitted to a third evaluation 8 weeks after treatment. Values of run distance and linear intercept measurement were expressed as mean������SD and compared applying a paired t-test. Effects of treatment on these parameters were analyzed applying a Repeated Measures ANOVA, followed by Tukey's post hoc analysis. p��<��0.05 was considered statistically significant. Twenty eight days later, animals ran significantly less in a treadmill compared to normal mice (549.7������181.2��m and 821.7������131.3��m, respectively; p��<��0.01). Treatment with G-CSF significantly increased the exercise capacity of emphysematous mice (719.6������200.5��m), whereas saline treatment had no effect on distance run (595.8������178.5��m). The PCR cytokines genes analysis did not detect difference between experimental groups. Morphometric analyses in the lung showed that saline-treated mice had a mean linear intercept significantly higher (p��<��0.01) when compared to mice treated with G-CSF, which did not significantly differ from that of normal mice. Treatment with G-CSF promoted the recovery of exercise capacity and regeneration of alveolar structural alterations in emphysematous mice. �� 2013.

Enfisema lobar cong��nito: s��rie de casos de 30 anos em dois hospitais universit��rios

Objetivo: Revisar os casos de enfisema lobar cong��nito (ELC) operados nos ��ltimos 30 anos em dois hospitais universit��rios. M��todos: Foram revistos os prontu��rios m��dicos das crian��as com ELC operadas no Hospital das Cl��nicas da Faculdade de Medicina de Botucatu e no Hospital da Universidade de Mogi das Cruzes entre 1979 e 2009. Dados sobre sintomas, exame f��sico, achados radiol��gicos, diagn��stico, tratamento cir��rgico e seguimento p��s-operat��rio mediato e tardio foram analisados. Resultados: Durante o per��odo estudado, 20 crian��as com ELC foram submetidas a tratamento cir��rgico. A m��dia de idade dos pacientes no momento da cirurgia foi 6,9 meses (varia����o, 9 dias a 4 anos). Todos os casos apresentaram sintomas ao nascimento ou nos primeiros meses de vida. Em todos os casos, a radiografia simples de t��rax foi importante na defini����o do diagn��stico. Em casos de dificuldade respirat��ria moderada, a TC de t��rax auxiliou no diagn��stico. Um paciente com desconforto respirat��rio grave foi diagnosticado erroneamente com pneumot��rax hipertensivo e submetido a drenagem tor��cica. A broncoscopia s�� foi realizada nos pacientes com dificuldade respirat��ria moderada e n��o foram encontrados sinais de anomalias traqueobr��nquicas. A abordagem cir��rgica foi realizada atrav��s de toracotomia lateral poupadora de m��sculo. O lobo superior esquerdo e o lobo m��dio foram os mais afetados, seguidos pelo lobo superior direito. A lobectomia foi realizada em 18 casos, enquanto a bilobectomia foi realizada em 2 casos (com ressec����o de cisto broncog��nico em 1 desses). Complica����es p��s-operat��rias n��o foram observadas. O acompanhamento p��s-operat��rio foi de pelo menos 24 meses (m��dia, 60 meses) e n��o foram observadas complica����es tardias nesta s��rie. Conclus��es: O ELC �� uma doen��a pouco comum, ainda negligenciada, de etiologia incerta, mas de f��cil diagn��stico radiol��gico e tratamento cir��rgico eficaz.

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.

Proposal to utilize simplified Swensen protocol in diagnosis of isolated pulmonary nodule

Background: The problem of diagnosing whether a solitary pulmonary nodule is benign or malignant is even greater in developing countries due to a higher prevalence of infectious diseases. These infections generate a large number of patients who are generally asymptomatic and with a pulmonary nodule that cannot be accurately defined as having benign or malignant etiology.Purpose: To verify the percentages of benign versus malignant non-calcified nodules, the length of time after contrast agent injection is spiral computed tomography (CT) most sensitive and specific, and whether three postcontrast phases are necessary.Material and Methods: We studied 23 patients with solitary pulmonary nodules identified on chest radiographs or CT. Spiral scans were obtained with Swensen protocol, but at 3, 4, and 5 min after contrast injection onset. Nodules were classified as benign or malignant by histopathological examination or by an absence or presence of growth after 2 years of follow-up CT.Results: Of the 23 patients studied, 18 (78.2%) showed a final diagnosis of benign and five (21.7%) malignant nodules. Despite the small sample size, we obtained results similar to those of Swensen et al., with 80.0% sensitivity, 55.5% specificity, and 60.8% accuracy. Four minutes gave the greatest mean enhancement in both malignant and benign lesions.Conclusion: Small non-calcified benign nodules were much more frequent than malignant nodules. The best time for dynamic contrast-enhanced CT density analysis was 4 min postcontrast. As well as saving time and money, this simplified Swensen protocol with only precontrast and 4 min postcontrast phases also reduces patient exposure to ionizing radiation.

Associa����o do treinamento resistido e aer��bico em pacientes com doen��a pulmonar cr��nica

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/m��. 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.

Identification of reference genes for expression analysis by real-time quantitative PCR in drought-stressed soybean

O objetivo deste trabalho foi validar, pela t��cnica de PCR quantitativo em tempo real (RT-qPCR) genes para serem utilizados como refer��ncia em estudos de express��o g��nica em soja, em ensaios de estresse h��drico. Foram avaliados quatro genes comumente utilizados em soja: Gm��-actin, GmGAPDH, GmLectin e GmRNAr18S. O RNA total foi extra��do de seis amostras: tr��s amostras de ra��zes em sistema de hidroponia com diferentes intensidades de d��ficit h��drico (0, 25, 50, 75 e 100 minutos de estresse h��drico), e tr��s amostras de folhas de plantas cultivadas em areia com diferentes umidades do solo (15, 5 e 2,5% de umidade gravim��trica). Os dados brutos do intervalo cycle threshold (Ct) foram analisados, e a efici��ncia de cada iniciador foi calculada para uma analise da Ct entre as diferentes amostras. A aplica����o do programa GeNorm foi utilizada para a avalia����o dos melhores genes de refer��ncia, de acordo com a estabilidade. O GmGAPDH foi o gene menos est��vel, com o maior valor m��dio de estabilidade de express��o (M), e os genes mais est��veis, com menor valor de M, foram o Gm��-actin e GmRNAr18S, tanto nas amostras de ra��zes como nas de folhas. Estes genes podem ser usados em RT-qPCR como gens de refer��ncia para an��lises de express��o g��nica.

Paracoccidioidomicose pulmonar agressiva, endotraque��te estenosante e cor-pulmonale subagudo: descri����o de um caso

A paracoccidioidomicose (Pbmicose) atinge os pulm��es pela via inalat��ria, onde se estabelece o complexo prim��rio semelhante ao da tuberculose. A traqu��ia comprometida pela via tubohemolinf��tica desenvolveria rea����o inflamat��ria em processo granulomatoso levando �� obstru����o estenosante com as��ixia. Acompanhou-se um doente, masculino, 32 anos, branco, natural de Sarutai�� (SP), lavrador, que h�� 8 meses desenvolveu tosse expectorativa branco-amarelada, di��ria, sem fatores de melhora ou piora e dispn��ia inicial discreta. H�� 4 meses, anorexia, fraqueza e astenia. H�� 1 m��s a dispneia se agravou. Perdeu 15 kg. Tabagista e etilista h�� 16 anos. Exame f��sico revelou: PA 10/7 mmHg, FR = 28 bpm, peso 31 kg, hipocratismo digital e hipotrofia muscular T��rax enfisematoso e s��ndrome obstrutivo aos testes de fun����o pulmonar. Cora����o: P2 desdobrada e hiperfon��tica. Hepatesplenomegalia. Desenvolveu cor-pulmonale e insufici��ncia adrenal �� interna����o, evoluindo ap��s 45 dias para ��bito em insufici��ncia respirat��ria aguda asfixiante, apesar da terapia antif��ngica ter sido completa. A literatura m��dica revista n��o mostrou registro de caso semelhante de cor-pulmonale e insufici��ncia adrenal de evolu����o subaguda.

Quantifica����o de fibrose e enfisema em pacientes com paracoccidioidomicose (PCM) pulmonar, atrav��s de imagens de tomografia computadorizada de alta resolu����o (TCAR)

Coordena����o de Aperfei��oamento de Pessoal de N��vel Superior (CAPES)

Estudo morfo-funcional, bioqu��mico e imunohistoqu��co do aparelho respirat��rio em ratos expostos �� fuma��a do cigarro e ao ��lcool

Funda����o de Amparo �� Pesquisa do Estado de S��o Paulo (FAPESP)

Laminados cer��micos em pr��-molares: an��lise tridimensional pelo m��todo dos elementos finitos

P��s-gradua����o em Odontologia - FOA