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

Several experimental studies of pulmonary emphysema using animal models have been described in the literature. However, only a few of these studies have focused on the assessment of ergometric function as a non-invasive technique to validate the methodology used for induction of experimental emphysema. Additionally, functional assessments of emphysema are rarely correlated with morphological pulmonary abnormalities caused by induced emphysema. The present study aimed to evaluate the effects of elastase administered by tracheal puncture on pulmonary parenchyma and their corresponding functional impairment. This was evaluated by measuring exercise capacity in C57Bl/6 mice in order to establish a reproducible and safe methodology of inducing experimental emphysema. Thirty six mice underwent ergometric tests before and 28 days after elastase administration. Pancreatic porcine elastase solution was administered by tracheal puncture, which resulted in a significantly decreased exercise capacity, shown by a shorter distance run (-30.5%) and a lower mean velocity (-15%), as well as in failure to increase the elimination of carbon dioxide. The mean linear intercept increased significantly by 50% in tracheal elastase administration. In conclusion, application of elastase by tracheal function in C57Bl/6 induces emphysema, as validated by morphometric analyses, and resulted in a significantly lower exercise capacity, while resulting in a low mortality rate. (C) 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Intervenções de enfermagem para o cuidado de pacientes com artrite: revisão integrativa da literatura

Esta revisão integrativa buscou analisar a produção científica relacionada aos cuidados de enfermagem para pacientes com artrite. Foram incluídos 12 estudos experimentais, randomizados e controlados, publicados nas bases de dados CINAHL, MEDLINE, SciELO e LILACS, utilizando os descritores controlados "arthritis" e "nursing". Os resultados apontaram a efetividade de musicoterapia, estimulação elétrica neuromuscular, toque terapêutico e imagem guiada associada a relaxamento, para o tratamento da dor. Ser atendido por enfermeira especialista aumentou a satisfação com o atendimento, melhorou o impacto da doença e aumento a procura por serviços de saúde. Programas educativos específicos para portadores de artrite estimularam a prática de exercícios físicos e aqueles direcionados a pessoas com problemas crônicos em geral mostraram-se efetivos para controlar a dor e a incapacidade funcional. Concluímos que existe um conjunto de intervenções que podem subsidiar a prática de enfermagem baseada em evidências junto aos idosos com artrite.

Tabagismo: o que tem sido abordado em periódicos brasileiros

O tema tabagismo, em seus vários aspectos, vem recebendo crescente atenção entre os pesquisadores ao longo dos últimos anos, o que tem se refletido em maior e mais sólida produção científica sobre o assunto em periódicos nacionais. Este artigo tem como objetivo comentar os estudos que abordaram o tema tabagismo publicados entre janeiro de 2010 e junho de 2012, nas revistas Arquivos Brasileiros de Cardiologia, Brazilian Journal of Medical and Biological Research, Clinics (São Paulo), Jornal Brasileiro de Pneumologia, Revista da Associação Médica Brasileira e Revista Brasileira de Cirurgia Cardiovascular. No período foram publicados 58 artigos, 52 originais, abordando variados aspectos, como efeitos na saúde, epidemiologia, cessação e estudos experimentais.

Imagem corporal e hábitos alimentares na anorexia nervosa: uma revisão integrativa da literatura

Revisão integrativa da literatura com objetivo de investigar os construtos da imagem corporal e hábitos alimentares na anorexia nervosa (AN). As bases consultadas foram MedLine, LILACS e PsycINFO, no período de 2005 a 2009. A maioria dos artigos encontrados é constituída de estudos não-experimentais e descritivos, provenientes de fontes internacionais. Os resultados evidenciaram que a personalidade de mulheres com AN é permeada por baixa autoestima, sentimentos de inferioridade, inadequação, insegurança, perfeccionismo e obsessividade, fatores que acarretam acentuada inibição e retraimento social, e que exercem influência na distorção da imagem corporal e na aquisição de hábitos alimentares disfuncionais. Como conclusão ressalta-se a necessidade de tratamento interdisciplinar, e de novos estudos experimentais e nacionais, que busquem compreender a relação entre os construtos.

Diretrizes para prevenção e tratamento da osteoporose induzida por glicocorticoide

Os glicocorticoides (GC) são prescritos por praticamente todas as especialidades médicas, e cerca de 0,5% da população geral do Reino Unido utiliza esses medicamentos. Com o aumento da sobrevida dos pacientes com doenças reumatológicas, a morbidade secundária ao uso dessa medicação representa um aspecto importante que deve ser considerado no manejo de nossos pacientes. As incidências de fraturas vertebrais e não vertebrais são elevadas, variando de 30%-50% em pessoas que usam GC por mais de três meses. Assim, a osteoporose e as fraturas por fragilidade devem ser prevenidas e tratadas em todos os pacientes que iniciarão ou que já estejam em uso desses esteroides. Diversas recomendações elaboradas por várias sociedades internacionais têm sido descritas na literatura, porém não há consenso entre elas. Recentemente, o Americam College of Rheumatology publicou novas recomendações, porém elas são fundamentadas na FRAX (WHO Fracture Risk Assessment Tool) para analisar o risco de cada indivíduo e, dessa maneira, não podem ser completamente utilizadas pela população brasileira. Dessa forma, a Comissão de Osteoporose e Doenças Osteometabólicas da Sociedade Brasileira de Reumatologia, em conjunto com a Associação Médica Brasileira e a Associação Brasileira de Medicina Física e Reabilitação, implementou as diretrizes brasileiras de osteoporose induzida por glicocorticoide (OPIG), baseando-se na melhor evidência científica disponível e/ou experiência de experts. DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIA: A revisão bibliográfica de artigos científicos desta diretriz foi realizada na base de dados MEDLINE. A busca de evidência partiu de cenários clínicos reais, e utilizou as seguintes palavras-chave (MeSH terms): Osteoporosis, Osteoporosis/chemically induced*= (Glucocorticoids= Adrenal Cortex Hormones, Steroids), Glucocorticoids, Glucocorticoids/administration and dosage, Glucocorticoids/therapeutic use, Glucocorticoids/adverse effects, Prednisone/adverse effects, Dose-Response Relationship, Drug, Bone Density/drug effects, Bone Density Conservation Agents/pharmacological action, Osteoporosis/ prevention&control, Calcium, Vitamin D, Vitamin D deficiency, Calcitriol, Receptors, Calcitriol; 1-hydroxycholecalciferol, Hydroxycholecalciferols, 25-Hydroxyvitamin D3 1-alpha-hydroxylase OR Steroid Hydroxylases, Prevention and Control, Spinal fractures/prevention & control, Fractures, Spontaneous, Lumbar Vertebrae/injuries, Lifestyle, Alcohol Drinking, Smoking OR tobacco use disorder, Movement, Resistance Training, Exercise Therapy, Bone density OR Bone and Bones, Dual-Energy X-Ray Absorptiometry OR Absorptiometry Photon OR DXA, Densitometry, Radiography, (Diphosphonates Alendronate OR Risedronate Pamidronate OR propanolamines OR Ibandronate OR Zoledronic acid, Teriparatide OR PTH 1-34, Men AND premenopause, pregnancy, pregnancy outcome maternal, fetus, lactation, breast-feeding, teratogens, Children (6-12 anos), adolescence (13-18 anos). GRAU DE RECOMENDAÇÃO E FORÇA DE EVIDÊNCIA: A) Estudos experimentais e observacionais de melhor consistência; B) Estudos experimentais e observacionais de menor consistência; C) Relatos de casos (estudos não controlados); D) Opinião desprovida de avaliação crítica, com base em consensos, estudos fisiológicos ou modelos animais. OBJETIVO: Estabelecer as diretrizes para a prevenção e o tratamento da OPIG.

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. (C) 2012 International Society for Advancement of Cytometry

TGF-beta 1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells

Background: Metastasis is the main factor responsible for death in breast cancer patients. Matrix metalloproteinases (MMPs) and their inhibitors, known as tissue inhibitors of MMPs (TIMPs), and the membrane-associated MMP inhibitor (RECK), are essential for the metastatic process. We have previously shown a positive correlation between MMPs and their inhibitors expression during breast cancer progression; however, the molecular mechanisms underlying this coordinate regulation remain unknown. In this report, we investigated whether TGF-beta 1 could be a common regulator for MMPs, TIMPs and RECK in human breast cancer cell models. Methods: The mRNA expression levels of TGF-beta isoforms and their receptors were analyzed by qRT-PCR in a panel of five human breast cancer cell lines displaying different degrees of invasiveness and metastatic potential. The highly invasive MDA-MB-231 cell line was treated with different concentrations of recombinant TGF-beta 1 and also with pharmacological inhibitors of p38 MAPK and ERK1/2. The migratory and invasive potential of these treated cells were examined in vitro by transwell assays. Results: In general, TGF-beta 2, T beta RI and T beta RII are over-expressed in more aggressive cells, except for T beta RI, which was also highly expressed in ZR-75-1 cells. In addition, TGF-beta 1-treated MDA-MB-231 cells presented significantly increased mRNA expression of MMP-2, MMP-9, MMP-14, TIMP-2 and RECK. TGF-beta 1 also increased TIMP-2, MMP-2 and MMP-9 protein levels but downregulated RECK expression. Furthermore, we analyzed the involvement of p38 MAPK and ERK1/2, representing two well established Smad-independent pathways, in the proposed mechanism. Inhibition of p38MAPK blocked TGF-beta 1-increased mRNA expression of all MMPs and MMP inhibitors analyzed, and prevented TGF-beta 1 upregulation of TIMP-2 and MMP-2 proteins. Moreover, ERK1/2 inhibition increased RECK and prevented the TGF-beta 1 induction of pro-MMP-9 and TIMP-2 proteins. TGF-beta 1-enhanced migration and invasion capacities were blocked by p38MAPK, ERK1/2 and MMP inhibitors. Conclusion: Altogether, our results support that TGF-beta 1 modulates the mRNA and protein levels of MMPs (MMP-2 and MMP-9) as much as their inhibitors (TIMP-2 and RECK). Therefore, this cytokine plays a crucial role in breast cancer progression by modulating key elements of ECM homeostasis control. Thus, although the complexity of this signaling network, TGF-beta 1 still remains a promising target for breast cancer treatment.

Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

Abstract Background Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Methods Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). Results 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. Conclusions To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted.

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

Abstract Background Rhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Results Treatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh2(H2cit)4, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh2(H2cit)4 induces cell death by apoptosis. Conclusions The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.

TGF-β1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells

Abstract Background Metastasis is the main factor responsible for death in breast cancer patients. Matrix metalloproteinases (MMPs) and their inhibitors, known as tissue inhibitors of MMPs (TIMPs), and the membrane-associated MMP inhibitor (RECK), are essential for the metastatic process. We have previously shown a positive correlation between MMPs and their inhibitors expression during breast cancer progression; however, the molecular mechanisms underlying this coordinate regulation remain unknown. In this report, we investigated whether TGF-β1 could be a common regulator for MMPs, TIMPs and RECK in human breast cancer cell models. Methods The mRNA expression levels of TGF-β isoforms and their receptors were analyzed by qRT-PCR in a panel of five human breast cancer cell lines displaying different degrees of invasiveness and metastatic potential. The highly invasive MDA-MB-231 cell line was treated with different concentrations of recombinant TGF-β1 and also with pharmacological inhibitors of p38 MAPK and ERK1/2. The migratory and invasive potential of these treated cells were examined in vitro by transwell assays. Results In general, TGF-β2, TβRI and TβRII are over-expressed in more aggressive cells, except for TβRI, which was also highly expressed in ZR-75-1 cells. In addition, TGF-β1-treated MDA-MB-231 cells presented significantly increased mRNA expression of MMP-2, MMP-9, MMP-14, TIMP-2 and RECK. TGF-β1 also increased TIMP-2, MMP-2 and MMP-9 protein levels but downregulated RECK expression. Furthermore, we analyzed the involvement of p38 MAPK and ERK1/2, representing two well established Smad-independent pathways, in the proposed mechanism. Inhibition of p38MAPK blocked TGF-β1-increased mRNA expression of all MMPs and MMP inhibitors analyzed, and prevented TGF-β1 upregulation of TIMP-2 and MMP-2 proteins. Moreover, ERK1/2 inhibition increased RECK and prevented the TGF-β1 induction of pro-MMP-9 and TIMP-2 proteins. TGF-β1-enhanced migration and invasion capacities were blocked by p38MAPK, ERK1/2 and MMP inhibitors. Conclusion Altogether, our results support that TGF-β1 modulates the mRNA and protein levels of MMPs (MMP-2 and MMP-9) as much as their inhibitors (TIMP-2 and RECK). Therefore, this cytokine plays a crucial role in breast cancer progression by modulating key elements of ECM homeostasis control. Thus, although the complexity of this signaling network, TGF-β1 still remains a promising target for breast cancer treatment.

Prognostic factors for survival in patients with colorectal liver metastases: experience of a single brazilian cancer center

CONTEXT: Liver metastases are a common event in the clinical outcome of patients with colorectal cancer and account for 2/3 of deaths from this disease. There is considerable controversy among the data in the literature regarding the results of surgical treatment and prognostic factors of survival, and no analysis have been done in a large cohort of patients in Brazil. OBJECTIVES: To characterize the results of surgical treatment of patients with colorectal liver metastases, and to establish prognostic factors of survival in a Brazilian population. METHOD: This was a retrospective study of patients undergoing liver resection for colorectal metastases in a tertiary cancer hospital from 1998 to 2009. We analyzed epidemiologic variables and the clinical characteristics of primary tumors, metastatic disease and its treatment, surgical procedures and follow-up, and survival results. Survival analyzes were done by the Kaplan-Meier method and the log-rank test was applied to determine the influence of variables on overall and disease-free survival. All variables associated with survival with P<0.20 in univariate analysis, were included in multivariate analysis using a Cox proportional hazard regression model. RESULTS: During the period analyzed, 209 procedures were performed on 170 patients. Postope-rative mortality in 90 days was 2.9% and 5-year overall survival was 64.9%. Its independent prognostic factors were the presence of extrahepatic disease at diagnosis of liver metastases, bilateral nodules and the occurrence of major complications after liver surgery. The estimated 5-year disease-free survival was 39.1% and its prognostic factors included R1 resection, extrahepatic disease, bilateral nodules, lymph node involvement in the primary tumor and primary tumors located in the rectum. CONCLUSION: Liver resection for colorectal metastases is safe and effective and the analysis of prognostic factors of survival in a large cohort of Brazilian patients showed similar results to those pointed in international series. The occurrence of major postoperative complications appears to be able to compromise overall survival and further investigation in needed in this topic.