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Acta cir. bras ; 33(12): 1067-1077, Dec. 2018. graf
Article in English | LILACS | ID: biblio-973486


Abstract Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

Animals , Male , Alprostadil/pharmacology , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide Synthase Type III/metabolism , Antioxidants/pharmacology , Superoxide Dismutase/analysis , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Catalase/analysis , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Troponin T/drug effects , Troponin T/blood , Enzyme Activation/drug effects , Creatine Kinase, MB Form/drug effects , Creatine Kinase, MB Form/blood , Heart Ventricles/drug effects , Heart Ventricles/pathology , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/blood , Malondialdehyde/analysis , Myocardial Infarction/pathology , Nitric Oxide/analysis
Biol. Res ; 50: 24, 2017. graf
Article in English | LILACS | ID: biblio-950875


BACKGROUND: The aim of the present study was to investigate the potential effects of the 5,10,15,20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4) on the proliferation and apoptosis of human cervical cancer cells and the underlying mechanisms by which TMPyP4 exerted its actions. RESULTS: After human cervical cancer cells were treated with different doses of TMPyP4, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, the apoptosis was observed by flow cytometry (FCM), and the expression of p38 mitogen-activated protein kinase (MAPK), phosphated p38 MAPK (p-p38 MAPK), capase-3, MAPKAPK2 (MK-2) and poly ADP-ribose polymerase (PARP) was measured by Western blot analysis. The analysis revealed that TMPyP4 potently suppressed cell viability and induced the apoptosis of human cervical cancer cells in a dose-dependent manner. In addition, the up-regulation of p-p38 MAPK expression levels was detected in TMPyP4-treated human cervical cancer cells. However, followed by the block of p38 MAPK signaling pathway using the inhibitor SB203580, the effects of TMPyP4 on proliferation and apoptosis of human cervical cancer cells were significantly changed. CONCLUSIONS: It was indicated that TMPyP4-inhibited proliferation and -induced apoptosis in human cervical cancer cells was accompanied by activating the p38 MAPK signaling pathway. Taken together, our study demonstrates that TMPyP4 may represent a potential therapeutic method for the treatment of cervical carcinoma.

Humans , Female , Porphyrins/pharmacology , Uterine Cervical Neoplasms/drug therapy , p38 Mitogen-Activated Protein Kinases/metabolism , Antineoplastic Agents/pharmacology , Tetrazolium Salts , HeLa Cells/drug effects , Cell Survival/drug effects , Cells, Cultured , Blotting, Western , Reproducibility of Results , Apoptosis/drug effects , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Cell Proliferation/drug effects , Enzyme Activation/drug effects , Caspase 3/analysis , Formazans
Article in English | WPRIM | ID: wpr-110764


Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and elevated intracellular free Ca2+ concentration, corresponding to a decrease in gap junctional intercellular communication. Gap junction blockage pretreatment with 18β-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial transmembrane electrical potential (Δψm). Additionally, GA was found to enhance ERK and p38 activation during Cd-induced activation of mitogen-activated protein kinases, but had no significant effect on JNK activation. Our results indicated the apoptosis-related proteins and the ERK and p38 signaling pathways may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A cells.

Animals , Apoptosis/drug effects , Cadmium/toxicity , Calcium/metabolism , Cell Communication/drug effects , Connexin 43/genetics , Enzyme Activation/drug effects , Gap Junctions/drug effects , Gene Expression Regulation/drug effects , Hepatocytes/cytology , Rats , Signal Transduction/drug effects
Article in English | WPRIM | ID: wpr-36486


Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked IFN-γ. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, 5 µM) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine (5 µM) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, 20 µM) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, 10 µM) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.

Antiparasitic Agents/pharmacology , Blotting, Western , Cell Line , Enzyme Activation/drug effects , Fluorescent Antibody Technique , Humans , Janus Kinase 1/metabolism , Janus Kinase 3/metabolism , Phosphorylation/drug effects , Quinazolines/pharmacology , STAT6 Transcription Factor/metabolism , Signal Transduction/drug effects , Toxoplasma/drug effects , Toxoplasmosis/physiopathology
Cad. saúde pública ; 31(4): 722-732, 04/2015.
Article in English | LILACS | ID: lil-744848


We aimed to verify doctor's perception of the qualitative research method, via a qualitative study of interviews with questions on the academic profile of doctors and on the methodology. We interviewed 42 professionals, of which 18 had experience with the qualitative method and 24 with the quantitative method. The results showed that knowledge on the qualitative method was virtually nil among "quantitative researchers", who did not value qualitative research, although some of those realized that it would be important to be more accepting in clinical practice. Others only considered the method as subsidiary to quantitative. The majority considered qualitative methods as lacking academic structure, taking too long to conduct empirical studies, and being difficult to publish. All of them criticized the misuse of the method, and the "quantitatives" pointed out the problem of being unable to reproduce. We concluded that widening the use of the qualitative method by doctors requires investment from the beginning of the academic career and participation in qualitative research projects.

El objetivo es verificar la percepción de médicos sobre el método de investigación cualitativa. Se trata de un estudio cualitativo por medio de entrevistas con preguntas sobre el perfil de los médicos y sobre el método. Entrevistamos a 42 profesionales, 18 con experiencia en el método cualitativo y 24 con el cuantitativo. Los resultados mostraron que el conocimiento sobre lo cualitativo es casi nulo entre los "cuantitativistas", que no valoran la investigación cualitativa, aunque algunos se dan cuenta de que sería importante tener un enfoque más amplio en la práctica clínica. Otros la ven como subsidiaria a lo cuantitativo. Sus dificultades para utilizar ese abordaje son: falta de formación, cantidad de tiempo que exigen y problemas de publicación. Todos han criticado el mal uso del método. Los "cuantitativistas" han destacado como fragilidad, la no reproductibilidad. Llegamos a la conclusión de que para ampliar el uso de los abordajes cualitativos entre los médicos es importante invertir en su formación desde el inicio del curso y la participación en proyectos de investigación cualitativa.

Objetivamos verificar a percepção de médicos sobre o método qualitativo de pesquisa. Estudo qualitativo por meio de entrevistas com questões sobre o perfil acadêmico do médico e perguntas abertas a respeito do método. Entrevistamos 42 profissionais, sendo 18 com experiência no método qualitativo e 24 com o quantitativo. Os resultados evidenciaram que o conhecimento sobre o qualitativo é quase nulo entre os pesquisadores "quantitativistas", os quais não valorizam a pesquisa qualitativa, embora alguns percebam que seria importante ter uma postura mais compreensiva na prática clínica. Outros só a veem como subsidiária ao quantitativo. As principais dificuldades da maioria são: falta de formação, tempo longo despendido nos estudos empíricos e dificuldade de publicação. Todos os entrevistados criticaram o mau uso do método, e os "quantitativistas" ressaltaram, como problema, sua não reprodutibilidade. Concluímos que ampliar o uso do método qualitativo por médicos exige investimento na formação desde o início da graduação e participação em projetos de pesquisa qualitativa.

Animals , Humans , Mice , Anilides/pharmacology , Benzodiazepinones/pharmacology , /pharmacology , Protein Kinase Inhibitors/pharmacology , Protein-Serine-Threonine Kinases/antagonists & inhibitors , Pyrimidines/pharmacology , Repressor Proteins/antagonists & inhibitors , Cells, Cultured , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Evaluation, Preclinical , Enzyme Activation/drug effects , Neoplasms/pathology , Protein Kinases/genetics , Protein-Serine-Threonine Kinases/genetics , Protein-Serine-Threonine Kinases/metabolism , Protein-Serine-Threonine Kinases/physiology , Repressor Proteins/agonists , Repressor Proteins/genetics , Substrate Specificity , Tumor Suppressor Proteins/physiology
Rev. Soc. Bras. Med. Trop ; 48(1): 50-55, jan-feb/2015. tab
Article in English | LILACS | ID: lil-742969


INTRODUCTION: Leptospirosis is a zoonosis that affects both humans and animals. Dogs may serve as sentinels and indicators of environmental contamination as well as potential carriers for Leptospira. This study aimed to evaluate the seroprevalence and seroincidence of leptospirosis infection in dogs in an urban low-income community in southern Brazil where human leptospirosis is endemic. METHODS: A prospective cohort study was designed that consisted of sampling at recruitment and four consecutive trimestral follow-up sampling trials. All households in the area were visited, and those that owned dogs were invited to participate in the study. The seroprevalence (MAT titers ≥100) of Leptospira infection in dogs was calculated for each visit, the seroincidence (seroconversion or four-fold increase in serogroup-specific MAT titer) density rate was calculated for each follow-up, and a global seroincidence density rate was calculated for the overall period. RESULTS: A total of 378 dogs and 902.7 dog-trimesters were recruited and followed, respectively. The seroprevalence of infection ranged from 9.3% (95% CI; 6.7 - 12.6) to 19% (14.1 - 25.2), the seroincidence density rate of infection ranged from 6% (3.3 - 10.6) to 15.3% (10.8 - 21.2), and the global seroincidence density rate of infection was 11% (9.1 - 13.2) per dog-trimester. Canicola and Icterohaemorraghiae were the most frequent incident serogroups observed in all follow-ups. CONCLUSIONS: Follow-ups with mean trimester intervals were incapable of detecting any increase in seroprevalence due to seroincident cases of canine leptospirosis, suggesting that antibody titers may fall within three months. Further studies on incident infections, disease burden or risk factors for incident Leptospira cases should take into account the detectable lifespan of the antibody. .

Animals , Female , Male , Mice , B-Lymphocytes/metabolism , Glycolysis , Lymphoma/metabolism , Poly(ADP-ribose) Polymerases/metabolism , AMP-Activated Protein Kinases/metabolism , Apoptosis/drug effects , B-Lymphocytes/pathology , Biological Transport/drug effects , Cells, Cultured , Enzyme Activation/drug effects , Glucose/metabolism , Glucose/pharmacokinetics , Immunoblotting , In Situ Nick-End Labeling , /pharmacology , Lymphoma/genetics , Lymphoma/pathology , Mice, Knockout , Mitochondria/drug effects , Mitochondria/metabolism , Oxidative Phosphorylation/drug effects , Poly(ADP-ribose) Polymerases/genetics , /genetics , /metabolism , Survival Analysis
Biol. Res ; 48: 1-9, 2015. ilus, graf, tab
Article in English | LILACS | ID: biblio-950810


BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE) induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin). This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs. RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP) cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK) pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK), p38 and c-Jun N-ter-minal kinase (JNK). Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE. CONCLUSION: Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment.

Humans , Plant Extracts/pharmacology , Cisplatin/pharmacology , Zanthoxylum/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , HeLa Cells , Apoptosis/drug effects , Mitogen-Activated Protein Kinases/drug effects , JNK Mitogen-Activated Protein Kinases/drug effects , Enzyme Activation/drug effects
ABCD arq. bras. cir. dig ; 28(1): 24-27, 2015. graf
Article in English | LILACS | ID: lil-742761


BACKGROUND: Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. AIM: To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. METHODS: A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. RESULTS: There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). CONCLUSIONS: Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. .

RACIONAL: Pancreatite aguda consiste de doença inflamatória do pâncreas por autodigestão enzimática que pode ocasionar necrose ou mesmo falência múltipla de órgãos e de fisiopatologia ainda não totalmente conhecida. OBJETIVO: Avaliar as correlações existentes entre dados clínicos e terapêuticos em pacientes com pancreatite aguda leve. MÉTODOS: Foi realizado estudo retrospectivo em 55 prontuários de pacientes internados por pancreatite aguda leve para análise de associação entre idade, leucocitose, dosagem sérica de transaminase glutâmico-oxalacética e de desidrogenase lática, glicemia, antibioticoterapia, tempo de internação e escores de Ranson. RESULTADOS: Houve associação positiva entre cuidados intensivos menores (hidratação rigorosa, analgesia e monitorização de sinais vitais), antibioticoterapia precoce (monoterapia), retorno precoce da dieta após 48 horas e controle laboratorial dos níveis séricos de amilase e lipase (elevados na primeira semana e decrescentes após 10 dias, porém sem valor prognóstico). CONCLUSÕES: Mudanças no manejo de pacientes com pancreatite aguda leve, tais como nutrição enteral, uso racional de antibióticos de menor espectro e cuidados intensivos têm contribuído significativamente para a redução do tempo de internação e mortalidade. .

Animals , Male , Rats , /antagonists & inhibitors , /metabolism , /metabolism , N-Methylaspartate/pharmacology , Peptides/pharmacology , Poly(ADP-ribose) Polymerases/metabolism , Retinal Neurons/physiology , Cell Death/drug effects , Cell Membrane/drug effects , Cell Survival/drug effects , Enzyme Activation/drug effects , Necrosis , Phenanthrenes/pharmacology , Rats, Sprague-Dawley , Retinal Neurons/cytology , Retinal Neurons/drug effects , Signal Transduction/drug effects
J. bras. nefrol ; 36(4): 446-450, Oct-Dec/2014. tab
Article in English | LILACS | ID: lil-731140


Introduction: Contrast induced nephropathy (CIN) is one of the complications of the use of intravascular contrast agents, being defined as a reduction of the glomerular filtration rate caused by the iodinated contrast. Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus. However, these studies limit their conclusions to a more specific patient population. Computerized tomography as a cause of CIN has been studied less often. Objective: To report on the incidence of computerized tomography contrast induced nephropathy (CIN) in an inpatient population of a tertiary general hospital, identifying potentially avoidable risk factors. Methods: We performed a prospective cohort study with inpatients admitted at a tertiary hospital requiring contrast-induced CT. The primary outcome was the development of CIN, measure by the alteration of serum creatinine or glomerular filtration rate in 48 or 72 hours. Through clinical interview, we verified possible risk factors and preventive measures instituted by the medical team and their association with development of CIN. Results: Of a total of 410 patients, 35 (8.5%) developed CIN. There was a positive correlation between CIN and the presence of diabetes mellitus (OR = 2.15; 95%CI 1.35-4.06; p = 0.02), heart failure (OR = 2.23; 95%CI 1.18-8.8; p = 0.022), and renal failure (OR = 3.36; 95%CI 1.57- 7.17; p = 0.002) Conclusion: Incidence of CIN varies according to the population. Diabetes mellitus, heart failure and renal failure were independent risk factors for the development of CT-associated CIN. Further studies are needed to better understand and treat CT-associated CIN. .

Introdução: Nefropatia induzida por contraste (NIC) é consequência do uso de meios de contraste intravenoso, sendo definida como uma redução da taxa de filtração glomerular. A maioria dos dados de NIC são da literatura cardiovascular, que identificou como fatores de risco insuficiência renal crônica e diabetes. Entretanto, esses estudos limitam suas conclusões a uma população especifica de pacientes. Tomografia Computadorizada contrastada como causa de NIC foi menos estudada. Objetivo: Reportar incidência de NIC numa população de pacientes internados em hospital terciário submetidos à tomografia computadorizada com contraste, identificando possíveis fatores de risco evitáveis. Métodos: Realizamos um estudo de coorte prospectivo com pacientes internados em hospital terciário e que necessitaram de tomografia computadorizada com contraste. O desfecho primário foi desenvolvimento de NIC, verificado por meio da variação da creatinina sérica ou taxa de filtração glomerular em 48 ou 72 horas. Em entrevista clínica, verificamos possíveis fatores de risco, assim como medidas preventivas instituídas pela equipe médica e suas possíveis associações com desenvolvimento de NIC. Resultados: Do total de 410 pacientes, 35 (8,5%) desenvolveram NIC. Houve correlação positiva entre desenvolvimento de NIC e a presença de diabetes mellitus (OR = 2,15; 95%CI 1,35-4,06; p = 0,02), insuficiência cardíaca (OR = 2,23; 95%CI 1,18-8,8; p = 0,022), e insuficiência renal (OR = 3,36; 95%CI 1,57-7,17; p = 0,002). Conclusão: A incidência de NIC varia de acordo com a população. Diabetes, insuficiência cardíaca e insuficiência renal foram fatores de risco independentes para o desenvolvimento de NIC. Mais estudos são ...

Humans , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Caspases/metabolism , Liver Neoplasms/drug therapy , Sulindac/analogs & derivatives , Sulindac/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/physiology , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/pathology , Cell Division/drug effects , DNA, Neoplasm/antagonists & inhibitors , DNA, Neoplasm/biosynthesis , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Liver Neoplasms/enzymology , Liver Neoplasms/pathology , Sphingomyelin Phosphodiesterase/metabolism , Tumor Cells, Cultured
Braz. j. phys. ther. (Impr.) ; 18(6): 513-520, 09/01/2015. graf
Article in English | LILACS | ID: lil-732354


BACKGROUND: Knowing the potential for and limitations of information generated using different evaluation instruments favors the development of more accurate functional diagnoses and therapeutic decision-making. OBJECTIVE: To investigate the relationship between the number of compensatory movements when climbing up and going down stairs, age, functional classification and time taken to perform a tested activity (TA) of going up and down stairs in boys with Duchenne muscular dystrophy (DMD). METHOD: A bank of movies featuring 30 boys with DMD performing functional activities was evaluated. Compensatory movements were assessed using the climbing up and going down stairs domain of the Functional Evaluation Scale for Duchenne Muscular Dystrophy (FES-DMD); age in years; functional classification using the Vignos Scale (VS), and TA using a timer. Statistical analyses were performed using the Spearman correlation test. RESULTS: There is a moderate relationship between the climbing up stairs domain of the FES-DMD and age (r=0.53, p=0.004) and strong relationships with VS (r=0.72, p=0.001) and TA for this task (r=0.83, p<0.001). There were weak relationships between the going down stairs domain of the FES-DMD-going down stairs with age (r=0.40, p=0.032), VS (r=0.65, p=0.002) and TA for this task (r=0.40, p=0.034). CONCLUSION: These findings indicate that the evaluation of compensatory movements used when climbing up stairs can provide more relevant information about the evolution of the disease, although the activity of going down stairs should be investigated, with the aim of enriching guidance and strengthening accident prevention. Data from the FES-DMD, age, VS and TA can be used in a complementary way to formulate functional diagnoses. Longitudinal studies and with broader age groups may supplement this information. .

CONTEXTUALIZAÇÃO: Conhecer as potencialidades e limitações das informações geradas por diferentes instrumentos de avaliação favorece o desenvolvimento mais preciso do diagnóstico funcional e da tomada de decisão terapêutica. OBJETIVO : Investigar a relação entre o número de movimentos compensatórios ao subir e descer escadas, idade, classificação funcional e tempo de realização de atividade (TA) em meninos com Distrofia Muscular de Duchenne (DMD). MÉTODO : Foi utilizado banco de filmes de 30 meninos com DMD realizando atividades funcionais. Os movimentos compensatórios foram avaliados pela Escala de Avaliação Funcional para Distrofia Muscular de Duchenne (FES-DMD), domínio subir e descer escada; a idade, mensurada em anos; a classificação funcional foi pesquisada pela Escala de Vignos (EV), e o TA foi cronometrado. Foi utilizado o teste de correlação de Spearman. RESULTADOS : Existe moderada relação entre a FES-DMD-subir escada e a idade (r=0,53, p=0,004) e forte relação com a EV (r=0,72, p=0,001) e TA dessa tarefa (r=0,83, p<0,001). Houve fraca relação entre a FES-DMD-descer escada e a idade (r=0,40, p=0,032), EV (r=0,65, p=0,002) e o TA dessa tarefa (r=0,40, p=0,034). CONCLUSÃO : Esses achados indicam que a avaliação da tarefa de subir escada pode trazer informações mais relevantes sobre a evolução da doença, embora a atividade de descer escada deva ser pesquisada visando à orientação e prevenção de acidentes. A utilização conjunta de dados provenientes da FES-DMD, da idade e do TA pode se complementar para formulação do diagnóstico funcional. Estudos longitudinais e com outras faixas etárias mais amplas podem complementar tal informação. .

Humans , Male , Prostatic Hyperplasia/metabolism , Receptors, Androgen/metabolism , Binding, Competitive , Buffers , Charcoal , Cytosol/metabolism , Dextrans , Dihydrotestosterone/metabolism , Electrophoresis, Agar Gel , Enzyme Activation/drug effects , Estrenes/metabolism , Metribolone , Molybdenum/pharmacology , Progesterone/metabolism , Protease Inhibitors/pharmacology , Temperature , Tartrates/pharmacology , Testosterone Congeners/metabolism
Rev. bras. enferm ; 67(5): 692-699, Sep-Oct/2014. tab
Article in Portuguese | LILACS, BDENF | ID: lil-731217


Estudo prospectivo, tipo coorte que visou identificar a influência da sobrecarga de trabalho da Enfermagem na ocorrência de incidentes sem lesão e eventos adversos em 399 pacientes internados em Unidades de Terapia Intensiva (UTI). Para coleta de dados, foi aplicado um questionário estruturado e feita análise de prontuários. Nessas admissões, aproximadamente 78% dos incidentes sem lesão e eventos adversos em pacientes foram relacionados à esfera da Enfermagem. Essas ocorrências foram atribuídas à sobrecarga de trabalho, aumentaram o número de dias de internação e o risco de óbito dos pacientes estudados. É fundamental que os gerentes de enfermagem atuem no processo de gestão de pessoas no âmbito hospitalar, evitando a sobrecarga de trabalho e proporcionando, consequentemente, aumento da segurança do paciente.

This prospective cohort study aimed to identify the influence of nursing work overload on the occurrence of incidents without injury and adverse events in 399 patients hospitalized in Intensive Care Units (ICU). For data collection, a structured questionnaire was administered and an analysis of medical records was performed. In these admissions, approximately 78% of incidents without injury and adverse events in patients were related to the sphere of Nursing. These occurrences were attributed to overwork, increased the number of days of hospitalization and the risk of death of patients. It is essential that nursing managers work on the staff hospital management avoiding work overload to contribute for patient safety.

Estudio de cohorte prospectivo que tuvo como objetivo identificar la influencia de la carga de trabajo de enfermería en la ocurrencia de incidentes sin lesión y los eventos adversos en 399 pacientes ingresados en Unidades de Cuidados Intensivos (UCI). Para la recolección de datos, se administró un cuestionario estructurado y realizó el análisis de los registros en prontuarios. En estos ingresos, aproximadamente el 78% de los incidentes sin lesión y los eventos adversos en los pacientes estaban relacionados con el ámbito de la Enfermería. Estos hechos fueron atribuidos al exceso de trabajo, aumentaran el número de días de hospitalización y el riesgo de muerte de los pacientes. Es esencial que los responsables de enfermería que actúan en el proceso de gestión de las personas en los hospitales, eviten el exceso de trabajo y por lo tanto proporcionar una mayor seguridad de los pacientes.

Animals , Rats , Drugs, Chinese Herbal/pharmacology , Hepatocytes/drug effects , Apoptosis/drug effects , Caspases/metabolism , Cell Division/drug effects , Cell Line , Enzyme Activation/drug effects , Hepatocytes/cytology , Liver Cirrhosis/drug therapy , Phytotherapy , Salvia miltiorrhiza
Mem. Inst. Oswaldo Cruz ; 109(3): 315-323, 06/2014. tab, graf
Article in English | LILACS | ID: lil-711722


Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

Animals , Humans , Male , Mice , Nitroreductases/drug effects , Thiadiazoles , Triazoles , Trypanocidal Agents , Trypanosoma brucei brucei/drug effects , Trypanosoma brucei brucei/enzymology , Comet Assay , DNA Damage/drug effects , Enzyme Activation/drug effects , Nitroreductases/metabolism , Parasitic Sensitivity Tests , Structure-Activity Relationship , Thiadiazoles/chemistry , Thiadiazoles/metabolism , Thiadiazoles/pharmacology , Thiadiazoles/toxicity , Triazoles/chemistry , Triazoles/metabolism , Triazoles/pharmacology , Triazoles/toxicity , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Trypanocidal Agents/toxicity , Trypanosoma cruzi/drug effects
Braz. j. med. biol. res ; 47(1): 60-69, 01/2014. graf
Article in English | LILACS | ID: lil-697674


MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

Animals , Female , Humans , Mice , Antibiotics, Antineoplastic/pharmacology , Drug Resistance, Neoplasm , Doxorubicin/pharmacology , MicroRNAs/physiology , Drug Resistance, Neoplasm/genetics , Enzyme Activation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , MicroRNAs/genetics , Tryptophan Hydroxylase/drug effects , /drug effects
Article in English | WPRIM | ID: wpr-191059


Wound healing is initiated and progressed by complex integrated process of cellular, physiologic, and biochemical events, such as inflammation, cell migration and proliferation. Interleukin 6 (IL-6) is a multifunctional cytokine, and it could regulate the inflammatory response of wound healing process in a timely manner. Hyaluronic acid (HA) is an essential component of the extracellular matrix, and contributes significantly to cell proliferation and migration. The purpose of this study was to investigate the effects of IL-6 or/and HA on the cell migration process in human keratinocytes. Combining IL-6 and HA significantly increased the cell migration in scratch based wound healing assay. The phosphorylation of extracellular-signal-regulated kinase (ERK) was significantly increased after 1 hr of IL-6 and HA treatment, but the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was not. We also found that significant increase of the NF-kappaB translocation from cytoplasm into nucleus after 1 hr of IL-6 or/and HA treatments. This study firstly showed that synergistic effects of combining IL-6 and HA on the cell migration of wound healing by activation of ERK and NF-kappaB signaling. Further studies might be required to confirm the synergistic effects of HA and IL-6 in the animal model for the development of a novel therapeutic mixture for stimulation of wound healing process.

Active Transport, Cell Nucleus/drug effects , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Enzyme Activation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Hyaluronic Acid/pharmacology , Interleukin-6/pharmacology , Keratinocytes/metabolism , MAP Kinase Signaling System/drug effects , NF-kappa B/metabolism , Phosphorylation/drug effects , Protein Transport/drug effects , Wound Healing , p38 Mitogen-Activated Protein Kinases/metabolism
Biol. Res ; 47: 1-5, 2014. ilus, graf, tab
Article in English | LILACS | ID: biblio-950716


BACKGROUND: This study evaluated the cytotoxic activity of extracts from Caesalpinia sappan heartwood against multiple cancer cell lines using an MTT cell viability assay. The cell death though induction of apoptosis was as indicated by DNA fragmentation and caspase-3 enzyme activation. RESULTS: A methanol extract from C. sappan (MECS) showed cytotoxic activity against several of the cancer cell lines. The most potent activity exhibited by the MECS was against HeLa cells with an IC50 value of 26.5 ± 3.2 µg/mL. Treatment of HeLa cells with various MECS concentrations resulted in growth inhibition and induction of apoptosis, as indicated by DNA fragmentation and caspase-3 enzyme activation. CONCLUSION: This study is the first report of the anticancer properties of the heartwood of C. sappan native to Vietnam. Our findings demonstrate that C. sappan heartwood may have beneficial applications in the field of anticancer drug discovery.

Humans , Animals , Female , Mice , Plant Extracts/pharmacology , Apoptosis , Caesalpinia/chemistry , Plant Vascular Bundle/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Tetrazolium Salts , Vietnam , Drug Screening Assays, Antitumor/methods , HeLa Cells , Cell Survival , Inhibitory Concentration 50 , Cytotoxins/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Methanol , Enzyme Activation/drug effects , Caspase 3/metabolism , DNA Fragmentation , Formazans , Growth Inhibitors/pharmacology , Indicators and Reagents , Mice, Inbred C57BL , Antineoplastic Agents, Phytogenic/isolation & purification
Indian J Biochem Biophys ; 2013 Dec; 50(6): 485-491
Article in English | IMSEAR | ID: sea-150261


Triptolide, a diterpene derived from Tripterygium wilfordii Hook f., a Chinese medicinal herb, has been reported to inhibit cell proliferation and induce apoptosis in various human cancer cells, but its anticancer effects on human osteosarcoma cells have not yet been elucidated. In this study, we investigated whether triptolide induces apoptosis in human osteosarcoma cells and the underlying molecular mechanisms. We firstly demonstrated that triptolide inhibited cell growth and induced apoptosis in U2OS cells. Western blot analysis showed that the levels of procaspase-8, -9, Bcl-2, Bid and mitochondrial cytochrome c were downregulated in triptolide-treated U2OS cells, whereas the levels of Fas, FasL, Bax, cytosolic cytochrome c, cleaved caspase-3 and cleaved PARP were upregulated. These results suggest that triptolide induces apoptosis in U2OS cells by activating both death receptor and mitochondrial apoptotic pathways.

Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Diterpenes/pharmacology , Enzyme Activation/drug effects , Epoxy Compounds/pharmacology , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , M Phase Cell Cycle Checkpoints/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Osteosarcoma/pathology , Phenanthrenes/pharmacology , Poly(ADP-ribose) Polymerases/metabolism , Proteolysis/drug effects
Indian J Biochem Biophys ; 2013 Oct; 50(5): 419-427
Article in English | IMSEAR | ID: sea-150251


There is growing evidence that ouabain, a cardiotonic steroid may promote growth of cardiac and vascular myocytes, indicating its novel role in cell growth and proliferation, without appreciable inhibition of the sodium pump. The mechanism(s) by which low dose of ouabain produces pulmonary artery smooth muscle cell proliferation, a prerequisite for right ventricular hypertrophy, is currently unknown. Here, we analyzed the effects of low dose of ouabain (10 nM) on increase in [Ca2+]i, m-calpain and protein kinase C (PKC) activities on pulmonary artery smooth muscle cell proliferation and determined their sequential involvement in this scenario. We treated bovine pulmonary artery smooth muscle cells with a low dose of ouabain (10 nM) and determined [Ca2+]i in the cells by fluorometric assay using fura2-AM, m-calpain activity by fluorometric assay using SLLVY-AMC as the substrate, PKC activity using an assay kit and assay of Na+/K+ATPase activity spectrophotometrically. We purified m-calpain and PKCα by standard chromatographic procedure by HPLC and then studied cleavage of the purified PKCα by m-calpain using Western immunoblot method. Subsequently, we performed cell proliferation assay utilizing the redox dye resazunin. We used selective inhibitors of [Ca2+]i (BAPTA-AM), m-calpain (MDL28170), PKCα (Go6976) and determined their involvement in ouabain (10 nM)-mediated smooth muscle cell proliferation. Our results suggested that treatment of bovine pulmonary artery smooth muscle cells with a low dose of ouabain (10 nM) increased [Ca2+]i and subsequently stimulated m-calpain activity and proteolytically activated PKCα in caveolae (signaling microdomain also known as signalosomes) of the cells. Upon activation, PKCα increased the smooth muscle cell proliferation via Go/G1 to S/G2-M phase transition. Thus, [Ca2+]i-mCalpain-PKCα signaling axis plays a crucial role during low dose of ouabain-mediated pulmonary artery smooth muscle cell proliferation.

Amino Acid Sequence , Animals , Calpain/metabolism , Cattle , Caveolae/drug effects , Caveolae/metabolism , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Molecular Sequence Data , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Ouabain/pharmacology , Protein Kinase C-alpha/chemistry , Protein Kinase C-alpha/metabolism , Proteolysis/drug effects , Pulmonary Artery/cytology , Sodium-Potassium-Exchanging ATPase/metabolism
Indian J Biochem Biophys ; 2013 Oct; 50(5): 387-401
Article in English | IMSEAR | ID: sea-150248


The purpose of this study was to elucidate the mechanism of the airborne poultry dust (particulate matter, PM)-induced respiratory tract inflammation, a common symptom in agricultural respiratory diseases. The study was based on the hypothesis that poultry PM would induce the release of inflammatory cytokine interleukin-8 (IL-8) by respiratory epithelial cells under the upstream regulation by cytosolic phospholipase A2 (cPLA2) activation and subsequent formation of cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites (eicosanoids). Human lung epithelial cells (A549) in culture were treated with the poultry PM (0.1-1.0 mg) for different lengths of time, following which PLA2 activity, release of eicosanoids and secretion of IL-8 in cells were determined. Poultry PM (1.0 mg/ml) caused a significant activation of PLA2 in a time-dependent manner (15-60 min), which was significantly attenuated by the calcium-chelating agents, cPLA2-specific inhibitor (AACOCF3) and antioxidant (vitamin C) in A549 cells. Poultry PM also significantly induced the release of COX- and LOX-catalyzed eicosanoids (prostaglandins, thromboxane A2 and leukotrienes B4 and C4) and upstream activation of AA LOX in the cells. Poultry PM also significantly induced release of IL-8 by the cells in a dose- and time-dependent manner, which was significantly attenuated by the calcium chelating agents, antioxidants and COX- and LOX-specific inhibitors. The current study for the first time revealed that the poultry PM-induced IL-8 release from the respiratory epithelial cells was regulated upstream by reactive oxygen species, cPLA2-, COX- and LOX-derived eicosanoid lipid signal mediators.

Agriculture , Animals , Antioxidants/pharmacology , Arachidonic Acid/metabolism , Arachidonic Acid/metabolism , Biocatalysis , Cell Line , Cytokines/metabolism , Dose-Response Relationship, Drug , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Eicosanoids/metabolism , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Humans , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-8/metabolism , Lipoxygenases/metabolism , Particulate Matter/chemistry , Particulate Matter/pharmacology , Phospholipases A2, Cytosolic/antagonists & inhibitors , Phospholipases A2, Cytosolic/metabolism , Poultry , Prostaglandin-Endoperoxide Synthases/metabolism , Reactive Oxygen Species/metabolism , Respiratory Mucosa/cytology , Respiratory Mucosa/metabolism , Respiratory Mucosa/metabolism , Signal Transduction/drug effects , Solvents/chemistry , Time Factors