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1.
Article in English | WPRIM | ID: wpr-880705

ABSTRACT

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).


Subject(s)
ADP-Ribosylation , COVID-19/metabolism , DNA Repair/physiology , Evolution, Molecular , Humans , Models, Biological , Models, Molecular , N-Glycosyl Hydrolases/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Protein Domains , SARS-CoV-2/pathogenicity
2.
Salud colect ; 11(1): 23-34, ene.-mar. 2015. tab
Article in Spanish | LILACS | ID: lil-746682

ABSTRACT

Un tercio de la población mundial carece de acceso a los medicamentos y la situación es peor en los países pobres, en los que hasta un 50% de la población carece de acceso. El fracaso de los sistemas actuales de incentivos, basados en la propiedad intelectual, para ofrecer los productos farmacéuticos necesarios, especialmente en los países del sur, llama a la acción. Los problemas relacionados con el acceso a medicamentos no pueden ser resueltos tan solo a través de mejoras o adaptaciones de los modelos de incentivos existentes. El modelo del sistema de propiedad intelectual no ofrece la innovación necesaria para los países en desarrollo, se necesitan nuevos mecanismos que de forma simultánea y eficaz promuevan la innovación y el acceso a los medicamentos. Un tratado internacional vinculante sobre investigación y desarrollo, que se negocie bajo los auspicios de la Organización Mundial de la Salud, puede proporcionar el marco adecuado para garantizar el establecimiento de prioridades, la coordinación y la financiación sostenible de los medicamentos a precios asequibles para los países en desarrollo.


One-third of the global population lacks access to medications; the situation is worse in poor countries, where up to 50% of the population lacks access. The failure of current incentive systems based in intellectual property to offer the necessary pharmaceutical products, especially in the global south, is a call to action. Problems related to drug access cannot be solved solely through improvements or modifications in the existing incentive models. The intellectual property system model does not offer sufficient innovation for developing countries; new mechanisms that effectively promote innovation and drug access simultaneously are needed. A binding international agreement on research and development, negotiated under the auspices of the World Health Organization, could provide an adequate framework for guaranteeing priority-setting, coordination, and sustainable financing of drugs at reasonable prices for developing countries.


Subject(s)
Animals , Humans , Mice , Chromatin/metabolism , Inflammation Mediators/metabolism , Oxidative Stress/physiology , Poly(ADP-ribose) Polymerases/metabolism , Cell Death/physiology , Chromatin/genetics , DNA Repair , Enzyme Activation , Poly(ADP-ribose) Polymerases/genetics , Signal Transduction , Transcription, Genetic
3.
Cad. saúde pública ; 31(3): 565-574, 03/2015.
Article in Portuguese | LILACS | ID: lil-744838

ABSTRACT

A epidemia de HIV/AIDS é um sério problema de saúde pública em Moçambique, que convive com altas taxas de prevalência do HIV. O impacto da epidemia é agravado pelo forte estigma que atinge as pessoas soropositivas. O objetivo deste estudo foi investigar, com base em uma perspectiva socioantropológica, a experiência de mulheres HIV positivo nos bairros populares de Maputo e como lidam com o estigma e a discriminação. Foram realizadas entrevistas semiestruturadas com dez mulheres HIV positivo, residentes nos bairros populares de Maputo. Os resultados mostram como a desigualdade de gênero atua de forma importante na construção da vulnerabilidade das mulheres ao HIV, assim como em sua estigmatização e discriminação. No enfrentamento do estigma, as mulheres procuram preservar o sigilo do diagnóstico buscando apoio na reunião em grupos de pares HIV positivo. É fundamental que se implementem políticas públicas voltadas para o empoderamento das mulheres e redução do estigma associado ao HIV/AIDS.


The HIV/AIDS epidemic is a serious public health problem in Mozambique. The country has high prevalence rates, and the epidemic's impact is aggravated by the stigma affecting HIV-positive persons. This study takes a socio-anthropological perspective to analyze the experience of HIV-positive women in poor neighborhoods of Maputo and the ways they cope with stigma and discrimination. Semi-structured interviews were conducted with 10 HIV-positive women. The results show how gender inequalities increase women's vulnerability to HIV and contribute to their stigmatization and discrimination. In dealing with stigma, women try to keep their diagnosis confidential, seeking support in group meetings with others living with HIV. Public policies should focus on women's empowerment and the reduction of HIV/AIDS-related stigma.


El VIH/SIDA es un problema de salud pública grave en Mozambique, que convive con altas tasas de prevalencia del VIH. El impacto de la epidemia se ve agravada por el fuerte estigma que afecta a las personas con VIH. El objetivo de este estudio fue investigar, desde una perspectiva antropológica, la experiencia de las mujeres VIH positivas en los barrios populares de Maputo y cómo enfrentan el estigma y la discriminación. Se realizaron entrevistas semi-estructuradas con 10 mujeres VIH positivas que viven en barrios pobres de Maputo. Los resultados muestran cómo la desigualdad de género juega un papel importante en la construcción de la vulnerabilidad de las mujeres frente al VIH, así como en la estigmatización y discriminación. Para hacer frente el estigma, las mujeres buscan preservar la confidencialidad del diagnóstico y buscar apoyo en la reunión de grupos de pares con VIH. Es imprescindible implementar políticas públicas enfocadas al empoderamiento de las mujeres y a la reducción del estigma asociado con el VIH/SIDA.


Subject(s)
Animals , Female , Humans , Mice , Fibrosarcoma/diagnosis , Fibrosarcoma/pathology , Gene Expression Profiling , Hybridization, Genetic/physiology , Lymphocytes/metabolism , Lymphocytes/pathology , Models, Biological , Transcription, Genetic/physiology , Adenosine Deaminase/metabolism , /metabolism , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , /metabolism , /pathology , /metabolism , /pathology , Cell Line, Tumor , /metabolism , Gene Expression Regulation, Neoplastic/physiology , Mice, Inbred BALB C , Poly(ADP-ribose) Polymerases/metabolism , Sensitivity and Specificity
4.
Cad. saúde pública ; 31(3): 463-475, 03/2015. tab, graf
Article in English | LILACS | ID: lil-744840

ABSTRACT

Cyberbullying is a new form of violence that is expressed through electronic media and has given rise to concern for parents, educators and researchers. In this paper, an association between cyberbullying and adolescent mental health will be assessed through a systematic review of two databases: PubMed and Virtual Health Library (BVS). The prevalence of cyberbullying ranged from 6.5% to 35.4%. Previous or current experiences of traditional bullying were associated with victims and perpetrators of cyberbullying. Daily use of three or more hours of Internet, web camera, text messages, posting personal information and harassing others online were associated with cyberbullying. Cybervictims and cyberbullies had more emotional and psychosomatic problems, social difficulties and did not feel safe and cared for in school. Cyberbullying was associated with moderate to severe depressive symptoms, substance use, ideation and suicide attempts. Health professionals should be aware of the violent nature of interactions occurring in the virtual environment and its harm to the mental health of adolescents.


Cyberbullying, uma nova forma de violência expressa por meio da mídia eletrônica, tem preocupado pais, educadores e pesquisadores. A associação entre cyberbullying e a saúde mental dos adolescentes será revisada. Revisão sistemática em duas bases de dados: PubMed e a Biblioteca Virtual em Saúde (BVS). A prevalência do cyberbullying variou entre 6,5% a 35,4%. Bullying tradicional prévio ou atual estava associado às vítimas e agressores do cyberbullying. Uso diário de três ou mais horas de Internet, web câmera, mensagens de texto, postar informações pessoais e assediar outros online estavam associados ao cyberbullying. "Cybervítimas" e cyberbullies tinham mais problemas emocionais, psicossomáticos, dificuldades sociais, e não se sentiam seguros e cuidados na escola. O cyberbullying estava associado à sintomatologia depressiva moderada e grave, uso de substâncias, ideação e tentativas de suicídio. Profissionais de saúde devem conhecer as interações de natureza violenta que ocorrem no ambiente virtual e de seus agravos para a saúde mental dos adolescentes.


Se revisa la asociación entre el acoso cibernético y la salud mental de los adolescentes. Se realiza una revisión sistemática de dos bases de datos: PubMed y la Biblioteca Virtual en Salud (BVS). La prevalencia de ciberacoso varió de un 6,5% a un 35,4%. Los acosos cibernéticos tradicionales -pasados o actuales- se asociaron con las víctimas y los acosadores cibernéticos. El uso diario de tres o más horas de Internet, cámara web, mensajes de texto, la publicación de información personal y acosar a los demás se asociaron con el acoso cibernético. Cibervíctimas y acosadores cibernéticos tenían más problemas emocionales, psicosomáticos, dificultades sociales y no se sentían seguros y cuidados en la escuela. El ciberacoso se asoció con síntomas de moderados a graves de depresión, abuso de sustancias, ideación suicida e intentos de suicidio. Los profesionales de salud deben conocer la naturaleza violenta de las interacciones que se producen en el entorno virtual y sus peligros para la salud mental de los adolescentes.


Subject(s)
Animals , Mice , Antibody Formation/immunology , Poly(ADP-ribose) Polymerases/deficiency , B-Lymphocytes/immunology , Cell Proliferation , Cells, Cultured , Germinal Center/immunology , Immunization , Immunoglobulin Class Switching/immunology , Immunoglobulins/blood , Lipopolysaccharides/immunology , Lymphocyte Activation/immunology , Lymphocyte Cooperation/immunology , Mice, Mutant Strains , Poly(ADP-ribose) Polymerases/metabolism , T-Lymphocytes/immunology
6.
Rev. Soc. Bras. Med. Trop ; 48(1): 11-17, jan-feb/2015. tab, graf
Article in English | LILACS, SES-SP | ID: lil-742966

ABSTRACT

INTRODUCTION : Brazilian spotted fever (BSF) is a disease transmitted by ticks for which the etiological agent is Rickettsia rickettsii. The present essay evaluates the risk factors associated with the transmission of cases of BSF in the time period between 2003 and 2013 in the Piracicaba river basin, state of São Paulo. METHODS : This essay presents a retrospective study to identify the factors associated with the transmission of cases of BSF among all suspected cases identified by the System for Epidemiological Surveillance of São Paulo (CVE). After the description of temporal distribution (onset of symptoms) and the environmental and demographic variations of the confirmed and discarded cases, a multiple logistic regression model was applied. RESULTS : We searched 569 probable locations of infection (PLI) with 210 (37%) confirmed cases of BSF and 359 (63%) discarded cases. The associated variables for the confirmation of BSF in the multiple logistic model using a confidence interval (CI) of 95% were age (OR = 1.025 CI: 1.015-1.035), the presence of Amblyomma sculptum in the environment (OR = 1.629 CI: 1.097-2.439), the collection of ticks from horses (OR = 1.939 CI: 0.999-3.764), the presence of capybaras (OR = 1.467 CI: 1.009-2.138), an urban environment (OR = 1.515 CI: 1.036-2.231), and the existence of a dirty pasture (OR = 1.759 CI: 1.028-3.003). CONCLUSIONS : The factors associated with the confirmation of BSF cases included an urban environment, age, presence of the A. sculptum vector, the collection of ticks from horses, the presence of a capybara population, and a dirty pasture environment. .


Subject(s)
Animals , Male , Rats , Apoptosis/genetics , Benzofurans/therapeutic use , Apoptosis/drug effects , Blotting, Western , Cell Line , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Electrophoresis, Gel, Two-Dimensional , Hemodynamics/drug effects , In Situ Nick-End Labeling , Microscopy, Electron, Transmission , Mitochondria/drug effects , Mitochondria/metabolism , Myocardial Infarction/metabolism , Myocardium/cytology , Myocardium/metabolism , Myocardium/ultrastructure , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , NF-kappa B/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Rats, Wistar , Signal Transduction/drug effects , Signal Transduction/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tandem Mass Spectrometry
7.
Rev. méd. Chile ; 143(2): 158-167, feb. 2015. ilus, graf, mapas, tab
Article in Spanish | LILACS | ID: lil-742566

ABSTRACT

Background: In Chile, gallbladder cancer (GBC) is one of the most important causes of death and gallstone disease (GSD) is its main risk factor. Abdominal ultrasonography (AU) is used for the diagnosis of GSD and cholecystectomy is used to prevent it. Aim: To estimate GSD prevalence in the general population and to assess the diagnostic and therapeutic coverage of GSD as a preventive strategy for GBC in Chile. Material and Methods: A standardized digestive symptoms questionnaire of the 2009-2010 Chilean National Health Survey was answered by 5412 adults over 15 years old. Self-reports of AU, GBD and cholecystectomies were recorded. Results: The prevalence of biliary-type pain was 7.1%. During the last five years, the prevalence of AU was 16%. GSD was reported in 20% of these tests and 84% of them were asymptomatic. The prevalence of AU was significantly lower in Araucanía region and among people with less than 12 years of education. Life cholecystectomy prevalence was 11% and reached 40% in people aged over 60 years. Women accounted for 75% of total cholecystectomies. Twenty-one percent of individuals who referred biliary-type pain, were studied with an AU. Only 60% of people with GSD confirmed by AU underwent a cholecystectomy. Conclusions: GSD affects at least 27% of the Chilean adult population. Important deficits and inequities in GSD diagnostic and therapeutic coverage were identified.


Subject(s)
Animals , Male , Rats , Gene Expression Regulation, Developmental , Poly(ADP-ribose) Polymerases/metabolism , Sertoli Cells/metabolism , Antioxidants , Cell Differentiation , Catalase/genetics , Catalase/metabolism , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Poly(ADP-ribose) Polymerases/genetics , Rats, Wistar , RNA, Messenger/metabolism , Sertoli Cells/cytology , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism
8.
Rev. méd. Chile ; 143(2): 175-182, feb. 2015. tab
Article in Spanish | LILACS | ID: lil-742568

ABSTRACT

Background: In 2007, a Clinical-Case-Portfolio (CCP) was introduced as a new assessment instrument for fourth grade undergraduate medical students. Since then, several changes have been implemented such as reduction on the number of clinical cases, peer review and the introduction of virtual patient to the portfolio. Aim: To describe the virtual patient model incorporated to the CCP and assess the perception of this change and its effects on the performance of undergraduate students. Material and Methods: Virtual patients were implemented based on prototype clinical cases with specific syndromes. Students’ perceptions about CCP before and after the introduction of virtual patients were evaluated using a validated questionnaire that was answered voluntarily and anonymously. Results: Overall perception of CCP significantly improved after the incorporation of virtual patients (97.1 ± 24.9 and 111.3 ± 25.7 points; 57.8 and 66.2% respectively). The same improvements were observed for the domains “Student Learning”, “Organization and Evaluation”, “Teaching Methodology” and “Integration”. In both years, students obtained high grades in CCP evaluations. However CCP grades were not significantly correlated with integrated final grades. Conclusions: The incorporation of virtual patients improved undergraduate students’ perception of CCP.


Subject(s)
Animals , Mice , Apoptosis , Axin Protein/metabolism , Enzyme Activation , Poly(ADP-ribose) Polymerases/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Aurora Kinases , Adenosine Triphosphate/metabolism , Apoptosis Inducing Factor/genetics , Apoptosis Inducing Factor/metabolism , Cell Line , Cell Membrane/metabolism , Cell Membrane/physiology , Mitochondria/metabolism , Protein Kinase Inhibitors/pharmacology , RNA Interference , Time-Lapse Imaging
9.
Rev. méd. Chile ; 143(2): 213-222, feb. 2015. graf, tab
Article in Spanish | LILACS | ID: lil-742573

ABSTRACT

Background: The Quality of life Bipolar Disorder (QoL.BD) Questionnaire specifically measures quality of life in patients with bipolar disorder. Aim: To adapt a version translated into Spanish of the questionnaire and assess its validity in Chilean patients. Material and Methods: The QoL. BD was adapted to the Chilean population through the back-translation method and then administered to 32 adult patients with a bipolar disorder and 31 subjects without the disease, both groups with similar socioeconomic status. To confirm the diagnosis, the International Neuropsychiatric Interview (MINI), Young (YMRS) and Hamilton (HAM-D) scales were applied. Quality of life was assessed using the SF-36v.2 survey. We determined internal consistency, reliability, convergent validity, the cut-off point, and the sensibility and specificity of the scale. Results: The Chilean version of the Questionnaire [QoL. BD-CL] had a high reliability (α = 0.95) and a high validity in reference to external criteria (correlation coefficients with SF-36 ranging from 0.453 and 0.819; p < 0.01). A cut-off point of 170, with sensitivity of 87.9% and specificity of 80% was determined. Conclusions: QoL.BD-CL has adequate psychometric properties, as well as an adequate sensitivity and specificity to distinguish between negative and positive perceptions of life quality in Chilean patients with bipolar disorders.


Subject(s)
Animals , Mice , Poly(ADP-ribose) Polymerases/metabolism , Cell Death/genetics , Cell Death/physiology , DNA Damage/genetics , DNA Damage/physiology , Embryo, Mammalian/metabolism , Genotype , In Situ Nick-End Labeling , Mice, Knockout , Polymerase Chain Reaction , Poly(ADP-ribose) Polymerases/deficiency , Poly(ADP-ribose) Polymerases/genetics
10.
Rev. méd. Chile ; 143(2): 237-243, feb. 2015. ilus
Article in Spanish | LILACS | ID: lil-742575

ABSTRACT

Currently, there is no discussion on the need to improve and strengthen the institutional health care modality of FONASA (MAI), the health care system used by the public services net and by most of the population, despite the widely known and long lasting problems such as waiting lists, hospital debt with suppliers, lack of specialists and increasing services purchase transference to the private sector, etc. In a dichotomous sectorial context, such as the one of health’s social security in Chile (the state on one side and the market on the other), points of view are polarized and stances tend to seek refuge within themselves. As a consequence, to protect the public solution is commonly associated with protecting the “status quo”, creating an environment that is reluctant to change. The author proposes a solution based on three basic core ideas, which, if proven effective, can strengthen each other if combined properly. These are: network financing management, governance of health care services in MAI and investments and human resources in networked self-managed institutions. The proposal of these core ideas was done introducing a reality testing that minimizes the politic complexity of their implementation.


Subject(s)
Animals , Humans , Rats , AMP-Activated Protein Kinases/metabolism , Antioxidants/therapeutic use , Autophagy/drug effects , Signal Transduction/drug effects , Sirtuin 1/metabolism , Stilbenes/therapeutic use , Cell Line, Transformed , Dose-Response Relationship, Drug , Doxycycline/pharmacology , Gene Expression Regulation/drug effects , Insecticides/toxicity , Microscopy, Immunoelectron/methods , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Mutation/genetics , Poly(ADP-ribose) Polymerases/metabolism , RNA, Small Interfering/pharmacology , Rotenone/toxicity , Time Factors , alpha-Synuclein/genetics , alpha-Synuclein/metabolism
11.
Rev. bras. cir. cardiovasc ; 30(1): 55-62, Jan-Mar/2015. tab
Article in English | LILACS | ID: lil-742887

ABSTRACT

Introduction: Complete denervation of transplanted heart exerts protective effect against postoperative atrial fibrillation; various degrees of autonomic denervation appear also after transection of ascending aorta during surgery for aortic aneurysm. Objective: This study aimed to evaluate if the level of cardiac denervation obtained by resection of ascending aorta could exert any effect on postoperative atrial fibrillation incidence. Methods: We retrospectively analysed the clinical records of 67 patients submitted to graft replacement of ascending aorta (group A) and 132 with aortic valve replacement (group B); all episodes of postoperative atrial fibrillation occurred during the 1-month follow-up have been reported. Heart Rate Variability parameters were obtained from a 24-h Holter recording; clinical, echocardiographic and treatment data were also evaluated. Results: Overall, 45% of patients (group A 43%, group B 46%) presented at least one episode of postoperative atrial fibrillation. Older age (but not gender, abnormal glucose tolerance, ejection fraction, left atrial diameter) was correlated with incidence of postoperative atrial fibrillation. Only among a subgroup of patients with aortic transection and signs of greater autonomic derangement (heart rate variability parameters below the median and mean heart rate over the 75th percentile), possibly indicating more profound autonomic denervation, a lower incidence of postoperative atrial fibrillation was observed (22% vs. 54%). Conclusion: Transection of ascending aorta for repair of an aortic aneurysm did not confer any significant protective effect from postoperative atrial fibrillation in comparison to patients with intact ascending aorta. It could be speculated that a limited and heterogeneous cardiac denervation was produced by the intervention, creating an eletrophysiological substrate for the high incidence of postoperative atrial fibrillation observed. .


Introdução: Denervação completa do coração transplantado exerce efeito protetor contra a fibrilação atrial no pós-operatório; vários graus de denervação autonômica aparecem também após a transecção da aorta ascendente durante a cirurgia de aneurisma da aorta. Objetivo: Este estudo teve como objetivo avaliar se o nível de denervação cardíaca obtida por ressecção da aorta ascendente poderia exercer algum efeito sobre a incidência de fibrilação atrial no pós-operatório. Métodos: Foram analisados retrospectivamente os prontuários de 67 pacientes submetidos a enxerto de substituição de aorta torácica (grupo A) e 132 com a substituição da valva aórtica (grupo B). Foram relatados todos os episódios de fibrilação atrial pós-operatória ocorridos durante 1 mês de seguimento. Parâmetros de variabilidade da frequência cardíaca foram obtidos a partir de 24 h de gravação do Holter; dados clínicos, ecocardiográficos e de tratamento também foram avaliados. Resultados: No geral, 45% dos pacientes (grupo A 43%, grupo B 46%) apresentaram pelo menos um episódio de fibrilação atrial no pós-operatório. Idade mais avançada (mas não gênero, tolerância à glicose anormal, fração de ejeção, diâmetro do átrio esquerdo) foi correlacionada com a incidência de fibrilação atrial pós-operatória. Apenas em um subgrupo de pacientes com transecção aórtica e sinais de maior desarranjo autonômico (parâmetros de variabilidade da frequência cardíaca abaixo da mediana e a média de frequência cardíaca acima do percentil 75), indicando possivelmente denervação autonômica mais profunda, foi observada menor incidência de fibrilação atrial pós-operatória (22% vs. 54%). Conclusão: Transecção da aorta ascendente para correção de um aneurisma da aorta não confere qualquer efeito protetor significativo de fibrilação atrial no pós-operatório em comparação com pacientes com aorta ascendente intacta. Pode-se especular que uma denervação cardíaca limitada e heterogênea foi produzida pela ...


Subject(s)
Animals , Mice , Brain/physiology , Nerve Tissue Proteins/physiology , Poly Adenosine Diphosphate Ribose/antagonists & inhibitors , Stroke/physiopathology , Apoptosis Inducing Factor/physiology , Blotting, Northern , Calcium/metabolism , Cell Death/physiology , Glutamic Acid/drug effects , Glutamic Acid/physiology , Mitochondria/metabolism , Nerve Tissue Proteins/metabolism , Protein Binding , Poly(ADP-ribose) Polymerases/metabolism , Poly(ADP-ribose) Polymerases/physiology , Receptors, N-Methyl-D-Aspartate/drug effects
12.
Rev. bras. cir. cardiovasc ; 30(1): 9-15, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-742890

ABSTRACT

Objective: To establish the determinants of the peak VO2 in heart transplant recipients. Methods: Patient's assessment was performed in two consecutive days. In the first day, patients performed the heart rate variability assessment followed by a cardiopulmonary exercise test. In the second day, patients performed a resting echocardiography. Heart transplant recipients were eligible if they were in a stable condition and without any evidence of tissue rejection diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular functional limitations such as osteoarthritis and chronic obstructive pulmonary disease were excluded from this study. Results: Sixty patients (68% male, 48 years and 64 months following heart transplantation) were assessed. Multivariate analysis selected the following variables: receptor's gender (P=0.001), receptor age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067 (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left atrium diameter). Conclusion: The determinants of the peak VO2 in heart transplant recipients were: receptor sex, age, Body Mass Index, heart rate reserve and left atrium diameter. Heart rate reserve was the unique variable positively associated with peak VO2. This data suggest the importance of the sympathetic reinnervation in peak VO2 in heart transplant recipients. .


Objetivo: Estabelecer os determinantes do VO2 pico em transplantados de coração. Métodos: Avaliação do paciente foi realizada em dois dias consecutivos. No primeiro dia, os pacientes realizaram a avaliação da variabilidade da frequência cardíaca seguida de um teste de esforço cardiopulmonar. No segundo dia, os pacientes realizaram ecocardiografia de repouso. Os transplantados foram elegíveis se estivessem em uma condição estável e sem qualquer evidência de rejeição diagnosticada por biópsia endomiocárdica. Pacientes com marca-passo, limitações funcionais não cardiovasculares, tais como osteoartrite e doença pulmonar obstrutiva crônica foram excluídos deste estudo. Resultados: Sessenta pacientes (68% do sexo masculino, 48 anos e 64 meses após o transplante cardíaco) foram avaliados. A análise multivariada selecionou as seguintes variáveis: sexo (P=0,001), idade (P=0,049), Índice de Massa Corporal (P=0,005), frequência cardíaca de reserva (P <0,0001), diâmetro do átrio esquerdo (P=0,016), variáveis do receptor. A análise multivariada mostrou r=0,77 e r2=0,6, com P <0,001. Equação: VO2=32,851 - 3,708 (sexo receptor) - 0,067 (idade receptor) - 0,318 (IMC receptor) + 0,145 (frequência cardíaca de reserva) - 0,111 (diâmetro de átrio esquerdo). Conclusão: Os determinantes do pico de VO2 em transplantados de coração foram: sexo receptor, idade, Índice de Massa Corporal, frequência cardíaca de reserva e diâmetro do átrio esquerdo. A frequência cardíaca de reserva foi a única variável positivamente associada com o pico de VO2. Estes dados sugerem a importância da reinervação simpática no pico de VO2 em transplantados de coração. .


Subject(s)
Animals , Female , Humans , Male , Mice , Asthma/immunology , Asthma/physiopathology , Calpain/metabolism , /metabolism , Poly(ADP-ribose) Polymerases/metabolism , /metabolism , Allergens/immunology , Asthma/metabolism , Disease Models, Animal , Eosinophilia/immunology , Inflammation/immunology , /antagonists & inhibitors , /immunology , Mice, Inbred BALB C , Mice, Knockout , Poly(ADP-ribose) Polymerases/genetics , Respiratory System/immunology , Respiratory System/physiopathology
13.
Rev. bras. cir. cardiovasc ; 30(1): 49-54, Jan-Mar/2015. tab
Article in English | LILACS | ID: lil-742891

ABSTRACT

Introduction: Perioperative myocardial infarction adversely affects the prognosis of patients undergoing coronary artery bypass graft and its diagnosis was hampered by numerous difficulties, because the pathophysiology is different from the traditional instability atherosclerotic and the clinical difficulty to be characterized. Objective: To identify the frequency of perioperative myocardial infarction and its outcome in patients undergoing coronary artery bypass graft. Methods: Retrospective cohort study performed in a tertiary hospital specialized in cardiology, from May 01, 2011 to April 30, 2012, which included all records containing coronary artery bypass graft records. To confirm the diagnosis of perioperative myocardial infarction criteria, the Third Universal Definition of Myocardial Infarction was used. Results: We analyzed 116 cases. Perioperative myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and use and cardiopulmonary bypass time were associated with this diagnosis and the mean age was significantly higher in this group. The diagnostic criteria elevated troponin I, which was positive in 99.1% of cases regardless of diagnosis of perioperative myocardial infarction. No significant difference was found between length of hospital stay and intensive care unit in patients with and without this complication, however patients with perioperative myocardial infarction progressed with worse left ventricular function and more death cases. Conclusion: The frequency of perioperative myocardial infarction found in this study was considered high and as a consequence the same observed average higher troponin I, more cases of worsening left ventricular function and death. .


Introdução: O infarto do miocárdio perioperatório afeta negativamente o prognóstico dos pacientes submetidos à cirurgia de revascularização do miocárdio e seu diagnóstico esbarra em inúmeras dificuldades, pois a fisiopatologia é diferente da tradicional instabilidade aterosclerótica e o quadro clínico de difícil caracterização. Objetivo: Identificar a frequência de infarto do miocárdio perioperatório e seu desfecho em pacientes submetidos à cirurgia de revascularização do miocárdio. Métodos: Coorte retrospectiva realizada em hospital terciário especializado em cardiologia, de 1 de maio de 2011 a 30 de abril de 2012, que incluiu todos os prontuários contendo registros de cirurgia de revascularização do miocárdio. Para confirmação diagnóstica do infarto do miocárdio perioperatório, foram utilizados os critérios da Third Universal Definition of Myocardial Infarction Resultados: Foram analisados 116 casos. Foi diagnosticado infarto do miocárdio perioperatório em 28 pacientes (24,1%). Número de enxertos e utilização e tempo de circulação extracorpórea foram fatores associados a este diagnóstico e a média de idade foi significativamente mais elevada neste grupo. O critério diagnóstico elevação de troponina I foi positivo em 99,1% dos casos, independentemente do diagnóstico de infarto do miocárdio perioperatório. Não foi encontrada diferença significativa entre tempo de internação hospitalar e em unidade de terapia intensiva nos grupos com e sem esta complicação, porém pacientes com infarto do miocárdio perioperatório evoluíram com pior função ventricular esquerda e mais casos de óbito. Conclusão: A frequência de infarto do miocárdio perioperatório encontrada neste trabalho foi considerada alta e como consequência do mesmo observou-se média mais elevada de troponina I, mais casos de piora da função ventricular esquerda e óbito. .


Subject(s)
Animals , Female , Male , Mice , Cell Death/physiology , Glucose/metabolism , Hypoxia-Ischemia, Brain/metabolism , Neurons/physiology , Oxygen/metabolism , Sex Characteristics , Signal Transduction/physiology , Adenosine Triphosphate/metabolism , Apoptosis Inducing Factor/metabolism , /metabolism , /metabolism , Cerebellum/cytology , Mice, Knockout , Mitochondria/metabolism , Neurons/cytology , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism
15.
Rev. bras. cir. cardiovasc ; 30(1): 77-83, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-742899

ABSTRACT

Introduction: Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. Objective: We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Methods: Thirty rats were divided into three groups as sham (n=10), control (n=10) and thymoquinone (TQ) treatment group (n=10). Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Results: Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI). Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons). Conclusion: Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model. .


Introdução: Estudos prévios demonstraram que a timoquinona tem efeitos protetores contra a lesão de isquemia/reperfusão em vários órgãos como pulmão, rins e fígado em diferentes modelos experimentais. Objetivo: Determinar se timoquinona tem efeitos positivos em tecidos do pulmão, rim e coração e no estresse oxidativo em lesão de isquemia/perfusão da aorta abdominal. Métodos: Trinta ratos foram divididos em três grupos: sham (n=10), controle (n=10) e tratamento com timoquinona (TQ) (n=10). Os grupos controle e de tratamento com TQ foram submetidos à isquemia da aorta abdominal durante 45 minutos, seguido por um período de 120 minutos de reperfusão. No grupo de tratamento com TQ, a timoquinona foi administrada 5 minutos antes da reperfusão, dose de 20 mg/kg através da via intraperitoneal. A capacidade total antioxidante, estado oxidativo total (TOS) e o índice de estresse oxidativo (OSI) no soro do sangue foram medidos, e a histopatologia dos tecidos do pulmão, rim e coração foram avaliados com microscopia de luz. Resultados: Estado oxidativo e índice de estresse oxidativo total em amostras de sangue foram estatisticamente mais altos no grupo controle em relação aos grupos sham e tratamento com TQ (P<0,001 para TOS e OSI). Escores de lesões no grupo controle foram estatisticamente mais altos em relação aos grupos sham e tratamento com TQ (P<0,001 para todas as comparações). Conclusão: A timoquinona administrada por via intraperitoneal foi eficaz na redução do estresse oxidativo e lesão histopatológica em modelo de rato de isquemia/reperfusão aguda da aorta abdominal. .


Subject(s)
Animals , Humans , Mice , Endothelial Cells/enzymology , Glucagon-Like Peptide 1/pharmacology , Microvessels/cytology , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Recombinant Proteins/pharmacology , Signal Transduction/drug effects , Apoptosis/drug effects , Cell Line , Cell Proliferation/drug effects , Cyclic AMP/metabolism , Endothelial Cells/drug effects , Gene Expression/drug effects , Lipoproteins, LDL/pharmacology
16.
Rev. bras. cir. cardiovasc ; 30(1): 70-76, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-742901

ABSTRACT

Objective: An unclear issue is whether gender may influence at cardiac remodeling after myocardial infarction (MI). We evaluated left ventricle remodeling in female and male rats post-MI. Methods: Rats were submitted to anterior descending coronary occlusion. Echocardiographic evaluations were performed on the first and sixth week post-occlusion to determine myocardial infarction size and left ventricle systolic function (FAC, fractional area change). Pulsed Doppler was applied to analyze left ventricle diastolic function using the following parameters: E wave, A wave, E/A ratio. Two-way ANOVA was applied for comparisons, complemented by the Bonferroni test. A P≤=0.05 was considered significant. Results: There were no significant differences between genders for morphometric parameters on first (MI [Female (FE): 44.0±5.0 vs. Male (MA): 42.0±3.0%]; diastolic [FE: 0.04±0.003 vs. MA: 0.037±0.005, mm/g] and systolic [FE: 0.03±0.0004 vs. MA: 0.028±0.005, mm/g] diameters of left ventricle) and sixth (MI [FE: 44.0±5.0 vs. MA: 42.0±3.0, %]; diastolic [FE: 0.043±0.01 vs. MA: 0.034±0.005, mm/g] and systolic [FE: 0.035±0.01 vs. MA: 0.027±0.005, mm/g] of LV) week. Similar findings were reported for left ventricle functional parameters on first (FAC [FE: 34.0±6.0 vs. MA: 32.0±4.0, %]; wave E [FE: 70.0±18.0 vs. MA: 73.0±14.0, cm/s]; wave A [FE: 20.0±12.0 vs. MA: 28.0±13.0, cm/s]; E/A [FE: 4.9±3.4 vs. MA: 3.3±1.8]) and sixth (FAC [FE: 29.0±7.0 vs. MA: 31.0±7.0, %]; wave E [FE: 85.0±18.0 vs. MA: 87.0±20.0, cm/s]; wave A [FE: 20.0±11.0 vs. MA: 28.0±17.0, cm/s]; E/A [FE: 6.2±4.0 vs. MA: 4.6±3.4]) week. Conclusion: Gender does not influence left ventricle remodeling post-MI in rats. .


Objetivo: A influência do gênero no remodelamento cardíaco após o infarto do miocárdio é uma questão em intenso debate. Nós avaliamos o remodelamento ventricular esquerdo em ratos infartados de ambos os gêneros. Métodos: O infarto do miocárdio foi induzido por oclusão da artéria coronária descendente anterior (fêmeas [FM]; machos [MC]). A ecocardiografia foi realizada na primeira e sexta semana pós-oclusão para determinar o tamanho do infarto do miocárdio e a função sistólica do ventricular esquerdo (mudança na área fracional [FAC]). A função diastólica derivou dos seguintes parâmetros: onda E; onda A; razão E/A. ANOVA duas vias com pós-teste de Bonferroni foi aplicado nas comparações (P≤=0,05). Resultados: Todas variáveis morfométricas foram similares (P>0,05) entre os gêneros com uma (infarto do miocárdio [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,04±0,003 vs. MC: 0,037±0,005, mm/g] e sistólico [FM: 0,03±0,0004 vs. MC: 0,028±0,005, mm/g] do VE) e seis (IM [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,043±0,01 vs. MC: 0,034±0,005, mm/g] e sistólico [FM: 0,035±0,01 vs. MC: 0,027±0,005, mm/g] do ventricular esquerdo) semanas. Achado similar ocorreu para os dados funcionais com uma (FAC [FM: 34,0±6,0 vs. MC: 32,0±4,0, %]; onda E [FM: 70,0±18,0 vs. MC: 73,0±14,0, cm/s]; onda A [FM: 20,0±12,0 vs. MC: 28,0±13,0, cm/s]; E/A [FM: 4,9±3,4 vs. MC: 3,3±1,8]) e seis (FAC [FM: 29,0±7,0 vs. MC: 31,0±7,0, %]; onda E [FM: 85,0±18,0 vs. MC: 87,0±20,0, cm/s]; onda A [FM: 20,0±11,0 vs. MC: 28,0±17,0 cm/s]; E/A [FM: 6,2±4,0 vs. MC: 4,6±3,4]) semanas. Conclusão: O gênero não é determinante para o remodelamento ventricular esquerdo pós-infarto do miocárdio em ratos. .


Subject(s)
Animals , Humans , Infant, Newborn , Rats , Enterocolitis, Necrotizing/drug therapy , Enzyme Inhibitors/pharmacology , Intestinal Mucosa/drug effects , Intestines/drug effects , Niacinamide/pharmacology , Poly(ADP-ribose) Polymerases/antagonists & inhibitors , Analysis of Variance , Animals, Newborn , Cell Death/drug effects , Disease Models, Animal , Enzyme Activation , Enterocolitis, Necrotizing/enzymology , Enterocolitis, Necrotizing/pathology , Intestinal Mucosa/enzymology , Intestinal Mucosa/pathology , Intestines/enzymology , Intestines/pathology , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Rats, Sprague-Dawley , Tyrosine/analogs & derivatives , Tyrosine/metabolism
18.
Rev. bras. cir. cardiovasc ; 30(1): 24-32, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-742904

ABSTRACT

Objective: A retrospective cohort study was preformed aiming to verify the presence of transient dysfunction of gas exchange in the postoperative period of cardiac surgery and determine if this disorder is linked to cardiorespiratory events. Methods: We included 942 consecutive patients undergoing cardiac surgery and cardiac procedures who were referred to the Intensive Care Unit between June 2007 and November 2011. Results: Fifteen patients had acute respiratory distress syndrome (2%), 199 (27.75%) had mild transient dysfunction of gas exchange, 402 (56.1%) had moderate transient dysfunction of gas exchange, and 39 (5.4%) had severe transient dysfunction of gas exchange. Hypertension and cardiogenic shock were associated with the emergence of moderate transient dysfunction of gas exchange postoperatively (P=0.02 and P=0.019, respectively) and were risk factors for this dysfunction (P=0.0023 and P=0.0017, respectively). Diabetes mellitus was also a risk factor for transient dysfunction of gas exchange (P=0.03). Pneumonia was present in 8.9% of cases and correlated with the presence of moderate transient dysfunction of gas exchange (P=0.001). Severe transient dysfunction of gas exchange was associated with patients who had renal replacement therapy (P=0.0005), hemotherapy (P=0.0001), enteral nutrition (P=0.0012), or cardiac arrhythmia (P=0.0451). Conclusion: Preoperative hypertension and cardiogenic shock were associated with the occurrence of postoperative transient dysfunction of gas exchange. The preoperative risk factors included hypertension, cardiogenic shock, and diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia, renal replacement therapy, hemotherapy, and cardiac arrhythmia were associated with the appearance of some degree of transient dysfunction of gas exchange, which was a risk factor for reintubation, pneumonia, ventilator-associated pneumonia, and renal replacement therapy in the postoperative period ...


Objetivo: Estudo de coorte retrospectivo com objetivo de verificar a presença de disfunção transitória da troca gasosa no pós-operatório de cirurgia cardíaca e determinar se esse transtorno está relacionado a eventos cardiorrespiratórios. Métodos: Foram incluídos 942 pacientes consecutivos submetidos à cirurgia cardíaca e procedimentos cardíacos, encaminhados para a Unidade de Terapia Intensiva, entre junho de 2007 e novembro de 2011. Resultados: A síndrome do desconforto respiratório agudo foi observada em 15 (2%) pacientes, 199 (27,75%) pacientes apresentaram disfunção transitória da troca gasosa leve, disfunção transitória da troca gasosa moderada foi observada em 402 (56,1%) pacientes e disfunção transitória da troca gasosa grave em 39 (5,4%). A presença de hipertensão arterial sistêmica e choque cardiogênico foi associada ao surgimento de disfunção transitória da troca gasosa moderada no período pós-operatório (P=0,02 e P=0,019, respectivamente) e foram considerados fatores de risco para essa disfunção (P=0,0023 e P=0,0017, respectivamente). A presença de diabetes mellitus também foi considerada um fator de risco para disfunção transitória da troca gasosa (P=0,03). Houve correlação entre a presença de pneumonia e a presença de disfunção transitória da troca gasosa moderada em 8,9% dos casos (P=0,001). A presença de disfunção transitória da troca gasosa grave foi associada a pacientes que necessitaram de hemodiálise (P=0,0005), hemoterapia (P=0,0001), nutrição enteral (P=0,0012), ou arritmia cardíaca (P=0,0451). Conclusão: A presença de hipertensão arterial sistêmica pré-operatória e choque cardiogênico foi associada à ocorrência de disfunção transitória da troca gasosa pós-operatória. Os fatores de risco pré-operatórios foram hipertensão arterial sistêmica, choque cardiogênico e diabetes. No pós-operatório, pneumonia, pneumonia associada à ventilação, hemodiálise, hemoterapia e arritmia cardíaca foram associadas com certo grau de ...


Subject(s)
Animals , Humans , Rats , Alcohol Oxidoreductases/metabolism , Endothelial Cells/metabolism , NAD(P)H Dehydrogenase (Quinone)/metabolism , Phenanthrenes/metabolism , Aldehyde Reductase , CCAAT-Binding Factor/metabolism , Caspases/metabolism , Endoplasmic Reticulum/metabolism , Leupeptins/pharmacology , Oxidation-Reduction , Oxidative Stress , Poly(ADP-ribose) Polymerases/metabolism , Reactive Oxygen Species/metabolism
19.
Rev. Soc. Bras. Med. Trop ; 48(1): 50-55, jan-feb/2015. tab
Article in English | LILACS | ID: lil-742969

ABSTRACT

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. .


Subject(s)
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
20.
Rev. méd. Chile ; 143(1): 14-21, ene. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-742546

ABSTRACT

Background: Domperidone is widely prescribed in patients with gastrointestinal disorders but some cardiac adverse effects have been recently reported. Aim: To evaluate the risk of QT prolongation, ventricular arrhythmias and sudden cardiac death associated with the use of oral domperidone in adults without cancer. Material and Methods: Systematic searches in MEDLINE, LILACS, SciELO, the Cochrane Library and regulatory agencies websites were performed, followed by a manual search of cited references. The search strategy consisted of combining free and indexed text words without any date or language restriction. Results: Three case-control studies met the inclusion criteria; none of them evaluated QT interval prolongation. With low risk of bias, each study quantified the risk of ventricular arrhythmia or sudden cardiac death (VA/SCD). The odds ratios for these events in these studies were 4.7 (95% confidence interval (CI): 1.4-16), 1.59 (95% CI: 1.28-1.98) and 11.02 (95% CI: 2.02-62.3) respectively. A significantly increased risk was observed in patients older than 60 years of age or receiving doses > 30 mg/day. Conclusions: Heterogeneity between selected studies did not allow the computation of a summary measure. However, evidence was found that an increased risk of VA/SCD is associated with the use of oral domperidone in adults.


Subject(s)
Animals , Female , Humans , Mice , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Diterpenes/administration & dosage , Epoxy Compounds/administration & dosage , Paclitaxel/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/chemistry , Apoptosis/drug effects , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Synergism , Diterpenes/chemistry , Epoxy Compounds/chemistry , Lactones/administration & dosage , Lactones/chemistry , Mice, Nude , Oxidative Stress/drug effects , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Tumor Burden , Transcriptional Activation/drug effects , Xenograft Model Antitumor Assays
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