Interação medicamentosa em pacientes com câncer: revisão integrativa da literatura / Drug interaction in cancer patients: an integrative literature review

Introdução: O câncer é uma patologia considerada como doença crônica não transmissível, que na sociedade atual, se encontra entre as 7 principais causas de morte no mundo, segundo estimativas da Organização Mundial da Saúde (OMS). Pacientes com neoplasias comumente realizam tratamentos paralelos além dos realizados para combater o câncer, como para tratar: outras doenças crônicas pré - existentes, reações adversas a medicamentos causadas pelo tratamento primário além da auto medicação o que causa as interações medicamentosas as quais desencadeiam efeitos prejudiciais à saúde do paciente, como intoxicação medicamentosa, efeito nulo do medicamento, não tratamento da doença e ênfase nos efeitos adversos daqueles medicamentos Objetivo: objetivou-se analisar as incidência de interação medicamentosa em pacientes com câncer, submetidos ao tratamento quimioterápico. Metodologia: Foi realizada uma revisão bibliográfica por meio da pesquisa de artigos científicos. As bases de dados utilizadas foram BVS, Scielo, Lilacs e PubMed, e foram utilizados como descritores para a pesquisa: “interação medicamentosa e câncer”, “interação medicamentosa, oncologia e quimioterapia” “potenciais interações medicamentosas, neoplasias e agentes anticâncer” “drug interaction and cancer”, “drug interaction oncology and chemotherapy” e “potential drug interactions neoplasms anticancer agents”. Resultados: Foram incluídos os artigos originais completos de acordo com o tema proposto. Foram selecionados quatorze artigos após aplicação dos critérios de inclusão e exclusão. O número médio de medicamentos ministrados por paciente foi entre 7 a 11,7 e as bases de dados variaram entre: Micromedex, Epocrats, Drug Interactions Facts, MedScape e Lexi Interact. O medicamento que foi comumente envolvido nas interações com agentes anticâncer foi a dexametasona, um agente indutor do Citocromo P450 (CYP 450). Considerações finais: Esta revisão demonstrou uma alta prevalência de interações medicamentosa devido à complexidade da farmacoterapia, sendo essencial que se adote métodos para minimização desses dados, enfatizando a necessidade de um foco global intensificado na prevenção de interação em doenças como o câncer

Estudo comparativo da biologia floral de variedades comerciais de melancieira em cultivo orgânico

A melancia (Citrullus lanatus) é uma cucurbitácea de importância econômica para a região nordeste, considerada a maior produtora do país. Os estudos relacionados a biologia floral sobre, são muito importantes para a produção e qualidade de frutos comerciais. O estudo objetivou comparar a biologia floral em quatro variedades de melancieira, sob cultivo orgânico irrigado, avaliando o período de floração, a antese e senescência floral, o percentual de viabilidade polínica, receptividade estigmática, a produção de néctar e produção de frutos. Foram avaliadas as variedades de melancieira ‘Charleston Gray’, ‘Congo’, ‘Crimson Select’ e ‘BRS Soleil’. O experimento foi conduzido em sistema orgânico durante o período de janeiro a junho de 2018, na área experimental do DTCS - CAMPUS III – UNEB, em Juazeiro – Bahia. As variedades BRS Soleil e Charleston apresentaram período de floração de 31 dias, a ‘Congo’ de 28, a ‘Crimson Select’ de 23 dias. Todas as variedades obtiveram alta viabilidade polínica, o teste de receptividade do estigmática registrou 100% para todos as variedades, as flores masculinas exibiram maior produção do volume de néctar. A maior razão sexual registrada foi registrada para a variedade Congo

Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis

In chronic schistosomiasis, liver fibrosis is linked to portal hypertension, which is a condition associated with high mortality and morbidity. High mobility group box 1 (HMGB1) was originally described as a nuclear protein that functions as a structural co-factor in transcriptional regulation. However, HMGB1 can also be secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 acts as a multifunctional cytokine that contributes to infection, injury, inflammation, and immune responses by binding to specific cell-surface receptors. HMGB1 is involved in fibrotic diseases. From a clinical perspective, HMGB1 inhibition may represent a promising therapeutic approach for treating tissue fibrosis. In this study, we demonstrate elevated levels of HMGB1 in the sera in experimental mice or in patients with schistosomiasis. Using immunohistochemistry, we demonstrated that HMGB1 trafficking in the hepatocytes of mice suffering from acute schistosomiasis was inhibited by Glycyrrhizin, a well-known HMGB1 direct inhibitor, as well as by DIC, a novel and potential anti-HMGB1 compound. HMGB1 inhibition led to significant downregulation of IL-6, IL4, IL-5, IL-13, IL-17A, which are involved in the exacerbation of the immune response and liver fibrogenesis. Importantly, infected mice that were treated with DIC or GZR to inhibit HMGB1 pro-inflammatory activity showed a significant increase in survival and a reduction of over 50% in the area of liver fibrosis. Taken together, our findings indicate that HMGB1 is a key mediator of schistosomotic granuloma formation and liver fibrosis and may represent an outstanding target for the treatment of schistosomiasis

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

The impact of microparticles in graft versus host disease

Graft-versus-host disease (GvHD) remains a leading cause of morbidity and mortality among allogeneic stem cell transplantation (SCT) patients. New research focusing on diagnostic methods and therapeutic interventions is needed. Microparticles (MPs) have been described as biomarkers of cellular damage, activation, and intercellular signaling in many diseases. This study examined the correlations of the levels of MPs with the incidence of acute GvHD. Circulating annexin V-positive (total microparticles - TMP), CD61+ platelet-derived microparticles (PMP) and CD235+ erythrocyte-derived microparticles (EMP) were measured at neutrophil engraftment in the plasma of 48 patients undergoing SCT. The levels of PMP were not associated with the risk of acute GvHD. However, higher TMP count (above 520/?L) and higher EMP count (above 360/?L) were associated with a greater incidence of acute GvHD (54% vs. 21%, p=0.02 and 59% vs. 26%, p=0.04, respectively) p=0.02). In patients exposed to reduced intensity conditioning regimens, an even stronger association of high TMP and EMP count and acute GvHD was observed (77% vs. 22%, p=0.003 and 89% vs. 23%, p=0.002, respectively). Our data suggest that higher total microparticles and erythrocyte derived microparticles counts at engraftment may be associated with a greater risk of acute GvHD.Introdução: A doença do enxerto contra o hospedeiro (DECH) permanece uma das principais complicações do transplante de células progenitoras hematopoiéticas (TCPH). Não existe ainda um marcador biológico estabelecido para DECH. Recentemente, micropartículas têm sido descritas como biomarcadores de diversos processos biológicos como lesão celular, sinalização intercelular e inflamação. O papel de micropartículas como biomarcador durante o TCPH ainda não foi elucidado. Objetivos: Estudar micropartículas anexina V positivas derivadas de plaquetas e eritrócitos durante o TCPH alogênico e associar os achados com incidência de DECH, recaída e sobrevida. Pacientes e métodos: Micropartículas foram quantificadas por citometria de fluxo multiparamétrica no sangue periférico de pacientes submetidos a TCPH em amostras colhidas semanalmente até o D+100 pós transplante. Foram incluídos na análise 48 pacientes (67% masculino, idade mediana de 44 anos, variação 2-73) recebendo células progenitoras de medula óssea (31%), cordão umbilical (19%) e sangue periférico (50%); a partir de doadores aparentados (58%) e não aparentados (42%). O diagnóstico mais comum foi leucemia aguda (mielóide 30%, linfóide 20%). A maioria dos pacientes recebeu condicionamento de intensidade reduzida (65%) e 33% receberam depleção linfocitária com timoglobulina. A mediana de seguimento foi de 40 meses (variação 25-50). Resultados: Contagens de micropartículas de plaquetas (MPP) apresentam incremento progressivo após a enxertia neutrofílica, sendo este incremento mais acentuado em pacientes que receberam transplantes de doador HLA idêntico, quando comparados aos que receberam de sangue de cordão umbilical ou de doador haploidêntico. Pacientes submetidos a regime de condicionamento mieloablativo apresentaram maiores níveis de micropartículas totais (MPT) e micropartículas de eritrócitos (MPE) quando comparado a pacientes submetidos a regime de condicionamento de intensidade reduzida (RIC) no dia da enxertia neutrofílica (MPT: 726/?l vs. 350/?l, p=0,044 e MPE: 348/?l vs. 152/?l, p=0,034). Níveis de MPT ? 520/?l no momento da enxertia foram associados a maior incidência global de DECH aguda (54% vs. 21%; p=0,02), DECH aguda de pele (48% vs. 13%; p=0,02), de fígado (26% vs. 0%; p=0,02) sem associação com DECH aguda de TGI (37% vs. 17%; p=0,14). Esta associação não foi observada para DECH crônica (40% vs. 18%; p=0,12). Para níveis de MPE ? 360/?l no momento da enxertia foram observados maior incidência global de DECH aguda (59% vs. 26%; p=0,04), DECH aguda de pele (53% vs. 17%; p=0,02), de fígado (33% vs. 0%; p=0,002) sem associação com DECH aguda de TGI (42% vs. 20%; p=0,12). Não houve associação com DECH crônica (41% vs. 19%; p=0,1). Em pacientes submetidos a transplante RIC, a associação entre níveis de MP e DECH é mais evidente. Maiores níveis de MPT na enxertia foram associadas a maior incidência de todas as formas de DECH agudo (DECH aguda global: 77% vs. 22%, p=0,003), sendo a mesma associação verificada para níveis de MPE (DECH aguda global: 89% vs. 27%, p=0,004). Não houve associação entre MPT ou MPE na enxertia com sobrevida livre de progressão, mortalidade não relacionada a recaída, recaída ou sobrevida global. Não houve associação entre MPP na enxertia com os desfechos citados. Conclusões: Contagens elevadas de micropatículas totais e micropartículas derivadas de eritrócitos no momento da enxertia neutrofílica foram associadas a maior incidência de DECH aguda na população estudada.Grupo FleuryGrupo Fleury: 18.07.2011Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Efeito do óleo de copaíba nos níveis séricos de uréia e creatinina em ratos submetidos à síndrome de isquemia e reperfusão renal Copaiba oil effect on urea and creatinine serum levels in rats submitted to kidney ischemia and reperfusion syndrome

OBJETIVO: Avaliar o efeito do óleo de copaíba nos níveis séricos de uréia e creatinina em ratos submetidos a síndrome de isquemia e reperfusão renal. MÉTODOS: Foram utilizados 18 ratos (Rattus norvegicus albinus),da linhagem Wistar, fêmeas, adultas, entre 90 e 120 dias de idade, pesando ente 200g e 250g, distribuídos em dois grupos: Isquemia e Reperfusão (GIR), e Isquemia e Reperfusão Copaíba (GIRC). Os animais dos dois grupos foram submetidos à isquemia renal, de ambos os rins, por 50 minutos, seguida de reperfusão por 24, 48 e 72 horas, com posterior coleta de sangue e análise dos níveis séricos de uréia e creatinina. No GIRC, realizou-se, além da isquemia e reperfusão, a administração diária do óleo de copaíba na dose de 0,63 ml/kg, por gavagem, sete dias antes do procedimento de isquemia renal. RESULTADOS: Foi observada uma diminuição estatisticamente significante dos níveis séricos de uréia no GIRC em 24 e 48 horas de reperfusão renal e uma diminuição do nível sérico de creatinina no GIRC em 48 horas de reperfusão renal quando comparados com o grupo Controle. CONCLUSÃO: Segundo os procedimentos aplicados, o óleo de copaíba diminuiu os níveis séricos de uréia em 24 horas e 48 horas e os de creatinina nas 48 horas após o procedimento de isquemia e reperfusão renal em ratos.<br>PURPOSE: To evaluate the copaiba oil effect on urea and creatinine levels in rats submitted to kidney ischemia and reperfusion syndrome. METHODS: Eighteen Wistar rats (Rattus norvegicus albinus), aged between 90 and 120 days, weight between 200g and 250g, were allocated in 2 groups (n=9) and submitted to 50 minutes of renal ischemia and reperfusion and treated or not with copaiba oil (0,63ml/kg daily seven days before ischemia). The nitrogen excrements were assessed at 24, 48 and 72 hours after ischemia period. RESULTS: The urea serum level was smaller (p d" 0,05) at 24 and 48 hours, and the creatinine serum level was smaller at 48 hours in animals treated with copaiba oil (GIRC) than the GIR. CONCLUSION: The copaiba oil decreased significantly the urea serum level at 24 and 48 hours and the creatinine level at 48 hours after kidney ischemia and reperfusion in rats

Chronic Myelogenous Leukemia with Double Philadelphia Chromosome and Coexpression of p210 and p190 Fusion Transcripts

The Philadelphia (Ph+) chromosome, t(9;22)(q34;q11.2), originates from a chimeric gene called BCR-ABL and is present in more than 90% of CML patients. Most patients with CML express the protein p210 BCR-ABL and, with a frequency lower than 5%, express rare isoforms, the main one being p190. In the transition from the chronic phase to the blast phase (BP), additional chromosomal abnormalities, such as the presence of the double Ph+ chromosome, are revealed. Of the 1132 patients analyzed via molecular biology in this study, two patients (0.17%) showed the co-expression of the p210 and p190 isoforms for the BCR-ABL transcript, with the concomitant presence of a double Ph+ chromosome, which was observed via conventional cytogenetics and confirmed by fluorescent in situ hybridization. The BCR-ABL/ABL% p210 and p190 ratio increased in these two patients from diagnosis to progression to blast crisis. To our knowledge, this is the first report in the literature of patients who co-expressed the two main BCR-ABL transcript isoforms and concomitantly presented Ph+ chromosome duplication. The evolution from the chronic phase to BP often occurs within 5 to 7 years, and, in this study, the evolution to BP was earlier, since disease-free survival was on average 4.5 months and overall survival was on average 9.5 months. The presence of the p190 transcript and the double Ph+ chromosome in CML may be related to the vertiginous progression of the disease