Actualización en fibrosis quística: uso de exacaftor/tezacaftor/ivacaftor/en pacientes con fibrosis quística port-trasplante pulmonar / Use of exacaftor/tezacaftor/ivacaftor in cystic patients post lung transplantation

El uso de moduladores de CFTR en pacientes con fibrosis quística post trasplante pulmonar es un tema todavía controversial. Varias publicaciones reportan los beneficios del modulador elexacaftor/tezacaftor/ivacaftor en los síntomas extrapulmonares de la fibrosis quística, especialmente enfermedad sinusal, síntomas gastrointestinales y diabetes. Un número alto de pacientes debe discontinuar el tratamiento por mala tolerancia, sin embargo, no se describen interacciones de importancia con el tratamiento inmunosupresor. Se debe considerar para su uso los riesgos versus beneficios en forma individual en cada paciente.

The use of CFTR modulators in patients with cystic fibrosis after lung transplantation is still a controversial issue. Several publications report the benefits of the use of the modulator elexacaftor/tezacaftor/ivacaftor on extrapulmonary symptoms of cystic fibrosis, especially sinus disease, gastrointestinal symptoms and diabetes. A high number of patients must discontinue treatment due to poor tolerance; however, no significant interactions with immunosuppressive treatment have been described. The individual risk-benefit of each patient should be considered for its use.

Clinical Application of Zanubrutinib in B-Cell Lymphoma --Review / 中国实验血液学杂志

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.

Ibrutinib combined with CAR-T cells in the treatment of del (17p) chronic lymphocytic leukemia with BCL-2 inhibitor resistance: a case report and literature review / 中华血液学杂志

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion: CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.

Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study / 中华血液学杂志

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

Economic evaluation of the new oral anticoagulants for the prevention of thromboembolic events: a cost-minimization analysis / Avaliação econômica dos novos anticoagulantes para a prevenção de eventos tromboembólicos: análise de custo-minimização

ABSTRACT CONTEXT AND OBJECTIVE: Randomized clinical trials have shown that the new oral anticoagulants have at least similar impact regarding reduction of thromboembolic events, compared with warfarin, with similar or improved safety profiles. There is little data on real costs within clinical practice. Our aim here was to perform economic analysis on these strategies from the perspective of Brazilian society and the public healthcare system. DESIGN AND SETTING: Cost-minimization analysis; anticoagulation clinic of Hospital Municipal Odilon Behrens, Belo Horizonte, MG, Brazil. METHODS: Patients at the anticoagulation clinic were recruited between August and October 2011, with minimum follow-up of four weeks. Operational and non-operational costs were calculated and corrected to 2015. RESULTS: This study included 633 patients (59% women) of median age 62 years (interquartile range ­49-73). The mean length of follow-up was 64 ± 28 days. The average cost per patient per month was $ 54.26 (US dollars). Direct costs accounted for 32.5% of the total cost. Of these, 69.5% were related to healthcare professionals. With regards to indirect costs, 52.4% were related to absence from work and 47.6% to transportation. Apixaban, dabigatran and rivaroxaban were being sold to Brazilian public institutions, on average, for $ 49.87, $ 51.40 and $ 52.16 per patient per month, respectively, which was lower than the costs relating to warfarin treatment. CONCLUSION: In the Brazilian context, from the perspective of society and the public healthcare system, the cumulative costs per patient using warfarin with follow-up in anticoagulation clinics is currently higher than the strategy of prescribing the new oral anticoagulants.

RESUMO CONTEXTO E OBJETIVO: Estudos clínicos randomizados demonstraram que novos anticoagulantes orais têm pelo menos impacto semelhante em reduzir eventos tromboembólicos quando comparados à varfarina, com perfil de segurança similar ou superior. Há pouca evidência acerca de custos reais na prática clínica. Nosso objetivo é realizar análise econômica dessas estratégias, na perspectiva do sistema de saúde pública e da sociedade brasileiros. TIPO DE ESTUDO E LOCAL: Análise de custo-minimização; Clínica de Anticoagulação do Hospital Municipal Odilon Behrens, Belo Horizonte, MG, Brasil. MÉTODOS: Os pacientes da clínica de anticoagulação foram recrutados de agosto a outubro de 2011, com tempo mínimo de acompanhamento de quatro semanas. Custos operacionais e não operacionais foram computados e corrigidos para 2015. RESULTADOS: Este estudo incluiu 633 pacientes, com idade mediana de 62 (intervalo interquartil 49-73) anos, sendo 59% mulheres. O tempo médio de acompanhamento foi de 64 ± 28 dias. O custo médio por paciente por mês foi de $ 54.26 (dólares). Custos diretos foram responsáveis por 32,5% do custo total. Destes, 69,5% foram relacionados aos profissionais de saúde. Em relação aos custos indiretos, 52,4% estavam relacionados ao absenteísmo ao trabalho e 47,6% ao transporte. Apixaban, dabigatran e rivaroxaban são vendidos a órgãos públicos brasileiros, respectivamente, a um preço médio mensal de $ 49.87, $ 51.40 e $ 52.26 por paciente por mês, valores inferiores aos custos relacionados ao tratamento com varfarina. CONCLUSÃO: No contexto brasileiro, na perspectiva do sistema de saúde pública e da sociedade, os custos cumulativos por paciente em uso de varfarina acompanhados em clínica de anticoagulação são atualmente superiores à estratégia de prescrever novos anticoagulantes orais.

New anticoagulants for the treatment of venous thromboembolism / Os novos anticoagulantes no tratamento do tromboembolismo venoso

Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.

O tromboembolismo venoso (TEV) está entre as principais causas de morte por doenças cardiovasculares no mundo, atrás apenas do infarto agudo do miocárdio e do acidente vascular cerebral. O TEV possui espectro de apresentação que vai desde a trombose venosa profunda até o tromboembolismo pulmonar agudo, de acordo com gravidade crescente de acometimento, sendo seu tratamento baseado na anticoagulação plena dos pacientes. Há muitas décadas, sabe-se que a anticoagulação interfere diretamente na mortalidade associada ao TEV. Até o início deste século a terapia anticoagulante se baseava no uso de heparina, em suas formas não fracionada ou de baixo peso molecular, e de antagonistas da vitamina K, principalmente a varfarina. Ao longo das últimas décadas, foram desenvolvidos novas classes de medicamentos anticoagulantes, inibidores do fator Xa e inibidores diretos da trombina, que mudaram significativamente o arsenal terapêutico do TEV, em função de suas características de eficácia e segurança em relação ao tratamento convencional, sendo o foco principal de esta revisão avaliar seu papel neste contexto clínico.

Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats

Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg-1·day-1 for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines.

Series with complete resolution of left atrial appendage thrombi with apixaban in elderly patients

No abstract available.

Association among measures of mobility-related disability and self-perceived fatigue among older people: a population-based study

Objective: To investigate the relationship between self-perceived fatigue with different physical functioning tests and functional performance scales used for evaluating mobility-related disability among community-dwelling older persons. Method: This is a cross-sectional, population-based study. The sample was composed of older persons with 65 years of age or more living in Cuiabá, MT, and Barueri, SP, Brazil. The data for this study is from the FIBRA Network Study. The presence of self-perceived fatigue was assessed using self-reports based on the Center for Epidemiologic Studies-Depression Scale. The Lawton instrumental activities of daily living scale (IADL) and the advanced activities of daily living scale (AADL) were used to assess performance and participation restriction. The following physical functioning tests were used: five-step test (FST), the Short Physical Performance Battery (SPPB), and usual gait speed (UGS). Three models of logistic regression analysis were conducted, and a significance level of α<0.05 was adopted. Results: The sample was composed of 776 older adults with a mean age (SD) of 71.9 (5.9) years, of whom the majority were women (74%). The prevalence of self-perceived fatigue within the participants was 20%. After adjusting for covariates, SPPB, UGS, IADL, and AADL remained associated with self-perceived fatigue in the final multivariate regression model. Conclusion: Our results suggest that there is an association between self-perceived fatigue and lower extremity function, usual gait speed and activity limitation and participation restriction in older adults. Further cohort studies are needed to investigate which physical performance measure may be able to predict the negative impact of fatigue in older adults. .

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Treatment of Bartter syndrome. Unsolved issue, / Tratamento da síndrome de Bartter. Problema não resolvido,

Objective: To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. Method: Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. Results: 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. Conclusion: The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies. .

Objetivo: Descrever os resultados de um acompanhamento de longo prazo de pacientes com síndrome de Bartter tratados com diferentes medicamentos. Método: Pacientes diagnosticados segundo os dados clínicos e laboratoriais. Protocolo de tratamento: suplementação de potássio, sódio, espironolactona e medicamento anti-inflamatório não esteroidal. Os pacientes que desenvolveram proteinúria foram submetidos a inibidor da enzima de conversão da angiotensina. As variáveis avaliadas durante o uso de cada medicamento foram: escore Z para peso e estatura, proteinúria, depuração da creatinina, queixas gastrointestinais, quantidade da suplementação de potássio, níveis séricos de potássio e bicarbonato e achados da endoscopia digestiva alta. Resultados: Foram incluídos 20 pacientes. O acompanhamento foi de 10,1 ± 5,2 anos. No total, 17 pacientes receberam indometacina por 5,9 ± 5,3 anos, 19 receberam celecoxib por aproximadamente 35 meses e cinco receberam enalapril por aproximadamente 23 meses. Durante o uso de indometacina, observamos um aumento estatístico significativo no escore Z para estatura e peso, sem alteração na depuração da creatinina. 7/17 pacientes apresentaram sintomas gastrointestinais, e a endoscopia digestiva alta mostrou gastrite em três pacientes e úlcera gástrica em quatro. Durante o uso de celecoxib, detectamos um aumento significativo no escore Z para estatura e peso e uma redução da hiperfiltração; sete pacientes apresentaram sintomas gastrointestinais e a endoscopia digestiva alta mostrou gastrite leve em três pacientes. Durante o uso de enalapril, não observamos alterações significativas no escore Z para estatura, peso e depuração da creatinina. A mudança da medicação para enalapril resultou em uma ...

Janus Activated Kinase inhibition in Myelofibrosis.

Janus Activated Kinase (JAK) 2 plays an important role in the pathogenesis of myelofibrosis (MF). Ruxolitinib (INCB018424, Jakafi) is a potent dual JAK1 and JAK2 inhibitor. In November 2011, it became approved by the US FDA for the treatment of intermediate or high-risk MF. This review shall outline the role of Ruxolitinib in the current management of MF and its potential future.

Inmunomodulación y antiangiogénesis en la terapéutica oncológica: De la investigación básica a la clínica / Immunomodulation and antiangiogenesis in cancer therapy: From basic to clinical research

La investigación básica y pre-clínica en oncología celular y molecular son pilares fundamentales en los que se apoyan la mayoría de los adelantos en la terapéutica del cáncer. Los hallazgos obtenidos y su aplicación en la práctica clínica constituyen la causa del avance sostenido en el tratamiento de la enfermedad neoplásica. El objetivo de este trabajo es resumir y discutir los resultados pre-clínicos en inmunomodulación y anti-angiogénesis para el tratamiento de diversos tipos de tumores, obtenidos en nuestro Instituto durante los últimos 15 años, y la posterior traslación y aplicación del conocimiento experimental en un Ensayo Clínico Fase I/II. Se describen los resultados que contribuyeron a descifrar los mecanismos de acción de la inmunomodulación antimetastásica con ciclofosfamida, la quimioterapia metronómica con diferentes drogas únicas o combinaciones, y finalmente el diseño y resultados preliminares de un ensayo clínico de quimioterapia metronómica para pacientes con cáncer de mama avanzado.

Basic and pre-clinic research in cellular and molecular oncology are the main supports accounting for the advancement in cancer therapeutics. The findings achieved, and their implementation in clinical practice are responsible for the permanent improvement in the treatment of the neoplastic disease. Our present objective is to summarize and discuss the pre-clinical findings in immunomodulation and anti-angiogenesis for the treatment of several types of tumors obtained in our Institute during the last 15 years, and the subsequent translation and application of the acquired experimental knowledge in a Phase I/II Clinical Trial. We present the results and mechanisms of action of antimetastatic immunomodulation with cyclophosphamide, the metronomic chemotherapy with different single drugs and their combinations, and finally the design and preliminary results of a clinical trial with metronomic chemotherapy for patients with advanced breast cancer.

Effects of Combination Therapy with Celecoxib and Doxycycline on Neointimal Hyperplasia and Inflammatory Biomarkers in Coronary Artery Disease Patients Treated with Bare Metal Stents

PURPOSE: Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia. MATERIALS AND METHODS: A total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers. RESULTS: Follow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups. CONCLUSION: Our study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.

Selective control of Rhipicephalus (Boophilus) microplus in fipronil-treated cattle raised on natural pastures in Lages, State of Santa Catarina, Brazil / Controle seletivo do Rhipicephalus (Boophilus) microplus em bovinos criados em campo nativo, no município de Lages, Santa Catarina, Brasil

An examination of a selective control of Rhipicephalus (Boophilus) microplus and consequent cost reduction was carried out in two areas of native pasture in the municipality of Lages, State of Santa Catarina, Southern Brazil, from May 2007 to April 2009. Forty cattle were divided into two groups of 20 animals each (conventional and selective control groups). At 14-day intervals female ticks larger than 4.5 mm found on the right flank of cattle bodies were counted, and these results multiplied by two. Fipronil 1 mg.kg-1 pour on was then administered for tick control. In the conventional group all the cattle were treated when tick count averaged more than 40 female ticks per animal while in the selective group only animals parasitized by more than 40 ticks were treated with acaricide. Every 28 days the cattle's weight was checked for cost-effective analysis. The conventional group required an additional 20 doses of fipronil compared with the selective one. There was no statistically significant differences regarding weight gain in both groups.

Com o objetivo de avaliar o método de controle seletivo do Rhipicephalus (Boophilus) microplus e reduzir os custos para o controle, de maio de 2007 a abril de 2009, em duas invernadas de campo nativo no município de Lages, SC, utilizaram-se 40 bovinos que foram divididos em dois grupos (convencional e seletivo), de 20 animais cada. A cada 14 dias foi realizada a contagem das fêmeas maiores ou igual a 4,5 mm, no lado direito do corpo dos animais, e o valor obtido, multiplicado por dois. Foi utilizado fipronil 1 mg.kg-1 pour on para o controle de carrapatos. No grupo convencional, foram tratados todos os bovinos quando a média do grupo foi igual ou superior a 40 fêmeas e no grupo seletivo, foram tratados apenas os animais que apresentaram uma infestação igual ou superior a 40. A cada 28 dias foi realizada a pesagem dos animais para análise da relação custo/benefício. Foram realizadas 20 aplicações a mais do carrapaticida no grupo convencional em relação ao seletivo. Não houve diferença estatística entre o ganho de peso do grupo convencional em relação ao grupo seletivo.

Uso terapêutico dos canabinoides em psiquiatria: [revisão] / Therapeutical use of the cannabinoids in psychiatry: [review]

OBJETIVO: Revisar os principais avanços no potencial uso terapêutico de alguns compostos canabinoides em psiquiatria. MÉTODO: Foi realizada busca nos bancos de dado PubMed, SciELO e Lilacs e identificados estudos e revisões da literatura sobre o uso terapêutico dos canabinoides em psiquiatria, em particular canabidiol, rimonabanto, Δ9-tetraidrocanabinol e seus análogos. RESULTADOS: O canabidiol demonstrou apresentar potencial terapêutico como antipsicótico, ansiolítico, antidepressivo e em diversas outras condições. O Δ9-tetraidrocanabinol e seus análogos demonstraram efeitos ansiolíticos, na dependência de cannabis, bem como adjuvantes no tratamento de esquizofrenia, apesar de ainda carecerem de mais estudos. O rimonabanto demonstrou eficácia no tratamento de sintomas subjetivos e fisiológicos da intoxicação pela cannabis e como adjuvante no tratamento do tabagismo. Os potenciais efeitos colaterais, de induzir depressão e ansiedade limitaram o uso clínico deste antagonista CB1. CONCLUSÃO: Os canabinoides têm demonstrado que podem ter amplo interesse terapêutico em psiquiatria, porém mais estudos controlados são necessários para confirmar estes achados e determinar a segurança destes compostos.

OBJECTIVE: To review the main advances related to the potential therapeutic use of cannabinoid compounds in psychiatry. METHOD: A search was performed in the online databases PubMed, ScieELO, and Lilacs for studies and literature reviews concerning therapeutic applications of cannabinoids in psychiatry, especially cannabidiol, rimonabant, Δ9-tetrahydrocannabinol, and their analogues. RESULTS: Cannabidiol was found to have therapeutic potential with antipsychotic, anxiolytic, and antidepressant properties, in addition to being effective in other conditions. Δ9-tetrahydrocannabinol and its analogues were shown to have anxiolytic effects in the treatment of cannabis dependence and to function as an adjuvant in the treatment of schizophrenia, although additional studies are necessary to support this finding. Rimonabant was effective in the treatment of the subjective and physiological symptoms of cannabis intoxication and functioned as an adjuvant in the treatment of tobacco addiction. The potential to induce adverse reactions such as depression and anxiety restrained the clinical use of this CB1 antagonist. CONCLUSION: Cannabinoids may be of great therapeutic interest to psychiatry; however, further controlled trials are necessary to confirm the existing findings and to establish the safety of such compounds.

Celecoxib reduces symptoms in men with difficult chronic pelvic pain syndrome (Category IIIA)

We investigated the effectiveness of celecoxib in reducing symptoms in patients with difficult chronic pelvic pain syndrome (CPPS), NIH category IIIA. Sixty-four patients with category IIIA CPPS were randomized into two groups of 32 subjects each. One group was treated with celecoxib (200 mg daily) and the other with placebo. All patients underwent treatment for 6 weeks and were evaluated clinically before (baseline) and after 1, 2, 4, 6, and 8 weeks of treatment. The evaluation included the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and a subjective global assessment (SGA). Repeated measures analysis of variance was used to evaluate treatment and time effects and their interaction. A decrease (means ± SD) in total NIH-CPSI score from 23.91 ± 5.27 to 15.88 ± 2.51 in the celecoxib group and from 24.25 ± 5.09 to 19.50 ± 2.50 in the placebo group was observed during treatment (0 to 6 weeks). A statistically significant decrease was observed in pain subscore (P < 0.006), quality of life subscore (P < 0.032) and total NIH-CPSI score (P < 0.015) after 2, 4 and 6 weeks, but not in urinary subscore. In addition, 38 percent of the celecoxib and 13 percent of the placebo subjects had at least a moderate improvement in SGA. The trend was similar for the NIH-CPSI scores. However, the response to treatment in terms of total NIH-CPSI score or subscore was not significantly different from placebo after interruption of treatment for 2 weeks. Our results show that celecoxib provides significant symptomatic improvement limited to the duration of the therapy in patients with difficult category IIIA CPPS compared to placebo.