Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Neumol. pediátr. (En línea) ; 18(1): 14-15, 2023.
Artigo em Espanhol | LILACS | ID: biblio-1442721

RESUMO

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.


Assuntos
Humanos , Fibrose Cística/tratamento farmacológico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Transplante de Pulmão , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística/cirurgia , Combinação de Medicamentos , Benzodioxóis/uso terapêutico , Aminofenóis/uso terapêutico , Indóis/uso terapêutico
3.
Rev. bras. parasitol. vet ; 30(1): e025220, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1156219

RESUMO

Abstract Southern cattle tick resistance to pour-on and injectable acaricides has yet to be evaluated on a broader scope, and the paucity of information on the subject may hinder efforts to control this parasite. The objective of this study was to evaluate the resistance profile of ten populations of Rhipicephalus microplus to the acaricides fluazuron, fipronil and ivermectin in cattle herds in Mato Grosso do Sul, Brazil. The larval immersion test (LIT) was used to evaluate susceptibility to ivermectin and fipronil and the adult immersion test (AIT) was performed to evaluate fluazuron. Samples were randomly obtained in ten farms, and in general, we found resistance in five samples to fluazuron and in four samples to ivermectin and fipronil. Six samples showed incipient resistance to ivermectin and fipronil. Five of the ten evaluated samples showed resistance and/or incipient resistance to all the active ingredients, and the other five to two active ingredients. Among the samples classified as resistant, the average resistance ratio for ivermectin was 2.75 and 3.26 for fipronil. These results demonstrate the advanced status of resistance to the most modern chemical groups for the control of R. microplus in the state of Mato Grosso do Sul.


Resumo A resistência do carrapato-do-boi a acaricidas com modo de aplicação "pour-on" e injetáveis é pouco avaliada em estudos mais abrangentes, e essa escassez de informação pode resultar falhas no seu controle. Este estudo teve como objetivo avaliar o perfil de resistência em dez populações de Rhipicephalus microplus aos acaricidas fluazuron, fipronil e ivermectina, em rebanhos bovinos em Mato Grosso do Sul, Brasil. A caracterização fenotípica da resistência foi realizada por meio do teste de imersão de adultos (AIT) para o fluazuron, e teste de imersão de larvas (LIT) para fipronil e ivermectina. As amostras foram obtidas aleatoriamente em dez fazendas, sendo diagnosticada resistência em cinco amostras ao fluazuron e em quatro amostras à ivermectina e fipronil. Seis amostras apresentaram resistência incipiente à ivermectina e fipronil. Cinco das dez amostras avaliadas apresentaram resistência e / ou resistência incipiente a todos os princípios ativos, e as outras cinco a dois princípios ativos. Entre as amostras classificadas como resistentes, a média do fator de resistência para ivermectina foi de 2,75 e de 3,26 para fipronil. Esses resultados demonstram o avançado estado de resistência aos mais modernos grupos químicos para o controle de R. microplus em Mato Grosso do Sul.


Assuntos
Animais , Infestações por Carrapato/parasitologia , Infestações por Carrapato/veterinária , Resistência a Medicamentos , Doenças dos Bovinos/parasitologia , Rhipicephalus/efeitos dos fármacos , Acaricidas/farmacologia , Compostos de Fenilureia/farmacologia , Pirazóis/farmacologia , Ivermectina/farmacologia , Brasil , Bovinos
4.
Braz. J. Pharm. Sci. (Online) ; 55: e00249, 2019. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1011652

RESUMO

A series of N-substituted-3-(napthalen-2-yl)-5-substituted phenyl-4,5-dihydropyrazole-1-carbothioamide derivatives (4a-n) were synthesized with the view of structural requirements of pharmacophore for potential anticonvulsant agents. The synthesized compounds were assayed intraperitoneally (i.p.) and subcutaneously (s.c.) in mice against seizures induced by MES and scPTZ methods, respectively.Neurologic deficit was evaluated by rotarod method. Among the tested compounds, 4g, 4i, 4j and 4n emerged as the most active molecule in the MES model at a dose of 30 mg/kg at 0.5h comparable to standardscarbamazepine and phenytoin. In the scPTZ test,4e and 4l were found to be most active compounds at the lowest dose of 30 mg/kg at 0.5h, in the management of the convulsive disorder. Molecular docking studies of the titled compounds were also donewith 3D crystal structure of human cytosolic branched chain amino transferase (hBCATc) enzyme and compound 4e was found to have five hydrogen bond interactions with the most important active site residues.In neurotoxicity studies, except compounds 4b, 4c, 4h and 4k, rest of the compounds showed no sign of toxicity.


Assuntos
Animais , Masculino , Feminino , Camundongos , Pirazóis/análise , Anticonvulsivantes/análise , Epilepsia/diagnóstico , Simulação de Acoplamento Molecular/classificação
5.
Rev. méd. Chile ; 147(1): 73-82, 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-991375

RESUMO

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.


Assuntos
Humanos , Fatores de Coagulação Sanguínea/uso terapêutico , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/terapia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Administração Oral , Fatores de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Antídotos/uso terapêutico
6.
Rev. méd. Chile ; 146(9): 1074-1078, set. 2018. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-978800

RESUMO

We report a 51-year-old female who had a first episode of thrombocytopenia at 23 years of age during a pregnancy. At the age of fifty, a hysterectomy was indicated due to a metrorrhagia: a platelet count of 21,000/ul was detected. She was treated with eltrombopag with a good response. The family history of the patient revealed the presence of thrombocytopenia in several family members. Suspecting a hereditary thrombocytopenia, a genetic study revealed a mutation in the MYH-9 gene. This mutation can be suspected when there is a family history of thrombocytopenia with autosomal dominant inheritance, macrothrombocytopenia and in this particular case, due to the response to thrombopoietin receptor agonist, eltrombopag.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Trombocitopenia/congênito , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Contagem de Plaquetas , Pirazóis , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Benzoatos , Biópsia , Doenças Genéticas Inatas , Hidrazinas , Mutação
8.
An. acad. bras. ciênc ; 90(1): 239-245, Mar. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-886915

RESUMO

ABSTRACT This study evaluated the in vitro toxicity and motor activity changes in African-derived adult honey bees (Apis mellifera L.) exposed to lethal or sublethal doses of the insecticides fipronil and imidacloprid. Mortality of bees was assessed to determine the ingestion and contact lethal dose for 24 h using probit analysis. Motor activities in bees exposed to lethal (LD50) and sublethal doses (1/500th of the lethal dose) of both insecticides were evaluated in a behavioral observation box at 1 and 4 h. Ingestion and contact lethal doses of fipronil were 0.2316 ? 0.0626 and 0.0080 ? 0.0021 μg/bee, respectively. Ingestion and contact lethal doses of imidacloprid were 0.1079 ? 0.0375 and 0.0308 ? 0.0218 μg/bee, respectively. Motor function of bees exposed to lethal doses of fipronil and imidacloprid was impaired; exposure to sublethal doses of fipronil but not imidacloprid impaired motor function. The insecticides evaluated in this study were highly toxic to African-derived A. mellifera and caused impaired motor function in these pollinators.


Assuntos
Animais , Pirazóis/toxicidade , Abelhas/efeitos dos fármacos , Neonicotinoides/toxicidade , Inseticidas/toxicidade , Atividade Motora/efeitos dos fármacos , Nitrocompostos/toxicidade , Abelhas/fisiologia , Comportamento Animal/efeitos dos fármacos , Dose Letal Mediana
9.
Clinics ; 73: e216, 2018. tab
Artigo em Inglês | LILACS | ID: biblio-890747

RESUMO

OBJECTIVES: Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension. METHODS: A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study. RESULTS: Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow-up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall. CONCLUSIONS: Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Embolia Pulmonar/tratamento farmacológico , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Antitrombinas/administração & dosagem , Dabigatrana/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Doença Crônica , Administração Oral , Reprodutibilidade dos Testes , Resultado do Tratamento
10.
Braz. j. med. biol. res ; 50(6): e6141, 2017. graf
Artigo em Inglês | LILACS | ID: biblio-839302

RESUMO

Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising strategies for the treatment of obesity and other related metabolic disorders. Although CB1R inhibition may cause adverse psychiatric effects including depression and anxiety, the investigation of the role of peripheral CB1R on weight loss and related metabolic parameters are urgently needed. We first explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist, on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice. Then, real-time PCR and electrophysiology were used to explore the contribution of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD feeding caused body weight gain, and decreased glucose/insulin tolerance in mice compared to those in the regular diet group (P<0.05), which was restored by rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the control group. Daily treatment with rimonabant for 5 weeks was shown to counter such decrease (P<0.05). Collectively, our findings provided a novel understanding for peripheral CB1R's role in the modulation of body weight and glucose homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as potential targets for obesity treatment.


Assuntos
Animais , Masculino , Glicemia/efeitos dos fármacos , Canais de Cálcio/efeitos dos fármacos , Antagonistas de Receptores de Canabinoides/farmacologia , Músculo Esquelético/efeitos dos fármacos , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Peso Corporal/efeitos dos fármacos , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/etiologia , Resistência à Insulina , Camundongos Endogâmicos C57BL , Modelos Animais , Músculo Esquelético/metabolismo , Obesidade/etiologia , Receptor CB1 de Canabinoide/fisiologia
11.
São Paulo med. j ; 134(4): 322-329, July-Aug. 2016. tab, graf
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: lil-792817

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tromboembolia/prevenção & controle , Custos de Medicamentos/estatística & dados numéricos , Anticoagulantes/economia , Anticoagulantes/uso terapêutico , Pirazóis/economia , Pirazóis/uso terapêutico , Piridonas/economia , Piridonas/uso terapêutico , Valores de Referência , Fibrilação Atrial/economia , Fibrilação Atrial/prevenção & controle , Varfarina/uso terapêutico , Brasil , Administração Oral , Reprodutibilidade dos Testes , Fatores Etários , Resultado do Tratamento , Custos e Análise de Custo , Atenção à Saúde/economia , Dabigatrana/economia , Dabigatrana/uso terapêutico
12.
J. bras. pneumol ; 42(2): 146-154, Mar.-Apr. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-780891

RESUMO

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.


Assuntos
Humanos , Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Dabigatrana/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Tiazóis/uso terapêutico , Fatores de Tempo , Varfarina/uso terapêutico
13.
Braz. j. med. biol. res ; 49(9): e5388, 2016. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951696

RESUMO

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.


Assuntos
Animais , Masculino , Pancreatite/tratamento farmacológico , Pirazóis/uso terapêutico , Quinolinas/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/patologia , Ensaio de Imunoadsorção Enzimática , Western Blotting , Doença Aguda , Interleucina-6/sangue , Resultado do Tratamento , Apoptose , Peroxidase/análise , Marcação In Situ das Extremidades Cortadas , Ensaio de Desvio de Mobilidade Eletroforética , Interleucina-1beta/sangue , Amilases/sangue , Lipase/sangue
14.
Braz. j. phys. ther. (Impr.) ; 19(3): 194-200, May-Jun/2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-751384

RESUMO

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. .


Assuntos
Adulto , Humanos , Masculino , Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Rearranjo Gênico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/genética , Receptores Proteína Tirosina Quinases/metabolismo
15.
Braz. j. med. biol. res ; 47(12): 1050-1056, 12/2014. graf
Artigo em Inglês | LILACS | ID: lil-727667

RESUMO

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.


Assuntos
Animais , Lesões Encefálicas/complicações , Córtex Cerebral/lesões , Ciclo-Oxigenase 1/fisiologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Pirazóis/uso terapêutico , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Descorticação Cerebral , Ciclo-Oxigenase 1/metabolismo , Modelos Animais de Doenças , Dinoprostona/análise , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Hipocampo/metabolismo , /sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Proteínas Proto-Oncogênicas c-sis/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Sinaptofisina/análise , Sinaptofisina/metabolismo
16.
J. pediatr. (Rio J.) ; 90(5): 512-517, Sep-Oct/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-723170

RESUMO

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 ...


Assuntos
Feminino , Humanos , Lactente , Masculino , Síndrome de Bartter/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Enalapril/uso terapêutico , Indometacina/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Síndrome de Bartter/complicações , Bicarbonatos/sangue , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Creatinina/análise , Seguimentos , Potássio/sangue , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Acta cir. bras ; 29(7): 423-428, 07/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-714578

RESUMO

PURPOSE: To evaluate the genotoxicity of propolis and L-lysine, as well as their effects on the possible cellular damage in erythroblasts (bone marrow) and leukocytes (peripheral blood) caused by the carcinogen BBN (n - butyl - n {4 - hydroxybutyl} nitrosamine) in rats subjected to bladder carcinogenesis and treated with green propolis and L-lysine. METHODS: One hundred and twenty five rats were distributed into the following groups: I, IIA, IIB, III, K, L M N, X, XI, XII and XIII. Groups I to X received BBN in drinking water for 14 weeks (wks). Group I was treated with intragastric (ig) propolis at 150 mg/kg body weight, for 44 wks, beginning 30 days before start of BBN. Groups IIA and III were treated with propolis (150 mg/kg), for 40 wks, subcutaneous (sc) and ig, respectively, beginning simultaneously with BBN. On the 32nd wk, the animals of groups L, M and N were treated ig with L-lysine (300 mg/kg), celecoxib (30 mg/kg) and propolis (300 mg/kg), respectively, up to the 40th wk. The groups that received only BBN (IIB and K) were treated with water, sc and orally, respectively, for 40 wks. Groups XI, XII and XIII received respectively propolis (150 mg/kg), L-lysine (150 mg/kg) and water ig for 40 wks. After 40 wks, the surviving animals were anesthetized and subjected to femoral bone marrow aspiration and blood collection from the aorta, for CA and MNT, respectively, for investigation of genotoxicity. RESULTS: Groups IIB and K, which received only BBN and water, showed the greatest DNA damage in peripheral leukocytes (CA) and largest number of micronuclei in bone marrow erythrocytes (MNT) in relation to all other groups that received BBN and lysine and/or propolis (p<0.001). CONCLUSIONS: Both propolis and L-lysine are effective in protecting against genotoxicity, as well not being genotoxic themselves toward the cells evaluated, at the doses and times administered and according to the two tests utilized. .


Assuntos
Animais , Células da Medula Óssea/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Lisina/farmacologia , Própole/farmacologia , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Anticarcinógenos/farmacologia , Testes de Carcinogenicidade , Ensaio Cometa , Dano ao DNA , Testes para Micronúcleos , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/prevenção & controle
18.
Braz. j. pharm. sci ; 50(1): 73-81, Jan-Mar/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-709533

RESUMO

This work evaluates the central nervous effects in ICR strain mice of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1,5-a][1,3,5]triazine (MH4b1), a compound obtained by an efficient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profile. The tests applied were: maximal electroshock seizure (MES), pentylenetetrazole (PTZ) seizures, forced swimming, plus maze, marble burying, sleeping time, rota-rod and catalepsy. In addition, MH4b1 binding to the benzodiazepine site of the GABA-A receptor and MH4b1 inhibition of monoamine oxidase (MAO) subtypes A and B were evaluated. MH4b1 showed anticonvulsant effects in a dose dependent manner (30-300 mg/kg, p.o.) against MES and inhibition of MAO-B (IC50: 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition.


Este trabalho avalia o efeito do 2-etiltio-7-metil-4-(4-metilfenil)pirazol[1,5-a][1,3,5]triazina (MH4b1) no sistema nervoso central de camundongos ICR. O MH4b1 foi obtido por a reação de 4-metilbenzoilimidoditiocarbonato de S,S-dietil e 5-amino-3-metil-1H-pirazol em uma única etapa. O perfil neurofarmacológico foi realizado por testes de convulsão induzida por eletrochoque (MES) e pentilenotetrazol (PTZ) e por testes de nado forçado, labirinto em cruz, esconder as esferas, sono barbitúrico, rota-rod e catalepsia. Também foi avaliada a união do MH4b1 ao o local de ligação de benzodiazepínicos do receptor GABA-A e a capacidade inibitória do MH4b1 sobre a monoaminoxidase (MAO) A e B. O MH4b1 mostrou efeito anticonvulsivante dependente da dose (30-300 mg) no teste do MES e apresentou atividade inibitória da MAO-B (CI50: 24.5 µM) sem interagir com o local de ligação de benzodiazepínicos do receptor. Os resultados sugerem que o MH4b1 tem atividade anticonvulsivante relacionada com a inibição da MAO-B.


Assuntos
Camundongos , Pirazóis/farmacocinética , Convulsivantes/agonistas , Triazinas/farmacocinética , Eletrochoque/métodos , Monoaminoxidase/efeitos dos fármacos
19.
Braz. j. med. biol. res ; 47(1): 50-59, 01/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-697673

RESUMO

Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.


Assuntos
Animais , Ratos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , /farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Mioblastos Cardíacos/efeitos dos fármacos , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Western Blotting , Linhagem Celular , Proliferação de Células/genética , Sobrevivência Celular/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , Espectroscopia de Luz Próxima ao Infravermelho , Fatores de Tempo
20.
Biol. Res ; 47: 1-9, 2014. ilus, graf
Artigo em Inglês | LILACS | ID: biblio-950723

RESUMO

BACKGROUND: During the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described. Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR). RESULTS: Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM), inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF) production and cell proliferation in the tumor. CONCLUSION: The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs) and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.


Assuntos
Animais , Feminino , Embrião de Galinha , Camundongos , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/secundário , Neovascularização Patológica/tratamento farmacológico , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Neoplasias da Mama/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Galinhas , Marcação In Situ das Extremidades Cortadas , Inibidores da Angiogênese/farmacologia , Linhagem Celular Tumoral , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Membrana Corioalantoide , Proliferação de Células/efeitos dos fármacos , Celecoxib
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...