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1.
Cancers (Basel) ; 16(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38473383

RESUMO

Introduction: Children with cancer experience significant pain and anxiety during needle-based procedures. Undertreated pain in children has long-lasting consequences and reduces the efficacy of subsequent analgesic efforts. A validated quality improvement (QI) intervention, known as the "Children's Comfort Promise", includes (1) topical anesthetics, (2) sucrose or breastfeeding for infants, (3) comfort positioning, and (4) distraction techniques, and has been shown to be highly effective in decreasing procedural pain and anxiety in children. However, there is limited data about the adoption, adaptation, and implementation of these interventions in low- and middle-income countries (LMICs). Methods: A QI pilot project utilizing the Model for Improvement of the "Global Comfort Promise" was implemented in four global pediatric cancer hospitals (Lima, Peru; Barretos, Brazil; Pietermaritzburg, South Africa; and Manila, Philippines). Between August 2021 and January 2023, the pilot sites identified a specific aim, co-designed the measurement strategy with St. Jude Children's Research Hospital, and adopted, adapted, and implemented the project at their individual sites. Results: A total of 2,185 different procedures were recorded in the first year of implementation. Most patients were less than 10 years old (60.5%) and solid tumors (37.9%) were the most common diagnosis. Overall, healthcare professionals (98.3%) were satisfied with the procedures. Parents and patients reported that only 33.7% of patients experienced pain during the procedure. All (100%) parents and patients felt the healthcare teams adequately addressed their child's pain. Median self-reported adherence to ≥2 interventions was 98.0%. Challenges to the implementation of the QI initiative included lack of training, turnover of the medical staff, maintaining staff enthusiasm, and access to topical anesthetics. Each site had unique change ideas to implement the initiative. Conclusions: This multi-site, multi-country QI initiative was feasible and was successfully adopted, adapted, and implemented in the LMIC context to improve procedural pain in children (Global Comfort Promise). Additionally, this intervention resulted in high satisfaction of both healthcare professionals and patients/families. Further work is needed to overcome the challenges of topical anesthetic access and education of the workforce. Additional plans include modifying the Global Comfort Promise to include high-quality communication and expanding to additional sites with further refinement of the implementation strategy.

2.
Lancet Glob Health ; 12(2): e331-e340, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190831

RESUMO

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.


Assuntos
Cuidados Críticos , Estado Terminal , Humanos , Criança , Adolescente , Consenso , Estado Terminal/terapia , Técnica Delphi , Coleta de Dados
3.
Probiotics Antimicrob Proteins ; 15(5): 1327-1341, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36066817

RESUMO

The poultry sector demands alternative additives to antibiotics that can be used as performance enhancers. Therefore, this experiment was conducted to evaluate the probiotics effects on performance, intestinal health, and redox status of 720 broilers exposed to heat stress from 15 days of age. Eight dietary treatments were evaluated: basal diet (BD) without antibiotic and probiotic (T1); BD supplemented with antibiotic zinc bacitracin (T2), BD supplemented with commercial probiotic of Bacillus subtilis DSM 17,299 (T3), BD supplemented with non-commercial probiotic of Lactococcus lactis NCDO 2118, Lactobacillus delbrueckii CNRZ 327, Escherichia coli CEC15, or Saccharomyces boulardii (T4 to T7), and BD simultaneously supplemented with the four non-commercial probiotics (T8). Feed intake, weight gain, and feed conversion were determined in the period from 1 to 42 days of age. Carcass and cuts yield, abdominal fat deposition, cloacal temperature, weight and length of intestine, activity of myeloperoxidase and eosinophilic peroxidase enzymes in the jejunum, jejunal histomorphometry, relative gene expression in the jejunum (occludin, zonulin, interleukin-8, cholecystokinin, ghrelin, and heat shock protein-70), and liver (heat shock protein-70), in addition to malondialdehyde level and superoxide dismutase activity in the intestine, liver, and blood, were measured in broilers at 42 days old. As main results, broilers fed T1 diet exhibited lower weight gain (3.222 kg) and worse feed conversion (1.70 kg/kg). However, diets containing non-commercial probiotics resulted in up to 3.584 kg of weight gain and improved feed conversion by up to 10%, similar to that observed for broilers of the T2 and T3 groups.


Assuntos
Galinhas , Probióticos , Animais , Galinhas/metabolismo , Suplementos Nutricionais , Dieta , Resposta ao Choque Térmico , Antibacterianos/metabolismo , Aumento de Peso , Proteínas de Choque Térmico/metabolismo , Ração Animal/análise
4.
Front Immunol ; 11: 521409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193300

RESUMO

Background: Chagas disease caused by Trypanosoma cruzi (T. cruzi) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between IL1B, IL6, IL17A, or IL18 polymorphism profiles and cardiomyopathy or T. cruzi parasitemia, as well as the impact of HIV infection on cardiopathy. Methods: Two hundred twenty-six patients and 90 control individuals were analyzed. IL1B rs1143627 T>C, IL6 rs1800795 C>G, IL17A rs2275913 G>A, IL18 rs187238 C>G, and IL18 rs1946518 C>A SNVs were analyzed by real-time PCR and T. cruzi parasitemia by PCR. Results: Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The IL6 rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between IL17A rs2275913 AA and IL18 s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively). IL18 rs1946518 AA and IL1B rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class ≥ 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for IL18 rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class ≥ 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA ≥ 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively). Conclusions: Our data support a protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the IL6 CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies.


Assuntos
Doença de Chagas , Genótipo , Interleucina-17 , Interleucina-18 , Interleucina-1beta , Interleucina-6 , Parasitemia , Polimorfismo Genético , Trypanosoma cruzi/imunologia , Adulto , Doença de Chagas/genética , Doença de Chagas/imunologia , Feminino , Humanos , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-18/genética , Interleucina-18/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Parasitemia/genética , Parasitemia/imunologia
5.
Fisioter. Bras ; 21(1): 59-68, mar 8, 2020.
Artigo em Português | LILACS | ID: biblio-1282620

RESUMO

Na Fisioterapia Oftálmica são realizados exercícios para aumentar a função ocular. A Miopia e o Astigmatismo são erros refrativos que causam alteração da visão à distância. Objetiva-se neste estudo, verificar a influência da Fisioterapia nas alterações visuais e nas dores e desconfortos musculares. Essa pesquisa qualitativa do tipo observacional descritivo foi realizada com um grupo de cinco voluntários que apresentavam Astigmatismo e/ou Miopia. Foram utilizados seis instrumentos para coleta de dados: um questionário no início e no final da intervenção, uma avaliação da Acuidade Visual pela Escala Optométrica de Snellen, um diário de campo, uma ficha individual do colaborador e laudos médicos. O protocolo consistiu em exercícios, baseado no método Self-Healing de Meir Schneider. Com a realização deste estudo, constatou-se um aumento da Acuidade Visual, efeitos na presbiopia, na satisfação com o corpo, na autoestima, na diminuição da fadiga ocular, no desapego do uso dos óculos, no aumento da ampliação periférica, na atenção do olhar, na memória e na aquisição do conhecimento sobre os cuidados com a visão. Considera-se que a Fisioterapia Oftálmica, por intermédio do método Self-Healing, é uma ferramenta de intervenção que pode recuperar e/ou prevenir problemas oculares e diminuir dores musculares. (AU)


In Ophthalmic Physiotherapy exercises are performed to increase eye function. Myopia and Astigmatism are refractive errors that cause changes in distance vision. The objective of this study was to verify the influence of Physical therapy on visual changes, muscle pain and discomfort. This qualitative, descriptive and observational research was performed with a group of five volunteers who presented Astigmatism and/or Myopia. Six instruments were used for data collection: a questionnaire at the beginning and at the end of the intervention, a Visual Acuity assessment by the Snellen Optometric Scale, a field diary, an individual employee record and also medical reports. The protocol consisted of exercises based on Meir Schneider's Self-Healing Method. With this study, we observed an increase in Visual Acuity, effects on presbyopia, body satisfaction, self-esteem, decreased eye fatigue, detachment from wearing glasses, increased peripheral magnification, eye attention, memory and acquisition of knowledge about vision care. Ophthalmic Physiotherapy, through the Self-Healing method, is an intervention tool that can recover and/or prevent eye problems and decrease muscle pain. (AU)


Assuntos
Humanos , Astigmatismo , Acuidade Visual , Modalidades de Fisioterapia , Miopia
6.
Artigo em Inglês | MEDLINE | ID: mdl-31737574

RESUMO

Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage milieu. Leishmania (L.) infantum parasites live inside macrophages and cause a fatal and neglected viscerotropic disease, with a toxic treatment. Sertraline was studied as a free formulation (SERT) and also entrapped into phosphatidylserine liposomes (LP-SERT) against intracellular amastigotes and in a murine model of visceral leishmaniasis. LP-SERT showed a potent activity against intracellular amastigotes with an EC50 value of 2.5 µM. The in vivo efficacy of SERT demonstrated a therapeutic failure. However, when entrapped into negatively charged liposomes (-58 mV) of 125 nm, it significantly reduced the parasite burden in the mice liver by 89% at 1 mg/kg, reducing the serum levels of the cytokine IL-6 and upregulating the levels of the chemokine MCP-1. Histopathological studies demonstrated the presence of an inflammatory infiltrate with the development of granulomas in the liver, suggesting the resolution of the infection in the treated group. Delivery studies showed fluorescent-labeled LP-SERT in the liver and spleen of mice even after 48 h of administration. This study demonstrates the efficacy of PS liposomes containing sertraline in experimental VL. Considering the urgent need for VL treatments, the repurposing approach of SERT could be a promising alternative.


Assuntos
Antiprotozoários/administração & dosagem , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Lipossomos , Fosfatidilserinas , Sertralina/administração & dosagem , Animais , Antiprotozoários/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Imunomodulação/efeitos dos fármacos , Leishmania donovani/imunologia , Leishmaniose Visceral/imunologia , Lipossomos/química , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Fosfatidilserinas/administração & dosagem , Sertralina/química , Baço/metabolismo , Baço/parasitologia , Baço/patologia
7.
Acta fisiátrica ; 26(3): 123-126, set. 2019.
Artigo em Inglês | LILACS | ID: biblio-1122742

RESUMO

Alterações no equilíbrio são observadas em hemiparéticos após um acidente vascular encefálico (AVE), gerando impactos físicos, sociais e econômicos significativos; assim, uma avaliação foi desenvolvida para facilitar os planos de tratamento para os pacientes. A goniometria é atualmente usada como ferramenta de avaliação da amplitude de movimento (ADM); no entanto, o desenvolvimento de exergames trouxe uma nova perspectiva para a avaliação, que utiliza um mecanismo dinâmico e tem pouca subjetividade. Objetivo: Este estudo avaliou a confiabilidade inter e intraexaminadores da medida da ADM da abdução do ombro em pacientes pós-AVE usando o exergame PhysioPlay™. Método: Treze voluntários com AVE crônico, com idade de 58,23 ± 9,96 anos (homens e mulheres), participaram deste estudo. Dois fisioterapeutas avaliaram a abdução do ombro usando goniometria e o exergame PhysioPlay™. Um reteste foi realizado uma semana depois. Resultados: Os resultados das análises utilizando o coeficiente de correlação intraclasse (CCI) mostraram excelente nível de confiabilidade inter e intraexaminadores (r> 0,90; p <0,05). A correlação de Pearson entre as medidas máximas obtidas na goniometria e o software PhysioPlay™ apresentou alta correlação (r> 0,90, p = 0,001). Conclusão: O Kinect associado ao exergame PhysioPlay™ apresentou excelente confiabilidade na captura da medida da ADM em comparação à goniometria.


Changes in balance are observed in some hemiparetics following a stroke, generating significant physical, social, and economic impacts; thus, an assessment was developed to facilitate treatment plans for patients. Goniometry is currently used as an evaluation tool for range of motion (ROM); however, the development of exergames has brought a new perspective to the assessment, which uses a dynamic mechanism and has little subjectivity. Objective: This study evaluates the inter-and intra-rater reliability of ROM measurement of the shoulder abduction in post-stroke patients using the exergame PhysioPlay™. Method: Thirteen volunteer chronic stroke survivors, aged 58.23 ± 9.96 years (men and women), participated in this study. Two physiotherapists evaluated the abduction of the shoulder using goniometry and the exergame PhysioPlay™. A retest was performed one week later. Clinical trial registry number ­ RBR-55smwr. Results: The results of the analyses using intraclass correlation coeficient (ICC) showed an excellent inter- and intra-rater reliability level (r > 0.90; p < .05). The Pearson correlation between the maximum measures obtained in the goniometry and the software PhysioPlay™ showed a high correlation (r > 0.90, p= .001). Conclusion: The Kinect associated with the exergame PhysioPlay™ presented excellent reliability in capturing the ROM measure compared to the conventional goniometry.


Assuntos
Reabilitação , Acidente Vascular Cerebral , Especialidade de Fisioterapia , Artrometria Articular
8.
Eur J Med Chem ; 176: 162-174, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103897

RESUMO

Chagas disease is a neglected protozoan disease that affects more than eight million people in developing countries. Due to the limited number and toxicity profiles of therapies in current use, new drugs are urgently needed. In previous studies, we reported the isolation of two related antitrypanosomal neolignans from Nectandra leucantha (Lauraceae). In this work, a semi-synthetic library of twenty-three neolignan derivatives was prepared to explore synthetically accessible structure activity relationships (SAR) against Trypanosoma cruzi. Five compounds demonstrated activity against trypomastigotes (IC50 values from 8 to 64 µM) and eight showed activity against intracellular amastigotes (IC50 values from 7 to 16 µM). Eighteen derivatives demonstrated no mammalian cytotoxicity up to 200 µM. The phenolic acetate derivative of natural dehydrodieugenol B was effective against both parasite forms and eliminated 100% of amastigotes inside macrophages. This compound caused rapid and intense depolarization of the mitochondrial membrane potential, with decreased levels of intracellular reactive oxygen species being observed. Fluorescence assays demonstrated that this derivative affected neither the permeability nor the electric potential of the parasitic plasma membrane, an effect also corroborated by scanning electron microscopy studies. Structure-activity relationship studies (SARs) demonstrated that the presence of at least one allyl side chain on the biaryl ether core was important for antitrypanosomal activity, and that the free phenol is not essential. This set of neolignan derivatives represents a promising starting point for future Chagas disease drug discovery studies.


Assuntos
Anisóis/farmacologia , Lignanas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Anisóis/síntese química , Anisóis/química , Anisóis/toxicidade , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Humanos , Lignanas/síntese química , Lignanas/química , Lignanas/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/metabolismo
9.
Bioorg Chem ; 89: 103001, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31129501

RESUMO

This work describes the isolation of six metabolites from leaves and branches of Piper cernuum (Piperaceae): (-)-cubebin (1), (-)-hinokinin (2), (-)-kusunokinin (3), trans-dehydroagarofuran (4), 11-hydroxi-4,5-secoeudesmane-4,5-dione (5), and (-)-bornyl p-coumarate (6). Antitrypanosomal activity and toxicity of purified compounds were performed in vitro against trypomastigote forms of Trypanosoma cruzi and NCTC cells, respectively. Compounds 2, 3 and 5 showed moderate activities with IC50 values of 33.1, 31.8 and 45.9 µM, respectively, while compounds 1 and 4 were inactive (IC50 > 100 µM). On the other hand, compound 6 displayed an IC50 value of 2.1 µM, a selectivity index (SI) of 18 and induced a considerable interference in the plasma membrane permeability (87%) in trypomastigotes of T. cruzi. Additionally, the lethal effect of compound 6 in T. cruzi could be associated to the plasma membrane permeability. Finally, experiments using scanning electron microscopy (SEM) confirmed the obtained results in which was possible to observe total alteration parasites topography after treatment with compound 6 in comparison to untreated parasites. These data indicated that the lethal action of compound 6 is directly related to structural disruption of the membrane.


Assuntos
Permeabilidade da Membrana Celular/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Piperaceae/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Células Cultivadas , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação
10.
Artigo em Português | LILACS, Sec. Est. Saúde SP, SESSP-IALPROD, Sec. Est. Saúde SP, SESSP-IALACERVO | ID: biblio-1007421

RESUMO

Chagas disease is a neglected protozoan disease that affects more than eight million people in developing countries. Due to the limited number and toxicity profiles of therapies in current use, new drugs are urgently needed. In previous studies, we reported the isolation of two related antitrypanosomal neo- lignans from Nectandra leucantha (Lauraceae). In this work, a semi-synthetic library of twenty-three neolignan derivatives was prepared to explore synthetically accessible structure activity relationships (SAR) against Trypanosoma cruzi. Five compounds demonstrated activity against trypomastigotes (IC50 values from 8 to 64 mM) and eight showed activity against intracellular amastigotes (IC50 values from 7 to 16 mM). Eighteen derivatives demonstrated no mammalian cytotoxicity up to 200 mM. The phenolic ac- etate derivative of natural dehydrodieugenol


Assuntos
Trypanosoma cruzi , Doença , Doença de Chagas
11.
Fisioter. Bras ; 19(5): 582-590, Dez 25, 2018.
Artigo em Português | LILACS | ID: biblio-1280858

RESUMO

Introdução: A laserpuntura é utilizada para analgesia, embora os protocolos para aplicação na dor neuropática permaneçam contraditórios. Objetivo: Avaliar o efeito da laserpuntura na modulação da dor neuropática, impacto na qualidade de vida e processo inflamatório local. Material e métodos: Cinco pacientes com diagnóstico de lesão nervosa periférica e dor neuropática associada receberam aplicação do laser AlGaInP, 658 nm, 10 mW, 9 J/cm2, em acupontos especí­ficos, durante 15 sessões, 3 vezes na semana, por 50 minutos. A avaliação pré e pós-intervenção foi realizada pela Escala Visual Analógica, questionário para dor (McGill), questionário de qualidade de vida (SF-36), Índice de incapacidade de Oswestry e termografia. Resultados: Foi observada redução da média da pontuação na Escala Visual Analógica em 3 de 5 pacientes e redução da média de dor após 15 sessões. A avaliação pelo McGill mostrou redução nas dimensões afetivo, avaliativo e total. No questionário SF-36 foi observada melhora das dimensões Capacidade Funcional e Limitação por Aspectos Emocionais. No Índice de Oswestry observou-se redução da média da porcentagem e na termografia não houve diferença nos valores pré e pós-intervenção. Conclusão: Estes resultados sugerem eficácia da laserpuntura na redução da dor e melhora da qualidade de vida em pacientes com dor neuropática decorrente de lesão nervosa periférica. (AU)


Introduction: Laserpuncture is used for analgesia, although the protocols for use in neuropathic pain remain contradictory. Objective: To evaluate the effect of laserpuncture in modulating neuropathic pain, impact on quality of life and local inflammatory process. Methods: Five patients with peripheral nerve injury and neuropathic pain associated application received AlGaInP laser, 658 nm, 10 mW, 9 J/cm2 at specific acupoints for 15 sessions, 3 times a week for 50 minutes. The pre- and post-intervention were performed by Visual Analogue Scale, questionnaire for pain (McGill), quality of life questionnaire (SF-36), Oswestry disability index and thermography. Results: A significant reduction in Visual Analogue Scale score average was observed in 3 of 5 patients in addition to an overall reduction of average pain after 15 sessions. The evaluation by McGill showed reduction in affective, evaluative and overall dimensions. In the SF-36 questionnaire was observed an increase of the dimensions Functional Capacity and Emotional Aspects. In Oswestry Index a reduction was observed in the average percentage and in the thermography no difference was noticed in pre and post-intervention. Conclusion: These results suggest effectiveness of laser acupuncture in reducing pain and improving quality of life in patients with neuropathic pain due to peripheral nerve injury. (AU)


Assuntos
Humanos , Masculino , Feminino , Dor , Modalidades de Fisioterapia , Traumatismos dos Nervos Periféricos , Lasers , Qualidade de Vida
12.
Artigo em Inglês | MEDLINE | ID: mdl-30450114

RESUMO

BACKGROUND: Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease. METHODS: In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches. RESULTS: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC50 values between 1 to 10 µM, and activity against bloodstream trypomastigotes, with IC50 of 14 µM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi, resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi (TcIDH2) as a potential target for sertraline. CONCLUSIONS: The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi, by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds.

13.
Bioorg Chem ; 78: 307-311, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29625270

RESUMO

Porcelia macrocarpa (Warm.) R. E. Fries (Annonaceae) is an endemic plant in Brazil where its tasty pulp has been eaten fresh. The hexane extract from its flowers was subjected to chromatographic procedures to afford four acetylene derivatives identified as octadec-9-ynoic (stearolic acid - 1), (11E)-octadec-11-en-9-ynoic (santalbic acid - 2), 8-hydroxyoctadec-9,11-diynoic (3) and 8-hydroxyoctadec-17-en-9,11-diynoic (isanolic acid - 4) acids by NMR and HRESIMS. Among tested compounds against trypomastigote forms of T. cruzi, octadec-9-ynoic acid (1) displayed higher potential with IC50 = 27.6 µM and a selectivity index (SI) higher than 7. Compounds 2 and 3 showed IC50 of approximately 60 µM while compound 4 was inactive. The lethal action of the compound 1 was investigated using spectrofluorometric techniques to detect ROS content, plasma membrane permeability and plasma membrane potential by flow cytometry. Compound 1 showed no alteration in the production of ROS of treated trypomastigotes and no alteration of the plasma membrane permeability was observed as detected by the fluorescent probe SYTOX-green after 120 min of incubation. However, by using the potential-sensitive fluorescent probe DiSBAC2(3), compound 1 caused depolarization of the plasma membrane potential when compared to untreated parasites. Our results demonstrated the anti-T. cruzi effects of compounds 1-3 isolated from flowers of P. macrocarpa and indicated that the lethal effect of compound 1 in T. cruzi could be associated to the plasma membrane disturbance of the parasite.


Assuntos
Alcinos/farmacologia , Annonaceae/química , Membrana Celular/efeitos dos fármacos , Ácidos Graxos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Alcinos/química , Alcinos/isolamento & purificação , Animais , Membrana Celular/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Flores/química , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação
14.
Fitoterapia ; 125: 55-58, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29269235

RESUMO

Baccharis retusa, a medicinal Brazilian plant from Asteraceae, has been used in Brazilian folk medicine to treatment of several illnesses, including parasitic diseases. Bioactivity-guided fractionation of the n-hexane extract from the aerial parts of B. retusa resulted in the isolation and characterization of three active related diterpenes: ent-15ß-senecioyl-oxy-kaur-16-en-19-oic acid (1), ent-kaur-16-en-19-oic (2) and ent-16-oxo-17-nor-kauran-19-oic (3) acids. The structures of isolated compounds were defined by spectroscopic analysis, including NMR and HRESIMS. Antitrypanosomal activity of 1-3 was performed against cell-derived trypomastigotes using the colorimetric resazurin assay. The obtained results demonstrated that isolated compounds displayed a reduced toxicity against NCTC cells and were effective against the trypomastigote forms of T. cruzi with IC50 values of 3.8µM (1), 75.3µM (2) and 44.2µM (3). Additionally, compound 3 displayed activity against amastigote forms of T. cruzi with IC50 of 83.2µM. Compound 1 displayed the highest selectivity index (SI) when considered the trypomastigote forms, and its effect in the plasma membrane of parasite was evaluated using the fluorescent probe SYTOX Green. A considerable permeabilization (57%) in the membrane of the parasite was observed when compared to the untreated trypomastigotes. These data demonstrate, for the first time, the antitrypanosomal activity and mechanism of action of 1 and related compounds 2 and 3, obtained from aerial parts of B. retusa.


Assuntos
Baccharis/química , Diterpenos/isolamento & purificação , Tripanossomicidas/isolamento & purificação , Animais , Brasil , Linhagem Celular , Camundongos , Componentes Aéreos da Planta/química , Plantas Medicinais/química , Trypanosoma cruzi/efeitos dos fármacos
15.
São Paulo; s.n; 2018. 126 p. ilus, graf, tab, mapas.
Tese em Português | LILACS, Coleciona SUS, Sec. Est. Saúde SP, CONASS, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-ACVSES, SESSP-TESESESSP, Sec. Est. Saúde SP | ID: biblio-1087660

RESUMO

A doença de Chagas afeta mais de 8 milhões de pessoas nos países em desenvolvimento, e dispõe de uma terapia ultrapassada e altamente tóxica. Considerando o Brasil uma das maiores biodiversidades do mundo, compostos de sua flora podem contribuir como novos protótipos farmacêuticos. Neolignanas, isoladas da planta Nectandra leucantha, apresentaram previamente atividade anti-Trypanosoma cruzi e neste trabalho, serviram como base para a semissíntese de uma série de 24 análogos. Estudos in vitro demonstratram que 19 compostos não apresentaram citotoxicidade em células de mamífero até 200 µM. Seis compostos apresentaram atividade contra as formas tripomastigotas (CE50 8 a 76 µM) e 8 compostos contra os amastigotas intracelulares (CE50 7 a 16 µM). Estudos da relação estrutura-atividade biológica (SAR), demonstraram que a presença de pelo menos uma cadeia lateral alílica era importante para a atividade anti-T. cruzi e que o grupo fenol não era essencial. O composto 8 foi eficaz contra as duas formas do parasita e eliminou 100% das formas amastigotas no interior dos macrófagos, sendo escolhido para estudos de mecanismo de ação. O composto 8 afetou rapidamente a mitocôndria do T. cruzi,...(AU)


Chagas disease affects more than 8 million people in developing countries and the available therapy is old and highly toxic. Considering Brazil one of the biggest biodiversity in the world, compounds from the flora can contribute as new pharmaceutical prototypes. Neolignans, isolated from the plant Nectandra leucantha, previously showed anti-Trypanosoma cruzi activity and served as the basis for the semi-synthesis of a series of 24 analogues. In vitro studies demonstrated that 19 compounds caused no cytotoxicity in mammalian cells up to 200 µM. Six compounds showed activity against trypomastigote forms (IC50 8 to 76 µM) and 8 compounds against intracellular amastigotes (IC50 7 to 16 µM). Studies of the structure activity relationships (SAR) showed that the presence of at least one allylic side chain was important for anti-T. cruzi activity and that the phenol group was not essential. Compound 8 was chosen for mechanism of action studies as it was effective against both forms of the parasite and eliminated 100% of the intracellular amastigotes. Compound 8 rapidly affected the mitochondria of T. cruzi, causing an intense depolarization of the mitochondrial membrane potential, with decreasing levels of reactive oxygen species...(AU)


Assuntos
Trypanosoma cruzi/parasitologia , Produtos Biológicos/uso terapêutico , Farmacocinética , Doença de Chagas/terapia , Lauraceae/química
16.
J. venom. anim. toxins incl. trop. dis ; 24: 30, 2018. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-976028

RESUMO

Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease. Methods: In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches. Results: Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC50 values between 1 to 10 µM, and activity against bloodstream trypomastigotes, with IC50 of 14 µM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi, resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi (TcIDH2) as a potential target for sertraline. Conclusions: The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi, by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds.(AU)


Assuntos
Trypanosoma cruzi , Técnicas In Vitro , Sertralina , Reposicionamento de Medicamentos
17.
Eur J Med Chem ; 139: 947-960, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28881289

RESUMO

The neglected tropical diseases Chagas disease and leishmaniasis affect together more than 20 million people living mainly in developing countries. The mainstay of treatment is chemotherapy, however the drugs of choice, which include benznidazole and miltefosine, are toxic and have numerous side effects. Safe and effective therapies are urgently needed. Marine alpha-pyrones have been previously identified as scaffolds with potential antiprotozoan activities. In this work, using a phenotypic screen, twenty-seven examples of 3-substituted 4-hydroxy-6-methyl alpha-pyrones were synthesized and their antiparasitic efficacy evaluated against Leishmania (L.) infantum and Trypanosoma cruzi in order to evaluate structure-activity relationships within the series. The mechanism of action and the in vivo efficacy of the most selective compound against T. cruzi were evaluated using different techniques. In vitro data indicated that compounds 8, 15, 25, 26 and 28 presented IC50 values in the range between 13 and 54 µM against L. infantum intracellular amastigotes. Among them, hexanoyl substituted pyrone 8 was the most selective and potent, with a Selectivity Index (SI) > 14. Fifteen of the alpha-pyrones were effective against T. cruzi trypomastigotes, with 3-undecanoyl (11) and 3-tetradecanoyl (12) substituted pyrones being the most potent against trypomastigotes, with IC50 values of 1 and 2 µM, respectively, and SI higher than 70. Using flow cytometry and fluorescent-based assays, pyrone 12 was found to induce hyperpolarization of the mitochondrial membrane potential of T. cruzi, without affecting plasma membrane permeability. An experimental acute phase-murine model, demonstrated that in vivo dosing of 12 (30 mg/kg/day; 5 days), had no efficacy at the first parasitemia onset of T. cruzi, but reduced the second onset by 55% (p < 0.05), suggesting a delayed action in BALB/c mice. Additionally, a histopathology study demonstrated no toxic effects to the treated mice. The finding that several 3-substituted alpha-pyrones have in vitro efficacy against both L. infantum and T. cruzi, and that one analogue exhibited moderate and non-toxic in vivo efficacy against T. cruzi is encouraging, and suggests that this compound class should be explored as long-term treatments in experimental Chagas disease.


Assuntos
Antiprotozoários/farmacologia , Leishmania infantum/efeitos dos fármacos , Pironas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Pironas/síntese química , Pironas/química , Relação Estrutura-Atividade
18.
Rev. bras. ativ. fís. saúde ; 22(2): 186-194, 20170301.
Artigo em Português | LILACS | ID: biblio-884226

RESUMO

A dança de salão pode representar uma alternativa de exercício físico para controle da pressão arterial (PA), tanto de forma crônica como aguda. O objetivo foi avaliar e comparar a resposta da PA após uma sessão de samba da gafieira e após uma sessão de bolero. Dezenove mulheres não hipertensas (21,9 ± 3,4 anos e IMC de 21,5 ± 2,5 kg/m2) praticantes da dança de salão avançada foram submetidas a duas sessões experimentais de dança de salão com dois ritmos, bolero e samba de gafieira, sendo avaliada a frequência cardíaca (FC) e a pressão arterial (PA) de repouso, durante as sessões (apenas FC) e a cada 10 min durante 60 min após as sessões. Durante as sessões, a FCmédia atingida no bolero foi 145 ± 15 bpm (78 ± 8 %FCmax) e no samba foi 178 ± 13 bpm (92 ± 6 %FCmax), representando intensidade moderada e vigorosa, respectivamente. No ritmo bolero, após 10 min do final da sessão, a pressão arterial sistólica (PAS) já apresentou valores semelhantes (p > 0,05) ao re-pouso (112,0 ± 12,9 mmHg), sendo mantidos até 60 min após a dança. No samba, a PAS entre os 30 a 60 min foi menor (p < 0,05) que em repouso (114,0 ± 13,0 mmHg), evidenciando hipotensão pós-exercício. Não foram observadas reduções da pressão arterial diastólica após as danças. O ritmo mais intenso, representado pelo samba, induziu hipotensão pós-exercício, o que não ocorreu com o ritmo bolero, que apresentou apenas uma diminuição do trabalho do miocárdio.


The ballroom dance could represent an alternative exercise to both acute and chronic control of blood pressure (BP). The objective was to evaluate and to compare the BP response after a single session of samba da gafieira and single session of bolero. Nineteen advanced ballroom dancers and normotensive women (21.9 ± 3.4 years and BMI of 21.5 ± 2.5 kg/m2) performed two experimental sessions of ballroom dancing with two rhythms, bolero and samba de gafieira. Heart rate (HR) and BP were measured before and every 10 min during 60 min following the experimental sessions. HR was also measured during the sessions. Mean HR was 145 ± 15 bpm (78 ± 8 %FCmax) and 178 ± 13 bpm (92 ± 6 %FCmax) for bolero and samba, respectively. This means that the intensity of bolero was moderate and samba was vigorous. After 10 min of bolero and at the end of the evaluation (60 min), systolic blood pressure (SBP) was not different (p > 0.05) from rest (112.0 ± 12.9 mmHg). SBP between the 30th and 60th min following the samba session was different (p < 0.05) from rest (114.0 ± 13.0 mmHg), showing post-exercise hypotension. Diastolic blood pressure did not present reduction following the experimental sessions. The most intense rhythm, representing by samba, elicited post-exercise hypotension, which did not occur with the bolero rhythm. Bolero only presented a decrease in myocardial work.


Assuntos
Exercício Físico , Pressão Arterial
19.
J Nat Prod ; 80(3): 720-725, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28191951

RESUMO

Marine sponges are a rich source of terpenoids with rearranged spongian carbon skeletons. Investigation of extracts from the sponge Darwinella cf. oxeata yielded four new rearranged diterpenoids, oxeatine (2) and oxeatamides H-J (3-5), as well as the known metabolites oxeatamide A (6), oxeatamide A methyl ester (7), and membranolide (1). Oxeatine (2) has a new heterocyclic skeleton, while oxeatamide J (5) has an N-methyl urea group included in a γ-lactam moiety. UPLC-QTOF analysis of the extract obtained from the mantle of the nudibranch Felimida grahami indicated the presence of 1 and 4.


Assuntos
Diterpenos/química , Diterpenos/isolamento & purificação , Gastrópodes/química , Poríferos/química , Terpenos/química , Terpenos/isolamento & purificação , Animais , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
20.
Eur J Med Chem ; 139: 947-960, 2017.
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, SESSP-CTDPROD, Sec. Est. Saúde SP, SESSP-IALPROD, Sec. Est. Saúde SP | ID: biblio-1048233

RESUMO

The neglected tropical diseases Chagas disease and leishmaniasis affect together more than 20 million people living mainly in developing countries. The mainstay of treatment is chemotherapy, however the drugs of choice, which include benznidazole and miltefosine, are toxic and have numerous side effects. Safe and effective therapies are urgently needed. Marine alpha-pyrones have been previously identified as scaffolds with potential antiprotozoan activities. In this work, using a phenotypic screen, twenty-seven examples of 3-substituted 4-hydroxy-6-methyl alpha-pyrones were synthesized and their antiparasitic efficacy evaluated against Leishmania (L.) infantum and Trypanosoma cruzi in order to evaluate structure-activity relationships within the series. The mechanism of action and the in vivo efficacy of the most selective compound against T. cruzi were evaluated using different techniques. In vitro data indicated that compounds 8, 15, 25, 26 and 28 presented IC50 values in the range between 13 and 54 µM against L. infantum intracellular amastigotes. Among them, hexanoyl substituted pyrone 8 was the most selective and potent, with a Selectivity Index (SI) > 14. Fifteen of the alpha-pyrones were effective against T. cruzi trypomastigotes, with 3-undecanoyl (11) and 3-tetradecanoyl (12) substituted pyrones being the most potent against trypomastigotes, with IC50 values of 1 and 2 µM, respectively, and SI higher than 70. Using flow cytometry and fluorescent-based assays, pyrone 12 was found to


As doenças tropicais negligenciadas A doença de Chagas e a leishmaniose afetam juntas mais de 20 milhões de pessoas que vivem principalmente nos países em desenvolvimento. O suporte principal do tratamento é a quimioterapia, no entanto, os medicamentos de escolha, que incluem benznidazol e miltefosina, são tóxicos e têm inúmeros efeitos colaterais. Terapias seguras e eficazes são urgentemente necessárias. As alfa-pironas marinhas foram previamente identificadas como andaimes com potenciais atividades antiprotozoárias. Neste trabalho, usando uma tela fenotípica, sintetizaram-se 27 exemplos de 4-hidroxi-6-metil alfa-pironas 3-substituídas e avaliou-se sua eficácia antiparasitária contra Leishmania (L.) infantum e Trypanosoma cruzi para avaliar a estrutura relações de atividade dentro da série. O mecanismo de ação e a eficácia in vivo do composto mais seletivo contra T. cruzi foram avaliados por diferentes técnicas. Dados in vitro indicaram que os compostos 8, 15, 25, 26 e 28 apresentaram valores de IC50 na faixa entre 13 e 54 µM contra amastigotas intracelulares de L. infantum. Entre elas, a pirona 8 substituída com hexanoílo foi a mais seletiva e potente, com um índice de seletividade (SI)> 14. Quinze das alfa-pironas foram eficazes contra as tripomastigotas de T. cruzi, com 3-undecanoil (11) e 3-tetradecanoil ( 12) pironas substituídas sendo as mais potentes contra tripomastigotas, com valores de IC50 de 1 e 2 µM, respectivamente, e SI superiores a 70. Usando citometria de fluxo e ensaios à base de fluorescência, a pirona 12 foi encontrada para


Assuntos
Trypanosoma cruzi , Preparações Farmacêuticas , Leishmania
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