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1.
Neurotoxicology ; 99: 217-225, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890558

RESUMO

Resistance physical exercise has neuroprotective and anti-inflammatory effects on many known diseases and, therefore, it has been increasingly explored. The way in which this type of exercise exerts these actions is still under investigation. In this study, we aimed to analyze the enzymes and components of the purinergic system involved in the inflammatory process triggered by the P2X7R. Rats were divided into four groups: control, exercise (EX), lipopolysaccharide (LPS), and EX + LPS. The animals in the exercise groups were subjected to a 12-week ladder-climbing resistance physical exercise and received LPS after the last session for sepsis induction. Enzymes activities (NTPDase, 5'-nucleotidase, and adenosine deaminase), purinoceptors' density (P2X7R, A1, and A2A), and the levels of inflammatory indicators (pyrin domain-containing protein 3 (NLRP3), Caspase-1, interleukin (IL)- 6, IL-1B, and tumor necrosis factor (TNF) -α) were measured in the cortex and hippocampus of the animals. The results show that exercise prevented (in the both structures) the increase of: 1) nucleoside-triphosphatase (NTPDase) and 5'-nucleotidase activities; 2) P2X7R density; 3) NLRP3 and Caspase-1; and 4) IL-6, IL-1ß, and TNF-α It is suggested that the purinergic system and the inflammatory pathway of P2X7R are of fundamental importance and influence the effects of resistance physical exercise on LPS-induced inflammation. Thus, the modulation of the P2X7R by resistance physical exercise offers new avenues for the management of inflammatory-related illnesses.


Assuntos
Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/toxicidade , 5'-Nucleotidase/metabolismo , Doenças Neuroinflamatórias , Hipocampo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Exercício Físico , Caspases/metabolismo , Receptores Purinérgicos P2X7/metabolismo
2.
J Hypertens ; 41(11): 1745-1752, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796209

RESUMO

BACKGROUND AND AIM: Essential arterial hypertension is a risk factor for stroke, myocardial infarction, heart failure, and arterial aneurysm, which are related to the activation of platelets. Purinergic signaling has a central role in platelet aggregation. Although ATP and ADP can act as a proaggregant agent, adenosine inhibits platelet aggregation and reduces vascular injury. Physical exercise exhibits antiaggregant properties and can modulate purinergic system. The aim of this study was to evaluate the effect of 6 months of resistance training on purinergic system components in platelets and on platelet activation, hemodynamic and anthropometric parameters in hypertensive woman. METHOD: A total of 31 hypertensive and 28 normotensive middle-aged sedentary women were submitted to 6 months of resistance training. Purinergic enzymes activities were assessed in platelets; ATP and Tromboxane B2 (TXB2) levels were measured in serum. Blood pressure (BP), BMI, and body fat were also measured. All variables were statistically analyzed, considering P value less than 0.05. RESULTS: Six months of resistance training was able to significantly reduce BP, ATP, and TXB2 levels as well as NTPDase, ecto-5'nucleotidase, and ADA activities in hypertensive group. After 6 months of resistance training, purinergic system components and TXB2 of hypertensive group were similar to normotensive group in platelets, demonstrating that resistance training was able to modulate platelet activation. A positive correlation was found between BP, enzyme activities, and levels of ATP and TXB2. CONCLUSION: Our findings demonstrated the relationship between purinergic signaling and platelet activation in hypertension and suggests that resistance training serve as tool to reduce platelet aggregation in hypertensive woman by modulating purinergic system.


Assuntos
Hipertensão , Treinamento de Força , Pessoa de Meia-Idade , Humanos , Feminino , Ativação Plaquetária , Plaquetas , Trifosfato de Adenosina
3.
Mol Cell Biochem ; 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37186275

RESUMO

This study analyzed the effects of a physical exercise program compared to the complexity of the motor task on the cognitive function, brain-derived neurotrophic factor (BDNF) levels, and lipid profile of older adults with mild cognitive impairment (MCI). Twenty-seven participants were randomized into three intervention groups: Physical Exercise (PE), Motor Task (MT), and Physical Exercise associated with Motor Task (PE + MT). Six months of intervention twice a week resulted in improvements in cognitive function, total cholesterol (TC), and LDL cholesterol (LDL-C) in the PE (p < 0.05). In the PE + MT, in addition to improved cognitive capacity, there was also a reduction in non-HDL cholesterol (NHDL-C) and LDL cholesterol (LDL-C) levels (p < 0.05), while in the MT, the values of TC, NHDL-C, and LDL-C decreased as a result of the intervention. BDNF levels were not affected by the interventions. In conclusion, PE alone or combined with MT is effective in promoting improvements in overall cognitive function and lipid profile in older adults with MCI; and BDNF seems not to be a sensitive marker for people with mild cognitive impairment.

4.
Neurochem Res ; 47(11): 3221-3240, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35962936

RESUMO

Neuroinflammation is an inflammatory process in the central nervous system (CNS), in addition to being one of the main features of Alzheimer's disease (AD) and Parkinson's disease (PD). Microglia are known for their immune functions and have multiple reactive phenotypes related to the types of stages involving neurodegenerative diseases. Depending on the state of activation of microglia in the CNS, it can be neuroprotective or neurotoxic. In this context, AD is a neurodegenerative and neuroinflammatory disease characterized by the deposition of beta-amyloid plaques, formation of fibrillar tangles of tau protein, and loss of neurons due to neurotoxic activation of microglia. However, PD is characterized by the loss of dopaminergic neurons in the substantia nigra and accumulation of alpha-synuclein in the cortical regions, spinal cord, and brain stem, which occurs by microglial activation, contributing to the neuroinflammatory process. In this aspect, the activation of microglia in both pathologies triggers high levels of inflammatory markers, such as interleukins, and causes the neuroinflammatory process of the diseases. Thus, physical exercise is pointed out as neuroprotective, as it can act to strengthen neurogenesis and reduce the inflammatory process. Therefore, the present review addresses the neuroprotective effect of microglia after different types of physical exercise protocols and evaluates the activity and effects of inflammatory and anti-inflammatory parameters and mechanisms of AD and PD. This review will discuss the anti-inflammatory effects of physical exercise through microglia activation with neuroprotective activity and the role of pro-and anti-inflammatory cytokines in AD and PD.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Doença de Parkinson , Doença de Alzheimer/metabolismo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Neurônios Dopaminérgicos/metabolismo , Exercício Físico , Humanos , Mediadores da Inflamação/metabolismo , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo
5.
Inflamm Res ; 71(7-8): 759-770, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35648156

RESUMO

Type 2 diabetes mellitus (T2DM) is an important chronic disease around the world, and according to the World Health Organization, it is the 9th principal cause of global death. This pathology is characterized by high levels of circulating glucose as a result of insulin resistance, and it is well stated that inflammation related to obesity is directly associated with the development of the disease. The purinergic signalling is involved in both pancreatic destruction, which impairs insulin secretion, and the cytokine production that favors insulin resistance in T2DM. In this review, the purinergic signalling aspects will be discussed, showing the impact of the enzymes, nucleotides, nucleosides, and receptors of this system and the cytokines that result in inflammation, in the development and progression of T2DM, besides, pointing the purinergic receptors as a possible therapeutic approach.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/patologia , Humanos , Inflamação/patologia , Obesidade/patologia , Transdução de Sinais
6.
Inflamm Res ; 71(5-6): 555-564, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35376994

RESUMO

INTRODUCTION AND OBJECTIVE: Cervical cancer is the fourth most prevalent type of cancer in the world. The tumor microenvironment of this disease is associated with the production of several cytokines, pro and anti-inflammatory, and with the purinergic signaling system so that changes in these components are observed throughout the pathological process. The aim of this review is to understand the pathophysiology of cervical cancer based on immunological processes and purinergic signaling pathways, in addition to suggesting possibilities of therapeutic targets. MATERIALS AND METHODS: To make up this review, studies covering topics of cervical cancer, inflammation and purinergic system were selected from the Pubmed. RESULTS: The main pro-inflammatory cytokines involved are IL-17, IL-1ß, IL-6, and IL-18, and among the anti-inflammatory ones, IL-10 and TGF-ß stand out. As new therapeutic targets, P2X7 and A2A receptors have been suggested, since blocking P2X7 would lead to reduced release of pro-inflammatory cytokines, and blocking A2A would increase activation of cytotoxic T lymphocytes in the context of tumor combat. The association between the immune system and the purinergic system, already known in other types of disease, also presents possibilities for a better understanding of biomolecular processes and therapeutic possibilities in the context of cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Transdução de Sinais , Microambiente Tumoral , Neoplasias do Colo do Útero/terapia
7.
Femina ; 50(6): 373-378, 2022. ilus
Artigo em Português | LILACS | ID: biblio-1380720

RESUMO

O câncer de colo uterino é o quarto tipo mais incidente e fatal entre as mulheres no Brasil e no mundo, o que representa mundialmente em torno de 600 mil novos casos e mais de 300 mil mortes a cada ano. Assim como o diagnóstico, o tratamento da doença pode impactar de forma significativa a qualidade de vida dessas pacientes. A aplicação de questionários que avaliem os diferentes aspectos da qualidade de vida das mulheres afetadas por esse câncer é uma ferramenta relevante, pois auxilia na compreensão e identificação dos principais danos relacionados ao tratamento. Este trabalho visa analisar a literatura atual que investiga e relata os principais efeitos à qualidade de vida de mulheres com câncer de colo uterino associados a diferentes modalidades terapêuticas e, desse modo, contribuir nas escolhas de tratamento e manejo clínico que resultem em menores impactos à qualidade de vida dessas mulheres.(AU)


Cervical cancer is the fourth most incident and fatal cancer type among women in Brazil and worldwide. This data represents around 600 thousand new cases worldwide each year and more than 300 thousand lives lost. Both diagnosis and treatment can significantly impact the quality of life of cervical cancer patients. The application of questionnaires that assess the different aspects of the quality of life of women affected by this cancer is a relevant tool, as it helps to understand and identify the main damages related to the treatment. This article aims to analyze the current literature that reports the main effects on the quality of life of women with cervical cancer associated with different therapeutic modalities. In this way, the review could assist in the treatment choices that imply less impact on the quality of life of these women.(AU)


Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Perfil de Impacto da Doença , Braquiterapia/efeitos adversos , Brasil/epidemiologia , Inquéritos e Questionários , Bases de Dados Bibliográficas , Laparoscopia/efeitos adversos , Traquelectomia/efeitos adversos , Histerectomia Vaginal/efeitos adversos , Antineoplásicos/efeitos adversos
8.
Estima (Online) ; 19(1): e1521, jan.-dez. 2021.
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1291477

RESUMO

Objetivo:Analisar as percepções dos pacientes com câncer colorretal em uso de colostomia sobre os cuidados de enfermagem das unidades de internação em oncologia de um hospital do oeste de Santa Catarina. Métodos: Estudo descritivo-exploratório de abordagem qualitativa realizado nas unidades de internação em oncologia do Hospital Regional do Oeste, no período de janeiro a agosto de 2020, por meio de um questionário contendo dados sociodemográficos e entrevista semiestruturada, aplicado a 20 pacientes com câncer colorretal em uso de colostomia. Os dados foram analisados por meio da Análise de Conteúdo de Laurence Bardin. Resultados: Os resultados apontaram prevalência de colostomizados do sexo masculino, com idade média de 60,25 anos, casados, aposentados e com ensino fundamental incompleto. A partir da análise qualitativa das entrevistas surgiu a categoria: percepções dos pacientes sobre os cuidados de enfermagem, a qual foi subdividida em: cuidados de enfermagem com a bolsa e a estomia e cuidados de enfermagem na internação. Conclusão: Ao término da pesquisa, conclui-se que os colostomizados percebem que a equipe de enfermagem realiza os cuidados essenciais à bolsa e à estomia, incluindo sua troca e higiene durante a internação, atendendo às necessidades dos pacientes. Além disso, fornecem orientações importantes sobre o uso dos dispositivos, promovendo educação em saúde.


Assuntos
Colostomia , Neoplasias Colorretais , Pesquisa Qualitativa , Estomaterapia , Oncologia , Cuidados de Enfermagem
9.
Purinergic Signal ; 17(4): 649-679, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34590239

RESUMO

In the last years, it has become evident that both acute and chronic physical exercise trigger responses/adaptations in the purinergic signaling and these adaptations can be considered one important mechanism related to the exercise benefits for health improvement. Purinergic system is composed of enzymes (ectonucleotidases), receptors (P1 and P2 families), and molecules (ATP, ADP, adenosine) that are able to activate these receptors. These components are widely distributed in almost all cell types, and they respond/act in a specific manner depending on the exercise types and/or intensities as well as the cell type (organ/tissue analyzed). For example, while acute intense exercise can be associated with tissue damage, inflammation, and platelet aggregation, chronic exercise exerts anti-inflammatory and anti-aggregant effects, promoting health and/or treating diseases. All of these effects are dependent on the purinergic signaling. Thus, this review was designed to cover the aspects related to the relationship between physical exercise and purinergic signaling, with emphasis on the modulation of ectonucleotidases and receptors. Here, we discuss the impact of different exercise protocols as well as the differences between acute and chronic effects of exercise on the extracellular signaling exerted by purinergic system components. We also reinforce the concept that purinergic signaling must be understood/considered as a mechanism by which exercise exerts its effects.


Assuntos
Trifosfato de Adenosina/metabolismo , Adenosina/metabolismo , Exercício Físico/fisiologia , Receptores Purinérgicos/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos
10.
Mol Cell Biochem ; 476(8): 2891-2898, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33740184

RESUMO

The coronavirus disease (COVID-19), caused by SARS-CoV-2 infection, accounts for more than 2.4 million deaths worldwide, making it the main public health problem in 2020. Purinergic signaling is involved in the pathophysiology of several viral infections which makes the purinergic system a potential target of investigation in COVID-19. During viral infections, the ATP release initiates a cascade that activates purinergic receptors. This receptor activation enhances the secretion of pro-inflammatory cytokines and performs the chemotaxis of macrophages and neutrophils, generating an association between the immune and the purinergic systems. This review was designed to cover the possible functions of purinergic signaling in COVID-19, focusing on the possible role of purinergic receptors such as P2X7 which contributes to cytokine storm and inflammasome NLRP3 activation and P2Y1 that activates the blood coagulation pathway. The possible role of ectonucleotidases, such as CD39 and CD73, which have the function of dephosphorylating ATP in an immunosuppressive component, adenosine, are also covered in detail. Moreover, therapeutic combination or association possibilities targeting purinergic system components are also suggested as a possible useful tool to be tested in future researches, aiming to unveil a novel option to treat COVID-19 patients.


Assuntos
COVID-19/metabolismo , Receptores Purinérgicos/metabolismo , Transdução de Sinais , Animais , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/virologia , Humanos , Modelos Biológicos , Terapia de Alvo Molecular , SARS-CoV-2/fisiologia
11.
J Transl Med ; 19(1): 3, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407612

RESUMO

BACKGROUND: The increasing prevalence of overweight and obesity among the worldwide population has been associated with a range of adverse health consequences such as Type 2 diabetes and cardiovascular diseases. The metabolic syndrome (MetS) is a cluster of cardiometabolic abnormalities that occur more commonly in overweight individuals. Time-restricted feeding (TRF) is a dietary approach used for weight loss and overall health. TRF may be an option for those subjects who struggle with extreme restriction diets with foods that generally do not belong to an individual's habits. OBJECTIVE: The purpose of this study was to determine the effect of TRF on body composition and the association of weight loss with metabolic and cardiovascular risks in obese middle-aged women. METHODS: A non-randomized controlled clinical trial was performed over 3 months in obese women (TRF group, n = 20, BMI 32.53 ± 1.13 vs. Control n = 12, BMI 34.55 ± 1.20). The TRF protocol adopted was 16 h without any energy intake followed by 8 h of normal food intake. MAIN OUTCOMES AND MEASURES: Anthropometric measurements, body composition, blood biomarkers, cardiovascular risk in 30 years (CVDRisk30y), and quality of life were evaluated at baseline and after the 3 months. RESULTS: TRF was effective in reducing weight (~ 4 kg), BMI, % of body fat (%BF), waist circumference from baseline without changes in blood biomarkers associated with MetS. TRF promoted a reduction in CVDRisk30y (12%) wich was moderately correlated with %BF (r = 0.62, n = 64, p < 0.001) and %MM (r = - 0.74, n = 64, p < 0.001). CONCLUSIONS: TRF protocol reduces body weight without changes in biomarkers related to MetS. In addition, the anthropometric evaluation that predicts %BF and %MM could be used as an approach to follow individuals engaged in the TRF regimen since they correlate with cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Índice de Massa Corporal , Doenças Cardiovasculares/complicações , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso , Qualidade de Vida , Fatores de Risco , Redução de Peso
12.
Int J Gynecol Cancer ; 31(2): 265-271, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33109527

RESUMO

The pathogenesis of cervical cancer is related to oxidative damage caused by persistent infection by one of the oncogenic types of human papillomavirus (HPV). This damage comes from oxidative stress, which is the imbalance caused by the increase in reactive oxygen and nitrogen species and impaired antioxidant mechanisms, promoting tumor progression through metabolic processes. The incorporation of HPV into the cellular genome leads to the expression of oncoproteins, which are associated with chronic inflammation and increased production of reactive oxygen species, oxidizing proteins, lipids and DNA. The increase in these parameters is related, in general, to the reduction of circulating levels of enzymatic antioxidants-superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase; and non-enzymatic antioxidants-reduced glutathione, coenzyme Q10 and vitamins A, C and E, according to tumor staging. In contrast, some enzymatic antioxidants suffer upregulation in the tumor tissue as a way of adapting to the oxidative environment generated by themselves, such as glutathione-S-transferase, reduced glutathione, glutathione peroxidase, superoxide dismutase 2, induced nitric oxide synthase, peroxiredoxins 1, 3 and 6, and thioredoxin reductase 2. The decrease in the expression and activity of certain circulatory antioxidants and increasing the redox status of the tumor cells are thus key to cervical carcinoma prognosis. In addition, vitamin deficit is considered a possible modifiable risk factor by supplementation, since the cellular functions can have a protective effect on the development of cervical cancer. In this review, we will discuss the impact of oxidative damage on cervical cancer progression, as well as the main oxidative markers and therapeutic potentialities of antioxidants.


Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo , Infecções por Papillomavirus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do Útero/virologia , Feminino , Humanos , Lesões Intraepiteliais Escamosas/sangue , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/fisiopatologia
13.
Clin Biochem ; 89: 63-69, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33333061

RESUMO

INTRODUCTION: Metabolic syndrome (MetS) is a disorder that is closely associated with risk factors that increase the chance of atherosclerosis and cardiovascular diseases. We demonstrate the presence of inflammation and oxidative stress in patients with MetS through levels of antioxidants and oxidative and inflammatory markers, in order to determine influential variables in therapy. METHODS: In this study, lipid peroxidation, carbonylated protein content and enzymatic and non-enzymatic antioxidants were evaluated in samples obtained from 30 patients with MetS and 30 control patients. In addition, acetylcholinesterase (AChE) activity, C-reactive protein (CRP) and uric acid (UA) levels were determined to investigate the inflammatory process in patients with MetS. RESULTS: Our results demonstrated an increase in the levels of oxidative markers, such as substances reactive to thiobarbituric acid (TBARS) and carbonyl protein. In addition, a decrease in the defense of non-enzymatic antioxidants, such as levels of vitamin C and glutathione (GSH) in patients with MetS. As for inflammatory markers, CRP and UA were increased in patients with MetS. Finally, activation of the cholinergic anti-inflammatory pathway was observed due to decreased AchE activity in patients with MetS. CONCLUSION: The analyzes indicated oxidative stress, together with a reduction in the levels of antioxidant enzymes, corroborating the high consumption of these proteins. In addition, inflammation and activation of the cholinergic anti-inflammatory pathway was observed by the AChE analysis. Thus, the activation of this pathway can be studied as a possible route to a potential therapy. In addition, the markers AChE, CRP and UA may be used as a focus for the treatment of MetS.


Assuntos
Acetilcolinesterase/metabolismo , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Síndrome Metabólica/patologia , Estresse Oxidativo , Adulto , Idoso , Proteína C-Reativa/metabolismo , Feminino , Seguimentos , Humanos , Peroxidação de Lipídeos , Masculino , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ácido Úrico/metabolismo
15.
J Exerc Sci Fit ; 18(3): 122-128, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32351589

RESUMO

BACKGROUND: Although the positive effects of resistance training (RT) on strength and functional capacity have been well evidenced in the scientific literature, the effects of RT on blood pressure and the relationship of these responses with performance improvement are not yet well established. OBJECTIVE: This study aimed to analyze the effects of three and six months of RT on the hemodynamic parameters and functional capacity of hypertensive and normotensive women. METHOD: Sixteen hypertensive and 15 normotensive elderly women participated in a RT protocol designed to increase muscle strength and hypertrophy, lasting six months, twice a week. RESULTS: Systolic blood pressure (SBP) had a reduction at six months only in hypertensive patients, while diastolic blood pressure (DBP) decreased at six months of intervention in both groups (p < 0.05). SBP showed differences between the groups in the pretest (p < 0.05), but not at three and six months of intervention (p > 0.05). Heart rate (HR) was reduced at three months in hypertensive patients, and at six months in the normotensive (p < 0.05). The strength and functional mobility of both hypertensive and normotensive individuals significantly increased at three and six months of intervention (p < 0.05). Hypertensive women showed increased strength at all moments, while normotensive ones showed improvement only at six months. CONCLUSION: Moderate to high intensity RT improves the hemodynamic parameters of hypertensive and normotensive women differently, and independently of strength gain and functional capacity improvement.

16.
Purinergic Signal ; 16(1): 123-135, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32170538

RESUMO

Cervical cancer is the fourth most common type of cancer incidence in the world female population, and it has become a public health problem worldwide. Several factors are involved in this type of cancer, including intrinsic factors related to the inflammatory process, such as extracellular nucleotides and adenosine-components of the purinergic system. The present review focuses on the role of the purinergic system in cervical cancer, especially regarding the interaction of extracellular nucleotides with their respective receptors expressed in the tumor microenvironment of cervical cancer and their role in the host immune response. The high concentrations of extracellular nucleotides in the tumor microenvironment of cervical cancer interfere in the regulation, proliferation, differentiation, and apoptosis of cancer cells of the uterine cervix through different P1 and P2 receptor subtypes. Such diverse cellular processes that are mediated by adenosine triphosphate and adenosine across the tumor microenvironment and that also have effects on host immune defense will be reviewed here in detail.


Assuntos
Receptores Purinérgicos/metabolismo , Transdução de Sinais/fisiologia , Microambiente Tumoral/fisiologia , Neoplasias do Colo do Útero/metabolismo , Animais , Feminino , Humanos
17.
Med Oncol ; 36(9): 78, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375946

RESUMO

Cigarette smoking is directly associated with lung cancer. Non-small cell lung carcinoma (NSCLC) represents approximately 80% from all types of lung cancer. This latter is hard to diagnose and to treat due to the lack of symptoms in early stages of the disease. The aim of this study was to evaluate ADA activity and the expression of P2X7, A1, and A2A receptors and in lymphocytes. In addition, the profile of pro-inflammatory and anti-inflammatory cytokines serum levels of patients with lung cancer in advanced stage was evaluated. Patients (n = 13) previously treated for lung cancer at stage IV (UICC) with chemotherapy had their blood collected. Cancer patients showed a decrease in ADA activity and an increase in A1 receptor expression in lymphocytes when compared to the control group. Moreover, patients exhibited an increase in IL-6 and TNF-α, while IL-17 and INF-ϒ serum levels were lower in patients with lung cancer. The decreased ADA activity and the increase in A1 receptor expression may contribute to adenosine pro-tumor effects by increasing IL-6 and TNF-α and decreasing IL-17 and INF-γ serum levels. Our data show an indirect evidence that purinergic signaling may have a role in promoting a profile of cytokines levels that favors tumor progression.


Assuntos
Adenosina Desaminase/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Linfócitos/enzimologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Citocinas/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptores Purinérgicos/metabolismo , Transdução de Sinais
18.
Cell Signal ; 59: 122-130, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30926387

RESUMO

Melanoma is a type of skin cancer originated by the malignant transformation of melanocytes. Increasing incidence and mortality require efforts focused on studies and research about this cancer. Its microenvironment is rich in extracellular ATP, but there are no studies evaluating the ectonucleotidases and ATP effects on tumor-derived melanoma cells with known amounts of ATP. This way, the objective of this work was to evaluate the purinergic signaling in the pathophysiology of in vivo melanoma and the in vitro effects of ATP signaling. We found increased and effective extracellular ATP hydrolysis in platelets and a significant decrease of extracellular ATP levels and adenosine hydrolysis. In addition, we cultured PBMCs of melanoma patients and used ATP salt with specific concentrations to evaluate its signaling effects. The enzymatic activity analysis revealed that even with higher ATP doses cells metabolize adenine nucleotides less efficiently, and present low ATP, ADP and AMP hydrolytic activity in CM compared to CT cells. In summary, we showed for the first time important data about the purinergic signaling in the pathophysiology of melanoma and ATP signaling exercising immunosuppressive effects. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for melanoma management and treatment and could offer novel therapeutic prospects.


Assuntos
Trifosfato de Adenosina/metabolismo , Plaquetas/metabolismo , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Plaquetas/citologia , Células Cultivadas , Feminino , Humanos , Hidrólise , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral
19.
J Hypertens ; 37(1): 135-143, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30507864

RESUMO

: Background: Central nervous system function has been emerging as an approach to understand hypertension-mediated memory dysfunction, and chronic exercise is able to modulate the purinergic system. METHOD: Herein, we investigated the effect of chronic swimming training on the purinergic system in cortex and hippocampus of L-NAME-induced hypertensive rats. Male Wistar rats were divided into four groups: Control, Exercise, L-NAME and Exercise L-NAME. Inhibitory avoidance test was used to assess memory status. NTPDase, CD73 and adenosine deaminase activities and expression, and P2 receptors expression were analyzed. Data were analyzed using two-way ANOVA and Kruskal-Wallis tests, considering P less than 0.05. RESULTS: Physical exercise reduced the blood pressure and prevented memory impairment induced by L-NAME model of hypertension. L-NAME treatment promoted an increase in NTPDase1, NTPDase3 and CD73 expression and activity in the cortex. A2A expression is increased in hippocampus and cortex in the hypertension group and exercise prevented this overexpression. CONCLUSION: These changes suggest that hypertension increases adenosine generation, which acts through A2A receptors, and exercise prevents these effects. These data may indicate a possible mechanism by which exercise may prevent memory impairment induced by L-NAME.


Assuntos
5'-Nucleotidase/metabolismo , Antígenos CD/metabolismo , Apirase/metabolismo , Hipertensão/fisiopatologia , Memória/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , NG-Nitroarginina Metil Éster/metabolismo , Ratos , Receptor A2A de Adenosina/metabolismo , Natação/fisiologia
20.
J Cell Biochem ; 120(3): 3232-3242, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30230598

RESUMO

Sepsis is a generalized infection that involves alterations in inflammatory parameters, oxidant status, and purinergic signaling in many tissues. Physical exercise has emerged as a tool to prevent this disease because of its anti-inflammatory and antioxidant properties. Thus, in this study, we investigated the effects of physical exercise on preventing alterations in purinergic system components, oxidative stress, and inflammatory parameters in lipopolysaccharide (LPS)-induced sepsis in rats. Male Wistar rats were divided into four groups: control, exercise (EX), LPS, and EX+LPS. The resisted physical exercise was performed for 12 weeks on a ladder with 1 m height. After 72 hours of the last exercise session, the animals received 2.5 mg/kg of LPS for induction of sepsis, and after 24 hours, lungs and blood samples were collected for analysis. The results showed that the exercise protocol used was able to prevent, in septic animals: (1) the increase in body temperature; (2) the increase of lipid peroxidation and reactive species levels in the lung, (3) the increase in adenosine triphosphate levels in serum; (4) the change in the activity of the enzymes ectonucleotidases in lymphocytes, partially; (5) the change in the density of purinergic enzymes and receptors in the lung, and (6) the increase of IL-6 and IL-1ß gene expression. Our results revealed the involvement of purinergic signaling and oxidative damage in the mechanisms by which exercise prevents sepsis aggravations. Therefore, the regular practice of physical exercise is encouraged as a better way to prepare the body against sepsis complications.


Assuntos
Lipopolissacarídeos/toxicidade , Condicionamento Físico Animal/fisiologia , Sepse/induzido quimicamente , Sepse/prevenção & controle , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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