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ATP and adenosine (ADO) are critical players in the context of cancer. In the tumor microenvironment, the signaling dependent on these molecules, and immune cells, is regulated by an enzymatic chain and purinergic receptors called purinome. Primarily, the A2A receptor (A2AR) has a pro-tumor action since it reduces the immune response and favors the growth of malignant melanoma. Therefore, this study aimed to verify the effects of A2AR antagonism with Istradefylline (IST) on the purinergic signaling profile of the melanoma tumor and immunological compartments. We observed reduced tumor growth of melanoma in IST-treated animals. IST inhibited AKT/mTOR pathway, which is involved with tumor growth. In the tumor, spleen, and thymus, the modulation of purinergic enzymes (CD39, CD73, and E-ADA) characterized a pro-inflammatory profile since it favored increased extracellular concentrations of ATP to the detriment of ADO. A2AR inhibition generated a compensatory feedback process with increased A2AR expression at the tumor level. However, there was also an increase in the expression of the P2X7 receptor (P2X7R), which culminated in an increase in pro-inflammatory pathways with the release of IL-1ß and pro-inflammatory cytokines such as IFN-γ and TNF-α. Our data evidence the cross-involvement between expression and action of the A2AR and P2X7R. We suggest that IST is a promising drug for off-label use in cancer since it promotes an anti-tumoral response by producing pro-inflammatory cytokines and blocking of AKT/mTOR tumor growth pathway.
Assuntos
Melanoma , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Citocinas/metabolismo , Adenosina/farmacologia , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Melanoma/tratamento farmacológico , Serina-Treonina Quinases TOR , Microambiente TumoralRESUMO
Metastatic melanoma is a very aggressive skin cancer. Platelets are constituents of the tumor microenvironment and, when activated, contribute to cancer progression, especially metastasis and inflammation. P2Y12 is an adenosine diphosphate receptor that triggers platelet activation. Inhibition of P2Y12 by clopidogrel bisulfate (CB) decreases platelet activation, which is also controlled by the extracellular concentration and the metabolism of purines by purinergic enzymes. We evaluated the effects of CB on the viability and proliferation of cultured B16-F10 cells. We also used a metastatic melanoma model with C57BL-6 mice to evaluate cancer development and purine metabolism modulation in platelets. B16-F10 cells were administered intraperitoneally to the mice. Two days later, the animals underwent a 12-day treatment with CB (30 mg/kg by gavage). We have found that CB reduced cell viability and proliferation in B16-F10 culture in 72 h at concentrations above 30 µm. In vivo, CB decreased tumor nodule counts and lactate dehydrogenase levels and increased platelet purine metabolism. Our results showed that CB has significant effects on melanoma progression.
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Melanoma Experimental , Melanoma , Neoplasias Cutâneas , Animais , Camundongos , Clopidogrel/farmacologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Melanoma Experimental/tratamento farmacológico , Microambiente TumoralRESUMO
ATP and adenosine exert pivotal roles in the development, maintenance, and metastatic spreading of melanoma. The action of such key melanoma tumor microenvironment (TME) constituents might be complementary or opposed, and their effects are not exclusive to immune cells but also to other host cells and tumor cells. The effects of ATP are controlled by the axis CD39/73, resulting in adenosine, the main actor in the TME, and A2A is the crucial mediator of its effects. We evaluated ATP and adenosine signaling through A2A on B16F10 melanoma cells using istradefylline (IST) (antiparkinsonian A2A antagonist) and caffeine (CAF) treatments after exposure to ATP and adenosine. Adenosine increased melanoma cell viability and proliferation in a concentration-dependent manner. ATP increases viability only as a substrate by CD39 to produce adenosine. Both IST and CAF are toxic to B16F10 cells, but only IST potentialized paclitaxel-induced cytotoxic effects, even decreasing its IC50 value. IST positively modulated CD39 and CD73 expression. CD39 activity was increased, and E-ADA was reduced, indicating that the melanoma cells promoted compensatory feedback in the production and maintenance of adenosine levels. A2A antagonism by IST reduced the factors associated with malignancy, like migration, adhesion, colony formation, and the capacity to produce melanin. Moreover, IST significantly increases nitric oxide (NO) production, which correlates to a decline in melanoma cell viability by apoptotic events. Altogether, our results suggest that adenosine signaling through A2A is essential for B16F10 cells, and its inhibition by IST causes compensatory purinergic enzymatic modulations. Furthermore, IST is a promising therapy that provides new ways to improve current melanoma treatments.
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Hyperlipidemia generates deposition of lipids, inflammation, and oxidative damage in cells and tissues, including those of the brain. Tucumã (Astrocaryum aculeatum) fruits contain bioactive compounds with antioxidant and anti-inflammatory effects. We evaluated the action of Tucumã extract on memory and brain cortex redox balance in hyperlipidemic rats. For 30 days, Wistar rats received Tucumã extract (250 mg/kg). Then, hyperlipidemia was induced by intraperitoneal administration of Poloxamer-407. Twenty-four hours later, the object recognition index was measured. The animals were euthanized for sample collection 36 hr postinduction. Hyperlipidemic animals showed memory loss and an imbalance between reactive species and intrinsic antioxidants. We found that Tucumã prevented memory loss and protein and lipid oxidative damage and prompted a better antioxidant response in the cerebral cortex of rats with hyperlipidemia. These findings suggest a neuroprotective effect and nutraceutical potential of Tucumã. PRACTICAL APPLICATIONS: In the present work, we demonstrated that induced hyperlipidemia in rats caused memory loss and redox unbalance, both factors prevented by the administration of Tucumã (Astrocaryum aculeatum) extract. Two aims were fulfilled with these results. The first was to show that hyperlipidemia affected brain function through oxidative damage and concerned basic research. The second was to offer a therapy that prevented this harm and could be applied in the clinic. Tucumã has ethnopharmacological importance through the consumption of fruits or the administration of extracts and oils by a population that was shown to enjoy improved health and longevity. Here, we show evidence that Tucumã contributes to the maintenance of brain health by preventing memory loss and oxidative damage, a nutraceutical supplement that may aid the prevention of vascular, inflammatory, and brain diseases.
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Hiperlipidemias , Animais , Encéfalo , Hiperlipidemias/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Oxirredução , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.
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Anti-Inflamatórios/farmacologia , Cafeína/farmacologia , Hiperlipidemias/tratamento farmacológico , Inflamação/prevenção & controle , Teobromina/farmacologia , Teofilina/farmacologia , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Cafeína/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperlipidemias/fisiopatologia , Inflamação/etiologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Ratos , Ratos Wistar , Sinvastatina/farmacologia , Teobromina/administração & dosagem , Teofilina/administração & dosagemRESUMO
The progression of the human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) can be efficiently interrupted by antiretroviral therapy (ART). However, even successfully treated HIV-infected individuals are prone to develop non-AIDS-related diseases that affect the metabolism and several organs and systems. Biomarkers that predict the occurrence of comorbidities may help develop preventive measures. Current research shows that CD4+ T cell counts and viral load do not predict the development of non-AIDS-related diseases. The CD4/CD8 ratio has been indicated as a suitable marker of persistent immune dysfunction and the occurrence of non-AIDS-related events in treated HIV-positive patients. In this study, we explored the relationship between CD4/CD8 ratios, comorbidities, and aging in ART-treated HIV patients on viral suppression. We collected and evaluated data from 352 HIV-positive adults who were virologically suppressed (<40 copies/mL) on ART and with CD4 counts above 350 cells/mm3 . The median age for participants was 46 years, 218 individuals had at least one comorbidity, and 239 had inverted CD4/CD8 ratios (<1). Current CD4/CD8 ratios were predicted by baseline CD4/CD8 ratios and nadir CD4 counts. Despite the high rates of inverted CD4/CD8 ratios and prevalence of comorbidities, no association between them was observed. The prevalence of comorbidities was significantly higher in older individuals, though aging alone did not explain the rate of all individual comorbidities. Low CD4/CD8 ratios were linked to neurocognitive disorders, suggesting that persistent T cell dysfunction contributes to neurocognitive decline.
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Rheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant-induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid-reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.
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Antioxidantes/metabolismo , Artrite/tratamento farmacológico , Artrite/metabolismo , Quercetina/farmacologia , Animais , Catalase/metabolismo , Ensaio Cometa , Dano ao DNA , Modelos Animais de Doenças , Feminino , Adjuvante de Freund , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Linfócitos/citologia , Mutagênicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures. MATERIALS AND METHODS: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1ß, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7â¯cells stimulated with phytohemagglutinin to mimic inflammation. RESULTS: The extract of A. aculeatum fruit inhibited macrophage proliferation (Pâ¯<â¯0.05), arrested the cell cycle in G0/G1 phase (Pâ¯<â¯0.001), increased antioxidant defenses (Pâ¯<â¯0.01), reduced oxidative stress (Pâ¯<â¯0.01), and modulated genes related to the inflammatory response (Pâ¯<â¯0.001). CONCLUSION: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases.
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Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Arecaceae/química , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Etnofarmacologia , Frutas/química , Inflamação/imunologia , Medicina Tradicional , Camundongos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Fito-Hemaglutininas/imunologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Plantas Comestíveis/química , Células RAW 264.7 , América do SulRESUMO
We analyzed the effects of a nanoencapsulated association of curcumin and vitamin D3 on purine metabolism enzymes in neutrophils, lymphocytes, and platelets in a model of adjuvant-induced arthritis (AIA) in rats. Following AIA induction, the animals were treated for 15 days with free and nanoencapsulated curcumin (4 mg/kg), nanocapsules of vitamin D3 (VD3) (15.84 IU/day), a nanoencapsulated combination of curcumin and VD3, vehicle, or blank nanocapsules. The animals were euthanized, and blood was collected to evaluate the activities of E-NTPDase, adenosine deaminase (ADA), and myeloperoxidase (MPO), as well as reactive oxygen species (ROS) levels and biochemical parameters. Also, the liver and kidney were collected for histological analysis. The changes in the activities of purinergic enzymes indicated that inflammation was significantly reverted by vitamin D3 and curcumin co-nanoencapsulation treatments in the arthritic rats. The reduction of inflammation was confirmed by the reduction in the signs and symptoms of AIA, as well as in MPO activity by all formulations. The treatments with nanocapsules reverted histological alterations in the kidney. Serum parameters were not altered by the induction or treatments. Our results suggest that co-nanoencapsulation of vitamin D3 and curcumin is an efficient alternative adjuvant treatment for rheumatoid arthritis as it reverts the changes in the purine metabolism and reduces arthritis-associated inflammation.
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Artrite Experimental/tratamento farmacológico , Colecalciferol/uso terapêutico , Curcumina/uso terapêutico , Inflamação/prevenção & controle , Purinas/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Cápsulas , Combinação de Medicamentos , Linfócitos/metabolismo , Neutrófilos/metabolismo , RatosRESUMO
Infection by human immunodeficiency virus (HIV) causes the acquired immune deficiency syndrome (AIDS), which has devastating effects on the host immune system. HIV entry into host cells and subsequent viral replication induce a proinflammatory response, hyperactivating immune cells and leading them to death, disfunction, and exhaustion. Adenosine is an immunomodulatory molecule that suppresses immune cell function to protect tissue integrity. The anti-inflammatory properties of adenosine modulate the chronic inflammation and immune activation caused by HIV. Lack of adenosine contributes to pathogenic events in HIV infection. However, immunosuppression by adenosine has its shortcomings, such as impairing the immune response, hindering the elimination of the virus and control of viral replication. By attempting to control inflammation, adenosine feeds a pathogenic cycle affecting immune cells. Deamination of adenosine by ADA (adenosine deaminase) counteracts the negative effects of adenosine in immune cells, boosting the immune response. This review comprises the connection between adenosinergic system and HIV immunopathogenesis, exploring defects in immune cell function and the role of ADA in protecting these cells against damage.
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Síndrome da Imunodeficiência Adquirida/virologia , Adenosina Desaminase/metabolismo , Adenosina/metabolismo , Infecções por HIV/imunologia , Linfócitos T/imunologia , Animais , Humanos , Transdução de Sinais/imunologiaRESUMO
HIV replication promotes atherogenesis and participates in the immune response to the virus, thereby influencing the inflammatory profile. These changes may, in turn, contribute to the risk of cardiovascular diseases with involvement of platelets. However, adenine nucleotides and nucleosides involved in thromboregulation and modulation of immune response may therefore be affected by these alterations. OBJECTIVES: This study sought to evaluate the profile of pro and anti-inflammatory cytokines (IL-10, IL-6, IL-17, TNF, IL-4, IL-2 and IFN-gamma), cardiac markers (troponin, CK, CK MB, LDH, CRP) in HIV-positive patients and assess the in vitro effect of antiretroviral therapy on the activities of ectonucleotidases (E-NTPDase and E-5'-nucleotidase) in human platelets. DESIGN AND METHODS: Blood samples were obtained from ten HIV positive patients at the Infectious Disease Clinic of the University Hospital of Santa Maria, Brazil and ten HIV negative individuals (control group) for this study. RESULTS: The results revealed that there were significant (P < 0.05) increases in serum levels of IL-6 and IFN-gamma with no significant (P > 0.05) changes in the serum levels of the cardiac markers investigated (CK, CK-MB, troponin, LDH and CRP). In addition, the ectonucleotidases (E-NTPDase and E-5'-nucleotidase) activities were not altered (P > 0.05) in human platelets when incubated with different antiretroviral drugs in vitro. CONCLUSIONS: The results of this study suggest that, despite successful treatment, a proinflammatory state is not altered in HIV patients, and that antiretroviral therapy per se does not change the purinergic profile.
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Biomarcadores/sangue , Infecções por HIV/sangue , Infecções por HIV/imunologia , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Citocinas/sangue , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Inflamação/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a promising compound to be used as an adjuvant in the treatment of hyperlipidemia.
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Adenosina Desaminase/metabolismo , Citocinas/metabolismo , Hiperlipidemias/metabolismo , Linfócitos/metabolismo , Pirofosfatases/metabolismo , Quercetina/farmacologia , Animais , Hiperlipidemias/patologia , Linfócitos/patologia , Masculino , Ratos , Ratos WistarRESUMO
Toxoplasma gondii, an intracellular protozoan, may cause chronic infection in the brain tissue of the host inducing a systemic pro-inflammatory profile. Chronic infections can induce numerous physiological changes, such as alterations in the immune and oxidative profiles. Diphenyl diselenide (PhSe)2, an organoselenium compound, has shown antioxidant and immunomodulatory activities in recent studies. So, the aim of this study was to investigate the activity of purinergic enzymes and reactive oxygen species (ROS) in serum and spleen of mice chronically infected by T. gondii, untreated and treated with (PhSe)2. For this experiment, were divided into four groups: Group A (healthy mice), Group B (healthy mice treated with (PhSe)2), Group C (infected mice) and Group D (infected mice treated with (PhSe)2). Group C and group D were infected via oral route with ME49 Toxoplasma gondii strain. Groups B and D were treated subcutaneously with 5 µmol kg-1 of (PhSe)2. Chronic T. gondii infection induced splenomegaly and physiological changes in the spleen and raised histologic inflammatory markers, ROS levels and the activity of purinergic enzymes activity such as NTPDase, 5´nucleotidase and ADA. In serum, the infection increased 5´nucleotidase and ADA activities. (PhSe)2per se has managed to decrease ROS levels and ADA activity and increase NTPDase and 5´nucleotidase in spleen. In infected mice, treatment with (PhSe)2 reversed splenomegaly, reduced histological inflammatory markers, ROS levels and ADA activity in the spleen. Our results prove that chronic toxoplasmosis can induce splenomegaly, heightens ROS levels and purinergic enzyme activity in mice. These results suggest that (PhSe)2 is a potential therapy for the alterations found in the spleen in chronic T. gondii infection.
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Derivados de Benzeno/uso terapêutico , Nucleotidases/sangue , Compostos Organosselênicos/uso terapêutico , Baço/patologia , Toxoplasmose Animal/tratamento farmacológico , 5'-Nucleotidase/sangue , 5'-Nucleotidase/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Derivados de Benzeno/farmacologia , Feminino , Inflamação/tratamento farmacológico , Camundongos , Nucleotidases/metabolismo , Compostos Organosselênicos/farmacologia , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo , Baço/efeitos dos fármacos , Baço/enzimologia , Baço/metabolismo , Toxoplasmose Animal/enzimologia , Toxoplasmose Animal/patologiaRESUMO
The human immunodeficiency virus (HIV) infection results in biochemical and vascular dysfunctions. The highly active antiretroviral therapy (HAART) markedly reduces mortality and opportunistic diseases associated with acquired immunodeficiency syndrome (AIDS). This increased survival time predisposes the development of cardiovascular diseases. Platelets present purinergic system ectoenzymes such as E-NTPDase, E-5'-nucleotidase and E-ADA on its surface. In view of this, the aim of this study was to evaluate the activity of these ectoenzymes in platelets as well as the platelet aggregation and lipid profile of patients with HIV infection and also patients receiving HAART. The results showed an increase in the E-NTPDase activity for ATP hydrolysis in the HIV group compared with the control group and the HIV/HAART group. When assessing the activity E-NTPDase hydrolysis to ADP, the results revealed an increase in activity in the HIV group when compared to the control group, and a decrease in activity when in the HIV/HAART group when compared to the control and HIV groups. The activity of E-5'-nucleotidase revealed an increase in AMP hydrolysis in the HIV group, as the results from control and HIV/HAART groups showed no statistical difference. Regarding the E-ADA activity, the HIV and HIV/HAART groups revealed a decreased deamination of adenosine when compared with the control group. Furthermore, we observed an increased platelet aggregation of HIV/HAART group compared with the control group. Thus, our results suggest that antiretroviral treatment against HIV has a significant effect on the activity of purinergic system ectoenzymes demonstrating that thromboregulation is involved in the process.
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Nucleotídeos de Adenina/metabolismo , Terapia Antirretroviral de Alta Atividade , Plaquetas/metabolismo , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Trombose/tratamento farmacológico , 5'-Nucleotidase/metabolismo , Adenosina Desaminase/metabolismo , Adulto , Antígenos CD/metabolismo , Coagulação Sanguínea , Plaquetas/enzimologia , Estudos de Casos e Controles , Citometria de Fluxo , Humanos , Hidrólise , Lipídeos/sangue , Agregação Plaquetária , Trombose/complicaçõesRESUMO
BACKGROUND: The purpose of the study is to examine the quality of life (QoL) in chronic periodontitis (CP) patients associated with or not with well-controlled type 2 diabetes mellitus (DM2). MATERIALS AND METHODS: Five hundred CP patients, 250 with DM2 (GDM2 group) and 250 age- and gender-matched controls without DM2 (GND), were enrolled in this cross-sectional case-controlled study from January to September 2015. They were interviewed by a QoL questionnaire (Functional Assessment of Chronic Illness Therapy-Fatigue) validated to Portuguese. Periodontal examinations were also performed to confirm CP: probing pocket depth and clinical attachment level must be >3 mm. RESULTS: An association between the presence of DM2 and a high negative impact on QoL was observed. All domains in GDM2 patients presented mean values above 19. On the other hand, three functional domains in GND (physical, social/family, and emotional) showed values below 19 (medium negative impact). Comparisons between GND and GDM2 revealed the statistical difference between them for all domains (P < 0.05). CONCLUSIONS: This study shows that DM2 associated with CP negatively affect QoL, even considering well-controlled diabetic patients.
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Human immunodeficiency virus (HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper.
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Relata o processo de elaboração da biblioteca virtual dedicada à vida e obra de Carlos Chagas Filho. A pesquisa foi realizada no arquivo do próprio cientista e no de algumas instituições científicas e culturais em que ele atuou como membro e/ou dirigente. Os resultados obtidos até o momento demonstram que as informações e os documentos coletados contribuem para o conhecimento da prática científica no Brasil ao longo do século XX, bem como revelam suas interações com os movimentos das ciências biomédicas no exterior.(AU)
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Saúde Pública/história , Ciência/história , Bibliotecas Digitais , BrasilRESUMO
Relata o processo de elaboração da biblioteca virtual dedicada à vida e obra de Carlos Chagas Filho. A pesquisa foi realizada no arquivo do próprio cientista e no de algumas instituições científicas e culturais em que ele atuou como membro e/ou dirigente. Os resultados obtidos até o momento demonstram que as informações e os documentos coletados contribuem para o conhecimento da prática científica no Brasil ao longo do século XX, bem como revelam suas interações com os movimentos das ciências biomédicas no exterior.
The article reports on the process of compiling a virtual library centered on the life and work of Carlos Chagas Filho. The research has included both the scientist's own archives as well as those of some scientific and cultural institutions where he was an active member or leader. Results on the information and documents collected to date show that these contribute to an understanding both of twentieth-century scientific practice in Brazil and of its interaction with movements in the biomedical sciences abroad.
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Humanos , Ciência/história , Saúde Pública/história , Bibliotecas Digitais , Arquivos , Brasil , Disseminação de Informação , DocumentaçãoRESUMO
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays important roles in various cellular processes. Here we report the sequence and analysis of a novel developmentally regulated gene and cDNA (Pbgadph), encoding a GAPDH homologue (PbGAPDH), of the pathogenic dimorphic fungus Paracoccidioides brasiliensis. We have analyzed the protein, the cDNA and genomic sequences to provide insights into the structure, function, and potential regulation of PbGAPDH. That Pbgapdh encodes PbGAPDH was demonstrated by micro-sequencing of the native protein homologue isolated from the fungus proteome. The deduced amino acid sequence of Pbgapdh showed identity to those of from other species (88-76%). Phylogenetic analysis indicated that GAPDH could be useful for the determination of evolutionary relationships. Expression of the Pbgapdh gene and the cognate protein were developmentally regulated in phases of P. brasiliensis, with a higher expression in the yeast parasitic phase and was induced during the transition from mycelium to yeast and decreased during the reverse process, transition from yeast to mycelium.