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1.
Neumol. pediátr. (En línea) ; 16(2): 62-68, 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1293286

ABSTRACT

El asma es la enfermedad respiratoria crónica pediátrica más frecuente. En la mayoría de los niños se caracteriza por inflamación de la vía aérea de tipo eosinofílica alérgica. La fracción espirada de óxido nítrico (FENO) es un biomarcador de inflamación eosinofílica de vía aérea, su medición es no invasiva y fácil de realizar y ha sido evaluado en los últimos años para su aplicación clínica en el diagnóstico y tratamiento del asma en niños y adultos. Esta revisión abordará el origen anatómico y bioquímico del FENO, aspectos prácticos de su medición, valores de referencia y su aplicación clínica en el diagnóstico y tratamiento del asma pediátrico.


Asthma is the most common pediatric chronic disease characterized in most children by allergic eosinophilic airway inflammation. The exhaled fraction of nitric oxide (FENO) is a biomarker of eosinophilic airway inflammation, constituting a non-invasive and easy-to-perform test that has been evaluated in recent years for its clinical application in the diagnosis and treatment of asthma in children and adults. This review will address the anatomical and biochemical origin of FENO, practical aspects of its measurement, reference values and its clinical application in the diagnosis and treatment of pediatric asthma.


Subject(s)
Humans , Asthma/diagnosis , Nitric Oxide/analysis , Asthma/metabolism , Breath Tests , Biomarkers , Exhalation , Eosinophilia , Inflammation , Nitric Oxide/metabolism
2.
Neumol. pediátr. (En línea) ; 15(1): 257-266, Mar. 2020. tab, ilus, graf
Article in Spanish | LILACS | ID: biblio-1088094

ABSTRACT

Pulmonary function testing in children includes a large number of methods and aspects. Children constitute a very heterogeneous group of individuals, among which are non-collaborative infants and preschoolers who represent a challenge in the development of new methods that do not require collaboration or coordination. This review attempts to achieve a comprehensive approach to pulmonary function tests in children that allow the physician working in pediatrics to get to know: their pathophysiological bases; the reasons for a request for a pulmonary function test taking into account the underlying pathophysiological process that is suspected; the study procedures; the possible clinical findings and their interpretation; the advantages and limitations of several of the tests. Information related to spirometry is developed more specifically, since it is the most widespread, accessible and widely validated methods.


El estudio de la función pulmonar (FP) en niños abarca un gran número de métodos y aspectos. La edad pediátrica en sí constituye un grupo muy heterogéneo de individuos, entre los que se encuentran los de edades más tempranas que son no colaborativos y que representan un desafío en el desarrollo de nuevos métodos que no requieran colaboración ni coordinación. En esta revisión se describirá un enfoque integral de los estudios de FP más utilizados en niños. Se mencionan sus bases fisiopatológicas; los motivos de un pedido de estudio de FP teniendo en cuenta el proceso fisiopatológico subyacente que se sospecha; los posibles hallazgos clínicos y su interpretación y las ventajas y limitaciones de varios de los test.


Subject(s)
Humans , Child , Respiratory Function Tests/methods , Lung Diseases/physiopathology , Plethysmography, Whole Body , Spirometry , Lung Diseases/diagnosis , Nitric Oxide/analysis
3.
Braz. j. med. biol. res ; 53(4): e8604, 2020. graf
Article in English | LILACS | ID: biblio-1100926

ABSTRACT

Maraba virus is a member of the genus Vesiculovirus of the Rhabdoviridae family that was isolated in 1983 from sandflies captured in the municipality of Maraba, state of Pará, Amazônia, Brazil. Despite 30 years having passed since its isolation, little is known about the neuropathology induced by the Maraba virus. Accordingly, in this study the histopathological features, inflammatory glial changes, cytokine concentrations, and nitric oxide activity in the encephalon of adult mice subjected to Maraba virus nostril infection were evaluated. The results showed that 6 days after intranasal inoculation, severe neuropathological-associated disease signs appeared, including edema, necrosis and pyknosis of neurons, generalized congestion of encephalic vessels, and intra- and perivascular meningeal lymphocytic infiltrates in several brain regions. Immunolabeling of viral antigens was observed in almost all central nervous system (CNS) areas and this was associated with intense microglial activation and astrogliosis. Compared to control animals, infected mice showed significant increases in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (INF)-γ, MCP-1, nitric oxide, and encephalic cytokine levels. We suggest that an exacerbated inflammatory response in several regions of the CNS of adult BALB/c mice might be responsible for their deaths.


Subject(s)
Animals , Male , Rabbits , Vesicular Stomatitis/complications , Meningoencephalitis/complications , Brazil , Astrocytes/metabolism , Cytokines/analysis , Vesiculovirus , Microglia/metabolism , Disease Models, Animal , Vesicular Stomatitis/pathology , Flow Cytometry , Meningoencephalitis/pathology , Mice, Inbred BALB C , Nitric Oxide/analysis
4.
Braz. J. Pharm. Sci. (Online) ; 56: e18430, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132056

ABSTRACT

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen


Subject(s)
Animals , Male , Rabbits , Iliac Aneurysm/classification , Endothelin-1/adverse effects , Natriuretic Peptide, Brain/analysis , Endothelial Cells/drug effects , Wounds and Injuries/classification , von Willebrand Factor/analysis , Catheters/classification , Iliac Artery , Nitric Oxide/analysis
5.
Neumol. pediátr. (En línea) ; 14(2): 76-80, jul. 2019. ilus
Article in Spanish | LILACS | ID: biblio-1014992

ABSTRACT

Primary ciliary dyskinesia is a congenital disorder due to abnormal motile ciliary function, especially in the airway epithelium. The mucociliary clearance is impaired, producing reoccurring respiratory tract infections, usually resulting in bronchiectasis as an adult. Patients also have frequent ear and sinus infections and almost 50% of them have situs inversus. Diagnosis of primary ciliary dyskinesia is difficult because there is not a single gold standard test, resulting in the need of a multi-test approach. Until recently in our country we only had transmission electron microscopy, but nasal nitric oxide and high speed video microscopy are now available. In this article we will detail the most important clinical characteristics that make us suspect the presence of primary ciliary dyskinesia at different ages and the methods available for its diagnosis.


La discinesia ciliar primaria es una enfermedad congénita debida a una alteración del movimiento normal de los cilios, especialmente a nivel del epitelio respiratorio. Esto se traduce en una alteración del clearance mucociliar lo que predispone al paciente a tener infecciones respiratorias repetidas, terminando en la aparición de bronquiectasias en la edad adulta. También son frecuentes las infecciones repetidas de oídos y cavidades perinasales. La presencia de situs inverso puede verse en hasta en 50% de los pacientes con esta enfermedad. El diagnóstico de discinesia ciliar primaria es difícil ya que no existe un examen que sea considerado patrón de oro, por lo que se requiere la realización de distintos exámenes. En nuestro país hasta hace poco tiempo solo contábamos con la microscopía electrónica, pero recientemente se ha sumado la medición de óxido nítrico nasal y la videomicroscopía de alta velocidad. En el presente artículo se detallarán las características clínicas más importantes que hacen sospechar la presencia de DCP en las distintas edades y los métodos disponibles para su diagnóstico.


Subject(s)
Humans , Infant, Newborn , Child, Preschool , Adult , Kartagener Syndrome/diagnosis , Kartagener Syndrome/genetics , Kartagener Syndrome/therapy , Cilia/ultrastructure , Biopsy , Algorithms , Genetic Testing , Microscopy, Video , Microscopy, Electron, Transmission , Nitric Oxide/analysis
6.
J. appl. oral sci ; 27: e20180108, 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-975873

ABSTRACT

Abstract Objective: This study aims to evaluate the clinical and biochemical (oxidative stress and pro-inflammatory mediators) effects of the gaseous ozone use accompanied by scaling and root planning (SRP) in periodontal treatment. Material and Methods: The study population consisted of 40 patients with chronic periodontitis (CP) randomly sorted into two groups of 20. The experimental group received SRP plus 3 watts gaseous ozone in two separate applications five days apart, whereas the control group received SRP plus placebo. Clinical periodontal parameters were assayed and saliva samples were taken before the initial and one month after the second treatment. Periodontal examination assessed plaque index (PI), gingival index (GI), probing depth, and clinical attachment level (CAL). Total antioxidant status (TAS), total oxidant status (TOS), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and transforming growth factor-beta (TGF-β) levels were evaluated from saliva samples. Results: Changes following treatment in PI, GI, probing depth, and CAL scores were similar for both groups (p>0.05). Of note, TGF-β levels were observed to be higher in the treatment group than in controls (p<0.05). Changes in 8-OHdG, TAS, TOS, NO, MPO, GSH and MDA levels, however, were not significantly different between groups (p>0.05). Conclusion: The findings of this study indicate that SRP plus gaseous ozone versus SRP alone does not correlate to a significant improvement in periodontal recovery.


Subject(s)
Humans , Male , Female , Adult , Oxidants, Photochemical/therapeutic use , Ozone/therapeutic use , Root Planing/methods , Chronic Periodontitis/therapy , Saliva/chemistry , Time Factors , Enzyme-Linked Immunosorbent Assay , Periodontal Index , Dental Plaque Index , Reproducibility of Results , Transforming Growth Factor beta/analysis , Treatment Outcome , Oxidants/antagonists & inhibitors , Peroxidase/analysis , Statistics, Nonparametric , Deoxyguanosine/analysis , Deoxyguanosine/analogs & derivatives , Chronic Periodontitis/pathology , Glutathione/analysis , Malondialdehyde/analysis , Middle Aged , Nitric Oxide/analysis , Antioxidants/analysis
7.
Braz. oral res. (Online) ; 33: e035, 2019. tab, graf
Article in English | LILACS | ID: biblio-1001616

ABSTRACT

Abstract: Eugenia dysenterica is a Brazilian tree investigated for its properties and bioactive compounds, which are believed to have both pharmacological and phytochemical therapeutic effects. The leaves of this tree contain tannins, flavonoids, terpenes, and saponins, with reportedly beneficial effects to the human body. Despite these therapeutic applications, its effects have never been tested on oral tissues. Therefore, the aim of the present study was to evaluate the cytotoxic and antioxidant effects and the anti-inflammatory and repair properties of the acetone fraction of E. dysenterica on primary culture of human gingival fibroblasts and on the immortalized murine macrophage cell line (RAW 264.7). For this purpose, a metabolic activity assay, a wound healing assay, a nitric oxide assay, and RT-qPCR were performed. The assays revealed a cytoprotective effect of this plant, suggested by the increase in the expression of SOD1 and NRF2. An antioxidant potential effect was observed in the DPPH• assay. However, the fraction of E. dysenterica did not show anti-inflammatory activity. In conclusion, Eugenia dysenterica may promote cytoprotection when associated with chlorhexidine digluconate because of its antioxidant effect. However, additional studies are necessary on other human dental tissues using other parts of the plant in order to develop a possible mouthwash to assist patients with oral disorders.


Subject(s)
Humans , Animals , Mice , Plant Extracts/pharmacology , Fibroblasts/drug effects , Eugenia/chemistry , Gingiva/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Reference Values , Time Factors , Wound Healing/drug effects , Brazil , Cells, Cultured , Chlorhexidine/analogs & derivatives , Chlorhexidine/pharmacology , Reproducibility of Results , Plant Leaves/chemistry , Reverse Transcriptase Polymerase Chain Reaction , RAW 264.7 Cells , Nitric Oxide/analysis
8.
Acta cir. bras ; 33(12): 1067-1077, Dec. 2018. graf
Article in English | LILACS | ID: biblio-973486

ABSTRACT

Abstract Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.


Subject(s)
Animals , Male , Alprostadil/pharmacology , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide Synthase Type III/metabolism , Antioxidants/pharmacology , Superoxide Dismutase/analysis , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Catalase/analysis , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Troponin T/drug effects , Troponin T/blood , Enzyme Activation/drug effects , Creatine Kinase, MB Form/drug effects , Creatine Kinase, MB Form/blood , Heart Ventricles/drug effects , Heart Ventricles/pathology , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/blood , Malondialdehyde/analysis , Myocardial Infarction/pathology , Nitric Oxide/analysis
9.
Rev. paul. pediatr ; 36(1): 17-24, jan.-mar. 2018. tab, graf
Article in Portuguese | LILACS | ID: biblio-902888

ABSTRACT

RESUMO Objetivo: Avaliar a associação entre os valores da fração exalada de óxido nítrico (FeNO) e do volume expiratório forçado no primeiro segundo (VEF1) e o grau de controle da asma, segundo proposta do Global Initiative for Asthma (GINA), em crianças e adolescentes asmáticos atendidos no Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira da Fundação Oswaldo Cruz(IFF/FIOCRUZ). Métodos: Estudo transversal, com revisão de prontuários de 90 asmáticos entre 7 e17 anos de idade, acompanhados no Ambulatório de Asma do IFF/FIOCRUZ e encaminhados ao setor de Prova de Função Respiratória (PFR) entre março de 2013 e setembro de 2014. Após classificação segundo o GINA, os pacientes realizaram espirometria completa e medida da FeNO. Posteriormente, foram separados em dois grupos: em uso regular e não regular de corticosteroide inalatório (CI), independentemente do padrão ventilatório na espirometria. Resultados: Observou-se associação entre os valores de VEF1 e o grau de controle da asma segundo o GINA (p=0,001) em todos os pacientes analisados, independentemente do uso de CI, mas não houve associação entre os valores de VEF1 e os níveis da FeNO. Conclusões: A correlação observada entre o GINA e o VEF1 reforça a importância da espirometria no seguimento clínico desses pacientes. Embora não tenha sido detectada associação entre o valor da FeNO e o grau de controle da asma e o VEF1,a FeNO pode constituir um método precoce para detectar inflamação nas vias aéreas, antes mesmo dos sintomas e das alterações espirométricas.


ABSTRACT Objective: To evaluate the association between fraction of exhaled nitric oxide (FeNO) values and forced expiratory volume in the first second (FEV1) and the level of asthma control, as proposed by the Global Initiative for Asthma (GINA), in asthmatic children and adolescents attended at the National Institute of Women, Children and Adolescents Health Fernandes Figueira of Fundação Oswaldo Cruz (IFF/FIOCRUZ). Methods: This was a cross-sectional study, with a review of medical records of 90 asthmatics between 7 and 17 years old, who were followed up at the IFF/FIOCRUZ Asthma Outpatient Clinic and were referred to perform respiratory function tests (RFT)between March 2013 and September 2014. After classification according to GINA, patients performed complete spirometry and FeNO measurement. Subsequently, they were separated into two groups: regular and non-regular inhaled corticosteroid (ICS) use, regardless of the ventilatory pattern in spirometry. Results: The association between FEV1 values and the degree of asthma control according to GINA (p=0.001) was observed in all patients, regardless of ICS use, but there was no association between FEV1 and levels of FeNO. Conclusions: The correlation observed between GINA and FEV1 reinforces the importance of spirometry in the clinical follow-up of these patients. Although no association was found between the value of FeNO and the degree of asthma control and FEV1, FeNO may be an early method to detect airway inflammation, even before the symptoms and spirometric changes.


Subject(s)
Humans , Male , Female , Child , Adolescent , Asthma/physiopathology , Asthma/therapy , Spirometry , Nitric Oxide/analysis , Forced Expiratory Volume , Cross-Sectional Studies , Retrospective Studies , Exhalation
10.
J. bras. pneumol ; 44(1): 52-54, Jan.-Feb. 2018. tab
Article in English | LILACS | ID: biblio-1040268

ABSTRACT

ABSTRACT The aim of the study was to assess short-term repeatability of measurements of fractional exhaled nitric oxide (FENO) and its correlates in children in the 6- to 9-year age bracket participating in a respiratory epidemiological survey. FENO was measured in two sessions one week apart in 101 children. Participants were divided into three groups: asymptomatic (n = 76); symptomatic (n = 14); and asthma (n = 11). Absolute and relative differences between the measurements, as well as concordance correlation coefficients, were used in order to assess repeatability. The two FENO measurements were strongly correlated (0.98). Although intragroup comparisons of the two measurements were not significantly different (p = 0.2), intergroup comparisons were. FENO measurements are reproducible in children in epidemiological settings.


RESUMO O objetivo do estudo foi avaliar a repetibilidade em curto prazo de medidas da fração de óxido nítrico exalado (FENO) e seus correlatos em crianças de 6-9 anos participantes de uma pesquisa epidemiológica respiratória. A FENO foi medida em duas sessões, com uma semana de intervalo, em 101 crianças. Os participantes foram divididos em três grupos: assintomático (n = 76), sintomático (n = 14) e asma (n = 11). A repetibilidade foi avaliada por meio de diferenças absolutas e relativas entre as medidas, bem como por coeficientes de correlação de concordância. As duas medidas da FENO correlacionaram-se fortemente (0,98). Embora as comparações entre as duas medidas em um mesmo grupo não tenham sido significativamente diferentes (p = 0,2), as comparações entre os grupos o foram. Medidas da FENO são reprodutíveis em crianças em cenários epidemiológicos.


Subject(s)
Humans , Male , Female , Child , Asthma/diagnosis , Exhalation/physiology , Nitric Oxide/analysis , Reference Standards , Respiratory Function Tests , Asthma/physiopathology , Breath Tests/methods , Reproducibility of Results , Statistics, Nonparametric
11.
Arq. neuropsiquiatr ; 76(1): 32-40, Jan. 2018. graf
Article in English | LILACS | ID: biblio-888340

ABSTRACT

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.


RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.


Subject(s)
Animals , Male , Benzoquinones/pharmacology , Oxidative Stress/drug effects , Hypothyroidism/complications , Learning Disabilities/drug therapy , Memory Disorders/drug therapy , Antioxidants/pharmacology , Propylthiouracil , Avoidance Learning/drug effects , Superoxide Dismutase/analysis , Antithyroid Agents , Brain Injuries/metabolism , Catalase/analysis , Rats, Wistar , Maze Learning/drug effects , Disease Models, Animal , Hippocampus/drug effects , Hypothyroidism/chemically induced , Learning Disabilities/chemically induced , Malondialdehyde/analysis , Memory Disorders/chemically induced , Nitric Oxide/analysis
12.
Braz. oral res. (Online) ; 32: e82, 2018. tab, graf
Article in English | LILACS | ID: biblio-952160

ABSTRACT

Abstract The etiopathogenesis of oral lichen planus (OLP) is still not fully elucidated, and it is believed that its development could involve a neuro-immune-endocrine profile. This systematic review investigated the relationship between cytokines, cortisol, and nitric oxide (NO) in the saliva of OLP patients. An electronic search was conducted in Pubmed/Medline, Scopus, LIVIVO, and Web of Science databases with no restriction of language to identify studies published up to December 2017. Data extraction was performed using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 140 articles were retrieved, and 32 articles fulfilled the inclusion criteria (cytokines = 17; cortisol = 9; NO = 6). The most studied cytokines in the saliva of OLP patients were interleukins IL-4, IL-6, IL-8, IFN-ү, and TNF-α, which were higher in OLP patients than in healthy controls (HC). Salivary cortisol was found to be higher in OLP than in HC in most (55.5%) of the selected studies, and all studies related to NO found higher levels of this marker in OLP than in HC. Despite controversial results, our review suggests that OLP patients have an increased inflammatory response, as indicated by the proinflammatory profile of salivary cytokines. In addition, we conclude that salivary cytokine and NO measurements may have significant diagnostic and prognostic potential for monitoring disease activity and therapeutic responses in OLP.


Subject(s)
Humans , Male , Female , Saliva/chemistry , Hydrocortisone/analysis , Cytokines/analysis , Lichen Planus, Oral/diagnosis , Nitric Oxide/analysis , Reference Standards , Biomarkers/analysis , Case-Control Studies , Lichen Planus, Oral/metabolism
13.
Braz. J. Pharm. Sci. (Online) ; 54(4): e17281, 2018. tab, graf
Article in English | LILACS | ID: biblio-1001574

ABSTRACT

A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs), in which an O 2-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-aminosulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids (6a-c), were synthesized. A low amount of NO was released from the diazen-1-ium-1,2-diolate compounds 6a-c upon incubation with phosphate buffer saline (PBS) at pH 7.4 (range: pH 7.97-8.51), whereas, the percentage of NO released was significantly higher (84.5%-85.05% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies demonstrated that both NO and the anti-inflammatory 1-(4-aminosulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3-carboxylic acid (4a-c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The parent compounds 4a-c displayed good anti-inflammatory effects (ID50=81.4-112.4 mg/kg p.o.) between those exhibited by the reference drugs, aspirin (ID50=114.3 mg/kg p.o.) and celecoxib (ID50=12.6 mg/kg p.o.). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO-coxibs) offer a potential drug-design concept directed toward the development of anti-inflammatory drugs that are lacking adverse ulcerogenic and/or cardiovascular effects.


Subject(s)
Prodrugs/analysis , Celecoxib/analysis , Nitric Oxide/analysis , Anti-Inflammatory Agents/classification
14.
J. appl. oral sci ; 25(3): 265-273, May-June 2017. tab, graf
Article in English | LILACS, BBO | ID: biblio-893620

ABSTRACT

Abstract Elderly denture wearers are commonly affected by Candida-associated denture stomatitis (DS), an inflammatory process of the oral mucosa strongly associated with Candida spp and other microorganisms, as well as local and systemic factors. The impaired immune response against pathogens is among the inherent host factors that have been also associated with the pathogenesis of DS. Mononuclear phagocytes respond to the pathogens through phagocytosis followed by the production of several substances inside the phagosomes, among them are the reactive nitrogen species (RNS). A failure in these mechanisms may contribute to the DS development. Objective The aim of this study was to investigate the influence of aging on the internalization and the production of nitric oxide (NO) by peritoneal adherent cells (PAC), in response to Candida albicans (C. albicans). Material and methods PAC obtained from young and aged mice were challenged with dead or viable C. albicans by using predetermined proportions (cells:yeast) for 30 and 120 minutes. Phagocytosis was analyzed by acridine orange dye, and NO production by the Griess reaction. Results C. albicans phagocytosis by PAC from aged mice was similar to that of young mice, although the cells from older mice cells present more internalized fungi compared with matched control. In addition, a tendency towards impaired NO production by peritoneal mononuclear phagocytes from aged mice was observed. Conclusions PAC from aged mice may capture and store many fungi, which in turn may mean that these cells are effectively unable to eliminate fungi, probably due to impaired NO production. Therefore, considering the important role of C. albicans overgrowth in the pathogenesis of DS and the aspects observed in this study, aging may favor the onset and severity of local candidosis such as DS and its systemic forms.


Subject(s)
Animals , Male , Phagocytosis/physiology , Stomatitis, Denture/metabolism , Stomatitis, Denture/microbiology , Candida albicans/pathogenicity , Aging/physiology , Cell Adhesion/physiology , Nitric Oxide/biosynthesis , Peritoneum/cytology , Reference Values , Time Factors , Candida albicans/isolation & purification , Candidiasis/microbiology , Age Factors , Mice, Inbred C57BL , Nitric Oxide/analysis
15.
Arq. bras. cardiol ; 108(3): 228-236, Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-838702

ABSTRACT

Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR). Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS1177) and inducible nitric oxide synthase (iNOS) and to generate concentration-response curves to acetylcholine (ACh) and to phenylephrine (PHE). The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin administration. The maximal response (Emax) and the sensitivity (EC50) to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex) rats (Emax= -80 ± 4.6%, p < 0.05) when compared to those of controls (Ct) (Emax = -50 ± 6.8%). The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05) when compared to control conditions (120 ± 4.2%). This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05). Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.


Resumo Fundamento: O exercício físico é uma importante ferramenta para o aprimoramento da função endotelial. Objetivo: Avaliar os efeitos do exercício dinâmico resistido agudo na função endotelial de ratos espontaneamente hipertensos (SHR). Métodos: Após 10 minutos de exercício, a aorta foi removida para avaliação da expressão de óxido nítrico sintase endotelial (eNOS), óxido nítrico sintase endotelial fosforilada (p-eNOS1177) e óxido nítrico sintase endotelial induzível (iNOS), e para a construção de curvas concentração-resposta de acetilcolina (ACT) e fenilefrina (FEN). O protocolo FEN foi também realizado com lesão endotelial e antes e depois da administração de N-nitro-L-arginina metil éster (L-NAME) e indometacina. A resposta máxima (Emax) e a sensibilidade (EC50) a esses fármacos foram avaliadas. Resultados: Houve aumento do relaxamento induzido por ACT nos anéis aórticos dos ratos exercitados (Ex) (Emax = -80 ± 4,6%; p < 0,05) quando comparado àquele dos controles (Ct) (Emax = -50 ± 6,8%). A Emax à FEN diminuiu após exercício (95 ± 7,9%; p < 0,05) quando comparada àquela dos controles (120 ± 4,2%). Tal resposta foi abolida após administração de L-NAME ou lesão endotelial. Na presença de indometacina, a reatividade dos anéis aórticos à FEN diminuiu nos dois grupos (EC50= Ex -5,9 ± 0,14 vs. Ct -6,6 ± 0,33 log µM; p < 0,05/ Emax = Ex 9,5 ± 2,9 vs. Ct 17 ± 6,2%; p < 0,05). O exercício não alterou a expressão de eNOS e de iNOS, mas aumentou o nível de p-eNOS. Conclusão: Uma única sessão de exercício resistido melhora a função endotelial em ratos hipertensos. Essa resposta parece ser mediada por elevação da produção de NO através de ativação de eNOS.


Subject(s)
Animals , Male , Aorta, Thoracic/physiopathology , Aorta, Thoracic/metabolism , Physical Conditioning, Animal/physiology , Endothelium, Vascular/physiopathology , Endothelium, Vascular/metabolism , Aorta, Thoracic/chemistry , Phenylephrine , Phosphorylation/physiology , Time Factors , Vasoconstriction/physiology , Endothelium, Vascular/chemistry , Acetylcholine , Prostaglandins/metabolism , Blotting, Western , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type III/analysis , Nitric Oxide Synthase Type III/metabolism , Exercise Test , Hypertension/physiopathology , Hypertension/metabolism , Nitric Oxide/analysis , Nitric Oxide/metabolism
16.
Braz. j. med. biol. res ; 50(12): e6145, 2017. tab, graf
Article in English | LILACS | ID: biblio-888968

ABSTRACT

Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5×106 cells/mL) were pre-exposed to 1 μg/mL of lipopolysaccharides (LPS) and incubated with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB) were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.


Subject(s)
Humans , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biocompatible Materials/pharmacology , Cinnamates/pharmacology , Depsides/pharmacology , Hemodialysis Solutions/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Inflammation/drug therapy , Analysis of Variance , Cell Survival/drug effects , Cells, Cultured , Cytokines/analysis , Cytokines/drug effects , Formazans , Hemodialysis Solutions/chemistry , Human Umbilical Vein Endothelial Cells/metabolism , Immunoblotting , Inflammation/metabolism , Lipopolysaccharides , NF-kappa B/analysis , Nitric Oxide/analysis , Phosphorylation , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Tetrazolium Salts
17.
Arq. bras. cardiol ; 106(6): 481-490, tab, graf
Article in English | LILACS | ID: lil-787323

ABSTRACT

Abstract Background: Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. Objective: The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Methods: Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Results: Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. Conclusion: The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.


Resumo Fundamento: Diterpenos do tipo labdano induzem uma queda da pressão arterial por meio do relaxamento do músculo liso vascular; todavia, não há estudos que descrevam os efeitos de labdanos em ratos hipertensos. Objetivo: O presente estudo foi desenvolvido para investigar as ações cardiovasculares do labdano ácido ent-3-acetóxi-labda-8(17),13-dieno-15-óico (labda-15-óico) na hipertensão renal dois rins-1 clipe (2R-1C). Métodos: Foram feitos experimentos de reatividade vascular em anéis aórticos isolados de ratos machos 2R-1C e normotensos (2R). A medição de Nitrato/Nitrito (NOx) foi feita nas aortas por meio de ensaio colorimétrico. As medidas de pressão arterial foram feitas em ratos conscientes. Resultados: O ácido labda-15-óico (0,1 - 300 µmol/l) e a forscolina (0,1 nmol/l - 1 µmol/l) relaxaram as aortas com endotélio intacto e as aortas sem endotélio dos ratos 2R-1C e 2R. O labda-15-óico mostrou-se mais eficaz na indução do relaxamento em aortas com endotélio intacto de 2R pré-contraídas com fenilefrina em comparação àquelas sem endotélio. A forscolina mostrou-se mais potente do que o ácido labda-15-óico na indução do relaxamento vascular nas artérias tanto de ratos 2R-1C quanto de ratos 2R. O aumento dos níveis de NOx induzido pelo ácido labda-15-óico foi menor nas artérias de ratos 2R-1C em comparação a ratos 2R. A administração intravenosa de ácido labda-15-óico (0,3-3 mg/kg) ou forscolina (0,1-1 mg/kg) induziu hipertensão em ratos 2R-1C e 2R conscientes. Conclusão: Os presentes resultados mostram que o labda-15-óico induz relaxamento vascular e hipotensão em ratos hipertensos.


Subject(s)
Animals , Male , Rats , Vasodilator Agents/pharmacology , Blood Pressure/drug effects , Colforsin/pharmacology , Diterpenes/pharmacology , Hypertension, Renovascular/drug therapy , Aorta, Thoracic/drug effects , Phenylephrine/antagonists & inhibitors , Vasoconstrictor Agents/antagonists & inhibitors , Vasodilation/drug effects , Vasodilator Agents/chemistry , Colforsin/chemistry , Rats, Wistar , Disease Models, Animal , Diterpenes/chemistry , Drug Evaluation, Preclinical , Hypertension, Renovascular/physiopathology , Muscle, Smooth, Vascular/drug effects , Nitric Oxide/analysis
18.
Int. braz. j. urol ; 42(3): 614-620, tab, graf
Article in English | LILACS | ID: lil-785739

ABSTRACT

ABSTRACT Aim Our aim is to measure asymmetric dimethyl arginine and nitric oxide levels in rats with induced unilateral acute ureteral obstruction to research the effects on the kidney. Material and Methods The study included 21 adolescent (average age 6 weeks) Sprague-Dawley male rats weighing between 240-290g divided at random into 3 groups. Group-1: Control group (n=6): underwent no procedures. Group-2: Sham group (n=6): underwent the same procedures as the experimental group without ureter and psoas muscle dissection. Group-3: Group with induced partial unilateral ureteral obstruction (n=9). All rats were sacrificed after 12 weeks. Superoxide dismutase enzyme activity and nitrite and nitrate salt levels were measured in renal tissue. Plasma nitrite-nitrate and ADMA levels were examined. Results In the experimental group histopathological changes observed included renal pelvis dilatation, flattened papillae, sclerotic glomerulus and fibrosis. In the experimental group tissue SOD and blood ADMA levels were higher than the control and sham groups (p<0.05) while tissue NO and plasma NO values were lower than in the sham and control groups (p<0.05). Conclusion Oxidative stress and disruption of NO synthesis play an important role in renal function and histopathological changes after obstructive renal disease. To prevent renal complications developing after obstructive nephropathy we believe that a new strategy may be research on reducing ADMA.


Subject(s)
Animals , Male , Arginine/analogs & derivatives , Ureteral Obstruction/complications , Hydronephrosis/etiology , Hydronephrosis/pathology , Nitric Oxide/analysis , Arginine/blood , Reference Values , Superoxide Dismutase/analysis , Ureteral Obstruction/metabolism , Enzyme-Linked Immunosorbent Assay , Random Allocation , Paraffin Embedding , Rats, Sprague-Dawley , Oxidative Stress/physiology , Disease Models, Animal , Hydronephrosis/metabolism , Kidney/pathology , Nitrates/analysis , Nitric Oxide/metabolism
19.
Mem. Inst. Oswaldo Cruz ; 111(3): 147-154, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-777370

ABSTRACT

The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.


Subject(s)
Animals , Cricetinae , Male , Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Plant Extracts/chemistry , Selaginellaceae/chemistry , Administration, Oral , Antiprotozoal Agents/isolation & purification , Biflavonoids/analysis , Chromatography, High Pressure Liquid , Drainage , Foot/parasitology , Glycosides/chemistry , Infusions, Intralesional , Leukocytes, Mononuclear/parasitology , Macrophages/parasitology , Meglumine/administration & dosage , Nitric Oxide/analysis , Organometallic Compounds/administration & dosage , Parasite Load , Plant Extracts/administration & dosage , Solvents , Tandem Mass Spectrometry
20.
Arq. bras. cardiol ; 106(1): 41-48, Jan. 2016. tab, graf
Article in Portuguese | LILACS | ID: lil-771055

ABSTRACT

Abstract Background: Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. Objective: To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. Method: SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. Results: In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. Conclusion: Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.


Resumo Fundamento: A privação de sono (PS) acha-se fortemente associada a alto risco cardiovascular. Objetivo: Determinar o efeito da PS nas funções hemodinâmicas basais e tolerância à lesão miocárdica de isquemia‑reperfusão (IR) em ratos machos. Métodos: A PS foi induzida com o método da plataforma única por 4 dias. Utilizou-se o modelo de perfusão de coração isolado de Langendorff, medindo-se os seguintes parâmetros nas condições basais e após IR: pressão desenvolvida no ventrículo esquerdo (PDVE), frequência cardíaca (FC) e taxa máxima de aumento e redução da pressão do ventrículo esquerdo (±dp/dt). O nível cardíaco de NOx, o tamanho do infarto e os níveis de CK-MB e LDH no efluente coronário foram medidos após IR. A pressão arterial sistólica (PAS) foi medida no início e no final do estudo. Resultados: No grupo PS, os valores basais de PDVE (19%), +dp/dt (18%) e-dp/dt (21%) foram significativamente mais baixos (p < 0,05), e a FC (32%) significativamente mais alta em comparação aos dos controles. Após isquemia, os corações do grupo PS apresentavam um significativo aumento da FC além de uma menor recuperação da função hemodinâmica em comparação aos dos controles. No grupo PS, os níveis de NOx no coração e de CK-MB e LDH no efluente coronário, além do tamanho do infarto, foram significativamente maiores após IR. O grupo PS também apresentou maior PAS após 4 dias. Conclusão: Os corações do grupo PS apresentaram menor função cardíaca basal e menor tolerância à lesão de IR, o que pode estar relacionado ao aumento da produção de NO após IR.


Subject(s)
Animals , Male , Heart/physiopathology , Hemodynamics/physiology , Myocardial Reperfusion Injury/physiopathology , Sleep Deprivation/physiopathology , Blood Pressure/physiology , Creatine Kinase, MB Form/analysis , L-Lactate Dehydrogenase/analysis , Myocardial Infarction , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Nitric Oxide/analysis , Nitric Oxide/metabolism , Random Allocation , Rats, Wistar , Reference Values , Risk Factors , Sleep Deprivation/metabolism , Time Factors
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