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1.
Anticancer Res ; 40(5): 2591-2599, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366404

RESUMO

BACKGROUND: Physical plasma is a mixture of reactive particles and electromagnetic radiation. Due to the antimicrobial, immunomodulatory, anti-inflammatory, wound-healing promoting, and antineoplastic effects of body tempered physical plasma under atmospheric pressure (cold atmospheric plasma: CAP), CAP therapy is increasingly becoming the focus of surgical and oncological disciplines. However, when applied in practice, a potential emission of harmful noxae such as toxic nitrogen oxides must be taken into account, which was investigated in the following study. MATERIALS AND METHODS: MiniJet-R Ar CAP device was characterized with respect to NOX-specific spectra, ultraviolet radiation C (UVC) intensity in the range of 200-275 nm and the formation of NOX gases. Instrument-specific parameters such as gas flow, energy setting of the high-frequency generator, and flow rate of the carrier gas Ar were varied. To test the toxic properties of the NO2 concentrations formed by CAP, SK-OV-3 human ovarian cancer cells were incubated with different NO2 concentrations and cell growth was monitored for 120 h. RESULTS: The operation of MiniJet-R led to the formation of NO2 in the proximity of the CAP effluent. Synthesis of NO led to a NO-specific spectrum in the range of 100-275 nm, whereby UVC radiation produced reached intensities of up to 90 mW/m2 NO gas itself, however, was not detectable, as it was converted to NO2 rapidly. Cell culture incubation experiments demonstrated that NO2 in these concentration ranges had no influence on the cell growth of human cancer cells. CONCLUSION: Although no limit values were exceeded in the present study, the emission of high-energy UVC radiation and toxic NO2 is a risk factor with regard to the legal regulations on workplace protection (operator hazard) and the approval of medical devices (patient hazard). This is important for considerations regarding treatment frequency and duration. The growth inhibitory effect of CAP treatment on human cancer cells principally suggests a medical application of the MiniJet-R device, although more extensive studies will have to follow.


Assuntos
Pressão Atmosférica , Dióxido de Nitrogênio/toxicidade , Gases em Plasma/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Óxido Nítrico/análise , Dióxido de Nitrogênio/análise , Raios Ultravioleta
2.
Anticancer Res ; 40(5): 2657-2665, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366410

RESUMO

BACKGROUND/AIM: Nitric oxide (NO) functions have been studied in many cancer types, but rarely in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the behavior of HNSCC cells following exposure to high NO (HNO). MATERIALS AND METHODS: Two pairs of isogenic HNSCC cell lines (HN18/HN17, HN30/HN31) were used, and were treated with a NO donor for 72 h. Cell viability, cell cycle, apoptosis, invasion, and MMP activity were determined using MTT, flow cytometry, Matrigel invasion, and gelatinase zymography assays, respectively. RESULTS: HNO induced HN18 and HN31 cell cycle progression in S and G2/M phases. Anti-invasion, MMP-2 inhibition, and apoptosis induction were observed in certain HNO-adapted cell lines. High NO did not affect MMP-9 activity in all cell lines. CONCLUSION: NO enhanced cell cycle progression and apoptosis but inhibited cell invasion in HNSCC cells.


Assuntos
Adaptação Fisiológica , Neoplasias de Cabeça e Pescoço/patologia , Óxido Nítrico/metabolismo , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/enzimologia , Humanos , Metaloproteinases da Matriz/metabolismo , Invasividade Neoplásica , Metástase Neoplásica
3.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276345

RESUMO

Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent.


Assuntos
Anti-Inflamatórios/farmacologia , Ginsenosídeos/farmacologia , Metabolômica , Úlcera Gástrica/prevenção & controle , Ácido Acético/toxicidade , Animais , Anti-Inflamatórios/uso terapêutico , Antiulcerosos/farmacologia , Endotelina-1/sangue , Ginsenosídeos/uso terapêutico , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Wistar , Úlcera Gástrica/sangue , Úlcera Gástrica/induzido quimicamente
4.
Braz J Med Biol Res ; 53(4): e8604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294697

RESUMO

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.


Assuntos
Meningoencefalite/complicações , Estomatite Vesicular/complicações , Animais , Astrócitos/metabolismo , Brasil , Citocinas/análise , Modelos Animais de Doenças , Citometria de Fluxo , Masculino , Meningoencefalite/patologia , Camundongos , Camundongos Endogâmicos BALB C , Microglia/metabolismo , Óxido Nítrico/análise , Estomatite Vesicular/patologia , Vesiculovirus
5.
Clín. investig. arterioscler. (Ed. impr.) ; 32(2): 70-78, mar.-abr. 2020. ilus
Artigo em Inglês | IBECS | ID: ibc-187150

RESUMO

The elevation of blood pressure produces specific organic lesions, including kidney and cardiac damage. On the other hand, cardiovascular disease usually leads to the development of hypertension. Thus, hypertension could be both a cause and a consequence of cardiovascular disease. Previous studies linked the lack of nitric oxide to cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced endothelium-derived hyperpolarizing factor responses, with shorter survival. The lack of this gas also leads to renal/cardiac abnormalities.It is widely known that nephrogenic deficiency is a risk factor for kidney disease. Besides, recent evidence suggests that alterations in WT-1, a key nephrogenic factor, could contribute to the development of hypertension. Moreover, some genes involved in the development of hypertension depend on WT-1.This knowledge makes it essential to investigate and understand the mechanisms regulating the expression of these genes during renal/cardiac development, and hypertension. As a consequence, the most in-depth knowledge of the complex aetiopathogenic mechanism responsible for the hypertensive disease will allow us to propose novel therapeutic tools


La hipertensión produce lesiones orgánicas específicas como daño renal/cardíaco, mientras que la enfermedad cardiovascular generalmente conduce a la hipertensión. Por ello, la hipertensión sería tanto una causa como una consecuencia de la enfermedad cardiovascular. Estudios previos refieren falta de óxido nítrico con anomalías cardiovasculares como hipertensión y reducción de las respuestas del factor hiperpolarizante derivado del endotelio. La falta de este gas también conduce a anomalías renales/cardíacas. Además, la deficiencia nefrogénicaes un factor de riesgo para la enfermedad renal. Así, alteraciones en WT-1, un factor nefrógeno clave, podrían contribuir al desarrollo de hipertensión. Finalmente, el conocimiento más profundo del complejo mecanismo etiopatogénico responsable de la enfermedad hipertensiva nos permitirá proponer nuevas herramientas terapéuticas


Assuntos
Humanos , Hipertensão/genética , Expressão Gênica/genética , Proteínas WT1/genética , Nefropatias/genética , Doenças Cardiovasculares/genética , Óxido Nítrico/genética
7.
Orv Hetil ; 161(17): 704-709, 2020 04 01.
Artigo em Húngaro | MEDLINE | ID: mdl-32324366

RESUMO

In critically ill COVID-19 patients, the failure of the cardiorespiratory system can be due to one of the following: (1) cytokine storm, haemophagocytosis ­ septic shock, (2) unmanageable hypoxemia, (3) isolated organ failure or as part of multi-organ failure. Herein we give an overview of the therapeutic options for treating or preventing these disease states. In recent years, CytoSorb-haemoperfusion to remove cytokines has shown promising results in the treatment of septic shock. Inhalational nitric oxide (iNO), inhalational epoprostenol and veno-venous extracorporeal membrane oxygenation (ECMO) are options in severe hypoxemia that is unresponsive to conventional mechanical ventilation. Renal failure is a frequent component of the multi-organ failure usually seen with disease progression and necessitates starting one of the available continuous renal replacement modalities. Orv Hetil. 2020; 161(17): 704­709.


Assuntos
Lesão Renal Aguda , Infecções por Coronavirus/terapia , Cuidados Críticos , Oxigenação por Membrana Extracorpórea , Hipóxia , Pneumonia Viral/terapia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Betacoronavirus , Infecções por Coronavirus/complicações , Estado Terminal , Citocinas/metabolismo , Hemoperfusão , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Óxido Nítrico/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Terapia de Substituição Renal
8.
Zhonghua Yi Xue Za Zhi ; 100(14): 1095-1101, 2020 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-32294875

RESUMO

Objective: To investigate the role of nitric oxide (NO) in hydrogen sulfide (H(2)S)-induced inhibition upon colonic smooth muscle contraction. Methods: Immunohistochemistry was applied to observe the distribution of H(2)S-producing enzymes CBS and CSE in adult male Wistar rats. Organ bath system was used to observe the spontaneous contraction of colonic smooth muscle. Patch clamp technique was applied to record currents of L-type calcium channel (I(Ca,L)) in smooth muscle cells. Results: Specific immunoreactivity for CSE and CBS was observed in mucosa, smooth muscle and enteric plexus of rat proximal colon. NaHS elicited relaxation in a concentration-dependent manner upon muscle contraction in the presence of tetrodotoxin. The NaHS IC(50) of LM was 917.6 µmol/L (95% CI: 776.3-1 085 µmol/L, n=6) and the NaHS IC(50) of CM was 730.4 µmol/L (95% CI: 592.2-900.8 µmol/L, n=6). The SNP-induced relaxation in muscle strips was partially reversed by NaHS (P<0.05). Instead, the relaxation caused by NaHS was decreased by the sGC inhibitor ODQ but affected neither by NO precursor L-arginine, the NO inhibitor L-NNA nor the competitive cGMP antagonist PET-cGMP. NaHS (100 µmol/L) increased I(Ca,L) while NaHS (300 µmol/L) decreased the peak I(Ca,L) with modifying the ion channel characteristics (P<0.05). Conclusions: Exogenous hydrogen sulfide might have a dual effect on colonic motility and its inhibitory effect might be independent of NO signaling system. L-type calcium channel may play an important role during the process of H(2)S modulating colonic contraction.


Assuntos
Contração Muscular , Animais , Colo , Sulfeto de Hidrogênio , Masculino , Óxido Nítrico , Ratos , Ratos Wistar
9.
Life Sci ; 251: 117640, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32259603

RESUMO

AIM: To evaluate the effects of P2X7 receptor blockade on renin-angiotensin system (RAS) in rats with diabetic nephropathy (DN). MAIN METHODS: Wistar rats were unilaterally nephrectomized and received streptozotocin for diabetes mellitus (DM) induction; control animals (CTL) received the drug vehicle. The animals were submitted to P2X7 receptor silencing, forming the group (DM + siRNA). The animals were placed in metabolic cages for data collection and evaluation of renal function; at the end of the protocol, the kidney was removed for analysis of P2X7, renin, angiotensin-converting enzyme (ACE), ACE2, angiotensin, thiobarbituric acid reactive substance levels (TBARS), nitric oxide (NO) and qualitative histological. KEY FINDINGS: The metabolic profile was attenuated in DM + siRNA vs. DM and there was a significant improvement in creatinine, urea and proteinuria levels in the same group. Renin expression was significantly decreased in DM + siRNA vs. DM. ACE and ACE2 were significantly reduced in DM + siRNA vs. DM. TBARS levels were decreased and NO showed an increase in DM + siRNA vs. DM, both significant. All histological alterations were improved in DM + siRNA vs. DM. SIGNIFICANCE: Data have shown that although silencing of the P2X7 receptor did not decrease fasting glucose, it promoted an improvement in the metabolic profile and a significant recovery of renal function, revealing a protective action by the inhibition of this receptor. This effect must have occurred due to the inhibition of RAS and the increase of NO, suggesting that the use of P2X7 receptors inhibitors could be used as adjuvant therapy against DN progression.


Assuntos
Diabetes Mellitus Experimental/terapia , Nefropatias Diabéticas/terapia , Inativação Gênica , Receptores Purinérgicos P2X7/genética , Sistema Renina-Angiotensina/genética , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , RNA Interferente Pequeno/administração & dosagem , Ratos , Ratos Wistar , Estreptozocina
10.
Mem Inst Oswaldo Cruz ; 115: e190408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321156

RESUMO

BACKGROUND: The mechanism of resistance to SbIII in Leishmania is complex, multifactorial and involves not only biochemical mechanisms, but also other elements, such as the immune system of the host. OBJECTIVES: In this study, putative changes in the immunological profile of human monocytes infected with wild-type (WT) and antimony (SbIII)-resistant Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum lines were evaluated. METHODS: Susceptibility assays WT and SbIII-resistant L. braziliensis and L. infantum were performed using lines THP-1 human monocytic lineage. Phagocytic capacity, cytokine profile, intracellular nitric oxide (NO) production and surface carbohydrate residues profile were performed in peripheral blood monocytes by flow cytometry. FINDINGS: The phagocytic capacity and intracellular NO production by classical (CD14++CD16-) and proinflammatory (CD14++CD16+) monocytes were higher in the presence of L. infantum lines compared to L. braziliensis lines. The results also highlight proinflammatory monocytes as the cellular subpopulation of major relevance in a phagocytosis event and NO expression. It is important to note that L. infantum induced a proinflammatory cytokine profile characterised by higher levels of TNF-α in culture supernatant than L. braziliensis. Conversely, both Leishmania lines induce high levels of IL-6 in culture supernatant. Analysis of the expression profile of surface carbohydrates showed that L. braziliensis presents 4.3-fold higher expression of galactose(ß1,4)N-acetylglucosamine than L. infantum line. Interestingly, the expression level of α-N-acetylgalactosamine residues was 2-fold lower in the SbIII-resistant L. braziliensis line than its counterpart WT line, indicating differences in surface glycoconjugates between these lines. MAIN CONCLUSIONS: Our results showed that L. braziliensis and L. infantum induce different innate immune responses and a highly inflammatory profile, which is characteristic of infection by L. infantum, the species associated with visceral disease.


Assuntos
Antimônio/farmacologia , Antiprotozoários/farmacologia , Leishmania braziliensis/imunologia , Leishmania infantum/imunologia , Monócitos/parasitologia , Óxido Nítrico/biossíntese , Fagocitose/imunologia , Adulto , Resistência a Medicamentos , Feminino , Citometria de Fluxo , Humanos , Imunidade Inata , Leishmania braziliensis/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Masculino , Monócitos/imunologia , Adulto Jovem
11.
Yonsei Med J ; 61(4): 310-316, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233173

RESUMO

PURPOSE: To evaluate the effects of air purifiers on the concentrations of indoor air pollutants and on asthma control in children. MATERIALS AND METHODS: In this randomized crossover trial, daily use of an air purifier filter was compared with a matched placebo with the filter off. Thirty elementary school students who had asthma were enrolled and randomly allocated to one of two groups. The primary endpoints were changes in indoor air quality, asthma severity, lung function, airway inflammatory, urine microbiome, and phthalate after the installation of air purifiers. PM2.5 and CO2 were measured as indoor air pollutants. Asthma severity was assessed in terms of both symptom and medication scores acquired using a daily questionnaire. The higher the score, the better the symptom or the less frequent the use of medication. Peak expiratory flow rate and fractional exhaled nitric oxide were also measured. RESULTS: The mean age of the enrolled patients was 9.2±1.98 years. The mean concentration of PM2.5 was 17.0 µg/m³ in the filter-off condition, but significantly lower at 9.26 µg/m³ in the filter-on condition. Medication scores were 6.9 for the filter-off and 7.12 for the filter-on conditions, reflecting a statistically significant decrease in the frequency of medications used during air purifier operation. Bacterial richness, as determined using the Chao 1 index, was markedly lower in the filter-on than the filter-off condition. CONCLUSION: This study suggests that air purifiers benefit medication burden in children with asthma by reducing PM2.5 levels.


Assuntos
Filtros de Ar/estatística & dados numéricos , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/prevenção & controle , Asma/epidemiologia , Pulmão/fisiologia , Material Particulado/efeitos adversos , Adolescente , Poluição do Ar em Ambientes Fechados/efeitos adversos , Criança , Estudos Cross-Over , Monitoramento Ambiental , Feminino , Humanos , Masculino , Óxido Nítrico , Avaliação de Resultados em Cuidados de Saúde , Material Particulado/análise , Testes de Função Respiratória , Índice de Gravidade de Doença
12.
J Environ Manage ; 262: 110343, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32250819

RESUMO

Series of AgNPs/TiO2-loaded carbon fiber cloth (CFC) composites were prepared by incorporation of pristine TiO2 and three AgNPs-modified TiO2 additives onto the surface of four commercial CFCs. AgNPs/TiO2 photocatalysts were synthesized by the wet impregnation method, including NaBH4 reduction of silver ions. The silver content in the modified photocatalyst was assessed by inductively coupled plasma optical emission spectrometry (ICP-OES) as well as XRD analysis. It can be indicated that silver was successfully reduced to Ag nanoparticles what was confirmed by UV-Vis/DRS as well as XRD methods. The photocatalytic activity of the AgNPs/TiO2-loaded CFCs was evaluated during the photocatalytic oxidation (PCO) tests of nitric oxide (NO) acting as a model air contaminant under UV light. It was found that the highest NO removal rate was observed for the AgNPs/TiO2-loaded CFC material containing 3.70 wt% of AgNPs. Modification of TiO2 with AgNPs stabilized the photocatalytic efficiency of the composites during 5 as well as 24 consecutive NO photooxidation cycles. It was also concluded that the presence of AgNPs was a key factor responsible for hindering NO2 formation.


Assuntos
Nanopartículas Metálicas , Prata , Fibra de Carbono , Catálise , Óxido Nítrico , Titânio
13.
Life Sci ; 249: 117537, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32165214

RESUMO

AIMS: To establish an animal model of diabetes mellitus (DM) with moderately elevated blood glucose levels, and to examine the nitric oxide (NO) mechanism controlling urethral function in streptozotocin (STZ)-induced DM rats. MAIN METHODS: Female Sprague-Dawley rats were used. DM was induced by intraperitoneal injection of STZ (65 mg/kg) and some of them received subcutaneous implantation of a low-dose insulin pellet. Voiding behavior was evaluated in metabolic cages. Isovolumetric cystometry and urethral perfusion pressure (UPP) were then evaluated under urethane anesthesia, during which L-arginine (100 mg/kg) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg/kg) were administered intravenously. In vitro urethral activity was also tested by organ bath muscle strip studies. KEY FINDINGS: UPP changes and high-frequency oscillation (HFO) were significantly (P < 0.05) smaller in 8-weeks DM rats vs. normal control (NC) rats or insulin-treated DM rats, which showed reductions in urine overproduction and voided volume per micturition vs. untreated DM rats. UPP nadir was decreased by L-arginine in NC and insulin-treated DM groups, and decreased by L-NAME in all groups. Five of 6 untreated DM rats showed a detrusor-sphincter dyssynergia pattern after L-NAME. In in vitro studies, the relative ratio of L-NAME-induced reductions of urethral relaxation against pre-drug urethral relaxation was significantly smaller in DM vs. NC rats (P < 0.05). SIGNIFICANCE: Low-dose insulin-treated DM rats would be a useful model for studying natural progression of DM-induced lower urinary tract dysfunction. The impaired NO-mediated urethral relaxation mechanisms play an important role in DM-induced urethral dysfunction, which could contribute to DM-induced inefficient voiding.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Insulina/uso terapêutico , Óxido Nítrico/metabolismo , Uretra/fisiopatologia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Insulina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estreptozocina
14.
PLoS One ; 15(3): e0224052, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32168344

RESUMO

BACKGROUND: Codeine, a 3-methylmorphine, and other related opioids have been implicated in androgen suppression, although the associated mechanisms remain unclear. AIM: Therefore, the objective of the current study was to elucidate the in vivo molecular mechanisms underlying codeine-induced androgen suppression. METHODS: This study made use of twenty-one healthy male rabbits, distributed into three groups randomly, control and codeine-treated groups. The control had 1ml of normal saline daily p.o. The codeine-treated groups received either 4mg/kg b.w of codeine or 10mg/kg b.w of codeine p.o. for six weeks. Reproductive hormonal profile, testicular weight, testicular enzymes, oxidative and inflammatory parameters, testicular DNA fragmentation, histological examination and apoptosis marker were evaluated to examine the effects of codeine use. KEY FINDINGS: Oral administration of codeine resulted in testicular atrophy and alterations in testicular histomorphology, elevated testicular enzymes, and suppression of circulatory and intra-testicular testosterone. These changes were associated with a marked rise in oxidative markers and decline in the activities of testicular enzymatic antioxidants, as well as oxidative DNA damage, inflammatory response, testicular DNA fragmentation, and caspase-dependent apoptosis (p<0.05). SIGNIFICANCE: In conclusion, chronic codeine use resulted in testicular degeneration and testosterone suppression, which is attributable to TNF-α/nitric oxide-/oxidative stress-mediated caspase-dependent apoptotic testicular cell death and loss of testicular function.


Assuntos
Caspase 3/metabolismo , Codeína/toxicidade , Fragmentação do DNA/efeitos dos fármacos , Óxido Nítrico/metabolismo , Testículo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Codeína/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo
15.
Neumol. pediátr. (En línea) ; 15(1): 257-266, Mar. 2020. tab, ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-1088094

RESUMO

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.


Assuntos
Humanos , Criança , Testes de Função Respiratória/métodos , Pneumopatias/fisiopatologia , Pletismografia Total , Espirometria , Pneumopatias/diagnóstico , Óxido Nítrico/análise
16.
Nihon Yakurigaku Zasshi ; 155(2): 62-68, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115479

RESUMO

The EDRF discovered in 1986 by Furchgott was later identified as NO by Ignarro. NO was a widely noted gas with diverse functions, having arginine (L-Arg) as a substrate for the NO synthase (NOS). L-Arg and L-citrulline (L-Cit) have long been associated with the urea cycle. L-Cit was produced with NO by the reaction of L-Arg and oxygen. It was shown that administration of L-Arg in animals and humans caused vasodilation and anti-arteriosclerosis effects. Despite the arginine paradox ratio of intracellular arginine concentration to the Km value of NOS gaining widespread attention, advanced arteriosclerosis is known to reduce vascular reactivity towards L-Arg. In recent years, the anti-arteriosclerosis and anti-cell aging effects of the reactive substance citrulline (L-Cit) have been studied. L-Cit and L-Arg combination therapy are starting to be considered in various clinical applications as well.


Assuntos
Envelhecimento/fisiologia , Aterosclerose/prevenção & controle , Óxido Nítrico/fisiologia , Animais , Arginina/farmacologia , Aterosclerose/patologia , Citrulina/farmacologia , Humanos , Óxido Nítrico Sintase , Vasodilatação
17.
Nihon Yakurigaku Zasshi ; 155(2): 69-73, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115480

RESUMO

Nitric oxide (NO), formed from NO synthases (NOSs), plays a pathogenetic role in pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains to be clarified. We addressed this point in clinical and basic studies. We demonstrated that, in 36 consecutive patients with idiopathic pulmonary fibrosis, pulmonary artery systolic pressure is inversely correlated with NOx levels in the bronchoalveolar lavage fluid, suggesting reduced pulmonary NO production in group III PH. We then revealed that transplantation of BM cells from mice lacking all NOSs aggravates hypoxia-induced PH in wild-type (WT) mice, and transplantation of BM cells from the WT mice ameliorates hypoxia-induced PH in the NOSs-/- mice, indicating a protective role of myelocytic NOSs in the pathogenesis of PH. Immune and inflammatory mechanisms appeared to be involved in the aggravation of hypoxia-induced PH caused by transplantation of BM cells from the NOSs-/- mice. Our findings provide novel insights into the cellular and molecular basis of group III PH.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Fibrose Pulmonar Idiopática/fisiopatologia , Óxido Nítrico Sintase/fisiologia , Óxido Nítrico/fisiologia , Animais , Pressão Sanguínea , Líquido da Lavagem Broncoalveolar , Humanos , Pulmão/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Artéria Pulmonar
18.
Planta Med ; 86(7): 496-504, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32219782

RESUMO

The present study was performed to examine the antihypertensive effect of neferine in hypertensive rats and its relaxant mechanisms in isolated rat thoracic aorta. The antihypertensive effect was evaluated by tail-cuff methods on NG-nitro-L-arginine methyl ester (L-NAME) (40 mg/kg BW) 4-week hypertensive-induced hypertensive rats. The vasorelaxant effect and its mechanisms were studied by the organ bath technique in the thoracic aorta isolated from normotensive rats. The results indicated that the treatment of neferine (1 mg/kg and 10 mg/kg) markedly decreased the systolic blood pressure (SBP) when compared with the hypertension group (137.75 ± 10.14 mmHg and 132.23 ± 9.5 mmHg, respectively, p < 0.001), without affecting the heart rate. Moreover, neferine (10-12 - 10-4 M) exhibited concentration-dependent vasorelaxation in endothelium-intact rings (Emax values = 98.95 ± 0.66% and pD2 = 7.93 ± 0.28) and endothelium-denuded rings (Emax values = 90.61 ± 1.91% and pD2 = 6.85 ± 0.36). The effects of neferine were reduced by pre-incubation with L-NAME and 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) but not with pre-incubation with indomethacin and K+channel blockers. Neferine attenuated the contractions induced by phenylephrine and caffeine in a Ca2+-free solution and also inhibited in CaCl2- and phenylephrine-induced contracted rings. Our study suggests that neferine exhibited hypertensive potential, induced vasorelaxation through the endothelium nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway and involved the modulation of Ca2+ influx through Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum.


Assuntos
Anti-Hipertensivos , Vasodilatadores , Animais , Aorta Torácica , Benzilisoquinolinas , Endotélio Vascular , Óxido Nítrico , Ratos , Vasodilatação
19.
Life Sci ; 248: 117471, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112868

RESUMO

AIMS: This study aimed to explore the protective effects and possible mechanisms of baicalein on Aß25-35-induced toxicity. MAIN METHODS: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aß25-35 aggregation in vitro. PC12 cells were stimulated with Aß25-35, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aß25-35-injured PC12 cells. KEY FINDINGS: The results showed that baicalein could inhibit the aggregation of Aß25-35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aß25-35-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism. SIGNIFICANCE: Our study revealed that baicalein has a protective effect on Aß25-35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Flavanonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Trifosfato de Adenosina/biossíntese , Peptídeos beta-Amiloides/toxicidade , Animais , Arginina/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Niacina/metabolismo , Niacinamida/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fragmentos de Peptídeos/toxicidade , Prolina/metabolismo , Agregados Proteicos/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo
20.
Medicine (Baltimore) ; 99(11): e19292, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176054

RESUMO

BACKGROUND: The aim of the study was to provide a theoretical basis for the early diagnosis and prediction of acute altitude sickness, to provide a better entry mode for healthy people from plain areas to plateau areas, and to preliminarily clarify the possible mechanism of this approach. METHODS: We measured endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), nitric oxide (NO), and hypoxia-inducible factor 1 (HIF-1) levels in each sample and determined flow-mediated dilation (FMD) values using a portable OMRON color Doppler with a 7.0- to 12.0-MHz linear array probe. We used the Lewis Lake score to diagnose acute mountain sickness (AMS) and to stratify the disease severity. RESULTS: We found no cases of AMS at any of the studied elevation gradients. We found significant differences in FMD values between individuals when at 400 m above sea level and when at 2200, 3200, and 4200 m above sea level (P < .05) but found no significant differences among those at 2200, 3200, and 4200 m. Our variance analysis showed that serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in individuals at ≥3000 m and those at subplateau and plain areas (<3000 m) significantly differed (P < .05). The level of these factors also significantly differed between individuals at elevation gradients of plateau areas (3260 m vs 4270 m) (P < .05). We found no significant differences in serum ET-1, VEGF, and ADMA levels between individuals at the plateau (2260 m) and plain (400 m) areas (P > .05). NO and HIF-1 levels were significantly different in serum samples from individuals between the plateau (2260 m) and plain (400 m) areas (P < .05). However, with increasing altitude, the NO level gradually increased, whereas ET-1, ADMA, VEGF, and HIF-1 levels showed a decreasing trend. With the increase of altitude, there is no correlation between the trend of FMD and hematologic-related factors such as VEGF, NO, and HIF-1. CONCLUSION: A healthy young male population ascending to a high-altitude area experiences a low incidence of AMS. Entering an acute plateau exposure environment from different altitude gradients may weaken the effect of acute highland exposure on vascular endothelial dysfunction in healthy individuals. Changes in serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in healthy young men may be related to the body's self-regulation and protect healthy individuals from AMS. A short stay in a subplateau region may initiate an oxygen-free preconditioning process in healthy individuals, thereby protecting them from AMS. Noninvasive brachial artery endothelial function test instead of the detection of invasive hematologic-related factors for early diagnosis and prediction of the occurrence and severity of acute high-altitude disease is still lack of sufficient theoretical basis.


Assuntos
Doença da Altitude/sangue , Altitude , Endotelina-1/sangue , Fator 1 Induzível por Hipóxia/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Doença Aguda , Adulto , Doença da Altitude/diagnóstico , Análise de Variância , Biomarcadores/sangue , China , Diagnóstico Precoce , Voluntários Saudáveis , Humanos , Masculino , Militares , Óxido Nítrico/sangue , Valores de Referência , Sensibilidade e Especificidade , Adulto Jovem
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