ABSTRACT
Exposure to nitrogen oxides (NOx) emitted by burning fossil fuels has been associated with respiratory diseases. We aimed to estimate the effects of NOx exposure on mortality owing to respiratory diseases in residents of Taubaté, São Paulo, Brazil, of all ages and both sexes. This time-series ecological study from August 1, 2011 to July 31, 2012 used information on deaths caused by respiratory diseases obtained from the Health Department of Taubaté. Estimated daily levels of pollutants (NOx, particulate matter, ozone, carbon monoxide) were obtained from the Centro de Previsão de Tempo e Estudos Climáticos Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System. These environmental variables were used to adjust the multipollutant model for apparent temperature. To estimate association between hospitalizations owing to asthma and air pollutants, generalized additive Poisson regression models were developed, with lags as much as 5 days. There were 385 deaths with a daily mean (±SD) of 1.05±1.03 (range: 0-5). Exposure to NOx was significantly associated with mortality owing to respiratory diseases: relative risk (RR)=1.035 (95% confidence interval [CI]: 1.008-1.063) for lag 2, RR=1.064 (95%CI: 1.017-1.112) lag 3, RR=1.055 (95%CI: 1.025-1.085) lag 4, and RR=1.042 (95%CI: 1.010-1.076) lag 5. A 3 µg/m3 reduction in NOx concentration resulted in a decrease of 10-18 percentage points in risk of death caused by respiratory diseases. Even at NOx concentrations below the acceptable standard, there is association with deaths caused by respiratory diseases.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Air Pollutants/toxicity , Air Pollution/adverse effects , Environmental Exposure/adverse effects , Nitric Oxide/toxicity , Respiration Disorders/etiology , Respiration Disorders/mortality , Air Pollution/analysis , Brazil/epidemiology , Carbon Monoxide/toxicity , Ozone/toxicity , Poisson Distribution , Particulate Matter/toxicity , Risk , ThermosensingABSTRACT
Nitric oxide [NO] is produced in different body organs in mammals and numerous physiological and pathological properties are attributed to this small molecule. The precursor of this substance in the body, L-arginine, is synthesized by the enzyme nitric oxide synthase [NOS], and it is catalyzed, and is inhibited by a substance called L-NG-nitroarginine methyl ester [L-NAME]. In this study we investigated the qualitative and quantitative effects of nitric oxide on cerebellar histopathology in vivo environment via increasing and decreasing its production. Forty Wister rats, weighing 200- 250 gr with a mean age of 8 weeks, were divided into 5 groups after making sure the rats were pregnant. Except the control group, the other pregnant groups, respectively received: 2 ml/kg normal saline, 200 mg/kg L-arginine, 20 mg/kg L-NAME and a mixture of the same doses of L-arginine and L-NAME on the third, fourth and fifth days of pregnancy. On day 18 of pregnancy, we anesthetized the rats, excised the cerebellum after craniotomy and fixed the organs in 10% formalin. We later prepared 5 to 6-micron in thickness tissue sections and dyed them by the routine Hematoxylin and eosin [HE] and Masson's Trichrom staining methods before studying them by light microscopy. There was a significant difference between the rats receiving L-arginine and the rats in other groups [P<0.01]. This study showed that L-NAME is capable of significantly decreasing the injury caused by nitric oxides in rat cerebellum
Subject(s)
Animals, Laboratory , Cerebellum/drug effects , Rats, Wistar , Arginine , NG-Nitroarginine Methyl Ester , Nitric Oxide/toxicityABSTRACT
A number of studies have demonstrated the potential antitumor effects of saffron and its constituents on different malignant cells in vitro. It has been reported that a novel glycoconjugate isolated from corms and callus of saffron possesses cytotoxic activity against different tumor cellswith nitric oxide [NO] production. These data suggest that the cytotoxic effect of saffron extract may be related to an effect on nitric oxide production. The aim of the study was to investigate the effect of whole saffron extract on NO production by the hepatocellular carcinoma cell line [HepG-2] and laryngeal carcinoma cell line [Hep-2]. The cell lines were treated with a saffron extract. The morphologic changes were observed and recorded after 24, 48 and 72 of incubation. The MTT test was used to assess cell viability and the quantitative changes in NO production was evaluated using Griess test in the aforementioned time intervals. The morphologic images showed qualitative changes in both cell lines. The MTT assay results indicated that there was an increase in cytotoxic effect by adding the extract at concentrations of 0, 200, 400 and 800 micro g/ml. However, the NO concentration decreased significantly after 6, 12, 18, 24, 48 and 72 hours of incubation, respectively. IC[50] of 400 micro g/ml was obtained for HepG2 cells; however, Hep2 and L929 cells did not respond to any extract concentrations. This study suggested that the saffron extract had a cytotoxic effect on HepG-2 and Hep-2 cell lines. The cytotoxic effect was probably related to a decrease in the NO concentration
Subject(s)
Nitric Oxide/toxicity , Carcinoma, Hepatocellular/physiopathology , Laryngeal Neoplasms/physiopathology , Antineoplastic Agents , Cytotoxicity, Immunologic , Plant Extracts , Cell Line, TumorABSTRACT
The exogenous nitric oxide donor, sodium nitroprusside, evaluated the recombinogenic potential of nitric oxide. Drug inhibited mycelial growth and conidiation in A757 Aspergillus nidulans master strain. Two heterozygous diploid strains, one wild (uvsH+//uvsH+) and the other defective to DNA repair (uvsH//uvsH) were used for recombinagenesis tests. Sodium nitroprusside recombinogenic effect was evaluated by the induction of homozygosis of recessive genes, originally present in heterozygous condition. Results show that sodium nitroprusside (40 uM, 80 uM and 160 uM) is effective in inducing mitotic crossing-over in diploid cells of A. nidulans
Subject(s)
Aspergillus nidulans/genetics , Nitric Oxide/toxicity , Fungi/genetics , Genotype , MitosisABSTRACT
Se realizó una revisión de los posibles mecanismos generadores de mutaciones, mediados por las especies reactivas derivadas del NO (RNOS), y su relación con la carcinogénesis. Las RNOS potencialmente pueden dañar el ADN de forma directa mediante procesos de oxidación, desaminación y metilación de bases; e indirecta inhibiendo la actividad de las enzimas reparadoras. La oxidación de bases conduce fundamentalmente a transversiones y la desaminación a transiciones. La especie reactiva N2O3 puede reaccionar con aminas biógenas generando N-nitrosaminas, reconocidos agentes alquilantes. La inhibición de las enzimas se manifiesta por la reacción de las RNOS con grupos nucleofílicos de aminoácidos críticos para la actividad enzimática. Todos estos mecanismos pudieran favorecer de una u otra forma a la ocurrencia de mutaciones en el ADN, implicadas en la activación de oncogenes o inhibición de genes supresores de tumores, o ambas, favoreciendo así el surgimiento y desarrollo tumoral
Subject(s)
DNA Damage , Mutagenesis , Neoplasms , Nitric Oxide/genetics , Nitric Oxide/toxicityABSTRACT
El óxido nítrico pasó de ser una molécula tóxica, producto de la combustión a ser un mediador de múltiples procesos biológicos. Los principales investigadores que trabajaron sobre el mismo recibieron en el año 1998 el premio Nobel. Se lo encuentra presente en las células del endotelio de todos los mamíferos y juega un papel fundamental en el proceso de relajación. Posteriormente se ha demostrado que se sintetiza en las plaquetas, células del sistema inmune, neuronas y otras células del organismo donde ejerce, otras acciones más allá de la vasodilatación. Su exceso o defecto permitió la comprensión de distintos mecanismos fisiopatológicos (shock séptico, hipertensión arterial). Su modulación permite tratar distintas entidades. La administración por vía inhalatoria tiene utilidad en diversas patologías. El tratamiento de la hipertensión pulmonar del recién nacido es el ejemplo más relevante, porque permitió mejorar la sobrevida y disminuyó el número de pacientes sometidos a Membrana de Oxigenación Extracorpórea. En el tratamiento de las cardiopatías congénitas que cursan con hipertensión pulmonar ocupa un lugar destacado en el intra, pre y postoperatorio. El Síndrome de Distrés Respiratorio del Adulto es quizá la entidad más cuestionada; ya que, si bien mejora la hipoxemia, no hay estudios que demuestren que mejora la sobrevida.
Subject(s)
Humans , Adult , Infant, Newborn , Nitric Oxide/administration & dosage , Nitric Oxide/pharmacokinetics , Nitric Oxide/pharmacology , Nitric Oxide/physiology , Nitric Oxide/chemical synthesis , Nitric Oxide/toxicity , Nitric Oxide/therapeutic use , Nitrous Acid/adverse effects , Administration, Inhalation , Anesthetics, Inhalation , Heart Defects, Congenital/therapy , Nitrogen Dioxide/toxicity , Endothelium , Extracorporeal Membrane Oxygenation , Hypertension, Pulmonary/therapy , Methemoglobin , Neonatology , Respiratory Insufficiency , Shock, SepticABSTRACT
The threat of free radical damage is opposed by coordinated responses that modulate expression of sets of gene products. In mammalian cells, 12 proteins are induced by exposure to nitric oxide (NO) levels that are sub-toxic but exceed the level needed to activate guanylate cyclase. Heme oxygenase 1 (HO-1) synthesis increases substantially, due to a 30- to 70-fold increase in the level of HO-1 mRNA. HO-1 induction is cGMP-independent and occurs mainly through increased mRNA stability, which therefore indicates a new NO-signaling pathway. HO-1 induction contributes to dramatically increased NO resistance and, together with the other inducible functions, constitutes an adaptive resistance pathway that also defends against oxidants such as H2O2. In E. coli, an oxidative stress response, the soxRS regulon, is activated by direct exposure of E. coli to NO, or by NO generated in murine macrophages after phagocytosis of the bacteria. This response is governed by the SoxR protein, a homodimeric transcription factor (17-kDa subunits) containing [2Fe-2S] clusters essential for its activity. SoxR responds to superoxide stress through one-electron oxidation of the iron-sulfur centers, but such oxidation is not observed in reactions of NO with SoxR. Instead, NO nitrosylates the iron-sulfur centers of SoxR both in vitro and in intact cells, which yields a form of the protein with maximal transcriptional activity. Although nitrosylated SoxR is very stable in purified form, the spectroscopic signals for the nitrosylated iron-sulfur centers disappear rapidly in vivo, indicating an active process to reverse or eliminate them.
Subject(s)
Humans , Animals , Heme Oxygenase (Decyclizing) , Nitric Oxide/physiology , Transcription Factors , Transcription, Genetic , Gene Expression , Nitric Oxide/toxicity , Oxidative StressABSTRACT
Objetivo: evaluar el papel del óxido nítrico (NO) en el síndrome de sjögren primario (SSp) y su relación con la apoptosis tisular en glándulas salivares menores (GSM). Métodos. Las GSM correspondieron a sialoadenitis focal propia del SSp, sialoadenitis crónica (SAC) y a GSM histológicamente normales. El progreso del SSp fue evaluado mediante el puntaje por focos inflamatorios en GSM. Los niveles salivares y séricos de nitrito (NO2) fueron medidos mediante la reacción de Griess. La expresión de la óxido nitrico sintetasa tipo 2 (NOS2) y de la cistatina C (Cis-C), un inhibidor fisiológico de proteasas, fue examinada en GSM por inmunohistoquímica, y analizada de manera semicuantitativa. La apoptosis tisular fue evaluada determinando la fragmentación del ADN mediante la incorporación de nucleótidos marcados. Resultados. Los niveles de NO2 en saliva fueron mayores en pacientes con SSp (n=17) que en controles sanos (n=17) (71.1ñ20.6 vs 3.7 uM, p=0.02), mientras que en suero fueron similares (22.3ñ3.8 vs 17ñ1.4 uM). En el infiltrado inflamatorio la expresión de NOs2 fue mayor en pacientes con SSp que con SAC (n=4) (94 por ciento vs 7 por ciento). La NOS2 fue observada también en células epiteliales canaliculares, células acinares y fibroblastos de pacientes (SSp y SAC), y de controles normales (n=5). En GSM de pacientes con SSp la expresión de NOS2 fue mayor en aquellas con focos inflamatorios <4(78 por ciento vs 17 por ciento, p=0.04) y con menor número de células apoptóticas en el inflitrado inflamatorio (0.6ñ0.2 vs 1.66ñ0.3, p=0.02). La expresión de Cls-C fue observada en los tres grupos estudiados, principalamente en células epiteliales canaliculares, en algunos plasmocitos y células acinares de pacientes con SSp. No se observó asociación entre la expresión de Cls-C y la apoptosis tisular. Conclusión. Este estudio confirma el aumento de la síntesis de NO en el SS primario, producido localmente en el sitio inflamatorio, principalamente durante las fases tempranas de la enfermedad, y sugiere su participación en el bloqueo de la apoptosis linfocitaria, la cual no es regulada por la Cis-C. el mecanismo de esta inhibición apoptótica podría estar asociada a la S-nitrosilación de caspasas
Subject(s)
Humans , Apoptosis/physiology , Lymphocytes/immunology , Nitric Oxide/immunology , Nitric Oxide/toxicity , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/physiopathology , Sjogren's Syndrome/immunologySubject(s)
Humans , Animals , Nitric Oxide/chemistry , Ligases/chemistry , Ligases/physiology , Nitric Oxide/physiology , Nitric Oxide/toxicityABSTRACT
O óxido nítrico, quando inalado, é rapidamente metabolizado na circulaçäo pulmonar, näo afetando a hemodinâmica sistêmica. Promovendo vasodilataçäo limitada aos segmentos ventilados dos pulmöes, o óxido nítrico reduz o shunt e a hipertensäo pulmonar. Este gás vem sendo aplicado em situaçöes graves, como a síndrome do desconforto respiratório agudo e outras condiçöes associadas a hipertensäo pulmonar aguda (cardiopatias congênitas, hipertensäo pulmonar persistente do recém-nascido etc.). Esta alternativa visa substituir procedimentos de alta complexidade, como a oxigenaçäo extracorpórea prolongada e a inspiraçäo de concetraçöes elevadas de oxigênio. O óxido nítrico pode ser administrado através de diversas técnicas. A toxicidade do óxido nítrico exige dosificaçäo precisa e monitorizaçäo das concentraçöes inaladas. Na maior parte das vezes, concentraçöes inaladas discretas, da ordem de 0,1 a 10 ppm parecem efetivas e seguras. Concentraçöes mais elevadas obrigam determinaçöes freqüentes dos níveis de metahemoglobinemia. A inalaçäo de óxido nítrico é intervençäo coadjuvante: na síndrome da angústia respiratória aguda ela é associada à hipercapnia permissiva e à ventilaçäo na posiçäo prona; em recém-nascidos, ela permite restaurar a oxigenaçäo e equilibra a funçäo circulatória até o controle definitivo do fator causal.