Pharmacodynamic of cilostazol for anti-altitude hypoxia / 中南大学学报(医学版)

OBJECTIVES@#The plateau environment is characterized by low oxygen partial pressure, leading to the reduction of oxygen carrying capacity in alveoli and the reduction of available oxygen in tissues, and thus causing tissue damage. Cilostazol is a phosphodiesterase III inhibitor that has been reported to increase the oxygen release of hemoglobin (Hb) in tissues. This study aims to explore the anti-hypoxic activity of cilostazol and its anti-hypoxic effect.@*METHODS@#A total of 40 male BALB/C mice were randomly divided into a low-dose cilostazol (6.5 mg/kg) group, a medium-dose (13 mg/kg) group, a high-dose (26 mg/kg) group, and a control group. The atmospheric airtight hypoxia experiment was used to investigate the anti-hypoxic activity of cilostazol and to screen the optimal dosage. Twenty-four male Wistar rats were randomly divided into a normoxia control group, a hypoxia model group, an acetazolamide (22.33 mg/kg) group, and a cilostazol (9 mg/kg) group. After 3 days of hypoxia in the 4 010 m high altitude, blood from the abdominal aorta was collected to determine blood gas indicators, the levels of IL-6 and TNF-α in plasma were determined by enzyme-linked immunosorbent assay, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutataione (GSH) were measured. The degree of pathological damage for rat tissues was observed with HE staining.@*RESULTS@#Compared with the control group, the survival time of mice in the low, medium, and high dose group of cilostazol was significantly prolonged, and the survival time of mice in the medium dose group was the longest, with an extension rate at 29.34%, so the medium dose was the best dose. Compared with the hypoxia model group, the P50 (oxygen partial pressure at Hb oxygen saturation of 50%) value of rats in the cilostazol group was significantly increased by 1.03%; Hb and Hct were significantly reduced by 8.46% and 8.43%, and the levels of IL-6 and TNF-α in plasma were reduced by 50.65% and 30.77%. The MDA contents in heart, brain, lung, liver, and kidney tissues were reduced by 37.12%, 29.55%, 25.00%, 39.34%, and 21.47%, respectively. The SOD activities were increased by 94.93%, 9.14%, 9.42%, 13.29%, and 20.80%, respectively. The GSH contents were increased by 95.24%, 28.62%, 28.57%, 20.80%, and 44.00%, respectively. The results of HE staining showed that compared with the hypoxia model group, cilostazol significantly improved the damage of heart, lung, and kidney tissues in rats after hypoxia.@*CONCLUSIONS@#Cilostazol can significantly improve the oxidative stress and inflammatory reaction caused by rapid altitude hypoxia, and it has a significant protective effect on tissue damage caused by hypoxia, suggesting that it has obvious anti-hypoxic activity.

Anemia falciforme: una revisión sobre el genotipo de la enfermedad, haplotipos, diagnóstico y estudios asociados / Disease genotype, haplotypes, diagnosis and associated studies in sickle cell anemia

Sickle cell anemia is a type of hemoglobinopathy characterized by a specific mutation in the beta globin gene with the consequent generation of an unstable hemoglobin that crystallizes in a state of hypoxia. This causes a change in the structure of the red blood cell, which ends up producing vaso-occlusion with the corresponding clinical complications for the patient. Worldwide, various diagnostic tests have been developed that allow the appropriate approach to the affected patient. These include techniques for the determination of hemoglobin and the use of molecular markers, among others. There are new therapeutic alternatives to the use of hydroxyurea and L-glutamine, such as the use of gene therapy tools. The most recent experimental trials are exploring gene editing techniques.

Blood mRNA Expression Profiles of Autophagy, Apoptosis, and Hypoxia Markers on Blood Cardioplegia and Custodiol Cardioplegia Groups

Abstract Introduction: Blood cardioplegia (BC) and Custodiol cardioplegia (CC) have been used for a long time in open heart surgery and are highly effective solutions. The most controversial issue among these two is whether there is any difference between them regarding myocardial damage after ischemia surgery. In this study, autophagy, apoptosis, and hypoxia markers were investigated and that way we evaluated the differences between BC and CC patients. Methods: A total of 30 patients were included in this study, using two different cardioplegic solutions. Three different whole blood samples of the patients were taken from a central vein (preoperatively, immediately postoperatively, and one day after surgery). Total ribonucleic acid was extracted from these samples. Quantitative real-time polymerase chain reaction was performed, and changes in gene expression were determined by the 2-∆∆Ct method of relative quantification. Results: In the CC group, Beclin gene expression level was found to be higher and this difference was statistically significant (P=0.0024). Similarly, cysteine-aspartic acid protease (caspase) 9 and hypoxia-inducible factor 1α messenger ribonucleic acid (mRNA) gene expression level increased and were significantly different in the CC group. In the BC group, Beclin and microtubule-associated protein light chain 3 expressions were higher in the samples taken one day after surgery. Caspases 3 and 8 gene expressions were significantly different in the BC group. Conclusion: As a result of the analysis performed between the two cardioplegia groups, it has been shown that CC harms the myocardium more than BC at the level of mRNA expression of related markers.

Lista de medicamentos esenciales para el manejo de pacientes que ingresan a unidades de cuidados intensivos con sospecha o diagnóstico confirmado de COVID-19 / List of essential drugs for the management of patients admitted to intensive care units with suspected or confirmed diagnosis of COVID-19

En el transcurso de la pandemia de COVID-19, numerosos países, de ingresos bajos, medianos y alto, han visto agotadas sus reservas de medicamentos esenciales necesarios para el manejo de los pacientes con COVID-19 en las unidades de cuidados intensivos (UCI). El plan de preparación para emergencias sanitarias de los países requiere incluir una lista de medicamentos esenciales y otros dispositivos médicos necesarios en las UCI para afrontar emergencias sanitarias. La lista de medicamentos esenciales para el manejo de pacientes que ingresan a unidades de cuidados intensivos con sospecha o diagnóstico confirmado de COVID-19 es un documento de orientación fundamental que ayuda a los sistemas de salud de los países a priorizar los medicamentos esenciales que deben estar ampliamente disponibles y ser asequibles para manejar los pacientes en las UCI durante las situaciones de emergencia sanitaria, en este caso con sospecha o diagnóstico confirmado de COVID-19. Está dirigida a las autoridades sanitaras y a los encargados del manejo del sistema de salud de los países. Esta lista incluye fundamentalmente los medicamentos considerados esenciales para el manejo de los cuadros clínicos que con se observan con mayor frecuencia en pacientes hospitalizados en UCI a causa de una infección por SARS-CoV-2. No se incluyen la mayoría de los medicamentos que comúnmente se encuentran en las UCI para el manejo de otras patologías, comorbilidades o la estabilización del paciente (p. ej., insulina o antihipertensivos), salvo aquellos que pueden requerirse para el tratamiento o apoyo (p. ej., bloqueantes neuromusculares o anestésicos) de las dolencias generadas por la infección. Tampoco se incluyen medicamentos específicos para el tratamiento de la infección por SARS-CoV-2, puesto que no existe, por el momento, evidencia científica de alta calidad que avale su uso, salvo en el contexto de ensayos clínicos controlados. Un equipo de expertos en el tema realizó una búsqueda de información sobre la atención de pacientes en UCI durante la pandemia de COVID-19, en Medline (a través de PubMed), Cochrane, Tripdatabase, Epistemonikos y en buscadores generales de internet (Google). Se identificaron también revisiones o guías generadas por ministerios de Salud de varios países de la Región de las Américas, la Organización Mundial de la Salud (OMS), la Organización Panamericana de la Salud (OPS), el Instituto Nacional de Salud y Excelencia Clínica (NICE) de Reino Unido, los Centros para el Control y la Prevención de Enfermedades (CDC) de Estados Unidos y los Institutos Nacionales de Salud (NIH) de Estados Unidos.

Antihypoxic and anti-ischemic properties of the North Caucasus flora plant extracts / Propiedades antihipóxicas y antiisquémicas de los extractos de plantas de la flora del norte del Cáucaso

Nowdays it is established that ischemic brain damage like ischemic stroke is one of the leading cause of death and disability in the population that assumes relevance development of anti-ischemic drugs. The work studied the anti-hypoxic and anti-ischemic effect of 7 plant extracts. Antihypoxic activity was assessed on models of hypobaric, hypercapnic, histotoxic, hematotoxic hypoxia. Anti-ischemic activity of test-extracts was studied on the focal cerebral ischemia model. Administration of Tagetes patula, Gaillardia pulchella, Sorbaria sorbifolia, Grossularia reclinata, Ribes nigrum, Rubus caesius and Lysimachia punctata extracts contributed to the necrosis zone reduction by 56.6% (p<0.05); 37.3% (p<0.05); 73.2% (p<0.05); 49.4% (p<0.05); 42.5% (p<0.05); 85.5% (p<0.05); 44.2% (p<0.05) and also restored aerobic metabolism in brain tissue. Test - objects increased of the animal lifespan under hypoxia conditions. Based on the data obtained, it is assumed that further studies of North Caucasus flora plant extracts as cerebro-protective agents are promising.

Hoy en día, se ha establecido que el daño cerebral isquémico, como el accidente cerebrovascular isquémico, es una de las principales causas de muerte y discapacidad en la población lo cual hace relevante el desarrollo fármacos antiisquémicos. En este trabajo se estudió el efecto antihipóxico y antiisquémico de siete extractos de plantas. La actividad antihipóxica se evaluó en modelos de hipoxia hipocrática, hipercápnica, histotóxica y hematotóxica. La actividad antiisquémica de los extractos de prueba se estudió en el modelo de isquemia cerebral focal. La administración de los extractos de Tagetes patula; Gaillardia pulchella; Sorbaria sorbifolia; Grossularia reclinata; Ribes nigrum; Rubus caesius y Lysimachia punctata contribuyeron a la reducción de la zona de necrosis en un 56,6% (p<0,05); 37,3% (p<0,05); 73,2% (p<0,05); 49,4% (p<0,05); 42,5% (p<0,05); 85,5% (p<0,05); 44.2% (p<0.05), respectivamente, además, de restaurar el metabolismo aeróbico en el tejido cerebral. Comparado con el control, se observó un aumento en el tiempo de sobrevida del animal en condiciones de hipoxia. Sobre la base de los interesantes datos obtenidos, se sugiere estudios adicionales de extractos de plantas de la flora del Cáucaso Norte como agentes protectores del cerebro.

Antihypoxic activities of Crataegus pentaegyn and Crataegus microphylla fruits-an in vivo assay

ABSTRACT The aim of this study was to evaluate anti-hypoxia activity of polyphenolic extracts of Crataegus microphylla and Crataegus pentaegyn on mice. Three experimental models of hypoxia were considered, including asphyctic hypoxia, haemic hypoxia, and circulatory hypoxia. Polyphenolic extract of both plants exhibited significant anti-hypoxic activity and prolonged animal survival time. Anti-hypoia activity of C. pentaegyn was found to be superior to that of C. microphylla in circulatory and asphyctic hypoxia. Antihypoxic activity of these extracts may be attributed to their phenolic compounds.

Efecto de la administración prenatal de melatonina en pulmones de neonatos de oveja crónicamente hipóxicos / Effect of prenatal administration of melatonin on lungs of chronic hypoxic sheep neonates

Introducción: Las patologías que podrían motivar el ingreso a una Sala de Reanimación (SR) son múltiples, y asimismo, presentarse en cualquier momento, independientemente del sexo y la edad. A pesar de esta versatilidad, no existen investigaciones que describan la realidad chilena y la literatura extranjera es escasa. En consecuencia, nuestro estudio buscó caracterizar clínico-demográficamente a los pacientes ingresados a SR del Hospital San Juan de Dios de Los Andes, Chile. Materiales y métodos: Estudio de corte transversal. Se trabajó con base de datos anonimizada. El tamaño muestral calculado fue de al menos 1014 sujetos (intervalo de confianza de 95%, precisión de 3%). Se incluyeron los ingresos entre enero de 2013 y junio de 2016, obteniendo una muestra de 1018 pacientes. Variables estudiadas: sexo, edad, diagnóstico general, diagnóstico específico, mes y horario. Se trabajó con Microsoft Excel® utilizando estadística descriptiva. Aprobado por comité éticocientífico. Resultados: 58,1% (n=593) hombres; 42,5% (n=434) mayores de 64 años. Diagnósticos generales más frecuentes: cardiovascular (50,3%) (n=512), neurológico (16,3%) (n=166) y traumático (11,7%) (n=119). Diagnósticos específicos más frecuentes: taquiarritmia (15,9%) (n=162) e infarto miocárdico (12,6%) (n=128). La mayor cantidad de ingresos se registró en enero, febrero y junio (promedio 28 ingresos), y entre las 20 y 00 hrs (22,8%) (n=232). Discusión: Existe un amplio predominio de las enfermedades cardiovasculares.La distribución por mes, sexo y edad parece estar supeditada al comportamiento de dicho grupo; no así la distribución por horarios, ya que las enfermedades cardiovasculares suelen presentarse matinalmente. En general, nuestros resultados coinciden con la literatura extranjera disponible

Introduction: Neonatal pulmonary hypertension (NPHT) caused by chronic hypobaric hypoxia during gestation is associated with oxidative stress and currently lacks of an effective treatment. The aim of this study was to evaluate the effects of melatonin administrated on pregnant sheep on endothelium-dependent vascular reactivity and expression of eNOS, COX-1 and COX-2 on the lungs of lambs gestated and born under chronic hypobaric hypoxia. Material and method: Ten pregnant ewes under chronic hypoxia of highlands (3600 masl) were divided in two groups: 1. Control group (CN), treated with vehicle (5 ml/d ethanol 1, 4%), and 2. Melatonin group (MM), treated with melatonin during gestation (10 mg/d in 5 ml ethanol 1, 4%), during the last third of gestation. Results: Ewes gave birth spontaneously and without assistance, and we obtained lung tissue from 12 days old lambs to determine endothelial vascular reactivity by wire myography. In addition, eNOS, COX-1 and COX-2 RNA and protein expression were measured through RT-PCR and Western Blot, respectively. Discussion: The endothelium dependent vasodilation response was significantly enhanced in MM. Further, MM showed a significant increase in eNOS, COX-1 and COX-2 protein levels, relative to CN group. In conclusion, prenatal melatonin induces endothelium dependent vasodilation mechanisms and positively modulates eNOS-NO and prostanoids pathways, which may favour a treatment for NPHT caused by chronic hypoxia at high-altitude

Cardioprotection against experimental myocardial ischemic injury using cornin

Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

Melatonin prevents hyperglycemia in a model of sleep apnea

Objective Obstructive sleep apnea is a common disorder associated with aging and obesity. Apneas cause repeated arousals, intermittent hypoxia, and oxidative stress. Changes in glucolipidic profile occur in apnea patients, independently of obesity. Animal models of sleep apnea induce hyperglycemia. This study aims to evaluate the effect of the antioxidants melatonin and N-acetylcysteine on glucose, triglyceride, and cholesterol levels in animals exposed to intermittent hypoxia. Materials and methods Two groups of Balb/c mice were exposed to intermittent hypoxia (n = 36) or sham intermittent hypoxia (n = 36) for 35 days. The intermittent hypoxia group underwent a total of 480 cycles of 30 seconds reducing the inspired oxygen fraction from 21% to 7 ± 1% followed by 30 seconds of normoxia, during 8 hours daily. Melatonin or N-acetylcysteine were injected intraperitonially daily from day 21 on. Results At day 35, glucose levels were significantly higher in the intermittent hypoxia group than in the control group. The intermittent hypoxia groups receiving N-acetylcysteine and vehicle showed higher glucose levels than the group receiving melatonin. The lipid profile was not affected by intermittent hypoxia or antioxidant administration. Conclusions The present results suggest that melatonin prevents the well-recognized increase in glucose levels that usually follows exposure to intermittent hypoxia. Further exploration of the role of melatonin in sleep apnea is warranted. Arch Endocrinol Metab. 2015;59(1):66-70 .

El pirofosfato de tiamina reduce el daño celular inducido por hipoxia en el cerebro de ratas neonatas / Thiamine pyrophosphate reduces hypoxia-induced cellular damage in neonatal rat brain

La encefalopatía por hipoxia es causa de discapacidad y requiere de nuevas estrategias terapéuticas. El pirofosfato de tiamina (PPT) es un cofactor esencial de enzimas fundamentales en el metabolismo de la glucosa, cuya disminución puede conducir a la falla en la síntesis de ATP y a la muerte celular. El objetivo de este estudio fue determinar si la administración de PPT, puede reducir el daño celular en un modelo de hipoxia neonatal en ratas. Animales de 11 días de edad fueron tratados con PPT (130 mg/kg) en dosis única o solución salina, una hora antes del protocolo de hipoxia o al término de ésta. Los cerebros fueron colectados para la evaluación del daño celular. Además, se tomaron muestras sanguíneas para evaluar los indicadores gasométricos de presión de dióxido de carbono (PaCO2) y de oxígeno (PaO2) en sangre arterial y pH. Los resultados muestran que la administración de PPT previa a la inducción de hipoxia, reduce el daño celular y restablece los indicadores gasométricos. Estos datos indican que el uso de PPT reduce el daño inducido por la hipoxia en animales neonatos.

Hypoxic encephalopathy is a leading cause of disability and requires new therapeutic strategies. Thiamine pyrophosphate (TPP) is an essential cofactor of fundamental enzymes involved in glucose metabolism. TPP reduction may lead to ATP synthesis failure and cell death. The objective of this study was to determine if TPP administration can reduce cellular damage in a model of neonatal hypoxia in rats. Eleven day old animals were treated with TPP (130 mg/kg) as a single dose or with saline solution one hour before the hypoxia protocol or after ending the protocol. The brains were collected to evaluate cellular damage. Blood samples were also collected to evaluate arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and acidity (pH). The results showed that TPP administration previous to hypoxia induction reduces cellular damage and reestablishes arterial blood gases. These data indicate that TPP use reduces the damage induced by hypoxia in neonatal animals.

The renoprotective effects of pentoxifylline: beyond its role in diabetic nephropathy

No abstract available.

Effect of Phosphodiesterase Inhibitor on Diabetic Nephropathy

No abstract available.

Phosphodiesterase Inhibitor Improves Renal Tubulointerstitial Hypoxia of the Diabetic Rat Kidney

BACKGROUND/AIMS: Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney. METHODS: PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1alpha (HIF-1alpha), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1alpha in renal tubule cells. RESULTS: PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1alpha, VEGF, and GLUT-1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1alpha and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT-1 at 4 weeks. The expression of HIF-1alpha protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1alpha protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 microM), which enhanced HIF-1alpha mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1alpha expression. CONCLUSIONS: PTX attenuates tubular hypoxia in the diabetic kidney.

Melatonin Protects the Heart, Lungs and Kidneys from Oxidative Stress under Intermittent Hypobaric Hypoxia in Rats

Melatonin (N-acetyl-5-methoxytryptamine) is the main secretory product of the pineal gland in all mammals including humans, but it is also produced in other organs. It has been previously demonstrated to be a powerful organ-protective substance under oxidative stress conditions. The aim of this study was to evaluate the protective effect of melatonin in several organs such as heart, lung, kidney, and of the reproductive system, such as testis and epididymis in animals exposed to intermittent hypobaric hypoxia and therefore exposed to oxidative stress and analyzed by lipid peroxidation. Ten-week-old male Wistar rats were divided into 6 groups for 96 hours during 32 days under: 1) Normobaric conditions, 2) plus physiologic solution, 3) plus melatonin, 4) intermittent hypobaric hypoxia, 5 plus physiologic solution and 6) plus melatonin. The animals were injected with melatonin (10 mg/kg body weight) at an interval of 96 hours during 32 days. Results indicated that melatonin decreased lipid peroxidation in heart, kidneys and lung under intermittent hypobaric hypoxia conditions. However, it did not exhibit any protective effect in liver, testis, epididymis and sperm count.

Cordyceps sinensis extract suppresses hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells

To investigate the effects of a Chinese herb Cordyceps sinensis [C. sinensis] extract on hypoxia-induced proliferation and the underlying mechanisms involved. This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells [PASMCs] was measured using 3-[4,5-dimethylthiazol-2-Yl]-2,5-diphenyltetrazolium bromide [MTT] assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen [PCNA], c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry. We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs. Our results indicated that C sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle [S+G[2]/M] phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension

Síntese e estudo das propriedades fotoinduzidas de derivados fenotiazínicos em sistemas biomiméticos / Synteses and study of photoinduced properties of phenothiazine derivatives on biomimetic systems

Neste trabalho são apresentados estudos do efeito de interfaces nas propriedades fotofísicas e fotoquímicas do azul de metileno (AM) e de derivados fenotiazínicos com o intuito de avaliar o potencial destes compostos como fotossensibilizadores (FS) em terapia fotodinâmica. As propriedades físico-químicas do AM foram estudadas em soluções de SDS e observou-se que a presença do AM em solução altera o equilíbrio entre as micelas de SDS, -diminuindo o valor da concentração micelar crítica de 7mmolL-1 para 70µmoIL-1. A presença das micelas em solução também interfere nas propriedades do AM. Em baixas concentrações de SDS há formação de dímeros de AM, constatados pelo aumento da absorbância em 580nm e diminuição da emissão de fluorescência. A caracterização das espécies transientes mostrou a existência de moléculas de azul de metileno no estado triplete (3AM) e de oxigênio singlete em soluções com altas concentrações de SDS e a formação de espécies radicalares do AM em baixas concentrações do tensoativo. Esta observação sugere que o mecanismo fotoquímico do AM é dependente da sua concentração local próxima de interfaces carregadas. As interações do AM e de alguns de seus derivados fenotiazínicos (tionina, azure A e azure B) com vesículas e com células...

Gabapentin attenuates acute hypoxic stress-induced behavioral alterations and oxidative damage in mice: possible involvement of GABAergic mechanism.

The effect of gabapentin has been investigated on acute hypoxic stress-induced behavioral alterations and oxidative damage in mice. Mice were subjected to hypoxia for 2 hr. Treatment with gabapentin (50 and 100 mg/kg) significantly increased ambulatory movements, exerted anti-anxiety like effect and reduced oxidative damage in mice subjected to acute hypoxic stress. Treatment with picrotoxin (1.0 mg/kg) per se had no significant effect on behavioral and biochemical parameters of stressed mice. Treatment with muscimol (0.05 mg/kg) per se significantly increased the locomotor activity of stressed mice, exerted significant anti anxiety effect and significantly reduced the oxidative damage. Further, pretreatment with picrotoxin (1.0 mg/kg) significantly blocked whereas pretreatment with muscimol (0.05 mg/kg) significantly potentiated the neuroprotective effect of gabapentin. These results suggest that gabapentin produces its neuroprotective effect in mice subjected to acute hypoxic stress through GABA(A) receptor mechanism.

Inhaled nitric oxide in newborns with severe hypoxic respiratory failure.

BACKGROUND: Respiratory failure in term and near term infants is often associated with persistent pulmonary hypertension of the newborn and contributes to hypoxemia in these infants. Inhaled nitric oxide (iNO) is currently used as a pulmonary vasodilator to improve oxygenation in neonates with severe respiratory failure. OBJECTIVE: To determine outcome of administration of iNO in severe hypoxic respiratory failure. MATERIAL AND METHOD: The present study was conducted from 1999 to 2004 in the neonatal intensive care unit (NICU) at Queen Sirikit National Institute of Child Health. Patients were selected from all infants > or = 34 weeks gestational age who required high frequency oscillatory ventilation (SLE 2000 HFO, SLE, UK) or conventional mechanical ventilation for hypoxemic respiratory failure caused by PPHN. Diagnosis was confirmed by 2-D echocardiogram visualization with right to left shunt through the foramen ovale or patent ductus arteriosus. Inhaled nitric oxide was given as standard therapy in patients who had two oxygenation indices > or = 20 at least 30 minutes apart after being on a mechanical ventilator. RESULTS: Fifty-five cases were enrolled and male to female ratio was 22.2 tol. The survival rate was 76.4 percent. Inhaled nitric oxide significantly improved oxygenation index, arterial alveolar oxygen tension ratio (a/A O2), and alveolar arterial oxygen gradient in survivors at one hour after treatment. The earliest improvement in oxygen saturation was within ten minutes. Meconium aspiration syndrome was the most common underlying cause of PPHN. No acute complication was found during nitric oxide administration. Chronic lung diseases, delayed development and severe hearing loss in long-term follow up were found in 10, 5, and 2 cases, respectively. CONCLUSION: Inhaled nitric oxide should be used early in severe hypoxic respiratory failure with persistent pulmonary hypertension of newborn and can improve survival rates without any major immediate side effects.