Glutamate and its ionotropic receptor agonists inhibit the response to acute hypoxia in carotid body of rats / 生理学报

The purpose of this study was to investigate the effect of glutamate and its ionotropic receptor agonists on the response to acute hypoxia in rat carotid body in vitro. Briefly, after SD rats were anesthetized and decapitated, the bilateral carotid bifurcations were rapidly isolated. Then bifurcation was placed into a recording chamber perfused with 95% O2-5% CO2 saturated Kreb's solution. The carotid body-sinus nerve complex was dissected, and the carotid sinus nerve discharge was recorded using a suction electrode. To detect the response of carotid body to acute hypoxia, the chamber was perfused with 5% O2-5% CO2-90% N2 saturated Kreb's solution for a period of 100 s at an interval of 15 min. To observe the effect of glutamate, ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonist AMPA or N-methyl-D-aspartate (NMDA) receptor agonist NMDA on the response to acute hypoxia in rat carotid body, the chamber was perfused with 5% O2-5% CO2-90% N2 saturated Kreb's solution containing the corresponding reagent. The results showed that glutamate (20 μmol/L), AMPA (5 μmol/L) or NMDA (10 μmol/L) inhibited the acute hypoxia-induced enhancement of carotid sinus nerve activity, and these inhibitory effects were dose-dependent. In summary, the activation of glutamate ionotropic receptors appears to exert an inhibitory effect on the response to acute hypoxia in carotid body of rats.

Clinical and therapeutic correlations in patients with slight acute pancreatitis / Correlações clínico-terapêuticas em pacientes com pancreatite aguda leve

BACKGROUND: Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. AIM: To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. METHODS: A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. RESULTS: There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). CONCLUSIONS: Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. .

RACIONAL: Pancreatite aguda consiste de doença inflamatória do pâncreas por autodigestão enzimática que pode ocasionar necrose ou mesmo falência múltipla de órgãos e de fisiopatologia ainda não totalmente conhecida. OBJETIVO: Avaliar as correlações existentes entre dados clínicos e terapêuticos em pacientes com pancreatite aguda leve. MÉTODOS: Foi realizado estudo retrospectivo em 55 prontuários de pacientes internados por pancreatite aguda leve para análise de associação entre idade, leucocitose, dosagem sérica de transaminase glutâmico-oxalacética e de desidrogenase lática, glicemia, antibioticoterapia, tempo de internação e escores de Ranson. RESULTADOS: Houve associação positiva entre cuidados intensivos menores (hidratação rigorosa, analgesia e monitorização de sinais vitais), antibioticoterapia precoce (monoterapia), retorno precoce da dieta após 48 horas e controle laboratorial dos níveis séricos de amilase e lipase (elevados na primeira semana e decrescentes após 10 dias, porém sem valor prognóstico). CONCLUSÕES: Mudanças no manejo de pacientes com pancreatite aguda leve, tais como nutrição enteral, uso racional de antibióticos de menor espectro e cuidados intensivos têm contribuído significativamente para a redução do tempo de internação e mortalidade. .

Effects of iontophoretically applied substance P, calcitonin gene-related peptide on excitability of dorsal horn neurones in rats

Spontaneous pain, allodynia and hyperalgesia are well known phenomena following peripheral nerve or tissue injury, and it is speculated that secondary hyperalgesia and allodynia, are generally thought to depend on a hyperexcitability (sensitization) of neurons in the dorsal horn. It is supposed that the sensitization may be due to various actions of neurotransmitters (SP, CGRP, excitatory amino acids) released from the primary afferent fibers. In this study, we examined effects of the iontophoretically applied SP and CGRP on the response to EAA receptor agonists (NMDA and non-NMDA) in the WDR dorsal horn neurones and see if the effects of SP or CGRP mimic the characteristic response pattern known in various pain models. The main results are summarized as follows: 1) SP specifically potentiated NMDA response. 2) CGRP non-specifically potentiated both NMDA and AMPA responses. Potentiation of NMDA response, however, was significantly greater than that of AMPA response. 3) 50% of SP applied cells and 15.8% of CGRP applied cells showed reciprocal changes(potentiation of NMDA response and suppression of AMPA response). These results are generally consistent with the sensitization characteristics in diverse pain models and suggests that the modulatory effects of SP and CGRP on NMDA and non-NMDA (AMPA) response are, at least in part, contribute to the development of sensitization in various pain models.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Anti-oxidative neuroprotection by estrogens in mouse cortical cultures

Estrogen replacement therapy in postmenopausal women may reduce the risk of Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the present study, we examined the neuroprotective spectrum of estrogen against excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100 microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30 microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25-35. However, all these neuroprotective effects were mediated by the anti-oxidative action of estrogens. When oxidative stress was blocked by an antioxidant trolox, estrogens did not show any additional protection. Addition of a specific estrogen receptor antagonist ICI182,780 did not reverse the protection offered by estrogens. These findings suggest that high concentrations of estrogen protect against various neuronal injuries mainly by its anti-oxidative effects as previously shown by Behl et al. Our results do not support the view that classical estrogen receptors mediate neuroprotection.

Effects of entorhinal cortex lesions on memory in different tasks

Lesions of the entorhinal cortex produce retrograde memory impairment in both animals and humans. Here we report the effects of bilateral entorhinal cortex lesions caused by the stereotaxic infusion of N-methyl-D-aspartate (NMDA) in rats at two different moments, before or after the training session, on memory of different tasks: two-way shuttle avoidance, inhibitory avoidance and habituation to an open field. Pre-or post-training entorhinal cortex lesions caused an impairment of performance in the shuttle avoidance task, which agrees with the previously described role of this area in the processing of memories acquired in sucessive sessions. In the inhibitory avoidance task, only the post-training lesions had an effect (amnesia). No effect was observed on the open field task. The findings suggest that the role of the entorhinal cortex in memory processing is task-dependent, perhaps related to the complexity of each task.

Rol de la oxido nitrico sintetasa inducible en el dano agudo de la mucosa gastrica en el estres, en ratas / Role of the inducible nitric oxide synthase in the acute gastric mucosal damage in the stress, in rats

En diferentes grupos de ratas Wistar, sometidas a estrés por inmovilización e inmersión en agua a 18 graus Celsius durante 6hs, fue estudiado el rol del óxido nítrico (NO) en su fisiopatología; donde fueron usados agonistas y antagonistas de las isoenzimas NO Sintetasa Constitutiva (NOSc) y de la NO Sintetasa inducible (NOSi). Como agonistas de la NOSc se usaron dosis de L-arginina y como antagonistas de la L-NMMA. Se comprobó que la sobredosis de L-arginina agravó las lesiones agudas gastricas. Como agonistas de la NOSi se usó la NMDA y como antagonista la dexametasona y la aminoguanidina. Se comprobó que el agonista agravó las lesiones g stricas del estrés, en contraste, tanto dexametasona como aminoguanidina dieron una marcada protección de la mucosa gastrica. Se concluyó que la producción del NO dado por la NOSi, desempeña un papel preponderante en la fisiopatologia de las lesiones agudas gastricas en el estrés.

Introducción al estudio del receptor al N-Metil-D-Aspartato / Introduction to the study of the N-Methyl-D-Aspartate receptor

Objetivos: Analizar toda la información publicada en los últimos diez años sobre el receptor al N-Metil-D-Aspartato (NMDA). Establecer una correlación farmaco-clínica con respecto a la modulación del dolor y determinar su importancia en anestesiología. Lugar: Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo. Base de datos: Base electrónica Medline de donde se seleccionaron todos los trabajos publicados en idioma inglés sobre el tema y búsqueda de información en castellano de lo publicado en los últimos 10 años. Estrategia de búsqueda: NMDA, dolor, modulación del dolor, protección cerebral. Discusión: Los receptores celulares son estructuras que permiten comandar el metabolismo íntimo de las células que los poseen. Estos interactúan en forma directa a través de un segundo mensajero citoplasmático. En el neuroeje de los mamíferos, se encuentran numerosas neuronas que contienen en su membrana el receptor al NMDA. El bloqueo de éste por drogas que actúan en forma competitiva o no competitiva, produciría analgesia, permitiría la modulación del estímulo doloroso y algunos trabajos demuestran su importancia como protectores cerebrales ante la isquemia. Conclusión: Los inhibidores de los receptores al NMDA como la dizocilpina, actualmente en fase experimental, o la ketamina, adquirirían un rol muy importante en nuestra especialidad en el manejo del dolor y la protección cerebral.