Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

La reserpina aumenta la expresión de BDNF y PCNA, y disminuye la de caspasa-3, en células intersticiales (células de Leydig) de ratas / Reserpine increases BDNF and PCNA expression, but decreases caspase-3, in rat interstitial cells (Leydig cells)

La reserpina es un antipsicótico e hipotensor arterial que reduce significativamente los niveles de monoaminas centrales, y también es utilizada para modelar los cuadros depresivos humanos en animales de laboratorio. Este trabajo estudió, en ratas Wistar machos adolescentes, cómo la reserpina afecta indicadores moleculares de la función testicular, la cual se ha visto alterada en humanos deprimidos. Una semana luego de finalizado el tratamiento con reserpina (4 dosis de 0,0 o 1,0 mg/Kg, cada 2 días) la respuesta ansiosa y depresiva fue evaluada en un laberinto en cruz elevado. Posteriormente, se sacrificaron los animales y disecaron los testículos, los cuales fueron fijados e incluidos en bloques de parafina de donde se obtuvieron cortes histológicos de 6 µm de espesor. Estos se utilizaron para medir el diámetro de los túbulos seminíferos y para medir por inmunohistoquímica el porcentaje de células intersticiales (células de Leydig) positivas a (1) Factor neurotrófico derivado del cerebro, (2) antígeno nuclear de células en proliferación (BDNF y PCNA, respectivamente, por sus siglas en inglés), y a (3) caspasa-3. Se obtuvo también un índice de positividad al receptor de andrógenos en las células intersticiales. La expresión del receptor de andrógeno fue evaluada utilizando una escala semicuantitativa de escores (0, 1, 2 y 3) y el resto de las moléculas por presencia o ausencia de expresión de cada antígeno investigado en 300 células por preparado. Los resultados comportamentales indicaron alteraciones en la respuesta de ansiedad y una significativa depresión motora (e.g., mayor latencia en conductas de escape del sector blanco) en los animales tratados con reserpina. No se observaron diferencias en los diámetros de los túbulos seminíferos ni en la expresión del receptor de andrógeno, mientras que sí se encontró mayor proporción de células intersticiales positivas a BDNF y PCNA, y menor proporción de células positivas a caspasa-3, en los animales tratados. Los resultados corroboran la capacidad de la reserpina para reproducir rasgos comportamentales de la depresión. La administración de la droga, sin embargo, no parece reproducir a nivel testicular los efectos deletéreos encontrados en humanos deprimidos, e incluso los resultados sugieren que la reserpina puede mejorar algunos aspectos de la funcionalidad testicular relacionadas con la actividad de las células intersticiales en ratas.

Reserpine, a drug that depletes central monoamines, has been used as an antipsychotic and arterial hypotensive, and to model depression in animals. The present study analyzed, in adolescent male rats, the effects of chronic reserpine treatment on molecular indexes of testicular function. A week after termination of the treatment (4 doses of 0,0 or 1,0 mg/Kg/every 48 h) the animals were tested for anxiety response and depression patterns in an elevated plus maze. They were then euthanized, their testes dissected, fixed and embedded in paraffin to obtain blocks. Histological sections (6 µm) were obtained and used to measure the diameter of seminiferous tubules and the expression in Leydig cells of Brain-derived neurotrophic factor (BDNF), Proliferating cell nuclear antigen (PCNA), Caspase-3 and androgen receptors, by immunohistochemistry. Behavioral results indicated significant alterations in anxiety responses and a significant motor depression (e.g., greater latency to escape from the white sector). There were no differences between groups in the diameter of seminiferous tubules nor in the androgen receptors positivity. Reserpine-treated animals, however, exhibited more BDNF and PCNA positive cells, and less positive Caspase-3 cells in Leydig cells, than control animals. The results corroborate the efficacy of reserpine to reproduce some of the behavioral components of depression. The drug, however, does not seem to exert in rats the same effects on testicular function that have been found in humans diagnosed with depression. Furthermore the drug seems to enhance some aspects of testicular function related to Leydig cells function in rats.

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

Alzheimer's disease (AD) is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM). Density Functional Theory (DFT) studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

A doença de Alzheimer (DA) é uma doença neurodegenerativado sistema nervoso central, em rápido crescimento, e antioxidantes ajudam a suprimir o estresse oxidativo causado por radicais livres, responsávies pela DA. Avaliou-se, biologicamente, série de derivados sintéticos de indol selecionados para identificar novos antioxidantes. A maioria dos compostos avaliados apresentou de significativa a boa propriedade antioxidante (valor de IC50 399,07140.0 ± 50 µM). Eftuaram-se estudos de Teoria do Funcional de Densidade (DFT) com os compostos e os seus correspondentes radicais livres. As diferenças de energia entre os compostos protótipos e os radicais livres correspondentes proporcionaram boa justificativa para a tendência encontrada nos seus valores de IC50. O ancoramento in silico dos compostos com a acetilcolinesterase (AChE) e com a butirilcolinesterase (BChE), que contribuem para a DA, foi, também, realizado para prever o seu potencial anti-DA.

Ação da fluoxetina sobre a dor aguda em ratos submetidos à constrição do nervo ciático / Fluoxetine action on acute pain in rats submitted to sciatic nerve constriction

JUSTIFICATIVA E OBJETIVOS: Os inibidores seletivos da recaptação de serotonina como a fluoxetina, têm sido apontados como alternativa ao uso dos antidepressivos tricíclicos para o tratamento da dor crônica, pela menor incidência de efeitos colaterais. O objetivo deste estudo foi estudar o efeito da serotonina na modulação da dor aguda, pela administração de fluoxetina, por meio do teste da formalina, em ratos, anteriormente submetidos à constrição do nervo ciático. MÉTODO: Foram estudados 24 ratos Wistar, machos, com peso médio de 300 g, distribuídos em 5 grupos: 1. Controle sem tratamento; 2. Constrição do nervo ciático; 3. Constrição do nervo ciático tratados com 5 mg.kg-1.dia de fluoxetina, por via oral durante 15 dias; 4. Constrição do nervo ciático tratados com 5 mg.kg-1 de reserpina, por via oral a cada 72h e com 5 mg.kg-1.dia de fluoxetina por via oral, durante 15 dias; 5. Constrição do nervo ciático tratados com 5 mg.kg-1 de reserpina por via oral em intervalos de 72h, durante 15 dias. Todos os animais foram submetidos ao teste da formalina modificado após os tratamentos especificados. RESULTADOS: A resposta na fase I, na fase intermediária e na fase II do teste da formalina não foi alterada pela constrição do ciático. O tratamento com reserpina ou fluoxetina não interferiu com as fases I e intermediária do teste da formalina nos grupos submetidos à constrição do ciático. O número de elevações da pata na fase II do teste da formalina aumentou nos animais tratados com fluoxetina e diminuiu nos animais tratados com reserpina. Nos animais tratados com a associação reserpina e fluoxetina houve redução do número de elevações da pata em comparação com os animais tratados apenas com a fluoxetina. CONCLUSÃO: O tratamento com fluoxetina aumentou a sensação dolorosa após estímulo agudo em ratos submetidos à constrição do ciático, evidenciando ação algogênica do fármaco neste modelo experimental.

BACKGROUND AND OBJECTIVES: Selective serotonin reuptake inhibitors, such as fluoxetine, have been suggested as alternative to tricyclic antidepressants to treat chronic pain, due to the lower incidence of side effects. This study aimed at observing the effects of serotonin on acute pain modulation, by the administration of fluoxetine through the formalin test in rats previously submitted to sciatic nerve constriction. METHOD: We used 24 male Wistar rats, with mean weight of 300 g and distributed in 5 groups: 1. Control untreated; 2. Sciatic nerve constriction; 3. Sciatic nerve constriction and treated with 5 mg.kg-1.day oral fluoxetine for 15 days; 4. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours and with 5 mg.kg-1.day oral fluoxetine for 15 days; 5. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours for 15 days. All animals were submitted to modified formalin test after treatment. RESULTS: Response in the phase I, intermediate and phase II formalin test was not changed by sciatic nerve constriction. Treatment with reserpine or fluoxetine has not interfered with first and intermediate formalin test phases in the groups submitted to sciatic nerve constriction. The number of flinches in the second formalin test phase has increased in animals treated with fluoxetine and has decreased in animals treated with reserpine. There has been decrease in the number of flinches in animals treated with the association reserpina and fluoxetine as compared to animals treated with fluoxetine alone. CONCLUSION: Fluoxetine has increased painful sensation after acute stimulation in rats submitted to sciatic nerve constriction, showing the algogenic action of the drug in this experimental model.

Efeitos da Marapuama (Ptychopeatalum Olacoides Benthan) nas alterações motoras induzidas por reserpina em camundongos / Motor fitness and work ability of the police officers of the Special Operations Group

Introdução e Objetivo: O motivo deste estudo foi avaliar a ação da Marapuama (Ptychopetatalum olacoides Benthan) nas alterações motoras induzidas pela droga reserpina em camundongos BalbC. Método: Foram utilizados doze camundongos Balb C, fêmeas, divididas em 2 grupos: controle (GC, n = 6 / 0,1 ml de solução oral,) e Marapuama (GM, n = 6 / 500mg/kg concentrada em 0,1 ml de solução oral por dia). A administração das soluções foi feita por gavagem durante 7 dias. Para a indução das alterações motoras semelhantes à Doença de Parkinson, os camundongos receberam por via intraperitoneal 1mg/Kg de resperpina (Sigma). A atividade motora foi avaliada pelo teste do Campo Aberto (BROADHURST,1960), 24 horas, 48 horas e 7 dias após a administração da reserpina. Para a análise estatística foi realizado o teste T-Student p ≤ 0,05. Resultados e discussão: os resultados obtidos mostraram que os camundongos tratados com Marapuama (Ptychopetatalum olacoides Benthan) apresentaram maior freqüência de locomoção do que os integrantes do grupo controle (GC). Quanto ao tempo de imobilidade, o grupo controle (GC) permaneceu mais tempo imóvel do que o grupo Marapuama (GM). A análise estatística mostrou-se significativa entrea comparação dos grupos nas primeiras 24 após a administração da reserpina. Conclusão: Concluiu-se que a fitoterápico Marapuma (Ptychopetatalum olacoides Benthan) apresentou a capacidade de aumentar a atividade motora dos animais sob ação da reserpina o que sugere uma possível capacidade de reduzir a bradicinesia que é um dos sintomas da doença de Parkinson.

Introduction and Objective: the aim of this study was to evaluate the action of Marapuama ( Ptychopetatalum olacoides Bentham ) in motor changes induced by reserpine in mice BalbC. Method: we used twelve Balb C female, divided into two groups: control group ( n = 6 / 0.1 ml of oral solution ) and Marapuama (GM, n = 6 / 500 mg / kg in 0.1 ml of concentrated oral solution per day). The drug administration was by gavage for 7 days. For the induction of motor disorders similar to Parkinson' s disease, the mice received intraperitoneal 1mg/kg resperpina (Sigma). The motor activity was evaluated by open test (BROADHURST, 1960), 24 hours, 48 hours and 7 days after administration of reserpine. For the statistical analysis was performed to test T-Student, p ≤ 0.05. Results and discussion: the results showed that mice treated with Marapuama ( Ptychopetatalum olacoides Bentham ) had higherfrequency of locomotion than members of the control group (CG). As for the immobility time, the control group ( CG ) remained immobile more time than the group Marapuama ( GM ). Statistical analysis was significant between the comparison groups in the first 24 after administration of reserpine. Conclusion: It was concluded that the phytotherapic Marapuma ( Ptychopetatalum olacoides Bentham ) had the ability to increase motor activity under the action of reserpine suggesting a possible ability to reduce bradykinesia, which is one of the symptoms of Parkinson' s disease.

Gentle handling temporarily increases c-Fos in the substantia nigra pars compacta

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.

Caracterizaçäo experimental e possível participaçäo de espécies reativas de oxigênio em um modelo animal de discinesia orofacial / Experimental characterization and participation possible the species reativ of oxygen in animal model of orofacial dyskinesia

Funcionalmente incapacitaste e esteticamente d esfigurante, a discinesia tardia é considerada não apenas o principal efeito colateral decorrente do tratamento com antipsicóticos, como a principal desordem iatrogênica do movimento. Caracterizada por hipercinesias buco-linguo-mastigatórias involuntárias e por vezes irreversíveis, a discinesia tardia e desprovida de tratamentos comprovadamente eficazes a longo prazo. Paralelamente, a característica tardia de seu desenvolvimento limita acentuadamente a viabilidade de estudos clínicos prolongados adequadamente controlados. Nesse contexto, a caracterização e validação de modelos animais dessa desordem de movimento torna-se imperiosa. Em meados da década de 1990, Neisewander e colaboradores propuseram um novo modelo animal para a discinesia tardia: o aumento do número de protrusões de língua induzido pela administração repetida do depletor monoaminérgico reserpina em ratos. Esse trabalho clássico aliado a outros estudos que se seguiram, trouxeram importantes evidências em suporte a essa proposição. Com efeito, o aumento de protrusões de língua induzido pela administração repetida de reserpina em ratos preenche alguns quesitos concernentes tanto a aspectos fenomenológicos e clínicos como a hipóteses fisiopatológicas da discinesia tardia em humanos. Não obstante, enquanto a caracterização fenomenológica/temporal e farmacológica/mecanicística do modelo ainda é incipiente, sua confrontação com os preconizados fatores de risco da doença é...(au)

Antipsychotic profile of alstonine: ethnopharmacology of a traditional Nigerian botanical remedy

Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, Which exbitited an antipsychotic-like profile, inhibiting amphetamine-induced lethaly, apomorphine-induced steotypy and potentiating barbiturate-induced slleping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.

The serotonin paradox: drug-receptor interaction in rat vas deferens

The contractile effect of serotonin was studied in rat vas deferens, in comparison with that of noradrenaline and tyramine, after reserpine treatment, surgical denervation, and transplantation to the colon. In reserpinized animals the effect of 5HT resembled that of tyramine, since it was strikingly reduced, in spite of a small residual effect, showing that in normal preparations the effects of 5HT and tyramine are predominantly duc to the release of endogenous noradrenaline. However, in denervated or transplanted vas deferens, in which the effect of tyramine is also abolished, the effect of 5HT was potentiated. It is suggested that after chronic, long lasting depletion of endogenous noradrenaline, there are alternate mechanisms that are generated to improve the contractile effect of 5HT, but not of tyramine. The nature of these mechanisms is still unknown.

¿Regresa la tan vilipendiada reserpina? / Is the so contemned reserpine back?

Se hizo una revisión de los ensayos clínicos recientes que emplearon reserpina a dosis menores o iguales a 0,25 mg/diarios con el propósito de determinar si a estas dosis puede ser eficaz y bien tolerada. Se analizaron las causas que han llevado a una disminución de su prescripción a pesar de haber reducido significativamente las complicaciones derivadas de la hipertensión arterial. En un análisis de costos, comparado con otros antihipertensivos, demostró ser el más barato. Se concluye que las características de: eficacia, buena tolerancia, duración de acción y bajo costo a dosis menores de 0,25 mg hacen que deba considerarse su empleo como fármaco de primera elección en el tratamiento de la hipertensión arterial primaria, administrada sola o en combinación con dosis, también bajas, de diuréticos tiacídicos

Radioprotection: mechanisms and radioprotective agents including honeybee venom

Since 1949, a great deal of research has been carried out on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radiprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules, formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radiprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom.

Effects of ovarian hormone tratment on Ca2+-induced contractions and Ca2+-antagonism in the depolarized rat myometrium

The effects of estrogen (E), progesterone (P) and estrogen plus progesterone (E+P) treatment on Cainduced contraction in the KCL-depolarized uterine muscle, and the influences on the Ca2+ antagonism induced by reserpine and verapamil "in vivo" were studied. Uterine muscles from rats in estrus were taken as controls. Uteri from spayed untreated rats showed the same sensivity to Ca2+ as those from estrus rats, but castration decreased maximal contractile tension to Ca2+ and Ca2+ thereshold. P tratment failed to modified the effects of castration on the responses to Ca2+. E or E+P treatments decreased the sensitivity to Ca2+ but only E+P increased slope values and maximal contractile tension. E and E+P increased the potency of verapamil Ca2+ antagonism but none the treatments modified reserpine direct inhibitory effects. The results obtained suggest that alterations on uterine contractility by hormone treatment are the result of complex interactions between both genomic effects on the contractile process as well as nongenomic direct actions of the hormones on Ca2+ membrane permeability.

Neurolépticos: os legítimos e verdadeiros antimanicomiais / Neuroleptic: the real antimanicomial drug

O autor analisa o advento dos neurolépticos e suas conseqüências. Faz ampla revisão do tema abordando a farmacologia destas substâncias, os aspectos clínicos, principais indicações e efeitos colaterais. Conclui mostrando o verdadeiro alcance antimanicomial dos neurolépticos

Influence of the pontomencephalic region upon PGO activity regulation at the aducens nucleus in cats

Se ha propuesto que en el tegmento pontomesencefálico, específicamente en la región denominada "área X" (AX) y en el núcleo parabraquial lateral (Pbl), se localizan las células generadoras de la actividad ponto-geniculo-occipital (PGO) que ocurre durante el sueño paradójico. Las evidencias se basan en el análisis de la actividad PGO registrada a nivel tálamico (en el núcleo geniculado lateral; NGL). Sin embargo, la actividad PGO también puede ser registrada en el núcleo abducens (VI par). Con el fin de determinar si la región pontomesencefálica también participa en la regulación de la actividad PGO que se registra a nivel pontino, realizamos pequeñas lesiones electroliticas en el Pbl en el AX, registrado simultáneamente la actividad PGO en el NGL y en el VI par. Se utilizaron gatos anestesiados, curarizados y pretratados con reserpina. La lesión del AX suprimió la actividad PGO registrada en el NGL pero no afectó las espigas registradas a nivel pontino. La lesión del Pbl no modificó la actividad PGO registrada en el NGL ni en el VI par. Estos datos no apoyan la influencia del AX del Pbl sobre la actividad PGO registrada a nivel pontino y sugieren que la región pontomesencefálica sólo juega un papel en la transmisión de las espigas PGO desde el puente al NGL.

Efeitos do bloqueio simpático na hipertrofia cardíaca após infarto e suas repercussöes na contratilidade miocárdica / Effects of sympathetic block on post-infarction cardiac hypertrophy and their repercussion on myocardial contractility

Objetivo Investigar os efeitos do uso crônico de reserpina (Res) ou propranolol (Prop), administrados subcutaneamente, na evolução da hipertrofia cardíaca e contratilidade miocárdica após infarto do miocárdio (IM). Métodos Ratos albinos com 3 meses de idade foram submetidos à ligadura dos ramos anteriores da artéria coronária esquerda para a produção de IM. Ratos submetidos a cirurgia fictícia foram usados como grupo controle. Os animais tratados com Res (0,5 mg/kp/dia) foram sacrificados 8-10 dias após a cirurgia e os tratados com Prop (2,5 mg/kg a cada 12h) foram sacrificados 15 (G-15) ou 30 (G-30) dias após. A hipertrofia foi avaliada pelo peso das câmaras cardíacas, corrigido para o peso corporal. A contratilidade miocárdica foi medida através da força (F) desenvolvida por tiras isoladas do ventrículo direito (VD) contraindo-se isometricamente. Resultados A Res inibiu completamente a hipertrofia dos átrios e do VD. A extensão do IM, medida pelo perceptual de área do ventrículo esquerdo (VE) coberta pela cicatriz fibrosa, não foi afetada pelo Prop (32 ± 4% nos animais com IM tratados com solução salina e 30 ± 3% nos tratados com Prop). O Prop também inibiu significativamente a hipertrofia atrial e do VD. No G-30, por exremplo, os pesos relativos (mg/ g) do AD e VD foram menores (P < 0,05) nos animais com IM e tratados com Prop (0,12 ± 0,01 e 0,79 ± 0,07) que naqueles com IM tratados com solução salina (0,22 ± 0,03 e 1,11 ± 0,07). A F basal produzida nos músculos de corações com IM foi 25 a 30% menor que nos controles. Essa queda foi reduzida para apenas 4% (G-15) e 8% (G-30) nos músculos de animais com IM tratados com Prop treatment...

Purpose — To investigate the effects of chronical subcutaneous administration of reserpine (Res) or propranolol (Prop) on the postinfarction myocardial hypertrophy and the effects of Prop treatment on myocardial contractility in rats. Methods — Male albino rats (3-month-old) were submitted to left coronary artery ligation to produce myocardial infarction. Rats submitted to a sham-operation were used as controls. Animals submitted to Res (0.5 mg/Kg/day) were killed 8-10 days after surgery and those submitted to Prop (2.5 mp/kg twice a day) were killed 15 (G-15) or 30 (G-30) days later. Hypertrophy was evaluated according to cardiac chambers weight corrected to body weights. Isometric force (F) developed by isolated right ventricular (RV) strips was used as a contractile index. Results — Atrial and RV hypertrophy were completely blocked by Res. Prop treatment did not significantly change infarct extension, evaluated by the fibrous scar area. Prop therapy also reduced atrial and RV hypertrophy. This effect was less intense compared to Res, however. In the G-30, for example, the relative right atrial and RV weights (mp/g) were 0.10 ± 0.01 and 0.59 ± 0.03 in sham-operated animais (n = 9), 0.12 ± 0.01 and 0.079 ± 0.07 in infarcted animals with Prop (n = 11) and 0.22 ± 0.03 and 1.11 ± 0.07 in those infarcted and treated with saline solution (n = 11). Basal F values were 25 to 30% lower in RV strips from infarcted than in sham-operated hearts. This reduction however was only 4% (G-15) and 8% (G-30) in infarcted hearts under Prop treatment...

Repetitive electrical stimulation of X area and parabrachial lateral nucleus: effects upon ponto-geniculo-occipital activity in the reserpinezed cat

La actividad ponto-geniculo-occipital (PGO) es un potencial de campo característico del sueño paradójico, que puede ser inducido por la administración de reserpina. Se ha postulado que el área X y el núcleo parabraquial lateral contienen las células que generan la actividad PGO. En el presente estudio, se analizan los efectos de la estimulación eléctrica repetida, tipo Kindling, aplicada en el área X y en el núcleo parabraquial lateral, con la finalidad de inducir cambios plásticos progresivos en la actividad PGO. Se utilizaron gatos reserpinizados, curarizados y con respiración articial. La actividad PGO se registró en el núcleo geniculado lateral y se analizó la frecuencia de estas espigas al minuto, a los 5 minutos y a la hora de aplicada la estimulación repetida (pulsos cuadrados del ms de duración con una frecuencia de 60Hz y una intensidad de 150 uA aplicados durante un segundo). La estimulación del área X no provoca modificaciones en la frecuencia de espigas PGO, mientras que en el núcleo parabraquial lateral se observa un incremento progresivo relativamente pobre en la frecuencia de este potencial. Los hallazgos obtenidos con la estimulación del área X descartan la posibilidad de inducir cambios funcionales plásticos de esta región. En cambio, la respuesta a la estimulación del parabraquial lateral indica una activación del sistema generador de espigas PGO. Estas diferencias sugerirían que ambos núcleos tienen distinta influencia sobre la actividad PGO, aunque es posible que las respuestas encontradas en el parabraquial lateral sean efectos indirectos, debido a sus relaciones anatómicas