Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Diabetic Foot Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route for a Successful Outcome.

Soon after epidermal growth factor (EGF) discovery, some in vivo models appeared demonstrating its property to enhance cutaneous wound healing. EGF was the first growth factor (GF) introduced in the clinical arena as a healing enhancer, exerting its mitogenic effects on epithelial, fibroblastoid, and endothelial cells via a tyrosine kinase membrane receptor. Compelling evidences from the 90s documented that, for EGF, locally prolonged bioavailability and hourly interaction with the receptor were necessary for a successful tissue response. Eventually, the enthusiasm on the clinical use of EGF to steer the healing process was wiped out as the topical route to deliver proteins started to be questioned. The simultaneous in vivo experiments, emphasizing the impact of the parenterally administered EGF on epithelial and nonepithelial organs in terms of mitogenesis and cytoprotection, rendered the theoretical fundamentals for the injectable use of EGF and shaped the hypothesis that locally infiltrating the diabetic ulcers would lead to an effective healing. Although the diabetic chronic wounds microenvironment is hostile for local GFs bioavailability, EGF local infiltration circumvented the limitations of its topical application, thus expanding its therapeutic prospect. Our clinical pharmacovigilance and basic studies attest the significance of the GF local infiltration for chronic wounds healing.

Assessment of dose-effect and therapeutic time window in preclinical studies of rhEGF and GHRP-6 coadministration for stroke therapy.

BACKGROUND: Stroke continues to be a leading cause of mortality and morbidity worldwide, and novel therapeutic options for ischaemic stroke are urgently needed. In this context, drug combination therapies seem to be a viable approach, which has not been fully explored in preclinical studies. OBJECTIVES: In this work, we assessed the dose-response relationship and therapeutic time window, in global brain ischaemia, of a combined therapeutic approach of recombinant human epidermal growth factor (EGF) and growth hormone-releasing peptide-6 (GHRP-6). METHODS: Mongolian gerbils underwent 15 minutes occlusion of both common carotid arteries. Four different doses of rhEGF, GHRP-6 and these combined agents were intraperitoneally administered immediately after the onset of reperfusion. Having identified a better response with both agents, rhEGF+GHRP-6 were administered at 2, 4, 6, 8 or 24 hours after the onset of reperfusion to assess the time window of effectiveness. Animals were evaluated daily for neurological deficits. Three days post-occlusion, the animals were sacrificed and 2,3,5-triphenyltetrazolium chloride was used to quantify infarcted tissues. RESULTS: The coadministration of rhEGF and GHRP-6 at doses of 100 and 600 µg/kg, respectively, administered up to 4 hours following the ischaemic insult, significantly improved survival and neurological outcome, and reduced infarct volume compared with vehicle treatment. These results are considered as an additional proof of concept as supporting a combined therapeutic approach and justify the further development of this preclinical research.

Efecto del zumo de Morinda citrifolia L (noni) en modelos de analgesia / Effect of Morinda citrifolia L. (noni) in analgesic models

Introducción: Morinda citrifolia L (noni) ha despertado gran interés y expectativa dentro de la población cubana debido a las propiedades medicinales que se le atribuyen. Investigaciones realizadas evidencian las propiedades analgésicas de algunas de sus partes. Objetivos: evaluar el efecto del zumo de noni en diferentes modelos de analgesia. Métodos: se utilizaron dosis (450, 900 y 1 800 mg/kg) del zumo de noni, a partir de contenido en peso seco; se administró por vía intraperitoneal a ratones OF1 en el modelo de irritación peritoneal por ácido acético 0,6 por ciento y se cuantificó el número de contorsiones o estiramientos. Además, se utilizó el modelo del plato caliente y el de la retirada de la cola. Resultados: el zumo de noni fue efectivo de manera dependiente de la dosis en reducir el número de contorsiones inducidas por el ácido acético. En los modelos del plato caliente y de retirada de la cola, solo la dosis más alta prolongó de manera estadísticamente significativa el tiempo de reacción. Conclusiones: los resultados sugieren que el efecto analgésico de noni es fundamentalmente de mecanismo periférico

Introduction: Morinda citrifolia L (noni) has aroused great interest and expectations in the Cuban population due to attributed medicinal properties. Several research works have suggested the analgesic effect of several parts of the plant. Objectives: to evaluate the effect of Noni juice in different analgesic models. Methods: there were used 450, 900, and 1 800 mg/kg doses of the juice, based on the dry content weight. They were administered intraperitonealy to adult male mice OF1 in the peritoneal irritation model induced by acetic acid at 0,6 percent concentration, and the number of contorsions or stretchings was quantified. Additionally, the hot plate and the tail immersed in hot water models were applied. Results: the noni juice was effective in reducing the number of contortions induced by the acetic acid in a dose-dependent manner. Just the highest dose of the juice increased significantly the time of reaction in the hot plate and in the tail immersion test. Conclusions: these results suggest that the analgesic effect of Noni juice is basically peripheral

Global brain ischemia in Mongolian gerbils: assessing the level of anastomosis in the cerebral circle of Willis.

The Mongolian gerbil has been widely used as a global brain ischemia model because of its incomplete cerebral circle of Willis. However, the inter-individual anatomic variability of this vascular structure interferes with the reliability of the model. The aim of this work was to introduce modifications to the protocol of global brain ischemia experiments in Mongolian gerbils in an attempt to increase the reliability and usefulness of this model. Our study focused on the assessment of the level of anastomosis of the cerebral circle of Willis in order to evaluate its contribution to clinicopathological outcomes in this model. Sham-operated, Ischemic, and Ischemic + Hypothermia animals were subjected to a 15-minute occlusion of the common carotid arteries. Transcardiac perfusion with bromophenol blue / gelatin solution was performed 72 hours after ischemia. Brains were processed for anatomopathological analysis. Tissue damage was observed in the hippocampus, caudate-putamen nucleus, neocortex, and thalamic nuclei of animals from the Ischemic group. The circles of Willis of the Sham-operated animals showed bilateral (38 percent), unilateral (48 percent) or no posterior communicating arteries (14 percent). A negative correlation between infarct volume and the level of anastomosis was revealed for the Ischemic, but not for the Ischemic + Hypothermia group. Additionally, Analysis of covariance (ANCOVA) was performed to assess the contribution of the level of anastomosis to the clinicopathological outcomes. It was confirmed that the infarct volume decreased in the Ischemic + Hypothermia group when compared to the Ischemic group. Since the level of anastomosis cannot be predicted, this variable should necessarily be considered when analyzing the results of global brain ischemia in Mongolian gerbils.

Efecto neurofarmacológico del zumo de Morinda citrifolia / Neuropharmacological properties of Morinda citrifolia juice

Morinda citrifolia Linn. (Rubiaceae) (Noni) is a plant, to which several therapeutic properties have assigned, but its neuropsicopharmacological effects have been poor studied. The aim of this work was to characterize the neuropharmacological properties of its juice, in male mice, by means of a battery of behavioral tests: Irwin test, exploratory behavior, barbiturate sleeping time and amphetamine-induced stereotypes. Doses of 450, 900 and 1800 mg/kg were administered, according to the juice dry weight. The results obtained from the different tests suggest the presence of non identified chemical compounds with sedative activity, specifically of neuroleptic type.

Morinda citrifolia Linn. (Rubiaceae) (Noni) es una planta que presenta diversas propiedades terapéuticas, pero sus efectos neuropsicofarmacológicos han sido poco estudiados. El objetivo del presente trabajo, fue caracterizar el perfil neurofarmacológico de su jugo, en ratones machos, por medio de una batería de pruebas de comportamiento: prueba de Irwin, conducta exploratoria, tiempo de sueño barbitúrico y estereotipias anfetamina-inducidas. Dosis de 450, 900 y 1800 mg/kg fueron administrada, de acuerdo con el peso de jugo seco. Los resultados obtenidos de las diferentes pruebas sugieren la presencia de compuestos químicos no identificados con actividad sedante, especialmente de tipo neuroléptica.

Therapeutic effect of the combined use of growth hormone releasing peptide-6 and epidermal growth factor in an axonopathy model.

Amyotrophic lateral sclerosis (ALS) is a disease of the central nervous system characterized by loss of spinal motor neurons, for which no effective treatment exists. Epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP-6) have been considered as good candidates for the treatment of this disease, due to their well documented effects in eliciting pleiotrophic and cell survival mechanisms. The aim of the present work was to evaluate the separate and combined effects of both peptides in an experimental animal model of ALS, the proximal axonopathy induced by 1,2 diacetylbenzene (1,2 DAB) in mice. The evaluations were conducted by means of behavioral tests (trapeze, tail suspension, gait pattern, and open field) and by recording the complex muscle action potential (CMAP) in three different hind limb segments: proximal S1, medial S2, and distal S3. Intraperitoneal daily administration of 1,2 DAB produced significant reduction in body weight, muscle strength, extensor reflex, spontaneous activity, and changes in gait pattern parameters. In parallel 1,2 DAB produced significant prolongation of onset latency and decrease in amplitude of CMAP and in the integrated complex action potential index. Daily administration of the separate compounds did not accelerate the recovery of the affected parameters, except for the gait pattern. The combined treatment produced significant improvement in behavioral parameters, as well as in electrophysiological recovery, particularly in the proximal segment of CMAP. The latter results confirm the proximal character of 1,2 DAB neuropathy, and suggest that combined therapy with EGF and GHRP-6 might be a good therapeutic strategy for the treatment of ALS.

Efecto de Spirulina platensis en la neuropatía axonal inducida por acrilamida en ratones / Effect of Spirulina platensis on acrylamide-induced axonal neuropathy in mice

INTRODUCCIÓN: Spirulina platensis es una microalga verde-azul de alto valor nutricional, la cual ha sido empleada como suplemento dietético. Varios de sus constituyentes ayudan al mantenimiento de la estructura y función de los tejidos nerviosos. OBJETIVO: determinar el efecto de esta microalga en un modelo de neuropatía axonal inducida por acrilamida, en ratones. MÉTODOS: el modelo consistió en la administración diaria de 70 mg/kg de acrilamida, por vía subcutánea, durante 3 semanas consecutivas; con la estimación del efecto neurotóxico de este compuesto mediante el registro, en los músculos de la pierna, del potencial de acción muscular compuesto, durante la estimulación supramáxima del nervio ciático. Después de finalizar las inyecciones de acrilamida, S. platensis se administró por vía oral, en dosis de 400 mg/kg, durante 5 semanas. RESULTADOS: al concluir la administración de acrilamida los animales presentaron una disminución estadísticamente significativa de los potenciales, acompañada de signos motores de neuropatía. La administración de S. platensis acortó el período recuperativo, lo que se evidenció por un restablecimiento más rápido del valor de los potenciales, así como por una disminución progresiva de la proporción de animales afectados. CONCLUSIONES: los resultados demuestran un efecto beneficioso de S. platensis en la neuropatía axonal inducida por acrilamida.

INTRODUCTION: Spirulina platensis is a green-blue microalga of a high nutritional value, which has been used as dietary supplement. Some of its constituents help in maintenance of structure and function of nerve tissues. OBJECTIVE: to determine the effect of this microalga on a model of acrylamide-induced axonal neuropathy in mice. METHODS: model included daily administration of 70 mg/kg of acrylamide (subcutaneous route) during 3 consecutive weeks; with estimation of neurotoxic effect of this compound by means of registry, in leg muscles, of composed muscular action potential, during supramaximal stimulation of sciatic nerve. After injections of acrylamide, S. platensis was administered per os, in doses of 400 mg/kg during 5 weeks. RESULTS: at the end of acrylamide administration animals showed a significance decrease of potentials, accompanied by the motor signs of neuropathy. Administration of S. platensis shortens recovery period, evidenced by a quicker restoration of potential values, as well as by a progressive decrease of affected animals' ratio. CONCLUSIONS: findings showed a beneficial effect of S. platensis on acrylamide-induced axonal neuropathy.

Behavioral and antiepileptic effects of acute administration of the extract of the plant Cestrum nocturnum Lin (lady of the night).

Cestrum nocturnum is a garden shrub from the family Solanaceae and is used as a remedy for different health disorders. The aim of the present work was to investigate the potential neuropharmacological action profile of decoctions obtained from dry leaves of the plant. Decoctions were tested in different neuropharmacological models-Irwin test, exploratory behavior, tests for analgesia, isoniazid- and picrotoxin-induced convulsions, and maximal electroshock seizures-in mice, as well as in amphetamine-induced stereotypies and penicillin epileptic foci in rats. Decoctions of 1 and 5% (D1 and D5) induced restlessness, and the 30% decoction (D30) induced passivity. D5 and D30 reduced significantly exploratory behavior and amphetamine-induced stereotypies within a 3-hour observation period. The latter effect was apparent during the second 60 minutes. Decoctions reduced the amount of writhes induced by acetic acid in a dose-dependent manner, but were not effective in the hot plate model. The decoctions were not effective against pharmacologically induced convulsions. However, repeated administration of five doses of D5, at 1-hour intervals, reduced the amplitude of penicillin-induced epileptic spikes in both primary and secondary foci, in curarized rats. Taken together, the results suggest that C. nocturnum possesses active substances with analgesic activity provided through a peripheral action mechanism, in parallel with some psychoactive activity that does not fit well the neuropharmacological action profile of known reference neurotropic drugs.

Behavioral and antiepileptic effect of acute administration of the extract of the aquatic plant Echinodorus berteroi (Sprengel) Fassett (upright burhead).

Echinodorus berteroi is an aquatic plant found in Central America and the Caribbean to which antiepileptic action has been attributed by folk medicine. The aim of the present study was to investigate the potential behavioral and antiepileptic effect of decoctions (1, 5, and 30%, intraperitoneally) of the dried roots. One and five percent decoctions produced hypoactivity in mice. Hyperactivity induced by amphetamine (3mg/kg, subcutaneously) was significantly reduced by the 30% decoction, in rats. The extracts did not modify the latency to the first clonic convulsion or the survival time of isoniazid (210 mg/kg, ip)-treated mice. The 30% decoction significantly increased the latency to the first picrotoxin-induced clonic convulsion (7 mg/kg, intraperitoneally), as well as survival time. Repeated administration of the 5% decoction (30-minute intervals) significantly reduced the amplitude (muV) of the epileptic spikes induced by topical application of penicillin to sensorimotor cortex, in curare-treated rats. In summary, the root decoctions of E. berteroi paradoxically exhibited neuroleptic and antiepileptic actions. Nevertheless, these results partly justify the use of the plant for the treatment of epilepsy by practitioners of folk medicine.

Efecto de los extractos acuoso y etanólico de Cestrum nocturnum L sobre la conducta exploratoria y pruebas de analgesia / Effect of aqueous and ethanol extracts of Cestrum nocturnum L on the animal´s exploring behaviour and on analgesia tests

Se estudió el efecto neurofarmacológico de las fracciones acuosa y etanólica obtenidas a partir de las hojas secas de Cestrum nocturnum L mediante su administración aguda sobre los modelos de conducta exploratoria y pruebas de analgesia. El propósito del estudio fue iniciar la búsqueda de los principios activos en estas fracciones responsables de los efectos analgésicos y sedantes. La fracción acuosa produjo una hipoactividad en la conducta exploratoria y redujo la respuesta al dolor en forma dependiente de las dosis en la prueba de las contorsiones inducida por ácido acético así como un aumento del tiempo de reacción en el método del plato caliente. La fracción etanólica provocó una disminución de la conducta exploratoria y de la permanencia en el círculo central, así como una disminución de las contorsiones inducidas por ácido acético en forma dependiente de las dosis y del tiempo de reacción en el plato caliente. Una ausencia de paralelismo entre las curvas dosis-efecto de ambos modelos sugirió una independencia molecular entre ambos efectos farmacológicos, los que parecen deberse a principios activos diferentes.

The neuropharmacological effect of aqueous and ethanol fractions from Cestrum nocturnum L. dry leaves through acute administration on animal´s exploring behaviour and analgesia test models was studied. The objective of this study was to begin searching for the active principles existing in these fractions, which are responsible for analgesic and sedative effects. The aqueous fraction caused hypoactivity animal's exploring behaviour and reduced dose-dependent response to pain in acetic acid-induced contortions as well as increase in reaction time in the hot-plate method. The ethanol fraction caused a reduction in animal's exploring behavior and in the length of stay in the 10-cm diameter central circle as well as a decrease in acetic acid-induced contortions depending on the dose, and in reaction time in the hot-plate method. The lack of parallelism between the dose-effect curves of both models suggested molecular independence in both pharmacological effects, which seem to be due to different active principles.

Efectos de los extractos acuoso, etanólico, clorofórmico y toluénico de Brunfelsia nitida Benth sobre la conducta exploratoria y pruebas de analgesia / Effects of aqueous, ethanol, chloroform and toluene extracts of Brunfelsia nitida Benth on the animal´s exploring behavior and analgesia tests

Se evaluó el efecto neurofarmacológico de las fracciones acuosa, etanólica, clorofórmica y toluénica a partir de hojas secas de Brunfelsia nitida Benth, mediante su administración aguda sobre modelos de la conducta exploratoria y pruebas de analgesia. La fracción acuosa produjo un efecto sedante en la conducta exploratoria en la dosis de 100 y 500 mg/kg y redujo significativamente la respuesta al dolor en forma dosis dependiente en la prueba inducida por ácido acético, sin producir cambios en el tiempo de reacción del método del plato caliente. La fracción etanólica provocó una disminución significativa de la conducta exploratoria en la dosis de 200 mg/kg sin afectar la latencia y el tiempo de permanencia en el círculo central, así como una disminución de las contorsiones inducidas por ácido acético en las dosis de 40 y 200 mg/kg y en el tiempo de reacción del plato caliente. La fracción clorofórmica produjo efecto sedante en la conducta exploratoria a la dosis de 40 y 200 mg/kg, sin modificar la latencia y el tiempo de permanencia en el círculo central. Estas dosis redujeron significativamente la respuesta al dolor inducida por ácido acético sin modificar el tiempo de reacción. La fracción toluénica no modificó ninguno de los modelos empleados. No se observó paralelismo entre las curvas dosis-efecto de la conducta exploratoria y analgesia de cada fracción, por tanto los resultados sugieren que no existe relación molecular entre ambos efectos farmacológicos. En conclusión, los efectos sedantes y analgésicos encontrados parece que se deben a distintos principios activos

The neuropharmacological effect of aqueous, ethanol, chloroform and toluene fractions from Brunfelsia nitida Benth dry leaves, through acute administration, on animal's exploring behavior and analgesia test models was assessed. The aqueous fraction had a sedative effect on animal's exploring behavior at doses of 100 and 500 mg/kg and significantly reduced dose-dependent response to pain in acetic acid-induced test, without changes in the reaction time of the hot-plate method. The ethanol fraction brought about a significant reduction of the animal's exploring behavior at a dose of 200 mg/kg without affecting latency and length of stay in the 10-cm central circle as well as a decrease in acetic acid-induced contortions at doses of 40 and 200 mg/kg and in the reaction time of the hot-plate method. The chloroform fraction had a sedative effect on the animal's exploring behavior at doses of 40 and 200 mg/kg without changing latency and length of stay in the 10-cm diameter. central circle. These doses significantly reduced acetic acid-induced response to pain without modifying the reaction time. The toluene fraction did not change any of the used models. No parallelism was observed between the dose-effect curves of the animal´s exploring behavior and the analgesia test of each fraction; therefore, the results indicate that there is no molecular relation between both pharmacological effects. In conclusion, the sedative and analgesic effects seem to be caused by different active principles.

Acute effect of an extract of Ambrosia paniculata (Willd.) O. E. Schultz (mugwort) in several models of experimental epilepsy.

The acute effect of Ambrosia paniculata was studied in several animal models of epilepsy. Intraperitoneal injections (0.01 mL/g body wt) of a decoction of the dry leaves significantly enhanced the latency to the first convulsion and survival time in mice injected with picrotoxin (7 mg/kg) or isoniazid (210 mg/kg). Epileptic spikes were induced by topical application of penicillin through a glass electrode filled with a penicillin-agar-saline mixture and recorded in sensorimotor and occipital cortices, in rats immobilized with d-tubocurarine. The plant decoction reduced significantly the spike amplitude in both sites. The mentioned effects were elicited at doses that also reduced general motor activity (Irwin test) and exploratory behavior. The decoctions were not effective against electroshock-induced convulsions in mice. The convulsions induced by isoniazid, picrotoxin, and penicillin differed from those induced by electroshock implicating selective disruption of GABAergic neurotransmission. The results suggest that A. paniculata, like several conventional antiepileptic drugs, might act by enhancing GABAergic neurotransmission, a hypothesis that requires further demonstration. These results explain and justify the traditional use of the plant in epilepsy.

Caracterización neurofarmacológica de la 2-fenil-4, 4-bis-(hidroximetil)-2-oxazolina obtenida bajo irradiación de microondas / Neuropharmachological characterization of 2-phenyl-4, 4-bis-(hydroxymethyl)-2-oxazoline obtained under microwaves irradiation

Algunas aril-oxazolinas han sido descritas como sustancias activas sobre el sistema nervioso central, con efectos y aplicaciones diversas como depresoras, anestésicos, anticonvulsivantes, etc. En el presente trabajo se realizó la caracterización neurofarmacológica primaria de la 2-fenil-4,4-bis-(hidroximetil)-2-oxazolina, obtenida por un método de síntesis bajo radiación de microondas como fuente energética. La realización de la prueba de Irwin mostró que este compuesto presenta un efecto depresor sobre el sistema nervioso central, con una notable inhibición de la actividad motora y del tono muscular, con pérdida de los reflejos posturales. A dosis moderadas estos efectos se acompañaron de signos de excitación central. Estas características sugirieron una acción de tipo periférica, confirmado por el efecto bloqueador de las contorsiones en la prueba de irritación peritoneal por ácido acético al 0,8 por ciento y la disminución de la amplitud del potencial de acción neuromuscular compuesto durante la estimulación supramáxima del nervio ciático, pruebas que evidenciaron una acción anestésica local para la 2-fenil-4,4-bis-(hidroximetil)-2-oxazolina

Bloqueo de las crisis audiogénicas y del choque electroconvulsivo por la 2-fenil-4, 4-bis-(hidroximetil)-2-oxazolina / Block of the audiogenic seizures and of the electroconvulsive shock by 2-phenyl-4, 4-bis-(hydroxymethyl)-2-oxazoline

Algunas aril-oxazolinas han sido descritas como sustancias activas sobre el sistema nervioso central, con efectos y aplicaciones diversas como depresoras, anestésicos, anticonvulsivos, etc. El presente trabajo se trazó como objetivo fundamental estudiar el posible efecto de la 2-fenil-4,4-bis (hidroximetil)-2-oxazolina (OX) obtenida por síntesis química bajo microondas, en 2 modelos experimentales de epilepsia: el choque electroconvulsivo por estimulación repetitiva en ratones y el de inducción de crisis convulsiva por estímulo audiogénico en el gerbo mongol. La dosis de 150 mg/kg de OX redujo el número de pulsos eléctricos necesarios para inducir la crisis tónica producida por el choque eléctrico, así como su duración. Esta misma dosis bloqueó las crisis inducidas por el estímulo audiogénico en el gerbo, y disminuyó significativamente su severidad (grados de crisis) y ocurrencia. Estos resultados permiten afirmar que OX presenta un efecto antiepiléptico relacionado posiblemente con una inhibición de la sinapsis glutamatérgica en el hipocampo

Efecto de la Spirulina platensis en la Toxicidad producida por acrilamida / Effect of Spirulina platensis in toxicity from acrylamide

La Spirulina platensis es una microalga verde-azul con alto valor nutritivo y con propiedades farmacológicas de interés. Se realizaron dos experimentos, en uno se determinó la letalidad: DL10, DL50 y DL90, de acrilamida en ratones y para ello se utilizaron 1 000 mg/kg por vía oral de Spirulina 1 hora o 5 días antes de la administración de acrilamida. En el otro, se suministró la Spirulina en dosis de 500 mg/kg por vía oral, diariamente durante 3 semanas previas a la administración de100 mg/kg de acrilamida por vía intraperitoneal durante 5 días. Se emplearon el método de Litchfield y Wilcoxon y la Probabilidad Exacta de Fischer con una p < 0,05. En ningún caso la Spirulina protegió contra la mortalidad provocada por acrilamida, bien empleada en dosis únicas o en repetidas durante un período corto. El resultado anterior descartó un antagonismo de carácter farmacológico, y ofreció la posibilidad de estudiar la influencia de esta microalga en neuropatía axonal inducida por la administración prolongada de acrilamida

Fundamentos de una posible acción beneficiosa de la Spirulina platensis en las neuropatías periféricas / Fundamentals of a possible beneficial of Spirulina platensis on action on peripheral neuropathies

La Spirulina platensis es una microalga verde-azul conocida por su alto valor nutritivo y considerada como una de las fuentes naturales más completas de proteínas, vitaminas, minerales y otros nutrientes. En el presente trabajo se analiza la potencialidad de esta alga en la prevención y tratamiento de las neuropatías sobre la base de sus principales constituyentes y de las diferentes causas de estos trastornos. Se hace mención a la neuropatía epidémica ocurrida en Cuba y a la hipotesis tóxico-nutricional como su causa más probable. Varios constituyentes de la S. platensis además de desempeñar una función importante en el balance nutritivo, participan de manera especial en el mantenimiento de la estructura y función normales del sistema nervioso. Sobre la base de estos antecedentes se sugiere un posible efecto beneficioso del alga en trastornos neuropáticos de diverso origen

Efectos agudos del extracto del Cestrum nocturnum (galán de noche) sobre diferentes modelos de epilepsia experimental / Acute effects of the extract from Cestrum nocturnum (night jessamine) on different models of experimental epilepsy

Se investiga la posible acción antiepiléptica de decocciones de hojas secas de C. nocturnum mediante la administración aguda intraperitoneal en modelos de epilepsia experimental inducidos por isoniacida, picrotoxina, electrochoque (en ratones) y en el foco epiléptico inducido por la administración tópica cortical de penicilina, en ratas curarizadas. El extracto al 30 (por ciento) prolongó significativamente la latencia de aparición de las crisis y la muerte provocadas por isoniacida, pero no las inducidas por electrochoque o picrotoxina. El extracto al 5 (por ciento) redujo significativamente la amplitud de espigas del foco penicilínico. Estos resultados apoyan o justifican el empleo tradicional de esta planta en los trastornos convulsivos

Efectos agudos del extracto de Ambrosia paniculata (Willd.) O.E. Schulz (artemisa) sobre diversos modelos de epilepsia experimental / Acute effects of the extract of Ambrosia paniculata (Willd.) O.E. Schulz (artemisa) on diverse models of experimental epilepsy

Se realizó una evaluación de la posible acción antiepiléptica de decocciones de hojas secas de Ambrosia paniculata mediante la administración aguda intraperitoneal en modelos de epilepsia experimental inducidos por isoniacida, picrotoxina, electrochoque (en ratones) y en el foco epiléptico inducido por la administración tópica cortical de penicilina, en ratas curarizadas. El extracto al 5 (por ciento) prolongó significativamente la latencia de aparición de las crisis y la muerte provocadas por isoniacida y picrotoxina, pero no las inducidas por electrochoque. El extracto al 5 (por ciento) redujo significativamente la amplitud de espigas del foco penicilínico. Estos resultados apoyaron o justificaron el empleo tradicional de esta planta en los trastornos convulsivos

Perfil neurofarmacológico del Plectranthus amboinicus (Lour) Spreng (Orégano francés). Potenciación de las esteriotipias inducidas por anfetamina / Neuropharmacologic rofile of Plectranthus amboinicus (Hour) Spreng (French origan). Increase of amphetamine-induced stereotypies

Se estudió el perfil neurofarmacológico de la decocción de hojas verdes de P. amboinicus mediante su administración aguda en la prueba de Irwin, la conducta exploratoria, el modelo de estereotipias inducidas por anfetamina y las pruebas de analgesia (plato caliente e irritación peritoneal inducida por ácido acético). Se prepararon decocciones de 1,5 y 30 g en 100 mL de agua destilada (D1,D5 y D30, respectivamente) y se estudiaron sus efectos sobre los perfiles neurológico, conductual y autonómico. En particular, D30 produjo un aumento del acicalamiento y una disminución del reflejo auricular. Por otra parte, los extractos no produjeron cambios significativos sobre la conducta exploratoria y las pruebas de analgesia. El extracto D5 potenció las esterotipias inducidas por anfetamina. Por lo tanto, los resultados obtenidos tomados en conjuntos sugieren un perfil faramacológico similar al de los antidepresivos