Histamine as a therapeutic alternative in migraine prophylaxis: a randomized, placebo-controlled, double-blind study.

This study was undertaken to test the efficacy of the subcutaneous administration (twice a week) of consecutively increasing doses of histamine (0.1 to 1 ng) in the prophylaxis of migraine, compared to placebo, under a controlled, double-blind, clinical trial for 12 weeks. Sixty patients were selected, under criteria established by the International Headache Society (both sexes, 18 to 65 years of age, a migraine history of more than 1 year, one to six headache attacks per month), having no additional neurological or cardiovascular pathologies, and after a complete clinical and laboratory examination including computer-assisted tomography. Comparison between the groups treated with placebo (n = 30) and histamine (n = 30), on data collected for the 4th, 8th, and 12th weeks of treatment, revealed that histamine exerted a significantly (P < .0001) greater reduction (compared to placebo) in the frequency, intensity, and duration of migraine attacks, as well as on the use of rescue medication. No significant (P > .05) adverse experiences or side effects in either group developed to impede the blinding of the study or the planned order of events. We conclude that the subcutaneous administration of histamine (at very low doses) constitutes a novel and effective therapeutic approach in migraine prophylaxis, aimed at limiting excessive inflammatory responses involved in the pathophysiology of migraine through the activation of H3 receptors.

Cardiac lymphatic dynamics after ischemia and reperfusion--experimental model.

ABSTRACT. The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of 99mTc-Re2S7 colloid (+/-10 microm), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A gamma-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

Análisis farmacológico conductual de la DL-4-hidroxi, 4-etil, 4-fenil butiramida (HEPB) sobre los componentes motor y discriminativo de la memoria de reconocimiento en la rata / Psychopharmacological analysis of DL-4-hydroxy, 4-ethyl, 4-phenyl butyramide (HEPB) on the motoric and discriminative components of recognition memory in the rat

Este estudio fue llevado a cabo con el objetivo de disociar entre las acciones motoras ejercidas por la administración aguda (1, 2, 5, 10, 20, 40, 60, 80, y 100 mg/kg-1 ip) de HEPB y fenobarbital y sus efectos sobre el componente descriminativo de la memoria de reconocimiento en la rata. A dosis mayores de 20 mg/kg-1, ambos anticonvulsionantes indujeron una reducción (dosis dependiente) en el número de corridas por ensayo (en ratas entradas para recorrer un corredor de 4.2 m de longitud), así como el número de elecciones efectuadas por ensayo en un laberinto en ®T¼ (continuo al corredor) para reconocer (mediante indicios no especiales) el brazo no electrificado que contenía alimento. Sin embargo, ninguno de estos fármacos afectó el porcentaje de elecciones correctas ejecutadas en el paradigma discriminativo, aún bajo condiciones de severa incoordinación motora ejercida por dosis de 60 mg/kg-1 de fenobarbital o de 100 mg/kg-1 de HEPB. Estos datos indican que si bien, a dosis subanestésicas, los anticonvulsionantes probados no alteran la memoria de reconocimiento en la rata, la eficiencia en general que resulta de la prueba conductual para dicha memoria es efectuada por un deterioro en la actividad y coordinación motora

Estudio comparativo entre los efectos de la DL-4-hidroxi, 4-etil, 4-fenil butiramida (HEPB) y fenobarbital sobre la memoria espacial dependiente del hipocampo / Comparative study of the effects of Dl-4-hydroxy, 4-ethil, 4-phenyl butyramide (HEPB) and phenobarbital on hippocampal dependent spacial memory

Este estudio farmacológico conductual fue llevado a cabo para determinar las acciones de los anticonvulsionantes HEPB y fenobarbital sobre los procesos de adquisición y retención de la memoria espacial dependiente de la integridad anatómica-funcional del hipocampo en la rata, utilizando un laberinto radial elevado de ocho brazos, y mediante la estrategia "acierto cambio". La administración diaria de estos fármacos, es un intervalo de dosis de 10 a 100 mg/kg-1, durante 25 días consecutivos, no afectó el curso temporal del proceso de adquisición de la información especial. Sin embargo, a la dosis de 100 mg/kg-1 de fenobarbital las máximas calificaciones obtenidas fueron consistentemente bajas (menores de 7.6). después de un periodo de ocho días sin entrenamiento, los grupos tratados con fenobarbital mostraron una extinción total de la información espacial similar a la obtenida para los grupos testigo, mientras que todos los grupos tratados con HEPB mantuvieron una retención total de dicha información. Estos resultados son indicativos de que HEBP puede ejercer una acción protectora sobre los procesos de extinción de memoria espacial a través de mecanismos neuronales que pueden involucrar una retención del mapa cognoscitivo adquirido

Evaluación de acciones colaterales del anticonvulsionante DL-4 hidroxi, 4-etil, 4-fenil butiramida (HEPB) sobre los sistemas cardiovascular y respiratorio / Evaluation of the collateral actions of the anticonvulsant DL-4-hydroxy, 4-ethyl, 4-phenyl butyramide (HEPB) on the cardiovascular and respiratory systems

Para llevar a cabo una evaluación de la seguridad farmacológica de la HEPB como anticonvulsionante, determinamos los efectos de la administración aguda de este fármaco (5, 25, 50, 100 y 125 mg/kg-1 ip) sobre los sistemas cardiovasculares y respiratorios de la rata. Mientras que en animales anestesiados con pentobarbital HEPB no modificó la frecuencia cardiaca, este anticonvulsionante indujo cambios significativos sobre la presión arterial media (PAM) y la frecuencia respiratoria (FR) a dosis mayores de 50 mg/kg-1 resultando en una inhibición del 37.18 por ciento de la PAM y del 49.5 por ciento de la FR después de la administración de 125 mg/kg-1 de HEPB. En animales no anestesiados, HEPB no alteró la presión arterial sistólica ni la frecuencia cardiaca a ninguna de las dosis probadas. Nuestros datos indican que dentro del intervalo de dosis encontradas para la acción anticonvulsionante de HEPB en diferentes modelos experimentales de epilepsia, este fármaco no ejerce acciones colaterales sobre los sistemas cardiovascular y respiratorio en la rata. Sin embargo, HEPB potencial las acciones depresivas de los barbitúricos sobre dichos sistemas

Evaluation of pulmonary systemic blood flow using ECG gated acquisition.

We propose a functional parametric analysis method using ECG-gated 99mTc-labeled red blood cell (RBC) imaging for detection and characterization of periodic variations in local blood activity in the lungs during cardiac cycle. We validated in animal experiments that such count variations correlate with cyclical pulmonary blood flow and may be used for evaluation of systemic-to-pulmonary shunts. Clinical studies were performed in 48 patients. After labeling the RBC pool with 99mTc, ECG-gated gamma camera images of both lung fields were acquired and processed to obtain Fourier transforms of time/activity functions in selected regions. The first harmonic parametric images of amplitude and phase were derived. There was an excellent correlation (r = 0.92) between activity variations and pulsatile flow measured by our method with that obtained by the thermodilution method in dog experiments (n = 10) after implantation of a systemic-to-pulmonary shunt. Patient studies showed the technique to be sensitive in detecting and quantifying abnormal systemic-to-pulmonary blood flow. Lung pulsatile flow can thus be noninvasively measured from functional parametric phase and amplitude images; the technique may be useful for detecting and quantifying abnormal systemic-to-pulmonary blood flow in man.

The effect of pentylenetetrazol on spike broadening and potassium inactivation.

The effect of the convulsant drug, pentylenetetrazol (PTZ) on spike broadening and potassium current inactivation was studied. PTZ was found to decrease the time taken for a cell to reach maximal broadening as well as causing a decrease in the total amount of broadening. Voltage clamp studies showed that in the presence of PTZ potassium current inactivated less but exhibited a faster time constant of inactivation. By exerting an effect on potassium inactivation and thereby spike broadening, PTZ may alter synaptic efficacy. Such an effect on synaptic efficacy may partially underlie the drug's convulsive activity.

TRH in the rat cerebellum: I. Distribution and concentration.

We determined the regional distribution and concentration of endogenous TRH in the rat cerebellum. Radioimmunoassay of endogenous TRH extracted and purified from five different regions of the rat cerebellum and whole hypothalamus showed that the cerebellar vermis contained 24 pg/mg, the hemispheres 74 pg/mg, the deep cerebellar nuclei 148 pg/mg, and the flocculo-nodular region 559 pg/mg of TRH. The highest concentration of TRH was in the cerebellar paraflocculi, which contained 786 pg/mg. The hypothalamic concentration of TRH was 465 pg/mg. Assay of the non-purified tissue fractions (crude extracts) resulted in lower TRH values in accordance with data previously reported by other authors. Bioassay analysis of TRH in purified fractions resulted in values similar to those obtained by radioimmunoassay. On the basis of these findings we hypothesize a functional role for TRH in the cerebellum.

Trh in the rat cerebellum: II. Uptake by cerebellar slices.

We investigated the in vitro uptake of exogenous TRH by rat cerebellar slices. TRH was found to be taken up via a process sharing many of the properties of a high affinity transport system, viz: (1) saturation kinetics; (2) high affinity kinetic constants (Km1 = 1.06 X 10(-5) M, Km2 = 5.6 X 10(-6) M); (3) temperature sensitivity (Q10 = 1.48); (4) dependency on the sodium concentration in the incubation medium; and (5) tissue/medium ratios greater than 1. After 60 min of incubation at 27 degrees C in the presence of Bacitracin, the tissue/medium ratio was 5:1. Under these conditions 70% of the total label was recovered as [3H-Pro]TRH. These findings demonstrated the existence of removal mechanisms for TRH in the cerebellum and gave further support to the hypothesis that TRH plays a functional role removal mechanisms for TRH in the cerebellum and gave further support to the hypothesis that TRH plays a functional role in this extrahypothalamic brain region.

How do normal subjects learn a simple adaptative task: how and why do paranoid schizophrenic patients fail?

The authors studied the behavior of normal subjects and paranoid schizophrenic patients in a simple problem-solving situation. The schizophrenics were divided into two sample groups, one of individuals under treatment and the other of individuals not under treatment. The learning process involved in this problem-solving situation is very similar to an instrumental conditioning, and can be understood by means of the following assumptions: (1) the subjects use decision functions in reacting to the stimuli, although they may be not fully aware of this; (2) learning is the result of successive transformations of these decisions in the course of time; (3) the changes have specific probabilities and are related to (a) those responses which are made to the latest stimuli, and (b) a differential probability for decision functions which were effective, or only interrupted painful reinforcement, or were completely ineffective. In schizophrenics further factors of importance were (1) an 'inertia' factor and (2) the rigidly continued use of unsuccessfuly or only partially successful decision criteria. The authors used a systems theory based on Galois field theory and a calculus of operators specifying three groups of subjects. A computer program based on thses hypotheses was tested in a stimulation experiment. The statistical evaluation of the results showed a congruence between the theoretical approach and the experimental data.