Peptides isolated from animal venom as a platform for new therapeutics for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that deeply affects patients, their family and society. Although scientists have made intense efforts in seeking the cure for AD, no drug available today is able to stop AD progression. In this context, compounds isolated from animal venom are potentially successful drugs for neuroprotection, since they selectively bind to nervous system targets. In this review, we presented different studies using peptides isolated from animal venom for the treatment of AD. This is a growing field that will be very helpful in understanding and even curing neurodegenerative diseases, especially AD.

[Epilepsies in an outpatient setting: a study of 150 cases]. / Epilepsias en el ámbito extrahospitalario. Estudio en 150 casos.

INTRODUCTION: In this paper we present epidemiological data from a register of cases of epilepsy attended in the Centro de Especialidades of the Alboraya street in Valencia. The sample corresponds to a particular type of healthcare setting, halfway between the family doctor and the specialist hospital department, which has recently begun to be developed in Spain in the field of neurology. PATIENTS AND METHODS: The sample consisted of 150 patients who completed a questionnaire-type protocol. RESULTS: The average age of the patients was 39.66 +/- 19.60 years, slightly more in the men than in the women. There were slightly more women than men included in the study. The epilepsy was either long-term or of recent onset. The average age of onset was 25.42 +/- 21.35 years. More than two thirds of the sample, that is 108 patients (72%) had partly controlled disease. However, a considerable number of them were irregularly controlled and another group of 23 (15.3%) were on polytherapy with three or more antiepileptic drugs. CONCLUSIONS: The data from this series of 150 cases is, in general, similar to that of other epidemiological studies done in Spain. However, it is noticeable that there is a high proportion of patients with problems of control, although this may be due simply to a bias in the selection. We hope that the publication of this new data will stimulate new studies to analyse the attention give to patients with epilepsy in this healthcare setting.

Epilepsias en el ámbito extrahospitalario. Estudio en 150 casos / Epilepsies in an outpatient setting. A study of 150 cases

Introducción. Presentamos en este trabajo datos de tipo epidemiológico procedentes de un registro de casos de epilepsia atendidos en el Centro de Especialidades de la calle Alboraya de Valencia. La muestra corresponde a un ámbito asistencial peculiar, a medio camino entre el médico de familia y los servicios especializados hospitalarios, en el que la neurología española tiene un reciente y creciente desarrollo. Pacientes y métodos. La muestra la componen 150 pacientes a quienes se les aplicó un protocolo tipo encuesta. Resultados. La edad media de los casos fue de 39,66 ñ 19,60 años, algo mayor en varones que en mujeres. Hubo un discreto predominio femenino en la muestra. La epilepsia podía ser tanto de larga evolución como de reciente diagnóstico; la edad media de inicio fue de 25,42 ñ 21,35 años. Más de dos terceras partes de la muestra, esto es, 108 pacientes (72 por ciento) tenían medianamente controlada su enfermedad; no obstante, todavía un buen grupo de ellos presentaban un control irregular y otro grupo de 23 (15,3 por ciento) estaba sometido a politerapia con tres o más fármacos antiepilépticos. Conclusiones. Los datos de esta serie de 150 casos son, en general, similares a los de otros estudios epidemiológicos de nuestro país, si bien llama la atención precisamente este alto porcentaje de pacientes cuya enfermedad presenta problemas de control, lo cual podría deberse simplemente a un sesgo de selección. Esperamos que la presentación de estos datos estimule nuevos estudios que analicen la atención prestada a los pacientes con epilepsia en este ámbito asistencial (AU)

[New forms of Parkinsonism in hospice care]. / Parkinsonismos de novo en ámbito extrahospitalario.

Parkinson's disease is a well known phenomenon with characteristic evolution and clinical picture although having considerable variation in its presenting symptoms. From an extra-hospital consulting room we carried out a study of the characteristics of the clinical presentation of parkinsonisms in a series of one hundred cases so diagnosed from onset. The average age of the patients was around 66 years with a slight female predominance. Most patients had been referred to us by their own GPs. Some 70% of patients came suffering from shaking, 23% for slowness or clumsiness and 10% for unsteadiness. 71% of cases had unilateral onset and 29% had bilateral onset. Most of the patients we saw arrived at level 2 on the Hoehn and Yahr scale. The duration of the symptoms was approximately one year. In some 27% of cases drug consumption might have brought on parkinsonism. Almost two-thirds of these cases brought about by medicaments were being treated with cinaricine or flunaricine and nearly one third were undergoing neuroleptic treatment. Practically one out of every four cases, and one out of three women, could be considered as having iatrogenic parkinsonism. The onset of shaking with bilateral affectation is particularly suggestive of drug induced parkinsonism.

[Misoprostol--a PGE1 analog for induction of labor at term: comparative and randomized study with oxytocin]. / Misoprostol--un análogo de la PGE1--para la induccíon de parto a término: estudio comparativo y randomizado con oxitocina.

The efficacy of misoprostol (a PGE1 analog) for induction of labor at term was compared with oxytocin by means of an open and randomized study in 153 pregnant women. A vaginal tablet containing 50 mcg of misoprostol was placed intravaginally in 78 women, the remaining 75 patients received i.v. oxytocin (2-32 mU/min). Bishop's score at the entry of the trial was similar in both groups. Delivery within 24 hours was achieved in 85.7% of the patients induced with misoprostol and in 64% of the patients infused with oxytocin (p < 0.05). Mean induction to delivery interval was significantly shorter in the misoprostol group (552 +/- 211 min; mean =SD) in comparison with that of the oxytocin group (745 +/- 292 min; mean +/- SD) (p < 0.05). The probability of still being pregnant at 24 hours (Life table analysis) was 14% (misoprostol group) and 26% (oxitocyn group). The difference was also statistically significant (p < 0.01). No undesirable side effects were observed in any of the patients, however, polisystoly (> 5 contractions in 10 min) was more frequently observed in the patients induced with misoprostol (24.6% vs 13.3%; p = NS). Cesarean section rate was higher in the oxytocin-induced patients (25.3%) than in the misoprostol-induced women (3.8%) (p < 0.05). The main cause of cesarean section was failure to progress in labor in both groups of patients. Neonatal outcome was good in both groups and there were no differences with respect to birthweight or to Apgar scores.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of arginine-vasopressin infusion on the secretion of tracheal fluid in sheep fetuses]. / Efecto de la infusión de arginina-vasopresina en la secreción de liquido traqueal en fetos de oveja.

Timely evacuation of alveolar fluid, release of surfactant and the beginning of continuous breathing, are key processes for an adequate adaptation of the fetus to the extrauterine life. Fetal vasopressin increases during labor and inhibit the secretion of tracheal fluid through a mechanism still unknown. The aim of this study was to elucidate the mechanism whereby vasopressin inhibit the secretion of lung fluid. We used fetal sheep chronically catheterized and infused either with vasopressin, vasopressin agonist (V2; dDAVP) or vasopressin antagonist (V1). Tracheal flow was measured during basal and infusions periods of 2 hours, monitoring fetal blood pressure, heart rate and blood pH and gases. Vasopressin and the V1 vasopressin antagonist caused a significant reduction in tracheal fluid flow, effect that was potentiated when both peptides were infused together. The V2 vasopressin agonist had no effect on the secretion of lung fluid. We concluded that vasopressin causes a significant inhibition of lung liquid secretion through a mechanism different to the activation of V1 and V2 receptors, and we propose the existence of other (s) kind of receptors (or receptors) for vasopressin that is (are) active during fetal life.

Synergistic effect of cortisol and thyrotrophin releasing hormone on lung maturation in the fetal sheep entails connective tissue maturation.

Pressure-volume relationships and collagen and elastin contents were measured in the lungs of fetal sheep infused either with saline (n = 4), thyrotrophin-releasing hormone (TRH; n = 6), cortisol (n = 9) or TRH plus cortisol (n = 10) at 128 days of gestation (term = 149 days) for 7 days. Lung distensibility (V40 = 1.8 +/- 0.1 ml/g wet wt; mean +/- SD) and stability (V5 = 0.6 +/- 0.1) increased along with collagen (C) (10.1 +/- 2.7 micrograms/mg) and elastin (E) contents (128 +/- 35 ng/mg) in the animals infused with TRH plus cortisol and were significantly higher (p < 0.05) than those observed in TRH (V40 0.62 +/- 0.07; V5 0.32 +/- 0.04; C 3.53 +/- 1.3; E 38.2 +/- 8.3), cortisol (V4 0.66 +/- 0.6; V5 0.27 +/- 0.03; C 4.27 +/- 0.8; E 41.02 +/- 12.7) or saline infused fetuses (V40 0.40 +/- 0.1; V5 0.20 +/- 0.06; C 3.28 +/- 0.9; E 31.5 +/- 9.2). Plasma concentrations of prolactin (PRL), triiodothyronine (T3) and cortisol (F) were also higher in the group of fetuses infused with both hormones in comparison with the other groups. In fetuses treated with TRH plus cortisol, PRL (32 +/- 8.3 ng/ml) and T3 (308.3 +/- 36 micrograms/dl) were significantly higher than in those infused with cortisol alone (PRL 3.7 +/- 2.3; T3 128 +/- 30) or with saline (PRL 4.2 +/- 1.6; T3 < 5 micrograms/dl). In the group treated with TRH alone, PRL also increased significantly (37 +/- 6.4), but T3 increased only slightly (18 +/- 3.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cholic acid infusion in fetal lambs.

The effects of prolonged intravenous infusions of cholic acid into fetal lambs are described in this study. The ewes (n = 10, 11 fetuses) were operated on at 114 days of gestation (term = 150 days) by placing plastic catheters in maternal and fetal vessels and in the amniotic cavity. Gestational ages were confirmed after delivery by radiographic examination of the ossification centers of the fetal legs. Infusions of cholic acid (1.6 mumoles/min-1) started 8 to 10 days after surgery in 5 fetuses (including one twin). The remaining 6 fetuses (also including one twin) were infused with 5% dextrose in water. Total plasma bile acids at the beginning of the experiment were similar in both groups (23.8 +/- 6.6 vs. 24.3 +/- 5.7 microM). No significant changes in fetal heart rate, blood pressure, blood gases or pH were detected during the infusion. Meconium-stained amniotic fluid was observed during the third day of infusion in all the fetuses infused with cholic acid and in one control fetus. Fetuses infused with cholic acid were delivered alive 19-26 days before term. The concentration of plasma bile acids in the experimental group at delivery was 829 +/- 305 microM, i.e. significantly higher than that of the control group (24.4 +/- 5.7 microM). Control fetuses (except one twin) were delivered at term. We concluded that cholic acid, even at the high dose infused, is neither lethal nor severely harmful for the fetus. Meconium passage of the fetuses infused with cholic acid, in our experiment, appeared to be related to the stimulatory effect of cholic acid on fetal colonic motility rather than to fetal hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Maximal response to oxytocin of the isolated myometrium from pregnant patients with intrahepatic cholestasis.

Prematurity and fetal death are common complications in patients with cholestasis of pregnancy. Both conditions appear to be associated with abnormal patterns of uterine activity. We studied the oxytocin-induced contractile activity in uterine strips taken from patients with cholestasis of pregnancy (n = 6) and from women with normal pregnancy (n = 6). Contractile activity of the myometrium in response to oxytocin was significantly higher in patients with cholestasis of pregnancy than in normally pregnant patients, at doses of 10(-6), 10(-4), and 10(-2) M. We found that there is a greater maximal response to oxytocin in strips of myometrium from patients with cholestasis of pregnancy than from normally pregnant patients.

Angiotensin II induced release of prostaglandins from rat uterus.

The effect of Angiotensin II (A-II) on 6-keto-prostaglandin F1 (6-keto-PGF1 alpha) and prostaglandin F (PGF) production by the rat uterus was studied using a novel superfusion technique. The method of superfusion used allows prostaglandin synthesis in the myometrium and endometrium to be measured independently while their anatomical relationship is undisturbed. Prostaglandins were measured by radioimmunoassay. In uterine horns from castrated, estrogen treated rats, A-II (10(-6)M) stimulated the production rate of 6-keto-PGF1 alpha in the myometrium nd PGF in the endometrium. Sterile horns and pregnant horns coexisting in the same animals showed different responses when superfused with culture medium containing A-II (10(-6)M). In the sterile horns A-II failed to stimulate prostaglandin synthesis whereas in the pregnant horns there was a significant increase in the production rate of both 6-keto-PGF1 alpha and PGF in the decidua (endometrium) and of 6-keto-PGF1 alpha in the myometrium. Our results suggests that the effect of A-II on prostaglandin synthesis by the rat uterus appears to be dependent of the hormonal milieu of the experimental animal. Estrogen stimulated A-II induced PG synthesis. Progesterone inhibited the synthesis of PGs caused by A-II in non-decidualized uterus but stimulated the release of PG in the decidualized uterus. The apparent differential effect of A-II in stimulating prostaglandin synthesis in the whole uterus indicates that there are different pathways for prostaglandin production in both the endometrium and myometrium.

Prepartum maturation of the lung in fetal sheep: relation to cortisol.

We studied the relationship of certain fetal and maternal hormones to indicators of lung maturation in 12 fetal lambs delivered at gestational ages (GA) of 123-149 days. Maternal estrogen, maternal progesterone, and fetal prolactin did not correlate with GA or the indicators of fetal lung maturation. Fetal cortisol (range 4-165 ng X ml-1) increased with advancing GA (r = 0.747, P less than 0.01). All of the following showed a wide range of late gestation and showed a significant positive correlation with fetal cortisol: lung volumes at 40 cmH2O and 10 cmH2O on the deflation during air pressure-volume studies; saturated phosphatidylcholine (SPC) in lung tissue and in lavage fluid expressed both as mg X g-1 of wet lung and as percent of total phospholipids (%PL); total SPC (lung tissue plus lavage fluid): and SPC in lavage fluid as percent of total SPC. Lung DNA correlated inversely with GA and cortisol. All variables (except lavage fluid SPC as %PL) correlated more closely with cortisol than GA. Morphological development of lung was also related more closely to cortisol than GA. These results suggest that functional lung maturity is attained late in gestation and that endogenous cortisol is an important physiological factor in control of fetal lung maturation.

The effect of spinal cord transection on lung development in fetal sheep.

The relationship of breathing movements to lung development in the ovine fetus was investigated by transecting the fetal cervical spinal cord above (C2-C3; n = 4) or below (C7-C8; n = 4) the phrenic nucleus at 114 days of gestation. The fetuses were delivered by hysterotomy at term and compared with a group of intact term fetuses (n = 8). Cord transection at C2-C3 resulted in a significant (P less than 0.05) reduction in wet weight of the lungs to 1.56 +/- 0.23% of body weight from 2.59 +/- 0.83% in the C7-C8 group. The diaphragms of the two groups did not differ in weight or histological appearance. Distensibility of the left lung with air at 40 cmH20 was significantly less in the C2-C3 group (6.8 +/- 3.5 ml.kg-1 body weight) than the C7-C8 group (19.9 +/- 3.7 ml.kg-1) or the intact controls (15.2 +/- 5.4 ml.kg-1). DNA content in the C2-C3 group (0.63 +/- 0.12 g) was less than in controls (0.99 +/- 0.19 g) but it was not different from the C7-C8 group (0.82 +/- 0.33 g.) DNA concentration, water content and saturated phosphatidylcholine concentration in lung tissue and lavage fluid were similar in the three groups. It is concluded that the absence of breathing movements caused by transection of the spinal cord above the phrenic nucleus is associated with retarded lung growth and maturation.

The effect of bilateral thoracoplasty on lung development in fetal sheep.

The relationship of breathing movements to lung development in the ovine fetus was investigated by partially removing ribs on each side of the chest and closing the deficiencies with silicone membranes at 114 days of gestation; the increase in compliance of the chest wall that resulted caused blunting of the amplitude of phasic negative pressures recorded in the trachea to less than 10 torr. Compared to sham operated controls (n = 5), the lungs of the thoracoplasty group (n = 5) at term weighed significantly (P less than 0.05) less, both wet (1.5 +/- 0.2 v. 2.3 +/- 0.1% of body weight) and dry (0.14 +/- 0.01 v. 0.18 +/- 0.01% of body weight. In addition, DNA content of the thoracoplasty group was less than that of the control group (0.47 +/- 0.05 mg v. 0.72 +/- 0.20 mg). Distensibility of the left lung with air at 40 cmH20 was less than in the thoracoplasty group than in controls (10.0 +/- 2.0 v. 18.9 +/- 3.0 ml.kg-1 body weight) but no differences were found in the concentrations of saturated phosphatidylcholine in lung tissue and lavage fluid, in DNA concentrations or in the amount of lung water (as % of wet weight of lung). It is concluded that phasic negative pressures of normal intensity are necessary for normal development of the fetal lungs.