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PURPOSE: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners. METHODS: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE). RESULTS: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 µg/L vs 1.18 ± 0.43 µg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 µg/L vs 13.7 ± 33.9 µg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033). CONCLUSION: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.
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Histamina/metabolismo , Carrera de Maratón , Mastocitos/enzimología , Hipotensión Posejercicio/diagnóstico por imagen , Hipotensión Posejercicio/metabolismo , Triptasas/metabolismo , Adulto , Biomarcadores , Determinación de la Presión Sanguínea , Composición Corporal , Temperatura Corporal , Estudios de Casos y Controles , Ecocardiografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Estudios ProspectivosRESUMEN
AIMS: The concept of using specific dietary components to selectively modulate the gut microbiota to confer a health benefit, defined as prebiotics, originated in 1995. In 2018, a group of scientists met at the International Scientific Association for Probiotics and Prebiotics annual meeting in Singapore to discuss advances in the prebiotic field, focussing on issues affecting functionality, research methodology and geographical differences. METHODS AND RESULTS: The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources. CONCLUSIONS: While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialization of new prebiotics with unique health benefits means that regulation must improve and remain up-to-date so as not to risk stifling research with potential health benefits for humans and other animals. SIGNIFICANCE AND IMPACT OF STUDY: This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer and guidance to better elucidate their activities in human studies.
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Investigación Biomédica/normas , Congresos como Asunto , Industria de Alimentos/normas , Prebióticos/normas , Animales , Dieta , Industria de Alimentos/legislación & jurisprudencia , Microbioma Gastrointestinal , Humanos , Prebióticos/administración & dosificación , Prebióticos/análisis , Singapur , Sociedades CientíficasRESUMEN
The effects of different dietary lipids on the fatty acid profiles of eggs produced by 20- and 54-wk-old Dekalb laying hens were investigated. The 4 treatments were based on the lipid source added to the diet: soybean oil, sunflower oil, linseed oil, or control (no added oil). The experimental design was a simple random-sample design using a 4 × 2 factorial arrangement (4 treatments and 2 ages). The fatty acid composition of the yolks of eggs produced by the laying hens was analyzed. The fatty acid profiles found in the egg yolks were the same as those provided in each diet. Eggs laid by hens fed the diet containing soybean oil had a large amount of n-6 polyunsaturated fatty acids (PUFA), whereas eggs laid by hens fed the diet containing linseed oil had the highest percentage of n-3 PUFA. A decrease in PUFA deposition in egg yolks was observed as the laying hens got older. Eggs of hens fed the diet containing linseed oil presented an n-6:n-3 ratio of 2.01 in younger chickens and 2.17 in older ones. The trans fat percentages found in the egg yolks of all treatments were very low. It was concluded that the quantity of fatty acids present in the egg yolk may be altered according to the source of lipids in the diets; the addition of linseed oil to the ration of laying hens resulted in the production of n-3-enriched eggs and excellent n-6:n-3 ratios, and the egg yolks had insignificant amounts of trans fat, irrespective of the different lipid sources added to the diets or the age of the chickens.
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Alimentación Animal , Pollos/fisiología , Yema de Huevo/química , Ácidos Grasos/metabolismo , Lípidos/administración & dosificación , Oviposición/fisiología , Animales , Ácidos Grasos/análisis , Femenino , Lípidos/farmacología , Estado Nutricional , Oviposición/efectos de los fármacos , Aceites de Plantas/farmacología , Aceite de Soja/farmacología , Aceite de GirasolRESUMEN
The modern cardiovascular imaging era has seen the introduction in clinical practice of highly innovative and performing diagnostic features. The negative side of this outstanding evolution risks to be an under-assessment of well-established classical diagnostic techniques. Thereby, to support the actual relevance of a properly executed chest X-ray, this article describes two paradigmatic cases of exceptional cardiac abnormalities, in which X-rays played a key diagnostic role.
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Electrocardiografía , Aneurisma Cardíaco/diagnóstico por imagen , Quiste Mediastínico/diagnóstico por imagen , Pericarditis/diagnóstico por imagen , Telemedicina , Tomografía Computarizada por Rayos X/métodos , Adulto , Enfermedad Crónica , Diagnóstico Diferencial , Aneurisma Cardíaco/diagnóstico , Aneurisma Cardíaco/cirugía , Humanos , Masculino , Quiste Mediastínico/complicaciones , Quiste Mediastínico/cirugía , Persona de Mediana Edad , Pericarditis/etiología , Pericarditis/cirugía , Resultado del TratamientoRESUMEN
A lot of epidemiological studies have shown that physical activity can prevent the development of chronic diseases such as obesity, diabetes, osteoporosis, cardiovascular diseases and cancer Physical activity can be classified by rate of energy expenditure: light intensity 1-3 METs, moderate 3-6 MET's, vigorous 6-9 MET's, very vigorous >9 MET's. Although it is evident that an active lifestyle has many health benefits and sedentary habits are associated with an increased risk of chronic diseases, the debate still continues as to how much, what type, how often, at what intensity physical activity should be performed to have a positive effect on the health. Reduction of cardiovascular risk is observed already with a moderate intensity physical activity (3-6METs); whilst to improve physical fitness training must be more vigorous (6-9 METs). In conclusion good goals are achieved when moderate levels of physical activity are performed on a regular basis (at least 3- 5 days a week for 30 minutes). But to reach also countable results on body weight control the frequency should be 5-7 days a week for 60 minutes.
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Enfermedad Crónica/prevención & control , Ejercicio Físico , Adulto , Peso Corporal , Enfermedades Cardiovasculares/prevención & control , Ensayos Clínicos como Asunto , Diabetes Mellitus/prevención & control , Progresión de la Enfermedad , Metabolismo Energético , Ejercicio Físico/fisiología , Femenino , Humanos , Estilo de Vida , Masculino , Enfermedades Musculoesqueléticas/prevención & control , Neoplasias/prevención & control , Obesidad/prevención & control , Aptitud Física , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVES: This study aimed to investigate whether measures of cardiopulmonary fitness and relative exercise intensity were associated with high sensitivity cardiac troponin T (cTnT) rise after a road marathon. METHODS: Fifty-two marathon runners (age 39±11 years, body mass 76.2±12.9kg, height 1.74±0.09m) attended the laboratory between 2 and 3 weeks prior to attempting the Brighton Marathon, UK. Running economy at 10kmh-1 (RE10) and race pace (RERP), ventilatory threshold (VT) and VO2max tests were completed. CTnT was measured within 48h prior to the marathon and within 10min of completing the marathon, using a high sensitivity assay. Heart rates (HR) were recorded throughout the marathon. RESULTS: Runners demonstrated a significant increase in cTnT over the marathon (pre-race 5.60±3.27ngL-1, post-race 74.52±30.39ngL-1, p<0.001). Markers of endurance performance such as running economy (10kmh-1 223±18mlkg-1km-1; race pace 225±22mlkg-1km-1), VT (38.5±6.4mlkg-1min-1) and VËO2max (50.9±7.7mlkg-1min-1) were not associated with post-race cTnT. Runners exercise intensity correlated with post-race cTnT (mean HR %VT 104±5%, r=0.50; peak HR %VT 118±8%, r=0.68; peak HR %VËO2max 96±6, r=0.60, p<0.05) and was different between the low, medium and high cTnT groups (p<0.05). CONCLUSIONS: CTnT increases above reference limits during a marathon. Magnitude of cTnT rise is related to exercise intensity relative to ventilatory threshold and VËO2max, but not individuals' absolute cardiopulmonary fitness, training state or running history.
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Capacidad Cardiovascular , Carrera/fisiología , Troponina T/sangre , Adulto , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Resistencia FísicaRESUMEN
Pendrin, first identified in 1997, belongs to a superfamily of anion transporters localized in the thyroid gland, inner ear and kidney. Immunohistochemical studies have shown that pendrin is expressed at the apical surface of follicular thyroid cells, where it acts as a Cl-/I- exchanger regulating the chloride transport from the cytoplasm to the colloid space. In the inner ear, pendrin has been found in the stria vascularis of the cochlea and in the endolymphatic duct and sac, where it functions as a Cl- /HCO-3 exchanger. Finally, pendrin is expressed in the kidney, where it is localized in the apical membrane of type-B intercalated cells and non-A, non-B intercalated cells of the cortical collecting ducts and connecting tubules, where it again acts as a Cl /HCO-3 exchanger regulating the acid-base status and chloride homeostasis. Pendrin is encoded by the PDS gene, which is mapped on chromosome 7 (7q22-31.1). Mutations of PDS lead to the Pendred syndrome, a genetic disorder transmitted as an autosomal recessive trait characterized by sensorineural deafness and goiter. It is reasonable to hypothesize that patients affected by Pendred's syndrome may have disturbances of renal function, especially in the regulation of electrolytes and acid-base balance in stress conditions.
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Proteínas de Transporte de Membrana , Oído Interno/química , Bocio/genética , Pérdida Auditiva Sensorineural/genética , Humanos , Riñón/química , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/aislamiento & purificación , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/fisiología , Mutación , Insuficiencia Renal/genética , Transportadores de Sulfato , Síndrome , Glándula Tiroides/químicaRESUMEN
Advances in anti-platelet therapy and improvement of stent deployment techniques have improved the safety and efficacy of stenting in the setting of ST-segment-elevation myocardial infarction (STEMI). However, in randomized trials, routine coronary stenting does not reduce mortality and re-infarction, compared to balloon angioplasty. Further, the benefits in target vessel revascularization seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future large randomized trials are needed to evaluate whether this strategy has a significant impact on outcome, and to provide a cost-benefit analysis of the unrestricted use of drug-eluting stents in this high-risk subset of patients. The additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pre-treatment may confer further advantages by early recanalization and shorter ischaemic time, particularly in high-risk patients. Further randomized trials are needed to clarify the potential benefits from early abciximab administration and the potential role of small molecules in primary angioplasty for STEMI.
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Angioplastia Coronaria con Balón/métodos , Anticuerpos Monoclonales/uso terapéutico , Anticoagulantes/uso terapéutico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Infarto del Miocardio/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents , Abciximab , Humanos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/cirugía , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.
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Antiparkinsonianos/uso terapéutico , Ergolinas/uso terapéutico , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Cabergolina , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive nerve terminal profiles and the glucocorticoid receptor-immunoreactive nuclear profiles have been characterized in the parvocellular part of the paraventricular hypothalamic nucleus of the adult (3 month) and the old (24 month) male rat. The phenylethanolamine-N-methyltransferase-, neuropeptide Y- and glucocorticoid receptor-immunoreactive structures have been demonstrated by means of the indirect immunoperoxidase procedure and analysed in a quantitative way by means of morphometrical and microdensitometrical approaches using both semiautomatic and automatic image analysis. During aging there is (a) a marked reduction in the number of neuropeptide Y-immunoreactive profiles, a moderate reduction of phenylethanolamine-N-methyltransferase-immunoreactive profiles and a small reduction in the number of glucocorticoid receptor-immunoreactive profiles without a significant change in the evenness of distribution of such profiles as evaluated by means of Gini's index; (b) a loss of the significant correlation in the distribution of the glucocorticoid receptor- and phenylethanolamine-N-methyltransferase-immunoreactive profiles at the two most caudal levels analysed (A5150 and A5270 micron) while a significant correlation developed between these two distributions at a more rostral level (A5400 micron); (c) a substantial decline in the overlap area of the glucocorticoid receptor- and phenylethanolamine-N-methyltransferase-immunoreactive profiles at four out of five rostrocaudal levels analysed; (d) a marked reduction in the density-intensity of the neuropeptide Y-immunoreactive profiles and a small significant reduction in the density-intensity of the phenylethanolamine-N-methyltransferase-immunoreactive profiles without any associated changes in the intensity of the glucocorticoid receptor-immunoreactive profiles. Furthermore, three-dimensional reconstructions of the overall distribution of the glucocorticoid receptor-, phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive structures have been made in the paraventricular hypothalamic nucleus of the adult male rat. The present results indicate a reduction of neuropeptide Y- and phenylethanolamine-N-methyltransferase-immunoreactive nerve terminal profiles in the parvocellular part of the paraventricular hypothalamic nucleus during aging. These results may in part reflect a loss of neuropeptide Y-like peptides in phenylethanolamine-N-methyltransferase-immunoreactive nerve terminals of the paraventricular hypothalamic nucleus, favouring our view that during aging the modulatory peptides may be lost, leading to a loss of
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Envejecimiento/metabolismo , Epinefrina/metabolismo , Neuropéptido Y/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Feniletanolamina N-Metiltransferasa/metabolismo , Receptores de Glucocorticoides/metabolismo , Animales , Epinefrina/fisiología , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Masculino , Neuropéptido Y/fisiología , Núcleo Hipotalámico Paraventricular/fisiología , Feniletanolamina N-Metiltransferasa/fisiología , Ratas , Ratas Endogámicas , Receptores de Glucocorticoides/fisiologíaRESUMEN
Serum drug concentration monitoring can be an invaluable aid to patient management, particularly in certain pathological conditions when individualisation of dosage is particularly critical. To be clinically useful, however, drug levels must be interpreted in the context of all factors that could influence the correlation between the concentration of the drug in plasma and the intensity of action. Several such factors may be operating in acute and chronic disease states. For example, a number of pathological conditions are associated with marked changes in the fraction of free, pharmacologically active drug in plasma and this will result in disruption of the normal relationship between total serum drug level and effect, as seen for phenytoin in uraemia. An altered response to a given serum drug level in disease states may also be caused by changes in tissue distribution, by abnormal accumulation of pharmacologically active metabolites in plasma or by changes in end-organ responsiveness. The latter are best illustrated by the altered sensitivity to digoxin in patients with various conditions, including hypokalaemia and thyroid disease. In addition to the factors listed above, consideration should also be given to potential interactions with concomitantly used drugs and to the possibility of analytical errors, especially in view of the evidence that the performance of otherwise reliable drug assays may be grossly impaired in certain diseases (e.g. uraemia), due to abnormal plasma composition and/or accumulation of interfering metabolites. In view of these complexities, a correct interpretation of serum drug levels requires a good knowledge of clinical pharmacology and a close collaboration between physician and laboratory. In any case, serum drug concentrations, like other laboratory tests, are not a substitute for careful patient observation, and any decision about drug treatment should be primarily based upon evaluation of the clinical state and, whenever possible, direct measurement of drug effects.
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Enfermedad/metabolismo , Preparaciones Farmacéuticas/metabolismo , Enfermedad Aguda , Biotransformación , Proteínas Sanguíneas/metabolismo , Enfermedad Crónica , Interacciones Farmacológicas , Humanos , Preparaciones Farmacéuticas/sangre , Unión Proteica , Distribución Tisular , Uremia/metabolismoRESUMEN
The subcellular distribution of ornithine decarboxylating activity in nucleus caudatus putamen, hippocampus, parietal cerebral cortex, cerebellum and hypothalamus of male rat brain has been investigated. The 7000 g supernatant (cytosolic fraction), the 7000 g sediment and the 700 g sediment (nuclear fraction) were incubated with (1 ? (14)C )- labeled ornithine and the (14)CO(2) released was measured. The results demonstrated that 70-75% of the decarboxylating activity was present in the nuclear fraction (700 g sediment), 10% in the 7000 g sediment and 10-20% was found in the cytosol. With more vigorous homogenization (30 strokes instead of 10) an increase in the 7000 g supernatant was obtained. The activity increased linearly with time and amount of tissue added for the 770 g sediment and the 7000 g sediment. A dose-dependent inhibition was found in the whole brain in nuclear and cytosolic fractions with ?-difluoromethylornithine. In all brain areas the nuclear decarboxylating activity was inhibited to 90% with 2.5 mM of ?-difluoromethylornithine except in the hypothalamus, where the inhibition amounted to 20%. An equimolar formation of (14)CO(2) and putrescine was found in the nuclear fraction of all brain regions except the nucleus caudatus putamen and the cerebral cortex, where (14)CO(2) formation exceeded that of putrescine with about 50% suggesting that part of the putrescine is rapidly converted into higher polyamines. It is concluded that with the exception of hypothalamus the major decarboxylating activity in the above mentioned brain regions is ornithine decarboxylase activity (ODC, EC 4.1.1.17) and that the most prominent subcellular localization of this enzyme is the nucleus.
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The possibility of using taxonomic techniques to classify neuronal populations was explored. In particular, coefficients of similarity such as the Canberra metric and the Shannon diversity index were examined. The theoretical work in the field of numerical classification was adapted to the aim of characterizing various brain areas in classes according to their transmitter contents. The study of neuropeptide distribution in 15 brain areas clearly demonstrated that, of these, the hypothalamus is particularly noteworthy due to its higher neuropeptide content.
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Some methodological aspects of the intracerebral microdialysis technique have been investigated: the existence of a pressure gradient at the level of the dialyzing membrane, the substance diffusion from the microdialysis probe and the extent of tissue damage induced by the implantation of the microdialysis probe. At the level of the dialyzing membrane a rough balance between the pressure inside the probe and the one present in the extracellular fluid compartment has been observed. The pattern of substance diffusion in the tissue showed a large variability depending on the substance used and the experimental conditions. Relevant deductions can be made by the use of labeled markers. By means of this approach, the diffusion pattern of tritiated ganglioside GM1 in the tissue around the probe could be shown to follow a biexponential pattern, suggesting a two-step process of diffusion. The degree of tissue damage induced by the microdialysis probe was assessed by analyzing the glial reaction, and was measured by means of semiquantitative immunocytochemistry of glial fibrillary acidic protein immunoreactivity. Only a limited area of neuronal damage was observed in the region surrounding the microdialysis probe. The amount of glial reaction after probe implantation was shown to be comparable with that induced by the implantation of a microinjection cannula.
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A morphological and functional characterization of the four-vessel occlusion model of transient (30 min) forebrain ischemia has been carried out. The rats were classified as fully ischemic when an isoelectric pattern of electroencephalographic activity was present within 5 min of the occlusion of carotid arteries. Otherwise they were considered as partially ischemic rats. The modifications of cerebral blood content during and after the ischemic insult were assessed by a histochemical method which visualizes red blood cells in cerebral vessels. The periods of increase and decrease of red blood cell content were found to correspond to previous reports of post-ischemic hyper- and hypoperfusion. Neuronal damage was assessed by a quantitative analysis of Nissl stained preparations of cingulate cortex, dorsal hippocampus and striatum. The signs of morphological damage were quantified by means of computer-assisted image analysis of Nissl preparations. The highest vulnerability to the ischemic insult was demonstrated in the pyramidal layer of the hippocampal CA1 field and in the lateral striatum. Arterial blood pressure measurements were performed during the ischemic and post-ischemic periods, demonstrating a peak increase of arterial blood pressure within 2 min after carotid artery occlusion, followed by a slow decrease towards basal levels during the ischemic period and a full recovery within 15 min of reperfusion. Ischemic rats were tested in a neurological test battery and in a passive avoidance task. While a full recovery of the relatively simple tasks of the neurological test battery was attained within 14 days of reperfusion, a highly significant impairment of passive avoidance behavior was still present 15 days after the ischemic insult. Finally, a discriminant analysis was applied to separate, on the basis of non-invasive techniques (neurological tests and hot plate), the group of completely ischemic rats from that of partially ischemic rats.
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Uridine was administered in the drinking water (0.5 mg/ml) in adult 6 month-old rats for 6 months. The mean daily dose of uridine was 12.5 mg/rat. The effects of this treatment on tyrosine hydroxylase, galanin, somatostatin, neuropeptide Y and cholecystokinin-like immunoreactivities were studied by means of semiquantitative immunocytochemistry using the peroxidase-antiperoxidase procedure in combination with image analysis. A decrease of somatostatin, cholecystokinin and galanin-like immunoreactivities in nerve terminals was observed in various brain areas of 12 month-old animals compared with 3 month-old animals, while the levels of tyrosine hydroxylase-like immunoreactivity were unchanged. Uridine-treated animals showed a decrease of galanin, neuropeptide Y and cholecystokinin-like immunoreactivities in nerve terminals of some diencephalic areas and an increase of cholecystokinin-like immunoreactivity in nerve terminals of most of the telencephalic brain areas in comparison with vehicle treated animals of the same age. It is suggested that the pyrimidine nucleoside uridine can affect the synthesis and/or degradation of mRNAs involved in the synthesis of neuropeptides via direct nuclear actions and/or indirect actions involving effects on receptor activated phosphoinositide metabolism. Uridine offers a new way to modulate central peptide synapses.
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The effects of gangliosides have been studied in two models of metabolic insult (insulin-induced hypoglycemia and transient forebrain ischemia) of the central nervous system. In the severe hypoglycemia experiments lactate extracellular fluid levels were evaluated by means of a microdialysis probe implanted in the frontoparietal cortex. Ganglioside GM1, given either peripherally (10 mg/kg, i.p.) or intracerebrally (2 x 10(?4) M, via the microdialysis probe) 2 h before insulin injection, was able to reduce the decay of the perfusate levels of lactate induced by the insulin injection. In the same animal model peripheral, but not central, administration of GM1 reduced the hypoglycemia-induced increase of cerebral blood flow and increased the survival time observed after the insulin injection. In the experiments on transient forebrain ischemia, a GM1 derivative, AGF2 (5 mg/kg/day, i.p.), was administered chronically, starting 5 days before or the day after the ischemic insult. With both treatment schedules a similar protective effect was observed in a neurological test battery and in the step-through latency in a passive avoidance test.
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The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.