RESUMEN
BACKGROUND AND PURPOSE: Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. EXPERIMENTAL APPROACH: In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg.kg(-1)) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. KEY RESULTS: ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. CONCLUSIONS AND IMPLICATIONS: The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of 'reintoxication' whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or 'flashbacks'.
Asunto(s)
Adipocitos/metabolismo , Hormona Adrenocorticotrópica/farmacología , Dronabinol/análogos & derivados , Privación de Alimentos/fisiología , Hormona Adrenocorticotrópica/fisiología , Animales , Células Cultivadas , Dronabinol/sangre , Glicerol/metabolismo , Lipólisis , Masculino , Ratas , Ratas WistarRESUMEN
Previous work has demonstrated that in the guinea pig, chronic prenatal ethanol exposure throughout gestation can result in deficits in spatial learning in the Morris water maze and impaired hippocampal long-term potentiation (LTP). The behavioural effects are known to be dose dependent because water maze deficits occur at a dose of 4 g ethanol/kg maternal body weight/day, but not at a dose of 3 g/kg/day, administered throughout gestation. It is possible that the gradual, progressive development of tolerance to ethanol throughout gestation limits ethanol toxicity, especially for lower doses of ethanol. The present study examined whether neurobehavioural deficits are produced by prenatal ethanol exposure at a dose of 3 g/kg/day, administered only during the brain growth spurt (BGS), a regimen designed to limit the development of ethanol tolerance. Pregnant guinea pigs [term, about gestational day (GD) 68] received oral administration of ethanol (1.5 g/kg maternal body weight/day on GD 43 and 44 and then 3 g/kg maternal body weight/day from GD 45 to 62), isocaloric-sucrose/pair-feeding, or water. Offsprings were studied between postnatal days (PD) 40 and 80. The maternal blood ethanol concentration (BEC) on GD 57 or 58, at 1 h after the daily dose, was 245+/-19 mg/dl (n=7). This BGS--prenatal ethanol exposure regimen did not affect spatial learning performance in the Morris water maze over a 7-day test period or in the LTP recorded in the CA1 region of the hippocampus. Thus, even when limiting the development of ethanol tolerance seen with chronic ethanol treatment throughout gestation, ethanol exposure during the BGS does not result in deficits in the behavioural and electrophysiological measures of hippocampal integrity assessed in the present study. These data indicate that in the guinea pig, the BGS may not constitute a critical period of vulnerability for ethanol-induced deficits in spatial learning or hippocampal synaptic plasticity in young adult offspring.
Asunto(s)
Etanol/farmacología , Hipocampo/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Conducta Espacial/efectos de los fármacos , Animales , Esquema de Medicación , Reacción de Fuga/efectos de los fármacos , Etanol/sangre , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Femenino , Cobayas , Hipocampo/embriología , Hipocampo/fisiopatología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Complicaciones del Embarazo/inducido químicamente , Complicaciones del Embarazo/fisiopatología , Factores de TiempoRESUMEN
Whole grains are important dietary constituents as they provide a plethora of nutrients and protective chemicals that may have synergistic actions in promoting health. Regular consumption of wholegrain foods has been associated with a reduced risk of several chronic diseases such as CHD and certain cancers, although their exact role in disease prevention is not yet fully elucidated. Studies reporting levels of whole grain consumption reveal that those subjects who include higher levels of whole grain foods in their diets also have many other favourable dietary and lifestyle practices. While the actions of these practices and whole grains may not be mutually exclusive, these variables do not appear to explain the reduction in risk of disease observed for high-whole grain consumers. Actual whole grain consumption levels are extremely low and many practical barriers exist to consumer uptake of these foods. Effective communication of the whole grain health message is an important strategy to increase awareness of the importance of whole grains in the diet. Increasing the variety and availability of acceptable wholegrain foods is also important. Whole grain consumption at breakfast can have an important impact on total daily nutrient intakes. This simple dietary modification is potentially relatively easy to achieve and could greatly contribute to increased whole grain intake for many individuals.
Asunto(s)
Fibras de la Dieta/administración & dosificación , Grano Comestible , Ingestión de Energía , Conducta Alimentaria , Ingestión de Alimentos , Manipulación de Alimentos/métodos , Alimentos Orgánicos , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud , Cardiopatías/prevención & control , Humanos , Neoplasias/prevención & control , Política NutricionalRESUMEN
In the hippocampus, the CA1 region is selectively vulnerable to the effects of chronic prenatal ethanol exposure. In the guinea-pig, the number of CA1 pyramidal cells is decreased after chronic prenatal ethanol exposure. We tested the hypotheses that chronic prenatal ethanol exposure (through maternal ethanol ingestion) results in impairments in spatial learning and short- and long-term plasticity in the CA1 region of the postnatal guinea-pig hippocampus. Timed, pregnant guinea-pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric sucrose/pair-feeding, or water throughout gestation. Offspring were studied between postnatal days 40 and 80. In the Morris water maze, animals exposed to ethanol prenatally showed slower acquisition of an escape response to a hidden platform over 5 days of training. The amplitude of the field excitatory postsynaptic potential in the CA1 region in response to contralateral CA3 stimulation was decreased in offspring exposed to ethanol prenatally. Two forms of short-term plasticity (paired-pulse and frequency facilitation) were unaffected by chronic prenatal ethanol exposure. Long-term potentiation (LTP) in response to high-frequency CA3 stimulation was induced reliably and maintained over 60 min in isocaloric-sucrose and water control animals. However, LTP failed to be induced in the CA1 area of the hippocampus in prenatal ethanol-exposed offspring. These data show that chronic prenatal ethanol exposure, through maternal ethanol administration, impairs spatial performance and LTP in CA1 neurons. Hippocampal dysfunction could contribute importantly to the cognitive and behavioural deficits resulting from chronic prenatal ethanol exposure.
Asunto(s)
Trastornos del Sistema Nervioso Inducidos por Alcohol/fisiopatología , Etanol/efectos adversos , Trastornos del Espectro Alcohólico Fetal/fisiopatología , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Potenciación a Largo Plazo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Trastornos del Sistema Nervioso Inducidos por Alcohol/patología , Animales , Animales Recién Nacidos , Enfermedad Crónica , Estimulación Eléctrica , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Trastornos del Espectro Alcohólico Fetal/patología , Cobayas , Hipocampo/patología , Potenciación a Largo Plazo/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Embarazo , Complicaciones del Embarazo/inducido químicamente , Complicaciones del Embarazo/fisiopatología , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Factores Sexuales , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
This paper provides the first report of spatial learning in guinea pigs using the Morris water maze (MWM). Male and female guinea pigs were trained for 5 consecutive days (8 trials/day; acquisition phase) in either the visible (cued) or the hidden (non-cued) platform version of the MWM. In both tests, guinea pigs learned to navigate to the escape platform, as indicated by a decrease in escape latency over the 5 training days. There were no sex differences in either test version. A comparison of guinea pigs and male Wistar rats showed that performance during acquisition training was not different for the two species in the visible platform test, but rats performed better during the early training days in the hidden platform test. A retention test (probe trial) was given 5 days after the last acquisition training day. Again, there was no sex difference, and no difference between guinea pigs and rats. Finally, acquisition of a new escape response to a shifted platform location was equivalent for rats and guinea pigs of both sexes. These results demonstrate that guinea pigs show robust cued and non-cued learning in the MWM. Both acquisition and retention performance in guinea pigs is similar to that in rats, even though rats appear to have a slight advantage in the acquisition of non-cued, spatial information in this test. We conclude that the MWM provides a valuable paradigm to assess behavior and learning/memory in the guinea pig.
Asunto(s)
Atención , Aprendizaje por Laberinto , Recuerdo Mental , Orientación , Animales , Señales (Psicología) , Reacción de Fuga , Femenino , Cobayas , Masculino , Ratas , Ratas Wistar , Retención en Psicología , Factores Sexuales , Especificidad de la EspecieRESUMEN
High field (400 and 600 MHz) proton NMR spectroscopy has been employed to investigate the thermally-induced autoxidation of glycerol-bound polyunsaturated fatty acids present in intact culinary frying oils and fats. Heating of these materials at 180 degrees C for periods of 30, 60 and 90 min. generated a variety of peroxidation products, notably aldehydes (alkanals, trans-2-alkenals and alka-2,4-dienals) and their conjugated hydroperoxydiene precursors. Since such aldehydes appear to be absorbed into the systemic circulation from the gut in vivo, the toxicological significance of their production during standard frying practices is discussed.
Asunto(s)
Aldehídos/análisis , Grasas Insaturadas en la Dieta/análisis , Grasas de la Dieta/análisis , Calor , Espectroscopía de Resonancia Magnética , Análisis de los Alimentos , Peroxidación de Lípido , Oxidación-ReducciónRESUMEN
The oxidative deterioration of glycerol-bound polyunsaturated fatty acids (PUFAs) in culinary oils and fats during episodes of heating associated with normal usage (30-90 min at 180 degrees C) has been monitored by high field 1H NMR spectroscopy. Thermal stressing of PUFA-rich culinary oils generated high levels of n-alkanals, trans-2-alkenals, alka-2,4-dienals and 4-hydroxy-trans-2-alkenals via decomposition of their conjugated hydroperoxydiene precursors, whereas only low concentrations of selected aldehydes were produced in oils with a low PUFA content, lard and dripping when subjected to the above heating episodes. Samples of repeatedly used, PUFA-rich culinary oils obtained from restaurants also contained high levels of each class of aldehyde. The dietary, physiological and toxicological ramifications of the results obtained are discussed.
Asunto(s)
Aldehídos/análisis , Grasas/química , Ácidos Grasos Insaturados/química , Calor , Peroxidación de Lípido , Aceites de Plantas/química , Espectroscopía de Resonancia MagnéticaRESUMEN
1. Arterial blood pressure, heart rate and cardiac contractility were measured in pentobarbitone-anaesthetized mongrel dogs and in conscious, instrumented dogs. 2. In anaesthetized dogs (n = 5), dose-response curves were obtained by intravenous infusion of increasing doses of dopexamine (5-20 micrograms kg-1 min-1). Infusions were administered three times to each animal to determine whether the responses were reproducible. Dopexamine increased heart rate and myocardial contractility and decreased blood pressure. The dose-response curves for dopexamine did not differ significantly over time. 3. In a second group of dogs (n = 6), dose-response curves (5-20 mg kg-1 min-1) were obtained as above and repeated after the administration of amitriptyline (2 mg kg-1, i.v.). Amitriptyline caused a non-significant reduction in the inotropic and chronotropic responses to dopexamine. 4. Control dose-response curves for dopexamine (5-50 micrograms kg-1 min-1) were similarly obtained in a third group of dogs (n = 6), and repeated after bilateral vagotomy and sympathetic denervation of the heart. In these animals, a third dose-response curve for dopexamine was obtained after the administration of ICI 118551 (0.2 mg kg-1, followed by 0.2 mg kg-1 h-1). The chronotropic response to dopexamine was significantly reduced after cardiac denervation. There was a small, non-significant reduction in the inotropic and depressor responses after denervation. Administration of ICI 115881 significantly reduced both the inotropic and chronotropic response to dopexamine and caused a non-significant reduction in the depressor response. 5. The effect of raclopride (0.2 mumol kg-1, p.o.) was investigated by comparison of the dose-response curves for dopexamine in a control group of dogs (n = 6) to those obtained in dogs which had been pretreated with raclopride (n = 5). Raclopride had no significant effect on the cardiovascular responses to dopexamine. 6. In conscious, instrumented dogs (n = 5), pretreated with raclopride, dose-related positive inotropic and chronotropic and depressor responses to dopexamine infusions were recorded. The chronotropic responses in conscious animals were significantly greater than those in the anaesthetized animals.7. The results of this study indicate that both the positive inotropic and chronotropic actions of dopamine are due to a combination of direct, Beta2-adrenoceptor-mediated effects and the baroreceptor reflex response to the depressor action of the drug.
Asunto(s)
Amitriptilina/farmacología , Presión Sanguínea/efectos de los fármacos , Dopamina/análogos & derivados , Frecuencia Cardíaca/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacología , Amitriptilina/administración & dosificación , Anestesia , Animales , Perros , Dopamina/administración & dosificación , Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Infusiones Intravenosas , Presorreceptores/efectos de los fármacos , Presorreceptores/metabolismo , Propanolaminas/administración & dosificación , Propanolaminas/farmacología , Racloprida , Reproducibilidad de los Resultados , Salicilamidas/farmacología , Estimulación QuímicaRESUMEN
1. This study was designed to assess the effects of exogenous neuropeptide Y (NPY) on cardiac contractility and coronary blood flow (CBF) in anaesthetized dogs and to evaluate the effect of NPY on the responses to sympathetic and parasympathetic stimulation and to inotropic agents. 2. Bolus doses of NPY (500 micrograms), administered via the femoral vein, increased mean arterial pressure. The pressor effect was associated with reductions in heart rate, CBF and cardiac contractility. 3. The effects of NPY (500 micrograms) on contractility and CBF were compared with that of vasopressin (VP) (1 unit). For similar reductions in CBF, NPY and VP had similar negative inotropic effects. Thus, it is likely that the negative inotropic response to NPY is not due to a direct effect of NPY on the heart muscle but is largely due to coronary vasoconstriction. 4. In the presence of NPY (500 micrograms, i.v.), there was an inhibition of the positive inotropic response to stimulation of the left cardiac sympathetic nerve (2 or 5 Hz, 0.05 ms). NPY also inhibited the negative inotropic response and chronotropic response to vagal stimulation (2, 3 or 5 Hz, 0.05 ms). 5. Dose-response curves were obtained for the inotropic, chronotropic and pressor responses to cumulative infusions of noradrenaline (n = 6) and dobutamine (n = 6). NPY had no effect on these dose-response curves. 6. The effect of NPY on the responses to salbutamol and impromidine was assessed. NPY did not alter the positive inotropic, chronotropic or depressor responses to these agonists. 7. Our results indicate that NPY has direct, postsynaptic vasoconstrictor activity and the reduction in myocardial contractility and heart rate are due to a combination of coronary vasoconstriction, baroreceptor reflex activation and presynaptic inhibition of transmitter release from sympathetic nerves. The welldocumented inhibitory effect of NPY on the chronotropic response to parasympathetic stimulation was confirmed and similar inhibition of the inotropic response to both sympathetic and parasympathetic stimulation was demonstrated. Since there was no modulation of the inotropic effects of exogenous alpha- and beta-adrenoceptor or H2-receptor agonists, it is concluded that the effects of NPY on myocardial contractility are exerted presynaptically.
Asunto(s)
Circulación Coronaria/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Neuropéptido Y/farmacología , Albuterol/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Dobutamina/farmacología , Perros , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Guanidinas/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Imidazoles/farmacología , Impromidina , Norepinefrina/farmacología , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Sistema Nervioso Simpático/fisiología , Nervio Vago/fisiología , Vasopresinas/farmacologíaRESUMEN
Pea (Pisum sativum) ornithine transcarbamylase (OTC) was purified to homogeneity from leaf homogenates in a single-step procedure, using delta-N-(phosphonacetyl)-L-ornithine-Sepharose 6B affinity chromatography. The 1581-fold purified OTC enzyme exhibited a specific activity of 139 micromoles citrulline per minute per milligram of protein at 37 degrees C, pH 8.5. Pea OTC represents approximately 0.05% of the total soluble protein in the leaf. The molecular weight of the native enzyme was approximately 108,200, as estimated by Sephacryl S-200 gel filtration chromatography. The purified protein ran as a single molecular weight band of 36,500 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results suggest that the pea OTC is a trimer of identical subunits. The overall amino acid composition of pea OTC is similar to that found in other eukaryotic and prokaryotic OTCs, but the number of arginine residues is approximately twofold higher. The increased number of arginine residues probably accounts for the observed isoelectric point of 7.6 for the pea enzyme, which is considerably more basic than isoelectric point values that have been reported for other OTCs.
Asunto(s)
Aminoácidos/análisis , Arginina/análisis , Ornitina Carbamoiltransferasa/química , Ornitina Carbamoiltransferasa/aislamiento & purificación , Pisum sativum/enzimología , Punto Isoeléctrico , Ornitina Carbamoiltransferasa/metabolismo , Hojas de la Planta/enzimología , Proteínas de Vegetales Comestibles/química , Proteínas de Vegetales Comestibles/aislamiento & purificación , Proteínas de Vegetales Comestibles/metabolismo , Tallos de la Planta/enzimologíaRESUMEN
Originally isolated fromDipterocarpus kerrii, the two previously uncharacterized sesquiterpenes,1 and20, were synthesized from α-gurjunene. A novel process involvingm-chloroperoxybenzoic acid oxidation ofα-gurjunene produced20 in one step. Spectroscopic studies determined that the diene moiety in20 is nonconjugated and also found the C-4 tertiary alcohol center to have theα-configuration, while the other stereocenters have configurations matching the corresponding centers inα-gurjunene. Bioassays with termites demonstrated that20 was more toxic than1, resulting in a 50% mortality in seven days when offered toNeotermes ?dalbergiae on filter papers. The chemicals appear to result from biotransformation ofα-gurjunene. In view of its similarity to the known sesquiterpeneγ-gurjunene, we suggest that20 be referred to asγ-gurjunenol.
RESUMEN
STUDY OBJECTIVE: The aim of the study was to evaluate the effect of chronic digoxin therapy on cardiac sensitivity to isoprenaline. DESIGN: Responses to isoprenaline were examined in both conscious and anaesthetised dogs pretreated with digoxin, and compared with conscious or anaesthetised controls with no digoxin pretreatment. Isoprenaline infusion (0.001-0.1 micrograms.kg-1.min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero. SUBJECTS: Mongrel dogs of either sex (15-25 kg) were used in the experiments, done under anaesthetic. They were divided into three groups (n = 6 per group): group A were controls; groups B and C were pretreated with digoxin 500-750 micrograms.d-1, for 14 d (B) and 7 d (C). For the experiments in conscious animals, six mongrel dogs (25-30 kg) and two greyhounds (25-30 kg) were used; group D (n = 6) were treated with digoxin for 20-40 d; group E (n = 2) were treated for 7 d. MEASUREMENTS AND RESULTS: Heart rate, blood pressure and myocardial contractility (dP/dt: integrated isometric tension) were measured during isoprenaline infusion. Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal. When the pretreatment period was reduced to 7 d there was no change in any of the responses to isoprenaline. In conscious dogs there was also a significant increase in inotropic sensitivity to isoprenaline after digoxin withdrawal, but this was not so marked as in anaesthetised dogs. In conscious dogs chronotropic sensitivity to isoprenaline was also increased. CONCLUSIONS: It is possible that the inotropic effect maintained during the 2 weeks of digoxin treatment may cause substantial withdrawal of sympathetic tone to the heart, with a consequent increase in beta adrenoceptor number or sensitivity, which could be detected a week after digoxin withdrawal.
Asunto(s)
Digoxina/farmacología , Corazón/efectos de los fármacos , Isoproterenol/farmacología , Anestesia General , Animales , Presión Sanguínea/efectos de los fármacos , Estado de Conciencia , Digoxina/administración & dosificación , Perros , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Contracción Miocárdica/efectos de los fármacos , Estimulación QuímicaRESUMEN
Four sesquiterpenoids (2, 4, 7, and9) have been isolated and characterized from the termiticidal fraction ofDipterocarpus kerrii resin. The major constituent of this resin is α-gurjunene (1).