RESUMEN
BACKGROUND: Competitive protein binding radioimmunoassay (CPB-RIA) is a principal method for quantifying serum digoxin concentration. The accuracy of this method is critically dependent on factors that influence the substitution reaction between unlabelled (Q) antigen (digoxin) with (125)I-labelled antigen (M) bound to anti-digoxin antibody (P). We studied the influence of initial concentration of M, ionic strength, and viscosity on the substitution reaction between M and Q. In addition, we propose a kinetic model for this reaction. METHODS: We used a commercially available CPB-RIA for digoxin, a gamma counter, and a viscosimeter to study the effect of initial concentration of M, ionic strength, viscosity, and temperature on the substitution reaction between M and Q. Data were analyzed using Statistica software. RESULTS: The apparent rate constant for the reaction between M and Q in the formation of PM is dependent on the initial concentration of M, and the ionic strength, viscosity, and temperature of the reaction medium, and independent of the concentration of Q. CONCLUSION: A kinetic model for the displacement of the (125)I-digoxin by the digoxin in its union to a specific antibody is proposed. Such model adjusts satisfactorily to the results and allows the prediction of the calibration curves of RIA (activity bound to the antibody vs. concentration of digoxin) showing the influence of the concentration of both species, the time of incubation, the viscosity and the ionic strength of the medium, on the sensitivity of the method of RIA on which the analytical determination of the digoxin is based.
Asunto(s)
Digoxina/análisis , Modelos Biológicos , Reacciones Antígeno-Anticuerpo , Unión Competitiva , Calibración , Radioisótopos de Yodo , Cinética , Modelos Teóricos , Concentración Osmolar , Valor Predictivo de las Pruebas , Radioinmunoensayo , Temperatura , ViscosidadRESUMEN
The influence of initial concentrations, ionic strength, viscosity and temperature on the substitution reaction of 125I-triiodothyronine (T3) (M) by unlabelled T3 (Q) in the immunocomplex PM (P = anti-T3 antibody) has been studied, and a kinetic model is proposed. The apparent rate constant is dependent on the initial concentration of labelled and unlabelled T3, viscosity and temperature, and independent of ionic strength. The reaction is endothermic and is not controlled by diffusion. The results obtained are in line with the proposed model. We propose some modifications for optimizing the technique.
Asunto(s)
Modelos Biológicos , Triyodotironina/análisis , Cinética , RadioinmunoensayoRESUMEN
Lipopolysaccharide (LPS) is an endotoxin causing sepsis. Studies from our laboratory revealed impaired intestinal absorption of L-leucine and D-fructose in LPS-treated rabbits. The aim of this study was to examine intestinal D-galactose transport following intravenous administration of LPS in the rabbit and to identify the cellular mechanisms driving this process. Endotoxin treatment diminished the buildup of D-galactose in intestinal tissue, the mucosal to serosal transepithelial flux of the sugar and its uptake by brush border membrane vesicles (BBMVs). Intracellular signaling pathways associated with protein kinase C (PKC), protein kinase A (PKA), p38 mitogen-activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK), MAPK/extracellular signal-regulated kinases 1 and 2 (MEK1/2) and proteasome were found to be involved in this reduction in sugar uptake. Na(+)/glucose cotransporter 1 (SGLT1) protein levels in BBMVs were lower for LPS-treated animals than control animals. These findings indicate that LPS inhibits the intestinal absorption of D-galactose via a complex cellular mechanism that could involve posttranscriptional regulation of the SGLT1 transporter.
Asunto(s)
Endotoxemia/metabolismo , Galactosa/metabolismo , Mucosa Intestinal/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Northern Blotting , Western Blotting , Butadienos/farmacología , Endotoxemia/inducido químicamente , Galactosa/farmacocinética , Imidazoles/farmacología , Intestinos/efectos de los fármacos , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/farmacología , Masculino , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Nitrilos/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Piridinas/farmacología , Conejos , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismoRESUMEN
Se presenta un modelo teórico para la justificación de las ecuaciones de los cuatro parámetros y logarítmico-logística, utilizadas empíricamente en el ajuste de las curvas de calibración en RIA. De dicho modelo se deducen otras dos ecuaciones. Se analiza el ajuste de 192 curvas de RIA para las cuatro ecuaciones y se interpretan los resultados en términos de las posibles características de enlace en la unión antígeno-anticuerpo
A theoretical model for the justification of the equations of the four parameters and logarithmic-logistic, used empirically in the fit of the calibration curves in RIA, is presented. From this model other two equations are deduced. The fit of 192 curves of RIA is analyzed for the four equations and the results are interpreted in terms of the possible characteristics of binding in the union antigen-antibody
Asunto(s)
Humanos , Radioinmunoensayo/métodos , Reacciones Antígeno-Anticuerpo/genética , Calibración , Sensibilidad y Especificidad , Aldosterona/inmunología , Androstenodiona/inmunología , Gastrinas/inmunología , Glucagón/inmunología , Insulina/inmunología , Osteocalcina/inmunología , Péptido C/inmunologíaRESUMEN
Sepsis is a systemic response to infection in which toxins, such as bacterial lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like the cytokine tumor necrosis factor alpha (TNF-alpha). Previous studies from our laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine and D-fructose in rabbit when it was intravenously administered, and that TNF-alpha seems to mediate this effect on amino acid absorption. To extend this work, the present study was designed to evaluate the possible effect of TNF-alpha on D-galactose intestinal absorption, identify the intracellular mechanisms involved and establish whether this cytokine mediates possible LPS effects. Our findings indicate that TNF-alpha decreases D-galactose absorption both in rabbit intestinal tissue preparations and brush-border membrane vesicles. Western blot analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1) protein in the plasma membrane attributable to the cytokine. On the contrary, TNF-alpha increased SGLT1 mRNA levels. Specific inhibitors of the secondary messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the proteasome, diminished the TNF-alpha-evoked inhibitory effect. LPS inhibition of the uptake of the sugar was blocked by a TNF-alpha antagonist. In conclusion, TNF-alpha inhibits D-galactose intestinal absorption by decreasing the number of SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which several protein-like kinases are involved.
Asunto(s)
Galactosa/antagonistas & inhibidores , Absorción Intestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Animales , Antracenos/administración & dosificación , Antracenos/farmacología , Northern Blotting , Western Blotting , Membrana Celular/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Imidazoles/administración & dosificación , Imidazoles/farmacología , Indoles/administración & dosificación , Indoles/farmacología , Inyecciones Intravenosas , Absorción Intestinal/fisiología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Masculino , Maleimidas/administración & dosificación , Maleimidas/farmacología , Microvellosidades/efectos de los fármacos , Microvellosidades/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Péptidos/administración & dosificación , Péptidos/farmacología , Inhibidores de Proteasoma , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/administración & dosificación , Piridinas/farmacología , ARN Mensajero/metabolismo , Conejos , Sepsis/metabolismo , Transportador 1 de Sodio-Glucosa/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidoresRESUMEN
A kinetic model is put forward for the study of the antigen-antibody reactions involved in the coated tube radioimmunoassay (RIA) of androstendione. Twenty experiments were conducted to determine the influence of initial concentrations, ionic strength, viscosity, and temperature on the substitution reaction of 125I-androstendione (M) by unlabelled androstendione (Q) in the immunocomplex PM (P = anti-androstendione antibody). The results obtained are in line with the proposed model. The concentration of radioactive immunocomplex is directly proportional to the initial concentration of labelled androstendione and independent of the concentration of unlabelled androstendione, ionic strength, and viscosity. The reaction is not diffusion-controlled.
Asunto(s)
Androstenodiona/química , Reacciones Antígeno-Anticuerpo , Ensayo Inmunorradiométrico , Androstenodiona/inmunología , Sitios de Unión de Anticuerpos , Difusión , Radioisótopos de Yodo , Cinética , Modelos Químicos , Concentración Osmolar , Temperatura , ViscosidadRESUMEN
OBJECTIVE: To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease (AD) who are treated with a cholinesterase inhibitor (ChEI). METHODS: Patients with mild cognitive impairment (MCI) (12), mild AD (48), and moderate AD (24) (Global Deterioration Scale stages 3, 4, and 5) were randomized to receive psychosocial support plus cognitive-motor intervention (experimental group) or psychosocial support alone (control group). Cognitive-motor intervention (CMI) consisted of a 1-year structured program of 103 sessions of cognitive exercises, plus social and psychomotor activities. The primary efficacy measure was the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary efficacy measures were the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Geriatric Depression Scale. Evaluations were conducted at 1, 3, 6, and 12 months by blinded evaluators. RESULTS: Patients in the CMI group maintained cognitive status at month 6, whereas patients in the control group had significantly declined at that time. Cognitive response was higher in the patients with fewer years of formal education. In addition, more patients in the experimental group maintained or improved their affective status at month 12 (experimental group, 75%; control group, 47%; p = 0.017). CONCLUSIONS: A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.
Asunto(s)
Enfermedad de Alzheimer/terapia , Trastornos del Conocimiento/terapia , Terapia Cognitivo-Conductual , Modalidades de Fisioterapia , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/tratamiento farmacológico , Cuidadores/psicología , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Terapia Combinada , Donepezilo , Femenino , Estudios de Seguimiento , Humanos , Indanos/uso terapéutico , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Pacientes/psicología , Fenilcarbamatos/uso terapéutico , Piperidinas/uso terapéutico , Trastornos Psicomotores/terapia , Rivastigmina , Método Simple Ciego , Resultado del TratamientoRESUMEN
Molecular topology was used to obtain substances with antimicrobial activity. Selected quinolones were employed to develop the corresponding connectivity functions and discriminant equation. Limiting functions were selected that allowed the discriminant function to more efficiently distinguish substances with and without antibacterial activity. Antibacterial tests were run to confirm the theoretically established activity.
Asunto(s)
Antibacterianos/síntesis química , Quinolonas/síntesis química , Animales , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Análisis Discriminante , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad Cuantitativa , Quinolonas/farmacologíaRESUMEN
Tumor necrosis factor-alpha (TNF-alpha) has been proposed as an early proximal mediator of many metabolic and physiologic responses during septic shock. We have previously shown that direct addition to tissue (local effect) or intravenous administration (systemic effect) of lipopolysaccharide (LPS) reduces L-leucine absorption across rabbit jejunum. In the present study, we investigated whether the inhibitory effect of LPS on L-leucine intestinal absorption in rabbit is related to TNF-alpha. The results shown that the addition of TNF-alpha to tissue does not produce any effect on L-leucine uptake by the enterocyte. When TNF-alpha was inoculated by intravenous administration, a strong inhibition on the L-leucine uptake (about 40%), mediated by a secretagogue effect on water and Cl-ions was induced. We also found that the LPS intestinal effect induced by intravenous administration, was blocked by a TNF-alpha antagonist, indicating that TNF-alpha is a mediator of the LPS systemic effect on L-leucine intestinal uptake inhibition. The study of possible mediators involved in the TNF-alpha effect showed that nitric oxide and prostaglandins are implicated in the L-leucine intestinal uptake.
Asunto(s)
Absorción Intestinal/fisiología , Leucina/metabolismo , Lipopolisacáridos/farmacología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Enterocitos/metabolismo , Absorción Intestinal/efectos de los fármacos , Masculino , ConejosRESUMEN
Lipopolysaccharide (LPS) is a known causative agent of sepsis. In previous studies, we have shown that it reduces L-leucine mediated transport across the rabbit jejunum by about 30%. In this study, the mechanism(s) of LPS inhibition on amino acid transport were analysed in detail. LPS did not inhibit L-leucine transport across brush border membrane vesicles, suggesting the need for an intracellular step. The inhibitory effect of LPS was not altered by the addition of protein kinase A (PKA) inhibitor (IP(20), 10(-7) M) or an analog of cAMP (DB-cAMP, 3 x 10(-4) M), indicating that the PKA signal transduction pathway was not involved in the LPS effect. However, the inhibitory effect of LPS was suppressed by trifluoroperazine (10(-7) M), a Ca(2+)/calmodulin inhibitor and staurosporine (10(-7) M), an protein kinase C (PKC) inhibitor. Likewise, LPS inhibition disappeared in media without calcium. These results suggest that LPS could inhibit the intestinal uptake of L-leucine across the small intestine in vitro by intracellular processes related to calcium, involving PKC and calmodulin protein.
Asunto(s)
Proteínas de Escherichia coli , Yeyuno/metabolismo , Leucina/metabolismo , Lipopolisacáridos/farmacología , Aminoácidos/metabolismo , Animales , Toxinas Bacterianas/toxicidad , Transporte Biológico Activo/efectos de los fármacos , Calcio/fisiología , Señalización del Calcio/efectos de los fármacos , AMP Cíclico/fisiología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Enterotoxinas/toxicidad , Inhibidores Enzimáticos/farmacología , Absorción Intestinal/efectos de los fármacos , Yeyuno/química , Yeyuno/efectos de los fármacos , Masculino , Microvellosidades/efectos de los fármacos , Microvellosidades/metabolismo , Proteína Quinasa C/metabolismo , Conejos , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Agua/metabolismoRESUMEN
The molecular topology model and discriminant analysis have been applied to the prediction of some pharmacological properties of hypoglycemic drugs using multiple regression equations with their statistical parameters. Regression analysis showed that the molecular topology model predicts these properties. The corresponding stability (cross-validation) studies performed on the selected prediction models confirmed the goodness of the fits. The method used for hypoglycemic activity selection was a linear discriminant analysis (LDA). We make use of the pharmacological distribution diagrams (PDDs) as a visualizing technique for the identification and selection of new hypoglycemic agents, and we tested on rats the predictive ability of the model.
Asunto(s)
Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Animales , Simulación por Computador , Diseño de Fármacos , Modelos Lineales , Relación Estructura-Actividad Cuantitativa , Ratas , Análisis de RegresiónRESUMEN
In the present study, we have investigated whether the lipopolysaccharide (LPS) endotoxin from Escherichia coli is able to alter the jejunal transport of L-leucine when the tissue is exposed to endotoxin. The results have shown that the LPS at 3 x 10(-5) microg/ml decreases the uptake of L-leucine into the enterocyte, as well as the mucosal to serosal flux of L-leucine. The secretagogue effect of LPS on the gut did not affect the inhibitory effect of LPS on the intestinal absorption of the amino acid. The endotoxin did not modify amino acid diffusion across the intestinal epithelium. However, from the mediated transport, only the Na+-dependent transport system was affected by LPS with a diminution of the transporter affinity (the apparent Km was increased). In addition, we found a reduction of the Na+, K+-ATPase activity, which could explain the L-leucine Na+-dependent transport inhibition.
Asunto(s)
Endotoxinas/farmacología , Escherichia coli , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Leucina/metabolismo , Lipopolisacáridos/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Técnicas In Vitro , Absorción Intestinal/efectos de los fármacos , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Masculino , Conejos , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Se ha aplicado la Topología molecular a la predicción de propiedades antimicrobianas (concentración mínima inhibitoria 50 por ciento, CMI50, en Neisseria meningitidis, Capilobacter jejunji y Clostridium difficile) para un grupo de quinolonas, utilizando un análisis de regresión multilineal. Se han obtenido las correspondientes funciones de conectividad, siendo el criterio de selección diversos parámetros estadísticos como F de Snedecor, t de Student, cp de Mallow, etc. Los análisis de regresión muestran que el modelo predictivo propuesto por la conectividad molecular predice estas propiedades. Los correspondientes estudios de estabilidad y aleatoriedad realizados a los modelos seleccionados muestran una buena estabilidad y una nula aleatoriedad (AU)
Asunto(s)
Quinolonas/farmacología , Antiinfecciosos/farmacología , Neisseria meningitidis , Campylobacter jejuni , Clostridioides difficile , Dosificación Letal Mediana , Pruebas de Sensibilidad MicrobianaRESUMEN
The objective of the present study was to determine the alterations in L-leucine intestinal uptake by intravenous administration of Lipopolysaccharide (LPS), which is a constituent of gram negative bacterial, causative agent of sepsis. The amino acid absorption in LPS treated rabbits was reduced compared to the control animals. The LPS effect on the amino acid uptake was due to an inhibition of the Na+-dependent system of transport, through both reduction of the apparent capacity transport (Vmax) and diminution of the Na+/K-ATPase activity. The results have also shown that the LPS decreases the mucosal to serosal transepithelial flux and the transport across brush border membrane vesicles of L-leucine. The study of possible intracellular mechanisms implicated in the LPS effect, showed that the second messengers calcium, protein kinase C and c-AMP did not play any role in this effect. However, the absence of ion chloride in the incubation medium removes the LPS inhibition and the intracellular tissue water was affected by the LPS treatment. Therefore, the inhibition in the L-leucine intestinal absorption, by intravenous administration of LPS, could be mainly produced by the secretagogue action of this endotoxin on the gut.
Asunto(s)
Escherichia coli/química , Absorción Intestinal/efectos de los fármacos , Yeyuno/efectos de los fármacos , Leucina/metabolismo , Lipopolisacáridos/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Cloruros/metabolismo , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas , Absorción Intestinal/fisiología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Iones , Yeyuno/enzimología , Yeyuno/patología , Lipopolisacáridos/administración & dosificación , Masculino , Microvellosidades/efectos de los fármacos , Microvellosidades/metabolismo , Técnicas de Cultivo de Órganos , Conejos , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Vesículas Transportadoras/efectos de los fármacos , Vesículas Transportadoras/metabolismoRESUMEN
Serotonin has been shown to alter the intestinal transport of ions and intestinal motility. These effects may interfere with each other, modulating the whole physiology of the intestine. We have previously shown that serotonin also alters the transport of nutrients. Thus, the aims of the present work were to determine the possible interference between the secretagogue effect of serotonin and the mechanism by which serotonin inhibits the absorption of nutrients, and to study the effect of serotonin on the digestive activity of nutrients of the brush border membrane jejunum enterocyte in the rabbit. The results show that the secretagogue effect of serotonin neither affects the inhibitory effect of serotonin on the intestinal absorption of the nutrients, nor affects the activity of Na+/K+-ATPase. The activity of sucrase and aminopeptidase N was also not affected by serotonin in the rabbit jejunum. Finally, we also studied different parameters of the motility in the rabbit small intestine. Serotonin seemed to stimulate the motility of the rabbit small intestine by increasing integrated mechanical activity and tone of muscle fibers in duodenum, jejunum, and ileum. In conclusion, serotonin might alter or modulate the whole intestinal physiology.
Asunto(s)
Intestino Delgado/fisiología , Serotonina/farmacología , Aminoácidos/metabolismo , Animales , Agua Corporal/metabolismo , Antígenos CD13/metabolismo , Metabolismo de los Hidratos de Carbono , Electrofisiología , Galactosa/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Técnicas In Vitro , Absorción Intestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Leucina/metabolismo , Masculino , Microvellosidades/metabolismo , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Conejos , Serotonina/sangre , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Sacarasa/metabolismoRESUMEN
A new topological method that makes it possible to predict the properties of molecules on the basis of their chemical structures is applied in the present study to quinolone antimicrobial agents. This method uses neural networks in which training algorithms are used as well as different concepts and methods of artificial intelligence with a suitable set of topological descriptors. This makes it possible to determine the minimal inhibitory concentration (MIC) of quinolones. Analysis of the results shows that the experimental and calculated values are highly similar. It is possible to obtain a QSAR interpretation of the information contained in the network after the training has been carried out.
Asunto(s)
Antiinfecciosos/química , Redes Neurales de la Computación , Algoritmos , Antiinfecciosos/farmacología , Fluoroquinolonas , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadAsunto(s)
Anticonvulsivantes/uso terapéutico , Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Demencia/complicaciones , Agitación Psicomotora/tratamiento farmacológico , Agitación Psicomotora/etiología , Anciano , Agresión/psicología , Femenino , Humanos , Masculino , Agitación Psicomotora/diagnósticoRESUMEN
BACKGROUND: Alzheimer's family caregivers suffer from psychological and physical morbidity associated with the care of the Alzheimer's patient. The objectives of the study were to compare stress and psychological morbidity between family caregivers of Alzheimer's disease patients and family caregivers of aged non-demented chronically ill patients and to explore the impact of cognitive and non-cognitive patient symptoms on caregivers. METHOD: Fifty-eight caregivers of Alzheimer's patients (cases) and 32 caregivers of non-demented chronically ill patients (controls) were studied. A cross-sectional case-control design was employed using validated scales to assess patient symptomatology and self-report questionnaires to measure stress and psychological morbidity in caregivers. RESULTS: Compared to controls, stress and psychological morbidity were higher in caregivers of Alzheimer's patients. Behavioral symptoms and impairment in instrumental activities of daily living were associated with caregiver stress. Length of care was associated with caregiver psychological morbidity. CONCLUSIONS: Caregiver stress may be reduced with special attention paid to the treatment and management of behavioral and functional symptoms in the Alzheimer's disease patient. Caregiver education and coping skills should also be included.
Asunto(s)
Enfermedad de Alzheimer , Cuidadores/psicología , Estrés Psicológico/epidemiología , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Índice de Severidad de la Enfermedad , España , Estrés Psicológico/psicologíaRESUMEN
The aim of the present study was to determine the 5-HT receptor subtypes involved in the serotonin-induced inhibition of L-leucine absorption across rabbit jejunum in vitro. A number of agonists and antagonists were used to characterize the receptors through which serotonin inhibits this absorption. The results show that 2.5x10(-6) M 5-HT inhibits the amino acid absorption by about 20%. The 5-HT receptor agonists, alpha-methyl-5-HT (5-HT2), 2-methyl-5-HT (5-HT3) and zacopride (5-HT4) at concentrations 2.5x10(-6) and 2.5x10(-5) M produced 10-30% inhibition on L-leucine intestinal absorption. 5-carboxyamidotryptamine (5-HT1) did not produce any inhibition. The 5-HT antagonists, GR 113808A (5-HT4) at 2.5x10(-6) M and ritanserin (5-HT2) and ondansetron (5-HT3) at 2.5x10(-5) M completely blocked the effect of 5-HT. However, methiothepin (5-HT1) did not produce any effect on serotonin action in the intestinal absorption of amino acid. It can be concluded that 5-HT2, 5-HT3 and 5-HT4 receptors could mediate inhibition of L-leucine absorption across rabbit jejunum.
Asunto(s)
Absorción Intestinal/efectos de los fármacos , Leucina/metabolismo , Receptores de Serotonina/fisiología , Serotonina/farmacología , Animales , Benzamidas/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Indoles/farmacología , Yeyuno/metabolismo , Masculino , Ondansetrón/farmacología , Conejos , Receptores de Serotonina 5-HT3 , Receptores de Serotonina 5-HT4 , Ritanserina/farmacología , Serotonina/análogos & derivados , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Sulfonamidas/farmacologíaRESUMEN
This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit. The results also demonstrated that the presence of substituents and molecular volume, determine the value of these properties in hypolipaemic drugs.