RESUMEN
Dental hypersensitivity has been observed in an increasing number of younger patients over the past few decades. The reasons for this include forced or false tooth-brushing techniques, and abrasions caused by bruxism or orthodontic procedures. The aim of the present study was to assess the possible benefits of a potassium chloride (KCl) containing chewing gum in dental hypersensitivity. The study population consisted of 59 selected university students (age: 25 +/- 4.4 years). Each subject suitable for entry into the study had more than 3 teeth sensitive to thermal stimulation (air stimulus range of 30-80 mm on a 100mm visual analogue scale (VAS), and showed signs of facial/cervical erosion, abrasion and/or gingival recession. Exclusion criteria were daily doses of medication, teeth with deep restorations, a gingival score of > 2, or periodontal surgery within the past 6 months. The total number of hypersensitive teeth was 217. Over a period of 3 weeks the subjects brushed with a non-desensitising toothpaste and, in addition, used the KCl chewing gum up to 6 times daily for 10 min on each occasion. This was followed by a period of 3 weeks of non-desensitising toothpaste use alone. The subjects were questioned on the severity of intraoral pain and asked to indicate the intensity of the pain on the VAS (baseline, 1, 3 and 6 weeks). Mean thermal sensitivity at baseline was 54.5 +/- 9 mm. There was a drop to 40.8 mm ( 1.9) after 1 week and to 28.6 mm (+/- 2) after 3 weeks. The reduction was statistically significant (p <0.001) at both measurement points. The mean rating increased to 29.1 mm after 6 weeks. The results of this study demonstrate that the daily use of a KCl containing chewing gum is a useful non-invasive method of reducing dental hypersensitivity over an extended period of time.
Asunto(s)
Sensibilidad de la Dentina/tratamiento farmacológico , Cloruro de Potasio/administración & dosificación , Adulto , Goma de Mascar , Frío , Femenino , Calor , Humanos , Masculino , Dimensión del Dolor , Satisfacción del Paciente , Pastas de DientesRESUMEN
Molecular determinants of P2Y2 receptor desensitization and sequestration have been investigated. Wild-type P2Y2 receptors and a series of five C-terminal truncation mutants of the receptor were epitope-tagged and stably expressed in 1321N1 cells. These constructs were used to assess the importance of the intracellular C terminus on 1) UTP-stimulated increases in intracellular calcium concentration, 2) homologous desensitization of the receptor, and 3) agonist-induced decreases in cell-surface density (receptor sequestration) of epitope-tagged receptors using fluorescence-activated cell sorting. The potency and efficacy of UTP were similar for the wild-type and all mutant P2Y2 receptors. Truncation of 18 or more amino acids from the C terminus increased by approximately 30-fold the concentration of UTP necessary to desensitize the receptor. Both the rate and magnitude of UTP-induced receptor sequestration were decreased with progressively larger truncations of the C terminus. Furthermore, the recovery from sequestration was slower for the most extensively truncated receptor. Complete desensitization was obtained with >50% of the original receptor complement remaining on the cell surface. Protein kinase C activation, which desensitizes the P2Y2 receptor, had no effect on sequestration, consistent with the ideas that desensitization and sequestration are discrete events and that agonist occupancy is required for receptor sequestration.
Asunto(s)
Agonistas del Receptor Purinérgico P2 , Uridina Trifosfato/farmacología , Secuencia de Aminoácidos , Línea Celular , Relación Dosis-Respuesta a Droga , Activación Enzimática , Humanos , Datos de Secuencia Molecular , Conformación Proteica , Proteína Quinasa C/metabolismo , Estructura Secundaria de Proteína , Receptores Purinérgicos P2/química , Receptores Purinérgicos P2Y2 , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/químicaRESUMEN
A controlled, long-term training process, extensive medical treatment as well as a satisfying social and familiar environment are the key factors for a healthy development of young athletes in high level gymnastics.
Asunto(s)
Gimnasia , Educación y Entrenamiento Físico/métodos , Pubertad , Adolescente , Traumatismos en Atletas/prevención & control , Niño , Relaciones Familiares , Femenino , Gimnasia/lesiones , Humanos , Masculino , Grupo de Atención al Paciente , Ajuste SocialRESUMEN
The wall-less mycoplasmas have revealed unusual microbial strategies for adaptive variation of antigenic membrane proteins exposed during their surface colonization of host cells. In particular, high-frequency mutations affecting the expression of selected surface lipoproteins have been increasingly documented for this group of organisms. A novel manifestation of mutational phase variation is shown here to occur in Mycoplasma fermentans, a chronic human infectious agent and possible AIDS-associated pathogen. A putative ABC type transport operon encoding four gene products is identified. The 3' distal gene encoding P78, a known surface-exposed antigen and the proposed substrate-binding lipoprotein of the transporter, is subject to localized hypermutation in a short homopolymeric tract of adenine residues located in the N-terminal coding region of the mature product. High-frequency, reversible insertion/deletion frameshift mutations lead to selective phase variation in P78 expression, whereas the putative nucleotide-binding protein, P63, encoded by the most 5' gene of the operon, is continually expressed. Mutation-based phase variation in specific surface-exposed microbial transporter components may provide an adaptive advantage for immune evasion, while continued expression of other elements of the same transporter may preserve essential metabolic functions and confer alternative substrate specificity. These features could be critical in mycoplasmas, where limitations in both transcriptional regulators and transport systems may prevail. This study also documents that P63 contains an uncharacteristic hydrophobic sequence between predicted nucleotide binding motifs and displays an amphiphilic character in detergent fractionation. Both features are consistent with an evolutionary adaptation favoring integral association of this putative energy-transducing component with the single mycoplasma membrane.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Genes Bacterianos , Lipoproteínas/genética , Mycoplasma fermentans/genética , Operón , Secuencia de Aminoácidos , Datos de Secuencia Molecular , MutaciónRESUMEN
Albert the Great (ca. 1193-1280) serves as an example to show how the Latin West successfully integrated Greco-Arabian psychology with Galenic physiology. He divised a model of perceptive, cognitive and mnestic powers located in different areas of the "brain cells" and interacting with the immaterial and man-specific intellect. He managed to describe anmesis, epileptic seizures and psychotic states as results of disturbed brain fuction. Finally, further aspects of Scholastic theorizing on mental disorders are discussed.
Asunto(s)
Trastornos Mentales/historia , Neurocirugia/historia , Filosofía/historia , Fisiología/historia , Psicología/historia , Europa (Continente) , Historia Medieval , HumanosRESUMEN
Antibodies to P29, a major lipid-modified surface protein of Mycoplasma fermentans, reveal phase variation of surface epitopes occurring with high frequency in clonal lineages of the organism. This occurs despite continuous expression of the entire epitope-bearing P29 product (detected by Western immunoblotting) and contrasts with phase variation of other surface antigens mediated by differential expression of proteins. To understand the structure and antigenic topology of P29, the single-copy p29 gene from strain PG18 was cloned and sequenced. The gene encodes a prolipoprotein containing a signal sequence predicted to be modified with lipid and cleaved at the N-terminal Cys-1 residue of the mature P29 lipoprotein. The remaining 218-residue hydrophilic sequence of P29 is predicted to be located external to the single plasma membrane. Additional Cys residues at positions 91 and 128 in the mature protein were shown to form a 36-residue disulfide loop by selectively labeling sulfhydryl groups that were liberated only after chemical reduction of monomeric P29. Two nearly identical charged amino acid sequences occurred in P29, within the disulfide loop and upstream of this structure. Two distinct epitopes binding different monoclonal antibodies were associated with opposite ends of the P29 protein, by mapping products expressed in Escherichia coli from PCR-generated 3' deletion mutations of the p29 gene. Each monoclonal antibody detected high-frequency and noncoordinate changes in accessibility of the corresponding epitopes in colony immunoblots of clonal variants, yet sequencing of the p29 gene from these variants and analysis of disulfide bonds revealed no associated changes in the primary sequence or disulfide loop structure of P29. These results suggest that P29 surface epitope variation may involve masking of selected regions of P29, possibly by other surface components undergoing phase variation by differential expression. Differential masking may be an important mechanism for altering the antigenic or functional surface topology of this mycoplasma and other wall-less mycoplasmas.
Asunto(s)
Antígenos Bacterianos/genética , Antígenos de Superficie/genética , Mycoplasma fermentans/inmunología , Secuencia de Aminoácidos , Animales , Variación Antigénica , Antígenos Bacterianos/química , Antígenos de Superficie/química , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Secuencia de Bases , Clonación Molecular , Cartilla de ADN/genética , ADN Bacteriano/genética , Epítopos/química , Epítopos/genética , Escherichia coli/genética , Genes Bacterianos , Lipoproteínas/química , Lipoproteínas/genética , Lipoproteínas/inmunología , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Ratones , Datos de Secuencia Molecular , Estructura Molecular , Mycoplasma fermentans/genética , Reacción en Cadena de la Polimerasa , Eliminación de SecuenciaRESUMEN
Albert the Great (Albertus Magnus, ca. 1197-1280) descended from a nobleman's family in Upper Suebia and studied natural philosophy and theology at the University of Padova, where he joined the Dominican order. Confronted with Aristotelian thought mainly in its Arabic modification (Avicenna, Al-Farabi, Averroes, Alhazen, Costa ben Luca and others) from his days in Padova, he elaborated in several books on the principles of natural philosophy, biology, brain and sense functions and psychology in addition to his theological and exegetic works. His observations and concepts on vision are discussed in detail. It is pointed out that Albert discovered some phenomena of vision not before known such as vestibular nystagmus and rod monochromacy, i.e. total colour blindness accompanied by photophobia. Based on clinical observations Albert also postulated a decussation of the optic nerve fibres at the optic chiasm. Albert's concept of higher order cognitive function is discussed and some of his explanations of dreams and neuropsychiatric disease on the basis of his cognitive model are mentioned. Albert's thoughts on vision and other sense perceptions, higher brain functions and cognition are considered as progressive elaborations of Galenic concepts as adapted by some Patristic theologians and the Arabic natural scientists and philosophers of the 9th-11th century.
Asunto(s)
Cognición , Filosofía/historia , Visión Ocular , Historia Medieval , HumanosRESUMEN
Mycoplasma fermentans, a wall-less prokaryote, is currently under investigation as a potential human pathogen. Recently, several surface lipoproteins have been shown to vary in expression between M. fermentans strains. Using specific antibodies to these lipoproteins, we investigated the extent and nature of antigenic variation within this species. Immunoscreening of type strain PG18 agar-grown colonies revealed marked heterogeneity in expression of distinct surface lipoproteins. Subsequent isolation and propagation of clonal isolates established isogenic lineages which displayed high-frequency (10(-2) to 10(-5) per generation) antigenic phase variation. [35S]cysteine-labeled protein profiles and Western immunoblots of phase-variant clones showed that several distinct integral membrane proteins undergo noncoordinate variation in expression. In addition to differential expression of epitope-bearing lipoproteins, differential accessibility of epitopes to antibodies was also documented as a mechanism generating surface phenotypic variation. Examination of one strain-variant antigen showed high-frequency phase variation to underlie previously observed antigenic differences between strains of this species. Thus, M. fermentans has a complex system capable of creating rapid changes in surface mosaics. This may profoundly affect mycoplasma-host interactions and may limit the methods by which populations of M. fermentans may be studied in vivo.
Asunto(s)
Variación Antigénica , Antígenos Bacterianos/genética , Proteínas Bacterianas/inmunología , Mycoplasma fermentans/inmunología , Anticuerpos Monoclonales , Proteínas Bacterianas/genética , Membrana Celular/inmunología , Epítopos/genética , Expresión Génica , Humanos , Mycoplasma fermentans/genética , Mycoplasma fermentans/patogenicidad , Especificidad de la EspecieRESUMEN
Sinclair miniature swine represent a breed of miniature swine which display a significant incidence of inheritable melanoma which undergo a developmentally regulated spontaneous regression. In an attempt to characterize the host cellular immune response to the melanoma, lymphocyte cell lines have been generated from peripheral blood and designated as peripheral blood lymphocyte cell lines (PBLCLs). The cell lines were expanded in vitro without the addition of exogenous mediators, cloned by limiting dilution, and characterized by flow microfluorimetry, Western, and Northern blot analysis. The cell lines were shown to be CD2-, CD4-, CD8-, and slg-, a phenotype consistent with a null cell population described in swine. The null cell population in swine has been reported to consist of a subpopulation of cells which express the gamma delta T cell receptor (TCR) heterodimer, swine gamma delta T lymphocytes. The PBLCLs were further analyzed by flow microfluorimetry and observed to express the IL-2R, swine MHC Class II antigens, and the endothelial lymphocyte adhesion marker (CD44), which can function as a homing receptor for the skin. In addition, the PBLCLs were observed to express the antigen which is recognized by mAb 86D, an antibody that has been reported to recognize an external epitope on a subset of gamma delta TCR bearing swine T lymphocytes. Western blot analysis of Triton X-114 phase fractions of a PBLCL revealed a protein recognized by the W6 antibody, an antibody which recognizes a conserved region of the C delta chain. Furthermore, Southern and Northern blot analysis indicated that the PBLCL have rearranged the TCR gamma chain gene and express mRNA from the TCR gamma and delta chain genes prior to and following treatment with ionomycin or Concanavalin A. Therefore, the data indicates that the PBLCLs represent swine gamma delta T lymphocyte cell lines which should enable us to enhance our understanding of the role of gamma delta T lymphocytes in the porcine immune system.
Asunto(s)
Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Porcinos Enanos/inmunología , Linfocitos T/inmunología , Animales , Antígenos de Superficie/inmunología , Línea Celular , Expresión Génica , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T/genética , Lisosomas/inmunología , Melanoma/genética , Melanoma/inmunología , Melanoma/veterinaria , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/veterinaria , Porcinos , Enfermedades de los Porcinos/genética , Enfermedades de los Porcinos/inmunologíaRESUMEN
The wall-less procaryote Mycoplasma fermentans is currently being examined as an agent potentially associated with human disease, including infectious processes affecting immunocompromised individuals. To delineate and understand the interactions of M. fermentans with its host, specific membrane surface components were characterized as markers for detecting the organism and for assessing heterogeneity in antigenic surface architecture within this mycoplasma species. Detergent phase fractionation of metabolically labeled organisms of type strain PG18 identified a family of prominent integral membrane proteins; several of these labeled with 35S-cysteine and 3H-palmitate, which are characteristics of procaryotic lipoproteins. Specific monoclonal and polyclonal antibodies raised to strain PG18 components further distinguished seven of these membrane proteins, which were localized on the organism's surface by monitoring their selective susceptibility during trypsin treatment of intact cells. With these antibodies, Western immunoblot profiles of surface membrane antigens expressed on strain PG18 were compared with those expressed on the recently identified Incognitus strain of M. fermentans, as well as with several other human and animal mycoplasma species. While the antibodies were specific for M. fermentans, marked differences were observed between the strains in the size of one surface lipoprotein and in the apparent levels of several antigens expressed in the cultured populations analyzed. Some monoclonal antibodies to strain PG18 and a previously described monoclonal antibody to strain Incognitus showed apparent selectivity for the strain used for immunization. Monoclonal antibodies developed here recognize stable epitopes defining a family of surface lipoproteins and provide critical tools to determine the basis of surface variation in this mycoplasma species and to assess the location and antigenic phenotypes of organisms in the human host.
Asunto(s)
Proteínas Bacterianas/análisis , Lipoproteínas/análisis , Proteínas de la Membrana/análisis , Mycoplasma fermentans/química , Animales , Anticuerpos Monoclonales/inmunología , Proteínas Bacterianas/inmunología , Femenino , Lipoproteínas/inmunología , Proteínas de la Membrana/inmunología , Ratones , Ratones Endogámicos BALB C , Mycoplasma fermentans/inmunología , Especificidad de la EspecieRESUMEN
VlpE is characterized as a new member in a family of variable surface lipoproteins (Vlps) of Mycoplasma hyorhinis. VlpE shows phenotypic variation in expression and size within isogenic lineages of some strains but is absent from lineages of other strains that express only three previously known Vlps. Expression of four Vlps in some cells further indicates the presence and usage of an expanded reservoir of Vlp coding sequences, which greatly increases the capacity for surface diversification.
Asunto(s)
Antígenos Bacterianos/química , Lipoproteínas/inmunología , Mycoplasma/inmunología , Anticuerpos Monoclonales/inmunología , Variación Antigénica , Antígenos Bacterianos/inmunología , Células Clonales , EpítoposRESUMEN
A process evaluation was conducted of the effectiveness of the "Know Your Body" curriculum in reducing coronary heart disease risk factors among black elementary and junior high school students. The evaluation, part of a five-year longitudinal study, linked effectiveness of teachers' implementation with student outcomes and identified program weaknesses during implementation. Teachers with higher effectiveness scores had significantly more favorable student outcomes in systolic blood pressure, diastolic blood pressure, HDL cholesterol, HDL/cholesterol ratio, serum thiocyanate, and fitness. Of 82 teachers, 38 (46%) had scores reflecting effective teaching. Lack of time and commitment and inadequate use of the behavioral teaching approach demanded by the curriculum contributed most to implementation failure. Teachers as insufficient role models emerged as an important factor. Future research needs appropriate reinforcement of teacher participation and measurement of the environmental factors and personal teacher characteristics that may affect program implementation. School health education programs need an intensive training component that will enable teachers to adopt behavioral teaching approaches, promote teacher's examination and change of their personal risk factors, and stress the classroom dynamic of teachers as role models.
Asunto(s)
Enfermedad Coronaria/prevención & control , Educación en Salud/normas , Servicios de Salud Escolar , Negro o Afroamericano , Enfermedad Coronaria/etiología , Curriculum , District of Columbia , Humanos , Evaluación de Programas y Proyectos de Salud , Factores de Riesgo , Rol , Enseñanza/métodos , Enseñanza/normasRESUMEN
A five-year intervention study of the effectiveness of the "Know Your Body" program in reducing coronary heart disease risk factors among black students in the District of Columbia, who were in grades 4-6 at baseline, was begun in 1983. Nine schools were stratified on socioeconomic status and randomly assigned to control and intervention groups. The "Know Your Body" curriculum focuses on nutrition, fitness, and the prevention of cigarette smoking. At baseline, 1,234 students were eligible for the screening in which the following target risk factors were measured: systolic and diastolic blood pressures, ponderosity index, triceps skinfold thickness, postexercise pulse recovery rate, serum total and high density lipoprotein (HDL) cholesterol, and serum thiocyanate. After two years of intervention, results indicated that the program may have had a favorable impact on the following risk factors: systolic and diastolic pressures, HDL cholesterol, ratio of total to HDL cholesterol, fitness (postexercise pulse recovery rate), and smoking. Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking. Blood pressure reduction was associated with decreased ponderosity and improved fitness, and increased HDL cholesterol was associated with decreased ponderosity. These results are consistent with other evaluations of the "Know Your Body" program, suggesting that the program may be effective in reducing chronic disease risk in diverse school populations.
Asunto(s)
Negro o Afroamericano , Enfermedades Cardiovasculares/prevención & control , Educación en Salud/métodos , Actitud Frente a la Salud , Presión Sanguínea , Niño , Colesterol/sangre , District of Columbia , Femenino , Humanos , Estudios Longitudinales , Masculino , Factores de Riesgo , Instituciones Académicas , Grosor de los Pliegues Cutáneos , Fumar/sangre , Factores Socioeconómicos , Población UrbanaRESUMEN
A longitudinal study of the effectiveness of the "Know Your Body" (KYB) program in reducing coronary heart disease risk factors was begun among black students in the District of Columbia in 1983. Subjects were in grades four through six at nine schools stratified on socioeconomic status and randomized into one control and two intervention groups. At baseline, 1,041 students were measured for systolic and diastolic blood pressure, ponderosity, triceps skinfold thickness, postexercise pulse recovery rate, serum thiocyanate, serum total cholesterol, and serum HDL cholesterol. Significant net changes in individual values occurred in the favorable direction at one or all four annual follow-up reexaminations for systolic blood pressure, diastolic blood pressure, HDL cholesterol, HDL/total cholesterol ratio, serum thiocyanate, and fitness. Favorable changes in diastolic blood pressure and serum thiocyanate were observed at all reexaminations, and these were substantiated by analyses that used the school grade as the unit of analysis. Intervention students who were judged to have had the best KYB teachers showed significant favorable net changes in total serum cholesterol after one year. Results are consistent with other evaluations of the Know Your Body program suggesting that KYB may reduce chronic disease risk in diverse school populations, and that increased efforts should be made to improve implementation methods.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Promoción de la Salud/educación , Servicios de Salud Escolar/organización & administración , Negro o Afroamericano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Niño , District of Columbia , Femenino , Humanos , Estudios Longitudinales , Masculino , Evaluación de Programas y Proyectos de Salud , Factores de RiesgoRESUMEN
Acute morphine induced a dose-dependent hypokinesia and rigidity, but only mild and non-dose-dependent catalepsy. AMT, injected 1/2 h after morphine, slightly potentiated catalepsy but not hypokinesia during 3 h after morphine; in contrast, rigidity was decreased. The behavioral changes induced by AMT were accelerated in onset and reached their usual development, although AMT toxicity and hypothermia were completely antagonized; thus, it would appear that AMT hypokinesia/catalepsy are not the consequence of toxicity. When morphine was injected 4 h after AMT, a mutual potentiation of the two drugs on hypokinesia and catalepsy was observed, although previous biochemical measurements had shown no effect of morphine on CA depletion under these conditions. Rigidity appeared to be antagonized. After 17 days of repeated injections, morphine no longer elicited hypokinesia and catalepsy, but no cross-tolerance developed to the AMT behavioral changes. A similar lack of cross-tolerance to the effects of AMT or haloperidol was observed when morphine tolerance was induced by pellet implantation. Catalepsy and hypokinesia developed in a much more pronounced way after two large i.p. doses than after small, multiple administration of AMT; this difference was accompanied by a significantly lower concentration of brain DA, but not NA in the former group. The hyperthermic response observed after a 40 mg/kg s.c. injection of morphine was reversed to hypothermia when the same dose was given 4 or 10 h after CA synthesis inhibition. Cocaine strongly antagonized AMT hypokinesia and catalepsy when given 8 1/2 h after AMT, and, although to a lesser extent, even when injected 12 1/2 h after AMT.
Asunto(s)
Catalepsia/inducido químicamente , Cocaína/farmacología , Metiltirosinas/farmacología , Morfina/farmacología , Trastornos Psicomotores/inducido químicamente , Animales , Temperatura Corporal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Catecolaminas/análisis , Interacciones Farmacológicas , Tolerancia a Medicamentos , Haloperidol/farmacología , Humanos , Masculino , RatasRESUMEN
Morphine increased the rate of brain dopamine (DA) depletion when given before alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide, but not when given after AMT. No effect of morphine was found on the rate of depletion of brain noradrenaline (NA) or serotonin (5-HT) after the two synthesis inhibitors. The accumulation of homovanillic acid and 5-hydroxy-indoleacetic acid induced by probenecid was significantly increased by morphine pretreatment, whereas the accumulation of 3-methoxy-4-hydroxy-phenylglycol sulphate was not changed. These findings can be best explained by the hypothesis that morphine increases the non-functional intraneuronal catabolism of newly synthesized DA and 5-HT, without much effect on the monoamines already taken up in the synaptic vesicles. NA turnover does not seem to be changed by acute morphine administration.
Asunto(s)
Encéfalo/metabolismo , Catecolaminas/metabolismo , Morfina/farmacología , Serotonina/metabolismo , 3-Metoxi-4-hidroxifenil Etanol/metabolismo , Animales , Transporte Biológico Activo/efectos de los fármacos , Encéfalo/efectos de los fármacos , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Metiltirosinas/farmacología , Morfina/administración & dosificación , Norepinefrina/metabolismo , Probenecid/farmacología , Ratas , Factores de TiempoRESUMEN
The turnover of brain monoamine was studied in rats in which different degrees of tolerance to and dependence on morphine were induced by pellet implantation. The degree of tolerance to morphine was assessed by measuring the increase in effective dose for an antinociceptive effect (vocalization test). The rate of depletion of brain dopamine (DA) and serotonin (5-ht) after alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide (dopacetamide) was not changed by chronic morphine treatment. In contrast, the accumulation of brain homovanillic acid HVA) and 5-hydroxyindoleacetic acid (5-HIAA) after probenecid was significantly increased, but there was no correlation between the biochemical changes and the degree of tolerance/dependence of the animals; at a very high degree of dependence 5-HIAA accumulation even became normal. In rats in which smaller amounts of morphine were repeatedly injected every 8 hr for 1 week the increased accumulation of HVA and 5-HIAA persisted in spite of complete tolerance to the antinociceptive effect. The rate of depletion of brain noradrenaline (NA) after AMT or dopacetamide was not changed and the accumulation of brain 3-methoxy-4-hydroxy-phenylglycol sulphate (MHPG-SO4) after probenecid was not affected in most chronic morphine groups. In the group with the highest degree of tolerance/dependence NA depletion after AMT was even retarded. The results suggest that chronic morphine treatment increases the synthesis and the intraneuronal destruction of newly synthesized DA and 5-HT without changing the rate of functional utilization of the monoamines. It is unlikely that the changes in monoamine metabolism are causally related to processes leading to morphine tolerance/dependence.
Asunto(s)
Encéfalo/metabolismo , Catecolaminas/metabolismo , Morfina/farmacología , Serotonina/metabolismo , 3-Metoxi-4-hidroxifenil Etanol/metabolismo , Animales , Encéfalo/efectos de los fármacos , Dopamina/metabolismo , Implantes de Medicamentos , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Masculino , Metiltirosinas/farmacología , Morfina/administración & dosificación , Norepinefrina/metabolismo , Ratas , Factores de Tiempo , Vocalización Animal/efectos de los fármacosRESUMEN
Yohimbine moderately increased the depletion of brain dopamine (DA) after alpha-methyl-p-tyrosine (AMT) only when the two drugs were given at the same time; the baseline concentration of brain homovanillic acid (HVA) and its accumulation after probenecid were strongly increased by yohimbine. Yohimbine markedly decreased the concentration of brain noradrenaline (NA), both when given alone and before or at the same time as AMT; when it was given at an increasing interval after AMT, the effect became progressively smaller. The baseline concentration of brain 3-methyoxy-4-hydroxyphenylethyleneglycol sulphate and its accumulation after probenecid were increased by yohimbine; this effect was not as marked as that on HVA and was proportional to the quantity of NA depleted in the Amt method. The accumulation of brain k-hydroxyindoleacetic acid after probenecid was decreased by yohimbine pretreatment.