RESUMEN
Primary blast-induced traumatic brain injury (bTBI) has been observed at the boundary of brain tissue and cerebrospinal fluid (CSF). Such injury can hardly be explained by using the theory of compressive wave propagation, since both the solid and fuid materials have similar compressibility and thus the intracranial pressure (ICP) has a continuous distribution across the boundary. Since they have completely different shear properties, it is hypothesized the injury at the interface is caused by shear wave. In the present study, a preliminary combined numerical and theoretical analysis was conducted based on the theory of shear wave propagation/reflection. Simulation results show that higher lateral acceleration of brain tissue particles is concentrated in the boundary region. Based on this fnding, a new biomechanical vector, termed as strain gradient, was suggested for primary bTBI. The subsequent simple theoretical analysis reveals that this parameter is proportional to the value of lateral acceleration. At the boundary of lateral ventricles, high spatial strain gradient implies that the brain tissue in this area (where neuron cells may be contained) undergo significantly different strains and large velocity discontinuity, which may result in mechanical damage of the neuron cells.
Asunto(s)
Traumatismos por Explosión/etiología , Lesiones Traumáticas del Encéfalo/etiología , Fenómenos Biomecánicos , Traumatismos por Explosión/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Fuerza Compresiva , Simulación por Computador , Análisis de Elementos Finitos , HumanosRESUMEN
Primary blast-induced traumatic brain injury (bTBI) has been observed at the boundary of brain tissue and cerebrospinal fluid (CSF). Such injury can hardly be explained by using the theory of compressive wave propagation, since both the solid and fuid materials have similar compressibility and thus the intracranial pressure (ICP) has a continuous distribution across the boundary. Since they have completely different shear properties, it is hypothesized the injury at the interface is caused by shear wave. In the present study, a preliminary combined numerical and theoretical analysis was conducted based on the theory of shear wave propagation/reflection. Simulation results show that higher lateral acceleration of brain tissue particles is concentrated in the boundary region. Based on this fnding, a new biomechanical vector, termed as strain gradient, was suggested for primary bTBI. The subsequent simple theoretical analysis reveals that this parameter is proportional to the value of lateral acceleration. At the boundary of lateral ventricles, high spatial strain gradient implies that the brain tissue in this area (where neuron cells may be contained) undergo significantly different strains and large velocity discontinuity, which may result in mechanical damage of the neuron cells.
Asunto(s)
Humanos , Fenómenos Biomecánicos , Traumatismos por Explosión , Lesiones Traumáticas del Encéfalo , Fuerza Compresiva , Simulación por Computador , Análisis de Elementos FinitosRESUMEN
Rice (Oryza sativa L.) is cultivated on approximately 230,000 ha in northern Italy. Since 2001, increasing economical losses presumably caused by Fusarium fujikuroi Nirenberg (Gibberella fujikuroi mating population C), an exotic fungus known as the etiological agent of Bakanae disease, have been reported in Italy. The spread of this disease is primarily seedborne. In 2009, during an annual survey of Italian rice seed, 69 samples were tested for the presence of strains belonging to the G. fujikuroi species complex. Four hundred seeds per sample were surface sterilized and then placed in 90-mm Petri dishes containing potato dextrose agar and incubated for 7 days at 21°C. Thirty two putative G. fujikuroi strains were single-spore purified and identified on the basis of their morphological features on Spezieller Nährstoffarmer agar plates with a piece of sterile filter paper. Strains were characterized at species level by morphological observations (1,2) and translation elongation factor 1-α (TEF) gene sequencing. Unexpectedly, 60% of the strains evaluated belonged to the species F. andiyazi Marasas, Rheeder, Lampr., K.A. Zeller & J.F. Leslie. This fungus, first described on sorghum (Sorghum bicolor L.) in Africa and the United States (1), has been reported to be one of the species associated with Bakanae in Asia and Africa (3). Two F. andiyazi strains, (E432 and E439), isolated in the district of Modena were chosen for pathogenicity testing and their TEF gene sequences were deposited in GenBank (Accession Nos. GU827420 and GU827419). A conidial suspension was produced on Mung-bean liquid media and adjusted to a concentration of 1 × 106 CFU/ml. Italian cv. Galileo was used in the test because of its high susceptibility to Bakanae (Ente Nazionale delle Sementi Elette, Verona, Italy, data unpublished). Rice seeds were heat sterilized for 20 min at 60°C, submerged for 30 min in the conidial suspensions, dried, and subjected to a blotter test. Uninoculated, sterilized seeds served as a control. Seeds were incubated for 15 days in a growth chamber (26°C, 80% relative humidity, and 12-h photoperiod). For each strain, the experiment was repeated three times on samples of 25 seedlings. Results were analyzed by analysis of variance and Tukey test. Symptoms consisted of a generic seedling wilt, a root length reduction ranging from 21 to 48%, and the presence of root discoloration. Seed germination was reduced by 9%. Shoot development was not significantly altered. Proof of pathogenicity was obtained through reisolation of F. andiyazi from symptomatic tissues. To our knowledge, this is the first report of F. andiyazi on rice in Europe. References: (1) W. F. O. Marasas et al. Mycologia 93:1203, 2001. (2) H. I. Niremberg and K. O'Donnell. Mycologia 90:434, 1998. (3) E. G. Wulff et al. Environ. Microbiol. 12:649, 2009.
RESUMEN
Los tumores malignos de laringe más frecuentes son los carcinomas escamosos. Los tumores carcinoides suelen crecer en el intestino, el hígado y bronquios pulmonares. La afectación de la laringe es muy infrecuente. Los tumores neuroendocrinos de laringe fueron descritos por vez primera como entidad clínica por Goldman, et al. en 1969. Desde entonces se han publicado 538 casos en la literatura inglesa. La clínica y pronóstico varía en función del tipo de tumor. Presentamos un nuevo caso de carcinoide atípico de aritenoides. Hemos revisado los métodos diagnósticos, el tratamiento y pronóstico de estos tumores poco frecuentes (AU)
Asunto(s)
Masculino , Persona de Mediana Edad , Humanos , Tumores Neuroendocrinos/diagnóstico , Cartílago Aritenoides/patología , Neoplasias Laríngeas/diagnóstico , Cartílagos Laríngeos/cirugía , Tumores Neuroendocrinos/cirugía , Neoplasias Laríngeas/cirugíaRESUMEN
Sarcoidosis is a chronic multisystemic granulomatosis of unknown etiology that affects mainly young adults. It characterized by bilateral hiliar adenopathies interstitial pulmonary infiltrate, and cutaneous and ocular lesions. Localization in upper respiratory tract is infrequent. In the present report we describe a 26-year-old male with a three-month history of a globus sensation, hoarse voice, loud snoring and obstructive sleep apnoea, because of a laryngeal noncaseating granulomatous infiltration. The diagnosis is made through the history, the radiology and the pathological examination. Treatment is symptomatic, due to its tendency to a spontaneous regression. The treatment is based on corticosteroids by systemic or aerosol routes. Micro surgical excision and tracheotomy may be useful in selected patients.
Asunto(s)
Enfermedades de la Laringe/complicaciones , Sarcoidosis/complicaciones , Adulto , Humanos , Enfermedades de la Laringe/diagnóstico por imagen , Enfermedades de la Laringe/cirugía , Masculino , Sarcoidosis/diagnóstico por imagen , Sarcoidosis/cirugía , Apnea Obstructiva del Sueño/etiología , Tomografía Computarizada por Rayos XRESUMEN
La sarcoidosis es una enfermedad granulomatosa crónica multisistémica de etiología desconocida que afecta principalmente a adultos jóvenes. Se caracteriza por adenopatías hiliares bilaterales, infiltrado pulmonar intersticial, lesiones cutáneas y oculares. La afectación de la vía respiratoria superior es rara. Presentamos un caso clínico de un varón de 26 años que refiere sensación de cuerpo extraño en hipofaringe, disfonía y apneas obstructivas del sueño de tres meses de evolución debido a la infiltración de las estructuras supraglóticas por tejido sarcoideo. El diagnóstico se establece a partir de la clínica, los estudios radiológicos, las pruebas de laboratorio y el estudio histológico. El tratamiento de base son medidas de soporte, debido a la remisión espontánea de la clínica. Los corticoides sistémicos y locales presentan buenos resultados. En ocasiones son necesarias técnicas microquirúrgicas y la traqueotomía (AU)
Sarcoidosis is a chronic multisystemic granulomatosis of unknown etiology that affects mainly young adults. It characterized by bilateral hiliar adenopathies interstitial pulmonary infiltrate, and cutaneous and ocular lesions. Localization in upper respiratory tract is infrequent. In the present report we describe a 26-year-old male with a three-month history of a globus sensation, hoarse voice, loud snoring and obstructive sleep apnoea, because of a laryngeal noncaseating granulomatous infiltration. The diagnosis is made through the history, the radiology and the pathological examination. Treatment is symptomatic, due to its tendency to a spontaneous regression. The treatment is based on corticosteroids by systemic or aerosol routes. Micro surgical excision and tracheotomy may be useful in selected patients (AU)
Asunto(s)
Adulto , Masculino , Humanos , Sarcoidosis/complicaciones , Enfermedades de la Laringe/complicaciones , Tomografía Computarizada por Rayos X , Apnea Obstructiva del Sueño/etiologíaAsunto(s)
Antifúngicos/farmacocinética , Naftalenos/farmacocinética , Administración Tópica , Adulto , Algoritmos , Antifúngicos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Difusión , Femenino , Humanos , Masculino , Modelos Biológicos , Naftalenos/administración & dosificación , Vehículos Farmacéuticos , Valor Predictivo de las Pruebas , Absorción Cutánea , TerbinafinaRESUMEN
Antagonists at substance P receptors of the neurokinin 1 (NK1) type have been shown to represent a novel class of antidepressant drugs, with comparable clinical efficacy to the selective serotonin (5-HT) reuptake inhibitors (SSRIs). Because 5-HT(1A) receptors may be critically involved in the mechanisms of action of SSRIs, we examined whether these receptors could also be affected in a model of whole-life blockade of NK1 receptors, i.e. knock-out mice lacking the latter receptors (NK1-/-). 5-HT(1A) receptor labeling by the selective antagonist radioligand [(3)H]N-[2-[4-(2-methoxyphenyl)1-piperazinyl]-ethyl]-N-(2-pyridinyl)-cyclohexanecarboxamide (WAY 100635) and 5-HT(1A)-dependent [(35)S]GTP-gamma-S binding at the level of the dorsal raphe nucleus (DRN) in brain sections, as well as the concentration of 5-HT(1A) mRNA in the anterior raphe area were significantly reduced (-19 to -46%) in NK1-/- compared with NK1+/+ mice. Furthermore, a approximately 10-fold decrease in the potency of the 5-HT(1A) receptor agonist ipsapirone to inhibit the discharge of serotoninergic neurons in the dorsal raphe nucleus within brainstem slices, and reduced hypothermic response to 8-OH-DPAT, were noted in NK1-/- versus NK1+/+ mice. On the other hand, cortical 5-HT overflow caused by systemic injection of the SSRI paroxetine was four- to sixfold higher in freely moving NK1-/- mutants than in wild-type NK1+/+ mice. Accordingly, the constitutive lack of NK1 receptors appears to be associated with a downregulation/functional desensitization of 5-HT(1A) autoreceptors resembling that induced by chronic treatment with SSRI antidepressants. Double immunocytochemical labeling experiments suggest that such a heteroregulation of 5-HT(1A) autoreceptors in NK1-/- mutants does not reflect the existence of direct NK1-5-HT(1A) receptor interactions in normal mice.
Asunto(s)
Antidepresivos/farmacología , Autorreceptores/metabolismo , Receptores de Neuroquinina-1/deficiencia , Receptores de Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Resistencia a Medicamentos/fisiología , Electrofisiología , Inmunohistoquímica , Técnicas In Vitro , Masculino , Ratones , Ratones Noqueados , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Paroxetina/farmacología , Piperazinas/farmacocinética , Piridinas/farmacocinética , Pirimidinas/farmacología , ARN Mensajero/metabolismo , Núcleos del Rafe/citología , Núcleos del Rafe/efectos de los fármacos , Núcleos del Rafe/metabolismo , Receptores de Neuroquinina-1/genética , Receptores de Serotonina/genética , Receptores de Serotonina 5-HT1 , Antagonistas de la Serotonina/farmacocinética , Agonistas de Receptores de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Sustancia P/metabolismoRESUMEN
We present a method to determine the cutaneous bioavailability and hence to evaluate the bioequivalence of topically applied drugs in vivo. The procedure uses serial tape-stripping and transepidermal water loss measurements to quantify the thickness of the removed stratum corneum (SC) and to determine the intact membrane thickness. Following tape-stripping, the drug is extracted from the tapes and assayed, e.g., by HPLC. This provides a drug concentration profile as a function of the normalized position within the SC. The data are fitted to a solution of Fick's second law of diffusion in order to calculate characteristic membrane transport parameters. Integration of the concentration profile over the entire SC thickness, that is, the 'area-under-the-curve', provides a measure of the cutaneous bioavailability and hence can be used to assess the bioequivalence of topically applied drugs.
Asunto(s)
Absorción Cutánea/fisiología , Piel/anatomía & histología , Administración Tópica , Animales , Disponibilidad Biológica , HumanosRESUMEN
PURPOSE: The objective of this study was to determine the availability of the topical drug terbinafine (TBF) in human stratum corneum (SC) in vivo following its administration in formulations containing isopropyl myristate and ethanol. METHODS: The ventral forearms of human volunteers were treated for 4 h with TBF, at a concentration equal to 1/4 saturation, in isopropyl myristate (IPM), in ethanol (EtOH) and in 50:50 v/v IPM/EtOH. At the end of the application period, the treated sites were carefully cleaned of excess vehicle and the SC was progressively removed by sequential tape stripping. TBF was quantified in the SC by: (a) extraction of the tape strips and subsequent HPLC analysis; and (b) attenuated total reflectance infrared spectroscopy (ATR-FTIR) of each sequentially exposed SC surface during the tape stripping procedure. RESULTS: The concentration profile of TBF in the SC (i.e. drug concentration as a function of depth in the membrane) was fitted to the appropriate solution of Fick's second law of diffusion, allowing thereby the drug's SC/vehicle partition coefficient (K) and characteristic diffusion parameter (D/L(2), where D is the diffusivity of TBF in the SC of thickness L) to be deduced. CONCLUSIONS: While D/L(2) for TBF derived from the three vehicles remained essentially constant, the drug's partitioning into the SC was significantly higher from formulations containing ethanol. Both the semi-quantitative infrared data and the more rigorous HPLC results supported these deductions.
Asunto(s)
Antifúngicos/farmacocinética , Depresores del Sistema Nervioso Central/farmacología , Etanol/farmacología , Miristatos/farmacología , Naftalenos/farmacocinética , Absorción Cutánea/efectos de los fármacos , Adulto , Algoritmos , Área Bajo la Curva , Difusión , Femenino , Humanos , Masculino , Modelos Biológicos , Vehículos Farmacéuticos , Solubilidad , Espectrofotometría Infrarroja , TerbinafinaRESUMEN
PURPOSE: The objective of this study was to evaluate, using attenuated total reflectance Fourier transform infrared spectroscopy, the stratum corneum (SC) bioavailability of terbinafine (TBF) following topical treatment with four different formulations. METHODS: Four skin sites on the ventral forearms of five healthy volunteers were treated for 2 h using one of four formulations based on a vehicle consisting of 50% ethanol and 50% isopropyl myristate. Three of these formulations included a percutaneous penetration enhancer: either 5% oleic acid, 10% 2-pyrrolidone or 1% urea. The SC concentration profile of TBF was measured by repeated infrared spectroscopic measurements while sequentially stripping off the layers of this barrier membrane with adhesive tape. This method was validated by HPLC analysis of TBF extracted from the stripped tapes. Transepidermal water loss (TEWL) measurements were also performed, to permit facile estimation of SC thickness. RESULTS: The SC concentration profiles of TBF were fitted to the appropriate solution of Fick's second law of diffusion, thereby allowing determination of the characteristic diffusion and partitioning parameters of the permeating drug. This analysis enabled the efficacies of the different formulations tested to be compared to the no-enhancer control. While it was found that the formulation containing 5% oleic acid significantly enhanced the SC availability of TBF, the other formulations did not improve the apparent drug delivery. CONCLUSIONS: A facile and minimally invasive methodology to evaluate an important aspect of topical drug bioavailability has been described. The analytical methods used (infrared spectroscopy and HPLC) allow estimates of both relative and absolute drug bioavailability in the SC and may be useful, therefore, in the critical determination of bioequivalence between topical formulations.
Asunto(s)
Antifúngicos/administración & dosificación , Antifúngicos/farmacocinética , Naftalenos/administración & dosificación , Naftalenos/farmacocinética , Absorción Cutánea , Administración Tópica , Adulto , Algoritmos , Difusión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectroscopía Infrarroja por Transformada de Fourier , TerbinafinaRESUMEN
CD99/E2 is an integral transmembrane protein which forms, together with Xga, a distinct family whose genes are located in the pseudoautosomal region. The number of T cells that firmly bound to vascular endothelial cells under physiological shear stress increased 2-14-fold upon CD99 stimulation, and bound cells became much more resistant to detachment forces and spread. T cell arrest occurred within 1 min and was dependent on the alpha4beta1-VCAM-1 pathway. In contrast, the alphaLbeta2-ICAM-1 pathway remained unactivated. This was observed with T cell lines and with activated peripheral blood lymphocytes, and was limited within the resting peripheral CD4+ T cells to the memory subset, while virgin cells were unaffected. This discloses a stepwise regulation of the T cell extravasation cascade.
Asunto(s)
Antígenos CD/fisiología , Moléculas de Adhesión Celular/fisiología , Endotelio Vascular/citología , Integrinas/fisiología , Receptores Mensajeros de Linfocitos/fisiología , Linfocitos T/citología , Antígeno 12E7 , Actinas/metabolismo , Transporte Biológico , Biopolímeros , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Tamaño de la Célula , Endotelio Vascular/efectos de los fármacos , Humanos , Integrina alfa4beta1 , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/fisiología , Células Jurkat , Leucemia-Linfoma de Células T del Adulto/patología , Proteínas de Neoplasias/fisiología , Fitohemaglutininas/farmacología , Proteínas Recombinantes de Fusión/fisiología , Reología , Estrés Mecánico , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/farmacología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/fisiologíaAsunto(s)
Epidermis/fisiología , Pérdida Insensible de Agua/fisiología , Adulto , Difusión , Femenino , Humanos , MasculinoRESUMEN
The nuclear matrix-intermediate filament complex (NM-IF) is a protein scaffold which spans the whole cell, and several lines of evidence suggest that this structural frame represents also a functional unit, which could be involved in the epigenetic control of cancer development. Here we report the characterization by high resolution two-dimensional gel electrophoresis and Western blot analysis of the NM-IF complex isolated from prostate cancer (PCa); tumor-associated proteins were identified by comparing the electrophoretic patterns with those of normal human prostate (NHP). Extensive changes in the expression of both the NM and IF proteins occur; they are, however, related in a different way to tumor progression. Poorly differentiated PCa (Gleason score 8-9) shows a strong down regulation of several constitutive cytokeratins (CKs 8, 18, and 19); their expression significantly (P < 0.05) decreases with respect to both NHP and benign prostatic hyperplasia (BPH) and, more interestingly, also with respect to moderately (Gleason score 6-7) and well (Gleason score 4-5) differentiated tumors. Moreover, we have identified a tumor-associated species which is present in all of the tumors examined, systematically absent in NHP and occurs only in a few samples of BPH; this polypeptide, of M(r) 48,000 and pI 6.0, represent a proteolytic fragment of CK8. At variance with these continuing alterations in the expression, the NM proteins undergo stepwise changes correlating with the level of differentiation. The development of less differentiated tumors is characterized by the appearance of several new proteins and by the decrease in the expression of others. Six proteins were found to be expressed with a frequency equal to one in poorly differentiated tumor, namely in all the samples of tumor examined, while in moderately and well differentiated tumors the frequency is less than one, and decreases with increasing the level of differentiation. When tumors of increasing Gleason score are compared with NHP a dramatic increase in the complexity of the protein patterns is observed, indicating that tumor dedifferentiation results in a considerable increase in the phenotypic diversity. These results suggest that tumor progression can be characterized using an appropriate subset of tumor-associated NM proteins.
Asunto(s)
Adenocarcinoma/patología , Regulación Neoplásica de la Expresión Génica , Queratinas/biosíntesis , Proteínas de Neoplasias/biosíntesis , Proteínas Nucleares/biosíntesis , Neoplasias de la Próstata/patología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Anciano , Antígenos Nucleares , Diferenciación Celular , Progresión de la Enfermedad , Electroforesis en Gel Bidimensional , Humanos , Focalización Isoeléctrica , Queratinas/genética , Sustancias Macromoleculares , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Fenotipo , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , Técnica de SustracciónRESUMEN
The effects of a daily injection of the delta selective opioid antagonist naltrindole (1 mg/kg), from birth to postnatal day 19, on antinociceptive responses to morphine (2 mg/kg) in 20-day-old rats of both sexes were investigated. The effects of postnatal handling were studied by including two control groups--one group receiving daily injections of saline, and a naive unhandled group. Antinociception was assessed using the tail-immersion test and time-response curves (5, 10, 15, and 30 min) were carried out for all experimental groups. In all treatment groups females showed greater sensitivity to the noxious stimuli compared to males. No significant effect of naltrindole treatment on baseline latencies was found. Postnatal handling increased sensitivity to thermal pain in both sexes, and reduced the effect of morphine in males. No significant effect of chronic naltrindole administration on morphine antinociception was found in this sex. Naltrindole-treated females showed an increased antinociception when compared to unhandled animals of the same gender. The results indicate that preweanling handling stress and chronic naltrindole treatment differentially affected morphine antinociception in male and female neonatal rats.
Asunto(s)
Analgésicos/farmacología , Manejo Psicológico , Morfina/farmacología , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/farmacología , Dolor , Caracteres Sexuales , Animales , Femenino , Masculino , Naltrexona/farmacología , Dimensión del Dolor , Ratas , Ratas Wistar , Estrés Fisiológico/fisiopatologíaRESUMEN
Using differential scanning calorimetry in combination with pulsed field gel electrophoresis, we relate here the changes in the thermal profile of rat liver nuclei induced by very mild digestion of chromatin by endogenous nuclease with the chain length distribution of the DNA fragments. The enthalpy of the endotherm at 106 degrees C, which reflects the denaturation of the heterochromatic domains, decreases dramatically after the induction of a very small number of double-strand breaks per chromosome; the thermal transition disappears when the loops have undergone on average one DNA chain scission event. Quantitative analysis of the experimental data shows that the loop behaves like a topologically isolated domain. Also discussed is the process of heterochromatin formation, which occurs according to an all-or-none mechanism. In the presence of spermine, a strong condensation agent, only the loops that have undergone one break are able to refold, in confirmation of the extremely cooperative nature of the transition. Furthermore, our results suggest a relationship between the states that give rise to the endotherms at 90 degrees C and 106 degrees C and the morphologies referred to as class II and class III in a previous physicochemical study of the folding of chromatin fragments (Widom, 1986. J. Mol. Biol. 190:411-424) and support the view that the overall process of condensation follows a sequential (two-step) pathway.
Asunto(s)
Cromatina/química , Cromatina/metabolismo , Animales , Cromatina/genética , Ensamble y Desensamble de Cromatina/efectos de los fármacos , ADN/química , ADN/metabolismo , Desoxirribonucleasas/metabolismo , Heterocromatina/química , Heterocromatina/genética , Heterocromatina/metabolismo , Hígado/citología , Masculino , Pliegue de Proteína/efectos de los fármacos , Estabilidad Proteica/efectos de los fármacos , Ratas , Espermina/farmacología , Temperatura , TermodinámicaRESUMEN
1. The influence of a chronic treatment with the delta-selective opioid antagonist naltrindole (1 mg kg-1) during the preweanling period (daily injections from birth to postnatal day 19), on the antinociceptive and sympatholytic effects of the alpha2-adrenergic agonist clonidine in male and female rats of 20 and 25 days of age was investigated. 2. Nociception was assessed using the tail immersion test (water at 50 degrees C) and plasma levels of adrenaline were measured by high-performance liquid chromatography. 3. The dose of clonidine (1.5 mg kg-1) and the time point at which nociceptive responses were recorded (30 min after the administration of the drug) were chosen on the basis of dose-response (0.5, 1, 1.5 and 2 mg kg-1) and time-response (5, 10, 15, 30 and 60 min) curves which were previously carried out in naive control neonatal rats. 4. In females, the functional blockade of the delta-receptor by neonatal naltrindole treatment did not modify the sympatholytic effect of clonidine but prevented clonidine induced antinociception. Conversely, in males naltrindole treatment allowed the appearance of clonidine antinociception and the sympatholytic effect of clonidine. 5. The results indicate that the delta-receptor is involved in the modulation of antinociceptive and sympatholytic responses to clonidine in neonatal rats and suggest the existence of sex differences in the interactions between delta-opioid and alpha2-adrenergic receptors.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Analgésicos/farmacología , Animales Recién Nacidos/metabolismo , Clonidina/farmacología , Epinefrina/sangre , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/farmacología , Receptores Opioides delta/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Naltrexona/administración & dosificación , Naltrexona/farmacología , Antagonistas de Narcóticos/administración & dosificación , Ratas , Ratas Wistar , Caracteres SexualesRESUMEN
To address the existence of possible functional interactions between delta- and mu- receptors in relation to the affective component of pain, we have studied the effects of functional blockade of delta-receptors by a chronic treatment with naltrindole (1 mg/kg, 8 consecutive days) on antinociceptive responses to morphine (2 and 5 mg/kg) in the tail electric stimulation test, in adult male rats. The thresholds for the motor response (tail withdrawal), vocalization during stimulus and vocalization afterdischarge were assessed. These responses are considered to be integrated at spinal, medulla oblongata and diencephalon-rhinencephalon levels, respectively. The results show that the vocalization during stimulus and the vocalization afterdischarge were significantly affected by morphine in a dose dependent manner, the latter response being the most sensitive to the effects of the mu-opioid agonist. However, no significant effect was observed on motor responses at the doses used in this study. Chronic naltrindole treatment did not modify the inhibitory effect of morphine on the vocalization responses. Since the vocalization afterdischarge is related to the affective component of pain, the data suggest that the delta-opioid receptor is not involved in the supraspinal mechanisms at which these responses are organized and that there is not a mu-delta interaction in the modulation of the affective responses to noxious electrical stimulation.
Asunto(s)
Estimulación Eléctrica/métodos , Morfina/metabolismo , Naltrexona/análogos & derivados , Vocalización Animal/efectos de los fármacos , Vocalización Animal/fisiología , Albinismo , Animales , Masculino , Movimiento/efectos de los fármacos , Movimiento/fisiología , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Ratas , Ratas Wistar , Cola (estructura animal)/fisiologíaRESUMEN
The effect of a daily injection of the delta-selective opioid antagonist naltrindole (1 mg/kg), from birth to postnatal day 19, on basal and post-stress corticosterone levels in 25-day old rats of both sexes was investigated. The effects of manipulation were studied by including two control groups, one group received daily injections of saline and a second one was not manipulated. The stress protocol consisted of a 3 min swimming session in water at 20 degrees C. Corticosterone determinations were performed by radioimmunoassay. Control non-manipulated animals showed a significant increase in corticosterone levels in response to stress. Manipulation decreased basal hormone levels in females and prevented the stress-induced rise in corticosterone in males. Functional blockade of the delta-receptor during the preweanling period by the naltrindole treatment inhibited the corticosterone response to stress in females. The results indicate the existence of sex differences in the effects of manipulation on hypothalamus-pituitary-adrenal axis activity and the involvement of the delta-opioid receptor in the modulation of the adrenocortical response to stress during the postnatal period.
Asunto(s)
Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/fisiología , Animales Lactantes/fisiología , Manejo Psicológico , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/farmacología , Animales , Corticosterona/sangre , Femenino , Masculino , Naltrexona/farmacología , Ratas , Ratas Wistar , Receptores Opioides delta/antagonistas & inhibidores , Caracteres Sexuales , Estrés Fisiológico/sangre , Natación , Temperatura , AguaRESUMEN
Chromatin condensation and DNA cleavage at internucleosomal sites have been recognized early as hallmarks of apoptosis, and it has been suggested that extensive DNA chain scission could directly result in the formation of dense chromatin bodies. Here we have shown that no causal relationship exists between DNA degradation and chromatin condensation in glucocorticoid-induced thymocyte apoptosis. The chromatin rearrangement occurred independent of as well as prior to DNA cleavage and involved a specific conformational change at the nucleosome level. In the early stages of the process, the core particles appeared to be tightly packed face-to-face in smooth 11-nm filaments that progressively folded to generate a closely woven network. The network finally collapsed, producing dense apoptotic bodies. Since trypsin digestion relaxed condensed chromatin and histone H4 underwent appreciable deacetylation in the apoptotic cell, we suggest that changes in the DNA-histone interactions represented a major modulating factor of condensation.