RESUMEN
INTRODUCTION: This retrospective cohort study examined the effects of the crossed raised arm (CRA) position in contrast-enhanced computed tomography (CECT) on contrast medium influx and image quality relative to the conventional position. METHODS: Contrast medium influx into the collateral veins on CECT images was evaluated in 92 participants. The CT values of the pulmonary artery, descending aorta, and spleen were obtained in both positions and compared. Anatomical changes in the diameters and area of the subclavian vein and costoclavicular distance were also analyzed. RESULTS: Contras 27 and 6 patients in the conventional and CRA positions, respectively. The influx risk ratio in the CRA position versus that in the conventional position was 0.22 (95% confidence interval, 0.10-0.51). Elevations in the median CT value of the pulmonary artery, descending aorta, and spleen in the CRA position were 7.0% (p < .001), 7.4% (p < .001), and 9.8% (p < .001), respectively. Enlargements in the major and minor diameters of the subclavian vein, subclavian vein area, and costoclavicular distance in the CRA position versus those in the conventional position were 19.3% (p < .001), 28.1% (p < .001), 53.6%, and 30.0% (p < .001), respectively. CONCLUSION: The CRA position effectively prevented contrast medium influx into the collateral veins due to SVS and increased CT values in the target organs in CECT. The diameters and area of the subclavian vein and costoclavicular distance were enlarged at the thoracic outlet, which improved the flow of the contrast medium into the targeted organs. IMPLICATIONS FOR PRACTICE: The CRA position can contribute to obtaining better CECT images during common clinical assessments at no additional cost.
Asunto(s)
Brazo , Tomografía Computarizada por Rayos X , Humanos , Brazo/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste , AbdomenRESUMEN
Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A(2A) receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) at Thr34 (the cAMP-dependent protein kinase [PKA] site) in striatopallidal neurons, and opposes dopamine D2 receptor signaling. In contrast, the role of adenosine A(1) receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A(1) receptors on D(1), D(2) and A(2A) receptor signaling using mouse neostriatal slices. An A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (100 nM), caused a transient increase, followed by a transient decrease, in DARPP-32 Thr34 phosphorylation. Our data support the following model for the actions of the A(1) receptor agonist. The A(1) receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D(2) receptors of A(2A) receptor/G(olf)/cAMP/PKA signaling. The A(1) receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic G(i) mechanism, resulting in inhibition of D(1) and A(2A) receptor-coupled G(olf)/cAMP/PKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A(1) receptors play a major modulatory role in dopamine and adenosine receptor signaling.
Asunto(s)
Neostriado/fisiología , Receptor de Adenosina A1/fisiología , Receptor de Adenosina A2A/metabolismo , Receptores de Dopamina D1/metabolismo , Transducción de Señal/fisiología , Adenosina/análogos & derivados , Adenosina/farmacología , Agonistas del Receptor de Adenosina A1 , Antagonistas del Receptor de Adenosina A1 , Antagonistas del Receptor de Adenosina A2 , Animales , Benzazepinas/farmacología , Antagonistas de Dopamina/farmacología , Fosfoproteína 32 Regulada por Dopamina y AMPc/metabolismo , Interacciones Farmacológicas , Expresión Génica/efectos de los fármacos , Técnicas In Vitro , Ratones , Ratones Endogámicos C57BL , Neostriado/citología , Fenetilaminas/farmacología , Racloprida/farmacología , Transducción de Señal/efectos de los fármacos , Treonina/metabolismo , Triazinas/farmacología , Triazoles/farmacología , Xantinas/farmacologíaRESUMEN
In March 1997, we analyzed the water of all tubewells used for drinking in Samta village in the Jessore district, Bangladesh. It has been confirmed from the survey that the arsenic contamination in Samta was one of the worst in the Ganges basin including West Bengal, India. 90% of the tubewells had arsenic concentrations above the Bangladesh standard of 0.05 mg/l. Tubewells with higher arsenic concentrations of over 0.50 mg/l were distributed in the southern area with a belt-like shape from east to west, and the distribution of arsenic concentration showed gradual decreasing toward northern area of the village. In order to examine the characteristics of the arsenic distribution in Samta, we have performed investigations such as: 1) the characteristics of groundwater flow, 2) the distribution of arsenic in the ground, 3) the concentration of arsenic and the other dissolved materials in groundwater, and 4) the distribution of arsenic concentration of trivalence and pentavalence. This paper examines the mechanism of arsenic release to groundwater and explains the above-mentioned characteristics of the arsenic contamination in Samta through the investigations of the survey results for these years.
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Arsénico/análisis , Contaminantes del Suelo/análisis , Contaminantes del Agua/análisis , Abastecimiento de Agua , Bangladesh , Monitoreo del Ambiente , Geografía , Valores de Referencia , Movimientos del AguaRESUMEN
A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats. One dose level of 2000 mg potency/kg was set in both studies. Single oral dose toxicity study of S-1090 No deaths occurred. Diarrhea occurred on the dosing day and slightly soft feces lasted until 6 days after administration. These changes were considered to result from changes of intestinal flora induced by the antibiotic activity of S-1090. Reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were also observed until the next day after administration. Body weights increased favorably, and no S-1090-related pathological changes were observed. The oral lethal dose of S-1090 was estimated to be more than 2000 mg potency/kg. Single intravenous dose toxicity study of S-1090-Na No deaths occurred. The rats showed characteristic clinical signs such as hypoactivity, abnormal gait and hypopnea immediately after dosing, and some rats showed prone position or paleness of eyeballs and ear auricles in due course. These signs disappeared by 4 hr after administration. Slightly soft feces and reddish-brown feces were observed much the same as in the orally-treated rats. Body weights increased favorably. In the pathological examinations, slight cecal enlargement and increased basophilia, dilatation and calcification of the renal tubules in the kidney were observed. The intravenous lethal dose of S-1090-Na was estimated to be more than 2000 mg potency/kg.
Asunto(s)
Cefalosporinas/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Cefalosporinas/administración & dosificación , Diarrea/inducido químicamente , Inyecciones Intravenosas , Intestinos/microbiología , Ratas , Ratas Sprague-DawleyRESUMEN
One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) in rats were conducted. Doses were set at 80, 200, 500 and 1250 mg potency/kg/day in the one-month toxicity study, and 100, 300 and 1000 mg potency/kg/day in the three-month toxicity study. Body weights increased favorably and no deaths occurred in all treated groups of both studies. The changes observed in both studies were soft feces, abdominal distention, increased food and water consumption, decreases of urine volume and pH, and a decrease of blood neutrophils in almost all treated groups, reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) in groups dosed at 300 mg potency/kg or more, and a lower mature granulocyte ratio in the bone marrow in groups dosed at 1000 mg potency/kg or more. In necropsy, cecal enlargement with a large amount of muddy content was observed in all treated groups of both studies. In the three-month toxicity study, elevated drug-metabolizing enzyme activities were noted in the liver of the males in the 1000 mg potency/kg group. These changes were slight except for the cecal enlargement and the rats recovered well with drug withdrawal. Since no toxicologically significant changes were noted in either study, the NOAEL of S-1090 was estimated to be 1250 mg potency/kg/day in the one-month toxicity study and 1000 mg potency/kg/day in the three-month toxicity study.
Asunto(s)
Cefalosporinas/toxicidad , Administración Oral , Animales , Células Sanguíneas/efectos de los fármacos , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Células de la Médula Ósea/efectos de los fármacos , Cefalosporinas/administración & dosificación , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Audición/efectos de los fármacos , Hígado/química , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , UrinálisisRESUMEN
Cefmatilen hydrochloride hydrate (S-1090) was administered at 500 and 1000 mg potency/kg once orally to beagle dogs. No deaths occurred. Vomiting, diarrhea or mucous feces occurred on the dosing day, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were also observed on the dosing and next day. Increases of plasma urea nitrogen and iron were observed on the next day after dosing. No remarkable changes were noted in other examination items. The animals in both groups were considered to be exposed to a similar level of S-1090 based on the toxicokinetic data. The oral lethal dose of S-1090 in dogs was estimated to be more than 1000 mg potency/kg.
Asunto(s)
Cefalosporinas/toxicidad , Administración Oral , Animales , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Cefalosporinas/administración & dosificación , Perros , Ingestión de Alimentos/efectos de los fármacos , Masculino , Sangre Oculta , UrinálisisRESUMEN
Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.
Asunto(s)
Cefalosporinas/toxicidad , Administración Oral , Animales , Antibacterianos/toxicidad , Células Sanguíneas/efectos de los fármacos , Análisis Químico de la Sangre , Peso Corporal/efectos de los fármacos , Células de la Médula Ósea/citología , Cefdinir , Clostridioides difficile/efectos de los fármacos , Ingestión de Líquidos/efectos de los fármacos , Esquema de Medicación , Ingestión de Alimentos/efectos de los fármacos , Enterobacteriaceae/efectos de los fármacos , Femenino , Audición/efectos de los fármacos , Intestinos/microbiología , Hígado/química , Masculino , Sangre Oculta , Tamaño de los Órganos/efectos de los fármacos , Ratas , Streptococcus/efectos de los fármacos , UrinálisisRESUMEN
Sulfamethoxazole (SMX), a hormone-mediated rodent-specific nongenotoxic carcinogen, was administered to CB6F1 mice carrying a human prototype c-Ha-ras gene (Tg-rasH2) at doses of 0, 25, 100 or 400 mg/kg/day and to the wild-type mice at a dose of 400 mg/kg/day in feed for 26 weeks to evaluate the carcinogenicity and to validate the Tg-rasH2 model. N-Methyl-N-nitrosourea was administered at an intraperitoneal dose of 75 mg/kg to Tg-rasH2 as a positive control and the experimental system was confirmed to be valid. Histopathological examination revealed adenomas of the lung and Harderian gland and hemangiosarcoma of the spleen at low frequencies in the Tg-rasH2 treated with SMX; however, no statistically significant differences were observed either in the onset or prevalence rates of these neoplasms compared with that in the control group. Between the wild-type mice and Tg-rasH2, the onset rate and prevalence of the neoplasms were not significantly different, but the neoplasms tended to be more frequent in Tg-rasH2 mice showing a sensitivity to tumorigenicity. Follicular epithelial cell hyperplasia was observed in the thyroid gland in the groups of Tg-rasH2 given 100 mg/kg SMX or more, but no neoplastic lesion was observed. SMX was judged to be negative for carcinogenic potential in Tg-rasH2 in the present study.
Asunto(s)
Carcinógenos/toxicidad , Neoplasias Experimentales/inducido químicamente , Sulfametoxazol/toxicidad , Animales , Peso Corporal , Pruebas de Carcinogenicidad , Femenino , Genes ras , Glándula de Harder/patología , Humanos , Hiperplasia , Neoplasias Pulmonares/patología , Masculino , Metilnitrosourea/toxicidad , Ratones , Ratones Transgénicos , Neoplasias Experimentales/patología , Neoplasias del Bazo/patología , Sulfametoxazol/administración & dosificación , Glándula Tiroides/patologíaRESUMEN
This paper will review 1) experimental models of drug-seeking behavior and 2) mechanisms underlying the behavior, focusing on cocaine self-administration. After the acquisition of self-administration, vigorous lever-pressing is generally observable after the drug was replaced by saline. This lever-pressing behavior under saline infusion can be considered "drug-seeking behavior". Drug-seeking behavior is reinstated by non-contingent injection of the drug, stress exposure and presentation of drug-associated stimuli even after extinction. This is called a relapse/reinstatement model. Electrophysiological studies showed that the majority of accumbal neurons is tonically inhibited during cocaine self-administration and exhibited phasic increases in firing time-locked to cocaine self-infusion, which might represent the craving state or drive animals to drug-seeking behavior. Voltammetry and microdialysis studies indicated that the timing of drug-seeking responses can be predicted from fluctuations in accumbal extracellular dopamine concentration. Whereas dopamine D2-like agonists reinstated extinguished cocaine-seeking behavior, D1-like agonists prevented the relapse in cocaine-seeking behavior induced by cocaine itself. Given that an AMPA receptor antagonist, but not dopamine antagonist, prevented cocaine-seeking behavior induced by cocaine, glutamate transmission in the nucleus accumbens is thought to be important for expression of craving or drug-seeking behavior.
Asunto(s)
Modelos Animales de Enfermedad , Autoadministración , Trastornos Relacionados con Sustancias , Animales , AMP Cíclico/fisiología , Proteínas Quinasas Dependientes de AMP Cíclico/fisiología , Dopamina/fisiología , Ácido Glutámico/fisiología , Humanos , Neuronas/fisiología , Núcleo Accumbens/fisiología , Recurrencia , Refuerzo en Psicología , Estrés Fisiológico , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day.
Asunto(s)
Borohidruros/toxicidad , Compuestos de Boro/toxicidad , Compuestos de Sulfhidrilo/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Boro/sangre , Femenino , Inyecciones Intravenosas , Enfermedades Renales/inducido químicamente , Hígado/química , Masculino , Intoxicación/sangre , Intoxicación/patología , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
Interleukin-1beta mRNA was induced by i.c.v. injection of the beta-adrenoceptor agonist isoproterenol. Lower doses of procaterol, a beta2-adrenoceptor agonist showed stronger induction of the mRNA than isoproterenol. These inductions were primarily observed in the glial cells. On the other hand, the beta1-adrenoceptor agonist dobutamine induced expression of this mRNA only in the meninges. These results suggest the existence of a system for regulation of interleukin-1beta gene expression via beta2-adrenoceptors in the brain parenchyma.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Encéfalo/fisiología , Ventrículos Cerebrales/fisiología , Interleucina-1/biosíntesis , Isoproterenol/farmacología , Neuroglía/fisiología , Receptores Adrenérgicos beta 2/fisiología , Transcripción Genética , Agonistas Adrenérgicos beta/administración & dosificación , Animales , Ventrículos Cerebrales/efectos de los fármacos , Dobutamina/farmacología , Inyecciones Intraventriculares , Isoproterenol/administración & dosificación , Masculino , Meninges/efectos de los fármacos , Meninges/fisiología , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos beta 1/fisiología , Receptores Adrenérgicos beta 2/efectos de los fármacosRESUMEN
The effects of isoproterenol, a beta-adrenoceptor agonist, on the production of interleukin-1beta in the brain and on mechanical nociception were examined in rats. Intracerebroventricular (i.c.v.) injection of isoproterenol at the dose of 3 microg/rat markedly induced interleukin-1beta mRNA in the molecular layer of the hippocampus, medial preoptic area, paraventricular thalamic nucleus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus and central gray 1 h after injection. In these regions, interleukin-1beta mRNA was expressed mainly in the glial cells. The thresholds to the mechanical stimulation to the hind paw were elevated by i.c.v. administration of isoproterenol (1 to 10 microg/rat). When isoproterenol was given at the dose of 3 microg/rat, the analgesic effect showed two peaks. The first peak was observed at 60 min after injection and the second was observed at 180 min. The second phase of analgesia was antagonized by coadministration of interleukin-1 receptor antagonist. These results suggest that isoproterenol produces an analgesic effect, at least in part, through the induction of interleukin-1beta expression in the brain.
Asunto(s)
Analgésicos/farmacología , Interleucina-1/biosíntesis , Isoproterenol/farmacología , Analgésicos/administración & dosificación , Animales , Northern Blotting , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Histocitoquímica , Hibridación in Situ , Inyecciones Intraventriculares , Interleucina-1/genética , Isoproterenol/administración & dosificación , Masculino , Dimensión del Dolor/efectos de los fármacos , Estimulación Física , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores de Interleucina-1/antagonistas & inhibidoresRESUMEN
The effects of interleukin-1 beta on the mechanical nociceptive threshold in rat were examined using the paw-pressure test. An intracerebroventricular (i.c.v.) injection of interleukin-1 beta at doses of 10 and 100 pg/rat caused hyperalgesia to mechanical stimuli. Higher doses of interleukin-1 beta (1 and 10 ng/rat) induced an analgesic effect. The coadministration of the interleukin-1 receptor antagonist completely antagonized the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of alpha-helical-corticotropin-releasing factor [9-41] 15 min prior to interleukin-1 beta administration completely blocked the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of sodium salicylate 15 min prior to interleukin-1 beta administration inhibited the hyperalgesic effect of interleukin-1 beta, but not the analgesic effect. These results suggest that interleukin-1 beta produces biphasic effects on the mechanical nociceptive threshold through the interleukin-1 receptor in the brain and that a corticotropin-releasing factor-mediated pathway is involved. Furthermore, the hyperalgesic effect of interleukin-1 beta may be mediated by prostaglandins.
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Hiperalgesia/fisiopatología , Interleucina-1/farmacología , Umbral del Dolor/efectos de los fármacos , Animales , Hormona Liberadora de Corticotropina/farmacología , Antagonistas de Hormonas/farmacología , Hiperalgesia/etiología , Inyecciones Intraventriculares , Interleucina-1/administración & dosificación , Masculino , Dimensión del Dolor , Fragmentos de Péptidos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Interleucina-1/antagonistas & inhibidores , Salicilato de Sodio/farmacologíaRESUMEN
The induction of interleukin-1 beta (IL-1 beta) mRNA in the rat brain following subcutaneous injection of formalin into the hind paws was investigated by in situ hydridization. IL-1 beta mRNA was markedly induced in the hypothalamus after the injection of formalin into both hind paws. On the other hand, IL-1 beta mRNA was scarcely observed in the hypothalamus of saline-injected control rats. The type of cells expressing IL-1 beta mRNA was likely glia because their nuclei were densely stained by Cresyl violet and were relatively small. The present results suggest that IL-1 beta mRNA is induced in the glial cells of the hypothalamus by persistent pain which is caused by formalin injection.
Asunto(s)
Formaldehído/farmacología , Miembro Posterior/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Interleucina-1/metabolismo , ARN Mensajero/metabolismo , Animales , Hibridación in Situ , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
We previously reported evidence of beta-adrenoceptor-mediated induction of IL-1 beta mRNA in the rat hypothalamus. The present in vitro studies using northern blot analysis showed that the beta-adrenoceptor agonist isoproterenol (1 x 10(-8) to 1 x 10(-5) M) caused a marked induction of IL-1 beta mRNA in microglia, but not in astrocytes. This induction was remarkably suppressed by pretreatment of cells with the beta-adrenoceptor antagonist propranolol. These phenomena were confirmed by in situ hybridization with digoxigenin-labelled IL-1 beta RNA probe. Furthermore, dibutyryl cyclicAMP (dbcAMP) (5 x 10(-4) and 5 x 10(-5) M) markedly induced IL-1 beta mRNA in microglia. The intracellular level of cAMP in microglia was elevated in a dose-dependent manner when they were treated with isoproterenol, and this elevation was completely blocked by propranolol. The induction of IL-1 beta mRNA by either isoproterenol or dbcAMP was strongly inhibited by a cAMP-dependent protein kinase inhibitor, H8. These results, taken together, suggest that (1) microglia primarily induce IL-1 beta mRNA by stimulation of beta-adrenoceptors, and (2) cAMP and cAMP-dependent protein kinase presumably participate in a signal transduction mechanism involved in the induction of IL-1 beta mRNA via beta-adrenoceptors.
Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/fisiología , AMP Cíclico/fisiología , Interleucina-1/biosíntesis , Microglía/metabolismo , ARN Mensajero/biosíntesis , Receptores Adrenérgicos beta/fisiología , Agonistas Adrenérgicos beta/farmacología , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Northern Blotting , Células Cultivadas , AMP Cíclico/metabolismo , Inmunohistoquímica , Hibridación in Situ , Isoproterenol/farmacología , Microglía/efectos de los fármacos , Sondas ARN , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos beta/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Coexistence of the mRNA for each subtype of opioid receptor (OPR) with the mRNA for preprotachykinin A (PPTA), a precursor protein of substance P (SP), in the rat dorsal root ganglia was examined by double in situ hybridization technique. About 90% and 30% of PPTA mRNA-positive neurons expressed mu- and kappa-OPR mRNAs at high level, respectively. However, only about 3% of PPTA mRNA-positive neurons expressed delta-OPR mRNA at high level. These results suggest that mu- and kappa-OPRs exist on most of and a part of the primary afferent terminals containing SP, respectively. On the other hand, among the neurons which highly expressed mu-, delta- or kappa-OPR mRNA, PPTA mRNA was not expressed in about 58%, 95% or 24% of those neurons, respectively. These findings suggest the possibility that OPRs co-exist with other neurotransmitters and/or neuromodulators than SP in the primary afferent neurons.
Asunto(s)
Ganglios Espinales/fisiología , Precursores de Proteínas/biosíntesis , ARN Mensajero/metabolismo , Receptores Opioides/biosíntesis , Taquicininas/biosíntesis , Animales , Northern Blotting , Hibridación in Situ , Masculino , Sondas ARN , Ratas , Ratas Sprague-Dawley , Receptores Opioides delta/biosíntesis , Receptores Opioides kappa/biosíntesis , Receptores Opioides mu/biosíntesis , Sustancia P/metabolismoRESUMEN
PURPOSE: To determine in rats whether there are time-dependent changes in interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) gene expression in transient retinal ischemia and to localize their mRNAs in the retina. METHODS: Retinal ischemia was induced in Sprague-Dawley rats by ligating the optic nerve. Two hours later, the ligature was released and reperfusion occurred. The levels of IL-1 alpha and IL-1 beta gene expression in the sensory retina were then compared at various times after reperfusion by a semiquantitative polymerase chain reaction method. Localization of their expressed mRNAs was examined by in situ hybridization histochemistry. RESULTS: Little expression of IL-1 alpha and IL-1 beta genes was observed in normal retina. IL-1 alpha gene expression rapidly increased (about 30-fold greater than that of the control) as early as 1 hour after cessation of ischemia, reached a peak (about 50-fold) at 3 to 12 hours, and then gradually decreased to near baseline levels. IL-1 beta gene expression began to increase 2 hours later than did that of IL-1 alpha and had two peaks. IL-1 beta gene was found by in situ hybridization histochemistry to be expressed by retinal glial cells, endothelial cells, and neutrophils infiltrating the retina and vitreous. No gene expression was found in the control retinas. CONCLUSIONS: Expression of IL-1 alpha and IL-1 beta genes was dramatically upregulated during reperfusion after induced retinal ischemia. IL-1 beta gene was expressed by retinal glial cells, endothelial cells, and neutrophils recruited into the retina. From these results, it appeared that IL-1 may have an important role in retinal ischemia-reperfusion injury.
Asunto(s)
Interleucina-1/biosíntesis , Isquemia/metabolismo , Vasos Retinianos/metabolismo , Animales , Secuencia de Bases , Cartilla de ADN , Endotelio/metabolismo , Expresión Génica , Hibridación in Situ , Interleucina-1/genética , Isquemia/patología , Masculino , Datos de Secuencia Molecular , Neuroglía/metabolismo , Neutrófilos/metabolismo , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Retina/metabolismo , Vasos Retinianos/patologíaRESUMEN
The distribution of type I interleukin-1 receptor (IL-1R1) mRNA in the rat brain was examined by in situ hybridization technique. IL-1R1 mRNA was expressed in several brain regions including the anterior olfactory nucleus, medial thalamic nucleus, posterior thalamic nucleus, basolateral amygdaloid nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, median eminence, mesencephalic trigeminal nucleus, motor trigeminal nucleus, facial nucleus and Purkinje cells of the cerebellum. Furthermore, we identified neuronal expression of IL-1R1 mRNA using simultaneous detection (double in situ hybridization) of IL-1R1 mRNA with neuron specific enolase mRNA. In addition to the expression in neuronal cells, IL-1R1 mRNA was also expressed on the vascular walls and the epithelial cells of the choroid plexus and the ventricles. These findings suggest the possibility that IL-1 produces its multiple effects on the central nervous system through the actions not only on neuronal cells but also on endothelial and epithelial cells.
Asunto(s)
Química Encefálica , Proteínas del Tejido Nervioso/biosíntesis , ARN Mensajero/análisis , Receptores de Interleucina-1/biosíntesis , Animales , Ventrículos Cerebrales/irrigación sanguínea , Plexo Coroideo/irrigación sanguínea , Endotelio Vascular/metabolismo , Epitelio/metabolismo , Hibridación in Situ , Proteínas del Tejido Nervioso/genética , Neuronas/metabolismo , Fosfopiruvato Hidratasa/biosíntesis , Fosfopiruvato Hidratasa/genética , Sondas ARN , Ratas , Ratas Sprague-Dawley , Receptores de Interleucina-1/genéticaRESUMEN
Expression of interleukin-1 beta (IL-1 beta) mRNA in the rat brain after transient forebrain ischemia was investigated by in situ hybridization histochemistry. Thirty min after the start of recirculation, IL-1 beta mRNA was induced in the several brain regions, including the olfactory bulb, cerebral cortex, hippocampus, striatum and thalamus where neuronal degeneration was reported to be observed after transient forebrain ischemia. The hybridization signals were observed both on the glial cells and around the vascular walls.
Asunto(s)
Encéfalo/metabolismo , Expresión Génica , Interleucina-1/biosíntesis , Ataque Isquémico Transitorio/metabolismo , Neuronas/metabolismo , ARN Mensajero/biosíntesis , Animales , Encéfalo/patología , Corteza Cerebral/metabolismo , Circulación Cerebrovascular , Cuerpo Estriado/metabolismo , Diencéfalo/metabolismo , Hipocampo/metabolismo , Hibridación in Situ , Masculino , Degeneración Nerviosa , Neuroglía/metabolismo , Neuronas/patología , Bulbo Olfatorio/metabolismo , Especificidad de Órganos , Sondas ARN , ARN Mensajero/análisis , Ratas , Ratas Wistar , Telencéfalo/metabolismo , Tálamo/metabolismoRESUMEN
Distributions of mu- and kappa-opioid receptor mRNAs in the lumbar spinal cord and dorsal root ganglia of the adult rat were examined using the in situ hybridization technique. In the lumbar spinal cord, mu-opioid receptor mRNA was expressed intensely in laminae I, II and VIII. On the other hand, kappa-opioid receptor mRNA was expressed intensely in laminae I and II, and moderately throughout laminae III-VIII. In the dorsal root ganglia, mu-opioid receptor mRNA was intensely expressed and kappa-opioid receptor mRNA was expressed in a smaller number of cells than mu-opioid receptor mRNA.