RESUMEN
The bile steroids (BS) cholic acid and chenodeoxycholic acid are produced in hepatocytes and in the brain. Nothing is known about neuronal actions of BS. Deficiency in a 27-hydroxylase enzyme coincides with reduced production of chenodeoxycholic acid (CDCA) and a relative increase in cholic acid in an inherited lipid storage disease, cerebrotendinous xanthomatosis, characterized by neurological dysfunctions, which can be treated by dietary CDCA. We have examined the modulation of hypothalamic network activity by nine common BS. Cholate and CDCA significantly reduced the firing of hypothalamic neurons and synchronized network activity with CDCA being nearly 10 times more potent. The synthetic BS dehydrocholate synchronized the activity without affecting the firing rate. Gabazine, a GABA(A) receptor antagonist, occluded synchronization by BS. Whole-cell patch clamp recordings revealed a block of NMDA- and GABA(A)-receptors by BS. Potencies of nine common BS differed between NMDA and GABA(A) receptors, however in both cases they correlated with BS affinities for albumin but not with their lipophilicity, supporting a direct action at ligand gated ion channels. GABAergic synaptic currents displayed a faster decay under BS. Our data provide new insight into extrahepatic functions of BS revealing their neuroactive potential.
Asunto(s)
Ácido Quenodesoxicólico/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Hipotálamo/efectos de los fármacos , Neuronas/efectos de los fármacos , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animales , Animales Recién Nacidos , Ácido Quenodesoxicólico/metabolismo , Antagonistas de Aminoácidos Excitadores/metabolismo , Antagonistas de Receptores de GABA-A/metabolismo , Hipotálamo/metabolismo , Ratones , Neuronas/metabolismo , Técnicas de Placa-Clamp , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
We recorded 872 single units across the complete sleep-waking cycle in the mouse preoptic area (POA) and basal forebrain (BFB), which are deeply involved in the regulation of sleep and wakefulness (W). Of these, 552 were sleep-active, 96 were waking-active, 106 were active during both waking and paradoxical sleep (PS), and the remaining 118 were state-indifferent. Among the 872, we distinguished slow-wave sleep (SWS)-specific, SWS/PS-specific, PS-specific, W-specific, and W/PS-specific neurons, the last group being further divided into specific tonic type I slow (TI-Ss) and specific tonic type I rapid (TI-Rs) both discharging specifically in association with cortical activation during both W and PS. Both the SWS/PS-specific and PS-specific neurons were distributed throughout a wide region of the POA and BFB, whereas the SWS-specific neurons were mainly located in the middle and ventral half of the POA and adjacent BFB, as were the W-specific and W/PS-specific neurons. At the transition from waking to sleep, the majority of SWS-specific and all SWS/PS-specific neurons fired after the onset of cortical synchronization (deactivation), whereas all W-specific and W/PS-specific neurons showed a significant decrease in firing rate >0.5 s before the onset. At the transition from SWS to W, the sleep-specific neurons showed a significant decrease in firing rate 0.1 s before the onset of cortical activation, while the W-specific and W/PS-specific neurons fired >0.5 s before the onset. TI-Ss neurons were characterized by a triphasic broad action potential, slow single isolated firing, and an antidromic response to cortical stimulation, whereas TI-Rs neurons were characterized by a narrow action potential and high frequency burst discharge in association with theta waves in PS. These data suggest that the forebrain sleep/waking switch is regulated by opposing activities of sleep-promoting (SWS-specific and SWS/PS-specific) and waking-promoting (W-specific and W/PS-specific) neurons, that the initiation of sleep is caused by decreased activity of the waking-promoting neurons (disfacilitation), and that the W/PS-specific neurons are deeply involved in the processes of cortical activation/deactivation.
Asunto(s)
Neuronas/fisiología , Prosencéfalo/citología , Sueño , Vigilia , Estimulación Acústica , Potenciales de Acción , Animales , Mapeo Encefálico , Estimulación Eléctrica , Masculino , Ratones , Ratones Endogámicos C57BL , Área Preóptica/citología , Área Preóptica/fisiología , Prosencéfalo/fisiología , Fases del SueñoRESUMEN
Using extracellular single unit recordings alone or in combination with neurobiotin juxtacellular labeling and orexin (hypocretin) immunohistochemistry in the mouse, we have recorded a total of 452 neurons in the orexin neuron field of the posterior hypothalamus. Of these, 76 exhibited tonic discharge highly specific to wakefulness, referred to as waking-active neurons. They showed differences from each other in terms of spike shape, activity profile, and response to an arousing sound stimulus and could be classified into three groups on the basis of spike shape as: 1) biphasic broad; 2) biphasic narrow; and 3) triphasic. Waking-active neurons characterized by biphasic broad spikes were orexin-immunopositive, whereas those characterized by either biphasic narrow or triphasic broad spikes were orexin-immunonegative. Unlike waking-specific histamine neurons, all orexin and non-orexin waking-active neurons exhibited slow (<10 Hz) tonic discharges during wakefulness and ceased firing shortly after the onset of electroencephalogram (EEG) synchronization (deactivation), the EEG sign of sleep (drowsy state). They remained virtually silent during slow-wave sleep, but displayed transient discharges during paradoxical (or rapid eye movement) sleep. During the transition from sleep to wakefulness, both orexin and triphasic non-orexin neurons fired in clusters prior to the onset of EEG activation, the EEG sign of wakefulness, and responded with a short latency to an arousing sound stimulus given during sleep. In contrast, the biphasic narrow non-orexin neurons fired in single spikes either prior to, or after, EEG activation during the same transition and responded to the stimulus with a longer latency. The activity of all waking-active neurons preceded the return of muscle tonus at the transition from paradoxical sleep to wakefulness. These data support the view that the activity of orexin and non-orexin waking-active neurons in the posterior hypothalamus plays an important wake-promoting role and that their activity antagonizes cortical deactivation and loss of muscle tone.
Asunto(s)
Hipotálamo/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuronas/fisiología , Neuropéptidos/metabolismo , Sueño/fisiología , Vigilia/fisiología , Animales , Sincronización Cortical , Electroencefalografía , Electromiografía , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Tono Muscular/fisiología , Orexinas , Técnicas de Placa-ClampRESUMEN
AIM: The purpose of the study was to investigate the effects of Huangqi Jianzhong Tang (HQJZT) on hematological and biochemical parameters in judo athletes. METHODS: Sixteen male and eight female judo athletes in Hsin-Ming senior high school were randomly and stratified divided into control and experimental group, which received placebo and HQJZT respectively during the five-week training program. The measurement of the hematological and biochemical parameters was performed twice, just before and after the training. The data was analyzed with paired-t test and ANOVA. RESULTS: The values of RBC, Hb, and Hct were obvious decreased after intervention, while the value of GOT, GPT, BUN, and CK was elevated. CONCLUSION: The results indicated the hematological and biochemical changes were caused by the physical training but not the effects of HQJZT. The HQJZT had no adverse effects on the judo athletes in our study.
Asunto(s)
Astragalus propinquus/química , Traumatismos en Atletas/sangre , Traumatismos en Atletas/prevención & control , Creatinina/sangre , Medicamentos Herbarios Chinos/uso terapéutico , Adolescente , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Nitrógeno de la Urea Sanguínea , Recuento de Eritrocitos , Femenino , Humanos , Recuento de Leucocitos , Masculino , Artes Marciales/fisiologíaRESUMEN
OBJECTIVE: To evaluate the long-term durability of transurethral microwave thermotherapy (TUMT) with Prostcare for symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From August 1993 to July 1994, a total of 65 patients with symptomatic BPH who underwent TUMT using the Prostcare apparatus (Bruker Spectospin, Wissembourg, France) with low-energy protocol (maximal power 52 W) were enrolled into a short-term evaluation. Subsequent follow-up information was collected in July 1999. If patients had had any further therapy for BPH, the date of retreatment was considered as an endpoint of TUMT efficacy. If no further therapy for BPH had been needed, they were re-assessed for overall satisfaction. RESULTS: The median follow-up period was 49 months. Twenty patients were excluded for various reasons, including 17 with loss of follow-up and 3 with new diseases that could affect the voiding status. Thirty-eight (84.4%) of 45 valuable patients had received further therapy for BPH, including medication (n = 21, 46.7%), and endoscopic surgery (n = 17, 37.7%). The times to pharmacologic or endoscopic retreatment after TUMT were 8.9+/-11.1 and 23.0+/-14.4 months, respectively (p = 0.0003, log rank test). Only 7 (15.5%) patients had no further treatment, with 3 having satisfactory improvements, but 4 feel dissatisfied yet not needing any further therapy. In addition, 2 patients complained of erectile dysfunction after TUMT and 1 was diagnosed with prostate cancer 50 months after TUMT. In addition, there was no significant difference for all baseline values among three groups with no retreatment or retreatment with medication or endoscopic surgery. CONCLUSION: At the 5-year follow-up, the long-term durability of low-energy TUMT with Prostcare is only exhibited in a few patients and the overall retreatment rate was 84.4%. Thus, patient should be informed of the high probability of supplementary treatment after TUMT.
Asunto(s)
Hipertermia Inducida , Microondas/uso terapéutico , Hiperplasia Prostática/terapia , Anciano , Estudios de Seguimiento , Humanos , Masculino , Satisfacción del Paciente , Factores de TiempoRESUMEN
PURPOSE: To assess our short-term experience with transurethral microwave thermotherapy (TUMT) for symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From August 1993 through July 1994, in total 65 patients with symptomatic BPH were enrolled into this study. The patients' ages ranged from 56 to 95 years with a mean of 70 years. Under local anesthesia with intraurethral instillation of Xylocaine jelly only, all patients received one session of TUMT for up to 60 min with Prostcare equipment. Uroflowmetry was performed and international prostatic symptom score (IPSS) determined before 3 and 6 months after TUMT for assessment of efficacy. All adverse events were recorded and evaluated for clinical relevance. RESULTS: At 3 and 6 months following TUMT, the mean IPSS decreased from 19.7 +/- 6.8 (baseline) to 12.8 +/- 8.2 (-46%) and to 15.5 +/- 9.0 (-21%), respectively; the maximal urine flow rate at 3 and 6 months increased from 9.1 +/- 4.8 ml/s (baseline) to 11.0 +/- 4.9 ml/s (+21%) and to 10.9 +/- 5.6 ml/s (+19%), respectively. During TUMT, burning sensation was the most frequent complaint (38.5%), followed by urethral discomfort (29.2%) and urgency (9.2%). Two patients (3.1%) interrupted TUMT, because of intolerable pain. Following TUMT micturition pain (73.8%) and gross hematuria (45.9%) were the most adverse events. Most of these adverse events disappeared within 2 weeks. One patient suffered from skin erosion over the penoscrotal junction 1 week later. None had retrograde ejaculation; 1 patient complained of erectile dysfunction. CONCLUSION: Although the efficacy of TUMT with Prostcare became less prominent 6 months after TUMT, TUMT was still a tolerable, safe alternative treatment of BPH, especially in patients who were not suitable for transurethral resection of the prostate or anesthesia.
Asunto(s)
Diatermia , Microondas/uso terapéutico , Hiperplasia Prostática/terapia , Anciano , Anciano de 80 o más Años , Diatermia/métodos , Humanos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/fisiopatología , Factores de Tiempo , Uretra , UrodinámicaRESUMEN
We have identified a novel cochlear gene, designated OTOR, from a comparative sequence analysis of over 4000 clones from a human fetal cochlear cDNA library. Northern blot analysis of human and chicken organs shows strong OTOR expression only in the cochlea; very low levels are detected in the chicken eye and spinal cord. Otor and Col2A1 are coexpressed in the cartilaginous plates of the neural and abneural limbs of the chicken cochlea, structures analogous to the mammalian spiral limbus, osseous spiral lamina, and spiral ligament, and not in any other tissues in head and body sections. The human OTOR gene localizes to chromosome 20 in bands p11.23-p12.1 and more precisely to STS marker WI-16380. We have isolated cDNAs orthologous to human OTOR in the mouse, chicken, and bullfrog. The encoded protein, designated otoraplin, has a predicted secretion signal peptide sequence and shows a high degree of cross-species conservation. Otoraplin is homologous to the protein encoded by CDRAP/MIA (cartilage-derived retinoic acid sensitive protein/melanoma inhibitory activity), which is expressed predominantly by chondrocytes, functions in cartilage development and maintenance, and has growth-inhibitory activity in melanoma cell lines.
Asunto(s)
Cóclea/metabolismo , Secuencia Conservada/genética , Mapeo Físico de Cromosoma , Proteínas/genética , Animales , Northern Blotting , Pollos , Cromosomas Humanos Par 20/genética , ADN Complementario/genética , Etiquetas de Secuencia Expresada , Proteínas de la Matriz Extracelular , Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Ratones , Datos de Secuencia Molecular , Proteínas de Neoplasias , Especificidad de Órganos , Biosíntesis de Proteínas , Señales de Clasificación de Proteína/genética , ARN Mensajero/biosíntesis , Rana catesbeiana , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
In order to delimit the supra-brainstem structures that are activated during the sleep-waking cycle, we have examined c-fos immunoreactivity in four groups of polygraphically recorded cats killed after 3 h of prolonged waking (W), slow-wave sleep (SWS), or paradoxical sleep (PS), following microinjection of muscimol (a gamma-aminobutyric acid, GABA agonist) into the periaqueductal grey matter and adjacent areas [Sastre et al. (1996), Neuroscience, 74, 415-426]. Our results demonstrate that there was a direct relationship between a significant increase in c-fos labelling and the amount of PS in the laterodorsalis tegmenti in the pons, supramamillary nucleus, septum, hippocampus, gyrus cingulate, amygdala, stria terminalis and the accumbens nuclei. Moreover, in all these structures, the number of Fos-like immunoreactive neurons in the PS group was significantly higher (three to 30-fold) than in the SWS and W groups. We suggest that the dense expression of the immediate-early gene c-fos in the rhinencephalon and striatum may be considered as a tonic component of PS at the molecular level and that, during PS, the rhinencephalon and striatum are the main targets of an excitatory system originating in the pons.
Asunto(s)
Cuerpo Estriado/metabolismo , Vías Olfatorias/metabolismo , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Sueño REM/fisiología , Vigilia/fisiología , Animales , Gatos , Corteza Cerebral/química , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Cuerpo Estriado/química , Cuerpo Estriado/citología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/análisis , Proteínas de Unión al ADN/análisis , Femenino , Agonistas del GABA/farmacología , Genes Inmediatos-Precoces/fisiología , Hipotálamo/química , Hipotálamo/citología , Hipotálamo/metabolismo , Sistema Límbico/química , Sistema Límbico/citología , Sistema Límbico/metabolismo , Masculino , Microinyecciones , Muscimol/farmacología , Vías Nerviosas , Vías Olfatorias/química , Vías Olfatorias/citología , Sustancia Gris Periacueductal/química , Sustancia Gris Periacueductal/citología , Sustancia Gris Periacueductal/metabolismo , Puente/química , Puente/citología , Puente/metabolismo , Proteínas Proto-Oncogénicas c-fos/análisis , Sueño/efectos de los fármacos , Sueño/fisiología , Sueño REM/efectos de los fármacos , Tálamo/química , Tálamo/citología , Tálamo/metabolismo , Factores de Transcripción/análisis , Vigilia/efectos de los fármacosRESUMEN
OBJECTIVES: To investigate the position, extent, and frequency of Y chromosome microdeletions in Taiwanese patients presenting with nonobstructive azoospermia, and to investigate the effect of microdeletions on reproductive decisions. METHODS: We studied 176 consecutive men with azoospermia in our urology clinic. Polymerase chain reaction tests were performed in 94 patients with nonobstructive azoospermia, and a series of 27 sequence-tagged sites (STSs) mapped within intervals 5 and 6 of Yq11 was selected for analysis. Clinical genetics counseling was provided to couples with microdeletions, and these couples made their own choices about further treatment modalities. RESULTS: Among 94 patients screened for microdeletion, 11 (11.7%) showed microdeletions of one or more STSs. One had a deletion confined to the azoospermia factor b (AZFb) region (encompassing the RBM gene). Two were found to have deletions of both the AZFb and AZFc regions. Eight patients had deletions in the AZFc region (encompassing the DAZ gene). Five had deletions distal to the DAZ gene family. One had multiple, noncontiguous deletions. In 8 patients with testicular histology available, a lack of genotype/phenotype correlation was noted. Of the 11 couples with deletions, 3 thought microdeletion was a serious defect and opted for an artificial insemination of donor or adoption, 5 chose intracytoplasmic sperm injection, and the other 3 decided to undergo treatment with Chinese medicinal herbs. CONCLUSIONS: The most commonly deleted region in the Taiwanese population is AZFc. The genes implicated in Taiwanese spermatogenesis defects are the DAZ and RBM gene families. Twenty-seven percent of couples with microdeletions deferred assisted reproductive technologies because of concern about their underlying genetic defects.
Asunto(s)
Deleción Cromosómica , Oligospermia/diagnóstico , Oligospermia/genética , Cromosoma Y/genética , Adopción/psicología , Mapeo Cromosómico , Femenino , Asesoramiento Genético , Humanos , Masculino , Reacción en Cadena de la Polimerasa/métodos , Reproducción/genética , Lugares Marcados de Secuencia , TaiwánRESUMEN
The first case of hemolytic disease of the newborn (HDN) possibly caused by anti-Di(a) in a Chinese infant in Taiwan is reported. The mother had two pregnancies before but no history of blood transfusion. Her first male infant was normal, but her second full-term male one developed mild jaundice soon after birth, and the total bilirubin level was 12.1 mg/dL, 18.3 mg/dL, 23.6 mg/dL at 24 hours, 48 hours, and 72 hours of age, respectively. Total bilirubin was 9.1 mg/dL on the eighth day after receiving phototherapy and compatible blood exchange transfusion. The infant recovered uneventfully. The immunohematological study revealed that the mother was group AB, Rh (D)+; Di(a - b+), the father was group O, Rh (D)+; Di(a + b+), the infant boy and his 2-year-old brother were group B, Rh(D)+; Di(a + b+). The direct antiglobulin test (DAT) on the infant red cells was positive (4+ with polyspecific AHG; 4+ with anti-IgG). The maternal serum and infant's eluate from red blood cells showed negative reactions in routine antibody detection tests, but they contained alloantibody reacting against the Di(a+) cells by the manual polybrene test (MP) and indirect antiglobulin test (IAT) in AHG phase. The anti-Di(a) titers in the mother's serum was MP 1:256 and AHG 1:256, and in the infant's eluate was MP 1:128 and AHC 1:64 against Di(a + b+) cells. Based on the above results we conclude that the jaundice in this newborn baby was caused by maternal anti-Di(a) which was most likely induced by previous pregnancy. In conclusion, Diego blood group is a system of high value in anthropology because it accounts for the Mongoloid origin of American Indians, Japanese and Chinese. Anti-Di(a) may cause HDN, as in our case of HDN due to maternal anti-Di(a) in a Chinese infant. But in Europe and America, where practically all people are Di(a - b+) phenotypes, the system seems of no interest in parental studies as well as in blood transfusions. Owing to the Di(a) antigen is of higher incidence in Chinese population, we suggest that the Diego system should be involved in routine compatibility testing or antibody identification problems in parental studies and in blood transfusions in Taiwan.
Asunto(s)
Antígenos de Grupos Sanguíneos/inmunología , Eritroblastosis Fetal/etiología , Femenino , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
It is known that histamine (HA) and type B monoamine oxidase (MAO-B), an enzyme involved in its metabolism, are present in the posterior hypothalamus, but the sites where MAO-B intervenes in HA metabolism remain uncertain. The present study examined and compared the detailed distribution and morphology of neurons immunoreactive to HA (HA-ir) and MAO-B (MAO-B-ir) in the cat hypothalamus. HA-ir neurons were localized almost exclusively in the posterior hypothalamus with the largest group in the tuberomammillary nucleus and adjacent areas. MAO-B-ir staining was detected in the vast majority of HA-ir neurons, suggesting that the degradation of tele-methylhistamine (t-MHA), the direct metabolite of HA, may occur within these cells. Nevertheless, a few HA-ir cells showed no detectable or very weak MAO-B-ir labeling; a small group of neurons containing MAO-B alone was detected in the area dorsolateral to the caudal part of the arcuate nucleus. Numerous HA-ir axons and terminal-like structures were distributed unevenly in virtually all hypothalamic regions. One of their principal trajectories ascended through the ventrolateral part of the hypothalamus and rostrally formed an axon column, which ascended into the preoptic area and contributed fibers to the diagonal band of Broca and bed nucleus of the stria terminalis. Other HA-ir axons passed laterally, dorsal to the zona incerta or ventrally through a narrow zone dorsal to the optic tract. Numerous long HA-ir axons coursed dorsomedially from the ventrolateral posterior hypothalamus to the dorsal hypothalamic area. Many are oriented vertically to the thalamus in the midline. MAO-B-ir axons and fibers were detectable throughout the hypothalamus and overlapped the areas distributing HA-ir fibers. They were, however, weaker in staining intensity and apparently fewer than the HA-ir fibers. MAO-B-ir glial cells were numerous in all hypothalamic structures rich in HA-ir fibers. These results suggest that the metabolism of t-MHA may also occur within HA terminals and glial cells.
Asunto(s)
Gatos/metabolismo , Histamina/metabolismo , Hipotálamo/metabolismo , Monoaminooxidasa/metabolismo , Animales , Hipotálamo/fisiología , Inmunohistoquímica/métodos , Fibras Nerviosas/metabolismo , Vías Nerviosas/fisiología , Coloración y Etiquetado , Distribución TisularRESUMEN
The present study, using a diaminobenzidine (DAB)-coupled peroxidation method, examined the distribution and morphological characteristics of neuronal structures containing type B monoamine oxidase (MAO-B) in the cat hypothalamus. Large and intensely stained, distinctive MAO-B-positive cells, multipolar and with long dendritic arbors, were principally distributed in the ventral hypothalamus extending from A7 to A12.5 of the Horsley-Clarke plane. These cells were located caudally in the ventral surface of the brain including the tuberomamillary nucleus (TM) and the region surrounding the mamillary nuclei. Rostrally, they were aggregated in the area surrounding the fornix, particularly in the lateral perifornical region, and dispersed in the anterior mamillary nucleus, lateral hypothalamic area (HLA), and the medial tip of the entopeduncular nucleus. The most rostral positive cell group was identified in a narrow space between the optic tract and the entopeduncular nucleus at the A12.5 level. In addition to these large cells, the present study disclosed the presence of "small" to "very small" MAO-B-positive cells in the area surrounding the mamillary recess and the lateral part of the caudal arcuate nucleus. Distinct MAO-B-stained fibers were identified in all regions of the hypothalamus. A large number of thick labeled fibers were observed in the ventral hypothalamus including the TM and premamillary nucleus and posterior and lateral hypothalamic areas. A dense network of MAO-B-positive terminal-like fibers was observed in the dorsomedial nucleus where very small labeled cells were scattered. Many intensely stained thick and straight fibers were seen running ventrolaterally in the anterior part of the HLA and in the narrow space between the entopeduncular nucleus and optic tract. In the area of the tuber cinereum and the ventral part of the HLA, there were many positive fibers cut transversely, possibly projecting to the more anterior parts of the brain such as the diagonal band of Broca or septal nuclei.
Asunto(s)
Química Encefálica , Hipotálamo/enzimología , Monoaminooxidasa/análisis , Neuronas/enzimología , Animales , Gatos , Femenino , Histocitoquímica , Hipotálamo/análisis , Hipotálamo/citología , Masculino , Neuronas/análisis , Especificidad de la EspecieRESUMEN
In order to determine critical sites within the hypothalamus responsible for the induction and maintenance of wakefulness (W), we performed microinjections of muscimol, a potent gamma-aminobutyric acid (GABA) agonist, in various lateral hypothalamic regions of freely moving cats. We found that bilateral injections of a small amount of muscimol (0.1-1.0 micrograms/0.5 microliters) in the preoptic and anterior hypothalamus and rostral mesencephalic tegmentum resulted in increased vigilance and insomnia. In contrast, microinjections of muscimol in the middle and anterior parts of the posterior hypothalamus induced long-lasting behavioral and electroencephalographic signs of sleep with short latency. The hypersomnia was characterized by a significant increase in both light and deep slow wave sleep (SWS), and a nearly complete suppression of paradoxical sleep (PS). Animals with muscimol microinjections in the ventrolateral part of the posterior hypothalamus, however, exhibited increased SWS followed by a significant increase in PS. When injected into the posterior hypothalamus of insomniac cats pretreated with p-chlorophenylalanine (PCPA), muscimol induced not only SWS but also PS with short latency. The present data thus support the hypotheses that the posterior hypothalamus plays a critical role in the mechanisms of W and that sleep might result from functional blockade of the hypothalamic waking center.
Asunto(s)
Hipotálamo Posterior/fisiología , Hipotálamo/fisiología , Muscimol/farmacología , Sueño/fisiología , Vigilia/fisiología , Animales , Gatos , Relación Dosis-Respuesta a Droga , Femenino , Hipotálamo Posterior/efectos de los fármacos , Masculino , Microinyecciones , Sueño/efectos de los fármacos , Vigilia/efectos de los fármacosRESUMEN
Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. alpha-Fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of alpha-FMH (50 micrograms/1 microliter) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 micrograms/1 microliter) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 micrograms/1 microliter), a specific inhibitor of histamine-N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 micrograms/1 microliter, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.
Asunto(s)
Nivel de Alerta/fisiología , Dimaprit/análogos & derivados , Histamina/fisiología , Hipotálamo/fisiología , Animales , Nivel de Alerta/efectos de los fármacos , Gatos , Femenino , Histamina/farmacología , Antagonistas de los Receptores Histamínicos/farmacología , Histidina Descarboxilasa/antagonistas & inhibidores , Hipotálamo Posterior , Inyecciones , Inyecciones Intraperitoneales , Masculino , Metilhistidinas/farmacología , Pirilamina/farmacología , Tiourea/farmacologíaAsunto(s)
Coagulación Intravascular Diseminada/tratamiento farmacológico , Medicina Tradicional China , Medicina Tradicional de Asia Oriental , Plantas Medicinales , Animales , Coagulación Intravascular Diseminada/etiología , Endotoxinas , Escherichia coli , Masculino , Fagocitosis/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , ConejosRESUMEN
The localization of histaminergic neurons in the cat brain was determined immunohistochemically with an antibody against histamine. We found that histamine-immunoreactive neurons are observed exclusively in the posterior hypothalamus of colchicine treated cats. The larger group of neurons was found in the ventrolateral part of the posterior hypothalamus, including the tuberomammillary nucleus. Histamine-positive neurons were also observed in the supramammillary area and adjacent posterior hypothalamic area, as well as in the peri- and premammillary regions. In addition, numerous histamine immunoreactive fibers were detected, not only in the posterior hypothalamus, but also in other brain areas, such as the preoptic area of the anterior hypothalamus.
Asunto(s)
Histamina/análisis , Hipotálamo Posterior/análisis , Hipotálamo/análisis , Neuronas/análisis , Animales , Gatos , Colchicina/farmacología , Histocitoquímica , Hipotálamo Posterior/efectos de los fármacos , Técnicas para Inmunoenzimas , FotomicrografíaRESUMEN
We have studied the effects of local injections of histaminergic and antihistaminic drugs on the sleep-waking cycle in the cat. Microinjections of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, in the ventrolateral posterior hypothalamus, where histamine-immunoreactive neurons have been recently identified, resulted in a significant decrease in wakefulness (W) and increase in deep slow wave sleep (SWS). On the other hand, microinjections of SKF-91488 (Homodimaprit), a specific inhibitor of histamine-N-methyltransferase, increased W and decreased SWS and paradoxical sleep (PS). Microinjections of histamine also produced an increase of W, while this effect was abolished by pretreatment with mepyramine, an H1-histamine receptor antagonist.