RESUMEN
Pain relief is an important component of modern obstetric care and can be produced by neuraxial, systemic, or inhalational analgesia or various physical techniques. We review the most recent evidence on the efficacy and safety of these techniques. Over the past decade, the availability of safer local anaesthetics, ultra-short acting opioids, combined spinal-epidural needles, patient-controlled analgesic devices, and ultrasound have revolutionised obstetric regional analgesia. Recent meta-analyses have supported epidural analgesia as the most efficacious technique, as it leads to higher maternal satisfaction and good maternal and fetal safety profiles. We examine the controversies and myths concerning the initiation, maintenance, and discontinuation of epidural analgesia. Recent evidence will also be reviewed to address concerns about the effects of epidural analgesia on the rates of instrumental and operative delivery, lower back pain, and breastfeeding. New developments in labour analgesia are also discussed.
Asunto(s)
Analgesia Obstétrica/tendencias , Dolor de Parto/tratamiento farmacológico , Manejo del Dolor/tendencias , Analgesia Epidural/tendencias , Analgesia Controlada por el Paciente/tendencias , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM). METHODS: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 µg kg-1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. RESULTS: The i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml-1. CONCLUSIONS: There is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method. CLINICAL TRIAL REGISTRATION: HKUCTR-1617.
Asunto(s)
Dexmedetomidina/farmacología , Hipnóticos y Sedantes/farmacología , Administración Intranasal , Administración Intravenosa , Adulto , Estudios Cruzados , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacocinética , Método Doble Ciego , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacocinética , Masculino , Estudios ProspectivosRESUMEN
Chloral hydrate is commonly used to sedate children for painless procedures. Children may recover more quickly after sedation with dexmedetomidine, which has a shorter half-life. We randomly allocated 196 children to chloral hydrate syrup 50 mg.kg-1 and intranasal saline spray, or placebo syrup and intranasal dexmedetomidine spray 3 µg.kg-1 , 30 min before computerised tomography studies. More children resisted or cried after drinking chloral hydrate syrup than placebo syrup, 72 of 107 (67%) vs. 42 of 87 (48%), p = 0.009, but there was no difference after intranasal saline vs. dexmedetomidine, 49 of 107 (46%) vs. 40 of 87 (46%), p = 0.98. Sedation was satisfactory in 81 of 107 (76%) children after chloral hydrate and 64 of 87 (74%) children after dexmedetomidine, p = 0.74. Of the 173 children followed up for at least 4 h after discharge, 38 of 97 (39%) had recovered normal function after chloral hydrate and 32 of 76 (42%) after dexmedetomidine, p = 0.76. Six children vomited after chloral hydrate syrup and placebo spray vs. none after placebo syrup and dexmedetomidine spray, p = 0.03.
Asunto(s)
Hidrato de Cloral/administración & dosificación , Sedación Consciente/métodos , Dexmedetomidina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Tomografía Computarizada por Rayos X , Administración Intranasal , Administración Oral , Niño , Preescolar , Hidrato de Cloral/efectos adversos , Sedación Consciente/efectos adversos , Dexmedetomidina/efectos adversos , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Lactante , Masculino , Recuperación de la Función , Vómitos/inducido químicamenteRESUMEN
Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer's disease (AD). As no effective drug can cure AD, early diagnosis and intervention for aMCI are urgently needed. The standard diagnostic procedure for aMCI primarily relies on subjective neuropsychological examinations that require the judgment of experienced clinicians. The development of other objective and reliable aMCI markers, such as neural markers, is therefore required. Previous neuroimaging findings revealed various abnormalities in resting-state activity in MCI patients, but the findings have been inconsistent. The current study provides an updated activation likelihood estimation meta-analysis of resting-state functional magnetic resonance imaging (fMRI) data on aMCI. The authors searched on the MEDLINE/PubMed databases for whole-brain resting-state fMRI studies on aMCI published until March 2015. We included 21 whole-brain resting-state fMRI studies that reported a total of 156 distinct foci. Significant regional resting-state differences were consistently found in aMCI patients relative to controls, including the posterior cingulate cortex, right angular gyrus, right parahippocampal gyrus, left fusiform gyrus, left supramarginal gyrus and bilateral middle temporal gyri. Our findings support that abnormalities in resting-state activities of these regions may serve as neuroimaging markers for aMCI.
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Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Imagen por Resonancia Magnética , Amnesia/complicaciones , Amnesia/diagnóstico por imagen , Amnesia/fisiopatología , Disfunción Cognitiva/complicaciones , Humanos , Neuroimagen/métodos , Reproducibilidad de los Resultados , DescansoRESUMEN
OBJECTIVES: To evaluate the efficacy of a birth ball exercise programme conducted by physiotherapists on pain relief, psychological care, and facilitation of the labour process at a labour ward in a regional hospital. DESIGN: Case series with before-after comparisons. SETTING: Kwong Wah Hospital, Hong Kong. PARTICIPANTS: Chinese women admitted to the labour ward for spontaneous vaginal delivery between April and August 2012 were recruited. Physiotherapists taught birth ball exercises in groups or individually for 30 minutes. Labour pain intensity, back pain intensity, frequency of labour pain, stress and anxiety levels, and subjective pressure level over the lower abdomen were captured before and after birth ball exercises. Most of the parameters were measured using self-reported visual analogue scales. After the exercise session, physiotherapists measured the women's satisfaction level. Midwives recorded pethidine usage. RESULTS: A total of 203 pregnant women participated in this programme; 181 were in the latent phase group, whereas 22 were categorised into the no-labour-pain group. In both groups, there were statistically and clinically significant differences in back pain level, stress and anxiety levels, as well as pressure level over the lower abdomen before and after the exercise (P<0.05). In the latent phase group, significant decreases in labour pain and frequency of labour pain were demonstrated. Mean satisfaction scores were high, with visual analogue scale scores higher than 8.2 in both groups. Pethidine usage showed a further decreasing trend (6.4%) compared with the past 2 years. CONCLUSION: Birth ball exercise could be an alternative means of relieving back pain and labour pain in the labour ward, and could decrease pethidine consumption in labouring women.
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Terapia por Ejercicio/métodos , Dolor de Parto/terapia , Trabajo de Parto , Satisfacción del Paciente , Adulto , Analgésicos Opioides/administración & dosificación , Ansiedad/etiología , Ansiedad/terapia , Parto Obstétrico , Femenino , Hong Kong , Humanos , Meperidina/administración & dosificación , Dimensión del Dolor , Embarazo , Estrés Psicológico/etiología , Estrés Psicológico/terapiaRESUMEN
Heroin abuse and natural aging exert common influences on immunological cell functioning. This observation led to a recent and untested idea that aging may be accelerated in abusers of heroin. We examined this claim by testing whether heroin use is associated with premature aging at both cellular and brain system levels. A group of abstinent heroin users (n=33) and matched healthy controls (n=30) were recruited and measured on various biological indicators of aging. These measures included peripheral blood telomerase activity, which reflects cellular aging, and both structural and functional measures of brain magnetic resonance imaging. We found that heroin users were characterized by significantly low telomerase activity (0.21 vs 1.78; 88% reduction; t(61)=6.96, P<0.001; 95% confidence interval=1.12-2.02), which interacted with heroin use to affect the structural integrity of gray and white matter of the prefrontal cortex (PFC; AlphaSim corrected P<0.05), a key brain region implicated in aging. Using the PFC location identified from the structural analyses as a 'seed' region, it was further revealed that telomerase activity interacted with heroin use to impact age-sensitive brain functional networks (AlphaSim corrected P<0.05), which correlated with behavioral performance on executive functioning, memory and attentional control (Pearson correlation, all P<0.05). To our knowledge, this study is the first to attempt a direct integration of peripheral molecular, brain system and behavioral measures in the context of substance abuse. The present finding that heroin abuse is associated with accelerated aging at both cellular and brain system levels is novel and forms a unique contribution to our knowledge in how the biological processes of drug abusers may be disrupted.
Asunto(s)
Envejecimiento/efectos de los fármacos , Encéfalo/efectos de los fármacos , Dependencia de Heroína/complicaciones , Telomerasa/efectos de los fármacos , Adulto , Encéfalo/patología , Encéfalo/fisiopatología , Estudios de Casos y Controles , Neuroimagen Funcional , Dependencia de Heroína/patología , Dependencia de Heroína/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Telomerasa/sangreAsunto(s)
Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Reoperación , Colgajos Quirúrgicos/irrigación sanguínea , Resultado del TratamientoRESUMEN
BACKGROUND: Reinnervation of the facial musculature when there is loss of the proximal facial nerve poses a difficult clinical problem. Restoration of spontaneous mimetic motion is the aim and, to this end, the use of cross-facial nerve grafts has long been considered the reconstruction of choice. The nerve to masseter has been used very successfully for reinnervation of microvascular functioning muscle transfers for facial reanimation in established facial palsy but its use as a direct nerve transfer to the facial nerve to reinnervate 'viable' facial musculature has been scarce. METHODS: Electron micrographic studies of axonal counts in the nerve to masseter and nerve to gracilis in a clinical series of seven patients undergoing surgery for facial nerve palsy were made. Based on these results, and previous success with the use of the nerve to masseter for reinnervation of free gracilis transfers, we report our experience with the transfer of the nerve to masseter for direct coaptation with the ipsilateral facial nerve to restore facial motion. RESULTS: Our axonal counts of the nerve to masseter have, on average, 1542+/-291.70 (SD) axons. Historical data have shown that the buccal branch of the facial nerve has 834+/-285 (SD) where the distal end of a cross-facial nerve graft has 100 to 200 axons. Our clinical use of the nerve to masseter as a direct nerve transfer in three patients based on these data has resulted in significant improvement in facial symmetry in repose (at a minimum of 1 year follow up), restoration of facial motion with occasional spontaneous activity and minimal synkinesis without any donor morbidity. CONCLUSIONS: The advantages of this technique include the ease of dissection, constant and reliable anatomy, powerful reinnervation of the facial muscles without donor site morbidity and the potential for return of spontaneous facial movement.
Asunto(s)
Nervio Facial/cirugía , Parálisis Facial/cirugía , Músculo Masetero/inervación , Axones/patología , Preescolar , Facies , Femenino , Humanos , Músculo Masetero/patología , Músculo Masetero/fisiopatología , Persona de Mediana Edad , Transferencia de Nervios/métodos , Resultado del TratamientoRESUMEN
P35srj is a ubiquitously expressed nuclear protein that binds the transcriptional coactivators p300 and CREB-binding protein (CBP). It is an alternatively spliced isoform of Mrg1, a cytokine-inducible factor that has transformation activity. P35srj interferes with the recruitment of p300/CBP by the transcription factor HIF-1alpha, a process that is essential for the transcriptional response to hypoxia. Here we report the cloning of the human gene CITED2, which encodes p35srj and Mrg1. The CITED2 gene is composed of three exons and two introns. An unusually large (3 kb) CpG island covers both the promoter and the transcribed portions of the gene. The 5'-flanking region of the gene is active as a promoter in transient transfection assays and contains multiple STAT-binding sites, in keeping with its responsiveness to different cytokines. Fluorescence in situ hybridization, and identity to a known human sequence-tagged site (D6S2114), was used to map the CITED2 gene to chromosome 6q23.3.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 6/genética , Clonación Molecular , Proteínas de Unión al ADN , Proteínas Represoras , Transactivadores/genética , Regiones no Traducidas 5' , Secuencia de Bases , Islas de CpG , Exones/genética , Eliminación de Gen , Humanos , Hibridación Fluorescente in Situ , Intrones/genética , Luciferasas/metabolismo , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , TransfecciónRESUMEN
Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of MRG1, a human protein of unknown function. Virtually all endogenous p35srj is bound to p300/CBP in vivo, and it inhibits HIF-1 transactivation by blocking the HIF-1alpha/p300 CH1 interaction. p35srj did not affect transactivation by transcription factors that bind p300/CBP outside the CH1 region. Endogenous p35srj is up-regulated markedly by the HIF-1 activators hypoxia or deferoxamine, suggesting that it could operate in a negative-feedback loop. In keeping with this notion, a p300 CH1 mutant domain, defective in HIF-1 but not p35srj binding, enhanced endogenous HIF-1 function. In hypoxic cells, p35srj may regulate HIF-1 transactivation by controlling access of HIF-1alpha to p300/CBP, and may keep a significant portion of p300/CBP available for interaction with other transcription factors by partially sequestering and functionally compartmentalizing cellular p300/CBP.
Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas Nucleares/genética , Proteínas Represoras , Transactivadores/genética , Activación Transcripcional/genética , Empalme Alternativo/genética , Secuencia de Aminoácidos , Unión Competitiva , Línea Celular , Clonación Molecular , Secuencia Conservada/genética , Humanos , Hipoxia/metabolismo , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Inmunohistoquímica , Datos de Secuencia Molecular , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Unión Proteica/genética , Proteínas Recombinantes de Fusión/metabolismo , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Transactivadores/química , Transactivadores/metabolismo , Factores de Transcripción/genéticaRESUMEN
Membrane cofactor protein (MCP; CD46) is a type 1 membrane glycoprotein that inhibits complement activation on host cells. It also is a measles virus (MV) receptor, an adherence factor for group A Streptococcus pyogenes, and a cellular pilus receptor for pathogenic Neisseria. The amino terminus of MCP consists of four complement control protein (CCP) repeats, three of which (CCP-1, -2, and -4) possess N-glycans. Immediately following the CCP modules is an alternatively spliced region for extensive O-glycosylation (termed the STP domain). Previous studies established that the N-glycan of CCP-2 is essential for MV binding and infection and that the splicing variants of the STP domain not only affect MV binding and fusion, but also differentially protect against complement-mediated cytolysis. In this report, we dissect the role of these carbohydrates on complement regulatory function. We constructed, expressed, and characterized proteins deleting these carbohydrates. For MCP-mediated protection against cytolysis, the N-glycans of CCP-2 and -4 were necessary, the STP segment influenced but was not essential, and the N-glycan of CCP-1 was not required. In addition, the rate and magnitude of cell surface cleavage of C4b to C4c and C4d by MCP and factor I correlated with cytoprotection. These studies expand the structure-function understanding of the active sites of MCP and elucidate an important role for carbohydrates in its function, a finding consistent with their conservation in the MCP of other species.
Asunto(s)
Antígenos CD/metabolismo , Activación de Complemento , Glicoproteínas de Membrana/metabolismo , Animales , Antígenos CD/genética , Asparagina/genética , Células CHO , Fraccionamiento Celular , Células Clonales , Activación de Complemento/genética , Complemento C3b/genética , Complemento C3b/metabolismo , Complemento C4b/genética , Complemento C4b/metabolismo , Cricetinae , Citoprotección/inmunología , Glutamina/genética , Glicosilación , Humanos , Hidrólisis , Cinética , Proteína Cofactora de Membrana , Glicoproteínas de Membrana/genética , Mutagénesis Sitio-Dirigida , Prolina/genética , Estructura Terciaria de Proteína , Eliminación de Secuencia/inmunología , Serina/genética , Treonina/genética , Transfección/inmunologíaRESUMEN
This study deals with a novel role of morphine in the modulation of cellular responsiveness to immunostimulatory substances that, at first glance, appears to be in contrast to the well documented immunoinhibitory short-term effects of opiate alkaloids on cells simultaneously exposed to stimulatory molecules. Vertebrate and invertebrate immunocytes pre-exposed to morphine (10(-6) M) in vitro for at least 24 h prior to the administration of lipopolysaccharide (LPS; 1.0 micrograms/ml) or other immunoactivating substances have revealed a distinct enhancement of their responsiveness to these signals, e.g. monocytes exposed to LPS alone resulted in 21% activation, whereas the morphine pretreated level was at 40% (P < 0.01). Prolonged pretreatment with morphine of naive human monocytes had the same effect on their sensitivity to plasma from patients having undergone cardiopulmonary bypass (CPB) operations followed by a diffuse inflammatory response. These results suggest that endogenous opiates may participate, in more than one way, in re-establishing an organism's readiness to meet a new demand on its immune system. Additional support for the concept of a role of endogenous opiates in immunomodulation was obtained by the results of in vivo tests with experimentally induced stress in Mytilus. Following their stress-induced stimulation, these animals' immunocytes could be shown to become exposed for some time to a measurable rise in endogenous morphine-like material (9 pmol/ml increasing to 59). These immunocytes, like those preincubated with exogenous morphine, displayed a heightened sensitivity to stimulation by LPS (control 21.3 +/- 3.1% activation compared to 47.2 +/- 5.1) when the morphine levels dropped. The mechanism of this enhancement of responsiveness to immunostimulation following the prolonged exposure of immunocytes to morphine, and its relationship with the known short-term immunoinhibitory opiate effects on the immune system, remains to be ascertained.
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Bivalvos/inmunología , Insectos/inmunología , Monocitos/inmunología , Morfina/inmunología , Animales , Encefalina Metionina/análisis , Hemolinfa/química , Humanos , Inmunización , Interleucina-1/farmacología , Interleucina-8/farmacología , Lipopolisacáridos/farmacología , N-Formilmetionina Leucil-Fenilalanina/farmacología , Factores de Tiempo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The present study demonstrates that morphine- and codeine-like molecules are present in Schistosoma mansoni following HPLC separation and identification with an appropriate commercially available antibody. Furthermore, the endogenous material, corresponding to morphine, mimics authentic morphine in its ability to induce immunocyte rounding and immobility, an action that is naloxone sensitive. The codeine-like material is not found at high concentrations compared to the morphine-like material, indicating, as in mammals and Mytilus edulis, the potential rapid conversion of codeine to morphine. Coincubation with human leukocytes increases the endogenous level of this material in adult worms, indicating the presence of a positive feedback loop. Last, EDTA, a chelator of divalent cations, has a strong stimulating effect in the synthesis of morphine-like material by the worm as noted by higher levels of this material in its presence. Taken together, the results suggest that this parasite may utilize this immune downregulating molecule in its effort to escape host immunosurveillance as well as in inhibiting an immune response directed against itself.
Asunto(s)
Analgésicos Opioides/aislamiento & purificación , Leucocitos/efectos de los fármacos , Morfina/aislamiento & purificación , Narcóticos/aislamiento & purificación , Schistosoma mansoni/química , Analgésicos Opioides/farmacología , Animales , Codeína/aislamiento & purificación , Codeína/metabolismo , Codeína/farmacología , Humanos , Leucocitos/citología , Morfina/metabolismo , Morfina/farmacología , Narcóticos/farmacologíaRESUMEN
OBJECTIVE: To identify a mechanism by which a matrix metalloproteinase (MMP) inhibitor might act synergistically with other agents to decrease MMP activity and thereby lessen the radiologic severity of adjuvant arthritis. METHODS: Rats with adjuvant arthritis were treated with either flurbiprofen (FBP) or tenidap (TDP), along with 4-dedimethylaminotetracycline (CMT-1), a potent MMP inhibitor. Indices of inflammatory severity and of radiologic destruction were assessed and compared to serum and bone levels of the MMP inhibitor. RESULTS: Combination therapy with the MMP inhibitor plus either of the other drugs led to synergistic improvement in radiologic severity. For example, CMT-1 combined with TDP reduced radiologic severity 45% while decreasing collagenase and gelatinase activities by 61 and 72%, respectively, more than doubling bone CMT-1 levels (7.6 micrograms/g to 16.4 micrograms/g). FBP had similar effects. CONCLUSION: MMP inhibitors need access to the arthritic joint to interact with their target enzymes. Concomitant antiinflammatory therapy is required to assure drug entry into the inflamed tissues.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Flurbiprofeno/uso terapéutico , Indoles/uso terapéutico , Inhibidores de Proteasas/farmacocinética , Tetraciclina/farmacocinética , Animales , Artritis Experimental/complicaciones , Artritis Experimental/patología , Colagenasas/efectos de los fármacos , Colagenasas/metabolismo , Sinergismo Farmacológico , Quimioterapia Combinada , Gelatinasas/efectos de los fármacos , Gelatinasas/metabolismo , Masculino , Oxindoles , Inhibidores de Proteasas/uso terapéutico , Ratas , Ratas Endogámicas Lew , Tetraciclina/uso terapéuticoAsunto(s)
Autoinmunidad , Endorfinas/inmunología , Invertebrados/inmunología , Hormona Adrenocorticotrópica/inmunología , Animales , Sitios de Unión , Evolución Biológica , Hormona Liberadora de Corticotropina/inmunología , Citocinas/inmunología , Endorfinas/metabolismo , Encefalina Metionina/inmunología , Encefalina Metionina/metabolismo , Hemolinfa/inmunología , Hemolinfa/metabolismo , Humanos , Invertebrados/metabolismo , Hormonas Estimuladoras de los Melanocitos/inmunología , Neprilisina/metabolismo , Neuroinmunomodulación , Neuropéptidos/inmunología , Neuropéptidos/metabolismo , Parásitos/inmunologíaRESUMEN
Various reports have shown that invertebrate hemocytes are responsive to mammalian neuropeptides and cytokines. In the present study, we demonstrate that corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH) fragments (1-24), (1-4), (4-9), (1-13), (1-17), and (11-24) significantly stimulate molluscan hemocyte migration, and the whole sequence (1-39) and the fragment (4-11) have an inhibitory effect. Differences between species were found with respect to the response to individual fragments. Additionally, the (4-11) fragment was able to antagonize some of the stimulatory fragments (4-9) as well as tumor necrosis factor (TNF-alpha)-induced chemotaxis. Our results suggest that invertebrate hemocytes are able to respond to CRF and ACTH fragments that in turn provide further evidence of the complexity of intercellular signaling within the immune system in relatively primitive animals. Thus, auto- and neuroimmunoregulatory activities in mammals must have had an earlier beginning than previously believed.
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Movimiento Celular/efectos de los fármacos , Hemocitos/efectos de los fármacos , Moluscos/citología , Fragmentos de Péptidos/farmacología , Hormonas Hipofisarias/farmacología , Hormona Adrenocorticotrópica/farmacología , Animales , Hormona Liberadora de Corticotropina/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresAsunto(s)
Cromatografía Líquida de Alta Presión/métodos , Morfina/aislamiento & purificación , Radioinmunoensayo , Animales , Anuros/metabolismo , Bovinos , Líquido Cefalorraquídeo/química , Fenómenos Químicos , Química Física , Codeína/aislamiento & purificación , Mamíferos/metabolismo , Morfina/análisis , Morfina/metabolismo , Sistema Nervioso/química , Ratas , Dióxido de Silicio , Piel/química , SolventesRESUMEN
The presence of morphine-like and codeine-like substances was demonstrated in the pedal ganglia, hemolymph, and mantle tissues of the mollusc Mytilus edulis. The pharmacological activities of the endogenous morphine-like material resemble those of authentic morphine. Both substances were found to counteract, in a dose-dependent manner, the stimulatory effect of tumor necrosis factor alpha or interleukin 1 alpha on human monocytes and Mytilus immunocytes, when added simultaneously to the incubation medium. The immunosuppressive effect of this opiate material expresses itself in a lowering of chemotactic activity, cellular velocity, and adherence. Codeine mimics the activity of authentic morphine, but only at much higher concentrations. Specific high-affinity receptor sites (mu 3) for morphine have been identified on human monocytes and Mytilus immunocytes. In Mytilus recovering from experimentally induced stress, the return of "altered" immunocytes to a more inactive state appears to be due to a significant rise in the content of morphine-like material in the pedal ganglia and hemolymph at this time. Thus, morphine may have a role in calming or terminating the state of immune alertness.
Asunto(s)
Bivalvos/fisiología , Monocitos/fisiología , Narcóticos/farmacología , Receptores Opioides/fisiología , Animales , Unión Competitiva , Quimiotaxis de Leucocito/efectos de los fármacos , Ganglios de Invertebrados/química , Hemolinfa/química , Humanos , Técnicas In Vitro , Ligandos , Morfina/farmacología , Estrés Fisiológico/fisiopatologíaRESUMEN
Substances that were immunoreactive in an RIA specific for met-enkephalin were detected following HPLC fractionation of earthworm coelomic fluid. Earthworm coelomocytes and human granulocytes were analyzed for changes in conformation based on measurements of cellular area and perimeter and expressed mathematically by using the Form Factor (FF). For coelomocytes the FF decreased following exposure to DAMA, a synthetic enkephalin analogue (D-Ala2, Met5-enkephalinamide). DAMA stimulated migration whereas untreated cells and those exposed to the specific opiate blocker naloxone did not move. The enkephalin-like molecule when exposed to human granulocytes stimulated an increased number of activated cells. Our results suggest a relationship between the immune and nervous systems of earthworms.