RESUMEN
Pain is a frequent symptom in leprosy patients. It may be predominantly nociceptive, as in neuritis, or neuropathic, due to injury or nerve dysfunction. The differential diagnosis of these two forms of pain is a challenge in clinical practice, especially because it is quite common for a patient to suffer from both types of pain. A better understanding of cytokine profile may serve as a tool in assessing patients and also help to comprehend pathophysiology of leprosy pain. Patients with leprosy and neural pain (n = 22), neuropathic pain (n = 18), neuritis (nociceptive pain) (n = 4), or no pain (n = 17), further to those with diabetic neuropathy and neuropathic pain (n = 17) were recruited at Souza Araujo Out-Patient Unit (Fiocruz, Rio de Janeiro, RJ, Brazil). Serum levels of IL1ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-γ, CXCL-10/IP-10, and TGF-ß were evaluated in the different Groups. Impairment in thermal or pain sensitivity was the most frequent clinical finding (95.5%) in leprosy neuropathy patients with and without pain, but less frequent in Diabetic Group (88.2%). Previous reactional episodes have occurred in patients in the leprosy and Pain Group (p = 0.027) more often. Analysis of cytokine levels have demonstrated that the concentrations of IL-1ß, TNF, TGF-ß, and IL-17 in serum samples of patients having leprosy neuropathy in combination with neuropathic or nociceptive pain were higher when compared to the samples of leprosy neuropathy patients without pain. In addition, these cytokine levels were significantly augmented in leprosy patients with neuropathic pain in relation to those with neuropathic pain due to diabetes. IL-1ß levels are an independent variable associated with both types of pain in patients with leprosy neuropathy. IL-6 concentration was increased in both groups with pain. Moreover, CCL-2/MCP-1 and CXCL-10/IP-10 levels were higher in patients with diabetic neuropathy over those with leprosy neuropathy. In brief, IL-1ß is an independent variable related to neuropathic and nociceptive pain in patients with leprosy, and could be an important biomarker for patient follow-up. IL-6 was higher in both groups with pain (leprosy and diabetic patients), and could be a therapeutic target in pain control.
Asunto(s)
Neuropatías Diabéticas/sangre , Interleucina-1beta/sangre , Interleucina-6/sangre , Lepra/sangre , Neuralgia/sangre , Neuritis/sangre , Anciano , Biomarcadores/sangre , Brasil/epidemiología , Estudios Transversales , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Diagnóstico Diferencial , Femenino , Humanos , Lepra/diagnóstico , Lepra/epidemiología , Masculino , Persona de Mediana Edad , Neuralgia/diagnóstico , Neuralgia/epidemiología , Neuritis/diagnóstico , Neuritis/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16â¯weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. METHODS: Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1ß, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. RESULTS: Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16â¯weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (-0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), pâ¯=â¯0.038. CONCLUSION: Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD.
Asunto(s)
Enfermedad de Alzheimer/rehabilitación , Terapia por Ejercicio/métodos , Neuritis/prevención & control , Actividades Cotidianas , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Índice de Masa Corporal , Cognición , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/líquido cefalorraquídeo , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Células Musculares/metabolismo , Neuritis/sangre , Neuritis/líquido cefalorraquídeo , Neuroprostanos/metabolismo , Calidad de Vida , Receptores Inmunológicos/metabolismoRESUMEN
Background: Leprosy is a complex infectious and neurological disease caused by Mycobacterium leprae. Nerve damage is related to immunological hypersensitivity responses known as leprosy reactions (LRs). Diagnostic tools to predict LRs are not available. We hypothesized that natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) would be helpful as an indicator of LRs and neuritis. Methods: To assess the utility of NDO-LID in indicating reactions, ELISA were used to detect specific antibodies in serum samples from 80 Colombian leprosy patients (40 with and 40 without history of LRs). Responses were detected using a range of detection reagents detecting IgG, IgM or both isotypes. Results: Patients with a history of LRs had an increased seropositivity rate for anti-NDO-LID antibodies compared to patients without (anti-NDO-LID protein A [p=0.02], IgG anti-NDO-LID [p=0.01] and IgM anti-NDO-LID [p=0.01]). Further analyses of patients with a history of LRs indicated that both seropositivity rate and magnitude of responses were elevated among patients with neuritis versus those without neuritis (anti-NDO-LID protein A [p=0.03], IgG anti-NDO-LID [p=0.001] and IgM anti-NDO-LID [p=0.06]). Conclusions: Our data indicate that testing for serum anti-NDO-LID antibodies can be a useful screen to identify patients at risk of developing LRs and neuritis.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Lepra/sangre , Mycobacterium leprae/enzimología , Neuritis/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Colombia , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G , Inmunoglobulina M , Lepra/inmunología , Lepra/fisiopatología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Neuritis/inmunología , Neuritis/fisiopatología , Valor Predictivo de las Pruebas , Pruebas Serológicas , Adulto JovenRESUMEN
Somatostatin (SST) is a peptide hormone that regulates the endocrine system and affects neurotransmission via interaction with G protein-coupled SST receptors and inhibition of the release of different hormones. The aim of this study was to investigate whether the analgesic properties of the selective SSTR4 agonist J-2156 are mediated via peripheral and/or spinal receptors. Effect on mechanical hyperalgesia in the Complete Freund׳s Adjuvant (CFA) model was measured after intraperitoneal application of J-2156. Electrophysiological neuronal recordings were conducted 24 h after injection of CFA or vehicle into the paw of Wistar rats. Mechanosensitivity of peripheral afferents of the saphenous nerve as well as of spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were measured after systemic or spinal application of J-2156. In CFA animals J-2156 dose dependently reduced hyperalgesia in behavioral studies. The minimal effective dose was 0.1 mg/kg. Mechanosensitivity of peripheral afferents and spinal neurons was significantly reduced by J-2156. NS neurons were dose dependently inhibited by J-2156 while in WDR neurons only the highest concentration of 100 µM had an effect. In sham controls, J-2156 had no effect on neuronal activity. We demonstrated that J-2156 dose-dependently reduces peripheral and spinal neuronal excitability in the CFA rat model without affecting physiological pain transmission. Given the high concentration of the compound required to inhibit spinal neurons, it is unlikely that the behavioral effect seen in CFA model is mediated centrally. Overall these data demonstrated that the analgesic effect of J-2156 is mediated mainly via peripheral SST4 receptors.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Butanos/uso terapéutico , Modelos Animales de Enfermedad , Hiperalgesia/tratamiento farmacológico , Naftalenos/uso terapéutico , Neuronas Aferentes/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Receptores de Somatostatina/agonistas , Sulfonas/uso terapéutico , Administración Cutánea , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/farmacocinética , Analgésicos no Narcóticos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/farmacocinética , Conducta Animal/efectos de los fármacos , Butanos/administración & dosificación , Butanos/sangre , Butanos/farmacocinética , Relación Dosis-Respuesta a Droga , Fenómenos Electrofisiológicos/efectos de los fármacos , Hiperalgesia/sangre , Hiperalgesia/inmunología , Hiperalgesia/metabolismo , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Masculino , Mecanorreceptores/efectos de los fármacos , Mecanorreceptores/inmunología , Mecanorreceptores/metabolismo , Naftalenos/administración & dosificación , Naftalenos/sangre , Naftalenos/farmacocinética , Neuritis/sangre , Neuritis/tratamiento farmacológico , Neuritis/inmunología , Neuritis/metabolismo , Neuronas Aferentes/inmunología , Neuronas Aferentes/metabolismo , Nociceptores/efectos de los fármacos , Nociceptores/inmunología , Nociceptores/metabolismo , Nervios Periféricos/inmunología , Nervios Periféricos/metabolismo , Ratas Wistar , Receptores de Somatostatina/metabolismo , Nervios Espinales/efectos de los fármacos , Nervios Espinales/inmunología , Nervios Espinales/metabolismo , Sulfonas/administración & dosificación , Sulfonas/sangre , Sulfonas/farmacocinéticaAsunto(s)
Glucemia/análisis , Neuropatías Diabéticas/etiología , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Modelos Neurológicos , Neuralgia/etiología , Neuritis/etiología , Enfermedad Aguda , Axones/fisiología , Biopsia , Diabetes Mellitus/tratamiento farmacológico , Neuropatías Diabéticas/sangre , Femenino , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/complicaciones , Hipoglucemia/fisiopatología , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Isquemia/etiología , Masculino , Regeneración Nerviosa , Neuralgia/sangre , Neuritis/sangre , Nervios Periféricos/irrigación sanguínea , Nervio Sural/patologíaRESUMEN
The authors report a 48-year-old Chinese woman who presented with acute peripheral neuritis with progressive alopecia. Laboratory examinations disclosed a high blood concentration of thallium (97 microg/L) versus a normal value (0.9 microg/L), and she was diagnosed as having acute thallotoxicosis. After her hospitalization, the cutantest of dimercaptopropansulfonate sodium was positive and the patient refused to take Prussian blue because it caused constipation. She rapidly entered remission after assistance via double-filtration plasmapheresis (DFPP), suggesting the potential efficacy of DFPP for thallotoxicosis.
Asunto(s)
Neuritis/terapia , Enfermedades del Sistema Nervioso Periférico/terapia , Plasmaféresis/métodos , Talio/toxicidad , Femenino , Humanos , Persona de Mediana Edad , Neuritis/sangre , Neuritis/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/sangre , Talio/sangreRESUMEN
In experimental animal models of multiple sclerosis demyelinating antibody responses are directed against the myelin oligodendrocyte glycoprotein (MOG). We have investigated whether a similar antibody response is also present in multiple sclerosis patients. Using the recombinant human extracellular immunoglobulin domain of MOG (MOG-Ig) we have screened the sera and CSFs of 130 multiple sclerosis patients, 32 patients with other inflammatory neurological diseases (OIND), 30 patients with other non-inflammatory neurological diseases (ONND) and 10 patients with rheumatoid arthritis. We report that 38% of multiple sclerosis patients are seropositive for IgG antibodies to MOG-Ig compared with 28% seropositive for anti-myelin basic protein (MBP). In contrast, OIND are characterized by similar frequencies of serum IgG antibody responses to MOG-Ig (53%) and MBP (47%), whereas serum IgG responses to MOG-Ig are rare in ONND (3%) and rheumatoid arthritis (10%). Anti-MBP IgG antibodies, however, are a frequent finding in ONND (23%) and rheumatoid arthritis (60%). Our results provide clear evidence that anti-MOG-Ig antibodies are common in CNS inflammation. However, in OIND these antibody responses are transient, whereas they persist in multiple sclerosis. We demonstrate that the serum anti-MOG-Ig response is already established in early multiple sclerosis (multiple sclerosis-R0; 36%). In later multiple sclerosis stages frequencies and titres are comparable with early multiple sclerosis. In contrast, the frequency of anti-MBP antibodies is low in multiple sclerosis-R0 (12%) and increases during disease progression in relapsing-remitting (32%) and chronic progressive multiple sclerosis (40%), thus suggesting that anti-MBP responses accumulate over time. Finally we provide evidence for intrathecal synthesis of IgG antibodies to MOG-Ig in multiple sclerosis.
Asunto(s)
Autoanticuerpos/inmunología , Esclerosis Múltiple/inmunología , Proteína Básica de Mielina/inmunología , Glicoproteína Asociada a Mielina/inmunología , Enfermedades del Sistema Nervioso/inmunología , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/líquido cefalorraquídeo , Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulinas/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Proteínas de la Mielina , Glicoproteína Mielina-Oligodendrócito , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Neuritis/sangre , Neuritis/líquido cefalorraquídeo , Neuritis/inmunología , Proteínas Recombinantes/inmunología , Estudios RetrospectivosRESUMEN
In order to clarify the IgE response to common environmental antigens, we measured the serum total IgE and allergen-specific IgE in 50 patients with Guillain-Barré syndrome (GBS), nine patients with Fisher syndrome (FS), 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 18 patients with mononeuritis multiplex (MNM), 43 patients with neurodegenerative disorders and 82 healthy controls by ELISA. The total IgE level was significantly higher in patients with GBS (median = 135 U/ml, P<0.05), CIDP (median = 175 U/ml, P<0.05) and MNM (median= 199 U/ml, P<0.05), than in the healthy controls (median = 79 U/ml), but not in those patients with neurodegenerative disorders. The specific IgE to Dermatophagoides pteronyssinus was significantly higher in the patients with GBS (56%, P<0.01) and MNM (72%, P<0.005) than in the healthy controls (32%). The level of specific IgE to Dermatophagoides farinae tended to be higher in the patients with GBS than in the healthy controls (0.05
Asunto(s)
Antígenos/inmunología , Enfermedades Desmielinizantes/inmunología , Síndrome de Guillain-Barré/inmunología , Inmunoglobulina E/sangre , Ácaros/inmunología , Enfermedades Neurodegenerativas/inmunología , Adolescente , Adulto , Anciano , Animales , Enfermedades Desmielinizantes/sangre , Femenino , Síndrome de Guillain-Barré/sangre , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Miller Fisher/sangre , Síndrome de Miller Fisher/inmunología , Neuritis/sangre , Neuritis/inmunología , Enfermedades Neurodegenerativas/sangreRESUMEN
Se estudió la respuesta inmune de un grupo de pacientes con neuropatía epidémica y de individuos controles mediante la tècnica de inmunoblotting frente a las proteinas del virus Coxsackie y a las proteínas de la cepa de efecto lento aislada en nuestro laboratorio. Se estudiaron 13 sueros de pacientes con neuropatía epidémica y 9 sueros controles. De los 13 sueros estudiados, 8 (61,5 por ciento) reconocieron a la proteína VPI y 2 sueros (15,3 por ciento) a la proteína VPO de la cepa 47/93. De los 9 controles estudiados, 4 (44,4 por ciento) reconocieron la proteína VPI y 3 sueros (33,3 por ciento) la proteína VPO solamente. Con el antígeno preparado a partir de la cepa de efecto lento, en 5(38,5 por ciento) sueros de pacientes con 2 sueros (22,5 por ciento) de controles se obtuvo una señal específica. Es de destacar en este último caso que la proteína observada tenía un peso molecular de 41 300 D, era de menor talla que la proteína precursora detectada frente a la cepa 47/93, que fue de 45 000 D
Asunto(s)
Humanos , Western Blotting , Brotes de Enfermedades , Enterovirus , Neuritis/sangre , Proteínas Virales , Formación de AnticuerposRESUMEN
Se estudió la respuesta inmune de un grupo de pacientes con neuropatía epidémica y de individuos controles mediante la tècnica de inmunoblotting frente a las proteinas del virus Coxsackie y a las proteínas de la cepa de efecto lento aislada en nuestro laboratorio. Se estudiaron 13 sueros de pacientes con neuropatía epidémica y 9 sueros controles. De los 13 sueros estudiados, 8 (61,5 por ciento) reconocieron a la proteína VPI y 2 sueros (15,3 por ciento) a la proteína VPO de la cepa 47/93. De los 9 controles estudiados, 4 (44,4 por ciento) reconocieron la proteína VPI y 3 sueros (33,3 por ciento) la proteína VPO solamente. Con el antígeno preparado a partir de la cepa de efecto lento, en 5(38,5 por ciento) sueros de pacientes con 2 sueros (22,5 por ciento) de controles se obtuvo una señal específica. Es de destacar en este último caso que la proteína observada tenía un peso molecular de 41 300 D, era de menor talla que la proteína precursora detectada frente a la cepa 47/93, que fue de 45 000 D(AU)
Asunto(s)
Humanos , Western Blotting/métodos , Neuritis/sangre , Brotes de Enfermedades , Proteínas Virales , Enterovirus , Formación de AnticuerposRESUMEN
1. The GABA transaminase inhibitor and activator of glutamic acid decarboxylase, valproic acid is being used for the treatment of migraine. Its mechanism of action is unknown. We tested the effects of sodium valproate and GABAA-agonist muscimol on dural plasma protein ([125I]-bovine serum albumin) extravasation evoked by either unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min) or substance P (SP) administration (1 nmol kg-1,i.v.) in anaesthetized Sprague-Dawley rats. 2. Intraperitoneal (i.p.) injection of sodium valproate or muscimol, but not baclofen (< or = 10 mg kg-1, i.p.) dose-dependently reduced dural plasma protein extravasation caused either by electrical trigeminal stimulation (ED50: 6.6 +/- 1.4 mg kg-1, i.p., and 58 +/- 18 micrograms kg-1, i.p. for valproate or muscimol, respectively) or by intravenous substance P administration (ED50: 3.2 +/- 1.4 mg kg-1, i.p. and 385 +/- 190 micrograms kg-1, i.p. for valproate or muscimol, respectively). 3. Valproate (6.6 mg kg-1, i.p.) or muscimol (58 micrograms kg-1, i.p.) had no effect on mean arterial blood pressure or heart rate when measured for 30 min after i.p. administration. 4. The GABAA-antagonist bicuculline (0.01 mg kg-1, i.p.) completely reversed the effect of valproate and muscimol on plasma extravasation following electrical stimulation or substance P administration, whereas the GABAB-receptor antagonist, phaclofen (0.01-1 mg kg-1, i.p.) did not. Bicuculline or phaclofen, given alone, did not alter the plasma extravasation response after either electrical stimulation or SP administration. 5. Valproate decreased plasma extravasation following substance P administration in adult animals, neonatally treated with capsaicin by a bicuculline-reversible mechanism. This suggests that GABAA receptors are not found primarily on those afferent neurones or fibres which are sensitive to capsaicin treatment in neonatal rats.6. We conclude that sodium valproate blocks plasma extravasation in the meninges through GABAA mediated postjunctional receptors probably within the meninges. The dosages required are comparable to those used clinically. Agonists and modulators at the GABAA receptor may become useful for the development of selective therapeutic agents for migraine and cluster headache.
Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Duramadre/irrigación sanguínea , Extravasación de Materiales Terapéuticos y Diagnósticos , GABAérgicos/farmacología , Neuritis/tratamiento farmacológico , Receptores de GABA-A/fisiología , Albúmina Sérica Bovina/farmacocinética , Sustancia P/farmacología , Ganglio del Trigémino/fisiología , Ácido Valproico/farmacología , Animales , Baclofeno/farmacología , Presión Sanguínea/efectos de los fármacos , Capsaicina/farmacología , Estimulación Eléctrica , Agonistas del GABA/farmacología , Agonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-A , Frecuencia Cardíaca/efectos de los fármacos , Radioisótopos de Yodo , Masculino , Muscimol/farmacología , Neuritis/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
Se estudió un total de 213 monosueros de pacientes con el diagnóstico de neuropatía epidémica y sus contactos, por las técnicas de inmunofluorescencia indirecta y neutralización, con el fin de demostrar la presencia de anticuerpos IgM y neutralizantes en los sueros frente a la cepa 47 IPK/93 identificada como Coxsackie A9. La edad promedio de estos pacientes osciló entre 20 y 50 años y la positividad a ambas técnicas no predominó. No hubo diferencia significativa en los resultados obtenidos entre pacientes y contactos en las técnicas empleadas (AU)
Asunto(s)
Adolescente , Adulto , Persona de Mediana Edad , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/sangre , Neuritis/líquido cefalorraquídeo , Neuritis/sangre , Inmunoglobulina M/análisis , Técnica del Anticuerpo Fluorescente , Células VeroRESUMEN
Se realizaron determinaciones de anticuerpos neutralizantes en sueros de pacientes con neuropatía epidémica y de grupos de personas aparentemente sanas, a la cepa 47/93 IPK (CA9) y la 590 productora de efecto citopático ligero (ECP-L), así como a las cepas de referencia de CA9 y CB1-6, por la técnica de microneutralización. Los enfermos y sus contactos mostraron porcentajes significativamente superiores de anticuerpos neutralizantes a la cepa 47-93 que el grupo considerado control y los residentes en municipios de baja tasa de la enfermedad. Esta diferencia también se comprobó en los títulos promedio geométrico (TPG) con las cepas de referencia de CA9 y CB2-4. Se comprobó un incremento de la circulación de la cepa 47/93 en la población infantil desde 1981 a 1993. Los enfermos mostraron porcentajes y TPG significativamente menores de anticuerpos neutralizantes a la cepa 590 que el grupo control, a pesar de que en 25/28 se habían aislados agentes con ECP-L. Se plantea la posibilidad de 2 mecanismos de neutralización y se formula una hipótesis sobre el mecanismo por el cual estos virus puedan participar en la fisiopatología de la enfermedad (AU)
Asunto(s)
Humanos , Neuritis/líquido cefalorraquídeo , Neuritis/sangre , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/sangre , Enterovirus/aislamiento & purificación , Células Vero , Efecto Citopatogénico Viral , CubaRESUMEN
Se realizaron determinaciones de anticuerpos neutralizantes en sueros de pacientes con neuropatia epidemica y de grupos de personas aparentemente sanas, a la cepa 47/93 IPK (CA9) y la 590 productora de efecto citopatico ligero (ECP-L), asi como a las cepas de referencia de CA9 y CB1-6, por la tecnica de microneutralizacion. Los enfermos y sus contactos mostraron porcentajes significativamente superiores de anticuerpos neutralizantes a la cepa 47-93 que el grupo considerado control y los residentes en municipios de baja tasa de la enfermedad. Esta diferencia tambien se comprobo en los titulos promedio geometrico (TPG) con las cepas de referencia de CA9 y CB2-4. Se comprobo un incremento de la circulacion de la cepa 47/93 en la poblacion infantil desde 1981 a 1993. Los enfermos mostraron porcentajes y TPG significativamente menores de anticuerpos neutralizantes a la cepa 590 que el grupo control, a pesar de que en 25/28 se habian aislados agentes con ECP-L. Se plantea la posibilidad de 2 mecanismos de neutralizacion y se formula una hipotesis sobre el mecanismo por el cual estos virus puedan participar en la fisiopatologia de la enfermedad
Asunto(s)
Humanos , Efecto Citopatogénico Viral , Enterovirus/aislamiento & purificación , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/sangre , Neuritis/sangre , Neuritis/líquido cefalorraquídeo , Células Vero , CubaRESUMEN
Se estudio un total de 213 monosueros de pacientes con el diagnostico de neuropatia epidemica y sus contactos, por las tecnicas de inmunofluorescencia indirecta y neutralizacion, con el fin de demostrar la presencia de anticuerpos IgM y neutralizantes en los sueros frente a la cepa 47 IPK/93 identificada como Coxsackie A9. La edad promedio de estos pacientes oscilo entre 20 y 50 anos y la positividad a ambas tecnicas no predomino. No hubo diferencia significativa en los resultados obtenidos entre pacientes y contactos en las tecnicas empleadas
Asunto(s)
Adolescente , Adulto , Persona de Mediana Edad , Técnica del Anticuerpo Fluorescente , Inmunoglobulina M/análisis , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/sangre , Neuritis/sangre , Neuritis/líquido cefalorraquídeo , Células VeroRESUMEN
Endothelial intercellular adhesion molecule-1 (ICAM-1) and glycoprotein E-selectin (ELAM-1) allow the homing of leukocytes to inflammation sites. A circulating form of ICAM-1 markedly increases in inflammatory CNS disorders. In the present study, the serum levels of ICAM-1, ELAM-1 and tumor necrosis factor-alpha (TNF-alpha) were measured in patients with acute (AIDP) and chronic (CIDP) inflammatory demyelinating polyneuropathies and cryoglobulinemic neuropathy (CGN). Immunoenzymometric assays revealed increased sICAM-1 levels in some of these patients; furthermore, high titres of ELAM-1 and TNF-alpha were detected in two patients with AIDP and one patient with CGN. Our data extend previous observations on inflammatory PNS disorders by showing that, in addition to ICAM-1, ELAM-1 also represents a useful marker of endothelial activation and that, taken together, the two molecules may serve as an indicator of specific pathogenetic mechanisms.
Asunto(s)
Moléculas de Adhesión Celular/sangre , Molécula 1 de Adhesión Intercelular/sangre , Glicoproteínas de Membrana/sangre , Neuritis/sangre , Enfermedades del Sistema Nervioso Periférico/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Crioglobulinemia/sangre , Enfermedades Desmielinizantes/sangre , Selectina E , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Polineuropatías/sangreRESUMEN
Intercellular adhesion molecule-1 (ICAM-1), a cell surface receptor important for cellular interactions in immune responses, especially leukocyte trafficking into inflamed tissue, is released in a soluble form (sICAM-1) into the extracellular space. In this study, we measured sICAM-1 in paired serum and CSF samples from patients with inflammatory diseases of the nervous system (IND) and calculated a sICAM-1 index as a measure of the intrathecal release of ICAM-1. In comparison with noninflammatory neurologic disease (NIND) controls, we found increased sICAM-1 index levels in viral meningoencephalitis, bacterial meningitis and, to a lesser degree, multiple sclerosis but not in Guillain-Barré syndrome. Serial examination of viral meningoencephalitis patients in most cases showed a decrease of sICAM-1 index in parallel with falling cell counts and clinical improvement. Except for those in bacterial meningitis, sICAM-1 serum levels of IND patients were not significantly different from those of NIND controls. The increased intrathecal release of sICAM-1 in viral meningoencephalitis and bacterial meningitis most likely reflects activation of macrophages and lymphocytes and provides evidence for a strong local immune response that itself, in addition to the infectious agent, may damage nervous tissue.
Asunto(s)
Moléculas de Adhesión Celular/sangre , Moléculas de Adhesión Celular/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/sangre , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Neuritis/sangre , Neuritis/líquido cefalorraquídeo , Humanos , Molécula 1 de Adhesión Intercelular , Meningitis Bacterianas/sangre , Meningitis Bacterianas/líquido cefalorraquídeo , Meningoencefalitis/sangre , Meningoencefalitis/líquido cefalorraquídeo , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Polirradiculoneuropatía/sangre , Polirradiculoneuropatía/líquido cefalorraquídeoRESUMEN
To determine whether neurogenic inflammation can be inhibited by prostaglandin E1 (PGE1), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1-1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P less than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P greater than 0.20). These results suggest that PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.
Asunto(s)
Alprostadil/uso terapéutico , Bronquios/irrigación sanguínea , Extravasación de Materiales Terapéuticos y Diagnósticos/prevención & control , Neuritis/sangre , Tráquea/irrigación sanguínea , Animales , Proteínas Sanguíneas/metabolismo , Bronquios/inervación , Capsaicina/farmacología , Estimulación Eléctrica , Azul de Evans/farmacocinética , Extravasación de Materiales Terapéuticos y Diagnósticos/etiología , Neuritis/inducido químicamente , Neuritis/prevención & control , Ratas , Ratas Sprague-Dawley , Sustancia P/farmacología , Tráquea/inervación , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiologíaRESUMEN
Patterns of highly glycosylated proteins with mainly cationic isoelectric points, pH 6.5-9.5, were observed in serum and cerebrospinal fluid of patients with various disorders. Detection was performed after isoelectric focusing, using an immunoassay specific for digoxigenylated carbohydrate moieties of glycoconjugates. To our knowledge, these glycoproteins have not hitherto been described as regular serum proteins. The patterns were found among 7% of the patients studied (n = 400). Similar bands were not detectable in a reference group of 100 persons without clinical symptoms. The glycoprotein pattern was specific for each individual. The pathophysiological meaning of these glycoproteins as well as the basic biochemistry has not yet been evaluated. The glycoproteins, however, were shown to differ from immunoglobulin G, oligoclonal immunoglobulin G, paraprotein or from regular cationic serum protein. By comparison with standard glycoproteins a carbohydrate content of 30 +/- 10% was roughly suggested. The oligosaccharides contain probably sialic acid as evidenced by lectin binding. Although the diagnoses varied, 90% of the patients with this glycoprotein pattern had inflammatory processes.