RESUMO
Class IA phosphoinositide 3-kinases (PI3Ks) are essential to function of normal and tumor cells, and to modulate immune responses. T lymphocytes express high levels of p110α and p110δ class IA PI3K. Whereas the functioning of PI3K p110δ in immune and autoimmune reactions is well established, the role of p110α is less well understood. Here, a novel dual p110α/δ inhibitor (ETP-46321) and highly specific p110α (A66) or p110δ (IC87114) inhibitors have been compared concerning T cell activation in vitro, as well as the effect on responses to protein antigen and collagen-induced arthritis in vivo. In vitro activation of naive CD4(+) T lymphocytes by anti-CD3 and anti-CD28 was inhibited more effectively by the p110δ inhibitor than by the p110α inhibitor as measured by cytokine secretion (IL-2, IL-10, and IFN-γ), T-bet expression and NFAT activation. In activated CD4(+) T cells re-stimulated through CD3 and ICOS, IC87114 inhibited Akt and Erk activation, and the secretion of IL-2, IL-4, IL-17A, and IFN-γ better than A66. The p110α/δ inhibitor ETP-46321, or p110α plus p110δ inhibitors also inhibited IL-21 secretion by differentiated CD4(+) T follicular (Tfh) or IL-17-producing (Th17) helper cells. In vivo, therapeutic administration of ETP-46321 significantly inhibited responses to protein antigen as well as collagen-induced arthritis, as measured by antigen-specific antibody responses, secretion of IL-10, IL-17A or IFN-γ, or clinical symptoms. Hence, p110α as well as p110δ Class IA PI3Ks are important to immune regulation; inhibition of both subunits may be an effective therapeutic approach in inflammatory autoimmune diseases like rheumatoid arthritis.
Assuntos
Artrite Experimental/tratamento farmacológico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Imidazóis/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Subunidades Proteicas/antagonistas & inibidores , Pirazinas/farmacologia , Animais , Anticorpos/farmacologia , Artrite Experimental/enzimologia , Artrite Experimental/imunologia , Artrite Experimental/patologia , Antígenos CD28/genética , Antígenos CD28/imunologia , Complexo CD3/genética , Complexo CD3/imunologia , Linfócitos T CD4-Positivos/enzimologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Classe Ia de Fosfatidilinositol 3-Quinase/genética , Classe Ia de Fosfatidilinositol 3-Quinase/imunologia , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Expressão Gênica , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/enzimologia , Linfonodos/imunologia , Linfonodos/patologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/imunologia , Subunidades Proteicas/genética , Subunidades Proteicas/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/imunologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologiaRESUMO
Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer therapy and are essential to immune responses, particularly through costimulation by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune intervention. PIK-75 is an efficient inhibitor of the PI3-K p110alpha catalytic subunits that suppresses tumor growth, and its effects on immune and autoimmune responses should be studied. Here, we describe the effect of PIK-75 on different immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in vitro (≥0.1 μM) inhibited T and B cell activation by Concanavalin A and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+ T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was prevented by caspase inhibitors. At low nanomolar concentrations (≤10 nM), PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-gamma production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts costimulated by ICOS, PIK-75 (less than 10 nM) inhibited IFN-gamma, IL-17A, or IL-21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG-specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE, modulating lymphocyte function and survival.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Hidrazonas/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Sulfonamidas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linfócitos T CD4-Positivos/enzimologia , Linfócitos T CD4-Positivos/patologia , Células Cultivadas , Citocinas/análise , Relação Dose-Resposta a Droga , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Hidrazonas/administração & dosagem , Hidrazonas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologiaRESUMO
INTRODUCTION: Tongue metastasis of renal cell carcinoma (RCC) is rare. Treatment is hindered by the proximity of anatomic structures involved in swallowing, speech and mastication. It is, moreover, radioresistant. CASE REPORT: We report a case of inaugural isolated tongue metastasis, where biopsy redirected diagnosis to RCC. To avoid potentially mutilating excision in a metastatic disease of poor prognosis, treatment was local, consisting in interstitial brachytherapy, enabling a high dose (65Gy) to be delivered. Despite initially complete response, recurrence at 10.5months required salvage surgery. DISCUSSION AND CONCLUSION: Brachytherapy allowed a higher dose to be delivered than with external beam radiation therapy, previously reported for similar cases. This dose, which can usually be expected to ensure local control in 90% of squamous cell carcinomas of the tongue, obtained 10months' response, insufficient to avoid salvage surgery.
Assuntos
Braquiterapia , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias Renais/radioterapia , Recidiva Local de Neoplasia , Neoplasias da Língua/radioterapia , Neoplasias da Língua/secundário , Idoso , Braquiterapia/métodos , Carcinoma de Células Renais/cirurgia , Evolução Fatal , Seguimentos , Glossectomia , Humanos , Neoplasias Renais/cirurgia , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Nefrectomia , Dosagem Radioterapêutica , Terapia de Salvação , Neoplasias da Língua/cirurgiaRESUMO
No disponible
Assuntos
Humanos , Masculino , Adulto , Artérias Carótidas/anormalidades , Aorta Torácica/anormalidades , Artéria Subclávia/anormalidades , Convulsões/diagnóstico , Malformações VascularesRESUMO
INTRODUCTION: Fibrous dysplasia is a bone disease that is usually accompanied by asymptomatic lesions but which may sometimes display neurological manifestations due to the involvement of the craniofacial bones. CASE REPORT: A 25-year-old female, with a history of migraines, who visited at the age of 18 due to pain in the right retro-ocular and maxillary region, although with characteristics that were unlike those of her usual migraines, and which was associated with ipsilateral ophthalmoparesis. The condition had a self-limiting course and responded well to corticoids, although it was recurring. Examination revealed intense pain on palpation of the right-hand maxillary sinus and incomplete paralysis of the ipsilateral oculomotor nerve with palpebral ptosis. Results of complementary studies were normal, except for magnetic resonance imaging of the head and computerised axial tomography of the face, which revealed an expansive lesion with involvement of the right superior maxillary sinus and the greater wing of the sphenoid bone, with probable compromise of the superior orbital fissure, consistent with the diagnosis of fibrous dysplasia, which was confirmed by means of a pathology study. CONCLUSIONS: Fibrous dysplasia is a benign bone disorder, of unknown causation, in which normal bone tissue is replaced by amorphous conjunctive tissue. There is sometimes craniofacial involvement and a hypertrophic bone mass is formed which can fill the paranasal sinuses and the orbit, resulting in exophthalmus and visual disorders. To date the scientific literature does not include any reports of this disease manifesting as bouts of recurrent painful ophthalmoparesis which responds to corticoids, as happened in the case of our patient.
Assuntos
Displasia Fibrosa Poliostótica/complicações , Displasia Fibrosa Poliostótica/patologia , Seio Maxilar/patologia , Órbita/patologia , Corticosteroides/uso terapêutico , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Seio Maxilar/diagnóstico por imagem , Órbita/diagnóstico por imagem , Osso Esfenoide/diagnóstico por imagem , Osso Esfenoide/patologia , Síndrome de Tolosa-Hunt/tratamento farmacológico , Síndrome de Tolosa-Hunt/etiologia , Tomografia Computadorizada por Raios XRESUMO
Resumen. Introducción. El perfil de síntomas autonómicos (PSA) es un cuestionario autorrellenable, que ha sido validado en lengua inglesa para valorar los síntomas autonómicos y diferenciar entre pacientes y sujetos sanos según dicha sintomatología. Nuestro grupo ha estudiado su aplicación en lengua castellana. Sujetos y métodos. Después de traducir al castellano la versión inglesa y retrotraducirla, se evaluó la fiabilidad y la validez de criterio de la versión española del test PSA en una muestra de 50 sujetos (27 controles y 23 enfermos). A todos los pacientes con síntomas de disfunción autonómica se les estudió mediante la batería de Ewing y Clarke. Resultados. La fiabilidad de la versión española del PSA fue alta, y se obtuvo un coeficiente de correlación intraclase de 0,93. Con una puntuación en el test de 47 o superior, se obtiene una sensibilidad del 73,9% y una especificidad del 100% para detectar disfunción autonómica. Además, la puntuación de la versión española del test PSA mostró diferencias estadísticamente significativas entre el grupo de pacientes y el grupo control. Conclusiones. La versión española del PSA es fiable y permite distinguir entre pacientes con disfunción autonómica y sujetos control. En nuestro conocimiento, se trata del primer test que valora la sintomatología del sistema nervioso autónomo de forma global y en castellano (AU)
Summary. Introduction. The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. Subjects and methods. After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. Results. The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. Conclusions. The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish (AU)
Assuntos
Humanos , Doenças do Sistema Nervoso Autônomo/diagnóstico , Testes Neuropsicológicos , Sensibilidade e Especificidade , Distribuição por Idade e Sexo , Programas de Rastreamento/métodosRESUMO
INTRODUCTION: The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. SUBJECTS AND METHODS: After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. RESULTS: The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. CONCLUSIONS: The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish.
Assuntos
Doenças do Sistema Nervoso Autônomo , Idioma , Inquéritos e Questionários , Adulto , Idoso , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , EspanhaRESUMO
INTRODUCTION: Lepra is an uncommon disease within our setting. However, it was considered the most frequent cause of polyneuropathy only 50 years ago. CASE REPORT: We present the case of a 37 year-old woman who consulted due to paresthesias in both hands and feet, livedo reticularis and complaints of frequent hand lesions. Examination of the skin detected nodular lesions and the neurophysiological study confirmed distal symmetric sensitive polyneuropathy with axonal predominance. The skin biopsy also showed histocytic infiltrate and mycobacterium lepra type intracytoplasmatic bacilli. This led to the diagnosis of Multibacillary lepromatous leprosy. Multiple treatment was begun, according to the World Health Organization recommendations, with good evolution. In spite of the attempts to eradicate lepra, its incidence continues to be elevated, especially in endemic areas, among which the south of Spain is included. It is generally associated to overcrowding and low social-economic level. CONCLUSIONS: This is the last endemic case in the Valencian Community. The possibility of lepra should be considered among the possible causes of sensitive polyneuropathy, above all in patients in endemic areas.
Assuntos
Hanseníase Virchowiana/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Adulto , Doenças Endêmicas , Feminino , Humanos , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Parestesia/etiologia , Doenças do Sistema Nervoso Periférico/microbiologia , Doenças do Sistema Nervoso Periférico/patologia , Pele/patologiaRESUMO
Temporal trends of serotypes from invasive pneumococcal disease (IPD) in Spain from 1979 to September 2007 under antibiotic and vaccine pressure were analyzed. A significant trend in pneumococcal conjugate 7-valent vaccine (PCV7) serotypes (except serotype 4) was found, whereby the prevalence increased from the early 1980s and decreased in the 2000s for all but serotype 23F, which began decreasing in the late 1980s. Among the major non-PCV7 serotypes, a significant decrease was observed for serotypes 1, 5, and 7F in the 1980s. From the late 1990s, serotypes 1, 5, 6A, 7F, and 19A increased significantly, while serotypes 3 and 8 showed similar but nonsignificant trends over time. The incidence of IPD cases was 10.7/100,000 for the period 1996 to 2006, with reporting coverage ranging from 18% to 43%. A significant decrease in IPD incidence due to PCV7 serotypes was observed, while the incidence of non-PCV7 serotypes increased, with the consequence that there was no clear pattern in the overall incidence of IPD. Penicillin nonsusceptibility was correlated with the proportion of PCV7 serotypes. Erythromycin nonsusceptibility increased in association with long-half-life macrolide consumption and then decreased in 2004 to 2007. The increase in PCV7 serotypes and antibiotic nonsusceptibility related to antibiotic consumption in the 1980s and 1990s was reversed in the 2000s, probably as a result of PCV7 immunization. The decrease in IPD incidence due to PCV7 serotypes was mirrored by an increase in that of non-PCV7 serotypes. The impact of various preventive/therapeutic strategies on pneumococcal evolution is serotype dependent, and the dynamics remain unpredictable.
Assuntos
Técnicas de Tipagem Bacteriana , Farmacorresistência Bacteriana , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Antibacterianos/farmacologia , Criança , Pré-Escolar , Uso de Medicamentos/estatística & dados numéricos , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Incidência , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Vacinas Pneumocócicas/imunologia , Prevalência , Sorotipagem , Espanha , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Introducción. La lepra es una enfermedad poco frecuente en nuestro entorno; sin embargo, hace tan sólo 50 años era considerada la causa más frecuente de polineuropatía. Caso clínico. Presentamos el caso de una mujer de 37 años que consulta por parestesias en manos y pies, livedo reticularis y quejas de frecuentes ulceraciones en las manos. En la exploración cútanea se detectaron lesiones nodulares y el estudio neurofisiológico puso de manifiesto una polineuropatía sensitiva simétrica distal de predominio axonal. La biopsia cutánea mostró un infiltrado histocitario y bacilos intracitoplasmáticos de tipo Mycobacterium leprae, lo que condujo al diagnóstico de lepra lepromatosa multibacilar. Se instauró tratamiento con politerapia, según recomendaciones de la Organización Mundial de la Salud, con buena evolución. A pesar de los intentos de erradicación de la lepra, su incidencia continúa siendo elevada, especialmente en áreas endémicas, entre las que se incluye el sur de España y, generalmente, asociada a hacinamiento y bajo nivel socioeconómico. Conclusiones. Éste es el último caso autóctono comunicado en la Comunidad Valenciana. Entre las posibles causas de polineuropatía sensitiva debe tenerse en cuenta todavía la posibilidad de la lepra, sobre todo en pacientes procedentes de áreas endémicas (AU)
Introduction: Lepra is an uncommon disease within our setting. However, it was considered the most frequent cause of polyneuropathy only 50 years ago. Case Report: We present the case of a 37 year-old woman who consulted due to paresthesias in both hands and feet, livedo reticularis and complaints of frequent hand lesions. Examination of the skin detected nodular lesions and the neurophysiological study confirmed distal symmetric sensitive polyneuropathy with axonal predominance. The skin biopsy also showed histocytic infiltrate and mycobacterium lepra type intracytoplasmatic bacilli. This led to the diagnosis of Multibacillary lepromatous leprosy. Multiple treatment was begun, according to the World Health Organization recommendations, with good evolution. In spite of the attempts to eradicate lepra, its incidence continues to be elevated, especially in endemic areas, among which the south of Spain is included. It is generally associated to overcrowding and low social-economic level. Conclusions: This is the last endemic case in the Valencian Community. The possibility of lepra should be considered among the possible causes of sensitive polyneuropathy, above all in patients in endemic areas (AU)
Assuntos
Adulto , Feminino , Humanos , Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/microbiologia , Doenças do Sistema Nervoso Periférico/patologia , Pele/patologia , Doenças Endêmicas , Parestesia/etiologiaRESUMO
OBJECTIVES: The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. METHODS: All invasive pneumococci received in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. RESULTS: In 2000-07, PCV-7 distribution (doses/1000 inhabitants =59 months age/year) increased from 0.0 to 411.90, and antibiotic consumption (DDD/1000 inhabitants/day) was maintained for beta-lactams ( approximately 16), decreased for macrolides (from 4.4 to 2.7) and increased for respiratory fluoroquinolones (from 0.3 to 2.7). The increase in PCV-7 distribution correlated with a decrease in PCV-7 serotypes prevalence among invasive isolates in children (r = -0.976; P < 0.001) and adults (r = -0.905; P = 0.002). This decrease in PCV-7 serotypes correlated with a decrease in penicillin non-susceptibility in children (r = 0.929; P < 0.001) and adults (r = 0.905; P = 0.002) and with erythromycin non-susceptibility in children (r = 0.833; P = 0.010). Penicillin/erythromycin non-susceptibility in 2000 was significantly higher in paediatric versus adult isolates (penicillin: 51.4% versus 29.2%; erythromycin: 39.5% versus 20.4%), but similar in 2006-07 (20% to 24%). The increase in respiratory quinolones consumption correlated with the increase in levofloxacin non-susceptibility in adults (r = 0.926; P = 0.008) but not in children, with different non-susceptibility rates in 2007 (1.6% versus 0.0%; P = 0.013). CONCLUSIONS: This ecological analysis suggests that PCV-7 vaccination in children had a herd effect in adults, but consumption of respiratory quinolones in adults had no effect on pneumococcal susceptibility to levofloxacin in children. Penicillin/erythromycin non-susceptibility decreased along the studied period among paediatric invasive S. pneumoniae isolates to a level similar to that seen in adults.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/transmissão , Vacinas Pneumocócicas/imunologia , Quinolonas/uso terapêutico , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologia , Adulto , Antibacterianos/farmacologia , Criança , Eritromicina/farmacologia , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Quinolonas/farmacologia , Sorotipagem , Espanha , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
INTRODUCTION: Statins represent a group of pharmaceutical agents with proven effectiveness and scarce side effects; however, their widespread use increases the probability of the appearance of such adverse effects. DEVELOPMENT: We reviewed the articles that have been published on myotoxicity, neurotoxicity and other cases of disorders affecting the peripheral nervous system, both in reviews and in clinical trials and isolated cases. The frequency of appearance, clinical repercussion, proposed physiopathogenetic mechanisms were analysed in order to draw conclusions regarding the therapeutic attitude that should be adopted. CONCLUSIONS: Generally speaking they are safe pharmaceuticals, but the physician must pay attention to the appearance of possible side effects, given their potential reversibility and lower degree of severity if they are diagnosed at an early stage.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Humanos , Doenças Musculares/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , PrevalênciaRESUMO
Introducción. Las estatinas representan un grupo de fármacos con eficacia probada y escasos efectos secundarios; sin embargo, su amplia difusión aumenta la probabilidad de su aparición. Desarrollo. Revisamos los artículos publicados sobre miotoxicidad, neurotoxicidad y otros casos de afectación del sistema nervioso periférico, tanto en revisiones como en ensayos clínicos y casos aislados, analizando la frecuencia de aparición, la repercusión clínica, los mecanismos fisiopatogénicos propuestos y extrayendo la actitud terapéutica que debe tomarse.Conclusiones. En general son fármacos seguros, pero el facultativo debe prestar atención a la aparición de posibles efectos adversos dada su potencial reversibilidad y menor gravedad si se diagnostican de forma precoz
Introduction. Statins represent a group of pharmaceutical agents with proven effectiveness and scarce side effects; however, their widespread use increases the probability of the appearance of such adverse effects. Development. We reviewed the articles that have been published on myotoxicity, neurotoxicity and other cases of disorders affecting the peripheral nervous system, both in reviews and in clinical trials and isolated cases. The frequency of appearance, clinical repercussion, proposed physiopathogenetic mechanisms were analysed in order to draw conclusions regarding the therapeutic attitude that should be adopted. Conclusions. Generally speaking they are safe pharmaceuticals, but the physician must pay attention tothe appearance of possible side effects, given their potential reversibility and lower degree of severity if they are diagnosed at an early stage
Assuntos
Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Neuromusculares/induzido quimicamente , Síndromes Neurotóxicas/diagnóstico , Doenças Musculares/induzido quimicamenteRESUMO
BACKGROUND AND PURPOSE: Dendritic cells (DCs) are dedicated antigen-presenting cells able to initiate specific immune responses and their maturation is critical for the induction of antigen-specific T-lymphocyte responses. Here, we have investigated the effects of Inmunoferon-active principle (AM3), the active agent of a commercial immunomodulatory drug, on human monocyte-derived DCs (MDDCs). EXPERIMENTAL APPROACH: MDDCs derived from healthy and hepatitis C virus (HCV)-infected patients were stimulated with AM3. We analysed the expression of cell surface proteins by flow cytometry, that of cytokine production by ELISA, and the expression of chemokines and chemokine receptors by RNase protection assays. T-lymphocyte proliferation was assessed in mixed lymphocyte reactions, protein expression by western blot and luciferase-based reporter methods, and Toll-like receptor (TLR)-blocking antibodies were employed to analyse TLR activity. KEY RESULTS: In MDDCs, AM3 induced or enhanced expression of CD54, CD83, CD86, HLA-DR, chemokines and chemokine receptors, interleukin (IL)-12p70 and IL-10. Furthermore, AM3 stimulated MDDCs to increase proliferation of allogenic T cells. AM3 triggered nuclear translocation of NF-kappaB and phosphorylation of p38 mitogen-activated protein kinase. AM3 promoted NF-kappaB activation in a TLR-4-dependent manner, and blocking TLR-4 activity attenuated the enhanced expression of CD80, CD83 and CD86 induced by AM3. AM3 enhanced the expression of maturation-associated markers in MDDCs from HCV-infected patients and increased the proliferation of T lymphocytes induced by these MDDCs. CONCLUSIONS AND IMPLICATIONS: These results underline the effects of AM3 in promoting maturation of MDDCs and suggest that AM3 might be useful in regulating immune responses in pathophysiological situations requiring DC maturation.
Assuntos
Adjuvantes Imunológicos/farmacologia , Fosfatos de Cálcio/farmacologia , Células Dendríticas/efeitos dos fármacos , Glicopeptídeos/farmacologia , Idoso , Western Blotting , Proliferação de Células/efeitos dos fármacos , Quimiocinas/efeitos dos fármacos , Quimiocinas/metabolismo , Células Dendríticas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatite C/metabolismo , Humanos , Pessoa de Meia-Idade , Receptores de Quimiocinas/efeitos dos fármacos , Receptores de Quimiocinas/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoAssuntos
Neurossífilis/complicações , Papiledema/etiologia , Adulto , Feminino , Humanos , Neurossífilis/diagnósticoRESUMO
No disponible
Assuntos
Humanos , Feminino , Adulto , Neurossífilis/complicações , Papiledema/etiologia , Treponema pallidum/patogenicidadeRESUMO
Dendritic cells are bone marrow-derived professional antigen-presenting cells that exert critical functions in innate and adaptive immune responses. Depending on their functional maturation status, dendritic cells trigger primary immune responses or promote immunological tolerance. This functional ambivalence has taken dendritic cells into the focus of attention of immunotherapy protocols for both vaccination and tolerance induction. The capacity of dendritic cells to generate anti-tumour immune responses has already been demonstrated, and numerous clinical trials are currently in progress to assess their therapeutic potential. In the present review we will briefly outline the types and effector functions of dendritic cells in the human system, and summarise the present state of anti-tumour immunotherapy protocols, emphasising the most relevant parameters currently evaluated in preclinical and clinical assays.
Assuntos
Células Dendríticas/imunologia , Imunoterapia Adotiva , Neoplasias/imunologia , Neoplasias/terapia , Humanos , Imunoterapia Adotiva/métodosRESUMO
Dendritic cells are bone marrow-derived professional antigen-presenting cells that exert critical functions in innate and adaptive immune responses. Depending on their functional maturation status, dendritic cells trigger primary immune responses or promote immunological tolerance. This functional ambivalence has taken dendritic cells into the focus of attention of immunotherapy protocols for both vaccination and tolerance induction. The capacity of dendritic cells to generate anti-tumour immune responses has already been demonstrated, and numerous clinical trials are currently in progress to assess their therapeutic potential. In the present review we will briefly outline the types and effector functions of dendritic cells in the human system, and summarise the present state of anti-tumour immunotherapy protocols, emphasising the most relevant parameters currently evaluated in preclinical and clinical assays (AU)
Assuntos
Humanos , Masculino , Feminino , Células Dendríticas/imunologia , Neoplasias/imunologia , Imunoterapia Adotiva/instrumentação , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Protocolos ClínicosRESUMO
Introducción. El edema de papila suele ser secundario a hipertensión intracraneal, pero en ocasiones puede ser la manifestación inicial de enfermedades sistémicas como síndrome de Guillain-Barré, neurosarcoidosis, enfermedad de Leber, enfermedad de Lyme, síndrome de POEMS y otros. Presentamos un caso ocurrido en el Hospital General Universitario de Alicante, en el que el edema de papila fue la manifestación inicial de un síndrome de POEMS. Caso clínico. Mujer de 36 años, sin antecedentes de interés, que consulta por cefalea opresiva frontal izquierda, de cinco días de evolución, de inicio brusco, sin náusea ni vómitos acompañantes, sin exacerbación con las maniobras de Valsalva y sin otra sintomatología acompañante. En la exploración destaca borramiento nasal del ojo derecho y papiledema en el ojo izquierdo, hiperpigmentación cutánea en cara y escote que respetaba pliegues, hipoestesia táctil dolorosa distal en miembros inferiores y arreflexia aquílea e hiporreflexia rotuliana bilateral. Tras realizar distintas pruebas complementarias se descartó lesión ocupante de espacio intracraneal e hipertensión intracraneal, y se llegó al diagnóstico de polineuropatía crónica sensitivomotora de tipo mixto en miembros superiores e inferiores con afectación predominantemente proximal, edema de papila bilateral y fotosensibilidad cutánea a estudio. Tras dos años, la paciente presentó hepatomegalia, hipotiroidismo subclínico y alteraciones cutáneas esclerodermiformes, con lo que se diagnosticó como probable síndrome de POEMS, confirmado por la presencia de componente monoclonal en sangre y orina. Conclusión. El edema de papila como manifestación inicial de un síndrome de POEMS es infrecuente, pero debe estar presente en el diagnóstico diferencial de esta patología por las implicaciones diagnósticas y terapéuticas que conlleva
INTRODUCTION. Oedema of the papilla, or papilloedema, is usually due to intracranial hypertension, but can sometimes be the initial symptom of systemic diseases like Guillain-Barre syndrome, neurosarcoidosis, Lebers disease, Lyme disease or POEMS syndrome, among others. We report on a case that occurred at the Hospital General Universitario in Alicante, in which papilloedema was the initial symptom of POEMS syndrome. CASE REPORT. A 36-year-old female, with no relevant past history, who visited after suffering a left-side frontal oppressive headache for five days; onset was sudden, there was no concomitant nausea or vomiting, it did not get worse when Valsalva manoeuvres were performed and there were no other accompanying symptoms. The examination revealed nasal blurring in the visual field of the right eye and papilloedema in the left eye, hyperpigmentation of the skin on the face and upper chest area that respected creases in the skin, painful distal tactile hypaesthesia in the lower limbs and bilateral areflexia of Achilles tendons and patellar hyperreflexia. After conducting a number of different complementary tests intracranial space-occupying lesions and intracranial hypotension were both ruled out and the patient was diagnosed with mixed-type sensory-motor chronic polyneuropathy in the upper limbs, and in the lower extremities with predominantly distal involvement, bilateral oedema of the papilla and skin photosensitivity. Two years later the patient had hepatomegaly, subclinical hypothyroidism and sclerodermiform alterations of the skin, which suggested a probable diagnosis of POEMS syndrome that was later confirmed by the presence of monoclonal component in blood and urine. CONCLUSIONS. Papilloedema is rarely seen as the initial symptom of POEMS syndrome, but it must be included in the differential diagnosis of this pathology due to the diagnostic and therapeutic implications it entails