RESUMEN
BACKGROUND: Major depressive disorder (MDD) and chronic heart failure (CHF) have in common heightening states of inflammation, manifested by elevated inflammation markers such as C-reactive protein. This study compared inflammatory biomarker profiles in patients with CHF and MDD to those without MDD. METHODS: The study recruited patients admitted to inpatient care for acute heart failure exacerbations, after psychiatric diagnostic interview. Patients with Beck Depression Inventory (BDI) scores lower than 10 and with no history of depression served as the nondepressed reference group (n = 25). MDD severity was defined as follows: mild (BDI 10-15; n = 48), moderate (BDI 16-23; n = 51), and severe (BDI ≥ 24; n = 33). A Bio-Plex assay measured 18 inflammation markers. Ordinal logistic models were used to examine the association of MDD severity and biomarker levels. RESULTS: Adjusting for age, sex, statin use, body mass index, left ventricular ejection fraction, tobacco use, and New York Heart Association class, the MDD overall group variable was significantly associated with elevated interleukin (IL)-2 (p = .019), IL-4 (p = .020), IL-6 (p = .026), interferon-γ (p = .010), monocyte chemoattractant protein 1 (p = .002), macrophage inflammatory protein 1ß (p = .003), and tumor necrosis factor α (p = .004). MDD severity subgroups had a greater probability of elevated IL-6, IL-8, interferon-γ, monocyte chemoattractant protein 1, macrophage inflammatory protein 1ß, and tumor necrosis factor α compared with nondepressed group. The nondepressed group had greater probability of elevated IL-17 (p < .001) and IL-1ß (p < .01). CONCLUSIONS: MDD in patients with CHF was associated with altered inflammation marker levels compared with patients with CHF who had no depression. Whether effective depression treatment will normalize the altered inflammation marker levels requires further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00078286.
Asunto(s)
Trastorno Depresivo Mayor/sangre , Insuficiencia Cardíaca/sangre , Inflamación/sangre , Anciano , Biomarcadores/sangre , Enfermedad Crónica , Comorbilidad , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/epidemiología , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Inflamación/epidemiología , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Sertralina/uso terapéuticoRESUMEN
INTRODUCTION: Autoantibodies (autoAbs) against desmoglein-1 (DSG1) and desmoglein-3 (DSG3) have conventionally been studied and well accepted in the pathogenesis of pemphigus vulgaris (PV) and foliaceus (PF). Recent studies have suggested that non-DSG autoAbs may contribute to the pathogenesis of pemphigus, including autoAbs directed at acetylcholine receptors (AChR) and thyroid peroxidase (TPO). The purpose of this study is to retrospectively analyze PV and PF patient sera to better understand the relationship between anti-AChR and -TPO Abs to disease activity and DSG reactivity between patients treated with prednisone and steroid sparing agents (SSA; n = 22) or prednisone and rituximab (n = 21). METHODS: Patients were evaluated at 2 time points, T1 and T2, for disease activity using the Pemphigus Disease Area Index (PDAI), and sera were tested for the presence of TPO, DSG1, DSG3, muscarinic (M3) and nicotinic (n) AChR IgG autoAbs, as well as antibodies against Varicella Zoster Virus (VZV) by ELISA. RESULTS: Disease activity significantly decreased in patients from T1 to T2 (p < .0001). A significant difference was seen in IgG anti-DSG1 (p < .0001) and anti-DSG3 (p = .0049) levels when T1 was compared to T2 in both treatment groups. A significant increase was found between pemphigus patients and normal subjects with nAChR (p < .0001) at T1 but not with m3AChR, TPO or VZV Abs. No significant difference was seen between T1 and T2 values in patients with pemphigus for the non-desmoglein Abs TPO (p = .7559), M3AChR (p = .9003), nAChR (p = .5143) or VZV (p = .2454). These findings demonstrate that although an increase in IgG anti-nAChR autoAbs was found in PV and PF subjects, these Abs did not decrease with treatment. No other non-DSG Abs were increased or significantly changed over time in patients with pemphigus. This suggests that anti -AChR and -TPO Abs may not play a direct role in the pathogenesis of most patients with pemphigus, but does not rule out a role for non-DSG auto antibodies in distinct subsets of pemphigus patient.
Asunto(s)
Autoanticuerpos/sangre , Desmogleína 1/inmunología , Desmogleína 3/inmunología , Inmunoglobulina G/sangre , Pénfigo/inmunología , Receptor Muscarínico M3/inmunología , Receptores Nicotínicos/inmunología , Adulto , Anciano , Autoantígenos/inmunología , Femenino , Humanos , Yoduro Peroxidasa/inmunología , Proteínas de Unión a Hierro/inmunología , Masculino , Persona de Mediana Edad , Pénfigo/tratamiento farmacológico , Prednisona/uso terapéutico , Estudios Retrospectivos , Rituximab/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Skin cancer and photoaging changes result from ultraviolet (UV)-induced oxidative stress. Topical antioxidants may protect skin from these effects. OBJECTIVE: We sought to determine whether a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid (CEFer) could protect human skin in vivo from substantial amounts of solar-simulated UV radiation. METHODS: CEFer and its vehicle were applied to separate patches of normal-appearing human skin for 4 days. Each patch was irradiated with solar-simulated UV, 2 to 10 minimal erythema doses, at 2-minimal erythema dose intervals. One day later, skin was evaluated for erythema and sunburn cells, and immunohistochemically for thymine dimers and p53. UV-induced cytokine formation, including interleukin (IL)-1alpha, IL-6, IL-8, and IL-10, and tumor necrosis factor-alpha, were evaluated by real-time polymerase chain reaction. RESULTS: CEFer provided significant and meaningful photoprotection for skin by all methods of evaluation. LIMITATIONS: The number of patients evaluated was relatively small. CONCLUSION: CEFer provided substantial UV photoprotection for skin. It is particularly effective for reducing thymine dimer mutations known to be associated with skin cancer. Its mechanism of action is different from sunscreens and would be expected to supplement the sun protection provided by sunscreens.
Asunto(s)
Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Ácidos Cumáricos/uso terapéutico , Daño del ADN/efectos de los fármacos , Piel/efectos de la radiación , Quemadura Solar/prevención & control , alfa-Tocoferol/uso terapéutico , Administración Cutánea , Adulto , Citocinas/genética , Citocinas/metabolismo , Cartilla de ADN , Combinación de Medicamentos , Eritema/etiología , Eritema/prevención & control , Humanos , Inmunohistoquímica , Reacción en Cadena de la Polimerasa , Dímeros de Pirimidina/análisis , ARN Mensajero/análisis , Dosis de Radiación , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/prevención & control , Estadísticas no Paramétricas , Quemadura Solar/genética , Proteína p53 Supresora de Tumor/análisis , Rayos Ultravioleta/efectos adversosRESUMEN
The mechanisms that lead to the development of skin lesions in patients with dermatitis herpetiformis (DH) are not known. We hypothesized that an ongoing immune response in the gut of patients with DH would result in an increase in circulating cytokines and be associated with endothelial cell activation, creating a proinflammatory environment in the skin. Skin biopsies from the normal-appearing inner arm of 11 DH patients, with no active skin lesions, and 12 normal subjects were analyzed for E-selectin (E-sel) and ICAM-1 mRNA. DH patients' skin expressed markedly increased levels of E-sel mRNA. Mean E-sel mRNA expression in DH skin was 1,271 (range 63.78-5861) times greater than that of a control, normal skin (P<0.001) with no significant increased expression of ICAM-1 mRNA. Serum levels of soluble E-selectin (sE-sel), IgA anti-tissue transglutaminase antibodies, and serum IL-8 levels were significantly increased in patients with DH. These studies demonstrate that patients with DH have evidence of endothelial cell activation in the skin and systemic manifestations of the ongoing inflammation associated with the mucosal immune response. Endothelial cell activation may play a critical role in the development of skin lesions in patients with DH and may represent a common mechanism for cutaneous manifestations of inflammatory gastrointestinal diseases.
Asunto(s)
Dermatitis Herpetiforme/inmunología , Selectina E/sangre , Células Endoteliales/inmunología , Interleucina-8/sangre , Piel/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Dermatitis Herpetiforme/patología , Selectina E/genética , Células Endoteliales/química , Células Endoteliales/patología , Femenino , Proteínas de Unión al GTP/inmunología , Gastroenteritis/complicaciones , Gastroenteritis/inmunología , Humanos , Inmunoglobulina A/sangre , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-8/genética , Selectina L/sangre , Masculino , Persona de Mediana Edad , Proteína Glutamina Gamma Glutamiltransferasa 2 , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Piel/química , Piel/patología , Transglutaminasas/inmunología , Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Linfocitos B Reguladores/efectos de los fármacos , Inmunosupresores/administración & dosificación , Pénfigo/tratamiento farmacológico , Rituximab/administración & dosificación , Azatioprina/administración & dosificación , Linfocitos B Reguladores/inmunología , Linfocitos B Reguladores/metabolismo , Quimioterapia Combinada/métodos , Glucocorticoides/administración & dosificación , Humanos , Interleucina-10/metabolismo , Recuento de Linfocitos , Ácido Micofenólico/administración & dosificación , Pénfigo/sangre , Pénfigo/inmunología , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antirreumáticos/uso terapéutico , Autoanticuerpos/química , Autoantígenos/química , Colágenos no Fibrilares/química , Penfigoide Ampolloso/tratamiento farmacológico , Estudios de Casos y Controles , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/química , Penfigoide Ampolloso/sangre , Penfigoide Ampolloso/inmunología , Estudios Prospectivos , Estructura Terciaria de Proteína , Rituximab , Colágeno Tipo XVIIAsunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Factor Activador de Células B/sangre , Memoria Inmunológica/inmunología , Penfigoide Ampolloso/tratamiento farmacológico , Células Precursoras de Linfocitos B/citología , Anciano , Autoanticuerpos/sangre , Vesícula/tratamiento farmacológico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Células Precursoras de Linfocitos B/efectos de los fármacos , Prednisona/uso terapéutico , Rituximab , Resultado del TratamientoRESUMEN
Patients with dermatitis herpetiformis (DH) have a gluten-sensitive enteropathy and while on gluten-containing diets have elevated levels of serum IL-8. We hypothesized that the mucosal immune response to gluten is responsible for the elevated serum IL-8. Six DH patients were studied while on a gluten-free diet (GFD), whereas four continued on a normal diet. Patients were followed for a mean 2.2 years and serum IL-8 was analyzed. Small bowel biopsies from five DH patients on normal diets, two DH patients on GFD, and six subjects with no small bowel abnormalities were analyzed for IL-8 mRNA. Serum IL-8 levels normalized in five of six patients on GFD and decreased in one, whereas serum IL-8 levels showed no statistically significant change in DH patients on normal diets. Small bowel biopsies from DH patients on normal diets had increased expression of IL-8 mRNA compared to normal subjects, whereas patients on a GFD showed no significant increase in small bowel mRNA. No significant IL-8 mRNA was detected in normal skin biopsies from patients with DH. These observations suggest that the IL-8 in the serum of patients with DH originates from the small bowel as a mucosal immune response to gluten ingestion.