RESUMEN
Sleep-disordered breathing (SDB) constitutes a highly prevalent comorbidity in patients with chronic heart failure (HF, approximately 45%). Both diseases are related in a bidirectional way: Obstructive sleep apnoea (OSA) can contribute to the development of HF via multiple mechanisms. Apnoea-related acute rise of cardiac afterload as well as manifest hypertension may contribute to the development of myocardial hypertrophy and thus HF. In addition, OSA increases the risk for myocardial infarction and impaired recovery of cardiac function after the event. Impaired cardiac function itself may contribute to the development of obstructive and central sleep apnoea (SA). Therefore, optimal medical management of HF is part of the therapy of SDB in such patients. Treatment of SDB with different modes of positive airway pressure suppresses apnoeas and hypopnoeas, improves sleep and may improve related symptoms and cardiac function of affected patients. Considering the high coincidence of SDB and HF, the adequate diagnosis of SDB and evaluation of indication for therapy of SDB performed in a specialised centre is advised.
Asunto(s)
Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Infarto del Miocardio/epidemiología , Infarto del Miocardio/terapia , Respiración con Presión Positiva/estadística & datos numéricos , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/terapia , Causalidad , Enfermedad Crónica , Comorbilidad , Insuficiencia Cardíaca/diagnóstico , Humanos , Infarto del Miocardio/diagnóstico , Prevalencia , Factores de Riesgo , Síndromes de la Apnea del Sueño/diagnósticoRESUMEN
BACKGROUND: In normal mucosa, intestinal lamina propria macrophages (IMACs) maintain tolerance against food antigens and the commensal bacterial flora. Several mechanisms have been identified that mediate tolerance. The ubiquitin-proteasome system (UPS) is a large multiprotein complex that degrades cellular proteins. As the UPS may modulate immune functions of IMACs, we performed a detailed investigation of UPS expression and function under normal conditions and in cells derived from patients suffering from inflammatory bowel disease (IBD). METHODS: IMACs were isolated from intestinal mucosa. mRNA expression of macrophages differentiated in vitro (i.v. MACs) and IMACs was compared by Affymetrix® oligonucleotide arrays. Quantitative Taqman-PCR was performed on five exemplary proteasomal and five ubiquitinylation genes each. Proteins were analyzed by immunohistochemistry and Western blotting. Proteasome function was assessed by a fluorimetric test. RESULTS: Affymetrix analysis showed downregulation of mRNA expression of almost all represented proteasomal and of 22 ubiquitination-associated genes in IMACs as compared to i.v. MACs and monocytes. By quantitative PCR, up to tenfold higher mRNA expression of 10 exemplary genes of the UPS (UBE2A, UBE2D2, UBE2L6, USP14, UBB and ATPase2, ß2, ß5, ß2i/MECL-1, ß5i/LMP7) was demonstrated in i.v. MACs as compared to IMACs. Immunohistochemistry and Western blots confirmed these findings in intestinal mucosa of controls and patients suffering from diverticulitis. In contrast, a significant increase in protein amounts was found in mucosa of patients with IBD. CONCLUSION: Reduced expression of subunits of the UPS in IMACs of normal mucosa supports the concept of the presence of a nonreactive, anergic macrophage phenotype in the gut under normal conditions. Reinduction in IMACs of IBD mucosa reflects activated IMACs which can present antigenic peptides and thus support inflammation.
Asunto(s)
Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Regulación hacia Abajo , Mucosa Intestinal/enzimología , Macrófagos/enzimología , Complejos de Ubiquitina-Proteína Ligasa/genética , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Adenosina Trifosfatasas/genética , Diferenciación Celular , Células Cultivadas , Colitis Ulcerosa/enzimología , Colon/enzimología , Enfermedad de Crohn/enzimología , Diverticulitis/enzimología , Diverticulitis/genética , Humanos , Análisis por Micromatrices , ATPasas de Translocación de Protón Mitocondriales/genética , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Complejos de Ubiquitina-Proteína Ligasa/sangreRESUMEN
A new clinical odour test was developed and validated in a clinical trial including 50 healthy volunteers as well as 35 patients suffering from smell disorders. The aromas were incorporated in an inert gas under disclosure from oxygen, avoiding impairment caused by oxidative transformation. Conventional smell test by Elsberg bottles was used as standard. The spray test proved to be equally effective in discriminating subjects suffering from smell disorders as the standard procedure. Moreover the spray test is feasible and long term constance of the substances is guaranteed.