RESUMEN
The occurrence of microalbuminuria or albuminuria indicates a disturbance of the barrier function of endothelial cells, basement membrane or of a structural-renal disease (including diseased podocytes). The prevalence of microalbuminuria in the general population is about 8 %, however, in high risk groups, prevalence rates of 50 % and more have been observed. Its incidence is strongly associated with increased cardiovascular morbidity and mortality. Blood pressure control and the blockade of the renin-angiotensin-aldosteron-system (RAAS), respectively, is the central mechanism to reduce cardio-vascular-renal end points as well as mortality.
Asunto(s)
Albuminuria/diagnóstico , Albuminuria/terapia , Enfermedades Cardiovasculares/epidemiología , Albuminuria/clasificación , Albuminuria/epidemiología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Diagnóstico Diferencial , Glomerulonefritis/complicaciones , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/prevención & control , Incidencia , Prevalencia , Sistema Renina-Angiotensina/efectos de los fármacos , Factores de RiesgoRESUMEN
OBJECTIVE: Growth differentiation factor-5 (GDF-5), a member of the transforming growth factor (TGF)-beta family, is involved in joint development during embryogenesis and has the potential to regenerate cartilage in adult animals. As progression of chronic joint diseases is influenced by cytokines of the synovial tissue, we examined the expression and effects of GDF-5 in this tissue. METHODS: Microarray experiments were investigated for differential expression of GDF-5 in synovial tissues, synovial fibroblasts, and peripheral blood cells. GDF-5 expression was validated by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, double immunofluorescence, and in situ hybridization in synovial tissue of normal donors (ND) and patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of inflammation and therapy were investigated in RA and OA fibroblasts after stimulation with interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, methotrexate (MTX), and prednisolone. The influence of GDF-5 on macrophages was studied by chemotaxis assay. RESULTS: Microarray analysis and immunostaining revealed expression predominantly in synovial fibroblasts. Compared to patients without immunomodulating drugs, expression of GDF-5 was decreased significantly in patients receiving glucocorticoids and/or disease-modifying antirheumatic drugs (DMARDs) (p = 0.007), but did not differ between the total group of ND, OA, and RA. Stimulation with prednisolone and TNFalpha reduced GDF-5 expression in OA and RA fibroblasts, whereas MTX and IL-1beta revealed minor or no relevant change. GDF-5 also reduced cell migration of macrophages (p<0.001). CONCLUSION: GDF-5 is expressed in synovial fibroblasts and may counteract macrophage infiltration. Its modulation by inflammation and therapy suggests that glucocorticoids play a conflicting role by suppressing not only inflammation but also putative mechanisms of repair.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/metabolismo , Glucocorticoides/uso terapéutico , Factor 5 de Diferenciación de Crecimiento/metabolismo , Membrana Sinovial/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Ensayos de Migración de Macrófagos , Citocinas/farmacología , Regulación hacia Abajo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Expresión Génica , Glucocorticoides/farmacología , Humanos , Inmunohistoquímica , Terapia de Inmunosupresión , Hibridación in Situ , Metotrexato/farmacología , Metotrexato/uso terapéutico , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Prednisolona/farmacología , Prednisolona/uso terapéutico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Membrana Sinovial/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The prevention of disease and the prevention of subsequent disease is one of the main themes in public health as well as in clinical medicine. Besides targeted interventions aiming at the total population (public health) individual steps like life style intervention and use of pharmacotherapy are important components. Taking acute myocardial infarction as an example it is illustrated, how risk factors can be targeted and which new drugs in development have been either just registered or are in late phase III of clinical testing shortly before registration and final approval. In this context it was shown that there are many exciting new options to reduce risk factors. On the other hand there are indications in which new drug development is likely not to contribute to an improvement of the situation (e. g. arterial hypertension) and in which further targeted intervention aiming at physicians (therapeutic pathways, guidelines, point of care research) and patients (life style intervention, compliance) has to be undertaken to improve the efficacy of currently available pharmacotherapy.
Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Dislipidemias/prevención & control , Hipertensión/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Obesidad/tratamiento farmacológico , Prevención del Hábito de Fumar , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Grasa Intraabdominal/efectos de los fármacos , Masculino , Prevención Primaria/métodos , Factores de Riesgo , Fumar/tratamiento farmacológicoRESUMEN
BACKGROUND: Intradialytic hypotension (IDH) is one of the most severe complications during hemodialysis. Its appearance is caused in part by rapid fluid removal with concomitant failure in blood pressure regulation but also by other dialytic-dependent and independent factors. PATIENTS AND METHODS: We investigated total (TBW), extracellular (ECW) and intracellular water (ICW) in chronic intermittent hemodialysis dialysis hypotension-prone (CRF-HP, n = 11) and nonhypotension-prone (CRF-NHP, n = 10) patients with end-stage renal disease before, every 30 minutes during, as well as after dialysis and within onset of intradialytic hypotension by multifrequent bioimpedance analysis (BIA). Additionally, intradialytic time course of BIA in patients with acute renal failure (ARF) and septic shock (n = 10) was observed. RESULTS: IDH occurred in 72.1% of CRF-HP and in 80% of ARF patients. In CRF-HP and CRF-NHP, ECW significantly decreased by -12.44 +/- 4.22% in CRF-HP and -9.0 +/- 6.2% in CRF-NHP comparing pre- and post-dialysis values (each p < 0.01). Conversely, ICW increased by +11.5 +/- 11.3% in CRF-HP and +18.4 +/- 25.2% in CRF-NHP (each p < 0.05). In patients with ARF no significant changes could be detected. Calculated ECW/ICW and ECW/TBW ratio significantly decreased in CRF patients with a higher rate in CRF-HP patients (p < 0.05). Neither ECW/ICW nor ECW/TBW ratio correlated with mean arterial pressure. The onset of intradialytic hypotension (n = 35) did not differ intraindividually compared to normotensive periods (n = 411). Fluid removal in CRF patients seems to be mainly from the extracellular space. The reduced decreases in ECW/ICW and ECW/TBW ratios in CRF-HP compared to CRF-NHP may indicate an insufficient refilling from intra- to extracellular compartment in CRF-HP. CONCLUSION: In conclusion, multifrequent BIA is not capable to predict hypotension in the individual patient during a particular dialysis session.
Asunto(s)
Hipotensión/etiología , Diálisis Renal/efectos adversos , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/terapia , Adulto , Anciano , Presión Sanguínea , Agua Corporal/metabolismo , Impedancia Eléctrica , Femenino , Humanos , Hipotensión/fisiopatología , Hipotensión/terapia , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pletismografía de Impedancia/métodos , Estudios Prospectivos , Diálisis Renal/métodos , Choque Séptico/fisiopatología , Choque Séptico/terapiaRESUMEN
Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta superfamily. Their potential for organ and tissue regeneration and repair has been intensively investigated in recent years. Studies on fetal development have demonstrated the important role of these proteins for the development and differentiation of different organs. Miss-expression or mutation of BMPs may lead to severe abnormalities or even abortion. However, a regenerative potential has also been recognized for the adult organism. BMPs support fracture healing and may contribute to treatment of joint diseases. Thus, BMP-7 is one of the first BMPs approved for clinical application in non-unions of bone fractures resistant to conventional therapy. In degenerative and inflammatory joint diseases, experimental data suggest a decrease of BMP expression in cartilage tissue. Therefore, BMPs could be promising therapeutic candidates in these diseases, although more detailed analyses are necessary. In this review we will focus on bone morphogenetic proteins and discuss present and putative future clinical applications.