FGF-23: estado da arte

Há aproximadamente 10 anos descobriuse um hormônio denominado FGF-23 (fator de crescimento de fibroblastos 23), um membro da família dos fatores de crescimento de fibroblastos, cujas funções atualmente conhecidas envolvem o metabolismo do fósforo (P) e a inibição da 1α hidroxilase, enzima responsável pela síntese de calcitriol. Tal descoberta possibilitou um novo entendimento sobre os mecanismos de controle do P, um elemento associado com mortalidade, especialmente na doença renal crônica (DRC). Nesta revisão descreveremos diversos aspectos deste hormônio, desde a sua descoberta, função, produção, mecanismo de ação, até os últimos estudos clínicos envolvendo o mesmo. Posteriormente, abordaremos as possíveis repercussões destes estudos na prática clínica.

Mecanismos de ação dos corticosteróides na polipose rinossinusal

Os glicocorticóides (GC) são drogas de escolha no tratamento clínico da polipose nasossinusal conforme recomendação da literatura. Entretanto, seus mecanismos de ação nas regressões dos sintomas clínicos e dos pólipos não são totalmente compreendidos. Sabe-se que a administração tópica e ou sistêmica dos glicocorticóides leva a variações na expressão de citocinas, quimiocinas e linfocinas, além das alterações celulares. Assim, os GC suprimem a expressão de citocinas pró-inflamatórias, de quimiocinas, de moléculas de adesão, além de estimular a transcrição de citocinas antiinflamatórias. Citocinas pró-fibróticas como a IL-11, fator básico de crescimento do fibroblasto (b-FGF) e fator de crescimento endotelial vascular (VEGF), relacionados com o crescimento do pólipo, também são suprimidos pela ação do GC. Tal ação depende fundamentalmente da interação com os seus receptores (GR), pois alguns indivíduos apresentam algum grau de resistência celular ao seu efeito, que parece estar relacionada com a presença da isoforma b do GR. Genes envolvidos nas fases de produção de imunoglobulinas, apresentação e processamento do antígeno também sofrem ação dos GC de forma variada. OBJETIVOS: Fazer uma revisão da literatura sobre os mecanismos de ação do GC na PNS. CONCLUSÃO: A compreensão desses mecanismos implicará no desenvolvimento de drogas mais eficazes na sua terapêutica.

Avaliação do fosfato natural de Gafsa para recuperação de pastagem degradada em latossolo vermelho-escuro

Este experimento de campo, instalado em janeiro de 1994, teve os objetivos: 1) avaliar a eficiência do fosfato natural de Gafsa farelado (FGF) na recuperação de pastagem de Brachiaria decumbens cv. Basilisk num Latossolo Vermelho-Escuro textura argilosa do Distrito Federal, e 2) verificar efeitos de interações entre fontes de P (fosfato natural de Gafsa e superfosfato triplo (SFT) e incorporação do fosfato com grade e adubação complementar (N, Ca, Mg, K, S e micronutrientes), sobre a disponibilidade de forragem. Os fosfatos foram aplicados na dose de 100 kg ha-1 de P2O5. O delineamento foi o de blocos casualizados, com parcelas subdivididas, com o tratamento incorporação nas parcelas e o fatorial, fontes de P vs. adubação complementar, nas subparcelas, perfazendo 12 tratamentos com quatro repetições. A resposta à aplicação dos fosfatos só foi efetivada com aplicação simultânea de adubação complementar; a incorporação com grade foi essencial para aumentar a eficiência do FGF; ao ser incorporado com grade, o FGF teve desempenho tão bom quanto o SFT; sem incorporação, o FGF proporcionou produção de matéria seca inferior à proporcionada pelo SFT (p<0,05).

Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

The actions of fibroblast growth factors (FGFs), particularly the basic form (bFGF), have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair

Glial fibrillary acidic protein (GFAP): modulation by growth factors and its implication in astrocyte differentiation

Intermediate filament (IF) proteins constitute an extremely large multigene family of developmentally and tissue-regulated cytoskeleton proteins abundant in most vertebrate cell types. Astrocyte precursors of the CNS usually express vimentin as the major IF. Astrocyte maturation is followed by a switch between vimentin and glial fibrillary acidic protein (GFAP) expression, with the latter being recognized as an astrocyte maturation marker. Levels of GFAP are regulated under developmental and pathological conditions. Upregulation of GFAP expression is one of the main characteristics of the astrocytic reaction commonly observed after CNS lesion. In this way, studies on GFAP regulation have been shown to be useful to understand not only brain physiology but also neurological disease. Modulators of GFAP expression include several hormones such as thyroid hormone, glucocorticoids and several growth factors such as FGF, CNTF and TGFß, among others. Studies of the GFAP gene have already identified several putative growth factor binding domains in its promoter region. Data obtained from transgenic and knockout mice have provided new insights into IF protein functions. This review highlights the most recent studies on the regulation of IF function by growth factors and hormones.

Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease

Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (χ2=14.33; P=0.002). Increased OPG levels were positively associated with IL-6 (r=0.38, P<0.001), FGF-23 (r=0.26, P<0.001) and hsCRP (r=0.0.24, P=0.003). In addition, OPG was positively associated with troponin I (r=0.54, P<0.001) and IMT (r=0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR=1.07, 95%CI=1.02-1.13) and hsCRP (HR=1.02, 95%CI=1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serum OPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease.

The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.