RESUMO
It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI.
Assuntos
Injúria Renal Aguda/sangue , Células da Medula Óssea/metabolismo , Células Precursoras Eritroides/metabolismo , Eritropoetina/sangue , Fatores de Crescimento de Fibroblastos/sangue , Injúria Renal Aguda/etiologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Células Precursoras Eritroides/efeitos dos fármacos , Eritropoetina/farmacologia , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Estudos Prospectivos , Ratos Sprague-Dawley , Receptores da Eritropoetina/agonistas , Receptores da Eritropoetina/metabolismo , Proteínas Recombinantes/farmacologia , Sepse/sangue , Sepse/complicações , Choque Hemorrágico/sangue , Choque Hemorrágico/complicações , Fatores de Tempo , Regulação para CimaRESUMO
El uso de estrógeno en pacientes con Lupus Eritematoso Sistémico (LES) sigue siendo un tema en discusión, debido a los múltiples efectos que esta hormona puede tener en el sistema inmune; entre los cuales incluso se ha postulado un rol promotor de esta enfermedad. Se presenta el caso de una paciente de 28 años con diagnóstico de LES, asociado a falla ovárica y osteoporosis en la cual se debe utilizar terapia de reemplazo hormonal (TRH) y se discuten sus posibles consecuencias.
Estrogen use in patients with Systemic Lupus Erythematosus (SLE) is still a matter under discussion, due to the multiple effects that this hormone can have on the immune system; it has been postulated a promoter role of this disease. The case of a patient of 28 years with a diagnosis of SLE associated with ovarian failure and osteoporosis in which to use hormone replacement therapy (HRT) and its possible consequences are discussed is presented.
Assuntos
Humanos , Adulto , Feminino , Lúpus Eritematoso Sistêmico/fisiopatologia , Osteoporose/tratamento farmacológico , Terapia de Reposição Hormonal/efeitos adversosRESUMO
Intestinal pneumatosis is a rare complication that can occur in systemic sclerosis (ES), its pathogenesis is not entirely specified and is characterized by the presence of gas in the submucosa wall and / or bowel subserosa. For a 37 year old woman presented with a diagnosis of diffuse variety EN who consults repeatedly by pain, bloating and intermittent episodes of chronic diarrhea associated with weight loss. The imaging study revealed an intestinal pneumatosis and pneumoperitoneum as the source of the picture...
La neumatosis intestinal es una complicación rara que puede presentarse en la Esclerosis Sistémica (ES), su etiopatogenia no está del todo precisada y se caracteriza por presencia de gas en la pared submucosa y/o subserosa del intestino. Se presenta el caso de una mujer de 37 años, con diagnóstico de ES variedad difusa quien consulta en repetidas ocasiones por dolor, distensión abdominal y episodios de diarrea crónica intermitente asociado a disminución de peso. El estudio con imágenes reveló una neumatosis intestinal y neumoperitoneo como origen del cuadro...
Assuntos
Humanos , Adulto , Feminino , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia , Pneumatose Cistoide Intestinal/etiologia , Pneumoperitônio/etiologiaRESUMO
Presents a case of a young woman with a recent diagnose of systemic lupus erythematosus (SLE), with a sligth initial skin condition that envolves into toxic epidermal necrolysis (TENS): On account of this case, areview is presented of the physiopathology, clinical presentation and treatment of this infrequent form of dermatological manifestation of (SLE).
Se presenta el caso de una joven con diagnóstico reciente de lupus eritematoso sistémico (LES), con compromiso cutáneo inicial leve que evoluciona hacia necrolisis epidérmico tóxica (NET). A propósito de ello, se revisa la fisioptología, presentación clínica y tratamiento de esta infrecuente forma de manifestación dermatológica de LES.
Assuntos
Humanos , Feminino , Adolescente , Lúpus Eritematoso Sistêmico/complicações , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Imunoglobulinas/uso terapêutico , Síndrome de Stevens-Johnson/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: . To compare the gastrointestinal (GI) tolerability, safety, and efficacy of etoricoxib and diclofenac in patients with osteoarthritis (OA). METHODS: In total, 7111 patients (mean age 64 yrs) diagnosed with OA were enrolled in a randomized, double-blind trial. Patients received etoricoxib 90 mg qd (n = 3593) or diclofenac sodium 50 mg tid (n = 3518). Gastroprotective agents and low-dose aspirin were prescribed per treatment guidelines. The primary endpoint was the cumulative rate of discontinuations due to clinical and laboratory GI adverse experiences (AE). General safety was assessed, including adjudication of thrombotic cardiovascular (CV) safety data. Efficacy was evaluated using the least-square (LS) mean change from baseline patient global assessment of disease status (PGADS; 0-4 point scale). RESULTS: Mean (SD, maximum) duration of treatment was 9.3 (4.4, 16.5) and 8.9 (4.5, 16.6) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AE was significantly lower with etoricoxib than diclofenac [9.4 vs 19.2 events per 100 patient-years (PY), respectively; hazard ratio (HR) 0.50 (95% CI 0.43, 0.58; p < 0.001). Rates of thrombotic CV events were similar with etoricoxib and diclofenac [1.25 vs 1.15 events per 100 PY, respectively; HR 1.07 (95% CI 0.65, 1.74)]. The incidence of patients who discontinued due to hypertension-related AE was significantly higher with etoricoxib compared to diclofenac (2.3% vs 0.7%; p < 0.001), although few AE were severe (3 etoricoxib, 1 diclofenac). Etoricoxib and diclofenac treatment resulted in similar improvements in PGADS from baseline of -0.78 (95% CI -0.80, -0.75) and -0.75 (95% CI -0.77, -0.72), respectively. CONCLUSION: Treatment with etoricoxib 90 mg was associated with significantly better GI tolerability compared to diclofenac in this population of patients with OA. Etoricoxib 90 mg, a dose 50% higher than indicated for OA, resulted in more discontinuations due to hypertension-related AE.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Diclofenaco/efeitos adversos , Gastroenteropatias/induzido quimicamente , Osteoartrite/tratamento farmacológico , Piridinas/efeitos adversos , Sulfonas/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/patologia , Método Duplo-Cego , Etoricoxib , Feminino , Gastroenteropatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Suspensão de TratamentoRESUMO
We report a patient with a nasal hemangiopericytoma associated with an oncogenic hypophosphatemic osteomalacia (OHO). This syndrome results from tumor products that decrease renal tubular phosphate resorption, leading to the osteomalacia. This patient presented with classic bone manifestations of osteomalacia and a nasal tumor. Laboratory studies performed before the first resection of the tumor included normal serum calcium, hypophosphatemia due to decreased tubular reabsorption of phosphate, and an undetectable serum 1,25 dihydroxy vitamin D level. Serum parathormone level was normal. Anterior iliac crest bone biopsy showed characteristic signs of osteomalacia that included increased osteoid and delayed mineralization. A partial resection of the nasal tumor was performed. After the first surgery the patient showed detectable serum level of 1,25 dihydroxy vitamin D, and transient normalization of the tubular reabsorption of phosphate. The patient was also treated with phosphate supplements and vitamin D with transient control of her clinical manifestations and improvement of the radiographic signs of osteomalacia. Three months after surgery, the serum level of 1,25 dihydroxy vitamin D level again became undetectable. After selective embolization of the tumor, followed by an apparent complete tumor resection and postoperative radiation therapy, her hypophosphatemia and decreased phosphate tubular reabsorption persisted. Therefore, biochemical changes associated with hemangiopericytoma induced OHO may persist even after apparent total tumor resection. Clinicians should be aware of the oncogenic basis for some osteomalacia, as seen in this patient.
RESUMO
Objetivos: Describir las principales características demográficas y clínicas de los pacientes chilenos con espondiloartritis ingresados en el Registro Iberoamericano de Espondiloartritis (RESPONDIA). Pacientes y métodos: Estudio descriptivo y transversal de un grupo de pacientes chilenos con espondiloartritis ingresados en RESPONDIA según criterios preestablecidos, entre enero de 2006 y diciembre de 2007. Participaron 5 centros universitarios chilenos, 4 de Santiago y uno de Valparaíso. Resultados: Se incluyó a 109 pacientes, 66 varones (58,4%), con una edad media desviación estándar de 42 22 años y una duración promedio de enfermedad en el momento del diagnóstico de 7,1 años (1-29 años). Los diagnósticos fueron de espondilitis anquilosante (58,7%), artritis psoriásica (25,6%), espondiloartritis indiferenciada (7,3%), artritis asociada a enfermedad inflamatoria intestinal (5,5%), espondiloartritis de inicio juvenil (1,8%) y artritis reactiva (0,9%). Respecto a su presentación clínica, el 42,5% tuvo afectación mixta (axial y periférica); el 36,3%, afectación axial exclusivo, y el 9,7%, afectación periférica exclusiva. El dolor lumbar inflamatorio fue el síntoma más frecuente (74,3%) seguido de artritis de las extremidades inferiores (59,3%). La manifestación extraarticular más frecuente fue la uveítis (18,6%). El 40% de los pacientes tenía algún grado de incapacidad laboral. Conclusiones: El perfil clínico más frecuente en este grupo de pacientes chilenos con espondiloartritis fue la combinación de manifestaciones axiales y periféricas. El diagnóstico más frecuente fue el de espondilitis anquilosante, seguido por el de artritis psoriásica (AU)
Objectives:To describe the main demographic and clinical characteristics of Chilean patients with Spondyloarthritis included in the Ibero American Spondyloarhtritis Registry (RESPONDIA). Patients and methods: Descriptive and cross-sectional study of Chilean patients with Spondyloarthritis registered in the RESPONDIA database. Five Chilean university hospitals participated in the inclusion of patients (4 from Santiago and 1 from Valparaiso), between January 2006 and December 2007, according to the defined protocol. Results: 109 patients were included in the registry, 66 males (58.4%) with an average age of 42 22 years, and average disease duration of 7.1 years (range 1-29 years). Diagnoses of the patients were Ankilosing Spondylitis (58.7%), Psoriatic Arthritis (25.6%), Undifferentiated Spondyloarthritis (7.3%), Inflammatory Bowel Disease Arthritis (5.5%), Juvenile Onset Spondyloarthritis (1.8%) and Reactive Arthritis (0.9%). Regarding clinical forms, 42.5% had mixed disease, 36.3% had axial disease, and 9.7% had peripheral disease. Inflammatory low back pain was the most frequent symptom reported (74.3%) followed by arthritis of the lower extremities (59.3%). The most common extra-articular disease manifestation was uveitis (18.6%). Some kinds of work disability were reported in 40% of the patients. Conclusions: The most frequent clinical profile in this group of Chilean patients with Spondiloarthritis was the combination of axial and peripheral diseases. The most common diagnosis was ankilosing spondylitis and psoriatic arthritis (AU)