RESUMO
Physical activity leads to changes in water and electrolyte homeostasis and to enhanced purine metabolism. The typical abnormalities observed after exercise are hyperkaliemia, hyper- or hyponatremia and hyperuricemia. The possible explanations of hyperuricemia are: increased metabolism and decreased elimination of uric acid. Changes in uric acid excretion are commonly observed in disturbances of sodium and water homeostasis. The aim of this study was to evaluate changes in electrolytes and uric acid excretion during a very long period of exercise. Twenty subjects with a mean age of 40.75±7.15 years took part in a 100 km run. The route of the run was based on the university stadium track. All subjects were experienced amateur runners, with a mean time of regular running of 6.11±7.19 years. Blood was collected before the start, after every 25 km and 12 hours after the run. The levels of electrolytes, creatinine, uric acid, cortisol, aldosterone, creatine kinase, C-reactive protein and interleukin-6 were measured. Creatinine clearance, urinary potassium-to-sodium ratio, fractional excretion of electrolytes and uric acid were calculated. Seventeen runners completed the study. Significant increases in sodium (from 141.65±1.90 to 144.29±3.65mmol/l), potassium (from 4.53±0.34 to 5.03±0.42mmol/l), creatinine (from 0.88±0.11 to 1.10±0.20mg/dl) and uric acid (from 5.15±0.87 to 5.94±1.50 mg/dl) were observed after 100 km (p less than 0.05). Other significant changes during the study were noted in fractional excretions of sodium (from 0.86±0.29 to 0.33±0.13%) and potassium (from 6.66±2.79 to 18.90±10.01%), probably reflecting the decrease in renal blood flow (RBF) and increase in renal tubule reabsorption. The fractional excretion of uric acid slightly increased but without statistical significance from 5.34±1.51 to 6.09±2.34%. The results of our study showed that during very long but not very intensive exercise there is no change in uric acid excretion, although at the same time profound changes in electrolyte excretion are found. Both hyperuricemia and hyperuricosuria may be harmful, therefore it seems logical that the best way to avoid those abnormalities is to maintain fractional uric acid excretion.
Assuntos
Corrida/fisiologia , Ácido Úrico/sangue , Adulto , Eletrólitos/sangue , Humanos , Potássio/sangue , Sódio/sangue , Fatores de TempoRESUMO
Giant cell tumor of bone (GCTB) is a very rare tumor entity, which is little examined owing to the lack of established cell lines and mouse models and the restriction of available primary cell lines. The stromal cells of GCTB have been made responsible for the aggressive growth and metastasis, emphasizing the presence of a cancer stem cell population. To identify and target such tumor-initiating cells, stromal cells were isolated from eight freshly resected GCTB tissues. Tumorigenic properties were examined by colony and spheroid formation, differentiation, migration, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, immunohistochemistry, antibody protein array, Alu in situ hybridization, FACS analysis and xenotransplantation into fertilized chicken eggs and mice. A sub-population of the neoplastic stromal cells formed spheroids and colonies, differentiated to osteoblasts, migrated to wounded regions and expressed the metastasis marker CXC-chemokine receptor type 4, indicating self-renewal, invasion and differentiation potential. Compared with adherent-growing cells, markers for pluripotency, stemness and cancer progression, including the CSC surface marker c-Met, were enhanced in spheroidal cells. This c-Met-enriched sub-population formed xenograft tumors in fertilized chicken eggs and mice. Cabozantinib, an inhibitor of c-Met in phase II trials, eliminated CSC features with a higher therapeutic effect than standard chemotherapy. This study identifies a c-Met(+) tumorigenic sub-population within stromal GCTB cells and suggests the c-Met inhibitor cabozantinib as a new therapeutic option for targeted elimination of unresectable or recurrent GCTB.
Assuntos
Anilidas/uso terapêutico , Carcinogênese/patologia , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/patologia , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-met/metabolismo , Piridinas/uso terapêutico , Anilidas/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Carcinogênese/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Galinhas , Feminino , Fertilização , Tumor de Células Gigantes do Osso/metabolismo , Humanos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Óvulo/metabolismo , Piridinas/farmacologia , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The renal benefits of agents inhibiting the renin-angiotensin-aldosterone system in renal transplant recipients, i.e. preventing the development of chronic graft nephropathy, are supposed but not finally proven. In a double-blind, placebo-controlled, cross-over study, we evaluated the influence of losartan on surrogate markers of tubular injury, urine excretion of transforming growth factor beta-1 (TGF-beta1) and amino-terminal propeptide of type III procollagen (PIIINP) in 16 patients after transplantation. The patients received randomly either losartan (50-100 mg daily) or the beta-blocker carvedilol (12.5-25 mg) for 8 weeks, allowing a placebo washout between treatments. The target office through blood pressure (BP) was below 130/85 mmHg. The BP did not differ in the treatment periods. Losartan significantly decreased N-acetyl-beta-d-glucosaminidase and alfa-1 microglobulin excretion relative to placebo and carvedilol. Urine excretion of TGF-beta1 and PIIINP was significantly lower after losartan. In conclusion, losartan reduces urine excretion of proteins associated with tubular damage and graft fibrosis.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Transplante de Rim/métodos , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Biomarcadores/análise , Carbazóis/administração & dosagem , Carbazóis/farmacologia , Carvedilol , Estudos Cross-Over , Método Duplo-Cego , Feminino , Fibrose/patologia , Fibrose/prevenção & controle , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Losartan/administração & dosagem , Losartan/farmacologia , Masculino , Pessoa de Meia-Idade , Propanolaminas/administração & dosagem , Propanolaminas/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Proteinúria/prevenção & controleRESUMO
Ozonated autohemotherapy is used as a complementary medical approach in the treatment of vascular disorders. One of the greatest problems concerning an application of ozone in medicine is its induction of oxidative stress. The standards of ozonotherapy were elaborated recently making this treatment useful and probably non toxic. The aim of the present study was to investigate the influence of ozonated autohemotherapy on the oxidative stress extent in hemodialyzed patients, known to be particularly exposed to generation and deleterious effects of free radicals. Twelve continuously hemodialyzed subjects with atherosclerotic ischemia of the lower limbs were examined in a prospective, controlled, single blind study. Autohemotherapy with blood exposure to oxygen served as a control. The protein and lipid peroxidation products, the reduced glutathione level in red blood cells and free hemoglobin plasma concentration were measured. The study showed that ozonated autohemotherapy with ozone concentration 50 microg/ml per gram of blood induced a significant decrease in glutathione level after 9 sessions of this procedure. Therapy did not cause either the enhancement of protein and lipid peroxidation, or erythrocytes damage. It seems likely that the antioxidant defense system, part of which is glutathione, neutralizes oxidative properties of ozone in this concentration and protects against oxidative cell damage.