RESUMO
Evidence points to a possible role of tubular sodium reabsorption in worsening renal injury. Proximal tubule (PT) albumin overload is a critical process in the development of tubule-interstitial injury (TII), and consequently in progression of renal disease. We studied the possible correlation between changes in albumin concentration in the lumen of PT with modification of Na+-ATPase activity. An albumin overload animal model and LLC-PK1 cells as a model of PT cells were used. Albumin overload was induced by intraperitoneal injection of BSA in 14-week-old male Wistar rats. An increase in sodium clearance, fractional excretion of sodium, proteinuria, ratio between urinary protein and creatinine, and albuminuria were observed. These observations indicate that there could be a correlation between an increase in albumin in the lumen of PTs and renal sodium excretion. We observed that the activity of both Na+-ATPase and (Na++K+)ATPase decreased in the renal cortex of an albumin overload animal model. Using LLC-PK1 cells as a model of PT cells, inhibition of Na+-ATPase activity was observed with higher albumin concentrations, similar to that observed in the animal model. The inhibition of protein kinase B by higher albumin concentration was found to be a critical step in the inhibition of Na+-ATPase activity. Interestingly, activation of the ERK1/2/mTORC1/S6K pathway was required for protein kinase B inhibition. This mechanism leads to a decrease in protein kinase C activity and, consequently to inhibition of Na+-ATPase activity. Taken together, our results indicate that the molecular mechanism underlying the modulation of PT Na+-ATPase activity by albumin overload involves activation of the ERK1/2/mTORC1/S6K pathway, which leads to inhibition of the mTORC2/PKB/PKC pathway. Our findings contribute to better understanding regarding handing of renal Na+ induced by albumin overload in the lumen of PTs and, consequently, in the progression of renal disease.
Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Túbulos Renais Proximais/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Bovinos , Linhagem Celular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Ratos Wistar , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , SuínosRESUMO
Purpose This retrospective study aims to analyze the clinical and functional results obtained over a seven-year period of performing reverse total shoulder arthroplasty (RTSA) and the subsequent postoperative rehabilitation protocol. Methods We analyzed data from 80 patients who were evaluated at a preoperative, as well as monthly postoperative outpatient consultation, until the discharge from the rehabilitation program, using Constant Score (CS). Results A comparison of preoperative and postoperative (after rehabilitation protocol) results revealed an improved functional score of absolute CS (20.8 increase), normal relative CS (29.1 increase), and individual relative CS (31.7 increase) with statistical significance (p<0.05). From the analysis of CS subscores, there was a positive evolution of the pain subscore, as well as flexion, abduction, and external rotation combined with abduction range of motion (ROM). Contrarily, there was a negative evolution of the combined internal rotation, extension, and adduction ROM, as well as deltoid muscle strength. No statistically significant correlations were found between age and postoperative CS, as well as between the time interval from surgery to the beginning of outpatient rehabilitation and CS evolution. Conclusion Our study demonstrates that RTSA is an effective therapeutic option that, if combined with a well-structured rehabilitation program, can improve pain, mobility, and upper limb functionality.