RESUMEN
Background: Hyperglycemia usually impairs wound healing by dysregulating the inflammatory response and angiogenesis. This study aimed to examine the synergistic effect of dapagliflozin and Zamzam water (ZW) on the healing of diabetic wounds and to explore their anti-inflammatory and proangiogenic effects.Materials and methods: A full-thickness excisional wound was made on the backs of all groups after two weeks of diabetes induction. Forty rats were divided into five groups, with eight rats per group; Group 1: Control non-diabetic rats; Group II: Untreated diabetic rats; Group III: Diabetic rats drinking ZW; Group IV: Diabetic rats receiving an oral dose of 1 mg/kg dapagliflozin; and Group V: Received both dapagliflozin and ZW. The healing of diabetic wounds was assessed by measuring wound closure, oxidative stress markers, immunohistochemical staining of NF-ßB, VEGF, CD34, CD45, Ki-67, and eNOS, gene expression of MMP-9, TGF-ß1, EGF-b1, FGF, and Col1A1, protein levels of TNFα, IL-1ß, IL6, Ang II, and HIF-1α by ELISA assay, and histological examination with H & E and Masson's trichrome. Combined treatment with dapagliflozin and ZW significantly (p < 0.05) enhanced the wound closure and antioxidant enzyme level, with apparent histological improvement, and shortened the inflammatory stage of the diabetic wound by decreasing the level of inflammatory markers NF-κB, TNF-α, IL-1ß, IL6, and CD45. Therefore, it improved angiogenesis markers VEGF, CD34, eNOS, EGF-ß1, FGF, Ang II, and HIF-1α, increasing Ki-67 cellular proliferation. Moreover, it enhanced the remodeling stage by increasing MMP-2, TGF-ß1, and Col1A1 levels compared to diabetic rats.
Asunto(s)
Diabetes Mellitus Experimental , Factor de Crecimiento Transformador beta1 , Ratas , Animales , Factor de Crecimiento Transformador beta1/farmacología , Factor de Crecimiento Transformador beta1/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Factor de Crecimiento Epidérmico/uso terapéutico , Interleucina-6 , Antígeno Ki-67 , Cicatrización de Heridas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Isolated involvement of the medial compartment of the knee in degenerative disease is encountered in about 25% of patients with gonarthrosis. We aim to show that in a well-selected group of such patients, medial unicompartmental knee arthroplasty (UKA) is a good option. OBJECTIVES: Review the functional outcomes of patients undergoing UKA and determine the long-term survivorship of the implants and complications of the procedure. DESIGN: Analytical retrospective chart review. SETTING: Academic tertiary care medical center and tertiary care private hospital in the western region of Saudi Arabia. PATIENTS AND METHODS: We selected patients who underwent medial UKAs by the same surgeon between December 1988 and December 2009. The life table approach and the Kaplan-Meier statistical method were used to estimate the survival rate (5-30 years) with revision as the endpoint. Functional outcome scores were determined according to the Knee Society Clinical Rating System. MAIN OUTCOME MEASURES: Change in performance scores for pain, walking, and range of movement. Survivorship of the implants with removal of the implant as the endpoint; post-operative complications. SAMPLE SIZE: 218 implants on 142 patients. RESULTS: The survival rate of UKA was 94.7% at 10 years (95% CI 0.906-0.970), 80.9% at 20 years (95%CI 0.724-0.871), and 77.8% at 30 years (95%CI 0.669-0.855). The average grand total functional score increased from 61 (maximum 200) at 0 months to above 150 at ≥6 months. CONCLUSION: UKA is a good option for isolated medial compartment gonarthrosis with excellent functional outcome and good survivorship in selected patients. LIMITATION: Single center experience, retrospective. We lost 6.0% of patients during follow-up. Comparison with other treatment modalities is based on literature review and not on our own data. CONFLICT OF INTEREST: None.