RESUMO
Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.
RESUMO
BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired myocardial infarction in children. Coronary artery involvement is the most serious feature of this vasculitis syndrome. Timely diagnosis of coronary artery involvement is of utmost importance since it can prevent long-term morbidity and mortality. The current methods for the diagnosis of coronary artery dilation in KD are inconsistent and are also not capable of detecting all the abnormal coronary arteries or the so-called occult dilations present. OBJECTIVES: The aim of this study was to determine the sensitivity and specificity of three novel allometric indices for the diagnosis of left main coronary artery (LMCA) involvement in KD. METHODS: We performed a prospective case-control study in 69 children (38 with KD and 31 healthy children). All the followed up patients underwent two complete echocardiographic examinations at the time of admission and 4 - 6 weeks later. We measured the size of the LMCA, coronary sinus (CS) and aorta (A) and calculated the LMCA/CS, LMCA/A and LMCA/CS/A ratios. We also calculated the cut-off scores for each index using receiver operating characteristic curves both in the acute phase and 4 - 6 weeks later. RESULTS: In the acute phase, the cut-off scores for the LMCA/A ratio was > 0.23; LMCA/CS, > 0.44; and LMCA/CS/A, > 0.03. This implied 60% sensitivity and 80% specificity for the detection of abnormal LMCA in KD. Four to six weeks after the acute phase, the LMCA/A cut-off score was > 0.23; LMCA/CS, > 0.73; and LMCA/CS/A, > 0.73. This implied 100% sensitivity and 100% specificity for the detection of abnormal LMCA. There was a significant decrease in the size of the CS in comparison with the control group (1.92 ± 0.363 mm; P = 0.007 and 0.023). CONCLUSIONS: The LMCA/A, LMCA/CS and LMCA/CS/A ratios seem to provide simple and patient-specific indices for the detection of abnormal LMCA in KD, both in the acute and subacute phase. Further, a decrease in the size of the CS may imply a decrease in coronary artery flow in the acute and subacute phases of KD.
