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Space reduction after the premature loss of the second primary molars is one of the important factors affecting the occurrence of malocclusion, often increasing the demand for orthodontic treatment. It has great significance to select and apply appropriate appliances to maintainthe space soon after the premature loss of the second primary molars. The space should be maintained until the adjacent teeth and the successors erupt successfully. This review summarizes the selection and clinical application of the space maintainer for the premature loss of the second primary molars in different periods, to improve dentists′ awareness of the importance of space maintainers and to provide advises for clinical choices.
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Objective To observe the protective effects of Diazoxide (DZ) on myocardial ischemia and reperfusion (I/R) in non-diabetic rats with stressed hyperglycemia and to explore its possible mechanism. Methods The stressed hyperglycemia (SHG) myocardical I/R model was prepared by ligation of the left anterior descending branch of the coronary artery for 30 minutes and reperfusion for 120 minutes on the healthy adult Sprague-Dawley (SD) rats. Blood sugar was required up to 10 mmol/L in the qualified animal model after ischemia for 30 minutes. The 48 successful model rats were randomly divided into 4 groups (12 in each group): I/R group, low, medium and high dose DZ treated group (LIPO group, MIPO group, HIPO group). Sham-operated group (sham group) was only threaded without deligation. I/R group, LIPO group, MIPO group and HIPO group were challenged to 0.1% dimethyl sulfoxide (DMSO), DZ (0.1% DMSO dissolved) 4, 7, 10 mg/kg for 2 mL, respectively after ischemia for 25 minutes. Hemodynamics indicators were continuously monitored. After reperfusion for 120 minutes, blood glucose, serum creatine kinase (CK) concentration and lactate dehydrogenase (LDH) activity were detected, myocardial infarction area was analyzed by triphenyltetrazolium chloride (TTC) staining, myocardial ultrastructure was observed by electron microscope, expressions of phosphorylated protein kinase B (p-Akt) and phosphorylated glycogen synthase kinase-3β (p-GSK-3β) were detected by Western Blot. Results Compared with sham group, I/R group had an elevated blood glucose, decreased heart rate (HR), systolic diastolic dysfunction, increased myocardial enzymes. Obvious necrosis of myocardium, myocardial tissue edema, mitochondria swelling, cristae, disappearing glycogen granules were observed under electron microscope with TTC staining. After reperfusion for 120 minutes, comparing with I/R group, blood glucose of HIPO group was significantly increased (mmol/L: 16.93±3.22 vs. 14.65±3.61, P < 0.05); the maximum rate of left ventricle internal pressure drop (-dp/dt max) of LIPO group was improved (mmHg/s: -1 055±16 vs. -982±10, P < 0.05) and the infarct size was evidently shrunk [(32.45±3.54)% vs. (41.30±3.21)%, P < 0.05]; left ventricular systolic pressure (LVSP) of MIPO group and HIPO group [LVSP (mmHg, 1 mmHg = 0.133 kPa): 60±2, 74±4 vs. 54±4], left ventricular end-diastolic pressure [LVEDP (mmHg): 24.6±1.5, 18.9±1.3 vs. 27.9±1.6], the maximum rate of left ventricle internal pressure were increased [+dp/dt max (mmHg/s): 1 049±37, 1 262±75 vs. 975±17], and -dp/dt max (mmHg/s: -1 068±21, -1 321±63 vs. -982±10) were improved in different degrees (all P < 0.05); CK (kU/L: 10.7±0.5, 11.0±1.3 vs. 12.9±1.0), LDH (kU/L: 6.8±0.2, 7.8±0.1 vs. 8.8±0.1) was evidently decreased (all P < 0.05), infarct size was smaller [(31.24±2.45)%, (30.81±2.68)% vs. (41.3±3.21)%, all P < 0.05], electron microscope showed that the myocardial injury was repaired. After reperfusion for 120 minutes, compared with sham group, expressions of p-Akt and p-GSK-3β in I/R group have obviously reduced (grey value: 0 vs. 0.187±0.018, 0.110±0.045 vs. 0.200±0.081, both P < 0.05). Compared with I/R group, expressions of p-Akt in HIPO group and p-GSK-3β in LIPO group, MIPO group and HIPO group were obviously increased (grey value: 0.101±0.009 vs. 0; 0.180±0.057, 0.270±0.062, 0.280±0.039 vs. 0.110±0.045, all P < 0.05). But there were significant increase in MIPO group and HIPO group. There was no significant difference in HR among different treatment groups. Conclusions I/R with SHG can significantly inhibit the activity of PI3K/Akt-GSK-3β signaling pathways, middle and high dose of DZ has a protective effect on I/R myocardium complicating with SHG, and middle dose will not lead to evident increase of blood glucose; DZ may act on GSK-3β through PI3K/Akt-GSK-3β signaling pathways, phosphorylate it and inhibit its activity, so as to develop the cardioprotective effect.
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Objective To study the effect and possible mechanism of diazoxide on myocardial ischemia/reperfusion (I/R) injury in diabetic rats, and the influence of insulin intervention which aims to maintain blood sugar levels within the normal range on the protective function of cardiomyocytes. Methods 126 health male Sprague-Dawley (SD) rats were intraperitoneally injected with one dose of 60 mg/kg streptozotocin (STZ) to reproduce diabetic model. The diabetic rats were randomly divided into seven groups, with 18 rats in each group. Myocardial I/R model was established by 30 minutes ligation of the left anterior descending branch of the coronary artery, and 120 minutes blood circulation recover. Sham group was only threaded without ligation. Rats in I/R group, diazoxide group (DZ group), and Ottawa vine penicillin (WNT) group were infused intravenously with 2 mL of 0.1% dimethyl sulphoxide (DMSO), DZ (7 mg/kg), and WNT (15 μg/kg), respectively, after 25 minutes of ischemia. Sham group was only injected with 2 mL of 0.1% DMSO. DZ+WNT group was infused with WNT 5 minutes before the injection of DZ. Insulin intervention (RI) group received a continuous insulin infusion to maintain the blood sugar at the level of 4-6 mmol/L. RI+DZ group was infused with DZ after ischemia for 25 minutes based on blood sugar control. Hemodynamic parameters in each group were monitored continuously. The pathological changes of myocardium were observed with hematoxylin and eosin (HE) staining. The expressions of phosphorylated protein kinase B (p-Akt) and phosphorylated glycogen synthase kinase-3β (p-GSK-3β) were determined by Western Blot. Results Compared with sham group, the cardiac functions of the intervention groups were significantly decreased, and severe myocardial injury was observed. Compared with I/R group, the cardiac functions of intervention groups were not obviously improved. However, after insulin intervention by which blood sugar was maintained within normal range, the cardiac function and myocardial injury were further aggravated. Compared with sham group (the expression value of sham group was set as 1), the expressions of p-Akt in other groups including I/R group, DZ group, RI group, and RI+DZ group showed no statistically significant difference (gray value: 1.07±0.09, 1.03±0.07, 1.07±0.07, 1.02±0.08 vs. 1.00, all P > 0.05). However, the expressions of p-Akt were decreased in WNT group and DZ+WNT group as compared with those of sham group and I/R group (gray value: 0.54±0.06, 0.51±0.05 vs. 1.00 and 1.07±0.09, all P 0.05). However, the expression of pGSK-3β was increased in RI group, RI+DZ group as compared with sham group and I/R group (gray value: 1.68±0.08, 1.70±0.05 vs. 1.00 and 0.97±0.08, all P < 0.05), and it was significantly higher in RI+DZ group than that of DZ group (gray value: 1.70±0.05 vs. 1.00±0.11, P < 0.05). Conclusions Diazoxide after myocardial injury could not protect the myocardium from I/R injury in diabetic rats, and did not trigger the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Insulin intervention by which blood sugar was maintaine d within the normal range exacerbates myocardial I/R injury in diabetic rats.