Exogenous hydrogen sulfide protects human umbilical vein endothelial cells against high glucose­induced injury by inhibiting the necroptosis pathway.

Hyperglycemia is a key factor in the development of diabetic complications, including the processes of atherosclerosis. Receptor­interacting protein 3 (RIP3), a mediator of necroptosis, is implicated in atherosclerosis development. Additionally, hydrogen sulfide (H2S) protects the vascular endothelium against hyperglycemia­induced injury and attenuates atherosclerosis. On the basis of these findings, the present study aimed to confirm the hypothesis that necroptosis mediates high glucose (HG)­induced injury in human umbilical vein endothelial cells (HUVECs), and that the inhibition of necroptosis contributes to the protective effect of exogenous H2S against this injury. The results revealed that exposure of HUVECs to 40 mM HG markedly enhanced the expression level of RIP3, along with multiple injuries, including a decrease in cell viability, an increase in the number of apoptotic cells, an increase in the expression level of cleaved caspase­3, generation of reactive oxygen species (ROS), as well as dissipation of the mitochondrial membrane potential (MMP). Treatment of the cells with sodium hydrogen sulfide (NaHS; a donor of H2S) prior to exposure to HG significantly attenuated the increased RIP3 expression and the aforementioned injuries by HG. Notably, treatment of cells with necrostatin­1 (Nec­1), an inhibitor of necroptosis, prior to exposure to HG ameliorated the HG­induced injuries, leading to a decrease in ROS generation and a loss of MMP. However, pre­treatment of the cells with Nec­1 enhanced the HG­induced increase in the expression levels of cleaved caspases­3 and ­9. By contrast, pre­treatment with Z­VAD­FMK, a pan ­caspase inhibitor, promoted the increased expression of RIP3 by HG. Taken together, the findings of the present study have demonstrated, to the best of our knowledge for the first time, that exogenous H2S protects HUVECs against HG­induced injury through inhibiting necroptosis. The present study has also provided novel evidence that there is a negative interaction between necroptosis and apoptosis in the HG­treated HUVECs.

[Therapeutic effect of vildagliptin and insulin aspart injection in elderly patients with type 2 diabetes].

OBJECTIVE: To observe the therapeutic effect and safety of vildagliptin combined with insulin aspart injection in elderly patients with type 2 diabetes. METHODS: Sixty-six elderly patients with type 2 diabetes who had poor blood glucose control with insulin aspart injection were divided into two groups to have additional Vildagliptin (50 mg, twice daily, n=36, observation group) or Acarbose (50 mg, three times a day, n=30, control group). Blood glucose (including FBG and 2hPG), HbA1C, fasting c-peptide, postprandial c-peptide, BMI and GFR were observed after 12 weeks. RESULTS: In the observation group, FBG, 2hPG and HbA1C decreased significantly (P<0.05), fasting and postprandial c-peptide increased (P<0.05), and BMI and GFR showed no obvious changes (P>0.05). In the control group, 2hPG and HbA1C were significant lowered (P<0.05) but FBG, fasting and postprandial c-peptide, BMI or GFR showed no changes (P>0.05). Compared with those in the control group, FBG in the observation group showed a significant reduction (P<0.05), but no significant differences were found in 2hPG, HbA1C, BMI or GFR (P>0.05). No hypoglycemia occurred in the two groups during the treatment. CONCLUSION: Vildagliptin with insulin aapart injection has equivalent effect with Acarbose combined with insulin aspart injection in decreasing 2hPG and HbA1C without increasing the body weight or the risk to hypoglycemia or causing lowered GFR. Vildagliptin has better effect in decreasing FBG and improving the function of the islet cells.

[Therapeutic effect of zoledronic acid on primary osteoporosis in elderly patients].

OBJECTIVE: To observe the effect of zoledronic acid on bone mineral density (BMD) and bone metabolic markers in elderly patients with primary osteoporosis. METHODS: Forty-eight elderly patients with osteoporosis were randomly assigned to zoledronic acid group (n=23) to receive treatment with 5 mg zoledronic acid once a year and the control group (n=25). In both groups, the patients were given Vitamin D3 and caltrate on a daily basis for a year. The bone mineral density (BMD) and bone metabolic markers were observed after the treatment. RESULTS: Compared with the control group, zoledronic acid group had significantly higher L1-4, neck, Inter and Ward's BMD (P<0.05) with reduced B-NTX (P<0.05). The N-MID and CT showed no significant differences between the two groups (P<0.05). CONCLUSION: Zoledronic acid administration once a year can increase BMD and lower the serum bone turnover metabolism, and can be used in the treatment of primary osteoporosis in elderly patients.

[Factors associated with acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis].

OBJECTIVE: To survey the incidence of acute febrile reaction in elderly patients receiving intravenous zoledronic acid for osteoporosis and identify the related factors. METHODS: Thirty-eight elderly patients with osteoporosis were hospitalized and treated with intravenous infusion of 5 mg zoledronic acid in 2010. The incidence of acute fever reaction was observed in these patients , and the time of fever onset, duration, average maximum temperature, and antipyretic drug used were recorded. The patients with and without acute febrile reaction were compared for age, duration of osteoporosis, sex ratio, use of parathyroid hormone before zoledronic acid treatment, ß-fragment of collagen breakdown, calcitonin, osteocalcin, serum calcium, and use of anti-osteoporosis drugs before the treatment. RESULTS: Acute fever reaction occurred in 12 (31.6%) of the patients. Two of the patients had fever on the day of zoledronic acid treatment, and the other patients developed fever after the first day of treatment, with a mean duration of 1 day and a maximum temperature of (38.5∓0.84) degrees celsius;. The fever was treated with a mean of 3.55∓1.21 pseudoephedrine tablets. The patients with fever showed significantly higher parathyroid hormone levels before treatment than those without fever (P<0.05); osteocalcin, calcitonin, ß-fragment of collagen breakdown, or serum calcium showed no significant difference between the two groups. CONCLUSION: Acute febrile reaction, often moderate and transient, is common in elderly patients receiving intravenous zoledronic acid for osteoporosis, and its occurrence is possibly associated with parathyroid hormone levels before the treatment.