Protective effects of triptolide on TLR4 mediated autoimmune and inflammatory response induced myocardial fibrosis in diabetic cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects. AIM OF THE STUDY: In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200µg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining. RESULTS: In the diabetic group, the expressions of TLR4 and NF-κB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-κB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-α, IL-1ß), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including α-SMA, TGF-ß1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups. CONCLUSIONS: Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-κB/IL-1ß immune pathway, suppression of NF-κB/TNF-α/VCAM-1 inflammatory pathway and down-regulation of TGF-ß1/α-SMA/Vimentin fibrosis pathway.

Efficacy and safety of vildagliptin, Saxagliptin or Sitagliptin as add-on therapy in Chinese patients with type 2 diabetes inadequately controlled with dual combination of traditional oral hypoglycemic agents.

BACKGROUND: The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients. METHODS: In this 24-week, randomized, open-label, parallel clinical trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7.5% to ≤10%) patients with type 2 diabetes, who were treated by dual combination of metformin and another traditional oral hypoglycemic agent (glimepiride, acarbose or pioglitazone). 207 patients had been randomized to add-on 5 mg saxagliptin group or 100 mg sitagliptin once daily group, or 50 mg vildagliptin twice daily group for 24 weeks. HbA1c, fasting and postprandial blood glucose (FBG and P2hBG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated. RESULT: After 24 weeks, HbA1c, FBG, and P2hBG of each group were significantly decreased. (saxagliptin vs vildagliptin vs sitagliptin: HbA1c: -1.2% vs -1.3% vs -1.1%; FBG: -1.8 mmol/l vs -2.4 mmol/l vs -1.5 mmol/l; P2hBG: -3.4 mmol/l vs -3.7 mmol/l vs -3.2 mmol/l). The changes of HbA1c and P2hBG among the three groups had no significance. However, vildagliptin-added group showed the greatest reduction (p < 0.001), while, sitagliptin-added group showed the lowest reduction (p < 0.001) in terms of FPG changes. Proportions of patients achieving HbA1c < 7% at the end were similar in three groups (saxagliptin 59%, vildagliptin 65%, sitagliptin 59%). Mild hypoglycemia was commonly reported among the three groups (saxagliptin 6%, vildagliptin 2%, sitagliptin 3%). No significant between-group difference was shown in other AEs. CONCLUSION: The three gliptins showed almost similar glycemic control and incidence of adverse events. However, for FBG control, saxagliptin demonstrated superiority to sitagliptin, while, inferiority to vildagliptin.

[Transurethral holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia].

OBJECTIVE: To evaluate the efficacy and safety of transurethral holmium laser enucleation of the prostate (HoLEP) for the treatment of benign prostatic hyperplasia (BPH). METHODS: A retrospective review was conducted of transurethral (HoLEP) performed on 68 patients, aged 65.7 (50 - 91) with benign prostatic hyperplasia. The efficacy and complications were all assessed. RESULTS: The mean procedure time was 87 mins (45 - 158 mins). The mean specimen weight was 61 g (31 - 128 g). The procedure allows a precise, bloodless field with no need for transfusion. No TUR syndrome and other major complications were encountered during the operation. The mean catheter time and hospital stay were 2.8 d (1 - 4 d) and 3.6 d (2 - 5 d), respectively. Follow-up of 7.6 months (1 - 13 months) revealed that the urination symptoms were markedly improved in all patients, and that the IPSS decreased from 25.7 +/- 6.9 to 7.7 +/- 4.3 (P < 0.01) and the maximum urine flow rate increased from 8.1 +/- 4.2 ml/s to 18.8 +/- 4.6 ml/s (P < 0.01). Postoperative complications occurred in 3 patients. 2 with transient incontinence were recovered within 3 months postoperatively. The other one with mild posterior urethral stricture was treated effectively with urethral sounding. CONCLUSIONS: Was associated with high effectiveness, safety, short hospital stay and less complications, HoLEP is a new minimally invasive surgical procedure for BPH.