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Diabetic nephropathy is a major complication of diabetes mellitus (DM). Recent studies suggest that immunological mechanisms have a key role in the pathogenesis of DM, therefore these mechanisms may be important targets for diabetes therapy. The present study evaluated the effects of anti-α 1 -adrenergic receptor antibody (α 1 -R Ab) mediation and doxazosin treatment in a rat model of DM. It was observed that levels of 24-h urinary protein, serum creatinine and transforming growth factor-β 1 in DM were significantly increased after α 1 -R Ab mediation (all P<0.05). In addition, electron microscopy identified severe damage in the renal tissue microstructures of DM rats following α 1 -R Ab mediation, while only mild abnormalities were observed in that of healthy rats mediated with α 1 -R Ab and of untreated DM rats. No marked abnormalities were observed in the renal tissue of healthy blank controls. Furthermore, in DM rats treated with α 1 -R Ab mediation + doxazosin intervention, the expression of TGF-β 1 significantly decreased, and renal functions and renal matrix remodeling were significantly improved, relative to untreated DM controls (P<0.01). These results suggest that α 1 -R Ab may be involved in renal matrix remodeling during DM, and that kidney protection during DM may be achieved through treatment with corresponding receptor antagonists.

To investigate the effect of prazosin on patients with diabetic nephropathy (DN), α1-adrenergic receptor (α1-R) autoantibodies and refractory hypertension, a total of 126 patients with DN and hypertension were recruited. The patients were divided into a refractory hypertension group, (n=76) and a non-refractory hypertension group (n=50). The epitope of the second extracellular loop of the α1-R (192-218) was synthesized and an enzyme-linked immunosorbent assay (ELISA) was performed to detect serum autoantibodies. In the group with DN-associated refractory hypertension, the positive rate of autoantibodies against the α1-R was 80.3% (n=61). The 61 patients who were positive for α1-R autoantibodies were randomly divided into a treatment group (n=31) and a control group (n=30). The patients were given drugs at the same dosage and administration, with the exception of prazosin, which was provided only to the patients in the treatment group [1 mg, three times a day (tid)] for a duration of six weeks. Subsequently, prazosin was added (1 mg, tid) to the therapeutic schedule of the patients in the control group and the α1-R autoantibody-negative group for another six weeks. The analysis was carried out on an intention-to-treat basis. The prazosin treatment resulted in significant improvements in hypertension in the treatment group (P<0.05), while there was no marked improvement in the control group. The total effective rate of hypertension improvement was 90.3% in the treatment group, which was higher compared with that of the control group (33.3%). In conclusion, α1-R autoantibodies may play an important role in the pathogenesis of DN with refractory hypertension. Prazosin was demonstrated to be effective and safe in the treatment of DN with refractory hypertension.

The title compound, CH(5)N(6) (+)·Cl(-), crystallized with two indepedent 1,5-diamino-tetra-zolium cations and two independent chloride anions in the asymmetric unit. In the crystal, there are a number of N-H⋯Cl hydrogen-bonding inter-actions, which generate a three-dimensional network.

Objective: To investigate the alteration of plasma osteoprotegerin (OPG) concentration before and after levothyroxine (L-T4) replacement therapy and its association with endothelium-dependent arterial dilation in patients with overt hypothyroidism (oHT) and subclinical hypothyroidism (sHT)., Methods: L-T4 therapy was given to 20 oHT patients and 20 sHT patients, all female, till the free serum triiodothyronine (FT3), free thyroxin (FT4), and thyroid-stimulating hormone (TSH) were near or within the respective normal ranges. Twenty healthy women were used as controls. Sandwich ELISA was used to measure the plasma OPG concentration before and after treatment., Results: The plasma OPG levels before treatment of the oHT and sHT patients were 3.13 ng/L +/- 0.27 ng/L and 2.95 ng/L +/- 0.24 ng/L respectively, both significantly higher than that of the controls (2.42 ng/L +/- 0.26 ng/L, both P = 0.000). Multivariate analysis showed that OPG was significantly associated with TSH (r = 0.306, P < 0.05) and endothelium-dependent arterial dilation (r = -0.675, P < 0.01) at baseline. After the normalization of thyroid function the OPG levels of the oHT and sHT patients decreased markedly to 2.53 ng/L +/- 0.28 ng/L and 2.54 ng/L +/- 0.21 ng/L respectively (both P = 0.000), very close to that in the controls. The absolute changes of OPG was significantly positively correlated with the changes of TSH (P < 0.05), negatively correlated with the changes of endothelium-dependent arterial dilation (P < 0.01), and not significantly correlated with other parameters in the hypothyroid patients during the course of treatment., Conclusion: OPG may act as an important regulatory molecule in the vasculature and, particularly, may be involved in the development of vascular dysfunction in hypothyroid patients.

Objective: To investigate the relationship between the plasma osteoprotegerin (OPG) level and endothelium-dependent arterial dilation in type 1 diabetic patients., Methods: Sandwich ELISA method was used to detect the plasma OPG levels of 22 newly diagnosed type 1 diabetic patients before and 6 months after treatment and of 28 healthy subjects. All patients were then given insulin therapy for 6 months. High resolution ultrasound was used to measure the brachial artery diameter at rest, after reactive hyperemia and after sublingual administration of glyceryltrinitrate (GTN)., Results: The plasma OPG level of the patients before treatment was 3.09 ng/L +/- 0.70 ng/L, significantly higher than that of the healthy controls (2.07 ng/L +/- 0.75 ng/L, P < 0.001). After 6 months treatment, the OPG level of the patients decreased to 2.58 ng/L +/- 0.59 ng/L, significantly lower than that before treatment (P < 0.001). The flow-mediated endothelium-dependent arterial dilation in the patients before treatment was 3.35% +/- 0.67%, significantly lower than that of the healthy controls (5.17% +/- 0.83%, P < 0.001), and was increased to 4.27% +/- 0.63% after 6 months treatment, significantly higher than that before (P < 0.001). Multivariate analysis showed that OPG level was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and ultra-sensitive C-reactive protein (CRP) at baseline (all P < 0.01). The absolute change in OPG level was significantly correlation with the changes in endothelium-dependent arterial dilation, FBG, HbA1c, and CRP in the diabetic patients during the course of treatment (all P < 0.01)., Conclusion: Plasma OPG level is elevated in newly diagnosed diabetic patients, and the plasma OPG level is significantly associated with endothelial function.