Exogenous kallikrein protects against diabetic nephropathy.

The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.

[Effect of kallikrein and its inhibitor on absorption from the abdominal cavity in peritonitis]. / Vliianie kallikreina i ego ingibitora na vsasyvanie iz briushnoi polosti pri peritonite.

Experiments were carried out in 195 albino rats. It was established that in acute peritonitis the rate of absorption of the colloid dye (tryptan blue) was sharply decreased. Kallikrein somewhat increased the absorption rate, especially at early terms while the inhibitor (kontrikal) was shown to substantially decrease it. The mode of injection (intravenous or intraperitoneal) failed to influence manifestations of the biological effect of the drug. The data obtained show that a disturbed absorption from the abdominal cavity may be corrected in acute peritonitis by injections of kallikrein.

[Effective therapy of chronic arterial circulatory disorders with Nico-Padutin forte (author's transl)]. / Effektive Therapie chronisch-arterieller Durchblutungsstörungen mit Nico-Padutin forte

Over a period of 6 weeks, 90 patients of both sexes (principally male) aged from 38 to 81 years were treated with Nico-Padutin forte (BAY b 7979; 40 units kallikrein + 300 mg inositol nicotinate) for chronic arterial disorders of the lower extremities. Positive therapeutic results were obtained in 82 cases (91.2%) with a dosage of 1 tablet 3 times daily. The effect of the treatment was assessed by the cardinal symptom of intermittent claudication. The walking test was used as the clinical parameter. The significant lowering of the raised blood lipid levels (both in the cholesterol and triglyceride ranges) by treatment with BAY b 7979 is to be considered relevant in the importance of hyperlipidemia as a risk factor in arterial vascular diseases. As long as the controindications (acute myocardial infarction, acute hemorrhages) were given attention, tolerance was outstanding.