Microvascular anastomotic thrombosis in experimental diabetes mellitus.

An experimental model was developed to investigate the effects of glycemic control and pentoxifylline administration on microvascular anastomotic patency rates in streptozotocin-induced diabetic rats. Diabetes was confirmed by blood glucose levels of more than 300 mg/dl prior to administering insulin and/or pentoxifylline. Microvascular anastomoses of the femoral artery and vein were performed 4 weeks after induction of diabetes. Subsequently, the comparative rates of anastomotic thrombosis in diabetic and nondiabetic groups with or without insulin or pentoxifylline administration were assessed by direct visualization of the anastomotic sites after 4 days. The results suggest that hyperglycemia impairs the post-operative patency of microvascular venous anastomoses. The diabetic animals maintained under insulin regimens that tightly controlled their serum glucose levels (100 to 200 mg/dl) experienced patency rates similar to those of nondiabetic controls (p < 0.05). Pentoxifylline improved microvenous patency at all levels of hyperglycemia studied, suggesting a possible hemorrheologic mechanism for microvascular venous anastomotic thrombus formation in diabetic animals.

Clinical study of the effect of the preparation DEODAN on leukopenia, induced by cytostatics.

The aim of the study is to establish the effect of the preparation DEODAN on leukopenia induced by chemotherapeutics in oncological patients. DEODAN is an oral preparation, obtained from lyzozyme lysates of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B-51" ATCC 21815, called shortly LB51. In the study there are included two groups of patients--from National Oncological Centre, Sofia, the other from Clinic of Medicine, Bertha Academic Hospital, Clinics of Duisburg, Duisburg. All the patients, (78) have undergone combined chemotherapy. In all patients, leukopenia has been established in moderate and medium levels. The scheme of the application of DEODAN has been 3 g, three times a day before meals, from the first day of establishing the disturbances of the haemopoesis. The treatment lasted until the restoration of the haematological values. Only DEODAN was applied. The results obtained show that the recovery of the WBC count (values above 3000) took place in all of the patients between days 3 and 5. None of the patients displayed any infectious or febrile complications, as a result of the applied chemotherapy and the treatment with the preparation. DEODAN also improves the general condition of the patients.

Stimulating effect of DEODAN (an oral preparation from Lactobacillus bulgaricus "LB51") on monocytes/macrophages and host resistance to experimental infections.

DEODAN is a lysozyme lysate from Lactobacillus bulgaricus for oral administration which has shown antitumor activity in mice and humans. The effects of this preparation on some functions of monocytes/macrophages and on host resistance to experimental infections were examined. The oral administration to mice of DEODAN-150 mg/kg daily (the recommended dose in humans) caused an increase of the spreading ability and phagocytic activity of peritoneal macrophages, which showed morphological signs of cell activation. The level of Interleukin-1 (IL-1) secreted in the culture supernatant of peritoneal macrophages of DEODAN-treated mice was found to be slightly increased only when the mice were treated with 150 mg/kg DEODAN for 10 days. However, the in vitro incubation of human blood monocytes with DEODAN resulted in induction of membrane-bound and cytoplasmic IL-1 and Tumor Necrosis Factor (TNF)-alpha. The oral treatment of mice with DEODAN also caused a decrease in mortality after experimental infections with Klebsiella pneumoniae and Listeria monocytogenes. These results indicate that DEODAN activates the phagocytic and secretory functions of mononuclear cells and increases host resistance to bacterial infections.

Endogenous production of tumor necrosis factor in normal mice orally treated with Deodan--a preparation from Lactobacillus bulgaricus "LB51".

The ability of orally administered Deodan, a product from the cell wall of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B51" ATCC #21815, shortly called "LB51", to induce endogenous tumor necrosis factor-alpha (TNF alpha) production in normal mice was evaluated. The priming and triggering activities of the preparation were investigated in combination with lipopolysaccharide (LPS) and live BCG vaccine. Deodan was applied at a dose of 150 mg/kg and various treatment schedules were employed. The serum levels of TNF alpha in treated mice were quantified by ELISA. Oral administration of Deodan at a dose of 150 mg/kg for 1, 3, 10 or 20 consecutive days only enhanced serum TNF alpha levels in treated mice. Maximal TNF alpha levels were reached 6 h after the last application of Deodan. Deodan was effective in priming TNF alpha in mice triggered intravenously (i.v.) with LPS. Deodan triggered the production of TNF alpha in BCG-primed mice. The preparation, however, was not an effective trigger of mice primed intradermally (i.d.) with 1 microgram/mouse LPS. These findings suggest that Deodan is both a primer and trigger of endogenous TNF alpha. The advantages of treatment of neoplastic disease with agents which induce endogenous TNF alpha is discussed.

Determination of cytokine release after in vivo and in vitro administration of Deodan (a preparation from Lactobacillus bulgaricus "LB51") by the rabbit pyrogen test.

We investigated the in vivo and in vitro cytokine inducing effects of Deodan, an oral preparation from Lactobacillus bulgaricus "LB-51", using the rabbit pyrogen test. In the first experimental approach we administered Deodan, or its chromatographically purified fraction, via the i.m. or i.v. routes. Low doses of Deodan i.m. caused the formation of a single temperature peak, whereas large doses produced a biphasic temperature curve. Intravenous injection of Deodan produced a monophasic fever in all tested doses. Chromatographically purified Deodan injected i.v. to rabbits caused a febrile response with a dose-dependent pattern, strikingly similar to that of lipopolysaccharide. LAL-testing of Deodan, however, showed that the preparation does not contain endotoxin. In in vivo neutralization studies we demonstrated that IL-1, TNF alpha, and IL-6 mediate the rabbit febrile response to Deodan. Interestingly, the effects of Deodan on the production of TNF alpha and IL-6 were more pronounced than its IL-1 inducing activity. In the second approach, we injected supernatants from mononuclear cells incubated with nonpyrogenic doses of Deodan, intravenously to rabbits ("monocyte type" of pyrogen test). Rapid-onset monophasic fevers were observed, typical for the rabbit pyrogen reaction to i.v. administration of exogenous IL-1 and TNF. Finally, we demonstrated the presence of pyrogenic cytokines in the supernatants from macrophages of Deodan-treated mice. Together, these results indicate that Deodan induces the production of cytokines with endogenous pyrogenic activity.