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G Dickneite

Publications and source records attributed to G Dickneite.

At least 37 records · Page 2Linked to original sources
PubMed1993

Reduction of mortality with antithrombin III in septicemic rats: a study of Klebsiella pneumoniae induced sepsis.

Experimental gram-negative sepsis was induced in the rat by Klebsiella pneumoniae. Although bacteria are susceptible to the treatment with the antibiotic Tobramycin, DIC could not be prevented. DIC was manifested by a leuko- and thrombocytopenia, decreases in fibrinogen and AT III and an increase of the aPTT. In this model the therapeutic treatment with human AT III was evaluated. To determine the optimal concentration of AT III a prestudy in a LPS induced DIC in the rat was performed. It was shown that a bolus i.v. injection of 500 U/kg improved survival and DIC, and was thus chosen for the Klebsiella sepsis model. The infectious load was adjusted to yield a mortality rate of 90-100% in the untreated Klebsiella group and a reduction to about 40-50% of the mortality rate by Tobramycin. It was found that AT III reduced mortality in the Klebsiella induced sepsis not only when given prophylactically but was effective even when administrated in a late stage of the DIC, i.e. 3 or 5 h post infection.

Animals↗
PubMed1993

Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15-deoxyspergualin.

According to its immunopharmacological profile, 15-deoxyspergualin (15-DOS) has been investigated as to its disease-modifying activity on HgCl2-induced glomerulonephritis (GN) and on tubulointerstitial nephritis (TIN) in Brown-Norway rats. Both models are induced autoimmune disorders in which afflicted animals display high levels of serum autoantibodies directed against the glomerular or tubular basement membrane (GBM or TBM), respectively. The diseases are manifested by high serum creatinine and urea levels with severe proteinuria. In the model of HgCl2-GN, administration of 15-DOS clearly led to a reduction of proteinuria and decreased the amount of rat IgG attached to the GBM. Furthermore, a therapeutic effect could be demonstrated when 15-DOS was given after the appearance of clinical symptoms. Not only urine-protein values but also anti-laminin antibodies returned to normal levels. Also in the experimental TIN-model, 15-DOS, either given during the induction phase, or even late in the onset of the disease, strongly prevented the proteinuria of this autoimmune disease and inhibited the formation of autoantibodies to TBN.

Animals↗
PubMed1993

Influence of C1-inhibitor on inflammation, edema and shock.

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone.

Angioedema↗
PubMed1991

Effect of the new immunostimulator HAB 439 on cell-mediated immunity against intracellular bacteria.

The isoxazoline derivative HAB 439 was tested for its enzyme inhibiting potency and was found to be an inhibitor of aminopeptidase B (IC50 = 22.5 micrograms/ml). In further immunopharmacological experiments its efficacy to stimulate cell-mediated immunity was evaluated. HAB 439 was shown to stimulate DTH-reaction against Salmonella typhimurium and Listeria monocytogenes. HAB 439 protected animals against infection by reducing the bacterial load in livers and spleens and by decreasing the mortality rate. Treatment with the antibiotic ampicillin induced a decreased DTH-reaction in mice which was demonstrated to be due to a reduction of the antigen to be presented to the immune system and not to immune suppression. HAB 439 restored the impaired immune response to S. typhimurium and L. monocytogenes in a dose-dependent way. Restoration of DTH was shown to lead to an improvement of protection in ampicillin-treated mice which were challenged with the intracellular bacteria.

Aminopeptidases↗
PubMed1989

Influence of the immunostimulating substance tiprotimod on Candida albicans infection in relation to activation of macrophages.

In an experimental model of persistent systemic candidiasis the effect of the thiazole compound Tiprotimod was examined. Balb/c mice infected intravenously with Candida albicans developed a fungal colonization of the kidneys with peak levels of about 10(6) colony forming units (cfu)/organ after 3 weeks of infection paralleled by the formation of necrotic alterations of the organs. Infected animals were treated with the immunostimulator Tiprotimod after the fungal colonization of kidney was manifested (3 days post infection). The treatment resulted in a decrease of the infectious load, abscess formation in kidney, as well as a reduction of Candida in the urine. The optimal dose in this model was in the range of 2 mg/kg, higher and lower doses appeared to be less effective, thus indicating a bell-shaped curve of response. By examining the time course of induction of protection by the drug it was noticed that protection does not occur before 10 days after infection. We therefore examined during the course of infection the phagocytic capacity and the production of O2- -radicals (chemiluminescence) of macrophages in Tiprotimod-treated animals. Activation of O2- -radical generation was stimulated rapidly (peak level at day 6) in the drug-treated animals, whereas stimulation of the phagocytic capacity was not observed until two weeks after infection. Activation of macrophage phagocytosis thus paralleled the reduction of the infectious load by Tiprotimod. Combination therapy with the antifungal agent ketoconazole resulted in at least additive decrease of mortality resulting from C. albicans infection.

Adjuvants, Immunologic↗
PubMed1989

Immunomodulation by the new synthetic thiazole derivative tiprotimod. 2nd communication: immunopharmacological activity.

The thiazole derivative [2-(3-carboxy-1-propylthio)-4-methyl-1,3-thiazole] acetic acid (tiprotimod, HBW 538) a new synthetic immunopotentiator of low molecular weight, has been tested in vivo and ex vivo in various experimental models. Its influence on parameters of macrophage functions, on DTH (delayed type hypersensitivity)-reaction and antibodies to sheep erythrocytes (SRBC), Tetanus toxoid and heatkilled E. coli bacteria in mice, and in the popliteal lymph node assay in rats was investigated. When mice were treated with the test substance i.v., i.p., or p.o. in a dose range from 1-100 mg/kg, a time and dose-dependent stimulation of macrophage activity was observed. The drug was able to enhance the DTH-response against SRBC and to stimulate the humoral immune response against Tetanus toxoid and heat-killed E. coli. In the popliteal lymph node assay, a murine graft-vs-host model, a stimulating effect of the substance was observed when it was administered at the same time of the grafts to rats. These results demonstrate that tiprotimod is a potent immunopotentiator for both humoral and cell mediated immune response in experimental animals.

Adjuvants, Immunologic↗
PubMed1989

Immunomodulation by the new synthetic thiazole derivative tiprotimod. 3rd communication: influence on host resistance to microorganisms, tumors and on experimental immune disorders.

To evaluate the influence of [2-(3-carboxy-1-probylthio)-4-methyl-1,3-thiazole]acetic acid (tiprotimod, HBW 538) on the host defense mechanisms, a number of experimental studies in different animal models were performed. The prophylactic treatment of NMRI mice with tiprotimod significantly prolonged the mean survival time of the animals after intravenous infection with Candida albicans 200/175 and increased the resistance to the fungal infection to 180% in comparison to controls. In vitro the drug showed no direct fungistatic or fungicidal activity. In an experimental model of persistent systemic candidiasis Balb/c mice infected intravenously with Candida albicans were treated with the immunomodulator tiprotimod after the fungal colonization of kidney was manifested (3 days post infection). The treatment of the mice after the infection resulted in a reduction of the infectious load and the abscess formation in kidney as well as in a decrease of numbers of yeasts in the urine. In the syngeneic B16 melanoma tumor model tiprotimod significantly prolonged the medium survival time and reduced the number of visuable metastases in the lungs even when applied after resection of the primary tumor graft. Tiprotimod also beneficially influenced the course of the disease in two murine graft-vs-host models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B cell mediated autoimmune disease with fatal outcome. The application of the drug in the induction phase mitigated the development of the diseases and prevented animals from dying.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1989

Immunomodulation by the new synthetic thiazole derivative tiprotimod. 1st communication: synthesis and structure-activity relationships.

A series of carboxyalkylthio-substituted thiazole-carboxylic acids was synthesized and examined for macrophage activation and stimulation of the DTH (delayed type of hypersensitivity)-reaction. The structure-activity relationship in this series of new immunomodulators is discussed. Broadest immunological activity was seen for [2-(3-carboxy-1-propylthio)-4-methyl-1,3-thiazole]acetic acid (tiprotimod, HBW 538) which was selected for further studies.

Animals↗
PubMed1988

15-deoxyspergualin: from cytostasis to immunosuppression.

This article gives a survey on the pharmacological action of the new polyamine compound 15-Deoxyspergualin (15-DS). 15-DS is a derivative of the antitumor antibiotic spergualin which has been isolated by Prof. Umezawa's group in Japan. Besides its antitumor activity 15-DS was shown to possess immunosuppressive properties making the substance suitable for the application in organ transplantation and autoimmune disorders. Due to its immunopharmacological mode of action known hitherto 15-DS clearly differs from other immunosuppressants as e.g. Cyclosporin A.

Animals↗
PubMed1987

Prolongation of graft survival in allogeneic islet transplantation by (-) 15-deoxyspergualin in the rat.

The effect of 15-Deoxyspergualin, a novel drug which has been described to have anti-tumour activity, on allogeneic graft survival (Dark Agouti----Lewis rats) after pancreatic islet transplantation was tested. A marked prolongation of graft survival could be shown using doses of 1.0, 2.5 and 5.0 mg Deoxyspergualin/kg on day 0 until day +9 post transplantation. A maximum of 55.6 days (average) survival time was observed using 2.5 mg/kg Deoxyspergualin compared to 5.2 +/- 0.6 days without immunosuppression. Using the chemiluminescence reaction of recipient monocytes after islet transplantation, a marked suppression of the monocyte system exceeding the treatment period could be observed. Since, in contrast to cyclosporin, B-cell toxicity could not be shown, the new drug seems to be a hopeful step towards successful allogeneic islet transplantation for treatment of diabetes.

Animals↗
PubMed1987

Decrease of mononuclear phagocyte cell functions and prolongation of graft survival in experimental transplantation by (+/-)-15-deoxyspergualin.

The new anti-tumor substance 15-deoxyspergualin was shown to have immunosuppressive properties. Immunosuppression seemed to be predominantly directed against mononuclear phagocytes and to monocyte dependent lymphocyte effector functions. The substance was shown to be effective in the prevention of the rejection of allogeneic transplants. This was shown in a rat tail skin transplantation model (LEW----Fischer). Prolongation of graft survival time was increased about two fold after either i.p. or p.o. administration of 15-deoxyspergualin. Suppression of monocyte activity would thus be a novel mode of action for an immunosuppressive substance being effective in organ transplantation.

Animals↗
PubMed1987

Prolongation of graft survival in allogeneic pancreas and liver transplantation by (-)15-deoxyspergualin.

(-)15-Deoxyspergualin, originally discovered as an antitumoral drug, was shown to have different immunosuppressive effects, when pancreas and orthotopic allogeneic liver transplantations in rats were compared. In the strong rejection model dark agouti----Lewis (RT1a----RT1(1)) we could only show a minor immunosuppressive effect, as far as pancreaticoduodenal and pancreas segment transplantations are concerned: graft survival was prolonged by 9 days in pancreas segment allografts (p less than 0.01) and by 6 days in pancreaticoduodenal allografts (p less than 0.01), when recipients were treated by ten doses of 2.5 mg/kg deoxyspergualin. Pretreatment of recipients with 15-deoxyspergualin was not efficient. On the contrary, in orthotopic liver transplantation done by the cuff technique, a remarkable prolongation of allograft survival could be demonstrated: about half of the animals showed prolongation of allograft survival for more than 80 days, compared with about 11 days in the control group (p less than 0.01). The substance is considered to be valuable for clinical application.

Animals↗