Inhibition of Candida albicans extracellular enzyme activity by selected natural substances and their application in Candida infection.

Extracellular enzymes secreted by Candida albicans are claimed to be virulence factors responsible for penetration of the yeast into host cells. Substances able to inhibit lipolytic and proteinase activities of the fungus might be of therapeutic use in some pathologic conditions caused by C. albicans. In the present work, we have tested the influence of the flavonoid compounds apigenin and kaempferol, the indole alkaloid ibogaine, and the protoberberine alkaloid berberine on the in vitro enzyme activity of C. albicans. The substances showed complex suppressive effects concerning the processes of adherence to epithelial cells, secreted aspartyl proteinase activity, and the rate of cell wall protein glycosylation. Apigenin and kaempferol were administered in systemic C. albicans infection, demonstrating an increased number of survivors by kaempferol. The application of apigenin, kaempferol, ibogaine, and berberine in cutaneous infection suppressed the symptoms and accelerated elimination of the yeast from the site of inoculation.

Etoposide attenuates zymosan-induced shock in mice.

Zymosan-induced generalized inflammation is a convenient model to study the process of acute and chronic inflammatory processes resulting in multiple organ dysfunction syndrome. Macrophages as a source of many pro-inflammatory mediators are the major players in shock and further organ failure. Etoposide is a cytostatic drug known to reduce macrophages and monocytes in blood circulation. In the present study we have investigated whether the ability of etoposide to diminish macrophage number would have an impact on the course of zymosan-induced shock. The drug injected at a dose of 10 mg/kg 1 day before zymosan, significantly reduced the mortality and decreased the organ toxicity in Balb/c mice. Simultaneously, an inhibition of TNF-alpha production by alveolar and peritoneal macrophages was observed. Etoposide administered into mice with severe combined immunodeficiency (SCID) did not change the survival rate and had a little influence on organ toxicity. Our findings suggest that the beneficial action of etoposide might be attributed to the reduction of macrophages and alteration of their functions. Its effect depends on the presence of functional T and B lymphocytes. The results deserve further investigation of etoposide as a perspective therapeutic tool for inhibiting the excessive inflammatory response and to be helpful for revealing mechanisms of shock development.

Modulation of complement activity in vitro and in vivo by Yersinia wild and mutant strains.

The ability of released proteins (Yops) and surface lipopolysaccharides (LPS) from the wild-type strain Yersinia enterocolitica 8081-L2, serotype 0:8 to influence the complement activity was determined. Yops and LPS from wild-type and mutant strains showed different ability to affect the classical pathway (CP) functional complement activity in vitro. The serum CP activity was inhibited during the infection induced with six Y. enterocolitica and three Y. pseudotuberculosis strains in rabbits. The changed complement activity might be of importance for the course of Yersinia infections.

Ibogaine reduces organ colonization in murine systemic and gastrointestinal Candida albicans infections.

In the present study the effect of the indole alkaloid ibogaine on the in vitro lipolytic activity and adherence to epithelial cells of Candida albicans was investigated. The substance was administered intraperitoneally at a dose of 5 mg kg(-1) day(-1) in mice with disseminated and gastrointestinal C. albicans infections. Ibogaine significantly decreased the rate of mortality and the number of C. albicans c.f.u. recovered from the kidney, liver and spleen. Ibogaine interfered with the early stages of both disseminated and gastrointestinal C. albicans infections but did not reduce the number of C. albicans c.f.u. in the organs at the late phase of infections. The development of a specific immune response was not influenced by ibogaine, since the delayed-type hypersensitivity reaction to C. albicans and the production of interferon (IFN)-gamma were similar in control and ibogaine-treated mice. The combined use of amphotericin B plus ibogaine in the treatment of mice with gastrointestinal infection reduced organ colonization more strongly than each substance alone.

Candida albicans cell-wall fraction exacerbates collagen-induced arthritis in mice.

The immune system generates a specific response against most pathogens, while developing tolerance to self-antigens. Commensal micro-organisms can express molecular structures that mimic self-epitopes. During acute infection, such pathogen may activate self-reactive T-cell clones promoting autoimmunity. In the present study, a beta-mercaptoethanol cell-wall fraction (MF) from Candida albicans was injected into the paw of naive ICR and BALB/c mice and into the paw of ICR mice with bovine collagen type II-induced arthritis (CIA). Development of inflammation was monitored for 6 weeks. MF provoked a stable swelling and histopathologic changes in the injected joint, with a predominance of T-helper 1 cytokines in ICR mice. In BALB/c strain, a swelling was observed only in the early period, with no evidence of joint pathology. Injection of the MF fraction exacerbated the disease in ICR mice with CIA, and this was associated with the elevation of interferon-gamma and anti-bovine type II collagen (bCII) immunoglobulin G2a antibodies. These results indicate that component(s) in the MF fraction cross-react with bCII-specific cells.

Effect of fangchinoline in murine models of multiple organ dysfunction syndrome and septic shock.

OBJECTIVE AND DESIGN: To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock. MATERIAL: Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study. TREATMENT: Fangchinoline was administered i.p. at a dose of 1 or 5 mg/kg into the mice. METHODS: MODS was induced by intraperitoneal (i.p.) injection of zymosan at a dose 1.0 or 0.8/g b.w. E. coli-induced septic shock was provoked by i.p. inoculation of 5 x 10(8) bacterial cells into mice. TNF-alpha in serum and supernatants from peritoneal macrophages was detected by the use of L-929 cell cytotoxic assay. Alternative pathway (AP) complement activity was determined by hemolytic assay. RESULTS: Fangchinoline increased the survival rate in lethal MODS and septic shock. The alkaloid prevented the loss of body weight and liver enlargement in MODS and suppressed serum tumor necrosis factor-alpha (TNF-alpha) accumulation in MODS and septic shock. CONCLUSIONS: The result suggest that fangchinoline due mainly to its ability to downregulate TNF-alpha production might have protective effect in murine models of zymosan-induced MODS and E. coli-induced septic shock.

Light-independent effect of the hematoporphyrin derivative Photofrin II on polytene chromosomes from salivary glands of larvae of Glyptotendipes salinus (Chironomidae, Diptera).

Decondensation of the centromeric heterochromatin and regression of the nucleolus, induced by the photosensitizer Photofrin II exclusively in chromosome IV of salivary glands of Glyptotendipes salinus larvae, are described. The process takes place both with and without light excitation of the photosensitizer.