Biomedical subjects

N Ivanovska

Publications and source records attributed to N Ivanovska.

At least 19 recordsLinked to original sources

PubMed2005

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.

Adhesiveness↗

PubMed2005

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.

Animals↗

PubMed2003

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.

Alkaline Phosphatase↗

PubMed2001

Protective effect of Nocardia opaca lysozyme digest in experimental murine Candida albicans infections.

Candida albicans, as an opportunistic pathogen, causes therapeutic problems in immunocompetent individuals and frequently it initiates severe infections in immunocompromised hosts. The application of a lysozyme digest preparation from the cell walls of Nocardia opaca (Nocardia lysozyme digest; NLD), recently classified as Rhodococcus opacus, has a protective effect in intravenous (i.v.) C. albicans infections in inbred ICR mice which have normal complement production. It also significantly reduces i.v. and intraperitoneal (i.p.) infections in DBA/2 mice which are deficient in C5 complement component. A significant decrease in C. albicans recovery from kidneys was found in NLD-treated DBA/2 animals. The preparation enhanced delayed type hypersensitivity to the yeast cells in both mouse strains. C. albicans-induced popliteal lymph node reactions were increased in ICR mice. In addition, mouse splenocytes that had been inhibited in their proliferative response to phytohaemagglutinin had this response restored after exposure to the preparation. NLD decreased the sensitivity of both mouse strains to a second challenge with the pathogen. The preparation restored the impaired host response to C. albicans infection in ICR mice treated with cobra venom and cyclophosphamide.

Animals↗

PubMed2000

Immunosuppression and recovery of drug-impaired host resistance against Candida albicans infection by oxoglaucine.

The immunosuppressive action of aporphinoid alkaloid oxoglaucine was studied in experimental Candida albicans (C. albicans) infection in mice. The alkaloid augmented host resistance to pathogen applied to mice (6-8 weeks of age) at a low dose of 2 mg kg(-1) in 3 days and impaired it at a high dose of 10 mg kg(-1). The suppressive activity observed under the latter schedule correlated with the inhibited proliferative response of splenic cells to mitogens and with decreased popliteal lymph node (PLN) reaction to C. albicans. Treatment of mice with oxoglaucine (at the age of 5 days) at a dose of 5 mg kg(-1) in 3 consecutive days increased the susceptibility to Candida inoculation at the age of 6 weeks. Delayed type hypersensitivity (DTH) response to C. albicans was enhanced after pretreatment of adult mice and was suppressed after administration to newborn mice. Long-time treatment (10 days) with oxoglaucine, cyclophoshamide or prednisolone at a dose of 10 mg kg(-1) increased the rate of mortality of Candida-infected mice. Combined pretreatment of mice with cyclophosphamide or prednisolone (5 days at a dose of 5 mg kg(-1)) followed by oxoglaucine (5 days at a dose of 5 mg kg(-1)), prolonged the survival of infected mice.

Animals↗

PubMed2000

Treatment with oxoglaucine can enhance host resistance to Candida albicans infection of mice with adjuvant arthritis.

The alkaloid oxoglaucine reduced CD4+ cell clones in adult mice and decreased CD4+, CD8+ and Ig+ levels in newborn mice. It prevented the increase of CD8+ and Ig+ clones induced by Candida albicans (C. albicans) in adult mice. TNF-alpha serum accumulation was inhibited by oxoglaucine in C. albicans infection and adjuvant arthritis. Treatment with oxoglaucine of arthritic mice, followed by inoculation with C. albicans enhanced the host resistance against the pathogen.

Adjuvants, Immunologic↗

PubMed2000

Phytochemical study and cytotoxic activity of alkaloids from Uvaria chamae P. Beauv.

Phytochemical study of leaves of Uvaria chamae resulted in the isolation for the first time for the genus Uvaria of benzylisoquinoline alkaloids (+)-armepavine (1) and racem. O,O-dimethylcoclaurine (2). The aporphines nornantenine (3), nantenine (4) and corydine (7) are new for the species. The alkaloids were found to express cytotoxic activity against L 929 transformed cells. The highest activity was shown by 1, 3, and 5. At a concentration corresponding to their IC50 against L929 cells, they were nontoxic against mouse thymocytes.

Alkaloids↗

PubMed1999

Complement modulatory activity of bisbenzylisoquinoline alkaloids isolated from Isopyrum thalictroides--I. Influence on classical pathway in human serum.

Eleven bisbenzylisoquinoline alkaloids (BBI) were isolated from the plant Isopyrum thalictroides (L.). Treatment of normal human serum (NHS) with BBI resulted in a diminution of the haemolytic activity of the classical pathway (CP). The mode of action of the main alkaloids isopyruthaline (It1), fangchinoline (It2) and isotalictrine (It3) on CP activation was investigated in vitro. The inhibition was time- and temperature-related and for Itl and It3 depended on the concentration of Ca2+ and Mg2+ ions. It was established that the substances reduced C1 haemolytic activity. It2 and It3 enhanced the complement consumption caused by heat aggregated human IgG (HAGG). The BBI prevented the formation of C3 convertase of the classical pathway. The loss of haemolytic activity was partially restored by the addition of C142 reagent (zymosan-treated guinea pig serum) to alkaloids-treated NHS. The addition of the late components C3-9 (EDTA-treated rat sera) recovered to some extent the haemolytic activity of It1-treated NHS, but not of It2- and It3-treated NHS.

Alkaloids↗

PubMed1999

Complement modulatory activity of bisbenzylisoquinoline alkaloids isolated from Isopyrum thalictroides--II. Influence on C3-9 reactions in vitro and antiinflammatory effect in vivo.

The main alkaloids isopyruthaline (It1), fangchinoline (It2) and isothalictrine (It3), isolated from Isopyrum thalictroides (L.) were investigated in complement-mediated reactions. The alkaloids influenced the alternative pathway (AP) activity in normal human serum (NHS). They enhanced the inhibitory action of complement activators--carrageenan (Car), zymosan (Zy), hydrogen peroxide (HP) and high temperature via classical pathway (CP) in NHS. Substances strongly potentiated the action of zymosan and cobra venom (CV) in guinea pig serum (GPS). It was established that they could provoke C3 conversion in NHS and mouse sera (MS). The antiinflammatory properties of the alkaloids were evaluated in mouse paw oedema induced by CV, Zy and histamine (His). Isopyruthaline and isothalictrine suppressed paw swelling in CV- and Zy-oedema. They were applied in Zy-induced multiple organ dysfunction syndrome (MODS) in mice. The alkaloids inhibited the increase of the serum complement activity provoked by the injection of zymosan. Itl lowered the mortality rate of mice with MODS if its application proceeded Zy. An increase of the number of mice without tissue injury was established after treatment with It1 and It3.

Alkaloids↗

PubMed1999

Influence of berberine on T-cell mediated immunity.

The protoberberine alkaloid berberine is isolated as a main alkaloid from the roots and bark of Berberis vulgaris. Berberine strongly inhibited in vitro the proliferative response of mouse spleen cells to T-dependent mitogens concanavalin A (Con A) and phytochemagglutinin (PHA). Spleen cells obtained from berberine-treated mice (10 mg/kg/3 days) expressed enhanced proliferative response to both mitogens. Berberine was applied to mice at different intervals before or after the induction of adjuvant arthritis (AIA) and Candida albicans (C. albicans) infection. The application of the alkaloid to new born mice (5 days after birth at a dose of 5 mg/kg/3 days) did not change the course of AIA and C. albicans infection. Its application at three 10 day intervals (5 mg/kg), starting from the 5 day after birth increased the joint inflammation in AIA. The host resistance to C. albicans infection was not affected, while the delayed type hypersensitivity (DTH)-reaction against the pathogen was enhanced. The alkaloid inhibited the development of AIA when applied after its onset (10 mg/kg from day +3 to +12 day). Berberine treatment during the ongoing infection did not influence its outcome (from +2 to +10 day).

Aging↗

PubMed1998

Immunomodulatory properties of Nocardia lysozyme digest (NLD) in complement normal and C5-deficient mice.

The constantly increasing number of substances with adjuvant activity outpaces the elucidation of their mode of action. This problem is of great importance as the immunomodulatory action of an adjuvant is time- and route-dependent, which implies that administration at a different moment or site may result in a reduced immune response. In the present work the possibility to achieve dual effect (stimulatory or inhibitory) is regarded in the light of the complement system. The object of the study is a preparation obtained by lysozyme digestion of Nocardia opaca cell walls (NLD). According to the results, the administration of NLD to mice (i.p. at a daily dose of 0.5 mg kg-1) during 3 days prior to the antigen resulted in an inhibition of serum antibody level against sheep red blood cells (SRBC) and lipopolysaccharide (LPS). At the same time, the preparation stimulated the antibody response to SRBC if it was applied after the antigen. The ability of NLD to ensure protection against experimental infection with Klebsiella pneumoniae was comparatively studied in complement-normal mice (strain ICR) and in C5-deficient mice (strain DBA/2). Firstly, it was established that complement-deficient mice were more resistant to infection than complement-normal. Secondly, the preparation expressed a protective effect in C5-deficient animals; nevertheless the inoculation was done s.c. or i.v. The departure of the infection depended on the rate of opsonization of K. pneumoniae. Under certain conditions NLD can provoke excessive C3 activation, which might aggravate the course of the infection. The preparation augmented the host response to second challenge with K. pneumoniae of complement-normal and C5-deficient mice.

Adjuvants, Immunologic↗

PubMed1998

Glaucine analogues as inhibitors of mouse splenocyte activity.

The inhibitory effect of 15 semi-synthetic analogues of glaucine (1) on the lipopolysaccharide (LPS)-induced and the concanavalin A (Con A)-induced proliferation of mouse splenocytes was compared in vitro. Isoboldine (3), bracteoline (4) and dehydroglaucine (9) showed a significantly higher potency to suppress LPS-induced proliferation than 1, while 7-hydroxy-4-methylglaucine (8), 7-formyldehydroglaucine (11), 7-acetyldehydroglaucine (13), 7-benzoyldehydroglaucine (14), oxoglaucine (15) and glaucine-quinol (16) were less inhibitory. Compounds 3, 4, boldine (5), 15 and 16 surpassed significantly the inhibition expressed by 1 on Con A-induced proliferative response. The effect was equal to the inhibition determined for mitomycin C (Mit C) with both mitogens. In contrast to all others analogues, thaliporphine (2) stimulated splenocyte proliferation in both assays. Antibody response against sheep red blood cells (SRBC) was lowered most strongly by cataline (6), 7-methyldehydroglaucine (10) and 16.

Animals↗

PubMed1997

Immunopharmacological activity of aporphinoid alkaloid oxoglaucine.

The ability of aporphinoid alkaloid oxoglaucine to influence T- and B-cell immune response was studied in mice models. The substance inhibited in vitro mitogen-induced lymphocyte proliferation and suppressed antibody response to sheep red blood cells (SRBC) and lipopolysaccharide (LPS) in vivo effectively. The action depended on the relative timing of antigen and oxoglaucine administration. The substance manifested stimulatory effect in popliteal lymph node (PLN) reaction and LPS-induced B-cell activation. In the chronic inflammatory model of adjuvant arthritis oxoglaucine exhibited stimulatory or suppressive action related to the kinetics of the process. At low doses (1 or 2 mg kg-1) oxoglaucine improved the outcome of Klebsiella pneumoniae infection, while at higher doses (10 or 20 mg kg-1) the substance caused an impairment of host resistance to infectious agent. The comparison with cyclophosphamide in some tests showed that oxoglaucine was effective in manifold lower doses. In conclusion, oxoglaucine exerted immunomodulatory effects in vivo in a dose-dependent and protocol-dependent manner. Yet, its overall action might be attributed to the different sensitivity of the cells involved in the developing immune response.

Adjuvants, Immunologic↗

PubMed1997

A low dose immunorestorative effect of aporphinoid alkaloid oxoglaucine on experimentally immunosuppressed and infected mice.

The immunoregulatory activity of aporphinoid alkaloid oxoglaucine was studied in delayed-type hypersensitivity (DTH) reaction and Klebsiella pneumoniae infection in normal and immunosuppressed mice. The alkaloid enhanced DTH reaction when applied during the developing phase and abolished the inhibitory action of cyclophosphamide. Oxoglaucine possessed a restorative effect in K. pneumoniae infection in immunosuppressed mice in combination with indomethacin, prednisolone or artemisinin, as evaluated by the number of survivors and mean survival time. These data suggest that oxoglaucine affects selected lymphocyte clones responsible for antiinfectious host resistance. Its use as a second agent in combination with another immunosuppressant might enable reduction in the dosage or time of application.

Adjuvants, Immunologic↗

PubMed1996

Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids.

Extracts obtained from the roots of Berberidaceae species have been used in Eastern and Bulgarian folk medicine in rheumatic and other chronic inflammatory disorders. The investigations of the chemical composition and immunological properties show that their activity is mainly due to the alkaloid constituents. In the present study the anti-inflammatory properties of total ethanol extract (TEE), three alkaloid fractions, a major alkaloid berberine and oxyacanthine isolated from Berberis vulgaris roots were compared. All these were applied in acute inflammation (carrageenan- and zymosan-induced paw oedema), as the TEE showed the highest reducing effect. Their ability to alter in vivo and in vitro complement activity was determined. Also, the TEE was most effective in a chronic inflammatory model of adjuvant arthritis. The protoberberine fractions Bv2, Bv3 and berberine suppressed a delayed type hypersensitivity (DTH) reaction. Fraction Bv1 and berberine diminished antibody response against SRBC in vivo. The in vitro treatment of splenocytes with berberine showed that the anti-SRBC antibody synthesis was influenced in a different manner depending on the time course of its application. Oxyacanthine was less effective than berberine in the tests used.

Alkaloids↗

PubMed1996

Antimicrobial and immunological activity of ethanol extracts and fractions from Isopyrum thalictroides.

The antimicrobial and immunological properties of ethanol extracts, non-alkaloid, tertiary alkaloid and quaternary alkaloid fractions, obtained from roots and aerial parts of Isopyrum thalictroides were examined. The non-alkaloid fraction from aerial parts inhibited the growth of seven test microorganisms and was the most effective suppressor of classical pathway (CP) complement activity in normal human serum (NHS) and guinea pig serum (GPS). The alkaloid fractions, containing quaternary alkaloids expressed suppressive effect on mitogen-induced splenocyte proliferation. The in vitro antibody response against sheep red blood cells (anti-SRBC) was inhibited by ethanol extracts and quaternary alkaloid fraction. The intraperitoneal (i.p.) application of ethanol extract and tertiary alkaloid fraction from aerial parts showed that they possess in vivo effect on alternative pathway (AP) complement activity, anti-SRBC response and delayed type hypersensitivity (DTH).

Adjuvants, Immunologic↗

PubMed1995

Effect of a total extract from Fraxinus ornus stem bark and esculin on zymosan- and carrageenan-induced paw oedema in mice.

This study investigates the total ethanol extract (TE) of the stem bark of Fraxinus ornus and its constituent esculin (EN). They inhibited classical pathway (CP) and alternative pathway (AP) of complement activation in mouse serum. After intraperitoneal administration the total extract displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw oedema in mice. The results suggest that the traditional use of Fraxinus ornus stem bark extracts in the treatment of inflammatory disorders is at least partially due to its coumarin constituents.

Animals↗

PubMed1994

Effect of some hydroxycoumarins on complement-mediated hemolysis in human serum.

Coumarin derivatives are known to possess antiinflammatory and antimetastatic properties due to their direct action on cells, predominantly on macrophages. In the present study the interactions between esculin, esculetin, fraxin, fraxetin, as well as their acetylated and methylated derivatives and non-cell system participating in inflammatory processes, comprised of serum complement proteins, were investigated in vitro. 7-Methylesculin, esculin 5Ac and esculetin 2Ac exhibited good inhibition on classical pathway (CP) activity and scoparone strongly reduced alternative pathway (AP) activity in normal human serum (NHS). Some of the hydroxycoumarins were able to enhance hemolysis. Seven derivatives were tested in C1 and C3 functional assays, as 7-methylesculin appeared to be the strongest inhibitor of both activities. Esculin (En) and scopoletin (St) altered the effect of other complement activators (heat aggregated IgG, suramin, and zymosan) when applied with them simultaneously in vitro.

Buffers↗