Anti-infective properties of the melanin-glucan complex obtained from medicinal tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr. (Aphyllophoromycetideae).

The goal of this investigation was to comparatively study the efficiency of traditionally used anti-infective drugs and biopolymer complexes originated from the medicinal mushroom Fomes fomentarius (L.:Fr.) Fr.

Novel inhibitors of HIV discovered among existing classes of pharmaceutical compounds indicated for unrelated clinical indications.

In vitro screening of 307 drugs with various clinical indications (cardiotropic, neurotropic, antibacterial, etc.) has revealed 6 compounds which displayed remarkable antiretroviral activity. Three of these drugs had a tendency to have undesirable side effects and were thus excluded from further consideration.

Synthesis, characterization, antifungal and anti-HIV activities of metal(II) complexes of 4,6-di-tert-butyl-3-[(2-hydroxyethyl)thio]benzene-1,2-diol.

Co(II) and Ni(II) complexes with 4,6-di-tert-butyl-3-[(2-hydroxyethyl)thio]benzene-1,2-diol (L) have been synthesized and characterized by means of elemental analysis, TG/DTA, FT-IR, ESR, UV-vis, XRD, magnetic susceptibility, cyclic voltammetry and conductance measurements. According to the data obtained the organic compound acts as a bidentate O,S-coordinated ligand and yields Co(II) and Ni(II) complexes of the stoichiometry ML(2) which is characterized by square planar geometry. Antifungal and anti-HIV activities of the ligand and its metal(II) complexes were found to decrease in the sequence CuL(2)>CoL(2) ~ NiL(2)>HL, along with their reducing ability (determined electrochemically).

Therapeutic AIDS vaccines.

Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983.

Sorbicillactone A: a structurally unprecedented bioactive novel-type alkaloid from a sponge-derived fungus.

This chapter deals with the discovery of sorbicillactone A, as an illustrative example of the fruitful cooperation within BIOTECmarin--its isolation and chemical characterization, and its biological activities. Sorbicillactone A was isolated from a strain of Penicillium chrysogenum cultured from a sample of the Mediterranean sponge Ircinia fasciculata; it possesses a unique bicyclic lactone structure, seemingly derived from sorbicillin. Among the numerous known sorbicillin-derived structures, it is the first found to contain nitrogen and thus the first representative of a novel type of 'sorbicillin alkaloids', apparently originating from a likewise remarkable biosynthesis.

Small animal model of HIV-1 infection.

Background: The lack convenient and inexpensive small animal model of HIV infection hampers significantly the research on immunopathogenesis, antiviral drugs, and vaccines.

Objectives: Development of HIV model in small animals, i.e.

Genetic instability in peripheral blood lymphocytes of Chernobyl clean-up workers.

The group of clean-up workers involved in the liquidation of the consequences of the major accident at the Chemobyl nuclear power plant (CNPP) was exposed to high doses of radiation. In this review, we summarize the results of a long-term study of the cytogenetic status of CNPP clean-up workers. The data revealed different trends of the parameters of the cytogenetic status in the course of the study.

Suppression of PrP(Sc)- and HIV-1 gp120 induced neuronal cell death by sulfated colominic acid.

The scrapie prion protein (PrP(Sc)) has been shown to induce apoptosis of rat cortical neurons in vitro. Here we demonstrate that the toxic effect displayed by PrP(Sc) can be blocked by sulfated colominic acid (polymer of N-acetylneuraminic acid). This compound acts neuroprotectively at a concentration of > or = 0.

[Serological properties of HIV-1 isolates from the focus of an epidemic in the Gomel region of the Belarus Republic (1996)].

Immunoreactivity of sera obtained in 1996 from HIV-1-infected intravenous narcomaniacs from an epidemic focus in Gomel region, Belarus, is studied with a panel of 10-16-component synthetic peptides simulating apical epitope of surface glycoprotein gp120 V3 loop of HIV-1 variants. Comparative analysis of resultant spectra with representative immunoreactivity spectra of sera from a sampling of HIV-1-positive sera collected in 1986-1997 in different regions of the former USSR demonstrated a high homogeneity of immunoreactivity spectra of sera from Gomel region. Serotypes of HIV-1 A/C variants circulating in populations of intravenous narcomaniacs in the focus in Gomel region in 1996 and in Southern and South-Eastern Ukraine in 1995-1996 are similar.

[A complex approach to the diagnosis of HIV-1 infection: the use of the polymerase chain reaction as an alternative confirmatory test].

The results of the three-year observation of female patient St. in whose blood antibodies to HIV disappeared in the course of time and the results of the laboratory study of the blood sera of children born of HIV-infected mothers are presented. In these patients correct diagnosis could be made only with the use of a complex of virological and molecular-biological methods.

Interaction of 68-kDa TAR RNA-binding protein and other cellular proteins with prion protein-RNA stem-loop.

The RNA stem-loop structure of the trans-activating region TAR sequence of human immunodeficiency virus-1 mRNA is the binding site for a number of host cell proteins. A virtually identical set of proteins from HeLa nuclear extracts was found to bind to the predicted RNA hairpin element of prion protein (PrP) mRNA, as demonstrated in UV cross-linking/RNase protection and Northwestern assays. We show that the cellular TAR loop-binding protein, p68, is among those proteins which associate with PrP RNA.

[The use of the polymerase chain reaction in modelling HIV infection in animals].

The data on observations, lasting over the period of 6 months, on cotton rats given large doses of highly replicating strain HIV-1zmb by retrobulbar and intraperitoneal injections are presented. The study revealed that in all animals subjected to intraperitoneal infection lymphoid tissue contained integrated areas of protovirus DNA of HIV-1 three months later and cerebral tissue, five months later. Six months after retrobulbar infection the specimens of lymphoid tissue contained protovirus DNA in 100% of cases and the specimens of cerebral tissue, in 80% of cases.

Simultaneous introduction of distinct HIV-1 subtypes into different risk groups in Russia, Byelorussia and Lithuania.

Objective: To investigate genotypes and serotypes of HIV-1 variants in Russia, Byelorussia and Lithuania.

Patients And Methods: Sera from 20 HIV-1-infected individuals were tested in an enzyme-linked immunosorbent assay (ELISA) with 19 V3 synthetic peptides, and serum HIV-1 V3 RNA was amplified and sequenced.

Results: Sequence comparison of the envelope V3 region among specimens tested revealed a 2-29% range nucleotide divergence, with a mean of 19%.

[Morphological characteristics of the course of HIV infection in laboratory animals].

The integrative form of infection was obtained in cotton rats intraperitoneally or retrobulbarly infected with the highly-productive strain Zmb HIV-1. Clinically, it appeared as reduced animal weight gain and high mortality rates in the disease terminal stage. The proviral DNA was detected by the polymerase chain reaction in the genomes of cerebral and splenic cells in most animals.

The triaminopyridine flupirtine prevents cell death in rat cortical cells induced by N-methyl-D-aspartate and gp120 of HIV-1.

Flupirtine, a triaminopyridine derivative, is a non-opiate centrally acting analgesic agent with muscle relaxant properties. Now we show that this drug displays a potent cytoprotective effect on neurons (rat cortical cells) treated with (i) the excitatory amino acid N-methyl-D-aspartate (NMDA) or (ii) with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. In the absence of the drug the two agents cause a > 90% reduction of cell viability after a 18 h incubation.

Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures.

Rat cortical cells were incubated with the Scrapie prion protein, PrionSc. At concentrations of 3 ng/ml of PrionSc and higher, the viability of the cells decreased significantly after a 12-h incubation period. Simultaneously, the degree of DNA fragmentation increased.

Mode of action of the anti-AIDS compound poly(I).poly(C12U) (Ampligen): activator of 2',5'-oligoadenylate synthetase and double-stranded RNA-dependent kinase.

The mismatched double-stranded RNA (dsRNA), poly(I).poly(C12U), also termed Ampligen, exhibits a strong antiviral and cytoprotective effect on cells (human T-lymphoblastoid CEM cells and human T-cell line H9) infected with the human immunodeficiency virus type 1 (HIV-1). Untreated H9 cells infected with HIV-1 start to release the virus 3 days post-infection, while in the presence of 40 micrograms/ml (80 micrograms/ml) of poly(I).

[The use of a primary astrocyte culture for modelling HIV neurological infection].

The article deals with the results of the experiment substantiating the in vitro model of HIV neuro-infection. In this work primary glial (astrocytic) tissue cultures obtained from normal human and animal (guinea pig) brain tissue were used. As revealed in this investigation, the following phenomena could be observed in human brain tissue monolayer culture, infected with HIV and subsequently subcultured: (a) the stimulation of tissue-cell growth; (b) the formation of multinuclear glial cells; (c) the presence of virus-specific proteins in astrocyte cytoplasm, detected by immunofluorescent and electrophoretic techniques; (d) the presence of HIV-1 DNA provirus in infected astrocytes.

Accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus.

The abnormal isoforms of the normal cellular prion protein (PrP), also termed Scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. The mRNA of PrP contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (HIV-1) cis-acting sequence TAR within the LTR; both structures contain the pentanucleotide CUGGG in the loop, and the uridine- and adenine-bulge in the stem. In this study, using purified HIV-encoded trans-activator, Tat, and HIV-1 TAR-RNA or PrP-mRNA containing the stem-loop structure, we demonstrate by use of gel-retardation and filter binding assays that Tat binds to TAR- and PrP-RNA with the dissociation constants of 2.

[Status of collective immunity to hepatitis A virus in urban residents in Byelorussia].

The large immune stratum and intense collective immunity to virus hepatitis A among the urban population of Byelorussia are characteristic of hyperendemic territory. The geometric mean of the antibody titer has been noted to increase with age, which is probably due to repeated infections of persons who have already had the disease. The use of this value for the characterization of collective immunity and epidemiological situation has been proposed.

[The clinico-pathogenetic characteristics of Kaposi's sarcoma].

The paper is concerned with clinicomorphological characteristics of endemic, immune and epidemic (AIDS-associated) forms of Kaposi's sarcoma (KS). Recent experimental and clinical evidence suggests pathogenic contribution to KS of virus-induced depression of sex-linked genes and immunosuppression. Combined action of these factors should be regarded when specifying current presentation of KS.

[The strain features of the HIV-1 circulating in the USSR based on data from a study of its properties in cell cultures].

Both variants of HIV-1 reported in the literature: slow/low and rapid/high types, were detected among the strains isolated from the subjects examined in 4 foci of HIV-1 infection in the south of the RSFSR and Byelorussia. All the 17 strains isolated in the southern RSFSR foci belonged to the slow/low type and had a low and unstable replication potential in donor peripheral blood mononuclear cells and in MT-4 cell line. All of them were isolated from subjects with asymptomatic infection and from children with initial clinical manifestations of the disease.