The rhamnolipid biosurfactant PS-17 and its complex with the polysaccharide alginate, both produced by the Pseudomonas sp. S-17 strain, were studied for their antiviral activity against herpes simplex virus (HSV) types 1 and 2. They significantly inhibited the herpesvirus cytopathic effect (CPE) in the Madin-Darby bovine kidney (MDBK) cell line. The investigations were carried out according to the CPE inhibition assay protocol. The suppressive effect of the compounds on HSV replication was dose-dependent and occurred at concentrations lower than the critical micelle concentration of the surfactant. The 50% inhibitory concentration (IC 50 ) of rhamnolipid PS-17 was 14.5 μg/ml against HSV-1 and 13 μg/ml against HSV-2. The IC 50 values of the complex were 435 μg/ml for HSV-1 and 482 μg/ml for HSV-2. The inhibitory effects of the substances were confirmed by measuring the infectious virus yields with the multicycle virus growth experimental design as well: Δlog CCID 50 of 1.84Ð2.0 against the two types of herpes simplex viruses by rhamnolipid PS-17 (20 μg/ml), and a strong reduction of the HSV-2 virus yield under the effect of the alginate complex at a concentration of 450 μg/ml. The results indicate that rhamnolipid PS-17 and its alginate complex may be considered as promising substances for the development of anti-herpetic compounds.

In the present study, we have investigated comparatively the inflammatory response of patients with active and inactive osteoarthritis. The sera from 31 healthy individuals, 37 patients with active OA, and 19 patients with inactive OA were assayed for TNF-alpha, IL-6, sRANKL, RANTES, and MRP8 using ELISA in order to evaluate their potential as markers of disease activity. Also, the spontaneous and LSP-induced release of TNF-alpha and IL-6 by peripheral blood neutrophils was determined. The activation of OA is associated with elevated TNF-alpha, IL-6, and RANTES serum levels while sRANKL and MRP8 appeared to be increased in both active and inactive OA. The neutrophil spontaneous and up-regulated by LPS cytokine release can contribute to the exacerbation of OA.

Various metal phthalocyanines have been studied for their capacity for photodynamic effects on viruses. Two newly synthesized water-soluble phthalocyanine Zn(II) complexes with different charges, cationic methylpyridyloxy-substituted Zn(II)- phthalocyanine (ZnPcMe) and anionic sulfophenoxy-substituted Zn(II)-phthalocyanine (ZnPcS), were used for photoinactivation of two DNA-containing enveloped viruses (herpes simplex virus type 1 and vaccinia virus), two RNA-containing enveloped viruses (bovine viral diarrhea virus and Newcastle disease virus) and two nude viruses (the enterovirus Coxsackie B1, a RNA-containing virus, and human adenovirus 5, a DNA virus). These two differently charged phthalocyanine complexes showed an identical marked virucidal effect against herpes simplex virus type 1, which was one and the same at an irradiation lasting 5 or 20 min (Δlog=3.0 and 4.0, respectively). Towards vaccinia virus this effect was lower, Δlog=1.8 under the effect of ZnPcMe and 2.0 for ZnPcS. Bovine viral diarrhea virus manifested a moderate sensitivity to ZnPcMe (Δlog=1.8) and a pronounced one to ZnPcS at 5- and 20-min irradiation (Δlog=5.8 and 5.3, respectively). The complexes were unable to inactivate Newcastle disease virus, Coxsackievirus B1 and human adenovirus type 5.

Two isochinoline alkaloids, glaucine and oxoglaucine were investigated for their suggested anti-inflammatory influence concerning nitric oxide and cytokine production. Mouse peritoneal macrophages were stimulated with different Toll-like receptor (TLR) ligands such as LPS for TLR4, zymosan for TLR2 and CpG for TLR9. The alkaloids inhibited TNF-alpha and IL-6 production induced by these ligands. In regard to IL-12 suppressive effect was registered in the case of CpG stimulation. Glaucine succeeded to enhance LPS and zymosan-induced IL-10 production. The reduction of pro-inflammatory cytokines and increase of anti-inflammatory IL-10 are indicative for their use in different acute and chronic inflammatory diseases.

The threat of bioterrorism in the recent years has once again posed to mankind the unresolved problems of contagious diseases, well forgotten in the past. Smallpox (variola) is among the most dangerous and highly contagious viral infections affecting humans. The last natural case in Somalia marked the end of a successful World Health Organization campaign for smallpox eradication by vaccination on worldwide scale. Smallpox virus still exists today in some laboratories, specially designated for that purpose. The contemporary response in the treatment of the post-vaccine complications, which would occur upon enforcing new programs for mass-scale smallpox immunization, includes application of effective chemotherapeutics and their combinations. The goals are to provide the highest possible level of protection and safety of the population in case of eventual terrorist attack. This review describes the characteristic features of the poxviruses, smallpox vaccination, its adverse reactions, and poxvirus chemotherapy.

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.

Neonates are highly sensitive to infections because they are biased to develop Th2 immune responses. When exposed to certain agents, such as DNA vaccines or CpG DNA motifs, neonates are capable to mount adult-like Th1 protective responses. This study investigates the capacity of Candida albicans (C. albicans) dsDNA to induce host resistance in newborn mice against gastrointestinal C. albicans infection. The protective properties of dsDNA are related to an increased number of spleen CD4+ T cells secreting IFN-gamma. In infected DNA-treated mice, an enhanced production of IFN-gamma by Peyer's patch cells was observed together with reduced colonization and histopathological changes in the stomach. Our results indicated that C. albicans dsDNA administration in neonates elicited the protective immune response against gastrointestinal Candida infection.

In view of the potential menace of a terrorism attack with smallpox virus, an intensive search of chemotherapeutic agents active against orthopoxviruses is underway. We comparatively studied the antiviral activity of cidofovir (CDV) and idoxuridine (IUdR) against two vaccinia virus (VV) strains, Bratislava and RIIPD, in cell cultures of chick embryo fibroblasts (CEF). The investigations were carried out according to cytopathic effect (CPE) inhibition assay protocols. To determine the cytotoxicity of the compounds, maximal tolerated concentration (MTC) was calculated in CEF cell monolayers and 50% cell growth inhibitory concentration (CGIC 50 ) was calculated in growing cell cultures. It was found that the antiviral effects were strongly dependent on virus inoculum size. There were no marked differences in the susceptibility to CDV and IUdR between the two VV strains. The individual half maximal inhibitory concentration (IC 50 ) for CDV varied from 7.1-8.5 µ µM at 10/100 virus 50% infectious dose (ID 50 ) to 13.6-26.5 µ µM Smallpox (variola) is among the most dangerous and highly contagious viral infections affecting humans. The last natural case in Somalia has marked the end of a successful WHO campaign for smallpox eradication by vaccination on a worldwide scale (Deria et al., 1972;Fenner et al., 1988). As a result, the smallpox virus can only be found in laboratories in Atlanta, Georgia, USA and Novosibirsk, Siberia, Russia. Despite smallpox eradication, infections caused by other members of the poxvirus family are also important for human health. The monkeypox virus can infect humans and occasional cases have been reported in Equatorial Africa (Heiner et al., 1998). Molluscum contagiosum and orf infections occur in immunocompromised patients (Kuhl et al., 2003;Murray, 2004). In addition, it has been highlighted that people not vaccinated with vaccinia virus (VV) could become the target of a potential terrorist attack with smallpox (Mahy, 2003). Therefore, there is a need to renew the search of chemotherapeutical agents active against poxviruses.Poxviruses encode a large number of enzymes including DNA polymerase and thymidine kinase, which are of potential interest as targets for antiviral compounds (Citarella et al., 1972;Kit et al., 1977). The first compound described in the literature was p-amino-benzaldehyde thiosemicarbazone, which Brownlee and Hamre (1951) established inhibited the replication of VV. Bauer and Sadler (1960) found 1-methyl-1H-indole-2,3-dione-3-thiosemicarbazone (methisazone, Marboran ® ) manifested a prophylactic and not a therapeutic effect against smallpox. Later, Borysiewicz et al., (1977) found a comparatively low selectivity ratio value for 1-methyl-1H-indole-2,3-dione-3-thiosemicarbazone based on its marked immunotoxicity. Among compounds showing an anti-poxvirus activity are idoxuridine (IUdR), ribavirin, cidofovir (CDV), interferon and polyacrylic acid (De Clercq, 2001).CDV is an acyclic nucleoside phosphonate licensed for the treatment of cytomegalovirus retinitis in AIDS pat...