The pyrimidine nucleus is a versatile core in the development of antiretroviral agents. On this basis, series pyrimidine-2,4-diones linked to an isoxazolidine have been synthesized and tested as nucleoside analogs, endowed with potential anti-HIV (human immunodeficiency virus) activity. Compounds

Fresh bone marrow mononuclear leukocytes were used as a target for infection by human T-cell leukemia-lymphoma virus subgroup 1 (HTLV-1) co-cultivation with virus-positive cell lines. The lines established from patients or HTLV-1-transformed umbilical cord-blood T cells. Clumps of transformed cells became visible 2-3 weeks after and developed at high frequency (greater than 90%) in the samples used. Stimulation lymphocyte mitogens facilitated this process but was not absolutely required....

Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of obtained compounds investigated. 2'-oxa-3'-aza-nucleosides, while showing low levels cytotoxicity, exert a specific inhibitor on two different transcriptases, which is comparable with that AZT, opening new perspectives their possible use as therapeutic agents, anti-retroviral anti-HBV chemotherapy.

Human T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell (ATL) and non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin. The disorders HTLV-1 are mediated by different proinflammatory cytokines as IL-1α, IL-6, TNF-α. release role of IL-17 still debated. Aims this study were analyze induction infection determine whether resveratrol (RES) able down regulate pathway production either in chronically infected MT-2 line human...

Phosphonated carbocyclic 2'-oxa-3'-azanucleosides have been synthesized and tested for their antiretroviral activity. The obtained results shown that some of the compounds were as powerful azydothymidine in inhibiting reverse transcriptase activity human retrovirus T-cell leukemia/lymphotropic virus type 1 protecting peripheral blood mononuclear cells against transmission vitro. These data indicate phosphonated possess necessary requirements to efficiently counteract infections caused by...

D-(−)-Lentiginosine [(−)-4], the nonnatural enantiomer of iminosugar indolizidine alkaloid L-(+)-lentiginosine, acts as apoptosis inducer on tumor cells different origin, in contrast to its natural enantiomer. Although D-(−)-4 exhibited a proapoptotic activity towards at level lower than chemotherapeutic agent, SN38, it was less normal and cytotoxic. Apoptosis induced by caspase-dependent, shown increased expression caspase-3 -8 treated cells, inhibition following treatment with pan caspase...

Since human T-lymphotropic virus type 1 (HTLV-1)-associated diseases are associated with a high HTLV-1 load, reducing this load may treat or prevent disease. However, despite in vitro evidence that certain nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs) active against HTLV-1, vivo results have been disappointing. We therefore assayed the sensitivity of primary isolates to panel RT inhibitors. were obtained, pre- and post- NRTI treatment, from patients...

Abstract Regulated cell death (RCD) plays an important role in the progression of viral replication and particle release cells infected by herpes simplex virus-1 (HSV-1). However, kind RCD (apoptosis, necroptosis, others) resulting cytopathic effect HSV-1 depends on type species. In this study, we further investigated molecular mechanisms apoptosis induced HSV-1. Although a caspase-8 has previously been suggested, now clearly show that is required for HSV-1-induced FADD-/death...

The effect of 3′-azido-3′-deoxythymidine (AZT) on in vitro infection peripheral blood mononuclear cells (PBMCs) isolated from normal adult individuals with human T cell leukaemia/lymphoma virus type I (HTLV-I) was evaluated. Different PBMC samples were exposed to HTLV-I by cocultivation MT-2 (a chronically infected line) the presence 20 U/ml recombinant interleukin 2 (IL-2) and graded concentrations AZT. Control drug-treated cultures, both uninfected PBMCs, then grown for several weeks...

We investigated the sensitivity to cell death of peripheral blood mononuclear cells (PBMCs) from patients with multiple sclerosis (MS). PBMCs MS patients, following PHA stimulation, were less sensitive than those healthy donors (mean ± s.e.m., 22.5 1.9 in vs 36.5 2.8 controls; p = 0.0003). However, when Fas-agonist antibody was added, increase respect apoptosis induced by mitogen alone even higher controls. In addition, PHA-activated showed surface expression Fas controls, while Bcl-2...

Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these vitro. Coat production is substantially enhanced by interaction cells with a macromolecular factor released peripheral blood mononuclear culture. This thus constitutes an unusual mechanism which inflammatory may nonspecifically suppress cellular immune at least one class solid tumors humans.

Diagnosis and therapeutic strategies in Alzheimers disease (AD) might greatly benefit of the present multidisciplinary approach for studying molecular pathogenesis disorder. Gene expression profile at peripheral level could be a promising tool pathogenic studies as well early diagnosis AD. A dysregulated inflammatory response, other systemic disorders, have been described Therefore, we investigated expression, level, number genes involved inflammatory, oxidative stress proliferative response...

We have recently found that D(−)lentiginosine, a synthetic iminosugar exerting glucosidase inhibitory activity, but not its natural enantiomer lentiginosine, is endowed with an unexpected, pro-apoptotic activity. Here, we investigated mechanisms involved in apoptosis induced by D(−)lentiginosine MOLT-3, HT-29 and SH-SY5Y tumour cell lines. The results showed increased caspase 9 expression at 18 h all the lines from 1.5–3.1 folds. Cytochrome c cytoplasm was to be 2.3–2.6 folds treated cells...

The transcription factor nuclear factor-kappa B (NF-κB) is a crucial player of the antiviral innate response. Intriguingly, however, NF-κB activation assumed to favour herpes simplex virus (HSV) infection rather than restrict it. Apoptosis, form response viruses, completely inhibited by HSV in fully permissive cells, but not cells incapable sustain replication, such as immunocompetent cells. To resolve intricate interplay among signalling, apoptosis and permissiveness HSV-1 monocytic we...

3′-Deoxy-4′-azaribonucleosides (15a−d) were synthesized starting from the commercially available (4R)-trans-4-hydroxy-l-proline 7. From biological evaluations, 15b and 15d emerged as potent inhibitors of HCV replication on a replicon assay. These findings demonstrate that pyrrolidine nucleosides represent new template for antiviral or other studies could be considered novel combination therapy against infection using nucleoside non-nucleoside NS5B.

Affairs of the HAART! The synthesis HEPT-derived, truncated reverse isoxazolidinyl nucleosides (shown) is reported. These compounds represent first examples isoxazolidines bearing a pyrimidine scaffold at C-3 position using glycoside-type linkage. Biological evaluation showed that some derivatives act as non-nucleoside inhibitors HIV-1 transcriptase, with an efficacy comparable to Nevirapine but reduced toxicity. Detailed facts importance specialist readers are published "Supporting...

The therapeutic efficacy of the AZT and IFN combination in ATL presumably reflects inhibition RT-related functions.HTLV-1-RT activity from short-term cultured PBMCs may represent a predictive correlate clinical response to AZT/IFN patients.