Antihuman Immunodeficiency Virus Type 1 (HIV-1) Activity of Rare Earth Metal Complexes of 4-Hydroxycoumarins in Cell Culture

The cerium Ce(III), lanthanum La(III), and neodymium Nd(III) complexes with 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one (warfarin) (W) and 3,3′-benzylidenebis[4-hydroxycoumarin] (1) were synthesized and studied for the first time for cytotoxicity (on MT-2 cells) and as anti-HIV agents under acute and chronic infection. The complexes were characterized by different physicochemical methods: mass spectrometry, (1)H NMR, (13)C NMR, and IR spectroscopy. The spectra of the complexes were interpreted on the basis of comparison with the spectrum of the free ligands. Anti-HIV effect of the complexes/ligands was measured in MT-2 cells by microtiter infection assay. Detection of endogenous reverse transcriptase (RT) activity and RT processivity by PCR indicative for proviral DNA synthesis demonstrated that anti-HIV activity has not been linked to early stages of viral replication. No effect on late steps of viral replication has been found using cells chronically producing HIV-1(LAI) virus. La(W) demonstrated anti-HIV activity (IC50=21.4 μM) close to maximal nontoxic concentration. Nd(W), Ce(1), and Nd(1) demonstrated limited anti-HIV potency, so none of the complexes seems appropriate to be used in clinic. Further targeting of HIV-1 inhibition by La(W) is under progress

Experimental model to study co-infection of human immunodeficiency virus-type 1 (HIV-1IIIB) and influenza virus in cell culture

People living with human immunodeficiency virus (HIV) demonstrate highly expressed immune deficiency and are vulnerable to exogenous viral infections (co-infections), including influenza. We were interested in developing an in vitro model to examine HIV-1 and influenza virus (Flu) co-infection based on HIV-1 sialoglycoprotein (Sgp) synthesis and virus replication in double-infected cells. A convenient and reproducible experimental model for studying the sialylation of HIV-1 glycoprotein 120 (Gp120) by direct radioactive precursors of sialic acid synthesis, [14C]N-acetylmannosamine) in cell culture was successfully introduced for investigation of co-infection. The co-infection provoked desialylation of viral Sgps, followed initially by decreased and later on, by increased HIV replication. Monoclonal antibodies (Mab) to the main Gp120 V3 neutralization epitope but not to broadly reactive Mab against Gp120 recognize and neutralize the newly exposed epitopes. A hypothesis was outlined that exogenous neuraminidase (NA) (Flu virus) changes the configuration of HIV-1 Gp120 through desialylation resulting in the exposure of a novel antigen. The proposed model could contribute to better understanding of pathogenesis of Flu co-infection in people living with HIV. In vivo, Flu co-infection most probably leads to desialylation of both HIV and the cell surface, thus facilitating the escape of HIV from immune control. The findings described here reflect the interaction between components of two viruses – NA of Flu virus and Sgps on HIV-1 surface without considering the cell surface. The hypothesis could be extended to other exogenous co-infections with agents containing NA in HIV-infected people

Social distance and stigma towards persons with serious mental illness among medical students in five European Central Asia countries

The study investigated behavioral measures of social distance (i.e., desired proximity between self and others in social contexts) as an index of stigma against those with mental illness among medical students in the Republic of North Macedonia, Turkey, Azerbaijan, Kazakhstan, and Poland, using the Reported and Intended Behavior Scale (RIBS), a standardized, self-administered behavioral measure based on the Star Social Distance Scale. The students' responses to standardized clinical vignettes on schizophrenia, and depression with suicidal ideation, were also assessed. A total of 257 North Macedonian (females, 31.5%; 1-4 grades, 189; 5-6 grades, 68); 268 Turkish (females, 43.3%; 1-4 grades, 90; 5-6 grades, 178); 450 Kazakh (females, 28.4%, 71.6%; 1-4 grades, 312; 5-6 grades, 138); 512 Azerbaijani (females, 24%; 1-4 grades, 468; 5-6 grades, 44; females, 24%), and 317 Polish (females, 59.0%; 1-4 grades, 208; 5-6 grades, 109) students were surveyed. The responses on the RIBS social distance behavior measures did not improve with advancing medical school grade, but students across all sites viewed schizophrenia and depression as real medical illnesses. The results support the development of enhanced range of integrated training opportunities for medical student to socially interact with persons with mental illness sharing their experiences with them. [Abstract copyright: Copyright © 2022. Published by Elsevier B.V.