Publications

Ethiopian medicinal plants used for the treatment of a variety of ailments including infectious diseases were screened for activity against human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). Seventy-one polar and nonpolar extracts derived from 21 plants belonging to 14 families were tested for inhibition of viral replication using HIV-1 (III(B)) and HIV-2 (ROD) strains. Selective inhibition of viral growth was assessed by the simultaneous determination of the in vitro cytotoxicity of each of the extracts against MT-4 cells. Six extracts made from the root bark of Bersama abyssinica Fresen, the leaves of Combretum paniculatum Vent., and Dodonaea angustifolia L.f., and the stem bark of Ximenia americana L. displayed antiviral activity at concentrations that were nontoxic to MT-4 cells. The highest selective inhibition of HIV-1 replication was observed with the acetone fraction of C. paniculatum and the methanol fraction of D. angustifolia which showed selectivity indices (ratio of 50% cytotoxic concentration to 50% effective antiviral concentration) of 6.4 and 4.9, and afforded cell protection of viral induced cytopathic effect of 100% and 99%, respectively, when compared with control samples. The greatest degree of antiviral activity against HIV-2 was achieved with the acetone extract of C. paniculatum (EC(50): 3 microg/mL), which also showed the highest selectivity index (32). The 50% cytotoxic concentration ranged from 0.5 microg/mL for the hexane extract of D. angustifolia L.f., the most cytotoxic of the extracts tested, to >250 microg/mL for some extracts such as the methanol fraction of Alcea rosea L., the least toxic tested. Only the polar extracts that were obtained by extraction with hydroalcohol, methanol or acetone exhibited inhibition of viral growth at subtoxic concentrations. The results obtained in this study enable the selection of extracts which show some specificity of action and support the further investigation of these extracts for their potential as new lead antiretroviral compounds.

An in-vitro method for maintaining rabbit corneal organ cultures for short periods of time is described. These cultures supported replication of strains of type 1 and 2 herpes simplex virus, and changes typical of herpetic infections of the cornea in vivo were observed by light microscopy, and by scanning and transmission electron microscopy. Infectious virus was readily recovered from inoculated corneal organ cultures. For practical, economic and humanitarian reasons, the full potential of this system warrants further investigation.

Apoptosis of uninfected bystander CD4(+) T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) pathogenesis. The viral and host mechanisms that lead to bystander apoptosis are not well understood. To investigate properties of the viral envelope glycoproteins (Env proteins) that influence the ability of HIV-1 to induce bystander apoptosis, we used molecularly cloned viruses that differ only in specific amino acids in Env. The ability of these strains to induce bystander apoptosis was tested in herpesvirus saimiri-immortalized primary CD4(+) T cells (CD4/HVS), which resemble activated primary T cells. Changes in Env that increase affinity for CD4 or CCR5 or increase coreceptor binding site exposure enhanced the capacity of HIV-1 to induce bystander apoptosis following viral infection or exposure to nonreplicating virions. Apoptosis induced by HIV-1 virions was inhibited by CD4, CXCR4, and CCR5 antibodies or by the CXCR4 inhibitor AMD3100, but not the fusion inhibitor T20. HIV-1 virions with mutant Envs that bind CXCR4 but are defective for CD4 binding or membrane fusion induced apoptosis, whereas CXCR4 binding-defective mutants did not. These results demonstrate that HIV-1 virions induce apoptosis through a CXCR4- or CCR5-dependent pathway that does not require Env/CD4 signaling or membrane fusion and suggest that HIV-1 variants with increased envelope/receptor affinity or coreceptor binding site exposure may promote T-cell depletion in vivo by accelerating bystander cell death.

It is reported that the ductility and strength of a metal matrix composite could be concurrently improved if the reinforcing particles were of the size of nanometers and distributed uniformly. In this paper, we revealed that gas atomization solidification could effectively disperse TiB2 nanoparticles in the Al alloy matrix due to its fast cooling rate and the coherent orientation relationship between TiB2 particles and α-Al. Besides, nano-TiB2 led to refined equiaxed grain structures. Furthermore, the composite powders with uniformly embedded nano-TiB2 showed improved laser absorptivity. The novel composite powders are well suited for selective laser melting.

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A series of novel 2,3-disubstituted/6,8-dibromo-2,3-disubstituted quinazolin-4(3H)-ones have been synthesized by condensing the primary amino group of lamotrigine with benzoxazin-4-one.The structure of the synthesised compounds was elucidated by spectral analysis (IR, NMR and Mass). The compounds synthesized were screened for antibacterial and antiHlV activities against replication of HIV-1 and HIV-2 in acutely infected LIT-4 cells. The compounds SPC-I, SPC-I Brand SPCIII Br (100 I¼g/ml) exhibited equivalent antibacterial activity with the standard ciprofloxacin (10 I¼g/ ml) against salmonella typhi. All the compounds exhibited cytotoxic properties in the MT-4 lymphocyte cell line.