4,552 publications from this institution
The growing interest for Selective Laser Melting (SLM) in orthopedic implant manufacturing is accompanied by the introduction of novel Ti alloys, in particular β-Ti for their excellent corrosion resistance as well as favorable combination of high mechanical strength, fatigue resistance and relatively low elastic modulus. As part of the SLM process for producing quality β-Ti parts powder flowability is essential to achieve uniform thickness of powder layers. In this work the flowability of different gas atomized β-Ti, including NiTi, powders has been studied. Their rheological properties were compared to those of commercially available plasma-atomized Ti–6Al–4V powder using a newly developed semi-automatic experimental set-up. Not only the particle size, shape and size distribution of the powders display a large influence on the powder flowability but also particle surface properties such as roughness, chemical composition and the presence of liquid on the surface of the particles. It was found that plasma or gas atomization production techniques for SLM powder have a considerable effect on the particle topography. Among the powders studied regarding SLM applicability only rheological properties of the fine size fraction (25–45μm) of Ti–45Nb didn't conform to SLM processing requirements. To improve flowability of the Ti–45Nb powder it was annealed both in air and argon atmosphere at 600°C during 1h, resulting in an improved rheological behavior suitable for SLM processing.
A marked virus-inhibiting potency is obtained in the serum after intraperitoneal injection of polyacrylic acid (PAA) and polymethacrylic acid (PMAA) in mice. Much higher antiviral levels were reached than for other related polymers including dextran sulfate, heparin, polyvinyl sulfate, pyran copolymer, polystyrene sulfonate, and macrodex. The broad antiviral action of PAA and PMAA was attributed both to a direct interference with the virus-cell interaction and the viral ribonucleic acid metabolism and to the formation of an interferon-like factor. Both polyanions differed in interferon-inducing ability: highest serum interferon titer was obtained 18 hr after the intraperitoneal injection of PAA. The mechanism of interferon production by PAA and PMAA is discussed. As described previously for Sindbis virus and endotoxin, the animals also became hyporeactive after injection of PAA.
A large variety of compounds have been reported to inhibit the replication of human immunodeficiency virus (HIV). The compounds that have been most intensively pursued for the treatment of HIV infection belong to three classes: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Within each of these classes, a number of compounds have been identified that inhibit HIV replication at nanomolar concentrations which are 10(4)- to 10(5)-fold lower than the cytotoxic concentrations. Yet, the potential usefulness of these compounds seems to be compromised by the rapid emergence of virus drug resistance. Here, we describe a strategy that, at least in cell culture, prevents the development of resistance. This strategy is based on the use, from the beginning, of sufficiently high drug concentrations. When added at such concentrations, that for some of the NNRTIs did not have to be higher than 10-100 times their 50% effective concentration (EC50), these compounds completely suppressed ("knocked out") HIV-1 replication in cell culture, and thus prevented drug-resistant virus strains from emerging. This "knock out" effect could be achieved for longer times and at lower drug concentrations when the compounds were combined (i.e. NNRTIs with one another or with NRTIs) than when used individually. Thus, when used at the appropriate doses, as such or in combination, NNRTIs proved able to completely clear ("cure") HIV-1-infected cell cultures from the virus.
Adenoviruses (Ads) are common opportunistic pathogens that are rarely associated with severe clinical symptoms in healthy individuals. In contrast, in patients with compromised immunity, Ad infections often result in disseminated and potentially life-threatening disease. Among these are AIDS patients, individuals with hereditary immunodeficiencies and recipients of solid organ or haematopoietic stem cell transplants (HSCT) who receive immunosuppressive therapy. The latter account for the largest number of severe Ad infections. There is currently no formally approved antiviral therapy for the treatment of severe Ad keratoconjunctivitis and life-threatening Ad infections in immunocompromised patients. Here we update current knowledge on Ad biology, the clinical features observed in different patient groups and specific immune responses towards Ad infections. In addition, we review current and future treatment options, including: (i) the antiviral drugs cidofovir, ribavirin and new investigational compounds, as evaluated in the clinic or in relevant animal models, as well as (ii) novel immunotherapeutic strategies.
Abstract In analogy with maribavir [1‐(β‐L‐ribofuranosyl)‐isopropylamino‐5,6‐dichlorobenzimidazole], a nucleoside analogue that acts against human cytomegalovirus (HCMV) by a non‐nucleoside mechanism, here I present three other examples of classes of nucleoside analogues (i.e. bicyclic furo[2,3‐d]pyrimidine as well as HEPT and TSAO derivatives) that act against either HCMV or human immunodeficiency virus (HIV) through a non‐nucleoside mode of action. †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend. Keywords: Neucloside analoguesHCMVHIV Acknowledgment I thank Christiane Callebaut for her proficient editorial assistance. Notes †In honor and celebration of the 70th birthday of Professor Leroy B. Townsend.
No abstract is provided for this article.
No abstract is provided for this article.
The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is composed of two subunits of 66 and 51 kDa in a 1 to 1 ratio. Because dimerization is a prerequisite for enzymatic activity, interference with the dimerization process could constitute an alternative antiviral strategy for RT inhibition. Here we describe an in vitro assay for the study of the dimerization state of HIV-1 reverse transcriptase based on chemical crosslinking of the subunits with dimethylsuberimidate. Crosslinking results in the formation of covalent bonds between the subunits, so that the crosslinked species can be resolved by denaturing gel electrophoresis. Crosslinked RT species with molecular weight greater than that of the dimeric form accumulate during a 1-15-min time course. Initial evidence suggests that those high molecular weight species represent trimers and tetramers and may be the result of intramolecular crosslinking of the subunits of a higher-order RT oligomer. A peptide that corresponds to part of the tryptophan repeat motif in the connection domain of HIV-1 RT inhibits crosslink formation as well as enzymatic activity. The crosslinking assay thus allows the investigation of the effect of inhibitors on the dimerization of HIV-1 RT.
