Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad-spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure-activity relationships for these pathogens in terms of their susceptibility to inhibition by polymers, and for polymers in terms of their anionic charge and hydrophobicity that make up broad-spectrum antiviral agents. The identified leads cannot be predicted based on prior data on polymer-based antivirals and represent promising candidates for further development as preventive microbicides.

The requirement for new antiviral therapeutics is an ever present need. Particularly lacking are broad spectrum antivirals that have low toxicity. We develop such agents based on macromolecular prodrugs whereby both the polymer chain and the drug released from the polymer upon cell entry have antiviral effects. Specifically, macromolecular prodrugs were designed herein based on poly(methacrylic acid) and ribavirin. Structure-function parameter space was analyzed via the synthesis of 10 polymer compositions varied by molar mass and drug content. Antiviral activity was tested in cell culture against both low and high pathogenic strains of influenza. Lead compounds were successfully used to counter infectivity of influenza in chicken embryos. The lead composition with the highest activity against influenza was also active against another respiratory pathogen, respiratory syncytial virus, providing opportunity to potentially treat infection by the two pathogens with one antiviral agent. In contrast, structure-function activity against the herpes simplex virus was drastically different, revealing limitations of the broad spectrum antiviral agents based on macromolecular prodrugs.

Macromolecular (pro)drugs hold much promise as broad-spectrum antiviral agents as either microbicides or carriers for intracellular delivery of antiviral drugs. Intriguing opportunity exists in combining the two modes of antiviral activity in the same polymer structure such that the same polymer acts as a microbicide and also serves to deliver the conjugated drug (ribavirin) into the cells. We explore this opportunity in detail and focus on the polymer backbone as a decisive constituent of such formulations. Fourteen polyanions (polycarboxylates, polyphosphates and polyphosphonates, and polysulfonates) were analyzed for blood pro/anti coagulation effects, albumin binding and albumin aggregation, inhibitory activity on polymerases, cytotoxicity, and anti-inflammatory activity in stimulated macrophages. Ribavirin containing monomers were designed to accommodate the synthesis of macromolecular prodrugs with disulfide-exchange triggered drug release. Kinetics of drug release was fast in all cases however enhanced hydrophobicity of the polymer significantly slowed release of ribavirin. Results of this study present a comprehensive view on polyanions as backbone for macromolecular prodrugs of ribavirin as broad-spectrum antiviral agents.

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP-2 (Pralmorelin), GHRP-6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1-29), which can be used as performance-enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N-terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.

Synthetic polymers make strong contributions as tools for delivery of biological drugs and chemotherapeutics. The most praised characteristic of polymers in these applications is complete lack of pharmacological function such as to minimize the side effects within the human body. In contrast, synthetic polymers with curative pharmacological activity are truly rare. Moreover, such activity is typically nonspecific rather than structure-defined. In this work, we present the discovery of poly­(ethylacrylic acid) (PEAA) as a polymer with a suit of structure-defined, unexpected, pharmacological, and pharmacokinetic properties not observed in close structural analogues. Specifically, PEAA reveals capacity to bind to albumin with ensuing natural hepatic deposition in vivo and exhibits concurrent inhibitory activity against the hepatitis C virus and inflammation in hepatic cells. Our findings provide a view on synthetic polymers as curative, functional agents and present PEAA as a unique biomedical tool with applications related to health of the human liver.

W artykule podjęto temat analizy oraz oceny ryzyka polityki zagranicznej USA w odniesieniu do bezpieczeństwa międzynarodowego. Stany Zjednoczone są mocarstwem światowym, dlatego też trudno zaprzeczyć, że mają one istotny wpływ na bezpieczeństwo. Nie da się nie zauważyć, że są inicjatorem chociażby tak wielkiego projektu, jakim jest NATO, które pośrednio oraz bezpośrednio wpływa na sytuację na arenie międzynarodowej, w tym na bezpieczeństwo. Wydaje się więc właściwe przeprowadzenie analizy w odniesieniu do zagrożeń, które mogą zakłócać proces, jakim jest polityka zagraniczna USA. Realizacja bowiem przez Stany Zjednoczone swojej polityki zagranicznej nie tylko wpływa na ich bezpieczeństwo narodowe, ale także na bezpieczeństwo ich sojuszników oraz ogólnie postrzegane bezpieczeństwo międzynarodowe.

Mycoplasma hominis is associated with various infections, for which the treatment can be complex. Lipoic acid (LA) plays a role as a cofactor in eukaryotes, most Bacteria, and some Archea. Research of recent years has increasingly pointed to the therapeutic proper¬ties of exogenously supplemented LA. The present study was con¬ducted on 40 strains of M. hominis cultured with the following LA concentrations: 1,200 μg/ml, 120 μg/ml, and 12 μg/ml. The bacterial colonies of each strain were counted and expressed as the number of colony-forming units/ml (CFU). The number of CFU in M. homi¬nis strains obtained in the presence of LA was compared with the number of CFU in the strains grown in the media without LA. The obtained results indicated that the presence of LA in the medium did not affect the growth of M. hominis. The investigation of the influence of LA on the growth and survival of microbial cells not only allows for obtaining an answer to the question of whether LA has antimicrobial activity and, therefore, can be used as a drug sup¬porting the treatment of patients infected with a given pathogenic microorganism. Such studies are also crucial for a better under¬standing of LA metabolism in the microbial cells, which is also important for the search for new antimicrobial drugs. This research is, therefore, an introduction to such further studies.

This is the first study to analyze the Polish population of patients undergoing arthroplasty in terms of health care-associated pneumonia. It identifies many factors that can be improved in the perioperative period, which can be of great benefit to patients. It also emphasizes the necessary modification of patient preparation procedures through the implementation of appropriate vaccinations and rehabilitation and puts attention to patients discharged with antibiotics as patients with an increased risk of infectious complications. The whole suggests the need to introduce appropriate infection prevention and control with the elimination of risk factors at the hospital and peri-hospital stages.