Faculty of Medicine
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Item type:Publication, PHARMACOEPIDEMIOLOGY AND ANTIMICROBIAL RESISTANCE DATA FOR BACTERIAL INFECTIONS IN HOSPITALIZED CHILDREN(Македонско лекарско друштво = Macedonian medical association/De Gruyter, 2019); Antimicrobial resistance is a global problem that needs an urgent action. The irrational use of antibiotics is widespread and leads to potential usefulness of medicines and negative therapeutic outcome.In April 2016, WHO stated that the problem of antibiotic resistance is a major clinical problem resulting in treatment failures even in a case ofeasy to treat diseases. Resistance to first line medicines results in huge spending on new generation of antibiotics. In some instances resistance to second- and third-line agents is seriously compromising treatment outcome.Seriousness of the situation requires extensive research and constantly monitoring of the spread of bacteria resistance.Another problem regarding bacteria resistance is the lack of new antibiotics reported by the US Center for Control and Prevention of Disease.A systematic literature search of databasesgave us enough information about the use of antibiotics, most often isolated bacteria and resistance to different classes of antibiotics. According to the official data, bacterial resistance is lowest in the countries where guidelines for prescribing and use of antibiotics are consistently implemented, such as Scandinavian countries, The Netherlands, Germany and Great Britain. It is necessary to create a complete database of bacterial resistance and information on whether patients receive medicines appropriate to their clinical conditionin our country. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, SMALL ANIMAL MODEL IN THE DEVELOPMENT OF RADIOPHARMACEUTICALS - THE STEP FORWARD TOCLINICAL STUDIES(Faculty of Veterinary Medicine - Skopje, 2022); ; Darkovska Serafimovska, MarijaExperimental design is a critical component for the success of research activities involving development and evaluation of new radiopharmaceuticals. Experimental animal models have substantially contributed to a better understanding of mechanisms of disease and show the novel approaches in imaging and image analysis were equally important to meet the challenges of analyzing the complex mechanisms underlying pathophysiological processes in vivo. Proper animal models are key factors for successful pharmaceutical and medicinal experiments. To reduce animal number for ethical and nancial reasons, cost-ef cient methods where high quantities of data are achieved fast are optimal. Biodistribution and pharmacokinetics studies diagnostic or therapeutic radiopharmaceuticals by SPECT or PET imaging followed by post mortem analysis in diseases model gives a good start point for further steps toward clinical applications. In this presentation, targeting properties, biodistribution and pharmacokinetics of different molecules, as potential radiopharmaceuticals have been studied in small animal models using suitable imaging modalities and post mortem analysis. The following experimentally designed animal models have been introduced in our work so far as an essential part in the development of new radiopharmaceutical products and quality control of existing radiopharmaceutical products. Rat models were used to establish: stasis-induced thrombus in the femoral vein after injection of thromboplastin to demonstrate Deep Venous Thrombosis; induced amyloidosis by multiple application of beta2-microglobulin for determination of the existence of the depositing osteoarticular tissues, condition associated with hemodialysis in patients with chronic kidney diseases; collagen-induced arthritis as a model of in ammatory arthritis; bacterial abscesses by the injection of Staphylococcus aureus. Mouse models were used for: in vivo evaluation of the radiolabelled conjugated antibodies in normal Balb/c mice and nude mice xenografts; per os administration of iodine labeled BSA loaded microspheres to show the strong adjuvant effect by inducing IgA secretion at the genito-urinary mucosa; athymic nude mice tumor bearning to demonstratespeci ty of pre-targeting technique referred to the Af nity Enhancement System (AES) uses bispeci c antibodies and radiolabeled bivalent haptens. The use of experimental animal models in the design of new drugs including radiopharmaceuticals is a key part of preclinical trials. Usually this approach can not fully replicate human disease or the varied and complex physical and psychological manifestations of human conditions. For these reasons the process of experimental design should be carried out routinely to ensure the generation of valid, reproducible and published data. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Pharmacological approach for treatment of influenza(INSTITUTE OF KNOWLEDGE MANAGEMENT SKOPJE, 2021-08); Darkovska Serafimovska, MarijaInfluenza is a viral disease which happens most often in the autumn and winter months. The most common symptoms that occur are fever, cold, sore throat, muscle aches, headaches, cough, weakness, and lethargy. There are several types of influenza viruses (A, B and C), of which the most common type in human are A (H1N1) and type B viruses. Influenza virus belongs to the group of enveloped viruses - it has a coating that originates from the membrane of the host cell that the virus carries with it when it leaves the cell. Hemagglutinin and neuraminidase are the two main types of glycoproteins present in the outer shell of influenza viruses. The M2 protein, which is a transmembrane channel present in the virus shell, passes through the lipid layer. Immediately below the lipid sheath is another protein called the matrix protein, or M1, which is positioned to enclose the nucleus of the virion on all sides. Inside the central nucleus of the virion are a non-structural protein and a ribonucleoprotein complex (RNP). The RNP complex consists of 8 gene segments of varying lengths, while the RNA-dependent RNA polymerase is a heterotrimer consisting of 2 polymerase bases (PB1 and PB2) and one polymerase acid subunit. All these sites are target sites for influenza medications. Methods for treatment to influenza vary depending on the severity of the disease. There are several approved medications for therapy of influenza available on the market. Neuraminidase inhibitors (oseltamivir, zanamir) are the most used medicines. To overcome the limitations of these medicines (due to rapid mutations and resistance of the virus to neuraminidase inhibitors), several attempts have been made to develop new medicines against the influenza virus. Some of them are already approved (baloxavir approved in 2018 in Japan and the United States and favipiravir - nucleoside analogue which after oral ingestion is phosphoribosylated intracellularly to be transformed into an active form) or are in an advanced (second) stage of development (pimodivir which inhibits viral replication and monoclonal antibodies). Oseltamivir due to its ease way of administration (perorally) remains the medicine of choice for the treatment of influenza. However, although neuraminidase inhibitors (especially oseltamivir) remain the medicine of choice for influenza treatment, their overuse should be avoided. Accurate selection of patients who really need this treatment is necessary. There are a number of preventive measures we can take to protect ourselves from this virus and to prevent its spread. But, vaccines remain the best option for reducing the number of infections and complications that can occur from the influenza virus.