Faculty of Medicine
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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, The role of TNF-α-based models in prognostication of the outcomes after ICH: a pilot study(2019-10); ; ; Abstract Introduction: Recently, we have developed TNF-α-based models for prognostication of the 3-month neurological outcome in patients after Intracerebral hemorrhage, ICH (Rendevski et al., 2018). In this pilot study, we aimed to test their utility in the clinical practice for the purposes of identification of the patients who will most likely end up with a poor outcome, as well as to test their utility for clinical decision making between conservative and surgical intervention. Methods: 20 patients with ICH were included initially in this pilot longitudinal study. Their peripheral blood TNF-α levels were screened, and the risk for poor outcome was assessed by using our previously determined cutoff value of > 110.35 pg/mL. The neurological outcome was determined 3 months after the initial hemorrhagic cerebrovascular insult. Another series of 20 threatened patients with TNF-α levels higher than 200 pg/mL were tested for the possibility of lowering the risk of the poor outcome by implementing early craniotomy with hematoma evacuation. Results: The value of > 110.35 pg/mL had fairly identified the patients who later fell into the group with poor outcome, 3 months after ICH (8 out of 9 identified patients with risk for poor outcome have resulted in a poor outcome). In the second series of 20 threatened patients with TNF-α levels higher than 200 pg/mL, early craniotomy and evacuation of the hematoma were shown beneficial; 7 out of 20 patients resulted in a good outcome. Conclusions: TNF-α screening at admission was shown as a useful method for identifying the ICH patients with the highest risk for ending with poor neurological outcome; early craniotomy with hematoma evacuation in the threatened group of patients with the highest TNF-α levels has also shown benefit in lowering the risk for poor outcome and improving patient's neurological state 3 months after ICH. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Validation of the ELISA Method for Quantitative Detection of TNF-α in Patients with Intracerebral Hemorrhage(Scientific Foundation SPIROSKI, 2017-09); - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Inflammatory and oxidative stress markers in intracerebral hemorrhage: preliminary new insights from machine learning and virtual models of infection(2022-12);