GJorgoski, Icko

Preferred name

GJorgoski, Icko

Official Name

GJorgoski, Icko

Main Affiliation

icko@pmf.ukim.mk

Now showing 1 - 10 of 16

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Inflammatory and oxidative stress markers in intracerebral hemorrhage: Relevance as prognostic markers for quantification of the edema volume
(Wiley, 2023-03)
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Aleksovski, Boris
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Mihajlovska Rendevska, Ana
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We aimed to analyze the inflammatory and oxidative stress (OS) markers after intracerebral hemorrhage (ICH) and their temporal changes, interaction effects, and prognostic values as biomarkers for the prediction of the edema volume. Our prospective, longitudinal study included a cohort group of 73 conservatively treated patients with ICH, without hematoma expansion or intraventricular bleeding, which were initialized with the same treatment and provided with the same in-hospital care during the disease course. Study procedures included multilevel comprehensive analyses of clinical and neuroimaging data, aligned with the exploration of 19 inflammatory and five OS markers. White blood cells (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophilia, and lymphopenia peaked 3 days post-ICH, and they showed much stronger correlations with clinical and neuroimaging variables, when compared to the admission values. An intricate interplay among inflammatory (WBC, CRP, neutrophils, neutrophil-to-lymphocyte ratio [NLR], interleukin (IL)-6, and IL-10) and OS mechanisms (catalase activity and advanced oxidation protein products [AOPP]) was detected operating 3-days post-ICH, being assessed as relevant for prediction of the edema. The overall results suggested complex pathology of formation of post-ICH edema, via: (A) Not additive, but statistically significant synergistic interactions between CRP-ESR, neutrophils-CRP, and neutrophils-IL-6 as drivers for the edema formation; (B) Significant antagonistic effect of high protein oxidation on the CRP-edema dependence, suggesting a mechanism of potential OS-CRP negative feedback loop and redox inactivation of CRP. The final multiple regression model separated the third-day variables NLR, CRP × AOPP, and WBC, as significant prognostic biomarkers for the prediction of the edema volume, with NLR being associated with the highest effect size. Our developed mathematical equation with 3D modeling for prediction and quantification of the edema volume might be beneficial for taking timely adequate strategies for prevention of delayed neurological deteriorations.
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A Comprehensive Molecular and Epidemiological Characterization of Influenza Viruses Circulating 2016-2020 in North Macedonia
(Frontiers Media SA, 2021)
Kuzmanovska, Maja
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Boshevska, Golubinka
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Janchevska, Elizabeta
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Buzharova, Teodora
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Simova, Milica
Influenza viruses know no boundaries, representing an example of rapid virus evolution combined with pressure exerted by the host's immune system. Seasonal influenza causes 4-50 million symptomatic cases in the EU/EEA each year, with a global death toll reaching 650,000 deaths. That being the case, in 2014 North Macedonia introduced the sentinel surveillance in addition to the existing influenza surveillance in order to obtain more precise data on the burden of disease, circulating viruses and to implement timely preventive measures. The aims of this study were to give a comprehensive virological and epidemiological overview of four influenza seasons (2016-2020), assess the frequency and distribution of influenza circulating in North Macedonia and to carry out molecular and phylogenetic analyses of the hemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09, A(H3N2) from ILI and SARI patients. Our results showed that out of 1,632 tested samples, 46.4% were influenza positive, with influenza A(H1N1)pdm09 accounting for the majority of cases (44%), followed by influenza B (32%) and A(H3N2) (17%). By comparing the sentinel surveillance system to the routine surveillance system, we showed that the newly applied system works efficiently and gives great results in the selection of cases. Statistically significant differences (p = < 0.0000001) were observed when comparing the number of reported ILI cases among patients aged 0-4, 5-14, 15-29, and 30-64 years to the reference age group. The phylogenetic analysis of the HA sequences unveiled the resemblance of mutations circulating seasonally worldwide, with a vast majority of circulating viruses belonging to subclade 6B.1A. The PROVEAN analysis showed that the D187A substitution in the receptor binding site (RBS) of the A(H1N1)pdm09 HA has a deleterious effect on the its function. The A(H3N2) viruses fell into the 3C.2a and 3C.3a throughout the analyzed seasons. Molecular characterization revealed that various substitutions in the A(H3N2) viruses gradually replaced the parental variant in subsequent seasons before becoming the dominant variant. With the introduction of sentinel surveillance, accompanied by the advances made in whole-genome sequencing and vaccine therapeutics, public health officials can now modify their approach in disease management and intervene effectively and in a timely manner to prevent major morbidity and mortality from influenza.
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In-depth genetic characterization of the SARS-CoV-2 pandemic in a two-year frame in North Macedonia using second and third generation sequencing technologies
(Frontiers Media SA, 2023-01-04)
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Boshevska, Golubinka
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Janchevska, Elizabeta
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Buzharova, Teodora
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Preshova, Ardian
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a persistent negative impact on both the public health and the global economy. To comprehend the origin, transmission routes and discover the mutations that alter the virus’s transmissibility and pathogenicity, full-length SARS-CoV-2 genomes have to be molecularly characterized. Focusing on a two-year time frame (2020-2021), we provide an in-depth virologic and epidemiological overview of the SARS-CoV-2 pandemic in the Republic of North Macedonia by assessing the frequency and distribution of the circulating SARS-CoV-2 variants. Using genetic characterization and phylogenetic analysis we shed light on the molecular evolution of the virus as well as test for a possible connection between specific SARS-CoV-2 haplotypes and the severity of the clinical symptoms. Our results show that one fifth (21.51%) of the tested respiratory samples for SARS-CoV-2 were positive. A noticeable trend in the incidence and severity of the COVID-19 infections was observed in the 60+ age group between males and females. Of the total number of positive cases, the highest incidence of SARS-CoV-2 was noticed in 60+ males (4,170.4/100,000), with a statistically significant (0,0001) difference between the two sexes. Additionally, a 1.8x increase in male mortality and consequentially significantly higher number of death cases was observed compared to females of the same age group (0.001). A total of 327 samples were sequenced in the period March 2020 - August 2021, showing the temporal distribution of SARS-CoV-2 variants circulating in North Macedonia. The phylogenetic analysis showed that most of the viral genomes were closely related and clustered in four distinctive lineages, B.1, B.1.1.7, B.1.351 and B.1.617.2. A statistically significant difference was observed in the 2C_1 haplotype (p=0.0013), where 10.5% of the patients were hospitalized due to severe clinical condition. By employing genetic sequencing, coupled with epidemiological investigations, we investigated viral distribution patterns, identified emerging variants and detected vaccine breakthrough infections. The present work is the first molecular study giving a comprehensive overview of the genetic landscape of circulating SARS-CoV-2 viruses in North Macedonia in a period of two years.
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Platelet-rich plasma as a promising bioscaffold for enhancing peripheral nerve regeneration: An experimental study in a rat sciatic nerve model
(Journal of Biological Methods, 2025)
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Aleksovski, Boris
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Tusheva, Sofija
Despite advancements in surgical treatments, impairments persist after peripheral nerve injuries, prompting a shift in research toward the microenvironment of injured axons. Platelet-rich plasma (PRP), rich in growth factors and derived from autologous blood, emerges as a potential candidate to accelerate nerve healing.
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Evaluation of peripheral serotonin content and α2-adrenergic receptor function as potential markers for life-long recurrent depressive disorder by using methodological improvements
(Informa UK Limited, 2018-09)
Aleksovski, Boris
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Vujović, Viktorija
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We aimed to evaluate the role and the relations between peripheral platelet serotonin content, blood plasma serotonin concentration and the function of platelet α2-adrenergic receptors (α2-AR) as potential state or trait biomarkers for recurrent depressive disorder (RDD).
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Modeling prognostic factors for poor neurological outcome in conservatively treated patients with intracerebral hemorrhage: A focus on TNF-α
(Elsevier BV, 2018-09)
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Aleksovski, Boris
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Stojanov, Dragan
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Mihajlovska Rendevska, Ana
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Aleksovski, Vasko
Prognostic models for Intracerebral hemorrhage (ICH), mainly based on clinical evaluation, have remained inherently confounded by subjective scoring assessments and limited accuracy. In this study, we aimed at assessing the risk for poor outcome after ICH based on peripheral biochemical markers (TNF-α, glutamate and glucose) and radiological variables (both at admission and five days after patient's care), for modeling purposes of prognostication.
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Surgical Outcome in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage
(Walter de Gruyter GmbH, 2017-12-01)
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Stojanov, Dragan
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Aleksovski, Boris
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Mihajlovska Rendevska, Ana
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<jats:title>Summary</jats:title> <jats:p>The aim of the paper was to evaluate the surgical outcome in patients with spontaneous supratentorial intracerebral hemorrhage (ICH) after surgical intervention, in respect to the initial clinical conditions, age, sex, hemispheric side and anatomic localization of ICH. Thirty-eight surgically treated patients with spontaneous supratentorial intracerebral hemorrhage were included in the study. The surgical outcome was evaluated three months after the initial admission, according to the Glasgow Outcome Scale (GOS). The surgical treatment was successful in 14 patients (37%), whereas it was unsuccessful in 24 patients (63%). We have detected a significant negative correlation between the Glasgow Coma Scale (GCS) scores on admission and the GOS scores after three months, suggesting worse neurological outcome in patients with initially lower GCS scores. The surgical outcome in patients with ICH was not affected by the sex, the hemispheric side and the anatomic localization of ICH, but the age of the patients was estimated as a significant factor for their functional outcome, with younger patients being more likely to be treated successfully. The surgical outcome is affected from the initial clinical state of the patients and their age. The treatment of ICH is still an unsolved clinical problem and the development of new surgical techniques with larger efficiency in the evacuation of the hematoma is necessary, thus making a minimal damage to the normal brain tissue, as well as decreasing the possibility of postoperative bleeding.</jats:p>
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Peripheral glutamate and TNF-α levels in patients with intracerebral hemorrhage: Their prognostic values and interactions toward the formation of the edemal volume
(VM Media SP. zo.o VM Group SK, 2018-03)
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Aleksovski, Boris
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Stojanov, Dragan
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Aleksovski, Vasko
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Mihajlovska Rendevska, Ana
We aimed to evaluate the prognostic values, contribution and interactions of the peripheral blood plasma glutamate and tumor-necrosis factor-α (TNF-α) levels toward the formation of the perifocal edema in patients with intracerebral hemorrhage (ICH).
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SSRI-reduced platelet reactivity in non-responding patients with life-long Recurrent Depressive Disorder: Detection and involved mechanisms
(Elsevier BV, 2018-05)
Aleksovski, Boris
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Neceva, Violeta
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Vujović, Viktorija
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Adverse effects with bleeding disorders are often associated with the administration of SSRI in depression, although the exact mechanisms remain contradicting. This study is aimed at detecting and exploring the mechanisms of SSRI-induced changes in platelet reactivity in non-responding patients with Recurrent Depressive Disorder (RDD) and life-long exposure to antidepressants.
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THE EFFECTS OF COENZYME Q10 MICELLAR SOLUTION AND NANOLIPOSOMES ON SUPEROXIDE DISMUTASE (SOD) ACTIVITY IN CISPLATIN-INDUCED OXIDATIVE STRESS IN RATS
(SHMSHM - AAMD, 2023)
Shikole, Emilija
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Introduction: CoenzymeQ10 (CoQ10) is a lipid-soluble antioxidant that plays a key role in the mitochondria respiratory chain in the synthesis of adenosine triphosphate (ATP). It combats the oxidative stress in the body via increasing endogenous cellular defense system represented by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Cisplatin is an antineoplastic drug used for treatment of various human malignances but because of its cytotoxicity, the therapeutic outcome of this drug is limited. Namely, it causes oxidative stress in the body by reducing the levels for glutathione (GSH), SOD, GpX, CAT and GR. Therefore, the aim of this study was to evaluate the influence of the CoQ10 supplementation (in a form of micellar solution or encapsulated into nanoliposomes) on SOD activity in oxidative stress, induced by the treatment with Cisplatin on rats. Materials and methods: 90 normotensive Wistar rats (250-300 g) were included in this study. The animals were divided in 6 groups, each consisting of 15 rats. Cisplatin (5 mg/kg) and different formulations/combinations with CoQ10 (micellar solution or nanoliposomes dispersion, 10 mg/kg) were administrated i.p. After 12 days, both kidneys were removed for measuring of SOD activity in the tissue. SOD activity was determined by the autoxidation of pyrogallol spectrophotometrically at 420 nm. Statistical analysis was performed using Statistica 7.1 for Windows. Significance was determined at p<0.05 Results: CoQ10 nanoliposome treated group showed significantly increased SOD activity, compared to all other five groups. CoQ10 nanoliposome/Cisplatin treated group showed significantly increased SOD activity compared to the Cisplatin group. Additionally, CoQ10/Cisplatin group showed increased kidney SOD activity, compared to the Cisplatin group. Conclusion: According to these results, CoQ10, as a potent antioxidant and encapsulated into nanoliposomes could be one of the possible solutions to reduce the oxidative stress and nephrotoxicity caused by the cisplatin treatment as a side effect, which is a common reason for reducing or discontinuing therapy.

GJorgoski, Icko

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