Trojachanec, Jasmina

Preferred name

Official Name

Trojachanec, Jasmina

Main Affiliation

jasmina.trojachanec@medf.ukim.edu.mk

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Distribution of CYP2C9 and VKORC1 Gene Polymorphisms in Healthy Macedonian Male Population
(ID Design 2012/Scientific Foundation SPIROSKI, 2013-12-15)
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Aleksandar Senev
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<jats:p>Background: Distribution of CYP2C9 and VKORC1 gene polymorphisms may vary significantly among different ethnic groups, and eventually influence the variation in drug metabolism or even failure.Objective: The aim of this study was to evaluate the prevalence of CYP2C9 and VKORC1 alleles in the healthy population of Republic of Macedonia compared to the global geographic data reported from different ethnic populations. Also, to genotype CYP2C9 and VKORC1 genes and eventually to divide individuals in poor, extensive, or intermediate metabolizer.Material and Methods: Blood samples were collected after signing written consent, DNA was isolated from peripheral blood, and CYP2C9 and VKORC1 genes were typed (n=124). Genotyping was performed by commercially available kits (GeneID GmbH, Strassberg, Germany, AID Diagnostica), based on the method of polymerase chain reaction with a subsequent hybridization. The population genetics analysis package, PyPop ver. 0.6.0, was used for analysis of the data.Results: The frequency of alleles varies from 0.931 for CYP2C9*3 to 0.109 for CYP2C9*2 indicating common “wild type” allele in those genes. The frequency ranges spanned ~50% for each allele of VKORC1 gene, indicating no common “wild type” allele in this gene. Test of neutrality showed significant negative value for VKORC1 polymorphism that indicates balancing selection operating on the alleles at that locus. All polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 showed a good fit with Hardy-Weinberg expectations.Conclusion: The results of polymorphic alleles of CYP2C9 and VKORC1 genes in Macedonian population can be used for the variation in drug metabolism studies as well for adapting dosage regimes for oral anticoagulant therapies.</jats:p>
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A New Solid-Phase Extraction Method for Determination of Pantoprazole in Human Plasma Using High-Performance Liquid Chromatography
(ID Design 2012/Scientific Foundation SPIROSKI, 2019-06-15)
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A new simple, selective and accurate high-performance liquid chromatographic (HPLC) method utilising solid-phase extraction for the determination of pantoprazole in human plasma samples has been developed.
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Comparative, single-dose bioavailability study of two 500 mg clarithromycin tablet formulations in healthy volunteers under fasting condition
(Macedonian Pharmaceutical Society, 2019)
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Clarithromycin is a semi-synthetic macrolide antibiotic, chemically 6-0- methylerythromycin, formulated as immediate-release tablets, extended-release tablets, and granules for oral suspension. The objective of this study was to evaluate and compare the relative bioavailability, and therefore the bioequivalence of Clarithromycin 500 mg test formulation versus a reference Klacid® forte 500 mg formulation, following a single dose administration under fasting conditions. The study was a single center, open, single dose, randomized, two-way crossover study in healthy male volunteers, with a wash-out period of one week between study periods. Twenty-four male healthy volunteers, aged 18-49 years were included into study. Blood samples for determination of clarithromycin and 14-OH clarithromycin concentrations were withdrawn at zero (pre-drug administration), 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 and 36 hours post-drug administration. The determination of clarithromycin and 14-OH clarithromycin concentrations in plasma was performed using validated LC/MS/MS method and internal standardization after liquid/liquid extraction with methyl t-butyl ether. The test formulation of clarithromycin, dosed at 500 mg is bioequivalent for primary clarithromycin and 14-OH clarithromycin parameters (Cmax, AUC0-t and AUC0-∞) to the reference formulation after a single oral administration of 500 mg clarithromycin. Both medications were well tolerated with no serious adverse events. Thus, in view of the clinical use, both formulations are exchangeable without restrictions.
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Prognostic significance of serum levels of tumor markers CEA and CA19-9 in patients with colorectal cancer
(Македонско лекарско друштво = Macedonian medical association/De Gruyter, 2012)
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Effects of Dual RAAS Blockade with Candesartan and Perindopril on Functional Renal Tests in Streptozotocin Induced Diabetic Nephropathy
(Scientific Foundation SPIROSKI, 2013-09-15)
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Serum Matrix Metalloproteinase-2, -7 and -9 (MMP-2, MMP-7, MMP-9) levels as Prognostic Markers in Patients with Colorectal Cancer
(University of Sarajevo Faculty of Health Sciences, 2012-12-15)
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<jats:p>Introduction: Matrix metalloproteinases are produced by tumour cells, hence, they may be associated with tumour progression including invasion, migration, angiogenesis and metastasis. Finding prognostic markers to better identify patients with higher risk for poor survival would be valuable in order to customize pre- and postoperative treatment as well as to enable closer follow-up of these patients. Aim of our study was to examineMMP-2, MMP-7 and MMP-9 serum levels and correlated them with pathological data such as stage of the colorectal cancer (CRC) and outcome.Methods: The investigation included 82 patients with operable CRC without distant metastases, who had underwent blood tests in order to determine the MMP-2, MMP-7 and MMP-9 serum levels in the following time periods: preoperatively, 3, 6, 9 and 12 months postoperatively.Results: The values of the investigated MMPs decrease postoperatively and start to increase 6 month later in patients of all stages of the disease, reaching the highest value 12 month postoperatively with statistically important differences of MMP-2, MMP-7 and MMP-7 serum levels in terms of disease staging and defined points of time. Analysis of the results showed that the MMP-2 serum levels obtained 3 and 12 months postoperatively,than MMP-7 serum levels 12 months postoperatively and the MMP-9 serum levels in all analyzed points in time were in significant association with the CRC patients’outcome.Conclusion: The MMP-2, MMP-7 and especially MMP-9 serum values could be important indicators for diagnosis of the patients with CRC and for monitoring of disease progression.</jats:p>
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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.
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AORTIC DISSECTION: OFTEN NEGLECTED DIFFERENTIAL DIAGNOSIS IN EMERGENCY AMBULANCE SERVICES
(MIT University Skopje, 2024-03)
Furnadjiski, Atanas
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Antova, I
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Abazi, A
Introduction: Aortic dissection is a rupture of the aortal medial layer produced by intramural hemorrhage that leads in a separation of the aortic wall layers, forming a false and true lumen with or without communication and is highly lethal. It causes a variety of symptoms, which can be discrete and subacute, or chronic, and is frequently misdiagnosed. Aim: This case report aims to present a case of a rare, subtle manifestation of transient ischemic attack caused by an aortic dissection. Case report: A 76-year-old man came to the Emergency Medical Service complaining of recent back and left shoulder pain accompanied by discomfort, as well as left-sided tingling of the face, arm, and leg, along with left hand weakness, that had occurred multiple times in the previous five days and lasted three to four minutes. On admission, he was clinically stable and had normal vital signs, without any neurological deficit. The ECG examination revealed RBBB without ST segment abnormalities. The anamnestic and hetero-anamnestic data were completely consistent with a cerebrovascular transient ischemic attack that occurred three days prior. After reevaluating the patient clinical status that was unchanged, he experienced temporary weakness, sweating, and dizziness revealed by shifting from supine to straight position, which was instantly relieved by kneeling down on the floor. The patient was immediately referred to secondary care. While a CT of the brain revealed normal findings, the CT angiography of the aorta showed an infrarenal aneurismatic dilatation with a 4cm wide flap indicative of impending aortal dissection. The patient was promptly referred to a tertiary care for further examination and medical care. Conclusion: Aortal dissection can easily go undetected in the Emergency Medical Services due to its pleomorphic clinical presentation, which oscillates between acute hemodynamic shocks to subtle, often undetectable symptomatology. Awareness of aortic dissection as differential diagnosis should be promptly lifted to a higher order thinking.
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The effect of Coenzyme Q10 in Cisplatin induced myelosuppression in rats
(Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, 2022-12)
Shikole, Emilija
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Kocheva, Nedica
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Coenzyme Q10 (2,3 dimethoxy-5 methyl-6decaprenyl benzoquinone - CoQ10) is a lipid-soluble antioxidant, vitamin-like quinone commonly known as ubiquinone or vitamin CoQ10 present in all tissues and membranes in the body. CoQ10 plays an important role in the mitochondrial respiratory chain, for synthesis of adenosine triphosphate (ATP). Further, it protects the phospholipids and the proteins in the mitochondrial membrane, from lipid peroxidation (Saini, 2011). On the contrary, Cisplatin, is an antineoplastic drug that is used for treating wide spectrum of human malignancies. However, its therapeutic outcome is limited due to development of nephrotoxicity and myelosuppression. Few mechanisms are involved such as generation of free radicals, inhibition of protein synthesis and lipid peroxidation of the membranes. One of the most important targets of Cisplatin are the mitochondrias, where it reduces the amount of ATP, and consequently increases the ROS species (Choy et al., 2015). The development of new pharmacological/therapeutical approaches and using supplements that aim the same targets as the chemotherapy but in the opposite direction, becomes a game-changer recently. Several clinical studies provided evidence supporting the use of supplements in preventing of Cisplatin induced damage of the bone marrow cells (Lin et al., 2020; Sinha et al., 2015). Therefore, the aim of this study was to evaluate the influence of the supplementation with CoQ10 on the myelosuppression induced by the treatment with Cisplatin on rats.
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Улогата на ендоетелин-1 во развојот на дијабетична нефропатија индуцирана со стрептозоцин
(Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, 2006)
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Dijabeticnata nefropatija pretstavuva edna od hronicnite mikrovaskularni komplikacii na dijabetot, so multifaktorijalna i ne do kraj rasvetlena etiopatogeneza. So ogled na toa sto kaj pacientite so dijabet, osobeno kaj onie so dijabeticna nefropatija, se najdeni zgolemeni vrednosti na endotelin-1, se pretpostavuva deka istiot mozhe da ima znacajna uloga vo razvojot na dijabeticnata nefropatija. Osnovna cel na nashata studija beshe da se detektiraat promenite vo plazmatskoto nivo na endotelin-1 po eksperimentalno induciran dijabet, i dijabeticna nefropatija kaj staorci so streptozocin. So ogled na dobro poznatite efekti na AKE-inhibitorite, vo ovaa studija go ispituvavme i vlijanieto na enalapril (AKE inhibitor) na plazmatskite koncentracii na endotelin-1, kako i negovite efekti vo tretmanot na dijabeticna nefropatija. Ednokratnata i.p. administracija na streptozocin (STZ) predizvika signifikantno zgolemuvawe na plazmatskite koncentracii na endotelin-1, proprateni so jasno izrazeni simptomi i znaci na dijabeticna nefropatija (mikroalbuminurija, zgolemeni urinarni vrednosti na N-acetyl-fl-D-glucosamidase, zgolemeni serumski koncentracii na urea, poliurija). Cetiri nedelniot tretman so enalapril dovede do signifikantno namaluvawe na plazmatskite koncentracii na endotelin-1 i do podobruvawe na simtomite i znacite na dijabeticnata nefropatija. Dobienite rezultati potvrduvaat deka endotelin-1 mozhe da ima znacajna uloga vo razvojot i progresijata na dijabeticnata nefropatija, a AKE inhibitorite, odnosno enalapril, mozhat da ja ublazhat i usporat progresijata na dijabeticnata nefropatija.

Trojachanec, Jasmina

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