Browsing by Author "Todorović, Zoran (7004371236)"

Statins might cause and/or aggravate the immune-mediated myositis in patients on long-term, stable treatment. We provide a case of polymyositis with an immunological background and gastrointestinal and urinary manifestations in patient on long-term, stable atorvastatin treatment for the past six years. The diagnose of polymyositis was established based on clinical symptoms and signs, electromyography and laboratory test results (elevated aspartate aminotransferase 279 U/L, reference range 0-40 U/L; alanine aminotransferase 198 U/L, 0-33 U/L; lactate dehydrogenase 2200 U/L, 103-227 U/L; creatine kinase 7820 U/L, 15-84 U/L; and positive antinuclear antibodies test, titer of 1:160, with suspect antisynthetase antibodies). Polymyositis was probably related to atorvastatin treatment (Naranjo score, 5). Other probable causes of the myositis were rejected. Coricosteroid therapy, methotrexate and supplementation with vitamin D did not improve the condition. The patient remained bedridden and died two months after the hospital discharge due to the acute myocardial infarction. © 2014 Versita and Springer-Verlag.

[No abstract available]

Acute coronary syndrome (ACS) in patients with COVID-19 is triggered by various mechanisms and can significantly affect the patient’s further treatment and prognosis. The study aimed to investigate the characteristics, major complications, and predictors of mortality in COVID-19 patients with ACS. All consecutive patients hospitalized from 5 July 2020 to 5 May 2021 for ACS with confirmed SARS-Co-2 were prospectively enrolled and tracked for mortality until 5 June 2021. Data from the electronic records for age and diagnosis, matched non-COVID-19 and COVID-19 ACS group, were extracted and compared. Overall, 83 COVID-19 ACS patients, when compared to 166 non-COVID ACS patients, had significantly more prevalent comorbidities, unfavorable clinical characteristics on admission (acute heart failure 21.7% vs. 6.6%, p < 0.01) and higher rates of major complications, 33.7% vs. 16.8%, p < 0.01, and intrahospital 30-day mortality, 6.7% vs. 26.5%, p < 0.01. The strongest predictors of mortality were aortic regurgitation, HR 9.98, 95% CI 1.88; 52.98, p < 0.01, serum creatinine levels, HR 1.03, 95% CI 1.01; 1.04, p < 0.01, and respiratory failure therapy, HR 13.05, 95% CI 3.62; 47.01, p < 0.01. Concomitant ACS and COVID-19 is linked to underlying comorbidi-ties, adverse presenting features, and poor outcomes. Urgent strategies are needed to improve the outcomes of these patients. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

The choice of an antiepileptic drug (AED) is usually based upon the epileptic seizure type. However, pharmacokinetic (PK) characteristics of AEDs may be valuable support in choosing the optimal therapeutic option for the individual patient. The novel (second and third generation) AEDs include: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. Although, these drugs belong to the same group, their individual PK characteristics differ. Gabapentin, unlike other new AEDs, is characterised by dose-dependent absorption, which is presumably caused by saturable L-amino acid transport system, and therefore its bioavailability ranges from 35-60%. Furthermore, gabapentin, pregabalin and vigabatrin are eliminated completely, while levetiracetam and topiramate are eliminated predominantly through the renal system. Therefore, PK variability of these individual drugs is less pronounced and more predictable in comparison to older AEDs. Their potential for drug interactions is minor, and consequently they have major clinical importance for patients with impaired hepatic function. On the other hand, felbamate, lamotrigine, oxcarbazepine, tiagabine and zonisamide are eliminated via metabolic pathways, either cytochrome P (CYP) 450, or conjugation dependent transformation. Oxcarbazepine is a prodrug, and its active metabolite is licarbazepine. These drugs interact with other drugs, and disease conditions, which alter the activity of metabolic enzymes; thus these changes in PK commonly have clinical implications. Gabapentin, levetiracetam and tiagabine do not induce or inhibit hepatic metabolism enzymes. Felbamate demonstrated an inducing effect on CYP 3A4 isoenzyme, and inhibition effect on CYP 2C19 and on β-oxidation of valproic acid. Lamotrigine induces its own metabolism, and some reports imply a decrease of valproic acid levels during concomitant treatment with lamotrigine. Oxcarbazepine induces CYP 3A4, 3A5, and uridine diphosphate glucuronyl transfereases (UGT), and inhibits the metabolism of phenytoin via CYP 2C19 isoenzyme. Similar induction and inhibition characteristics are attributed to topiramate, while some studies indicate that zonisamide may have inhibition potential on phenytoin metabolism. In general, novel AEDs have linear PK, low plasma protein binding, and renal elimination, so their PK is more favorable in comparison with carbamazepine, phenobarbitone and valproic acid. This chapter gives a review of PK parameters of novel AEDs and its' variability based on age, comorbidities, concomitant therapy, and highlights the need of therapeutic drug monitoring. © 2012 Nova Science Publishers, Inc. All rights reserved.

The choice of an antiepileptic drug (AED) is usually based upon the epileptic seizure type. However, pharmacokinetic (PK) characteristics of AEDs may be valuable support in choosing the optimal therapeutic option for the individual patient. The novel (second and third generation) AEDs include: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. Although, these drugs belong to the same group, their individual PK characteristics differ. Gabapentin, unlike other new AEDs, is characterised by dose-dependent absorption, which is presumably caused by saturable L-amino acid transport system, and therefore its bioavailability ranges from 35-60%. Furthermore, gabapentin, pregabalin and vigabatrin are eliminated completely, while levetiracetam and topiramate are eliminated predominantly through the renal system. Therefore, PK variability of these individual drugs is less pronounced and more predictable in comparison to older AEDs. Their potential for drug interactions is minor, and consequently they have major clinical importance for patients with impaired hepatic function. On the other hand, felbamate, lamotrigine, oxcarbazepine, tiagabine and zonisamide are eliminated via metabolic pathways, either cytochrome P (CYP) 450, or conjugation dependent transformation. Oxcarbazepine is a prodrug, and its active metabolite is licarbazepine. These drugs interact with other drugs, and disease conditions, which alter the activity of metabolic enzymes; thus these changes in PK commonly have clinical implications. Gabapentin, levetiracetam and tiagabine do not induce or inhibit hepatic metabolism enzymes. Felbamate demonstrated an inducing effect on CYP 3A4 isoenzyme, and inhibition effect on CYP 2C19 and on β-oxidation of valproic acid. Lamotrigine induces its own metabolism, and some reports imply a decrease of valproic acid levels during concomitant treatment with lamotrigine. Oxcarbazepine induces CYP 3A4, 3A5, and uridine diphosphate glucuronyl transfereases (UGT), and inhibits the metabolism of phenytoin via CYP 2C19 isoenzyme. Similar induction and inhibition characteristics are attributed to topiramate, while some studies indicate that zonisamide may have inhibition potential on phenytoin metabolism. In general, novel AEDs have linear PK, low plasma protein binding, and renal elimination, so their PK is more favorable in comparison with carbamazepine, phenobarbitone and valproic acid. This chapter gives a review of PK parameters of novel AEDs and its' variability based on age, comorbidities, concomitant therapy, and highlights the need of therapeutic drug monitoring. © 2012 Nova Science Publishers, Inc. All rights reserved.

In the published article, there was an error in the Author list, and author Elise Courtot was erroneously excluded. The corrected author list appears below. “Maja Stojković1, Zoran Todorović1, Dragana Protić1, Strahinja Stevanovic2, Dragana Medić3, Claude L. Charvet4, Elise Courtot4, Djordje S. Marjanović3, Jelena Nedeljković Trailović5, Saša M. Trailović3,*” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Copyright © 2024 Stojković, Todorović, Protic, Stevanovic, Medić, L. Charvet, Courtot, Marjanović, Nedeljković Trailović and Trailović.

In the published article, there was an error in the Author list, and author Elise Courtot was erroneously excluded. The corrected author list appears below. “Maja Stojković1, Zoran Todorović1, Dragana Protić1, Strahinja Stevanovic2, Dragana Medić3, Claude L. Charvet4, Elise Courtot4, Djordje S. Marjanović3, Jelena Nedeljković Trailović5, Saša M. Trailović3,*” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Copyright © 2024 Stojković, Todorović, Protic, Stevanovic, Medić, L. Charvet, Courtot, Marjanović, Nedeljković Trailović and Trailović.

Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgin coconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to control glycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementation with coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity of steatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on heart histology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither in non-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementation with coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development of severe insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contraindicated in diabetic condition. © 2019 Elsevier Ltd

Non-diabetic and alloxan-induced diabetic rats were fed with standard laboratory food enriched with 20% virgin coconut oil for 16 weeks. In non-diabetic animals coconut oil improved insulin sensitivity and ability to control glycaemia and decreased the serum triglycerides for almost 50% in comparison with controls. Supplementation with coconut oil caused liver steatosis in both non-diabetic and diabetic animals. However, the severity of steatosis was lower in diabetic animals compared to non-diabetic animals. Coconut oil had no effects on heart histology, ascending and abdominal aorta wall thickening and atherosclerotic plaques development neither in non-diabetic nor in diabetic animals. While alloxan treatment caused Type I diabetes in rats, supplementation with coconut oil in combination with the alloxan unexpectedly resulted in Type II diabetes. The development of severe insulin resistance and deterioration in serum lipid profile implied that the use of coconut oil is contraindicated in diabetic condition. © 2019 Elsevier Ltd

Background: This study aimed to calculate the frequency of elevated liver enzymes in hospitalized patients with coronavirus disease 2019 (COVID-19) infection and to test if liver enzyme biochemistry levels on admission could predict the computed tomography (CT) scan severity score of bilateral interstitial pneumonia. Methods: This single-center study comprised of 323 patients including their demographic data, laboratory analyses, and radiological findings. All the information was taken from electronic health records, followed by statistical analysis. Results: Out of 323 patients, 115 of them (35.60%) had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) over 40 U/L on admission. AST was the best predictor of CT scan severity score of bilateral interstitial pneumonia (R2 = 0.313, Adjusted R2 = 0.299). CT scan severity score in the peak of the infection could be predicted with the value of AST, neutrophils, platelets, and monocytes count (R2 = 0.535, Adjusted R2 = 0.495). Conclusion: AST, neutrophils, platelets, and monocytes count on admission can account for almost half (49.5%) of the variability in CT scan severity score at peak of the disease, predicting the extensiveness of interstitial pneumonia related to COVID-19 infection. Liver enzymes should be closely monitored in order to stratify COVID-19 patients with a higher risk of developing severe forms of the disease and to plan the beforehand step-up treatment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Wearing face masks is recommended as part of personal protective equipment and as a public health measure to prevent the spread of coronavirus disease 2019 (COVID-19) pandemic. Their use, however, is deeply connected to social and cultural practices and has acquired a variety of personal and social meanings. This article aims to identify the diversity of sociocultural, ethical, and political meanings attributed to face masks, how they might impact public health policies, and how they should be considered in health communication. In May 2020, we involved 29 experts of an interdisciplinary research network on health and society to provide their testimonies on the use of face masks in 20 European and 2 Asian countries (China and South Korea). They reflected on regulations in the corresponding jurisdictions as well as the personal and social aspects of face mask wearing. We analyzed those testimonies thematically, employing the method of qualitative descriptive analysis. The analysis framed the four dimensions of the societal and personal practices of wearing (or not wearing) face masks: individual perceptions of infection risk, personal interpretations of responsibility and solidarity, cultural traditions and religious imprinting, and the need of expressing self-identity. Our study points to the importance for an in-depth understanding of the cultural and sociopolitical considerations around the personal and social meaning of mask wearing in different contexts as a necessary prerequisite for the assessment of the effectiveness of face masks as a public health measure. Improving the personal and collective understanding of citizens' behaviors and attitudes appears essential for designing more effective health communications about COVID-19 pandemic or other global crises in the future.    To wear a face mask or not to wear a face mask?    Nowadays, this question has been analogous    to the famous line from Shakespeare's Hamlet:    “To be or not to be, that is the question.”    This is a bit allegorical,    but certainly not far from the current circumstances    where a deadly virus is spreading amongst us.. Vanja Kopilaš, Croatia. © Copyright © 2021 Martinelli, Kopilaš, Vidmar, Heavin, Machado, Todorović, Buzas, Pot, Prainsack and Gajović.

The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. © 2016 Mugoša et al.

The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. © 2016 Mugoša et al.

Background/Aim. Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients with Parkinson's disease (PD). The aim of our study was to assess the influence of fluoxetine (Flu) on motor functions in patients with PD. Methods. In this prospective, controlled, open-label study, 18 patients with PD and mild depression [(10 ≤ Hamilton Rating Scale for Depression (HDRS) ≤ 23)] without dementia [(25 ≤ Mini-Mental State Examination (MMSE)] were treated with Flu. Both single and repeated dose effects of Flu were assessed on days 1-80. Plasma concentrations of Flu and norfluoxetine (NORFlu) were correlated with the results of selected motor function performance scores: The Unified Parkinsons Disease Rating Score (UPDRS), Finger Tapping Test (FTT) and Purdue Pegboard Test (PPT). Severity of PD, depression and dementia were evaluated using standard tests [(Hoehn and Yahr stages (HY), activity of daily living (ADL), UPDRS, HDRS, MMSE)]. Results. Steady-state for Flu/NORFlu was reached after 18 days of treatment. Such a plateau correlated with significant improvements in both scores of depression and Parkinson's disability (HDRS, UPDRS and ADL, respectively). In addition, FTT and PPT scores also increased until day 18, with further slight fluctuations around the plateau. Optimal motor performances correlated with Flu concentrations of approximately 60-110 μg/L. Conclusion. Flu (20 mg/day) significantly reduced depression in PD patients while it did not impair their motor performances. Because substantial placebo effects may arise in studies of PD and depression, large, prospective, randomized, placebo-controlled clinical trials are warranted.

Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N = 83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients. © 2006 Elsevier B.V. All rights reserved.

Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N = 83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients. © 2006 Elsevier B.V. All rights reserved.

The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic paralysis in C. elegans. In A. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic ACh receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a non-competitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh, but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre- and post-synaptic action at the neuromuscular junction. Copyright © 2024 Stojković, Todorović, Protic, Stevanovic, Medić, Charvet, Marjanović, Nedeljković Trailović and Trailović.

The control of parasitic nematode infections relies mostly on anthelmintics. The potential pharmacotherapeutic application of phytochemicals, in order to overcome parasite resistance and enhance the effect of existing drugs, is becoming increasingly important. The antinematodal effects of carveol was tested on the free-living nematode Caenorhabditis elegans and the neuromuscular preparation of the parasitic nematode Ascaris suum. Carveol caused spastic paralysis in C. elegans. In A. suum carveol potentiated contractions induced by acetylcholine (ACh) and this effect was confirmed with two-electrode voltage-clamp electrophysiology on the A. suum nicotinic ACh receptor expressed in Xenopus oocytes. However, potentiating effect of carveol on ACh-induced contractions was partially sensitive to atropine, indicates a dominant nicotine effect but also the involvement of some muscarinic structures. The effects of carveol on the neuromuscular system of mammals are also specific. In micromolar concentrations, carveol acts as a non-competitive ACh antagonist on ileum contractions. Unlike atropine, it does not change the EC50 of ACh, but reduces the amplitude of contractions. Carveol caused an increase in Electrical Field Stimulation-evoked contractions of the isolated rat diaphragm, but at higher concentrations it caused an inhibition. Also, carveol neutralized the mecamylamine-induced tetanic fade, indicating a possibly different pre- and post-synaptic action at the neuromuscular junction. Copyright © 2024 Stojković, Todorović, Protic, Stevanovic, Medić, Charvet, Marjanović, Nedeljković Trailović and Trailović.

[No abstract available]

[No abstract available]