Browsing by Author "Samardžić, Janko (23987984500)"

Alcohol use disorder among aging women is rising at unprecedented rates. Postmenopausal drinkers may be especially at risk for alcohol use disorder (AUD)-related problems for numerous reasons such as: metabolic specificities due to aging process, overall longer life expectancy, facing losses leading to grief and depression, etc. Furthermore, age and gender differences may potentially affect the time course of medication absorption, distribution, metabolism, and excretion. Moreover, current researches on interventions and treatments that aim to reduce AUD or to prevent its occurrence in middle-aged and elderly women are limited, and limited number of medication treatments has been approved by the US FDA. Here, we provide an overview by evaluating medications’ efficacy, side effects, and contraindications focusing on age and gender differences. Also, we discuss emerging themes and different pharmacotherapies with the aim to identify optimal gender-specific pharmacotherapy options in postmenopausal patients. © 2021 Elsevier Inc. All rights reserved.

Alcohol use disorder among aging women is rising at unprecedented rates. Postmenopausal drinkers may be especially at risk for alcohol use disorder (AUD)-related problems for numerous reasons such as: metabolic specificities due to aging process, overall longer life expectancy, facing losses leading to grief and depression, etc. Furthermore, age and gender differences may potentially affect the time course of medication absorption, distribution, metabolism, and excretion. Moreover, current researches on interventions and treatments that aim to reduce AUD or to prevent its occurrence in middle-aged and elderly women are limited, and limited number of medication treatments has been approved by the US FDA. Here, we provide an overview by evaluating medications’ efficacy, side effects, and contraindications focusing on age and gender differences. Also, we discuss emerging themes and different pharmacotherapies with the aim to identify optimal gender-specific pharmacotherapy options in postmenopausal patients. © 2021 Elsevier Inc. All rights reserved.

Recently, pharmacological research has shifted from pathophysiological causes of diseases associated with cognitive disorders such as attention deficit hyperactivity disorder Alzheimer’s disease (AD), and schizophrenia, to cognitive enhancement potential of certain drugs in healthy individuals-“smart drugs”. Studies have shown that some of the current drugs for mental illness also show modest cognitive improvement in healthy individuals. The list of potential drugs that may enhance memory and/or attention is rather extensive, including substances acting on neurotransmitters, hormones, transduction systems, and brain perfusion and metabolism. While reports suggest that cognitive enhancers possess the potential to provide benefits in healthy population, their effectiveness and safety are still under investigation. Furthermore, age is a factor associated with cognition decline so the potential use of these drugs in healthy and young population could lower the rate of cognition decline with age. However, such drugs are often misused and abused. In this chapter, we will focus on the pharmacological properties of cognition-enhancing drugs and their safety profile, including current/potential clinical benefits and encouraging research strategies. © 2021 Elsevier Inc. All rights reserved.

Recently, pharmacological research has shifted from pathophysiological causes of diseases associated with cognitive disorders such as attention deficit hyperactivity disorder Alzheimer’s disease (AD), and schizophrenia, to cognitive enhancement potential of certain drugs in healthy individuals-“smart drugs”. Studies have shown that some of the current drugs for mental illness also show modest cognitive improvement in healthy individuals. The list of potential drugs that may enhance memory and/or attention is rather extensive, including substances acting on neurotransmitters, hormones, transduction systems, and brain perfusion and metabolism. While reports suggest that cognitive enhancers possess the potential to provide benefits in healthy population, their effectiveness and safety are still under investigation. Furthermore, age is a factor associated with cognition decline so the potential use of these drugs in healthy and young population could lower the rate of cognition decline with age. However, such drugs are often misused and abused. In this chapter, we will focus on the pharmacological properties of cognition-enhancing drugs and their safety profile, including current/potential clinical benefits and encouraging research strategies. © 2021 Elsevier Inc. All rights reserved.

Background/Objectives: Mental diseases are one of the leading groups of health disorders worldwide, with depressive and anxiety disorders being the most prevalent. Depressive disorders can be treated with pharmacotherapy, psychotherapy, or a combination of both. In cases where these approaches prove ineffective, electroconvulsive therapy may be considered as an alternative. The drugs of choice for treating depressive disorders are selective serotonin reuptake inhibitors (SSRIs). In the Republic of Serbia, commonly prescribed SSRIs include fluoxetine, citalopram, paroxetine, sertraline, and escitalopram. Methods: Data on drug sales for human medicine from the Agency for Medicines and Medical Devices of Serbia (ALIMS) were used for the analysis of consumption in the period 2018–2022. Data on drug consumption in other European countries were obtained from the respective national registers. Results: From 2018 to 2021, sertraline was the best-selling drug in this group, but with a statistically significant decrease (R2 = 0.7948, p = 0.042), while escitalopram showed a statistically significant increase (p = 0.006) and became the best-selling drug in the SSRI group in 2022. Overall, SSRI group consumption fluctuated from 2018 to 2022, with the highest values in 2020. However, these variations were not statistically significant (p = 0.6223). Compared to Serbia, out of 12 European countries, 8 had higher and 4 had lower consumption in 2019 and 2020. A positive correlation was found between antidepressant consumption and GDP per capita. Conclusions: Sertraline was the most commonly prescribed SSRI drug in Serbia from 2018 to 2021. However, in 2022, escitalopram became the most commonly used drug in this group both in Serbia and worldwide, with a consistent increase in consumption. © 2025 by the authors.

[No abstract available]

Background Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. However, few countries have published their population-based findings related to this multisystemic disease. The aim In order to get a better insight into the epidemiological and clinical picture of this maternally inherited disorder, we performed the first population-based clinical and molecular-genetic study of LHON in the Serbian population. Methods Prospective study included patients who were diagnosed with LHON after detailed medical examination and molecular-genetic confirmation. Results We identified 41 individuals from 12 genealogically unrelated families, carrying one of the three "primary" mitochondrial (mt) DNA point mutations associated with LHON. Fourteen of them were clinically affected, giving a minimum point prevalence of 1.9 per 1 000 000. The minimum point prevalence for mtDNA LHON mutations was 5.2 per 1 000 000. Male to female ratio was 6:1. Only one affected patient harboured mutant mtDNA in heteroplasmic condition. All patients were presented with common clinical findings. Conclusion We observed significantly lower prevalence and higher gender ratio than expected. However, frequencies of primary mutations, incidence of heteroplasmy and clinical findings are in accordance with other studies in Caucasoid populations. Our results might be a consequence of poor recognition and misdiagnosis due to lack of diagnostic possibilities of the entity in different region of our country or less likely be in part due to specific haplotype background of Serbian population which should be further investigated. © 2013 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.

Multiple sclerosis (MS) is an autoimmune, chronic, inflammatory, and demyelinating disease of the central nervous system (CNS). The etiology of MS is most likely multifactorial; it is dependent on genetic, autoimmune, and environmental factors, with a variable course among patients. The two main clinical events that characterize MS are relapses and progression. In recent years, diagnosis and treatment of pediatric MS has drawn attention of the scientific community. Management of pediatric MS focuses on reducing relapses and symptoms via administration of disease-modifying drugs (DMDs) and specific symptomatic treatment. A multidisciplinary approach to pediatric MS treatment is preferred, which aims at alleviating and preventing the accumulation of neurological deficits. MS therapy should be based on DMDs, that is, immunomodulatory drugs. These drugs, which sequester immune system activity, are further subdivided into two categories: first-line and second-line immunomodulatory therapy. First-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, and glatiramer acetate) is ineffective (either no response or partial response) in roughly 30% of patients. Patients with a poor response to first-line therapy require second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab, alemtuzumab, and ocrelizumab). In addition to immunomodulatory drugs, treatment of relapses also involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis. © The Authors.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats. © 2024 by the authors.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats. © 2024 by the authors.

Background/Aim. Presepsin (soluble CD14-subtype) is a fragment of CD14 produced in response to bacterial infections and a novel biomarker of pneumonia, sepsis and septic shock. The aim of this study was to compare sensitivity and specificity of persepsin, soluble CD14-subtype (sCD14-ST) with other biomarkers: procalcitonine (PCT), C-reactive protein (CRP) and leukocyte count (Le) in mechanically ventilated injured patients, as a marker of pneumonia, sepsis and septic shock. Methods. The prospective study was undertaken in trauma and surgery intensive care unit of the Emergency Center, the Clinical Center of Serbia from January to April 2013. The study included 39 trauma patients requiring mechanical ventilation, and who developed one of the following inclusion criteria: Systemic Inflammatory Response Syndrome (SIRS), ventilator associated pneumonia (VAP), sepsis and/or septic shock. On admission Acute Physiology and Chronic Health Evaluation II (APACHE II) Score and Injury Severity Score (ISS) were calculated. Seventy-two measurements of four biomarkers (presepsin, PCT, CRP and Le) were performed in 39 patients at the moments of diagnosis of SIRS, VAP, sepsis and/or septic shock (21 when SIRS diagnosis was established, 21 after the diagnosis of VAP, 18 at the moment of diagnosis of sepsis and the remaining 12 measurements were conducted while diagnosing the septic shock). The Sequential Organ Failure Assessment (SOFA) score was calculated at these points as well. Results. Patients were mainly severely injured (mean ISS = 24.2) and had moderately severe medical condition at admission (mean Apache II score, 14.5). Presepsin concentration significantly differed among all the four groups, except between sepsis and septic shock. The strongest positive correlation of presepsin evinced with PCT (r = 0.741, p < 0.001). The sCD14-ST indicated better performance in diagnosis of both VAP (AUC = 0.909) and sepsis (AUC = 0.899), compared to PCT (AUCs: 0.863, 0.885, respectively), CRP (AUCs: 0.703, 0.677, respectively) and Le (AUCs: 0.668, 0.700, respectively). Conclusion. This study revealed that sCD14-ST is a reliable biomarker for distinguishing sepsis severity. It also showed a good correlation with the infection development as well as worsening in injured patients. © 2018, Routledge. All rights reserved.

Benzodiazepine (BZ) site ligands affect vigilance, anxiety, memory processes, muscle tone and epileptogenic propensity through modulation of neurotransmission at GABAA receptors containing α1, α2, α3 or α5 subunits, and may have numerous experimental and clinical applications. The ability of non-selective BZ site inverse agonists to enhance cognition, documented in animal models and human studies, is clinically not feasible due to potentially unacceptable psychomotor effects. Most investigations to date have proposed the α1 and/or α5 subunit-containing GABAA receptors as comprising the memory-modulating population of these receptors. The novel ligand PWZ-029, which we synthesized and characterized electrophysiologically, possesses in vitro binding selectivity and moderate inverse agonist functional selectivity at α5-containing GABAA receptors. This ligand has also been examined in rats in the passive and active avoidance, spontaneous locomotor activity, elevated plus maze and grip strength tests, primarily predictive of the effects on the memory acquisition, basal locomotor activity, anxiety level and muscle tone, respectively. The improvement of task learning was detected at the dose of 5 mg/kg in the passive, but not active avoidance test. The inverse agonist PWZ-029 had no effect on anxiety or muscle tone, whereas at higher doses (10 and 20 mg/kg) it decreased locomotor activity. This effect was antagonized by flumazenil and also by the lower (but not the higher) dose of an agonist (SH-053-R-CH3-2′F) selective for GABAA receptors containing the α5 subunit. The hypolocomotor effect of PWZ-029 was not antagonized by the antagonist ß-CCt exhibiting a preferential affinity for α1-subunit-containing receptors. These data suggest that moderate negative modulation at GABAA receptors containing the α5 subunit is a sufficient condition for eliciting enhanced encoding/consolidation of declarative memory, while the influence of higher doses of modulators at these receptors on motor activity shows an intricate pattern whose relevance and mechanism await to be defined. © 2008 Elsevier B.V. All rights reserved.

Benzodiazepine (BZ) site ligands affect vigilance, anxiety, memory processes, muscle tone and epileptogenic propensity through modulation of neurotransmission at GABAA receptors containing α1, α2, α3 or α5 subunits, and may have numerous experimental and clinical applications. The ability of non-selective BZ site inverse agonists to enhance cognition, documented in animal models and human studies, is clinically not feasible due to potentially unacceptable psychomotor effects. Most investigations to date have proposed the α1 and/or α5 subunit-containing GABAA receptors as comprising the memory-modulating population of these receptors. The novel ligand PWZ-029, which we synthesized and characterized electrophysiologically, possesses in vitro binding selectivity and moderate inverse agonist functional selectivity at α5-containing GABAA receptors. This ligand has also been examined in rats in the passive and active avoidance, spontaneous locomotor activity, elevated plus maze and grip strength tests, primarily predictive of the effects on the memory acquisition, basal locomotor activity, anxiety level and muscle tone, respectively. The improvement of task learning was detected at the dose of 5 mg/kg in the passive, but not active avoidance test. The inverse agonist PWZ-029 had no effect on anxiety or muscle tone, whereas at higher doses (10 and 20 mg/kg) it decreased locomotor activity. This effect was antagonized by flumazenil and also by the lower (but not the higher) dose of an agonist (SH-053-R-CH3-2′F) selective for GABAA receptors containing the α5 subunit. The hypolocomotor effect of PWZ-029 was not antagonized by the antagonist ß-CCt exhibiting a preferential affinity for α1-subunit-containing receptors. These data suggest that moderate negative modulation at GABAA receptors containing the α5 subunit is a sufficient condition for eliciting enhanced encoding/consolidation of declarative memory, while the influence of higher doses of modulators at these receptors on motor activity shows an intricate pattern whose relevance and mechanism await to be defined. © 2008 Elsevier B.V. All rights reserved.

Currently, arterial hypertension is the most massive chronic non-infectious disease of mankind. It may remain undiagnosed for years, provoking later complications, such as acute heart failure, cerebrovascular stroke, myocardial infarction, renal failure, hypertensive retinopathy, or sudden death. Primary arterial hypertension is more common, while secondary occurs in about 5–20% of cases. The recent studies have shown that stress may be a core factor in the development of essential hypertension in some patients. For the patients suffering from post-traumatic stress disorder, stress is the dominant etiological factor that leads to the disease. It has been proven that chronic stress can affect blood pressure regulation and endocrine-metabolic functions through the limbic-hypothalamic centers; therefore, it can affect the arterial hypertension development. The strong association between stress and arterial hypertension has also been confirmed in preclinical and animal studies. For the pharmacotherapy approach, the most important are beta-adrenergic blockers, angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor blockers (sartans). As a second line treatment, calcium channel blockers, diuretics, alpha-adrenergic blockers, and central antihypertensive agents may be required. The anxiolytics, such as benzodiazepines, should be considered if chronic anxiety and psychosomatic disorders are present. © 2021, Serbia Medical Society. All rights reserved.

Introduction The trans-isomer of resveratrol is the active ingredient of Poligonum cuspidatum, known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders. It is also found abundantly in the skin of red grapes and red wine. Previous studies have suggested that trans-resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, as well as neuroprotective properties and procognitive effects. Objective The goal of the present study was to examine the influence of trans-resveratrol on behavior in rats and its antidepressant properties. Methods Male Wistar rats were treated intraperitoneally (i.p.) with the increasing doses of trans-resveratrol (5, 10 and 20 mg/kg) or vehicle (dimethyl sulfoxide - DMSO), 30 minutes before testing of the spontaneous locomotor activity or forced swimming. For the experiments, the behavior of the animals was recorded by a digital camera, and the data were analyzed by one-way ANOVA, followed by Tukey post-hoc test. Results Testing of spontaneous locomotor activity, after the application of vehicle or increasing doses of trans-resveratrol, showed no statistically significant difference between groups (p>0.05). In the forced swim test, one-way ANOVA indicated statistically significant effects of trans-resveratrol (p<0.001). Tukey post-hoc test showed that resveratrol significantly decreased immobility time at the doses of 10 mg/kg and 20 mg/kg, manifesting the acute antidepressant-like effects. There were no statistically significant differences between the resveratrol treatment of 5 mg/kg and vehicle (p>0.05). Conclusion The results from our study suggest that transresveratrol produces significant effects in the central nervous system. After single application, it has acute antidepressant effects, but without influence on locomotor activity.

[No abstract available]

We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression. © 2015 S. Karger AG.