Browsing by Author "Pešić, Vesna (57194109901)"

To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (S FE , n = 19), patients in relapse (S R , n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between S FE , S R and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls. Activities of SOD and CAT were 40% decreased in S FE and these reductions were ameliorated by antipsychotic treatment. GPX activity was 20% decreased in both patient groups compared with controls. A negative correlation between NSS intensity and GPX activity was specifically found in the S FE patients. The data in this report argue that a reduction of GPX activity might be one of the causes for the emergence of NSS at the onset of schizophrenia, and provide the evidence that antipsychotic therapy can attenuate activity reductions of SOD and CAT, but not the activity reduction of GPX and the intensity of NSS. © 2018

To determine the relationship between alterations in the activity of the enzymes participating in antioxidative defense system and neurological soft signs (NSS) in schizophrenic patients with the first episode psychosis (S FE , n = 19), patients in relapse (S R , n = 46), and healthy controls (HC, n = 20). NSS intensity and enzymatic plasma activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were compared between S FE , S R and HC subjects and a follow-up correlation analyses between the enzyme activities and NSS intensity was performed. NSS intensity was increased four times in schizophrenic patients compared with healthy controls. Activities of SOD and CAT were 40% decreased in S FE and these reductions were ameliorated by antipsychotic treatment. GPX activity was 20% decreased in both patient groups compared with controls. A negative correlation between NSS intensity and GPX activity was specifically found in the S FE patients. The data in this report argue that a reduction of GPX activity might be one of the causes for the emergence of NSS at the onset of schizophrenia, and provide the evidence that antipsychotic therapy can attenuate activity reductions of SOD and CAT, but not the activity reduction of GPX and the intensity of NSS. © 2018

Importance: Precise estimation of the drug metabolism capacity for individual patients is crucial for adequate dose personalization. Objective: To quantify the difference in the antipsychotic and antidepressant exposure among patients with genetically associated CYP2C19 and CYP2D6 poor (PM), intermediate (IM), and normal (NM) metabolizers. Data Sources: PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to June 30, 2020, with no language restrictions. Study Selection: Two independent reviewers performed study screening and assessed the following inclusion criteria: (1) appropriate CYP2C19 or CYP2D6 genotyping was performed, (2) genotype-based classification into CYP2C19 or CYP2D6 NM, IM, and PM categories was possible, and (3) 3 patients per metabolizer category were available. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for extracting data and quality, validity, and risk of bias assessments. A fixed-effects model was used for pooling the effect sizes of the included studies. Main Outcomes and Measures: Drug exposure was measured as (1) dose-normalized area under the plasma level (time) curve, (2) dose-normalized steady-state plasma level, or (3) reciprocal apparent total drug clearance. The ratio of means (RoM) was calculated by dividing the mean drug exposure for PM, IM, or pooled PM plus IM categories by the mean drug exposure for the NM category. Results: Based on the data derived from 94 unique studies and 8379 unique individuals, the most profound differences were observed in the patients treated with aripiprazole (CYP2D6 PM plus IM vs NM RoM, 1.48; 95% CI, 1.41-1.57; 12 studies; 1038 patients), haloperidol lactate (CYP2D6 PM vs NM RoM, 1.68; 95% CI, 1.40-2.02; 9 studies; 423 patients), risperidone (CYP2D6 PM plus IM vs NM RoM, 1.36; 95% CI, 1.28-1.44; 23 studies; 1492 patients), escitalopram oxalate (CYP2C19 PM vs NM, RoM, 2.63; 95% CI, 2.40-2.89; 4 studies; 1262 patients), and sertraline hydrochloride (CYP2C19 IM vs NM RoM, 1.38; 95% CI, 1.27-1.51; 3 studies; 917 patients). Exposure differences were also observed for clozapine, quetiapine fumarate, amitriptyline hydrochloride, mirtazapine, nortriptyline hydrochloride, fluoxetine hydrochloride, fluvoxamine maleate, paroxetine hydrochloride, and venlafaxine hydrochloride; however, these differences were marginal, ambiguous, or based on less than 3 independent studies. Conclusions and Relevance: In this systematic review and meta-analysis, the association between CYP2C19/CYP2D6 genotype and drug levels of several psychiatric drugs was quantified with sufficient precision as to be useful as a scientific foundation for CYP2D6/CYP2C19 genotype-based dosing recommendations.. © 2021 American Medical Association. All rights reserved.

The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated. We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5 g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10 min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00±0.00 to 1.25±0.54‰ (P<0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2=3008±638 vs. 2900±543 ml/min, ns; peak workload=269±53 vs. 249±40 W, ns; test duration 13.7±2.2 vs. 13.3±1.7 min, ns; VE/VCO2 22.1±1.4 vs. 23.3±2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28±2.5 vs. 30.4±3.2, P=0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17±0.02 vs. 1.14±0.04, P=0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism. © 2016 Italian Federation of Cardiology. All rights reserved.

Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/go - n adal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p<0.05), and a trend toward a lymphocyte percentage increase. Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level.

Background: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/go - n adal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p<0.05), and a trend toward a lymphocyte percentage increase. Conclusions: The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level.

Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia. Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride. Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice. Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development. © 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Aims: CYP2C19 transgenic mouse expresses the human CYP2C19 gene in the liver and developing brain, and it exhibits altered neurodevelopment associated with impairments in emotionality and locomotion. Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in CYP2C19 transgenic mice and to investigate its validity as a new animal model of ataxia. Methods: The rotarod, paw-print and beam-walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in CYP2C19 transgenic and wild-type mice were quantified by 9.4T gadolinium-enhanced post-mortem structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam-walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride. Results: CYP2C19 transgenic mice exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips in the beam-walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity. CYP2C19 mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in CYP2C19 mice. Conclusions: Humanised CYP2C19 transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development. © 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.