Browsing by Author "Ostojic, Jelena (12797904900)"

The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe. © 2013 Springer-Verlag Berlin Heidelberg.

The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe. © 2013 Springer-Verlag Berlin Heidelberg.

Objective: This study was conducted in order to test the hypothesis that proton MR spectroscopic (1H MRS) profile of Leber's hereditary optic neuropathy (LHON) mutation carriers group (including both symptomatic and asymptomatic) differs from group of healthy individuals and to determine metabolite or ratio that contributes most to differentiation. Patients and methods: We performed single voxel 1H MRS in normal appearing white matter of eighteen LHON mtDNA mutation carriers bearing one of three LHON mtDNA point mutations and in fifty control subjects. Results: ANOVA showed significant difference for absolute concentration of creatine (Cr) (p < 0.01) and N-acetylaspartate to creatine ratio (NAAVCr) (p < 0.01). Discriminant analysis revealed that decreased absolute Cr followed by decreased absolute NAA concentration have the most significant contribution in discriminating LHON mutation carriers from healthy controls. Conclusion: Abnormal metabolic profile in normal appearing white matter on MR imaging seems to be significantly present in LHON mutation carriers.

We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Objective Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention. Methods Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. Results Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention. Conclusions Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease. © 2016 Elsevier Inc.

Objective Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention. Methods Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. Results Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05). Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05). No participants reported any neurologic adverse event (e.g., seizures, tingling, convulsions) during the intervention. Conclusions Supplemental GAA led to a region-dependent increase of the creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease. © 2016 Elsevier Inc.

[No abstract available]

[No abstract available]

In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues. © 2016, Canadian Science Publishing. All right reserved.

In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues. © 2016, Canadian Science Publishing. All right reserved.

Purpose: Co-administration of creatine and guanidinoacetic acid (GAA) has been recently put forward as an advanced dietary strategy to optimize tissue bioenergetics. We hypothesized that creatine-GAA mixture would result in more powerful rise in brain and skeletal muscle creatine, as compared to creatine supplementation alone. Methods: A randomized, double-blinded, crossover superiority trial has been performed at the University of Novi Sad from December 2016 to November 2017. A total of 14 healthy young men were randomized to receive GAA-creatine mixture (1 grams of GAA and 3 grams of creatine per day) or equimolar creatine (4 grams per day) by oral administration for 4 weeks. Results: Creatine-GAA mixture was superior to creatine alone to increase mean creatine levels in skeletal muscle (16.9 ± 20.2 vs. 2.0 ± 6.0%; P = 0.02) and grey matter (5.8 ± 5.3% vs. 1.5 ± 3.2%; P = 0.02), also for bench press performance (6.0% vs. 5.1%; P < 0.01). Compared with creatine administration alone, combined GAA and creatine resulted in less weight gain (1.6 ± 0.2 kg vs. 0.7 ± 0.2 kg; P < 0.01). No inter-group differences were observed in terms of cardiorespiratory endurance, serum biomarkers, or adverse events. Conclusions: Creatine-GAA mixture appeared to be superior to sole creatine for up-swinging tissue creatine content and upper body strength, and resulted toward a lower risk of weight gain in healthy active men. The formulation might be considered as a novel energy-boosting alternative to creatine alone in weight-sensitive setups. Trial registration: ClinicalTrials.gov NCT03350282. © 2018 Elsevier Inc.

Purpose: Co-administration of creatine and guanidinoacetic acid (GAA) has been recently put forward as an advanced dietary strategy to optimize tissue bioenergetics. We hypothesized that creatine-GAA mixture would result in more powerful rise in brain and skeletal muscle creatine, as compared to creatine supplementation alone. Methods: A randomized, double-blinded, crossover superiority trial has been performed at the University of Novi Sad from December 2016 to November 2017. A total of 14 healthy young men were randomized to receive GAA-creatine mixture (1 grams of GAA and 3 grams of creatine per day) or equimolar creatine (4 grams per day) by oral administration for 4 weeks. Results: Creatine-GAA mixture was superior to creatine alone to increase mean creatine levels in skeletal muscle (16.9 ± 20.2 vs. 2.0 ± 6.0%; P = 0.02) and grey matter (5.8 ± 5.3% vs. 1.5 ± 3.2%; P = 0.02), also for bench press performance (6.0% vs. 5.1%; P < 0.01). Compared with creatine administration alone, combined GAA and creatine resulted in less weight gain (1.6 ± 0.2 kg vs. 0.7 ± 0.2 kg; P < 0.01). No inter-group differences were observed in terms of cardiorespiratory endurance, serum biomarkers, or adverse events. Conclusions: Creatine-GAA mixture appeared to be superior to sole creatine for up-swinging tissue creatine content and upper body strength, and resulted toward a lower risk of weight gain in healthy active men. The formulation might be considered as a novel energy-boosting alternative to creatine alone in weight-sensitive setups. Trial registration: ClinicalTrials.gov NCT03350282. © 2018 Elsevier Inc.

To explore microstructural integrity of hippocampus in vascular dementia (VD) using DTI. Twenty-five individuals with VD, without magnetic resonance imaging (MRI) evidence of gray matter pathology, and 25 matched healthy control (HC) individuals underwent a 3T MRI protocol including T2, FLAIR, and PD in the axial plane, 3D whole-brain T1-weighted with an isotropic resolution of 1 mm, and DTI acquired using 64 diffusion sensitizing directions, b value of 1,500 s/mm2, 65 axial slices, isotropic resolution of 1.8 mm. Images were processed to obtain indices of microstructural variations of bilateral hippocampi. Mean diffusivity (MD) in the hippocampus of patients with VD was significantly increased (p < 0.05) bilaterally with respect to that of the group of HC examinees. In VD group left hippocampal MD (10−6× mm2/s) was 833.4 ± 92.8; in HC group left MD was 699.8 ± 56. In VD group, right hippocampal MD was 859.1 ± 69.8; in HC group right MD was 730.4 ± 40.2. No group differences were found in hippocampal FA. DTI shows microstructural hippocampal damage in VD in patients with normal appearing gray matter structures on conventional MRI, indicating the need for further research on the link between VD and AD. © 2014, Belgian Neurological Society.

Background: Pol III-related leukodystrophies, including 4H leukodystrophy, are recently recognized disorders that comprise hypomyelination and various neurologic and non-neurologic clinical manifestations. We report the unique neurologic presentation of the micturition dysfunction in Pol III-related leukodystrophy and describe the novel endocrine abnormalities in this entity. Case presentation: A 32-year-old Caucasian female exhibited chronic urinary incontinence that commenced at the age of 7 years and remained the unexplained symptom more than two decades before the onset of progressive neurologic decline. A transient growth failure and absent sexual development with hypoprolactinemia appeared in the meanwhile. Neurologic, endocrine, neuroradiologic, and genetic evaluation performed only in the patient's thirties, confirmed the diagnosis of 4H leukodystrophy as the only cause of the micturition disturbance. Conclusion: The report shows for the first time that an unexplained chronic bladder dysfunction should be evaluated also as a possible 4H leukodystrophy, thus alerting to the unexpected neurologic and endocrine features in 4H leukodystrophy. © 2015 Potic et al.