Publications by authors named "Branislav Filipovic"

49 Publications

Anatomical Brain Changes and Cognitive Abilities in Patients with Obstructive Sleep Apnea Syndrome and Nonalcoholic Fatty Liver Disease.

Can J Gastroenterol Hepatol 2021 20;2021:8873652. Epub 2021 Oct 20.

University of Belgrade, Faculty of Medicine, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia.

Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial collapse of the upper airway and reduction of airflow during sleep. It is associated with significantly increased daytime muscle sympathetic nerve activity thought to result from the repetitive intermittent periods of hypoxemia during sleep and brain alterations that are likely to result. Different brain regions are affected by subsequent hypoxia/anoxia. Neurodegenerative processes result in measurable atrophy of cortical gray matter in the temporal lobes and posterior cingulate cortex, as well as in subcortical structures such as the hippocampus, amygdala, and thalamus. This study involved a group of firstly diagnosed, therapy-naive, nonalcoholic fatty liver disease (NAFLD) patients, out of which 144 (96 males and 48 females), aged 34-57 (mean 47.88 ± 6.07), satisfied the recruiting criteria for the study and control groups. All the patients underwent MRI scanning, polysomnography testing, and cognitive evaluation. Cognitively, worse results were obtained in the group with OSA ( < 0.05) and NAFLD (=0.047). A significant decrease in volumes of cortical and subcortical structures was revealed ( < 0.001). In conclusion, brain deterioration followed by cognitive impairment is, most likely, the result of intermittent hypoxia and anoxia episodes that initiate the domino process of deteriorating biochemical reactions in the brain.
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http://dx.doi.org/10.1155/2021/8873652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550849PMC
December 2021

Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus.

Front Neuroanat 2021 8;15:670766. Epub 2021 Jun 8.

Abteilung für Neuroanatomie und Molekulare Hirnforschung, Ruhr-Universität Bochum, Bochum, Germany.

Early life stress has profound effects on the development of the central nervous system. We exposed 9-day-old rat pups to a 24 h maternal deprivation (MD) and sacrificed them as young adults (60-day-old), with the aim to study the effects of early stress on forebrain circuitry. We estimated numbers of various immunohistochemically defined interneuron subpopulations in several neocortical regions and in the hippocampus. MD rats showed reduced numbers of parvalbumin-expressing interneurons in the CA1 region of the hippocampus and in the prefrontal cortex, compared with controls. Numbers of reelin-expressing and calretinin-expressing interneurons were also reduced in the CA1 and CA3 hippocampal areas, but unaltered in the neocortex of MD rats. The number of calbinin-expressing interneurons in the neocortex was similar in the MD rats compared with controls. We analyzed cell death in 15-day-old rats after MD and found no difference compared to control rats. Thus, our results more likely reflect the downregulation of markers than the actual loss of interneurons. To investigate synaptic activity in the hippocampus we immunostained for glutamatergic and inhibitory vesicular transporters. The number of inhibitory synapses was decreased in the CA1 and CA3 regions of the hippocampus in MD rats, with the normal number of excitatory synapses. Our results indicate complex, cell type-specific, and region-specific alterations in the inhibitory circuitry induced by maternal deprivation. Such alterations may underlie symptoms of MD at the behavioral level and possibly contribute to mechanisms by which early life stress causes neuropsychiatric disorders, such as schizophrenia.
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http://dx.doi.org/10.3389/fnana.2021.670766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217609PMC
June 2021

Long-Term Effects of Maternal Deprivation on the Volume of Dopaminergic Nuclei and Number of Dopaminergic Neurons in Substantia Nigra and Ventral Tegmental Area in Rats.

Front Neuroanat 2020 23;14:578900. Epub 2020 Oct 23.

School of Medicine, Institute of Anatomy "Niko Miljanić", University of Belgrade, Belgrade, Serbia.

Early life adversities leave long-lasting structural and functional consequences on the brain, which may persist later in life. Dopamine is a neurotransmitter that is extremely important in mood and motor control. The aim of this study was to investigate the effect of maternal deprivation during the ninth postnatal day on the volume of dopaminergic nuclei and the number of dopaminergic neurons in adolescence and adulthood. Maternally deprived and control Wistar rats were sacrificed on postnatal day 35 or 60, and the dopaminergic neurons were stained in coronal histological sections of ventral midbrain with the tyrosine hydroxylase antibody. The volume of dopaminergic nuclei and the number of dopaminergic neurons in the substantia nigra (SN) and ventral tegmental area (VTA) were analyzed in three representative coordinates. Maternal deprivation caused weight loss on postnatal day 21 (weaning) and corticosterone blood level elevation on postnatal days 35 and 60 in stressed compared to control rats. In maternally deprived animals, the volumes of SN and VTA were increased compared to the controls. This increase was accompanied by an elevation in the number of dopaminergic neurons in both nuclei. Altogether, based on somatic and corticosterone level measurements, maternal deprivation represents a substantial adversity, and the phenotype it causes in adulthood includes increased volume of the dopaminergic nuclei and number of dopaminergic neurons.
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http://dx.doi.org/10.3389/fnana.2020.578900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645037PMC
October 2020

Reliability of the bicaudate parameter in the revealing of the enlarged lateral Ventricles in schizophrenia patients.

Psychiatr Danub 2018 Jun;30(2):150-156

Clinics for Psychiatry "Laza Lazarević", Belgrade, Serbia.

Introduction: In schizophrenia patients the lateral ventricle enlargement has mostly been reported in relationship with smaller cortical and/or subcortical brain volumes; and it has been observed that ventricular system growth may be a consequence of the smaller caudate nucleus volume. Bicaudate parameters have been used in the Alzheimer dementia and Huntington's chorea diagnosing in order to evaluate brain changes and the enlargement of the lateral ventricles.

Subjects And Methods: This study has been carried out on 140 patients out of which 70 patients (30 men and 40 women) who met the ICD 10 criteria for schizophrenia and 70 healthy controls (30 men and 40 women) matched on sex and age with the studied group. All of them underwent direct caudatometry and volume computation based on MRI scans.

Results: Except for the bicorporal line, for all the parameters were obtained the statistically highly significant differences between the examined and control groups. Significant correlation was established for the majority of bicaudate parameters and volumes of the caudate nuclei and lateral ventricles.

Discussion: Enlargement of the lateral ventricles is one of the most frequent MRI finding in schizophrenia patients. Ventricles are enlarging gradually and frontal horns are more affected than other parts. The increased volumes of the caudate nuclei signalized that ventricular enlargement is not the consequence of the caudate atrophy.

Conclusion: Bicaudate parameters are reliable parameters for the quick orientation in order to assess the enlarged ventricles in schizophrenia patients.
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http://dx.doi.org/10.24869/psyd.2018.150DOI Listing
June 2018

Cognitive Changes and Brain Volume Reduction in Patients with Nonalcoholic Fatty Liver Disease.

Can J Gastroenterol Hepatol 2018 27;2018:9638797. Epub 2018 Feb 27.

Faculty of Medicine, University of Belgrade, Dr Subotića Starijeg 8, Belgrade, Serbia.

Studies of psychological condition of patients suffering from nonalcoholic fatty liver disease are rather equivocal about the results: while some claim that NAFLD patients suffer from anxiety and depression more than non-NAFLD controls, others do not withstand those findings. Lower cognitive potentials have also been reported, both in patient related and in animal model-based investigations, and correlated with assessed brain tissue changes. We hypothesized that NAFLD, as a condition, affects the brain tissue and, subsequently, the cognitive state. So we compared findings in 40 NAFLD positive and 36 NAFLD negative patients and correlated their brain tissue volumes with the results of Montreal Cognitive Assessment (MoCA) test. Binomial logistic regression verified the influence of NAFLD state leading to lower cognitive potentials: odds ratio 0.096; 95% confidence interval (CI) 0.032-0.289; < 0.001. Patients with NAFLD had a greater risk to suffer from the cognitive impairment and depression: RR = 3.9; 95% CI 1.815-8.381; = 0.0005 and RR = 1.65; 95% CI 1.16-2.36; = 0.006. NAFLD significantly influenced the cognitive deficit and tissue volume reduction and patients suffering from NAFLD had about four times higher risk of having a cognitive impairment.
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http://dx.doi.org/10.1155/2018/9638797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848059PMC
March 2019

Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

Croat Med J 2017 Dec;58(6):406-415

Tamara Jakimov, Department of Cardiology, Clinical and Hospital Center "Bežanijska kosa", Autoput s/n, 11000 Belgrade, Serbia,

Aim: To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI).

Methods: This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI).

Results: The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058).

Conclusions: In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778677PMC
http://dx.doi.org/10.3325/cmj.2017.58.406DOI Listing
December 2017

Long-Term Effects of Maternal Deprivation on Redox Regulation in Rat Brain: Involvement of NADPH Oxidase.

Oxid Med Cell Longev 2017 20;2017:7390516. Epub 2017 Mar 20.

Institute of Clinical and Medical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, Belgrade, Serbia.

Maternal deprivation (MD) causes perinatal stress, with subsequent behavioral changes which resemble the symptoms of schizophrenia. The NADPH oxidase is one of the major generators of reactive oxygen species, known to play a role in stress response in different tissues. The aim of this study was to elucidate the long-term effects of MD on the expression of NADPH oxidase subunits (gp91, p22, p67, p47, and p40). Activities of cytochrome C oxidase and respiratory chain Complex I, as well as the oxidative stress parameters using appropriate spectrophotometric techniques were analyzed. Nine-day-old Wistar rats were exposed to a 24 h maternal deprivation and sacrificed at young adult age. The structures affected by perinatal stress, cortex, hippocampus, thalamus, and caudate nuclei were investigated. The most prominent findings were increased expressions of gp91 in the cortex and hippocampus, increased expression of p22 and p40, and decreased expression of gp91, p22, and p47 in the caudate nuclei. Complex I activity was increased in all structures except cortex. Content of reduced glutathione was decreased in all sections while region-specific changes of other oxidative stress parameters were found. Our results indicate the presence of long-term redox alterations in MD rats.
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http://dx.doi.org/10.1155/2017/7390516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376945PMC
May 2017

Long-term Effects of Maternal Deprivation on the Volume, Number and Size of Neurons in the Amygdala and Nucleus Accumbens of Rats.

Psychiatr Danub 2016 09;28(3):211-219

Institute of Anatomy "Niko Miljanić", Faculty of Medicine, University of Belgrade, dr Subotića 4/2, Belgrade 11000, Serbia,

Background: Maternal deprivation (MD) in rodents is an important neurodevelopmental model for studying a variety of behavioral changes which closely resemble the symptoms of schizophrenia in humans.

Subjects And Methods: To determine whether early-life stress leads to changes in the limbic system structures: the amygdala and the nucleus accumbens, 9-day-old Wistar rats were exposed to 24 hour MD. On P60 the rats were sacrificed for morphometric analysis and their brains were compared to the control group.

Results: Results show that MD affected important limbic system structures: the amygdala and the nucleus accumbens, whose volume was decreased (17% of the control value for the amygdala and 9% of the control value for the nucleus accumbens ), as well as the number of neurons (41% of the control value for the amygdala and 43% of the control value for the nucleus accumbens ) and the size of their cells soma (12% of the control value for the amygdala and 33% of the control value for the nucleus accumbens ).

Conclusion: This study indicates that early stress in life leads to changes in the morphology of the limbic areas of the brain, most probably due to the loss of neurons during postnatal development, and it further contributes to our understanding of the effects of maternal deprivation on brain development.
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September 2016

Glucocorticoid levels after exposure to predator odor and chronic psychosocial stress with dexamethasone application in rats.

Kaohsiung J Med Sci 2016 May 21;32(5):235-40. Epub 2016 May 21.

Institute of Anatomy, Medical Faculty, University of Belgrade, Belgrade, Serbia.

This study was conducted to explore the effects of specific psychosocial paradigm on predator animal posttraumatic stress model and to test the hypothesis that psychosocially stressed rats would exibit abnormal levels of cortisol and a larger suppression of cortisol levels after the application of dexamethasone. Animals were divided in two groups: experimental and control groups. The experimental group was exposed to two types of stressors: acute immobilization stress, and combined predator stress and daily social stress with application of dexamethasone. Blood sampling was performed at three different times. We found statistically significant results after analyzing the differences between cortisol levels in different times of blood sampling in the group of animals exposed to stress with dexamethasone application. Statistical significance was found when we compared the experimental group with the control group in terms of elevated cortisol levels during blood sampling after stress paradigm exposition. Many significant disruptions in the functioning of the hypothalamic-pituitary-adrenal axis were observed, such as decrease in basal cortisol levels and enhanced dexamethasone-induced inhibition of cortisol levels. These findings are important because their impact can translate to human individuals with posttraumatic stress disorder, which is the most important role of every animal model in research.
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http://dx.doi.org/10.1016/j.kjms.2016.04.011DOI Listing
May 2016

Benign Hydronephrosis and Elevated of Serum Levels of Carbohydrate Antigen CA 19-9: A Case Report.

Am J Case Rep 2016 Jun 11;17:395-7. Epub 2016 Jun 11.

Faculty of Medicine, University of Belgrad, Belgrade, Serbia.

Background: Carbohydrate tumor-associated antigen (CA 19-9) has been shown to be upregulated in other malignant tumors including gastric, ovarian, hepatocellular, and colorectal carcinoma as well as benign diseases of the biliary track such as pancreatitis, cholangitis, and choledocholithiasis. According to the available literature, in several cases of benign hydronephrosis and in a few cases of benign renal diseases, elevated CA 19-9 has been noted.

Case Report: A 58-year-old Caucasian male patient was admitted in our clinic with complaints about blunt abdominal pain in the past two-month period localized in the right lumbar region and irradiating into the right inguinal area, constipation, abdominal bloating, and intermittent hematuria. The concentration of serum CA 19-9 was 3500 U/mL. Urine cytology provided no signs of abnormality. Intravenous urography visualized right-sided pyelon and ureter duplex with the defect in contrast shade of the pyelon, caused by a stag horn calculus. Contrast added computerized axial tomography of the abdomen and pelvis visualized the pyelon casted concretion spreading throughout the right pyelon, with ureterohydronephrosis with the distal block for passage of the contrast to the distal part of the ureter.

Conclusions: There is no doubt that CA 19-9 level is occasionally elevated in patients with obstructive urolithiasis as it was in our case. In the routine medical praxis, urolithiasis should not be neglected in the differential diagnosis of elevated concentrations of CA 19-9 marker.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917065PMC
http://dx.doi.org/10.12659/ajcr.897900DOI Listing
June 2016

Addenbrooke's cognitive examination test for brief cognitive assessment of adolescents suffering from migraine with aura.

Acta Neurol Belg 2017 Mar 2;117(1):97-102. Epub 2016 Jun 2.

Clinic of Neurology and Psychiatry for Children and Youth, Doktora Subotica 6a, 11000, Belgrade, Serbia.

The aim of this study was to assess the role of the Addenbrooke's cognitive examination test (ACE-R) in the evaluation of cognitive status in migraineurs interictally. A total of 44 adolescent patients and 44 healthy controls, matched by age and gender, have undergone ACE-R testing. Migraineurs were additionally questioned about migraine aura features and presence of higher cortical dysfunctions (HCD) during an aura. According to the questionnaire results, patients were subsequently divided into HCD and Non-HCD group. ACE-R scores of migraine patients were significantly lower than in healthy controls (93.68 ± 3.64 vs 96.91 ± 2.49; t = 4.852, p < 0.001). Also, subscores of memory and verbal fluency were significantly higher in the control population. There was no correlation of HCD occurrence with cognitive examination score, although Non-HCD subgroup achieved better score (93.13 ± 3.91 vs 94.29 ± 3.30; t = 1.053, p = 0.298). Findings have shown that migraineurs get lower ACE-R test scores, with a tendency to have a poorer outcome in more complex aura. Also, our study has revealed that the ACE-R test is an easily administered test for brief assessment of cognitive status in migraineurs. Future perspectives could be further evaluation of ACE-R test in larger sample size and the impact of migraine with aura on cognitive function in adolescents.
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http://dx.doi.org/10.1007/s13760-016-0655-9DOI Listing
March 2017

Brain changes in patients with posttraumatic stress disorder and associated alcoholism: MRI based study.

Psychiatr Danub 2015 Mar;27(1):78-83

University of Belgrade, School of Medicine, Pasterova 2, 11000 Belgrade, Serbia.

Background: Studies imposing rigorous control over lifetime alcohol intake usually have not found smaller hippocampal volumes in persons with posttraumatic stress disorder (PTSD). Since the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. We have hypothesized that the volumes of hippocampus, amygdale, prefrontal cortex and the intracranial volume are reduced in the patients with PTSD and excessive alcohol intake.

Subjects And Methods: Study has been carried out on 54 therapy naive PTSD suffering subjects and healthy controls, divided in two groups: 29 with PTSD and consequent alcoholism, 25 with PTSD but without problems of excessive alcohol intake, and 25 healthy volunteers. All of the patients underwent same magnetic resonance imaging (MRI) protocol and volumetric evaluation of the region of interest.

Results: Only hippocampal volume appeared to be significantly reduced in patients with PTSD and alcoholism. Other differences in the volumes obtained remained to be insignificant.

Conclusion: Alcohol intake definitely worsens the deterioration of the hippocampal formation in PTSD suffering patients. Nevertheless, other structures of interest for this study did not manifest any kind of statistical differences in volumetric analysis.
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March 2015

Thermomineral water promotes axonal sprouting but does not reduce glial scar formation in a mouse model of spinal cord injury.

Neural Regen Res 2014 Dec;9(24):2174-81

Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Thermomineral water from the Atomic Spa Gornja Trepča has been used for a century in the treatment of neurologic disease. The thermomineral water contains microelements, including lithium and magnesium, which show neural regeneration-promoting effects after central nervous system injury. In this study, we investigated the effects of oral intake of thermomineral water from the Atomic Spa Gornja Trepča on nerve regeneration in a 3-month-old mouse model of spinal cord injury. The mice receiving oral intake of thermomineral water showed better locomotor recovery than those without administration of thermomineral water at 8 and 12 weeks after lower thoracic spinal cord compression. At 12 weeks after injury, sprouting of catecholaminergic axons was better in mice that drank thermomineral water than in those without administration of thermomineral water, but there was no difference in glial reaction to injury between mice with and without administration of thermomineral water. These findings suggest that thermomineral water can promote the nerve regeneration but cannot reduce glial scar formation in a mouse model of spinal cord injury.
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http://dx.doi.org/10.4103/1673-5374.147950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316451PMC
December 2014

Anatomic description of the anterolateral ligament of the knee.

Knee Surg Sports Traumatol Arthrosc 2016 Jul 8;24(7):2083-8. Epub 2014 Nov 8.

Department of Anatomy, School of Medicine, University of Belgrade, dr Subotića 4, 11000, Belgrade, Serbia.

Purpose: The anterolateral ligament, a structure that has been known for 130 years, has again attracted the attention both of orthopaedic doctors and anatomists. Since its initial description until now, this structure has had different names. Whether labelled as the mid-third lateral capsular ligament, the anterior oblique band of the fibular collateral ligament or the anterolateral ligament of the knee, this structure has been responsible for the so-called Segond avulsion fractures. The aim of this study was to determine the precise position and layer of the lateral knee compartment within which the anterolateral ligament is located, as well as its type.

Methods: In this study, the anatomical dissection of the lateral segment of 14 cadaveric knees (six male, eight female; seven right, seven left; average age of subjects: 78 years) was performed. The dissection was carried out in keeping with Seebacher, layer by layer.

Results: The anterolateral ligament was identified in seven out of 14 cadaveric knee joints (50 %). The length of the ligament was 41 ± 3 mm, while the width was 4 ± 1 mm and the thickness 1 mm (in the middle section). In 14 % of the cases, the anterior oblique band was identified as a part of the FCL. In all of the knee joints, a part of the fibres of the ITT with the same insertions and direction as the ALL was found, located, however, at a much more superficial level than the ALL.

Conclusion: Analysis of the current scientific literature related to the anterolateral ligament and layer-by-layer dissection of the lateral region of 14 cadaveric knees has led to the conclusion that the anterolateral ligament is a thickening of the knee joint capsule located in the third layer of the lateral region of the knee (according to Seebacher) which is not always clearly morphologically differentiated from the remainder of the joint capsule. The anterolateral ligament is unequivocally a part of the joint capsule, which is why any damage to it should be treated in the same way as any other damage to the joint capsule.
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http://dx.doi.org/10.1007/s00167-014-3422-6DOI Listing
July 2016

The influence of sex hormones on anterior cruciate ligament ruptures in males.

Knee Surg Sports Traumatol Arthrosc 2015 Dec 27;23(12):3578-84. Epub 2014 Aug 27.

Department of Anatomy, School of Medicine, University of Belgrade, Dr Subotića 4, 11000, Belgrade, Serbia.

Purpose: The purpose of this study is to determine the difference in the concentrations of testosterone, 17-β estradiol and progesterone between male patients with and without ACL rupture, as well as the possible effect of these hormones on generalized joint laxity.

Methods: Male subjects with non-contact knee joint injury were included in this study. Two groups were formed: the examined group, consisting of subjects with ACL rupture and the control group consisting of patients without ACL rupture. After this, the patients from these two groups were paired off on the basis of three factors, level of professional involvement in sports (including the type of sports activity), left or right side of the body and the age of the subjects. In the end, there were 29 pairs (58 subjects). The concentration of sex hormones was determined from saliva specimens with the aid of the Salimetrics enzyme immunoassay. The testing of generalized joint laxity was performed with the aid of the "laxity score" according to Beighton et al.

Results: Subjects with ACL rupture have highly statistically significantly greater concentrations of testosterone (p < 0.01), statistically significantly greater concentrations of 17-β estradiol (p < 0.05), and a highly statistically significantly greater generalized joint laxity score than subjects with an intact ACL (p < 0.01).

Conclusion: Increased concentrations of testosterone or 17-β estradiol may be a risk factor leading to ACL rupture. Also, generalized joint laxity may be a factor leading to ACL rupture, but none of the monitored hormones can be set down as the cause of its existence. Young male athletes with higher concentrations of testosterone and greater hyperelasticity should plan preventive programs of physiotherapy for ACL preservation since they present a vulnerable group susceptible to ACL rupture.

Level Of Evidence: Diagnostic study, Level II.
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http://dx.doi.org/10.1007/s00167-014-3247-3DOI Listing
December 2015

Immunolocalization of different neuropeptides in human interthalamic adhaesion indicates its functionality.

Vojnosanit Pregl 2014 Jul;71(7):646-50

Background/aim: The interthalamic adhaesion (IA), gray matter connecting both thalami, is absent in about a quarter of human brains. Controversies are present about the nature and functional significance of the human IA.

Methods: In six adult human brains we investigated the expression of different neuropeptides: somatosatin (SOM), neuropeptide Y (NPY), ghrelin, neurotensin (NT), adrenocorticotropic hormone (ACTH), substance P (SP) and L-enkephalin (L-Enk) in neurons and/or neuropil of the IA, using immunohistochemistry (streptavidin-biotin technique).

Results: In neurons, as well as in fibers, we found immunoreactivity for ghrelin, SOM, L-Enk and NT. However, reactivity for NPY, SP and ACTH was present only in fibers within the IA. Fusiform neurons were immunoreactive for SOM, Ghrelin, L-Enk, and NT, neurons with oval perikaryon for SOM, and L-Enk, triangular neurons showed immunoreactivity mainly for NT and multipolar neurons for NT and L-Enk.

Conclusion: These findings can contribute to the understanding of the function of interthalamic adhaesion, and to resolving the question whether it is a vestigial structure. No mather if the interthalamic adhaesion is vestigial structure or not, its presence or absence could be a marker for other, genetic or functional differences between human brains. Our findings indicate the presence of certain neuronal organization in the human interthalamic adhaesion which could have functional significance, and do not support its vestigial nature.
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http://dx.doi.org/10.2298/vsp1407646pDOI Listing
July 2014

Novelties in the anatomy of the central nervous system and related disorders.

Biomed Res Int 2014 15;2014:514974. Epub 2014 Jun 15.

Cellular Neurobiology and Neurophysiology Laboratories, Centro de Investigación Médica Aplicada y Universidad de Navarra, Pamplona, Spain.

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http://dx.doi.org/10.1155/2014/514974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082860PMC
October 2015

Long-term effects of maternal deprivation on the neuronal soma area in the rat neocortex.

Biomed Res Int 2014 8;2014:235238. Epub 2014 May 8.

Institute of Anatomy "Niko Miljanic", Faculty of Medicine, University of Belgrade, dr Subotića 4, Belgrade 11000, Serbia.

Early separation of rat pups from their mothers (separatio a matrem) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group. The results of this study demonstrate that stress in early life has a long-term effect on neuronal soma size in cingulate and retrosplenial cortex and is potentially interesting as these structures play an important role in cognition.
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http://dx.doi.org/10.1155/2014/235238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034405PMC
January 2015

The influence of sex hormones on anterior cruciate ligament rupture: female study.

Knee Surg Sports Traumatol Arthrosc 2015 Sep 16;23(9):2742-9. Epub 2014 May 16.

Department of Anatomy, School of Medicine, University of Belgrade, dr Subotića 4, 11000, Belgrade, Serbia,

Purpose: The purpose of this study was to determine the difference in the concentrations of testosterone, 17-β estradiol and progesterone between female patients with and without ACL rupture and the possible effect of these hormones on generalised joint laxity.

Methods: Female subjects with non-contact knee joint injury were included in this study. They were divided into two groups: the examined group, consisting of female subjects with ACL rupture, and the control group, consisting of female patients without ACL rupture. In the next step, the patients from these two groups were paired off on the basis of three factors: the level of professional sports involvement (including the type of sports activity), the side of the body where the injury had occurred (left or right) and the age of the subjects. In the end, there were 12 pairs (24 subjects). The concentrations of sex hormones were established from saliva specimens with the aid of the Salimetrics enzyme immunoassay. Generalised joint laxity was tested with the aid of the "laxity score" according to Beighton, Solomon and Soskolne.

Results: Female subjects with ACL rupture had significantly lower concentrations of testosterone (p < 0.01), significantly lower concentrations of 17-β estradiol (p < 0.05) and significantly lower concentrations of progesterone (p < 0.01) than female subjects with intact ACL.

Conclusions: Decreased concentrations of testosterone, 17-β estradiol or progesterone may be a risk factor leading to ACL rupture. The concentrations of these hormones do not affect generalised joint laxity. Additional research on a larger group of patients is necessary to further determine the effects of these hormones on generalised joint laxity and ACL ruptures. Young female athletes with lower concentrations of sex hormones are more prone to anterior cruciate ligament rupture which is why they need to reduce their sports activities during the pre-ovulatory phase of the menstrual cycle, when these concentrations are additionally reduced.
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http://dx.doi.org/10.1007/s00167-014-3077-3DOI Listing
September 2015

Alternative method for direct measurement of tibial slope.

Vojnosanit Pregl 2014 Apr;71(4):335-40

Background/aim: The tibial slope is one of the most frequently cited anatomical causes of anterior cruciate ligament trauma. The aim of this study was to determine the possibility of direct measuring of the tibial slope of the knee without prior soft tissue dissection in cadavers.

Methods: Measurement was performed on the two groups of samples: osteological and cadaveric. The osteological group consisted of 102 matured tibiae and measurement was performed: indirectly by sagittal photographing of the tibia, and directly by a set of parallel bars. The cadaveric group consisted of 50 cadaveric knees and measurement was performed directly by a set of parallel bars. The difference and correlation between indirect and the direct measurements were observed, which included also measuring of the difference and correlation of the tibial slope on the medial and lateral condyles.

Results: A statistically significant difference between the direct and indirect method of measuring (p < 0.01) of 1 degree was found for the tibial slope on the medial condyle, which is of no practical importance. Direct measurement of the osteological and cadaveric groups of samples did not show a statistically significant difference regarding the values of the tibial slope on the lateral condyle (p > 0.05). However, the slope on the medial condyle, as well as indirect measurement showed a statistically significant difference (p < 0.01).

Conclusion: By the use of a set of parallel bars it is possible to measure the tibial slope directly without removal of the soft tissue. The results of indirect, photographic measurement did not statistically differ from the results of direct measurement of the tibial slope.
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http://dx.doi.org/10.2298/vsp1404335sDOI Listing
April 2014

Long-term effects of maternal deprivation on cholinergic system in rat brain.

Biomed Res Int 2014 10;2014:636574. Epub 2014 Mar 10.

Institute of Clinical and Medical Biochemistry, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade, Serbia.

Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD) produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach) release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE) activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS) cortex. Wistar rats were separated from their mothers on the postnatal day (P) 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.
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http://dx.doi.org/10.1155/2014/636574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966323PMC
December 2014

Psychiatric comorbidity in the treatment of patients with inflammatory bowel disease.

World J Gastroenterol 2014 Apr;20(13):3552-63

Branislav R Filipovic, Faculty of Medicine, Institute of Anatomy "Niko Miljanic", 11000 Belgrade, Serbia.

Ulcerative colitis and Crohn's disease, commonly known as inflammatory bowel disease (IBD), draw attention from specialists of various disorders, including gastroenterology, psychiatry, and radiology. The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD. The involvement of structures the limbic system, such as the anterior cingulate cortex, the prefrontal cortex, and the amygdala, paves the way for the discovery of the mechanisms underlying depression depression, anxiety, alexithymia, personality traits, and other psychological impairments following the onset of IBD. Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy. Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects, and psychotropic medication can provoke the worsening of IBD symptoms. Thus, both approaches must be applied with awareness of the possibility of side effects. We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.
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http://dx.doi.org/10.3748/wjg.v20.i13.3552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974522PMC
April 2014

Morphometric parameters as risk factors for anterior cruciate ligament injuries - a MRI case-control study.

Vojnosanit Pregl 2014 Mar;71(3):271-6

Background/aim: The anterior cruciate ligament (ACL) is the most frequently injured ligament of the knee, representing 50% of all knee injuries. The aim of this study was todeter mine the differences in the morphometry of knee injury patients with an intact and a ruptured anterior cruciate ligament.

Methods: The study included 33 matched pairs of patients divided into two groups: the study group with the diagnosis of anterior cruciate ligament rupture, and the control group with the diagnosis of patellofemoral pain but no anterior cruciate ligament lesion. The patients were matched on the basis of 4 attributes: age, sex, type of lesion (whether it was profession-related), and whether the lesion was left- or right-sided. Measurements were carried out using magnetic resonance imaging (MRI).

Results: The anterior and posterior edges of the anterior cruciate ligament in the control group were highly significantly smaller (p < 0.01; in both cases). The control group showed a statistically significantly larger width of the anterior cruciate ligament (p < 0.05). A significant correlation between the width of the anterior cruciate ligament and the width (p < 0.01) and height (p < 0.05) of the intercondylar notch was found to exist in the control group, but not in the study group (p > 0.05). The patients in the control group showed a shorter but wider anterior cruciate ligament in comparison to their matched pairs. The control group of patients was also characterized by the correlation between the width of the intercondylar notch and the width of the anterior cruciate ligament, which was not the case in the study group.

Conclusions: According to the results of our study we can say that a narrow intercondylar notch contains a proportionally thin anterior cruciate ligament, but we cannot say that this factor necessarily leads to rupture of the anterior cruciate ligament.
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http://dx.doi.org/10.2298/vsp1403271sDOI Listing
March 2014

Polysomnographic sleep patterns in depressive, schizophrenic and healthy subjects.

Psychiatr Danub 2014 Mar;26(1):20-6

Center of Clinical Neurophysiology & Sleep Research, University Psychiatric Clinic, Pasterova 2, 11000 Belgrade, Serbia,

Background: Sleep disorders are frequent symptoms described in psychiatric patients with major depression and schizophrenia. These patients also exhibit changes in sleep architecture measured by polysomnography (PSG) during sleep. The aim of the present study was to identify potential biomarkers to facilitate diagnosis based on PSG measurements.

Subjects And Methods: Thirty (30) patients with schizophrenia, 30 patients with major depression and 30 healthy control subjects were investigated in the present study. All subjects underwent PSG measurements for a minimum time of 8 hours according to the criteria of Rechtscahffen & Kales (1968). We tested the potential of multiple sleep variables to predict diagnosis in different groups by using linear discriminant analysis (LDA).

Results: There were significant differences in PSG variables between healthy control subjects and psychiatric patients (total sleep time, sleep latency, number of awakenings, time of awakening after sleep onset, REM 1 latency, REM 1 and index of endogenous periodicity). Importantly, LDA was able to predict the correct diagnosis in 88% of all cases.

Conclusions: The presented analysis showed commonalities and differences in PSG changes in patients with major depressive disorder and in patients with schizophrenia. Our results underline the potential of PSG measurements to facilitate diagnostic processes.
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March 2014

Profiling differences in chemical composition of brain structures using Raman spectroscopy.

Talanta 2013 Dec 6;117:133-8. Epub 2013 Sep 6.

Faculty of Physical Chemistry, Studentski trg 12-16, University of Belgrade, Belgrade, Serbia. Electronic address:

Raman spectroscopy enables non-invasive investigation of chemical composition of biological tissues. Due to similar chemical composition, the analysis of Raman spectra of brain structures and assignment of their spectral features to chemical constituents presents a particular challenge. In this study we demonstrate that standard and independent component analysis of Raman spectra is capable of assessment of differences in chemical composition between functionally related gray and white matter structures. Our results show the ability of Raman spectroscopy to successfully depict variation in chemical composition between structurally similar and/or functionally connected brain structures. The observed differences were attributed to variations in content of proteins and lipids in these structures. Independent component analysis enabled separation of contributions of major constituents in spectra and revealed spectral signatures of low-concentration metabolites. This provided finding of discrepancies between structures of striatum as well as between white matter structures. Raman spectroscopy can provide information about variations in contents of major chemical constituents in brain structures, while the application of independent component analysis performed on obtained spectra can help in revealing minute differences between closely related brain structures.
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http://dx.doi.org/10.1016/j.talanta.2013.08.058DOI Listing
December 2013

Long-term effects of the maternal deprivation on the volume and number of neurons in the rat neocortex and hippocampus.

Acta Neurobiol Exp (Wars) 2013 ;73(3):394-403

Institute of Anatomy "Niko Miljanic", Faculty of Medicine, University of Belgrade, Belgrade, Serbia,

Maternal deprivation (MD) leads to a variety of behavioral changes in rats which closely resemble the symptoms of schizophrenia in humans. With the aim to investigate the morphological changes which underlie the behavioral insults in this experimental paradigm we exposed 9-day-old Wistar rats to a 24 h MD. At the period of young adulthood rats were sacrificed for morphometric analysis and their brains were compared to the control group. Rats exposed to MD had a decrease in hippocampal volume (71 percent of the control value) as well as a decrease in the size of pyramidal (62 percent of the control) and granular (60 percent of the control) cell layers. Also, there was a decrease in the thickness of the prefrontal, retrosplenial and motor cortex compared to the control group. Analysis of the density of NeuN-immunolabeled neurons revealed a reduction in retrosplenial and prefrontal cortex (70 percent and 81 percent of the control, respectively), while there was no difference in the motor cortex. Western blot analysis confirmed a decrease in NeuN expression in the MD group compared to the control rat brain homogenates. The results of this study show that early stress in life has a long-term effect on the morphology of cognitive brain regions, most probably due to the loss of neurons during postnatal development and further contributes to our understanding of the effects of maternal separation on brain development.
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April 2014

Ultrasonography analysis of gallbladder motility in patients with functional dyspepsia.

Eur J Intern Med 2014 Feb 4;25(2):156-9. Epub 2013 Sep 4.

Faculty of Medicine, University of Belgrade, Serbia; Institute of Anatomy "Niko Miljanic," Belgrade, Serbia.

Background: Gallbladder motility has been studied in patients with functional gastrointestinal disorders, such as functional dyspepsia, irritable bowel syndrome and biliary disorders without gallstones and results of these observations are often inconclusive and conflicting.

Methods: The investigation was performed on 180 therapy-naïve newly diagnosed patients with functional dyspepsia (97 females and 83 males), aged 20-79 in which we have investigate ultrasonographically parameters of gallbladder motility.

Results: Bonferroni post hoc correction stressed that fasting gallbladder volume and ejection fraction were significantly distorted in individuals with postprandial distress syndrome, although, the residual gallbladder volume was significantly lower in patients with epigastric pain syndrome comparing with other examinees. Ejection fraction of the gallbladder negatively correlated with body mass index.

Conclusion: The impaired contractibility of the gall bladder in patients with functional dyspepsia, based on the results of this study, is illustrated by the changes in the ejection fraction, which was more pronounced in patients with the postprandial distress syndrome.
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http://dx.doi.org/10.1016/j.ejim.2013.08.699DOI Listing
February 2014

[The role of the posterior tibial slope on rupture of the anterior cruciate ligament].

Vojnosanit Pregl 2012 Oct;69(10):864-8

Institut za anatomiju dr Niko Miljanić, Medicinski fakultet Univerziteta u Beogradu, Beograd, Srbija.

Background/aim: Posterior tibial slope is one of the most citated factors wich cause rupture of the anterior cruciate ligament (ACL). The aim of this study was to determine the association of a greather posterior tibial slope on the lateral condyle, that is a lesser posterior tibial slope on the medial condyle, with ACL rupture.

Methods: The patients were divided into two groups. The study group included the patients with chronic instability of the knee besause of a previous rupture of ACL. The control group included the patients with knee lesion, but without ACL rupture. Posterior tibial slope measuring was performed by sagittal MR slices supported by lateral radiograph of the knee. We measured posterior tibial slope on lateral and medial condyles of the tibia. Using these values we calculated an average posterior tibial slope as well as the difference between slopes on lateral and medial condyles.

Results: Patients with ACL rupture have highly statistically significantly greather posterior tibial slope (p < 0.01) on lateral tibial condyle (7.1 degrees : 4.5 degrees) as well as statistically significantly lesser posterior tibial slope (p < 0.05) on medial tibial condyle (5.9 degrees : 6.6 degrees) than patients with intact ACL.

Conclusion: Great posterior tibial slope on lateral tibial condyle associated with the small posterior tibial slope on the medial tibial condyle, that is a positive differentce between lateral and medial tibial condyles are factors wich may cause ACL rupture.
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http://dx.doi.org/10.2298/vsp101230022sDOI Listing
October 2012
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