Papers by Marija Bjelakovic
Pediatric Nephrology, Dec 23, 2017
Background Human fetal kidney development is a complex and stepwise process. The number, shape, s... more Background Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Methods Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. Results During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. Conclusions The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.
The Scientific World Journal, 2012
Development of germ cells is a process starting in fetus and completed only in puberty. Spermatog... more Development of germ cells is a process starting in fetus and completed only in puberty. Spermatogonial stem cells maintain spermatogenesis throughout the reproductive life of mammals. They are undifferentiated cells defined by their ability to both selfrenew and differentiate into mature spermatozoa. This self-renewal and differentiation in turn is tightly regulated by a combination of intrinsic gene expression as well as the extrinsic gene signals from the local tissue microenvironment. The human testis is prone to damage, either for therapeutic reasons or because of toxic agents from the environment. For preservation of fertility, patients who will undergo radiotherapy and/or chemotherapy have an attractive possibility to keep in store and afterwards make a transfer of spermatogonial stem cells. Germ cell transplantation is not yet ready for the human fertility clinic, but it may be reasonable for young cancer patients, with no other options to preserve their fertility. Whereas this technique has become an important research tool in rodents, a clinical application must still be regarded as experimental, and many aspects of the procedure need to be optimized prior to a clinical application in men. In future, a range of options for the preservation of male fertility will get a new significance.
Journal of Cellular and Molecular Medicine, Feb 1, 2009
The term 'interstitial cells of Cajal' (ICC) has been adopted to refer to several types of cells ... more The term 'interstitial cells of Cajal' (ICC) has been adopted to refer to several types of cells located in the musculature of the gastrointestinal tract (GIT), morphologically and functionally intercalated between the segments of the enteric nervous system and smooth muscle cells (SMCs). Some ICC groups act as sources of spontaneous electric slow waves responsible for paced contractions of the intestinal musculature ('intestinal pacemakers'), whereas other ICC groups are involved in the modulation of enteric neurotransmission [1-4]. ICC have been found throughout the human digestive tract, including the oesophagus, stomach, small and large intestines to the inner sphincter region of the anus [5-9]. ICC express the gene product of c-kit, a proto-oncogene that encodes the receptor tyrosine kinase Kit [10, 11]. Labelling of Kit receptors or c-kit mRNA have provided efficient means of identifying ICC at the light level in a variety of preparations, including human specimens [12]. A cytokine, termed steel factor or stem cell factor (SCF), has been identified as a c-kit ligand [13]. Recent studies have shown that ICC are not derived from the neural crest, but rather are mesodermal in origin [14-16]. Developmental studies suggest that some ICC and SMCs have a common precursor that expresses c-kit [15, 17]. Kit is important in dividing the original line of mesenchymal precursors during differentiation towards ICC or SMCs, for normal postnatal development and for maintenance of the ICC phenotype [18, 19]. SCF/Kit signalling favours the development of ICC at the myenteric plexus
Nephrology Dialysis Transplantation, May 1, 2016
Cells Tissues Organs
This study aimed to morphometrically examine the development of glomeruli and tubules in the kidn... more This study aimed to morphometrically examine the development of glomeruli and tubules in the kidney cortex of human foetuses at different gestational ages (GAs). We also investigated the expression of the proliferation marker Ki-67 and apoptosis-related markers Bcl-2 and Bax during nephrogenesis using immunohistochemistry. Kidney samples from 38 human foetuses of both sexes with GA ranging from 13 to 40 weeks were analysed. The average area, perimeter, and Feret's diameter of the glomeruli gradually decreased up to a period of 29–32 weeks of gestation and subsequently increased until a period of 37–40 weeks. There was a weak negative correlation with GA. In contrast, the areal density of glomeruli increased up to a period of 21–24 weeks and then gradually decreased until a period of 37–40 weeks, showing a moderate negative correlation with GA. The average area of renal tubules slightly decreased until a period of 21–24 weeks of gestation and then gradually increased until a peri...
RAD Association Journal, 2017
In this study, we aimed to analyze the variability in the size and localization of infraorbital f... more In this study, we aimed to analyze the variability in the size and localization of infraorbital foramen (IOF) with respect to the surrounding anatomical bony landmarks using the three-dimensional computed tomography (3D-CT) with the volume rendering and evaluate these morphometric parameters in relation to the gender and side. The cranial CT scans of 60 living adult subjects, without any trauma or malformation of facial bones were included in the study. Data of the subjects were collected in the Center of Radiology, Clinical Center Nis, Serbia. Measurements included the transverse and vertical diameter of the IOF foramen, the distance from IOF to facial midline, the distance to lateral margin of the piriform aperture, the distance to infraorbital margin and the distance to maxillary alveolar border. All measurements were done bilaterally and performed with a digital coordinate caliper. Obtained results were statistically analyzed. Observation of 120 hemi-skulls revealed that the IOF was present in all of them. The mean transverse diameter of the IOF was 2.81 ± 0.69 mm and the mean vertical diameter was 3.41 ± 0.88 mm. The IOF was located at an mean distance 26.17 ± 1.69 mm from facial midline, 14.99 ± 1.30 mm from the lateral margin of the piriform aperture, 9.06 ± 1.01 mm below the IOM and 28.22 ± 2.78 mm above the maxillary alveolar border. Statistically significant difference was found between males and females for the distance from IOF to PA (p < 0.05). These morphometric characteristics may have important implications for the surgical and local anesthetic planning.
The fact that cell death is not ultimately a bad thing came as a surprise to many researchers. Ph... more The fact that cell death is not ultimately a bad thing came as a surprise to many researchers. Physiological cell death has been observed in various multicellular organisms. Apoptosis or programmed cell death is the predominant form of physiological cell death by which the organism eliminates unnecessary or damaged single cells. It is a major component of normal development and disease. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change to assure that apoptotic cells will be immediately recognized and engulfed by neighboring cells or phagocytes leading to little or no inflammation. A wide variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Death receptors that initiate apoptosis include the Fas receptor and the TNF receptor systems. After an appropriate stimulus, the first stage of apoptosis or "decision phase" is the genetic control point of cell death. This is followed by the second stage or "execution phase", which is responsible for the morphological change in apoptosis. The third stage is engulfment of the dying cell followed by degradation of the engulfed cell DNA. There are two overlapping signaling pathways leading to apoptosis, termed the intrinsic and extrinsic pathways. In the intrinsic, various stimuli, such as oxidative stress, lead to mitochondrial dysfunction and the release of pro-apoptotic factors. Ligand binding to cell surface death receptors, such as Fas, activates the extrinsic pathway. During the last decades the molecular mechanisms involved in disordered apoptosis were unraveled, suggesting that cancer, chronic disease, and fetal developmental abnormalities can occur as a result of disordered apoptosis.
Medicinski pregled, 2010
Introduction. Malformations in kidney development and kidney diseases are accompanied with change... more Introduction. Malformations in kidney development and kidney diseases are accompanied with changes in their size. For kidney evaluation in clinical practice, the kidney length is the most widely used measurement, since it provides the most precise results and it is easy to perform. Recently, the measurement of relative renal length has become more preferable as it takes into account the body height. The aim of this study was to measure both the absolute and relative length of normal cadaveric kidneys according to the body height, sex and age. Material and methods. In this study, we examined 95 adult cadaveric kidneys, without renal and vascular impairment, their age ranging from 23-87 years. To determine the period of the most abundant changes in kidney length, we separated them into a 10-year range. The relative renal length was calculated using the kidney length anybody height ratio (kidney/body ratio). Results. The absolute and relative length of left kidney in males was longer t...
International Journal of Basic and Applied Sciences, 2015
Background: During the pregnancy the amount of polyamines spermine, spermidine and putrescine, ri... more Background: During the pregnancy the amount of polyamines spermine, spermidine and putrescine, rise rapidly in amniotic fluid. Polyamine oxidase (PAO) represents one of the key enzymes in catabolic pathway of polyamines. PAO catalyzes the oxidative deamination of spermine (Sp) or spermidine (Spd). The literature data documented that serum PAO activity increases in pregnancy. Diamine oxidase (DAO), histaminase, catalyses the oxidation of diamine putrescine or histamine. DAO is present in high concentrations in amniotic fluid. Amniotic fluid is the protective liquid for the baby in the mother's uterus. The determination of the lecithin to sphyngomyelin (L/S) ratio is by far the most widely used and accepted method to assess the fetal lung immaturity. The idea of the present study was to elucidate the polyamine metabolism in amniotic fluid during the pregnancy, through investigation of polyamine oxidase (PAO) and diamine oxidase (DAO) activities, and to compare their activities with the values of lecithin/ sphingomielin ratio (L/S) ratio. Methods: The study included 170 pregnant women. The amniotic fluid samples were obtained using amniocentesis. The values of L/S ratio were estimated by a thin layer chromatography. PAO and DAO activities were measured by the spectrophotometric methods. Results: Our results confirmed that amniotic fluid possess PAO and DAO activity. The activities of both enzymes in amniotic fluid samples increase in parallel with the L/S ratio increase. Diamine oxidase activity was higher than polyamine oxidase activity. Conclusions: DAO and PAO activities may serve as markers of fetal lung maturity.
Journal of Cellular and Molecular Medicine, 2009
The term 'interstitial cells of Cajal' (ICC) has been adopted to refer to several types of cells ... more The term 'interstitial cells of Cajal' (ICC) has been adopted to refer to several types of cells located in the musculature of the gastrointestinal tract (GIT), morphologically and functionally intercalated between the segments of the enteric nervous system and smooth muscle cells (SMCs). Some ICC groups act as sources of spontaneous electric slow waves responsible for paced contractions of the intestinal musculature ('intestinal pacemakers'), whereas other ICC groups are involved in the modulation of enteric neurotransmission [1-4]. ICC have been found throughout the human digestive tract, including the oesophagus, stomach, small and large intestines to the inner sphincter region of the anus [5-9]. ICC express the gene product of c-kit, a proto-oncogene that encodes the receptor tyrosine kinase Kit [10, 11]. Labelling of Kit receptors or c-kit mRNA have provided efficient means of identifying ICC at the light level in a variety of preparations, including human specimens [12]. A cytokine, termed steel factor or stem cell factor (SCF), has been identified as a c-kit ligand [13]. Recent studies have shown that ICC are not derived from the neural crest, but rather are mesodermal in origin [14-16]. Developmental studies suggest that some ICC and SMCs have a common precursor that expresses c-kit [15, 17]. Kit is important in dividing the original line of mesenchymal precursors during differentiation towards ICC or SMCs, for normal postnatal development and for maintenance of the ICC phenotype [18, 19]. SCF/Kit signalling favours the development of ICC at the myenteric plexus
TheScientificWorldJournal, 2012
Development of germ cells is a process starting in fetus and completed only in puberty. Spermatog... more Development of germ cells is a process starting in fetus and completed only in puberty. Spermatogonial stem cells maintain spermatogenesis throughout the reproductive life of mammals. They are undifferentiated cells defined by their ability to both self-renew and differentiate into mature spermatozoa. This self-renewal and differentiation in turn is tightly regulated by a combination of intrinsic gene expression as well as the extrinsic gene signals from the local tissue microenvironment. The human testis is prone to damage, either for therapeutic reasons or because of toxic agents from the environment. For preservation of fertility, patients who will undergo radiotherapy and/or chemotherapy have an attractive possibility to keep in store and afterwards make a transfer of spermatogonial stem cells. Germ cell transplantation is not yet ready for the human fertility clinic, but it may be reasonable for young cancer patients, with no other options to preserve their fertility. Whereas t...
Srpski arhiv za celokupno lekarstvo, 2006
Introduction. Newborns adaptation on postnatal conditions includes significant morphological and ... more Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diamete...
Acta Medica Medianae
The aim of this study was to analyze the variability in the shape and number of supraorbital tran... more The aim of this study was to analyze the variability in the shape and number of supraorbital transcranial passages, supraorbital notch or foramen (SON/F) in southeast Serbian population using three-dimensional computer tomography (3D-CT) with the volume rendering and to evaluate these variations in relation to gender and side. One hundred and fifteen CT scans of adult subjects (59 men and 56 women) without any skull trauma or malformation, aged 21 to 83 years, were analyzed in our study. Of 230 supraorbital regions, a smooth supraorbital rim with absent SON/F was observed in 37.39%. The most common type of the supraorbital passage was single SON (53.48%). Single SOF was found in 5.22% and incomplete SOF in 0.44%. The frequency of double SON was 1.30%, double SOF 0.87% and SON with SOF on the same side was 1.30%. There was no statistically significant difference between genders and sides (p˃0.05). Fourteen various combinations of different types were observed in our material. The most common combination was bilateral SON (33.91%) and bilateral absence of SON/F (20.87%). A very frequent combination was SON on one side and the absence of SON/F on the contralateral side (32.17%). Other combinations of types were rare. The knowledge of the frequency of the types of supraorbital transcranial passages and their bilateral distribution may be helpful for clinicians in anticipating the exit point of the supraorbital neurovascular bundle during surgical procedures and planning of local anesthesia.
RAD Association Journal, 2017
The identification of the mental foramen is important for both diagnostic and clinical procedures... more The identification of the mental foramen is important for both diagnostic and clinical procedures. The knowledge about its accurate location is significant in reducing complications that may occur during surgical and endodontic treatments involving the mental area. The purpose of this study was to determine the position of mental foramen in relation to the radiographic apex of the mandibular second premolar on panoramic radiographs. Two hundred digital panoramic radiographs were analyzed in this study. Horizontal and vertical position of the mental foramen was determined in relation to the two reference lines which passed through the apex of the mandibular second premolar. The possible positions were: mesial below, mesial intersecting, mesial above, intersecting below, centered, intersecting above, distal below, distal intersecting and distal above. Fifty percent of the panoramic radiographs showed that the mental foramen position was mesial and below the radiographic apex of the second premolar. Mesial and intersecting position was observed in 21% of the radiographs, centered in 13%, intersecting and below in 8%, distal and below in 6%, while 2% of the radiographs showed distal and intersecting position of the mental foramen. No statistically significant differences in the position and the symmetry of the mental foramen were observed in relation to the gender and the side of the mandible. The most common position of the mental foramen was mesial and below the radiographic apex of the mandibular second premolar. For an accurate assessment of the location of the mental foramen, a preoperative radiological study with a panoramic radiograph is necessary.
Cells Tissues Organs, 2006
Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/cto_issues 226 Assessing a Non-Traditional View of Adipogenesis: Adipocyte Dediff erentiation-Mountains or Molehills?
Cells Tissues Organs
The aim of this study was to determine the developmental characteristics of podocytes in the huma... more The aim of this study was to determine the developmental characteristics of podocytes in the human fetal metanephros using scanning electron microscopy, light microscopy, and transmission electron microscopy. Kidney samples of 15 human fetuses of both sexes (gestational age 10–22 weeks) were analyzed. At the S-shaped body stage, primitive podocytes were arranged in a layer of cuboidal cells beneath the vascular cleft. When observed from Bowman’s space, the demarcation between adjacent podocytes was not clear, but mild depressions indicated cell boundaries. At the more advanced S-shaped body stage, podocytes were polygonal, with a flat apical surface. They were in close contact, but boundaries between adjacent cells were distinct. After initial separation of their apical parts, podocytes continued to separate from each other along their lateral sides. Their shape changed from polygonal to spherical, resembling clusters of grapes. Cytoplasmic buds could be seen at the base of some pod...
Annals of Plastic Surgery
Glasnik Antropoloskog drustva Srbije
The mental foramen is an important anatomic landmark not only in dentistry but also in forensics,... more The mental foramen is an important anatomic landmark not only in dentistry but also in forensics, and the knowledge about its accurate location is important in receiving local anesthesia, during surgical and endodontic procedures. The purpose of this study was to determine the most common position and shape of the mental foramen in the Southeast Serbian population. Three hundred panoramic radiographs were analyzed and the horizontal position of the mental foramen was determined according to the reference lines drawn at the longitudinal axes of the first and the second premolar and the mesial root of the first molar. In 62% of the cases mental foramen was between longitudinal axes of the first and the second premolar, in 21% it was in line with the second premolar, in 9% in line with the first premolar, in 8% between the axes of the second premolar and the first molar. The most common shape was round (54%). The horizontal position and shape were asymmetrical in 26% and 32% of the cases, respectively. The most common position of the mental foramen was between the first and the second premolar, while the most common shape was round. Knowledge about variable positions of the mental foramen is important in establishing diagnosis and clinical procedures in the region of the mandible.
Vojnosanitetski pregled
Background/Aim. Lower-leg septocutaneous system of perforating blood vessels represents the vascu... more Background/Aim. Lower-leg septocutaneous system of perforating blood vessels represents the vascular basis of fasciocutaneous flaps. Additionally, it is of a particular importance when designing distally based fasciocutaneous flaps which represent the ?workhorse? in the reconstruction of the distal third of the lower leg and foot. The aim of this study was to analyse the vascular anatomy of posterior tibial artery and its septocutaneous (fasciocutaneous) perforating arterial vessels. Methods. The dissection was conducted on 20 fetuses of both sexes and of gestational age from 20 to 28 weeks. Cluster analysis was applied to the data on vascular anatomy of posterior tibial artery and its septocutaneous performating arterial vessels. Results. A total of 212 perforating arterial vessels was identified. The average number of perforating arterial vessels was 5.32 (ranging from 4 to 7). It was identified that septocutaneous perforating blood vessels are more likely to be found at certain l...
Vojnosanitetski pregled
The idea that precursors for a growing list of cancers are 'cancer stem cells' is very old. It ha... more The idea that precursors for a growing list of cancers are 'cancer stem cells' is very old. It has been speculated that tumours are initiated and maintained by a population of cancer cells with stem cell properties known as 'cancer stem cells'. It has been hypothesised that testicular carcinoma in situ cells resemble cancer stem cells in body. Testicular cancer is an uncommon malignancy in men and is curable in most instances. More than 90% of all testicular cancers are germ-cell tumours almost equally divided in seminomas and nonseminomas. During testicular carcinogenesis, pre-invasive cells gave rise to overt tumour. Testicular germ cell cancer is derived from cells in the germ cell lineage that are blocked in maturation. The pre-invasive stage of testicular germ cell tumour of the adolescents and young adults is carcinoma in situ or intratubular germ cell neoplasia unclassified, which is thought to arise from a malignant transformation of a primordial germ cells or gonocyte. Understanding the biology and cellular chemistry of carcinoma in situ is important for developing new strategies for prevention and treatment of testicular germ cell tumours. Efforts should be made to obtain diagnosis of testicular germ cell tumours at the carcinoma in situ stage as early intervention is warranted before an invasive tumour develops. Further research is needed to obtain a method of non-invasive carcinoma in situ. It would make possible to offer the patient the optimal treatment.
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Papers by Marija Bjelakovic