Ivan Jovanović

Viral Infection in Renal Transplant Recipients

Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

Glomerular basement membrane alterations induced by gentamicin administration in rats

The widespread therapeutic use of the aminoglycoside antibiotic gentamicin (GM) is limited by its nephrotoxic side effect, which can lead to acute renal failure. This study aimed at examining effects of high, supratherapeutic doses of gentamicin on morphological, structural and functional alterations of the glomerular basement membrane in adult rats. Experiments were done on 30 male Wistar rats, divided into two experimental groups. GM-group (20 rats) received gentamicin at a dose of 100mg/kg intraperitoneally during eight consecutive days. Control or C-group (10 rats) received 1 ml/day saline intraperitoneally. For histological analysis, 5 microm thick sections were stained with hematoxylin and eosin (HE), periodic acid Schiff (PAS), and Jones methenamine silver. Glomerular basement membrane thickness, glomerular area, major and minor axes, perimeter, diameter, roundness and mean optical density were analyzed. Biochemical analyses were used to determine concentrations of blood urea, serum creatinine, sodium and potassium. In GM-group rats, glomeruli were larger and glomerular basement membrane was diffusely and irregularly thickened with neutrophil cell infiltration. Glomerular area, major axis, minor axis, diameter and perimeter were significantly higher in GM-group compared to C-group rats. Opposite to this, glomerular optical density and average roundness were larger in C-group than in gentamicin-treated animals. Our results clearly showed morphological and structural alterations of glomeruli and glomerular basement membrane as well as alterations of proximal tubules in adult rats exposed to high doses of gentamicin.

Frequency of the C1236T, G2677T/A and C3435T MDR1 gene polymorphisms in the Serbian population.

The multi-drug resistance 1 (MDR1) gene encodes for a P-glycoprotein (PGP), which acts as a gate-keeper against various kinds of xenobiotics. Several single nucleotide polymorphisms (SNPs) in the MDR1 gene that may influence PGP level and function have been identified. The aim of this study was to simultaneously analyze the three most important MDR1 SNPs, C3435T, G2677T/A and C1236T, in the Serbian population and to compare the results with those published for other ethnic groups. A group of 158 unrelated, healthy subjects was included in the present study. For determination of MDR1 SNPs, a multiplexed mutagenically separated PCR was performed. The genotype frequency of the analyzed MDR1 SNPs was as follows: 3435 nt - 0.19 (CC), 0.54 (CT) and 0.27 (TT); 2677 nt - 0.26 (GG), 0.52 (GT), 0.15 (TT), 0.03 (GA) and 0.064 (TA), and 1236 nt - 0.23 (CC), 0.61 (CT) and 0.16 (TT). Our results for the Serbian population could be relevant for further investigation of drugs that are substrates of PGPand for studies of interethnic diversity in MDR1 polymorphism frequency.

Trigeminal artery: a review of normal and pathological features

ObjectsCarotid–vertebrobasilar anastomoses—the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries—serve as transitory channels between primitive internal carotid arteries and bilateral longitudinal neural arterial plexus, which is the precursor of future basilar artery, when the human embryo reaches about 4-mm length.Material and methodsNormal and/or abnormal morphofunctional aspects of the prenatal and postnatal forms of the trigeminal artery are described according to personal and literature data. Many arteries of similar origin and course are also noted in the differential diagnosis of the trigeminal artery.ConclusionsThe persistent primitive trigeminal artery, as the most commonly carotid–vertebrobasilar anastomosis, has a reported incidence of 0.03–2.2% in the literature. There is female sex predilection, and it may be discovered in patients of any age, on either side, and in association with many vascular variants. Although the significance of persistent primitive trigeminal artery regarding the development of an aneurysm or association with another pathological condition may not be clear, its (ab)normal morphology is the inspiration for anatomists, especially for neurosurgeons, before planning diagnostic and therapeutic procedures.

Peculiarities of the sural nerve complex morphologic types in human fetuses

The sural nerve is the most frequently used sensory nerve in nerve transplantation. It can be transplanted alone or together with the other elements of the neurovascular stalk within the superficial sural flap. The aim of this study was to define the morphologic types of the sural nerve complex, as well as to describe their specific characteristics. Microdissection was performed on 100 human fetuses (200 calves) after 10% formalin fixation. Five morphologic types of sural nerve complex with different incidence were defined. Two morphologic types dominated: type I (58.5%) in which the sural nerve was formed by merging of a fibular communicating branch and the medial sural cutaneous nerve, and type III (26%) in which the medial sural cutaneous nerve took over the function of the sural nerve. Other morphologic variations were less common.

Beta2-Microglobulin and Alpha1-Microglobulin as Markers of Balkan Endemic Nephropathy, a Worldwide Disease

Background: Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined. Methods: This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families. Results: In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker. Conclusion: All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.

Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats.

AIMS One of the most popular beverages worldwide, green tea, was investigated for its potential protective effect in a rat model of gentamicin-induced nephrotoxicity by monitoring functional and morphological changes in kidneys. MAIN METHODS The study was conducted on four groups of rats: control group (C), treated with only gentamicin (GM), treated with only green tea (GT) and treated with both gentamicin and green tea (GT+GM). Kidney function, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. Morphometric analysis was used to quantify these histopathological changes. KEY FINDINGS Gentamicin caused significant elevations in serum creatinine and urea and oxidative stress parameter (AOPP), while antioxidative enzyme catalase was significantly decreased. Histological sections of kidneys in GM group revealed necrosis of proximal tubules, vacuolation of cytoplasm and massive mononuclear inflammatory infiltrates in interstitium. Coadministration of green tea with gentamicin histologically showed renoprotective effect. Histological results were confirmed and quantified by morphometric analysis. Also in this group we measured ameliorated parameters of renal functions and antioxidative defense. SIGNIFICANCE Regenerative potential of green tea after renal injury induced by gentamicin could be explained through the decrease of oxidative stress and lipid peroxidation. Green tea is a natural antioxidant, with many health promoting effects, widely available and in accordance to that affordable. Because of the established habits, people largely consume it as a beverage. It could be beneficial in the reduction of oxidative stress and changes caused by it primarily in renal tubules and interstitium.

Human Basilar Artery Abnormalities in the Prenatal and Postnatal Period

OBJECTIVE Although complex and varied, adult cerebral angioarchitecture has its origins in embryologic development, where normal components, variations, and abnormalities evolve from modifications of primitive vessels. Therefore, the aim of this report was the study of the morphologic features of the basilar fenestrations in prenatal and postnatal period and associated variants and/or pathologies. METHODS We studied the brain vessels of 120 fetuses microscopically (i.e., with an operative microscope) and 112 adult cadavers macroscopically. RESULTS We described 10 cases of basilar abnormalities, five fetal and four adult fenestrations, as well as one adult case with a basilar aneurysm. The location of the vertebrobasilar junction on a caudal myelencephalon and a prolongation of the basilar trunk followed both fetal and adult forms of fenestrations. The same caliber values of the basilar and internal carotid arteries, a variation in the number and origin of some of the basilar side branches, and a tendency of fenestrations to be multiple in number, as particular fetal features, were mostly present in adults. CONCLUSION The fact that basilar fenestrations in adult specimens shared similar features with fetal ones and without aneurysms, as well as the fact that a basilar aneurysm was without fenestration in its base, lead us to hypothesis that the basilar fenestration is a vascular developmental variant related to the maintenance of vascular symmetry in the midline of the human brain base.

Morphology of the cerebral arterial circle in the prenatal and postnatal period of Serbian population

BackgroundIn the literature, there are descriptions of morphological types of the cerebral arterial circle (CAC) of different human populations around the world, but not the Serbian population. This additionally inspired the authors to present the results of previous and current researches of CAC’s configuration in the prenatal, as well as in the postnatal period.MethodThe study was performed on CACs of 190 human fetuses and 143 adult cadavers. The caliber and configuration of fetal vessels were examined under the operating microscope, while the same of adults were studied using the ImageJ. Statistical analysis of CACs vessels’ calibers was performed. Classification into one of CAC morphological types was based on the presence of hypoplasia of corresponding vessel(s).ResultsThere was not only significant difference of the three communicating arteries calibers before and beyond the 16th week of gestation. Calibers of the right pre-communicating part of the posterior cerebral artery and right cerebral part of the internal carotid artery were significantly higher in male than in female adults. There were 13 morphological types of CACs from the prenatal to the postnatal period. Most frequent CAC types were the type I (normal CAC) prenatally and type IV (unilateral hypoplasia of the posterior communicating artery) in the postnatal period. There were not relationships between the cerebral cause of death and a presence of aneurysm.ConclusionResults of this study will be the basis for future investigation of CACs according to the same or different ages and causes of disease and/or death.

Psammoma bodies - friends or foes of the aging choroid plexus.

Psammoma bodies are structures classified in the group of dystrophic calcifications, which occur in some kind of tumors and in choroid plexus during the aging process. Despite early discovery of their presence in choroid plexus stroma, mechanisms responsible for their formation remained unclear. Their presence in some kind of tumors was even more extensively studied, but significant breakthrough in the field of their etiology was not attained, too. However, till today correlation between their presence in tumors and aging is not established. Also, there are not any data about structural differences between ones found in tumors and ones found in choroid plexus. This might points to the assumption that besides the aging, some other causes might be involved in their formation in choroid plexus. Furthermore, it is contradictory that forms, like psammoma bodies, present in such malignant formations as tumors, represent quite benign phenomenon in choroid plexus. Literature data and the results of our previous researches revealed that there might be connections between, these, on the first sight quite different processes. Firstly, psammoma bodies are present in stroma of tumors with predominantly papillomatous morphology, which is present in choroid plexus, too. Initial forms of psammoma bodies might be formed in fibrovascular core of choroid plexus villi, similarly like in tumors papillae of papillary thyroid cancer. Their further growth leads to the progressive destruction of both tumors papillae and choroidal villi. Choroid plexus stroma is characterized by the fenestrated blood vessels presence, which are similar to newly formed vessels in tumors. This makes it vulnerable to the noxious agents from circulation. It can contain lymphocytes, macrophages, dendritic cells and myofibroblasts in cases with psammoma bodies, similarly to tumors stroma which is in activated, proinflammatory state. So, all these facts can suggest that similar processes can lead to psammoma bodies formation in both tumors and choroid plexus and, that they might have harmful effect on choroid plexus structure and function during the aging process. Significantly higher degree of choroidal epithelial cells atrophy, in cases with present psammoma bodies proves that partially. Further researches should be focused on detection of osteopontin and nanobacteria, already detected in tumors psammoma bodies, in choroid plexus ones. Discovery of choroidal psammoma bodies mechanisms formation can be important for elucidation of some aspects in pathogenesis of some tumors, too. Application of choroid plexus epithelial cells functional markers in cases with psammoma bodies should show their functional status.