Kamelija Zarković

University Hospital Centre Zagreb, Zagreb, Grad Zagreb, Croatia

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Publications (12)21.67 Total impact

  • Article: The effects of angiotensin II and oxidative stress mediator 4-hydroxynonenal on the human osteoblast-like cell growth: Possible relevance to otosclerosis.
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    ABSTRACT: Otosclerosis is a complex disease characterized by an abnormal bone turnover of the otic capsule resulting in conductive hearing loss. Recent findings have shown that Angiotensin II (Ang II), a major effector peptide of the renin-angiotensin system, plays important role in pathophysiology of otosclerosis, most likely by its pro-inflammatory effects on the bone cells. Since reactive oxygen species play a role both in inflammation and in cellular signalling pathway of Ang II, the appearance of the "second messenger of free radicals" the aldehyde 4-hydroxynonenal (HNE) protein adducts in otosclerotic bone has been analysed. Immunohistochemical analysis of HNE-modified proteins on tissue samples of the stapedial bones performed on 15 otosclerotic patients and 6 controls, revealed regular HNE-protein adducts presence in the subperiosteal parts of control bone specimens, while irregular areas of the pronounced HNE-protein adducts presence were found within stapedial bone in case of otosclerosis. To study possible interference of HNE and Ang II in human bone cell proliferation, differentiation and induction of apoptosis we used an in vitro model of osteoblast-like cells. HNE interacted with Ang II in a dose-dependent manner, both by forming HNE-Ang II adducts, as revealed by immunoblotting, and by modification of effects on cultured cells. Namely, treatment with 0.1nM Ang II and 2.5μM HNE stimulated proliferation, while treatment with 10μM HNE or in combination with Ang II (0.1, 0.5 and 1nM) decreased cell proliferation. Moreover, 10μM HNE alone and with Ang II (except if 1nM Ang II was used) increased cellular differentiation and apoptosis. HNE 5μM did not affect differentiation or significantly changed apoptosis. On the other hand, when cells were treated with lower concentrations of HNE and Ang II we have observed decrease in cellular differentiation (combination of 1.0 or 2.5μM HNE with 0.1nM Ang II) and decrease in apoptosis (0.1 and 0.5nM Ang II). Cellular necrosis was increased with 5 and 10μM HNE if given alone or combined with Ang II, while 0.5nM Ang II and combination of 1μM HNE with Ang II (0.1 and 0.5nM) reduced necrosis. These results indicate that HNE and Ang II might act mutually dependent in regulation of the bone cell growth and in pathophysiology of otosclerosis.
    Free radical biology & medicine 12/2012; · 5.42 Impact Factor
  • Article: Multiple brain cysts: an unusual form of demyelinating disease.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 09/2011; 38(5):774-6. · 0.97 Impact Factor
  • Article: C-myc expression in the microvessels of medulloblastoma.
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    ABSTRACT: The increased expression of c-myc is related to neoplastic transformation and angiogenesis. Therefore, the assessment of expression of c-myc in endothelial cells and neovascularization could help to determine the biological behavior of the tumor. We analyzed neovascularization and c-myc expression in 36 medulloblastoma specimens. The results were shown by determining immunohistochemical staining index (ISI), the sum of staining intensity (SI) and the percentage of positive cells (PPC) in the blood vessels endothelium of the tumor. We also performed the microvessel count (MVC) in 10 high-power fields (400X) with the most prominent vascularization and expressed it as microvessel density per mm2 (MVD). C-myc immunostaining intensity index in blood vessel endothelium is grouped into four groups, 0--no reaction, I-weak reaction (ISI = 1 or 2), II--moderate reaction (ISI = 3 or 4), III--strong reaction (ISI = 5 or 6). Statistically significant differences (p = 0.0214) have been found between groups 0 and 1 compared to groups 2 and 3. A higher percentage of positive cells has been found in male patients than in female ones (p = 0.0483). C-myc PPC 0 or 1 has on the average smaller density of blood vessels per mm2 than c-myc PPC 2 or 3, but the difference is not statistically significant. C-myc ISI 0 or 1 has, on the average, smaller density of blood vessels per mm2 than c-myc ISI 2 or 3, but the difference is not statistically significant. We concluded that c-myc staining intensity was associated with higher microvessels density.
    Collegium antropologicum 03/2011; 35(1):39-42. · 0.61 Impact Factor
  • Article: Diagnostic pitfalls in parathyroid gland cytology.
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    ABSTRACT: The aim of this study is to establish possibilities of using cytology in the diagnosis of parathyroid gland adenoma. 475 patients, all suspected to have parathyroid gland disease, were examined over a three-year period (from 1 of January 2006 to 31 of December 2008) in the Clinical Department of Nuclear Medicine and Radiation Protection, University Hospital Center Zagreb, Croatia. Ultrasound guided fine needle aspiration biopsy (UG-FNAB) of suspected occurrences determined by ultrasound was done. Samples obtained by UG-FNAB were air-dried and stained using the May-Grünwald-Giemsa (MGG) staining procedure. PTH levels were determined in all punctate and sera obtained on the day of UG-FNAB. Samples adequate for cytological analysis were obtained from 288 patients, while 187 punctates did not contain epithelial elements. The parathyroid hormone (PTH) analysis was made for all punctates. The adenoma was diagnosed via morphological characteristics in 71 out of 288 punctates that were proven adequate for cytological analysis. Increased PTH levels were later on established in all diagnosed adenomas. All patients with cytology-based diagnosis of parathyroid gland adenoma were sent to surgery, and the cytological diagnosis was confirmed by pathohistology. In three cases, the parathyroid gland adenoma was established by pathohistology, although in these cases the cytological diagnosis was negative. The cytological diagnosis of parathyroid gland adenoma can be considered reliable in 96% of cases, provided that the echosonographic structure and localisation of the punctured node is noted, and assuming that material adequate for cytological analysis is obtained by FNAB. Possible pitfalls are oncocytic types of parathyroid adenoma, intranuclear inclusions and papillary formation of epithelial cells, and cystic degeneration of nodules. These errors can be avoided by defining the PTH level on the same punctate.
    Collegium antropologicum 03/2010; 34(1):25-9. · 0.61 Impact Factor
  • Article: Frontal variant of Alzheimer's disease: clinico-CSF-pathological correlation.
    The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 01/2010; 37(1):118-20. · 0.97 Impact Factor
  • Article: Cyp4a14 overexpression induced by hyperoxia in female CBA mice as a possible contributor of increased resistance to oxidative stress.
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    ABSTRACT: The beneficial effects of hyperoxia have been noted in treatment of several diseases and pathological states. However, the excessive production of ROS under hyperoxic conditions can directly damage cellular macromolecules if the imbalance in antioxidant status exists. Cytochrome P450 (Cyp) 4a14 has an important role in the metabolism of lipids and as a source of ROS in oxidative stress. This study investigated the oxidant/antioxidant status as a response to hyperoxia treatment in liver of young CBA/Hr mice of both sexes and whether the observed response is mediated by Cyp4a14 via PPAR isoforms in a sex-dependent manner. The overexpression of Cyp4a14, lack of both LPO and of 4-hydroxynonenal(HNE)-protein adducts revealed by immunohistochemical analysis in hyperoxia-treated females indicates their greater resistance to hyperoxia compared to males, which is parallelled to changes in PPARbeta/delta and PPARgamma expression. These results suggest the presence of sex-dependent changes in all investigated parameters, which points out sex-related susceptibility towards oxidative stress and hyperoxia treatment of various pathological conditions and diseases.
    Free radical research 11/2009; 44(2):181-90. · 2.22 Impact Factor
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    Article: Persistent accumulation of 4-hydroxynonenal-protein adducts in gastric mucosa after Helicobacter pylori eradication.
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    ABSTRACT: Recent studies indicate that oxidative stress caused by Helicobacter pylori and insufficient host antioxidant defense could play important role in pathogenesis of gastrointestinal ulcerations. By specific monoclonal antibodies we have detected weak presence of the major lipid peroxidation bioactive marker 4-hydroxynonenal (HNE) in healthy human gastric mucosa, which strongly increased in case of H. pylori-associated peptic ulcer. Considering physiological presence of HNE on one hand, and high prevalence of H. pylori associated disorders on the other, evaluation of oxidative stress after treatment is important. Therefore, in current study immunohistochemical accumulation and distribution of HNE-protein adducts in gastric mucosa was evaluated with 21 patients having H. pylori-associated duodenal peptic ulcer (DPU) before and one month after eradication of H. pylori. Although dramatic decrease in histological manifestations of inflammation was demonstrated after eradication of H. pylori, initially high immunopositivity for the HNE-protein adducts remained elevated in antrum and even increased in stomach corpus. The observed accumulation and redistribution to higher grades of HNE-immunopositivity in nuclei of glandular cells in gastric corpus indicate augmentation of oxidative stress after treatment and open possibilities for adjuvant antioxidant treatments to protect gastric mucosa from progressive oxidative stress after eradication of H. pylori infection.
    Collegium antropologicum 09/2009; 33(3):815-21. · 0.61 Impact Factor
  • Article: Unusual cause of dementia in an immunocompetent host: toxoplasmic encephalitis.
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    ABSTRACT: A 69-year-old male was presented with a 2-month history of cognitive decline. The most profound deficit was observed in short-term verbal and visual memory and recognition. He was otherwise healthy, apart from atrial fibrillation diagnosed 5 months before. Brain MRI revealed T2 hyperintensities in the left thalamus, right pulvinar thalami, both putamina and right head of caudate nucleus without diffusion restriction on DWI sequences. CSF examination revealed elevated proteins. He was HIV negative. The course of the disease was complicated with gram negative sepsis and the patient died 14 days later. Autopsy revealed the brain lesions to have been caused by toxoplasmic encephalitis. Toxoplasmic encephalitis is an extremely rare cause of rapidly progressive dementia in immunocompetent patients. In patients with multiple lesions, hyperintense on T2 and hypointense on T1 weighted sequences, without diffusion restriction and some expansive effect, infectious causes should be considered, even in the absence of classical signs of infectious diseases and CSF pleocythosis.
    Neurological Sciences 02/2009; 30(1):45-9. · 1.32 Impact Factor
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    Article: Sellar angiolipomas: two case reports and a review of the literature.
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    ABSTRACT: Angiolipomas are mesenchymal hamartomas composed of abnormal blood vessels and mature adipose tissue, most commonly found in the subcutaneous tissue of the extremities. Intracranial location is extremely rare, and only five cases have been described in the sellar region. We report on two patients that were initially diagnosed with pituitary adenomas that were postoperatively verified as angiolipomas. Sellar angiolipomas should be considered in the differential diagnosis of pituitary lesions due to the potential catastrophic bleeding during surgery. Preoperative diagnosis is very difficult; however, some MRI characteristics can help make an accurate diagnosis. Adequate MRI sequences should be used in the evaluation of pituitary lesions, as they can help optimize the microsurgical management.
    Journal of Neuro-Oncology 09/2008; 89(1):109-12. · 3.21 Impact Factor
  • Article: Is there sentinel demyelination before development of primary CNS lymphoma?
    Mario Habek, Vesna V Brinar, Kamelija Zarković, David Ozretić
    Journal of Clinical Neuroscience 08/2008; 15(9):1069-70; author reply 1071. · 1.25 Impact Factor
  • Article: Brain MRI abnormalities in ataxia-telangiectasia.
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    ABSTRACT: Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder, initially characterized by normal brain magnetic resonance imaging (MRI). In a 34-year-old woman patient with AT, MRI revealed extensive and diffuse white matter dismyelination, T1 and T2 hypointense lesions, T1 hypointense but T2 hyperintense lesions, and numerous dilated telangiectases upon gadolinium enhancement. In our patient, brain MRI confirmed extensive extracerebellar lesions in AT. Our report broadens the spectrum of brain MRI abnormalities in AT and supports the hypothesis on cerebrovascular abnormalities occurring in later stages of AT.
    The Neurologist 06/2008; 14(3):192-5. · 1.26 Impact Factor
  • Article: Bilateral thalamic astrocytoma.
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    ABSTRACT: We present a 68-year-old woman who presented with symptoms of frontotemporal dementia. Brain MRI revealed tumor mass in both thalami and according to WHO classification, the tumor corresponded to diffuse fibrillary astrocytoma grade II. This case points to the role of neuroimaging in patients presenting with classical symptoms of dementia.
    Journal of Neuro-Oncology 10/2007; 84(2):175-7. · 3.21 Impact Factor