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Open access

Aleksandar Perić, Danilo Vojvodić, Nenad Baletić, Aneta Perić and Olivera Miljanović

Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Chronic Rhinosinusitis with Nasal Polyposis

Immunomodulatory treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) by macrolide antibiotics represents a challenging alternative to conventional therapy and surgery, still being at the very beginning. Immune and inflammatory processes in nasal and paranasal sinus mucosa, crucial in the etiopathogenesis of nasal polyps (NPs) are reflected in levels of various local mediators, found both in mucosa and nasal fluid. In this prospective study, we assessed the immunomodulatory and clinical effects of longterm low-dose oral macrolide treatment in the management of CRSwNP. Twenty-two (n = 22) nonasthmatic, nonallergic patients with CRSwNP were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory cytokines TNF-α, TNF-β, and IL-1β, Th1 cytokines IL-2, IL-12, and IFN-γ, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using a flow cytometric method. We also scored each of the 22 patients before and after therapy according to Tsicopoulos' global nasal symptom score and Malm's endoscopic score. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-α (p<0.01) in nasal secretions. Macrolide therapy decreased the size of polyps in 45.45% of the patients. We concluded that long-term low-dose treatment with CAM was effective in the management of CRSwNP. We suggest that macrolides can be an alternative to topical and systemic corticosteroids in the management of CRSwNP.

Open access

Aleksandar Perić, Danilo Vojvodić and Vesna Radulović

Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric Study

Biological markers in nasal fluid provide valuable information on nasal pathophysiology. The aims of this study were to compare the cytokine profiles of nasal fluid in subjects with nasal polyps (NP) and co-morbid asthma and NP patients without asthma and to determine the role of these cytokines in the development of NP. Thirty patients with NP (15 asthmatic and 15 non asthmatic) were included in this prospective study. Nasal secretion samples were collected from nasal cavities of all 30 subjects. The levels of eleven cytokines (TNF-α, TNF-β, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IFN-γ) were measured using flow cytometry. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher in patients with NP and asthma compared with subjects with NP without asthma. We also found significantly higher levels of IFN-α, IL-4, IL-6 and IL-10 in allergic patients with NP and asthma compared with those without asthma. In nonallergic patients with NP and asthma, the concentrations of TNF-α, IL-5 and IL-6 were significantly higher than in nonallergic patients with NP without asthma. Our results show that the presence of Th2 cytokines, especially IL-5 and IL-6 in patients with NP and asthma is a more prominent feature than in those without asthma that relates to the increased eosinophilic inflammation. We have also found a significant influence of allergy on the cytokine profiles both in asthmatic and nonasthmatic patients.

Open access

Aleksandar Perić, Cveta Špadijer Mirković and Danilo Vojvodić


Clara cell protein 16 (CC16) is a small protein mainly produced by non-ciliated Clara cells in the respiratory epithelium. It has an anti-inflammatory role in chronic upper and lower airway eosinophilic inflammations. Decreased levels of CC16 are found in the nasal secretions and plasma of patients with chronic eosinophilic inflammatory disorders, such as asthma, allergic rhinitis, and chronic rhinosinusitis with or without nasal polyps, as well as in people exposed to high levels of air pollutants. Intranasal corticosteroid administration suppresses chronic inflammation of the nasal mucosa driven by eosinophils and stimulates local CC16 production. CC16 can be a reliable biomarker of the beneficial effects of perennial allergic rhinitis and chronic rhinosinusitis therapy and of the functional recovery of the nasal mucosa after treatment with topical glucocorticoids.

Open access

Aleksandar Perić, Danilo Vojvodić, Biserka Vukomanović-Đurđević and Nenad Baletić

Eosinophilic Inflammation in Allergic Rhinitis and Nasal Polyposis

On histopathological examination, nasal polyps and nasal mucosa in allergic rhinitis show different forms of pseudostratified respiratory epithelium, whereas the dominant characteristic of lamina propria is an eosinophilic infiltration. The aim of this study was to compare interleukin (IL)-5 and eosinophilic cationic protein (ECP) levels in the nasal fluid of 42 patients: 12 with allergic rhinitis and nasal septal deviation, 17 non-atopic patients with nasal polyposis, and 13 atopic nasal polyp patients were enrolled in this cross-sectional study. Nasal secretion samples were collected a few days before surgery. The levels of IL-5 were measured using flow cytometry and the ECP using a commercial ELISA kit. In addition, we counted eosinophils in hematoxylin-and-eosin-stained sections of all nasal polyp and all nasal mucosa samples taken from the inferior nasal turbinates during septoplasty. A significantly higher concentration of IL-5 was found in the nasal fluid of atopic patients with nasal polyposis than in non-atopic nasal polyp patients (p=0.025) and patients with allergic rhinitis (p=0.05). ECP was higher in atopic nasal polyp patients than in patients with allergic rhinitis (p<0.0001) and than in non-atopic nasal polyp patients (p<0.0001). Polyp eosinophils were higher in atopic' than in non-atopic patients (p<0.0001) and higher than in the mucosa of patients with allergic rhinitis (p<0.0001). These however had significantly more mucosal eosinophils than was found in the polyps of non-atopic patients' (p=0.025). ECP levels in nasal fluid and eosinophil counts in tissue specimens correlated well in all three groups of patients. Our study has shown that atopic nasal polyp patients have a higher level of eosinophilic inflammation than non-atopic patients with nasal polyps and patients with allergic rhinitis.

Open access

Aleksandar Sovtic, Tamara Peric, Predrag Minic and Dejan Markovic


The most frequent chronic respiratory problems in childhood are asthma and cystic fibrosis (CF). The purpose of this paper is to review basic knowledge and recent advances in oral health and associated dental morbidities in children with asthma and CF. This review considered clinical trials and systematic reviews related to oral health in children with CRD. An online base Medline was searched to determine relevant papers, using the combination of the following terms: “asthma”, “cystic fibrosis”, “caries”, “dental erosion”, and “oral health”. Oral health problems in children with chronic respiratory diseases (CRD) may be influenced by natural course of the disease, pharmacotherapy (inhalation therapy with bronchodilators and inhaled corticosteroids in asthmatic patients, systemic antibiotics and pancreatic enzyme replacement therapy in CF patients), medication administration technique and nutritional habits. Children with CRD may have higher prevalence of oral diseases. Patients and their parents, but also general paediatricians and pulmonologists, should be aware of importance of good oral health. Dental practitioners should be more informed about risk factors and specificities of oral health in these patients. Preventive measures, early diagnosis and effective treatment strategies in children with CRD can reduce occurrence of oral diseases and improve patient’s quality of life.

Open access

Aleksandar Perić, Milan Erdoglija, Nenad Mladenović and Biserka Vukomanović Đurđević


The paranasal sinus mucocele is an epithelized cystic lesion containing fluid and is characterized by non-neoplastic expansion of the paranasal sinus due to its capacity to erode the overlying bone. Etiology of these lesions is still under debate. In this report, we described a case of a patient with frontal recess mucocele, associated with contralateral frontal recess osteoma. A 55-year-old man was admitted to the Department of Otorhinolaryngology of our hospital with the complaints of a headache affecting the fronto-ethmoidal region, left-sided nasal obstruction, and postnasal discharge. Computed tomography (CT) scan of the paranasal sinuses showed a dense bony lesion in the left and a cystic hypodense mass in the right-sided frontal recess. The patient was treated surgically, with a combined endoscopicexternal approach, bilaterally. Histopathological examination showed that the wall of the cyst was mucocele, and the bony formation was osteoma. The frontal recess osteoma is regarded as the primary condition. Thus, better ventilation and drainage of the frontal sinus were reestablished.

Open access

Milan S. Savić, Zoran H. Perić, Stefan R. Panić and Aleksandar V. Mosić

A novel semilogarithmic hybrid quantizer for non-uniform scalar quantization of Laplacian source, which consist of uniform quantizer and companding quantizer is introduced. Uniform quantizer has unit gain in area around zero. Companding quantizer is defined with a novel logarithm characteristic. Also an analysis of classic semilogarithmic A-law for various values of A parameter is provided. Comparation with classic semilogarithmic A-law is performed. The main advantage of hybrid quantizer is that number of representation levels for both uniform and companding quantizer are not unambiguously determined function of the A parameter value, as it is the case with classic semilogarithmic A companding characteristic. It is shown that by using hybrid quantizer, average of signal-to-quantization noise ratio SQNR quality obtained by using classic A companding law can be overachieved for 0.47 dB. Numbers of representation levels of hybrid quantizer are adapted to the input signal variances, in order to achieve high SQNR in a wide range of signal volumes (variances). By using this adaptation higher average SQNR quality of 2.52 dB could be achieved compared to classic A companding law. Forward adaptation of hybrid quantizer is analyzed and obtained performances correspond to adaptive classic A companding law case but possible advantage arises in simpler practical realization of hybrid quantizers. Obtained performances correspond to classic A-law companding case, because during the adaptation process, optimal values of parameter A are chosen. For each other A parameter values proposed hybrid quantizer provides better results. For value of A = 50 hybrid model has higher SQNR value for 0.79 dB

Open access

Cecilia Costa, Ralph Büchler, Stefan Berg, Malgorzata Bienkowska, Maria Bouga, Dragan Bubalo, Leonidas Charistos, Yves Le Conte, Maja Drazic, Winfried Dyrba, Janja Fillipi, Fani Hatjina, Evgeniya Ivanova, Nikola Kezic, Hrisula Kiprijanovska, Michalis Kokinis, Seppo Korpela, Per Kryger, Marco Lodesani, Marina Meixner, Beata Panasiuk, Hermann Pechhacker, Plamen Petrov, Eugenia Oliveri, Lauri Ruottinen, Aleksandar Uzunov, Giacomo Vaccari and Jerzy Wilde

A Europe-Wide Experiment for Assessing the Impact of Genotype-Environment Interactions on the Vitality and Performance of Honey Bee Colonies: Experimental Design and Trait Evaluation

An international experiment to estimate the importance of genotype-environment interactions on vitality and performance of honey bees and on colony losses was run between July 2009 and March 2012. Altogether 621 bee colonies, involving 16 different genetic origins of European honey bees, were tested in 21 locations spread in 11 countries. The genetic strains belonged to the subspecies A. m. carnica, A. m. ligustica, A. m. macedonica, A. m. mellifera, A. m. siciliana. At each location, the local strain of bees was tested together with at least two "foreign" origins, with a minimum starting number of 10 colonies per origin. The common test protocol for all the colonies took into account colony survival, bee population in spring, summer and autumn, honey production, pollen collection, swarming, gentleness, hygienic behaviour, Varroa destructor infestation, Nosema spp. infection and viruses. Data collection was performed according to uniform methods. No chemical treatments against Varroa or other diseases were applied during the experiment. This article describes the details of the experiment set-up and the work protocol.