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  • Author: Ivan Kovačević x
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Open access

Marija Ilić, Ivan Kovačević and Jelena Parojčić

Abstract

With the increased reliance on in vitro dissolution testing as an indicator of in vivo drug behavior and the trend towards the in silico modeling of dosage form performance, the need for bioperformance dissolution methodology development has been enhanced. Determination of the in vivo drug delivery profile is essential for the bioperformance dissolution test development and in vitro/in vivo correlation modeling, as well as the understanding of absorption mechanisms. The aim of this study was to compare different methods in terms of their usefulness and applicability in deciphering in vivo delivery of nifedipine administered in modified release dosage forms. A detailed survey of publications on nifedipine pharmacokinetics was done and used to identify the magnitude of food effect. In vitro dissolution testing was performed under various experimental conditions. Obtained results indicate the potential for using the developed in silico model coupled with discriminative in vitro dissolution data for identification of the in vivo drug product behavior

Open access

Ivan Trajkov, Dejan Kovacevic and Nikola Gjorgov

Premature Atrial Contractions Managed With Slow Pathway Ablation

We present data from 18 year old male patient referred to our clinic for evaluation and treatment due to persistent premature atrial contractions (PAC). Up to the time of admission, the patient never experienced paroxysmal tachycardia, and his principal complaint was the irregular heart rhythm refractory to all types of antiarrhytmic drug therapy. Electrophysiological study was performed and it revealed that continuous pacing in the right ventricle produced a retrograde conduction block at rates 500 msec. Decremental programmed electrical stimulation in the right atrium (S1S2 540/340 to 540/330 ms induced a sudden prolongation of A - H interval (AH jump of 98 ms) and a nonreentrant tachycardia (cycle length = 492 ms). Intracardiac electrogram showed that supraventricular activity emerged from simultaneous conduction over the slow and fast pathways of the atrioventricular node. This type of conduction is usually seen in patients with atrioventricular nodal reentry tachycardia, but our patient never previously complained of tachycardia, and the electrogram during tachycardia was not suggestive for atrioventricular nodal reentry tachycardia. Subsequent ablation of the slow pathway at the base of the Koch triangle yielded a cessation of the supraventricular premature activity, absence of the nonreentrant tachycardia and disappearance of the A-H jump.

Open access

Nataša Spasojević, Ljubica Gavrilović, Ivan Kovačević and Slađana Dronjak

Endocrinological and Behavioural Effects of Chronic Fluxilan Administration in Rats

Chronic stress induces changes in the neuroendocrine and neuronal system, including elevation of catecholamines and corticosterone (CORT) levels, and could be an important factor in initial depression. Antidepressants affect monoaminergic neurotransmission and modulate central neuropeptides involved in the coordination of stress response and the control of HPA axis activity. We studied the effects of chronic treatment with fluxilan, a selective inhibitor of serotonin reuptake, in unstressed controls and chronic unpredictable mild stress (CUMS) rats, on behaviour and plasma noradrenaline (NA), adrenaline (A), corticosterone (CORT) and adrenocorticotropic hormone (ACTH). CUMS did not affect plasma NA, A and ACTH, but elevated plasma CORT content. Plasma concentration of catecholamines after fluxilan administration was significantly increased in control and CUMS group. On the other hand, fluxilan expressed no effect on plasma ACTH and CORT concentrations in control animals, but decreased ACTH and CORT levels in CUMS animals. Behaviourally, fluxilan treated animals displayed enhanced anxiety. The results demonstrate that the anxiogenic effects of chronic fluxilan administration are similar to those reported by many other studies. The findings described here suggest that elevated plasma catecholamines may contribute to an adverse effect of this drug on cardiovascular parameters during antidepressant therapy.

Open access

Jelena Danilović Luković, Aleksandra Korać, Ivan Milošević, Tijana Lužajić, Zorana Milanović, Milica Kovačević Filipović and Anita Radovanović

Abstract

Induced prenatal hypothyroidism in rat pups leads to accelerated primordial follicle assembly and premature follicular atresia with ovary failure. This work investigates the influence of maternal hypothyroidism induced with 6-n-propyl-2-thyouracil (PTU) on the number and morphology of oogonia/oocytes in newborn rat pups with light and transmission electron microscopy. Expression of apoptosis and autophagy markers in oogonia/oocytes were examined using immunohistochemistry. Hypothyroid newborn pups had a decreased number of mitotic and resting oogonia, while the number of altered oogonia/oocytes was increased. Ultrastructural observations revealed the increased presence of degenerated pachytene oocytes (Z-cells) and oogonia/oocytes undergoing autophagy, apoptosis and combined apoptosis and autophagy, in this group. The most abundant altered oogonia/oocytes in the hypothyroid group were those with morphological features of advanced autophagy and Z-cells. The percentage of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) positive oogonia/oocytes was significantly lower in the hypothyroid group. No significant difference was recorded in the expression of caspase-3, ATG7 and LC3 possibly reflecting that these proteins were not involved in the oogonia/oocyte alteration process during prenatal rat hypothyroidism. The obtained results indicate that developmental hypothyroidism in the offspring enhances the number of Z-cells and oogonia/oocytes altered with the advanced process of autophagy.

Open access

Aleksandar Janicijevic, Anica Jevremovic, Vojin Kovacevic, Vuk Scepanovic, Ivan Bogdanovic, Nikola Repac, Igor Djoric and Goran Tasic

Abstract

Aneurysms of the temporal superficial artery (TSA) are very rare clinical entity. From 1861 to the present day, is described less than 200 cases. The most common cause of these aneurysms is so called blunt head trauma but there are described many cases of iatrogenic aneurysms, very rarely, aneurysms arise spontaneously. We report a case of 17-year-old patient with spontaneously formatting aneurysm of TSA. Three months prior to admission, he noticed the existence of tumefaction localized frontotemporal on the right side. MSCT angiography of blood vessels of the scalp showed an aneurysm on the frontal branch of TSA diameter of 15 mm. The aneurysm was resected with uneventful postoperative course. PH findings pointed to a true aneurysm. Treatment protocol for the aneurysms of the TSA include clinical monitoring, compression of the aneurysm, the injection of thrombin, endovascular treatment and surgical resection. Surgical resection has proven to be a safe and effective treatment modality and still is the method of choice.

Open access

Ivan Milošević, Anita Radovanović, Luković Jelena Danilović, Tijana Lužajić Božinovski, Sophie Sourice-Petit, Sarah Beck-Cormier, Jerome Guicheux, Vejnović Branislav and Milica Kovačevič Filipović

Abstract

Maternal hypothyroidism in its overt form affects skeletal development of the offspring, but these data are not available for the subclinical form which is becoming very frequent among pregnant women. We hypothesized that the subclinical form of hypothyroidism in rat dams, infl uences the process of offspring endochondral ossifi cation affecting proliferation and differentiation of chondrocytes, osteoclasts and osteoblasts in pups. Seven-day-old male pups (n=18) derived from control dams and dams treated with a low dose (1.5 mg/L) or high dose (150 mg/L) of propylthiouracil in drinking water during pregnancy and lactation were used. Histomorphometric analysis of pups’ tibia proximal growth plate, expression of mRNA, immunohistochemical and histochemical visualization of extracellular matrix components was performed. The length of the tibia was reduced in hypothyroid pups. Secretion of type 2 and 10 collagens in the subclinical and overt form were lower while the amount of glycosaminoglycans was higher when compared with controls. Down-regulated tartrate resistant acid phosphatase mRNA indicated altered osteoclasts function while lower expression of dentin matrix acid protein-1 mRNA and reduced synthesis of type 1 collagen accentuated a compromised bone formation in the overt form of hypothyroidism. The subclinical form of maternal hypothyroidism had a negative effect on the differentiation of hypertrophic chondrocytes and calcifi ed cartilage removal in 7-day-old pups. In addition, overt hypothyroidism had a negative effect on the proliferation of chondrocytes and deposition of osteoid. Both forms of hypothyroidism resulted in a decrease of tibia length due to changes in growth plate formation.