Maja Vulovic

Naloxone Antagonizes Soman-induced Central Respiratory Depression in Rats

The influence of naloxone on respiration impaired by the highly toxic organophosphate nerve agent soman in anaesthetized rats was investigated. Soman, administered in a dose that was ineffective in blocking the electrically induced contractions of the phrenic nerve‐diaphragm preparation in situ, induced a complete block of the spontaneous respiratory movements of the diaphragm, indicating the domination of central over the peripheral effects. Naloxone dose‐dependently antagonized the soman‐induced respiratory blockade. Atropine, at a dose that was per se ineffective in counteracting soman‐induced respiratory depression, potentiated the protective effects of naloxone and completely restored respiration. Naloxone remained completely ineffective in antagonizing respiratory depression induced by the muscarinic receptor agonist the oxotremorine. It is assumed that naloxone antagonizes soman‐induced respiratory inhibition by blocking endogenous opioidergic respiratory control pathways that are independent of the stimulation of muscarinic receptors.

Efficacy of antidotes and their combinations in the treatment of acute carbamate poisoning in rats

BACKGROUND Physostigmine and its analogues neostigmine, pyridostigmine and rivastigmine are carbamates nowadays used in many indications, including antidotal effects against antimuscarinic poisonings, reversal of competitive neuromuscular block, myasthenia gravis, Alzheimers disease and prophylaxis against nerve agent intoxications. Use of these medicinal carbamates, but also of carbamate insecticides, created need for research into the potential and mechanisms of action of several antidotes against carbamate poisonings, including anticholinergics and oximes. AIM The goal of this experimental study was to ascertain the life-preserving potential of anticholinergics atropine, hexamethonium and d-tubocurarine, oxime HI-6 and their combinations in rats poisoned with physostigmine or pyridostigmine. MATERIALS AND METHODS Experiments were performed in Wistar rats. Carbamates were injected subcutaneously (sc) and antidotes intramuscularly (im). Median lethal dose (LD50) in animals treated with antidotes were compared to the ones in saline-treated rats and protective ratios (PRs) were calculated. Atropine (5, 10 and 20 mg/kg), hexamethonium (5, 10 and 20 mg/kg), d-tubocurarine (0.005, 0.010 and 0.020 mg/kg) and oxime HI-6 (25, 50 and 100 mg/kg) were used as monotherapies and in dual combinations, where atropine was the obligatory antidote. Biochemical experiments consisted in measuring of the cholinesterase activities in brain, whole blood and diaphragm in rats 5, 15, 30, 60, 120 and 240 min after poisoning with 0.8 LD50 of physostigmine or pyridostigmine. RESULTS All the tested antidotes assured some degree of protection against the two carbamates. Atropine and hexamethonium produced better protection in physostigmine-poisoned rats, while d-tubocurarine and HI-6 were more efficacious in pyridostigmine-intoxicated animals. Oxime HI-6 50 mg/kg reactivated acetylcholinesterase (AChE) in brain inhibited by physostigmine and in diaphragm inhibited by pyridostigmine. CONCLUSIONS Mechanism of physostigmine-induced lethal effect is predominantly central and it involves inhibition of brain AChE, while pyridostigmine produces the same effect exclusively outside the central nervous system, by inhibiting AChE in the respiratory muscles. As a consequence, increasing doses of atropine and their combination with hexamethonium assure excellent protection against physostigmine toxicity, while the best protection against pyridostigmine is provided by a strictly peripherally acting antinicotinic d-tubocurarine and bispyridinium oxime HI-6. The oxime acts as antidote against physostigmine and pyridostigmine poisoning by reactivating AChE in the brain and diaphragm, respectively.

The impact of pain on functionality and health related quality of life in patients with knee osteoarthritis

Aleksandra Jurišić-Škevin1,2, Vesna Grbović1,2, Ivana Stanković3, Aleksandar Radunović4, Jasmin Nurković5, Bojan Milošević6,2, Aleksandar Cvetković6,2, Ana Divjak1, Maja Vulović7 1University of Kragujevac, Faculty of Medical Sciences, Department of Physical medicine and rehabilitation, Kragujevac, Serbia; 2Clinical center Kragujevac, Kragujevac, Serbia; 3University of Defence in Belgrade, Military Medical Academy, Institute for Medical Research, Belgrade, Serbia; 4Military medical academy, Clinic for orthopedic surgery and traumatology, Belgrade, Serbia; 5State University of Novi Pazar, Department of Biomedical Sciences, Novi Pazar, Serbia; 6University of Kragujevac, Faculty of Medical Sciences, Department of Surgery, Kragujevac, Serbia; 7University of Kragujevac, Faculty of Medical Sciences, Department of Anatomy, Kragujevac, Serbia;

The treatment of hemangioma of the larynx in children is still a dilemma

1 University of Kragujevac, Faculty of Medical Sciences, Department of Paediatrics, Kragujevac, Serbia; 2 Clinical Centre of Kragujevac, Pediatric Clinic, Kragujevac, Serbia; 3 Clinical Centre of Kragujevac, Department of Clinical Pharmacology, Kragujevac, Serbia; 4 Clinical Centre of Kragujevac, Clinic for Otorhinolaryngology, Kragujevac, Serbia; 5 Clinical Hospital Center, Department of Child Surgery, Kosovska Mitrovica, Serbia; 6 University of Kragujevac, Faculty of Medical Sciences, Department of Anatomy, Kragujevac, Serbia

Total Endoprothesis of Hip Joint: Characteristics and Application in Patients in the Central Region of Serbia

Total hip arthroplasty is a surgical procedure in which the hip joint is replaced with an artificial one. Performance of this procedure requires knowledge of the anatomical features of the joint, the characteristics of the endoprosthesis, and the needs and pathological and physiological characteristics of the patient. This retrospective analysis includes the data contained in 874 medical histories of patients of both sexes implanted with a unilateral total hip endoprosthesis who were treated at the Orthopedic Clinic of the Clinical Center, Kragujevac, from January 1st, 2009 to December 1st, 2014. Analysis of the data revealed that 69.3% of the patients were women. The most common type of implanted prosthesis was the cementless one, and the most frequent indication was degenerative joint damage. Total arthroplasty of the hip joint has become one of the most common interventions in orthopedic surgery. The increasing need for this method of treatment required the development of new biomaterials, as well as new types of prosthesis, which, in the future, will decrease the occurrence of adverse reactions and complications during and after implantation of the prosthesis, as well as extending their useful life.

Biodegradable Metals as Biomaterials for Clinical Practice: Iron-Based Materials

This review presents the state-of-the-art in the development of iron-based degradable medical implants. Basic properties demanded by the new concept of degradable implants are elaborated, along with the work devoted to understand the underlying mechanism and to improve the properties towards best fitted to the natural tissue. Three application areas are considered: vascular stents, orthopedic implants and tissue engineering scaffolds. Each of these has its own specific demands imposed upon the artificial substitution materials. Biocompatibility is an essential feature that each medical implant must have, but different aspects can be considered depending on the end application. Furthermore, adequate mechanical properties and various characteristics related to the fabrication and in vitro and in vivo testing are presented for pure iron, alloys and composites, as well as joint structures. Corrosion control is a foundation in the development of these materials development and different aspects are also given. Iron-based materials need increased degradation rate because they are still more similar to the permanent implants, due to the slow corrosion process and various methods to overcome this issue have been tried. Porosity and its relation to material structures, mechanical properties, degradation behaviour, magnetic properties, and fabrication technologies, as well as methods of numerical simulations as a supporting tool have been elaborated. Porous structures represent one way to enhance corrosion, while maintaining intact other necessary properties of the biomaterial. Economic impact of the biomaterials sector in general is significant and justifies large investments in research. Iron-based materials for degradable implants are not in clinical practice yet, but the research results achieved so far promise the future applications.

Confocal Synaptology: Synaptic Rearrangements in Neurodegenerative Disorders and upon Nervous System Injury

The nervous system is a notable exception to the rule that the cell is the structural and functional unit of tissue systems and organs. The functional unit of the nervous system is the synapse, the contact between two nerve cells. As such, synapses are the foci of investigations of nervous system organization and function, as well as a potential readout for the progression of various disorders of the nervous system. In the past decade the development of antibodies specific to presynaptic terminals has enabled us to assess, at the optical, laser scanning microscopy level, these subcellular structures, and has provided a simple method for the quantification of various synapses. Indeed, excitatory (glutamatergic) and inhibitory synapses can be visualized using antibodies against the respective vesicular transporters, and choline-acetyl transferase (ChAT) immunoreactivity identifies cholinergic synapses throughout the central nervous system. Here we review the results of several studies in which these methods were used to estimate synaptic numbers as the structural equivalent of functional outcome measures in spinal cord and femoral nerve injuries, as well as in genetic mouse models of neurodegeneration, including Alzheimer’s disease (AD). The results implicate disease- and brain region-specific changes in specific types of synapses, which correlate well with the degree of functional deficit caused by the disease process. Additionally, results are reproducible between various studies and experimental paradigms, supporting the reliability of the method. To conclude, this quantitative approach enables fast and reliable estimation of the degree of the progression of neurodegenerative changes and can be used as a parameter of recovery in experimental models.

Sneezing - a symptom of respiratory or psychogenic superposition of illness in a teenager?

Introduction. The coincidental combination of allergic respiratory diseases and psychogenic or psychiatric illness is possible but rarely associated in a female teenager. Case report. A girl aged 12.5 years was admitted to the Pediatrics Clinic in the Clinical Centre Kragujevac with the main difficulty of sneezing as 10 sneezes in each of the 500–600 series a day, only in the waking state. Working diagnoses were tic disorders associated with Allergic rhinitis, asthma and biochemically determined rickets. The patient was treated with chlorpromazine, desloratadine, montelukast, fluticasone propionate, vitamin D, azelastine hydrochloride along with the elimination diet. After a year and a half, the patient rarely sneezed, but periods without sneezing were not longer than 3 months, and she ‘cleared her throat’ occasionally. Although her clinical condition is less severe now and without additional motor tics or symptoms of Tourettes disorder, because of its length we suspect the tic turned into a chronic vocal tic disorder. Conclusion. We reported a case of rare association between allergic rhinitis and condition of tic-related conversion in a female teenager and emphasized the necessity of revising the systematisation for the tic disorders and protocol for the allergic rhinitis in terms of their association.

Mechanism and Clinical Importance of Respiratory Failure Induced by Anticholinesterases

Abstract Respiratory failure is the predominant cause of death in humans and animals poisoned with anticholinesterases. Organophosphorus and carbamate anticholinesterases inhibit acetylcholinesterase irreversibly and reversibly, respectively. Some of them contain a quaternary atom that makes them lipophobic, limiting their action at the periphery, i.e. outside the central nervous system. They impair respiratory function primarily by inducing a desensitization block of nicotinic receptors in the neuromuscular synapse. Lipophilic anticholinesterases inhibit the acetylcholinesterase both in the brain and in other tissues, including respiratory muscles. Their doses needed for cessation of central respiratory drive are significantly less than doses needed for paralysis of the neuromuscular transmission. Antagonist of muscarinic receptors atropine blocks both the central and peripheral muscarinic receptors and effectively antagonizes the central respiratory depression produced by anticholinesterases. To manage the peripheral nicotinic receptor hyperstimulation phenomena, oximes as acetylcholinesterase reactivators are used. Addition of diazepam is useful for treatment of seizures, since they are cholinergic only in their initial phase and can contribute to the occurrence of central respiratory depression. Possible involvement of central nicotinic receptors as well as the other neurotransmitter systems – glutamatergic, opioidergic – necessitates further research of additional antidotes.

Anatomical Parameters of the Acetabulum in Heavy Vehicle Operators

Abstract It has been suggested that long-term exposure by heavy vehicle operators to whole-body vibration (WBV) may be related to an increased risk of pathological changes in the anatomical parameters of the hip. The aim of this study was to explore the difference in anatomical parameters of acetabulum in drivers of heavy vehicles (experimental group; n=60) and subjects who have not been exposed to WBV (control group; n=60). The anteroposterior radiographic view of the hips was used to measure the following parameters: the vertical centre edge (VCE), the ‘horizontal toit externe’ angle (HTE), the neck shaft angle (NSA) and the acetabular depth (AD). Compared with the control group, the mean VCE angle values and AD were signifi cantly lower, while the average HTE and NSA values were signifi cantly higher in the experimental group. This study supports the hypothesis that exposure to whole-body vibration during operation of a vehicle causes an increased risk of acetabular dysplasia.