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Irfan Zulić

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The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration), especially with antiparkinsonics. The research (study) is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg), not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as well as nitrazepam and diazepam. The importance of this study is following: data are useful for the current mental health care reform in FBiH, results will point out place and position of FBiH in contemporary world trends in the treatment of schizophrenia, they will contribute to rational use of antipsychotic therapy, they will point out possible ways in reduction of side effects, often dangerous adverse effects of antipsychotics, and they will give contribution to faster rehabilitation of schizophrenics with the reduction of financial means for the treatment of patients with schizophrenia.

I. Vucković, A. Hadžić, F. Dilberović, A. Kulenović, Z. Mornjaković, I. Zulić, Kucuk-Alija Divanović, Eldan Kapur, E. Ćosović et al.

In the last few decades there has been a great development of regional anesthesia; all the postulates are defined and all the techniques of usage are perfected. However, like any other medical procedure, the block of brachial plexus carries a risk of certain unwanted complications, like possible intraneural and intravascular injections. The reason for great discrepancy between the injury of brachial plexus and other periphery nerves while performing the nerve blockade is the frequent usage of this block, but also the specific proximity of neurovascular structures in axilla. The purpose of this work is to determine the values of pressures which appear in para-neural, intraneural and intravascular injection applications of local anesthetic, and to compare those values in order to avoid cases of intraneural and intravascular injections in clinical practice with consequential complications. In experimental study there have been used 12 Wistar rats of both genders. After anesthesia with ether and mid-humoral access to the neurovascular structures in axilla, the injection of 2% lidocaine with epinephrine was performed with the help of automatic syringe charge. The needle was at first placed para-neural, and then also intraneural and intravascular. During every application the pressure values were monitored using the manometer, and then they were analyzed by special software program. All para-neural injections resulted with the pressure between 13,96-27,92 kPa. The majority of intraneural injections were combined with the injection pressure greater than 69,8 kPa, while the intravascular injections were combined with injection pressure less than 6,98 kPa. Based on the available data it can be noticed that so far none of the methods of prevention from unwanted complications of regional anesthesia can insure the avoidance of intraneural and intravascular injection of local anesthetic. Based on our research it is obvious that the measuring of pressure during the nerve blockade is very important in order to decrease the risk of neurological and possible systematic complications. It is also clear that a small, mobile, and financially quite available apparatus for pressure measurement can help in differentiation between para-neural, intraneural and intravascular injection. Avoiding high injection pressure prevents from lodging the needle into intraneural space, while avoiding a very low injection pressure prevents from lodging the needle into intravascular space followed by consequential complications. The usage of this apparatus can find its application in other blockades of periphery nerves, and in other branches of medicine as well.

Sanja Krosnjar, Maida Todić, Sanela Bakić, B. Begović, I. Zulić, M. Vehabović

Endogen phospholipids play a major role in determining the structure and nature of cell membranes. A deficiency of phospholipids in cellular membranes makes it almost impossible for the cell membrane to perform its function as a selective barrier between what passes in and out of the cell. Polyenylphosphatidylcholine chemical structure corresponds to that of endogen phospholipids, but it possesses functional superiority because of its content of unsaturated fatty acids. Polyenylphosphatidylcholine integrates in the cell membrane and organelle systems while becoming their constitutive elements. A healthy cell membrane leads to healthy cells and then healthy tissue and then to healthy organs or body systems and finally, healthy bodies and minds. For a long time, polyenylphosphatidylcholine in combination with vitamins has been used in the treatment of numerous health problems such as liver diseases, dyslipoproteinaemias and different intoxications with consequent liver failure. The main aim of toxicology studies is evaluation of the toxic potential and risks of human exposition to the substance. According to the Organization for Economic Cooperation and Development (OECD) acute oral toxicity refers to those adverse effects occurring following oral administration of a single dose of a substance or multiple doses given within 24 hours. LD50 (median lethal dose), oral, is a statistically derived single dose of a substance that can be expected to cause death in 50 per cent of animals when administered by the oral route. Our acute toxicity study was performed on albino Wistar rats. Animals were randomised in three experimental and one control group, each of 5 males and 5 females. Study was based on the administration of a single oral dose of the test substance (polyenylphosphatidylcholine) to each experimental animal. There were three dose-levels of the test substance: 300, 500 and 1000 mg/kg. Test substance administration day was the first day of the observation period that lasted 14 days. Control animals were given milk vehicle. At the end of the study, no statistically significant differences between experimental and control animals were observed concerning the recorded parameters: body weight, respiratory rate, tremor, faeces and phonation quality, indicating the absence of the test substance acute toxicity.

A. Arslanagić, I. Zulić, A. Bajraktarević

AIM Evaluation of efficacy and safety of long-term (24 weeks) administration of a combined therapy of ACE inhibitors (lisinopril) and calcium-channel antagonists with long-term action (amlodipine) (with or without diuretics). METHOD A total number of 98 patients of both genders were included in the prospective, open trial. Evaluation of efficacy of the trial was carried out by careful monitoring of anamnesis and physical examination, blood-pressure values, pulse, body weight, ECG test and echocardiographic test. Evaluation of safety of the trial was based on the evaluation of a physician, standard laboratory evaluation, adverse effects. RESULT Mean value of blood pressure in the beginning of clinical trial was significantly reduced (from 197.65 +/- 18.05/107.1+/-13.1 mm Hg, to 139.85 +/-10.45/82.6+/-5.47 mmHg) after 24 weeks, without special oscillations in last three months. The pulse remained within physiological limits. In 73.08% patients, echocardiographic test has proven an improvement of ejection fraction. Minor adverse effects have been reported, which were not a reason for interruption of the treatment, with the exception of 3 cases (lower leg oedema, dry cough). CONCLUSION An extremely good effect in patients with moderate hypertension was reported in the trial, as well as in patients with severe hypertension with good tolerance.

Amra Begović, I. Zulić, F. Becic

Fluoxetine is used in treatment of depression caused by a variety of different factors and from year to year new indications are being added, especially in conditions followed with strong bouts of pain. Additional fluoxetine based therapy that is known to help in improvement of mental state and mood stabilization can significantly increase analgesic effects. Analgesic effects of fluoxetine as well as of fluoxetine in combination with morphine were analyzed on albino mice of both genders. The sense of pain was induced by thermal stimulus by the method of hot plate. Analgesic effect was measured 30, 60, 90 and 120 minutes after a single i.p. administration of fluoxetine in following dosages: 5, 10 and 20 mg/kg. The control group was treated with 0.1 ml/10 g physiological solution. Test group injected with morphine s.c. (7 mg/kg) was used to observe the effect of fluoxetine in combination with morphine. Fluoxetine applied in 5 mg/kg dosage causes increased pain reaction 60 and 90 minutes (p=0.049 and p=0.002) (t-test) following application when compared with corresponding values of control group. When fluoxetine is applied in 10 mg/kg dosage duration of pain reaction is significantly increased after 30 (p=0.01), 60 (p=0.001) and 90 minutes (p=0.026), when compared to the control group. When fluoxetine is applied in 20 mg/kg dosage duration of pain reaction is increased 60 and 120 minutes (p<0.001) after application when compared to the control group. After application of fluoxetine (5 mg/kg) in combination with morphine, reaction time to pain is significantly extended (p<0.001) 60, 90 and 120 minutes after application when compared to the control group injected exclusively with morphine. Fluoxetine causes analgesic effect in all three applied dosages as well as it significantly increases analgesic effect when applied in 5 mg/kg dosage in combination with morphine.

R. Jadric, I. Zulić, S. Hasić, E. Kiseljaković, B. Zecević, J. Radovanović, E. Ićindić-Nakas, M. Winterhalter-Jadrić

Some 25 years ago it was found that parts of CNS could produce strong analgesic response on little morphine quantities. Later studies proved the existence for dozen of morphine-like substances, called opioids, which are normally produced in the brain. The most important are endorphins, met- and leu-encephalin and dinorphin produced both in hypothalamus and pituitary gland. The aim of our study was to found whether and how strong produce of beta-endorphins is to be expected when psychotropic drugs are used. Trazodon as antidepressant was used, and RIA technique for quantification of sera beta-endorphins. The results showed significant difference in rat sera beta-endorphins between certain days of drug application. These studies showed that beta-endorphins could be of great importance, used as markers for evaluation of patient treatment and eventual abuse of psychotropic drugs.

Endodontic pathology is a bacterial disease. It is well established that periapical disease is the result of bacteria, their product, and the host response to them. Periradicular disease will occur after microorganisms and their metabolic products affect the periradicular tissue. Aim of using antibiotics as part of a treatment regimen is to achieve, within the periodontal environment, a concentration of the drug that is sufficient either to kill (bactericidal) or arrest the growth (bacteriostatic) of pathogenic microorganisms. There are two possible approaches to improve the drug action: sustained and controlled drug release to reduce or eliminate side effects by improving the therapeutic index and site-specific drug delivery to minimize systemic effects. These two strategies have been explored by the association of drugs with different vehicles, either naturals or synthetics. A wide variety of specialized local delivery systems (i.e.intrapocket devices) have been designed to maintain the antibiotic in the GCF (gingival crevicular fluid) at a concentration higher than the MIC (minimum inhibitory concentration). Fibres, films, strips and microparticles made of biodegradable or non-biodegradable polymers have been reported as effective methods to administer antibacterial agents for periodontal therapy. Together with these solid devices, semisolid adhesive or non-adhesive formulations have also been proposed.

The endodontium and periodontium are closely related and disease of one may lead to secondary disease in the other. The differential diagnosis of endodontic and periodontal disease is of vital importance, so that the appropriate treatment can be done. Microorganisms play a primary role in endodontic and periodontal infections. The magnitude of the host response will be directly proportional to the virulence and the number of microbial cells present. Tissue damage caused by bacteria is mediated by either direct or indirect mechanisms. Direct harmful effects caused by bacteria involve their products, such as enzymes (collagenase, hyaluronidase, condroitinase, acid phosphatase), exotoxins and metabolites (bytrate, propionate, ammonium polyamines, sulphured compounds). In addition, bacterial components such as peptidoglycan, teichoic acid, fimbriae, outer membrane proteins, capsule, and lypopolysaccharide, stimulate the development of host immune reaction capable of causing severe tissue destruction.

UNLABELLED Left ventricular hypertrophy (LVH) is commonly present in hemodialysis patients (HD pts) and is considered as an independent risk factor for high mortality. Many studies have confirmed sound connection between anemia and LVH in this patients. OBJECTIVE To analyse dystolic function of LVH in uraemic pts during the 6 months human recombinant erythropoectin (rHu-Epo) treatment of anemia, with emphasis on the role of nitric oxide (NO), whose role in regulation of LV diastolic distensibility has been hinted in some recent studies. PATIENTS AND METHODS The study included 20 HD pts, aged 39.6 +/- 5.3 yrs, with the same condition of HD treatment, signs of anemia and echocardiographically verified LVH. Pulse Doppler echocardiography confirmed LV diastolic function as a ratio of early to late diastolic mitral flow velocity (E/A). Nitrate concentration was determined by colorimetric method using Greiss reagent. Renal anemia was treated with rHuEpo. RESULTS Six months rHuEpo treatment of anemia in HD pts with LVH caused significant reduction of LV mass index (p = 0.008). However, we observed unfavourable fall in LV diastolic function (E/A = 0.83, p = 0.007). In the same time, it was found that the serum NO level was higher for 11.8% in HD pts with LVH as compared with the pts with normal LV mass. Also, the significant positive correlation was found between the level of NO and LV mass index before (p = 0.004) and after rHuEpo therapy (p = 0.03), as well as a significant positive correlation between NO and E/A in the same conditions (p = 0.002) and p = 0.049). Level of NO negatively correlates with blood hemoglobin level, but without statistical significance. CONCLUSIONS Correction of anemia with rHuEpo leads to the significant partial regression of LVH. Reduction of diastolic function of LV, observed after diminished LV mass index, could be related to the significant fall of NO level and damaged response of LV to NO. The results of the study strongy suggest that NO can present an important determinant of LV diastolic function in uraemic pts.

BACKGROUND AND PURPOSE Clinical research of drugs is a researching step subsequent to the preclinical studies in experimental animals. The aim of our research was to evaluate animal model of wound healing process after the burn inducement and effects of the ointment containing natural plants on the process of burn healing. MATERIAL AND METHODS Burn wounds were experimentally induced in two species of experimental animals which were treated with topically applied herbal preparation with concomitant monitoring of the healing process. Experimental groups (1) of 15 animals each (mice and rats), while control group (2) of 10 animals each (mice and rats) that were not being treated with herbal ointment. After the hair removal, burn was induced on the back of animals by heated brass seal. Different clinical symptoms including oedema of surrounding tissue, redness, exudation, size of the burn surface, histological and microbiological findings were monitored on the days 1, 3, 7, 14 and 21. A statistically significant difference was observed throughout descriptive statistics and paired Student's t-test. CONCLUSION Physiological healing processes of the acute burn wound following the topical application of herbal preparation can be monitored on the utilized animal model. A three-week treatment resulted in the 90% of completed epithelization in both animal species, indicating the effectiveness of topically applied herbal preparation.

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