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Olanzapine is a thienobenzodiazepine class antipsychotic that strongly antagonises the 5-HT2A serotonin receptor, but acute poisonings are reported rarely. Symptoms of an overdose include disorder of consciousness, hypersalivation, myosis, and coma. Serum concentration higher than 0.1 mg/L is toxic, while concentration above 1 mg/L can be fatal. Here we report key data about 61 patients admitted to the National Poison Control Centre in Belgrade, Serbia over olanzapine poisoning in 2017 and 2018. The ingested doses ranged from 35 to 1680 mg, and time from ingestion to determination from two to 24 hours. In 34 patients olanzapine serum concentrations were in the therapeutic range and in 27 in the toxic range. In five patients they were higher than fatal, but only one patient died. The most common symptoms of poisoning were depressed consciousness (fluctuating from somnolence to coma), tachycardia, hypersalivation, hypotension, myosis, and high creatine kinase. All patients but one recovered fully after nonspecific detoxification and symptomatic and supportive therapy.

Introduction: Ogilvie syndrome and gastrointestinal bleeding as complications after reversal of typical clinical picture of acute Clozapine overdose is described. Case Report: A previously healthy 31-year-old man was found unconscious with Glasgow Coma Score of 6, non-reactive miotic pupils, hypersalivation and heart rate of 115 bpm. In the blood, the presence of Clozapine, Diazepam, haloperidol and biperiden were confirmed. The patient was referred to the intensive care unit for symptomatic and supportive treatment. Clinical signs registered on admission, except for sinus tachycardia, were completely resolved by the day 3. The patient began to eat and had regular bowel movements. From the seventh day, gastrointestinal complications were noticed. Nonobstructive dilatation of the stomach and intestine was confirmed on computed tomography scan. Nasogastric suction, the usage of laxatives and prostigmin injections as well as colonic irrigation was performed with a good clinical response. Conclusion: Clinicians should be aware of the potential of atypical antipsychotics to cause ileus, particulary in combination with other drugs with antimuscarinic properties, and ready to rapidly detect and treat intestinal atony thus preventing life-threatening complications. Serum Clozapine levels may not equate to clinical toxicity and the drug-näive patient require more careful observation for complications in Clozapine toxicity settings.

This paper deals with the poorly researched concept of fenced settlements (housing policy), which was developed in the USA in the middle of the 20th century, but has recently been particularly affirmed in NEO-liberal society, all over the world. Walled settlements also exist in social-democratic Europe, and the article studies the consequences of applying this concept, i.e. the influence of fenced settlements on the democratic spirit of the city and the democratic and development potential of the city, on the example of cities in Europe (France, Britain and Ireland) with lessons learned. Gated settlements have a number of negative effects on the community. For the needs of fenced communities, authorities often privatize roads, public spaces, and access to remaining public areas, to the detriment of the majority of residents, for whom entire complexes in the city remain inaccessible. This creates numerous social and spatial injustices, which actively undermines the democratic capacity of the city. These processes are in conflict with the democratic concept of the open city and the model of mixed housing, cultivated during the welfare state. The article relies on the analyses of existing research and studies of fenced settlements in the world through indicative examples and case studies (content analysis, synthesis, generalization, comparison). Statistical methods, analysis of regulatory changes, interviews and surveys of tenants, development managers, politicians and officials were often used in these studies. The comparative method in this paper compares the similarities and differences of fenced settlements in various countries, which is the basis for conclusions and recommendations for optimal housing policy and urban development (synthesis). The article introduces this challenging topic into the debate space of political and social sciences (field of urban studies), presents the existing consequences, and through comparison allows us to synthetically arrive at recommendations for choosing the optimal housing policy (learning from experience).

In this paper, the influence of cut at two maturity stages (the beginning of the flowering stage and mid bloom stage and bacterial inoculant "Silko za lucerku" (contains Lactobacillus plantarum and Pediococcus spp.) on the quality of red clover silage were presented. The commercial cultivar Nada selected at the Bc Institute in Zagreb was used for investigation. The silage was examined in mini-silos (glass jars of 1.5 l volume with plastic fermentation valve) in the laboratory. The chemical composition, energy and fermentation characteristics of silages were analyzed 90 days after ensiling. The values of dry matter, acid (ADF) and neutral detergent fibre (NDF), lactic acid and pH were significantly lower, while the crude protein content, total digestible nutrients (TDN), relative feed value (RFV), ammonia nitrogen in total nitrogen (NH3-N/TN), acetic and butyric acids were significantly higher in the first cutting stage. The inoculation with inoculant "Silko za lucerku" improved the chemical, energy and fermentation parameters of silages. Inoculant-treated silage had lower contents of ADF, NDF, NH3-N/TN, acetic and butyric acids and pH, and higher contents of dry matter, crude protein, TDN, RFV and lactic acid than control. Accordingly, timely cutting stage and application of microbial inoculant can contribute to a lesser loss of nutritional value of the forage and promote silage quality.

Background/Aim. Injury to the anterior cruciate ligament (ACL) of the knee is the most common ligament injury that requires operative treatment. So far, multiple ACL reconstruction (ACLR) techniques using a variety of graft types and implants that fixate the grafts have been described. The aim of the study was to compare two different ACLR techniques using two implant types for suspensory graft fixation in the femoral tunnel. Methods. This randomized-prospective study encompassed 60 patients/subjects who underwent ACLR in the period between January 2015 and December 2017 at the Department of Orthopaedics and Traumatology of Military Hospital “Dr Vladan Djordjević” Niš. The ACLR in all patients included in the study was per-formed using a quadruple semitendinosus-gracilis (STG) graft with two types of suspensory fixation on the lateral femoral cortex, whereas the graft fixation in the tibial tunnel was performed using an osteoconductive bioresorbable screw. The post-operative knee stability was assessed 24 months after surgery using the Lachman test and the lateral pivot shift test, as well as the KT-1000 arthrometer test. Results. In patients whose graft was fixated using a fixed-length loop implant, the mean post-surgery knee stability, measured with the KT-1000, was 1.167 ± 0.780; in patients whose graft was fixated using an adjustable-length loop implant, the mean value of the KT-1000 was 1.100 ± 0.894 (p = 0.605). The mean post-surgery International Knee Documentation Committee (IKDC) score for the fixed-length loop group was 84.887 ± 9.0207, while for the adjustable-length loop the score was 88.327 ± 7.302. The mean Lysholm score was 93.50 ± 6.872 for the fixed-length loop group of patients and 94.00 ± 5.527 for the adjustable-length loop group of patients. Conclusion. Both types of implants can be used with success during ACLR, because the functional results of operative treatment using both implants were identical after surgery.

Immunochromatographic strips for urine drug screening tests (UDSTs) are common and very suitable for drug abuse monitoring, but are also highly susceptible to adulterants kept in the household, which can significantly alter test results. The aim of this study was to see how some of these common adulterants affect UDST results in practice and whether they can be detected by sample validity tests with pH and URIT 11G test strips. To this end we added household chemicals (acids, alkalis, oxidizing agents, surfactants, and miscellaneous substances) to urine samples positive for amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), tetrahydrocannabinol, heroin, cocaine, or benzodiazepines (diazepam or alprazolam) and tested them with one-component immunochromatographic UDST strips. The UDST for cocaine resisted adulteration the most, while the cannabis test produced the most false negative results. The most potent adulterant that barely changed the physiological properties of urine specimens and therefore escaped adulteration detection was vinegar. Besides lemon juice, it produced the most false negative test results. In conclusion, some urine adulterants, such as vinegar, could pass urine specimen validity test and remain undetected by laboratory testing. Our findings raise concern about this issue of preventing urine tampering and call for better control at sampling, privacy concerns notwithstanding, and better sample validity tests.

Background/Aim. Congenital malformations still represent one of the most important causes of prenatal and infant death. The study aim was to analyze occurrence, outcomes and risk factors of different types of congenital anomalies. Methods. The study included all pregnant women directed to Clinic of Obstetrics and Gynecology, Clinical Center of Serbia, Belgrade due to prenatally diagnosed congenital fetal anomalies during past ten years (January 1, 2008–December 31, 2017). Upon admission to our Clinic a detailed general medical and obstetrical history were taken from every patient. All women underwent genetic testing. Ultrasonography and magnetic resonance were diagnostic methods for fetal malformations confirmation. Results. The study included 773 pregnant women aged from 18 to 46 years. Out of registered nine different groups of fetal anomalies/malformations, the most common were malformations of the central nervous system, while majority of fetuses had combined multiple anomalies. Genetic cause for congenital anomalies was present in 25.2% of pregnancies. Medical pregnancy abortion was performed in 71.8% of cases. Only 10.2% of pregnancies ended in term. The best outcome for children was obtained in case of gastrointestinal anomalies (52% live born). Contrary, only one child with neck and thorax malformations could be saved. According to logistic regression the most important predictor of having a child with combined multiple anomalies was mother’s age, while predictor of central nervous system anomalies was gestational diabetes. The significant predictor of genetic anomalies was mother’s age. Conclusion. In our sample neurological congenital anomalies were the most common, although abnormalities of all organ systems were registered. Majority of pregnancies had to be discontinued due to combined multiple anomalies caused by genetic disorders. Older mother’s age and diabetes can imply on the increased risk for fetal malformations.

The main aim of these studies was the characterisation and identification of lactic acid (LAB) bacteria isolated from untreated silage, and the effect of selected bacteria (inoculant was called Silko for maize) on ensiling of maize high-moisture grain. Four isolates of LAB (L1, L2, L3 and L4) were characterised by the use of phenotypic assays and identified by phylogenetic analysis of 16S rRNA as L. plantarum. The fresh maize high-moisture grain was ensiled with a Silko for maize inoculant, inoculant available in the market (positive control) and no additive (untreated; negative control). After 60 days of ensiling, the results showed that the chemical composition and fermentation characteristics were better in treated silages with inoculants compared to the negative control. The contents of ash, fat and lactic acid (LA) were significantly higher in the silages treated with inoculants than in negative control. In comparison, the contents of cellulose, acid detergent fibre (ADF), neutral detergent fibre (NDF), NH3-N/total nitrogen and butyric acids (BA) were considerably lower in silage treated with Silko for maize compared to the positive control. The Silko for maize improve nutritional value and fermentation of maize grain silage and is a competitive product on the market.

Using of silage and haylage of forage legumes in ruminant nutrition and promotion of promoting proper forage conservation techniques should be an important strategy in livestock production in our country. Forage legumes are difficult to ensile, so it is necessary to apply the starter culture of selected strains of lactic acid bacteria that support the ensiling process and prevent bacterial butyric fermentation and thus contribute to the preservation and improvement of silage and haylage quality. In this paper, the influence of bacterial inoculant 'Silko for alfalfa' on the quality of silage and haylage of alfalfa in two separate trials is presented. The inoculant is a combination of homofermentative lactic bacteria Lactobacillus plantarum and Pediococcus spp. The first-cut alfalfa in the second year was used for silage and haylage. The silage was examined in mini-silos in the laboratory, and the haylage at the cattle farm where the plant material was cuts were collected in experimental silo bags. The treatments were control (untreated silage, i.e. haylage) and silage, i.e. haylage treated with inoculant 'Silko for alfalfa' (rate of 5 ml t-1 fresh material). The silages were analyzed after 90 days, and haylage after 40. The inoculant 'Silko for alfalfa' has been found to maintain the nutritive value of silage and haylage and to improve their chemical, energy and fermentation parameters relative to the control. Since 'Silko for alfalfa' positively affects the correct lactic acid fermentation of silage and haylage and contributes to a lesser loss of nutritional value and energy it is expected that it can promote a high level of productivity of ruminants, and thus contribute to the growth of profit in livestock production.

Introduction. During the last few years, intravenous lipid emulsions have been effectively used in treatment of acute poisonings with lipophilic substances, including verapamil. Case report. A 37-year-old women presented 1 hour after ingestion of 2.8 g verapamil with hypotension and complete heart block. Because of the applied standard therapy failure and further patients impairment, Intralipid® 20% was used. Sinus rhythm was restored, arterial blood pressure increased and verapamile concentrations, both total and free decreased. Conclusion. Intravenous lipid emulsion can be important in treatment of severe acute intoxication and cardiotoxicity caused by verapamil.

In the winter time in Serbia, maize silage is the main ruminant feed. Therefore, managing maize silage is an important contributor to maintain the silage quality for livestock feed. In the study were evaluated the chemical composition, energetic and fermentation characteristics in whole-crop maize silage inoculated with different bacterial inoculants under field conditions in the commercial dairy farm, during the 2015. Three treatments were tested: negative control (untreated silage), a positive control (competitor inoculant) and Silko treatment (contains a mixture of 4 strains of Lactobacillus plantarum (LP1, LP2, LP3 and LP4). Maize is ensiled in the milk-wax grain maturity. After 90 days of ensiling, the maize silages were analyzed. The application of bacterial inoculants improved the chemical composition and energetic characteristics of silage. The inoculant Silko was more effective at improving the fermentation characteristics than competitor inoculant. Ash, cellulose, soluble N/TN, NH3-N/TN, ADF, NDF, acetic acid and pH were significantly lower in Silko treatment than positive control. There were no differences in crude fat, crude protein, ME, NEL, lactic acid and butyric acid between the treated silages. Generally, the new product bacterial inoculant Silko proved in field trials its ability to support the ensiling process in maize. The main action of the bacterial inoculant Silko is performed in two ways: the reduced degradation of protein in silage and the improvement of the aerobic stability due to the lower pH, higher content of acetic acid than negative control.

The standard technology of seed processing uses mainly chemical products. Recent researches showed that toxic materials from chemical fertilizers can be harmful to humans, animals and the environment. Currently the attention of researches is shifting away from chemical fertlizers and toward alternative that consumers perceive to be natural, Plant Growth Promoting bacteria (PGP). PGP bacteria could be a way to reduce chemical fertilizer doses. This was the reason to test the ability of Bacillus megaterium, Azotobacter chroococcum to produce hormone auxin (IAA). Bacterial strains were identified by PCR amplification and sequencing of the 16S rRNA gene. Indole-3-acetic acid (IAA) was detected and quantified by MRM experiment. This study conducted that maize seed inoculation with IAA from species mentioned above showed positive effects. They had statistically significantly higher root and steam height compared to control seedlings. Bacterial strains tested in this study may be recommended as PGP (Plant Growth Promoting) bacteria, due to their positive effects and eventually can be used to reduce chemical fertilizers doses.

Backgound/Aim. Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylline may reduce the need for repeated dosing of flumazenil in patients with acute diazepam poisoning. The aim of this study was to introduce a reliable and accurate method for determining the concentration of flumazenil after therapeutic application in patients with acute poisoning, and using that method to assess whether the kinetics of flumazenil change in the presence of aminophylline (combination of theophylline and ethylenediamine in a 2 : 1 ratio) applied as concomitant therapy. Methods. Blood samples from patients with acute diazepam poisoning that received flumazenil at the dose of 0.5 mg, or the same dose with 3 mg/kg of body weight of aminophylline, were collected 1, 3, 10, 30, 60, 120 and 240 min after its intravenous administration. Samples were prepared by solid-phase extraction on Oasis HLB cartridges with ethylacetate as extracting agens. Flumazenil was determined by liquid chromatography with mass spectrometry (LC-MS) in single ion monitoring mode at m/z 304. Separation of flumazenil from matrix compound was performed on Lichrospher RP-8 column using the mixture of acidic acetonitrile and 20 mM of ammonium acetate in water (55 : 45) as a mobile phase. Results. The applied analitycal method showed excellent recovery (94.65%). The obtained extracts were much cleaner than the extracts obtained by the same extractant in the process of liquid-liquid extraction. The limit of detection of the LC-MS method described in this paper was 0.5 ng/mL and the limit of quantitation was 1 ng/mL. In the patients treated with both flumazenil and aminophylline, the elimination constant for flumazenil was significantly lower and the elimination half-life was longer (p < 0.05) in comparison with the same parameters in the patients who received flumazenil alone. Conclusion. The applied LC-MS method for the determination of flumazenil in serum samples of patients with acute diazepam poisoning is rapid, sensitive, precise and specific. Concomitant use with theophylline significantly prolonged elimination of flumazenil during the treatment of acute poisonings with diazepam.

Introduction. Calcium channel blockers and beta-blockers are among the most frequently ingested cardiovascular drugs in self-poisoning causing significant mortality. Intravenous lipid emulsion (ILE) is reported as a potentially novel antidote for treatment of acute poisoning caused by some of these drugs. Case report. We presented two cases of poisoning with these drugs. The case 1, a 24-year-old woman ingested amplodipine, metformin and gliclazide for self-poisoning. She presented with tachycardia and hypotension. Laboratory analyses revealed hyperglycaemia and metabolic acidosis. Despite the treatment which included fluid resuscitation, vasopressors, intravenous calcium, glucagon and ILE, circulatory shock occurred. The patient died 10 hours after admission due to cardiac arrest refractory to cardiopulmonary resuscitation. The case 2, a 41-year old man, was found in a coma with empty packages of nifedipine, metoprolol and diazepam tablets. On admission vital signs included Glasgow Coma Scale (GCS) of 3, weak palpable pulses, undetectable blood pressure, and irregular breathing with oxygen saturation of 60%. An electrocardiography showed AV block (Mobitz II) with ventricular rate of 44/min with progression to third degree of AV block. In attempt to increase heart rate and blood pressure the following agents were administered: atropine boluses, normal saline with dopamine, glucagon, calcium chloride and ILE. Temporary transvenous pacemaker was placed, electrical capture was recorded, but without improvement in haemodynamics. Three hours after admission cardiac arrest happened and cardiopulmonary resuscitation was unsuccessful. Conclusion. Intravenous lipid emulsion may be ineffective in acute poisonings with amlodipine, nifedipine or metoprolol.

Background/Aim. Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity to benzodiazepines. The aim of this study was to assess toxicity of benzodiazepines in elderly attempted suicide. Methods. A retrospective study of consecutive presentations to hospital after self-poisoning with benzodiazepines was done. Collected data consisted of patient's characteristics (age, gender), benzodiazepine ingested with its blood concentrations at admission, clinical findings including vital signs and Glasgow coma score, routine blood chemistry, complications of poisoning, details of management, length of hospital stay and outcome. According the age, patients are classified as young (15-40-year old), middle aged (41-65-year old) and elderly (older than 65). Results. During a 2-year observational period 387 patients were admitted because of pure benzodiazepine poisoning. The most frequently ingested drug was bromazepam, the second was diazepam. The incidence of coma was significantly higher, and the length of hospital stay significantly longer in elderly. Respiratory failure and aspiration pneumonia occurred more frequently in old age. Also, flumazenil was more frequently required in the group of elderly patients. Conclusion. Massive benzodiazepines overdose in elderly may be associated with a significant morbidity, including deep coma with aspiration pneumonia, respiratory failure, and even death. Flumazenil is indicated more often to reduce CNS depression and prevent complications of prolonged unconsciousness, but supportive treatment and proper airway management of comatose patients is the mainstay of the treatment of acute benzodiazepine poisoning.

Topic: Neuroleptic Malignant Syndrome is a rare but specific lethal reaction to neuroleptics / antipsychotics.It occurs in 0.02% to 3.3% of patients in the treatment applying conventional neuroleptic drugs. Neuroleptic malignant syndrome is associated with highly potent antipsychotic drugs. However, it can occur more frequently in patients treated with atypical antipsychotics such as clozapine. Topic position in medical public: Neuroleptic malignant syndrome is critical medical condition, potentially threatening complication associated with side effects of neuroleptic drugs. High levels of creatine kinase (CK) and leukocytosis are associated with neuroleptic malignant syndrome. Future action: Neuroleptic malignant syndrome as a psychiatric entity requires permanent research, early diagnosis, adequate therapy, exchange of clinical experiences, and what's of particular importance, rational antipsychotic administration.

Alfalfa silage is a useful source of protein for feeding ruminants. Therefore, managing alfalfa silage in livestock production systems is an important issue in order to maintain the silage quality and achieve maximum profitable production of milk and meat. The aim of this investigation was to estimate the effects of bacterial inoculant Silko, containing Lactobacillus plantarum (strains: LP1, LP2, LP3 and LP4) on chemical composition, energetic characteristics and fermentation alfalfa silage under field conditions in the commercial dairy farm, during the 2016. The first-cut alfalfa in the second year has been conserved in silage form. The silage mass was subdivided into two equal parts (control (silage without inoculant) and silages treated with bacterial inoculant Silko) and ensiled in trench silo. After 60 days of ensiling, the silages were analyzed. Dry matter, ash, crude protein, lactic acid, acetic acid, total digestible nutrients value and relative feed value were significantly higher in silage treated with bacterial inoculant Silko compared to control. Contrary, alfalfa silage treated with a bacterial inoculant Silko had lower values of cellulose, acid detergent fibre, neutral detergent fibre, nonnitro extractive matter, pH, butyric acid, soluble nitrogen/total nitrogen and NH3- N/total nitrogen than untreated silage. Results showed that bacterial inoculant Silko increases silage quality compared to control so that research should be directed toward the use of such prepared silage in ruminant diets and its impact on milk and meat production on farms.

Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated diphenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p < 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 x external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely exposed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent substances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly. [Projekat Ministarstva nauke Republike Srbije, br. III 46009]