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Various forensic techniques are used to identify a human corpse, depending on the circumstances and the state of remains. Unfortunately, the standard forensic identification methods were not sufficient in 30–35% of all victims, therefore DNA identification was necessary. We have found that a forensic autopsy does not always give reliable answers to important questions, for example: What is the amount of time lapsed between the moment of death and the skeletal remains discovery? and What is the age of the deceased? In fact, it could often cause an erroneous identification strategy choice. This paper describes the forensic application of current DNA technology to solve a missing person’s case. The disappearance of a 57 year old male was reported in a town in the north of Serbia in August 2017. In January 2018, in that geographical area parts of skeletal remains, remains of clothes and a watch were found and sent to the Institute for Forensic Medicine. The age of the person was estimated to be between 75–80 years, and it was estimated that the remains had been buried for more than 10 years. This report confused the police, because they did not have a missing person of the above description on record. However, the DNA analysis of a bone sample has shown that the remains belong to the 57 year old missing person who disappeared 5 months prior and for whom the son was the reference sample donor. Complete DNA profiles obtained using AmpFlSTR® Identifiler® Plus, AmpFlSTR® NGM™, GlobalFiler™, Investigator® 24plex QS kit, AmpFlSTR® Yfiler® and AmpFlSTR® Yfiler® Plus PCR Amplification kits were a match with the reference sample of the victim’s son (probability 99.9995147%). This work has shown that for identification of skeletal remains and solving missing persons cases, the forensic application of the latest DNA technology is of utmost importance.

Since the beginning of our work in 2003 our laboratory has focused exclusively on STR DNA from bone, a powerful tool in missing person cases. In cases such as mass disasters or missing persons, human remains are challenging to identify as they may be fragmented, burnt, recovered from water, degraded, and/or contain inhibitory substances. To address these challenges, this study has evaluated the performance of relatively new STR kits Investigator® 24plex QS kit (Qiagen) and GlobalFiler™ PCR Amplification kit (Thermo Fisher Scientific) by comparing it with current uses of the AmpFLSTR® Identifiler® Plus kit (Applied Biosystems) to obtain genetic information from skeletal remains. We analyzed 20 bone samples of skeletal remains from routine casework submitted for body identifications by law enforcement corresponding using Investigator® 24plex QS kit and GlobalFiler™ PCR Amplification kit, previously analysed AmpFLSTR® Identifiler® Plus kit (Thermo Fisher Scientific). The data indicates that the STR profiles obtained using the GlobalFiler™ and Investigator® 24plex QS kit for analysis of skeletal remains has shown results in an increased number of reportable genetic loci, and provide greater power of discrimination in comparison to the Identifiler® Plus Kit. Advanced extraction and purification techniques, together with more sensitive and robust new amplification kits allowed us to overcome the challenges associated with processing compromised skeletal remains and ultimately obtain full STR DNA profiles in 99% of the bones.

To assess our laboratory’s success with skeletal remains and provide a benchmark for the forensic community involved in identification of these remains, we retrospectively examined our ability to develop DNA profiles from the remains analyzed in our laboratory in the last 7 years. Between January 2009 and December 2016, 70 DNA extractions were completed on skeletal remains from routine casework. 92% of skeletal remains analyzed were samples submitted for body identifications by law enforcement and only 8% were samples submitted to answer family identity or historical questions. Overall, the ability to obtain a full or partial profile primarily reflects the difference in the average age and the condition of the samples in these two categories and thus, difference in the quantity and quality of the DNA. We describe here the approximate age and type of remains we have received, whether a full, partial, or no profile was obtained, as well as the condition of the samples.

Recently, the interest of the forensic community has been focused on new Y-chromosomal short tandem repeats (Y-STRs), termed Rapidly Mutating Y-STRs (RM-YSTRs), which is able to differentiate between close males belonging to the same paternal lineage due to their high mutation rates. In this study, we have estimated a mutation rate for 13 RM-YSTR in 85 pairs of male relatives in the population of Serbia. We analysed 74 father-son pairs, and 11 twin pairs, to evaluate the capacity of distinguishing between male subjects within a single lineage. Each father-son couple was previously confirmed by autosomal STRs testing (AmpFlSTR® Identifiler Plus™ kit, Applied Biosystems) with paternity probability ≥99.99% and also confirmed monozygotic or dizygotic twins. Results showed that, in the 74 father-son pairs 23 mutations were detected of which 22 were one-step mutations and 1 was two-step mutation, while in the 11 twin pairs 1 mutation was observed in one dizygotic twin pair. Five father-son pairs were found to have mutations at two loci, while one pair at four loci. Overall, the most mutable markers were DYF399S1, DYF387S1, DYF403S1a and DYS612. Our findings are encouraging and concur with previous studies showing that by RM-YSTR typing the discrimination power of male relatives could be considerably increased in comparison to every YSTR markers commonly used in forensic genetics.

The aim of this study was primarily to evaluate inebriated fatally injured drivers (FIDs) according to blood alcohol concentration (BAC) in a 10-year period (2004-2013) in Autonomous Province (AP) of Vojvodina, Republic of Serbia, to analyze the efficacy of alcohol polices in the new law on road traffic safety through changes in the number of inebriated FIDs before and after implementation of the law, as well as to identify factors that influence the occurrence of FIDs with BACs above the legal limit.All data for this retrospective study were obtained from the Centre of Forensic Medicine, Toxicology and Molecular Genetics of Clinical Centre of Vojvodina, Novi Sad. Autopsy records for each case included age, gender, BAC, type of vehicle, and date of accident (year, month, and recalculated day of the week). BAC was determined by gas chromatography with flame ionization detection. Statistical analysis was carried out by chi-square tests and Student's t test, with P.05 as a statistical significance, and multiple binary logistic regression.Of the 354 inebriated FIDs (60% of all FIDs), the majority had BACs between of 0.031 and 0.3 mg/ml (28%), followed by those with BAC2.01 mg/ml (23%). The average BAC of those driving under the influence of alcohol (DUIA) for the whole period was 1.235 ± 1.00 mg/ml and the average number of DUIA/year was 35. Among the total number of FIDs there were significantly more males (93.7%; P.001) than females (6.3%), though the distribution of intoxicated men and women was not different (P.05). There was a statistically significant difference in the distribution of sober and inebriated FIDs according to age (P.001) with the predominance of inebriated FIDs between 21 and 30 years. Although gender and age were found to be significant predictors of BAC above legal limit in FIDs, the area under the receiver operating characteristics (ROC) curve showed that the model had poor discrimination (ROC = 0.673). Of all observed FIDs, 65 cases per year were attributed to the first 5-year period (2004-2009) and 49 to the second 5-year (2010-2013) period, which indicates that there was no statistically significant decrease in the number of FIDs after implementation of the new law.The highest number of intoxicated FIDs during the period in AP Vojvodina were mildly and completely inebriated. In the 4-year post-policy period (2010-2013), the number of FIDs and average BAC levels of inebriated FIDs did not significantly change. The abolition of a permissible BAC should be considered.

For identification of skeletal remains and solving missing persons cases, the forensic application of the latest DNA technology is of utmost importance. In our casework, most extraction attempts of skeletal remains from cases of criminal burning, with intention to destroy the body, were successful. This paper represents our approach and the results obtained during identification of burned skeletal remains. The body of the missing fifty-two-year-old taxi driver was found burned in the trunk of a car. The DNA was extracted from the powder bone using organic protocol and amplified by AmpFlSTR ® Identifiler ® Plus (Applied Biosystems), AmpFlSTR ® NGM™ (Applied Biosystems) and AmpFlSTR ® Yfiler ® (Applied Biosystems). Complete DNA profiles obtained using all three applied kits, were a match with the reference sample victim's son. In addition, we analyzed 5 DNA extracts, corresponding to 5 different burned body identification cases from 2009 using AmpFlSTR ® NGM™ kit. Concordant results were obtained for the STR loci between AmpFlSTR ® Identifiler ® kit which was used back then and AmpFlSTR ® NGM™ which is on our disposal today, including 5 additional loci expanded ESS.

The aim is to evaluate the role of diazepam concentrations in development of low-concentration-methadone-associated QTc prolongation in patients with opioid use disorder during methadone maintenance treatment (MMT) induction.Individuals with addiction disorder on MMT were studied before the beginning of MMT and after one and six months of MMT. Serum concentrations of methadone, diazepam, electrolytes and ECG were analyzed.Thirty patients were enrolled. The mean methadone concentration at time points was 177 ± 119 ng/ml and 343 ± 182 ng/ml, while the mean diazepam concentration was 561 ± 437 ng/ml and 1045 ± 933 ng/ml. The QTc interval before the introduction of MMT, after 1 and 6 months of MMT were 412 ± 27 ms, 425 ± 18 ms and 424 ± 15 ms, respectively, showing statistically significant increase in the length of QTc interval after 1 and 6 months of MMT. Statistically significant correlation between the concentration of methadone and QTc interval length at observed time points (RThe prolongation of QTc below the risk threshold in low methadone therapeutic doses has been recorded and concomitant use of diazepam could be a co-factor in such issue.

The number of methadone-related deaths (MRDs) during a 10-year period (2002-2011) in the region of Vojvodina, Serbia, was increased. The cases were evaluated according to epidemiological parameters, pathohistological findings, and toxicological screening. The majority of victims were men, aged from 20 to 38. Pathohistologically, the signs of acute focal myocardial damage were present in the heart of victims with drug abuse history shorter than 2 years, while both signs of recent and chronic focal myocardial damage were developed among victims with longer drug abuse history (2-5 years). In postmortem blood samples of 54.84% of victims, methadone was detected in combination with diazepam, both in therapeutic range. Alcohol was absent in most cases. Other detected drugs were antipsychotics and antidepressants in therapeutic concentrations. These findings raise the attention to the concomitant use of methadone and benzodiazepines with the need for further studies to clarify the mechanism of death in such cases.

Recent research with Rapidly Mutating Y-STRs (RM Y-STRs) have shown that these loci provide substantially higher haplotype diversity and haplotype discrimination capacity in worldwide populations when compared with the Y-STRs commonly used in genetic forensics. The aim of this study was to develop an allelic frequency database for the population of Serbia in order to evaluate the resolution power of 13 RM Y-STRs. A total of 279 unrelated males from the population of Serbia were typed with 13 RM Y-STRs loci: DYF387S1, DYF399S1, DYF403S1a/b, DYF404S1, DYS449, DYS518, DYS526a/b, DYS547, DYS570, DYS576, DYS612, DYS626 and DYS627. A high Y-STR haplotype diversity was found (0.999768) in our samples. As expected, the RM Y-STR loci showed high genetics diversity (GD) values (>0.73) in the Serbian population. The highest GD was observed for the locus DYF399S1 (0.991), followed by loci DYF403S1a (0.976), DYF387S1 (0.907) and DYF404S1 (0.899). Based on the results of this study, the RM Y-STR loci showed remarkable haplotype resolution power in the population of Serbia, high genetics diversity and, therefore, demonstrating their usefulness in forensic identification cases.

It is possible that sexually driven homicides are the consequence of sexual deviation, but more often than not the main cause of such homicides stems from a non-paraphilic person's emotional component. It is known that homicides which involve multiple stabbing are very often the result of the assailant's highly expressed affect. This study tries to establish whether such homicides are essentially related to the sexual motives of the murderer. This paper is conducted through a retrospective autopsy study that includes 766 cases of homicides. These were reviewed and analysed according to the motive of the homicide, as well as by method, age, and gender of the victim, and the relationship between the victim and the assailant. The motives of homicides are classified as non-sexual and sexual, including homicides related to rape, jealousy, amorous affairs outside of an established relationship, deviant sexual behaviour of psychiatric patients, paraphilia, and disturbed emotional relationships between the victim and the assailant. Cases include both hetero- and homosexual relationships. Multiple stabbing occurs significantly more frequently in sex-related homicides (≥ 3 stab wounds) than in other homicide types. When the criteria for multiple stabbing are changed (≥ 4, 5, or 25 stab wounds), the percentage of sex-related homicides rises in every group in relation to the increased number of wounds. Sensitivity and specificity are represented by ROC curves for 3, 5 and 7 stab wounds. The correlation coefficients between multiple stabbing and sex-related homicides regarding gender are all near 0.9. For female victims, all homicides committed by 25 and more stab wounds were found to be sex-related. Statistically, jealousy was the most frequent motive for sex-related multiple stabbing homicides. Regardless of age, homicides involving multiple stabbings should be considered sex-related, especially when the victim is female.

Anise (Pimpinella anisum L.; Apiaceae) and its essential oil have been widely used in folk medicine, pharmacy and food industry. Since there are some data about the impact of anise on functions of central nervous system (CNS), the issue of possible interactions with drugs acting in CNS should be considered. This survey aimed to examine the influence of aniseed essential oil (EO) intake on the effects of drugs that act in CNS. The chemical profile of essential oil determined by GC-MS revealed as the main components: trans-anethole (88.49%), γ-himachalene (3.13%), cis-isoeugenol (1.99%), and linalool (1.79%). The effects of codeine, diazepam, midazolam, pentobarbital, imipramine and fluoxetine were tested in mice after 5days of peroral pretreatment with human equivalent dose of aniseed EO (0.3mg/kg). The intake of EO led to significant increase of analgesic effect of codeine. The motor impairment caused by midazolam was enhanced in the group treated by EO. The application of diazepam decreased the number and percentage of entries in open arm in elevated maze plus test in the group pretreated with EO indicating augmented effect of drug on motor activity. EO pretreatment caused significant shortage of pentobarbital induced sleeping time when compared to control. The decrease in antidepressant effect of imipramine and fluoxetine was diminished by the pretreatment with aniseed EO. Based on the results of this study we conclude that concomitant intake of aniseed EO preparations and drugs that act on CNS should be avoided due to potential herb-drug interactions, which also need further clinical confirmation.

Water intoxication (WI) is a rare condition that originates from over-consumption of water, with a potentially fatal outcome. Increased water intake (polydipsia) is followed by urination of high amount of diluted urine (polyuria) which are the main initial symptoms of WI. We present four case reports of WI. Two of them are unusual pediatric clinical cases using medical documentation and police case files, one of which is related to child abuse, and the other to a psychiatric disorder. The other two cases are fatal adult cases submitted to autopsy from a psychiatric hospital. Also, we present a diagnostic algorithm for polydipsia and polyuria before death. WI is usually seen in patients with psychiatric disorders, victims of child abuse or torture, drug abusers or it can be iatrogenically induced.

The appearance of common and self-initiative usage of various herbal preparations in everyday practice and life imposes the question of possible interactions with drugs. This survey examined the influence of acute and chronic peppermint oil (PO – Mentha × piperita L., Lamiaceae; prepared as emulsion for oral use) on pentobarbitone-induced sleeping time, analgesic effect of codeine and impairment of motor coordination caused by midazolam in mice. The chemical profile of essential oil was determined by GC-MS. Applied doses of PO were 0.1 and 0.2 mL/kg. Chronic PO intake (in both doses) led to significant decrease of analgesic effect of codeine, while acute intake of PO did not change this effect. Acute PO pretreatment in higher dose caused significant prolongation of pentobarbitone-induced sleeping time, while it was significantly shortened by chronic PO pretreatment at the same dose. Midazolam effect was enhanced and prolonged significantly by chronic PO intake at higher dose, while acute intake of PO did not change this effect. Gut motility was increased only by acute intake of higher PO dose. Regarding the fact that PO produces changes in tested drug effects, the interaction between drugs and phytopreparations containing PO should be additionally followed/confirmed in humans. Copyright © 2011 John Wiley & Sons, Ltd.

Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological interest. We present a case of a 59-year-old woman with a history of paranoid disorder, who was found dead in the house where she lived alone. The autopsy findings revealed no marked pathological changes. Toxicological analysis based on gas chromatography-mass spectrometry (GC-MS) analysis revealed THP and its major metabolite (hydroxy-THP) in blood and urine, with THP concentrations of 0.053 and 0.560 mg/L, respectively. The blood and urine ethanol concentrations were low 0.096 and 0.100 g/L, respectively. Based on these results, we determined the cause of death to be THP poisoning. It is suggested that rare case of death associated with THP overdosage should be taken in conjunction with central nervous system depressants (benzodiazepines, ethanol) and/or with other pathological disorders. Thus, our case could not be supportive for this allegation.

Complex suicides (CSs) are committed by using more than one method. They account for 1.5-5% of all suicides. We present a case of CSs of a 44-year-old man, found dead in the vicinity of his car, in a deserted frozen field. Police investigation excluded homicide, and no medical data confirmed mental illnesses. Autopsy revealed wrist cuts, neck cuts, acid burns in the GI tract, multiple stab wounds to the head by a screwdriver, and several uncertain signs of hypothermia. Toxicology analysis (gas chromatography-mass spectrometry) confirmed ingestion of insecticide. We concluded that stab wounds to the head were the cause of death, while external hemorrhage and hypothermia were contributing factors. This is the first case of CSs reviewed in the literature where six suicide methods were applied. This particular case is interesting because the victim used a screwdriver as a tool for inflicting stab wounds to the head, which is a rare suicidal method. Language: en

Aniseed (Pimpinella anisum L., Apiaceae) and its essential oil (EO) have been widely used. Because there are some data about the impact of aniseed EO on drug effects, this survey aimed to assess the potential of pharmacokinetic herb-drug interaction between aniseed EO and acetaminophen and caffeine in mice. The chemical analysis (gas chromatography-mass spectrometry) of aniseed EO has confirmed trans-anethole (87.96%) as the main component. The pharmacokinetic studies of intraperitoneally (i.p.) and orally applied acetaminophen (200 mg/kg) and caffeine (20 mg/kg) were performed in mice after 5 days of oral treatment with human equivalent dose of aniseed EO (0.3 mg/kg/day). The analysis of pharmacokinetic data showed that in the group treated by aniseed EO, the significant decrease in the peak plasma concentration of acetaminophen after oral application (p = 0.024) was revealed when compared with control group and the reduction of systemic exposure to the drug after oral application (74 ± 32% vs. 85 ± 35% in the control) was noted. The bioavailability of orally applied caffeine was also significantly decreased (p = 0.022) after the EO treatment in comparison with the control (57 ± 24% vs. 101 ± 29%). Therefore, the compromised therapeutic efficacy of acetaminophen and caffeine during the usage of aniseed EO preparations should be considered.

Despite a large number of modern contraceptive methods available in the market today, numerous studies have shown insufficient awareness of young women about these forms for birth control. The aim of this study was to compare characteristics of common use of contraceptives as well as the awareness of hormonal contraception among female students of the Faculty of Medicine and the Faculty of Technical Sciences in Novi Sad.In the study which was conducted in 2012 240 female students of the Faculty of Medicine and the Faculty of Technical Sciences participated. The average age of students of the Faculty of Medicine and the Faculty of Technical Sciences was 24.06 ± 3.24 and 22.72 ± 0.90 years, respectively. They completed an anonymous questionnaire, which consisted of three parts. The first part comprised general questions, the second part included characteristics of the sexual life of students and their contraceptive habits, while in the third part students were asked to evaluate the accuracy of statements about hormonal contraception. The obtained data were statistically processed by using appropriate methods.The average age when the students of the Faculty of Medicine and the Faculty of Technical Sciences had the first sexual intercourse was 18.74 ± 2.61 and 18.75 ± 2.59, respectively. One third of students from both faculties (30.91% from the Faculty of Medicine and 35% from the Faculty of Technical Sciences) had only one sexual partner. Modern contraception was used by 83.64% of the medical students and by 80% of those from the Faculty of Technical Sciences. Contraception was used regularly by 54.54% of the medical students and 43% of those from the Faculty of Technical Sciences. The most frequently applied contraceptive method was condom (90% of the medical students and 93% of the Faculty of Technical Sciences students, respectively). Oral contraceptives were used by 24.54% of the medical students and 11% of those from the Faculty of Technical Sciences. There was a statistically significant difference in the knowledge level between the two groups since the medical students gave quantitatively higher range of expected responses than the students from the Faculty of Technical Sciences.It is necessary to increase the availability of adequate information on various types of contraception to student population in Vojvodina.

The aim of this study was to follow the postmortem ethanol production phenomenon under controlled experimental conditions (temperature, time interval) in different tissues. Specimens of blood, liver, skeletal muscle and kidney were taken from 30 corpses and no chemical preservatives were used in the specimens collected. Ethanol concentrations were detected by gas chromatography. All specimens stored at -20 degrees C and 4 degrees C did not show any change in ethanol concentration in an eight-day time interval. At 20 degrees C and 30 degrees C, all tissues, except blood, showed statistically significant ethanol production over the time interval tested. However, blood sample kept at 30 degrees C, showed statistically significant increase in ethanol production on the 2nd and 4th day comparing to the controls. Thus, we can state that postmortem ethanol production occurs in different tissues, and is increased at higher temperatures and, in general, it is in accordance with the course of time.

Aim: The change of antemortem blood alcohol concentration (BAC) in inadequately processed samples was examined. Methods: The study was performed on nine healthy, sober volunteers after overnight fasting. Blood samples were divided into groups and stored, with or without NaF, for varying time periods (12, 24 and 48 h) and at different temperatures (4°C and 20°C). BAC analysis was performed by the gas-chromatography method. Result: All groups showed very low values of BAC. Conclusion: Surprisingly, this study showed no ethanol production in improperly processed antemortem blood samples in healthy and sober individuals who were subjected to overnight fasting.

Background Methadone is an effective analgesic and it is widely used to suppress withdrawal symptoms from other opiates. Its consumption is usually associated with concomitant drug use in heroin addicts, and this combination is a possible risk factor for lethal outcome. The aim of this study was to analyze characteristics of methadone-related deaths (MRDs), and to evaluate the concomitant use of the drugs that can contribute to methadone toxicity.

Suicides using hand grenades are very rare. The aim of this retrospective study was to evaluate the cases of nonterrorist suicides using hand grenades according to the number of cases per year, sex, age categories, season of the year, day of the week, ethanol blood level, type of hand grenade, pattern of injuries, risk factors, and suicide place over a 20-year period, from 1990 to 2009 in Vojvodina, Serbia. The total number of the cases in this period was 81, with the highest number of cases in 1997 and 2002. Twelwe victims were part of six double suicides, where one grenade was used to commit suicide to both victims. The results highlighted male predominance of the victims, sober state, the use of military hand grenades (M75 and M52 type), posttraumatic stress disorder due to participation in military clashes as the main risk factor, and countryside as the place of suicide.

Trihexyphenidyl (THP) is an anticholinergic agent with forensic toxicological interest. We present a case of a 59-year-old woman with a history of paranoid disorder, who was found dead in the house where she lived alone. The autopsy findings revealed no marked pathological changes. Toxicological analysis based on gas chromatography-mass spectrometry (GC-MS) analysis revealed THP and its major metabolite (hydroxy-THP) in blood and urine, with THP concentrations of 0.053 and 0.560 mg/L, respectively. The blood and urine ethanol concentrations were low 0.096 and 0.100 g/L, respectively. Based on these results, we determined the cause of death to be THP poisoning. It is suggested that rare case of death associated with THP overdosage should be taken in conjunction with central nervous system depressants (benzodiazepines, ethanol) and/or with other pathological disorders. Thus, our case could not be supportive for this allegation.

Complex suicides (CSs) are committed by using more than one method. They account for 1.5-5% of all suicides. We present a case of CSs of a 44-year-old man, found dead in the vicinity of his car, in a deserted frozen field. Police investigation excluded homicide, and no medical data confirmed mental illnesses. Autopsy revealed wrist cuts, neck cuts, acid burns in the GI tract, multiple stab wounds to the head by a screwdriver, and several uncertain signs of hypothermia. Toxicology analysis (gas chromatography-mass spectrometry) confirmed ingestion of insecticide. We concluded that stab wounds to the head were the cause of death, while external hemorrhage and hypothermia were contributing factors. This is the first case of CSs reviewed in the literature where six suicide methods were applied. This particular case is interesting because the victim used a screwdriver as a tool for inflicting stab wounds to the head, which is a rare suicidal method.

Retrospective examination of 5-year autopsy material showed the presence of posttraumatic gastroduodenal ulcers (PGDU) in 17.7% of decedents deemed to be at risk. They were more common in males (77%) and in patients aged over 50. In the majority of cases (76%) the survival period was

In this article, we present a case of sudden death of a 17-year-old boy, in which diagnosis of Williams syndrome was firstly suspected after medicolegal autopsy, on the basis of typical macroscopical changes (facial appearance, dental status, supravalvular aortic stenosis with mild enlargement of the heart and significant thickening of the left ventricular myocardium) as well as heteroanamnestic data (slight mental retardation and nervousness). All other causes of sudden death were excluded. The definite diagnosis of this syndrome could not be corroborated as specific genetic analysis (fluorescent in situ hybridization test) could not be performed because of the lack of appropriate technical facilities.

Role of BeNzodiazepiNeS iN CaRdiaC SafeTy of low MeThadoNe doSeS iN paTieNTS duRiNg MeThadoNe MaiNTeNaNCe TReaTMeNT S. Petkovic ; V. Mijatovic ; I. Samojlik; S. Vukmirovic ; A. Dickov; and T. Popov Faculty of Medicine, University of Novi Sad, Vojvodina, Serbia; and Institute of Cardiovascular Diseases Vojvodina, Sremska Kamenica, Serbia Introduction: Despite the fact that most of health care professionals are aware of possible respiratory depressant effect of methadone and benzodiazepines coadministration, recently published data reveal that ventricular arrhythmia and cardiac arrest are currently the most frequent adverse event attributed to methadone and benzodiazepine comedication. The aim of this study is to assess cardiac safety of low methadone doses used concomitantely with benzodiazepines in opiate addicts in methadone maintenance treatment (MMT). Material and Methods: A clinical trial in which participated 30 opiate addicts at the start of MMT was performed. ECG (to calculate corrected QT (QTc) interval) and blood sampling (to determine methadone and diazepam concentrations ) were performed in all study participants at 3 time points (before the introduction of MMT, after 1 and 6 mo of MMT). Methadone and diazepam concentrations in serum were determined by using liquid chromatography-mass spectrometry (LC-MS). Results: The length of QTc interval before the introduction of MMT was 411.87 ± 27.22 ms, after 1 month of MMT 425.20 ± 17.71 ms and after 6 months of MMT 423.50 ± 14.72 ms. The mean methadone concentration at observed time points was 176.77 ± 118.56 ng/ mL and 342.86 ± 181.54 ng/mL, respectively, while the mean diazepam concentration was 560.74 ± 436.72 ng/mL and 1045.32 ± 932.72 ng/mL, respectively. There was a statistically significant increase in the length of QTc interval after 1 and 6 months of MMT in comparison to the value before the application of MMT. A statistically significant correlation between the concentration of methadone and QTc interval length after 1 and 6 months of MMT was observed and it remained statistically significant if concentration of diazepam was included. Conclusions: Further studies could clarify the possible role of benzodiazepines in the increasing cardiotoxicity of methadone in opiate addicts in MMT. Acknowledgement: The Ministry of Education and Science of the Republic of Serbia (grant numbered 41012) supported this research work.