Synthesis, Characterization, and Biological Evaluation of Tetrahydropyrimidines: Dual-Activity and Mechanism of Action.

In this paper, the synthesis, characterization, and biological evaluation of the novel tetrahydropyrimidines-THPMs are described. THPMs are well-known for wide pharmacological activities such as antimicrobial, anticancer, antiviral, etc. This research includes obtained results of in vitro antimicrobial, anticancer, and α-glucosidase inhibitory activities of the eleven novel THPMs. An antibiotic assessment was done against five bacteria (two Gram-positive and three Gram-negative) and five fungi by determining the minimal inhibitory concentration (MIC), using the broth tube dilution method. The most active antibacterial compounds were 4a, 4b, and 4d, while the best antifungal activity was shown by 4e, 4f, and 4k. The lowest MIC value (0.20 mg/mL) was measured for 4e, 4f, and 4k against the Trichophyton mentagrophytes. Moreover, examining the α-glucosidase inhibitory activity revealed the compound 4g as the one with the best activity. The cytotoxic activity was performed on the tumor cell lines (HeLa, K562, and MDA-MB-231) and normal cells (MRC-5). The best antitumor activity was shown by compounds 4b and 4k against HeLa cell lines. The influence on cell cycle and mechanism of action of the most active compounds were examined too. Compound 4b had good antibacterial and anticancer activities, while 4k showed promising antifungal and anticancer activities.

Ochratoxin A potentiates citrinin accumulation in kidney and liver of rats.

Ochratoxin A (OTA) and citrinin (CTN) are nephrotoxic mycotoxins often found together in grain. The aim of this study was to measure their accumulation in the kidney and liver of adult male Wistar rats, see how it would be affected by combined treatment, and to determine if resveratrol (RSV) would decrease their levels in these organs. The rats received 125 or 250 mg/kg bw of OTA by gavage every day for 21 days and/or 20 mg/kg bw of CTN a day for two days. Two groups of rats treated with OTA+CTN were also receiving 20 mg/kg bw of RSV a day for 21 days. In animals receiving OTA alone, its accumulation in both organs was dose-dependent. OTA+CTN treatment resulted in lower OTA but higher CTN accumulation in both organs at both OTA doses. RSV treatment increased OTA levels in the kidney and liver and decreased CTN levels in the kidney. Our findings point to the competition between CTN and OTA for organic anion transporters 1 and 3.

Summer Season-Related Heat Stress Affects the Mineral Composition of Holstein Dams' Colostrum, and Neonatal Calves' Mineral Status and Hematological Profile.

This study examines the effect of season-related heat stress in dams on mineral status, and hematological profile of their calves. Ten Holstein dams (LowT group) were exposed to the 49-day-long period of low air temperature (5.2 ± 0.5 °C) and ten dams (HighT group) were exposed to a 53-day-long high air temperature (27.4 ± 0.4 °C). The dams' blood samples were taken one hour after parturition, while colostrum was sampled at 2, 14, and 26 h after calving. Ca, P, Mg, Na, K, Fe, Zn, Mn, and Se concentrations were significantly lower while Cu and Co concentrations were significantly higher at least in two examined colostrum sampling points in HighT group. Calf`s blood samples were taken before 1st colostrum intake, and on days 1, 2, 3, and 7 postnatal. Ca, P, Na, K, Fe, Cu, Zn, Mn, Se, and Co were significantly lower while concentration of Mg was significantly higher in calves that originated from HighT group at least at two examined sampling points. Season affected dam's blood mineral status but the pattern was not always the same as in calves, since Na, K, Cu, and Co were significantly higher in HighT group. Calves that originated from HighT group had significantly lower hemoglobin, hematocrit, MCV, MCH, and MPV values, as well as neutrophils and monocyte counts, while platelets, eosinophils, basophils, and lymphocyte counts were significantly higher. Season-related heat stress leads to a reduction of the most minerals in both dams' colostrum and calves' blood and certain minerals' deficiencies are linked to impaired calves' hematological adaptation.

The effects of selective serotonin reuptake inhibitors on male and female fertility: a brief literature review.

Objective: The aim of this review was to determine whether selective serotonin reuptake inhibitors (SSRIs) affect the ability to conceive in men and women of reproductive age, as well as to find out whether there are certain differencies between them in terms of effects on fertility. Methods: Our review was based on systematic search of literature in four online databases: Medline (PubMed), Scopus, Web of Science and SCIndex (Serbian Citation Index). Results: Several clinical studies reported that SSRIs can decrease the number and viability of sperm, and cause a disruption of their morphological structure. Regarding the effect of these antidepressants on female fertility, some experimental findings suggest that paroxetine and escitalopram may have a negative effect on the ability to conceive due to their stimulatory effect on fallopian tube motility. However, several observational studies favor the use of SSRIs in women with depression/anxiety undergoing in vitro fertilization (IVF) given their efficiency in suppressing these unpleasant symptoms without a relevant negative impact on IVF outcomes. Conclusions: SSRIs should be avoided male patients of reproductive age who wish to conceive, while the use of these antidepressants seems to be justified in women with depression or anxiety who have undergone IVF.Key pointsSSRIs could cause dose and duration-dependent reversible adverse effects on male fertility parameters.In depressed or anxious male patients of reproductive age who wish to conceive mirtazapine or bupropion should be used because of their lower potential to cause sexual side effects.The results of certain experimental studies indicate that paroxetine and escitalopram may have a negative effect on the fertility of female patients.The use of SSRIs in women with depression or anxiety who have undergone IVF seems to be justified, because these psychiatric disorders reduce the likelihood of becoming pregnant.

Efficacy of a Modified Clinoptilolite Based Adsorbent in Reducing Detrimental Effects of Ochratoxin A in Laying Hens.

BACKGROUND: The objective of this study was to evaluate the efficacy of modified clinoptilolite (Minazel Plus®, MZ) as a mycotoxin adsorbent for preventing the negative the effects of ochratoxin A (OTA) on performance, pathohistological changes, and OTA residue in the eggs of laying hens. METHODS: Forty eight (n = 48) laying hens (27 weeks old) were equally divided into six groups and depending on the type of addition were allocated to the following experimental treatments for 7 weeks: E-I group-1 mg/kg OTA; E-II group 0.25 mg/kg OTA; E-III group 1 mg/kg OTA + 0.2% of MZ; E-IV group 0.25 mg/kg OTA + 0.2% of MZ; MZ group supplemented with 0.2% of the adsorbent; and control (K, without feed additive). RESULTS: Overall, the addition of 0.2% MZ to laying hen feed mitigated the harmful effects of OTA on target organs and reduced the presence of OTA residue in eggs. The groups that received 0.2% of MZ achieved better production results in terms of body weight, number of eggs, and feed consumption, compared to the other treatments. CONCLUSIONS: The current findings confirm the efficacy of MZ in preventing performance losses in laying hens exposed to OTA, as well as for improving the welfare and health of food producing animals.

Risk factors for potential drug-drug interactions in patients with myasthenia gravis.

OBJECTIVES: Our aim was to determine risk factors for and frequency of potential drug-drug interactions (pDDIs) among hospitalized patients with myasthenia gravis (MG). METHODS: This was a retrospective cross-sectional study of the-first time hospitalized MG patients or patients hospitalized because of the exacerbation of MG at the Neurology Clinic of the Clinical Center of Serbia, Belgrade. Medical records and discharge summaries of hospitalized MG patients over a 10-year period were reviewed. The pDDIs were identified by means of Micromedex, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. RESULTS: The study included 687 patients with MG. In total, 2041 pDDIs were detected in 608 (88.5%) patients. Among the discovered pDDIs, 329 different pDDIs were observed. The most frequent pDDIs were pyridostigmine-prednisone (487patients/70.9%) and aspirin-prednisone (90 patients/13.1%) classified as moderate, and enalapril-potassium chloride (71patients/10.3%) classified as major pDDI. Five drugs (aspirin, insulin, prednisone, cyclosporine, metformin) were responsible for 22.6% of different pDDIs. Dyspnea, generalized form of MG, diabetes mellitus, hypertension, total number of drugs-used, use of antiplatelets were identified as the relevant risk factors for total number of pDDIs (R2 = 0.626,F = 73.797, p < 0.001), while age of patients and history of cancer were inversely correlated with such an outcome. CONCLUSION: The frequency of the pDDIs in hospitalized MG patients is high, and adversely influenced by dyspnea, generalized MG, diabetes mellitus, hypertension, total number of drugs-used and use of antiplatelets.

Trace elements in different tissues in aging rats.

BACKGROUND: Trace elements (TE) in the human body provide a connecting link between the environment, lifestyle and biochemical modulation of homeodynamics. On the other hand, many non-essential (toxic) elements are linked to numerous diseases. Our study tried to identify differences in TE levels between healthy old and young Wistar rats in blood and the tissues of kidney, liver, heart, and testicles. Furthermore, we wanted to see if there were age-related differences in correlations between essential and/or non-essential (toxic) TE within and between mentioned tissues. METHODS: We used 28 healthy male Wistar rats which were divided into two age groups: young, aged 10 weeks (n = 15) and old, aged 36 months (n = 13). The animals were sacrificed under general anesthesia and the blood samples, and samples from the tissues of the heart, kidneys, testicles, and liver were used for the determination of TE content in them. Analysis of the 16 elements was performed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Toxic elements in old rats (As, Hg, and Cd) were significantly higher in all of the tissues where the difference in levels of these elements was found. Tissues of the kidney and liver had the most correlations between TE in old and young rats, respectively. In both old and young rats, arsenic was the toxic element that had most of the correlations with other essential or non-essential elements. In old rats, most of the TE correlations were detected between the tissues of the kidney and heart (11 correlations), while in young rats most of the correlations were observed between the tissues of kidney and liver, and kidney and testicles (with 9 correlations both). CONCLUSIONS: Our study has found significant changes in levels of trace elements in all of the mentioned tissues, with kidney and testicles being the tissues with the most TE differences between the two aged groups. This and other similar studies should encourage other investigators to evaluate the mutual connections between TE and physiological, or the "unhealthy" aging. More studies with more tissues included, more biomarkers of the systemic function, and even molecular methods are needed to provide the answers to numerous questions relating to TE and aging.

Presence of natural radionuclides and toxic elements in monocalcium phosphate, complete feed and pig manure.

Naturally occurring radionuclides and toxic elements are ubiquitous in the environment and can pose a great risk to animals' health. Control of these toxic substances in animal diet is essential for animal's welfare, human nutrition risk management as well as environmental protection. Our study addresses these issues by determining a content of natural radionuclides (40K, 238U and 226Ra), and toxic elements (Cd, Cr, As) in total of 108 samples: 36 monocalcium phosphate, 36 complete feed and 36 pig manure samples that were collected from 6 different commercial farms in the Republic of Serbia. In monocalcium phosphate the content of 40K, 238U and 226Ra ranged from 7.6-23.4 Bq kg-1, 13.2-1778 Bq kg-1 and 3.6-13.5 Bq kg-1, respectively. In complete feed samples, 40K ranged from 170 to 306 Bq kg-1, 238U from minimum detectable activity (MDA) to 9.1 Bq kg-1, and 226Ra from MDA-5.5 Bq kg-1, while in pig manure 40K ranged from 146 to 531 Bq kg-1, 238U from MDA-30.1 Bq kg-1, and 226Ra from MDA-10 Bq kg-1. The concentrations of Cd, Cr and As in monocalcium phosphate were 0.26-14.9 mg kg-1, 10.3-497 mg kg-1, and 4.2-5.5 mg kg-1, respectively. In complete feed, the content of Cd, Cr and As ranged from minimum detectable concentration (MDC) - 0.78 mg kg-1, 0.30-7.41 mg kg-1, and 0.09-0.31 mg kg-1, respectively. In pig manure Cd, Cr and As ranged from 0.8-2.3 mg kg-1, 2.3-22.2 mg kg-1, and 0.51-5.45 mg kg-1, respectively. The obtained results showed that Cd concentration in monocalcium phosphate exceeded the maximum permissible legislative concentrations for phosphate additives. Monocalcium phosphate is the main source of 238U and Cr in complete feed, while Cd derives from other sources. For that reason excessive use of monocalcium phosphate can lead to high levels of these pollutants in complete feed and consequently in manure.

Colorectal cancer and trace elements alteration.

BACKGROUND: Trace elements have important influence on body function primarily because of the vital role they have in many physiological processes. Their alterations have been found in many disorders, including cancer. It has been well known for decades that disturbances in elemental concentration may lead to cell damaging, DNA injuries and imbalance in oxidative burden. Our study tried to determine the difference of trace elements concentrations between colorectal adenocarcinoma and adjacent healthy intestinal tissue. METHODS: 59 subjects participated in this study. Healthy colon mucosa samples and colon tumor tissue samples were obtained from patients previously diagnosed with colon carcinoma by standard diagnostic procedures. Analysis of the elements was performed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The results showed that Na, K, Mg, Ca, Cu, Zn, Se, Mn, Cd, Cr and Hg significantly differ between malignant tissue of colorectal cancer (CRC) and adjacent healthy bowel tissue. We have, also, found that Cu/Zn tissue ratio was significantly higher in CRC compared to a healthy tissue and that patients with higher CRC stages had also significantly higher ratio. CONCLUSIONS: Since this is the first such study in Balkan region, we assume that results of our study could be a good indicator of elemental alterations in colorectal cancer of Balkan population, due to similarity in lifestyle, dietary intake, pollution and exposure to toxic elements.

Cost-utility of tafenoquine vs. primaquine for the radical cure (prevention of relapse) of Plasmodium vivax malaria.

The aim of this study was to compare cost-utility of tafenoquine (TQ) and primaquine (PQ) for a radical cure (prevention of relapse) of Plasmodium vivax (PV) malaria in Serbia using A five-state, 1-month cycle Markov model. The perspective of Republic Health Insurance Fund was chosen, and the time horizon was 10 years. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients. After base case analysis PQ was dominated by TQ, as the net monetary benefit was positive (20,713.84 ± 7,167.46 RSD (99% CI) (174.95 ± 60.54 €)) and incremental cost-effectiveness ratio was below the willingness-to-pay line of 1 Serbian gross national product per capita per quality-adjusted life year gained. Multiple one-way sensitivity analysis and probabilistic sensitivity analysis confirmed the results of the base case simulation. In conclusion, TQ was cost-effective in comparison to PQ for radical cure of PV malaria in socio-economic settings of a South-Eastern European country.

Contemporary surgical management of drug-resistant focal epilepsy.

Introduction: Seizures, which could not be controlled by drug therapy, have profound negative influence on the quality of life of the affected person. If with clear locus of origin and accompanied by loss of consciousness, drug-resistant epilepsy could be treated by surgery.Areas covered: The aim of this article was to review current status of epilepsy surgery through description of the most important operative methods and narrative comparison of their benefits and harms. In total 1154 articles were retrieved from MEDLINE, SCOPUS, EBSCO, and SCINDEKS databases, and 78 included in the review. The review included systematic reviews, meta-analyses, clinical trials, observational studies on humans, case series, and case reports.Expert opinion: Sophisticated diagnostic methods nowadays offer much more precise localization of epileptogenic focus and detailed planning of a surgical procedure which will make minimal damage of neural pathways and structures essential for movements, speech, cognition, and emotions. Advent of perioperative care, and improved diagnostics and surgical techniques resulted with significant drop in rates of postoperative complications, long-term neurological deficit, and mortality in the last decade, while seizure freedom rate and quality of life increased.

Clinical Pharmacokinetics of Second-Generation Triazoles for the Treatment of Invasive Aspergillosis and Candidiasis.

Second-generation triazoles were developed in response to the quest for more efficacious and safer therapeutic options for the treatment of severe systemic aspergillosis and candidiasis. These agents include voriconazole, posaconazole, isavuconazole, and ravuconazole. The aim of this review was to present and compare the pharmacokinetic characteristics of second-generation triazoles for the treatment of invasive aspergillosis and candidiasis, emphasizing their clinical implications. The MEDLINE, Scopus, EBSCO, Google Scholar, and SCIndeks databases were searched using advanced search options, including the names of second-generation triazoles and pharmacokinetic terms as keywords. The intravenous administration of voriconazole, posaconazole, and isavuconazole results in stable pharmacokinetics of these drugs, with mostly predictable variations influenced by common and usually known factors in routine clinical settings. The high oral bioavailability of isavuconazole and, to some extent, voriconazole makes them suitable for intravenous-to-oral switch strategies. Except for intravenous voriconazole (due to the accumulation of the toxic vehicle hydroxypropyl betadex), dose reduction of second-generation triazoles is not needed in patients with renal failure; patients with hepatic insufficiency require dose reduction only in advanced disease stages. The introduction of therapeutic drug monitoring could aid attempts to optimize the blood concentrations of triazoles and other drugs that are known to or that possibly interact, thus increasing treatment efficacy and safety. There is a need for new studies that are designed to provide useful data on second-generation triazole pharmacokinetics, particularly in special circumstances such as central nervous system and ocular infections, infections in newborns and infants, and in subjects with genetic polymorphisms of metabolizing enzymes.

Effects of combined treatment with ochratoxin A and citrinin on oxidative damage in kidneys and liver of rats.

A multimycotoxin analysis approach in grains results in frequent simultaneous findings of nephrotoxic mycotoxins ochratoxin A (OTA) and citrinin (CTN). The mechanism of CTN and OTA toxicities in biological systems is not fully understood but it is known that oxidative stress is involved. In this study, oxidative damage of DNA, lipids, and the concentration of glutathione (GSH), as well as possible antioxidative effects of resveratrol (RSV) were studied in vivo. Male adult Wistar rats were treated orally with OTA (0.125 and 0.250 mg kg-1 b.w.), RSV (20 mg kg-1 b.w.) for 21 days, CTN (20 mg kg-1 b.w.) for two days or with their combinations. The hOGG1 modified comet assay revealed kidneys and liver oxidative DNA damage in OTA + CTN treated animals, which was not reversed by RSV. CTN did not reduce glutathione (GSH) or increase malondialdehyde (MDA) concentration in any tissue, while OTA reduced kidneys GSH and increased kidneys and liver MDA. RSV increased GSH concentrations in all tissues and decreased MDA concentration in the liver only. Oxidative stress is involved in the toxicity of OTA and CTN but it seems that it differs significantly in organs. Most of the effects on GSH and MDA in combined toxicity may be attributed to the toxic effects of OTA. RSV was effective in restoring the depleted GSH in all tissues but had no effect on the MDA concentration and DNA damage.

Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs.

INTRODUCTION: Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

Mapping differential elemental accumulation in fish tissues: assessment of metal and trace element concentrations in wels catfish (Silurus glanis) from the Danube River by ICP-MS.

Studies of metal accumulation in fish are mainly focused on the muscle tissue, while the metal accumulation patterns in other tissues have been largely neglected. Muscle is not always a good indicator of the whole fish body contamination. Elemental accumulation in many fish tissues and organs and their potential use in monitoring programs have not received proper attention. In the present study, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn concentrations were assessed by inductively coupled plasma mass spectrometry (ICP-MS) in the following 14 tissues of the wels catfish (Silurus glanis) from the Danube River: muscle, gills, spleen, liver, kidneys, intestine, gizzard, heart, brain, gallbladder, swim bladder, vertebra, operculum, and gonads. A high level of differential elemental accumulation among the studied tissues was observed. The maximum overall metal accumulation was observed in the vertebra, followed by the kidneys and liver, with the metal pollution index (MPI) values of 0.26, 0.25, and 0.24, respectively. The minimum values were observed in the gallbladder, muscle, brain, and swim bladder, with MPI values of 0.03, 0.06, 0.07, and 0.09, respectively. Average metal concentrations in the fish muscle were below the maximum allowed concentrations for human consumption. The mean As, Cd, Pb, Cu, Fe, and Zn concentrations in the muscle were 0.028, 0.001, 0.001, 0.192, 3.966, and 3.969 µg/g wet weight, respectively. We believe that the presented findings could be of interest for the scientific community and freshwater ecosystem managers. There is a need for further research that would assess less studied tissues in different fish species.

When pulmonary nodules, epistaxis and renal lesion do not add up to Wegener's granulomatosis?

Wegener's granulomatosis usually presents with clinical features of systemic vasculitis affecting lung, upper respiratory tract, kidney and even a nervous system. Yet, invasive pulmonary aspergillosis is characterised by invasion of blood vessels in the lungs, but the infection often spreads to kidneys, skin and central nervous system. We report a case of a 46-year-old male patient with no prior medical history. Clinical presentation included epistaxis, hemoptysis, hematuria and proteinuria, along with pulmonary nodular infiltrates. Differential diagnosis included invasive aspergillosis and Wegener's granulomatosis, but the diagnosis was only confirmed after autopsy. Establishing diagnosis of invasive aspergillosis remains a challenge for clinicians in acute care setting.

Risk factors for intraoperative arrhythmias in general surgery patients operated under general anesthesia: our one-year experience.

AIM: To analyze the importance of previously un-investigated (or not completely investigated) potential risk factors for new-onset intra-operative arrhythmias in general surgery patients, operated under general anesthesia. METHODS: In this case-control study the population consisted of all patients who underwent elective non-cardiovascular, non-thoracic surgery under general inhalation anesthesia during the period of 12 months in a secondary care hospital in Foca, Republic of Srpska, Bosnia and Herzegovina, and were classified according to the American Society of Anesthesiologists classification to class I or II. Cases (n=57) included patients with at least one episode of ECG-recorded arrhythmia during general anesthesia, and controls (n=90) were sex and age matched. RESULTS: Significant association was found between intra-operative arrhythmias and history of cardiac arrhythmias in the last five years (adjusted OR 43.5; CI 2.3, 820.1; p = 0.012). Synergistic effects on intra-operative arrhythmias were found for history of cardiac arrhythmias and history of abnormal ECG, as well as for history of cardiac arrhythmias and use of propofol for induction of anesthesia. CONCLUSION: The non-cardiovascular, non-thoracic surgery patients with history of arrhythmias and ECG abnormalities deserve special attention, correction of electrolyte disturbances and avoidance of propofol for induction of general anesthesia.

Non-dioxin-like PCBs in ten different fish species from the Danube river in Serbia.

This work has been developed to examine the level of non-dioxin-like (ndl) PCBs (28, 52, 101, 138, 153 and 180) in (a) ten different freshwater fish species from the Danube river, (b) two sampling points: up and downstream of the industrial zone of the city of Pancevo (ecological hot spot in Serbia) and (c) two time points i.e., in 2001 and 2006. Obtained results would serve to analyse spatial, temporal and congener profile characteristics of ndl PCBs cumulated in fish tissues due to environmental pollution. Sixty-four samples of the following species were collected: wels (Silirus glanus), pike (Esox lucius), bream (Abramis brama), crucian carp (Carassius carassius), pike pearch (Stizostedion lucioperca), barbel (Barbus barbus), tench (Tinca tinca), sterlet (Acipenser ruthenus L.), common carp (Cyprinus carpio) and bighead carp (Hypophthalmichthys nobilis). Gas chromatography coupled with electron capture detector was used for analysis of ndl PCBs. Total ndl PCBs content in upstream samples ranged from 2.7 to 98.1 ng/g and from 4.9 to 68.3 ng/g in 2001 and 2006, respectively. During the 5 years, ndl PCBs content increased significantly in downstream samples i.e., ndl PCBs varied from 13.7 to 46.1 ng/g and from 14.4 to 107.2 ng/g in 2001 and 2006, respectively. PCBs 138 and 180 were predominant congeners in 2001, while in 2006 the most abundant PCB congeners were 138 and 153. In 2006, the presence of PCB 28 and PCB 52 has indicated a recent contamination event. Data on continual monitoring of PCBs in all relevant environmental compartments together with appropriate biomonitoring data are expected to give comprehensive insight into the fate and behaviour profile of these contaminants.

WITHDRAWN: Comparison of high performance liquid chromatography and liquid chromatography/tandem mass spectrometry methods in the quantification and confirmation of ochratoxin A in pig tissue.

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Evaluation and validation of two chromatographic methods (HPLC-fluorescence and LC-MS/MS) for the determination and confirmation of ochratoxin A in pig tissues.

Two different analytical methods for the determination and confirmation of ochratoxin A (OTA) in blood serum, kidney, and liver of pigs have been compared. Sample cleanup was based on liquid-liquid phase extraction. The detection of OTA was accomplished with high-performance liquid chromatography (HPLC) combined either with fluorescence detection (FLD) or electrospray ionization (ESI+) tandem mass spectrometry (MS/MS). The comparative method of evaluation was based on the investigation of 90 samples of blood serum, kidney, and liver per animal originating from different regions of Serbia. The analytical results are discussed in view of the respective method validation data and the corresponding experimental protocols. In general, analytical data obtained with liquid chromatography (LC)-MS/MS detection offered comparable good results in the sub-ppb concentration level indicating that the electrospray tandem mass spectrometric (LC-MS/MS) method was more selective and sensitive for the analysis and confirmation of OTA in pig tissues than the HPLC method after the methylation of OTA.