The impact of treatment choices on potential drug-drug interactions in hypertensive patients.

AIMS: The aim of this study was to analyse potential drug-drug interactions (pDDIs) and their potential adverse drug reactions (ADRs) among hypertensive patients. Moreover, we investigated the possibility of reducing pDDIs with different treatment choices. METHODS: This was a cross-sectional study including all outpatients with hypertension and two or more medications, treated in a university hospital in Serbia. Lexicomp Interact (Lexi-Comp, Inc., Hudson, OH) was used for identification of pDDIs and potential ADRs. Treatment choices were explored according to patient characteristics, treatment guidelines and the interacting potential of drugs. Data were analysed using descriptive analysis and multiple logistic regression. RESULTS: A total of 350 patients were included in this study, with average age (77 [36-98] years and 6.1 [2.5]) medications. The majority of patients (86.0%) had at least one clinically significant pDDI, and the average was 3.78 (3.90) (range 1-25). Suggestions for treatment change aimed mainly at eliminating drug duplications, reducing the use of thiazide diuretics, sulfonylureas, alpha-lipoic acid and pentoxifylline and increasing the use of calcium-channel blockers, when appropriate. pDDIs would have decreased to 2.10 (2.52), P <.001, yet male gender, ≥6 medications, cardiovascular diseases, diabetes, benign prostatic hyperplasia, would be predictive of two or more pDDIs. The main potential adverse outcomes of pDDIs were hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis. CONCLUSION: Careful choice of drugs can reduce but not eliminate pDDIs and their potential ADRs in hypertensive patients. Close monitoring for hypotension, renal failure, hypoglycaemia, bradycardia and lactic acidosis is necessary.

Potentially Inappropriate Prescribing and Potential Clinically Significant Drug-Drug Interactions in Older Outpatients: Is There Any Association?

Background and Objectives: The purpose of the study was to determine the prevalence rate of potentially inappropriate prescribing (PIP), by using the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP) criteria in older outpatients, and its association with potential clinically significant drug-drug interactions (csDDIs). Materials and Methods: A cross-sectional study included 248 outpatients ≥65 years old divided into two groups depending on the presence of csDDIs. For estimating the clinical significance of csDDIs we used Medscape's "Drug Interaction Checker". We applied the thirty PIP indicators from the STOPP criteria. Results: The presence of PIP (25.00%; all patients) was significantly higher in the group with potential csDDIs compared to the other group (43 vs. 19, respectively; Chi-square test, χ2 = 9.947; p < 0.01). The most common PIP included the inappropriate use of proton pump inhibitors, long acting benzodiazepines, usage of thiazide diuretic in patients with gout, and duplication of therapeutic class. Patients with potential csDDIs had 43 potentially inappropriate medications (PIMs) prescribed. Out of this number, 12 (27.91%) PIMs were identified to participate in potential csDDIs. There was a correlation between the number of medications prescribed and the number of PIMs (ρ = 0.297; p < 0.01) and between the number of PIPs and the number of potential csDDIs (ρ = 0.170; p < 0.01). Conclusions: Older outpatients with potential csDDIs in relation to those with no potential csDDIs had significantly more prescribed drugs in total as well as inappropriate drugs. Almost 30% of these PIMs were included in potential csDDIs.

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats.

Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals' whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales-hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.

Antioxidative and anti-inflammatory activities of Erica spiculifolia extracts and fractions.

There is little data on the phytochemical/pharmacological properties of Erica spiculifolia Salisb. (syn. Bruckentalia spiculifolia (Salisb.) Rchb.). This study examines the antioxidative and anti-inflammatory activities of different extracts and fractions of E. spiculifolia in vitro on isolated rat peritoneal macrophages, in the carrageenan-induced rat paw oedema test, BSA test, and two complementary antioxidant assays. Ethanolic extracts of leaves, flowers, and aboveground parts, and petroleum ether, ether, ethyl acetate, and water fractionations of the ethanol extract of E. spiculifolia applied at doses of 50-200 mg/kg p.o. exhibited dose-dependent anti-inflammatory activity comparable with indomethacin. All tested samples, except for the petroleum ether fraction, exerted excellent in vitro antioxidant activity, and all of them exhibited significant and similar inhibition of BSA denaturation comparable with diclofenac. Ethanolic extract of the aboveground parts obtained by percolation, ethyl acetate and water fractions had the highest efficiency, attenuating inflammation by more than 50% in the lowest applied concentration alongside exceptional radical scavenging activity.

Anti-inflammatory, gastroprotective, and cytotoxic effects of Sideritis scardica extracts.

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity.

Consistency between causality assessments obtained with two scales and their agreement with clinical judgments in hepatotoxicity.

PURPOSE: Reliability and usefulness of scales for causality assessment in hepatotoxicity have not been fully explored. The goal of this study was to examine consistency between causality assessments obtained with two commonly used scales and their agreement with initial clinical assessments in hepatotoxicity reported in Serbia, and to review usefulness of these scales. METHODS: We compared the two scales (CIOMS/RUCAM and NARANJO) in 80 cases reported during 1995-2009. The initial clinical assessments performed at the time of reporting served as a control for comparison with the subsequent causality assessments. The agreement between obtained causality assessments and the initial clinical assessments were analysed by Kappa weighted (K(w)) statistical test. RESULTS: In the 80 cases, the NARANJO scale showed better agreement with the initial clinical assessments (K(w): 0.62) than the CIOMS/RUCAM scale (K(w): 0.50) with moderate mutual agreement (K(w): 0.58). Results for 69 cases reported before the start of the study showed the same. In 11 cases reported in 2009 (after the start of the study) the CIOMS/RUCAM scale showed better agreement with the initial clinical assessments (K(w): 0.80) than the NARANJO scale (K(w): 0.70) with perfect mutual agreement (K(w): 1.0). CONCLUSION: The two scales showed good similarity and the same was true when their outcomes were compared with the clinical judgments provided by the reporting physicians. Both scales may be useful in pharmacovigilance and clinical practice, but the CIOMS/RUCAM scale provides more specific data. Our results also confirmed that the quality of data and documentation influence the reliability of the method.

Effect of simvastatin on proinflammatory cytokines production during lipopolysaccharide-induced inflammation in rats.

The effect of simvastatin applied in a short-term pretreatment on proinflammatory cytokines production in acute systemic inflammation induced by endotoxin - lipopolysaccharide (LPS) in rats was investigated. Both LPS and simvastatin doses were established in separate experiments in which increasing doses of both compounds were given to obtain the LD(50) LPS and the maximally protective dose of simvastatin against LD(50) LPS. To determine the anti-inflammatory effect, simvastatin was given orally for 5 days, followed by a single intraperitoneal non-lethal dose of LPS (0.25 LD(50)). Plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were measured by enzyme-linked immunosorbent assay. The acute i.p. LD(50) LPS amounted to 22.15 mg/kg. Simvastatin of 20 mg/kg p.o. was maximally protective against LD(50) LPS, and this dose was used for studying its effects on LPS-induced cytokines production. Cytokines concentrations were significantly increased upon challenge of non-lethal dose of LPS. The peak levels of TNF-alpha and IL-1beta were significantly suppressed by simvastatin, compared to control rats only treated with dimethylsulfoxide before LPS. In contrast, simvastatin did not affect IL-6 levels at all timepoints. Simvastatin pretreatment given orally produced acute anti-inflammatory effects by inhibiting TNF-alpha and IL-1beta, but no IL-6 production.

The antiinflammatory, gastroprotective and antioxidant activities of Hieracium gymnocephalum extract.

The present study investigated the antiinflammatory, gastroprotective and antioxidant activities of a CH(2)Cl(2) extract of western Balkan endemic Hieracium gymnocephalum Griseb. ex Pant. (Compositae). The carrageenan-induced rat paw oedema test was used as an experimental model for screening the antiinflammatory activity. The extract was administrated p.o. in doses of 25, 50, 100 and 200 mg/kg to rats and its effects compared with indomethacin, used p.o. as a reference drug. The results showed that the investigated extract reduced the oedema in a concentration-dependent manner. The obtained antiinflammatory effect was 5.9%, 11.7%, 31.2% and 44.1% at doses of 25, 50, 100 and 200 mg/kg, respectively, being statistically significant at a dose of 100 mg/kg. Indomethacin had a strong antiinflammatory effect of 73.4% at a dose of 8 mg/kg, but caused large gastric lesions. When the plant extract in the highest tested dose (200 mg/kg) was concomitantly given with indomethacin, the antiinflammatory effect was slightly enhanced, but the gastric lesions were significantly reduced. The antioxidant activity of the H. gymnocephalum extract, investigated using DPPH radical assay, OH-radical assay and TBA-test, was not substantial.

Docking studies and anti-inflammatory activity of beta-hydroxy-beta-arylpropanoic acids.

The article describes a two-step synthesis of diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylyl)butanoic acids. In the first step an intermediate alpha-bromo propanoic acid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatsky reaction in presence of Zn in tetrahydrofuran (THF) at -5 to 10 degrees C between the previously synthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied beta-hydroxy-beta-arylpropanoic acids has already been reported. These beta-hydroxy-beta-arylpropanoic acids belong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDs such as ibuprofen. The anti-inflammatory activity and gastric tolerability of the synthesized compounds were evaluated. Molecular docking experiments were carried out to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl-alkanoic acids class. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration and that the compounds 2-(9-(9-hydroxy-fluorenyl))-2-methylpropanoic acid (5) and 3-hydroxy-3,3-diphenyl-propanoic acid (3) possess the strongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID,and that none of tested substances or ibuprofen produced any significant gastric lesions.

Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats.

Polyhydroxylated fullerenes, named fullerenols (C(60)(OH)(n); n=12-26) are excellent antioxidants. Harmful effects of ionizing radiation on living organism are mainly mediated by free radical species and fullerenols attract an attention as a potential radioprotectors. Our preliminary investigations on mice and rats subjected to radiation injury show that fullerenol C(60)(OH)(24) provides high survival rate of irradiated small rodents. Radioprotective effect was comparable to that of the standard radioprotector amifostine. The aim of this study was to compare the efficacy of fullerenol C(60)(OH)(24) (10 and 100mg/kg i.p.) and amifostine (300 mg/kg i.p.) in protection of rats against harmful effects of ionizing radiation. The animals were whole-body irradiated by X-rays (8 MV). Both compounds were given 30 min before irradiation. In order to evaluate the general radioprotective efficacy of fullerenol and amifostine rats were irradiated with an absolutely lethal dose of X-rays (8 Gy) and their survival and body mass gain were monitored during the period of 30 days after irradiation. The aim of the second part of the study is to investigate the tissue-protective effects of tested compounds (100 mg/kg i.p. of fullerenol and 300 mg/kg i.p. of amifostine, 30 min before irradiation). It was carried out on rats irradiated with a sublethal dose of X-rays (7 Gy). Influence of ionizing radiation on hematopoesis as well as the radioprotective efficiency of the compounds given were evaluated by determining blood cell count during 28 days after irradiation. For this purpose the blood was taken from tail vein before irradiation and on the 3rd, 7th, 14th, 21st and 28th day after irradiation. In order to estimate the radioprotective effects of fullerenol and amifostine on other rat tissue, the animals were sacrificed on the 7th and 28th day after irradiation and their main organs (lung, heart, liver, kidney, small intestine and spleen) were taken for histopathological analysis. In the experiment in which the general radioprotective efficacy of fullerenol and amifostine was examined, fullerenol given in a dose of 100mg/kg produced better protection than given in a dose of 10mg/kg. This effect was comparable to that of amifostine. The results of hematological investigations showed that fullerenol better than amifostine prevented radiation-induced reduction in the white cell count (granulocytes and lymphocytes), particularly in the first 7 days after irradiation. Pathohistology examinations revealed better radioprotective effects of fullerenol compared to those of amifostine on the spleen, small intestine and lung, while amifostine had better radioprotective effects than fullerenol in protection of the heart, liver and kidney. These results confirm satisfactory radioprotective efficacy of fullerenol and encourage further investigations as a potential radioprotector.

Antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities of Carlina acanthifolia root essential oil.

The root of Carlina acanthifolia All. (Asteraceae) has been traditionally used in the treatment of various disorders including stomach and skin diseases. We studied antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities of Carlina acanthifolia root essential oil, in order to validate some of the ethnopharmacological claims. Antimicrobial activity was tested on 15 bacteria and three strains of fungi using the agar diffusion and broth microdilution methods. In assessing anti-inflammatory activity the carrageenan-induced rat paw oedema test was used, while ethanol-induced stress gastric ulcer test in rats was used in testing anti-ulcer activity. Antioxidant properties were evaluated trough the effect of the essential oil on lipid peroxidation (TBA assay) and its capability of quenching 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radicals. The oil expressed significant antimicrobial activity, being the most active against Gram (+) bacteria: Streptococcus pyogenes, Enterococcus faecalis, Bacillus subtilis and against Candida albicans. In all applied concentrations, Carlina acanthifolia root essential oil reduced carrageenan-induced rat paw oedema in dose-dependent manner, achieving high degree of anti-inflammatory activity. The effect was comparable with that of indomethacin used as a reference drug. In the ethanol-induced stress gastric ulcer test in rats, it was shown that the tested essential oil produced significant dose-dependent gastroprotective activity. The results also pointed out substantial and dose-dependent antioxidant activity of the investigated essential oil, with carlina oxide as the main antioxidant component.

Naloxone Antagonizes Soman-induced Central Respiratory Depression in Rats.

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

The First Mediterranean Seminar on Science Writing, Editing and Publishing, Sarajevo, December 2-3, 2016.

The First Mediterranean Seminar on Science Writing, Editing & Publishing (SWEP 2016) was held in Sarajevo, Bosnia & Herzegovina from 2nd to 3rd December 2016. It was organized by Academy of Medical Sciences of Bosnia and Herzegovina, running concurrent sessions as part of its Annual Meeting titled " "Days of AMNuBiH - Theory and Practice in Science Communication and Scientometrics". Hotel Bosnia in the city centre was the chosen venue. On the first day, nineteen presentations on various issues of science writing and publication ethics were delivered by speakers from Croatia, Serbia, Macedonia, Albania, Bosnia & Herzegovina and the UK (Asim Kurjak, Milivoj Boranic, Doncho Donev, Osman Sinanovic, Miro Jakovljevic, Enver Zerem, Dejan Milosevic, Silva Dobric, Srecko Gajovic, Izet Masic, Armen Yuri Gasparyan, Sekib Sokolovic, Nermin Salkic, Selma Uzunovic, Admir Kurtcehajic, Edin Begic and Floreta Kurti). Each presentation had a take-home message for novice and seasoned authors, encountering numerous problems in non-Anglophone research environment. Lecturers, who were internationally recognized editors of regional journals, generously shared their experience of adhering to the best ethical guidance. Elegant presentations by Srecko Gajovic (Editor-in-Chief of the Croatian Medical Journal) and Armen Yuri Gasparyan (past Chief Editor of the European Science Editing) showcased their accomplishments that strengthened ties between authors from all over the world. Gasparyan reflected on educational resources of editorial associations, such as the International Committee of Medical Journal Editors (ICMJE) and the Committee on Publication Ethics (COPE), and called not just to declare the adherence to, but also to enforce their ethical guidance in daily practice. Editors of Medical Archives, Croatian Medica Journal, Vojnosanitetski Pregled, Psychiatria Danubina, Acta Informatica Medica, Materia Socio-Medica, The Donald School Journal of Ultrasound in Obstretics and Gynecology, Acta Medica Saliniana and Medicinski Glasnik presented their editorial strategies aimed at attracting best authors and resolving problems with authorship, conflicts of interest, and plagiarism. Topical education on science writing and editing was considered as an inseparable part of continuing professional development in biomedicine. Armen Yuri Gasparyan (UK) was offered an opportunity to interact with more than 70 participants, attending the SWEP 2016 on the second day. The lecturer talked about author contributions, disclosures of conflicts of interests, plagiarism of ideas and words, research performance and impact indicators, and targeting ethical journals. Topics were presented in a way to help non-Anglophone authors, reviewers and editors avoid common ethical problems. Dr Gasparyan stressed the importance of regularly arranging such meetings across Balkan and Mediterranean countries to eradicate plagiarism and other forms research misconduct. The organizers of the SWEP 2016 awarded selected keynote speakers with certificates of lifetime achievement in journal editing, and decided to run the Seminar annually with support of Balkan and Mediterranean editors and publishers. The SWEP 2016 marked a turning point in the process of regional developments since all attending editors opted for nurturing enthusiasm of the organizers and launching the Mediterranean Association of Science Editors and Publishers (MASEP). The Seminar was a great success with its impressive scientific and social activities. It attracted more than 100 students, researchers, editors, and publishers from Bosnia & Herzegovina and neighbouring countries. Proceedings, in the form of short reports, were published in Acta Informatica Medica and archived in PubMed Central. New friendships were forged between regional experts in editing and young specialists during those unforgettable two days of intensive discussions and informal interactions (a-y).

The radioprotective activities of turpentine-induced inflammation and alpha2-macroglobulin: the effect of dexamethasone on the radioprotective efficacy of the inflammation.

This work was aimed at the radioprotective efficacy of turpentine oil (TO), alpha2-Macroglobulin (alpha2-M), Amifostine (Ami) and/or dexamethasone (Dex). These agents were administrated, alone or in combination, prior to irradiation of rats with 6.7 Gy (LD(50/30)). The survival was recorded daily for 4 weeks after irradiation and body weight, peripheral leukocytes and thrombocytes were measured. The plasma concentration of alpha2-M and other acute phase proteins were determined by crossed immunoelectrophoresis. All rats receiving alpha2-M and Ami alone or in combination survived the radiation injury, whereas the rate of survival of TO-treated rats was 90%. Radiation and therapy-induced changes in the expression of acute phase protein genes were atypical for the acute phase reaction. Dex alone was lethal for 45% and 55% of control and irradiated rats, respectively. Pretreatment with 1mg Dex reduced radioprotective efficacy of TO and Ami to 30% and 40%, respectively. Given together TO and Ami provided 70% protection to rats receiving Dex. The TO and alpha2-M enhanced the rate of survival from 50% to 90% and 100%, respectively. In the presence of 1mg Dex the TO-induced radioprotectors and Ami exhibited radiosensitizing rather than radioprotecting activities.

Evaluation of Tanacetum larvatum for an anti-inflammatory activity and for the protection against indomethacin-induced ulcerogenesis in rats.

Oral administration of the chloroform extract from Tanacetum larvatum (Griseb. ex Pant.) Kanitz caused a dose-dependent anti-inflammatory effect in the carrageenan-induced rat paw oedema test. The obtained anti-inflammatory effect was 8.6, 32.8, 37.0 and 49.5% for the extract doses of 25, 50, 100 and 200mg/kg, respectively, being statistically significant at a dose of 50mg/kg. Indomethacin had a strong anti-inflammatory effect of 73.4% at a dose of 8mg/kg, but large gastric lesions were detected. When the plant extract in the highest tested dose (200mg/kg) was concomitantly given with indomethacin, the anti-inflammatory effect was slightly enhanced, but the gastric lesions were significantly reduced. The anti-inflammatory and anti-ulcer activity may be mainly due to the inhibition of DNA binding of the transcription factor NF-kappaB by components of the plant extract. This was proven in an electrophoretic mobility shift assay at a concentration of 50microg/ml. Due to its anti-inflammatory as well as anti-ulcer effects, Tanacetum larvatum should especially be used combined with those drugs that are known both for their strong anti-inflammatory activities and the ulcerogenic side effects such as NSAIDs.

Maternal and fetal cadmium and selenium status in normotensive and hypertensive pregnancy.

Cadmium and selenium concentrations in maternal and umbilical cord blood and amniotic fluid were determined in 37 normotensive and 23 hypertensive women during the last trimester of pregnancy in relation to their smoking status. Thiocyanate concentration in plasma was used as the index of smoking status. Cadmium and selenium were determined with atomic absorption spectrometry (graphite furnace and mercury hydride system). In the group of normotensive and hypertensive women, significantly higher cadmium and lower selenium concentrations in blood in smokers were observed than in nonsmokers. Umbilical cord blood selenium concentrations in both normotensive and hypertensive smokers were significantly lower than in nonsmokers as well. In the group of normotensive women, significant differences in selenium concentrations in amniotic fluid were observed between smokers and non-smokers. In conclusion, the results of this study show that hypertension in pregnant women smokers is related to significantly higher blood cadmium concentrations, which indicates that cadmium may be considered as an independent factor involved in hypertension.

Factors influencing antibiotic treatment cost and outcome in critically ill patients: a "real-life" study.

UNLABELLED: BACKGROUND/AIM. Critically ill patients are at very high risk of developing severe infections in intensive care units (ICUs). Procalcitonin (PCT) levels are eleveted in the circulation in patients with bacterial sepsis and PCT might be useful in guiding antibiotic treatment. The aim of this study was to estimate factors influencing patients survival and treatment cost in ICU with special emphasis on the impact of PCT serum levels use in guiding antimicrobial therapy. METHODS: The study was conducted from August 2010 to May 2012 in the Intensive Therapy Unit, Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy (MMA), Belgrade, Serbia. All adult critically ill patients with sepsis and/or trauma admitted in the ICU were included in the study. This study included only the cost of antimicrobial therapy in the ICU and the cost for PCT analysis. We used prices valid in the MMA for the year 2012. PCT in serum was measured by homogeneous immunoassay on a Brahms Kryptor analyzer. RESULTS: A total of 102 patients were enrolled. The mean patients age was 55 ± 19 years and 61.8% of patients were male. The mean length of stay (LOS) in the ICU was 12 ± 21 days. There was a statistically significant difference (p < 0.001) between the sepsis and trauma group regarding outcome (higher mortality rate was in the sepsis group, particularly in the patients with peritonitis who were mostly women). The patients younger than 70 years had better chance of survival. LOS, the use of carbapenems and PCT-measurement influenced the cost of therapy in the ICU. CONCLUSIONS: The obtained results show that age, the diagnosis and gender were the main predictors of survival of critically ill patients in the ICU. The cost of ICU stay was dependent on LOS, use of carbapenems and PCT-measurement although the influence of these three factors on the outcome in the patients did not reach a statistical significance.

Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats.

BACKGROUND/AIM: Amifostine (AMI) is a broad-spectrum cytoprotector which protects against variety of radio- and chemotherapy-related toxicities without decreasing their antitumor action. The aim of the study was to investigate the potential protective effects of AMI against acute cardiotoxic effects of doxorubicin (DOX) in male Wistar rats. METHODS: AMI (300 mg/kg ip) was given 30 min before DOX (6 mg/kg and 10mg/kg b.w., iv). The evaluation of DOX-induced cardiotoxic effects, as well as cardioprotective efficacy of AMI was performed 48 h after their administration by determining serum activities of enzymes known to be markers of cardiac damage (creatine kinase - CK, aspartate aminotransferase - AST, lactate dehydrogenase - LDH, and its isoenzyme alpha-hydroxybutirate dehydrogenase - alpha - HBDH), as well as the histopathological and ultrastructural analysis of the heart tissue. RESULTS: AMI successfully prevented a significant increase in serum activity of CK, AST, LDH and alpha-HBDH in animals treated with DOX in the dose of 6 mg/kg (121.14 +/- 18.37 vs 167.70 +/- 44.24; 771.42 +/- 161.99 vs 1057.00 +/- 300.00; 3230.00 +/- 1031.73 vs 4243.10 +/- 904.06; 202.57 +/- 42.46 vs 294.90 +/- 80.20 UI/l, respectively), and ameliorated DOX-induced structural damage of the rat myocardium. Pretreatment with AMI in rats given 10 mg/kg DOX reduced the cardiac damage score (CDS) from 2.62 +/- 0.51 to 1.62 +/- 0.51, i.e. to the CDS value obtained with the lower dose of DOX (6 mg/kg). The ultrastructural analysis of the rat myocardium showed that AMI successfully protected the sarcolemma of cardiomyocytes and reduced mitochondria damage induced by DOX given in the dose of 6 mg/kg. Besides, capillaries were less morphologically changed and apoptosis of endothelial cells was extremely rare in AMI-protected animals. AMI itself did not cause any prominent changes in the examined parameters in comparison with the control rats. CONCLUSION: AMI provided a significant protection against DOX-induced acute cardiotoxic effects in rats. This finding implies its potential to be a successful cardioprotector in patients treated with DOX due to malignant diseases.

[In vitro study of vitamins B1, B2 and B6 adsorption on zeolite].

BACKGROUND/AIM: Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the characteristics of the process (saturability, reversibility and competitiveness). METHODS: The specific and sensitive HPLC method with fluorescent detector was used for determination of vitamins B1, B2 and B6. Analyte separation and detection were carried out by applying the reverse-phase method on column C18. An in vitro experiment was done by testing the influence of pH value (2 and 7), concentration of vitamin solution (1, 2 and 5 mg/L), the length of contact with zeolite (10-180 min) and cation competitiveness on the exchange capacity, which is achieved by media and zeolite contact, as well as a possible vitamins desorption through changing pH value of the solution at 37 degrees C. Jon competitiveness was examined by adding commercial feed mixture (grower) with a defined content of the examined vitamins in zeolite solutions the pH = 2 and pH = 7. RESULTS: Vitamins B1, B2 and B6 were stable in both pH=2 and pH = 7 solutions at 37 degrees C, in the defined time intervals. In acid solution concentrations of vitamins significantly declined in the first 10 min, with no significant decline in further 30 min for all the three concentrations tests. In neutral solution, after the addition of 1% zeolite, decrease in vitamins concentrations was slightly lower than in acid solution, but also significant in the first 10 min of the contact with zeolite. It was found that zeolite, which adsorbed vitamins in acid solution, transferred in the neutral one released a significant quantity of adsorbed vitamins after 30 min of extraction on 37 degrees C. Vitamins B1, B2 and B6, from a commercial feed mixture in pH = 2 solution, at 37 degrees C, were significantly adsorbed on zeolite after 30 min of the contact (21.87%, 20.15% and 4.53%, respectively), while in neutral solution there was no statistically significant adsorption. Conclusion. Zeolite significantly adsorbs vitamins B1, B2 and B6 in acid and neutral solutions at 37 degrees C, already in the first 10 min of the contact. Adsorption was irreversible, but partly reversible after changing pH from acid to neutral. This is a significant ions competition for adsorption on zeolite in neutral solution, so no statistically significant vitamins B1, B2 and B6 adsorption occurs, while in acid solution competition is less, thus zeolite significantly adsorbs these vitamins, although in less degree than in conditions with no concurrent ions.