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.

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.

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).

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.