All strains were susceptible to the antibiotics traditionally used to treat tularaemia, such as streptomycin (MIC(90) 1.5 mg/L), gentamicin (MIC(90) 0.25 mg/L), tetracycline (MIC(90) 0.38 mg/L) and chloramphenicol (MIC(90) 0.25 mg/L). Since fluoroquinolones showed the lowest MIC values, and have important advantages over aminoglycosides, including ease of oral administration and lower toxicities, quinolones have the potential for being effective first-line therapy for tularaemia.

AIM: The present study aimed to determine the protective effect of melatonin and agomelatine on DOX-induced cardiotoxicity in rats by electrocardiographic, scintigraphic and biochemical methods. MATERIALS AND METHODS: Forty-nine male Wistar rats were randomly separated into seven groups; control (CON), doxorubicin (DOX), melatonin (MEL), agomelatine (AGO), melatonin+doxorubicin (MEL+DOX), agomelatine+doxorubicin (AGO+DOX) and melatonin+agomelatine+doxorubicin (MEL+AGO+DOX) groups. Cardiotoxicity was induced by intraperitoneal (i.p.) injection of DOX (18 mg/kg daily for three days). Rats receiving MEL and AGO treatment in the DOX-induced cardiotoxicity group received MEL and AGO (40 mg/kg/day, i.p., for seven days). They were injected with doxorubicin (18 mg/kg, i.p.) on days 5, 6, and 7. The rats were given MEL and AGO as substance control (40 mg/kg/day, i.p., for 7 days). On day 8 of the experiment, animals were evaluated by means of electrocardiography (ECG) and 99m technetium pyrophosphate (99m Tc PYP) scintigraphy and their biochemical parameters [blood urea nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)] were examined. RESULTS: DOX-induced acute cardiotoxicity in rats is characterized by conduction abnormalities in the ECG pattern (including decreased P wave and QRS complex duration, increased QT and RR intervals, and STsegment elevation), increased serum BUN, CK, and cTnT parameters and increased 99m Tc PYP uptake (p < 0.001). Pretreatment with MEL, AGO, or MEL+AGO effectively alleviated DOX-induced ECG abnormalities close to normal (p < 0.001). Moreover, serum biochemical evidence and 99m Tc PYP uptake values demonstrated that pretreatment with MEL, AGO, or MEL+AGO has the same protective effect against the abnormalities produced in the heart by DOX (p < 0.001). CONCLUSIONS: MEL and AGO have a potential protective effect on DOX-induced cardiotoxicity. At the same time, this study suggests that 99m Tc PYP is a non-invasive method suitable for early determination of DOX-induced cardiotoxicity (Tab. 3, Fig. 5, Ref. 41).

BackgroundImproper use of antimicrobials can cause adverse drug events and high costs. The purpose of this study was to investigate the frequency and potential drug–drug interactions associated with antimicrobials among hospitalized patients.Material/MethodsThis study was conducted on the same day in 5 different hospitals in Turkey. We included patients aged ≥18 years who received at least 1 antimicrobial drug and at least 1 of any other drug. The Micromedex® online drug reference system was used to control and describe the interactions. Drug interactions were classified as contraindicated, major, moderate, and minor.ResultsPotential drug–drug interactions with antimicrobials were 26.4% of all interactions. Five (42%) of 12 contraindicated interactions and 61 (38%) of 159 major interactions were with antimicrobials. Quinolones, triazoles, metronidazole, linezolid, and clarithromycin accounted for 173 (25.7%) of 673 prescribed antimicrobials, but were responsible for 141 (92.1%) of 153 interactions. In multivariate analysis, number of prescribed antimicrobials (odds ratio: 2.3001, 95% CI: 1.6237–3.2582), number of prescribed drugs (odds ratio: 1.2008, 95% CI: 1.0943–1.3177), and hospitalization in the university hospital (odds ratio: 1.7798, 95% CI: 1.0035–3.1564) were independent risk factors for developing drug interactions.ConclusionsDue to risk of drug interactions, physicians should be more cautious when prescribing antimicrobials, particularly when prescribing quinolones, linezolid, azoles, metronidazole, and macrolides.

Introduction: Thyroid hormones are essential for the normal development, differentiation, metabolic balance and physiological function of all tissues. Mean platelet volume (MPV) indicates mean platelet size and reflects platelet production rate and stimulation. Increased platelet size has been observed in association with known cardiovascular risk factors. The neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) are known markers of the systemic inflammatory response. This study aimed to investigate the effect of thyroid hormone changes by comparing platelet count, MPV values, NLR and PLR in thyroid papillary carcinoma. Methods: Forty-nine females and nine males comprising a total of 58 patients were included in the study. Clinical and laboratory parameters of patients were recorded in the following three phases of the disease: euthyroid phase (before thyroid surgery), overt hypothyroid (OH) phase (before radioactive iodine [RAI] treatment) and subclinical hyperthyroid (SCH) phase (six months after RAI treatment). Results: The mean thyroid-stimulating hormone (TSH) values of the patients in the euthyroid, OH and SCH phases were 1.62±1.17, 76.4±37.5 and 0.09±0.07 μIU/mL, respectively. The mean MPV values of the patients in the euthyroid, OH and SCH phases were 9.45±1.33, 9.81±1.35 and 9.96±1.21 fL, respectively. MPV was significantly higher in the SCH phase than in the euthyroid phase (p=0.013). Platelet count, NLR and PLR were not statistically different between the euthyroid, OH and SCH phases. Conclusion: The results of this study demonstrated that the levels of MPV increased significantly in the SCH phase in patients with papillary thyroid carcinoma (PTC), and increased MPV values contributed to increased risk of cardiovascular complications. These findings suggest that MPV can be a valuable, practical parameter for monitoring the haemostatic condition in thyroid disorders. No significant difference was observed in platelet count, NLR and PLR in all stages of PTC.

Background and Objectives: The HUC-HEART Trial (ClinicalTrials.gov Identifier: NCT02323477) was a controlled, prospective, phase I/II, multicenter, single-blind, three-arm randomized study of intramyocardial delivery of human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) combined with coronary artery bypass-grafting (CABG) in patients with chronic ischemic cardiomyopathy (CIC). The trial aimed to assess (i) the safety and the efficacy of cell transplantation during one-year follow-up, (ii) to compare the efficacy of HUC-MSCs with autologous bone-marrow-derived mononuclear cells (BM-MNCs) in the same clinical settings. Methods and Results: Fifty-four patients who were randomized to receive HUC-MSCs (23×10 6) (n=26) or BM-MNCs (70×10 7) (n=12) in combination with CABG surgery. The control patients (n=16) received no cells/vehicles but CABG intervention. All patients were screened at baseline and 1, 3, 6, 12 months after transplantation. Forty-six (85%) patients completed 12 months follow-up. No short/mid-term adverse events were encountered. Decline in NT-proBNP (baseline∼ 6 months) in both cell-treated groups; an increase in left ventricular ejection fraction (LVEF) (5.4%) and stroke volume (19.7%) were noted (baseline∼6 or 12 months) only in the HUC-MSC group. Decreases were also detected in necrotic myocardium as 2.3% in the control, 4.5% in BM-MNC, and 7.7% in the HUC-MSC groups. The 6-min walking test revealed an increase in the control (14.4%) and HUC-MSC (23.1%) groups. Conclusions: Significant findings directly related to the intramyocardial delivery of HUC-MSCs justified their efficacy in CIC. Stricter patient selection criteria with precisely aligned cell dose and delivery intervals, rigorous follow-up by detailed diagnostic approaches would further help to clarify the responsiveness to the therapy.

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Objectives: Doxorubicin (DOX) is an antineoplastic drug that is widely used in chemotherapy but its cardiotoxicity is the most important side effect that limits the clinical use of this drug. We investigated DOX treatment and the effects of vitamin D and melatonin on heart by electrocardiography, scintigraphic and biochemical methods. Methods: In this study, forty-nine adult male Wistar albino rats (220 ± 15 g) were randomly divided into seven groups (n = 7 each), namely control (CON, n = 7), doxorubicin (DOX, n = 7), melatonin (MEL, n = 7), vitamin D (Vit D, n = 7), doxorubicin plus melatonin (DOX+MEL, n = 7), doxorubicin plus vitamin D (DOX+Vit D, n = 7), and doxorubicin plus melatonin and vitamin D (DOX+MEL+Vit D, n = 7) groups. Cardiotoxicity was induced by intraperitoneal injection (i.p.) of DOX (18 mg/kg, i.p.) on the 15 th , 16 th and 17 th days. Rats receiving vitamin D and melatonin treatment in the DOX-induced cardiotoxicity group received vitamin D (60,000 IU/kg, i.p.) were administered in a single dose and melatonin (40 mg/kg/day, i.p.) for 17 days and were injected with (18 mg/kg, i.p.) on doxorubicin 15 th , 16 th , and 17 th days. On the 18 th day electrocardiography (ECG), 99m Technetium pyrophosphate scintigraphy and biochemical parameters were assessed. Results: DOX caused changes in the ECG pattern, a significant decrease in heartbeat (p < 0.01), P wave (p < 0.001) and QRS complex durations (p < 0.001), R wave amplitude (p < 0.001); elevation in ST-segment (p < 0.001) and decrease in QT interval (p < 0,001), and R-R interval durations (p < 0.001); increase in the serum levels of cardiac injury markers (CK, BUN, cardiac troponin T), (p < 0.01), and increased 99m Technetium pyrophosphate uptake (p < 0.001) as compared to the CON group. MEL, Vit D and MEL+Vit D administration showed a same protective effect against DOX-induced altered ECG pattern. Pre-treatment with MEL, Vit D and MEL+Vit D significantly protected the heart from the toxic effect of DOX, by decreasing the levels of of cardiac injury markers (CK, BUN, cardiac troponin T) (p < 0.001) and decreased the elevated level of 99m Technetium pyrophosphate uptake (p < 0.001). Conclusion: Vitamin D and melatonin treatment prevented all the parameters of DOX-induced cardiotoxicity in rats.

Tularemia during pregnancy is exceedingly rare and has been reported infrequently in Europe. A review of the literature identified only 3 documented cases. Herein we report 4 tularemia cases occurring early in the second and third trimesters, which were successfully managed without any adverse pregnancy outcomes.