Search

In an attempt to develop effective and potentially active antibacterial and/or antifungal agents, we designed, synthesized, and characterized thiolated CoQ analogs (CoQ1-8) with an extensive antimicrobial study. The antimicrobial profile of these analogs was determined using four Gram-negative bacteria, three Gram-positive bacteria, and three fungi. Because of the fact that the thiolated CoQ analogs were quite effective on all tested Gram-positive bacterial strains, including

Objective: The aim of this study is to compare Matricaria chamomilla samples collected from nature and supplied from pharmacies and herbalists by performing quality control analyses and investigate the antimicrobial activities of them. Methods: These samples were examined according to Matricariae flos monograph analysis in European Pharmacopoeia. Macroscopic and microscopic examination, loss on drying and total ash experiment were performed. Essential oil was obtained from the drugs and analyzed by thin layer chromatography. Additionally, aqueous and ethanolic extracts of all samples were compared by thin layer chromatography. Antimicrobial activity was determined by microdilution method in aqueous and ethanolic extracts. Results: According to the pharmacopoeia analysis; in macroscopic and microscopic examinations, all samples except 2 herbalist samples were found to suitable for the pharmacopoeia standards. In loss on drying, none of the samples were found to suitable for the standards except 2 herbalist samples. In total ash, all samples were suitable for the standards. While the essential oil of M. chamomilla samples collected from nature was yellow-orange colored, we obtained the blue essential oil containing chamazulene from pharmacy samples and 3 of herbalist samples. The highest activity in antimicrobial activity assay was observed in ethanol extracts against Staphylococcus aureus, Staphylococcus epidermidis and Candida tropicalis strains. Conclusion: Examples of true M. chamomilla were found among herbalist samples, contrary to the previous studies. Pharmacy samples were qualified but limited in terms of variety. Essential oil analyses pointed out the importance of geographical location among natural samples. Antimicrobial activity tests did not provide significant results.

This study investigates the presence of the different classes of micro-pollutants such as pharmaceutical active compounds (PhACs) (20 antibiotics, 8 analgesics and anti-inflammatories, 5 cytostatic agents, 7 beta-blockers, 4 lipid regulators, 13 psychiatrics, 1 antidiabetic, 1 receptor antagonist, 1 local anaesthetic, 1 antihypertensive and their 5 metabolites), hormones (8 compounds), X-ray contrast agents (6 compounds), benzotriazoles (3 compounds) and pesticides (6 compounds), and antibiotic resistance in hospital wastewater (HWW) of a medical faculty in Istanbul, Turkey. In addition, the seasonal variations of the selected PhACs and X-ray contrast agents and antibiotic resistance were evaluated for 2 years in a total of eight samples. In the PhACs, sulfamethoxazole and its metabolite (4 N-acethyl-sulfamethoxazole) in the antibiotic group and paracetamol in the analgesic and anti-inflammatory group were found at 100% of frequency and the highest concentrations as 35, 43 and 210 mu g/L, respectively. The mean concentrations of psychiatric compounds were found less than 0.25 mu g/L except carbamazepine (1.36 mu g/L). Bisphenol A in hormone group had the highest concentration up to 14 mu g/L. In the hormone group compounds, 17-alpha-Ethinylestradiol and 17-beta-Estradiol were detected at lower mean concentrations of 0.2 and 0.05 mu g/L, respectively. 1H-benzotriazole had the highest concentration with the mean concentration of 24.8 mu g/L in benzotriazole group compounds. The compounds in X-ray contrast agents group were noted as compounds detected at the highest concentration in HWW up to 3000 mu g/L. Antibiotic resistance against azithromycin, clindamycin and trimethoprim-sulfamethoxazole antibiotics was observed around 50% in the winter period. The seasonal variation was detected for the most of the investigated PhACs, especially in antibiotic group which was in line with those significant differences in antibiotic resistance rates in the studied antibiotics between winter and summer seasons.

Objective: In our country, herbal drugs used for medical purposes by the folk are generally purchased from the herbal stores. The quality and reliability of the plants sold in the herbal stores have been discussed for many years. The present study aims to investigate samples of Hypericum perforatum, which is one of the important medicinal plants and widely used by the folk.Material and Method: The drugs sold as “St John’s Wort” were purchased from 12 different herbal stores which were randomly chosen in Istanbul. Quality control of the collected part and collection time of the plant were examined by using macroscopic and microscopic methods. The suitability of the plant storage conditions were investigated by microbiological test. The ash and moisture contents, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), mineral and heavy metal levels of the plant were determined. Hypericin contents of the methanol extracts prepared from the plant samples were analyzed by High Performance Liquid Chromatography (HPLC).Result and Discussion: In this study, it was determined that most of the samples were contaminated by impurities, 6 of them did not contain hypericin, and 2 of them contained high levels of aluminium (Al). As a result, it was once again understood that it might be inconvenient to sell the medicinal plants in the herbal stores unless inspected for public health. Sale of the medicinal plants in herbal stores should be prevented, and it should be ensured that the public can reach the high quality medicinal plants., Amaç: Ülkemizde, halk arasında tedavi amacıyla kullanılan bitkisel droglar genellikle aktarlardan temin edilmektedir. Aktarlarda satılan drogların kalitesi ve güvenilirliği uzun yıllardır tartışılmaktadır. Bu çalışma ile önemli tıbbi bitkilerimizden biri olan ve halk arasında yaygın olarak kullanılan Hypericum perforatum türünün İstanbul aktarlarından satın alınan örnekleri incelenmiştir.Gereç ve Yöntem: Sarı Kantaron adı ile satılan droglar, İstanbul’da faaliyet gösteren, rastgele seçilmiş 12 farklı aktardan temin edilmiştir. Bitkinin toplanan kısmının (drog) ve toplanma zamanının kontrolü makroskobik ve mikroskobik incelemelerle; saklama koşullarının uygunluğu ise mikrobiyolojik test ile araştırılmıştır. Drogların kül ve nem miktarı, total antioksidan statü (TAS) ve total oksidan statü (TOS) değerleri, oksidatif stres indeksi (OSI), mineral ve ağır metal madde düzeyleri tespit edilmiştir. Droglardan hazırlanan metanol ekstrelerinin hiperisin içeriği Yüksek Performanslı Sıvı Kromatografisi (YPSK) ile analiz edilmiştir.Sonuç ve Tartışma: Bu çalışma ile örneklerin çoğunun gözle görülebilen kirlilikler ile kontamine olduğu, 6 tanesinin hiperisin içermediği, 2 tanesinin çok yüksek oranda alüminyum (Al) içerdiği belirlenmiştir. Sonuç olarak tıbbi bitkilerin gerekli denetimlere tabi tutulmadan aktarlarda satılmasının halk sağlığı açısından uygun olmadığı bir kez daha anlaşılmıştır. Mevcut bu durumun önüne geçilmesi, halkın doğru ve standart kalitede droglara ulaşabilmesi sağlanmalıdır.

Background: The aerial parts of Dipsacus laciniatus are traditionally used in the treatment of colds as cold tea; decoction prepared from its roots and aerial parts are used for the treatment of diabetes and cancer, respectively. The extraction procedures and solvents are important steps in the processing of bioactive constituents from the plant materials. Objective: The aim of this study was to evaluate in vitro antioxidant, antimicrobial, anticholinesterase and cytotoxic activities for the first time in plant’s different extracts. Methods: The antioxidant activities of extracts were examined using FRAP and CUPRAC methods, including total phenolic and flavonoids contents. In addition, the antimicrobial, anticholinesterase and cytotoxic activities of extracts were investigated using microdilution, Ellman and MTT methods, respectively. Results: In the present study, methanol extract showed stronger iron (III) ion reduction (FRAP) and copper (II) ion reducing antioxidant capacity (CUPRAC) than other extracts and also contained higher total phenolic and flavonoid compounds. It was also found that there was a linear relationship between antioxidant activity and phenolic compounds in this study. It was demonstrated that the chloroform and methanol extracts showed moderate antimicrobial activity against S. epidermidis and C. albicans strains. The chloroform extract had a strong and selective cytotoxic activity for the MCF-7 and HT-29 cell lines, while the methanol extract showed low cytotoxic activity on the same cell lines. In addition, according to the obtained data, chloroform extract showed a toxic effect on normal cell line (NIH/3T3), but other extracts showed no toxic effect. Conclusion: Since methanol extract has no toxic effect on normal cell line and has strong antioxidant, anticholinesterase and antimicrobial activity, it is thought that this extract may be useful as an antioxidant, anticholinesterase and antimicrobial agents in the future.

Study design An experimental design. Objectives The aim of this study was to determine the latencies of vibration-induced reflexes in individuals with and without spinal cord injury (SCI), and to compare these latencies to identify differences in reflex circuitries. Setting A tertiary rehabilitation center in Istanbul. Methods Seventeen individuals with chronic SCI (SCI group) and 23 participants without SCI (Control group) were included in this study. Latency of tonic vibration reflex (TVR) and whole-body vibration-induced muscular reflex (WBV-IMR) of the left soleus muscle was tested for estimating the reflex origins. The local tendon vibration was applied at six different vibration frequencies (50, 85, 140, 185, 235, and 265 Hz), each lasting for 15 s with 3-s rest intervals. The WBV was applied at six different vibration frequencies (35, 37, 39, 41, 43, and 45 Hz), each lasting for 15 s with 3-s rest intervals. Results Mean (SD) TVR latency was 39.7 (5.3) ms in the SCI group and 35.9 (2.7) ms in the Control group with a mean (95% CI) difference of -3.8 (-6.7 to -0.9) ms. Mean (SD) WBV-IMR latency was 45.8 (7.4) ms in the SCI group and 43.3 (3.0) ms in the Control group with a mean (95% CI) difference of -2.5 (-6.5 to 1.4) ms. There were significant differences between TVR latency and WBV-IMR latency in both the groups (mean (95% CI) difference; -6.2 (-9.3 to -3.0) ms, p = 0.0001 for the SCI group and -7.4 (-9.3 to -5.6) ms, p = 0.011 for Control group). Conclusions The results suggest that the receptor of origin of TVR and WBV-IMR may be different.

New organic compounds containing quinone moiety continue to be developed and used for a broad spectrum of applications as dyes, drugs, herbicides, fungicides, bactericides, plant-growth regulators, analytical reagents, photoresistors, catalysts, and dehydrogenating agents in organic synthesis. Therefore, in this paper, new plastoquinone analogs possessing arylthio side chain at the 2-position and 2- and 3-positions have been synthesized as possible antibacterial and antifungal agents. Besides single crystal X-ray structural characterization of 3d, 3e, and 4e, the structures of all compounds (3a-h and 4a-h) have been determined based on spectral (IR, 1H NMR, 13C NMR, and mass) data. The current study also contains in vitro antimicrobial screening (using microbroth dilutions method) of synthesized thiolated plastoquinone analogs. The analog containing dimethyl groups within thio moiety (3d) shows moderate antibacterial activity against E. faecalis compared to that of Amikacin. Additionally, the compounds (3d, 3h, and 4f) possessed the activity against S. aureus. 3d was also able to induce appreciable growth inhibitory activity against C. albicans and C. tropicalis with the MIC value of 78.12 μg/mL and 19.53 μg/mL, respectively. This study suggests that four analogs (3d, 3e, 3h, and 4f) could be potential candidates for further development since they show a broad spectrum.

A series of aminobenzoquinones, denoted as PQ analogs (PQ1-13), were synthesized by employing a green methodology approach using water as solvent developed by Tandon et al. Subsequently, in vitro antimicrobial potential of all PQ analogs was evaluated in a panel of seven bacterial strains (three gram positive and four gram negative bacteria) and three fungi. The antifungal profile of all PQ analogs indicated that four analogs (while PQ2, PQ9, and PQ10 were effective against Candida tropicalis, PQ11 is effective against Candida albicans) have potent antifungal activity. The results revealed that PQ9 showed similar antibacterial activity against Staphylococcus epidermidis compared clinically prevalent antibacterial drugs cefuroxime. PQ11 exhibited the highest antibacterial activity against S. epidermidis, which was about fourfold better than that of cefuroxime. Owing to their outstanding activities, PQ9 and PQ11 were chosen for a further investigation for biofilm and cytotoxicity evaluation. Based on the tests performed, there was a significant positive correlation between inhibition of the biofilm attachment and time. In addition, PQ9 and PQ11 showed cytotoxic effects at high concentrations on Balb/3T3, HaCaT, HUVEC, and NRK-52E cells (>24 and >18 μg/mL, respectively). Thus, two analogs (PQ9 and PQ11) were identified as the hits with the strong antibacterial efficiency against the S. epidermidis with low MIC values.

The antimicrobial and cytotoxic effects of various endemic and non-endemic Eryngium species from Turkey were investigated. Nine endemic and two non-endemic Eryngium species were analyzed using a microdilution assay for their antibacterial and antifungal activities. Cytotoxic activities of E. pseudothoriifolium, E. thorifolium, E. davisii, and E. falcatum, on prostate carcinoma and endometrial cancer cells were analyzed by cytotoxic activity assay. It was observed that 16 out of 22 extracts (aerial or root part) showed antibacterial activities. Fifteen out of 22 extracts showed antifungal activity with the lowest MIC (156 mg/l) value against Candida albicans ATCC 10231 and C. tropicalis ATCC 750. Aerial parts of E. pseudothoriifolium, E. thorifolium, E. davisii, and E. falcatum exhibited cytotoxic effects on endometrial cancer cells. This evaluation of tested endemic Eryngium species’ antimicrobial and cytotoxic activities is the first of its kind.

Achromobacter species, which are recognized as emerging pathogens isolated from patients with cystic fibrosis, are capable of forming biofilm in the respiratory tract in patients and innate multidrug resistance to antimicrobials. CSAs are cationic salt derivatives that mimic the activity of antimicrobial peptides and exhibit antimicrobial activity against bacteria. In this study, the in vitro activities of various ceragenins against Achromobacter-species biofilms were investigated comparatively with a conventional antibiotic (meropenem). Biofilm-formation inhibition and biofilm-adhesion inhibition were investigated on five strong biofilm-producing strains. The lowest MIC

Objectives: Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF) disease, although relatively limited is known about its clinical impact and optimal management. Pharmacodynamics such as post-antibiotic effect (PAE) are increasingly being applied to the design of antibiotic dosing regimens. In the present study, meropenem, doripenem, colistin, levofloxacin, tigecycline, tobramycin, and chloramphenicol were tested for their PAE. Materials and Methods: The in vitro activities of meropenem, doripenem, colistin, levofloxacin, tigecycline, tobramycin, and chloramphenicol were determined by the microbroth dilution technique. To determine the PAEs, A. xylosoxidans strains in the logarithmic phase of growth were exposed for 1 h to antibiotics. Recovery periods of test cultures were evaluated using viable counting after centrifugation. Results: The mean values of in vitro PAEs at 1xMIC and 4xMIC concentrations were 3.21 ± 0.66 and 3.58 ± 0.68 hours for colistin, 1.54 ± 0.46 and 2.27 ± 0.41 hours for levofloxacin, 2.34 ± 0.48 and 3.47 ± 0.64 hours for tobramycin, 1.72 ± 0.47 and 2.24 ± 0.41 hours for tigecycline 1.91 ± 0.14 and 2.13 ± 0.13 hours for chloramphenicol, respectively. The carbapenem antibiotics exhibited weak PAEs, as expected. Conclusions: This study’s findings could have important implications for the timing of doses during antimicrobial therapy with tested antibiotics.

In Turkey, Helichrysum genus is represented by 26 taxa belonging to 20 species in Turkish flora of which 14 ones are endemic to Turkey. The aerial parts of Helichrysum plicatum subsp. plicatum are used kidney stones, kidney and stomach ailments. The extraction procedures and solvents are important step in processing of bioactive constituents from the plant materials. Therefore, the aim of this study was to evaluate in vitro antioxidant, antimicrobial, anti-urease, anticholinesterase and in vivo anti-inflammatory activities of Helichrysum plicatum subsp. plicatum different extracts. In addition, the phenolic characterization of the Soxhlet and maceration methanol extracts which showed significant antioxidant, anti-urease, antimicrobial, anti-inflammatory and anticholinesterase activities were performed by HPLC-DAD and LC-MS/MS. In the present study, the Soxhlet methanol extract exhibited strong antioxidant, antimicrobial and anticholinesterase activities than other extracts. The maceration methanol extract showed the strongest anti-urease activity. The Soxhlet methanol and maceration methanol extracts showed in vivo anti-inflammatory activities very close to each other. As a result of this study, chlorogenic acid, dicaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, naringenin-O-hexoside and isoquercitrin compounds were analysed in plant. Therefore, it is thought that methanol extracts can be used as a natural source in the future for food and pharmaceutical industries.

Phytochemical composition of ethyl acetate fraction and total phenolic content, in vitro antioxidant, anti-inflammatory, antimicrobial activities of petroleum ether, chloroform, ethyl acetate and n-butanol fractions of the ethanol extract obtained from the subaerial parts of Scorzonera pygmaea Sibth. & Sm. (Asteraceae) were investigated. Nine compounds; scorzopygmaecoside (1), scorzonerol (2), cudrabibenzyl A (3), thunberginol C (4), scorzocreticoside I (5) and II (6), chlorogenic acid (7), chlorogenic acid methyl ester (8), 3,5-di-O-caffeoylquinic acid (9) were isolated and identified using spectroscopic methods. All substances were isolated for the first time from this species. Compounds 1 and 2 are new. The fractions showed high antioxidant capacity correlated with their phenolic content and no significant antimicrobial activity against tested bacteria and fungi. COX inhibition test was used to evaluate the anti-inflammatory activity and all the fractions showed low inhibition in comparison with indomethacin.

Ferulago trachycarpa (Apiaceae) is a plant used traditionally for its sedative, digestive, carminative and aphrodisiac properties with distribution in West, Southwest and South Anatolian part of Turkey. In this study the antimicrobial activities of fractionally n-hexane, dichloromethane, methanol and only methanol extracts from rhizomes of F. trachycarpa were screened against Stapylococcus aureus ATCC 6538, S. epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 14153, Enterococcus feacalis ATCC 29212 bacterial strains and fungal strains such as Candida albicans ATCC 10231, C. tropicalis ATCC 750 and C. parapsilosis ATCC 22019 by microdilution method. All extracts have been shown to possess antimicrobial activities against bacteria and fungal strains and according to the antimicrobial results, the isolation of the active constituents was made from the most active n-hexane and dichloromethane extracts. So, four pure compounds are known as coumarin derivatives, crenulatin (6-formyl-7-methoxycoumarin), suberosin (7-methoxy-6-prenylcoumarin), marmesin senecioate ((-)-prantschimgin) as dihydrofuranocoumarin derivative and ulopterol [6- (2’, 3’-dihydroxy-3’-methylbutyl)-7-methoxy-coumarin] were isolated. Crenulatin (6-formyl-7-methoxycoumarin), suberosin (7-methoxy-6-prenylcoumarin), marmesin senecioate ((-)-prantschimgin) which are pure compounds demonstrated antifungal activity with 625 mg/L MIC against C. albicans and antibacterial activity with 1250 mg/L MIC against S. aureus (MRSA). These results indicate that extracts and pure compounds obtained from Ferulago trachycarpa could be a potential for pharmaceutical products which have antimicrobial activity.

Amaç: Gram negatif, genellikle kapsüllü, hareketsiz, sporsuz, çomak şeklinde bir bakteri olan Klebsiella pneumoniae günümüzde toplum ve hastane kökenli enfeksiyonların önemli etkenlerinden biridir. Bu bakteri kateter yüzeyinde bir mikrobiyal biyofilm oluşturarak kateter ilişkili enfeksiyonlara neden olabilmektedir. Kateter ilişkili enfeksiyonların tedavisinde en etkili tedavi yöntemi enfekte kateteri çıkarmak ve sistemik antibiyotik tedavisine başlamak olsa da bu işlem hastanın sağlık durumu ile ilgili nedenlerle her zaman yapılamamaktadır. Enfekte kateterin çıkartılamadığı hastalarda sistemik antimikrobiyal tedavi ile birlikte yardımcı bir tedavi seçeneği olarak antibiyotik kilit (AK) tedavisi kullanılması Infectious Diseases Society of America ve Centers for Disease Control and Prevention gibi sağlık kuruluşları tarafından önerilmektedir. Gereç ve Yöntemler: Çalışmamızda, in vitro yöntemle santral venöz kateter (SVK) modeli oluşturularak biyofilm oluşturduğu tespit edilen iki SVK ilişkili bakteriyemi enfeksiyon etkeni Klebsiella pneumoniae suşuna karşı bir yüzey aktif ajan olan lesitinin tek başına ve çeşitli antibiyotiklerle kombinasyonlarının 96 saatlik etkisi araştırılmıştır. Bulgular: Çalışmamızdan elde ettiğimiz sonuçlara göre, lesitin+tobramisin ve lesitin+doripenem kombinasyonlarını içeren AK çözeltisinin her iki suş içinde en az 2-log10’luk bir artış sağlayarak biyofilme gömülmüş suşlar üzerinde antagonist etki oluşturduğu, lesitin+kolistin, lesitin+tigesiklin ve lesitin+siprofloksasin içeren AK çözeltilerinin ise her iki suşa ait kateter biyofilm modelinde antibiyotiklerin tek başına oluşturduğu etkiden daha az etki gösterdiği saptanmıştır. Sonuç: Çalışmamızda lesitin+tobramisin ve lesitin+doripenem kombinasyonlarının antagonist etki göstermesi günlük hayatta tükettiğimiz pek çok üründe gıda takviyesi olarak bulunan lesitinin enfeksiyon hastalıklarının tedavisindeki etkilerinin ortaya koyulması açısından önemli olduğu düşüncesindeyiz.

This study aims to analyze the effect of ceftazidime/avibactam plus various antibiotics against OXA-48-producing Enterobacterales isolated from Intensive Care Units. Seventy-four non-duplicate OXA-48-producing Enterobacterales isolates were screened for their MICs by the microbroth dilution method. The in-vitro bactericidal and synergistic activities of ceftazidime/avibactam alone or in combination with other antibiotics were determined by time-kill curve assays. According to our results, colistin was the most active drug with higher susceptibility rates in the strains. Colistin, levofloxacin, tobramycin, and doripenem showed bactericidal effects against different isolates. The best synergistic interactions were achieved with ceftazidime/avibactam + colistin, ceftazidime/avibactam + tobramycin, and ceftazidime/avibactam + tigecycline against studied strains used at 1xMIC concentrations at 24 h. No antagonism was observed against studied OXA-48-producing Enterobacterales strains. The findings of this study suggest that ceftazidime/avibactam plus colistin, tobramycin, or tigecycline were more effective against OXA-48-producing Enterobacterales strains. This combination therapy could be an alternative antibiotic therapy for carbapenemase-producing Enterobacterales strains. Bilimsel Araştırma Projeleri Birimi, İstanbul Üniversitesi

WOS:000605357000022 Abstract Background and Aims: Scorzonera L. genus contains several medicinal and edible plants. Both roots and aerial parts of Scorzonera species are used. S. pygmaea is endemic to Turkey. in a previous study, nine phenolic compounds were reported from the roots of the plant alongside certain biological activities. The current study was designed to investigate the aerial parts of the plant in the same manner and compare the potentials of the two parts. Methods: Chromatographic and spectroscopic methods were used to isolate and identify the phenolics. Total phenolic contents were determined by Folin-Ciocalteu method. FRAP assay, anti-LPO, scavenging DPPH, ABTS and superoxide radicals were employed to evaluate the antioxidant activity. COX inhibition test and micro broth dilution technique were used for anti-inflammatory and antimicrobial activities, respectively. Results: Seven phenolic compounds; thunberginol C (1), protocatechuic acid (2), chlorogenic acid methyl ester (3), cudrabibenzyl A (4), scorzocreticin (5), scorzocreticoside I (6) and II (7) were purified. All the compounds are new for the aerial parts of the plant and 2 is new for the genus. The aerial parts showed a high antioxidant capacity which correlated with its phenolic content. COX inhibitory activity was found to be lower compared to Indomethacin. Weak antimicrobial activity was determined against Staphylococcus aureus and S. epidermidis. Conclusion: Aerial parts possess significant/infrequent phenolics and the ethyl acetate (EtOAc) fraction of the ethanol extract is the most promising fraction for isolating these compounds. Phenolic compositions of aerial parts and roots are very similar. However, aerial parts can be a better rich source of natural antioxidants with protocatechuic acid and higher antioxidant potential.

Background: This study aims to analyse the effect of ceftazidime-avibactam plus various antibiotics against multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from Intensive Care Units. Methods: 40 non-duplicate P. aeruginosa isolates were screened for their MICs of ceftazidime, ceftazidime-avibactam, colistin, levofloxacin, doripenem and tobramycin. MICs were determined by the broth microdilution method. The in vitro bactericidal activities of ceftazidime-avibactam compared to studied antibiotics were also determined by time-kill curve assays both at 1xMIC and at 4xMIC against carbapenemase-producing or -not producing six colistin-nonsusceptible MDR clinical strains of P. aeruginosa. Additionally, synergistic interactions were investigated by the time-kill curve assay. Results: The MIC90 values for ceftazidime, ceftazidime-avibactam, colistin, levofloxacin, doripenem and tobramycin against MDR P. aeruginosa isolates were found to be >256, 64, 8, 64, 128, and >256 mg/L, respectively. The minimum bactericidal concentration90 values for those antibiotics were also >256, 64, 16, 128, 256, and >256 mg/L, respectively. While doripenem, tobramycin and levofloxacin were bactericidal (>3 log10 killing) against the 2/6, 3/6 and 1/6 P. aeruginosa isolates at 4xMIC concentrations, respectively, levofloxacin and tobramycin were bactericidal against only one isolate (1/6) at 1xMIC concentrations at 24 h. The synergistic interactions of these antimicrobial agents were also achieved with ceftazidime/avibactam + colistin (4/6), ceftazidime/avibactam + tobramycin (3/6), and ceftazidime/avibactam + levofloxacin (3/6) combinations. No antagonism was observed against studied P. aeruginosa strains. Conclusions: The findings of this study suggest that ceftazidime/avibactam with colistin, or tobramycin, were effective against colistin-nonsusceptible strains. This combination therapy could be an alternative antibiotic therapy for resistant P. aeruginosa strains.

Infectious diseases are the significant global health problem because of drug resistance to most classes of antimicrobials. Interest is growing in the development of new antimicrobials in pharmaceutical discovery. For that reason, the urgency for scientists to find and/or develop new important molecules is needed. Many natural active molecules that exhibit various biological activities have been isolated from the nature. For the present research, a new selected set of aminobenzoquinones, denoted as plastoquinone analogs (PQ1–24), was employed for their in vitro antimicrobial potential in a panel of seven bacterial strains (three Gram-positive and four Gram-negative bacteria) and three fungi. The results revealed PQ analogs with specific activity against bacteria including Staphylococcus epidermidis and pathogenic fungi, including Candida albicans. PQ8 containing methoxy group at the ortho position on the phenylamino moiety exhibited the highest growth inhibition against S. epidermidis with a minimum inhibitory concentration of 9.76 μg/mL. The antifungal profile of all PQ analogs indicated that five analogs (while PQ1, PQ8, PQ9, PQ11, and PQ18 were effective against Candida albicans, PQ1 and PQ18 were effective against Candida tropicalis) have potent antifungal activity. Selected analogs, PQ1 and PQ18, were studied for biofilm evaluation and time-kill kinetic study for better understanding.

Objective: Naphthoquinone derivatives are known to have antibacterial activity and are likely to succeed a new class of compound that can be applied as antimicrobial agents. Materials and Methods: The purpose of this experiment was to evaluate the potential antimicrobial, antibiofilm, anticancer, and cytotoxic activities of six naphthoquinone compounds previously reported in the literature. Results: According to our studies, 2-(4-(trifluoromethyl)phenylamino)-3-(propylthio)naphthalene-1,4-dione (5a) and 2-(4-(trifluoromethyl)phenylamino)-3-(pentylthio)naphthalene-1,4-dione (5b) were found to have good antimicrobial activity against Staphylococcus aureus ATCC 29213 with 1.22 and 19.53 µg/mL MIC values, respectively. When we carried out the test against biofilm, the most effective agent, 5a, showed up to 40% inhibition of the S. aureus’s biofilm at the 1 x MIC concentration. However, when we investigated the cytotoxic effect of 5a on the cancer and non-cancer cell lines, we found that 5a showed higher toxicity to cancer cell lines. Conclusion: The findings of our study suggest that further studies to develop these compounds and investigate its pharmacological properties could be useful to define the functionality of them as antimicrobial or anticancer agents.

Antibacterial and antifungal organic compounds are becoming increasingly important for biomedical applications. This study deals with the synthesis, characterization of structures, in silico PASS prediction, and the discovery of antibacterial and antifungal properties based on new sulfanyl-1,4-naphthoquinone derivatives containing an arylamine with a trifluoromethyl group at different positions, which can be further applied in drug discovery and development. The in vitro antimicrobial potential of the newly synthesized compounds was evaluated in a panel of seven bacterial strains (three Gram-positive and four Gram-negative bacteria) and one yeast, with an additional study on antibiofilm activities. The compounds (5b and 5e) were identified as having strong antibacterial efficiency against the human-originated pathogen S. epidermidis, with minimal inhibitory concentration values (4.88 and 2.44 μg mL−1, respectively). The toxicity of both compounds (5b and 5e) was studied in detail to compare these compounds with Cefuroxime (a clinically proven drug). The antibacterial activity of the compound 5f was equal to that of Cefuroxime. Moreover, three compounds (5b, 5e, and 5f) exhibited excellent antibacterial activity, and 5b and 5e were two and four times more active than the reference antimicrobial compound (Cefuroxime), respectively. For this reason, these three compounds (5b, 5e, and 5f) are being considered as promising antibacterial agents. In addition, docking studies were used to better rationalize the action and prediction of the binding modes of these compounds.

A series of brominated PQ analogs (BrPQ1-13) was synthesized by employing two different routes: 1) dibromination followed by oxidation and amination of dimethyl hydroquinone, respectively, 2) oxidation of dimethyl hydroquinone followed by amination and bromination, respectively. In addition to the single-crystal X-ray structural characterization of two analogs (BrPQ2 and BrPQ3), the structures of all analogs were determined based on spectral (FTIR, 1H NMR, 13C NMR, and HRMS) data. We evaluated the analogs for in vitro antibacterial and antifungal activity against ATCC® strains (panel of seven bacterial strains with three Gram-positive and four Gram-negative bacteria and three fungi) using the broth microdilution method. The structure–activity relationship of brominated PQ analogs indicated that the electron-withdrawing group (EWG) on the phenyl ring (-CF3, trifluoromethyl group) has a positive effect on antibacterial activity. These in vitro data show that brominated analogs, especially for BrPQ 1, BrPQ2, and BrPQ3, have the potential to be developed as new antibacterial agents against S. aureus and/or S. epidermidis with low MIC values.

Phytochemical composition of ethyl acetate fraction and total phenolic content, in vitro antioxidant, anti-inflammatory, antimicrobial activities of petroleum ether, chloroform, ethyl acetate and

WOS: 000471951900029 PubMed ID: 30576787 Objectives: Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) are a growing problem because of the limited options for treatment. The number of antimicrobials that are currently being developed is still insufficient to control this global threat. Combination therapies of antibiotics with different antimicrobial mechanisms have been proposed as the best options for treating MDR A. baumannii infections. The objective of this study was to investigate the in-vitro effectiveness of ceftazidime/avibactam alone or in combination with antibiotics against MDR A. baumannii isolates using time-kill assays. Methods: Forty clinical MDR strains were screened, and minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of ceftazidime/avibactam, colistin, levofloxacin, meropenem, tigecycline, and tobramycin were determined by microbroth dilution method. The in-vitro synergistic activities of ceftazidime/avibactam with antibiotic combinations were determined by time-kill assays at 1 x MIC and 4 x MIC against five MDR A. baumannii isolates. Results: Based on MIC results, all isolates of A. baumannii were resistant to ceftazidime/avibactam, except for AB-5. All isolates were found to be resistant to meropenem and levofloxacin. At 4 x MIC, all of the tested antibiotics showed bactericidal effect (>= 3 log(10)killing). The synergistic activities of ceftazidime/avibactam + colistin, ceftazidime/avibactam + tobramycin and ceftazidime/avibactam + tigecycline combinations at 1 x MIC were observed against studied 5/5, 4/5 and 4/5 strains, respectively. Furthermore, all of the tested combinations at 4 x MIC were additive at 24 h. No antagonism was observed. Conclusions: The findings of this study suggest that a significant bactericidal effect was seen with all tested combinations. These findings present significant implications for antibiotic choice for the treatment of infections caused by MDR A. baumannii. (C) 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved. Research Fund of the University of Istanbul (Istanbul, Turkey) [21897] This work was supported by a grant from the Research Fund of the University of Istanbul (Istanbul, Turkey). Project number: 21897.

The antioxidant, anti-inflammatory, acetylcholinesterase (AChE) inhibitory and antimicrobial activities of extract from the Centaurea antiochia Boiss. var. praealta (Boiss. & Bal.) Wagenitz, an endemic plant species from Turkey, were investigated. The results indicated that the extract inhibits FeCl3/ascorbic acid-induced phosphatidylcholine liposome oxidation, scavenges stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radicals, and reduces Fe3+ to Fe2+ in the ferric-reducing antioxidant power (FRAP) assay. The extract inhibited AChE and both cyclooxygenase (COX)-1 and COX-2, which suggests this species might be a potential source of plant-derived anti-inflammatory and anti-AChE substances. The extract may also act as an antimicrobial agent because it inhibited the growth of Gram-positive and Gram-negative bacteria as well as yeast. These findings may scientifically explain some uses of this species in Turkish folk medicine as an antimicrobial, anti-inflammatory and wound healing agent. Practical Applications The Centaurea species are known by the vernacular name “peygamber cicegi” in Turkish folk medicine. Ethnobotanical reports indicate the Centaurea species have antidiabetic, anti-inflammatory, wound healing, digestive, stomachic, diuretic, astringent, hypotensive, antipyretic, laxative, analgesic, tonic, hemostatic and antibacterial properties. Considering the important role oxidative stress and inflammation play in the pathogenesis of neurological diseases, C. antiochia var. praealta may be used as a medicinal plant to treat Alzheimer's disease. This study also confirms the efficacy of this plant as a natural antimicrobial agent.

Bisphosphonates are widely used, effective medications of documented osteoporosis. They accumulate in bone and are released for months or years despite the termination of treatment. Cortical stress reaction and related low energy atypical fractures of femoral shaft are amongst the main complications in patients with osteoporosis who are on long-term bisphosphonate therapy. Contralateral femoral cortical stress reaction may also be observed. In this article, we present two female patients who admitted to our outpatient clinic with anterior thigh pain, and review their clinical presentation. Lateral cortical thickening of both femurs were diagnosed in both patients.

Klebsiella pneumoniae continues to be an important cause of community-acquired and nosocomial infection. This bacterium can cause catheter related infections by forming biofilm on the surface of catheter. The aim of our study is to determine the in vitro stability and efficacy of colistin, ciprofloxacin, tobramycin, doripenem and tigecycline alone, or in combination with clarithromycin or esomeprazole, as 24-h lock solutions against biofilm-embedded K. pneumoniae strains. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against K. pneumoniae. In our study, we observed that the use of doripenem and tobramycin as a lock solution had potent bactericidal effects. When colistin was used in combination with clarithromycin or esomeprazole, the combinations had a synergistic effect. No antagonistic effect was observed. The findings of our study have important information for effectiveness of tested antibiotic lock solution in the catheter-related infections with K. pneumoniae.

Ferulago W. Koch is a genus in the Apiaceae family comprising 34 species, of which 18 are endemic in Turkey. Ferulago species have been known since the time of Dioscorides and have been used in folk medicine for their sedative, tonic, digestive, carminative, and aphrodisiac effects, as well as for the treatment of intestinal worms and hemorrhoids. This study was conducted to evaluate the polyphenolic contents and antioxidant activities of methanol extracts of the aerial parts (HFT) and rhizomes (RFT) of Ferulago trojana E. Akalin & Pimenov by measuring their ability to inhibit lipid peroxidation induced by Fe3+-ascorbate, their DPPH· and ABTS·+ scavenging activities, and their ferric reducing antioxidant power (FRAP value). The methanol extracts were also examined for their antimicrobial activity using the microbroth dilution technique. Results showed that the methanol extracts of the aerial parts of the plant, containing the highest amount of total phenolic content and flavonoids, exhibited antioxidative potential for the chain-breaking inhibition of lipid peroxidation and showed the strongest hydrogen and single electron donor activities, which could thus serve as a free radical scavenger, act as a reductant, and provide protection against oxidative stress. Although the methanol extract of rhizomes did not exhibit any inhibitory effect on lipid peroxidation, it is possible that it might also have protective effects against oxidative damage by scavenging free radicals and acting as a reductant. While both the methanol extracts of the aerial parts and rhizomes of F. trojana were effective against Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), and S. epidermidis, the extracts showed no activity against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. In addition, the methanol extract of rhizomes of F. trojana exhibited antibacterial activity against Proteus mirabilis and antifungal activity against the yeast Candida albicans.

The chemical composition of methanolic extract of Hypericum pamphylicum (HPM) was analyzed by using high performance liquid chromatography–diode array detector (HPLC-DAD). The plant contained hypericin (0.00002 ± 0.000001%), hyperforin (trace), chlorogenic acid (5.58 ± 1.59%), hyperoside (0.46 ± 0.05%), isoquercitrin (0.134 ± 0.02%) and quercetin (0.087 ± 0.008%). The antioxidant activity of HPM was evaluated by using several antioxidant tests. HPM exhibits inhibitory capacity against phosphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HPM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. HPM demonstrated no cytotoxicity against HeLa and NRK-52E cell lines with IC50 values of 1.89 mg/ml and 1.05 mg/ml, respectively. The different crude extracts of H. pamphylicum were analyzed using a microdilution assay for antimicrobial activity against several microorganisms. The most active extract was HPM which showed activity against Staphylococcus aureus. It is observed that nearly all extracts showed activity against Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella thypi, Shigella flexneri, Proteus mirabilis and Candida albicans.

The aim of the study was to present first preliminary characterization of Turkish hospital wastewaters, their environmental risk, and a method for toxicity assessment. The hospital wastewater samples were collected from two of the largest medical faculty hospitals and a training and research hospital in Istanbul, Turkey. The samples from the selected hospitals were taken as grab samples on March 2014. Overall, 55 substances including pharmaceuticals and their metabolites, pesticides, and corrosion inhibitors were analyzed in all hospital wastewaters. Analysis of toxicity and the antibiotic resistance bacteria were investigated in addition to the chemical analysis in the wastewater of one hospital. Hazard quotients (HQs) and toxic units (TUs) were calculated as basis of the environmental risk assessment. Fourteen pharmaceuticals in hospital wastewater (HWW) were classified as “high risk” with HQ > 10. HQHWW values higher than 100 were determined for five antibiotics and one analgesic, namely, ofloxacin, clarithromycin, ciprofloxacin, sulfapyridine, trimethoprim, and diclofenac. Ofloxacin with an HQHWW of 9090 was observed to be the most hazardous compound. HQ and TU values of the wastewater treatment plant (WWTP) effluent dropped significantly due to dilution in the sewer. Further elimination by biological degradation or adsorption was observed only in some cases. However, the decreased HQWWTPeffluent values do not the change environmental load significantly. Therefore, advanced treatment processes should be applied to remove the persistent compounds. In combination with the results on antibiotic resistance, we would prefer on-site treatment of hospital wastewater. Toxicological assessment was performed using cytotoxic and mutagenic screening tests. The results of the Ames assay showed that the native hospital wastewaters had strongly mutagenic activity with a ≤10-fold increase relative to negative controls. The mutagenic potentials of the samples were generally concentration and metabolic activation dependent. Multiple antibiotic resistances were demonstrated with the tested isolates to ciprofloxacin, trimethoprim, and ceftazidime. This study demonstrates that the hospital wastewaters in Istanbul exhibit strong environmental and toxicological risks, as well as high multiple drug resistance to commonly used antibiotics.

The aim of this study was to compare the body composition, including lean tissue mass, fat tissue mass, and bone mineral content, of the paretic leg with that of the nonaffected leg in patients with stroke and to evaluate the effects of time since stroke, spasticity, and motor recovery on the body composition specifically within the first year after stroke. Thirty-five stroke patients with mean age and standard deviation of 62.69+/-9.54 years were included in the study. A full physical examination including Brunnstrom motor recovery and modified Ashworth spasticity scale was performed. Fat tissue mass (grams), lean tissue mass (grams), and bone mineral content (grams) of both the paretic and nonaffected lower extremities were obtained from the total body scans determined by using dual-energy X-ray absorptiometry (Lunar DPX-PRO). Lean tissue mass and bone mineral content of the paretic side were found to be significantly lower than those of the nonaffected side (P

The objective of the study was to describe the domain-specific quality of life in persons with spinal cord injury, and to evaluate the influences of injury level, time since injury, age at time of injury, marital status and education level on quality of life subscales. A cross-sectional questionnaire study was used. Thirty persons with spinal cord injury and 32 age-sex-matched healthy controls were included in the study. The SF-36 Health Survey was administered by telephone to patients. Correlations between the SF-36 subscale scores and time since injury; motor, sensory and radiologic injury levels were evaluated and comparison of scores from different sex, marital status and education level were performed. Quality of life scores were significantly lower in patients with spinal cord injury than in the control group in all subscales. A positive correlation between time since injury, neurologic level and physical functioning score; and between bodily pain subscale and all the remaining subscales was apparent. The spinal cord injury affects quality of life, mainly impairing its physical functioning domain. The most important determinant seems to be motor level of injury and bodily pain. Those who fall in the latter group can be modified by rehabilitation and medical treatment.

A series of 2-arylamino-3-chloro-1,4-naphthoquinone derivatives (3a–h) by the reaction of 2,3-dichloro-1,4-naphthoquinone with aryl amines (2a–h) and benzo[b]phenazine-6,11-dione derivatives (4a–c) by the treatment of 2-arylamino-3-chloro-1,4-naphthoquinone derivatives (3a–h) with sodium azide were synthesized and tested for theirin vitroantibacterial and antifungal activities. The results suggest that compounds3dand3ghad potent antifungal activity againstCandida albicans(MIC = 78.12 μg/mL). All synthesized compounds (3a–h,4a–c) possessed activity againstE. faecaliswith MIC values of between 312.5 and 1250 μg/mL. Benzo[b]phenazine-6,11-dione derivatives (4a–c) were mostly active against Gram-positive bacteria. The structures of the new members of the series were established on the basis of their spectral properties (IR,1H NMR,13C NMR, and mass spectrometry).

Colistin, tigecycline, levofloxacin, tobramycin, and rifampin alone and in combination with doripenem were investigated for their in vitro activities and postantibiotic effects (PAEs) onKlebsiella pneumoniae. The in vitro activities of tested antibiotics in combination with doripenem were determined using a microbroth checkerboard technique. To determine the PAEs,K. pneumoniaestrains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation. Colistin, tobramycin, and levofloxacin produced strong PAEs ranging from 2.71 to 4.23 h, from 1.31 to 3.82 h, and from 1.35 to 4.72, respectively, in a concentration-dependent manner. Tigecycline and rifampin displayed modest PAEs ranging from 1.18 h to 1.55 h and 0.92 to 1.19, respectively. Because it is a beta-lactam, PAEs were not exactly induced by doripenem (ranging from 0.10 to 0.18 h). In combination, doripenem scarcely changed the duration of PAE of each tested antibiotic alone. The findings of this study may have important implications for the timing of doses duringK. pneumoniaetherapy with tested antibiotics.

Prospective cohort study. To compare the health-related quality of life (HRQoL) in people with spinal cord injury (SCI) who use the Internet versus those who don’t and with a control group of able-bodied individuals. To investigate the frequency of Internet usage before and after injury. To evaluate the differences in terms of demographic features of both groups, analyze the variation in the Internet usage pattern of people with SCI before and after the injury. Istanbul, Turkey. A total of 60 people with SCI (38 Internet users, 22 nonusers) were included in the study. The control group consisted of 33 healthy persons of similar age and sex. The HRQoL was evaluated with the SF-36 Health Survey. The scores of all the subscales of the SF-36, except vitality, were significantly lower in people with SCI than those of the controls’. The bodily pain subscale and physical component scores were found to be significantly higher in people with SCI using the Internet than the nonuser group with SCI (P