Olea europaea Leaf Extract Improves the Efficacy of Temozolomide Therapy by Inducing MGMT Methylation and Reducing P53 Expression in Glioblastoma

Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation. Exposure to 1 mg/mL OLE caused a significant induction of CpG island methylation in the MGMT gene using Methyl quantitative PCR assay (P < 0.001). In WST-1 analysis, the use of 350 µM TMZ plus 1 mg/mL OLE significantly increased the TMZ response of MGMT unmethylated cells (P = 0.003). Using the comet assay, the impact of 1 mg/mL OLE plus 350 µM TMZ on the formation of DNA strand breaks was significantly higher than that of 450 µM TMZ alone (P < 0.001) and Western blot analysis revealed that, when cells are treated with 1-mg/mL OLE, the total p53 protein levels tended to decrease. The results presented in this study uniquely demonstrated that OLE synergistically increased the TMZ response of GBM tumors by regulating MGMT gene methylation and p53 expression. However, further studies to validate our findings are required.     

Protective effects of catechin and quercetin on antioxidant status, lipid peroxidation and testis-histoarchitecture induced by chlorpyrifos in male rats

Mature male Wistar rats were given chlorpyrifos (5.4 mg/kg, 1/25 of the oral LD(50)), catechin (20 mg/kg),quercetin (20 mg/kg), catechin plus chlorpyrifos, and quercetin plus chlorpyrifos daily via gavage for four weeks. No statistical differences were found in the catechin-only and quercetin-only groups compared with the control group. By the end of the fourth week, chlorpyrifos alone increased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), while decreased glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities compared with the control group in rat testis tissues. In the catechin-plus-chlorpyrifos and quercetin-plus-chlorpyrifos groups, there were statistically significantly decreased MDA levels, SOD and CAT activities, while increased GPx and GST activities compared with the chlorpyrifos-only group. Light microscopic analyses revealed that chlorpyrifos-only induced numerous histopathological changes in the testis tissues. Milder pathological alterations were observed in rats catechin-plus-chlorpyrifos, and quercetin-plus-chlorpyrifos. Thus, it appears that catechin and quercetin ameliorate chlorpyrifos induced toxicity except histopathological changes in rat testis tissues.     

Ethnobotanical research of medicinal plants in Mihalgazi (Eskişehir,Turkey)

Context: Human beings have long utilized plants for medicinal purposes. Investigation of these plants has led to the discovery of several modern drugs.

Objective: This paper documents and evaluates traditional knowledge on medicinal plants used by the local people of Mihalgazi district of Eski?ehir, Turkey.

Materials and methods: Six villages of the study area were visited between February 2014 and April 2015 to collect the data. One hundred and eighty-nine informants were interviewed by the survey method and face to face semi-structured interviews. Taxonomic identification, the most commonly used plant parts, preparation and administration methods were evaluated. Ethnomedicinal data were analyzed quantitatively with relative importance (RI) and the informant consensus factor (FIC).

Results: This paper reported a total of 52 medicinal plants (37 wild, 15 cultivated) belonging to 34 families. Some uses of 22 plants were not found in the literature and are reported for the first time in this study. Furthermore, one of the plants, Calamagrostis arundinacea (L.) Roth (Poaceae), was reported for the first time as being used within the scope of traditional therapies.

Discussion and conclusion: This study recorded traditional knowledge on medicinal plants used in Mihalgazi, Turkey. This paper provides a basis for further investigations to discover efficient pharmaceuticals.     

Clinical outcomes and therapeutic options of bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli

This study was conducted to assess the clinical outcomes of bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. A total of 53 patients were included in the study. Forty-five patients (84.9%) received appropriate antibiotic therapy. Initial empirical treatment was appropriate in 12 patients, whereas the antibiotic was changed according to susceptibility results in the remaining 33 patients. Carbapenems were active against all strains and were the choice of therapy for 71.6% of patients. The 30-day mortality rate was 26.4%. The presence of diabetes mellitus and Intensive Care Unit stay at the time of bacteraemia were significantly associated with a poor outcome. The 'appropriateness' of the antibiotic regimen had no significant influence on survival.     

Prospective neurobiological effects of the aerial and root extracts and some pure compounds of randomly selected Scorzonera species

Context: Scorzonera L. species (Asteraceae) are edible and as medicinal plants are used for various purposed in folk medicine.

Objective: The methanol extracts of the aerial parts and roots from 27 Scorzonera taxa were investigated for their possible neurobiological effects.

Materials and methods: Inhibitory potential of the Scorzonera species was tested against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYRO) at 100?µg?mL^?1 using ELISA microtiter assay. Antioxidant activity of the extracts was tested with radical scavenging activity, metal-chelation capacity, ferric- (FRAP), and phosphomolibdenum-reducing antioxidant power (PRAP) assays. Chlorogenic acid, hyperoside, rutin, and scorzotomentosin-4-O-β-glucoside were also screened in the same manner. Total phenol and flavonoid quantification in the extracts were determined spectrophotometrically.

Results: The aerial parts of Scorzonera pisidica (40.25?±?0.74%) and chlorogenic acid (46.97?±?0.82%) displayed the highest TYRO inhibition, while the remaining samples showed only trivial inhibition against cholinesterases (2.08?±?1.35%–25.32?±?1.37%). The same extract of S. pisidica was revealed to be the most potent in scavenging of all three radicals and FRAP assay.

Discussion and conclusion: Out of 27 taxa, S. pisidica, in particular, may deserve further investigation for its neuroprotective potential.     

Substance Use Disorders in Men with Antisocial Personality Disorder: A Study in Turkish Sample

This study investigated the prevalence of substance use disorders (SUDs) and “substance of choice” in 500 male Turkish psychiatric outpatients manifesting a DSM-IV diagnosed antisocial personality disorder (APD) and a SUD diagnoses (the Structured Clinical Interview for DSM-IV). Lifetime SUDs were diagnosed in 86% of APD subjects. Alcohol, cannabis, and inhalant use disorders were the most frequent among substance use, 75.6%, 67.4%, and 35.6%, respectively. This sample's “substance of choice” differed from reported Western populations; a result which may be influenced by socio-cultural variations. The study's limitations are noted.     

A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia

The focus of this study was the systematic evaluation of the clinical effects of the extract of ginkgo biloba (EGb) as an adjunct to the atypical antipsychotic clozapine in the treatment of refractory schizophrenia. In a placebo-controlled study, 42 patients with chronic, treatment-resistant schizophrenia, who were maintained on optimal doses of clozapine, were administered either 120 mg/day of EGb (N=20) or placebo (N=22) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms were completed biweekly. The use of EGb as an adjunct to clozapine was effective in decreasing negative symptoms, but not positive and overall psychopathology symptoms. EGb produced a mean 7.9+/-7.0 point reduction in the total Scale for the Assessment of Negative Symptoms score compared with a mean 1.8+/-3.5 point reduction in the placebo group (P=0.034). These preliminary data suggested that EGb was found useful for enhancing the effect of clozapine on negative symptoms in patients with treatment-resistant schizophrenia.     

Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from Turkey with OXA-48-like carbapenemases and outer membrane protein loss

Treatment options are limited in infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, with carbapenems generally preferred. Disturbingly, however, carbapenem-resistant strains are emerging worldwide. Here we report two clinical isolates, one Escherichia coli and one Klebsiella pneumoniae, each with high-level carbapenem resistance (imipenem minimum inhibitory concentration of 32 microg/mL). They were isolated following imipenem therapy from two hospital patients who had received imipenem therapy in different regions of Turkey. Both isolates produced OXA-48-like carbapenemases, enzymes so far reported only from Turkey. Both isolates also had group 1 CTX-M-type ESBLs and had lost major outer membrane proteins. OXA-48-like carbapenemases appear to be scattered in Turkey and surveillance to determine their prevalence is warranted.     

Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships

In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl) imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5-substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized. The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 microg/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice.     

Thrombotic thrombocytopenic purpura associated with multiple myeloma

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathic disease. Associations with collagen vascular diseases, pregnancy, some drugs, surgical intervention, and infections are documented (known). Malignancy is also one of the known factors associated with thrombotic thrombocytopenic purpura. These malignancies are usually the disseminated solid organ tumors. Hematological malignancies constitute a rare association. Here, we present a patient with thrombotic thrombocytopenic purpura associated with multiple myeloma and discuss the pathogenesis. To our knowledge, this is the first case report of thrombotic thrombocytopenic purpura associated with multiple myeloma.