Perifosine and vitamin D combination induces apoptotic and non-apoptotic cell death in endometrial cancer cells

Endometrial cancer is the most common cancer of the female reproductive system. Combination treatment with specific agents has been widely used as a targeted therapy for cancer. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of varying concentrations of perifosine and vitamin D on the human endometrial cancer cell line (HEC-1A). HEC-1A cells were exposed to perifosine (10 μM, 30 μM), vitamin D (50 nM, 200 nM) and combinations of both for 48 h and 72 h. Monitoring of cell proliferation in a time-dependent manner was performed with the xCELLigence RTCA DP system. The levels of BCL2, BAX and P53 mRNA expression were examined using RT-qPCR. Apoptosis was determined using Annexin V, which were followed by flow cytometry analysis. Ultra-structural morphology of cells was analyzed by transmission electron microscopy (TEM) for 72 h. The anti-proliferative and apoptotic effects of the perifosine+vitamin D combination (30 μM + 200 nM at 48 h and 10 μM + 200 nM at 72 h) on HEC-1A cells were higher than in perifosine and vitamin D alone. It was observed that perifosine has increased the expression of BAX mRNA in HEC-1A cells in a dose-dependent manner. While perifosine+vitamin D combinations increased P53 mRNA expression in HEC-1A cells we did not find any significant change in BCL2, BAX mRNA expression levels. In TEM examinations of HEC-1A cells, perifosine appeared to lead autophagic cell death, whereas vitamin D caused paraptosis-like cell death and combination of perifosine+vitamin D caused apoptotic and non-apoptotic (paraptotic, autophagic and necrotic) cell death. Therefore, it is considered that the combination of both drugs in the treatment of endometrial cancer might be an alternative and effective treatment option through activating the apoptotic and non-apoptotic cell death mechanisms in cancer cells

Investigation of the effect of binding material and Thiobacillus thiooxidans on the heavy metals mobilization in the mine tailings

The total concentrations of arsenic (As), boron (B), cadmium (Cd), copper (Cu), manganese (Mn), lead (Pb), thallium (Tl) and zinc (Zn) in the mine tailings of an abandoned Pb-Zn mining site and an open boron mining site are investigated in this study. In addition, heavy metals' distributions in chemical binding forms and their mobilities with the presence of binding materials and acidic bacteria are examined. The amounts of sulfur and carbonate in the waste and binding materials are also determined according to the static method, in order to define the acid neutralization potential of the wastes. For mobilization studies, mine tailings are mixed with with leonardite and domestic solid waste compost in different ratios (10/0, 9.5/0.5, 9/1; 8/2). Independent from the binding materials, the mobilization effect of sulfur oxidizing Thiobacillus thiooxidans bacteria has been tested and evaluated. Experiments are conducted using a standard leach test EPA 1310B Extraction Procedure, and correlations between the parameters studied were statistically evaluated using the findings of SPSS 24. Although there is no statistically significant reduction in metals' mobilization with the use of leonardite and waste compost, it has been concluded that different binding agents may have different impacts due to the metal type. As a result, it is understood that metals mobility increases in the presence of Thiobacillus thiooxidans in the environment, and that the heavy metal mobility is directly proportional to the exchangeable and acid soluble fraction, followed by the reducible fraction and the amount of metals bound to the organic fractions

Resistance to macrolide, lincosamide and streptogramin antibiotics in Staphylococci isolated in Istanbul, Turkey

The purpose of this study was to investigate the prevalence and genetic mechanisms of erythromycin resistance in staphylococci. A total of 102 erythromycin resistant non-duplicate clinical isolates of staphylococci [78 coagulase negative stapylococci (CNS), 24 Staphylococcus aureus] were collected between October 2003 and August 2004 in Istanbul Faculty of Medicine in Turkey. The majority of the isolates were from blood and urine specimens. Antimicrobial susceptibilities were determined by the agar dilution procedure and the resistance phenotypes by the double disk induction test. A multiplex PCR was performed, using primers specific for erm(A), erm(B), erm(C), and msrA genes. Among the 78 CNS isolates, 57.8% expressed the MLSB-constitutive, 20.6% the MLSB-inducible, and 21.6% the MSB phenotypes. By PCR, 78.2% of these isolates harbored the erm(C) gene, 8.9% erm(A), 6.4% erm(B), and 11.5% msrA genes. In S. aureus, the constitutive MLSB (58.3%) was more common than the inducible phenotype (20.8%). erm(A) was detected in 50% and erm(C) in 62.5% of the isolates, while 37.5% contained both erm(A) and erm(Q. erm(C)-associated macrolide resistance was the most prevalent in CNS, while erm(C) and erm(A, Q was the most prevalent in S. aureus

Catheter-associated urinary tract infections in intensive care units at a university hospital in Turkey

In this study, urinary catheter utilization rates, the causative agents for catheter-associated urinary tract infection (CAUTI) and their antimicrobial susceptibilities in intensive care units (ICUs) in 2009 were investigated at Gazi university hospital. We aimed to determine the causative agents and risk factors for CAUTIs, and antimicrobial susceptibilities of the pathogens; and also sensitivities of Candida spp. to antifungal agents with Microdilution and E-test. The most common etiological agents of CAUTIs were Candida spp. (34.7%). The most frequently isolated Candida spp. was C.albicans  (52.4%). All C. albicans spp. were sensitive to fluconazole. Microdilution, used as a reference method to determine the sensitivity to antifungal agents, was compared with E test. E test was found to be sufficient to analyze sensitivity to amphotericin B, caspofungin, fluconazole and voriconazole, but inappropriate for itraconazole. E.coli and Klebsiella spp. were found to be causative agents for CAUTI in 20.6% and 9.9% of cases respectively. Pseudomonas spp. and Acinetobacter spp.  were isolated in 14% and 8.2% of the cases, respectively. All E.coli and Klebsiella strains were found sensitive to carbapenems. Carbapenem sensitivity was found in 47.1% and 30% of the cases infected with Pseudomonas and  Acinetobacter  strains, respectively. According to our results, fluconazole therapy seems to be an appropriate choice for the treatment of CAUTIs caused by  C.albicans. Third and fourth generation cephalosporins should not be used for empirical treatment because of the high prevalence of extended spectrum beta-lactamase production among E.coli and Klebsiella isolates.

An unusual dual hypersensitivity reaction to moxifloxacin in a patient

Both immediate and nonimmediate type hypersensitivity reactions (HRs) with a single dose of quinolone in the same patient have not been previously reported. A 47-year-old female patient referred to us because of the history of a nonimmediate type HR to radio contrast agent and immediate type HR to clarithromycin. She experienced anaphylaxis in minutes after the second dose of 50 mg when she was provocated with moxifloxacin. She was treated immediately with epinephrine, fluid replacement and methylprednisole and pheniramine. On the following day she came with macular eruptions, and she was treated with methylprednisolone. The positive patch test performed with moxifloxacin as well as the lymphocyte transformation test proved the T-cell mediated HR. In order to prove the immediate type HR, basophil activation test was performed but was found negative. This case report presents for the first time the 2 different types of HRs in a patient with a test dose of quinolone

DNA-damage and cell cycle arrest initiated anti-cancer potency of super tiny carbon dots on MCF7 cell line

While carbon-based materials have spearheaded numerous breakthroughs in biomedicine, they also have procreated many logical concerns on their overall toxicity. Carbon dots (CDs) as a respectively new member have been extensively explored in nucleus directed delivery and bioimaging due to their intrinsic fluorescence properties coupled with their small size and surface properties. Although various in vitro/in vivo studies have shown that CDs are mostly biocompatible, sufficient information is lacking regarding genotoxicity of them and underlying mechanisms. This study aims to analyze the real-time cytotoxicity of super tiny CDs (2.05 +/- 0.22 nm) on human breast cancer cells (MCF7) and human primary dermal fibroblast cell cultures (HDFa) by xCELLigence analysis system for further evaluating their genotoxicity and clastogenicity to evaluate the anti-tumor potential of CDs on breast adenocarcinoma. As combined with flow cytometry studies, comet assay and cytokinesis-block micronucleus assay suggest that the CDs can penetrate to the cell nuclei, interact with the genetic material, and explode DNA damage and G0/G1 phase arrest in cancer cells even at very low concentrations (0.025 ppm) which provide a strong foundation for the design of potentially promising CD-based functional nanomaterials for DNA-damage induced treatment in cancer therapy

Interleulen-10 is increased in successful drug desensitization regardless of the hypersensitivity reaction type

Background: Little is known about the mechanism of desensitization in hypersensitivity drug reactions

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A ComprehenSive Study Including the Latest Quinolone Gemifloxacin

Purpose: Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. Methods: We studied 54 patients (mean age 42.31 +/- 10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. Results: The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. Conclusions: These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones