Fusaric acid inhibits cell proliferation and downregulates expressions of toll-like receptors pathway genes in Ishikawa endometrial cancer cells.

OBJECTIVE: Fusaric acid is a derivative of picolinic acid produced by some Fusarium species. In this study, we aimed to determine the mRNA expression and antiproliferative effects of fusaric acid in Ishikawa endometrium cancer cells in signal pathway genes associated with Toll-like receptors (TLRs). The effect of fusaric acid on the viability of Ishikawa cells was evaluated using XTT. PATIENTS AND METHODS: After total RNA was isolated from control and dose group cells, cDNA synthesis was performed, and mRNA expression changes of genes involved in the Toll-like signaling pathway were evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: The decrease in viability of Ishikawa cells was observed in a time- and dose-dependent manner. The inhibitory concentration (IC50) dose of fusaric acid at the 72nd hour in the Ishikawa cell line was 142.81 µM. When the dose group treated with 125 µM fusaric acid at the 72nd hour was compared with the control group, significantly decreased toll-like receptor 1 (TLR1), TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, and Myeloid differentiation primary response protein 88 (MYD88) gene expressions were observed. CONCLUSIONS: Fusaric acid inhibits cell proliferation and downregulates Toll-like receptors pathway gene expression in Ishikawa endometrial cancer cells.

Morphological changes of the retinal layers in the central macula in children with anisometropic amblyopia.

PURPOSE: The goal of this study was to evaluate the morphological characteristics of the retinal layers in the central macula in children with anisometropic amblyopia. METHODS: This comparative, observational, prospective study included 28 patients who were diagnosed with anisometropic amblyopia and 30 age- and sex-matched healthy controls. All children were evaluated using the automatic calculation software system available on spectral-domain optical coherence tomography (SD-OCT) for automated segmentation of the macula. RESULTS: Of the included patients, 18 (64.3%) were male and 10 (35.7%) were female, with a mean age of 10.3±3.4 years. Mean spherical equivalent and best-corrected visual acuity (BCVA) were 4.13±1.95 diopters and 0.707±0.36 logMAR, respectively. The mean axial length was significantly lower in amblyopic eyes compared to fellow eyes (22.1±0.34mm vs. 23.3±0.42mm, P<0.0001), and control eyes (22.1±0.34mm vs. 23.1±0.40mm, P<0.0001). The mean thickness of the outer nuclear layer was significantly lower in amblyopic eyes compared to fellow eyes (79.8±11.9µm vs. 86.8±7.9µm, P=0.007), and healthy controls (79.8±11.9µm vs. 87.4±10.5µm, P=0.012). CONCLUSION: The results of this study showed that there are quantitative differences in retinal microstructures of the macula in eyes with anisometropic amblyopia compared to fellow eyes and healthy controls. These findings suggest that anisometropic amblyopia may result in abnormal development of macular structure in the inner retinal layer. A detailed analysis of retinal layers may be able to provide a guide to the depth of amblyopia and visual prognosis.

Synthesis and Cytotoxic Evaluation of Kojic Acid Derivatives with Inhibitory Activity on Melanogenesis in Human Melanoma Cells.

BACKGROUND: Malignant melanoma is an agressive tumour related to the overproduction of melanin, which provides colors of skin, eyes and hair. In addition contributing to the risk of malignant melanoma, abnormal production of melanin has many drawbacks, including hyperpigmentation, post-inflammatory pigmentation, melasma and skin aging. Kojic acid is currently employed in order to lighten skin pigmentation and provide depigmentation. OBJECTIVE: Mannich bases of kojic acid with the structure of 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/ methyl/morpholinomethyl/piperidinylmethyl/pyrrolidinylmethyl-4H-pyran-4-one (compounds 1-23) were synthesized by the reaction of kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in the presence of formaline. To obtain the cyclic amine (morpholine, piperidine and pyrrolidine) derivatives, nucleophilic substitutions were carried out. METHOD: Cytotoxic effects on A375 human malignant melanoma, HGF-1 human gingival fibroblasts, and MRC-5 human lung cell lines were investigated by sulphorhodamine B assay. Control agents were vemurafenib, dacarbazine, temozolomide, and lenalidomide, which are the commercially available drugs for the treatment of malignant melanoma. RESULTS: Cytotoxic action against melanoma cells was significantly more efficacious (IC50: 11.26-68.58 µM) than the FDA-approved drugs except for vemurafenib. Fourteen of the compounds were proven to have higher IC50 values for the non-cancerous cell lines, HGF-1, and MRC-5 cells. Melanogenesis inhibition assay was performed to observe the ability of the drugs to inhibit melanin production and certain compounds were shown to be capable of actively inhibiting melanin production in melanoma cells. CONCLUSION: Mannich bases of kojic acid derivatives may be promising therapeutic agents, since some have more potent effects on melanoma cells than previously FDA-approved drugs for the treatment of malignant melanoma.

Comparison of four methods for rapid identification of Staphylococcus aureus directly from BACTEC 9240 blood culture system.

PURPOSE: Differentiation of Staphylococcus aureus (S. aureus) from coagulase-negative staphylococci is very important in blood stream infections. Identification of S. aureus and coagulase-negative staphylococci (CoNS) from blood cultures takes generally 18-24 h after positive signaling on continuously monitored automated blood culture system. In this study, we evaluated the performance of tube coagulase test (TCT), slide agglutination test (Dry Spot Staphytect Plus), conventional polymerase chain reaction (PCR) and LightCycler Staphylococcus MGrade kit directly from blood culture bottles to achieve rapid identification of S. aureus by using the BACTEC 9240 blood culture system. MATERIALS AND METHODS: A total of 129 BACTEC 9240 bottles growing gram-positive cocci suggesting Staphylococci were tested directly from blood culture broths (BCBs) with TCT, Dry Spot Staphytect Plus, conventional PCR and LightCycler Staphylococcus MGrade kit for rapid identification of S. aureus. RESULTS: The sensitivities of the tests were 99, 68, 99 and 100%, respectively. CONCLUSION: Our results suggested that 2 h TCT was found to be simple and inexpensive method for the rapid identification of S. aureus directly from positive blood cultures.

Turkish female immigrants' intentions to participate in preconception carrier screening for hemoglobinopathies in the Netherlands: an empirical study.

BACKGROUND: Preconception carrier screening for hemoglobinopathies (HbPs) is debated in the Netherlands. OBJECTIVES: Intentions to participate in preconception carrier screening for HbPs as well as informed reproductive options were assessed in 109 Turkish female immigrants. METHOD: Participants completed a structured questionnaire. RESULTS: 83.5% of 109 Turkish female immigrants intended to participate in preconception carrier screening. Intention to participate was related to the desire to reduce uncertainty about having offspring affected by HbPs, but not with socio-demographic variables, risk-estimation and worrying. If the tests concerning carrier status for HbPs were confirmative for both partners, 36.3% (n = 33) of the women with the intention of preconception carrier screening would refrain from getting children of their own, including 14.3% (n = 13) opting for adoption, 37.4% (n = 34) would decide to become pregnant and to opt for prenatal testing on HbPs. Finally, among 37.4% of the women opting for prenatal testing, 30.3% (n = 10) would terminate an affected pregnancy, 18.2% (n = 6) not and 51.5% (n = 17) could not decide (1 missing value). CONCLUSION: A large majority of Turkish female immigrants would participate in preconception carrier screening for HbPs.

Amido-3-hydroxypyridin-4-ones as iron(III) ligands.

The synthesis and physicochemical properties of a range of 2- and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pK(a) values than 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pK(a) values of the 3-hydroxy group in 1-nonsubstituted pyridinones are dramatically lower than those of the corresponding 1-alkyl analogues, indicating that a strong hydrogen bond exists between the 2-amido function and the 3-oxygen anion, which stabilises the anion. As a result of the decreased competition with protons, the pFe(3+) values of this group of molecules are higher than that of deferiprone. The distribution coefficients of these molecules are also increased despite the lack of a hydrophobic 1-alkyl substituent and this is ascribed to the intramolecular hydrogen bond. X-ray diffraction studies confirm the existence of the intramolecular hydrogen bond.

Synthesis of some oxime ether derivatives of 1-(2-naphthyl)-2-(1,2,4-triazol-1-yl)ethanone and their anticonvulsant and antimicrobial activities.

In this study, oxime and oxime ether derivatives of [1-(2-naphthyl)-2-(1,2,4-triazol-1-yl)ethanone] were prepared as potential anticonvulsant and antimicrobial compounds. The oxime was synthesized by the reaction of ketone and hydroxylamine hydrochloride. O-Alkylation of the oxime by various alkyl halides gave the oxime ether derivatives. Anticonvulsant activity of the compounds was determined by maximal electroshock and subcutaneous metrazole tests in mice and rats according to procedures of the Anticonvulsant Screening Program of National Institutes of Health. Neurotoxicity was determined by the rotorod test in mice and the positional sense test, gait and stance test in rats. In addition to anticonvulsant tests, all compounds were also evaluated against the following microorganisms: S. aureus, E. coli, P. aeruginosa, E. faecalis, C. albicans, C. parapsilosis, and C. krusei using microdilution broth method for possible antibacterial and antifungal activities. Although most of the O-alkyl substituted oxime ethers exhibited both anticonvulsant and antimicrobial activities, the O-arylalkyl substituted compounds were found to be inactive in both screening paradigms.

A rare case of HSV-2 encephalitis.

Herpes simplex viruses (HSV), and especially HSV-1, are the most common cause of acute, sporadic viral encephalitis. HSV-2 is an uncommon cause of encephalitis. We report a rare case of HSV-2 encephalitis that was free of genital lesions. In terms of the patient's case history, she had a Cesarean section four months before, herpes labialis 30 days before, varicella zoster 20 days before. We discuss the possibility that postpartum stress may be one of the factors in this case.

Seroprevalence of antibodies to legionella pneumophila in hemodialysis patients.

Patients with chronic renal failure are at increased risk for infections because of impaired cellular immunity. This study was designed to determine the prevalence of antibodies to Legionella pneumophila serogroups 1 to 6 and to evaluate the possible risk factors for Legionnaires' disease in hemodialysis patients. Serum samples to be screened for antibodies against L pneumophila and risk factor data were collected from 252 hemodialysis patients. The overall prevalence of L pneumophila antibodies in hemodialysis patients was found to be 5.16% There was no statistically significant difference between L pneumophila seropositivity and potential risk factors. Further studies are needed to determine possible risk factors for Legionnaires' disease in hemodialysis patients.