Ethionamide boosters: synthesis, biological activity, and structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors.

We report in this article an extensive structure-activity relationships (SAR) study with 58 thiophen-2-yl-1,2,4-oxadiazoles as inhibitors of EthR, a transcriptional regulator controling ethionamide bioactivation in Mycobacterium tuberculosis. We explored the replacement of two key fragments of the starting lead BDM31343. We investigated the potency of all analogues to boost subactive doses of ethionamide on a phenotypic assay involving M. tuberculosis infected macrophages and then ascertained the mode of action of the most active compounds using a functional target-based surface plasmon resonance assay. This process revealed that introduction of 4,4,4-trifluorobutyryl chain instead of cyanoacetyl group was crucial for intracellular activity. Replacement of 1,4-piperidyl by (R)-1,3-pyrrolidyl scaffold did not enhance activity but led to improved pharmacokinetic properties. Furthermore, the crystal structures of ligand-EthR complexes were consistent with the observed SAR. In conclusion, we identified EthR inhibitors that boost antibacterial activity of ethionamide with nanomolar potency while improving solubility and metabolic stability.

The prevalence of root dilacerations in a Turkish population

Objectives: The aim of this study was to determine the prevalence of root dilaceration in a Turkish dental patientpopulation with respect to sexes and dental localization in relation between sex and this anomaly.Study Design: A retrospective study was performed using periapical radiography of 2,124 patients ranging in agefrom 15 to 65. All data (age, sex and systemic disease or syndrome) was obtained from the files. These patientswere analyzed for root dilaceration. Descriptive characteristics of sexes, jaws, and dental localization were recorded.The Pearson chi-squared test was used.Results: Of 2,251 patients, 214 (9.5%) had root dilaceration. Root dilacerations were determined in 276 (4.3%)of 6386 teeth belong to 2251 patients. Anomalies were found in 9.8% of males compared with 9.3% of females.However, this difference was not statistically significant (p>0.05). Root dilacerations were similarly distributedbetween maxilla and mandible. The most frequently root dilacerated teeth were found to be mandibular third molars(12.8%), followed by maxillary third molars (7.4%), maxillary first molars (6.7%). Root dilaceration was notdetected in maxillary central incisors, mandibular central incisors and mandibular lateral incisors.Conclusion: According to our results, root dilaceration is an uncommon developmental anomaly which mostlyoccurs in the posterior teeth that is not also possible to have trauma. The radiographic diagnosis of this anomalyis important before surgery and orthodontics treatment, but firstly endodontic treatment (AU)

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The prevalence of root dilacerations in a Turkish population.

OBJECTIVES: The aim of this study was to determine the prevalence of root dilaceration in a Turkish dental patient population, considering factors such as dental localization and the relationship between the sexes in this anomaly. STUDY DESIGN: A retrospective study was performed using periapical radiography of 2,124 patients, who ranged in age from 15 to 65 years old. All data (age, sex and systemic disease or syndrome) were obtained from the patient files and analyzed for root dilaceration. Descriptive characteristics of sexes, jaws, and dental localization were recorded. The Pearson chi-squared test was used. RESULTS: Of the 2,251 patients, 214 (9.5%) were found to have root dilaceration. Root dilacerations were determined in 276 (4.3%) of 6386 teeth, belonging to a total of 2251 patients. Anomalies were found in 9.8% of males, compared with 9.3% of females, a difference that was not statistically significant (p>0.05). Root dilacerations were distributed fairly evenly between the maxilla and mandible. The most frequently root dilacerated teeth were found to be mandibular third molars (12.8%), followed by maxillary third molars (7.4%), and maxillary first molars (6.7%). Root dilaceration was not detected in maxillary central incisors, mandibular central incisors or mandibular lateral incisors. CONCLUSION: root dilaceration is an uncommon developmental anomaly which occurs mostly in the posterior teeth, which are not prone to suffer trauma. The radiographic diagnosis of this anomaly is important before surgery, and especially before endodontic treatment or orthodontic treatment.

Simple GC-FID method development and validation for determination of alpha-tocopherol (vitamin E) in human plasma.

This paper describes the development and validation of a novel GC-FID method for the determination of alpha-tocopherol concentration in human plasma which does not requires derivatization. The standard solutions and the plasma working solutions were prepared in absolute ethanol. To determine the concentration of alpha-tocopherol in human plasma, an aliquot of the plasma sample was deproteinized with ethanol. alpha-tocopherol was extracted with a mixture of hexane and dichloromethane (9:1). GC separation was performed using a HP-5 capillary column. Nitrogen was used as carrier gas at a flow-rate of 2 ml min(-1). Calibration curves were linear over the concentration range 1-30 microg ml(-1) (for standard solutions and solutions without endogenous alpha-tocopherol in plasma) and 5-34 microg ml(-1) (for solutions with endogenous alpha-tocopherol in plasma). Absolute recovery, precision, sensitivity and accuracy assays were carried out. The analytical recovery of alpha-tocopherol from plasma averaged 97.44%. The limit of quantification (LOQ) and the limit of detection (LOD) of method for standard samples were 0.35 microg.ml(-1) and 0.30 microg.ml(-1), respectively. Within-day and between-day precision, expressed as the relative standard deviation (RSD) were less than 4%, and accuracy (relative error) was better than 8%. This novel method, developed and validated in our laboratory, could be successfully applied to the in-vivo determination of alpha-tocopherol. The endogenous alpha-tocopherol amounts in blood of twelve healthy volunteers with no vitamin drug usage were measured with this method.