Human endometrial cell coculture reduces the endocrine disruptor toxicity on mouse embryo development

BACKGROUNDS: Previous studies suggested that endocrine disruptors (ED) are toxic on preimplantation embryos and inhibit development of embryos in vitro culture. However, information about the toxicity of endocrine disruptors on preimplantation development of embryo in human reproductive environment is lacking. METHODS: Bisphenol A (BPA) and Aroclor 1254 (polychlorinated biphenyls) were used as endocrine disruptors in this study. Mouse 2-cell embryos were cultured in medium alone or vehicle or co-cultured with human endometrial epithelial layers in increasing ED concentrations. RESULTS: At 72 hours the percentage of normal blastocyst were decreased by ED in a dose-dependent manner while the co-culture system significantly enhanced the rate and reduced the toxicity of endocrine disruptors on the embryonic development in vitro. CONCLUSIONS: In conclusion, although EDs have the toxic effect on embryo development, the co-culture with human endometrial cell reduced the preimplantation embryo from it thereby making human reproductive environment protective to preimplantation embryo from the toxicity of endocrine disruptors

Identification of new CYP2C19 variants exhibiting decreased enzyme activity in the metabolism of S-mephenytoin and omeprazole. Drug Metab

ABSTRACT: Although many cases of interindividual variation in the metabolism of CYP2C19 drugs are explained by the CYP2C19*2, *3, and *17, a wide range of metabolic variation still occurs in people who do not carry these genetic variants. The objectives of this study were to identify new genetic variants and to characterize functional consequences of these variants in metabolism of CYP2C19 substrates. In total, 21 single-nucleotide polymorphisms including three new coding variants, V394M, E405K, and D256N, were identified by direct DNA sequencing in 50 randomly selected subjects and in individuals who exhibited an outlier phenotype response in the omeprazole study. Recombinant proteins produced from the coding variants V394M, E405K, and D256N were prepared by using an Escherichia coli expression system and purified. Metabolism of S-mephenytoin and omeprazole by V394M was comparable with that of the wild-type protein. E405K showed a moderate decrease in metabolism of the substrates. However, D256N exhibited a significantly decreased activity in S-mephenytoin metabolism, resulting in 50 and 76% decreases in V max and intrinsic clearance, respectively, compared with the wild type. This variant also exhibited a significant decrease in omeprazole metabolism in vivo. CYP2C19 D256N and E405K were assigned as CYP2C19*26 and *2D, respectively, by the Cytochrome P450 Nomenclature Committee. In summary, this report characterizes the allele frequency and haplotype distribution of CYP2C19 in a Korean population and provides functional analysis of new coding variants of the CYP2C19 gene. Our findings suggest that individuals carrying CYP2C19*26 would have lower activity for metabolizing CYP2C19 substrate drugs

Complete Atrioventricular Block Secondary to Bortezomib Use in Multiple Myeloma

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared

Randomized Comparison of Four-Times-Daily versus Once-Daily Intravenous Busulfan in Conditioning Therapy for Hematopoietic Cell Transplantation

AbstractSixty patients were randomized to receive intravenous busulfan (iBU) either as 0.8 mg/kg, over 2 hours 4 times a day (BU4 arm) or 3.2 mg/kg, over 3 hours once a day (BU1 arm) in conditioning therapy for hematopoietic cell transplantation. The complete pharmacokinetic parameters for the first busulfan dose were obtained from all patients and were comparable between the 2 arms: for the BU4 and BU1 groups, elimination half-life (mean ± SD) was 2.75 ± 0.22 versus 2.83 ± 0.21 hours, estimated daily AUC was 6058.0 ± 1091.9 versus 6475.5 ± 1099.4 μM·min per day, and clearance was 2.05 ± 0.36 versus 1.91 ± 0.31 mL/min/kg, respectively. Times to engraftment after transplantation were similar between the 2 arms. No significant differences were evident in the occurrence of acute graft-versus-host disease (aGVHD) and hepatic veno-occlusion disease (VOD). Moreover, other toxicities observed within 100 days after transplantation were not significantly different between the 2 arms. The cumulative incidence of nonrelapse mortality was 20.8% in BU4 arm and 13.3% in BU1 arm. In conclusion, our randomized study demonstrates that the pharmacokinetic profiles and posttransplant complications are similar for once-daily iBU and traditional 4-times-daily iBU

Relationships between non-acoustic factors and subjective reactions to floor impact noise in apartment buildings

The aim of this study was to provide an understanding of how residents in apartment buildings perceive and react to impact sounds coming from the upstairs neighbours' dwellings. Based on existing theoretical and empirical studies on environmental noise, a conceptual model was developed to explain relationships among noise annoyance and non-acoustic factors. The model was then tested using structural equation modelling with survey data from residents living in apartment buildings (N = 487). The findings showed that the conceptual model was consistent with other models developed for environmental noises. The results indicated that annoyance induced by floor impact noise was associated with perceived disturbance, coping, and self-reported health complaints. Noise sensitivity had a direct impact on perceived disturbance and an indirect impact on annoyance, and moderating variables affected the non-acoustic factors. Exposure to footstep noises increased the impact size of noise sensitivity to disturbance. Predictability, marital status, and house ownership were found to influence the relationship between attitudes towards authorities and coping. In addition, a negative attitude towards neighbours (i.e., the noise source) moderated the positive relationship between annoyance and coping

A Case of Malignant Pericardial Mesothelioma With Constrictive Pericarditis Physiology Misdiagnosed as Pericardial Metastatic Cancer

Malignant pericardial mesothelioma is a rare and progressive cardiac tumor. There is no established standard treatment and the prognosis is poor. Most patients were retrospectively diagnosed from surgery or autopsy due to absence of specific clinical manifestation. Most patients with pericardial mesothelioma have demonstrated constrictive physiology on echocardiography or cardiac catheterization. Therefore, pericardial mesothelioma was often misdiagnosed as other causes of constrictive pericarditis. We report a case of primary pericardial mesothelioma misdiagnosed as pericardial metastasis of unknown origin

Discovery of a novel allelic variant of CYP2C8, CYP2C8∗11, in asian populations and its clinical effect on the rosiglitazone disposition

ABSTRACT: The objectives of this study were to identify the genetic variants of CYP2C8, analyze CYP2C8 single nucleotide polymorphisms (SNPs), and characterize their functional consequences in the CYP2C8 substrate drug rosiglitazone in humans. The direct full sequencing of CYP2C8 genomic DNA was performed in a Korean population (n ‫؍‬ 50). A total of 17 CYP2C8 variants including a novel coding variant (E274Stop) were identified. The novel CYP2C8 E274Stop variant was assigned as CYP2C8*11 by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Seventeen SNPs were used to characterize linkage disequilibrium, haplotype structures, and haplotype tagging SNPs. Genotyping for CYP2C8*11 in an extended set of Koreans (n ‫؍‬ 400), whites (n ‫؍‬ 100), Han Chinese (n ‫؍‬ 348), Vietnamese (n ‫؍‬ 100), and African Americans (n ‫؍‬ 93) was performed by a newly developed pyrosequencing method. The frequency of CYP2C8*11 was 0.3% in Koreans, 1% in Vietnamese, and 0.14% in Chinese. However, none of the whites or African Americans contained the CYP2C8*11 allele. Subjects with CYP2C8*1/*11 exhibited higher plasma concentration-time profiles of rosiglitazone than those of nine control subjects carrying CYP2C8*1/*1. The area under the concentrationtime curve and peak plasma concentration of rosiglitazone in individuals carrying CYP2C8*1/*11 (n ‫؍‬ 5) were 54 and 34% higher than the mean values observed in the control subjects carrying CYP2C8*1/*1 (P ‫؍‬ 0.015 and P ‫؍‬ 0.025, respectively). In summary, this is the first report to characterize the allele frequency and haplotype distribution of CYP2C8 in a Korean population, and it provides functional analysis of a new variant CYP2C8*11. Our findings suggest that individuals carrying CYP2C8*11, a null allele found in Asians only, may have lower activity for metabolizing CYP2C8 substrate drugs

Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement

The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm3 was the cutoff value. The low MTV group (<220 cm3) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm3) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP

Etiquette for medical students email communication with faculty members: a single-institution study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Email is widely used as a means of communication between faculty members and students in medical education because of its practical and educational advantages. However, because of the distinctive nature of medical education, students inappropriate email etiquette may adversely affect their learning as well as faculty members perception of them. Little data on medical students competency in professional email writing is available; therefore, this study explored the strengths and weaknesses of medical students email etiquette and factors that contribute to professional email writing. Methods A total of 210 emails from four faculty members at Seoul National University College of Medicine were collected. An evaluation criteria and a scoring rubric were developed based on the various email-writing guidelines. The rubric comprised 10 items, including nine items for evaluation related to the email components and one item for the assessment of global impression of politeness. Three evaluators independently assessed all emails according to the criteria. Results Students were identified as being 61.0 % male and 52.8 % were in the undergraduate-entry program. The sum of each component score was 62.21 out of 100 and the mean value for global impression was 2.6 out of 4. The results demonstrated that students email etiquettes remained low-to-mediocre for most criteria, except for readability and honorifics. Three criteria, salutation (r=0.668), closing (r=0.653), and sign-off (r=0.646), showed a strong positive correlation with the global impression of politeness. Whether a student entered a graduate-entry program or an undergraduate-entry program significantly contributed to professional email writing after other variables were controlled. Conclusions Although students in the graduate-entry program demonstrated a relatively superior level of email etiquette, the majority of medical students did not write emails professionally. Educating all medical students in email etiquette may well contribute to the improvement of student–faculty relationships as well as their email writing

Vasorelaxing Activity of Ulmus davidiana Ethanol Extracts in Rats: Activation of Endothelial Nitric Oxide Synthase

Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD (10~100µg/ml) did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of 0.1~10µg/ml with an ED50 value of 2µg/ml. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high K+ and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium