Two novel alleles HLA‐DRB1*11:150 and HLA‐DRB1*14:145 identified in Saudi individuals

Two new HLA‐ DRB1 alleles were identified by sequence‐based typing method (SBT) in 1100 participants in the Saudi Stem Cell Donor Registry. HLA‐DRB1*11:150 differs from HLA‐DRB1*11:01:01G by a single C to A substitution at nucleotide position 5580 in exon 2, resulting in an amino acid change from alanine to glutamic acid at position 74. HLA‐DRB1*14:145 differs from HLA‐DRB1*14:04 by a C to G substitution at nucleotide position 5511 in exon 2, resulting in an amino acid change from threonine to arginine at position 51.     

Undetected chronic obstructive pulmonary disease and asthma in people over 50 years with persistent cough

Background

Chronic obstructive pulmonary disease (COPD) and asthma are underdiagnosed in primary care.

Aim

To determine how often COPD or asthma are present in middle-aged and older patients who consult their GP for persistent cough.

Design of study

A cross-sectional study in 353 patients older than 50 years, visiting their GP for persistent cough and not known to have COPD or asthma.

Setting

General practice in the Netherlands.

Method

All participants underwent extensive diagnostic work-up, including symptoms, signs, spirometry, and body plethysmography. All results were studied by an expert panel to diagnose or exclude COPD and/or asthma. The reproducibility of the panel diagnosis was assessed by calculation of Cohen''s κ statistic in a sample of 41 participants.

Results

Of the 353 participants, 102 (29%, 95% confidence interval [CI] = 24 to 34%) were diagnosed with COPD. In 14 of these 102 participants, both COPD and asthma were diagnosed (4%, 95% CI = 2 to 7%). Asthma (without COPD) was diagnosed in 23 (7%, 95% CI = 4 to 10%) participants. Mean duration of cough was 93 days (median 40 days). The reproducibility of the expert panel was good (Cohen''s κ = 0.90).

Conclusion

In patients aged over 50 years who consult their GP for persistent cough, undetected COPD or asthma is frequently present.     

Incidence and correlates of cesarean section in a capital city of a middle-income country

OBJECTIVE: To determine the prevalence and correlates of cesarean deliveries (CS) in Beirut. METHODS: A cross-sectional study conducted on 18,837 consecutive infants born at nine hospitals from the National Collaborative Perinatal Neonatal Network (NCPNN). Stepwise Logistic Regression was performed to determine CS correlates. RESULTS: The rate of CS was 26.4% and correlated with socio-demographic, obstetrical and provider-related variables. Regression analysis identified age, paternal occupation, mode of payment, parity, birth weight, gestational age, multiple pregnancies, adequate prenatal care, complications during pregnancy, body mass index at delivery, hospital teaching status, day of the week and year of delivery to be significant correlates of CS. CONCLUSION: This study shows an increased CS rate in a middle-income country, and identifies the correlates of women delivering by the abdominal route. These correlates may be used for effective reduction policies in the future.     

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD)

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were collected in the clinic and frozen until analysis. Blood samples were obtained by phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD concentrations were determined by high-performance liquid chromatography in the Clinical Laboratory at the Cincinnati Children's Hospital Medical Center. Linear regression analysis was used to evaluate correlations. Saliva and blood specimens were collected from 28 epilepsy patients, but usable samples were obtained from only 23. The mean serum MHD concentration was 23.9 +/- 10.0 microg/mL, and the mean saliva concentration was 23.1 +/- 10.1 microg/mL. There was a significant positive correlation between the serum and saliva concentrations: saliva (y) = 0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD concentration ratio was 0.96 +/- 0.15. The results of the current study indicate that the relationship between freely flowing (unstimulated) saliva and serum concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation of saliva MHD monitoring is that individuals who have difficulty producing small quantities of saliva or who have viscous saliva should generally be avoided for this type of monitoring. It is also recommended to avoid saliva collection within 8 hours after OXC dosing to allow complete absorption and transformation of the parent drug.     

Curcumin for the Prevention of Epithelial-Mesenchymal Transition in Endoxifen-Treated MCF-7 Breast Cancer Cells

Background: Curcumin was shown to reduce epithelial-mesenchymal transition (EMT) markers in previous shortterm studies. This study was aimed to investigate the potential of curcumin in the prevention of EMT activation inMCF-7 cells induced by endoxifen. Methods: MCF-7 breast cancer cells were treated with Endoxifen 1000 nM+betaestradiol1 nM with or without curcumin (8.5μM or 17 μM). Cells treated with dimethyl sulfoxide (DMSO) 0.001%were used as negative control. After 8 weeks of continuous treatment, the cells were counted, analyzed for mRNAE-cadherin, vimentin, TGF-β expression, total reactive oxygen species (ROS) and observed for morphological changesusing confocal microscope and transmission electron microscope. Result: MCF-7 cell viability was increased inendoxifen + β-estradiol group. Cell viability was significantly decreased in curcumin 17 μM, but not in curcumin8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNAexpressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. Theresults showed that administration of curcumin in all the dose administered were incapable improving the expressionsof vimentin, TGF-β1 and E-cadherin. There was a decrease in ROS concentration in curcumin treated cells (8.5 μM)while in curcumin 17 μM, ROS concentration was increased. Morphological observation using confocal microscopeand TEM showed the presence of mesenchymal cells and adherens junction. Conclusion: endoxifen treatments foreight weeks resulted in upregulation of EMT markers and changes in morphology of MCF-7 breast cancer cells. Theaddition of curcumin did not prevent the activation of EMT.     

Outcomes following treatment for patients with cranial nerve involvement from nasopharyngeal cancer

Introduction: Patients with locally advanced nasopharyngeal carcinoma (NPC) commonly present with cranial nerve (CN) involvement, which can cause significant morbidity. We aimed to characterise the pattern of involvement and outcomes of these patients, as well as determine if these differed according to the mode of diagnosis. Methods: Patients were included if they had non‐distant metastatic NPC, presented with CN involvement and completed radiotherapy treatment between 2002 and 2008. The clinical response was categorised as complete response, partial response, stable or progressive disease. The radiological response was assessed using the Response Evaluation Criteria in Solid Tumors criteria. The loco‐regional control and disease‐free survival rates were estimated with the Kaplan–Meier method. Results: Forty‐seven patients fulfilled the inclusion criteria. CN lesions were diagnosed on clinical examination in 15% of patients, radiologically in 40% and both clinically and radiologically in 45% of patients. A complete or partial response of the CN lesions was seen clinically in 82% and radiologically in 95% of patients. The 3‐year local relapse free survival was 64.3%, distant metastasis‐free survival was 46.1% and overall survival was 82.8%. There were no differences in outcomes between patients with clinically versus radiologically detected CN lesions. Conclusion: Most of these patients are likely to undergo clinical and/or radiological resolution of the nerve lesions following chemoradiotherapy, but the outcome was not determined by the mode of diagnosis (radiological or clinical).     

Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P- postlabeling and electrochemical detection

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for oxidative DNA damage. Reported basal levels determined by 32P- postlabeling (PPL) method were 10-fold or more higher than those obtained with HPLC/electrochemical detection (ECD). This discrepancy was investigated. In commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per 10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen phosphodiesterase and nuclease P1 (as used in the standard PPL method), followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA spiked with chemically synthesized 8-oxo-dGp to give an increment of 9 8-oxo-dG/10(6) dN, the added standard produced a significant increase with HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of 65%. In order to investigate the role of ionizing radiation from 32P for the higher 8-oxo-dG levels in PPL, incubation times and amounts of radioactivity in the phosphorylation reaction with commercial dGp were increased, and external irradiation of commercial dG with 32P was investigated. All modifications resulted in higher values of 8-oxo-dG measured, but the effect was not large enough to fully explain the discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of [gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during the PPL workup is attributed to the presence and oxidation of unmodified dGp in the reaction mixture. For a determination of true basal levels, the PPL method will have to be modified, including the removal of dGp prior to the phosphorylation reaction.      

朝藿甙A的结构

从朝鲜淫羊藿(Epimedium koreanum Nakai)地上部分分离得到一个新黄酮醇甙类成分:朝藿甙A(ChaohuosideA,I),经光谱分析证明,其结构为7-O-β-D-吡喃葡萄糖-脱水淫羊藿素-3-O-β-D-(3,6-O-二乙酰基)-吡喃葡萄糖-(1→3)-α-L-(4-O-乙酰基)-吡喃鼠李糖甙。