Search

Summary Background Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis. Methods We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul–Seongnam, South Korea). Patients, aged 20–80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460. Findings Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI −4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and −1·1% (−11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient. Interpretation Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis. Funding Ministry of Health and Welfare, South Korea.

Objectives The aim of this study was to investigate the seroprevalence of antibodies against scrub typhus, murine typhus and spotted fever groups among North Korean refugees within 1 year of their arrival in South Korea. Methods We recruited North Korean refugees who had settled in South Korea after a short stay in a third country and did not have any health problems. The antibody titer was measured using a commercial indirect fluorescence assay immunoglobulin G antibody kit. Results The seroprevalence of antibodies against scrub typhus, murine typhus, and spotted fever groups among the 99 participants was 22.2%, 17.2%, and 10.1%, respectively, with 8.1% of participants testing positive for both spotted fever and murine typhus. Conclusions Refugees may be exposed to rickettsial infections in North Korea and their journey from North Korea. This study is the first to report the seroprevalence of antibodies against the 3 common rickettsial diseases among North Korean refugees. The findings suggest that rickettsial infections should be added to the list of differential diagnoses for North Koreans with fever after entering South Korea.

Direct influences of dietary trans-11 18:1 vaccenic acid (TVA) at physiological concentrations of 50-200 μM were evaluated for cell growth, cytotoxic activity, and cytokine production in leukocytes isolated from the mouse spleen. TVA supplementation for 24 h induced growth of splenocytes at concentrations of 50-200 μM, except for 100 μM. The cytokines TNFα, IFNγ, and IL-10 of splenocytes were stimulated by 100 μM TVA. Induced production of TNFα in splenocytes challenged with lipopolisaccharides was suppressed by 100 μM TVA. Physiological levels of TVA had direct effects on growth and cytokine production in splenocytes. Further in vivo studies are needed to improve understanding of the precise influence of trans fatty acids on production of pro-inflammatory markers under acute inflammation conditions.

cis-9, trans-11 Conjugated linoleic acid (CLA) is one of the most extensively studied CLA isomers due to its multiple isomer-specific effects. However, the molecular mechanisms of cis-9,trans-11 CLA synthesis in ruminant mammary gland are still not clearly understood. This process may be mediated, to a certain extent, by trans-11 C18:1 regulated by stearoyl-CoA desaturase-1 (SCD1) and/or its syntrophic proteins. This study aimed to investigate the effects of TVA on SCD1-mediated cis-9,trans-11 CLA synthesis in MAC-T cells and its potential molecular mechanism. Results showed that trans-11 C18:1 was continually taken up and converted into cis-9,trans-11 CLA in MAC-T cells during the 4-h incubation of 50 μM trans-11 C18:1. SCD1 protein expression increased more than twofold at 2 h (P

The role of TVA in suppressing proliferation of various human cancer cell lines was investigated that TVA and c9, t11-CLA both suppressed cell proliferation. The suppressive effect of TVA was clearly observed in T47D breast carcinoma cells after stearoyl-CoA desaturase-1 (SCD) knockdown using small interfering RNA (siRNA), demonstrating TVA directly affects suppression of human breast carcinogenesis.

Trans vaccenic acid (TVA; trans-11 18:1) is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA), a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1) in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs) from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products.

BACKGROUND The effects of the individual variation among dairy cows on the synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) are still not well characterised. Therefore, the protein expression profiles of isolated milk epithelial cells (MECs) were detected by two-dimensional electrophoresis and their correlation with the various proportion of cis-9, trans-11 CLA were evaluated. RESULTS Although animals were offered the same diet, the proportion of cis-9, trans-11 CLA in group High (1.02 ± 0.10%) was twice as high as that in group Low (0.59 ± 0.14%) (P < 0.05). MECs with the characteristics of native epithelial cells were successfully isolated from the milk and these cells had no obvious RNA degradation or were hardly contaminated with leucocytes or blood red cells. Moreover, the protein expression pattern of cathelicidin 5 in isolated MECs was positive, whereas annexin I (confirmed by real-time polymerase chain reaction), ZW10 interactor and κ-casein were negatively related to the proportion of cis-9, trans-11 CLA in the milk fat. CONCLUSION The varied individual content of cis-9, trans-11 CLA in cows may be associated with annexin I. These findings may provide some theoretical basis for studies concerning the effects of the individual variation among dairy cows of the synthesis of cis-9, trans-11 CLA. © 2013 Society of Chemical Industry

In 2-dimensional gel electrophoresis (2-DE) analysis, quantification of protein expression difference is difficult because of the high variation of spot sizes among gels. Therefore, identification of a reference marker for data normalization is necessary. In this study, consistent spot size and high reproducibility of myoglobin in 2-DE gels were successfully achieved. The use of myoglobin not only improved quantification of protein expression differences in images from different samples of the same tissue, but also made the comparison of difference in protein expression among different tissues possible. Thus, myoglobin is promising as a reference marker for data normalization in proteomic analysis.

The aim of the present study was to investigate the effects of dietary trans fatty acids in mice. Following the administration of a 0.5/100 g diet of trans-9 octadecenoic acid (EA), trans-11 vaccenic acid (TVA) or cis-9, trans-11 conjugated linoleic acid (CLA) for 4 weeks, the body weights and the weights of the liver, testis and mediastinal adipose tissue (MAT) of the animals gradually decreased (P

The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic α-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, 10.0μg/kg BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of 10.0 μg/kg body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p < 0.05). Although there was no statistically significant, the α-amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down- regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.

The effects of the individual variation among dairy cows on the synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) are still not well characterised. Therefore, the protein expression profiles of isolated milk epithelial cells (MECs) were detected by two-dimensional electrophoresis and their correlation with the various proportion of cis-9, trans-11 CLA were evaluated.Although animals were offered the same diet, the proportion of cis-9, trans-11 CLA in group High (1.02 ± 0.10%) was twice as high as that in group Low (0.59 ± 0.14%) (P0.05). MECs with the characteristics of native epithelial cells were successfully isolated from the milk and these cells had no obvious RNA degradation or were hardly contaminated with leucocytes or blood red cells. Moreover, the protein expression pattern of cathelicidin 5 in isolated MECs was positive, whereas annexin I (confirmed by real-time polymerase chain reaction), ZW10 interactor and κ-casein were negatively related to the proportion of cis-9, trans-11 CLA in the milk fat.The varied individual content of cis-9, trans-11 CLA in cows may be associated with annexin I. These findings may provide some theoretical basis for studies concerning the effects of the individual variation among dairy cows of the synthesis of cis-9, trans-11 CLA. © 2013 Society of Chemical Industry.