Objective: Recently, a subtype of obesity characterized as a metabolically healthy but obese (MHO) individual has been identified. However, limited data are available on these MHO individuals' metabolic and inflammatory profiles, and the effect of weight loss on these profiles. We investigated metabolic and inflammatory markers in MHO women to determine the effects of a 12-week weight loss on those markers. Subjects: One hundred and twenty-nine overweight-obese Korean women participated for 12 weeks in a clinical intervention study involving a 300 kcal/day intake reduction. The subjects were divided into two groups: MHO and metabolically abnormal obese (MAO) individuals. Methods: Computed tomography was performed. C-reactive protein (CRP), interkeukin-6 (IL-6) and oxidized low-density lipoprotein (LDL), as well as blood lipids, glucose and insulin concentrations were determined at baseline and after weight loss. Results: At baseline, plasma CRP (Po0.001), IL-6 (Po0.05) and oxidized LDL (Po0.001) levels were significantly lower in the MHO group than in the MAO group. Visceral fat at L1 (Po0.005) and visceral fat at L4 (Po0.001) were significantly lower in the MHO group than in the MAO group. The treatment induced weight loss averaging 3.11% of initial body weight, and the degree of weight loss between the two groups was similar. Visceral fat at L1 and L4 was reduced from its initial values by 3.2 and 5.4%, respectively, after weight loss. The levels of CRP (Po0.05) and oxidized LDL (Po0.01) were significantly reduced in the MAO group after the 12-week weight loss, whereas these effects were not seen in the MHO group. Conclusions: Our results showed that MHO individuals exhibited lower visceral fat accumulation and more favorable metabolic and inflammatory states than MAO individuals. After a 12-week weight loss program, significant reductions in blood lipids, CRP and oxidized LDL levels were observed in MAO individuals. However, there was no measurable effect of weight loss on lipid profiles and inflammation in MHO individuals, indicating differing effects of weight loss on these markers between MAO and MHO groups.

We investigated the objective coexisting rate of stress urinary incontinence and pelvic organ prolapse, and also compared the treatment outcomes in patients who had both conditions, treated by a corrective operation on the basis of a precise preoperative evaluation. We reviewed 97 cases who underwent urodynamic studies and evaluation of the prolapse according to the Pelvic Organ Prolapse Quantification (POP-Q) system from among patients who were admitted for treatment of either stress urinary incontinence or pelvic organ prolapse. A Burch urethropexy, either alone or with a parvaginal repair, was done to correct the stress urinary incontinence, as well as additional operations to correct prolapse of stage II or more. The patients were evaluated postoperatively for the stress urinary incontinence and the degree of prolapse at every visit. Nineteen of 30 (63.3%) patients who were admitted with stress urinary incontinence had a coexisting pelvic organ prolapse, most often of the anterior wall. In 42 of 67 (62.7%) cases admitted with pelvic organ prolapse there was a coexisting stress urinary incontinence. A total of 61 patients who had both conditions were followed for 12 months postoperatively. The recurrence rate of stress urinary incontinence and prolapse (all of which were stage II) was 3.3% and 18.0%, respectively. It was noted that the greater the preoperative stage, the higher the recurrence rate (stage II 4.35%; stage III 25.0%; stage IV 33.6%). The coexisting rates of pelvic organ prolapse in patients having stress urinary incontinence, and stress urinary incontinence in patients having a pelvic organ prolapse, were both high. Therefore, when a preoperative evaluation that simultaneously considers both conditions and the correcting surgery is based on this evaluation, the recurrence rates of both conditions could be lowered.

Background/Objectives: The purpose of diet-quality indices is to assess and guide individual dietary intake for the promotion of health and prevention of disease, and food based dietary-quality indices need to be applied by using each country's own unique diet. We assessed the relationships between relatively simple dietary quality scores modified for a Korean diet, such as the Recommended Food Score (RFS) and alternate Mediterranean Diet Score (aMDS), and oxidative stress biomarkers in Korean adults. Subjects/Methods: A total of 976 adults were recruited for the Biomarker Monitoring for Environmental Health Study between April and December 2005 in Seoul and Incheon, Korea. RFS and aMDS were calculated by using a food-frequency questionnaire. We used regression analyses to assess the associations between diet quality scores and urinary malondialdehyde (MDA) and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG). Results: RFS and aMDS were negatively associated with urinary MDA concentrations (P ¼ 0.032 for RFS, P ¼ 0.043 for aMDS), but not with 8-OHdG after adjusted for potential covariates. After stratified analyses by sex, negative associations between the both scores and urinary MDA concentrations were not significant in both men and women. There were no significant associations of RFS and aMDS with urinary 8-OHdG concentrations. Conclusions: Higher RFS and aMDS scores were related to lower oxidative stress. Therefore, good quality of diet may be useful in reducing oxidative stress.

Previous studies have shown that Th2 cytokine genes on mouse chromosome 11 are coordinately regulated by the Th2 locus control region (LCR). To examine the in vivo function of Th2 LCR, we generated CD4-specific Th2 LCR-deficient (cLCR KO) mice using CreLoxP recombination. The number of CD4 T cells in the cLCR KO mouse was comparable to that in wild-type mice. The expression of Th2 cytokines was dramatically reduced in in vitro-stimulated naïve CD4 T cells. Deletion of the LCR led to a loss of general histone H3 acetylation and histone H3-K4 methylation, and demethylation of DNA in the Th2 cytokine locus. Upon ovalbumin challenge in the mouse model of allergic asthma, cLCR KO mice exhibited marked reduction in the recruitment of eosinophils and lymphocytes in the bronchoalveolar lavage fluid, serum IgE level, lung airway inflammation, mucus production in the airway walls, and airway hyperresponsiveness. These results directly demonstrate that the Th2 LCR is critically important in the regulation of Th2 cytokine genes, in chromatin remodeling of the Th2 cytokine locus, and in the pathogenesis of allergic asthma.chromatin remodeling | differentiation | locus control region C D4 T cells play an essential role in the activation and regulation of a variety of immune responses. Effector CD4 T cells are composed of several different subsets including Th1, Th2, and Th17 cells (1-5). The expression of subset-specific cytokines is critical for the differentiation and function of T helper cells (6, 7). The Th2 cytokine genes, il4, il5, and il13, are clustered on human chromosome 5 and mouse chromosome 11. The Th2 cytokine locus undergoes structural changes in its chromatin upon Th2 cell differentiation to accommodate the high level expression of Th2 cytokine genes. The changes include acquisition of DNase I hypersensitivity (8, 9), restriction enzyme accessibility (10), histone acetylation (11-16), histone methylation (17), and DNA demethylation (8,13,18,19). Chromatin remodeling and enhancement of transcription of a gene are regulated by trans-acting factors that bind to specific DNA regulatory elements. Many laboratories including ours have shown that the Th2 cytokine locus is regulated by a number of regulatory elements including enhancers [CNS-1/ HSS (9, 20-22), CNS-2/HSV (20, 23), IE/HSII (20)], a silencer (HSIV) (20,24), and a locus control region (LCR) (25).We have shown previously that the expression of Th2 cytokines is coordinately regulated by the Th2 LCR that is located in the 3′ region of the rad50 gene (25). The Th2 LCR is composed of four DNase I-hypersensitive sites, namely RHS4, RHS5, RHS6, and RHS7 (13, 26). We have shown that deletion of RHS7 causes marked reduction of Th2 cytokine genes under Th0 conditions and partial reduction under Th2 conditions (27), suggesting that RHS7 is important for Th2 cytokine expression. The Th2 LCR interacts with the promoters of Th2 cytokine genes through intrachromosomal associations (28). Deletion of RHS7 disrupts these (27), suggesting that RHS7 is critical for these int...

Obesity is a known risk factor for allergic asthma. It has been recognized as a key player in the pathogenesis of several inflammatory disorders via activation of macrophages, which is also vital to the development of allergic asthma. We investigated the mechanism of obesity-related asthma and whether treating obesity through exercise or diet ameliorates the severity of asthma in the obesity-related asthma model. We generated diet-induced obesity (DIO) in C57BL/6 mice by high-fat-feeding and ovalbumin-induced asthma (lean-OVA or DIO-OVA). The DIO-OVA mice were then treated with tumor necrosis factor (TNF)-α neutralizing antibody as a TNF-α blockade or a Cl2MDP-containing liposome to induce an alveolar macrophage deficiency. To treat obesity, the DIO-OVA mice were under dietary restrictions or exercised. The pathophysiological and immunological responses were analyzed. Airway hyperresponsiveness (AHR), serum IgE and TNF-α levels in the lung tissue increased in the DIO-OVA mice compared to the lean-OVA mice. Both the TNF-α blockade and depletion of alveolar macrophages in the DIO-OVA mice decreased AHR compared to the DIO-OVA mice. Treating obesity by exercise or through dietary means also reduced pulmonary TNF-α levels and AHR in the DIO-OVA mice. These results suggest that restoring normal body weight is an appropriate strategy for reducing TNF-α levels, and controlling inflammation may help improve asthma severity and control in obesity-related asthma.