Cross-calibration of multi-frequency bioelectrical impedance analysis with eight-point tactile electrodes and dual-energy X-ray absorptiometry for assessment of body composition in healthy children aged 6–18 years

Background:  In diagnosis and treatment of obesity, body composition analysis including percent body fat (%BF) is useful in the clinical setting. Because bioelectrical impedance analysis (BIA) could be used quickly, easily and was non-invasive in clinical setting, the purpose of the present study was to evaluate the usefulness of multi-frequency BIA with eight-point tactile electrodes (MF-BIA8; InBody 720, Biospace) compared with dual-energy X-ray absorptiometry (DXA) in healthy children and adolescents.
Methods:  A total of 166 children and adolescents under 18 (male, n  = 86; female, n  = 80) were recruited. Height, weight, body mass index (BMI) and Tanner stage were measured for each subject. The body composition such as fat-free mass (FFM), fat mass (FM), and %BF was measured on BIA and DXA and compared.
Results:  On linear regression analysis, DXA FFM = 1.006(BIA FFM) + 0.554, R ² = 0.99 and the standard error of the estimate (SEE) was 1.16 kg; DXA FM = 0.971(BIA FM) – 0.596, R ² = 0.93; SEE, 1.34 kg; and DXA %BF = 0.940(BIA %BF) – 1.026, R ² = 0.858; SEE, 3.03%. Limit of agreement in FFM, FM, and %BF was 0.7 ± 2.3 kg, −0.9 ± 2.9 kg and –2.2 ± 6.1%, respectively.
Conclusions:  Although the %BF was not interchangeable with DXA, MF-BIA8 (InBody 720; Biospace) could be used to measure body composition of children and adolescents in the clinical field because of its high precision.     

CpG oligodeoxynucleotides induce IL-8 expression in CD34+ cells via mitogen-activated protein kinase-dependent and NF-kappaB-independent pathways

To elucidate the role of Toll-like receptor 9 (TLR9) activation along with the intracellular signaling pathways triggered by CpG DNA in CD34+ cells, we investigated whether synthetic oligodeoxynucleotides (ODNs), containing unmethylated CpG motifs, could induce IL-8 expression in CD34+ cells through mitogen-activated protein kinase (MAPK) or nuclear factor-kappaB (NF-kappaB) pathway. We demonstrated evidence for the first time that CD34+ cells constitutively expressed TLR9. Exposure of the cells to CpG ODN resulted in a time- and dose-dependent increase of IL-8 expression, and activation of phosphorylated ERK1/2 and phosphorylated p38. In addition, CpG ODN stimulated AP-1, but not NF-kappaB, signals. Moreover, inhibitors of MAPK (U0126 and SB203580) significantly reduced the IL-8 production, while the inhibition of NF-kappaB (pyrrolidinedithiocarbamate and retrovirus containing dominant-negative IkappaB alpha plasmid) did not affect the IL-8 expression increased by CpG ODN. Moreover, co-stimulation with LPS and CpG synergistically up-regulates IL-8 in CD34+ cells. These results suggest that CpG DNA, acting on TLR9, activates CD34+ cells to express IL-8 through MAPK-dependent and NF-kappaB-independent pathways.     

Prevention of tissue injury by ribbon antisense to TGF-beta1 in the kidney

Transforming growth factor-beta1 (TGF-beta1) is an important mediator of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. We designed ribbon-type antisense oligos of TGF-beta1, TGF-beta1 RiAS, and combined them with a short peptide of the nuclear localization signal to form a transfection complex of DNA/peptide/liposomes (DPL) for enhanced cellular uptake. When H4IIE cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was reduced by >70%. We then examined the ratio of the kidney weight per body weight in rats. Whereas the weight ratio was 0.47% for the normal kidney, the ratio was 0.99% on day 5 after unilateral ureteric obstruction (UUO). The ratios were 0.95% with PBS injection, 1.07% with scrambled RiAS, and 0.68% with TGF-beta1 RiAS. When examined for TGF-beta1 expression in the tissue, the level of TGF-beta1 mRNA was also significantly reduced following treatment with TGF-beta1 RiAS. Further, physical changes such as diminished dilation, atrophy, as well as apoptosis caused by UUO were also found to be markedly reduced by TGF-beta1 RiAS. The results show that ribbon antisense to TGF-beta1 when combined with efficient uptake can effectively block TGF-beta1 expression and preserve tissue integrity in kidneys with UUO.     

Development of anthropometry-based equations for the estimation of the total body water in Koreans

For developing race-specific anthropometry-based total body water (TBW) equations, we measured TBW using bioelectrical impedance analysis (TBW(BIA)) in 2,943 healthy Korean adults. Among them, 2,223 were used as a reference group. Two equations (TBW(K1) and TBW(K2)) were developed based on age, sex, height, and body weight. The adjusted R2 was 0.908 for TBW(K1) and 0.910 for TBW(K2). The remaining 720 subjects were used for the validation of our results. Watson (TBW(W)) and Hume-Weyers (TBW(H)) formulas were also used. In men, TBW(BIA) showed the highest correlation with TBW(H), followed by TBW(K1), TBW(K2) and TBW(W). TBW(K1) and TBW(K2) showed the lower root mean square errors (RMSE) and mean prediction errors (ME) than TBW(W) and TBW(H). On the Bland-Altman plot, the correlations between the differences and means were smaller for TBW(K2) than for TBW(K1). On the contrary, TBW(BIA) showed the highest correlation with TBW(W), followed by TBW(K2), TBW(K1), and TBW(H) in females. RMSE was smallest in TBW(W), followed by TBW(K2), TBW(K1) and TBW(H). ME was closest to zero for TBW(K2), followed by TBW(K1), TBW(W) and TBW(H). The correlation coefficients between the means and differences were highest in TBW(W), and lowest in TBW(K2). In conclusion, TBW(K2) provides better accuracy with a smaller bias than the TBW(W) or TBW(H) in males. TBW(K2) shows a similar accuracy, but with a smaller bias than TBW(W) in females.     

The relationship between maximal urethral closure pressure and functional urethral length in anterior vaginal wall prolapse patients according to stage and age

MUCP (Maximal urethral closure pressure) is known to be increased in patients with vaginal wall prolapse due to the mechanical obstruction of the urethra. However, urethral function following reduction has not yet been completely elucidated. Predicting postoperative urethral function may provide patients with important, additional information prior to surgery. Thus, this study was performed to evaluate the relationship between MUCP and functional urethral length (FUL) according to stage and age in anterior vaginal wall prolapse patients. 139 patients diagnosed with anterior vaginal wall prolapse at Yonsei University Medical College (YUMC) from March 1999 to May 2003 who had underwent urethral pressure profilometry following reduction were included in this study. The stage of pelvic organ prolapse (POP) was determined according to the dependent portion of the anterior vaginal wall (Aa, Ba). (By International Continence Society's POP Quantification system) Patients were divided into one of four age groups: patients in their 40s (n = 13), 50s (n = 53), 60s (n = 54), and 70 and over (n = 16). No difference in MUCP was found between the age groups. The FUL of patients in their 40s was shorter than that of patient's in their 50s and 60s. Patients were also divided into stages: stage II (n = 35), stage III (n = 76), and stage IV (n = 25). No significant difference in MUCP was found according to stage and FUL. However, a significant difference was noted between stage III and IV as stage IV was longer. Anterior vaginal wall prolapse is known to affect urethral function due to prolapse itself, but according to our study, prolapse itself did not alter urethral function. This suggests that, regardless of age and stage, prolapse corrective surgery does not affect the urethral function.     

Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of inflammatory bowel disease

4-1BB (CDw 137), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of agonistic anti-4-1BB monoclonal antibody (mAb) enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of anti-4-1BB mAb reduced the incidence and severity of inflammatory bowel disease. In this study, we investigated the effects of anti-4-1BB mAb in a murine intestinal inflammation model, which induced by the hapten reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS) and mimics immunologic characteristics of human Crohn's disease (CD). Colitis was induced by rectal administration of 2mg of TNBS in 35% ethanol using a vinyl catheter positioned 4cm from the anus. All mice were sacrificed 3 and 10 days after the TNBS administration. The disease activity index (DAI), histological changes of the colon and production of cytokines (IL-2, IL-4, IL-10 and IFN-gamma) were evaluated. The surface molecules of T cells in peripheral blood, spleen and mesenteric lymph nodes were analyzed by flow cytometry. When mice were treated with anti-4-1BB mAb, improvement in both wasting and histopathologic signs of colonic inflammation was observed. The increase a number of splenic CD4(+)CD25(+) T cells and decreased synthesis of the Th1 cytokine IL-2 also occurred. Interestingly, increased production of Th1 cytokine IFN-gamma and proportion of CD8(+) T cells were observed in mice treated with anti-4-1BB mAb in comparison to the colitic mice. These studies show, for the first time, that agonistic anti-4-1BB mAb can improve experimental colitis by reduction of IL-2 and augmentation of CD4(+)CD25(+) regulatory T cells. TNBS colitis is Th1-mediated and has similar histologic features and distribution of inflammation to CD. This study suggests that anti-4-1BB mAb therapy could be effective in the treatment of patients with CD.