Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Reactivation of Silenced WT1 Transgene by Hypomethylating Agents: Implications for in vitro Modeling of Chemoimmunotherapy

BACKGROUND: A cell line with transfected Wilms' tumor protein 1 (WT1) is has been used for the preclinical evaluation of novel treatment strategies of WT1 immunotherapy for leukemia due to the lack of appropriate murine leukemia cell line with endogenous WT1. However, silencing of the transgene occurs. Regarding the effects of hypomethylating agents (HMAs) on reactivation of silenced genes, HMAs are considered to be immune enhancers. METHODS: We treated murine WT1- transfected C1498 (mWT1-C1498) with increasing doses of decitabine (DAC) and azacitidine (AZA) to analyze their effects on transgene reactivation. RESULTS: DAC and AZA decreased the number of viable cells in a dose- or time-dependent manner. Quantification of WT1 mRNA level was analyzed by real-time polymerase chain reaction after mWT1-C1498 treated with increasing dose of HMA. DAC treatment for 48 h induced 1.4-, 14.6-, and 15.5-fold increment of WT1 mRNA level, compared to untreated sample, at 0.1, 1, and 10microM, respectively. Further increment of WT1 expression in the presence of 1 and 10microM DAC was evident at 72 h. AZA treatment also induced up-regulation of mRNA, but not to the same degree as with DAC treatment. The correlation between the incremental increases in WT1 mRNA by DAC was confirmed by Western blot and concomitant down-regulation of WT1 promoter methylation was revealed. CONCLUSION: The in vitro data show that HMA can induce reactivation of WT1 transgene and that DAC is more effective, at least in mWT1-C1498 cells, which suggests that the combination of DAC and mWT1-C1498 can be used for the development of the experimental model of HMA-combined WT1 immunotherapy targeting leukemia.

Development and Effects' Analysis of Nutrition Education Pamphlet for the Lower Grades Elementary Students -Focused on Individual Daily Needed Food Exchange Units- / 대한지역사회영양학회지

The purpose of this study was to investigate effects of nutrition education program and pamphlet for the lower grades elementary students focused on individual daily needed food exchange units using Food Exchange System. Program consisted of four lessons (40 min/lesson), "5 major nutrients & function", "6 food group and sources", "daily needed food exchange units for normal body weight", and "smart snack choice and exercise". Pamphlet as activity book was developed for the program. The subjects were 3rd grade elementary students (educated group, 31 vs. non-educated group, 31). Educated group were lessoned as group and/or individual. We examined the differences in nutrition knowledge, dietary attitudes, dietary intakes and satisfaction of the program and pamphlet. In educated group, there were positive improvements on nutrition knowledge score "function and foods of 5 nutrients" and on dietary attitudes "type of breakfast and snacks". In the evaluation of dietary intakes according to KDRI, there were positive improvements on intakes level of riboflavin, vit. C, folate, Ca, P, Fe and Zn in educated group. In satisfaction with the program and pamphlet, contents, font size, visual, figure, difficulty and program curriculum were over 2.90/3.0. It showed that the developed nutrition education program and pamphlet focused on individual daily needed food exchange units using Food Exchange System improved nutrition knowledge, dietary attitudes and nutrients intake level in the lower grades elementary students.

The Regulation of MMP-2 and -14 Expressions by TGF-beta in Lens Epithelial Cells

PURPOSE: TGF-beta is a key regulator of epithelial-mesenchymal transition. Among the TGF-beta responses, cell migration is closely associated with the expression of matrix metalloproteinases (MMPs). Therefore, we determined which MMPs are regulated by TGF-beta and examined the TGF-beta signaling involved in this event, focusing on Src family tyrosine kinases (SFKs) METHODS: First we examined the expression of MMPs in rat lens explant culture treated with TGF-beta and LECs attached to the anterior capsules of patients with nuclear (N), anterior polar (AP) cataracts using RT-PCR and immunofluorescence staining. It was examined whether the expression of MMPs is regulated by SFKs. RESULTS: The study using RT-PCR and immunofluorescence staining showed the expression of MMP-2 and -14 in explants and the expression of MMP-14 LECs of AP cataracts. The expression of MMP-2 and -14 was blocked by PP2 in explants. Furthermore, the activated form of SFKs was observed in LECs of AP cataracts by immunofluorescence staining. CONCLUSIONS: We suggest a novel role of SFKs signaling in the expression of MMP-14 induced by TGF-beta.

Absence of intact thiazide-sensitive sodium-chloride cotransporter in the renal tissue of a Gitelman's syndrome patient / 대한내과학회지

BACKGROUND: Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is known to be caused by a mutation of SLC12A3 gene coding the sodium-chloride cotransporter (NCCT) in the distal tubule. The defect of NCCT in human renal tissues has not been investigated, and we tested whether the defect of NCCT can be detected in renal tissue of a patient with Gitelman's syndrome by using immunohistochemistry. METHODS: In an adult patient with Gitelman's syndrome, blood and urine samples were collected for measurement of biochemical parameters. Renal clearance study and gene analysis were performed. Immunohistochemistry was performed on the renal tissue of the patient using a rabbit polyclonal antibody directed against a synthetic peptide corresponding to a portion in the amino terminal tail for human NCCT. Normal human renal tissues from surgical nephrectomy due to renal cell carcinoma and renal biopsy tissues from patients with glomerulonephritis but without any electrolyte disturbance were used as controls. RESULTS: The patient had hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia. Renal clearance study revealed a decrease in distal fractional chloride reabsorption after the administration of furosemide. SLC12A3 gene mutation (S967F) was found by direct sequencing method. Immunohistochemistry showed the absence of NCCT staining in the renal tissue of the patient. On the other hand, the immunostaining of other transporters was all positive in renal tissues from both Gitelman's syndrome patients and controls. CONCLUSIONS: We report the absence of intact NCCT in the renal tissue of a Gitelman's syndrome patient.

The Change of the Mother's Stress Pattern with Time Elapse after Giving Birth to Premature Babies / 간호학회지

PURPOSE: This study tries to explore mothers' stress patterns and the related factors influencing mothers' stress over time after giving birth to premature babies. METHOD: Eighty four mothers who had given birth to premature babies were selected from Hospitals in B city. Data was collected using a self-reporting questionnaire that the mothers' stress level. RESULT: The mothers' stress after giving birth to premature babies gradually diminished and the stress pattern of mothers changed over time. Mother's age, occupation, income level, gestational period of the measures baby, weight at birth, nutrition type, lactation mode, number of complications, and existence or non-existence of an operation were analyzed as the factors that affected the mother's stress. CONCLUSION: The stress pattern of mothers giving birth to premature babies changed overtime. Based on the study results, it is considered that the nursing intervention programs should be developed in order to reduce the stress of premature baby's mothers with time elapse.