Health and Productivity Management has been promoted in Japan since 2014. Certification criteria for Health and Productivity Management include the improvement of employee health literacy. This ...report provides an overview of the “Eat, Sleep, Walk” health literacy development project using ICT+incentives+nudges developed for companies, and describes its preliminary evaluation and challenges.
AIM：To investigate the predictors of success in stepdown of proton pump inhibitor and to assess the quality of life（QOL）.METHODS：Patients who had heartburn twice a week or more were treated with 20 ...mg omeprazole（OPZ） once daily for 8 wk as an initial therapy（study 1）.Patients whose heartburn decreased to once a week or less at the end of the initial therapy were enrolled in study 2 and treated with 10 mg OPZ as maintenance therapy for an additional 6 mo（study 2）.QOL was in-vestigated using the gastrointestinal symptom rating scale（GSRS）before initial therapy,after both 4 and 8 wk of initial therapy,and at 1,2,3,and 6 mo after starting maintenance therapy.RESULTS：In study 1,108 patients were analyzed.Their characteristics were as follows;median age：63（range： 20-88）years,sex：46 women and 62 men.The success rate of the initial therapy was 76%.In the patients with successful initial therapy,abdominal pain,indigestion and reflux GSRS scores were improved.In study 2,83 patients were analyzed.Seventy of 83 patients completed the study 2 protocol.In the per-protocol analysis,80%of 70 patients were successful for stepdown.On multivariate analysis of baseline demographic data and clinical information,no previous treatment for gastroesophageal reflux disease（GERD）odds ratio （OR）0.255,95%CI：0.06-0.98and a lower indigestion score in GSRS at the beginning of step-down therapy（OR 0.214,95%CI：0.06-0.73）were found to be the predictors of successful step-down therapy.The improved GSRS scores by initial therapy were maintained through the step-down therapy.CONCLUSION：OPZ was effective for most GERD patients.However,those who have had previous treatment for GERD and experience dyspepsia before stepdown require particular monitoring for relapse.
We describe two cases of dermatomyositis (DM), which subsequently developed into rapidly progressive fatal interstitial pneumonitis and pneumomediastinum during steroid therapy. Both cases showed the ...classical cutaneous manifestations of DM, but the muscular symptoms were absent or mild. Both rapidly progressive interstitial pneumonitis and pneumomediastinum can occur in DM showing less inflammatory changes in the muscles. Patients with this form should be treated with extreme caution.
The high
stability of 2,2-dihydroxymethyl-3-
Ffluoropropyl-2-nitroimidazole (
FDiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and ...astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all
I-labeled compounds remained stable against nucleophilic substitution, only a
I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against
deiodination.
At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism.
At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the
I/
At-labeled benzoate pair. The urine analyses confirmed that
At-labeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free
AtAt
. These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and
At.
Display omitted
Prostate-specific membrane antigen (PSMA), expressed in prostate cancer cells, is being investigated extensively worldwide as a target for imaging and therapy of prostate cancer. ...Various radioiodinated PSMA imaging probes have been developed, and their structure has a peptidomimetic urea-based skeleton as a pharmacophore. For direct radioiodination of molecules containing these peptidomimetic structures, prior studies performed radioiododestannylation or electrophilic radioiodination of tyrosine residues. However, although these radiolabeling methods are frequently used, there are some issues with precursor toxicity and by-product production. Therefore, it is required to investigate a radiolabeling method that can be used for the radiosynthesis of radioiodinated PSMA imaging probes with urea-based peptidomimetic structures. We recently reported that copper-mediated radioiodination via a boronic precursor is an effective method for directly labeling a peptide. This radiohalogenation method was expected to be an effective method for radiosynthesis of PSMA imaging probes with a peptidomimetic structure. In this study, to confirm that this labeling method applies to the synthesis of the PSMA imaging probe, we synthesized PSMA imaging probes labeled with 125I and 77Br (125ImIB-PS and 77BrmBrB-PS) using a copper-mediated radiohalogenation via common boronic precursors and investigated optimal boronic precursor and labeling conditions. As a result, the radiochemical yields of 125ImIB-PS and 77BrmBrB-PS were improved to > 93% at room temperature by optimizing the structure of the boronic precursor. We demonstrate that copper-mediated nucleophilic radiochemistry using a boronic precursor is a promising radiosynthetic method of PSMA imaging probes. Although we focused on the synthesis of PSMA imaging probes, the results in this study will also be useful for the synthesis of various radioiodine or radiobromine-labeled bioactive molecules.
(1) Background: Deferoxamine B (DFO) is the most widely used chelator for labeling of zirconium-89 (89Zr) to monoclonal antibody (mAb). Despite the remarkable developments of the clinical ...89Zr-immuno-PET, chemical species and stability constants of the Zr-DFO complexes remain controversial. The aim of this study was to re-evaluate their stability constants by identifying species of Zr-DFO complexes and demonstrate that the stability constants can estimate radiochemical yield (RCY) and chelator-to-antibody ratio (CAR). (2) Methods: Zr-DFO species were determined by UV and ESI-MS spectroscopy. Stability constants and speciation of the Zr-DFO complex were redetermined by potentiometric titration. Complexation inhibition of Zr-DFO by residual impurities was investigated by competition titration. (3) Results: Unknown species, ZrHqDFO2, were successfully detected by nano-ESI-Q-MS analysis. We revealed that a dominant specie under radiolabeling condition (pH 7) was ZrHDFO, and its stability constant (logβ111) was 49.1 ± 0.3. Competition titration revealed that residual oxalate inhibits Zr-DFO complex formation. RCYs in different oxalate concentration (0.1 and 0.04 mol/L) were estimated to be 86% and >99%, which was in good agreement with reported results (87%, 97%). (4) Conclusion: This study succeeded in obtaining accurate stability constants of Zr-DFO complexes and estimating RCY and CAR from accurate stability constants established in this study.
Background
Aldehyde dehydrogenase 2 (
ALDH2
; rs671, Glu504Lys) and alcohol dehydrogenase 1B (
ADH1B
; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde ...accumulation after alcohol drinking. To date, however, evidence for a significant
ALDH2
–alcohol drinking interaction and a mediation effect of
ALDH2
/
ADH1B
through alcohol drinking on gastric cancer have remained unclear. We conducted two case–control studies to validate the interaction and to estimate the mediation effect on gastric cancer.
Methods
We calculated odds ratios (OR) and 95% confidence intervals (CI) for
ALDH2
/
ADH1B
genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways.
Results
ALDH2
Lys alleles had a higher risk with increased alcohol consumption compared with
ALDH2
Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04–6.27;
P
for trend = 0.007), indicating a significant
ALDH2
–alcohol drinking interaction (
P
interaction
= 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38–2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76–0.92) of the
ALDH2
Lys alleles with the
ALDH2
–alcohol drinking interaction. No significant association of
ADH1B
with gastric cancer was observed.
Conclusion
The observed
ALDH2
–alcohol drinking interaction and the direct effect of
ALDH2
Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.
System l amino acid transporter 1 (LAT1) is highly expressed in various types of human cancer, and contributes to cancer growth and survival. Recently, we have shown that LAT1 expression is closely ...related to the growth and aggressiveness of esophageal cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal cancer growth. In this study, we investigated the tumor‐suppressive effects of the inhibition of LAT1. Both LAT1 and CD98, which covalently associates to LAT1 on the membrane, were expressed in human esophageal cancer cell lines KYSE30 and KYSE150. Quantitative PCR analysis showed that the expression of LAT1 was much higher than other subtypes of LAT. A selective inhibitor of LAT, 2‐aminobicyclo‐(2,2,1)‐heptane‐2‐carboxylic acid (BCH), suppressed cellular uptake of l‐14C‐leucine and cell proliferation in a dose‐dependent manner. It also suppressed phosphorylation of mammalian target of rapamycin, 4E‐BP1, and p70S6K protein, and induced cell cycle arrest at G1 phase. These results suggest that suppression of both mammalian target of rapamycin signaling and cell cycle progression is involved in BCH‐induced growth inhibition. In tumor‐bearing mice, daily treatment with BCH significantly delayed tumor growth and decreased glucose metabolism, indicating that LAT1 inhibition potentially suppresses esophageal cancer growth in vivo. Thus, our results suggest that LAT1 inhibition could be a promising molecular target for the esophageal cancer therapy.
This paper shows the tumor suppressive effects by the inhibition of LAT1 in esophageal cancer. Inhibition of LAT1 with 2‐aminobicyclo‐(2,2,1)‐heptane‐2‐carboxylic acid (BCH) suppressed cell proliferation, mTOR signaling, and induced cell cycle arrest at G1 phase in esophageal cancer cells. Moreover, daily administration of BCH significantly delayed tumor growth and decreased glucose metabolism in tumor‐bearing mice, suggesting that LAT1 inhibition would be a promising molecular target for the therapy of esophageal cancer.
PDF
