A1330V polymorphism of the <Emphasis Type="Italic">low</Emphasis>-<Emphasis Type="Italic">density lipoprotein receptor</Emphasis>-<Emphasis Type="Italic">related protein 5</Emphasis> gene and bone mineral density in Japanese male workers

Objectives  

Both genetic and lifestyle factors have been shown to influence bone mineral density (BMD). We investigated the correlations between BMD and low-density lipoprotein receptor-related protein 5 (LRP5) A1330V (rs3736228) polymorphism, exercise, smoking, and alcohol intake in Japanese male workers.     

Epidural blood patch for postdural puncture headache in a five-year-old child

A case was presented of a 5-year-old girl who suffered an accidental dural puncture during placement of an epidural catheter under general anesthesia for orthopedic surgery. She complained of headache 4 days after the operation, which was relieved on supine position but became worse on sitting position. Her symptoms failed to respond to conservative management. An epidural blood patch was performed under general anesthesia and completely resolved her symptoms. The reported incidence of epidural blood patch for post dural puncture headache following accidental dural puncture in children is low. We outline this case and the consideration for management for epidural blood patch in pediatric patients.     

Polymorphisms in TGFB1 and PDGFRB are associated with Moyamoya disease in European patients

Background  

The etiology of Moyamoya disease (MMD) is still widely unknown. Several publications on Moyamoya describe differences of cytokine and growth factor concentrations in different specimen. We analyzed the DNA of patients with MMD for single nucleotide polymorphisms (SNPs) in and upstream of the genes for previously described associated cytokines and growth factors.     

Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cox Inhibitory Activity

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1,2,3-triazole-containing uracil derivatives with excellent pharmacokinetics as a novel class of potent human deoxyuridine triphosphatase inhibitors

Deoxyuridine triphosphatase (dUTPase) has emerged as a potential target for drug development as a 5-fluorouracil-based combination chemotherapy. We describe the design and synthesis of a novel class of human dUTPase inhibitors, 1,2,3-triazole-containing uracil derivatives. Compound 45a, which possesses 1,5-disubstituted 1,2,3-triazole moiety that mimics the amide bond of tert-amide-containing inhibitor 6b locked in a cis conformation showed potent inhibitory activity, and its structure-activity relationship studies led us to the discovery of highly potent inhibitors 48c and 50c (IC(50) = ~0.029 μM). These derivatives dramatically enhanced the growth inhibition activity of 5-fluoro-2'-deoxyuridine against HeLa S3 cells in vitro (EC(50) = ~0.05 μM). In addition, compound 50c exhibited a markedly improved pharmacokinetic profile as a result of the introduction of a benzylic hydroxy group and significantly enhanced the antitumor activity of 5-fluorouracil against human breast cancer MX-1 xenograft model in mice. These data indicate that 50c is a promising candidate for combination cancer chemotherapies with TS inhibitors.     

Inhibition of galactosyltransferases by a novel class of donor analogues

Galactosyltransferases (GalT) are important molecular targets in a range of therapeutic areas, including infection, inflammation, and cancer. GalT inhibitors are therefore sought after as potential lead compounds for drug discovery. We have recently discovered a new class of GalT inhibitors with a novel mode of action. In this publication, we describe a series of analogues which provide insights, for the first time, into SAR for this new mode of GalT inhibition. We also report that a new C-glycoside, designed as a chemically stable analogue of the most potent inhibitor in this series, retains inhibitory activity against a panel of GalTs. Initial results from cellular studies suggest that despite their polarity, these sugar-nucleotides are taken up by HL-60 cells. Results from molecular modeling studies with a representative bacterial GalT provide a rationale for the differences in bioactivity observed in this series. These findings may provide a blueprint for the rational development of new GalT inhibitors with improved potency.     

Comparison of the effect of mesalazine and sulfasalazine on laboratory parameters: a retrospective observational study

Purpose

Mesalazine and sulfasalazine are commonly used drugs for the treatment of inflammatory bowel disease. However, there have been few reports with a strict statistical analysis comparing the effects of mesalazine and sulfasalazine on laboratory test results. Therefore, we designed a retrospective cohort study to investigate whether or not differences in clinical laboratory parameters exist between mesalazine and sulfasalazine users.

Methods

We used data from the Clinical Data Warehouse of Nihon University School of Medicine to identify cohorts of new mesalazine users (n?=?303) and sulfasalazine users (n?=?67). We used a multivariate regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between mesalazine and sulfasalazine users, and compared serum levels of creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and hematological parameters including red and white blood cell counts and platelet count.

Results

After adjustment, in sulfasalazine users, the mean values for all tests showed no significant change between baseline and during the exposure period. In contrast, in mesalazine users, the mean WBC and platelet counts during the exposure period were significantly lower than those at baseline. Furthermore, mean serum urea nitrogen level during the exposure period was significantly higher than that at baseline. In terms of mean changes in laboratory test values during the exposure period compared with baseline, the reduction of platelet count in mesalazine users was significant in comparison to that in sulfasalazine users.

Conclusion

Our findings suggested that the hematological adverse effects of mesalazine treatment might be greater than those of sulfasalazine treatment.     

Obesity and depressive symptoms in elderly Japanese: the Tsurugaya Project

OBJECTIVE: The aim of this study is to examine the association between obesity and depressive symptoms in Japan. METHODS: We conducted a cross-sectional study of 1128 community-dwelling elderly Japanese aged 70 years or older in 2002. We calculated the body mass index [BMI=weight (kg)/height (m)2] from measured weight and height and evaluated depressive symptoms using the 30-item Geriatric Depression Scale (GDS 30), with a cut-off point of 11. RESULTS: In men, no apparent association was observed between BMI and depressive symptoms. An inverse linear trend was observed in women overall, but stratified analysis of chronic medical conditions, such as stroke or cancer, showed an inverse association was evident only among women with the conditions. Among women without these chronic conditions, no apparent association was evident. CONCLUSION: No apparent association was observed in men overall or in apparently healthy women. An inverse trend was observed only in women with chronic medical conditions.