Reversal of slow growth and heartbeat through the restoration of mitochondrial function in clk-1-deficient mouse embryos by exogenous administration of coenzyme Q10

The longevity gene clk-1/coq7 encodes an enzyme that is essential for the biosynthesis of coenzyme Q (CoQ) in mitochondria and regulates the lifespan and behavioral timing in Caenorhabditis elegans and the chronological lifespan in fission yeast. However, whether the mammalian clk-1/coq7 ortholog (clk-1) regulates these phenotypes in mammals remains to be fully evaluated due to the embryonic lethality of clk-1-deficient (clk-1(-/-)) mice. To investigate whether clk-1 regulates biological functions, such as growth and heartbeat, through CoQ in mouse embryos, we cultivated the cells and hearts of clk-1(-/-) mouse embryos at embryonic day 10.5 (E10.5) for at least 10 days in the presence of fetal bovine serum. In embryonic cells, cardiomyocytes, and hearts, the growth and heart rates were significantly slowed in clk-1(-/-) compared with wild-type or heterozygous mouse tissues. Moreover, frequent apoptosis and a significant reduction in mitochondrial functions, including membrane potential and ATP production, were observed in the clk-1(-/-) cells and hearts. The slowed growth and heart rates and the reduced mitochondrial function of clk-1(-/-) embryonic cells and hearts in culture were almost completely rescued by the administration of exogenous CoQ(10). The results indicate that clk-1 regulates growth and heart rates through CoQ-mediated mitochondrial functions in mouse embryos.     

Fall Risk Index predicts functional decline regardless of fall experiences among community‐dwelling elderly

Aim: The 21‐item Fall Risk Index (FRI‐21) has been used to detect elderly persons at risk for falls. The aim of this longitudinal study was to evaluate the FRI‐21 as a predictor of decline in basic activities of daily living (BADL) among Japanese community‐dwelling elderly persons independent of fall risk. Methods: The study population consisted of 518 elderly participants aged 65 years and older who were BADL independent at baseline in Tosa, Japan. We examined risk factors for BADL decline from 2008 to 2009 by multiple logistic regression analysis on the FRI‐21 and other functional status measures in all participants. We carried out the same analysis in selected participants who had no experience of falls to remove the effect of falls. Results: A total of 45 of 518 participants showed decline in BADL within 1 year. Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.05–1.20), FRI‐21 ≥ 10 (OR 3.81, 95% CI 1.49–9.27), intellectual activity dependence (OR 3.25, 95% CI 1.42–7.44) and history of osteoarthropathy (OR 3.17, 95% CI 1.40–7.21) were significant independent risk factors for BADL decline within 1 year. FRI‐21 ≥ 10 and intellectual activity dependence (≤3) remained significant predictors, even in selected non‐fallers. Conclusion: FRI‐21 ≥ 10 and intellectual activity dependence were significant predictive factors of BADL decline, regardless of fall experience, after adjustment for confounding variables. The FRI‐21 is a brief, useful tool not only for predicting falls, but also future decline in functional ability in community‐dwelling elderly persons. Geriatr Gerontol Int 2012; ??: ??–?? .     

Stability of di-butyl-dichalcogenide-capped gold nanoparticles: experimental data and theoretical insights

Metals capped with organochalcogenides have attracted considerable interest due to their practical applications, which include catalysis, sensing, and biosensing, due to their optical, magnetic, electrochemical, adhesive, lubrication, and antibacterial properties. There are numerous reports of metals capped with organothiol molecules; however, there are few studies on metals capped with organoselenium or organotellurium. Thus, there is a gap to be filled regarding the properties of organochalcogenide systems which can be improved by replacing sulfur with selenium or tellurium. In the last decade, there has been significant development in the synthesis of selenium and tellurium compounds; however, it is difficult to find commercial applications of these compounds because there are few studies showing the feasibility of their synthesis and their advantages compared to organothiol compounds. Stability against oxidation by molecular oxygen under ambient conditions is one of the properties which can be improved by choosing the correct organochalcogenide; this can confer important advantages for many more suitable applications. This paper reports the successful synthesis and characterization of gold nanoparticles functionalized with organochalcogenide molecules (dibutyl-disulfide, dibutyl-diselenide and dibutyl-ditelluride) and evaluates the oxidation stability of the organochalcogenides. Spherical gold nanoparticles with diameters of 24 nm were capped with organochalcogenides and were investigated using X-ray photoelectron spectroscopy (XPS) to show the improved stability of organoselenium compared with organothiol and organotellurium. The results suggest that the organoselenium is a promising candidate to replace organothiol because of its enhanced stability towards oxidation by molecular oxygen under ambient conditions and its slow oxidation rate. The observed difference in the oxidation processes, as discussed, is also in agreement with theoretical calculations.

This study presents the improved stability against oxidation by molecular oxygen under ambient conditions of organoselenium compared with organothiol, and organotellurium.     

Spontaneous remission in children with IgA nephropathy

Background

Some patients with IgA nephropathy (IgAN) achieve spontaneous remission even when not receiving medication. However, details on such remissions remain unknown. The aim of our study was to clarify this information in the clinical setting of childhood IgAN with minor glomerular abnormalities or focal mesangial proliferation (MGA/FMP).

Methods

This study was a retrospective analysis of 96 children with MGA/FMP who did not receive medication from among the 555 patients with newly diagnosed childhood IgAN treated between January 1972 and December 2000. The Kaplan?CMeier method and Cox proportional hazard model were used for the analysis.

Results

Of the 96 pediatric patients who did not receive medication, 57 (59.4?%) achieved spontaneous remission. The cumulative spontaneous remission rates among these patients were 57.5? and 77.4 % at 5?and 10 years, respectively, from onset. The mean time from onset to remission was 5.9?±?0.4?years. Clinical and histological findings were similar between the remission and non-remission groups. Of the 57 patients with spontaneous remissions, ten (17.5?%) also developed a recurrence of urinary abnormalities. The cumulative recurrence-free rates were 79.9?and 67.9 % at 5 and 10?years, respectively, after remission.

Conclusions

The spontaneous remission rate in childhood IgAN with MGA/FMP was higher than expected. Our results suggest that physicians should consider the potential for spontaneous remission and refrain from very aggressive treatment in IgAN patients with MGA/FMP.     

Micro-mechanical bond strength tests for the assessment of the adhesion of GIC to dentine

Abstract Background. The aim of this study is to critically evaluate the bond strength (BS) of Glass-Ionomer Cements (GIC) to dentine with microtensile (μTBS) and microshear (μSBS) BS tests by assessing their rankings and failure patterns. Methods. Samples were made on flat dentine surfaces and submitted to μTBS and μSBS. The materials used were: high viscosity GIC (Ketac(?) Molar Aplicap-KM), resin-modified GIC (Fuji II-FII), nano-filled resin-modified GIC (Ketac(?) N100-N100) and an etch-and-rinse adhesive system with a composite resin (Adper(?) Single Bond 2 and Z100(?)-Z100). All tests were performed with a Universal Testing Machine (24 h water storage, crosshead speed of 1 mm/min). Debonded surfaces were examined with a stereomicroscope (×40) to identify the failure mode. The data was analyzed with two-way ANOVA (p < 0.05) and LSD test. Results. Means were statistically different regarding the tests and materials, indicating that values for BS obtained for each material depend on the test performed. Failure analysis revealed that failures produced by μTBS were mainly cohesive for KM and FII. μSBS failures were mainly adhesive or mixed for all materials. For the μTBS, the rank was Z100 > FII > KM = N100, whereas for the μSBS it was Z100 = FII = KM > N100. Conclusion: It may be concluded that distinct micro-mechanical tests present different failure patterns and rankings depending on the material to be considered.     

Regioisomeric differentiation of the alkyl-substituted synthetic cannabinoids JWH-122 and JWH-210 by GC-EI-MS/MS

Synthetic cannabinoids (SCs) are known to have structural or positional isomers. While regulations on synthetic drugs like synthetic cathinones and SCs have been placed worldwide for the ever-growing variety of new designer drugs, laws may not necessarily be applicable to their isomers. Toxicological differences may also exist among isomers for which most new designer drugs are still uninvestigated; thus, isomer differentiation becomes of forensic importance. The aim of this study was to differentiate the regioisomers of alkyl-substituted naphthoylindole-type SCs JWH-122 and JWH-210. Reference standards of the two drugs and their regioisomers were analyzed by gas chromatography–electron ionization-mass spectrometry (GC–EI-MS) first in full scan mode. Isomers that produced identical EI spectra were further analyzed by GC-tandem mass spectrometry (MS/MS) by selecting appropriate precursor ions. For JWH-210, comparison of the product ion spectra and the relative ion intensity ratios obtained from precursor ions at m/z 312 and 183 enabled differentiation between all seven regioisomers. Complete isomeric differentiation by MS/MS analysis was not attainable for JWH-122; however, combining chromatographic results with MS/MS analysis results enabled differentiation for all isomers. Two basic fragmentation pathways were speculated for both SCs; for JWH-210, fragmentation pathway tendencies differed among the isomers, resulting in their distinguishability. Our results demonstrated that the difference between the methyl (JWH-122) and ethyl (JWH-210) group substituents contributed to fragmentation pathway tendency differences and further distinguishability between the regioisomers. Functional group differences, especially their stereochemistries, were indicated to be critical factors in positional isomer differentiation by GC-MS/MS.