EACH BODY SEGMENT FUNCTION DURING THE SUPPORT PHASE OF THE DROP JUMP

INTRODUCTION: The purpose of this study was to investigate each body segment function in the takeoff motion of the drop jump. Ten male athletes performed a drop jump with the height of 40cm. They were instructed to use arm action. Their takeoff motions were filmed at 20OHz with a high speed camera. Two-dimensional coordinates were obtained by digitizing the motion with a sampling frequency of 20OHz. The data was filtered with a Butterworth digital filter at 8.5Hz. BSP of Chandler et al. (1975) were used to estimate the segmental centers of gravity and the mass center of the whole body. This data were used to calculate the generated momenta of the arms trunk (head and trunk), takeoff legs, thighs, shanks and feet in the vertical direction using method of Ae et al. (1985). Accelerative forces were calculated generated momenta by numerical differentiation. RESULTS: The arms showed a positive (but small) accelerative force (accelerating the body upward) in the early half of the support phase, and a small negative force (checking the body downward) in the later half. The trunk showed a negative accelerative force immediately after the touchdown, then gave a twopeaked pattern of positive force in the midpoint of phase and a negative force in the phase immediately before the takeoff. The takeoff legs showed the positive accelerative force throughout the overall takeoff phase, which is especially large immediately after the touchdown and before the takeoff. The force of the takeoff legs was larger than that of other parts. The thighs showed a negative accelerative force immediately after touchdown, then gave a two-peaked pattern of positive one in the midpoint of phase, and the negative one. The thighs showed the same pattern as the trunk. The shanks gave both positive and negative force alternately during takeoff. The feet showed the positive accelerative force throughout the overall takeoff phase, having the larger one immediately after the touchdown and before the takeoff. CONCLUSIONS: The arms are charged with the function of accelerating the body upward in the early half of the support phase. The trunk takes the charge of accelerating around the midpoint of phase. The takeoff legs have the accelerating function throughout the overall takeoff phase. The thighs are charged with the function around the midpoint, the shanks in the phase immediately after the touchdown and before the takeoff, and the feet during the overall takeoff phase. The positive force of the feet is especially large in the phase immediately after the touchdown and before the takeoff, which accelerate the body upward

One-pot esterification and amidation of phenolic acids

We developed a new one-pot reaction of phenolic acids to afford the corresponding esters and amides through acyl-protected and activated phenolic acid intermediates. The simultaneous protection/activation of phenolic acids with alkylchloroformates proceeded readily in the presence of DMAP at room temperature; subsequent addition of alcohols or amines afforded the corresponding esters or amides. The use of iso-butyloxycarbonyl as the protecting and activating group in the one-pot reactions afforded phenolic esters or amides in 91% average yield. As a practical example of this convenient synthesis, caffeic acid phenethyl ester (CAPE) was readily synthesized from commercially available caffeic acid and phenethyl alcohol in 95% yield, and an isotopomer of CAPE, [3,10-13C2]CAPE, was synthesized in 91% yield from [3-13C]caffeic acid and 2-[1-13C]phenethyl alcohol. This method may be useful for the convenient esterification and amidation of diverse phenolic acids.ArticleTETRAHEDRON. 70(43):8097-8107 (2014)journal articl

Fatty Acid Accumulation and Resulting PPARα Activation in Fibroblasts due to Trifunctional Protein Deficiency

To examine fatty acid accumulation and its toxic effects in cells, we analyzed skin fibroblasts from six patients with mitochondrial trifunctional protein deficiency, who had abnormalities in the second through fourth reactions in fatty acid β-oxidation system. We found free fatty acid accumulation, enhanced three acyl-CoA dehydrogenases, catalyzing the first reaction in the β-oxidation system and being assumed to have normal activities in these patients, and PPARα activation that was confirmed in the experiments using MK886, a PPARα specific antagonist and fenofibrate, a PPARα specific agonist. These novel findings suggest that the fatty acid accumulation and the resulting PPARα activation are major causes of the increase in the β-oxidation ability as probable compensation for fatty acid metabolism in the patients' fibroblasts, and that enhanced cell proliferation and increased oxidative stress due to the PPARα activation relate to the development of specific clinical features such as hypertrophic cardiomyopathy, slight hepatomegaly, and skeletal myopathy. Additionally, significant suppression of the PPARα activation by means of MK886 treatment is assumed to provide a new method of treating this deficiency

PPARα Activation Protects against Anti-Thy1 Nephritis by Suppressing Glomerular NF-κB Signaling

The vast increase of chronic kidney disease (CKD) has attracted considerable attention worldwide, and the development of a novel therapeutic option against a representative kidney disease that leads to CKD, mesangial proliferative glomerulonephritis (MsPGN) would be significant. Peroxisome proliferator-activated receptor α (PPARα), a member of the steroid/nuclear receptor superfamily, is known to perform various physiological functions. Recently, we reported that PPARα in activated mesangial cells exerted anti-inflammatory effects and that the deficiency of PPARα resulted in high susceptibility to glomerulonephritis. To investigate whether PPARα activation improves the disease activity of MsPGN, we examined the protective effects of a PPARα agonist, clofibrate, in a well-established model of human MsPGN, anti-Thy1 nephritis, for the first time. This study demonstrated that pretreatment with clofibrate (via a 0.02% or 0.1% clofibrate-containing diet) continuously activated the glomerular PPARα, which outweighed the PPARα deterioration associated with the nephritic process. The PPARα activation appeared to suppress the NF-κB signaling pathway in glomeruli by the induction of IκBα, resulting in the reduction of proteinuria and the amelioration of the active inflammatory pathologic glomerular changes. These findings suggest the antinephritic potential of PPARα-related medicines against MsPGN. PPARα-related medicines might be useful as a treatment option for CKD

Kidney transplantation recovers the reduction level of serum sulfatide in ESRD patients via processes correlated to oxidative stress and platelet count

Sulfatide is a major component of glycosphingolipids in lipoproteins. Recently, we reported that a low serum level of sulfatide in hemodialysis patients might be related to the high incidence of cardiovascular diseases. However, the serum kinetics of sulfatide in kidney disease patients and the function of endogenous serum sulfatide are still unclear. To obtain novel knowledge concerning these issues, we investigated the serum kinetics of sulfatide in 5 adult kidney transplant recipients. We also analyzed the correlated factors influencing the serum sulfatide level, using multiple regression analysis. Kidney transplantation caused a dramatic increase of serum sulfatide without an alteration of its composition in all recipients in a time-dependent manner; however, the recovery speed was slower than that of the improvement of kidney function and the serum sulfatide reached a nearly normal level after 1 year. Multiple regression analysis showed that the significant correlated factor influencing the serum sulfatide level was log duration (time parameter) throughout the observation period, and the correlated factors detected in the stable phase were the decrease of serum concentration of malondialdehyde (an oxidative stress marker) as well as the elevation of platelet count. The current study results demonstrated the gradual but reliable recovery of the serum sulfatide level in kidney transplant recipients for the first time, suggesting a close correlation between serum sulfatide and kidney function. The recovery of serum sulfatide might derive from the attenuation of systemic oxidative stress. The normal level of serum sulfatide in kidney transplant recipients might affect platelet function, and contribute to the reduction of cardiovascular disease incidence.ArticleGLYCOCONJUGATE JOURNAL. 28(3-4):125-135 (2011)journal articl

Acute kidney injury induced by protein-overload nephropathy down-regulates gene expression of hepatic cerebroside sulfotransferase in mice, resulting in reduction of liver and serum sulfatides

Sulfatides, possible antithrombotic factors belonging to sphingoglycolipids, are widely distributed in mammalian tissues and serum. We recently found that the level of serum sulfatides was significantly lower in hemodialysis patients than that in normal subjects, and that the m serum level closely correlated to the incidence of cardiovascular disease. These findings suggest a relationship between the level of serum sulfatides and kidney function; however, the molecular mechanism underlying this relationship remains unclear. In the present study, the influence of kidney dysfunction on the metabolism of sulfatides was examined using an established murine model of acute kidney injury, protein-overload nephropathy in mice. Protein-overload treatment caused severe proximal tubular injuries within 4 days, and this treatment obviously decreased both serum and hepatic sulfatide levels. The sphingoid composition of serum sulfatides was very similar to that of hepatic ones at each time point, suggesting that the serum sulfatide level is dependent on the hepatic secretory ability of sulfatides. The treatment also decreased hepatic expression of cerebroside sulfotransferase (CST), a key enzyme in sulfatide metabolism, while it scarcely influenced the expression of the other sulfatide-metabolizing enzymes, including arylsulfatase A, ceramide galactosyltransferase, and galactosylceramidase. Pro-inflammatory responses were not detected in the liver of these mice: however, potential oxidative stress was increased. These results suggest that down-regulation of hepatic CST expression, probably affected by oxidative stress from kidney injury, causes reduction in liver and serum sulfatide levels. This novel mechanism, indicating the crosstalk between kidney injury and specific liver function, may prove useful for helping to understand the situation where human hemodialysis patients have low levels of serum sulfatides.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 390(4):1382-1388 (2009)journal articl

Peroxisome proliferator-activated receptor alpha mediates enhancement of gene expression of cerebroside sulfotransferase in several murine organs

Sulfatides, 3-O-sulfogalactosylceramides, are known to have multifunctional properties. These molecules are distributed in various tissues of mammals, where they are synthesized from galactosylceramides by sulfation at C3 of the galactosyl residue. Although this reaction is specifically catalyzed by cerebroside sulfotransferase (CST), the mechanisms underlying the transcriptional regulation of this enzyme are not understood. With respect to this issue, we previously found potential sequences of peroxisome proliferator-activated receptor (PPAR) response element on upstream regions of the mouse CST gene and presumed the possible regulation by the nuclear receptor PPAR alpha. To confirm this hypothesis, we treated wild-type and Ppara-null mice with the specific PPAR alpha agonist fenofibrate and examined the amounts of sulfatides and CST gene expression in various tissues. Fenofibrate treatment increased sulfatides and CST mRNA levels in the kidney, heart, liver, and small intestine in a PPAR alpha-dependent manner. However, these effects of fenofibrate were absent in the brain or colon. Fenofibrate treatment did not affect the mRNA level of arylsulfatase A, which is the key enzyme for catalyzing desulfation of sulfatides, in any of these six tissues. Analyses of the DNA-binding activity and conventional gene expression targets of PPAR alpha has demonstrated that fenofibrate treatment activated PPAR alpha in the kidney, heart, liver, and small intestine but did not affect the brain or colon. These findings suggest that PPAR alpha activation induces CST gene expression and enhances sulfatide synthesis in mice, which suggests that PPAR alpha is a possible transcriptional regulator for the mouse CST gene.ArticleGLYCOCONJUGATE JOURNAL. 30(6):553-560 (2013)journal articl

Kidney dysfunction induced by protein overload nephropathy reduces serum sulfatide levels in mice

We recently proposed serum sulfatides as a novel biomarker for cardiovascular disease in patients with end-stage renal failure (ESRF), based on the possible antithrombotic properties of this molecule. In this earlier study, the level of serum sulfatides was gradually decreased in parallel with kidney dysfunction; however the precise mechanism underlying this decrease was unknown. The aim of the present study was to investigate the mechanism underlying the decrease in serum sulfatide levels caused by kidney dysfunction in an experimental animal model. To produce a kidney dysfunction animal model, we prepared a mouse model of protein overload nephropathy. Using high-throughput analysis combined with matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, we measured the levels of sulfatides in the sera, livers, small intestines and kidneys of protein overload nephropathy mice. As the disease progressed, the levels of sulfatides in sera decreased. Also, the levels in livers and small intestines decreased in a similar manner to those in sera, to approximately 60% of the original levels. On the contrary, those in kidneys increased by approximately 1.4-fold. Our results indicate that kidney dysfunction affects the levels of sulfatides in lipoprotein-producing organs, such as livers and small intestines, and lowers the levels of sulfatides in sera.ArticleNEPHROLOGY. 14(7):658-662 (2009)journal articl

Two mechanistically distinct effects of dihydropyridine nifedipine on Ca(V)1.2 L-type Ca2+ channels revealed by Timothy syndrome mutation

Dihydropyridine Ca2+ channel antagonists (DHPs) block Ca(V)1.2 L-type Ca2+ channels (LTCCs) by stabilizing their voltage-dependent inactivation (VDI); however, it is still not clear how DHPs allosterically interact with the kinetically distinct (fast and slow) VDI. Thus, we analyzed the effect of a prototypical DHP, nifedipine on LTCCs with or without the Timothy syndrome mutation that resides in the I-II linker (LI-II) of Ca(V)1.2 subunits and impairs VDI. Whole-cell Ba2+ currents mediated by rabbit Ca(V)1.2 with or without the Timothy mutation (G436R) (analogous to the human G406R mutation) were analyzed in the presence and absence of nifedipine. In the absence of nifedipine, the mutation significantly impaired fast closed-and open-state VDI (CSI and OSI) at -40 and 0 mV, respectively, but did not affect channels' kinetics at -100 mV. Nifedipine equipotently blocked these channels at -80 mV. In wild-type LTCCs, nifedipine promoted fast CSI and OSI at -40 and 0 mV and promoted or stabilized slow CSI at -40 and -100 mV, respectively. In LTCCs with the mutation, nifedipine resumed the impaired fast CSI and OSI at -40 and 0 mV, respectively, and had the same effect on slow CSI as in wild-type LTCCs. Therefore, nifedipine has two mechanistically distinct effects on LTCCs: the promotion of fast CSI/OSI caused by LI-II at potentials positive to the sub-threshold potential and the promotion or stabilization of slow CSI caused by different mechanisms at potentials negative to the subthreshold potential.ArticleEUROPEAN JOURNAL OF PHARMACOLOGY. 685(1-3):15-23 (2012)journal articl

Efficacy and safety of addition of minor bloodletting (petit phlebotomy) in hepatitis C virus-infected patients receiving regular glycyrrhizin injections

The original publication is available at www.springerlink.comBackground: Hepatoprotective therapies that include regular glycyrrhizin injection (GI) are beneficial for chronic hepatitis C patients, but are sometimes unable to normalize serum alanine aminotransferase (ALT) levels. Here, we evaluated whether the addition of minor bloodletting, named petit phlebotomy (PP), prior to each GI could further reduce serum ALT concentrations in such patients. Methods: Seventy-six HCV-infected patients receiving regular GI with persistently abnormal serum ALT levels were randomly divided into GI+PP or GI groups and monitored for 12 months. PP was performed before every GI to a total 60 ml of blood a week. The primary PP endpoint was serum ferritin levels of less than 20 ng/ml. PP was suspended upon reaching the endpoint, but was resumed as needed. The efficacy of the addition of PP was evaluated by measuring changes in serum ALT levels. Results: Two patients in each group dropped out because of apparition of hepatocellular carcinoma. The remainder completed the 12-month treatment with no serious adverse events. Serum ALT and ferritin levels were significantly decreased in the GI+PP group (from 67 + 34 to 44 + 14 U/l and from 163 + 127 to 25 + 21 ng/ml, respectively, both P<0.001), but these changes were not seen in the GI group. Although twenty patients in the GI+PP group had compensated cirrhosis, no significant reductions in serum albumin concentrations were observed. Conclusions: The addition of PP is effective and safe for improving serum aminotransferase levels in HCV-infected patients receiving regular GI, even in those with compensated cirrhosis.ArticleJournal of Gastroenterology 44(6): 577-582(2009)journal articl