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Activation of pyruvate dehydrogenase (PDH) by inhibition of pyruvate dehydrogenase kinase (PDHK) has the potential for the treatment of diabetes mellitus and its complications, caused by the malfunction of the glycolytic system and glucose oxidation. In this paper, we describe the identification of novel PDHK inhibitors with a fluorene structure. High-throughput screening using our in-house library provided compound 6 as a weak inhibitor that occupied the allosteric lipoyl group binding site in PDHK2. Structure-based drug design (SBDD) while addressing physicochemical properties succeeded in boosting inhibitory activity approximately 700-fold. Thus obtained compound 32 showed favorable pharmacokinetics profiles supported by high membrane permeability and metabolic stability, and exhibited activation of PDH in rat livers and a glucose lowering effect in Zucker fatty rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

[Purpose] We investigated the effects of low-intensity pulsed ultrasound (LIPUS) irradiation of the infrapatellar fat pad (IFP) combined with therapeutic exercise for management of knee osteoarthritis (knee OA). [Participants and Methods] The study included 26 patients with knee OA, who were randomized into the LIPUS group (patients underwent LIPUS + therapeutic exercise) and the therapeutic exercise group (patients underwent sham LIPUS + therapeutic exercise). We measured changes in the patellar tendon-tibial angle (PTTA) and in IFP thickness, IFP gliding, and IFP echo intensity after 10 treatment sessions to determine the effects of the aforementioned interventions. We additionally recorded changes in the visual analog scale, Timed Up and Go Test, the Western Ontario and McMaster Universities Osteoarthritis Index, and Kujala scores, as well as range of motion in each group at the same end-point. [Results] Compared with patients in the therapeutic exercise group, those in the LIPUS group showed significant post-treatment improvements in PTTA, VAS, and Kujala scores, as well as in range of motion. [Conclusion] The combined use of LIPUS irradiation of the IFP and therapeutic exercise is a safe and effective modality to reduce IFP swelling, relieve pain, and improve function in patients with knee OA., Competing Interests: None of the authors has any conflict of interest to declare., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

X-ray absorption near-edge structure (XANES) suffers from core-hole lifetime broadening at a higher energy absorption edge, such as Sn K (29 keV, Gamma(K) = 8.49 eV). To overcome this problem, emitted Sn Kalpha1 fluorescence from sample was counted using high-energy-resolution fluorescence spectrometer in the XANES measurements. Experimental energy resolution (5.0 eV) was consistent with theoretical values based on the Rowland configuration of the spectrometer. The absorption edge became steeper compared to conventional spectra. The white-line peak due to Sn(II) species became remarkably sharper and more intense in the Sn Kalpha1-detecting Sn K-edge XANES for Pt-Sn/SiO2. To support the semiclassical theory of resonant Raman scattering for the explanation of observed elimination of lifetime width, more resolved XANES data at Cu K, Pb L3, and Sn K in this work were convoluted (filtered) with a Lorentzian of each core-hole lifetime width. The processed data resembled generally well corresponding XANES spectrum measured in transmission mode. The verification based on ab initio XANES calculations was also performed.

Antioxidant activity of green tea extract or tea-derived polyphenols has been extensively studied. However, antioxidant activity in the non-polyphenolic fraction of green tea has been poorly analyzed. In the present study, we analyzed the antioxidant activity of the non-polyphenolic fraction of the residual green tea (Camellia sinensis) after hot water extraction using the aluminum chloride method. The non-polyphenolic fraction of residual green tea caused a significant suppression against hydroperoxide generation from oxidized linoleic acid in a dose-dependent manner. When the concentrate of the non-polyphenolic fraction was applied to a silica gel TLC plate and developed, six color spots were observed, which were considered to be chlorophylls a and b, pheophytins a and b, carotenoids, such as beta-carotene and lutein according to their specific colors, Rf values of silica gel TLC and spectrophotometric properties. Among these pigments, pheophytins a and b showed relatively abundant amounts, and the second major group of the pigment was chlorophylls a and b, and carotenoids such as beta-carotene and lutein indicated lower concentrations. Although all these pigments exhibited significant antioxidant activities, the ranks of suppressive activity against hydroperoxide generation were chlorophyll a > lutein > pheophytin a > chlorophyll b > beta-carotene > pheophytin b. These results suggest that the non-polyphenolic fraction of residual green tea has a potent suppressive activity against hydroperoxide generation from oxidized linoleic acid, which is derived from the antioxidant activities of chlorophylls a and b, pheophytins a and b, beta-carotene and lutein. This finding also implies that the combined intake of polyphenols in water-soluble fraction and antioxidative pigments in the non-polyphenolic fraction of green tea will be more efficient to prevent life style-related chronic diseases.

XAFS (X-ray absorption fine structure) spectra were measured by using the fluorescence spectrometer for the emitted X-ray from sample. The chemical shifts between Cu0 and Cu1 and between CrIII and CrVI were evaluated. Tuning the fluorescence spectrometer to each energy, the Cu0 and CuI site-selective XANES for Cu/ZnO catalyst were measured. The first one was similar to the XANES of Cu metal and the second one was the 5 : 5 average of XANES for CuI sites + Cu metal. The population ratio of copper site of the Cu/ZnO catalyst was found to be Cu metal: Cu2O : CuI atomically dispersed on surface = 70(+/-23) : 22(+/-14) : 8(+/-5). Site-selective XANES for CrIII site of Cr/SiO2 catalyst was also studied.

The responsiveness of melanophores of the medaka fish (wild type, Oryzias latipes) to a neurotransmitter and hormones is changed differentially after long-term adaptation to a black or white background. In the present study, we further examined whether this phenomenon involved some change in the intracellular signaling system. Using a permeabilized melanophore model, in which pigment granules could be dispersed by exogenously applied cAMP, the requirement of cAMP for pigment-dispersing reaction was revealed to be higher in melanophores of fish adapted to a black background (B cells) than in those of white background-adapted fish (W cells). Specific inhibitors of cAMP-dependent protein kinase (PKA) and cyclic nucleotide phosphodiesterase did not reduce the difference in the pigment dispersion level between B and W cells. A similar result was obtained with the free catalytic subunit of PKA. In contrast, the inhibition of protein phosphatase activity by okadaic acid diminished the difference in the responsiveness between B and W cells. These results suggest that the activity of protein phosphatase in B cell is higher than that in W cells, and that the change in the melanophore responsiveness by long-term chromatic adaptation to a background involves the change in the enzyme activity in the intracellular signaling system.

Medicolegal evaluation of 1495 cases of unnatural death of last 10 years was carried out in our department and the data so obtained were statistically analysed. The cases consisted of 260 inspections, 865 judicial autopsies and 370 administrative autopsies. The most frequent category was death from diseases followed by suicide, homicide, traffic accidents, other accidents and self originated accidents. In homicide cases, sharp objects were mainly used. Six cases of accident of scuba diving were included within the group of 28 cases of drowning of self originated variety. Although Okinawa is subtropical 12 cases of death by accidental hypothermia were found. Gangland fight using rifles cost 7 lives, 2 policemen, a high school student and 4 members of locally originated gangsters during last 18 months. Cardiac insufficiency was the most common of sudden unexpected death cases that complied with the data of Tokyo and Osaka. Death from alimentary disorder in Okinawa was 1.5 times more frequent than that in Tokyo and Osaka and liver disorder accounted for about 41%. The 68 cases of death from suckling contained 10 SIDS cases. Complication of medical treatment was encountered in 9 cases during the past 10 years.

Both aconite toxins (aconitine, mesaconitine, and hypaconitine) and a pufferfish toxin (tetrodotoxin, TTX) were detected in the blood of a legal autopsy case. In order to elucidate the in vivo influence of TTX on the toxic effects of aconitine, a mixture of aconitine and TTX was administered to male ICR mice orally or intraperitoneally. The animal experiments revealed that the time of death due to aconitine was significantly delayed in proportion to the dose of TTX compared with the case for aconitine alone, and that the mortality of aconitine was lowered by TTX when the dose ratio of the two toxins was in a particular range. Accordingly, it is thought that the toxic effects of aconitine are attenuated by TTX in vivo.

The effects of paraquat on human embryonic somatic cells were studied. Monolayer cultured cells, from several different organs, were exposed to various concentrations of paraquat. Then, the cells were stained with nigrosine and Sudan IV to demonstrate dead or damaged cells and fatty granules, respectively. The lowest paraquat concentration that caused morphological changes varied from 1 to 10 ppm, and the lowest concentration that caused fatty degeneration varied from 1 to 5 ppm. In both types of staining, the lowest degenerative concentration was lower as the culture generation was younger, and the degree of degeneration did not differ with the cell origin. The protein content per cell in paraquat-treated cells was not significantly decreased in comparison with control cells.

Serum samples from 738 unrelated individuals of three populations in the Miyako Islands were tested for twelve Gm allotypes to investigate the variability of phenotypes and haplotypes. Nine phenotypes observed in these populations as well as mainland Japanese could be explained by the presence of the four Gm haplotypes, ag, axg, ab3st, and afb1b3. A good agreement was obtained in the samples of each populations between the observed and expected frequencies on the basis of the Hardy-Weinberg equilibrium of phenotypes. These populations showed remarkable heterogeneities with one another on the basis of Gm haplotype frequency analysis. Moreover they exhibited no homogeneities with the Ryukyuans nor with the mainland Japanese. Homogeneity was found between the Ainu and the people in Ueno village but not in the other two locations. However, Gm xg haplotype, only detected in the Ainu, was not found in Ueno. These may imply a racial relationship between the Ainu and the inhabitants in Miyako in the remote past. However, there is no certainty that both of Ainu and the people in Ueno derived from the same origin, or that genetic drift due to endogamy in this village took place. The Gm phenotype and haplotype frequencies observed in Miyako show that they belong to the northern mongoloid group characterized by a high frequency of Gm ag and an extremely low frequency of Gm afb1b3. It is therefore reasonable to assume that they came from northern Asia as well as mainland Japanese.

The effects of paraquat on human embryonic somatic cells were compared with those of diquat, which is a bipyridylium compound similar to paraquat. Cell lesions, mainly fatty degeneration, were observed after staining with Sudan Black B. Both herbicides caused fatty degeneration in the cells even at a concentration of 1 ppm; paraquat also caused more vacuolar degeneration at 200 to 400 ppm, than did diquat. Paraquat caused slightly higher lactate dehydrogenase activity than did diquat. The cell mortality was examined by staining with nigrosine and calculating the number of dead and damaged cells. The cell mortality for diquat was higher than that for paraquat at all concentrations but not significantly (p less than 0.05).

The method and its reliability for sex determination by examining X-chromatin in the nucleus of hair root cell and buccal mucosa cell are presented: 1) X-chromatin in the nucleus of hair cortex cell was stained by Feulgen reaction after bleaching melanin granules and the frequency of X-chromatin was calculated under a ordinary microscope. An another method, fluorescent Feulgen reaction with acriflavine using a fluorescence microscope, was attempted. The results obtained from both methods indicated significantly higher values in the female samples than those in the male ones. 2) The other hand, the frequency of Y-chromatin was determined after quinacrine staining using a fluorescence microscope, and was also distinguishable between the male and female samples. 3) Using a single specimen, sex determination from the frequency of X- or Y-chromatin was practicable through combined treatment of quinacrine staining and fluorescent Feulgen reaction. 4) These methods were available during 16 to 64 weeks at least regarding samples kept dry. It is concluded that sex determination from frequency of sex chromatin after treatment described above is reliable.