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Food includes not only nutrients, which are essential in ATP-producing energy metabolisms, sugars, proteins, lipids, vitamins, and minerals, but also non-nutrients that are not, such as phenolics, terpenoids, sulfate-containing chemicals, alkaloids, and indigestible polysaccharides. Plant-derived non-nutrients were recently found to play important roles in modulating the metabolism and preventing degenerative diseases. At intestinal absorption process, most non-nutrients undergo conjugation with glucuronic acid or sulfate on their functional groups and are excreted into the digestive lumen. In order to better understand how non-nutrients work to prevent disease, it is critical that these bioavailable functional compounds be identified in the diets. The bioactive functions of these compounds include: antioxidant potential to scavenge reactive oxygen species and protein function-modulating activity that dynamically regulates the metabolic functions of proteins, enzymes, transporters, receptors, and signaling transduction proteins that related to various lifestyle-related diseases, e.g., obesity, type 2 diabetes, cardiovascular disease. The Japanese Society for Food Factors (JSoFF) is interested in bioavailability and investigates the preventative functions of non-nutrients in vegetables, fruits and teas. In this review, the work of the JSoFF will be summarized including their work on classifying bioavailable and disease-preventive phytochemicals.

During cytokinesis in brown algal cells, Golgi-derived vesicles (GVs) and flat cisternae (FCs) are involved in building the new cell partition membrane. In this study, we followed the membrane fusion process in Silvetia babingtonii zygotes using electron microscopy together with rapid freezing and freeze substitution. After mitosis, many FCs were formed around endoplasmic reticulum clusters and these then spread toward the future cytokinetic plane. Actin depolymerization using latrunculin B prevented the appearance of the FCs. Fusion of GVs to FCs resulted in structures that were thicker and more elongated (EFCs; expanded flat cisternae). Some complicated membranous structures (MN; membranous network) were formed by interconnection of EFCs and following the arrival of additional GVs. The MN grew into membranous sacs (MSs) as gaps between the MNs disappeared. The MSs were observed in patches along the cytokinetic plane. Neighboring MSs were united to form the new cell partition membrane. An immunocytochemical analysis indicated that fucoidan was synthesized in Golgi bodies and transported by vesicles to the future cytokinetic plane, where the vesicles fused with the FCs. Alginate was not detected until the MS phase. Incubation of sections with cellulase-gold showed that the cellulose content of the new cross wall was not comparable to that of the parent cell wall.

Fucoxanthin is an oxygenated carotenoid present in edible brown sea algae, and dietary fucoxanthin is recognized to exhibit various beneficial effects. In the present study, the effects of fucoxanthin on osteoclastogenesis were investigated using cells from the macrophage cell line RAW264.7, which have the capacity to differentiate into osteoclast-like cells when stimulated by receptor activator of nuclear factor kappaB ligand. Fucoxanthin significantly suppressed the differentiation of RAW264.7 cells at 2.5 microM, which was not toxic to RAW264.7 cells. Treatment with 2.5 microM fucoxanthin also induced apoptosis accompanied by activation of caspase-3 in osteoclast-like cells. On the other hand, 2.5 microM fucoxanthin did not decrease cell viability in cells of the osteoblast-like cell line MC3T3-E1, indicating that the apoptosis-inducing activity of fucoxanthin in osteoclasts is stronger than that in osteoblasts. The present in vitro study suggests that fucoxanthin suppresses osteoclastogenesis via the inhibition of osteoclast differentiation and the induction of apoptosis in osteoclasts, but not bone formation.

外反母趾を合併した外反扁平足に対して外側支柱延長固定術とdistal lineal metatarsal osteotomy（以下DLMO法）を施行した2例を経験した．症例1 68歳女性 HV角40°，M1M2角17°の重症の外反母趾とJohnson分類stage IIの外反扁平足を認めた．症例2 64歳女性 HV角50°，M1M2角21°と重症の外反母趾とJohnson分類stage IIの外反扁平足を認めた．2症例ともにDLMO法と外側支柱延長固定術を同時に施行した．術後1年のX線で，HV角（症例1：10°，症例2：12°），M1M2角（症例1：12°，症例2：12°）は改善し，また外反扁平足も矯正されていた．

The establishment of a simple technique to determine the concentration of fucoidan was developed by using a monoclonal antibody against fucoidan. This antibody reacted with fucoidans purified from Laminaria japonica Areschoug (Makombu in Japanese) and Kjellmaniella gyrate Miyabe (Gagome), but not with polysaccharides from Undaria pinnatifida Suringar (Wakame). Neither laminarin nor algenic acid, which are constituents in Laminaria japonica, were recognized by the prepared antibody. Application of the enzymed-linked immunosorbent assay (ELISA) inhibition assay increased the specificity of fucoidan in measuring the fucoidan contents. On the basis of these results, it was ascertained that the ELISA inhibition assay of using the anti-fucoidan monoclonal antibody was rapid, accurate, and sensitive in measuring the content of fucoidan. In addition, the localization of fucoidan in Laminaria japonica was investigated. This is the first report of fucoidan being restricted to the outer cortical layer.

The oxidative formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA is closely associated with the induction of degenerative diseases, including cancer. However, the oxidant species participating in the formation of 8-OHdG has yet to be fully clarified. On the basis that peroxyl radicals are a strong candidate for this species, we employed 2,2'-azobis(2-amidinopropane) (AAPH) as a peroxyl radical generator. Exposure of calf thymus DNA to AAPH formed 8-OHdG, but the exposure of 2'-deoxyguanosine (dG) alone did not. From the exposure of various combinations of nucleotides, 8-OHdG was formed only in the presence of dG and thymidine (dT). A mix of dG with an oxidation product of dT, 5-(hydroperoxymethyl)-2'-deoxyuridine, produced 8-OHdG, but the amount formed was small. In contrast, 8-OHdG was produced abundantly by the addition of dG to peroxidized dT with AAPH. Thus, the formation of 8-OHdG was mediated by the peroxidized dT. Instead of artificial AAPH, endogenous peroxyl radicals are known to be lipid peroxides, which are probably the oxidant species for 8-OHdG formation mediated by thymidine in vivo.

A system for assessing the anti-inflammatory effect of food factors was developed by establishing a co-culture system with intestinal epithelial Caco-2 cells (apical side) and macrophage RAW264.7 cells (basolateral side). In this system, the stimulation of RAW264.7 cells with lipopolysaccharide was followed by a decrease in transepithelial electrical resistance, which is a marker of the integrity of the Caco-2 monolayer and an increase in TNF-alpha production from RAW264.7 cells and IL-8 mRNA expression in Caco-2 cells. Treatment with anti-TNF-alpha antibodies or budesonide suppressed in increase in TNF-alpha production and IL-8 mRNA expression. These results indicated that this co-culture model could imitate the gut inflammation in vivo. In addition, fucoidan, sulphated polysaccharides from brown algae, was employed as a candidate of evolution and added to the apical side of this model. Fucoidan suppressed IL-8 gene expression through a reduction in TNF-alpha production from RAW264.7 cells stimulated with lipopolysaccharide.

Fucoxanthin, a major carotenoid in brown sea algae, has recently been demonstrated by us to inhibit the proliferation of colon cancer cells, and this effect was associated with growth arrest. These results, taken together with previous studies with fucoxanthin, suggest that it may be useful in chemoprevention of other human malignancies. The present study was designed to evaluate the molecular mechanisms of fucoxanthin against hepatic cancer using the human hepatocarcinoma HepG2 cell line (HepG2). Fucoxanthin reduced the viability of HepG2 cells accompanied with the induction of cell cycle arrest during the G0/G1 phase at 25 microM. This concentration of fucoxanthin inhibited the phosphorylation of the retinoblastoma protein (Rb) at Serine 780 (Ser780) position 18 h after treatment. The kinase activity of cyclin D and cdk4 complex, responsible for the phosphorylation of Rb Ser780 site, was down-regulated 18 h after the treatment. Western blotting analysis revealed that the expression of cyclin D-type protein was suppressed by treatment of fucoxanthin. This reduction was partially blocked by concurrent treatment with the proteasome inhibitor MG132, indicating the involvement of the proteasome-mediated degradation. In addition, RT-PCR analysis revealed that fucoxanthin also appeared to repress cyclin D mRNA. Thus, both the protein degradation and transcriptional repression seem to be responsible for suppressed cyclin D level in fucoxanthin-treated HepG2 cells which may be related to the antitumorgenic activity.

A Maisonneuve fracture consists of a proximal fibular fracture with associated syndesmotic ligament disruption and injury to the medial ankle structures. The treatment outcome is good in most cases, although poor results have also been reported. The purpose of this study was to investigate intra-articular lesions in Maisonneuve fractures.The subjects consisted of four patients (four ankle joints) who had suffered a Maisonneuve fracture and had undergone surgical treatment between June 2005 and November 2005. The mean age was 24. 2 years. At the time of surgery, we performed ankle arthroscopy and determined the presence of tibiofibular syndesmosis disruption, cartilaginous damage, and ligament damage. Lesions of the articular cartilage were graded by depth as determined by inspection and probing.All four of the cases had cartilaginous damage to the medial section of the talar dome. Lateral lesions were not observed. Chondral debris and hemarthrosis were noted in virtually all cases, and each ankle had a tear on the anterior inferior tibiofibular ligament and interosseous tibiofibular ligament. No patients had a tear of the posterior inferior tibiofibular ligament.Arthroscopy was useful in identifying associated intra-articular lesions in Maisonneuve fractures.

Fucoxanthin exhibits a preventative function with degenerative diseases such as cancer and metabolic syndrome without side effects. Therefore, commercial-scale preparation of fucoxanthin is needed, but it has been very difficult to find the required resources to do so. The aim of this study is to develop a preparation method of fucoxanthin using waste parts of cultured kombu (Laminalia japonica). Around 79,000 t of cultured kombu is discarded in Japan during thinning out and forming processes, which includes a high amount of fucoxanthin (21.3-17.8 mg/100 g fresh weight). Waste parts of kombu were examined to obtain better quality fucoxanthin. Heating increased fucoxanthin recovery, and additional washing with tap water reduced the salt content of the fucoxanthin extract. Cutting waste parts of kombu into 5-mm wide strips made extraction easier without the leakage of fucoxanthin during handling. After freezing and transportation to the extraction factory, kombu showed the best recovery of fucoxanthin and the lowest content of salt following two extractions with 3 volumes of absolute ethanol. To remove chlorophylls the extract was subjected to silica gel column chromatography. Finally, 1490 g fucoxanthin was obtained from 10 t of waste parts of kombu and the recovery ratio was 82%. The fucoxanthin obtained was stable and reduced by only 2% in 6 months storage at 4°C. Thus, waste parts of cultured kombu are a good bioresource for fucoxanthin extraction.

Quercetin exhibits a potent anticarcinogenic activity. However, ingested quercetin circulates as the glucuronide/sulfate conjugates, which are less active compared to the aglycone in healthy individuals. This study aimed to develop further understandings of the cancer-preventing mechanism with dietary quercetin. According to a two-stage hepatocarcinogenesis model with N-diethylnitrosamine (DEN) and phenobarbital (PB), preneoplasms were induced specifically in the liver of Fisher 344 rats. In the liver, glutathione S-transferase placental form (GST-P) positive foci were produced 14 weeks later. beta-Glucuronidase activity increased significantly in the liver by 1.2-fold in the DEN/PB group compared to the activity in a saline group. In the kidney, thymus, lung, heart, and plasma, the activities were similar between both groups. When quercetin was dosed intragastrically 15 min before sacrifice, the aglycone level of quercetin in liver was significantly 1.9-fold higher in the DEN/PB group than in the saline group. On the other hand, quercetin was dosed to rats 3 times a week for 14 weeks. The treatment kept the aglycone level of quercetin at a significantly higher level and tended to suppress the formation of GST-P positive foci. The increase in beta-glucuronidase activity with carcinogenesis induction became insignificant following the frequent doses of quercetin. It was considered that quercetin aglycone played a preventative role and, thus, the conjugates were converted to the active aglycone by beta-glucuronidase that was induced by the generation of preneoplasms.

Carotenoids are compounds contained in foods and possess anticarcinogenic activity. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, some tumors remain tolerant to TRAIL-induced apoptosis. Therefore, it is important to develop agents that overcome this resistance. We show, for the first time, that certain carotenoids sensitize cancer cells to TRAIL-induced apoptosis. Combined treatment with halocynthiaxanthin, a dietary carotenoid contained in oysters and sea squirts, and TRAIL drastically induced apoptosis in colon cancer DLD-1 cells, whereas each agent alone only slightly induced apoptosis. The combination induced nuclear condensation and poly(ADP-ribose) polymerase cleavage, which are major features of apoptosis. Various caspase inhibitors could attenuate the apoptosis induced by this combination. Furthermore, the dominant-negative form of a TRAIL receptor could block the apoptosis, suggesting that halocynthiaxanthin specifically facilitated the TRAIL signaling pathway. To examine the molecular mechanism of the synergistic effect of the combined treatment, we did an RNase protection assay. Halocynthiaxanthin markedly up-regulated a TRAIL receptor, death receptor 5 (DR5), among the death receptor–related genes, suggesting a possible mechanism for the combined effects. Moreover, we examined whether other carotenoids also possess the same effects. Peridinin, but not alloxanthin, diadinochrome, and pyrrhoxanthin, induced DR5 expression and sensitized DLD-1 cells to TRAIL-induced apoptosis. These results indicate that the combination of certain carotenoids and TRAIL is a new strategy to overcome TRAIL resistance in cancer cells. (Mol Cancer Res 2007;5(6):615–25)

1996～2004年の間に治療を行ったリスフラン関節脱臼骨折は7例7足（全例男性）で，このうち陳旧例1例を除く6例6足に対し後ろ向き調査を施行した．年齢は21～58歳（平均34.7歳）で，経過観察期間は4～30ヶ月（平均15.3ヶ月）であった．骨折型は Hardcastle 分類で type A は3足，type B は2足，type C は1足で受傷原因は交通事故3足，労働災害3足であった．リスフラン関節脱臼骨折は見逃され陳旧化した場合やリスフラン関節の正確な整復を怠ると疼痛の原因になるため注意が必要である．

〈はじめに〉今回我々は，新鮮足関節果部骨折時に足関節鏡を施行した症例の関節内病変について検討を行ったので報告する．〈対象・方法〉2002年9月～2006年6月までに当院で手術を施行した足関節果部骨折は18例18足で，このうち骨接合術直前に足関節鏡を施行した9例9足を対象とした．骨折型はLauge-Hansen分類でSER型8足，PER型1足，PA型1足であった．全例足関節鏡視後に螺子，プレート，鋼線締結圧迫固定による骨接合術を施行した．〈結果〉9足中7足（78％）に骨軟骨損傷を認めた．〈考察〉足関節果部骨折における足関節鏡は単純X線像・CTでは評価困難である軟骨・靭帯損傷を的確に診断できるため有用と思われた．

Summary The use of flaxseed is increasing in foodstuffs; however, it contains a considerable amount of cyanogen glycosides. We have, therefore, developed a convenient method to remove cyanides from processed flaxseed, which involves the enzymic release of HCN from cyanogen glycosides and the steam-evaporation of HCN. Freshly ground flaxseed showed strong activity to transform cyanogen glycosides to HCN, while commercial enzymes, such as sweet almond β-glycosidase and butter bean linamarase, did not. To remove cyanides from flaxseed, 5% or 10% of freshly ground flaxseed by weight could be added to cold-pressed or heat-pressed flaxseed, respectively, with incubation at 30 °C for 18 h followed by steam heat to evaporate HCN. This simple method could remove cyanides from flaxseed up to the detection limit in commercial-scale treatment. The cyanide-free flaxseed meal retained the beneficial nutrients, protein, fat, fibre, and lignans at the same level as untreated flaxseed meal.

Antioxidative flavonoids, ubiquitously included in vegetables, fruits and teas, are expected to prevent degenerative diseases. It is unclear, however, whether flavonoids can enter the cellular nuclei and suppress the oxidative damage of DNA. Here, several flavonoids at the physiological concentration of 10 μM were dosed to 2.5 × 107 HepG2 cells. The nuclei were isolated and determined in the incorporated flavonoid levels, and simultaneously exposed to reactive oxygen generated from 25 mM of 2,2′-azobis(2-amidinopropane) dihydrochloride. Most of the tested flavonoids were incorporated into the cells in the range between 1000 and 1600 pmol/107 cells, and were in the nuclei at 250–450 pmol/107 cells at the maximum incorporation after 30 min of cell incubation. In the cells, 23% of quercetin (3,5,7,3′,4′-OH) and 8% of luteolin (5,7,3′,4′-OH) were the original aglycone forms and the others were the methylated and gulucuronide/sulfate conjugates, while 72% of kaempferol (3,5,7,4′-OH) and 85% of apigenin (5,7,4′-OH) were aglycones and located in the nuclei at the similar ratio of metabolites. Quercetin and luteolin significantly suppressed the formation of 8-oxo-7,8-dihydrodeoxyguanosine by 25% and 15%, respectively, compared to those in 0-time incubated cells with the flavonoids. Under such conditions of low level and hydroxyl-masked in the nuclei, the limited flavonoids were bioavailable antioxidants to prevent genetic damage and they were B-ring catechols such as quercetin and luteolin.

Artepillin C, a prenylated phenylpropanoid found specifically in Brazilian propolis, has been shown to be a bioavailable antioxidant. In this study, artepillin C was tested for colon cancer-preventing activity using azoxymethane-challenged ddY mice. Oral doses of 80 and 160 mg/kg body weight of propolis or 10 mg/kg of artepillin C (equi-amounts to 160 mg propolis) reduced significantly the frequency of colonic aberrant crypt foci (ACF) by 39.2, 43.7 and 43.4%, respectively. In liver of the mice, glutathione S-transferase and NADPH:quinone reductase activity increased with the doses of propolis or artepillin C, and an antioxidant-responsive element (ARE) was found to be activated for binding DNA. Artepillin C is considered to suppress the formation of colonic ACF through the activation of ARE and induction of phase II enzymes in liver.

Japanese kelp (kombu) includes a xanthophy, fucoxanthin. In the present study, the chemopreventive activity against the formation of aberrant crypt foci (ACF, a preneoplastic marker for colon cancer) was examined. Four groups of mice were housed with drinking water containing 5 mg/ml of a kombu ethanol extract, and 0.05 mg/ml and 0.1 mg/ml of purified fucoxanthin, and with water alone as the positive control. They were subcutaneously injected with 10 mg/kg b.w. of azoxymethane (AOM) on the 1st and 8th days. Another group served as a negative control without kombu and AOM. The positive control produced a substantial number of ACF by the 28th day. Significant reductions were found in the frequency of ACF: 36% for the kombu extract, 30% for 0.05 mg/ml fucoxanthin and 35% for 0.1 mg/ml fucoxanthin. In the liver of these mice, the kombu extract raised the level of activity of glutathione S-transferase (GST) and quinone reductase, and stimulated the antioxidant responsive element (ARE). Fucoxanthin enhanced the GST activity but did not affect the ARE. Thus, one of the kombu ingredients, fucoxanthin, can suppress the ACF formation induced by the colon carcinogen AOM, and other unknown ingredients can induce the ARE activation.

Endogenous antioxidative potential was examined in rats given green tea as daily drinking water for 4 weeks. Rats ingested 196 μmol/kg body weight/day of catechins (sum total of 8 kinds of catechins), and plasma levels were around 0.24 μM. The green tea also contained 2.1 mM ascorbic acid, but the plasma level was similar to that in control rats drinking water, about 30 μM. The tea-drinking rats had significantly lower levels of lipid peroxidation in the small intestines and kidneys, 30% and 40% lower, respectively, than the controls, and their erythrocytes showed significant resistance to aqueous peroxyl radicals generated from azo initiator. Then, the effects of 8 catechins were examined on the antioxidative potency of ascorbic acid in in vitro. Catechins suppressed the oxidation of deoxyguanosine after the immediate exhaustion of ascorbic acid. Thus, frequent daily drinking of green tea improved the antioxidative potential of ascorbic acid.

Fucoxanthin, a natural carotenoid, has been reported to have antitumorigenic activity in mouse colon, skin and duodenum models. The present study was designed to evaluate the molecular mechanisms of fucoxanthin against colon cancer using the human colon adenocarcinoma cell lines. Fucoxanthin reduced the viability of WiDr cells in a dose-dependent manner accompanied by the induction of cell cycle arrest during the G0/G1 phase at 25 microM and apoptosis at 50 microM. Fucoxanthin at 25 microM inhibited the phosphorylation of the retinoblastoma protein (pRb) at Ser780 and Ser807/811 24 h after treatment without changes in the protein levels of the D-types of cyclin and cyclin-dependent kinase (cdk) 4, whose complexes are responsible for the phosphorylation of pRb at these sites. A cdk inhibitory protein, p21WAF1/Cip1 increased 24 h after the treatment with 25 microM of fucoxanthin, but not p27Kip1. In addition, the mRNA of p21WAF1/Cip1 also increased in a dose-dependent manner. According to the experiments using the isogenic human colon adenocarcinoma cell lines, fucoxanthin failed to induce G0/G1 arrest in the p21-deficient HCT116 cells, but not in HCT116 wild-type cells. All of these findings showed that fucoxanthin inhibited proliferation of colon cancer cells. The inhibitory mechanism is due to the cell cycle arrest during the G0/G1 phase mediated through the up-regulation of p21WAF1/Cip1, which may be related to the antitumorigenic activity.

Potential chemopreventive agents exist in foods. Artepillin C in Brazilian propolis was investigated for its effects on colon carcinogenesis. We had found that artepillin C was a bioavailable antioxidant, which could be incorporated into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and inhibited the oxidation of intracellular DNA. Artepillin C was then added to human colon cancer WiDr cells. It dose-dependently inhibited cell growth, inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex, Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand, Northern blotting showed that artepillin C did not affect the expression of Kip1/p27 mRNA. According to the experiments using isogenic human colorectal carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis.

Soybean isoflavones have structures similar to that of estrogen and have received attention as alternatives to hormone replacement therapy for the prevention of postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is metabolized to equol by gut microflora, and the metabolite exhibits a stronger estrogenic activity than daidzein. However, there is no direct evidence that equol affects bone metabolism. In this study, we examined the effect of equol on the inhibition of bone loss in ovariectomized (OVX) mice. Female mice (8 wk old) were assigned to 5 groups as follows: sham-operated (sham), OVX, OVX + 0.1 mg/d equol administration (0.1 Eq), OVX + 0.5 mg/d equol administration (0.5 Eq), and OVX + 0.03 microg/d 17beta-estradiol administration (E(2)). Equol and E(2) were administered s.c., using a mini-osmotic pump. At 4 wk after the intervention, uterine weight was less in the OVX mice than in sham-operated mice (P < 0.05). The weight was maintained in the E(2) group. In contrast, administration of equol at doses used in this study did not affect uterine atrophy in OVX mice. Bone mineral density (BMD) for the whole body in the OVX group measured by dual-energy X-ray absorptiometry was lower than that in the sham group, whereas administration of 0.5 mg/d Eq as well as E(2) maintained the BMD. The BMD of the femur and lumbar spine in the OVX group was also lower than those in the sham group, and treatment with 0.5 mg/d Eq maintained it. Notably, the BMD of the proximal femur in the 0.5 Eq group was the same as that of the sham group. E(2) inhibited bone loss from all regions induced by OVX. These results suggest that equol, a major metabolite of daidzein, inhibits bone loss apparently without estrogenic activity in the reproductive organs of OVX mice.

It is well known that rupture of the flexor hallucis longus tendon can be associated with open injuries and that closed rupture of the flexor hallucis longus tendon is rare. Tendon injuries of the foot can occur secondary to direct, indirect, or repetitive injury. Repetitive tendon injuries can cause tendinitis or stenosing tenosynovitis. Tendinitis is associated with internal tendon injury that can present with tendon thickening, mucinoid degeneration, nodule development, or in situ partial tears. Stenosing tenosynovitis is the development of tendon adhesions within the tendon sheath that interfere with tendon gliding, known as trigger toe. The flexor hallucis longus tendon is susceptible to injury along its entire course. A total of 35 cases of complete or partial closed ruptures of the flexor hallucis longus tendon have been reported. We present the case of complete subcutaneous rupture of the flexor hallucis longus tendon associated with trauma at the proximal phalangeal head.

Beta-carotene and alpha-tocopherol are important antioxidants biologically, but whether their oxidized products are toxic or not remains to be discovered. Here, we chromatographically separated 5 pure products or isomeric mixtures from reaction mixtures of beta-carotene and reactive oxygens, and 17 lipid-radical scavenging products of alpha-tocopherol. The products were tested for mutagenicity using Salmonella typhimurium TA98, TA100, TA102, and TA104, in the presence and absence of S9. None showed mutagenicity against any of the four strains, or cytotoxicity that influenced the survival of the bacteria. Lipid-peroxides have been known to increase the formation of mutagens from dietary procarcinogens such as heterocyclic amines. So, we also measured the activity to increase 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) mutagenicity. The products from beta-carotene and alpha-tocopherol did not increase, but rather several of them suppressed, the mutagenicity of Trp-P-2. Thus, the products of beta-carotene and alpha-tocopherol formed after the antioxidant actions were not genotoxic.

【目的】足関節内遊離体に対する鏡視下遊離体摘出術の治療成績について検討した．【対象と方法】対象は足関節内遊離体に対し，鏡視下遊離体摘出術を施行した9例9足（男性4名，女性5名，平均年齢35.3歳）とした．手術は仰臥位にて足関節前内外側ポータルと必要に応じて後外側ポータルを作成し，鉗子を用いて遊離体を摘出した．評価項目は術前後の臨床症状，鏡視所見とし，臨床評価として日本足の外科学会足関節判定基準（JSSF scale）を用いた．【結果】術前に足関節の腫脹2足，LockingやCatching症状8足，可動域制限2足認めたが，術後全例症状は改善した．鏡視所見で遊離体の存在部位は足関節前方2足，外側3足，後方4足であった．JSSF scaleは術前平均75.0点が術後96.7点に改善した．【まとめ】足関節内遊離体に対する鏡視下遊離体摘出術を施行し，全例良好な成績を得ることができた．

Little is known about the additional prognostic value of computed tomography (CT) in addition to computed radiography in displaced intra-articular calcaneal fractures. Thepresent study was undertaken to examine and compare the final radiographic outcomes and the prevalence of treatment methods of displaced intra-articular calcaneal fractures in patients with preoperative computed radiography alone vs. a combination ofcomputed radiography and computed tomogra- phy.Thirty-four patients with 38 displaced intra-articular calcaneal fractures were divided into two groups: a group that was evaluated with computed tomography and computed radiography (17 patients; 20 fractures) and a group that was evaluated with computed radiography alone (17 patients; 18 fractures). Patient demographics, pre- operative and postoperative Bohler's angles, and fracture classifications were recorded. Postoperative outcomes were evaluated using calcanealfracture radiographic scores (modified Zwipp score).The mean age ofour patients in the present study was 43.3 ± 12.3 years. The mean age ofthe patients in the computed tomography group (48.4 ± 11.6 years) was significantly higher than that of the non-computed tomography group (37.6 ± 10.7 years, p = 0.005). The mean follow-up time was 17.4 ± 9.8 months. There was a significantly higher prevalence of open reduction and internalfixation in the computed tomography group versus the non-computed tomography group (p = 0.019). However there was no significant difference observed for the mean radiographic scores. Postoperatively, outcomes were satisfactory in both groups, although intra-articular alignment was significantly better in the computed tomography group (p = 0.020).The overall outcomes were comparable between the patient groups with computed tomography vs. those without computed tomography, exceptfor the superiority of postoperative intra-articular alignment in patients with computed tomography. Open reduction and internal fixation were more frequently performed in the patients with computed tomography than patients without computed tomography.

The mechanism of cytotoxicity induced by the DNA-damaging carcinogen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b] indole (Trp-P-1) was investigated in primary cultured rat hepatocytes. Cytotoxicity was caused by intact Trp-P-1 and not by metabolically activated derivatives prepared using a recombinant yeast strain AH22/pAMR2 expressing rat cytochrome P450 1A1, and not by metabolically activated derivatives. We also found internucleosomal DNA fragmentation 6 h after treatment with 30 microM Trp-P-1, indicating that the cytotoxicity was due to the induction of apoptosis. After treatment with Trp-P-1, c-Myc protein level increased in a time-dependent manner and p53 protein also increased transiently with a subsequent increase in Bax protein level. This apoptotic pathway required the activation of caspase-9 as an initiator after leakage of cytochrome c into the cytosol from mitochondria and the activation of caspase-3 and -7 as executioners, but not caspase-1, -6 or -8 as measured using the corresponding peptide inhibitors and substrates or western blotting. The activated caspases in turn cleaved poly(ADP-ribose) polymerase as an intracellular substrate. Furthermore, we detected NUC18-like endonuclease activity during apoptosis induced by Trp-P-1. These findings suggest that this apoptosis may have a role against heterocyclic amine-type carcinogens in normal cells.

3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), one of the tryptophan pyrolysates, is a dietary carcinogen and is formed in cooked meat and fish in our daily diet. Trp-P-1 will affect the cells in the blood circulation system before it causes carcinogenicity in target organs such as the liver. In this study, the cytotoxicity of Trp-P-1 was investigated in mononuclear cells (MNCs) from blood. Trp-P-1 (10-15 microM) decreased cell viability and induced apoptosis characterized both by morphological changes and by DNA fragmentation 4 h after treatment. DNA fragmentation was also observed following treatment at 1 nM after 24 h in culture. This result suggested that apoptosis would occur in the body following unexpected intake of foods containing Trp-P-1. To determine the mechanism of apoptosis, we investigated the activation of the caspase cascade in MNCs. Trp-P-1 (10-15 microM) activated the caspase cascade, i.e. the activity of caspase-3, -6, -7, -8 and -9 increased dose-dependently using peptide substrates, the active forms of caspase-3, -8 and -9 were detected by immunoblotting, and cleavage of poly(ADP-ribose) polymerase and protein kinase C-delta as the intracellular substrates for caspases was observed. A peptide inhibitor of caspase-8 completely suppressed activation of all other caspases, while an inhibitor of caspase-9 did not. These results indicated that caspase-8 may act as an apical caspase in the Trp-P-1-activated cascade.

A strong water-soluble antioxidant was identified in the popular commercial banana Musa cavendishii. It is dopamine, one of the catecholamines. For suppressing the oxygen uptake of linoleic acid in an emulsion and scavenging a diphenylpicrylhydrazyl radical, dopamine had greater antioxidative potency than glutathione, food additives such as butylated hydroxyanisole and hydroxytoluene, flavone luteolin, flavonol quercetin, and catechin, and similar potency to the strongest antioxidants gallocatechin gallate and ascorbic acid. Banana contained dopamine at high levels in both the peel and pulp. Dopamine levels ranged from 80-560 mg per 100 g in peel and 2.5-10 mg in pulp, even in ripened bananas ready to eat. Banana is thus one of the antioxidative foods.

The synergistic effect of food additives or food colors on the toxicity of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was investigated using primary cultured rat hepatocytes. When hepatocytes from rats fed a standard diet were treated with a mixture of four major food additives (sorbitol, sodium 1.(+)-glutamate, benzoic acid, and propylene glycol) or a mixture of six typical artificial food colors (erythrosine, allura red, new coccine, brilliant blue, tertrazine, and fast green), the in vitro treated food-color mixture itself showed cytotoxicity: the reduction of cell viability and decreases in the activities of gluconeogenesis and ureogenesis. The food-color mixture enhanced cytotoxicity of Trp-P-1 obviously. We then investigated the effects of in vivo-dosed food additives or food colors on Trp-P-1-caused toxicity. Hepatocytes were isolated and cultured from rats fed a diet containing a mixture of food additives or a mixture of food colors with half the amount of their respective acceptable daily intake for 4 wk. Trp-P-1 was administered to the hepatocytes at various concentrations for 12 h. Synergistic effects of in vivo-dosed food additives and food colors were not observed on Trp-P-1-caused cytotoxicity as estimated by a loss of cell viability and the reductions of DNA and protein syntheses. On the contrary, we have observed that in vivo administered food colors synergistically facilitated to reduce the activities of gluconeogenesis and ureogenesis in Trp-P-1-treated hepatocytes. These results suggest that the daily intake of artificial food colors may impair hepatic functions such as gluconeogenesis and ureogenesis, when dietary carcinogens are exposed to the liver cells.

Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the formation of 8-hydroxyl (8-OHdG) from 2'-deoxyguanosine (2'-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2'-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only alpha-tocopherol had a suppressive effect with an IC50 of 1.5 microM. Thus, except alpha-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2'-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis.

In mutagenicity and antimutagenicity tests, the toxicants have been activated to the ultimate mutagenic forms usually with rat cytochrome P450 (CYP) enzymes. An understanding is important of whether these data can be available for human. In this paper are compared the activating abilities of CYP1A1 between human and rat using recombinant yeast cells that express respective CYP1A1 and yeast NADPH−CYP−oxidoreductase simultaneously. Three different types of dietary procarcinogens, heterocyclic amines, were tested by two methods: a bioassay with Salmonella mutagenicity test and a chemical determination of N-hydroxyls as the ultimate mutagenic forms. Compared with ED50 values, saturation levels, and Vmax/Km values at an initial stage of the enzyme activity, human and rat CYP1A1 showed almost similar abilities for the metabolic activation on heterocyclic amines. The two enzymes also had the same preference for the tested procarcinogens and the same affinities to the specific inhibitors such as flavonoids. Keyw...

The present study compared the effects of six Chinese teas categorized by their production process: green, white, yellow, oolong, black and pu-erh teas, on carbon tetrachloride (CCl4)-induced liver injury. Wistar rats were given ad libitum the Chinese teas prepared according to the home-style methods for 1 week, and then intraperitoneally injected with CCl4 (1 mg/kg body weight) or olive oil as a vehicle. The yellow tea significantly ameliorated the increase in the activity of the alanine- and aspartate-aminotransferases in plasma. Thus, the drinking of yellow tea may contribute to protection against liver injury.

A novel antimutagen in bay laurel (Laurus nobilis L.) acts against the dietary carcinogen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). The antimutagen was purified chromatographically from et...

The cytotoxicity of heterocyclic amines, dietary carcinogens derived from cooked foods, to primary cultured rat hepatocytes was studied. A tryptophan pyrolysis product, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was the most cytotoxic of 11 compounds tested. Trp-P-1 was found to induce apoptosis as measured by morphological changes in nuclear chromatin and internucleosomal DNA fragmentation. 3-Amino-1-methyl-5H-pyrido[4,3-b] indole (Trp-P-2) showed a moderate apoptotic effect, and other compounds had a similar but weaker effect.

Quercetin, rutin, the extract of white radish sprout rich in kaempferol glycosides, and their combination were intragastrically administered to Wistar rats to investigate the interactive metabolism of these flavonoids. The combined administration of these flavonoids changed the concentrations of the metabolites in plasma as compared with the concentrations after the administration of a single compound.

Brazilian propolis, a folk medicine, is used worldwide as an alternative medicine to prevent colon cancer. The objective of the study was to test in a small pilot biomarker study in a high-risk group the safety and efficacy of propolis for colon cancer prevention, which has not been evaluated in humans.Subjects with adenoma polyps recently removed from the colon were randomly assigned to a propolis group of 15 and a placebo group of 16. In a double-blind study, the propolis group received capsules containing 165 μmol artepillin C and 150 μmol other polyphenols per day for 3 months. Prior to and at the end of the experiments, their blood was analyzed using biochemical tests, and specimens from the normal-appearing sigmoid colon mucosa were biopsied endoscopically to examine the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and mRNA expressions of proliferating cell nuclear antigen, cyclin D1, and Bax.Propolis extract significantly increased the mRNA level of cyclin D1 in the sigmoid colon mucosa, and the other biomarkers remained unchanged. Blood biochemical tests showed significantly higher activity of creatine phosphokinase (CPK), 143 ± 52 units/ml in the propolis group and 104 ± 38 units/ml in the placebo group (p = 0.026), at the end of the study. The increase in CPK activity in the propolis group was due to the increase of the myocardial band form of CPK. On the other hand, laxative treatment prior to endoscopic biopsy significantly increased 8-OHdG levels.The results from our pilot study did not provide evidence that Brazilian propolis was effective in preventing changes occurring during early stages of colon cancer. In contrast, propolis may have detrimental side effects on muscle tissue, including myocardial cells.

Background: The defect size of an osteochondral lesion of the talus is one of the most important prognostic factors for deciding clinical outcomes. However, the prognostic factors for small osteochondral lesions of the talus are unknown. Purpose: To investigate the significant prognostic factors for small osteochondral lesions of the talus using arthroscopic bone marrow stimulation techniques. Study Design: Case series; Level of evidence, 4. Methods: Fifty ankles in 50 patients treated with arthroscopic bone marrow stimulation techniques for an osteochondral lesion of the talus (2) were evaluated for prognostic factors. The patients were 22 men and 28 women (mean age, 35.0 years). Outcomes were measured using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, Berndt and Harty scale, and Saxena criteria. Results: The mean lesion size was 62 mm2 (range, 7-119 mm2). The mean AOFAS score improved from 74 (range, 18-90) preoperatively to 90 (range, 67-100) postoperatively. The Saxena criteria results were excellent, good, fair, and poor in 36 (72%), 8 (16%), 5 (10%), and 1 (2%) patients, respectively. The Berndt and Harty scale results were good in 34 (68%), fair in 6 (12%), and poor in 10 (20%) patients. Linear regression analyses showed prognostic significance for lesion depth and outcome. Medial lesions had a significantly higher incidence of poor outcomes than lateral lesions ( P < .05). Among the medial lesions, lesions uncovered with the medial malleolus had inferior outcomes compared with covered lesions ( P < .0001). There was no association between clinical outcome and lesion size or body mass index. In older patients (≥40 years), there was a significant trend toward inferior clinical outcomes ( P < .05). Conclusion: Arthroscopic bone marrow stimulation techniques provided satisfactory clinical outcomes. However, older patients, deep lesions, and medial lesions uncovered with the medial malleolus were associated with inferior clinical outcomes.

Induction of xenobiotics metabolizing enzymes is related to the formation and chemoprevention of cancer. Since cytochrome P450s (CYPs) including CYP1A subfamily metabolize certain pro-carcinogens to their ultimate forms, down-regulation of CYP1As by food factors leads to the prevention of cancer. Mushroom polysaccharides, especially beta-glucans such as lentinan from Lentinus edodes, possess the anti-tumor and immunomodulating activities through the cytokine production from immunocytes. Recent our studies have demonstrated that lentinan suppresses hepatic CYP1As expression in the both constitutive and inducible levels through the production of tumor necrosis factor-alpha and an increase in the DNA-binding activity of nuclear factor-kappaB. This paper discusses on the effective lentinan dosage and route of administration for suppression of CYP1As.

Category: Hindfoot Introduction/Purpose: Distal first metatarsal osteotomies are recommended for surgical treatment of mild to severe hallux valgus (HV) deformities. Angthong et al. reported that minimally invasive distal linear metatarsal osteotomy (DLMO) exhibited good outcomes, with no major complications. However, avascular necrosis of the metatarsal head following a distal osteotomy has been reported, because an aggressive plantar cut can disrupt the soft tissue plantarly, thereby disrupting the blood supply of digital arteries. The purpose of this study was to evaluate the in vivo blood flow of the pre- and post-osterotomy metatarsal head in patients with HV using laser Doppler flowmetry (LDF). Methods: Between April and November 2015, DLMO was performed on seven patients with HV. The patients comprised one male and four females, with a mean age at surgery of 43.4 (21–62) years. The primary surgical indications for DLMO were all levels of severity of possible manual correction in patients with foot pain. The patients were placed in the supine position, and without a tourniquet, a 1.5-cm skin incision was centered over the medial aspect of the first metatarsal neck. A 2.0-mm Kirschner wire was inserted manually from the wound to the medial side of the hallux using a retrograde technique. Under direct vision, the Kirschner wire was introduced into the medullary canal of the first metatarsal shaft. Blood flow measurements of the pre- and post-osteotomy first metatarsal head in the seven patients were performed by LDF (ALF21 N; ADVANCE Co., Tokyo, Japan). The probe was touched to the first metatarsal head. The blood flow measurements were repeated three times, and the mean values were calculated. Results: On preoperative plain radiographs, the mean hallux valgus angle was 38.0° (range: 22.4–45.8°), and the mean intermetatarsal angle was 17.0° (range: 10.4–21.9°). The mean pre- and post-DLMO systolic blood pressure at the time of the measurements was 87.3±7.76 and 88.1±8.25 mmHg, respectively (P=0.85). The mean pre- and post-DLMO blood flow rate was 1.71±0.68 and 1.66±0.49 ml/min/100 g, respectively (P=0.90). Conclusion: Steven et al. reported that a distal osteotomy can lead to avascular necrosis of the metatarsal head, because an aggressive plantar cut can disrupt the soft tissue plantarly, thereby disrupting the blood supply of digital arteries. However, we found that blood flow of the pre- and post-osteotomy metatarsal head was present in all patients examined, with no significant difference in the blood flow rates of the metatarsal head before and after DLMO. Based on the present results, it is possible to avoid major complications, such as avascular necrosis of the metatarsal head, because DLMO is minimally invasive and involves less release of the soft tissue.

This study found two compounds which strongly suppressed the mutagenicity of one of the dietary carcinogens, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in oregano (Origanum vulgare). The compounds were purified chromatographically monitoring the suppressing activity with Salmonella typhimurium TA98. An instrumental elucidation identified two flavonoids as 3,5,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (galangin) and 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one (quercetin). Galangin and quercetin are strong desmutagens that neutralized Trp-P-2 before mutating the bacteria. The amounts of galangin and quercetin required for 50% inhibition against the mutagenicity of 20 ng of Trp-P-2 (IC 50 ) were 0.12 and 0.81 μg, respectively, while the IC 50 of chlorophyll in oregano was 230 μg. Toward the other mutagens, benzo[a]pyrene, 1-nitro-pyrene, 2-(acetylamino)fluorene, and N-methyl-N'-nitro-N-nitrosoguanidine, they were not effective. Galangin and quercetin are the specific desmutagens against the dietary carcinogen Trp-P-2

In this study, the biological activity of 20 essential oils (EOs) from herbal plants and citrus fruits were investigated in terms of mammalian DNA polymerase (pol) inhibitory activity, cancer cell (human colon carcinoma, HCT116) growth inhibitory activity, antiallergic activity, as anti-β-hexosaminidase release activity in rat basophilic leukemia RBL-2H3 cells treated with calcium ionophore A23187, and antioxidant activity by a lipophilic-oxygen radical absorbance capacity method. These EOs showed patterns of inhibition of pol α, a DNA replicative pol, similar to their cancer cell growth inhibitory activity, and their inhibitory activity on pol λ, a DNA repair/recombination pol, by the EOs showed correlation with anti-β-hexosaminidase release activity. Among these EOs, chamomile (Matricaria chamomilla L.) was the strongest inhibitor of pols α and λ and showed significant effects on both cancer cell growth and mast cell degranulation. On the basis of these results, chamomile EO can be recommended as a potentially useful, bioactive candidate for therapeutic applications.

To date, actual results of a minimally invasive distal linear metatarsal osteotomy (DLMO) via more explicit radiographic delineation are poorly understood and radiographic findings and clinical results have not been systematically correlated. Purposes of this study were (1) to evaluate the effectiveness of DLMO using a precise radiographic mapping system; and (2) to determine the relationship between radiographic outcomes and clinical results.In 2008-2011, DLMO was performed in 30 patients (36 feet) who had reducible symptomatic hallux valgus. Clinical data were assessed using American Orthopaedic Foot and Ankle Society (AOFAS) score. Radiographs were reviewed at preoperative and final follow-up for delineations of first ray construct, hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular angle, and other radiographic profiles. Correlation between postoperative AOFAS score and degree of malalignment was also analyzed.A total of 36 feet had predominantly moderate hallux valgus (26 feet with HVA: 21-39°; 23 feet with IMA: 12-17°). Mean preoperative and postoperative AOFAS scores were 70.2 ± 11.3 and 95 ± 6.4, respectively (p 0.001). Mapping system revealed improvements of first ray construct deformity (p 0.05). Significant reductions in all angular measurements were observed at final follow-up period (p 0.001) and correlated significantly with changes in AOFAS score (p 0.001). Nine feet (25 %) were observed with recurrence of deformity which showed HVA15°. Significant sesamoid lateralization was observed (p 0.05). Twenty-four feet (66.7 %) showing overall sagittal malunions were found with significant plantar angulation (p = 0.026) and non-significant plantar displacement compared with preoperative reference (p = 0.43). These radiographic abnormalities were not related to clinical outcomes including postoperative AOFAS scores (p 0.05).DLMO is an acceptable procedure to correct reducible hallux valgus in most patients with moderate level of severity. Sagittal malunion, recurrence, and sesamoid lateralization are possibly radiographic abnormalities but are not associated with clinical impairments.