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Maltobionic acid (MA), formed by a gluconic acid and glucose linked by an α‐1,4 bond, may have the properties of a nondigestible oligosaccharide. The objective of this study was to elucidate the bioavailability of MA in rats and humans by observing digestion of MA by small intestinal enzymes, the fermentation of MA by gut microbiota, and the effect of adaptation following prolonged ingestion of MA. MA digestion was assessed using brush border membrane vesicles (BBMV) from rat small intestine. A within‐subject repeated measures design was used for ingestion experiments in 10 healthy female participants. After MA ingestion, postprandial plasma glucose and insulin levels, breath hydrogen excretion, and urinary MA were measured. The effect of adaptation following prolonged MA ingestion was investigated in rats. MA was minimally hydrolyzed by BBMV. Ingestion of 10 g of MA by healthy females did not elevate postprandial plasma glucose and insulin levels. Breath hydrogen and urinary MA were negligibly excreted over 8 hr following ingestion. Adaptation to prolonged MA ingestion produced no significant difference in exhaled hydrogen levels over 8 hr following administration compared with controls. MA is a new food material that is highly resistant to digestion and fermentation. It expresses the characteristics of a nondigestible oligosaccharide, including being low energy, improving the flavor of food and juice, and mineral solubilization., The objective of this study was to elucidate the bioavailability of maltobionic acid in rats and humans. Maltrobionic acid is a new food material that is highly resistant to digestion and fermentation. It expresses the characteristics of a nondigestible oligosaccharide, including being low energy.

Gut microbiota improved using prebiotics may delay the onset of senescence-related health problems. We hypothesized that prolonged intake of prebiotics delays senile osteoporosis. Forty-five male senescence-accelerated mouse prone 6 (SAMP6) aged four weeks were raised on 5% fructooligosaccharide (FOS), 5% glucomannan (GM), or a control diet for 31 weeks. Gut microbiota were identified using culture-dependent analytical methods. Mineral content in femoral bone was analyzed using atomic absorption spectrophotometry. Bone metabolism and inflammatory markers were measured using enzyme-linked immunosorbent assay. The numbers of Lactobacillus and Bacteroides in cecal contents were significantly higher in the FOS than in the control group ( p < 0.05); the number of Clostridium was significantly higher in the GM than in the control group ( p < 0.05). Calcium content was significantly higher in the femoral bones of the FOS group (30.5 ± 0.8 mg) than in the control group (27.5 ± 1.5 mg) ( p < 0.05). There was no difference between the GM (29.1 ± 2.0 mg) and control groups. During senescence, urinary deoxypyridinoline and serum high-sensitivity C-reactive protein levels significantly decreased in the FOS (1.2 ± 0.2 nmol/3 d and 80 ± 6.1 ng/100 mL) and GM groups (1.2 ± 0.2 nmol/3 d and 80 ± 6.1 ng/100 mL) compared with the control group (1.8 ± 0.5 nmol/3 d and 93 ± 7.4 ng/100 mL) ( p < 0.05). Thus, dietary FOS and GM modified gut microbiota and reduced bone resorption by reducing systemic inflammation in SAMP6.

The inhibition by 1,5-anhydro-d-glucitol (1,5-AG) was determined on disaccharidases of rats and humans. Then, the metabolism and fate of 1,5-AG was investigated in rats and humans. Although 1,5-AG inhibited about 50 % of sucrase activity in rat small intestine, the inhibition was less than half of d-sorbose. 1,5-AG strongly inhibited trehalase and lactase, whereas d-sorbose inhibited them very weakly. 1,5-AG noncompetitively inhibited sucrase. The inhibition of 1,5-AG on sucrase and maltase was similar between humans and rats. 1,5-AG in serum increased 30 min after oral administration of 1,5-AG (600 mg) in rats, and mostly 100 % of 1,5-AG was excreted into the urine 24 h after administration. 1,5-AG in serum showed a peak 30 min after ingestion of 1,5-AG (20 g) by healthy subjects, and decreased gradually over 180 min. About 60 % of 1,5-AG was excreted into the urine for 9 h following ingestion. Hydrogen was scarcely excreted in both rats and humans 24 h after administration of 1,5-AG. Furthermore, 1,5-AG significantly suppressed the blood glucose elevation, and hydrogen excretion was increased following the simultaneous ingestion of sucrose and 1,5-AG in healthy subjects. 1,5-AG also significantly suppressed the blood glucose elevation following the simultaneous ingestion of glucose and 1,5-AG; however, hydrogen excretion was negligible. The available energy of 1,5-AG, which is absorbed readily from the small intestine and excreted quickly into the urine, is 0 kJ/g (0 kcal/g). Furthermore, 1,5-AG might suppress the blood glucose elevation through the inhibition of sucrase, as well as intestinal glucose absorption.

Nutrition and dietary habits contribute to the onset and progression of sensorineural hearing loss (SNHL). Fructo-oligosaccharides (FOS) are non-digestible oligosaccharides and are known as prebiotics, which enhance short-chain fatty acid (SCFA) production and antioxidant activity. Although a substantial number of studies have shown that FOS play a role in the prevention of lifestyle-related diseases as prebiotics, little is known about the effects on the inner ear. The purpose of this study is to investigate the effect of FOS on gene expression and spiral ganglion neuron (SGN) protection in the inner ear of DBA/2 J mice, which is a model for early-onset progressive hearing loss. DBA/2 J mice were fed either control diet or FOS diet contained 10% (w/w) of FOS for 8 weeks. Analysis of mice fed the FOS diet revealed a change in intestinal flora including an inversion of the ratio of Bacteroidetes and Firmicutes, which was followed by a significant increase in SCFAs in the cecum and a decrease in an oxidative stress marker in the serum. In the inner ear, gene expression of neurotrophin, brain-derived neurotrophic factor (BDNF), its receptor, tyrosine kinase receptor b (Trkb), and the SCFA receptor, free fatty acid receptor 3 (FFAR3), were increased by FOS. In addition, the survival rate of SGNs in the inner ear was maintained in FOS-fed mice. Altogether, these results suggest that a compositional variation of the intestinal flora due to a prebiotic effect may be involved in the progression of SNHL.

We hypothesized that daily intake of nondigestible saccharides delays senescence onset through the improvement of intestinal microflora. Here, we raised senescence accelerated mice prone 8 (SAMP8) on the AIN93 diet (CONT), with sucrose being substituted for 5% of fructooligosaccharide (FOS) or 5% of glucomannan (GM), 15 mice per group. Ten SAMR1 were raised as reference of normal aging with control diet. Grading of senescence was conducted using the method developed by Hosokawa, and body weight, dietary intake, and drinking water intake were measured on alternate days. Following 38 weeks of these diets we evaluated learning and memory abilities using a passive avoidance apparatus and investigated effects on the intestinal microflora, measured oxidative stress markers, and inflammatory cytokines. Continuous intake of FOS and GM significantly enhanced learning and memory ability and decelerated senescence development when compared with the CONT group. Bifidobacterium levels were significantly increased in FOS and GM-fed mice. Urinary 8OHdG, 15-isoprostane, serum TNF-α, and IL-6 were also lower in FOS-fed mice, while IL-10 in FOS and GM groups was higher than in CONT group. These findings suggest that daily intake of nondigestible saccharides delays the onset of senescence via improvement of intestinal microflora., Gastroenterology Research and Practice, 2014, 303184; 2014

The objective of this study was to test the hypothesis that repeated ingestion of diet containing the leaf extract from a Morus alba (LEM) maintains the postprandial hypoglycemic response and suppresses the progression of insulin resistance in high-sucrose diet-fed KK-Ay mice with spontaneous type 2 diabetes mellitus (DM). This hypothesis is based on our previous studies where LEM competitively inhibited intestinal disaccharidases and suppressed the elevation of postprandial plasma glucose and insulin levels. Ten KK-Ay mice in each group were raised on 0%, 3%, or 6% LEM powder-containing high-sucrose diets for 8 weeks. Blood samples were collected to measure fasting plasma glucose and insulin levels at weeks 2, 4, and 7 after the start of feeding. Urinary glucose excretion was monitored as a parameter of insulin resistance in 3-day intervals. Fasting plasma glucose level and urinary glucose excretion were significantly lower in both 3% and 6% LEM groups compared with the control group throughout the experiment. The plasma insulin of the 6% LEM group was significantly lower compared with the 3% LEM and control groups. Maintenance of low blood glucose and insulin delayed the onset time of urinary glucose excretion and were reflected by the ratio of additional LEM to sucrose in the diet. We observed the suppressive effects on the progression of hyperglycemia and hyperinsulinemia in the repeated ingestion of the LEM-containing diet. Namely, repeated ingestion of the LEM-containing diet reduces insulin resistance and may delay the appearance of DM, especially type 2 DM. Therefore, daily intake of LEM may be suitable for the prevention of obesity and DM.

Chronic leg ulcers have various causes and can be difficult to treat, although topical treatments, including basic fibroblast growth factor and PGE1, have been used. We applied an allogeneic cultured dermal substitute (CDS) to eight patients with intractable ulcers. The patients had various underlying diseases, including diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome, necrobiosis lipoidica, stasis dermatitis, livedo vasculopathy, and rheumatoid arthritis. The CDS was prepared by seeding cultured human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelocollagen. Good clinical results were achieved, as demonstrated by reepithelization, healthy granulation tissue formation, and a subsequent decrease in wound size. Daily dressing changes became unnecessary when the allogeneic CDS was used. Based on these results, we suggest that CDS may be useful for the treatment of intractable skin ulcers.

Human papillomaviruses (HPVs) have been detected in lesions of Bowen's disease (BD) and Bowen's carcinoma (BC); the invasive tumor retains the cytological characteristics of BD. Previous reports suggest that nestin-expressing hair follicle stem cells are undifferentiated and pluripotent, and nestin expression in some tumors indicates poor differentiation and high grade of malignancy. We identified HPV-DNA in BD (n=25) and BC (n=23) by in situ hybridization (ISH) analysis with INFORM(®) HPV III (Ventana Medical Systems. AZ, USA) and determined nestin expression by indirect immunohistochemical staining with anti-nestin polyclonal antibody (IBL, Gunma, Japan). We detected HPV-DNA in 68% of BD and in 87% of BC. In BD, 13 cases demonstrated the punctuate pattern, and four showed nestin expression. In BC, 19 cases showed the punctuate pattern and 16 showed nestin expression. HPV-DNA integrates into the host genome, and this is observed as the punctuate pattern on ISH. The nestin expression was statistically high in group of BC than BD (P0.01). These results therefore suggest that HPV-DNA integrated in the genome of tumor cells of these diseases and contributed to malignant alteration. From the standpoint of tumorigenesis, BC might represent one type of poorly differentiated, high-grade squamous cell carcinoma.

68歳，女性。1999年より関節リウマチ（以下RA）にて加療中であった。2005年6月より左下腿に外傷などの誘因なく潰瘍が出現し，徐々に拡大した。臨床・病理組織より壊疽性膿皮症（以下PG）と診断した。中等量のプレドニゾロン（以下PSL）内服を行うも潰瘍は拡大傾向にあるため，シクロスポリン（以下CYA）を併用したところ急速に縮小した。しかし，その後PSLとCYAを漸減中に胸部に肺病変が出現した。気管支鏡下肺生検の病理組織所見は無菌性の肉芽腫反応であった。同組織の培養は結核を含めて陰性で，抗真菌剤および抗生剤は無効であった。肺の結節は特に治療を加えることなく消退傾向を示したことからPGに伴う肺病変と考えた。

Nestin is an intermediate filament protein, and serves as a hair follicle stem cell and neural stem cell marker. Recent studies have suggested that nestin expression is also important for tumorigenesis. Previous reports from our laboratory have revealed that nestin is a marker of HMB-45-negative melanoma cells in dermal invasive lesions of nodular malignant melanoma. The present study examines nestin expression in malignant melanoma and investigates the relationship between nestin expression and prognosis in patients. We immunohistochemically stained 78 formalin-fixed and paraffin-embedded malignant melanomas for nestin, HMB-45 and S100 reactivity. We found that nestin, HMB-45 and S100 protein were detected in 56.5%, 88.4% and 100% of malignant melanomas, respectively. The 5-year survival rate of stage I and II nestin-positive cases was significantly decreased compared to the nestin-negative cases (p < 0.05). In addition, the 5-year survival rate exceeded 80% in nestin-negative malignant melanomas at all stages of tumor development. We conclude that nestin expression may be a predictor of poor prognosis in patients with malignant melanoma.

Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

A 68-year-old woman developed an upper respiratory tract infection in November 2002 and was treated with eprazinone hydrochloride, serrapeptase, carbocysteine and clarithromycin. Three days after the start of treatment, the patient noted erythema on her axilla, buttock and inguinal regions. The erythema subsided in 7 days although slight pigmentation remained. However, 7 days later the pigmentation completely disappeared. Oral eprazinone hydrochloride was given as a challenge, and 1 day later the erythema re-appeared in the same areas as on initial presentation (axilla, buttock, and inguinal regions). A fixed erythema without lasting pigmentation is attributed to eprazinone hydrochloride. Therefore, the patient was diagnosed as having a nonpigmented fixed drug eruption associated with eprazinone hydrochloride.

ejd.2012.1713 Auteur(s) : Yasuyuki Amoh Yasuyukiamoh@aol.com, Kenichi Tanabe, Hiroshi Takasu, Kensei Katsuoka Department of Dermatology, Kitasato University School of Medicine, 1-15-1 Kitasato Minami Ward, Sagamihara Kanagawa 252-0374, Japan In this report, a rare case of primary cutaneous anaplastic large cell lymphoma (PCALCL) arising from a burn scar is described. A 35-year-old Japanese male suffered a second-degree, deep, dermal burn measuring 4×3 cm, on his right upper arm, caused by [...]