A Blended Vitamin Supplement Improves Spatial Cognitive and Short-Term Memory in Aged Mice.

Although many types of antioxidant supplements are available, the effect is greater if multiple types are taken simultaneously rather than one type. However, it is difficult to know which type and how much to take, as it is possible to take too many of some vitamins. As it is difficult for general consumers to make this choice, it is important to provide information based on scientific evidence. This study investigated the various effects of continuous administration of a blended supplement to aging mice. In 18-month-old C57BL/6 mice given a blended supplement ad libitum for 1 month, spatial cognition and short-term memory in the Morris water maze and Y-maze improved compared with the normal aged mice (spontaneous alternative ratio, normal aged mice, 49.5%, supplement-treated mice, 68.67%, p < 0.01). No significant differences in brain levels of secreted neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, were observed between these two groups. In treadmill durability tests before and after administration, the rate of increase in running distance after administration was significantly higher than that of the untreated group (increase rate, normal aged mice, 91.17%, supplement-treated aged mice, 111.4%, p < 0.04). However, training had no reinforcing effect, and post-mortem serum tests showed a significant decrease in aspartate aminotransferase, alanine aminotransferase, and total cholesterol values. These results suggest continuous intake of a blended supplement may improve cognitive function and suppress age-related muscle decline.

The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic skin hardening, which combines Raynaud's phenomenon and other vascular disorders, skin and internal organ fibrosis, immune disorders, and a variety of other abnormalities. Symptoms vary widely among individuals, and personalized treatment is sought for each patient. Since there is no fundamental cure for SSc, it is designated as an intractable disease with patients receiving government subsidies for medical expenses in Japan. Oxidative stress (OS) has been reported to play an important role in the cause and symptoms of SSc. HOCl-induced SSc mouse models are known to exhibit skin and visceral fibrosis, vascular damage, and autoimmune-like symptoms observed in human SSc. The antioxidant combination Twendee X® (TwX) is a dietary supplement consisting of vitamins, amino acids, and CoQ10. TwX has been proven to prevent dementia in humans with mild cognitive impairment and significantly improve cognitive impairment in an Alzheimer's disease mouse model by regulating OS through a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. We evaluated the effectiveness of TwX on various symptoms of HOCl-induced SSc mice. TwX-treated HOCl-induced SSc mice showed significantly reduced lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced highly oxidized protein products (AOPP) in serum and suppressed Col-1 gene expression and activation of B cells involved in autoimmunity. These findings suggest that TwX has the potential to be a new antioxidant treatment for SSc without side effects.

Twendee X, a mixed antioxidant supplement, improves cognitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice.

Oxidation products gradually accumulate during senescence, enhancing the risk of onset of many severe diseases. One such disease is dementia, and the number of cases of dementia, including Alzheimer's disease, has been increasing world-wide. These diseases can be prevented via attenuation of age-related physiological dysfunction; one preventive approach is the ingestion of antioxidants such as vitamin C and vitamin E. Many antioxidants are readily available commercially. Ingestion of mixed antioxidants is expected to provide further beneficial effects for human health. In this study, we used vitamin E-deficient mice as an animal model of increased oxidative stress and assessed the effects of dosing with mixed antioxidants. Administration of a commercial mixed antioxidant formula, Twendee X significantly improved cognitive function and coordination compared to untreated vitamin E-deficient animals. Furthermore, the levels of brain-derived neurotrophic factor and nerve growth factor were significantly increased in the cerebral cortex of Twendee X-dosed vitamin E-deficient mice compared to untreated animals. These results indicate that intake of a mixed antioxidant supplement may be beneficial to human health, even after oxidative stress has begun. In the next stage, it will be necessary to compare with other antioxidants and consider whether it is effective in the aged model.

Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study.

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.

Antioxidant action of fermented grain food supplement: Scavenging of peroxyl radicals and inhibition of plasma lipid oxidation induced by multiple oxidants.

Unregulated oxidative modification of biological molecules induced by multiple oxidants in vivo has been implicated in the pathogenesis of various diseases. Accordingly, the role of antioxidants contained in foods in the maintenance of health and prevention of diseases has received much attention. The efficacy of antioxidants against oxidative stress depends on the nature of oxidants. In the present study, the antioxidant action of fermented grain food supplement, Antioxidant Biofactor (AOB), for scavenging peroxyl radical and inhibition of plasma lipid oxidation induced by multiple oxidants was measured. The antioxidant efficacy against lipid oxidation was assessed by the level of lipid hydroperoxides produced using diphenyl-1-pyrenylphosphine, which is not fluorescent per se but reacts with lipid hydroperoxides stoichiometrically to yield highly fluorescent diphenyl-1-pyrenylphosphine oxide. AOB acted as a potent peroxyl radical scavenger and suppressed lipid oxidation induced by peroxyl radical, peroxynitrite, hypochlorite, and singlet oxygen, but not by 15-lipoxygenase.

Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice.

High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis.

Assessment of radical scavenging capacity of antioxidants contained in foods and beverages in plasma solution.

The assessment of the radical scavenging capacity of antioxidants has been the subject of extensive studies and controversy. The aim of this study is to develop a simple and inexpensive method for the assessment of the radical scavenging capacity of antioxidants contained in foods and beverages in plasma solution, a biologically relevant heterogeneous medium. Three types of probes, hydrophilic pyranine, with low reactivity, hydrophilic pyrogallol red (PGR), with high reactivity, and lipophilic BODIPY, with moderate reactivity, were separately used to measure the amount and rate of peroxyl radical scavenging. The amount of radicals scavenged by antioxidants was assessed from the lag phase produced by antioxidants in the decay of pyranine and BODIPY, while the reactivity of the antioxidants was assessed from their effect on the decay rate of PGR. Two liquid and two solid samples were tested. Commercial bottled green tea and vegetable juice were found to scavenge 15.6 and 3.45 mmol radicals L(-1) and the former scavenged peroxyl radicals 81 times faster than the latter. As for the solid samples, instant coffee powder was found to scavenge several times more radicals and more rapidly than green tea powder. This method may be applied to the assessment of the radical scavenging capacity of antioxidants contained in foods, beverages, and supplements in biologically relevant heterogeneous media.

Beneficial effects of heat-treated Enterococcus faecalis FK-23 on high-fat diet-induced hepatic steatosis in mice.

A high-fat diet (HFD) is one of the causes of hepatic steatosis. We previously demonstrated that Enterococcus faecalis FK-23 (FK-23), a type of lactic acid bacteria, exhibits an anti-obesity effect in mice fed a HFD. In the present study, we examined the effects of FK-23 on HFD-induced hepatic steatosis. Male C57BL/6 mice were divided into four groups and given one of four treatments: standard diet (SD); standard diet supplemented with FK-23 (SD+FK); HFD; or HFD supplemented with FK-23 (HFD+FK). For the administration of FK-23, the drinking water was supplemented with FK-23 at a concentration of 2% (w/w). After 11 weeks, histological findings revealed hepatic steatosis in the liver of HFD-fed mice; however, this effect was attenuated by the administration of FK-23. The expression levels of genes involved in fatty acid oxidation in the liver tissue were significantly reduced in the HFD group compared with the SD group, but FK-23 supplementation tended to up-regulate the expression levels of these genes. Our findings show that the inhibitory effect of FK-23 against hepatic steatosis in HFD-fed mice can be explained by the prevention of fat accumulation in the liver through the modulation of the activities of genes involved in hepatic fatty acid oxidation.

Anti-inflammatory effects of carbon monoxide-releasing molecule on trinitrobenzene sulfonic acid-induced colitis in mice.

BACKGROUND AND AIM: Recent findings indicate that carbon monoxide (CO) in non-toxic doses exerts a beneficial anti-inflammatory action in various experimental models. However, the precise anti-inflammatory mechanism of CO in the intestine remains unclear. Here, we assessed the effects of a novel water-soluble CO-releasing molecule, CORM-3, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. METHODS: To induce colitis, C57BL/6 male mice received an enema of TNBS. CORM-3 or its inactive compound, iCORM-3, were administered intraperitoneally, once immediately before, and twice daily after receiving an enema of TNBS. Three days after TNBS administration, the distal colon was removed, assessed for colonic damage and histological scores, polymorphonuclear leukocyte recruitment (tissue-associated myeloperoxidase, MPO activity), and TNF-α, IFN-γ and IL-17A expression (mRNA and protein levels in the colon mucosa). CD4(+) T cells isolated from murine spleens were stimulated with anti-CD3/CD28, in the presence or absence of CORM-3/iCORM-3. The cell supernatants were assessed for TNF-α and IFN-γ expression, 24 h following stimulation. RESULTS: Colonic damage and histological scores were significantly increased in TNBS-induced mice compared to sham-operated mice. Tissue-associated MPO activity and expression of TNF-α, IFN-γ, and IL-17A in the colonic mucosa were higher in TNBS-induced colitis mice. The above changes were attenuated in CORM-3-treated mice. Further, CORM-3 was effective in reducing TNF-α and IFN-γ production in anti-CD3/CD28-stimulated CD4(+) T cells. CONCLUSIONS: These findings indicate that CO released from CORM-3 ameliorates inflammatory responses in the colon of TNBS-challenged mice at least in part through a mechanism that involves the suppression of inflammatory cell recruitment/activation.

A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA.

Milk-derived peptides, Val-Pro-Pro and Ile-Pro-Pro, attenuate atherosclerosis development in apolipoprotein e-deficient mice: a preliminary study.

Milk-derived peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), have angiotensin I-converting enzyme inhibitory activities and blood pressure-lowering effects. We examined the effects of these peptides on the development of atherosclerosis in apolipoprotein E-deficient [apoE(-/-)] mice. For 31 weeks, six-week-old male apoE(-/-) mice received a diet that included one of the following: fermented milk containing both VPP and IPP; casein hydrolysate containing both of these peptides; synthesized VPP; synthesized IPP; enalapril; captopril; or control diet. At the end of feeding, blood biochemistry, aortic atherogenesis, and gene expression by DNA microarray analysis were evaluated. There were no significant changes in the plasma lipid levels and 8-isoprostane, a marker of oxidative stress. The area ratio of intima to media in the aortic arch was significantly lower in the fermented milk, casein hydrolysate, synthesized VPP, enalapril, and captopril groups than in the control group. As is common with diets containing VPP and/or IPP, we observed reductions in mRNA expression of inflammatory cytokines, such as interleukin (IL)-6 and IL-1ß, oxidized low-density lipoprotein receptor, and transcription regulators. These results suggest that a continuous intake of VPP and IPP might be beneficial for preventing atherosclerosis caused by hypercholesterolemia.

BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1.

BACKGROUND: BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 system's effects on the pathogenesis of experimental colitis. METHODS: This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly. RESULTS: TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice. CONCLUSIONS: Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease.

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect.

BACKGROUND: TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. METHODS: Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. RESULTS: After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. CONCLUSION: This study indicates that bone marrow suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myelosuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.

Phase II trial of combined regional hyperthermia and gemcitabine for locally advanced or metastatic pancreatic cancer.

PURPOSE: Despite advances in cancer therapy, treating pancreatic cancer remains one of the major challenges in the field of medical oncology. We conducted this phase II study to evaluate the efficacy and safety of regional hyperthermia combined with gemcitabine for the treatment of unresectable advanced pancreatic cancer. METHODS: Eligibility criteria included histologically proven, locally advanced or metastatic pancreatic cancer. Gemcitabine was administered intravenously at a dose of 1000 mg/m(2) on days 1, 8, and 15 every 4 weeks. Regional hyperthermia was performed once weekly, 1 day preceding or following gemcitabine administration. The primary end point was the 1-year survival rate. Secondary objectives were determination of tumour response and safety. RESULTS: We enrolled 18 patients with advanced pancreatic cancer between November 2008 and May 2010. The major grade 3-4 adverse events were neutropenia and anaemia; however, there were no episodes of infection. The objective response rate (ORR) and disease control rate (ORR + stable disease) were 11.1% and 61.1%, respectively. Median overall survival (OS) was 8 months, and the 1-year survival rate was 33.3%. Median OS of patients with locally advanced pancreatic cancer was 17.7 months. CONCLUSIONS: Regional hyperthermia combined with gemcitabine is well tolerated and active in patients with locally advanced pancreatic cancer.

Angelica keiskei extract improves insulin resistance and hypertriglyceridemia in rats fed a high-fructose drink.

Angelica keiskei is a traditional herb peculiar to Japan and abundantly contains vitamins, dietary fiber and such polyphenols as chalcone. We investigated in the present study the effect of A. keiskei on insulin resistance and hypertriglyceridemia in fructose-drinking rats as a model for the metabolic syndrome. Male Wistar rats were given a 15% fructose solution as drinking water for 11 weeks. Fructose significantly increased the levels of serum insulin and triglyceride (TG) compared with the control level. Treatment with an ethanol extract of A. keiskei (AE) significantly reduced the levels of blood glucose (-16.5%), serum insulin (-47.3%), HOMA-R (-56.4%) and TG (-24.2%). A hepatic gene analysis showed that fructose reduced the expression of the genes related to fatty acid ß-oxidation and high-density lipoprotein (HDL) production. Treatment with AE enhanced the expression of the acyl-CoA oxidase 1 (ACO1), medium-chain acyl-CoA dehydrogenase (MCAD), ATP-binding membrane cassette transporter A1 (ABCA1) and apolipoprotein A1 (Apo-A1) genes. These results suggest that AE improved the insulin resistance and hypertriglyceridemia of the fructose-drinking rats.

Dietary supplementation with fructooligosaccharides attenuates allergic peritonitis in mice.

Fructooligosaccharides (FOS) are a prebiotic supplement, which can enhance immunological responses in the host to activate mucosal immunity probably through regulation of gastrointestinal microflora. Nonetheless, the therapeutic potential of prebiotics on allergic pathologies has not been fully elucidated. Therefore, the purpose of this study was to evaluate the preventive and therapeutic effects of dietary supplementation with FOS on a murine model of allergic peritonitis induced by ovalbumin (OVA). Male C3H/HeN mice were intraperitoneally administrated with OVA (1 µg) bi-weekly (Day 0-42, total four times) and were fed a diet containing 0 or 2.5% FOS ad libitum (Day 7-43). At Day 43, mice were killed and several parameters were evaluated. As results, supplementation with FOS alleviated OVA-related peritoneal inflammation characterized by trafficking of polymorphonuclear leukocytes such as eosinophils and neutrophils in the peritoneal cavity. Also, FOS significantly suppressed the protein level of interleukin (IL)-5 and eotaxin in the peritoneal lavage fluid elicited by OVA. In addition, a FOS-supplemented diet significantly reduced the serum allergen specific-IgG(1) level, whereas it significantly increased total IgA levels in the cecal contents as compared with a control diet in the presence of OVA. These results suggest that dietary supplementation with FOS can prevent/ameliorate allergic peritoneal inflammation induced by OVA. The efficacy can at least partially be associated with the regulation of Ig class switching and inhibition of the local expression of IL-5 and eotaxin.

Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor ß1 (TGF-ß1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-ß1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

Rebamipide promotes healing of colonic ulceration through enhanced epithelial restitution.

AIM: To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro. METHODS: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration. The distal colon was removed to evaluate the various parameters of inflammation. Moreover, wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with rebamipide. RESULTS: Intracolonic administration of rebamipide accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide. The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signal-regulated kinase (ERK) and activation of Rho kinase. CONCLUSION: Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells, via ERK activation. Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.

Dietary whey hydrolysate with exercise alters the plasma protein profile: a comprehensive protein analysis.

OBJECTIVE: It has been shown that dietary whey protein accelerates glucose uptake by altering glycoregulatory enzyme activity in skeletal muscle. In the present study, we investigated the effect of dietary whey protein on endurance and glycogen resynthesis and attempted to identify plasma proteins that reflected the physical condition by a comprehensive proteomics approach. METHODS: Male c57BL/6 mice were divided into four groups: sedentary, sedentary with whey protein hydrolysate, exercise, and exercise with whey protein hydrolysate. The mice in the exercise groups performed treadmill running exercise five times per week for 4 wk. Protein profiling of plasma sample obtained from individuals was performed, as were measurements of endurance performance and the glycogen content of gastrocnemius muscle. RESULTS: After the training period, the endurance of mice fed the whey diet was improved compared with that of mice fed the control diet. Muscle glycogen content was significantly increased after 4 wk of exercise, and intake of whey protein led to a further increase in glycogen. Apolipoproteins A-II and C-I and ß(2)-glycoprotein-1 were found to be altered by training combined with the intake of whey protein, without significant changes induced by exercise or whey protein alone. CONCLUSION: Results of the present study suggest that these three proteins may be potential biomarkers of improved endurance and glycogen resynthesis and part of the mechanism that mediates the benefits of whey protein.

Inverse association between Helicobacter pylori infection and allergic rhinitis in young Japanese.

BACKGROUND AND AIM: The prevalence of allergic disorders, including asthma, atopic dermatitis, and allergic rhinitis has been increasing, and the prevalence of Helicobacter pylori (H. pylori) infection has been decreasing. Chronic bacterial infection during childhood is reported to protect the development of allergic diseases. The aim of the present study was to identify whether H. pylori infection influences the prevalence of allergic rhinitis, which has become a serious social problem, especially in the developed countries. METHODS: We initially investigated the association between the prevalence of H. pylori and pollinosis symptoms in 97 healthy volunteers. We had investigated the association between the serum H. pylori-immunoglobulin (Ig) G antibodies and specific IgE antibodies for pollen, mites, and house dust in 211 consecutive patients. RESULTS: There were 52.2% (36/69) of H. pylori-negative volunteers with allergic symptoms, which was significantly higher than H. pylori-positive volunteers (14.3%, 4/28, P < 0.05). The risk of pollinosis symptoms by H. pylori infection was 0.148 (95% confidence interval): 0.046-0.475, P < 0.05). The prevalence of H. pylori infection increased according to age, whereas that of specific IgE-positive patients gradually decreased. Among the IgE-positive patients, the prevalence of H. pylori-negative patients was significantly higher than H. pylori-positive patients who were younger in age (P < 0.05). CONCLUSION: H. pylori infection decreased the pollinosis effects, especially among the younger volunteers. However, the prevalence of pollinosis in patients who were 50 years or older were almost same between H. pylori-positive and H. pylori-negative patients; therefore, the recent increase of pollinosis might relate to not only H. pylori infection, but also change in social environment.