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Oxidative stress is a high-profile element among the risk factors for aging. Although several stress markers have been proposed for the evaluation of oxidative stress, there remains much room for improvement in testing and evaluation methods. In the Current Concept Session “Oxidative Stress Markers” at the of the most recent research works were presented under the titles “Present Status and New Development of Evaluation of Oxidative Stress Markers,” “Oxidative Modification of Proteins and Its Quantitative Detection,” and “Modification/Degeneration of Proteins and Advanced Glycation Endproducts (AGEs)”.Several markers are available for evaluation of the oxidative stress status. Methods of detecting oxidatively modified substances as new markers by mass spectrography (MS) have been developed. Oxidative modifications of highly reactive cysteine residues in several target proteins such as tyrosine phosphatase and thioredoxin-related proteins control the functions of relevant molecules, and thereby play an important role in signal transmission. Advanced glycation endproducts (AGEs) gradually accumulate with aging and are involved in the development of diabetic complications, Alzheimer's disease, and arteriosclerosis. Basic studies of the indicators of glycation are also important.This general article outlines oxidative stress markers with a focus on oxidative modification of proteins and glycation of proteins, both of which have received attention in recent years, and introduces information regarding newly discovered markers for oxidative stress.

Objective: We developed an easily maintained health promotion program for factory workers in a company which introduced an anti-aging medical checkup with pedometer-based walking management. Here, we describe it's effect on body and mind.Methods: Subjects were 17 male employees (mean age, 50.6±4.3 years old; mean body weight 82.8±9.2kg; mean BMI, 27.2±1.9kg/m2: mean abdominal circumference; 95.6±5.7cm) of a machine factory (Murata Machinery, Inuyama-city, Aichi) who were judged to require lifestyle guidance. They were provided with pedometers and encouraged to walk. Data records for the number of steps taken were collected every four weeks. An anti-aging medical checkup was conducted three times before, 12 weeks and 24 weeks after the study.Results: Collection ratio for information on the number of steps walked was 82.8%. The average daily number of steps walked increased from a baseline of 10277 steps by 1096 steps (10.7%) at 24 weeks. Anthropometry showed significant improvements in weight (−3.9%, p=0.013) BMI (−3.6%, p=0.014) and abdominal circumference (−4.8%, p=0.003). Clinical laboratory tests showed significant improvements in HDL cholesterol (pre-value 51.0±10.0mg/dl, 12.7%, p=0.043), HbA1c (pre-value 5.5±0.6%, −8.4%, p‹0.001) and adiponectin (pre-value 5.17±1.03μg/ml, 39.9%, p=0.001). Anti-aging medical checkup showed the highest functional age, 35.3% in nerves, 35.3% in bone, and 29.4% in blood vessels, as well as significant changes in vascular age by acceleration plethysmography SDP-100 (pre-value 52.1±12.0 years old, −12.7%, p=0.024), calcaneus bone stiffness by ultrasonography A-1000 (9.5%, p=0.007), and response time by the Wisconsin card sorting test (p=0.024). No significant change was noted in muscle age as evaluated by bioelectrical impedance analysis (Physion MD). The questionnaire showed that the major reason for continuation with the program was “the presence of an anti-aging medical checkup”, health promotion was assisted by “results of anti-aging medical checkup”, and the modified behavior was “increased amount of exercise”.Conclusion: This health promotion program, consisting of an anti-aging medical checkup and pedometer-guided walking program, appears effective in improving the lifestyle and condition of factory workers.

Carbohydrates are indispensable nutrients for life. However, due to the presence of a carbonyl group, reducing sugars such as glucose react non-enzymatically with amino groups on proteins in glycation (or Maillard) reactions. This reaction is divided into early and advanced phase reactions: the former covers the reaction progression up to the Amadori rearrangement, and the latter covers the reaction through the subsequent alterations of oxidation, dehydration, condensation, and so on, eventually generating advanced glycation end products (AGEs). Among post-translational modifications, processes such as phosphorylation or acetylation are known as “post-translational modifications with order,” because the target proteins and the time of modification are controlled. However, glycation is a “post-translational modification with disorder” because post-translational modification of proteins by glucose progresses non-enzymatically, irreversibly, and at random, and because the progression depends on the existing time (aging) and the concentration of glucose, rather than the variety of proteins involved. While AGEs were initially considered simply as rust or waste matter in the body, significant attention is now afforded these compounds as a target molecule for newly-developing drugs, for the following reasons: AGEs damage the body by changing the structure and affecting the function proteins; receptors that recognizes AGEs, such as RAGE (receptor for AGE), exist in the body and mediate cellular derangements to induce morbidity; and inhibitors for AGE generation, such as aminoguanidine, pyridoxamine, and benfotiamine, delay the pathogenesis of diabetic nephropathy and retinopathy. Further, racemization proteins containing D-amino acids have been noted, along with AGEs, in drusen, which are characteristic of age-related macular degeneration (AMD). Here, we introduce current topics and future goals of AGEs research, particularly with regard to kidney disease associated with aging and diabetes mellitus, and touch on the involvement of AGEs in the progression of ocular diseases and the function of RAGE.

Objective: We conducted an anti-aging medical checkup and health promotion program, including facial mimetic muscle training, in residents of a geriatric medical care facility. Here, we evaluate the physical and mental effects of these activities.Methods: Three male and 16 female residents (83.7±6.8 years, BMI 22.2±3.0) underwent occupational therapy, with the addition of facial mimetic muscle training with a medical device, “M Patakara”, for 3.0 — 4.5 minutes four times per day for 24 weeks. Efficacy was evaluated by anti-aging medical checkup before and after the study.Results: The Anti-Aging QOL Common Questionnaire (AAQol) showed a significant improvement in the symptom scores of “anorexia”, “early satiety”, “epigastralgia”, “constipation”, “headache”, “dizziness”, and “arthralgia” (p‹0.05). Laboratory results showed significant changes in LDL cholesterol (111.6±24.8 mg/dl → 120.2±27.5mg/dl, p=0.022) and IGF-I (123.2±50.9ng/ml → 109.6±55.5ng/ml, p=0.005) at 24 weeks. Serum cortisol (11.7±3.8μg/dl → 15.6±5.3μg/dl, p=0.001) significantly increased while DHEA-s/cortisol ratio did not change. The Wisconsin card sorting test showed a significant reduction in total errors (32.6±4.6 → 27.8 ±7.5, p=0.022) and unique errors (5.2±5.1 → 1.9 ±2.7, p=0.026). Body composition analysis (Physion MD) revealed a decrease in muscle mass in the upper arms (0.50±0.14kg → 0.45±0.12kg, p=0.005) and lower limbs (4.4±1.2kg → 4.1±1.0kg, p=0.006). There was no significant change in vascular age by fingertip acceleration plethysmogram (SDP-100) or in osteo-sono-assessment index of the calcaneus by ultrasonography (AOS-100NW). Saliva secretion increased significantly, from 8.0±5.0 mm/min to 12.6±2.3 mm/min (p‹0.001) by the coffee filter method. Labial closure strength and electromyographic activity of the facial mimetic muscles increased significantly. No serious adverse event occurred during or after the study.Conclusion: This health promotion program with facial mimetic muscle training improved saliva secretion and subjective symptoms, indicating that it improved QOL in these aged facility patients. On anti-aging medical checkup, however, it was ineffective in preventing sufficiently the muscle weakening.

Objective: To determine the effect of beet extract on skin elasticity in female volunteers with dry skin and in human dermal fibroblasts.Method: To assess the effects of oral administration of glucosyl ceramide contained in beet extract (beet ceramide), we conducted an 8-week double-blind comparison study with 35 females (mean age: 40.9±4.2 years) with mild subjective symptoms of dry skin and declining keratin moisture levels. The compound was administered as glucosyl ceramide at 0, 0.6, or 1.8 mg/day to 3 groups (n=11, 12, 12, respectively).Results: Scores improved significantly for the following subjective skin symptoms: “concerned about dull skin,” “concerned about spots or freckles,” “sticky, oily skin,” “coarse and desiccated skin,” “not elastic, not glossy,” “concerned about rough skin,” “bags under eyes.” In addition, perspiration levels improved. The skin elasticity test (Cutometer) indicated that the elasticity index (R2 and R7) improved in a dose-dependent manner. However, we were unable to confirm the effects of ceramide on increasing skin moisture as reported in previous studies. In experiments involving human dermal fibroblasts, addition of beet ceramide promoted fibronectin synthesis and mRNA expression but had no effect on fibroblast proliferation or collagen synthesis.Conclusion: Results from clinical trials and experiments suggested that oral ingestion of beet ceramide may stimulate intracellular signals and exert favorable effects on the extracellular matrix, including the induction of fibronectin synthesis. In addition, we confirmed the safety of administering beet ceramide to humans.

Objective: Brewer’s yeast contains vitamins, minerals, amino acids and other nutrients, and has been reported to control intestinal function as well as to exert anti-ulceration, anti-tumor and anti-allergy effects. The present study evaluated the effects of oral treatment with dried brewer’s yeast tablets (study product) on skin in a single-blind placebo-controlled design in humans.Methods: Thirty-two healthy volunteer women (37.0±4.8 years) were allocated as follows: Group E-30 (n=11) were treated with 30 tablets/day of the study product (containing 7,125mg/day of dried brewer’s yeast), Group E-9 (n=10) were given 9 tablets/day of the study product, and the control group (n=11) were given 30 placebo tablets/day. The treatment period was 8 weeks. Two patients prematurely discontinued the study (discontinuation rate: 5.9%) and were excluded from the analyses. The study product (Ebios Tablet®) was provided by Asahi Food & Healthcare Co., Ltd. Before and at 4 and 8 weeks after the study, subjective symptoms were evaluated using the Anti-Aging QOL Common Questionnaire (AAQol) and checking skin symptoms, skin images were analyzed with SK Info (SKI, Integral Co.) and Aphrodite-III (PSI), and skin color (CM-700d, Konica Minolta Sensing, Inc.) and elasticity (Cutometer MPA580, Courage & Khazaka electronic GmbH) were measured.Results: In Group E-30, the AAQol physical symptom “cold skin” score was significantly improved at 8 weeks (p‹0.05). The skin symptoms “make-up runs easily” and “desiccated and gritty skin,” as well as the physical symptom “menstruation-related troubles” were improved in a significant and dose-dependent way from the control group (p‹0.01). On skin analysis, SKI demonstrated an increase in moisture content (15.4%, p=0.010), decrease in erythema (−18.3%, p‹0.001) and increase in elasticity (13.3%, p=0.003), while PSI revealed an increase in hydration (Total: 14.5%, T zone: 13.7%, U zone: 18.2%, p‹0.01) and decrease in pores (− 32.7%, p=0.022). Cutometer analysis showed a dose-dependent increase in skin elasticity, while analysis of skin color showed a decrease in hemoglobin (−9.5%, p=0.016), improved lightness (− 0.7%, p=0.045) and decrease in redness (−8.3%, p=0.013). During the study period, no serious adverse events were noted.Conclusion: These results suggest that treatment with dried brewer’s yeast is useful in improving skin condition, e.g. moisture content and elasticity, and also QOL.

Objective: We conducted a double-blind, placebo-controlled, parallel group study to assess the anti-glycation effect of mixed herbal extract (MHE) in individuals with pre-diabetes mellitus. MHE was produced using hot water extraction from Anthemis nobilis (Roman chamomile), Crataegus oxyacantha (hawthorn berry), Houttuynia cordata (dokudami), and Vitis vinifera (grape leaf). We also assessed whether MHE showed favorable effects on one's quality of life (QOL).Design: The subjects consisted of 26 volunteers (male: 21; female: 5; age: 50.5 ± 8.5 years) with pre- diabetes mellitus (HbA1c: 5.5 - 6.7%). They were divided into two groups, the Test Group (13 subjects, age: 52.8 ± 8.2 years) and the Control Group (12 subjects, age: 49.3 ± 7.8 years). The Test Group was administered 1,200 mg of MHE (solid substance) per day for 8 weeks. The Control Group was administered a placebo.Results: The inter-group analysis using the Anti-Aging QOL Common Questionnaire (AAQol) showed that the score for the parameters, “muscular pain/stiffness”, “headache”, “easily angered”, “reluctance to talk with others”, “memory lapse”, and “inability to readily make judgments” was significantly improved in the Test Group (p ‹ 0.05). In terms of sugar metabolism, no significant variation was observed in fasting blood glucose, HbA1c, glycoalbumin, and insulin. A significant variation was not observed in the Test Group with regard to 3-deoxyglucosone (3DG), an intermediate of glycation, and Ne-(carboxymethyl)lysine (CML) and pentosidine, advanced glycation endproducts (AGEs), in blood after 8 weeks. However, in the subjects with HbA1c of equal to or higher than 5.9%, the subclass inter-group analysis showed that the supplementation of MHE significantly inhibited (p ‹ 0.05) an increase of CML in the Test Group, while CML increased in the Control Group. There was no significant variation in the Test Group regarding the oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and isoprostane in urine. The skin elasticity index (R2) obtained by using the cutometer started to decrease significantly in the Control Group after 4 weeks (p ‹ 0.05), while the index showed a tendency that the skin elasticity was successfully maintained in the Test Group. There was no adverse event which was associated with the test product.Conclusion: These results suggest that MHE may improve the symptoms related to QOL as well as inhibit the generation of CML, one of AGEs, in individuals with abnormal sugar metabolism. Furthermore, the 8 weeks supplementation of MHE was considered to be safe.

Objective: The purpose of this study was to establish a long-term pedometer-based physical activity program for a group of community-dwelling older people and examine the effects on health and Anti-Aging medical indicators using an Anti-Aging medical checkup. We report here on the findings in the first 5 months (21 weeks) of the in-progress program.Methods: Subjects in the present study were 43 healthy middle-aged and older adults (17 men, 26 women, mean age: 69.0±5.9 years; mean body mass index: 22.9±3.0kg/m2) in the Shimogyo district of Kyoto-city, Japan. Each subject was provided a pedometer and instructed to walk with a goal of steps per day. Further, to motivate subjects, newsletters were delivered every four weeks. Checkups were conducted at the start of the study and 21 weeks later.Results: The average number of steps taken during the first five months of the study was significantly higher than at the start of the study (at 5 months: increase of 1,506.1 steps, p‹0.001). Two subjects dropped out of the study. Significant improvements were seen in body weight (p‹0.05), BMI (p‹0.01), waist circumference (p‹0.001), fasting plasma glucose (p‹0.05), insulin (p‹0.05), and bone density increased significantly (p‹0.05). With regard to stress indicators, DHEA-s (p‹0.01) and DHEA-s/cortisol (p‹0.01) increased, and cortisol (p‹0.01) decreased. With regard to Anti-Aging indicators, DHEA-s increased (p‹0.01), functioning as a hormonal age indicator, and bone density increased, functioning as a bone age indicator. A significant positive correlation was observed between change in steps/day and change in IGF-I concentration(r=0.382, p‹0.05). The functional ages did not change. Subjects were divided into 3 groups based on the gap between their functional age and actual age. In regard to vascular age, the group with the lowest (diagnosed younger) age gap tended to walk more than the group with the highest (diagnosed older) age gap. (p=0.095).Conclusion: Although ours is a relatively simple program, significant improvements were noted in many health and Anti-Aging indicators among community-dwelling older adults. IGF-I concentration increased in parallel with increase of steps. Further, our study had a low drop-out rate. Given that all of our subjects were healthy from study initiation, functional ages did not change. However, telling subjects their vascular age may be related to the increase of steps/day. This program is on-going, and therefore further reports are expected to follow.

Objective: An open-label noncontrolled study was conducted in subjects with increased oxidative stress burden to evaluate the mental and physical effects of antioxidant astaxanthin.Methods: Of 35 healthy postmenopausal women, 21 with high oxidative stress (diacron-reactive oxygen metabolites; d-ROM) were selected, and 20 (55.7±4.8 years old, BMI 22.1±3.9) were included in the study, after excluding 1 dropout. In subjects orally treated with astaxanthin (Fuji Chemical Industry) at a daily dose of 12 mg for eight weeks, Anti-Aging QOL Common Questionnaire, somatometry, hematological examination/urinalysis, oxidative stress test, and vascular function tests (cardio ankle vascular index, CAVI; ankle brachial pressure index, ABI; fingertip acceleration pulse wave; flow-mediated dilation FMD) were performed before and four and eight weeks after the start of the study.Results: After eight-week treatment with astaxanthin, significant improvement was observed in 5 of 34 physical symptoms listed in the common questionnaire, including “tired eyes”, “stiff shoulders”, “constipation”, “gray hair”, and “cold skin”, and in 3 of 21 mental symptoms, including “daily life is not enjoyable”, “difficulty in falling asleep”, and “a sense of tension”. In addition, systolic (118.0±16.4 mmHg at baseline, −4.6%, p=0.021) and diastolic blood pressure (74.1±11.7 mmHg at baseline, −6.9%, p‹0.001) significantly decreased. In the vascular function test, CAVI, fingertip acceleration pulse wave, and FMD did not change, but ABI significantly increased from 1.06±0.10 at baseline to 1.10±0.06 at Week 8 (+3.7%, p=0.030). In the oxidative stress test, d-ROM did not change, but BAP significantly increased (+4.6%, p=0.030). In biochemical examination, AST (−19.2%, p=0.044), LDH (−6.4%, p=0.006), and HbA1c (−3.2%, p‹0.001) significantly improved. Although IGF-I and insulin did not change, DHEA-s (−15.1%, p‹0.001), cortisol (−22.8%, p=0.002), and adiponectin (−14.1%, p=0.003) decreased. No serious adverse event occurred during or after the study.Conclusion: Results show that astaxanthin may enhance antioxidant capacity (increase BAP), reduce lower limb vascular resistance (increase ABI), decrease blood pressure, and improve physical symptoms in women with high oxidative stress.

Objective: Although the importance of exercise instruction in preventing metabolic syndrome and lifestyle-related diseases is evident, there exists little knowledge regarding specific types of exercise which is easily accepted by exercise beginners and provide strong motivation to continuing such exercise, and its expected effect. In the present open-label, comparative study, two types of exercise program were compared in exercise beginners.Methods: Twenty-three healthy premenopausal volunteer women aged between 35 (inclusive) and 45 (exclusive) years without experience of exercise were randomly allocated to Group M, which was prescribed a composite exercise program with muscle resistance training (n=12), or Group W, which was prescribed a simple exercise program with walking as a main component (n=11). The participants were instructed to perform their assigned exercise program for 40 minutes at a time, three times a week for 8 consecutive weeks at a fitness studio. After three withdrawals were excluded, 10 women (40.3 ± 1.9 years) in Group M and 10 (39.7 ± 2.7) in Group W were included in analyses of the following data obtained at baseline and after 8 weeks: examination for subjective symptoms (using the Anti-Aging QOL Common Questionnaire (AAQol), the State Trait Anxiety Inventory (SATI) for evaluation of anxiety, Young’s Symptom Distress Scale (SDS) for evaluation of depressed state, and the Kupperman Menopausal Index (KMI) for evaluation of symptoms of climacteric disturbance), physical examination, vascular function tests (cardio-ankle vascular index (CAVI), ankle brachial pressure index (ABI), and fingertip acceleration plethysmogram), blood tests (including but not limited to IGF-I and DHEA-s), oxidative stress tests (with a biological antioxidant potential (BAP) test and measurement of diacron-reactive oxygen metabolites (-ROMs), and skin image analysis.(View PDF for the rest of the abstract.)

109 Objective: To elucidate the effects of sea salt and various other soap ingredients on skin in humans. Methods: Forty healthy women (age 30.4 ± 6.0 years) were assigned to one of four test-soap groups (sea salt, SS; collagen added, SS+C; humic added, SS+H; or, fucoidan added, SS+F) or a control group. Subjects washed their face with the soap twice daily for eight weeks. Before and after the study, subjects undertook the Anti-Aging QOL Common Questionnaire (AAQol), skin image analysis (VISIAII), elasticity tests by a Cutometer (MPA580), and moisture tests by a Corneometer (CM825). Results: At 8 weeks, significant improvements were seen in symptoms scores for “noticeable blackheads in pores” and “oily face” in the SS group, the score for “concerned about spots or freckles” in the SS+H group, and the scores for “noticeable pores”, “concerned about pore opening”, “dry skin”, “rough skin”, “concerned about rough skin”, and “corner of eyes sagging” in the SS+F group. There was no significant change in skin moisture. Compared to controls, the R2 index of skin elasticity showed improvement in the SS+C group by inter-group analysis (p=0.009). On skin image analysis, the number of face wrinkles bilaterally (– 26.6%, p=0.008) in the SS+F group and the number of wrinkles on the right side of the face (– 45.5%, p＝0.005) in the SS group) showed significant improvement. Although an increase in ultraviolet (UV) spots was seen in the SS and control groups, this increase was significantly attenuated in the SS+C group (inter-group analysis: p

Objective: To-date, in middle-aged men the collection of data regarding the measurement of a wide range of health indicators, and the mutual relationships among these indicators, has been insufficient. Here, we evaluated from the viewpoint of anti-aging medicine, the effects on various anti-aging indicators in middle-aged men of a long-term intervention to prevent lifestyle-related diseases.Methods: Subjects were 18 male employees (mean age, 54.4 ± 7.4 years; mean body weight 77.5 ± 12.5 kg; mean BMI, 26.1 ± 3.6 kg/m2) of a machine manufacturer located in Kyoto City on whom a company-wide anti-aging medical checkup was performed. On the basis of the medical checkup results, exercise and nutritional instructions were given to the study subjects. In addition, subjects were lent pedometers and encouraged to walk, and the data recording the number of steps taken was collected once every four weeks. Anti-aging related indicators were measured before the study as well as 12 and 24 weeks thereafter. Muscle mass was measured with a body composition measuring device by bioelectrical impedance analysis (Physion MD), higher-brain functions were determined by the Wisconsin card sorting test (WCST), the degree of arteriosclerosis was evaluated by acceleration plethysmography (SDP-100), and bone mineral density was measured by ultrasonography (A-1000).(View PDF for the rest of the abstract.)

Objective: Vascular function testing and microarray analysis were performed to evaluate the physical effects of cassis (Ribes nigrum L.) juice in women.Methods: In healthy women (Study I: n=21, age 53.6±3.6 years, BMI 24.2±3.9; Study II: n=40, age 47.4±8.8 years, BMI 22.4±3.9) assigned to one of four cassis groups (polysaccharide (PS) content: 0, 50, 125, and 250 mg) or a water control group (duration of intake: 2 to 8 weeks), the following parameters were assessed: for vascular function, blood pressure, thermographically measured body surface temperature, CAVI (cardio-ankle vascular index), ABI (ankle-brachial pressure index), accelerated plethysmography, and FMD (flow-mediated dilation) were determined. In the PS 250 mg (n=3) and water (n=4) groups, total RNA was extracted from blood collected before and 2 weeks after the study to perform gene expression analysis using Human Whole Genome 4 × 44K kit (Agilent).Results: Cassis juice (PS content: 125 to 250 mg) (n=16) increased body fat percentage (+2.5%, p=0.011), decreased systolic (121.3±15.8 mmHg at baseline, −4.8%, p=0.001) and diastolic blood pressure (76.9±11.2 mmHg at baseline, −5.9%, p=0.001), and increased FMD blood flow (p=0.004), upper limb temperature (+0.23±0.47oC, p=0.011), and lower limb temperature (+0.55±0.50oC, p‹0.001). The percentage increase in lower limb temperature was dependent on PS (p‹0.05) and polyphenol (p‹0.01) contents. In gene analysis, inhibition of expression of α-adrenoceptor ADRA1D and thromboxane A2 receptor TBXA2R was prominent. Pathway analysis revealed significant accumulation of less frequently expressed genes (CACNA1B, GJB3, etc.) in the “Ca regulation in the cardiac cell” pathway (p=0.006). No serious adverse events occurred during the study.Conclusion: Cassis juice induced limb peripheral vasodilatation, increase in blood flow, and decrease in blood pressure. The microarray analysis showed inhibited expression of genes of α-adrenoceptor, thromboxane A2 receptor and Ca channel, and an inhibited pathway of Ca influx into vascular smooth muscle. Couppled with the fact that vascular endothelium plays a role in vasodilatation associated with various mRNA expressions, it is suggested that cassis juice may improve the function of endothelial cells.

Objective: Double filtration plasmapheresis (DFPP) removal of LDL cholesterol (LDL-C) and other pathogenic substances in the blood has attracted attention as an effective treatment of arteriosclerotic lesions. We conducted a controlled open-label study to understand the physical and mental effects of DFPP.Methods: Seven (7) male patients with borderline hyper-LDL-C (134.0±41.1 mg/dL) were assigned to a DFPP group (age 43.0±5.3 years, BMI 26.0±4.5) and 7 others were assigned to a control group (age 39.1±11.4 years, BMI 28.9±8.1). The observation period was 8 weeks. Patients in the DFPP group received DFPP twice. The evaluation included the Anti-Aging QOL Common Questionnaire (AAQol) and the blood vessel tests of Pulse wave velocity (PWV) and ankle-brachial index (ABI).Results: Among physical symptoms in AAQol, “tired eyes,” “blurry eyes,” “stiff shoulders,” and “feeling of ill-health” significantly decreased after 8 weeks in the DFPP group. Hematology revealed that hemoglobin (+3.6%, p=0.047), total protein (+4.1%, p=0.019), and albumin (+4.9%, p=0.018) were maintained at higher levels after 8 weeks in the DFPP group than the control group. Despite LDL-C removal, the hepatic steatosis index ALT (+5.7%, p=0.008) and lipid metabolism index LDL-C (+11.6%, p=0.012) were apparently higher in the DFPP group. Endocrinology showed a decreasing trend of DHEA-s (−13.7%, p=0.003), increasing trend of cortisol (+27.5%, p=0.005), and increasing trend of progesterone (+50%, p=0.030) in the DFPP group compared with the control group. High-sensitivity CRP tended to decrease in the DFPP group compared with the control group (−26.5%, p=0.030). There was no significant change in PWV or ABI in the DFPP group. No serious adverse events were caused by DFPP.Conclusion: LDL-C removal by DFPP might suppress inflammation and improve tissue environment in visceral adipose and liver tissues with fatty deposits.

Objectives: Accumulation of end-stage products of the Maillard reaction, also called advanced glycation end products (AGEs), is a hallmark of aging and the pathogenesis of chronic diabetic complications. The aim of this study was to determine whether safe and effective substances contained in four extracts of foodstuffs might slow the development of diabetic complications as well as slow the progression of aging.Design: We evaluated the in-vitro activity of four extracts of dried herbs available in Japan (Anthemis nobilis, Crataegus oxyacantha, Houttuynia coradata, Vitis vinifera) and a mixture of these to inhibit the Maillard reaction. We also assessed whether a 12-week feeding of mixed herbal extract (MHE) admixed in MF chow to streptozotocin (STZ)-induced diabetic rats prevented the development of diabetic complications.Results: Each of the four herbal extracts as well as the mixed extract dose-dependently inhibited the generation of Maillard reaction products in vitro with a potency similar to that of aminoguanidine (AG), a drug used for treating diabetic complications. Furthermore, after a 12-week, MHE supplemental feeding to STZ-induced diabetic rats, serum pentosidine and Ne-(carboxymethyl)lysine levels and wet weight of the kidney tended to decrease. MHE elicited AG-like actions and produced an inhibitory effect on pentosidine generation at lower concentrations than those observed for AG.Conclusion: Through the inhibition of the Maillard reaction, MHE may slow the development of chronic diabetic complications as well as slow the progression of aging.

A double-blind, randomized and placebo controlled study was carried out to examine the anti-aging efficacy and safety of Rokkaku Reishi in 22 overweight Japanese women (46.5±7.9 years old, BMI 26.8±2.7) consisting of 11 in the Analyte Group and 11 in the Placebo Group. Total cholesterol, LDL cholesterol and neutral fat values in the blood, which had been checked as background factors of the subjects, were mismatched, significantly higher respectively in the Analyte Group than in the Placebo Group. Evaluation of efficacy for lipid profiles was inevitable. In the Analyte Group the values of Hematocrit (-3.5%) and γ-GTP (-15.0%) significantly declined while HbAlc (2.3%) and K (5.4%) significantly increased after supplementation. The rate of increase of HbAlc in the Analyte Group was significantly higher than that in the Placebo Group. NK-cell activity showed no difference pre- and post-supplementation in either group. Oxidative-stress markers showed no significant difference pre- and post-supplementation for either group. A Common questionnaire on physical symptoms showed that the categories “Coughing and sputum” and “Grey hair” significantly declined after supplementation in the Analyte Group while no difference was found in the Placebo Group. For skin age scores measured using a Roboskinanalyzer, the scores for the categories “Noticeable pores”, “Large noticeable pores” and “Dusky noticeable pores” were significantly lower in the Analyte Group compared to the Placebo Group. A significant correlation was found between 8-OHdG in terms of its level, creatinine-corrected value and generation rate, and the number of “Noticeable pores”. No adverse reaction was found during the study. These results suggest that the four weeks supplementation of Rokkaku Reishi showed favorable effects on skin condition.

We conducted an open parallel comparison study between Groups to evaluate the possible influence on mental and physical conditions of using a mattress and pillow in which a gel was embedded for 4 weeks. The study subjects consisted of 41 Japanese healthy adult volunteers with high total scores (7 or more) of Pittsburgh Sleep Quality Index and of both sexes aged between 35 to 57 (42.8±5.5) years old. They were divided into 2 groups; the Control Group consisting of 21 subjects and the Study Group consisting of 20 subjects. In the Study Group, DHEA-s (-9.8%) and the creatinine-corrected urinary 8-OHdG (-16.7%) was significantly decreased, and cortisol (27.7%) significantly increased. Of the physical symptoms, “Blurry eyes”, “Lethargy”, and “Coughing and sputum” significantly improved in the Study Group compared with control. Of the mental conditions, “No feeling of happiness”, “Shallow sleep” and “Difficulty falling asleep” significantly improved in the Study Group. For Lifestyle, only the Study Group was affected. Specifically, the “Frequency of alcohol intake” significantly increased along with the “Sleeping hours” (p

We investigated the health claims of food containing Kabanoanatake (Charga: Fuscoporia obliqua) in terms of general body function in a double blind study using three Groups, control, Charga 5ml Group and Charga 15ml Group, each of which consisted of 20 subjects totaling 60 healthy adult volunteers (male: 23; female; 37, age: 45.7±6.9 years).For the Charga 5ml Group, systolic blood pressure (-3.72 %, p=0.046) and diastolic blood pressure (-3.47 %, p=0.018) were significantly lowered, while triglyceride (36.01 %, p=0.050) was increased. Also, slight changes were observed in total body water (-0.70 %, p=0.036), total body muscle (-0.69 %, p=0.034), fat-free mass (-0.72 %, p=0.022), total skeletal muscle (-1.35 %, p=0.005), basal metabolism (-0.60 %, p=0.013), HbAlc (1.57 %, p=0.034) and Cl (-1.19 %, p=0.019). Among oxidization stress markers, lipid peroxide (-7.89 %, p=0.006) was significantly improved. For mental and physical symptoms, significant improvements were observed in “Cold skin” (p=0.008) and “Inability to sleep because of worries” (p=0.008), while no parameter showed any aggravation. The Charga 15ml Group showed a significant improvement in the score for “loss of motivation” (p=0.042) for physical and mental symptoms. Apart from this, a slight but significant change was observed in Cl (-1.18 %, p=0.016), while aggravation was noted for “frequent urination” (p=0.049).The parameters which showed a dose-dependent change in terms of administration of Charga were from the blood test (lowering of fasting insulin level), physical symptoms on the common interview sheet on aging and the QOL (improved score in “stiff shoulders”), mental symptoms (an improvement in the scores for “loss of motivation”, “daily life is not enjoyable”, “pessimism” and “feeling of anxiety for no special reason”. While “weight loss; thin” and “Easily breaking into a sweat” showed a slight increases in their respective scores, the increase in the score for “frequent urination” was comparatively remarkable. There was no significant change in immune activity using the number of NK cells as a benchmark parameter. In conclusion, taking the balance between parameters that showed effects and aggravation into consideration, the preferability of two doses of Charga 5ml or 15ml/day seemed equivocal. As unfavorable phenomenon, frequent urination and mild elevation of γ-GTP and triglyceride were observed during the study.

In the present study, we investigated the physical effect of health food (supplement) which contains L-carnitine (200mg) and conjugated linoleic acid (700mg) for 8 weeks with a double-blind, randomized controlled non-crossover design. Overweight individuals (17 males and 18 females; age: 48.3±6.6yrs; BMI: 25.5±2.6) were assigned to either Study Group (n=18) or Control Group (n=17). A small increase in serum levels of HbAlc (3.3%) and CRP (35.3%) was noted in the Study Group (p

The case report of a 53-year-old woman with abdominal pain and bloody diarrhoea is described. Prior to the onset of symptoms the patient had taken royal jelly for 25 days. Colonoscopy revealed that the mucosa was haemorrhagic and oedematous throughout the 20 cm long sigmoid colon. Histopathologically, mucosal haemorrhage, oedema, and infiltration of inflammatory cells were observed. Transmission electron microscopic examination revealed platelet aggregation in 30% of capillaries in the mucosal lesions. The drug-induced lymphocyte stimulation test was slightly positive for royal jelly (847 c.p.m., SI = 147%) compared with the control (576 c.p.m.). The patient's signs and symptoms disappeared within a few days after the initiation of conservative therapy, and the colonic lesions disappeared after 2 weeks of this therapy. This is the first reported case of haemorrhagic colitis associated with royal jelly intake.

The aim of this study was to investigate whethergastrin regulates morphological changes andalpha-subunit gene expression in parietal cells throughthe gastrin/CCK-B receptor on enterochromaffin-likecells by histamine release. Treatment with 100 mg/kgof YM022, a potent and selective gastrin/CCK-B receptorantagonist, for one week in rats did not alter mRNAlevels of histidine decarboxylase or H+,K-ATPase. However, parietal cell morphology predominantlychanged to the resting form, although the serum gastrinconcentration was significantly increased. Additionaltreatment with YM022 and oral omeprazole, 100 mg/kg, for one week markedly suppressed theincreases of mRNA levels of histidine decarboxylase andH+, K-ATPase and completely blocked themorphological transformation of the parietal cells to astimulated form induced by treatment with omeprazolealone. This indicates that the morphologicaltransformation of parietal cells to an activated formwith a subsequent increase in H+, K-ATPasesynthesis caused by hypergastrinemia is mediated by increasedhistidine decarboxylase gene expression inenterochromaffin-like cells via gastrin/CCK-Breceptors.

ADH/GPT比が高値を示した成人発症Still病(AOSD)の2例を報告する.症例1は30歳女性.39℃台の弛張熱,発疹および関節痛を主訴に当院を受診.GOT 133IU/l, GPT 417IU/l, LDH 514IU/lと肝機能障害が認められ入院した.ADH/GPT比が高値を示し,さらに急性期の肝生検像で,中心静脈周囲に限局した肝細胞壊死が確認された.症例2は重症肝障害および播種性血管内血液凝固症を合併した44歳女性.ADH/GPT比が高値を示した.いずれの症例も副腎皮質ステロイド薬が著効し軽快した.これらAOSD 2例における肝障害の主座は中心静脈領域であることが示され,さらに血清ADH活性測定は肝障害の鑑別にも有用と考えられた.

Although previous studies have shown that consumption of green tea catechins (GTC) and walking might prevent development of cardiovascular disease (CVD), the effects of GTC supplementation on CVD risk in active older people are unknown.A total of 52 older adults (male/female 20/32, mean age 69.1 ± 5.9 years) participating in a pedometer-based walking program were randomly assigned to a GTC group with an intake of 630.9 mg GTC daily (n=26) or a control group (n=26) for 14 weeks. Cardiovascular risk markers were measured before and after this trial.In the GTC group, values of the following markers were significantly reduced (P0.05) from the beginning to the end of the trial: waist circumference (from 84.2 ± 8.4 to 82.2 ± 8.5 cm), hip circumference (from 95.1 ± 6.9 to 92.2 ± 6.3 cm), total cholesterol (from 233.0 ± 46.3 to 218.8 ± 42.3 mg/dL), low-density lipoprotein cholesterol (from 130.4 ± 36.2 to 119.1 ± 33.4 mg/dL) and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (from 2.0 ± 1.7 to 1.7 ± 0.5); only hip circumference (from 95.6 ± 8.1 to 94.1 ± 7.6 cm) was significantly reduced (P0.05) in the control group. No significant between-group differences were found for any parameter measured.Although GTC might reduce cholesterol levels, the present randomized control trial suggests that GTC supplementation in active older participants did not significantly affect cardiovascular risk markers. Future studies should identify more effective combinations of GTC supplementation and physical activity.

The biological basis of variability in histological progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone, has been shown to influence sensitivity to reactive oxygen species, insulin sensitivity and expression of peroxisome proliferator-activated receptor-α. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA in Japanese patients. Serum samples were obtained in 133 Japanese patients with biopsy-proven NAFLD and in 399 sex- and age-matched healthy people undergoing health checkups. Serum levels of sulfated DHEA (DHEA-S) were measured by chemiluminescent enzyme immunoassay. Serum DHEA-S levels in NAFLD patients were similar to those in the control group. Of 133 patients, 90 patients were diagnosed as non-alcoholic steatohepatitis (NASH): 73 patients had stage 0-2, and 17 had stage 3 or 4. Patients with advanced NAFLD (NASH with fibrosis stage 3 or 4) had lower plasma levels of DHEA-S than patients with mild NAFLD (simple steatosis or NASH with fibrosis stage 0-2). The area under the receiver operating characteristic curve for DHEA in separating patients with and without advanced fibrosis was 0.788. A "dose effect" of lower DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 170.4 ± 129.2, 137.6 ± 110.5, 96.2 ± 79.3, 61.2 ± 46.3 and 30.0 ± 32.0 µg/dL for fibrosis stages 0, 1, 2, 3, and 4, respectively. The association between DHEA-S and severity of NAFLD persisted after adjusting for age, sex and insulin resistance. Low circulating DHEA-S might have a role in the development of advanced NASH.

The aging balance and the risk factor are considered from a whole body viewpoint whenever it thinks about the anti-aging treatment for calcium metabolism. The aging balance attaches to the muscles, the blood vessel, the nerve, the hormone, and the bone, and the aging risk factor evaluates immunity, the oxidation stress, the mental stress, the lifestyle, and the metabolic states. The basis of treatment is improvement of life styles in daily meal, physical activities, and the spirit. The drug therapy is used to the end assisting. It thought about the aging risk factor by describing the calcium abnormal metabolizing according to aging influence on the whole body, the prevention, and treatment in this text.

Laparotomy significantly attenuates ethanol-induced gastric mucosal lesions in the rat. The effects of sensory denervation by capsaicin, indomethacin, atropine, guanethidine, and hexamethonium on laparotomy-induced protection were studied in the rat. Gastric mucosal injury was induced by the intragastric instillation of 1 mL of 75% ethanol. The laparotomy-induced protection against ethanol injury was abolished by sensory denervation by capsaicin (total dose, 125 mg/kg, SC) and also by pretreatment with indomethacin (5 mg/kg, SC). In contrast, pretreatment with atropine (0.5 mg/kg, IP), guanethidine (total dose, 20 mg/kg, SC), or hexamethonium (20 mg/kg, IP) had no significant effect on laparotomy-induced protection. These data indicate that capsaicin-sensitive sensory afferent neurons, but not cholinergic or adrenergic autonomic neurons, mediate laparotomy-induced protection against ethanol injury. The hypothesis is put forward that the protective response to laparotomy arises from a somatovisceral and/or viscerovisceral axon reflex of capsaicin-sensitive afferent neurons. Prostaglandins might play a mediator role in the activation by laparotomy of somatic and/or visceral branches of the afferent neurons.

The purpose of anti-aging medicine is to raise quality of life (QOL) and to aim at healthy longevity. Melatonin, DHEA(-s) (dehydroepiandrosterone [sulfate]), somatotropin/IGF-I (insulin-like growth factor-I), male and female hormone decrease with aging, that can be prevented by hormone replacement therapy. This therapy has two sides of supplement of the deficit and a healthy increase. Hormone age is "the function age that expressed whether you are equivalent to a hormone secretion state of how old average" and 30 years old or 70-80% of chronological age regard the targeted value of hormone age. We do not decide quantity of hormone replacement uniformly. The reasonable quantity should be determined based on each figure, active mass, life level, and/or blood levels of hormones. Data accumulation for a long term in multiple institutions is important.

The effect of a dietary supplement with L-carnitine (600 mg/day) and Garcinia cambogia extract (500 mg/day as hydroxycitric acid) as main ingredients was studied in 35 healthy volunteers {48.3 +/- 6.9 years, body mass index (BMI): 26.3 +/- 1.7} in a double-blind test (18 subjects in the Test Group and 17 in the Control Group). The yearly examination includes the standard yearly medical tests done in Japan, tests for assessing hormonal age, and a survey for assessing physical and mental fitness of the subjects, called the Anti-Aging QOL Common Questionnaire (AAQol). Use of this supplement significantly improved the level of lipid peroxides (-12.8%) in the blood as well as physical symptoms such as "tired eyes," "blurry eyes," "muscle pain/stiffness," "early satiety," "epigastralgia," "dizziness," "arthralgia" and "easily breaking into a sweat." The Control Group showed a significantly favorable improvement rate, especially for "dizziness." On the other hand, groups of subjects using the test compounds saw a significant rise in total cholesterol (4.5%), fasting blood sugar (4.1%) and HbA1c (3.4%). Our findings suggest that the consumption of the supplement can reduce the oxidative damage; however, the effect on QOL was equivocal. Garcinia cambogia extract did not show dietary efficacy.

We investigated the effects of rabe-prazole compared with those of omeprazole on enterochromaffin-like cells and parietal cells in rats. Methods. Rabeprazole or omeprazole was administered for 7 days by intraperitoneal injection (100 mg/kg or 20 mg/kg once a day) and the serum gastrin concentration, the antral density of G cells and D cells, fundic histamine content, fundic H+, K+-ATPase mRNA level, and parietal cell morphology were determined. Results. Both rabeprazole and omeprazole inhibited gastric acid secretion and increased the intragastric pH to over 6.5, as well as causing a marked increase in the serum gastrin concentration. The serum gastrin level was lower with rabeprazole treatment than with omeprazole treatment at both doses. Also, the antral G-cell density was higher with omeprazole than with rabeprazole, while the increase in both the histamine content and the H+, K+-ATPase mRNA level in the fundic mucosa was higher with omeprazole treatment at both doses, with the difference being significant at 100 mg/kg. Ultrastructural examination indicated that the stimulation of parietal cells by omeprazole was stronger than that by rabeprazole. Conclusions. Rabeprazole treatment does not drive enterochromaffin-like cells and parietal cells as strongly as omeprazole treatment despite its potent acid suppressive effect, suggesting that it represents a new generation of proton pump inhibitors.

Erythropoietic protoporphyria (EPP) was diagnosed in a 27-year-old man based on a typical clinical history, and a marked increase in erythrocyte and fecal protoporphyrin concentrations. Although liver disease is not a common feature in EPP, he had slight liver dysfunction. A percutaneous liver biopsy was performed and it showed minimal hepatocellular damage and many reddish brown pigment deposits in hepatocytes, Kupffer cells, portal histiocytes, bile canaliculi and small biliary radicles. Electron microscopic findings confirmed that these deposits were composed of protoporphyrin crystals. Liver biochemistry remained well for >2 years, but deteriorated rapidly and second liver biopsy obtained 28 months after the first biopsy revealed the development of liver cirrhosis. We treated the patient with intravenous administration of dl-a-tocopherol acetate (vitamin E; 500 IU/body/day). Following the administration of vitamin E, the concentration of protoporphyrin in erythrocytes decreased significantly and the liver function tests were improved. Sixteen weeks later he showed the full clinical and biochemical recovery suggesting that vitamin E supplementation might be useful in treating patients with EPP who developed liver damage.

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.

We report a case of severe hypoglycemia and hepatic masses suspected to be an insulin-like growth factor-II (IGF-II)-producing hepatocellular carcinoma. A 62-year-old man presented with mental disorder in the night and early morning associated with extremely low blood sugar levels (less than 21 mg/dl). Computerized axial tomography and ultrasonography revealed a massive tumor in the right lobe of the liver with multiple secondary nodules, and a tumor thrombus in the portal vein. At autopsy 107 days after admission, the liver weighed 3070 g, histologically showing an Edmondson type II tumor with liver cirrhosis. IGF-II in plasma (899 ng/ml) and tumor tissue (2.4 micrograms/g) was higher than that in normal plasma (374-804 ng/ml) and non-tumor liver tissue (0.2 micrograms/ml), while IGF-I (14 ng/ml) was significantly reduced. IGF-II, probably produced by the liver tumor, appeared to be involved in the mechanism of hypoglycemia.

Under in vivo microscopic observation, intragastric ethanol instillation has been seen to cause a prompt, marked constriction of submucosal venules, followed by congestion in mucosal capillaries and severe gross mucosal lesion formation. This study was designed to test the hypothesis that the venoconstriction is mediated by leukotrienes and that inhibition of the venoconstriction would protect against ethanol injury. Intragastric application of the leukotriene receptor antagonist MK-571 inhibited both venoconstriction and gross lesion formation. However, although local submucosal application of MK-571 inhibited venoconstriction, it did not protect the overlying gastric mucosa against ethanol injury. We conclude that leukotrienes play a significant pathogenetic role in ethanol-induced gastric mucosal injury, but while the venoconstriction, mediated by leukotrienes, is one of the factors that promote lesion formation, it is not an essential one.

1. The effect of the intravenous administration of lipopolysaccharide from Salmonella typhosa endotoxin on arterial blood pressure (BP), gastric mucosal blood flow (GMBF) and gastric damage was studied in anaesthetized rats. The effect of the inhibition of endogenous prostaglandin generation by indomethacin on these parameters was also investigated in this model of endotoxin shock. 2. A similar and dose-dependent percentage of reduction in BP and GMBF was observed 5 min after a bolus injection of 20 or 30 mg kg-1 endotoxin. A transient recovery in GMBF at 15 min was observed followed by a second fall at 30 min, at a time when BP was slowly increasing. 3. Pretreatment with indomethacin (5 mg kg-1, s.c.) one hour before the administration of 30 mg kg-1 endotoxin, significantly augmented the reduction in GMBF without affecting the reduction in BP. 4. The gastric damage, assessed histologically, was similar and confined to the superficial mucosa 30 min after the administration of 20 or 30 mg kg-1 endotoxin. The histologically-assessed damage was significantly greater in indomethacin pretreated rats injected with 30 mg kg-1 endotoxin. 5. These findings suggest that endogenous prostaglandin generation plays a protective role in endotoxin-induced gastric mucosal microcirculatory disturbances and mucosal damage.

In vivo microscopy in the anesthetized rat unexpectedly revealed that the topical application of 75% ethanol to the gastric mucosa had no effect on the mucosal microcirculation. If, however, the synthesis of endogenous prostaglandin was inhibited by indomethacin, the topical application of 75% ethanol resulted in complete superficial mucosal microcirculatory stasis in the majority of rats. In indomethacin-pretreated rats, Rioprostil, a synthetic prostaglandin El analogue, reversed this effect of topical ethanol. The degree of ethanolinduced histologic gastric mucosal damage was inversely correlated with time to complete stasis. Ethanol injury studies under various conditions revealed that laparotomy stimulated a gastric protective mechanism that persisted for between 1 and 2 h and that was blocked by indomethacin. In conclusion, (a) laparotomy stimulates a gastric mucosal protective mechanism that probably is mediated by prostaglandin synthesis, and (b) cessation of mucosal blood flow appears to be an important early step in ethanol-induced gastric mucosal injury, and maintenance of mucosal blood flow by endogenous or exogenous prostaglandin may play a major role in prostaglandin protection.

The rate of obesity in Japan, defined as having a body mass index (BMI) of 25 kg/m(2) or greater, is reportedly at 24 %, a lower level of severe obesity than in the EU and US. However, the incidence of obesity-related health problems is reportedly higher among Asians. Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed bariatric surgery in Japan and accounted for 54 % of such surgeries in 2011; procedures such as laparoscopic adjustable gastric banding and laparoscopic Roux-en-Y gastric bypass (LRYGB), practiced frequently worldwide, were uncommon. Possible reasons include concern over delayed postoperative discovery of gastric cancer in LRYGB, and rapid adoption of the comparatively simple LSG procedure. In type 2 diabetes mellitus (T2DM) patients, where continued pursuit of medical treatment is difficult and a potential exists for future deterioration of diabetes-complicated diseases, the criterion for surgical indication in the EU and US is a BMI of 30-35 kg/m(2), with priority given to BMI35 kg/m(2). For Asian patients, the recommendation is to lower this indication criterion by 2.5 kg/m(2). Efficacy of metabolic surgery is anticipated particularly among T2DM patients with obesity complication, a short history of insulin treatment, and intact insulin secreting ability, and in these cases bariatric surgery should be contemplated.

The role of lipoxygenase metabolites in ethanol-induced gastric mucosal injury and submucosal microvascular change in the rat was studied by in vivo microscopy. Intragastric ethanol-instillation caused marked submucosal venular constriction, dilatation of small arterioles, and corpus mucosal gross lesion formation. The venoconstriction was greater in the lesion than in the nonlesion area. Intragastric pretreatment with either BW755C, a lipoxygenase inhibitor, or Rioprostil, a synthetic prostaglandin E1 analogue, significantly inhibited both the ethanol-induced venoconstriction and the gross lesion formation. In contrast, pretreatment by the submucosal application of either BW755C (50 micrograms/ml) or Rioprostil (50-500 ng/ml) had no effect on either the submucosal venoconstriction or the mucosal lesion formation. In conclusion, leukotrienes released from the gastric mucosa appear to be involved in the ethanol-induced submucosal venoconstriction associated with gastric mucosal injury. Prostaglandin pretreatment protects against this venoconstriction and gross lesion by a mucosal effect but not by a direct effect on submucosal venules.