The molecular mechanism for activating IgA production by Pediococcus acidilactici K15 and the clinical impact in a randomized trial.

IgA secretion at mucosal sites is important for host defence against pathogens as well as maintaining the symbiosis with microorganisms present in the small intestine that affect IgA production. In the present study, we tested the ability of 5 strains of lactic acid bacteria stimulating IgA production, being Pediococcus acidilactici K15 selected as the most effective on inducing this protective immunoglobulin. We found that this response was mainly induced via IL-10, as efficiently as IL-6, secreted by K15-stimulated dendritic cells. Furthermore, bacterial RNA was largely responsible for the induction of these cytokines; double-stranded RNA was a major causative molecule for IL-6 production whereas single-stranded RNA was critical factor for IL-10 production. In a randomized, double-blind, placebo-controlled clinical trial, ingestion of K15 significantly increased the secretory IgA (sIgA) concentration in saliva compared with the basal level observed before this intervention. These results indicate that functional lactic acid bacteria induce IL-6 and IL-10 production by dendritic cells, which contribute to upregulating the sIgA concentration at mucosal sites in humans.

Double-Stranded RNA Derived from Lactic Acid Bacteria Augments Th1 Immunity via Interferon-ß from Human Dendritic Cells.

Lactic acid bacteria (LAB) are one of the major commensal species in the small intestine and known for contributing to maintenance of protective immunity and immune homeostasis. However, currently there has been no evidence regarding the cellular mechanisms involved in the probiotic effects of LAB on human immune cells. Here, we demonstrated that LAB double-stranded RNA (dsRNA) triggered interferon-ß (IFN-ß) production by human dendritic cells (DCs), which activated IFN-γ-producing T cells. Interleukin-12 (IL-12) secretion from human DCs in response to LAB was abrogated by depletion of bacterial dsRNA, and was attenuated by neutralizing IFN-ß, indicating LAB dsRNA primarily activated the IFN-ß/IL-12 pathway. Moreover, the induction of IL-12 secretion from DCs by LAB was abolished by the inhibition of endosomal acidification, confirming the critical role of the endosomal digestion of LAB. In a coculture of human naïve CD4+ T cells and BDCA1+ DCs, DCs stimulated with LAB containing dsRNA induced IFN-γ-producing T cells. These results indicate that human DCs activated by LAB enhance Th1 immunity depending on IFN-ß secretion in response to bacterial dsRNA.

Psychotomimetic-like behavioral effects of memantine in the mouse.

A single administration of mice with memantine (1-amino-3,5-dimethyladamantane), a glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist, induced stereotyped behaviors in dose- and time-dependent manners. The predominant behavioral component of the stereotypy was a continuous, exaggerated sniffing which was accompanied by persistent locomotion. In contrast, a psychostimulant methamphetamine (METH) predominantly induced a stereotyped biting and other forms of intense stationary stereotypical behaviors. Memantine-induced stereotyped sniffing was attenuated by pretreatment with haloperidol, a dopamine D2 receptor antagonist, in a dose-dependent manner. The memantine-induced stereotyped sniffing was also attenuated by pretreatment with betahistine (2-[2-(methylamino)ethyl]pyridine), an agent which increases histamine turnover and releases histamine in the brain. These observations suggest that memantine might induce stereotypies through neuronal mechanisms that are somewhat different from those of METH, but still overlap to a certain extent, since memantine-induced stereotypies can be attenuated by the mechanisms that also suppress METH-induced stereotypy. Importantly, these data suggests that the effects of memantine may be more limited to the ventral striatum including nucleus accumbens than those of METH, which is associated with dorsal striatal stimulation at high doses. In this respect memantine may also have pharmacological properties such as compartmentation (i.e. brain distribution) and neuronal mechanisms different from those of other NMDA receptor antagonists, such as ketamine, which may have important implications for therapeutic uses of these drugs.

A giant mucinous cystadenocarcinoma of the appendix: a case report and review of the literature.

BACKGROUND: Mucinous cystadenocarcinoma is the second most common etiology of appendiceal mucocele. We report a relatively rare case of a giant appendiceal mucocele caused by mucinous cystadenocarcinoma, which occupied the entire abdomen of an adult woman. CASE PRESENTATION: A 63-year-old woman presented with a chief complaint of abdominal distention. Imaging studies showed a giant cystic mass occupying her entire abdomen. Laparotomy confirmed a giant appendiceal mucocele, and the patient underwent ileocecal resection. A mucinous deposit was not found in her abdominal cavity, and the ovaries were grossly normal bilaterally. The pathological diagnosis was mucinous adenocarcinoma with a low-grade mucinous neoplasm that invaded the subserosa. Regional lymph node metastasis was not found. She has had recurrence-free survival for 5 years. CONCLUSIONS: The present case is the largest appendiceal cystadenocarcinoma ever reported. The optimal treatment of an appendiceal neoplasm requires further research based on consensus terminology of an appendiceal mucocele.

[Twenty-one new recipes recommended by the Kikkoman Corporation to reduce the impact of chemotherapy on the sense of taste].

A change in the sense of taste is a side effect of chemotherapy. Patients have an increased sensitivity to the bitter taste and a decreased sensitivity to the sweet, sour, and salty tastes, among other flavors. Therefore, sweet foods do not taste as sweet as they used to before chemotherapy. Kikkoman Corporation recommends 21 new recipes for cancer patients to reduce the impact of side effect on their appetite and to maintain their well-being.

The serum level of soluble CD26/dipeptidyl peptidase 4 increases in response to acute hyperglycemia after an oral glucose load in healthy subjects: association with high-molecular weight adiponectin and hepatic enzymes.

A soluble form of CD26/dipeptidyl peptidase 4 (sCD26/DPP4) is found in serum and it has DPP4 enzymatic activity. We investigated whether the serum level of sCD26/DPP4 was influenced by the oral glucose tolerance test (OGTT) in healthy subjects. The serum sCD26/DPP4 level increased significantly from 824.5 ng/mL (interquartile range, from 699.0 to 1050 ng/mL) at baseline to a peak of 985.0 ng/mL (interquartile range, from 796.5 to 1215 ng/mL) during the OGTT (P < 0.0001). The peak sCD26/DPP4 level correlated positively with the baseline age and body mass index, and fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), alanine aminotransferase, and γ-glutamyl transpeptidase (GGT) levels whereas it correlated negatively with high-density lipoprotein (HDL) cholesterol and the serum levels of total and high-molecular weight (HMW) adiponectin. Stepwise regression analysis was done with forward selection of variables, including age, FPG, HOMA-IR, TG, HDL cholesterol, uric acid, GGT, C-reactive protein, and HMW adiponectin. In a model that explained 57.5% of the variation of the peak sCD26/DPP4 level, GGT (ß = 0.382, P = 0.007) and HOMA-IR (ß = 0.307, P = 0.034) were independent determinants of the peak serum level of sCD26/DPP4. Serum HMW adiponectin decreased significantly from 4.43 µg/mL (interquartile range, from 2.80 to 6.65 µg/mL) at baseline to 4.17 µg/mL (interquartile range, from 2.48 to 6.96 µg/mL) 120 minutes after the oral glucose load (P < 0.0001). The baseline serum level of sCD26/DPP4 showed a significant negative correlation with the percent change of HMW adiponectin during the OGTT. In conclusion, the serum level of sCD26/DPP4 increased acutely after an oral glucose load in apparently healthy subjects. The abrupt increase of serum sCD26/DPP4 after a glucose load may be a marker of insulin resistance that could come from liver or muscle.

Single-incision laparoscopic cholecystectomy for cholecystolithiasis coinciding with cavernous transformation of the portal vein: report of a case.

BACKGROUND: Cavernous transformation of the portal vein (CTPV) is a rare vascular deformity. It is thought to be secondary to extra-hepatic portal vein obstruction, with formation of serpiginous collateral vessels around the extra-hepatic bile duct, and even the gallbladder. Surgery is difficult because the vessels have irregular courses, are somewhat fragile and bleed easily. Single-incision laparoscopic cholecystectomy, an emerging procedure for symptomatic cholecystolithiasis, has limitations especially in anatomically complex cases. CASE PRESENTATION: We describe a 44-year-old woman with symptomatic cholecystolithiasis. Computed tomography revealed a series of tortuous collateral veins at the liver hilum, with the extra-hepatic portal vein occluded at the level of the spleno-portal junction. However, the distended vessels were not particularly close to the cystic duct. We performed single-incision laparoscopic surgery (SILS) for cholecystectomy via a trans-umbilical incision. By pulling the cystic duct out along with neighboring cavernous vessels, we were able to secure detachment of the cystic duct from Calot's triangle and ligation of the cystic artery. Total operating time was 132 minutes and blood loss was 370 grams. The patient was discharged on postoperative day 2 with no perfusion abnormalities in the liver. CONCLUSION: We must pay meticulous attention to the area of Calot's triangle when performing SILS cholecystectomy with CTPV. SILS cholecystectomy might be an option in highly experienced facilities.

Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma.

Chloasma (melasma), an acquired hypermelanosis, is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidin, a powerful antioxidant, on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract (GSE) was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of GSE intake improved or slightly improved chloasma in 10 of the 12 women (83%, p < 0.01) and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates (54%, p < 0.01). L* values also increased after GSE intake (57.8 +/- 2.5 at the start vs 59.3 +/- 2.3 at 6 months and 58.7 +/- 2.5 at the end of study). Melanin-index significantly decreased after 6 months of the intake (0.025 +/- 0.005 at the start vs 0.019 +/- 0.004 at 6 months) (p < 0.01), and also decreased at the end of study (0.021 +/- 0.005) (p < 0.05). GSE is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of GSE was maximally achieved after 6 months and these was no further improvement after this period. The latter GSE intake for 5 months may prevent chloasma from becoming worse prior to the summer season. GSE is safe and useful for improving chloasma.

Preoperative grading system for predicting operative conditions in laparoscopic cholecystectomy.

PURPOSE: In a previous retrospective study, we predicted the operative conditions for abdominal wall-lifting laparoscopic cholecystectomy (ALLC), using a new preoperative grading system. We conducted the present study to evaluate the validity of our grading system prospectively, and to improve the operative outcome. METHODS: Ninety-seven patients underwent cholecystectomy between January 2000 and March 2002, and were prospectively examined according to our preoperative grading system. Allotting 0-5 points for nine preoperative factors, the total combined score was defined as the predictive score. The postoperative score was defined by allotting 0-8 points to five operative factors. The ratio of the preoperative score / postoperative score was defined as the skill score. RESULTS: The mean postoperative score was significantly correlated with the predictive score (P < 0.01). The mean operation time and the mean postoperative score differed significantly among surgeons with skill scores higher or less than 1.25 (P < 0.05). They were significantly improved (P < 0.05) by choosing an operator according to the predictive score and skill score. CONCLUSION: Our preoperative grading system using the predictive score is a valid method of predicting the actual operative conditions of ALLC. An adequately skilled operator should be chosen according to the difficulty of each case, to ensure the best possible operative outcome.

Lightening effect on ultraviolet-induced pigmentation of guinea pig skin by oral administration of a proanthocyanidin-rich extract from grape seeds.

Antioxidants such as vitamins C and E have been reported to inhibit the progression of ultraviolet (UV) radiation-induced pigmentation in the skin of hairless mice. However, little is known of the lightening effect of proanthocyanidin, a powerful polyphenolic antioxidant, on UV-induced pigmentation of the skin. We investigated the lightening effect of oral administration of a proanthocyanidin-rich grape seed extract (GSE) using guinea pigs with UV-induced pigmentation. These pigmented guinea pigs were fed diets containing 1% GSE or 1% vitamin C (w/w) for 8 weeks. GSE-feeding had an apparent lightening effect on the guinea pigs' pigmented skin. Histologic evaluation demonstrated a decrease in the number of 3,4-dihydroxyphenylalanine (DOPA)-positive melanocytes as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive, Ki-67-positive, proliferating cell nuclear antigen (PCNA)-positive melanin-containing cells in the basal epidermal layer of the UV-irradiated skin in GSE-fed guinea pigs. In contrast, these parameters did not change in the skin of vitamin C-fed or control guinea pigs. GSE inhibited the activity of mushroom tyrosinase and also inhibited melanogenesis without inhibiting the growth of cultured B16 mouse melanoma cells. In conclusion, we demonstrated that oral administration of GSE is effective in lightening the UV-induced pigmentation of guinea pig skin. This effect may be related to the inhibition of melanin synthesis by tyrosinase in melanocytes and the reactive oxygen species (ROS)-related proliferation of melanocytes.

Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract.

To confirm the absorption of proanthocyanidin (PA) into the human body, four healthy adults were administered 2.0 g of PA-rich grape seed extract (GSE). Blood were drawn before intake and 2 h after intake. Through the enzymatic treatment of sulfatase and beta-glucuronidase, blood samples were analyzed by HPLC coupled with mass-spectrometry (LC/MS). Procyanidin B1 [epicatechin-(4beta-->8)-catechin] was detected in human serum 2 h after intake. Its concentration was 10.6 +/- 2.5 nmol/l.

Impact of a clinical pathway and standardization of treatment for acute appendicitis.

PURPOSE: Acute appendicitis is one of the most common surgical diseases. Simple and precise guidelines for treating acute appendicitis are necessary for improving the treatment outcome of this disease. The purpose of this study was to determine the impact of a clinical pathway and standardization of treatment for acute appendicitis at our hospital. METHODS: The clinical pathway and standardization of treatment for acute appendicitis were introduced to our hospital in January 2000. We compared the length of hospitalization, postoperative stay, hospital costs, and operation time during the years before and the years after their introduction. RESULTS: There was no significant difference in the clinical characteristics of the 73 patients in the control group and the 112 patients in the pathway group. There were 6 (8.2%) and 24 (21.4%) cases of perforated appendicitis in the respective groups. The mean length of hospitalization ( P < 0.001), postoperative stay ( P < 0.001), and hospital costs ( P < 0.01) were significantly less in the patients in the pathway group who underwent surgery. CONCLUSION: Our clinical pathway and standardization of treatment for acute appendicitis proved effective for treating patients with acute appendicitis and minimizing costs without compromising patient care.

Minilaparotomy approach to colon cancer.

PURPOSE: Many studies have proved the feasibility and safety of a laparoscopic colectomy in comparison to a conventional laparotomy. However, a laparoscopic colectomy requires a minilaparotomy incision to perform the operative procedure. We have introduced a minilaparotomy technique which can perform all the operative procedures through incisions measuring from 3 to 7 cm in length. METHODS: A retrospective comparison of the outcome after a potentially curative resection of colon cancers via minilaparotomy (July 2000 to May 2002) and by conventional laparotomy (May 1997 to June 2000) is reported. RESULTS: The patient cohort consisted of 27 minilaparotomy cases and 24 conventional laparotomy cases. The patients' characteristics were similar in the two groups. The oncological clearance, in terms of the length of resected specimens, was similar in the two groups, whereas the number of lymph nodes removed was significantly higher in the minilaparotomy group. In addition, the mean operation time, blood loss, length of the laparotomy incision, postoperative time to walking, starting oral intake, and postoperative hospitalization were significantly smaller in the minilaparotomy group. CONCLUSION: Our minilaparotomy approach maintained the same curative resection for colon cancers as a conventional laparotomy, but it was less invasive and allowed for an earlier recovery and hospital discharge than conventional laparotomy. The minilaparotomy approach is thus considered to be an attractive alternative to conventional colon surgery.

A new preoperative grading system for predicting the operative conditions for abdominal wall-lifting laparoscopic cholecystectomy.

PURPOSE: This study was performed to evaluate the operative conditions for an abdominal wall-lifting laparoscopic cholecystectomy (ALLC) using a new preoperative grading system. METHODS: One hundred forty-five patients who underwent a cholecystectomy for cholecystolithiasis from January 1997 to December 1999 were retrospectively analyzed. Allotting 0-5 points for coexisting cholecystitis, past history, previous upper abdominal laparotomy, preoperative drainage, location of the stones, and body mass index, the total combined score was defined as the predictive score. The cases were graded into four risk groups according to the predictive score. The postoperative score, which evaluated the actual conditions of ALLC, was defined by allotting 0-8 points to operative factors: operation time, blood loss, additional trocars and procedures, conversion to open surgery, and postoperative complications. RESULTS: Ten cases (6.9%) were converted to open surgery and three cases (2.1%) had minor postoperative complications. The conversion rate for each risk group was 0% (minimum-risk group), 5.4% (low-risk group), 10.7% (intermediate-risk group), and 17.9% (high-risk group). The mean operation time was 63.0, 87.5, 89.0, and 120.2 min. The mean postoperative score was 1.08, 2.81, 3.96, and 6.36, and showed a respectively strong correlation with the predictive score (correlation coefficient: 0.997). CONCLUSIONS: Our preoperative grading system using the predictive score was found to be a reliable and feasible method for predicting the actual operative conditions for ALLC.