Heat-killed Lactobacillus gasseri can enhance immunity in the elderly in a double-blind, placebo-controlled clinical study.

This double-blind, placebo-controlled clinical trial was conducted to test whether Lactobacillus gasseri TMC0356 (TMC0356) can modify the immune response in the elderly. Heat-killed TMC0356 or placebo was orally administered to 28 healthy subjects aged 50-70 years old for 4 weeks at a dosage of 1.0×10(9) cfu/day. Peripheral blood mononuclear cells (PBMCs) were collected from the subjects before and after the study completion, together with general health and blood examination records. Isolated PBMCs were examined for the number of T cells, CD8(+)CD28(+) cells, native T cells, B cells, natural killer (NK) cells and the ratios of CD4/CD8 T cells and native/memory T cells. NK cell activation and concanavalin A-induced lymphocyte transformation of the isolated PBMCs were also examined. The number of CD8(+) T cells significantly increased in the subjects after TMC0356 oral administration (P<0.05). Furthermore, the population of CD8(+)CD28(+) T cells and the amount of lymphocyte transformation both significantly decreased in PBMCs from the placebo group (P<0.05). However, such changes were not observed in the subjects exposed to TMC0356. These results suggest that TMC0356 can increase the number of CD8(+) T cells and reduce CD28 expression loss in CD8(+) T cells of the elderly. The effect of TMC0356 on immune responses in the elderly may enhance their natural defence mechanisms against pathogenic infections.

Autosomal recessive cystinuria caused by genome-wide paternal uniparental isodisomy in a patient with Beckwith-Wiedemann syndrome.

Approximately 20% of Beckwith-Wiedemann syndrome (BWS) cases are caused by mosaic paternal uniparental disomy of chromosome 11 (pUPD11). Although pUPD11 is usually limited to the short arm of chromosome 11, a small minority of BWS cases show genome-wide mosaic pUPD (GWpUPD). These patients show variable clinical features depending on mosaic ratio, imprinting status of other chromosomes, and paternally inherited recessive mutations. To date, there have been no reports of a mosaic GWpUPD patient with an autosomal recessive disease caused by a paternally inherited recessive mutation. Here, we describe a patient concurrently showing the clinical features of BWS and autosomal recessive cystinuria. Genetic analyses revealed that the patient has mosaic GWpUPD and an inherited paternal homozygous mutation in SLC7A9. This is the first report indicating that a paternally inherited recessive mutation can cause an autosomal recessive disease in cases of GWpUPD mosaicism. Investigation into recessive mutations and the dysregulation of imprinting domains is critical in understanding precise clinical conditions of patients with mosaic GWpUPD.

Vision-based endoscope tracking for 3D ultrasound image-guided surgical navigation.

This work introduces a self-contained framework for endoscopic camera tracking by combining 3D ultrasonography with endoscopy. The approach can be readily incorporated into surgical workflows without installing external tracking devices. By fusing the ultrasound-constructed scene geometry with endoscopic vision, this integrated approach addresses issues related to initialization, scale ambiguity, and interest point inadequacy that may be faced by conventional vision-based approaches when applied to fetoscopic procedures. Vision-based pose estimations were demonstrated by phantom and ex vivo monkey placenta imaging. The potential contribution of this method may extend beyond fetoscopic procedures to include general augmented reality applications in minimally invasive procedures.

Long-term efficacy and safety of sitagliptin in the treatment of Japanese Type 2 diabetes (ASSET-K1) to a target of HbA1c <7%.

BACKGROUND: Few studies have investigated the factors related to improvement and maintenance of glycemic control with sitagliptin in Type 2 diabetes (T2D) patients. AIM: To identify factors contributing to reaching and maintaining glycated hemoglobin (HbA1c) <7% with sitagliptin in Japanese T2D patients. SUBJECTS AND METHODS: This study included 1327 patients who were: taking sitagliptin as monotherapy; switched to sitagliptin; or taking sitagliptin in combination therapy. At baseline and 1, 3, 6, and 12 months after starting sitagliptin, weight, body mass index (BMI), HbA1c, fasting plasma glucose (FPG), and post-prandial plasma glucose (PPG) were measured. The subjects were divided into a group that achieved HbA1c<7% at 12 months, a poor control group (HbA1c≥8% at 12 months), and a discontinued group. Multiple regression analysis was performed to identify factors contributing to long-term control and maintenance with sitagliptin treatment. RESULTS: HbA1c decreased significantly from 8.0% at baseline to 7.3%, but weight was unchanged. FPG and PPG improved significantly. The HbA1c<7% group had a significantly higher age and a signifi cant ly lower BMI at baseline than the HbA1c≥8% group and the discontinued group. On multivariate regression analysis, baseline HbA1c, baseline BMI, and Δbody weight after 12 months were significantly related to HbA1c reduction. The most common adverse event was hypoglycemia, and the most common adverse event responsible for discontinuation was constipation. CONCLUSIONS: HbA1c<7.0% was achieved in 31% of T2D patients who had poor control with conventional treatment. Weight management is important for maintaining good long-term control with sitagliptin.

Orally administered heat-killed Lactobacillus gasseri TMC0356 alters respiratory immune responses and intestinal microbiota of diet-induced obese mice.

AIMS: To investigate the influence of heat-killed Lactobacillus gasseri TMC0356 on changes in respiratory immune function and intestinal microbiota in a diet-induced obese mouse model. METHODS AND RESULTS: Male C57BL/6J mice were fed a high-fat diet for 16 weeks. After 8 weeks, the high-fat-diet-induced obese mice (DIO mice) were randomly divided into two 0067roups, the DIO and DIO0356 groups. DIO0356 group mice were orally fed with heat-killed TMC0356 every day for 8 weeks, while DIO group mice were exposed to 0·85% NaCl over the same time period as controls. After intervention, the pulmonary mRNA expression of cytokines and other immune molecules in DIO0356 mice compared to those in DIO group mice was significantly increased (P < 0·05, P < 0·01). In faecal bacterial profiles, analysed using the terminal restriction fragment length polymorphism (T-RFLP) method, T-RFLP patterns in 75% of the DIO0356 group mice were apparently changed compared with those in control group mice. CONCLUSION: These results suggest that inactive lactobacilli may stimulate the respiratory immune responses of obese host animals to enhance their natural defences against respiratory infection, partially associating with their potent impact on intestinal microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: We have demonstrated that oral administration of inactive lactobacilli may protect host animals from the lung immune dysfunction caused by obesity.

Enhancement of immunoregulatory effects of Lactobacillus gasseri TMC0356 by heat treatment and culture medium.

AIMS: The aim of this study was to investigate the influence of heat treatment and culture media on the immunoregulatory effects of a probiotic strain, Lactobacillus gasseri TMC0356 (TMC0356). METHODS AND RESULTS: TMC0356 cultured in deMan-Rogosa-Sharpe and same food grade (FG) media were inactivated with the heat treatment at 70 and 90°C. Viable and heat-killed TMC0356 were tested for their ability to induce interleukin (IL)-12 production in the murine macrophage cell line J774.1. These TMC0356 were examined for their resistance to N-acetylmuramidase. Their morphology was observed by scanning electron microscopy. The heat-killed TMC0356 significantly induced IL-12 production in J774.1 cells and exhibited enhanced resistance to N-acetylmuramidase compared with viable TMC0356. Morphological changes were observed in TMC0356 when cultured in FG medium. Cell morphology and induction of IL-12 production in J774.1 cells were also associated. CONCLUSIONS: These results suggest that heat treatment and culture medium composition modified the immunoregulatory effects of TMC0356 to induce IL-12 production in macrophages. SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate that probiotic immunoregulatory effects may be modified by the processing technology of cell preparation.

Postoperative chylothorax in congenital diaphragmatic hernia.

INTRODUCTION: The mechanisms responsible for postoperative chylothorax in Congenital Diaphragmatic Hernia (CDH) patients remain unclear. The aim of the present study was to examine the clinical features of CDH that may contribute to an association with postoperative chylothorax. MATERIAL AND METHODS: 198 neonates with CDH, in whom surgical repair of a diaphragmatic defect was performed between 1981 and 2008, were retrospectively studied. The patients were divided into 2 groups; patients with postoperative chylothorax (group I, n=11) and patients without postoperative chylothorax (group II, n=187). The clinical findings were compared between group I and group II to investigate potential predictive parameters for an association with chylothorax. Moreover, the clinical findings and treatments were evaluated in patients with chylothorax. RESULTS: 11 of the 198 infants (5.5%) developed a chylothorax. Although the incidence of a prenatal diagnosis was slightly higher in group I, no relationship with other clinical features was found which would indicate the severity of CDH or the occurrence of postoperative chylothorax. Treatment for chylothorax was drainage alone in 2 cases, total parenteral nutrition with drainage in 8 infants and additional intrathoracic OK-432 infusion in 1 patient. No patients required surgical intervention for chylothorax. No recurrences were observed in this patient series. CONCLUSIONS: It was concluded that postoperative chylothorax is not rare in infants after CDH repair. However, no statistically significant predictive parameters for chylothorax were identified, except for the presence of a prenatal diagnosis.

Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection.

AIMS: Our study was conducted to evaluate the potent protective effects of oral administration of probiotic Lactobacillus strains against influenza virus (Flu) infection in a mouse model. METHOD AND RESULTS: Lyophilized Lactobacillus rhamnosus GG (LGG) and Lactobacillus gasseri TMC0356 (TMC0356) were orally administered to BALB/c mice for 19 days. The test mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and any changes in clinical symptoms were monitored. After 6 days of infection, the mice were killed and pulmonary virus titres were determined. The clinical symptom scores of mice administered oral LGG and TMC0356 were significantly ameliorated, compared to those of the control mice (P < 0.01). The pulmonary virus titres of the mice fed LGG and TMC0356 were also significantly decreased compared to those of control mice (P < 0.05). CONCLUSIONS: These results indicate that oral administration of lactobacilli, such as LGG and TMC0356, might protect a host animal against Flu infection. SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate that oral administration of selected lactobacilli might protect host animals from Flu infection by interactions with gut immunity.

Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses.

AIMS: To investigate whether intranasal Lactobacillus administration protects host animals from influenza virus (IFV) infection by enhancing respiratory immune responses in a mouse model. METHODS AND RESULTS: After 3 days of intranasal exposure to Lactobacillus rhamnosus GG (LGG), BALB/c mice were infected with IFV A/PR/8/34 (H1N1). Mice treated with LGG showed a lower frequency of accumulated symptoms and a higher survival rate than control mice (P < 0.05). The YAC-1 cell-killing activity of lung cells isolated from mice treated with LGG was significantly greater than those isolated from control mice (P < 0.01). Intranasal administration of LGG significantly increased mRNA expression of interleukin (IL)-1 beta, tumour necrosis factor (TNF) and monocyte chemotactic protein (MCP)-1 (P < 0.01). CONCLUSIONS: These results suggest that intranasal administration of LGG protects the host animal from IFV infection by enhancing respiratory cell-mediated immune responses following up-regulation of lung natural killer (NK) cell activation. SIGNIFICANCE AND IMPACT OF STUDY: We have demonstrated that probiotics might protect host animals from viral infection by stimulating immune responses in the respiratory tract.

Frey procedure for chronic pancreatitis in a child with duodenal atresia and complex pancreaticobiliary disorders.

A boy aged 2 years and 7 months who had undergone duodeno-duodenostomy for duodenal atresia and annular pancreas in the neonatal period presented with recurrent pancreatitis. ERCP showed an incomplete pancreas divisum associated with pancreaticobiliary maljunction. At 3 years and 8 months of age, we performed a Frey procedure in combination with total excision of the extrahepatic bile duct. The main pancreatic duct was opened in the body and the head was cored out anteriorly. The pancreaticobiliary system was reconstructed with a Roux-en-Y anastomosis. The patient has been free from symptoms with excellent weight gain in the follow-up period of 20 months. The Frey procedure can be a safe and effective operation in children with chronic pancreatitis caused by complex pancreatobiliary disorders associated with duodenal atresia.

Residual of 17beta-estradiol in digestion liquid generated from a biogas plant using livestock waste.

A biogas plant using livestock waste in which a methane fermentation process is applied is a useful facility for generating energy. The digestion liquid generated from the biogas plant as a residue has high potential for use as a crop fertilizer. However, high-density estrogens such as 17beta-estradiol (E2) are included in livestock waste, and there is little information on the behavior of E2 in the digestion liquid. In this study, a survey of E2 concentration at each process in a biogas plant using livestock waste was carried out. In addition, the efficiencies of E2 removal from the digestion liquid by activated carbon adsorption and soil infiltration were examined. The total concentration of E2 in raw livestock waste was reduced to 2 microg/l after treatment, and the removal efficiency of E2 was about 80% for the plant. The methane fermentation process is important not only for the generation of methane but also for the removal of E2. The proportion of E2 conjugates comprising the total E2 concentration was 10% or less in all treated samples. In the plant, there is no likelihood of an increase in estrogen activity by the cleaving of E2 conjugates. By carrying out activated carbon adsorption to remove E2 from the digestion liquid, a large portion of E2 was removed from the digestion liquid, but an E2 concentration of 0.5 microg/l still remained in the treated digestion liquid. In contrast, it was possible to purify the digestion liquid to an E2 concentration of less than 0.002-0.011 microg/l by soil infiltration. It is thus possible to utilize the digestion liquid as a fertilizer without causing aquatic environmental pollution, but factors such as application rate, soil characteristics, and the E2 concentration of digestion liquid should be considered first.

Alteration in articular cartilage of rat knee joints after spinal cord injury.

OBJECTIVE: Mechanical forces are crucial for the maintenance of the morphologic and functional integrity of articular cartilage. The alteration of the articular cartilage after spinal cord injury (SCI) has been described in relation to a suppression of mechanical forces, since the joint is unloaded and restricted in movement. However, the morphological and biochemical characteristics of the cartilage after SCI are still poorly understood. We identified the localization of cartilage alterations after SCI and verified the influence of mechanical forces on the articular cartilage. METHOD: A total of 32 Wistar rats were used. Sixteen animals underwent an SCI and 16 animals served as control. The articular cartilage of the knee joint was assessed, respectively, at 4, 8, 10, and 12 weeks after intervention by histochemical, histomorphometric, immunohistochemical, and biochemical analyses. RESULTS: Cartilage thickness of spinal cord-injured knees decreased at the tibial and posterior femoral (FP) regions and increased at the anterior femoral (FA) region. Spinal cord injuries decreased the number of chondrocytes at the anterior regions and decreased the cartilage matrix staining only at the tibial regions. Immunolabeling to collagen type II was noted comparably in the superficial layer but noted weakly from the middle to deep layer. Collagen type I existed excessively at the cartilage surface and the pericellular regions. CONCLUSION: Cartilage alterations after SCI would not be explained by only a suppression of mechanical forces by unloading and immobilization, but there may be influences on the cartilage in addition to the change in mechanical forces.

Cystic lymphangioma of Retzius space manifested as acute abdomen.

The authors describe a rare pediatric case of cystic lymphangioma arising from the Retzius space. A 9-year-old boy underwent an appendectomy in a nearby hospital after a sudden onset of severe hypogastralgia. When laparotomy revealed a retroperitoneal mass, he was referred to our hospital. After diagnosis of a multicystic mass in the Retzius space, extirpation of the cystic lesion was performed. Histological evaluation of the resected specimens revealed cystic lymphangioma. The patient has been free of symptoms for 6 years since the operation.

Laparoscopic percutaneous extraperitoneal closure (LPEC) method for the exploration and treatment of inguinal hernia in girls.

We recently introduced the laparoscopic percutaneous extraperitoneal closure (LPEC) method for the treatment of girls with inguinal hernia. Using the LPEC method, 129 girls underwent laparoscopic herniorrhaphy. A 5 mm laparoscope was inserted via the umbilicus. A 3 mm "snake retractor" was advanced through the lateral abdominal wall to measure the length of the hernia sac and contralateral patent processus vaginalis (PPV), respectively. The hernia sac and PPV were closed at the level of the internal inguinal ring with a 2-0 non-absorbable purse-string suture using Lapaherclosure, a special 19G needle that can hold a suture at the tip. The length of the hernial sac was significantly longer than that of contralateral PPV (mean 41 mm; range 18-70 mm; P < 0.05). There were no serious complications associated with the procedure. No recurrence of hernia or metachronous contralateral hernia has been identified so far. This approach enables us to perform contralateral exploration without any additional techniques, followed by immediate and accurate closure of the hernia sac and PPV. We conclude that the LPEC method is a safe and efficacious procedure with a low recurrence rate that should be viewed as an acceptable alternative to the traditional open approach.

Clinical outcome of laparoscopically assisted endorectal pull-through in Hirschsprung's disease: comparison of abdominal and perineal approaches.

BACKGROUND/PURPOSE: Laparoscopically assisted endorectal pull-through (EPT) via a perineal approach using a prolapsing technique (PA) for Hirschsprung's disease (HD) has been reported. However, the clinical outcome after this approach has not been reported. The purpose of this study was to compare the clinical outcome of PA and the conventional transabdominal approach (TA). METHODS: In the period between 1990 and 2001, 20 cases of HD underwent EPT with TA (group O), and 21 underwent EPT with PA (group L). There was no difference in age and weight distribution between the 2 groups. Clinical outcome was assessed 3 years after surgery. RESULTS: The operation time was comparable in the 2 groups (4.9 +/- 0.8 v 5.2 +/- 0.8 hr), whereas blood loss (98 +/- 52 v 36 +/- 30 mL) and postoperative complications requiring surgical intervention (26% v 0%) were significantly lower in group L. The incidence of postoperative enteritis (27% v 28%) and voluntary defecation (more than once every/2 days) were compatible in the 2 groups (70% v 87%). Soiling (small amount of involuntary stooling; >1 per month) was significantly less frequent in group L (45% v 14%). CONCLUSIONS: Laparoscopically assisted ETP with PA is less invasive and can provide a better clinical outcome compared with TA in terms of postoperative soiling.

Features of retinal arterial macroaneurysms in patients with uveitis.

AIM: To determine the frequency and clinical characteristics of retinal arterial macroaneurysms in patients with uveitis. METHODS: A retrospective review of the clinical, photographic, and angiographic records of 1007 patients with uveitis, examined at the Osaka University Hospital uveitis clinic between January 1995 and April 2002, was performed. All of the records were examined to determine whether macroaneurysms were present, and when present, to determine the laterality, type, location, clinical course, and the presence of associated systemic and ocular diseases. RESULTS: Of the 1007 patients with uveitis, only 14 (1.4%) had macroaneurysms. 12 of these 14 patients had peripheral multifocal chorioretinitis (PMC), and five of these 12 were diagnosed with sarcoidosis and the other seven without sarcoidosis. There was only one case with sarcoidosis without PMC, and the remaining case was uveitis of unknown origin. There were 18 macroaneurysms in all cases and 17 (94.4%) were the exudative type, and the remaining one was the haemorrhagic type. Two patients had been treated for systemic hypertension but the others had no signs of systemic hypertension or cardiovascular disease. CONCLUSIONS: Macroaneurysms are not characteristically found in patients with uveitis, but the majority are found in patients with PMC. The majority of the macroaneurysms were the exudative type, and the conclusion is that patients with PMC should be carefully examined for exudative macroaneurysms.

Role of IL-18 in pathogenesis of endometriosis.

BACKGROUND: Endometriosis is a complex disease associated with a wide range of immune responses, including pain, adhesion, exudation of peritoneal fluid, elevation of cytokine levels and generation of autoantibodies. Interleukin (IL)-18 is a strong pleiotropic cytokine known to be involved in various immune diseases. The aim of this study is to elucidate the role of IL-18 in the pathogenesis of endometriosis. METHODS: IL-18 and IL-1beta concentrations were measured in the peritoneal fluid and sera of 39 endometriosis patients and 15 control women. Expression of IL-18 and IL-18 receptor alpha-chain (IL-18Ralpha) was analysed in endometriotic tissues immunohistochemically. The effects of IL-18 on cyclooxygenase (COX)-II gene expression were analysed in peritoneal fluid monocytes and endometriotic cells of endometriosis patients. RESULTS: IL-18 concentrations in the peritoneal fluid of endometriosis patients averaged 592.57 +/- 108.27 pg/ml, significantly higher than 260.50 +/- 55.88 pg/ml in non-endometriotic samples. IL-18 concentrations in the serum did not differ significantly between endometriosis and control patients. Similarly, no significant differences were observed in IL-1beta concentrations in either the peritoneal fluid or the serum. IL-18 and IL-18Ralpha were expressed in endometriotic tissues. IL-18Ralpha expression was also observed in cells infiltrating into the inflammatory area of the endometriosis patients. COX-II was induced in peritoneal fluid monocytes and in endometriotic cells in response to IL-18 stimulation. CONCLUSIONS: The elevation of IL-18 in the peritoneal fluid of endometriosis patients and the induction of COX-II in peritoneal monocytes by IL-18 suggest that IL-18 plays a pathogenic role in endometriosis.