Size-mismatched transplantation from large donors to small recipients is associated with pancreas graft thrombosis: A retrospective national observational study.

INTRODUCTION: Donor-recipient (D/R) size mismatch has been evaluated for a number of organs but not for pancreas transplantation. METHODS: We retrospectively evaluated 438 patients who had undergone pancreas transplantation. The D/R body surface area (BSA) ratio was calculated, and the relationship between the ratio and graft prognosis was evaluated. We divided the patients into two groups and evaluated graft survival. The incidence of pancreas graft thrombosis resulting in graft failure within 14 days and 1-year graft survival were compared using Kaplan-Meier curves, and the prognostic factors associated with graft thrombosis were identified by univariate and multivariate analyses. RESULTS: The mean/median donor and recipient BSAs were 1.63 m2 /1.65 m2 , and 1.57 m2 /1.55 m2 , respectively; the mean and median D/R BSAs were both 1.05. The receiver operating characteristic curve cutoff for the D/R BSA ratio was 1.09, and significant differences were identified between patients with ratios of ≥1.09 (high group) versus <1.09 (low group). The incidence of graft thrombosis resulting in pancreas graft failure within 14 days was significantly higher in the high group than in the low group (p < .01). One-year overall and death-censored pancreas graft survival were significantly higher in the low group than in the high group (p < .01). Multivariate analysis identified recipient height, donor BSA, and donor hemoglobin A1c as significant independent factors for graft thrombosis. Cubic spline curve analysis indicated an increased risk of graft thrombosis with increasing D/R BSA ratio. CONCLUSION: D/R size mismatch is associated with graft thrombosis after pancreas transplantation.

Utilization of the Pancreas From Donors With an Extremely High Pancreas Donor Risk Index: Report of the National Registry of Pancreas Transplantation.

Pancreas transplants from expanded criteria donors are performed widely in Japan because there is a shortage of brain-dead donors. However, the effectiveness of this strategy is unknown. We retrospectively studied 371 pancreas transplants to evaluate the possibility of pancreas transplantation from expanded criteria donors by the Pancreas Donor Risk Index (PDRI). Patients were divided into five groups according to quintiles of PDRI values (Q1-Q5). The 1-year pancreas graft survival rates were 94.5% for Q1, 91.9% for Q2, 90.5% for Q3, 89.3% for Q4, and 79.6% for Q5, and were significantly lower with a lower PDRI (p = 0.04). A multivariate analysis showed that the PDRI, donor hemoglobin A1c values, and pancreas transplantation alone significantly predicted 1-year pancreas graft survival (all p < 0.05). Spline curve analysis showed that the PDRI was incrementally associated with an increased risk of 1-year graft failure. In the group with a PDRI ≥ 2.87, 8/56 patients had graft failures within 1 month, and all were due to graft thrombosis. The PDRI is a prognostic factor related to the 1-year graft survival rate. However, pancreas transplantation from high-PDRI donors shows acceptable results and could be an alternative when the donor pool is insufficient.

Clinical impact of pancreas donor age on outcomes following pancreas transplantation: Analysis of a nationwide registry in Japan.

OBJECTIVES: Clinical impact of pancreas donor age on pancreas transplantation (PTx) outcome has not been well investigated. Here we analyzed the nationwide PTx registry in Japan to assess posttransplant outcomes in donor age-stratified groups. METHODS: This study included 410 cases of PTx performed in Japan between 2000 and 2019. Analyses were performed using clinical data from the Japan Pancreas Transplant Registry of Japan Society for Pancreas and Islet Transplantation. RESULTS: The 410 PTx cases were classified based on donor age: <10 years (n = 10, 2.4%), 10-19 years (n = 30, 7.3%), 20-29 years (n = 64, 15.6%), 30-39 years (n = 75, 18.3%), 40-49 years (n = 114, 27.8%), 50-59 years (n = 90, 22.0%), and ≥60 years (n = 27, 6.6%). The incidence of early pancreas graft loss (8.9%, 36/410 cases) did not exhibit a significant linear correlation with donor age. Posttransplant pancreas graft survival (1-/3-/5-/10-year rates of 85.9%/80.6%/76.2%/67.4% among all cases) was also not significantly associated with donor age. CONCLUSION: Pancreas donor age was not significantly associated with posttransplant outcome. This finding supports the use of expanded criteria donors, with regards to pancreas donor age, for PTx in cases of type 1 diabetes mellitus.

Remote Reminiscence Using Immersive Virtual Reality May Be Efficacious for Reducing Anxiety in Patients with Mild Cognitive Impairment Even in COVID-19 Pandemic: A Case Report.

To prevent cognitive decline, non-pharmacological therapies such as reminiscence for mild cognitive impairment (MCI) are required, however, the use of nursing homes was limited due to coronavirus disease 2019 (COVID-19). Therefore, the demand for remote-care is increasing. We hypothesized that immersive virtual reality (iVR) could be used more effectively than conventional reminiscence for anxiety. We first examined the effectiveness and safety of reminiscence using iVR (iVR reminiscence session) in patients with MCI. After COVID-19 imposed restriction on visiting nursing homes, we conducted online iVR reminiscence session (remote iVR reminiscence session) and compared its effectiveness with that of interpersonal iVR reminiscence session (face-to-face iVR reminiscence session). The results of two elderly with MCI suggested that iVR reminiscence could reduce anxiety and the burden of care without serious side effects. The effects of remote iVR reminiscence might be almost as effective as those of face-to-face one.

Outcomes of pancreas transplantation in older versus younger recipients: a comparative analysis.

PURPOSE: The feasibility of pancreas transplantation (PT) in older recipients remains a matter of debate. We examined the influence of recipient age on PT outcomes and identified the prognostic factors for older recipients. METHODS: We compared the outcomes of PT in recipients aged < 50 years (younger group; n = 285) with those in recipients aged ≥ 50 years (older group; n = 94). Prognostic factors in the older group were analyzed by a logistic regression model and the influence of recipient age on survival outcomes were analyzed using propensity score matching. RESULTS: The patient survival rate was significantly worse in the older group (P < 0.001). Patient death from infection or/and multiple organ failure or cardiac/cerebrovascular events was also more frequent in the older group than in the younger group (P = 0.012 and P = 0.045, respectively). A longer duration of diabetes was an independent risk factor of 1-year mortality in the older group. In a propensity score-matched comparison, the older recipients (n = 77) had significantly poorer survival than the younger recipients (n = 77) (P = 0.026). CONCLUSIONS: PT should be considered with appropriate caution, especially for older recipients with a long duration of diabetes.

Impact of an older donor pancreas on the outcome of pancreas transplantation: single-center experience of the expansion of donor criteria.

PURPOSE: The impact of using an older donor pancreas on the clinical outcomes of pancreas transplantation (PTx) is unknown. We investigated this by comparing the outcomes of PTx using older and younger donors in a single Japanese center, to expand the donor criteria. METHODS: The subjects were 54 patients who received PTx from deceased donors in our institution. Posttransplant outcomes were analyzed based on donor age, with older donors defined as those aged ≥ 60 years. RESULTS: The donors included six older (11.1%; aged 64 ± 4 years) and 48 younger donors (88.9%; aged 43 ± 12 years). There was no significant difference in the donor age between the recipients with vs. those without postoperative complications or between those with vs. those without early pancreas graft loss. Long-term outcomes, including overall, pancreas graft, and kidney graft survival after PTx, did not differ significantly between the older and younger donor groups. Graft age, defined as the age of the donor at the time of procurement plus the graft survival period, was not associated with graft loss. CONCLUSION: Our results suggest that post-transplant outcomes of PTx using pancreas from older donors aged ≥ 60 years are comparable to those using pancreas from younger donors, and support expansion of the donor pool for transplantation therapy for type 1 diabetes mellitus.

Are the outcomes of Japanese pancreas transplantation utilizing extended-criteria donors acceptable? A propensity score matching analysis for donors <50 or ≥50 years old.

In Japan, about 30% of pancreatic transplant donors are ≥50 years old, making them "extended-criteria donors (ECDs)." We analyzed 361 cases of transplantation involving donors from the Japanese pancreas transplantation registry to evaluate the acceptability of ECDs. The patient survival rates at 1, 5, and 10 years after transplantation were 96.6%, 94.9%, and 88.3%, respectively. The survival rates of pancreas and kidney grafts at 1, 5, and 10 years were 85.3%, 74.8%, and 70.6%, and 94.2%, 90.9%, and 80.9%, respectively. Multivariate analysis revealed that no particular donor factors significantly influenced the pancreatic graft survival. Patients were divided into 2 groups: donors ≥50 years old (older group) and those <50 years old (younger group). After propensity score matching, the overall pancreatic graft survival at 1, 5, and 10 years after transplantation in the older group was 82.8%, 71.8%, and 69.5%, respectively, which was almost the same as in the younger group (84.9%, 70.2%, and 67.4%, respectively). No donor factors markedly influenced the pancreatic graft survival, and the outcomes of pancreas transplantation from ECDs ≥50 years old were comparable to those from younger donors.

Predictive factors of posttransplant glucose intolerance in Japanese patients with type 1 diabetes after pancreas transplantation.

Pancreas transplantation (PTx) has been performed worldwide for patients with type 1 diabetes accompanied with end-stage renal disease or uncontrollable glycemic fluctuation. Nevertheless, risk factors of posttransplant glucose intolerance, which is responsible for progress of diabetic complications, remains unclear, especially in cases without pancreatic graft function loss. Therefore, this study was conducted to search for predictive factors of future glucose tolerance in PTx recipients without pancreatic graft function loss. Subjects were selected from among 41 Japanese patients with type 1 diabetes who received PTx between 2000 and 2016 in Osaka University Hospital, and 24 subjects free from rejections and thromboses were analyzed. Several examinations to evaluate insulin secretion and insulin sensitivity within 6 months after transplantation (initial examination) were performed. Glucose tolerance was evaluated by 120-minute post-load plasma glucose level during 75-g oral glucose tolerance tests (OGTT), referred to as PGOGTT120, at the initial examination and between 1 year and 2 years posttransplantation (maintenance period). The initial examination factors that were correlated with PGOGTT120 in the maintenance period were PGOGTT120 [r = 0.52 (p = 0.01)], insulinogenic index [r = -0.65 (p < 0.01)], and the ratio of incremental area under the curve of insulin to that of plasma glucose (iAUCR) calculated from data of OGTT [r = -0.65 (p < 0.01)]. Insulinogenic index [ß = -0.28 (p = 0.02)] and iAUCR [ß = -0.29 (p = 0.02)] were still significantly correlated with PGOGTT120 in the maintenance period after adjustment for PGOGTT120 at the initial examination. In conclusion, insulinogenic index and iAUCR from OGTT performed in the early posttransplantation period were predictive factors of future glucose intolerance.

The association between the increased performance of laparoscopic colon surgery and a reduced risk of surgical site infection.

PURPOSE: Surgical site infection (SSI) is the most frequently occurring nosocomial infection. Remarkable surgical progress has recently been made in laparoscopic surgery. Therefore, our objective was to investigate the association between increased rates of laparoscopic colon surgery and SSI. METHODS: We retrospectively investigated SSI surveillance data from July 2003 to December 2015. Two university hospitals and 25 university-affiliated hospitals participated in prospective SSI surveillance. Univariate and multivariate analyses were performed to detect significant associations. RESULTS: We investigated 9655 colon surgeries. The year in which surgery was performed was significantly associated with the SSI rate (p = 0.0381). The rate of laparoscopic surgery gradually increased during the study period, and by 2012 it was routinely used for > 50% of colon surgeries. Laparoscopic surgery became a significant factor associated with reduced SSI rates compared with conventional open surgery once the performance rate of laparoscopic surgery reached > 50%. CONCLUSIONS: Increasing rates of laparoscopic colon surgery tended to be associated with a reduction in the SSI risk after surgical treatment of colonic disease. The results of this study might encourage surgeons to view laparoscopic surgical techniques as an evidence-based approach for reducing the risk of SSI.

Clinical Impact of Preoperative Sarcopenia on the Postoperative Outcomes After Pancreas Transplantation.

BACKGROUND: The importance of evaluating sarcopenia is increasingly being recognized in the field of transplantation because sarcopenia can have an adverse effect on the treatment outcomes. However, the clinical significance of preoperative sarcopenia on the postoperative outcomes following pancreas transplantation (PTx) has been largely unknown. The objective of this study was to investigate the role of preoperative sarcopenia in predicting the postoperative outcomes following PTx in recipients with type 1 diabetes mellitus (T1D). METHODS: Forty-one recipients with severe T1D who underwent PTx were retrospectively reviewed. The psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), as determined by preoperative computed tomography, were substituted for the quantity and quality of skeletal muscle for the definition of sarcopenia, respectively. Gender-specific quartiles were generated, and PMI lower than the first quantile or IMAC higher than the third quantile was considered to represent sarcopenia. The postoperative outcomes included postoperative surgical complications and pancreas graft survival. RESULTS: Sarcopenia was identified in 11 recipients according to both the PMI and IMAC stratifications. The multivariate analyses revealed that high IMAC was independently associated with the development of postoperative surgical complications (odds ratio, 9.35; p = 0.016). In addition, the recipients with high IMAC showed unfavorable graft survival compared to those with normal IMAC (log-rank test; p = 0.038). In contrast, low PMI was not significantly associated with the postoperative outcomes. CONCLUSIONS: Our data suggested that preoperative sarcopenia, especially a decline in the quality of skeletal muscle, predicted poorer postoperative outcomes in T1D recipients undergoing PTx.

A Novel Monoclonal Antibody Against Neuroepithelial and Ependymal Cells and Characteristics of Its Positive Cells in Neurospheres.

There are still few useful cell membrane surface antigens suitable for identification and isolation of neural stem cells (NSCs). We generated a novel monoclonal antibody (mAb), designated as mAb against immature neural cell antigens (INCA mAb), which reacted with the areas around a lateral ventricle of a fetal cerebrum. INCA mAb specifically reacted with neuroepithelial cells in fetal cerebrums and ependymal cells in adult cerebrums. The recognition molecules were O-linked 40 and 42 kDa glycoproteins on the cell membrane surface (gp40 INCA and gp42 INCA). Based on expression pattern analysis of the recognition molecules in developing cerebrums, it was concluded that gp42 INCA was a stage-specific antigen expressed on undifferentiated neuroepithelial cells, while gp40 INCA was a cell lineage-specific antigen expressed at the stages of differentiation from neuroepithelial cells to ependymal cells. A flow cytometric analysis showed that fetal and young adult neurospheres were divided into INCA mAb(-) CD133 polyclonal antibody (pAb)(-), INCA mAb(+) CD133 pAb(-), and INCA mAb(+) CD133 pAb(+) cell populations based on the reactivity against INCA mAb and CD133 pAb. The proportion of cells having the neurosphere formation capability in the INCA mAb(+) CD133 pAb(+) cell population was significantly larger than that of undivided neurospheres. Neurospheres formed by clonal expansion of INCA mAb(+) CD133 pAb(+) cells gave rise to neurons and glial cells. INCA mAb will be a useful immunological probe in the study of NSCs.

Risk factors for superficial incisional surgical site infection after gastrectomy: analysis of patients enrolled in a prospective randomized trial comparing skin closure methods.

BACKGROUND: Surgical site infection is one of the commonest complications of gastrointestinal surgery. The nature of surgical procedures and wound closure methods may influence the incidence of superficial incisional surgical site infection. Patients enrolled in a prospective randomized controlled trial comparing skin closure methods are the best subjects for analyzing surgical site infection risk. METHOD: From a cohort of 1080 patients who had been enrolled in our previous randomized controlled trial, data for 685 patients who had undergone elective open total gastrectomy or distal gastrectomy for gastric cancer were extracted. The incidences of superficial incisional surgical site infection after total gastrectomy and distal gastrectomy were compared and risk factors for superficial incisional surgical site infection were investigated by univariate analyses using logistic regression models. RESULTS: In all, 42 patients (6.1 %) developed superficial incisional surgical site infections after gastrectomy; 15 of 288 patients (5.2 %) developed these infections after total gastrectomy, and 27 of 397 patients (6.8 %) developed these infections after distal gastrectomy-these differences are not significant. According to univariate analysis, age (75 years or older or younger than 75 years) was the only risk factor for superficial incisional surgical site infections (P = 0.049). There was a tendency for the incidence of superficial incisional surgical site infection to increase in parallel with age. CONCLUSION: The incidence of superficial incisional surgical site infection did not differ between total gastrectomy and distal gastrectomy. Advanced age was the only identified risk factor for superficial incisional surgical site infections after gastrectomy.

Influence of nutritional status on the therapeutic effect of infliximab in patients with Crohn's disease.

PURPOSE: Crohn's disease (CD) is a refractory inflammatory bowel disease of unknown etiology, frequently complicated by malnutrition. It is thought that the delayed wound healing associated with this malnutrition in CD patients might adversely affect the therapeutic benefits of infliximab (IFX). Therefore, we investigated the effects of nutritional status on IFX treatment. METHODS: We assessed nutritional status and CD activity when IFX therapy was initiated and following the third dose, 6 weeks later. Nutritional status was assessed using the body mass index (BMI) and nutritional risk index (NRI), whereas CD activity was assessed using the CD activity index (CDAI). RESULTS: All patients with a BMI ≥ 18.5 kg/m(2) at the time of IFX therapy met the effective criteria for the CDAI, and IFX treatment was considered responsive in these patients. Furthermore, IFX treatment was responsive, with a high level of effectiveness, in all five subjects (31.3 %) with NRI scores of 97.5 and above with no risk of malnutrition (p = 0.037). CONCLUSIONS: Our results suggest that nutritional status does influence the therapeutic effect of IFX in CD patients. The response rate to IFX treatment thus could be improved by optimizing the nutritional status. We recommend comprehensive nutritional assessment and intervention prior to IFX treatment schedules.

The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is a chronic, relapsing, and refractory disorder of the intestine. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the preferred and standard surgical procedure for patients' refractory to medical therapy. Pouchitis is one of the most common long-term complications after IPAA. In the present study, the safety and efficacy of Clostridium butyricum MIYAIRI (CBM) as a probiotic were examined. METHODS: A randomized and placebo-controlled study was performed. Seventeen patients were recruited from 2007 to 2013. Nine tablets of MIYA-BM(®) or placebo were orally administered once daily. The cumulative pouchitis-free survival, pouch condition (using the modified pouch disease activity index), and blood parameters were evaluated. A fecal sample analysis was also performed. RESULTS: Subjects were randomly allocated to receive MIYA-BM or placebo (9 and 8 subjects, respectively). One subject in the MIYA-BM group and four subjects in the placebo group developed pouchitis. No side effects occurred in either group. Characteristic intestinal flora was observed in each group. CONCLUSIONS: Our results suggest that probiotic therapy with CBM achieved favorable results with minimal side effects and might be a useful complementary therapy for the prevention of pouchitis in patients with UC who have undergone IPAA.

Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines.

Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-ß was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1ß, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.

The effects of androgen deprivation therapy with weight management on serum aP2 and adiponectin levels in prostate cancer patients.

Androgen deprivation therapy (ADT) for the treatment of prostate cancer (PCa) causes an increase in total body fat, leading to a net gain in body weight. Moreover, the use of the luteinizing hormone-releasing hormone agonists in ADT causes a decrease in serum androgen levels, leading to the development of metabolic syndrome (MetS). Androgen blockade significantly increases plasma adiponectin levels, which has some efficacy against MetS, whereas ADT increases fasting plasma insulin and decreases insulin sensitivity, suggesting that there are other mechanisms involved in the onset of MetS besides adiponectin activation. We investigated the effects of ADT on serum aP2 and adiponectin in PCa patients. Six months post-ADT, serum aP2 and adiponectin levels were significantly increased, although there were no changes in patient body weight and no correlation between the changes in serum aP2 and total adiponectin levels. The serum adiponectin and aP2 levels have independent implications in ADT for PCa; therefore, their combined measurement will clarify the impact on the development of obesity-related diseases during ADT. Contrary to adiponectin, high serum aP2 levels were correlated with the late development of MetS. Further studies are needed to investigate the future occurrence of metabolic diseases post-ADT.

[The present status and perspective of pancreas transplantation in Japan].

Two hundred and ten cases of pancreas transplantation from deceased and non-heart beating donors have been performed in 17 institutions in Japan until the end of 2014 since April, 2000. The following donor- and recipient-related factors were analyzed; i.e., age and gender of donor and recipient, cause of death, histories of diabetes and dialysis, waiting period, total cold ischemic time, operative procedure, immunosuppression and survival rates of patient and graft. The patient survivals were 96.5%, 95.8%, and 95.8% while the pancreas graft survivals were 84.7%, 77.0%, and 70.4% at 1 year, 3 years and 5 years posttransplantation, respectively. In spite of donor poor conditions which were mostly marginal (67.1%) in Japan, the outcome of pancreas transplants was considered to be comparable to that of the US and Europe.

Subcuticular sutures versus staples for skin closure after open gastrointestinal surgery: a phase 3, multicentre, open-label, randomised controlled trial.

BACKGROUND: Staples have been widely used for skin closure after open gastrointestinal surgery. The potential advantages of subcuticular sutures compared with staples have not been assessed. We assessed the differences in the frequency of wound complications, including superficial incisional surgical site infection and hypertrophic scar formation, depending on whether subcuticular sutures or staples are used. METHODS: We did a multicentre, open-label, randomised controlled trial at 24 institutions between June 1, 2009, and Feb 28, 2012. Eligible patients aged 20 years or older, with adequate organ function and undergoing elective open upper or lower gastrointestinal surgery, were randomly assigned preoperatively to either staples or subcuticular sutures for skin closure. Randomisation was done via a computer-generated permuted-block sequence, and was stratified by institution, sex, and type of surgery (ie, upper or lower gastrointestinal surgery). Our primary endpoint was the incidence of wound complications within 30 days of surgery. Analysis was done by intention to treat. This study is registered with UMINCTR, UMIN000002480. FINDINGS: 1080 patients were enrolled and randomly assigned in a one to one ratio: 562 to subcuticular sutures and 518 to staples. 1072 were eligible for the primary endpoint and 1058 for the secondary endpoint. Of the 558 patients who received subcuticular sutures, 382 underwent upper gastrointestinal surgery and 176 underwent lower gastrointestinal surgery. Wound complications occurred in 47 of 558 patients (8·4%, 95% CI 6·3-11·0). Of the 514 who received staples, 413 underwent upper gastrointestinal surgery and 101 underwent lower gastrointestinal surgery. Wound complications occurred in 59 of 514 (11·5%, 95% CI 8·9-14·6). Overall, the rate of wound complications did not differ significantly between the subcuticular sutures and staples groups (odds ratio 0·709, 95% CI 0·474-1·062; p=0·12). INTERPRETATION: The efficacy of subcuticular sutures was not validated as an improvement over a standard procedure for skin closure to reduce the incidence of wound complications after open gastrointestinal surgery. FUNDING: Johnson & Johnson.

Molecular expression of adiponectin in human saliva.

Adiponectin (APN) is an adipocyte-specific secretory protein that is highly and specifically expressed in adipose tissue. Serum APN consists of trimers, hexamers, and larger high-molecular-weight (HMW) multimers, and these HMW multimers appear to be of more bioactive forms. Evidence indicates that APN is produced by salivary gland epithelial cells, might be implicated in the regulation of local immune responses. Salivary APN was investigated in 52 healthy individuals. Western blotting under non-reducing conditions revealed that salivary APN consisted predominantly of a super HMW (SHMW) form of APN. In Western blotting, no significant differences were observed in SHMW APN levels in saliva samples with or without occult blood contamination, but non-SHMW APN levels were elevated in the samples with occult blood contamination. In the saliva samples without occult blood contamination, APN levels were significantly elevated in females than in males, in agreement with the results of previous reports for serum samples. In summary, salivary SHMW APN is suggesting a possible promising oral biomarker.

Inhibition of epithelial cell death by Bcl-2 improved chronic colitis in IL-10 KO mice.

IL-10-deficient mice spontaneously develop intestinal inflammation, which has many similarities to Crohn's disease. Several reports suggest that epithelial cell death may increase the severity of colitis; however, decisive evidence is lacking. In the present report, we addressed whether and how epithelial cell death plays a role in the development of chronic colitis. We first examined the morphological characteristics of intestines of IL-10-deficient mice and found two forms of epithelial cell death (typical apoptosis and necrosis-like cell death) in colitis. To elucidate the pathological roles of epithelial cell death, we crossbred IL-10-deficient knockout mice with Bcl-2 transgenic mice, in which the anti-apoptosis protein Bcl-2 was overexpressed in intestinal epithelial cells, but not in immune cells. Epithelial cell-specific Bcl-2 protected IL-10 deficiency-induced colitis and markedly reduced their symptoms. Interestingly, morphological analysis revealed that Bcl-2 suppressed apoptosis and necrosis-like cell death, and better maintained mucosal barrier in IL-10-deficient mice. From the immunological aspect, Bcl-2 did not alter the activation of T-helper cell 1 but inhibited the growth of T-helper cell 17, suggesting that mucosal integrity may control the immune responses. These results provide genetic evidence demonstrating that epithelial cell death is crucial for the development of chronic colitis.