Peritoneal Expression of Membrane Complement Regulators Is Decreased in Peritoneal Dialysis Patients with Infected Peritonitis.

In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Time to remission of proteinuria and incidence of relapse in patients with steroid-sensitive minimal change disease and focal segmental glomerulosclerosis: the Japan Nephrotic Syndrome Cohort Study.

BACKGROUND: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. METHODS: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. RESULTS: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). CONCLUSION: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects.

BACKGROUND: Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation. METHODS: DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (ß-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation. RESULTS: Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL. CONCLUSIONS: These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis.

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague-Dawley (SD) rats (n = 30) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

Therapeutic potential for insulin on type 1 diabetes-associated periodontitis: Analysis of experimental periodontitis in streptozotocin-induced diabetic rats.

AIMS/INTRODUCTION: The association between diabetes and periodontal disease is considered to be bidirectional. However, there is still controversy surrounding the relationship between periodontal disease and type 1 diabetes. We investigated whether insulin improves periodontitis without any local treatments for periodontitis under type 1 diabetes conditions using the ligature-induced experimental periodontitis model. MATERIALS AND METHODS: Type 1 diabetic rats were induced by streptozotocin injection. Experimental periodontitis was induced by ligature in normal and diabetic rats. Half of the diabetic rats were treated with insulin. Two weeks after the ligature, periodontitis was evaluated. RESULTS: Insulin treatment significantly improved inflammatory cell infiltration and inflammatory cytokine gene expression, leading to suppression of alveolar bone loss, in the periodontitis of diabetic rats. Insulin also suppressed the periodontitis-increased nitric oxide synthase-positive cells in periodontal tissue of the diabetic rats. Even without induction of periodontitis, diabetic rats showed decreased gingival blood flow and an increased number of nitric oxide synthase-positive cells in the gingiva and alveolar bone loss compared with normal rats, all of which were ameliorated by insulin treatment. We further confirmed that insulin directly suppressed lipopolysaccharide-induced inflammatory cytokine expressions in THP-1 cells. CONCLUSIONS: There were abnormalities of periodontal tissue even without the induction of periodontitis in streptozotocin-induced diabetic rats. Insulin treatment significantly ameliorated periodontitis without local periodontitis treatment in diabetic rats. These data suggest the therapeutic impacts of insulin on periodontitis in type 1 diabetes.

Serum soluble ST2 as a marker of renal scar in pediatric upper urinary tract infection.

BACKGROUND AND OBJECTIVES: Upper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars. RESULTS: Serum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-ß between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively. CONCLUSION: These results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection.

Burden of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Asthmatic Children.

BACKGROUND: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory illness in children. Clinical burden of each infection on the respiratory distress in asthmatic patients remains unclear. The purpose of the study was to clarify the effect of these infections on the severity of asthmatic children in the seasonal outbreaks. METHODS: A total of 1,217 pediatric inpatients with hMPV (n = 114) or RSV (n = 1,103) infection in Yamaguchi prefecture, Japan, between 2011 and 2014 were enrolled. Bronchial asthma was defined as having more than 3 episodes of wheezing illness over 1 year of age. Infection was determined by the positive antigen test for each virus in the nasal specimens. RESULTS: The number of patients peaked at age 12-15 months in hMPV infection and at age 0-3 months in RSV infection. The proportion of hypoxic patients (40-50%) did not differ at any age between hMPV-infected and RSV-infected children. In the analysis of date from > 1 year old patients with hypoxia, hMPV-infection group was older (P = 0.036), and more frequently had history of asthma (P = 0.015) or abnormal chest roentgenogram (P < 0.001) than RSV-infection group. Multivariate analysis indicated that the hypoxia-associated factors were history of asthma in both hMPV (odds ratio [OR]: 15.8; P < 0.001) and RSV infections (OR, 2.2; P = 0.005), higher body temperature in hMPV infection (OR, 2.2; P = 0.009), and younger age in RSV infection (OR, 1.4; P = 0.004). CONCLUSIONS: Outbreaks of hMPV, rather than, RSV infection may have a greater impact on the development of hypoxic respiratory illness in asthmatic children.

Acute focal bacterial nephritis characterized by acute encephalopathy with biphasic seizures and late reduced diffusion.

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney presenting as an inflammatory mass, and some patients show deterioration of clinical condition with neurological symptoms. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome that is characterized by biphasic seizures and impaired consciousness with reduced diffusion in the subcortical white matter on magnetic resonance imaging, typically observed between days 3 and 9 after clinical onset. Although AFBN sometimes causes neurological symptoms, no cases of AFBN with AESD have been reported, and no studies have presented the cytokine profiles of patients with a severe form of acute encephalopathy with AFBN. We report here a very rare case involving a 6-month-old boy who developed AFBN due to Enterococcus faecalis with both the clinical and radiological features of AESD. In our patient, serum interleukin (IL)-6, IL-10, and interferon (IFN)-γ levels markedly increased on admission, and on day 4, only IL-6 levels significantly increased in the cerebrospinal fluid (CSF). These results suggest that high serum cytokines are produced locally in response to AFBN and elevated IL-6 levels in CSF may have neuroprotective roles.

Distinctive inflammatory profile between acute focal bacterial nephritis and acute pyelonephritis in children.

BACKGROUND: Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs. METHODS: Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n=17) or APN (n=21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN. RESULTS: AFBN patients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine ß2-microglobulin levels. AFBN patients showed higher serum levels of IFN-γ, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p<0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-γ and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis. CONCLUSIONS: Circulating 4 out of 7 cytokines in AFBN patients were at higher levels compared with those in APN patients. IFN-γ and IL-6 levels might most effectively distinguish AFBN from APN.

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of periodontitis in diabetes.

AIM: The aetiology of progressive periodontitis in diabetes has not yet been elucidated. We previously demonstrated that nitrosative stress is increased in diabetic rats with periodontitis. Nitrosative stress induces poly(ADP-ribose) polymerase (PARP) activation. Here, we demonstrated the involvement of PARP activation in diabetic periodontitis and detailed the therapeutic effects of PARP inhibitor. MATERIALS AND METHODS: Experimental periodontitis was induced by placing a nylon thread ligature. Half of the normal and diabetic rats received the PARP inhibitor, 1,5-isoquinolinediol, for 2 weeks. Gingival PARP activation was detected by immunostaining for poly(ADP-ribose). Periodontitis was evaluated by gingival inflammatory cell infiltration, inflammatory gene expressions and micro-CT analyses. RESULTS: Although both periodontitis and the presence of diabetes increased PARP activation in the gingiva, diabetic rats with periodontitis had the highest activation of PARP. Diabetic rats with periodontitis also showed significant increases in monocyte/macrophage invasion into the gingiva, inflammatory gene expressions, nitrotyrosine-positive cells in the gingiva and alveolar bone loss, all of which were suppressed by treatment with the PARP inhibitor. CONCLUSIONS: These results indicate the involvement of PARP activation in the pathogenesis and aggravation of periodontal disease in diabetes and suggest the therapeutic potential of PARP inhibition for treating periodontal disease, especially in patients with diabetes.

Genetic Divergence in Domestic Japanese Quail Inferred from Mitochondrial DNA D-Loop and Microsatellite Markers.

To assess the genetic diversity of domestic Japanese quail (Coturnix japonica) populations, and their genetic relationships, we examined mitochondrial DNA (mtDNA) D-loop sequences and microsatellite markers for 19 Japanese quail populations. The populations included nine laboratory lines established in Japan (LWC, Quv, RWN, WE, AWE, AMRP, rb-TKP, NIES-L, and W), six meat-type quail lines reimported from Western countries (JD, JW, Estonia, NIES-Br, NIES-Fr, and NIES-Hn), one commercial population in Japan, and three wild quail populations collected from three Asian areas. The phylogenetic tree of mtDNA D-loop sequences revealed two distinct haplotype groups, Dloop-Group1 and Dloop-Group2. Dloop-Group1 included a dominant haplotype representing most of the quail populations, including wild quail. Dloop-Group2 was composed of minor haplotypes found in several laboratory lines, two meat-type lines, and a few individuals in commercial and wild quail populations. Taking the breeding histories of domestic populations into consideration, these results suggest that domestic quail populations may have derived from two sources, i.e., domestic populations established before and after World War II in Japan. A discriminant analysis of principal components and a Bayesian clustering analysis with microsatellite markers indicated that the domestic populations are clustered into four genetic groups. The two major groups were Microsat-Group1, which contained WE, and four WE-derived laboratory lines (LWC, Quv, RWN, and AWE), and Microsat-Group2 consisting of NIES-L, JD, JW, Estonia, NIES-Br, NIES-Fr, NIES-Hn, W, and commercial and wild populations. The remaining two lines (AMRP and rb-TKP) were each clustered into a separate clade. This hierarchical genetic difference between domestic quail populations is attributed to the genetic background derived from two different genetic sources-the pre-war and post-war populations-which is well supported by their breeding histories.

Successful Treatment of Peritoneal Dialysis-related Peritonitis due to Mycobacterium iranicum.

A 68-year-old man on peritoneal dialysis (PD) was hospitalized with the clinical picture of peritonitis. The patient was diagnosed with peritonitis caused by nontuberculous mycobacteria (NTM) according to positive Ziehl-Neelsen staining and negative Mycobacterium tuberculosis polymerase chain reaction results. Oral levofloxacin and clarithromycin, and later intraperitoneal imipenem were started. According to the anti-NTM susceptibility test results, oral minocycline was administered. The patient was treated for 6 months. He recovered without PD catheter removal; thus, PD was successfully continued. A genetic analysis identified the isolate as Mycobacterium iranicum. This is the first report of PD-related peritonitis caused by M. iranicum.

[Effect of the angiotensin II receptor antagonist (ARB), Irbesartan, on urinary markers in hypertensive patients].

PURPOSE: We examined the effect of the angiotensin II receptor antagonist (ARB), irbesartan (Irb), on urinary markers in hypertensive patients. SUBJECTS AND METHODS: We evaluated 87 patients in a 12-month prospective study: Group 1) 33 patients who were newly administered Irb (100 mg); Group 2) 33 patients who were switched to Irb ; and Group 3) 21 patients who did not undergo change to pre-existing Irb administration. Height, weight, systolic and diastolic blood pressure, clinical parameters, urine protein : creatinine ratio (UPC), and urinary markers (liver-type fatty acid binding protein (L-FABP), N-acetyl-ß-d-glucosaminidase, α1-microglobulin, and ß2-microglobulin) were measured at the baseline and at 12, 24, and 48 weeks. We examined changes in the clinical parameters, UPC, and urinary markers from the baseline. RESULTS: A tendency toward hypotension was observed in all groups (group newly administered Irb, group switched to Irb, and group without changes to Irb), but the difference was not statistically significant. Urinary L-FABP concentration (µg/g x Cr) decreased from 13.2 --> 8.9 and13.2 --> 10.2 at 24 and 48 weeks, respectively, after administration (p < 0.01) in the group newly administered Irb, from 19.5 --> 10.1 at 48 weeks after administration (p < 0.01) in the switched group, and from 9.6 --> 8.3, 8.1, and 6.2 (p < 0.01) in the group without changes to Irb. Changes in the Irb-administered groups were readily apparent. UPC decreased in the Irb-administered groups (p < 0.05), but there were no significant differences in the other urinary markers. Changes in urinary L-FABP and UPC were positively correlated in all cases of the Irb-administered groups (r = 0.25-0.57, p < 0.05), but were not positively correlated in the group without changes to Irb administration. The change in UPC was positively correlated with changes in systolic and diastolic blood pressure in all cases (r = 0.23-0.57, p < 0.05). CONCLUSION: It was concluded that the urinary L-FABP level, blood pressure, and UPC of hypertensive patients should be managed in daily practice using an ARB, including Irb.

Anti-inflammatory role of glucose-dependent insulinotropic polypeptide in periodontitis.

AIMS/INTRODUCTION: The involvement of glucose-dependent insulinotropic polypeptide (GIP) on inflammation was explored in atherosclerosis and adipose tissue. Periodontal disease is a chronic inflammatory disease, and is considered one of the diabetic complications. In the present study, to examine the effect of GIP on periodontitis, we induced experimental periodontitis in glucose-dependent insulinotropic polypeptide receptor-knockout mice (GIPRKO). We also investigated the anti-inflammatory effect of GIP in a culture system. MATERIALS AND METHODS: Experimental periodontitis was induced by ligature wire in GIPRKO and C57BL/C mice. Two weeks after the ligature, immunohistological evaluation and inflammatory messenger ribonucleic acid expression in the gingiva was examined. To elucidate the role of GIP in inflammation, the effects of GIP on lipopolysaccharide-induced gene expressions in THP-1 cells were evaluated. RESULTS: Periodontitis increased inflammatory cell infiltration, macrophage accumulation and tumor necrosis factor-α and nitric oxide synthase gene expressions in the gingiva. Periodontitis in GIPRKO showed a marked increase of inflammatory cells in the gingivomucosal tissue. Mac-1-positive macrophages and the inflammatory gene expressions were significantly increased in periodontitis in GIPRKO compared with C57BL/C mice periodontitis. Immunohistochemical staining confirmed that GIP receptors were expressed in residual and infiltrated Mac-1-positive macrophages. The in vitro study showed that GIP suppressed lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide synthase gene expression in a dose-dependent manner. Furthermore, the inhibitory effect of GIP on lipopolysaccharide-induced inflammatory gene expressions was at least partially through cyclic adenosine monophosphate/protein kinase A pathway. CONCLUSIONS: These results suggest the beneficial effects of GIP on periodontal disease. In diabetic patients, GIP is expected to have a direct anti-inflammatory effect on periodontitis in addition to its glucose-lowering effect.

Recent analysis of status and outcomes of peritoneal dialysis in the Tokai area of Japan: the second report of the Tokai peritoneal dialysis registry.

BACKGROUND: Early withdrawal within 3 years after starting peritoneal dialysis (PD) and PD-related peritonitis have been major obstacles preventing increases in the population of PD patients. To address these problems, we implemented education programs for medical staff. This study analyzed the recent status and outcomes of PD therapy, focusing on findings such as the incidence and prognosis of peritonitis as of 5 years after our last study. METHODS: We investigated background, laboratory data and status of PD therapy, reasons for withdrawal from PD and incidental statements on peritonitis from 2010 to 2012 (R2), and compared findings with those from our last study of 2005-2007 (R1). RESULTS: Early PD therapy withdrawal in R2 clearly improved to 44.7 %, compared with 50.9 % in R1. Peritonitis incidence improved slightly from once per 42.8 months/patient in R1 to once per 47.3 months/patient in R2. Notably, PD-related peritonitis as a cause of mortality improved markedly in R2, but outcomes of PD-related peritonitis did not change significantly between R1 and R2. In contrast, social problems increased as a reason for withdrawal from PD therapy. CONCLUSION: Our efforts at education might have been useful for improving early withdrawal from PD and deaths attributable to PD-related peritonitis. However, since improvements to incidence of PD-related peritonitis were limited by education, further improvement in PD-related peritonitis incidence requires development of new sterilized connecting systems during PD-bag exchanges to decrease PD-related peritonitis opportunities. Construction of medical support systems to address social problems is required to maintain long-term PD therapy.