Prevalence of chronic periodontitis in patients undergoing peritoneal dialysis and its correlation with peritoneal dialysis-related complications.

OBJECTIVE: The microinflammatory state can influence the occurrence of dialysis-related complications in dialysis patients. Chronic periodontitis (CP), in which plaque biofilm is considered to be the initiating factor, is a chronic infectious disease in the oral cavity. It is still uncertain whether CP affects the microinflammatory state in peritoneal dialysis (PD) and the occurrence of dialysis-related complications. The purpose of this study was to investigate the correlation between the periodontal index and clinical parameters in peritoneal dialysis patients with CP and dialysis-related complications, including peritoneal dialysis-associated peritonitis (PDAP) and cardiovascular and cerebrovascular events (CCEs). METHODS: This was a retrospective cohort study, and 76 patients undergoing PD were enrolled. Clinical parameters, the occurrence of PD-related complications and periodontitis-related indicators, including the gingival index (GI), plaque index (PLI), probing depth (PPD) and clinical attachment loss (CAL), were collected. Correlation analysis was used to explore the correlation between periodontal or clinical parameters and the occurrence of PD-related complications. RESULTS: All the patients had different degrees of periodontitis (mild 9.2%, moderate 72.4%, severe 18.4%); PPD was inversely related to serum albumin (r = - 0.235, p = 0.041); CAL has a positive correlation with serum C-reactive protein (rs = 0.242, p = 0.035); PLI was positively correlated with serum calcium (r = 0.314, p = 0.006). ANOVA, multivariate logistic regression analysis and Kaplan-Meier Survival curve suggested that CAL was a risk factor for the occurrence of PDAP. There was no correlation between periodontal parameters and CCEs or poor prognosis. CONCLUSION: CP is universally present in PD patients, and the presentation of periodontitis influences the systemic inflammatory state in PD patients. CP is a risk factor for PDAP.

Dynamic equilibrium of B7-1 dimers and monomers differentially affects immunological synapse formation and T cell activation in response to TCR/CD28 stimulation.

Under steady-state conditions, B7-1 is present as a mixed population of noncovalent dimers and monomers on the cell surface. In this study, we examined the physiological significance of this unique dimer-monomer equilibrium state of B7-1. We demonstrate that altering B7-1 to create a uniformly covalent dimeric state results in enhanced CD28-mediated formation of T cell-APC conjugates. The enhanced T cell-APC conjugate formation correlates with persistent concentration of signaling molecules PKC- and lck at the immunological synapse. In contrast, T cell acquisition of B7-1 from APCs, an event that occurs as a consequence of CD28 engagement with B7-1/B7-2 and is thought to play a role in the dissociation of T cell-APC conjugates, is highly reduced when B7-1 is present in the covalently dimeric state. The ability of covalently dimeric and wild type B7-1 to costimulate Ag-specific T cell proliferation was also assessed. In contrast to the enhanced ability of dimeric B7-1 to support conjugate formation and early parameters of T cell signaling, sensitivity to competitive inhibition by soluble CTLA-4-Ig indicated that the covalent dimeric form of B7-1 is less efficient in costimulating T cell proliferation. These findings suggest a novel model in which optimal T cell costimulatory function of B7-1 requires high-avidity CD28 engagement by dimeric B7-1, followed by dissociation of these noncovalent B7-1 dimers, facilitating downregulation of CD28 and internalization of B7-1. These events regulate signaling through TCR/CD28 to maximize T cell activation to proliferation.

The mitochondrial protein hTID-1 partners with the caspase-cleaved adenomatous polyposis cell tumor suppressor to facilitate apoptosis.

BACKGROUND & AIMS: The adenomatous polyposis cell (APC) tumor suppressor is a multifunctional protein involved in cell migration, proliferation, differentiation, and apoptosis. Cleavage of APC and the subsequent release of an amino-terminal segment are necessary for a transcription-independent mechanism of APC-mediated apoptosis. The aim of the current study is to elucidate the mechanism by which the amino-terminus of APC contributes to the enhancement of apoptosis. METHODS: Previous yeast 2-hybrid screens, using the armadillo repeat domain of APC as bait, identified hTID-1 as a potential binding partner. Coimmunoprecipitations, coimmunofluorescence, and binding assays confirm a direct interaction between caspase-cleaved APC and hTID-1 in vivo at the mitochondria. Overexpression and small interfering RNA (siRNA) knockdown studies were designed to determine the significance of this interaction. RESULTS: These experiments have identified hTID-1 as a directly interacting protein partner of caspase-cleaved APC. hTID-1 is an apoptosis modulator: 2 of its known mitochondrial protein isoforms, 43-kilodaltons and 40-kilodaltons, have opposing effects in apoptosis. We demonstrate that the amino-terminal segment of APC interacts with both hTID-1 isoforms directly, although there is a stronger association with the apoptotic suppressor 40-kilodalton isoform in vitro. This interaction localizes to amino acids 202-512 of APC, a region including 2 of the 7 armadillo repeats. Overexpression of the 40-kilodalton hTID-1 isoform partially rescues cells from apoptosis mediated by APC 1-777, whereas siRNA knockdown of this hTID-1 isoform enhances apoptosis. CONCLUSIONS: These data suggest that the amino-terminal segment of APC promotes cell sensitivity to apoptosis modulated through its binding to 40- and 43-kilodalton hTID-1 isoforms.

Assessment of Alveolar Bone and Periodontal Status in Peritoneal Dialysis Patients.

Chronic kidney disease (CKD) affects 8-13% of the global population and has become one of the largest burdens on healthcare systems around the world. Peritoneal dialysis is one of the ultimate treatments for patients with severe CKD. Recently, increasing severe periodontal problems have been found in CKD patients. Periodontitis has been identified as a new variable risk factor for CKD. The aim of this study was to investigate the periodontal status and severity of alveolar bone loss in CKD patients with peritoneal dialysis (PD). One hundred and six patients undergoing PD (PD group) and 97 systemically healthy periodontitis patients (control group) were enrolled. The differences in the dimensions of the alveolar bone between two groups were compared, and the distribution of alveolar bone defects was analyzed by cone-beam computed tomography (CBCT). Gingival index (GI), plaque index (PLI), periodontal probing depth (PPD), and attachment loss (AL) were recorded. The levels of inflammatory factors in gingival crevicular fluid were assessed by ELISA. Compared to control group, there was a higher degree of alveolar bone loss in maxillary premolars, maxillary 2nd molar and mandibular 1st molar in patients with PD (p < 0.05). A comparison of bone loss in different sites revealed that the area with the highest degree of bone loss were on the mesial-buccal, mid-buccal, distal-buccal, and mesial-lingual site in PD patients. The expression levels of inflammatory factors were higher in PD group (p < 0.01). In conclusion, PD patients presented more severe periodontal and inflammatory status than systemically healthy periodontitis patients. The loss of the alveolar bone differed between the two groups. Different sites and teeth exhibited a diverse degree of bone loss. This study highlights that clinicians should pay close attention to periodontal status of peritoneal dialysis patients and provides a new thinking to improve healthcare for CKD.