Outcomes of Recipients With Pancreas Transplant Alone Who Develop End-Stage Renal Disease.

Recipients of pancreas transplant alone (PTA) may be at increased risk for developing end-stage renal disease (ESRD). The survival experience of PTA recipients developing ESRD has not been described. Furthermore, the relative survival of these patients as compared to diabetics on chronic dialysis is unknown. We studied all adult PTA recipients from January 1, 1990 to September 1, 2008 using the Scientific Registry of Transplant Recipients. Each PTA recipient developing ESRD was matched to 10 diabetics on chronic dialysis from the United States Renal Data System. Cox proportional hazards models were fitted to determine the relation between ESRD and mortality among PTA recipients, and the relation between PTA and mortality among diabetics on chronic dialysis. There were 1597 PTA recipients in the study, of which 207 developed ESRD. Those with ESRD had a threefold increase in mortality versus those without (adjusted hazard ratio 3.28 [95% confidence interval: 2.27, 4.76]). There was no significant difference in the risk of death among PTA recipients with ESRD versus diabetics on dialysis. PTA recipients developing ESRD are three times more likely to die than PTA recipients without ESRD; however, the risk of death in these patients was similar to diabetics on chronic dialysis without PTA.

Microfluidic platform for assessing pancreatic islet functionality through dielectric spectroscopy.

Human pancreatic islets are seldom assessed for dynamic responses to external stimuli. Thus, the elucidation of human islet functionality would provide insights into the progression of diabetes mellitus, evaluation of preparations for clinical transplantation, as well as for the development of novel therapeutics. The objective of this study was to develop a microfluidic platform for in vitro islet culture, allowing the multi-parametric investigation of islet response to chemical and biochemical stimuli. This was accomplished through the fabrication and implementation of a microfluidic platform that allowed the perifusion of islet culture while integrating real-time monitoring using impedance spectroscopy, through microfabricated, interdigitated electrodes located along the microchamber arrays. Real-time impedance measurements provide important dielectric parameters, such as cell membrane capacitance and cytoplasmic conductivity, representing proliferation, differentiation, viability, and functionality. The perifusion of varying glucose concentrations and monitoring of the resulting impedance of pancreatic islets were performed as proof-of-concept validation of the lab-on-chip platform. This novel technique to elucidate the underlying mechanisms that dictate islet functionality is presented, providing new information regarding islet function that could improve the evaluation of islet preparations for transplantation. In addition, it will lead to a better understanding of fundamental diabetes-related islet dysfunction and the development of therapeutics through evaluation of potential drug effects.

Assessment of human islet grafts in frozen sections of CD-1 athymic nu/nu mouse liver for molecular analysis.

BACKGROUND: Post-transplantation islet graft monitoring is hampered by a lack of efficient methods to locate and analyze islets in situ. We evaluated histologic methods to rapidly locate islets within the liver parenchyma post-transplantation, using several staining strategies, prior to analysis using laser capture microdissection. METHODS: Human islets were isolated (n = 8) from brain dead, multiorgan donor pancreases at the McGill University Health Centre Islet Transplant Laboratory. Mean yield was 247,609 ± 195,272 IE and 3172 ± 1645 IE/g (purity and viability, respectively, 84.5 ± 8.6% and 95 ± 5% average; mean ± SD). Diabetic athymic CD-1 nu/nu mice (streptozotocin intraperitoneal injection, 200 mg/kg) were maintained with sustained release insulin pellets until a suitable islet preparation was available for transplant. Intraportal islet transplantation of 2000 IE/mouse was performed via the ileocecal vein, as previously described. Frozen sections of liver containing human islets were prepared from specimens collected on days 0, 4, and 30 post-transplant. Every twentieth slide from serial sectioned liver was stained using a rapid protocol to determine if islets were present. Sections were fixed and stained for 5 minutes with either an anti-human insulin fluorescein isothiocyanate (FITC)-conjugated primary antibody (Ins-FITC), Newport Green (NG), or diphenylthiocarbazone (dithizone, DZ). RESULTS: Islets were readily localized using each technique, mostly toward the liver periphery. However, DZ had a faint appearance in 10-µm-thick sections and was best utilized to locate sections containing islets during sectioning. CONCLUSION: Ins-FITC, NG, and DZ are all good candidates for a rapid islet staining protocol to evaluate human islet grafts in situ, with DZ being best for sectioning and Ins-FITC and NG being equal in locating islets during processing for laser capture microdissection.

Evaluation of herpes simplex virus infection morbidity and mortality in pancreas and kidney-pancreas transplant recipients.

BACKGROUND: Infections remain a major cause of morbidity and mortality in solid organ transplant recipients. An increased risk of up to 50% of herpes simplex virus (HSV) reactivation in transplant recipients in the first months posttransplantation was well-documented during the pre-cytomegalovirus prophylaxis era. Previous reports suggest that these patients are likely to experience a more aggressive disease course and a higher rate of acyclovir-resistant HSV. No data currently exist regarding the course of HSV infection in pancreas or pancreas-kidney transplant (PKT) recipients. The goal of this study was to evaluate the incidence and severity of HSV infections in pancreas transplant and PKT recipients. STUDY DESIGN: We analyzed a transplant patient database of the Royal Victoria Hospital to identify 137 pancreas transplant or PKT performed between January 1999 and October 2010. A retrospective chart review was subsequently performed to evaluate the incidence and severity of herpetic infections post transplantation. RESULTS: Our findings show that the incidence of HSV infection in our patients was approximately 10% (10/98 cases). The majority of infections (80%) took place within the first 2 years after the transplantation. Most patients (90%) experienced a uniform, mild disease course and responded well to treatment. One patient died of an unrelated cause. Six patients were treated in hospital with a mean stay of 12.3 ± 6.35 days. The initial immunosuppressive regimen remained unchanged for half of the affected patients. None of our patients developed a drug-resistant HSV. CONCLUSION: These findings are intriguing and warrant a larger, multicenter, prospective study. Most important, they suggest that the new incidence of HSV reactivation is now much lower in the "cytomegalovirus prophylaxis era" and that with timely diagnosis and proper treatment most patients recover well from their HSV infections and respond to the current treatment regimens.

Evaluation of varicella zoster virus infection morbidity and mortality in pancreas and kidney-pancreas transplant recipients.

BACKGROUND: Solid organ transplant recipients are at increased risk of infection due to chronic immunosuppression. The incidence of varicella zoster virus (VZV) infection is known to be increased in these patients compared with the immunocompetent population. Previous reports suggested that these patients are likely to experience a morbid disease course. Few data currently exist on the course of VZV infections in pancreas or pancreas plus kidney (PK) transplant recipients. OBJECTIVE: The goal of this study was to evaluate the incidence and severity of VZV infections in pancreas or PK recipients. STUDY DESIGN: We analyzed the transplantation patient database of the Royal Victoria Hospital, identifying 137 pancreas or PK transplantation procedures performed between January 1999 and October 2010, among which we included 98 patients in the study. We subsequently performed a retrospective chart review to evaluate the incidence and severity of VZV infections posttransplantation. RESULTS: Our analysis revealed that 11/98 patients developed VZV infections. The majority of infections (~90.9%) occurred within the first 5 years. Most patients (63.6%) were treated on an outpatient basis, whereas only 4 (36.4%) were hospitalized with a mean hospital stay of 9.5 ± 8.42 days. The initial immunosuppressive regimen remained unchanged for the majority of patients. All patients experienced a mild disease course without intensive care unit admission or death. Only 3 patients (27.3%) developed postherpetic neuralgia. CONCLUSION: These findings suggest that with timely diagnosis and proper treatment, most patients recover well from a VZV infection.

Prolonged lymphopenia following anti-thymocyte globulin induction is associated with decreased long-term graft survival in liver transplant recipients.

BACKGROUND AND AIM: Induction with anti-thymocyte globulin (ATG) during solid organ transplantation is associated with an improved clinical course and leads to prolonged lymphopenia. This study aims to investigate whether prolonged lymphopenia, caused by ATG induction, has an impact on patient and graft survival following liver and kidney transplantation. PATIENTS AND METHODS: This was a single-center, retrospective study. A total of 292 liver and 417 kidney transplants were performed with ATG induction (6 mg/kgr, divided into four doses), and the transplant recipients were followed for at least three months. The average lymphocyte count for the first 30 days after the operation was calculated, and the cut-off value for defining lymphopenia was arbitrarily set to ≤ 500 cells/mm(3). RESULTS: There were 210 liver transplant recipients (71.9%) who achieved prolonged lymphopenia, whereas the remaining 82 recipients (28.1%) did not. The mean survival time of these patient groups was 10.27 and 12.71 years, respectively (p = 0.1217), and the mean graft survival time was 8.98 and 12.25 years, respectively (p = 0.0147). Of the kidney transplant patients, 330 (79.1%) recipients achieved prolonged lymphopenia, whereas the remaining 87 (20.9%) did not. The mean survival time of these patient groups was 13.94 and 14.59 years, respectively, (p = 0.4490), and the mean graft survival time was 11.84 and 11.54 years, respectively (p = 0.7410). CONCLUSION: The efficacy and safety of ATG induction partially depend on decreased total lymphocyte counts. Following ATG induction in liver transplant recipients, a reasonable average lymphocyte count during the first postoperative month would be above 500 cells/mm(3).

Allocation of renal grafts to older recipients does not result in loss of functioning graft-years.

BACKGROUND: Most deceased donor kidney allocation protocols are based on waiting time and do not take into account either recipient's life expectancy. This study investigates whether graft survival is affected by patient life expectancy. METHODS: A total of 640 adult kidney transplants were performed. Recipients were divided in group A (patients ≤ 50 years) and group B (patients > 50 years). The status of graft+recipient combination was characterized as: a) deceased recipient with functional graft, b) alive recipient with functional graft and c) deceased or alive recipient with nonfunctional graft. RESULTS: Mean kidney recipient survival was 15.15 (95% CI: 14.54, 15.77) and 12.40 (95% CI: 11.47, 13.33) years for groups A and B respectively (p < 0.0001). Mean graft survival was 13.62 (95% CI: 12.81, 14.43) and 12.42 (95% CI: 11.59, 13.25) years for groups A and B respectively (p=0.6516). Non-functional grafts were identified in 18.4% (n=57) and 16.4% (n=54) of group A and B respectively. CONCLUSIONS: Allocation of renal grafts to older patients does not result in significant loss of graft-years. Recipients' life expectancy has a small impact on graft survival. We should not deviate from the basic principles of equality, when kidney allocation systems are designed.

Guidelines for the diagnosis of antibody-mediated rejection in pancreas allografts-updated Banff grading schema.

The first Banff proposal for the diagnosis of pancreas rejection (Am J Transplant 2008; 8: 237) dealt primarily with the diagnosis of acute T-cell-mediated rejection (ACMR), while only tentatively addressing issues pertaining to antibody-mediated rejection (AMR). This document presents comprehensive guidelines for the diagnosis of AMR, first proposed at the 10th Banff Conference on Allograft Pathology and refined by a broad-based multidisciplinary panel. Pancreatic AMR is best identified by a combination of serological and immunohistopathological findings consisting of (i) identification of circulating donor-specific antibodies, and histopathological data including (ii) morphological evidence of microvascular tissue injury and (iii) C4d staining in interacinar capillaries. Acute AMR is diagnosed conclusively if these three elements are present, whereas a diagnosis of suspicious for AMR is rendered if only two elements are identified. The identification of only one diagnostic element is not sufficient for the diagnosis of AMR but should prompt heightened clinical vigilance. AMR and ACMR may coexist, and should be recognized and graded independently. This proposal is based on our current knowledge of the pathogenesis of pancreas rejection and currently available tools for diagnosis. A systematized clinicopathological approach to AMR is essential for the development and assessment of much needed therapeutic interventions.

Re-vascularization may not increase graft survival after hepatic artery thrombosis in liver transplant recipients.

BACKGROUND AND AIM: Hepatic artery thrombosis (HAT) occurs in 3% to 11% of all liver transplantations. Some authors have reported good outcomes with early thrombectomy. To investgate the impact of re-vascularization on graft survival. METHODS: A total of 566 primary, cadaveric, single organ, adult liver transplants were performed. Hepatic arterial Doppler was performed routinely and patients with abnormal findings during the first two post-operative weeks were reexplored. Abnormal findings after this time-point were verified by non-invasive angiogram. The 47 patients that were diagnosed with arterial thrombosis, either intra-operatively or by angiogram, were divided into three groups. No further action was taken for group A, thrombectomy alone was performed for group B1, thrombectomy and anastomotic revision was employed for group B2. RESULTS: Arterial thrombosis was diagnosed in 47 (8.3%) patients. Mean patient survival was 42, 62 and 98 months for groups A, B1 and B2 respectively (p: 0.0629). Mean graft survival was 24, 29 and 60 months for groups A, B1 and B2 respectively (p: 0.3386). Re-transplant incidence was 8.7%, 40% and 28.6% for groups A, B1, and B2 respectively (p: 0.035). CONCLUSIONS: Early diagnosis of HAT by surveillance Doppler may lead to improved recipient survival secondary to earlier re-transplantation and not because of successful graft re-vascularization.

Successful salvage of kidney allografts threatened by ureteral stricture using pyelovesical bypass.

Ureteral stricture is the most common urologic complication after renal transplantation. When endourologic management fails, open ureteral reconstruction remains the standard treatment. The complexity of some of these procedures makes it necessary to explore other means of repair. This study evaluated the intermediate-term outcome of subcutaneous pyelovesical bypass graft (SPBG) on renal transplant recipients. We reviewed 8 patients (6 male and 2 female; mean age 52 years) with refractory ureteral strictures postrenal transplantation, who received SPBG as salvage therapy. All patients failed endourologic management and half failed open management of their strictures. After a mean follow-up of 19.4 months, 7 out of 8 renal grafts have good function with mean GFR of 58.5 mL/min/1.73 m(2), without evidence of obstruction or infection. One patient lost his graft due to persistent infection of the SPBG and one patient developed a recurrent urinary tract infection managed with long-term antibiotics. SPBG offers a last resort in the treatment of ureteral stricture after renal transplantation refractory to conventional therapy.

Recovery of graft function early posttransplant determines long-term graft survival in deceased donor renal transplants.

INTRODUCTION: Because kidneys show remarkable resilience and can recover function, we examined the impact on long-term graft survival in deceased donor renal transplants of both immediate graft function (IGF) and the rate of renal function recovery over the first 3 months after transplantation. METHODS: We included all cadaveric renal transplants from 1990 to 2007 (n = 583). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined by serum creatinine falls of <20% or >20% in the first 24 hours posttransplant respectively. Recovery of renal function was expressed as either the best creatinine clearance (CrCl) in the first 3 months post-renal transplantation (BCrCl-3mos) as calculated using the Cockcroft-Gault formula or as a percentage of actual versus expected value (as calculated from the donors' CrCl at procurement). RESULTS: There were 140 (23.6%) subjects who received extended criteria donor (ECD) organs. The overall graft survival at 1 and 5 years was 87.8% and 74%, respectively. The 5-year graft survivals for patients with IGF, SGF, and DGF were 85%, 76%, and 54%, respectively (P < .02). ECD kidneys showed twice the DGF rate (49% vs 23%, P < .001). BCrCl-3mos of <30 mL/min displayed a 5-year graft survival of 34%; 30 to 39 mL/min, 72%; 40 to 49 mL/min, 85%; and >50 mL/min, 82% (P < .001). Similarly, a recovery within 90% of expected CrCl in the first 3 months posttransplant correlated with 5-year graft survival of 81%; a recovery of 70% to 90%, with 65%; and a recovery of <70%, with 51% (P < .001). CONCLUSION: Early graft function in the first 3 months showed a significant impact on long-term graft survival after deceased donor renal transplantation.

Delayed graft function has an equally bad impact on deceased donor renal graft survival in both standard criteria donors and expanded criteria donors.

INTRODUCTION: The use of expanded criteria donors (ECDs) is still limited because of inferior graft survival compared to standard criteria donors (SCDs). We assessed the impact of immediate graft function (IGF) on renal graft survival among recipients of SCD and ECD grafts to determine whether these kidneys performed equally well under "ideal" conditions favoring IGF. METHODS: We included all cadaveric renal transplants performed from 1990 to 2002 (n = 335). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined as a serum creatinine fall by <20% versus >20% in the first 24 hours posttransplant, respectively. Non-death censored actual graft survivals are reported herein. RESULTS: Seventy-two of the 335 subjects (21.5%) received organs from ECDs and displayed IGF in 54.7%, SGF 16.2%, and DGF 29.1%. Among SCDs, the SGF and DGF rates were 15.3% and 23.4%, respectively. In ECD, the SGF and DGF rates were 19.4% and 50% (P < .02). Actual graft survivals at 1 and 5 years was 86.3% and 70.4%, respectively. Patients with IGF had higher actual graft survival at 5 years compared to SGF and DGF (83.5% vs 74.1% vs 45.4%). DGF had an equally bad impact on actual 5-year graft survival in SCDs and ECDs (42.6% vs 50%). CONCLUSION: DGF has a strong detrimental impact on 5-year graft survival. There is a higher rate of DGF in ECD versus SCD kidneys. The detrimental impact on 5-year actual graft survival is equal in SCD and ECD kidneys. Minimizing DGF should be our goal.

The effect of the Vector scaler system on human teeth: a systematic review.

AIM: To review the available literature, considering the effect of instrumentation with the Vector ultrasonic scaler on human teeth in vitro and in vivo compared to conventional ultrasonic instruments and/or hand instrumentation. The assessed effects are calculus removal, time of instrumentation, root surface aspects, cell attachment, patients' perception, bleeding upon probing, pocket depth, clinical attachment loss and microbiological effects. MATERIALS AND METHODS: MEDLINE-PubMed and the Cochrane Central register of controlled trials (CENTRAL) were searched up through January 2008 to identify appropriate studies. RESULTS: Independent screening of the titles and abstracts of 270 MEDLINE-PubMed and 15 Cochrane papers resulted in 15 suitable publications. The studies differed in design and outcome, so this review summarizes the outcomes in a descriptive manner. Comparisons are presented against conventional ultrasonic system and scaling and root planing. CONCLUSION: The Vector ultrasonic scaler provided comparable clinical and microbiological periodontal healing results as scaling and root planing and conventional ultrasonic system in moderately deep pockets. The Vector ultrasonic scaler may be used as a gentle root debridement device for supportive periodontal therapy, as an alternative to other conventional ultrasonic system. The operator should however consider the extra time needed for instrumentation.

A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients.

In a randomized, open-label, multicenter study, de novo renal transplant patients received no steroids (n = 112), steroids to day 7 (n = 115), or standard steroids (n = 109) with cyclosporine microemulsion (CsA-ME), enteric-coated mycophenolate sodium (EC-MPS) and basiliximab. The primary objective, to demonstrate noninferiority of 12-month GFR in the steroid-free or steroid-withdrawal groups versus standard steroids, was not met in the intent-to-treat population. However, investigational groups were not inferior to standard steroids in the observed-case analysis. Median 12-month GFR was not significantly different in the steroid-free or steroid-withdrawal groups (58.6 mL/min/1.73 m(2) and 59.1 mL/min/1.73 m(2)) versus standard steroids (60.8 mL/min/1.73 m(2)). The 12-month incidence of biopsy-proven acute rejection (BPAR), graft loss or death was 36.0% in the steroid-free group (p = 0.007 vs. standard steroids), 29.6% with steroid withdrawal (N.S.) and 19.3% with standard steroids. BPAR was significantly less frequent with standard steroids than either of the other two regimens. Reduced de novo use of antidiabetic and lipid-lowering medication, triglycerides and weight gain were observed in one or both steroid-minimization group versus standard steroids. For standard-risk renal transplant patients receiving CsA-ME, EC-MPS and basiliximab, steroid withdrawal by the end of week 1 achieves similar 1-year renal function to a standard-steroids regimen, and may be more desirable than complete steroid avoidance.

The efficacy of woodsticks on plaque and gingival inflammation: a systematic review.

OBJECTIVE: To review the literature on whether a hand-held triangular woodstick, as compared with no adjunct or other interdental cleaning device in addition to daily toothbrushing, can improve clinical parameters of gingival inflammation. MATERIAL AND METHODS: MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched through February 2008 to identify appropriate studies. Plaque and gingivitis were selected as outcome variables. RESULTS: Independent screening of the titles and abstracts of 181 MEDLINE and 65 CENTRAL papers yielded seven publications with eight clinical experiments that met the eligibility criteria. The improvement in gingival health, as observed in seven studies, represents a significant incremental benefit realized by the use of triangular woodsticks. None of the studies that scored plaque demonstrated any significant advantage to the use of woodsticks, as opposed to alternative methods, in gingivitis patients. CONCLUSION: Evidence from controlled trials, most of which were also randomized, shows that woodsticks do not have an additional effect on visible interdental plaque or gingival index, but do, however, provide an improvement in interdental gingival inflammation by reducing the bleeding tendency.

Fluoride interventions for root caries: a review.

PURPOSE: To review in a systematic approach the effectiveness of specific fluoride treatments on the root caries activity in adults. MATERIALS AND METHODS: An electronic search of the National Library of Medicine, Washington DC (Medline-PubMed), and the specialist trials register of the Cochrane Oral Health Group up to and including April 2005 was performed using specific search terms to identify randomised controlled trials, controlled clinical trials and longitudinal studies of at least 3 months duration, which investigated the effect of specific fluoride treatments with regard to root caries activity and/or incidence in healthy adults. Comparisons were made against the root caries status before the initiation of the additional fluoride application regimen and between groups in controlled studies. The papers were screened independently by two reviewers (MH and SP). RESULTS: Out of 348 titles and abstracts, six papers fulfilled the selection criteria and were processed for data extraction. The highest level of evidence was presented in the two papers using a double-blind controlled randomised clinical trial (Wallace et al, 1993; Baysan et al, 2001). Both these studies indicate that the increased application of fluoride in the form of a high concentration dentifrice or additional mouthwash had a positive effect on the root caries incidence/severity. CONCLUSION: Additional fluoride appears to be a preventive and therapeutic treatment for root caries.

The additional effect of a dentifrice on the instant efficacy of toothbrushing: a crossover study.

BACKGROUND: Inconclusive evidence exists in the literature with regard to the additional (beneficial) mechanical effect of a dentifrice on plaque removal. A previous split-mouth study found that a dentifrice did not contribute to plaque removal. Because of limitations of the split-mouth model, a crossover design was used to evaluate whether a commercially available dentifrice had an additional effect on mechanical plaque removal during manual toothbrushing. METHODS: Thirty-six subjects were given a manual toothbrush and a standard dentifrice. After a 48-hour plaque accumulation, subjects brushed under supervision with or without a dentifrice (total time of 2 minutes) in a 2 x 2 crossover design. RESULTS: Plaque reductions were 50% with and 56% without the use of dentifrice. This 6% difference was statistically significant (P = 0.034). Explorative analysis showed that brushing without a dentifrice was more effective in removing plaque on the approximal surfaces. CONCLUSIONS: The use of a dentifrice did not contribute to mechanical plaque removal during manual toothbrushing. It seemed that the mechanical action provided by the toothbrush was the main factor in the plaque-removing process.

Evaluation of several brushing motion combinations in relation to plaque-removing efficacy with Oral-B CrossAction Power: a professional brushing study.

AIM: The aim of this study was to evaluate the additional effect of a newly developed battery-operated brush Oral-B CrossAction Power with a hybrid brush head design (CAPB). The brush combines an oscillating/rotating part, a PowerHead(R), with a non-moving part with CrissCross bristles. It was compared with a manual control toothbrush Butler GUM 311 (CTB). MATERIAL AND METHODS: Thirty subjects were requested not to brush their teeth 48 h prior to the examination, when plaque removal efficacy was assessed by scoring plaque before and after brushing. Plaque was assessed according to the Silness & Loë Index at six sites per tooth. Subjects were brushed by a dentist using one of the four randomly chosen procedures of brushing in each quadrant. The CAPB was used with three different modes of brushing each in different randomly chosen quadrants, with the manual toothbrush being used in the remaining quadrant as a control. RESULTS: The baseline plaque levels ranged from 1.69 to 1.74 and the end levels ranged from 0.39 to 0.45. In terms of percentage, the results with the four procedures run from 75% to 79%. These differences between the battery brush and manual brush irrespective of the brushing mode used were not statistically significant. CONCLUSION: The results of this Professional Brushing Study show that the CrossAction Power toothbrush was as effective as a regular manual toothbrush.

Autocrine insulin action activates Akt and increases survival of isolated human islets.

AIMS/HYPOTHESIS: The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a critical role in promoting the survival of pancreatic beta cells. Akt becomes activated in isolated human islets following overnight culture despite significant levels of cell death. The aim of the current study was to identify the cause of the observed increase in Akt phosphorylation in isolated islets. We hypothesised that a factor secreted by the islets in culture was acting in an autocrine manner to activate Akt. METHODS: In order to identify the stimulus of the PI3K/Akt pathway in culture, we examined the effects of different culture conditions on Akt phosphorylation and islet survival during the immediate post-isolation period. RESULTS: We demonstrated that islet-conditioned medium induced Akt phosphorylation in freshly isolated human islets, whereas frequent medium replacement decreased Akt phosphorylation. Following overnight culture, islet-conditioned medium contained significantly elevated levels of insulin, indicating that insulin may be responsible for the observed increase in Akt phosphorylation. Indeed, treatment with an anti-insulin antibody or with inhibitors of insulin receptor/IGF receptor 1 kinase activity suppressed Akt phosphorylation, leading to decreased islet survival. In addition, dispersion of islets into single cells also suppressed Akt phosphorylation and induced islet cell death, indicating that islet integrity is also required for maximal Akt phosphorylation. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that insulin acts in an autocrine manner to activate Akt and mediate the survival of isolated human islets. These findings provide new information on how culturing islets prior to transplantation may be beneficial to their survival by allowing for autocrine activation of the pro-survival Akt pathway.

Additional effect of dentifrices on the instant efficacy of toothbrushing.

BACKGROUND: Inconclusive evidence exists in the literature with regard to the additional effect of the use of dentifrice on plaque removal. The present study was undertaken to test whether the use of dentifrice during toothbrushing contributes to the instant cleaning efficacy of the brushing procedure. METHODS: Three groups of patients, 40 subjects each, were randomly assigned to one of three dentifrices that differed with respect to the relative dentin abrasivity (RDA) value. After a 48-hour plaque accumulation, subjects brushed under supervision in a split-mouth order with or without the use of dentifrice (total time=2 minutes). RESULTS: Plaque reductions varied between 51% and 58% for the three dentifrices. The overall analysis showed a mean difference of 3% in plaque reduction in favor of brushing without dentifrice (P=0.017). The type of dentifrice did not influence this observed difference (P=0.506). Also, the order of the brushing procedure (starting the brushing procedure with or without dentifrice) had no interaction with the effect of dentifrice on the brushing (P=0.187). CONCLUSIONS: The use of dentifrice does not contribute to the instant mechanical plaque removal during manual toothbrushing. A higher dentifrice abrasivity does not seem to contribute to increased plaque removal with a manual toothbrush. It appears that the mechanical action provided by the use of a toothbrush is the main factor in the plaque-removing process.