Search

Copyright of IBS, Immuno-analyse & Biologie Specialisee is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: We report two cases of percutaneous portal embolization of pancreatic islets performed after double lung transplantation in cystic fibrosis (CF) patients using the pancreas of the same donor. Case 1: A 19-year-old man with CF had insulin-dependent diabetes, which was poorly controlled despite an external insulin pump (96 IU/d): HbA1c = 9.8% and 1 to 3 hypoglycemic events per day. On October 29, 2007, he received a double lung graft because of chronic respiratory failure. For days after lung transplantation, 149,000 cultured IEQ (Islet EQuivalent) were injected by percutaneous intraportal infusion under local anesthesia. Immunosuppression consisted of steroids, cyclosporine, and azathioprine. Two years later, the forced expiratory volume (FEV) was 83%; C peptide level reached 1.4 μg/L, and the diabetes was satisfactorily controlled with an HbA1c of 7.5% and a decrease in insulin requirements to 30 U/d in the absence of hypoglycemic events. Case 2: On July 10, 2006, a 32-year-old man with CF-related diabetes received a double lung graft because of chronic respiratory failure. Under multiple insulin injections, the HbA1c was 9.6% with numerous hypoglycemic events. On March 11, 2008, he again received a double lung graft because of persistent humoral rejection. Despite severe bleeding during the postoperative course, 234,000 IEQ were injected via the portal vein one week after lung transplantation. Immunosuppression consisted of steroids, tacrolimus, and mycophenolate mofetil. Eighteen months after the combined graft, the FEV was 52%; the plasma C-peptide reached 0.79 μg/L, the HbA1c, 6% and the insulin requirements decreased to 55 U/d in the absence of hypoglycemic events. Conclusion: Combined lung–islet transplantation for patients with CF-related diabetes improved pulmonary and metabolic function. [Copyright &y& Elsevier]

The majority of patients with metastatic breast cancer (MBC) receive non-targeted cytotoxic chemotherapy during their disease trajectory. Its use however near the end of life has not been extensively studied and it's possible that patients with advanced disease may be exposed to unnecessary aggressive treatment. Patients who were diagnosed with MBC in 2010-2015 were identified from the Stockholm-Gotland Breast Cancer Registry. Data regarding tumor characteristics, date of MBC diagnosis and death were collected from the registry. Data on chemotherapy use during the final month of the patient's life, type of chemotherapy regimen used and albumin levels – a surrogate marker for performance status – were collected from individual patient files. Analysis of overall survival of the entire cohort was made in order to estimate contemporary survival of MBC patients. In total, 1571 patients were identified. Out of 1559 patients included in the survival analysis, there were 1357 deaths and 202 patients still alive. Chemotherapy during the last month of life was given to 23.2% of the patients, more commonly to patients ≤60 years old (35.6% versus 18.5%, p < 0.001). A new treatment regimen was initiated in 8.4% of patients. Both albumin (OR 0.95, 95% CI 0.92 – 0.98, p = 0.002) and age at the time of diagnosis (OR 1.04, 95% CI 1.02 – 1.05, p < 0.001) predicted the administration of chemotherapy. The most commonly used chemotherapeutic was capecitabine (24.8%), followed by paclitaxel (14.6%) and vinorelbine (9.8%). After a median follow-up of 73.4 months, median overall survival in the entire cohort was 16.73 months (95% CI 15.22–18.24); patients ≤60 years-old had better median survival compared to older ones (24.83, 95% CI 20.61-29.05 versus 13.86 months, 95% CI 12.72-15.74; p < 0.001). Chemotherapy use near the end of life was common, especially among younger patients. Median overall survival at the population level is considerably worse as compared to results from randomized trials. This may reflect on the differences in patient characteristics and completeness of registry data, which include patients that were never treated for MBC. The authors. Has not received any funding. J. Bergh: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Sanofi-Aventis; Honoraria (self): UpToDate. T. Foukakis: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Novartis; Honoraria (self): UpToDate. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Introduction Endothelial senescence is thought to promote endothelial dysfunction and the subsequent development of cardiovascular diseases. The EMPA-REG trial has shown that sodium-glucose cotransporter 2 (SGLT2) inhibition is associated with a reduced risk of cardiovascular mortality in type 2 diabetic patients, but the protective mechanism remains unclear. SGLT2 mRNA has not been detected in control endothelial cells (ECs). Aim This study examined the possibility that SGLT2 contributes to endothelial senescence and dysfunction and, if so, to characterize the underlying mechanism. Methods Endothelial cells isolated from porcine coronary arteries were used at passage 1. Senescence was assessed using senescence-associated beta-galactosidase activity (SA-beta-gal activity), protein level by Western blot analysis, oxidative stress using dihydroethidium, and NO formation by electronic paramagnetic resonance. Results Exposure of ECs to HG (25 mM) for 96 h increased the level of SA-beta-gal activity and of senescence markers (p21 and p16) and oxidative stress, decreased eNOS expression and NO formation, and increased the expression of VCAM-1 and tissue factor (TF). Both HG and H 2 O 2 induced the appearance of SGLT2 mRNA, increased SGLT2 protein level and SGLT2-mediated glucose entry in ECs. An increased expression level of SGLT2 and VCAM-1, and a down-regulation of eNOS were observed at arterial sites at risk (aortic cross) compared with those at low risk (thoracic aorta) in young rats. Conclusion These findings indicate that premature ECs ageing is characterized by the down-regulation of NO formation and the expression of pro-atherothrombotic factors, and is associated with the redox-sensitive upregulation of SGLT2 expression promoting excessive glucose entry. The fact that an increased SGLT2 expression level is observed in vivo at arterial sites at risk, suggests that inhibition of SGLT2 might be an attractive strategy to protect the cardiovascular system. [ABSTRACT FROM AUTHOR]

Résumé L'insuffisance pancréatique exocrine affecte plus de 80% des nourrissons atteints de mucoviscidose (CF). Le diagnostic d'insuffisance pancréatique exocrine est posé devant des valeurs basses d'élastase fécale. Un apport calorique optimal, une enzymothérapie substitutive optimale adaptée à la teneur en graisse des aliments, sont les clés du maintien d'un bon état nutritionnel. La supplémentation en vitamines liposolubles sera associée à la prise d'EP et sera adaptée aux dosages plasmatiques. La carence en fer et en oligoéléments tel que le zinc est fréquente. L'action des EP reste imparfaite: le pH intraluminal intestinal est trop acide par défaut de libération de bicarbonates par le pancréas. L'utilisation d'inhibiteurs de la pompe à protons pourrait améliorer la fonctionnalité des EP. Les nouvelles thérapeutiques telles que l'ivacaftor chez les patients porteurs d'une mutation G551D permet un gain pondéral en rétablissant en particulier un pH intestinal comparable aux sujets témoins. L'allongement de l'espérance de vie des patients atteints de mucoviscidose s'accompagne de l'apparition de nouveaux aspects de la maladie, en particulier d'un diabète, favorisée par la fibrose kystique pancréatique entrainant une destruction anatomique des îlots pancréatiques. Actuellement, le diabète touche un tiers des patients après 20 ans, et la moitié des patients après 30 ans. Le diabète de la mucoviscidose est un facteur majeur de morbi-mortalité à tous les stades de la maladie, et se caractérise par une phase préclinique d'intolérance au glucose particulièrement longue débutant très tôt dans l'enfance. Sa physiopathologie associe une insuffisance de sécrétion d'insuline, une insulino-résistance secondaire à l'infection chronique, et une diminution de la production du GIP et GLP-1. L'insulino-sécrétion dépendante de l'activité du canal chlore ( Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) au niveau de la cellule à insuline est diminuée avant la survenue des lésions histologiques pancréatiques. Au stade de diabète, l'obtention d'une normoglycémie par un traitement insulinique débuté très précocement permet de ralentir le déclin de la fonction respiratoire et de l'état nutritionnel. Compte tenu de la phase silencieuse du diabète de la mucoviscidose, le dépistage systématique de celui-ci est recommandé par la réalisation d'une HGPO annuelle à partir de l'âge de 10 ans, ou plus tôt dans les formes sévères, d'autant que l'hyperglycémie est un facteur aggravant de la mucoviscidose. Les nouveaux traitements correcteurs du CFTR ont montré leur efficacité en ralentissant le déclin de la fonction pulmonaire, et pourrait contribuer également à ralentir – ou prévenir – la survenue du diabète. The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine ( Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent phase of diabetes, screening it is recommended by the realization of an annual OGTT from 10 years of age, or before in severe forms of CF. New treatments of CF able to target CFTR showed their efficacy in slowing the decline of lung function, and could also contribute to slow or prevent the onset of diabetes. [ABSTRACT FROM AUTHOR]

An abstract of the presentation "Improving Dietetic Curriculum with Latino Community Nutrition Intervention" by Charlotte Kerber and colleagues is presented.

Abstract: Insulin has shown to have cardioprotective effect in diabetic patient after digoxin intoxication. The latter, prompted us to study whether insulin interacts directly with Na+/K+-ATPase. The interaction of insulin with Na+/K+-ATPase was explored using enzyme activity, Biacore and Western blot. We also used, flow cytometry, immunohistochemistry and chronotropy on both neonatal and adult rats cardiomyocytes. Insulin at concentration 1.7e−7 M blunted the effect of digoxin on Na+/K+-ATPase activity. In Western blot, the same insulin concentration decreased enzyme α subunit immunoreactivity. Insulin and digoxin decreased both enzyme α subunit immunoreactivity but insulin/digoxin co-treatment did not. Biacore confirmed a direct interaction between insulin and Na+/K+-ATPase. In neonatal rat cardiomyocytes, insulin plus digoxin induced cell apoptosis but not alone. In adult rat cardiomyocytes, insulin at optimal dose did not induce apoptosis but prevented the one induced by digoxin. In immunocytochemsitry both insulin and digoxin altered Na+/K+-ATPase α subunit immunoreactivity while their association did not. Finally, insulin increased the beating rate of neonatal rat cardiomyocytes (45±7 beats/min); so did digoxin (36±13 beats/min). The effect of insulin was prevented after pre-treated with digoxin. These results demonstrate that insulin interacts directly with Na+/K+-ATPase pump and alters the effect of digoxin. This would have important clinical relevance in cardiac complications related to type I and II diabetes. [Copyright &y& Elsevier]

Abstract: An inverse calibration strategy to determine the constitutive parameters of phenomenological advanced yield criteria in a convenient and economical manner is presented. The studies on the shape of the yield loci for various steel types revealed that their work contours exhibit almost no evolution in the vicinity of the equibiaxial tension after roughly 4% equivalent strain. In other words, the ratio between balanced biaxial and uniaxial stresses of the yield locus reaches a saturation value after undergoing some deformation. Accordingly, the balanced biaxial stresses can be associated with the tensile flow stresses in the rolling direction by means of a constant factor, which can be generalized for different steel families. Based on this, an alternative inverse-analysis strategy using the tensile and plane strain tension tests will be proposed and validated within this work. Cup drawing tests have been applied to assess the accuracy of the optimized yield loci for different strain paths. [Copyright &y& Elsevier]

Introduction – objectifs La prise en charge des infections du pied diabétique est pluri-disciplinaire et prend en compte de multiples éléments : conditions socio-économiques, terrain (insuffisance rénale, artériopathie…), gravité de la plaie, prélèvements microbiologiques, décharge. Le suivi est long notamment en cas d’atteinte ostéo-articulaire. Environ 30 % des patients reviennent dans l’année qui suit un premier épisode pour une nouvelle infection. L’objectif est de développer et de tester la faisabilité d’un outil informatique permettant de synthétiser les données nécessaires à la prise en charge et le suivi de ces patients. Matériels et méthodes Développement par le CHU d’un logiciel, Happy@feet, permettant de gérer les différents aspects (terrain, diagnostic, suivi) de ces patients ; mise en application et évaluation lors de la consultation pluri-disciplinaire dédiée aux infections du pied diabétique. Résultats Happy@feet a été progressivement testé sur 44 patients (âge moyen : 70 ans, odds ratio de 0,5 ; distance moyenne du CHU : 43 km). Toutes les plaies étaient de grade 1 ou 3 (classification University of Texas). Les données sociales sont remplies par le secrétariat. Le temps de remplissage pour les antécédents est d’environ 5 min (remplie que pour une 1re consultation), pour l’observation de la plaie en cours (iconographie, description, traitement, ordonnances) d’environ 10 min Les ordonnances (biologie, radiologie, traitement, soins infirmiers), l’observation et le courrier sont édités en fin de consultation. Conclusion L’outil Happy@feet permet d’optimiser la prise en charge des patients atteints d’infection du pied diabétique en permettant l’établissement d’une base de données pouvant servir à la recherche. Il servira de base au développement d’une activité de télémédecine pour le diagnostic et le suivi de ces patients. [ABSTRACT FROM AUTHOR]

Abstract: The loss of graft function after intraportal islet transplantation is likely multifactorial involving allogeneic rejection, recurrent autoimmunity, graft exhaustion due to a marginally implanted islet mass, immunosuppressant toxicity, and impaired β-cell regeneration. Because early markers of the loss of β-cell mass or function are lacking, monitoring of islet function remains a challenging issue. We have reported herein monitoring of membrane procoagulant microparticles (MPs) as markers of cell stress in the plasma of three recipients with various clinical histories. Early kinetics of C-peptide and MPs followed identical patterns during the first weeks after transplantation; a major increase probably reflected processes related to cell infusion and islet engraftment. Importantly in the case of rejection, MPs and C-peptide showed opposite patterns. A fall in C-peptide was associated with enhanced insulin needs. Our results suggested that a peak in MP levels might indicate rejection with prognotic value. Treatment of the loss of islet function by a new islet infusion or steroid therapy returned MP and C-peptide levels to their baselines with concomitant restoration of islet function. In the patient with suspected acute cellular rejection, MPs also appeared to be sensors of immunosuppressive steroid therapy. [Copyright &y& Elsevier]

The percutaneous transhepatic portal approach is the most commonly used technique for islet transplantation, largely owing to its safety and minimally invasive characteristic. Bleeding complications after islet transplantation are rare and include portal vein thrombosis and subcapsular liver hematoma. We report a massive hemothorax after portal vein catheterization in a patient with brittle type 1 diabetes undergoing hepatic islet embolization. The patient was under long-term aspirin therapy because of vascular complications and received heparin in low doses to prevent the instant blood-mediated inflammatory reaction and reduce the risk of portal vein thrombosis. The present case illustrates the particular risk of bleeding complications in patients with brittle type 1 diabetes, who represent a frail population. This uncommon adverse event highlights the importance of close monitoring in the first days following islet transplantation. [ABSTRACT FROM AUTHOR]

Abstract: During pancreatic islet transplantation, delayed and insufficient revascularization can deprive islets of oxygen and nutrients, resulting in cell death and early graft failure. Deferoxamine (DFO), an iron chelator, increases vascular endothelial growth factor (VEGF) expression in cells. The aim of this work was to study the effect of DFO on β-cell and pancreatic islet viability as well as VEGF expression. β-cell lines from rat insulinoma (Rin m5f) and primary cultures of pancreatic islets from Wistar rats were incubated with DFO (10, 100, and 1000 μmol/L). The viability was evaluated using fluorescein diacetate/propidium iodide for dying pancreatic islets and using cell titers for Rin m5f. Expression of VEGF messenger RNA (mRNA) was quantified using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, VEGF secretion was determined using enzyme-linked immunosorbent assays at 1 to 3 days after treatment. The addition of 10 μmol/L of DFO preserved Rin m5F viability at 24 hours after treatment (10 μmol/L; 101.33% ± 5.66%; n = 7). However, 100 and 1000 μmol/L of DFO induced cell death (68.92% ± 5.83% and 65.89% ± 5.83%, respectively; n = 4). In the same way, viability of pancreatic islets in the presence of DFO was preserved. RT-PCR analysis showed stimulation of VEGF mRNA in the presence of 10 μmol/L of DFO in islets at 3 days after culture. Finally, 10 μmol/L of DFO stimulated secretion of VEGF 7.95 ± 0.84 versus 1.80 ± 1.10 pg/μg total protein with 10 μmol/L of DFO in rat islets at 3 days after culture, n = 3; P < .001). The use of DFO to stimulate VEGF expression and increase islet vascularization may be a realistic approach to improve islet viability during transplantation. [Copyright &y& Elsevier]

Abstract: We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose–insulin infusion on mortality and ECG abnormalities during acute digoxin toxicity in rats. Before and after a hyperinsulinemia–euglycemia clamp, rats in glucose–insulin–digoxin (GID) group (n =10) received an intravenous infusion of 12ml/h or 2,5ml/h digoxin (0.25mg/ml) respectively until death occured. Animals receiving digoxin or saline solution intravenously served as control (n =10). ECG recording was performed in all animals over the entire period. Serum insulin and digoxin concentrations were measured by ELISA method after digoxin administration. When digoxin was administered after the clamp, all animals in GID group were alive, whereas 80% of animals in the digoxin group were dead (p <0.001) after 30min. The administration of Digoxin provoked rapid death of rats in the digoxin group in 15±12min whereas in GID group the survival period was significantly increased to 38±3min (p <0.001). Twenty minutes after digoxin administration, P waves disappeared for 78% of animals in digoxin group while they were present in all rats of GID group (p <0.001). Animal death occurred after a digoxin infusion volume of 7.7±0.6ml and 3.0±2.4ml in GID and digoxin group respectively (p <0.001). Five minutes after digoxin administration, potassium plasmatic level increased significantly in digoxin group as compared to GID group: 7.1±2mmol/l versus 4.4±0.4mmol/l (p <0.001). When digoxin was infused before the clamp, 40% of animals in GID group were alive after 180min and the other 60% died after 137±40min whereas death of rats in the digoxin group occurred within 80±10min (p <0.001). The death of animals was preceded by the P waves disappearing. Thirty minutes after digoxin administration, the potassium plasmatic level increased significantly in the digoxin group as compared to the GID group: 6.9±0.5mmol/l versus 4.9±0.3mmol/l (p <0.001). At the time of death, both volume of digoxin infusion and serum digoxin concentration were increased in GID group as compared to digoxin group: 5.7±1.6ml versus 3.3±0.4ml (p <0.001) and 10.7±8.3mg/l versus 8.5±4.6mg/l. Conclusion: Glucose–insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute digoxin toxicity. These results suggest a cardioprotective effect of insulin in case of acute digoxin toxicity. [Copyright &y& Elsevier]

Case reports were received of a fatal tachycardia caused by a malfunction of an implantable cardioverter defibrillator (ICD), a device that is subject to the tracking regulations of the Food and Drug Administration's Center for Devices and Radiological Health. The case reports led to a decision to notify 5,604 patients of the need for reprogramming of their ICDs to prevent the tachycordia. In the first 60 days, a total of 98.7% of the patients were successfully located and their devices reprogrammed. Multiple logistic regression analysis was conducted to examine an extensive array of factors that might have been related to the time to reprogramming. Patient-specific factors such as age, sex, and ejection fraction did not serve as a barrier to reprogramming in the first week (p = NS). Patients whose regular physician had >5 patients with the ICD subject to the recall were significantly more likely to have their ICDs reprogrammed in the first week (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.85 to 2.43, p<0.001). Patients who changed physicians were significantly less likely to undergo reprogramming in the first week (OR 0.73, 95% CI 0.63 to 0.86, p<0.001). The experience of the recall of this tracked device is highly encouraging because it demonstrates that most tracked device recipients can be successfully located and receive medical intervention. Although tracking devices is a manufacturer's responsibility, the clinical community plays a critical role in its success. This report highlights the importance of understanding that role among physicians. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work was to evaluate the effects of rapamycin on rat macrophage viability and chemotaxis toward allogereic pancreatic islet supernates. Macrophages were isolated from rats by peritoneal lavage at 3 days after intraperitoneal injection of thioglycolate. Macrophage viability was studied after 7 days of culture by Cell Titer assays in the presence of rapamycin at 0.1, 1, and 10 ng/mL (n = 6). After 48 hours of culture, pancreatic rat islet supernates were studied for there chemotactic properties toward freshly isolated macrophages in the presence of rapamycin at 0.1, 1, and 10 ng/mL. Chemotaxis was expressed as a migration index defined as the number of macrophages attracted by the test solution (islet supernate +/− rapamycin)/number of macrophages attracted by the supernate (n = 6). After 3 days of culture, macrophage viability decreased significantly by 22%, 36%, and 32% in the presence of 0.1, 1, and 10 ng/mL rapamycin, respectively (P = .008). Macrophage viability remained stable at about 70% after 7 days of culture. In the presence of islet supernates, macrophage migration increased two-fold compared with those obtained by culture medium. Rapamycin did not influence macrophage migration toward culture medium. However, the drug significantly reduced the migration of macrophages toward islet supernates from 2 ± 0.6 to 0.9 ± 0.4, 0.7 ± 0.3, or 0.8 ± 0.4 in the presence of 0.1, 1, or 10 ng/mL rapamycin, respectively (P = .04). Rapamycin decreased the survival of cultured rat macrophages and their migration toward allogenic islet supernates. These results suggested that, besides its anti-proliferative effect on T cells, rapamycin reduced macrophage attraction to the graft site. [Copyright &y& Elsevier]

Abstract: During transplantation, pancreatic islets release chemokines promoting macrophage attraction, hampering engraftment of islets. The aim of this work was to examine the mechanism of macrophage–pancreatic islets interaction that mediates islet rejection during transplantation. Human macrophages exposed to supernates of human and porcine pancreatic islets for the allogeneic and xenogeneic models, respectively, were evaluated for chemotaxis and expression of chemokine receptors (CCR-5). To modulate migration and identify the signaling pathway of macrophages, we tested pertussis toxin (PTX) to block Gi protein, and staurosporin and wortmannin to inhibit the protein kinase, and phosphoinositol-3 kinase, respectively. The addition of these agents significantly reduced macrophage migration induced by human islet supernates from 3.2 ± 0.5 to 1.5 ± 0.2, 0.9 ± 0.1, and 1 ± 0.1, respectively (P < .001, n = 3). In a xenotransplantation model, the reduction was less decreased, from 4.1 ± 0.4 to 2.7 ± 0.3 (P < .01), to 2.5 ± 0.3 (P < .01), or to 1 ± 0.1 (P < .001). Western blot analysis of chemokine receptor expression showed increased CCR-5 expression with human pancreatic islet supernates. Moreover, decreased islet purity increased CCR-5 expression. Pharmacologic study showed that PTX induced an increase in CCR-5 expression in allogeneic transplantation, whereas only staurosporin induced an increased receptor expression in the xenogeneic model, suggesting that chemokines participate in islet rejection even though the chemokine signaling pathways differ between allo- and xenotransplantation. Understanding the molecular mechanisms of islet rejection may improve graft survival. [Copyright &y& Elsevier]

Introduction: Complications associated with intraportal islet infusion have been reported. In this study, we analyzed the relationship between occurrence of complications and islet preparation characteristics/infusion technique.Methods: We reviewed all intraportal islet infusions from 1992 to 2003.Results: Sixteen islet autotransplantations were performed without infusion-related complications. The tissue volume injected was 13 ± 11 mL with basal and peak portal pressures of 13 ± 6 and 21 ± 6 mm Hg. Seventy-seven intraportal islet allotransplantations were performed in 51 patients. Fifteen islet infusions were done by laparotomy during simultaneous islet/kidney transplantation without complication. Among 62 percutaneous transhepatic injections, nine complications (two portal branch thrombosis and seven intra-abdominal hemorrhages) were recorded. Rise in portal pressure was related to tissue volume injected (P < .05). Basal and peak portal pressures were 14 ± 5 and 18 ± 6 mm Hg in uncomplicated infusions, 14 ± 9 and 18 ± 9 mm Hg in the thrombosis group, and 13 ± 7 and 18 ± 5 mm Hg in the hemorrhage group (P > .05). Complications occurred only after percutaneous islet infusion (P < .03).Conclusions: Procedure-related morbidity of intraportal islet infusion is low. Changes in portal pressure are related to volume of tissue injected but do not seem to be associated with the occurrence of complications. Percutaneous infusion is a minimally invasive procedure, but this advantage must be balanced by the higher rate of complications. [Copyright &y& Elsevier]