204 results on '"Poggioli R"'
Search Results
52. Semiclassical approximation to time-dependent Hartree--Fock theory
- Author
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Poggioli, R
- Published
- 1976
53. Vertex and propagator renormalizations in nuclear calculations
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Poggioli, R
- Published
- 1975
54. Impact of GAD65 and IA2 autoantibodies on islet allograft survival.
- Author
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Lemos JRN, Poggioli R, Ambut J, Bozkurt NC, Alvarez AM, Padilla N, Vendrame F, Ricordi C, Baidal DA, and Alejandro R
- Abstract
Introduction: Islet transplantation (ITx) shows promise in treating T1D, but the role of islet autoantibodies on graft survival has not been clearly elucidated. We aimed to analyze the effect of GAD65 and IA2 autoantibody status on graft survival and attainment of insulin independence in subjects with T1D who underwent ITx., Method: We conducted a retrospective cohort study on 47 ITx recipients from 2000 to 2018. Islet infusion was performed via intrahepatic portal (n=44) or onto the omentum via laparoscopic approach (n=3). Immunosuppression involved anti-IL2 receptor antibody, anti-TNF, and dual combinations of sirolimus, tacrolimus, or mycophenolate mofetil (Edmonton-like) in 38 subjects (80.9%). T-cell depletion induction with Edmonton-like maintenance was used in 9 subjects (19%). GAD65 and IA2 autoantibodies were assessed pre-transplant and post-transplant (monthly) until graft failure, and categorized as persistently negative, persistently positive, or seroconverters. Graft survival was analyzed using U-Mann-Whitney test, and Quade's nonparametric ANCOVA adjusted for confounders. Kaplan-Meier and Log-Rank tests were employed to analyze attainment of insulin independence. P value <0.05 indicated statistical significance., Results: ITx recipients with persistent autoantibody negativity (n = 21) showed longer graft function (98 [61 - 182] months) than those with persistent autoantibody positivity (n = 18; 38 [13 - 163] months), even after adjusting for immunosuppressive induction protocol (P = 0.027). Seroconverters (n=8) had a median graft survival time of 73 (7.7 - 167) months, which did not significantly differ from the other 2 groups. Subjects with persistently single antibody positivity to GAD65 (n = 8) had shorter graft survival compared to negative islet autoantibody (GAD65/IA2) subjects (n = 21; P = 0.016). Time of graft survival did not differ in subjects with single antibody positivity to IA2. The proportion of insulin independence attainment was similar irrespective of autoantibody status., Conclusion: The persistence of islet autoantibodies, as markers of islet autoimmunity, may represent an underappreciated contributing factor to the failure of transplanted β cells. Whether induction with T-cell depletion may lead to improved graft survival, independent of islet autoantibody status, could not be evaluated in our cohort. Larger prospective studies are needed to further address the role of islet autoantibody status on islet graft survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lemos, Poggioli, Ambut, Bozkurt, Alvarez, Padilla, Vendrame, Ricordi, Baidal and Alejandro.)
- Published
- 2023
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55. HLA-B Matching Prolongs Allograft Survival in Islet Cell Transplantation.
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Lemos JRN, Baidal DA, Poggioli R, Fuenmayor V, Chavez C, Alvarez A, Ricordi C, and Alejandro R
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- Female, Humans, Male, Allografts, Graft Rejection, Graft Survival, Histocompatibility Testing methods, HLA Antigens, HLA-B Antigens genetics, HLA-B Antigens analysis, Prospective Studies, Retrospective Studies, Adult, Middle Aged, Hypoglycemia, Islets of Langerhans Transplantation
- Abstract
Islet cell transplantation (ITx) is an effective therapeutic approach for selected patients with type 1 diabetes with hypoglycemia unawareness and severe hypoglycemia events. In organ transplantation, human leukocyte antigen (HLA) mismatching between donor and recipient negatively impacts transplant outcomes. We aimed to determine whether HLA matching has an impact on islet allograft survival. Forty-eight patients were followed up after islet transplantation at our institution from 2000 to 2020 in a retrospective cohort. Patients underwent intrahepatic ITx or laparoscopic omental approach. Immunosuppression was dependent upon the protocol. We analyzed HLA data restricted to A, B, and DR loci on allograft survival using survival and subsequent multivariable analyses. Patients were aged 42.8 ± 8.4 years, and 64.3% were female. Diabetes duration was 28.6 ± 11.6 years. Patients matching all three HLA loci presented longer graft survival ( P = 0.030). Patients with ≥1 HLA-B matching had longer graft survival compared with zero matching ( P = 0.025). The number of HLA-B matching was positively associated with time of graft survival (Spearman's rho = 0.590; P = 0.034). Analyses adjusted for confounders showed that ≥1 matching for HLA-B decreased the risk of allograft failure ( P = 0.009). Our data suggest that HLA-B matching between recipients and donors improved islet allograft survival. Matching all three HLA loci (A, B, and DR) was also associated with prolonged islet allograft survival. Prospective studies and a larger sample size are warranted to validate our findings.
- Published
- 2023
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56. Prolonged Islet Allograft Function is Associated With Female Sex in Patients After Islet Transplantation.
- Author
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Lemos JRN, Baidal DA, Poggioli R, Fuenmayor V, Chavez C, Alvarez A, Linetsky E, Mauvais-Jarvis F, Ricordi C, and Alejandro R
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- Adult, Female, Glycated Hemoglobin analysis, Humans, Male, Middle Aged, Retrospective Studies, Sex Characteristics, Transplantation, Homologous, Diabetes Mellitus, Type 1 surgery, Graft Survival, Islets of Langerhans Transplantation, Tissue Donors
- Abstract
Background: Islet transplantation (ITx) has proved to be effective in preventing severe hypoglycemia and improving metabolic control in selected subjects with type 1 diabetes. Long-term graft function remains a challenge. Estrogens have been shown to protect β cells from metabolic stresses and improve revascularization of transplanted human islets in the mouse. We aimed to evaluate the influence of sex in allograft survival of ITx recipients., Methods: We analyzed a retrospective cohort of ITx recipients (n = 56) followed-up for up to 20 years. Allograft failure was defined as a stimulated C-peptide <0.3 ng/mL during a mixed-meal tolerance test. Subjects were divided into recipients of at least 1 female donor (group 1) and recipients of male donors only (group 2)., Results: Group 1 subjects (n = 25) were aged 41.5 ± 8.4 years and group 2 subjects (n = 22) 45.9 ± 7.3 years (P = 0.062). Female recipient frequency was 44.8% (n = 13) in group 1 and 55.2% (n = 16) in group 2 (P = 0.145). Group 2 developed graft failure earlier than group 1 (680 [286-1624] vs 1906 [756-3256] days, P = 0.038). We performed additional analyses on female recipients only from each group (group 1, n = 16; group 2, n = 20). Female recipients in group 1 exhibited prolonged allograft function compared with group 2, after adjustment for confounders (odds ratio, 28.6; 95% CI, 1.3-619.1; P < 0.05)., Conclusion: Recipients of islets from at least 1 female donor exhibited prolonged graft survival compared with recipients of islets from exclusively male donors. In addition, female recipients exhibited prolonged survival compared with male recipients following ITx of at least 1 female donor., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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57. Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.
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Lanzoni G, Linetsky E, Correa D, Messinger Cayetano S, Alvarez RA, Kouroupis D, Alvarez Gil A, Poggioli R, Ruiz P, Marttos AC, Hirani K, Bell CA, Kusack H, Rafkin L, Baidal D, Pastewski A, Gawri K, Leñero C, Mantero AMA, Metalonis SW, Wang X, Roque L, Masters B, Kenyon NS, Ginzburg E, Xu X, Tan J, Caplan AI, Glassberg MK, Alejandro R, and Ricordi C
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- Cytokines blood, Double-Blind Method, Female, Humans, Male, Mesenchymal Stem Cell Transplantation adverse effects, Mesenchymal Stem Cells, Middle Aged, SARS-CoV-2 drug effects, Severity of Illness Index, Treatment Outcome, Umbilical Cord cytology, Anti-Inflammatory Agents therapeutic use, COVID-19 therapy, Mesenchymal Stem Cell Transplantation methods
- Abstract
Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 10
6 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P = .015), SAE-free survival (P = .008), and time to recovery (P = .03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS., (© 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)- Published
- 2021
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58. Epicardial adipose tissue has a unique transcriptome modified in severe coronary artery disease.
- Author
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McAninch EA, Fonseca TL, Poggioli R, Panos AL, Salerno TA, Deng Y, Li Y, Bianco AC, and Iacobellis G
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- Coronary Artery Disease genetics, Female, Gene Expression Regulation, Humans, Male, Pilot Projects, Adipose Tissue metabolism, Coronary Artery Disease metabolism, Pericardium metabolism, Transcriptome
- Abstract
Objective: To explore the transcriptome of epicardial adipose tissue (EAT) as compared to subcutaneous adipose tissue (SAT) and its modifications in a small number of patients with coronary artery disease (CAD) versus valvulopathy., Methods: SAT and EAT samples were obtained during elective cardiothoracic surgeries. The transcriptome of EAT was evaluated, as compared to SAT, using an unbiased, whole-genome approach in subjects with CAD (n = 6) and without CAD (n = 5), where the patients without CAD had cardiac valvulopathy., Results: Relative to SAT, EAT is a highly inflammatory tissue enriched with genes involved in endothelial function, coagulation, immune signaling, potassium transport, and apoptosis. EAT is lacking in expression of genes involved in protein metabolism, tranforming growth factor-beta (TGF-beta) signaling, and oxidative stress. Although underpowered, in subjects with severe CAD, there is an expression trend suggesting widespread downregulation of EAT encompassing a diverse group of gene sets related to intracellular trafficking, proliferation/transcription regulation, protein catabolism, innate immunity/lectin pathway, and ER stress., Conclusions: The EAT transcriptome is unique when compared to SAT. In the setting of CAD versus valvulopathy, there is possible alteration of the EAT transcriptome with gene suppression. This pilot study explores the transcriptome of EAT in CAD and valvulopathy, providing new insight into its physiologic and pathophysiologic roles., Competing Interests: Statement The authors declare no conflicts of interest., (© 2015 The Obesity Society.)
- Published
- 2015
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59. Dexamethasone reduces energy expenditure and increases susceptibility to diet-induced obesity in mice.
- Author
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Poggioli R, Ueta CB, Drigo RA, Castillo M, Fonseca TL, and Bianco AC
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- Adipose Tissue metabolism, Adipose Tissue, Brown metabolism, Adiposity drug effects, Animals, Basal Metabolism drug effects, Dexamethasone pharmacology, Dietary Fats administration & dosage, Disease Models, Animal, Fatty Liver etiology, Glucocorticoids pharmacology, Ion Channels genetics, Ion Channels metabolism, Liver drug effects, Male, Mice, Mice, Inbred C57BL, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Obesity genetics, Obesity metabolism, Oxygen Consumption drug effects, RNA, Messenger metabolism, Respiration drug effects, Uncoupling Protein 1, Adipose Tissue drug effects, Dexamethasone adverse effects, Diet, High-Fat adverse effects, Energy Metabolism drug effects, Glucocorticoids adverse effects, Obesity etiology, Thermogenesis drug effects
- Abstract
Objective: To investigate how long-term treatment with dexamethasone affects energy expenditure and adiposity in mice and whether this is influenced by feeding on a high-fat diet (HFD)., Design and Methods: Mice were placed on a HFD for 2 weeks and started on dexamethasone at 5 mg/kg every other day during the next 7 weeks., Results: Treatment with dexamethasone increased body fat, an effect that was more pronounced in the animals kept on HFD; dexamethasone treatment also worsened liver steatosis caused by the HFD. At the same time, treatment with dexamethasone lowered the respiratory quotient in chow-fed animals and slowed nightly metabolic rate in the animals kept on HFD. In addition, the acute VO2 acceleration in response to β3 adrenergic-stimulation was significantly limited in the dexamethasone-treated animals, as a result of marked decrease in UCP-1 mRNA observed in the brown adipose tissue of these animals., Conclusions: Long-term treatment with dexamethasone in a mouse model of diet-induced obesity decreases brown adipose tissue thermogenesis and exaggerates adiposity and liver steatosis. © 2013 American Institute of Chemical Engineers AIChE J, 2013., (Copyright © 2013 The Obesity Society.)
- Published
- 2013
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60. Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation.
- Author
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Cure P, Pileggi A, Froud T, Messinger S, Faradji RN, Baidal DA, Cardani R, Curry A, Poggioli R, Pugliese A, Betancourt A, Esquenazi V, Ciancio G, Selvaggi G, Burke GW 3rd, Ricordi C, and Alejandro R
- Subjects
- Adult, Blood Glucose metabolism, Female, Humans, Immunosuppressive Agents therapeutic use, Islets of Langerhans Transplantation immunology, Islets of Langerhans Transplantation psychology, Kidney Function Tests, Kidney Transplantation immunology, Kidney Transplantation psychology, Male, Middle Aged, Postoperative Complications classification, Postoperative Complications epidemiology, Diabetes Mellitus, Type 1 surgery, Diabetic Nephropathies surgery, Islets of Langerhans Transplantation physiology, Kidney Transplantation physiology, Quality of Life
- Abstract
Background: The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) have been recognized., Methods: Herein, we present the clinical outcome of a single-center pilot trial of islet after kidney (IAK) transplantation in seven patients with T1DM. The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function. Primary endpoint was achievement of insulin independence after transplantation. Clinical outcome, metabolic control, severe hypoglycemia, kidney function, Quality of Life (QOL) psychometric measures, and adverse events were monitored., Results: Seven patients showed graft function with improved metabolic control (A1c, fasting glycemia, and metabolic tests) after IAK (14,779+/-3,800 IEQ/kg). One-year insulin independence was 30% with persistent graft function in 86% (C-peptide-positive). A1c reduction was 1.95+/-0.31% from baseline (P<0.0001). No episodes of severe hypoglycemia were observed, even after resuming insulin. The direct consequence of these benefits was a significant improvement in diabetes QOL. Adverse events included procedure-related pleural effusion (n=2), cholecystitis (n=1), and additional immunosuppression-related, all resolved without sequelae. Kidney function (by estimated glomerular filtration rate) remained stable during follow-up in six of seven patients., Conclusions: Islet transplantation represents a feasible therapeutic option for patients with T1DM bearing a stable kidney allograft. Insulin independence at 1 year is lower than what reported in islet transplant alone. Nevertheless, clear benefits in terms of optimal metabolic control and absence of severe hypoglycemia are invariably present.
- Published
- 2008
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61. Nutritional status and behavior in subjects with type 1 diabetes, before and after islet transplantation.
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Poggioli R, Enfield G, Messinger S, Faradji RN, Tharavanij T, Pisani L, Cure P, Ponte G, Baidal DA, Froud T, Ricordi C, and Alejandro R
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- Adult, Body Mass Index, Bone Marrow Transplantation physiology, Bone Marrow Transplantation psychology, Diabetes Mellitus, Type 1 psychology, Diabetes Mellitus, Type 1 rehabilitation, Diet, Diabetic, Energy Intake, Exenatide, Follow-Up Studies, Humans, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Interviews as Topic, Kidney Transplantation physiology, Kidney Transplantation psychology, Peptides therapeutic use, Perception, Surveys and Questionnaires, Venoms therapeutic use, Diabetes Mellitus, Type 1 surgery, Islets of Langerhans Transplantation physiology, Islets of Langerhans Transplantation psychology, Nutritional Status
- Abstract
Background: To investigate whether changes of nutritional status and behavior are associated with islet transplantation (ITx) and to assess their possible mechanisms., Methods: In this observational study, 52 subjects with type 1 diabetes, 30 of whom received ITx, underwent nutritional assessments. The study consisted of questionnaires complemented by a dietary intake recording, anthropometric measurements, and body composition analysis. Laboratory tests were also reviewed as part of the follow up., Results: After ITx, significant reductions in body weight (3.7 kg; P<0.0001), body mass index (1.39 kg/m2; P<0.0001), waist circumference (3.96 cm; P=0.006), and fat weight (3.28 kg; P<0.01) were observed. The average consumption of carbohydrate and protein were also lower than pretransplant, together with some micronutrients (vitamins B12 and B6, zinc, and phosphorus). Insulin administration and changes in A1C were not associated with a significant change in anthropometric measurements. Subjects on exenatide after ITx showed significantly lower weight and body mass index than those not taking exenatide., Conclusions: ITx is associated with modifications in nutritional behavior and status. Drugs and health conditions are likely to be at least in part responsible for these changes, but a voluntary modification of eating habits by the patients also plays a role. Strict monitoring of nutritional parameters, counseling by experts in nutrition, and multivitamin/mineral supplement after ITx could be of benefit to the patients.
- Published
- 2008
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62. Dapsone-induced artifactual a1c reduction in islet transplant recipients.
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Froud T, Faradji RN, Gorn L, Monroy K, Paz C, Baidal DA, Ponte G, Cure P, Poggioli R, Pileggi A, Ricordi C, and Alejandro R
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- Diabetes Mellitus, Type 1 surgery, False Positive Reactions, Humans, Reproducibility of Results, Treatment Outcome, Dapsone adverse effects, Glycated Hemoglobin metabolism, Immunosuppressive Agents adverse effects, Islets of Langerhans Transplantation methods
- Published
- 2007
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63. Resolution of severe atopic dermatitis after tacrolimus withdrawal.
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Ponte GM, Baidal DA, Romanelli P, Faradji RN, Poggioli R, Cure P, Froud T, Selvaggi G, Pileggi A, Ricordi C, and Alejandro R
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- Adult, Alopecia Areata pathology, Alopecia Areata prevention & control, Dermatitis, Atopic pathology, Diabetes Mellitus, Type 1 complications, Female, Humans, Immunosuppressive Agents therapeutic use, Tacrolimus therapeutic use, Transplantation, Homologous, Treatment Outcome, Dermatitis, Atopic etiology, Diabetes Mellitus, Type 1 surgery, Immunosuppressive Agents adverse effects, Islets of Langerhans Transplantation, Tacrolimus adverse effects
- Abstract
Tacrolimus is an immunosuppressive agent used in solid organ and islet transplantation. Its topical form has shown benefit in the treatment of inflammatory skin conditions. Although tacrolimus has a wide spectrum of side effects, dermatological complications related to systemic tacrolimus therapy are limited in the literature. Atopic dermatitis (AD) is a chronic pruritic cutaneous condition that usually begins in infancy and is characterized by an increased Th2 response. We report the case of a patient with type 1 diabetes mellitus (T1DM) and history of AD latent for 10 years who developed severe dermatitis and alopecia 5 months after undergoing allogeneic islet transplantation and initiating a steroid-free immunosuppressive regimen with sirolimus and tacrolimus maintenance. After exclusion of other possible causes for the progression and exacerbation of the clinical presentation of AD, discontinuation of tacrolimus and introduction of mycophenolate mofetil resulted in full remission of the symptoms. The beneficial effects of tacrolimus withdrawal suggest a cause-effect relationship between this adverse event and the utilization of the drug. Islet graft function remained stable after modification of the therapeutic regimen (stable glycemic control and unchanged C-peptide).
- Published
- 2007
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64. The use of the BD oxygen biosensor system to assess isolated human islets of langerhans: oxygen consumption as a potential measure of islet potency.
- Author
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Fraker C, Timmins MR, Guarino RD, Haaland PD, Ichii H, Molano D, Pileggi A, Poggioli R, Presnell SC, Inverardi L, Zehtab M, and Ricordi C
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- Animals, Graft Survival physiology, Humans, In Vitro Techniques, Islets of Langerhans physiology, Islets of Langerhans Transplantation methods, Logistic Models, Male, Mice, Mice, Nude, Oxygen Consumption physiology, Transplantation, Heterologous, Biosensing Techniques, Islets of Langerhans metabolism, Oxygen metabolism
- Abstract
The measurement of cellular oxygen consumption rate (OCR) is a potential tool for the assessment of metabolic potency of isolated islets of Langerhans prior to clinical transplantation. We used a commercially available 96-well plate fluoroprobe, the BD Oxygen Biosensor System (OBS), to estimate OCR in 27 human islet preparations, and compared these results to those of concurrent mouse transplantations. OCR was estimated both from the dO2 at steady state and from the transient rate of change of dO2 during the initial culture period immediately after seeding ("dO2 slope"). To demonstrate the validity of the OBS-derived values, it was shown that they scaled linearly with islet equivalent number/DNA concentration and with each other. These measurements were obtained for each preparation of islets incubated in media supplemented with either low (2.2 mM) or high (22 mM) glucose. Concurrently, one to three athymic nude mice were transplanted with 2,000 IEQs under the kidney capsule. The OCR Index, defined as the ratio of the DNA-normalized "dO2 slope" in high glucose to that in low glucose, proved highly predictive of mouse transplant results. Of the 69 mice transplanted, those receiving islets where the OCR Index exceeded 1.27 were 90% likely to reverse within 3 days, whereas those receiving islets with an OCR Index below 1.27 took significantly longer, often failing to reverse at all over a 35-day time period. These results suggest that the OBS could be a useful tool for the pretransplant assessment of islet cell potency.
- Published
- 2006
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65. Immunosuppression and procedure-related complications in 26 patients with type 1 diabetes mellitus receiving allogeneic islet cell transplantation.
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Hafiz MM, Faradji RN, Froud T, Pileggi A, Baidal DA, Cure P, Ponte G, Poggioli R, Cornejo A, Messinger S, Ricordi C, and Alejandro R
- Subjects
- Adult, C-Peptide blood, Female, Humans, Immunosuppressive Agents adverse effects, Kidney Transplantation, Male, Middle Aged, Retrospective Studies, Transplantation, Homologous immunology, Diabetes Mellitus, Type 1 surgery, Immunosuppression Therapy adverse effects, Islets of Langerhans Transplantation immunology, Postoperative Complications chemically induced
- Abstract
Background: The success of sirolimus and low-dose tacrolimus in islet cell transplantation has influenced many transplant centers to utilize this novel regimen. The long-term safety and tolerability of this steroid-free immunosuppressive protocol for allogeneic islet transplantation has yet to be determined., Methods: We transplanted 26 adult patients with long standing type 1 diabetes mellitus between April 2000 and June 2004. Immunosuppression consisted of induction with daclizumab and maintenance therapy with tacrolimus and sirolimus. Adverse events (AEs) in patients were followed and graded using the Common Terminology Criteria for Adverse Events, version 3.0 (National Cancer Institute)., Results: To date, the majority of patients were able to remain on the immunosuppression combination for up to 22+/-11 months. Four patients were successfully converted to Mycophenolate Mofetil due to tacrolimus-related toxicity. Withdrawal from immunosuppression was decided in four patients due to hypereosinophilic syndrome, parvovirus infection, aspiration pneumonia, and severe depression, respectively. Six patients required filgrastim therapy for neutropenia. Transient elevation of liver enzymes was observed in most patients early after islet infusion. Increased LDL in 20 patients required medical treatment., Conclusion: There was a varying range of AEs, most of them mild and self-limiting; however, some required urgent medical attention. The majority of patients were able to tolerate and remain on this effective regimen. To date, no deaths, cytomegalovirus disease, graft-versus-host disease, or posttransplant lymphoproliferative disease has been observed.
- Published
- 2005
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66. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience.
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Froud T, Ricordi C, Baidal DA, Hafiz MM, Ponte G, Cure P, Pileggi A, Poggioli R, Ichii H, Khan A, Ferreira JV, Pugliese A, Esquenazi VV, Kenyon NS, and Alejandro R
- Subjects
- Adult, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Blood Glucose metabolism, C-Peptide blood, Daclizumab, Female, Humans, Immunoglobulin G therapeutic use, Infliximab, Islets of Langerhans physiology, Male, Middle Aged, Prospective Studies, Sirolimus therapeutic use, Tacrolimus therapeutic use, Tissue Culture Techniques, Tumor Necrosis Factors pharmacology, Diabetes Mellitus, Type 1 surgery, Graft Survival, Immunosuppressive Agents therapeutic use, Insulin blood, Islets of Langerhans Transplantation
- Abstract
Following the success obtained with transplantation of fresh human islets under steroid-free immunosuppression, this trial evaluated the transplantation of islets that had undergone a period of in vitro culture and the potential of tumor necrosis factor (TNF-alpha) blockade to improve islet engraftment. Subjects included 16 patients with type 1 diabetes mellitus (T1DM); half were randomly assigned to receive Infliximab immediately preceding initial infusion. Immunosuppression consisted of daclizumab induction and sirolimus/tacrolimus maintenance. Out of 16 subjects 14 achieved insulin independence with one or two islet infusions; adverse events precluded completion in two. Without supplemental infusions, 11/14 (79%) subjects were insulin independent at 1 year, 6/14 (43%) at 18 months; these same subjects remain insulin independent at 33+/-6 months. While on immunosuppression, all patients maintained graft function. Out of 14 patients, 8 suffered chronic partial graft loss, likely immunological in nature, 5 of these received supplemental infusions. Currently, 11 subjects remain on immunosuppression, 8 (73%) are insulin independent, two with supplemental infusions. Insulin independent subjects demonstrated normalization of HbA1c, fructosamine and Mean Amplitude of Glycemic Excursions (MAGE) values. No clinical benefit of infliximab was identified. These results demonstrate that transplantation of cultured human islet allografts results in reproducible insulin independence in all subjects under this immunosuppressive regimen, comparable to that of freshly transplanted islets (Edmonton protocol).
- Published
- 2005
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67. Hypereosinophilia in an islet transplant recipient.
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Poggioli R, Froud T, Baidal DA, Ferreira JV, Hafiz MM, Ricordi C, Gleich GJ, and Alejandro R
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- Adult, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 therapy, Follow-Up Studies, Humans, Hypereosinophilic Syndrome etiology, Immunosuppression Therapy, Leukocyte Count, Male, Transplantation, Hypereosinophilic Syndrome complications, Hypereosinophilic Syndrome pathology, Islets of Langerhans Transplantation adverse effects, Islets of Langerhans Transplantation immunology
- Published
- 2005
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68. Prolonged Allogeneic Islet Graft Survival by Protoporphyrins.
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Pileggi A, Molano RD, Berney T, Ichii H, Jose SS, Zahr E, Poggioli R, Linetsky E, Ricordi C, and Inverardi L
- Abstract
Transplantation of islets of Langerhans in patients with type 1 diabetes allows for improved metabolic control and insulin independence. The need for chronic immunosuppression limits this procedure to selected patients with brittle diabetes. Definition of therapeutic strategies allowing permanent engraftment without the need for chronic immunosuppression could overcome such limitations. We tested the effect of the use of protoporphyrins (CoPP and FePP), powerful inducers of the cytoprotective protein hemeoxygenase 1 (HO-1), on allogeneic islet graft survival. Chemically induced diabetic C57BL/6 mice received DBA/2 islets. Treatment consisted in peritransplant administration of CoPP or saline. Islets were either cultured in the presence of FePP or vehicle before implant. Short-course administration of CoPP led to long-term islet allograft survival in a sizable proportion of recipients. Long-term graft-bearing animals rejected third-party islets while accepting a second set donor-specific graft permanently, without additional treatment. Preconditioning of islets with FePP by itself led to improved graft survival in untreated recipients, and provided additional advantage in CoPP-treated recipients, resulting in an increased proportion of long-term surviving grafts. Preconditioning of the graft with protoporphyrins prior to implant resulted in reduction of class II expression. Administration of protoporphyrins to the recipients of allogeneic islets also resulted in transient powerful immunosuppression with reduced lymphocyte proliferative responses, increased proportion of regulatory cells (CD4+CD25+), decreased mononuclear cell infiltrating the graft, paralleled by a systemic upregulation of HO-1 expression. All these mechanisms may have contributed to the induction of donor-specific hyporesponsiveness in a proportion of the protoporphyrintreated animals.
- Published
- 2005
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69. Alterations of the female reproductive system in recipients of islet grafts.
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Cure P, Pileggi A, Froud T, Norris PM, Baidal DA, Cornejo A, Hafiz MM, Ponte G, Poggioli R, Yu J, Saab A, Selvaggi G, Ricordi C, and Alejandro R
- Subjects
- Adolescent, Adult, Child, Preschool, Estradiol blood, Female, Follicle Stimulating Hormone blood, Humans, Immunosuppressive Agents adverse effects, Luteinizing Hormone blood, Middle Aged, Ovarian Cysts etiology, Pelvis diagnostic imaging, Progesterone blood, Ultrasonography, Islets of Langerhans Transplantation adverse effects, Menstrual Cycle, Ovary physiopathology
- Abstract
Background: Transplantation of allogeneic tissues is becoming a wider practice for the replacement of organ function lost to congenital or acquired pathologies. Chronic immunosuppression remains a necessity to prevent organ rejection, despite increased risks of infection, organ toxicity, and malignancies. Abnormalities of female gonadal function in patients of reproductive age are recognized, however, pathological alterations of the reproductive system in patients treated with new generation immunosuppressive drugs are still poorly documented., Methods: We report herein our observations of abnormalities of the reproductive system in 13 female recipients of allogeneic islets for type 1 diabetes, under immunosuppression therapy based on daclizumab induction and tacrolimus/sirolimus maintenance., Results: Menstrual cycle alterations and clinically significant ovarian cysts were frequently observed in our patients, some requiring medical or surgical intervention. All ovarian cysts appeared of benign nature., Conclusions: Our findings suggest that pre- and posttransplant evaluation of female patients should include menstrual history, baseline pelvic ultrasound, and hormonal levels to assess the presence and monitor the progression of such alterations.
- Published
- 2004
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- View/download PDF
70. Cytomegalovirus prevalence and transmission after islet allograft transplant in patients with type 1 diabetes mellitus.
- Author
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Hafiz MM, Poggioli R, Caulfield A, Messinger S, Geiger MC, Baidal DA, Froud T, Ferreira JV, Tzakis AG, Ricordi C, and Alejandro R
- Subjects
- Adolescent, Adult, Aged, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, Cytomegalovirus Infections transmission, Diabetes Mellitus, Type 1 virology, Female, Humans, Male, Middle Aged, Prevalence, Regression Analysis, Risk Factors, Tissue Donors, Cytomegalovirus Infections epidemiology, Diabetes Mellitus, Type 1 surgery, Islets of Langerhans Transplantation
- Abstract
Cytomegalovirus (CMV) serological status of transplant donors and recipients has important implications on antiviral prophylaxis, morbidity/mortality, donor selection and hospital stay. We evaluated CMV prevalence in our islet transplant candidates (ITC) in comparison with organ donors. We correlated the CMV serological status of our ITC with serology for Epstein-Barr virus and Parvovirus B19, auto-antibodies, patient's age, age at DM onset, duration of DM, gender, race, ABO group, HLA haplotype and C-peptide levels. Cytomegalovirus transmission after islet transplant using the Edmonton regimen was also evaluated. Cytomegalovirus seropositivity varied according to patient group, age, gender and race. Type 1 DM patients had reduced odds of CMV seropositivity when compared with organ donors. In all groups studied, older patients, females, and non-Caucasians were more likely to be CMV seropositive. In addition, no CMV reactivation, infection or disease was observed among our transplanted patients using this steroid-free regimen even after donor/recipient CMV mismatch.
- Published
- 2004
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- View/download PDF
71. The effect of simultaneous CD154 and LFA-1 blockade on the survival of allogeneic islet grafts in nonobese diabetic mice.
- Author
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Berney T, Pileggi A, Molano RD, Poggioli R, Zahr E, Ricordi C, and Inverardi L
- Subjects
- Animals, Blood Glucose metabolism, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 surgery, Disease Models, Animal, Graft Survival drug effects, Immunosuppressive Agents therapeutic use, In Vitro Techniques, Islets of Langerhans Transplantation methods, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Transplantation, Homologous immunology, Antibodies, Monoclonal therapeutic use, CD40 Ligand immunology, Graft Survival immunology, Islets of Langerhans Transplantation immunology, Lymphocyte Function-Associated Antigen-1 immunology
- Abstract
Background: The rate of success in clinical transplantation of islets of Langerhans has dramatically improved with perspectives of wide-scale applicability for patients with type 1 diabetes. One drawback is the need for lifelong immunosuppression, which is associated with significant side effects. Immunomodulatory strategies devoid of side effects and with tolerogenic potential, such as co-stimulatory blockade, would be a great improvement if successful. In this study, the authors have explored the effect of simultaneous blockade of CD40/CD154 and intercellular adhesion molecule (ICAM)/lymphocyte function-associated antigen (LFA)-1 interactions., Methods: Spontaneously diabetic nonobese diabetic (NOD) mice underwent transplantation with allogeneic (C57BL/6) islets and were treated with anti-CD154 monoclonal antibody (mAb) (500 microg, three doses), anti-LFA-1 mAb (100 microg, three doses), or a combination of both in the early peritransplant period. In another set of experiments, LFA-1 engagement was impaired by transplanting islets isolated from ICAM-1-knockout (KO) mice., Results: Untreated animals rejected their grafts within 10 days. LFA-1 blockade alone did not result in improved islet graft survival, whereas CD154 blockade alone increased graft survival to 18 days. Simultaneous blockade of both pathways led to significantly improved islet graft survival to 30 days (ICAM-1-KO islets plus anti-CD154), 35 days (anti-LFA-1 plus anti-CD154), and 44 days (ICAM-1-KO islets plus anti-LFA-1 plus anti-CD154)., Conclusions: These data suggest that a synergistic effect for prolonged graft survival can be obtained by simultaneously targeting CD154 and LFA-1 in the challenging model of islet allotransplantation in NOD mice. The observation of similar results with anti-LFA-1 mAb and with ICAM-1-KO grafts suggests a key role of direct antigen presentation for the activation of LFA-1-driven signaling.
- Published
- 2003
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72. Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody.
- Author
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Molano RD, Pileggi A, Berney T, Poggioli R, Zahr E, Oliver R, Malek TR, Ricordi C, and Inverardi L
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Body Weight, Cytokines biosynthesis, Drug Therapy, Combination, Female, Graft Survival drug effects, Graft Survival immunology, Immunophenotyping, In Vitro Techniques, Islets of Langerhans immunology, Islets of Langerhans pathology, Lymphocytes immunology, Lymphocytes metabolism, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Transplantation, Homologous, Diabetes Mellitus, Type 1 surgery, Immunosuppressive Agents pharmacology, Interleukin-2 immunology, Islets of Langerhans Transplantation, Sirolimus pharmacology, Tacrolimus pharmacology
- Abstract
Background: Nonobese diabetic (NOD) mice develop autoimmune diabetes with features similar to those observed in the human disease. The concurrence of allorecognition and recurrence of autoimmunity might explain why most of the treatments successful in preventing islet allograft destruction in other nonautoimmune combinations often fail in NOD recipients. To assess the value of the NOD mouse model for the evaluation of treatments relevant to clinical islet transplantation, the authors have tested the effect of a protocol closely resembling the one successfully used in the Edmonton clinical trial on the survival of islet allografts in NOD mice., Methods: C57BL/6 islets were transplanted under the kidney capsule of spontaneously diabetic NOD mice. Treatment consisted of a combination of rapamycin, tacrolimus, and anti-interleukin (IL)-2 monoclonal antibody. Control groups received each treatment alone, a combination of two agents, or no treatment., Results: Untreated animals invariably lost their graft within 13 days. Administration of rapamycin and tacrolimus significantly prolonged graft survival, with two of seven animals bearing a functional graft longer than 100 days. Addition of anti-IL-2 antibody therapy further improved graft survival, with six of eight grafts functioning longer than 100 days and two of eight grafts functioning longer than 200 days., Conclusions: In view of the limited success obtained with other treatments in this model, the dramatic prolongation of graft survival observed in the authors' study, by using a therapy that mimics one successfully used in clinical trials, seems to validate the NOD mouse as a meaningful model for the study of therapeutic interventions for the prevention of islet graft loss.
- Published
- 2003
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73. Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to the cold-storage solution.
- Author
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Ricordi C, Fraker C, Szust J, Al-Abdullah I, Poggioli R, Kirlew T, Khan A, and Alejandro R
- Subjects
- Adult, Aged, Humans, Middle Aged, Oxygen metabolism, Adenosine pharmacology, Allopurinol pharmacology, Cryopreservation, Fluorocarbons pharmacology, Glutathione pharmacology, Insulin pharmacology, Islets of Langerhans Transplantation, Organ Preservation methods, Organ Preservation Solutions, Raffinose pharmacology, Tissue Donors
- Abstract
Last year, from the approximately 6,000 organ donors, only approximately 1,500 pancreata were used for clinical transplantation. Factors that contribute to this poor pancreas use include strict donor selection criteria and the requirement for short cold-ischemia time (CIT). Numerous pancreata have not been used because of long ischemia times postprocurement. Given the oxygen-rich environment of the islets in the native pancreas, it is conceivable that islets are highly susceptible to irreversible damage following prolonged ischemia. The use of continuously oxygenated perfluorohydrocarbons (PFCs), known for their high oxygen-solubility coefficients, in a two-layer culture with standard University of Wisconsin preservation media, has extended the acceptable range CIT, and, furthermore, there has been no evidence of adverse effects from PFCs on the outcome of transplanted cells, whereas they often enhance islet cell function. The purpose of this study was to use the two-layer culture method to improve donor-organ use from marginal donors. Fifteen organs were procured using the two-layer method, and 18 without using it, from donors greater than 50 years of age. Despite nonsignificant differences in age, weight of the donors, weight of the organ and CIT, the PFC group yielded an average of twofold more islet equivalents than those harvested from the control group. As a result, from the control group, only 2 of 18 organs were used for clinical islet transplantation, whereas 8 of 15 were used from the PFC group. To this end, the two-layer method may help clinicians overcome the problem of organ underuse.
- Published
- 2003
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74. Prolonged islet allograft survival in diabetic NOD mice by targeting CD45RB and CD154.
- Author
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Molano RD, Pileggi A, Berney T, Poggioli R, Zahr E, Oliver R, Ricordi C, Rothstein DM, Basadonna GP, and Inverardi L
- Subjects
- Animals, Antibodies, Monoclonal administration & dosage, CD3 Complex immunology, CD8-Positive T-Lymphocytes immunology, Female, Interferon-gamma biosynthesis, Interferon-gamma genetics, Interleukin-10 genetics, Interleukin-2 genetics, Interleukin-7 pharmacology, Islets of Langerhans Transplantation, Lymphocyte Activation, Mice, Mice, Inbred NOD, RNA, Messenger analysis, Transplantation, Homologous, CD40 Ligand immunology, Graft Survival, Leukocyte Common Antigens immunology
- Abstract
Clinical islet transplantation is a successful procedure that can improve the quality of life in recipients with diabetes. A drawback of the procedure is the need for chronic administration of immunosuppressive drugs that, among other side effects, are potentially diabetogenic. Definition of immunosuppressive protocols that utilize nondiabetogenic compounds could further improve islet transplantation outcome. We used the NOD mouse to assess the effect of targeting the T-lymphocyte surface receptors CD45RB and CD154 in preventing loss of allogeneic islet grafts as a result of recurrence of autoimmunity and allorejection. Administration of the two antibodies led to significantly prolonged allograft survival, with a percentage of grafts surviving long-term. The therapeutic efficacy of the treatment was paralleled by a shift in CD45RB isoform expression on T-lymphocytes, increased in vitro responsiveness to interleukin-7, and increased in vitro gamma-interferon production after anti-CD3 antibody stimulation. Furthermore, graft infiltration by CD8+ T-cells was remarkably reduced. Recipient mice bearing functioning allografts were otherwise immunocompetent, as assessed in vivo and in vitro by numerous tests, including intragraft cytokine production, responsiveness to polyclonal stimulation and alloantigens, and analysis of cell subset phenotype. These data show that nondiabetogenic regimens of immunomodulation can lead to prolonged islet allograft survival in the challenging NOD mouse model.
- Published
- 2003
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75. Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice.
- Author
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Zhang YC, Pileggi A, Agarwal A, Molano RD, Powers M, Brusko T, Wasserfall C, Goudy K, Zahr E, Poggioli R, Scott-Jorgensen M, Campbell-Thompson M, Crawford JM, Nick H, Flotte T, Ellis TM, Ricordi C, Inverardi L, and Atkinson MA
- Subjects
- Animals, Autoimmunity, Diabetes Mellitus, Type 1 immunology, Gene Expression, Genetic Vectors, Graft Survival, Green Fluorescent Proteins, Heme Oxygenase (Decyclizing) biosynthesis, Heme Oxygenase-1, Inflammation pathology, Islets of Langerhans immunology, Islets of Langerhans pathology, Luminescent Proteins genetics, Lymphocytes pathology, Membrane Proteins, Mice, Mice, Inbred NOD, Muscle, Skeletal metabolism, Superoxide Dismutase biosynthesis, Dependovirus genetics, Diabetes Mellitus, Type 1 therapy, Genetic Therapy, Interleukin-10 genetics, Islets of Langerhans Transplantation, Secondary Prevention
- Abstract
Islet transplantation represents a potential cure for type 1 diabetes, yet persistent autoimmune and allogeneic immunities currently limit its clinical efficacy. For alleviating the autoimmune destruction of transplanted islets, newly diagnosed NOD mice were provided a single intramuscular injection of recombinant adeno-associated viral vector encoding murine IL-10 (rAAV-IL-10) 4 weeks before renal capsule delivery of 650 syngeneic islets. A dose-dependent protection of islet grafts was observed. Sixty percent (3 of 5) of NOD mice that received a transduction of a high-dose (4 x 10(9) infectious units) rAAV-IL-10 remained normoglycemic for at least 117 days, whereas diabetes recurred within 17 days in mice that received a low-dose rAAV-IL-10 (4 x 10(8) infectious units; 5 of 5) as well as in all of the control mice (5 of 5 untreated and 4 of 4 rAAV-green fluorescent protein-transduced). Serum IL-10 levels positively correlated with prolonged graft survival and were negatively associated with the intensity of autoimmunity. The mechanism of rAAV-IL-10 protection involved a reduction of lymphocytic infiltration as well as induction of antioxidant enzymes manganese superoxide dismutase and heme oxygenase 1 in islet grafts. These studies support the utility of immunoregulatory cytokine gene therapy delivered by rAAV for preventing autoimmune disease recurrence in transplant-based therapies for type 1 diabetes.
- Published
- 2003
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- View/download PDF
76. Article Commentary: Islet Xenotransplantation.
- Author
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Poggioli R, Inverardi L, and Ricordi C
- Published
- 2002
- Full Text
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77. Islet xenotransplantation.
- Author
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Poggioli R, Inverardi L, and Ricordi C
- Subjects
- Animals, Cell Culture Techniques methods, Cell Culture Techniques standards, Cell Culture Techniques trends, Cell Separation methods, Cell Separation standards, Cell Separation trends, Graft Rejection immunology, Graft Rejection prevention & control, Humans, Inflammation immunology, Inflammation prevention & control, Islets of Langerhans Transplantation methods, Sus scrofa immunology, Sus scrofa surgery, Transplantation, Heterologous methods, Diabetes Mellitus surgery, Islets of Langerhans Transplantation standards, Islets of Langerhans Transplantation trends, Transplantation, Heterologous standards, Transplantation, Heterologous trends
- Published
- 2002
78. Behavioral and developmental outcomes of prenatal and postnatal vanadium exposure in the rat.
- Author
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Poggioli R, Arletti R, Bertolini A, Frigeri C, and Benelli A
- Subjects
- Animals, Animals, Newborn, Body Weight drug effects, Drinking drug effects, Eating drug effects, Female, Male, Memory drug effects, Motor Activity drug effects, Pregnancy, Rats, Rats, Wistar, Sodium Chloride administration & dosage, Sodium Chloride pharmacology, Survival Rate, Vanadium administration & dosage, Weaning, Behavior, Animal drug effects, Growth drug effects, Prenatal Exposure Delayed Effects, Vanadium toxicity
- Abstract
The developmental and behavioral outcomes of uninterrupted exposure to vanadium was studied in the rat. Starting 3 days before birth and up to the 100th day of extrauterine life, rats received as drink either a water solution of vanadyl sulphate (300 mg l(-1)containing 70 mg l(-1)of vanadium element, which is equal to an ingested dose of about 10 mg kg(-1)per day of vanadium element) plus NaCl 5 g l(-1), or a water solution of NaCl 5 g l(-1), or plain water [up to weaning (25th day of extrauterine life) treatment was given to dams and offspring]. At weaning, survivors were fewer and body weight was found to be significantly lower in the offspring of vanadium plus NaCl-treated dams than in the offspring of the other two groups. After weaning, growth retardation continued to be significant in both vanadium plus NaCl- and NaCl-treated rats. Such an effect was more pronounced in males than in females. Locomotor activity--evaluated at 1 month of age--was not significantly different in the three groups of rats. In the open-field, male (but not female) vanadium plus NaCl-treated rats had a reduced outer ambulation, rearing posture and grooming activity, and an increased defecation, in comparison with the males of the NaCl group, and reduced rearing in comparison with control males. As concerns ingestive behaviors, the only significant datum was an increased water intake in NaCl-treated males. Finally, at the 100th day of life, working memory was significantly impaired in both vanadium plus NaCl- and NaCl-treated rats., (Copyright 2001 Academic Press.)
- Published
- 2001
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79. Effect of potassium channel modulators on male sexual behavior.
- Author
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Benelli A, Arletti R, Poggioli R, Cavazzuti E, Mameli M, and Bertolini A
- Subjects
- Animals, Female, Glyburide administration & dosage, Guanidines administration & dosage, Injections, Intraventricular, Male, Pinacidil, Potassium Channel Blockers, Potassium Channels metabolism, Rats, Rats, Sprague-Dawley, Glyburide pharmacology, Guanidines pharmacology, Potassium Channels drug effects, Sexual Behavior, Animal drug effects
- Abstract
In the adult sexually experienced male rat, the intracerebroventricular (i.c.v.) injection of pinacidil, a KATP channel opener, at the dose of 100-150-300 micrograms/rat worsened the copulatory performance in the presence of a receptive female, whereas the administration of glibenclamide, a KATP channel blocker, at the dose of 0.5 and 3 mg/kg intraperitoneally (i.p.) had an improving effect. These data indicate that KATP channels in target neurons may play an important role in the physiology of male sexual behavior.
- Published
- 1997
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80. Use of calcium provocative test in the diagnosis of gastroenteropancreatic endocrine tumors.
- Author
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Vezzadini C, Poggioli R, Casoni I, and Vezzadini P
- Subjects
- Humans, Calcium, Carcinoid Tumor diagnosis, Gastrinoma diagnosis, Gastrointestinal Neoplasms diagnosis, Insulinoma diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
Calcium infusion has been advocated as a provocative test for the diagnosis of some endocrine tumors of the pancreas and gastrointestinal tract (gastrinoma, insulinoma, intestinal carcinoids). The release of gastrin from gastrinoma tissue is very sensitive to alterations in the serum calcium level, and the calcium infusion test is recommended in Zollinger-Ellison syndrome when the results of secretin stimulation are equivocal. The calcium provocative test in the detection of insulinoma and carcinoid tumors is less reliable than other safer and simpler procedures. Intravenous injection of calcium followed by pentagastrin stimulates the release of somatostatin in patients with somatostatinoma and offers a reliable means for establishing the diagnosis of this tumor. Calcium administration has not proven to be useful in the diagnosis of other endocrine tumors of the digestive system.
- Published
- 1996
81. [Duodenal somatostatinoma associated with von Recklinghausen's neurofibromatosis].
- Author
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Vezzadini P, Poggioli R, Vezzadini C, Alberani A, and Dal Monte PR
- Subjects
- Adult, Duodenal Neoplasms pathology, Humans, Male, Somatostatinoma pathology, Duodenal Neoplasms complications, Neurofibromatosis 1 complications, Somatostatinoma complications
- Abstract
This case report describes a 27-year-old man with von Recklinghausen's neurofibromatosis, manifested as cutaneous cafè au lait spots and neurofibromas, associated with duodenal somatostatinoma. The patient presented with ultrasonographic evidence of dilatation of the biliary and pancreatic ducts, in absence of clinical symptoms. The reason for the performance of ultrasonography was to identify the cause of an increase of hepatic enzymes during the last two years. Diagnostic ERCP showed an ulcerated tumor in the papillary region and pathological findings were compatible with somatostatinoma. Endoscopic sphincterotomy with placement of endoprostheses was successful in achieving biliary and pancreatic drainage. Subsequently a curative resection of the tumor was performed by the Whipple procedure and provocative tests demonstrated normal plasma somatostatin concentrations.
- Published
- 1996
82. Old rats are unresponsive to the behavioral effects of adrenocorticotropin.
- Author
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Poggioli R, Benelli A, Arletti R, Vergoni AV, Menozzi B, and Bertolini A
- Subjects
- Animals, Male, Melanocyte-Stimulating Hormones pharmacology, Rats, Rats, Wistar, Aging psychology, Behavior, Animal drug effects, Cosyntropin pharmacology, Peptide Fragments pharmacology
- Abstract
In 28 month-old male rats, the i.c.v. injection of adrenocorticotropin [ACTH-(1-24)] (4 micrograms/rat) did not induce the typical behavioral syndrome (excessive grooming, stretching, yawning, penile erections). This indicates that the behavioral effects of melanocortins are age-dependent, suggesting either an aging-linked impairment of the nervous circuitries involved or a reduction of the number (or affinity, or both) of the brain melanocortin receptors in the elderly.
- Published
- 1994
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83. [Endogenous anti-analgesic systems].
- Author
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Bertolini A, Poggioli R, Bernardi M, Genedani S, Guarini S, Bazzani C, Arletti R, Benelli A, Bertolini E, and Balugani A
- Subjects
- Analgesia, Cholecystokinin physiology, Humans, Melanocyte-Stimulating Hormones physiology, Pain drug therapy, Receptors, Cholecystokinin physiology, Receptors, Pituitary Hormone physiology, Pain physiopathology
- Abstract
Nociception is of vital importance for the organism, while its inhibition by endogenous opioid systems is usually a sign of surrender. Therefore, it must be assumed that endogenous analgesic systems are balanced, and in fact, under normal conditions, overwhelmed, by teleologically far more important anti-analgesic systems. The two main anti-analgesic systems--i.e., the melanotropinergic and the cholecystokininergic--are here reviewed for their role, not only in nociception, but in a wide variety of vital functions (endocrine, gastrointestinal, ingestive, reproductive, cardiovascular, immune, etc.). Available data strongly suggest that these systems (particularly the melanotropinergic one) play a key role in the overall homeostasis of the body. Moreover, modulation of endogenous anti-analgesic systems may disclose a new, unforeseen approach to the treatment of pain.
- Published
- 1994
84. Galantide stimulates sexual behaviour in male rats.
- Author
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Benelli A, Arletti R, Bertolini A, Menozzi B, Basaglia R, and Poggioli R
- Subjects
- Animals, Female, Galanin, Injections, Intraventricular, Male, Motor Activity drug effects, Neuropeptides administration & dosage, Neuropeptides pharmacology, Ovariectomy, Peptides administration & dosage, Rats, Rats, Sprague-Dawley, Peptides antagonists & inhibitors, Peptides pharmacology, Sexual Behavior, Animal drug effects, Substance P analogs & derivatives
- Abstract
While intracerebroventricular injection of galanin (5 micrograms/rat) inhibited sexual behavior in experienced male rats--without producing any other locomotor or behavioral deficit-, injection of the galanin antagonist, galantide, by the same route (1 or 2 micrograms/rat) stimulated sexual behavior (improving arousal, motivation and performance indexes) and antagonized the effect of galanin. These data further suggest that galanin plays a physiological role in male sexual behavior.
- Published
- 1994
- Full Text
- View/download PDF
85. The behavioral syndrome induced by adreno corticotropic hormone in rats is prevented by Ca++ channel blockade.
- Author
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Poggioli R, Rasori E, and Bertolini A
- Subjects
- Animals, Cosyntropin administration & dosage, Injections, Intraventricular, Male, Rats, Rats, Wistar, Behavior, Animal drug effects, Calcium physiology, Cosyntropin pharmacology, Nicardipine pharmacology
- Abstract
The most typical signs (stretchings, yawnings, penile erections, excessive grooming) of the behavioral syndrome induced in rats by the intracerebroventricular administration of ACTH- (1-24) (4 micrograms/rat) were dose-dependently antagonized by the intraperitoneal injection of the selective Ca++ channel inhibitor, nicardipine (dose range: 0.1-1 mg/kg). These data suggest that the influx of Ca++ into target neurons is a step of key importance for the occurrence of ACTH-induced behavioral signs, and that Ca++ may play the role of second intracellular messenger for the behavioral effects of melanocortins.
- Published
- 1993
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86. Galanin inhibits sexual behavior in male rats.
- Author
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Poggioli R, Rasori E, and Bertolini A
- Subjects
- Animals, Feeding Behavior drug effects, Female, Galanin, Injections, Intraventricular, Male, Motor Activity drug effects, Peptides administration & dosage, Rats, Rats, Inbred Strains, Peptides pharmacology, Sexual Behavior, Animal drug effects
- Abstract
Intracerebroventricular injection of galanin potently inhibited (0.5 micrograms/rat) or completely suppressed (5.0 micrograms/rat) copulatory activity in sexually experienced male rats, without producing any other obvious behavioral deficit. It is suggested that galanin, known to potently stimulate feeding behavior, may be involved in the inverse modulation of feeding and sexual behaviors.
- Published
- 1992
- Full Text
- View/download PDF
87. Influence of the selective cholecystokinin antagonist L-364,718 on pain threshold and morphine analgesia.
- Author
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Poggioli R, Vergoni AV, Sandrini M, Barbafiera L, Marrama D, and Bertolini A
- Subjects
- Animals, Benzodiazepinones metabolism, Brain Stem metabolism, Devazepide, Female, Male, Mice, Pain drug therapy, Pain metabolism, Receptors, Cholecystokinin antagonists & inhibitors, Sensory Thresholds, Analgesia, Benzodiazepinones pharmacology, Cholecystokinin antagonists & inhibitors, Morphine, Pain physiopathology
- Abstract
The intracerebroventricular injection of the cholecystokinin-A receptor antagonist L-364,718, at the doses of 0.5, 5, 10 or 20 micrograms/mouse, while having no effect on pain threshold (hot plate, 51 degrees C), antagonized the analgesic activity of morphine (10 mg/kg i.p.). This effect was obtained with a dose of 10 micrograms/mouse and was associated with a reduction of brainstem opiate-binding sites.
- Published
- 1991
- Full Text
- View/download PDF
88. Influence of bestatin on feeding behavior.
- Author
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Rasori E, Poggioli R, and Bertolini A
- Subjects
- Animals, Benzomorphans pharmacology, Injections, Intraventricular, Leucine pharmacology, Naloxone pharmacology, Narcotic Antagonists pharmacology, Rats, Rats, Inbred Strains, Stimulation, Chemical, Feeding Behavior drug effects, Leucine analogs & derivatives
- Published
- 1990
- Full Text
- View/download PDF
89. Inhibition of feeding by ACTH-(1-24): behavioral and pharmacological aspects.
- Author
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Vergoni AV, Poggioli R, Marrama D, and Bertolini A
- Subjects
- Adrenalectomy, Animals, Grooming drug effects, Injections, Intraventricular, Insulin pharmacology, Male, Models, Psychological, Muscimol pharmacology, Rats, Rats, Inbred Strains, Cosyntropin pharmacology, Feeding Behavior drug effects
- Abstract
The time course of the behavior of rats fasted for 24 h was analyzed with observation starting either 10 or 60 min after the i.c.v. administration of ACTH-(1-24) (4 micrograms/animal). The anorectic effect of this peptide was direct and specific because it could be dissociated in time from the grooming-inducing effect. The effect is a central one, not linked either to an interaction with the peripheral feeding-regulatory system, or to the release of adrenal steroids. ACTH-(1-24), like corticotropin-releasing factor (CRF), is capable of antagonizing the stimulation of feeding seen during starvation, insulin (10 IU/kg s.c.)-induced hypoglycemia, stimulation of GABAergic (muscimol, 250 ng/rat i.c.v.), noradrenergic (norepinephrine, 20 micrograms/rat i.c.v.) or opioidergic systems. The data suggest that both CRF and ACTH may be considered as putative mediators in the production of stress-induced anorexia.
- Published
- 1990
- Full Text
- View/download PDF
90. Influence of clonidine on the ACTH-induced behavioral syndrome.
- Author
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Poggioli R, Vergoni AV, Guarini S, and Bertolini A
- Subjects
- Animals, Blood Pressure drug effects, Injections, Intraventricular, Male, Penis drug effects, Rats, Rats, Inbred Strains, Adrenocorticotropic Hormone antagonists & inhibitors, Behavior, Animal drug effects, Clonidine pharmacology
- Abstract
In male rats, clonidine in a dose range of 1-3000 micrograms/kg i.p. antagonized the stretching-yawning syndrome induced by the intraventricular injection of ACTH-(1-24) (3 micrograms/rat) dose-dependently. On the other hand, the effect of clonidine on ACTH-induced penile erections was potentiation at low doses (5 and 10 micrograms/kg) and inhibition at the highest doses (1000 and 3000 micrograms/kg), the intermediate doses (50 and 100 micrograms/kg) being without effect. There was no relationship between these behavioral effects and the effect on arterial blood pressure.
- Published
- 1984
- Full Text
- View/download PDF
91. Cross-species comparison of the ACTH-induced behavioral syndrome.
- Author
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Bertolini A, Poggioli R, and Vergoni AV
- Subjects
- Animals, Dose-Response Relationship, Drug, Eating drug effects, Grooming drug effects, Injections, Intraventricular, Male, Mice, Pain, Penile Erection drug effects, Rabbits, Rats, Sensory Thresholds, Syndrome, Yawning drug effects, Adrenocorticotropic Hormone pharmacology, Behavior, Animal drug effects, Cerebral Ventricles physiology
- Published
- 1988
- Full Text
- View/download PDF
92. [ACTH and eating behavior].
- Author
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Vergoni AV, Poggioli R, Vaccina F, and Bertolini A
- Subjects
- Animals, Brain drug effects, Cosyntropin administration & dosage, Injections, Intraventricular, Male, Rats, Rats, Inbred Strains, Cosyntropin pharmacology, Feeding Behavior drug effects
- Published
- 1988
93. Possible physiological role of ACTH-peptides in nociception.
- Author
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Bertolini A, Poggioli R, and Ferrari W
- Subjects
- Adrenocorticotropic Hormone administration & dosage, Adrenocorticotropic Hormone analogs & derivatives, Adrenocorticotropic Hormone pharmacology, Animals, Behavior, Animal drug effects, Electric Stimulation, Injections, Intraventricular, Morphine pharmacology, Morphine toxicity, Naloxone pharmacology, Peptide Fragments physiology, Rats, Reaction Time drug effects, Adrenocorticotropic Hormone physiology, Pain physiopathology
- Published
- 1980
94. Withdrawal symptoms in morphine-dependent rats intracerebroventricularly injected with ACTH1-24 and with beta-MSH.
- Author
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Bertolini A, Poggioli R, and Fratta W
- Subjects
- Animals, Cosyntropin administration & dosage, Humans, Injections, Intraventricular, Kinetics, Male, Melanocyte-Stimulating Hormones administration & dosage, Naloxone pharmacology, Rats, Rats, Inbred Strains, Adrenocorticotropic Hormone analogs & derivatives, Cosyntropin pharmacology, Melanocyte-Stimulating Hormones pharmacology, Morphine Dependence physiopathology, Substance Withdrawal Syndrome chemically induced
- Published
- 1981
- Full Text
- View/download PDF
95. Influence of yohimbine on the ACTH-induced behavioural syndrome, in rats.
- Author
-
Poggioli R, Vergoni AV, and Bertolini A
- Subjects
- Adrenocorticotropic Hormone administration & dosage, Animals, Brain drug effects, Cosyntropin administration & dosage, Cosyntropin pharmacology, Dose-Response Relationship, Drug, Drug Synergism, Injections, Intraventricular, Male, Rats, Rats, Inbred Strains, Adrenocorticotropic Hormone pharmacology, Behavior, Animal drug effects, Yohimbine pharmacology
- Abstract
In adult male rats, yohimbine at low doses (0.1, 0.5 and 1 mg/kg i.p.) potentiated, and at high doses (30.0 mg/Kg) antagonized, the behavioural syndrome induced by the intracerebroventricular injection of ACTH 1-24 (3 micrograms/rat) (stretching-yawning syndrome and penile erections). These results support the hypothesis that brain catecholaminergic systems play a positive role in the ACTH-induced behavioural syndrome.
- Published
- 1985
- Full Text
- View/download PDF
96. ACTH-(1-24) antagonizes the cholestatic and constipating effects of morphine.
- Author
-
Poggioli R, Arletti R, Vergoni AV, Castelli M, and Bertolini A
- Subjects
- Animals, Bile drug effects, Cholestasis chemically induced, Constipation chemically induced, Defecation drug effects, Female, Gastrointestinal Motility drug effects, Guinea Pigs, Male, Morphine toxicity, Rats, Rats, Inbred Strains, Cholestasis prevention & control, Constipation prevention & control, Cosyntropin pharmacology, Morphine antagonists & inhibitors, Morphine Dependence complications
- Abstract
In guinea-pigs and rats, ACTH-(1-24), i.m. injected in a dose-range of 10-150 micrograms/kg, dose-dependently antagonized the cholestatic effect of morphine (15 mg/kg i.m.). In guinea-pigs, however, the effect of morphine (66 +/- 7.7% bile flow) was only partially antagonized even by the highest dose of ACTH-(1-24) (89.21 +/- 3.4%), while in rats it was completely prevented by the dose of 75 micrograms/kg of ACTH. In morphine-dependent rats, ACTH-(1-24), injected i.p. at doses of 50, 100 and 150 micrograms/kg, dose-dependently increased the number of fecal pellets during the first 3 hr after treatment. These results show that ACTH antagonizes morphine in vivo at the biliary and intestinal level, and further support the idea that ACTH-MSH peptides are physiological antagonists of opioids.
- Published
- 1988
97. ACTH-(1-24) and alpha-MSH antagonize feeding behavior stimulated by kappa opiate agonists.
- Author
-
Poggioli R, Vergoni AV, and Bertolini A
- Subjects
- Animals, Benzodiazepines antagonists & inhibitors, Benzomorphans antagonists & inhibitors, Male, Pentazocine antagonists & inhibitors, Rats, Rats, Inbred Strains, Adrenocorticotropic Hormone pharmacology, Benzodiazepines pharmacology, Benzomorphans pharmacology, Cosyntropin pharmacology, Feeding Behavior drug effects, Melanocyte-Stimulating Hormones pharmacology, Morphinans pharmacology, Pentazocine pharmacology
- Abstract
ACTH-(1-24) and alpha-MSH, intracerebroventricularly (ICV) injected at the doses of 4 and 10 micrograms/animal, respectively, markedly inhibited spontaneous feeding in adult Sprague-Dawley rats, the effect remaining significant for 6-9 hours. At these same doses, ACTH-(1-24) and alpha-MSH abolished the feeding-stimulatory effect of the kappa opiate receptor agonist pentazocine, intraperitoneally (IP) injected at the dose of 10 mg/kg. The same antagonism was obtained by ICV injection of ACTH-(1-24) into rats IP treated with other kappa opiate agonists, bremazocine and tifluadom, at the doses of 1 and 5 mg/kg, respectively. These data suggest that melanocortin peptides play an inhibitory role in the complex regulation of food intake, and further support and extend the hypothesis of a melanocortin-opioid homeostatic system, its two neuropeptide components usually having opposite, mutually-balancing effects.
- Published
- 1986
- Full Text
- View/download PDF
98. Morphine and beta-endorphin antagonize posture and locomotor disorders induced by the injection of ACTH 1-24 in the rat locus coeruleus.
- Author
-
Bertolini A, Vergoni AV, Poggioli R, and Gessa GL
- Subjects
- Animals, Cosyntropin administration & dosage, Cosyntropin pharmacology, Endorphins administration & dosage, Male, Microinjections, Morphine administration & dosage, Naloxone administration & dosage, Naloxone pharmacology, Rats, Rats, Inbred Strains, beta-Endorphin, Adrenocorticotropic Hormone analogs & derivatives, Cosyntropin antagonists & inhibitors, Dyskinesia, Drug-Induced, Endorphins pharmacology, Locus Coeruleus drug effects, Morphine pharmacology, Posture
- Abstract
The unilateral microinjection of ACTH 1-24 (20 nmol) into the locus coeruleus (LC) produced a long lasting (2-3 hr) posture asymmetry and movement disorder in all rats tested. This response was readily suppressed by the subsequent local microinjection of an equimolar dose of beta-endorphin or morphine or by the intraperitoneal injection of morphine sulphate (50 mg/kg). Microinjection of naloxone (20 nmol) into the LC produced the above syndrome in a lower percentage of animals. The results support the hypothesis that ACTH peptides and opioids play opposite roles in the control of different brain functions.
- Published
- 1986
- Full Text
- View/download PDF
99. Is the role of melatonin in induction of ovulation in the light-induced constant estrous anovulatory state mediated through the brain serotonergic system?
- Author
-
De Gaetani CF, Poggioli R, Ferrari P, Mess B, and Trentini GP
- Subjects
- Animals, Anovulation etiology, Female, Hydroxyindoleacetic Acid metabolism, Mesencephalon metabolism, Ovulation drug effects, Pregnancy, Rats, Rats, Inbred Strains, Anovulation metabolism, Brain metabolism, Estrus radiation effects, Light, Melatonin pharmacology, Serotonin metabolism
- Published
- 1980
- Full Text
- View/download PDF
100. Mice protection with 2,4-monofurfurylidene-tetra-O-methyl-sorbitol (MSF) against acute toxicity due to Amanita phalloides.
- Author
-
Zanoli P, Poggioli R, and Sannicola Botticelli C
- Subjects
- Alanine Transaminase blood, Amanita, Animals, Aspartate Aminotransferases blood, Drug Administration Schedule, Female, Furans administration & dosage, Furans therapeutic use, Kidney pathology, Liver pathology, Mice, Mushroom Poisoning pathology, Mushroom Poisoning prevention & control, Plant Extracts toxicity, Rats, Sorbitol administration & dosage, Sorbitol therapeutic use, Mushroom Poisoning drug therapy, Sorbitol analogs & derivatives
- Abstract
2,4-Monofurfurylidene-tetra-O-methyl-sorbitol (MSF), which protects rats against a number of hepatotoxins, also reduces the death rate in mice receiving a crude Amanita phalloides powder (APP) by i.p. route, this protective effect being dose- and time-dependent. MSF-pretreatment greatly reduces APP-induced liver damage and blood serum GOT and GPT increase. MSF antagonizes APP more effectively than do mercaptopropionylglycine (MPG) and silymarin. The results are briefly discussed.
- Published
- 1979
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