Determination of intracellular Ca2+ concentration can be a useful tool to predict neuronal damage and neuroprotective properties of drugs

Ferger, Dorothee; Krieglstein, Josef

doi:10.1016/0006-8993(96)00494-5

Cited by 23 publications

(10 citation statements)

References 47 publications

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“…The Ca 2+ indicator served as a viability probe, since it measures both the enzymatic activity that is required to activate their fluorescence and the cell-membrane integrity that is required for intracellular retention of its fluorescent product [13][14][15]. A minimum of 20 different islets were examined per preparation.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

Islet isolation for allotransplantation: variables associated with successful islet yield and graft function

et al. 2005

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Aims/hypothesis: Efficient islet isolation is an important prerequisite for successful clinical islet transplantation. Although progressively improved, islet yield and quality are, however, unpredictable and variable and require standardisation. Methods: Since 1989 we have processed 437 pancreases using the automated method. The donor characteristics, pancreas procurement, and digestion and purification procedures including a wide enzyme characterisation of these pancreases were analysed and correlated with islet yield and transplant outcome. Results: By univariate analysis, islet yield was significantly associated with donor age (r=0.16; p=0.0009), BMI (r=0.19; p= 0.0004), good pancreas condition (p=0.0031) and weight (r=0.15; p=0.0056), total collagenase activity (r=0.22; p= 0.0001), adjusted collagenase activity/mg (r=0.18; p=0.0002), collagenase activity/solution volume (r=0.18; p=0.0002) and neutral protease activity/solution volume (r=0.14; p= 0.0029). A statistically significant contribution to the variability of islet yield in a multivariate analysis performed on donor variables was found for donor BMI (p=0.0008). In a multivariate analysis performed on pancreas variables a contribution was found for pancreas weight (p=0.0064), and for a multivariate analysis performed on digestion variables we found a contribution for digestion time (p= 0.0048) and total collagenase activity (p=0.0001). Twenty-four patients with type 1 diabetes received single islet preparations from single donors. In these patients, multivariate analyses showed that the reduction in insulin requirement was significantly associated with morphological aspects of islets (p= 0.0010) and that 1-month C-peptide values were associated with islet purity (p=0.0071). Conclusions/interpretation: These data provide baseline donor, digestion and purification selection criteria for islet isolation using the automated method and indicate that the morphological aspect may be a clinically relevant measure of islets on which the decision for transplant can be based.

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Section: Subjects Materials and Methodsmentioning

confidence: 99%

Islet isolation for allotransplantation: variables associated with successful islet yield and graft function

et al. 2005

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“…Patients 25,26,28,30,32,34,35,38,40 and 41 also received a treatment based on pentoxyfillin (1200 mg/ day), nicotinamide (1500 mg/day) [10] and metformin (1000 mg/day) to improve islet engraftment. During follow-up, exogenous insulin was administered to maintain glycaemic values within 4.4 to 9.9 mmol/l.…”

Section: Methodsmentioning

confidence: 99%

Succesful transplantation of human islets in recipients bearing a kidney graft

Bertuzzi

Grohovaz²,

Maffi³

et al. 2002

Diabetologia

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Refinements in procedures of pancreas enzymatic digestion, and new immunosuppression strategies have allowed clinical trials of islet transplantation in patients with Type I (insulin-dependent) diabetes mellitus [1]. Until recently, the majority of transplants were done in patients who also receive kidney allografts [2]. Clinical results in these patients have not been satisfactory, with a 12 month survival of islet allografts (as defined by basal C-peptide > 0.17 nmol/l) being achieved in less than 40 % of recipients, and insulin independence in only 13 % of recipients [2]. The number of recipients who become insulin independent after transplantation is low and so the procedure has also been considered successful when recipients maintained detectable serum C-peptide during follow-up [3±4] or HbA 1 c was normalized [5]. Regardless of which outcome measure is used, around 30 % of the cases reported in the International Registry of Transplantation (ITR) showed the absence of islet function af- Diabetologia (2002) Abstract Aims/hypothesis. Islet transplantation is a minimally invasive approach to curing Type I (insulin-dependent) diabetes mellitus. Success has recently been reported in patients receiving solitary islet transplants but the outcome in patients receiving islets together with, or after, kidney transplants has been limited and unpredictable. Methods. Here we report successful islet transplantation in a cohort of 15 patients with Type I diabetes who were followed for at least 1 year after islet transplantation, after having already received kidney allografts because of end-stage nephropathy. Results. C-peptide after transplantation was higher than 0.17 nmol/l in all 15 recipients, reflecting the absence of primary non-function. Insulin requirement was reduced by over 50 % in all but one patient, and insulin independence was achieved in 10 (66 %) recipients, five of whom now have stable, prolonged insulin independence, well controlled fasting glycaemia, a substantial first-phase and normal secondphase response to glucose, normal insulin sensitivity (HOMA analyses) and HbA 1 c of under 6.2 % (33, 26, 18, 13 and 12 months after transplantation respectively). Of importance for patient management, an assessment of fasting blood glucose and proinsulin values following overnight withdrawal of insulin administration one month after transplantation was a potent predictor of insulin independence, and could be used to decide patients who should have further islet preparations. Conclusion/interpretation. These findings support the use of islet transplantation as a cure for Type I diabetes in patients with severe complications. [Diabetologia (2002) 45: 77±84]

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“…Several lines of evidence support the involvement of oxidative stress as an active factor in A␤-mediated neuropathology, by triggering or facilitating neurodegeneration through a wide range of molecular events that disturb neuronal homeostasis (Ekinci et al, 2000). However, the clinical benefit of NMDA receptor antagonists and direct blockers of neuronal Ca 2+ channels is debatable, since they lack convincing effectiveness or have serious side-effects (Ferger and Krieglstein, 1996;Li et al, 2002). There is much effort to develop beneficial agents from medicinal plants to achieve neuroprotection.…”

Section: Abbreviationsmentioning

confidence: 98%

Protection of amyloid β protein (25–35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons

Ban

Cho

Koh

et al. 2006

Journal of Ethnopharmacology

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Determination of intracellular Ca2+ concentration can be a useful tool to predict neuronal damage and neuroprotective properties of drugs

Cited by 23 publications

References 47 publications

Islet isolation for allotransplantation: variables associated with successful islet yield and graft function

Islet isolation for allotransplantation: variables associated with successful islet yield and graft function

Succesful transplantation of human islets in recipients bearing a kidney graft

Protection of amyloid β protein (25–35)-induced neurotoxicity by methanol extract of Smilacis chinae rhizome in cultured rat cortical neurons

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