Effect of Cyclosporin a on Rejection of Pancreatic Islets Transplanted Under the Renal Capsule

H, Reece-Smith; Df, Du Toit; McShane, Paul; Pj, Morris

doi:10.1097/00007890-198110000-00014

Cited by 8 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although no ideal site has been identified as yet, some indications of the optimal site are available from experimental studies. It was suggested that the sparsely vascularized subcutaneous and intramuscular site may be associated with absent or poor integration of islet tissue (24), whereas highly vascularized sites such as liver (25), spleen (26), or kidney capsule (27) would allow better functional results.…”

Section: Resultsmentioning

confidence: 99%

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Menger¹,

Vajkoczy²,

Leiderer³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

The influence of hyperglycemia on the microvascular blood perfusion of pancreatic islet isografts of Syrian golden hamsters was analyzed by direct visualization ofthe islet's microvasculature by means of in vivo fluorescence microscopy. The experiments were performed using the hamster dorsal skinfold preparation, which allows for quantitative analysis of the microcirculation of islets grafted on the striated skin muscle. Islets were isolated from inbred hamsters by collagenase digestion and subsequently transplanted in normoglycemic (controls; n = 8) and hyperglycemic (65 mg/kg streptozotocin intravenously; n = 10) recipients. In both groups, revascularization of the islet grafts was completed on day 10 after transplantation. Quantitative analysis of capillary blood perfusion on days 6, 10, and 14 revealed no differences in functional capillary density and capillary red blood cell velocity of islets grafted into normoglycemic as compared to hyperglycemic animals. However, islet capillaries were significantly wider in hyperglycemic recipients (11.9±1.3 gm, P < 0.01) as compared to normoglycemic controls (8.9±0.4 Mm). The increase of capillary diameters resulted in a significant rise (P < 0.01) of mean capillary blood perfusion from 1.76±0.39 nl/min in controls to 2.88±0.63 nl/min in hyperglycemic recipients, indicating an increase in microvascular blood perfusion due to hyperglycemia. From these results it is concluded that hyperglycemia is associated with higher capillary blood perfusion in revascularized islet isografts, similarly as known for pancreatic islets in situ. (J. Clin. Invest. 1992. 90:1361-1369.) Key words: intravital fluorescence microscopy*quantitative microcirculatory analysis * hamster * revascularization * islet microvasculature

show abstract

Section: Resultsmentioning

confidence: 99%

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Menger¹,

Vajkoczy²,

Leiderer³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…These include pancreatic ailografts, which are difficult to transplant with conventional drugs. The minimum effective dosage required to prolong survival of isolated pancreatic islets in incompatible rats is considerably in excess of that needed to produce indefinite renal allograft survival in the same species [47,137]. Isolated pancreatic islets implanted under the renal capsule have also been transplanted to CsA treated allogeneic diabetic hosts with indefinite survival of the islets [138].…”

Section: (E) Graft Rejectionmentioning

confidence: 99%

Cyclosporine: Immunology, toxicity and pharmacology in experimental animals

1984

View full text Add to dashboard Cite

Cyclosporine (CsA) is the first of a new order of pharmacological immune suppressants and represents a significant advance in the clinical control of graft rejection. In laboratory animals, its capacity to prolong allograft survival has been well documented, including reports of indefinite donor-specific immunological tolerance after shortterm CsA treatment. There is also evidence that CsA can inhibit the onset or progress of a variety of experimental autoimmune diseases. Underlying these properties of the drug is its capacity to selectively interfere with T helper cell activation and lymphokine production, although some direct effects on B cells have also been reported. In addition, sparing of suppressor cells may in part explain the mode of action of CsA which, at the molecular level, is not understood. CsA-induced nephrotoxicity in the rat has been extensively studied and is characterized by reversible proximal tubular cell damage. This problem may be aggravated by concomitant administration of other potentially nephrotoxic drugs, such as gentamicin, or by therapeutic agents which interfere with the metabolism of CsA. CsA is metabolized in the liver and excreted in the bile. Although the pathway of hepatic metabolism of CsA has not been precisely elucidated, animal studies suggest that agents capable of inducing metabolism of the drug CsA could be used to alleviate its nephrotoxic properties.

show abstract

“…An endotracheal been induced by total surgical pancreatectomy with or ing anaesthesia. Ringer's lactate was administered during stmction of the betacell (ie, streptozotocin or alloxan) received Ringer's lactate solution for 4 days, during [7]. Surgical extirpation of the pancreas has been more which period they were starved Of food and water.…”

Section: Introductionmentioning

confidence: 99%

“…Partion of the islet cell mass has found wider application in commencing on the day of Pancreatectomy. Thereafter rodent models [7,8]. oral administration of liquids and a standard primate The purpose of this study was to investigate the out-p ellet diet (Epol Ltd, South Africa) were given without come of total pancreatectomy in the chacma baboon and the addition Of pancreatic extract* to assess the glucose and endocrine derangements which present during the early postpancreatectomy period.…”

Section: Introductionmentioning

confidence: 99%

“…oral administration of liquids and a standard primate The purpose of this study was to investigate the out-p ellet diet (Epol Ltd, South Africa) were given without come of total pancreatectomy in the chacma baboon and the addition Of pancreatic extract* to assess the glucose and endocrine derangements which present during the early postpancreatectomy period. [2,3,6,7,8]. In these models the diabetic state has either tube was without duodenectomy [ 1,4] or by specific chemical de-for continuous Of Oxygen dur-Postoperatively all baboons at a rate Of loo practical in the large animal model, while chemical &la-e n t e d penicillin and streptomycin were given for 4 days,…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diabetes in pancreatectomized baboons: A model for pancreatin transplantation studies

Toit

Heydenrych

Louw

et al. 1987

Journal of Surgical Oncology

View full text Add to dashboard Cite

This study was designed to assess plasma glucose levels (PLG) and insulin release in totally pancreatectomized baboons when challenged with intravenous glucose administration (IVGTT). Ten animals (Papio ursinus) were used and duodenectomy was intentionally avoided. The PLG at death was 18.0 +/- mmol/L, and the mean K-value within 3 days after pancreatectomy was 0.4% +/- 0.2%, indicating a significant impairment of glucose disappearance from the blood when compared to the control animals (P less than 0.01). Plasma insulin levels before and after stimulation with glucose were below the lowest level of insulin assay sensitivity. We conclude that in the primate, as in the dog, surgical pancreatectomy produced a reliable diabetic model, which is uniformly lethal if left untreated.

show abstract

Effect of Cyclosporin a on Rejection of Pancreatic Islets Transplanted Under the Renal Capsule

Cited by 8 publications

References 0 publications

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts.

Cyclosporine: Immunology, toxicity and pharmacology in experimental animals

Diabetes in pancreatectomized baboons: A model for pancreatin transplantation studies

Contact Info

Product

Resources

About