Search PubMed⌕ Search

Biomedical subjects

A M Sun

Publications and source records attributed to A M Sun.

At least 19 recordsLinked to original sources
PubMed1992

Xenografts of rat islets into diabetic mice. An evaluation of new smaller capsules.

Healthy rat islets were encapsulated in alginate-polylysine-alginate capsules measuring 0.25-0.35 mm in diameter using a modified encapsulation technique. The encapsulated islets were transplanted intraperitoneally in nonimmunosuppressed streptozotocin-induced diabetic BALB/c mice. The diabetic condition of the experimental animals was reversed within two days following the transplantation and the animals remained normoglycemic for up to 308 days, with a mean xenograft survival of 219.8 +/- 46.2 days. Four and six months posttransplant the capsules were removed from two recipients. This resulted in regression to a hyperglycemic state. After a second transplant of encapsulated islets, the animals returned to normoglycemia. In control mice that received free unencapsulated islets, the xenografts remained functional for no more than 12 days. Our study clearly demonstrates that the encapsulation of islets in the new smaller capsules can effectively prolong xenograft survival without immunosuppression.

Animals↗
PubMed1992

Vasopressin regulates apical and basolateral Na(+)-H+ antiporters in mouse medullary thick ascending limbs.

We assessed in isolated perfused mouse medullary thick ascending limb (MTAL) segments Na(+)-H+ antiporter activity in both apical and basolateral membranes and the effects of arginine vasopressin (AVP) on the activities of these antiporters under isotonic conditions using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein to monitor intracellular pH (pHi). When the apical Na(+)-H+ antiporter was inhibited in the absence of AVP with removal of luminal Na+ plus addition of 0.5 mM amiloride, a small but significant increase in pHi was observed after luminal NH4Cl-induced acidification of MTAL cells to pHi less than 6.7. This increase in pHi was dependent on basolateral Na+ and inhibited with 0.5 mM basolateral amiloride, consistent with the function of a basolateral Na(+)-H+ antiporter. Basolateral AVP (100 microU/ml) enhanced the rate of pHi recovery due to the basolateral Na(+)-H+ antiporter by more than twofold. In contrast, AVP decreased the apical Na(+)-H+ antiporter activity by 50%. In the absence of AVP, addition of 0.5 mM amiloride to the luminal perfusate reduced steady-state pHi by 0.40 +/- 0.07 units, whereas exposure of the basolateral membrane to the same concentration of amiloride had no effect on pHi (delta pHi = 0.01 +/- 0.01 units). AVP reduced the magnitude of cell acidification on exposure of apical membranes to amiloride (delta pHi = 0.16 +/- 0.03) but increased the pHi response to basolateral amiloride (delta pHi = 0.09 +/- 0.00). Thus Na(+)-H+ antiporters are present on both apical and basolateral membranes of the mouse MTAL in the absence of AVP. AVP stimulates the basolateral, while inhibiting the apical, Na(+)-H+ antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1992

Maintenance of long-term secretory function by microencapsulated islets of Langerhans.

Continuous responses of insulin and glucagon to physiological challenges are essential for the maintenance of normoglycemia and for avoiding subsequent health complications. Transplantation of microencapsulated islets of Langerhans is a promising solution to obtain such a physiological system in diabetic patients. The integrity of the islets' secretory mechanism after encapsulation was studied using rat islets. Islets were isolated by collagenase digestion after which half of the islets were encapsulated with an alginate-poly-L-lysine-alginate membrane. The islets were then challenged for 24 h with glucose (0, 2.7, 5.5, or 20 mM) alone or with 0.1 mM 3-isobutyl-1-methyl-xanthine or 0.1 microM phorbol 12-myristate 13-acetate (PMA), protein kinase A and C pathway stimulators, respectively. The bathing media and cellular contents were radioimmunoassayed for insulin and glucagon. Results obtained using a three-way analysis of variance for microencapsulated and free islets demonstrated that high glucose (P less than 0.05), 3-isobutyl-1-methyl-xanthine (P less than 0.05), and PMA (P less than 0.01) increased insulin secretion, and that glucagon secretion was decreased by high glucose (P less than 0.01) but increased by PMA (P less than 0.05). Free islets secreted more insulin than those which were microencapsulated under all conditions (P less than 0.01). This appeared to be due to the encapsulation process itself, however, as islets which had been 'freed' from the capsules also exhibited a reduced capacity for insulin secretion (P less than 0.05). Analysis of the hormone content of islets after microencapsulation demonstrated reduced insulin levels (P less than 0.01), thus, accounting for the reduction in insulin secretion. As the responses of microencapsulated islets to physiological regulation by glucose and protein kinases A and C were qualitatively identical to those of free islets, transplantation of microencapsulated islets into diabetic patients could mimic the physiological responses of the normal pancreas.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Free versus microencapsulated pancreatic islet xenografts producing amelioration of streptozotocin toxicity.

This study examines the effect of pancreatic islet transplants on the streptozotocin(STZ)-associated toxicity in diabetic animals. Mice with STZ-induced diabetes were implanted with microencapsulated or free rat islets. The effectiveness of the transplant was evaluated in terms of: (A) blood glucose monitoring, (B) determination of subset levels of the helper and cytotoxic T-lymphocytes, and (C) STZ-associated mortality. The experimental results demonstrate that the transplanted islets can quickly restore normoglycemia. The restoration of normal blood glucose levels is accompanied by a significant increase in proportions of helper and cytotoxic T-cells. There was no mortality in the transplant recipients as a result of the STZ administrations, whereas a significant mortality was observed in the control group of mice. No significant differences between the encapsulated and free islet transplant recipients were observed.

Animals↗
PubMed1992

Microencapsulated pancreatic islets: a pathologic study.

Dog pancreatic islets isolated by an enzymatic digestion method were encapsulated in an alginate-poly L-lysine-alginate membrane. These microencapsulated pancreatic islets were cultured in vitro to study their ability of insulin secretion. Portions of these in vitro-cultured microencapsulated pancreatic islets were taken out for a viability dye exclusion study as well as for pathologic studies to correlate them with insulin secretion ability. We found that there was a strong correlation between them. Good insulin-secreting microcapsules showed well-preserved cell membranes and beta-cell granules. An in vitro culture for one to two days in RPMI-1640 made the islets more stable, the cellular surface became smoother and the beta-granules were in better shape. The microencapsulated pancreatic islets were also injected into the peritoneum of streptozotocin-induced diabetic CDF1 mice. Blood glucose levels dropped and stayed low for up to 60 days. But, when non-encapsulated dog pancreatic islets were used, the blood glucose levels remained low for only about 14 days. A small portion of the injected microcapsules were washed out at specific times for pathologic study. Up to 28 days after injection, only a few of the injected microcapsules showed pericapsular cellular infiltrate. However, after 56 days, most of the microcapsules showed dense pericapsular cellular infiltrate. Immunohistochemical analysis of these infiltrates showed that the majority of cells were fibroblasts and macrophages. Most of the cells located in the inner portion of the infiltrate were fibroblasts, while the macrophages were located mainly on the outer portion. Both scanning and transmission electron microscopy showed that the surface of the microcapsule outer wall was much smoother than the inner wall. The size of the microcapsules was approximately 0.6-0.8 mm and the thickness of the wall measured around 10 nm. The smaller the microcapsule is, the less chance there is of rupture with release of the xenographic islets. Once the wall of the transplanted microcapsules was ruptured, the inner surface showed more increased inflammatory cell and fibroblast infiltration than the outer surface.

Animals↗
PubMed1991

Prolonged reversal of diabetic state in NOD mice by xenografts of microencapsulated rat islets.

Transplantation of the islets of Langerhans could be the most promising approach to the clinical treatment of insulin-dependent (type I) diabetes mellitus. In this study, we report on a modified encapsulation technique that produces small alginate-polylysine capsules (0.25-0.35 mm diam). In an in vitro study, both encapsulated and unencapsulated islets showed comparable responses to glucose challenge in terms of insulin secretion. With the new capsules, 16 spontaneously diabetic NOD mice received transplants of 800 encapsulated rat islets/animal. Nonfasting blood glucose concentration decreased from 24.4 +/- 1.4 to 4.0 +/- 1.3 mM. At 4 and 5 mo posttransplantation, the capsules were removed from 2 recipients. Both animals regressed to a hyperglycemic state after capsule removal. However, after another islet transplantation, normoglycemia was again restored in these 2 animals. In control mice, which received unencapsulated islets, the xenografts remained functional for less than 10 days. A high mortality rate was observed among these animals within 2 mo of the recurrence of the hyperglycemic state. Our results clearly indicate that encapsulation of pancreatic islets in the improved capsules can effectively prolong xenograft survival without immunosuppression in an animal model that mimics human type I diabetes mellitus.

Animals↗
PubMed1990

Reversal of diabetes in BB rats by transplantation of encapsulated pancreatic islets.

Prolonged survival of pancreatic islet allografts implanted in diabetic BB rats was achieved by encapsulation of individual islets in a protective biocompatible alginate-polylysine-alginate membrane without immunosuppression. Intraperitoneal transplantation of the encapsulated islets reversed the diabetic state of the recipients within 3 days and maintained normoglycemia for 190 days. Normal body weight and urine volume were maintained during this period, and no cataracts were detected in the transplant recipients. In contrast, control rats receiving transplants of unencapsulated islets experienced normoglycemia for less than 2 wk. These results demonstrated that microencapsulation can protect allografted islets from both graft rejection and autoimmune destruction without immunosuppression in an animal model that mimics human insulin-dependent diabetes.

Alginates↗
PubMed1989

Development and evaluation of a system of microencapsulation of primary rat hepatocytes.

To determine the in vitro function of microencapsulated hepatocytes, viable hepatocytes were isolated from rats and encapsulated within biocompatible alginate-polylysine membranes for in vitro studies. Urea formation, prothrombin and cholinesterase activity, the incorporation of tritiated leucine into intracellular proteins and the immunolocation of synthesized albumin were monitored in culture. Despite a decrease in some of these activities, the cultured hepatocytes continued to function throughout the 5-week observation period, producing and excreting urea, prothrombin and cholinesterase activity into the medium. In addition, albumin could be demonstrated within encapsulated hepatocytes for up to 5 weeks. Scanning and transmission electron microscopy showed the cells to be embedded within the alginate matrix and to retain a globular shape.

Albumins↗
PubMed1989

Sodium-coupled ion cotransport and the volume regulatory increase response.

In conclusion, maintenance of volume homeostasis is a fundamental requirement of all cells. For many cell types, this process requires expression of ion cotransport mechanisms as well as accumulation of osmotically-active organic compounds. Recent observations have indicated that the cellular mechanisms responsible for modulating hypertonic volume regulation are complex and appear to involve hormonal, biochemical and physico-chemical stimuli. Knowledge of the specific ion-transport mechanisms involved in the initial phase of VRI, the factors that control their expression, and the interrelationships between inorganic and organic solute accumulation will be required before an in depth understanding of hypertonic cell volume regulation in medullary nephron segments can be achieved.

Animals↗
PubMed1989

Microencapsulated parathyroid cells as a bioartificial parathyroid. In vivo studies.

Parathyroid cells were isolated from healthy rats, encapsulated in alginate-polylysine membranes, and injected intraperitoneally into rats on which total parathyroidectomies had been performed. Three days posttransplant, serum calcium and PTH-M concentrations had increased to near-normal levels in the recipient animals. Similar results were observed in a separate group of parathyroidectomized rats 3 days after free parathyroid cells were implanted, but within 4 weeks serum calcium and PTH-M concentrations had decreased almost to pretransplant levels in these rats. In the rats with encapsulated cell transplants, by contrast, serum calcium and PTH-M levels were significantly higher, even after 8 weeks. No therapeutic effects were observed in rats injected with empty capsules or in the control group, which received no capsules or cells. These results indicate that transplants of microencapsulated parathyroid cells can temporarily reverse aparathyroidism in rats without the use of immunosuppressive drugs, and that further studies are warranted to investigate possible future clinical applications of this treatment.

Animals↗
PubMed1989

Stimulative effect of substance P on insulin secretion from isolated rat islets under normobaric oxygen incubation.

The effects of substance P (SP), physalaemin, and [D-Pro2, D-Phe7, D-Trp9]-SP on insulin release from isolated, cultured rat islets were investigated. Substance P stimulated insulin secretion in a dose-dependent manner at 0.1-100 nmol/L under one atmosphere of air with glucose 2.75, 5.5 and 20 mmol/L in the culture medium. Physalaemin 100 nmol/L was added to the culture medium, also stimulated insulin secretion. [D-Pro2, D-Phe7, D-Trp9]-SP 10 nmol/L reversed the stimulative effect of substance P. However, substance P 1 nmol/L inhibited insulin secretion from isolated rat islets under hyperbaric oxygen condations.

Animals↗
PubMed1988

Microencapsulation of pancreatic islet cells: a bioartificial endocrine pancreas.

It was about two decades ago that Chang proposed the use of microencapsulated islets as artificial beta cells. By using alginate-poly(L-lysine)-alginate membranes, biocompatible, durable capsules containing viable islet cells can be produced which are impermeable to cells and effector molecules of the immune system, thus providing a total protection to transplanted islets against rejection. The capsule wall contains 93% (w/w) water and can be classified as a hydrogel. Many hydrogels have gained general acceptance as being biocompatible materials. Microencapsulation of pancreatic islets for use as an artificial endocrine pancreas would not only obviate the need for immunosuppressive therapy but also has the potential to prevent the long-term complications of diabetes. Furthermore, the microencapsulation technique can be applied to other types of cells to produce antibodies or enzymes, and to treat a whole range of diseases requiring endocrine replacement therapy.

Alginates↗
PubMed1988

Microencapsulated hepatocytes for bioartificial liver support.

Free hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, were encapsulated within alginate-polylysine membranes and served as a liver support system. The encapsulated hepatocytes remained viable and were able to synthesize protein for up to 3 weeks in culture. Allografts of encapsulated hepatocytes replaced the function of a damaged liver and reduced the mortality rate among rats with galactosamine-induced fulminant hepatic failure.

Albumins↗
PubMed1987

Microencapsulated hepatocytes: an in vitro and in vivo study.

Using a modified alginate-polylysine membrane, we have successfully encapsulated rat hepatocytes with little loss of viability. Urea and albumin release from encapsulated liver cells was comparable to that from non-encapsulated cells during the first 4 days in culture. Histological studies also showed that more than 50% of the encapsulated hepatocytes remained viable 35 days after implantation in the peritoneal cavity of both normal rats and rats with galactosamine induced fulminant hepatic failure. Transplantation of microencapsulated hepatocytes provides a potential clinical treatment for liver failure.

Albumins↗