Bioartificial endocrine pancreas: foreign-body reaction and effectiveness of diffusional transport of insulin and oxygen after long-term implantation of hollow fibers into rats.

Foreign body reaction of the liver, kidney, and subcutaneous tissue of rats after implantation of hollow fibers (HF) for 1, 3, 6, and 12 months and its influence on the effectiveness of diffusional transport of insulin and oxygen were investigated. The highest degree of fibrosis was observed after subcutaneous implantation of HF and the lowest degree after implantation into the kidney. Histochemical staining of the fibrous capsule showed a tissue-dependent domination of the collagenous fibrils. After 90 min of perfusion 33% of the insulin contained in HF diffused out of the nonimplanted fiber, after 120 min, 73% and after 180 min, 100%. Hollow fibers, which were removed with a surrounding connective capsule after an implantation period of 1 year, showed even better permeability for insulin than nonimplanted HF. The tension of oxygen in the lumen of the implanted hollow fibers was 42 mm Hg after implantation into the kidney and 30 mmHg after implantation into the liver. The oxygen present inside an HF that is implanted into a kidney and liver was consumed by 100 islets in 3.9 and 2.8 min, respectively. It was concluded that to achieve acceptable results in the construction of bioartificial pancreas more research activities should be performed on the diffusion and consumption of oxygen in the bioreactor.

Pancreatic islets obtained from pancreases with short-term exocrine atrophy disturbed morphology but normal in vitro response to various stimuli.

The morphology and function islets isolated from rat pancreases with short-term (16 days) exocrine atrophy was investigated. It was found that this type of atrophy induced changes in the shape and morphological structure of pancreatic islets. However, the function of isolate islets did not change, as investigated by the basal or glucose-stimulated secretion of insulin, glucagon and somatostatin, and by the CCK-stimulated secretion of insulin. We conclude that the rat pancreas brought to atrophy by a short-term ligation of the pancreatic duct can be considered as a rich source of functionally viable islets.

In vitro secretion of hormones from the islets of pancreas with acinar atrophy--influence of digestion with collagenase.

The release of insulin, glucagon and somatostatin from islets isolated by microdissection, and islets isolated by aid of different duration of collagenase digestion from pancreases with exocrine atrophy was assessed. Prior collagenase digestion caused an increased release of insulin and glucagon, but not somatostatin; also, the non-suppressibility of glucagon secretion despite high glucose concentration in the medium was characteristic for those islets. Additional data suggest that in the absence of intrinsic pancreatic proteases the nature of the damage conferred by collagenase to islet B- and A-cells is different. In the light of action of epinephrine, an inhibitor of insulin secretion, possible mechanisms responsible for disturbed hormone release in the presence of proteolytic enzymes are discussed.

Pancreatic perivascular lipid droplets--observations on adverse effects in the rat.

A standardized method for the isolation of so-called pancreatis perivascular lipid droplets (PPD) together with cells scattered on their surface is described. After implantation of PPD into the diabetic rat, a long term increase in glycaemia was found. After prior damage to PPD by the actions of enzymes a shortening of the post implantation survival period or even death of recipients within hours was observed. Possibility of participation of PPD in toxic effects observed during pancreatitis is discussed.

[Functional estimation of the isolated islands of Langerhans in semipermeable membrane chambers]. / Funktionsbeurteilung isolierter Langerhansscher Inseln in semipermeablen Kammern.

The possibility for the use of membranes of regenerated cellulose was tested for constructing semipermeable chambers for the cultivation and implantation of the isolated islets of Langerhans. The membranes of regenerated cellulose was well-permeable for insulin. An implantation for one month had no influence at the rate of diffusion of insulin. This shows that the pores of the membrane were not occluded by protein. The occlusion of the pores was one of the greatest hindrances for the use hitherto. The islets of Langerhans in semipermeable chambers with membranes of regenerated cellulose showed a sufficient glucose utilization and lactate production during the whole investigation period within 37 days. A considerable decrease of the insulin secretion of the islets in the chambers was to be observed especially in the first 14 days of the experimental period.

[Treatment of diabetes by implantation of isolated islands of Langerhans in semipermeable chambers]. / Die Behandlung des Diabetes durch Implantationen von isolierten Langerhansschen Inseln in semipermeablen Kammern.

The biological tolerance of chambers with membranes of regenerated cellulose and the influence of the implantation of isolated islets of Langerhans in these chambers on the blood sugar level of rats with experimental diabetes was investigated. It was concluded that retroperitoneal space offers the best conditions for the implantation of such chambers. The technique of implantation and the preparation of the chambers are the critical factors for the degree of foreign body reaction. The implantation normalized the blood sugar level in rats with an experimental diabetes of a slight degree for a duration of 3 weeks and the glycemia in severe diabetes was soothed for the period of 11 days.

A method for inducing exocrine atrophy and collecting juice from the nonatrophied pancreas in the rat.

A method for the long-term diversion of bile in the rat is described. It was used to induce complete and uniform pancreatic exocrine atrophy, as confirmed by a marked loss of weight of the gland, very low pancreatic tissue amylase, and by histological examination. The technique induces changes in endocrinal function of the pancreas, since it increases pancreas insulin by a factor of 2.7, decreases glucagon by a factor of 0.19, and somatostatin by a factor of 0.6. The method was also used for collecting juice from the nonatrophied pancreas in the conscious rat, and may facilitate studies on pancreas physiology and pathophysiology.

Monitoring treatment of pulmonary carcinomas by serial determination of monoamine oxidase and diamine oxidase in blood serum.

We investigated monoamine oxidase (MAO--E.C. 1.4.3.4.) and diamine oxidase (DAO--E. C. 1.4.3.6.) in the serum of patients with lung cancer, treated with chemo- and radiotherapy. These enzyme activities were determined with tyramine and putrescine as substrates. The MAO activities of serum and DAO serum increased notably in some cases of lung cancer. These results are discussed in light of the postulated role of this enzyme in cell division and in the tumor development process.