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Biomedical subjects

E Morsiani

Publications and source records attributed to E Morsiani.

At least 37 records · Page 2Linked to original sources

Teleost fish islets: a potential source of endocrine tissue for the treatment of diabetes.

Anatomical separation of pancreatic islets in some teleost fish makes them a useful source of pancreatic endocrine tissue. Islets were harvested from tropical Tilapia fish (Oreochromis nilotica) and cultured for 24 hr at 37 degrees C. Eight athymic nude mice were rendered diabetic by streptozotocin (STZ) and transplanted under the kidney capsule with fish islets. After transplantation (Tx), nonfasting blood glucose (n-FBG), which was in all recipients > 450 mg/dl, decreased to < 100 mg/dl. At 4 and 7 weeks post-Tx, the intraperitoneal (ip) glucose tolerance test was performed in the normoglycemic Tx mice and in six normal controls. In controls, K value (percentage of decline in blood glucose/min) was 1.076 +/- 0.383 and in Tx mice it was 0.956 +/- 0.336 and 0.869 +/- 0.483 at 4 and 7 weeks, respectively (P = n.s.). Nephrectomy raised the n-FBG to pre-Tx levels. On immunohistochemistry, recipient's pancreata showed atrophic islets with no beta-cell granules, while the islet-bearing kidneys had distinct beta-cells under their capsules. Alginate-embedded fish islets were encapsulated in permselective (25-kDa) cellulose membranes and implanted ip in six STZ-diabetic nude mice. On the following day, all recipients became normoglycemic and their n-FBG remained normal for 7 days. In one animal, the n-FBG was < 200 mg/dl for 14 days and subsequent removal of the capsule raised the n-FBG to the pre-Tx level. Finally, it was found that fish islets can be cultured at 37 degrees C for extended periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Early clinical experience with a hybrid bioartificial liver.

BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation.

Adult↗

Increased sinusoidal wall permeability and liver fatty change after two-thirds hepatectomy: an ultrastructural study in the rat.

Accumulation of lipids in the hepatocyte cytoplasm after partial hepatectomy (PH) has long been recognized, but the mechanism behind this phenomenon is still poorly understood. In this study, rats subjected to a standard two-thirds PH showed early and marked increase in portal venous pressure (P < .01). On scanning electron microscopy, the regenerating liver fixed by portal perfusion under hemodynamic conditions identical to that found in vivo during the first 24 hours showed a significant (P < .01) 10-fold increase in the sinusoidal wall porosity (percentage open area by fenestrations). This was paralleled by the disappearance of the sieve-plate arrangement of small fenestrations and by a significant decrease in the number of fenestrations per micrometers squared of sinusoidal surface at 6 (P < .01) and 12 hours (P < .05). In addition, there were major changes in the frequency and distribution of all three classes of fenestrations. At 6 and 12 hours, there was a marked decrease of small class 1 fenestrations and a marked increase of intermediate class 2 fenestrations and large class 3 fenestrations (P < .0001). A concurrent accumulation of lipid droplets in the hepatocyte cytoplasm produced a 20-fold increase in the hepatocyte total lipid volume. A statistically significant linear correlation (r = 0.907; P < .01) was found between the amount of intracellular lipids and the data quantitating the changes in porosity of liver sinusoids at 24 hours. It is concluded that an increased sinusoidal wall permeability to lipids may be the primum moves in the pathogenesis of transient liver fatty change after PH in the rat.

Animals↗

A bioartificial liver to treat severe acute liver failure.

OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients.

Adolescent↗

Control of cerebral oedema by total hepatectomy and extracorporeal liver support in fulminant hepatic failure.

Keeping a patient with fulminant hepatic failure (FHF) alive until a donor liver is available for transplantation can be a problem. We describe an 18-year-old woman with paracetamol-induced FHF, who was treated by total hepatectomy, hypothermia, plasma exchange, and extracorporeal liver support. The patient was anhepatic for 14 h. The liver-support system consisted of plasma separation and perfusion through a charcoal filter and a hollow-fibre module seeded with matrix-attached porcine hepatocytes. With artificial liver treatment there was reversal of severe neurological dysfunction, normalisation of intracranial pressure, and decreased serum ammonia. The patient underwent emergency transplantation with an ABO-incompatible liver, followed by transplantation with a compatible organ eight days later. The patient has fully recovered and is neurologically intact.

Adolescent↗

Effect of low-temperature culture and L3T4 antibody on the survival of pancreatic islets xenograft (fish to mouse).

Catfish (Ictalurus punctatus) islets were transplanted into the renal subcapsular space of diabetic C57BL/6J mice. The xenograft mean survival time (MST) of islets cultured for 6 days at 24 degrees C was 4.9 +/- 0.5 days, while xenotransplantation of 1-hour-cultured islets did not restore normoglycemia in the diabetic mice. A modest but significant prolongation of the MST was obtained by administration of anti-L3T4 monoclonal antibody to the recipients (13.4 +/- 2.1 days). Anti-L3T4 in conjunction with low-temperature culture did not produce a further increase of the MST (9.1 +/- 2.7 days). These findings indicate that catfish islets may be a source of islet tissue for transplantation in diabetic recipients. However, procedures that demonstrated to be effective in prolonging the MST of xenografts transplanted across wide species barrier, such as low-temperature culture and anti-L3T4 treatment, failed to prolong markedly the xenograft survival. Further experimental work is needed to study the possibility of improving islets survival after xenotransplantation across distant species barrier (fish to mouse).

Animals↗

Effect of intravenous and intraperivenous injections of sclerosants (sodium tetradecyl sulfate and hydroxy polyethoxy dodecan) on the rat femoral vein.

The sclerosant effect of injected tetradecyl sulfate of sodium (STS) and hydroxy polyethoxy dodecan (HPD) was studied in the rat femoral vein. Intravenous (i.v.) and intravenous plus perivenous (i.v. + p.v.) injections of both sclerosants and physiologic saline were compared as to vein lumen occlusion, fibrosis, phlogosis, and damage to the artery and surrounding nervous and muscular tissues. The study was carried out in 30 rats treated by STS, in 30 treated by HPD, and 15 animals were injected with saline. The neurovascular bundle and adjacent muscle were removed at 48 h, 7 and 30 days and examined histologically. I.v. injections of STS produced a solid occlusion of the vein in a significant number of cases, after 30 days (P less than 0.01). A statistically significant number of solid occlusions of the femoral vein resulted after i.v. + p.v. injection of STS and HPD, at 48 h, 7 and 30 days (P less than 0.05; P less than 0.01). There was no significant difference between STS and HPD after i.v. + p.v. injection. After i.v. + p.v. we recorded a marked inflammation of muscle with signs of focal necrosis, at 48 h and 7 days. Our study indicated that i.v. + p.v. injection of STS and HPD provided a high degree of efficacy as regards vein occlusion. On the other hand, i.v. + p.v. injection induced a severe inflammation and necrosis of the tissues surrounding the sclerosed vein. Extrapolating our results to the endoscopic sclerotherapy for esophageal variceal bleeding, we conclude that paravariceal injection of sclerosants is a dangerous procedure, even though efficacious to reduce variceal hemorrhage, owing to the high risk of iatrogenic ulcers and esophageal perforation caused by muscular and mucosal necrosis.

Animals↗

Argyrophil cells in the rat duodenum after gastrectomy.

Two different techniques of reconstruction after total gastrectomy were performed in rats: Roux-en-Y (RY) and jejunal interposition (JI). Sham-operated rats were used as controls. Sixteen weeks after surgery the animals were sacrificed. The distribution of the enteroendocrine cells in the duodenal and proximal jejunal mucosa was examined using the Grimelius silver nitrate stain. The frequency of the Grimelius-positive cells was estimated as number of cells per square millimeter of gut surface and as number of cells per transverse section of intestine. Intestinal villi height was also measured in the same duodenojejunal tracts. After gastrectomy, the JI rats showed a better weight gain than RY rats (p less than 0.05). A significant difference in the distribution of intestinal argyrophil cells was seen. The bypassed duodenojejunal tracts in RY rats showed a marked reduction of the Grimelius-positive cells in comparison with JI rats and controls (p less than 0.01). A reduction in the number of argyrophil cells in the proximal duodenum was also noticed in the JI rats in comparison with controls (p less than 0.01). A decrease in the villi height resulted in all the gastrectomized rats (p less than 0.01), but a significant decrease was also noticed in RY rats in comparison with JI (p less than 0.01). Our experimental observations suggested that the exclusion of the duodenum from intestinal transit after gastrectomy caused atrophy of the gut mucosa and a marked reduction in the number of argyrophil enteroendocrine cells in the bypassed tracts.

Anastomosis, Roux-en-Y↗

The origin of bile ductular-like structures after transplantation of regenerating hepatocytes into the spleen of syngeneic rats.

Normal and 24-h regenerating hepatocytes were transplanted into the spleen of 70% partially hepatectomized, syngeneic rats, which were sacrificed after 2, 4, 6, 10, and 12 months from the transplant. Altogether 50 rats served as recipients. Histological examination of splenic sections showed a small number of surviving hepatocytes both in normal hepatocytes recipients and in the regenerating hepatocytes recipients. In the latter group marked bile ductular proliferation was present from 4 to 12 months after transplantation. This experimental evidence supports the theory that intrahepatic bile duct cells can originate from hepatocytes.

Animals↗