Interactions of cholecystokinin and glucose in rat pancreatic islets

The effects of sulfated cholecystokinin (CCK-8S) and glucose on insulin secretion and polyphosphoinositide (PPI) metabolism were studied in isolated rat islets. Both agonists stimulate PPI hydrolysis, inositol phosphate accumulation, 3H efflux from [3H]inositol-prelabeled tissue, and 45Ca efflux from prelabeled cells. However, the effects of CCK-8S on PPI metabolism are considerably greater than those of glucose. Furthermore, the effects of CCK-8S on PPI and Ca2+ metabolism are observed whether islets are incubated in either 2.75 or 7 mM glucose, but CCK-8S only stimulates insulin secretion (a biphasic response) when the higher glucose concentration is present. Addition of 1 microM forskolin to islets incubated in media containing 2.75 mM glucose does not influence basal insulin secretion but sensitizes the islets to the action of CCK-8S. In the presence of forskolin, CCK-8S induces a very marked first phase but no second phase of insulin secretion. We postulate that CCK-8S acts in this tissue via receptor-linked PPI hydrolysis, leading to an inositol trisphosphate-induced Ca2+ efflux. These receptor-mediated effects of CCK-8S are not altered either by the ambient glucose concentration or the cAMP content of the islets, but these two factors determine the responsiveness of the islets (in terms of insulin secretion) to a given CCK-8S signal.     

Early and late results of orthotopic liver transplantation

Between 4/1986 to 1/1989, 74 orthotopic liver transplantation were performed in 62 patients (62 first liver transplants, 10 as second graft and two as a third graft); 57 in adults and 17 in children. The main indication for the operation was liver cirrhosis (61.4%) (the most frequent etiology was alcoholic cirrhosis, 28.5%). Six cirrhotic patients had a hepatocarcinoma (9.6%). Two received a liver and kidney transplant due to terminal renal insufficiency and hemodialysis. The most frequent indication in children was biliary atresia (33.3%). Six patients had a fulminal liver failure (9.6%). AB0 blood group compatibility was identical in 87.5%, compatible in six and incompatible in three patients. Total orthotopic liver transplantation was performed in 67 patients, and size-reduced liver was indicated in 7 patients. Extracorporeal veno-venous bypass was used in adults but never in children. In 93.1% of the transplants a single hepatic artery was anastomosed to the recipient and in 6.9% a double anastomosis was performed. In 62.5% of the patients a end-to-end choledocho-choledochostomy was performed and in 34.8% hepatico-jejunostomy was indicated. Three months postoperative mortality rate was 12.9%. Arterial stenosis and thrombosis were the most frequent complication.     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.