Experimental isolation and transplantation of hepatocytes with the use of antibody against interleukin-2 receptor (daclizumab) as immunosuppressive agent.

INTRODUCTION: Daclizumab (Dmab) is a genetically engineered humanized IgG1 monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (Tac, CD25, p55) expressed on activated human T lymphocytes. Dmab has been used in a clinical protocol of islet transplantation with satisfactory results. The aim of the present study was to evaluate the use of an antibody against the interleukin-2 receptor (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte allotransplantation (allo-Tx) in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 48 Lewis rats as recipients: four groups of 12 animals each with induction of FHF and 24 hour later hepatocyte Tx--group A: no treatment; group B: cyclosporin (20 mg/kg days 0 to 5 and 10 mg/kg days 6 to 15); group C: Dmab (0.05 mg day of Tx and 0.05 mg day 7); and group D: Dmab and cyclosporine. Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: Statistical analysis showed better survival among groups C (83%, MST = 13) and D (92%, MST = 14.25) compared to groups A (max 72, MST = 1.5) or B (50%, MST = 9). Survival in group D was better but not significantly than group C. Biochemical evaluation and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model showed the safe, effective use of Dmab.

Intracellular diglycerides in relation to glycaemic control in the myocardium: A pilot study in humans.

AIM: Intramyocellular diglycerides have been implicated in the development of insulin resistance in skeletal muscle. In the myocardium, excess lipid storage may also contribute to the appearance of diabetic cardiomyopathy, while diglycerides may have certain cardio-protective functions. However, little is known on intracellular diglyceride accumulation in the human heart. We aimed to determine diglyceride accumulation in the human myocardium in relation to diabetes status. METHODS: Six diabetic and six non-diabetic aged human subjects undergoing by-pass surgery participated in the study. Subjects were matched for age and body mass index. Intracellular diglyceride levels were measured in heart biopsy samples. Additional samples were taken from pectoralis major muscle that served as control. Whole body glycaemic control was assessed as the percent glycated haemoglobin. RESULTS: Intracellular diglycerides were significantly higher in the myocardium compared to pectoralis major (P<0.05). Although not statistically significant, diabetic subjects tended to accumulate smaller amounts of diglycerides compared to non-diabetic subjects in the myocardium. A linear negative correlation was observed between myocardial diglycerides and glycaemic control (r=0.632, P<0.05). CONCLUSIONS: Our data suggest that poor glycaemic control and diabetes may be associated with a defective accumulation of myocardial diglycerides, possibly blunting intracellular processes and contributing to the development of cardiomyopathy.

Videothoracoscopic surgery.

Although thoracoscopy has been used for diagnostic and minor therapeutic procedures for many years, there have been few reports of its use in performing major intrathoracic procedures which have traditionally required formal thoracotomy. We report our initial experience in this field. Fifty patients (M:F = 1.63:1, mean +/- SD age = 41.8 +/- 20.4 years, range = 14-80) underwent 54 endoscopic intrathoracic operations. The procedures carried out included wedge excision of solid pulmonary mass (10), pleurectomy (25), lung biopsy (14), and miscellaneous procedures (5). Under general anaesthesia a laparoscope attached to a video monitor was introduced into the chest. One or two additional stab incisions were made as needed for the introduction of standard surgical or endoscopic instruments and staplers. There were no deaths. One patient developed a second pneumothorax 7 days after endoscopic pleurectomy, necessitating open pleurodesis. All patients were discharged home between 2 and 11 days after surgery (mean +/- SD = 3.8 +/- 2.0 days). Endoscopic thoracic surgery is a safe and useful technique for certain cases. It merits further investigation and assessment.

Use of mycophenolate mofetil in the experimental allo-transplantation of hepatocytes in rats with fulminant hepatic failure.

AIM: The aim of the study was to evaluate the beneficial effect of mycophenolate mofetil (MMF) as an immunosuppressive agent for experimental transplantation of hepatocytes in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 40 Lewis rats at recipients, including four groups of 10 animals each. Group A received no treatment; Group B, cyclosporine (20 mg/kg days 0-5 and 10 mg/kg days 6-15); Group C, MMF (12 mg/kg per os every day); and Group D, MMF (23 mg/kg per os every day). Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: The survival rates for Group A were maximum 72 h, whereas Groups B, C, and D showed 50%, 70%, and 80%, respectively. Biochemical evaluation and histology showed satisfactory function and engraftment, respectively. CONCLUSION: The use of MMF in this experimental model yielded safe, satisfactory immunosuppression especially at the dose of 23 mg/kg.