Induction of islet cytodifferentiation by fetal mesenchyme in adult pancreatic ductal epithelium.

Recombinant tissue consisting of adult ductal epithelium isolated from pancreas and fetal mesenchyme was transplanted subcutaneously in the inguinal region of nude mice or epididymal fat pads of rats with a tissue chamber device for short-term (8-day) or long-term (6- to 12-wk) duration. We found that recombinant tissue underwent morphogenesis and cytodifferentiation, thereby forming islets that contained cells immunocytochemically positive for insulin and glucagon. Islet cytodifferentiation occurred in approximately 20% of the recombinants. In recombinants that developed into islets, the tissue was always in close association with an extracellular matrix, nerves, and blood vessels. Controls consisting of mesenchyme alone or duct epithelium alone showed no evidence of morphogenesis of cytodifferentiation. Pancreatic rudiments were also implanted to serve as positive controls. This is the first demonstration of islet cytodifferentiation from adult duct epithelium.     

Porcine colostrum and milk stimulate visceral organ and skeletal muscle protein synthesis in neonatal piglets.

Our objective was to determine the relative contributions of protein synthesis and protein absorption in the rapid accretion of gastrointestinal protein in suckling piglets during the early neonatal period. We measured the rates of tissue protein synthesis using a flooding dose of L-[4-3H]phenylalanine in various visceral and peripheral tissues of neonatal piglets fed water, mature milk or colostrum for 6 h. The jejunal and ileal protein synthesis rates in piglets fed either colostrum or milk were three- to fourfold higher than in piglets fed water. The increased jejunal and ileal protein synthesis could not, however, account for the differences in protein mass between the colostrum-fed and water-fed groups. The relative abundance of IgG, a major porcine colostral protein, in jejunal tissue was markedly higher in piglets fed colostrum than in piglets fed either milk or water. The fractional protein synthesis rates in liver, kidney, spleen and skeletal muscle and the absolute protein synthesis rates in liver and spleen were also greater in piglets fed colostrum than in those fed milk or water. Increased endogenous protein synthesis made only a minor contribution to the increased intestinal protein accretion in neonatal piglets fed colostrum. A much larger proportion of this increase seemed to be a result of absorption and retention of ingested immunoglobulins.     

NMR Investigation of the Futile Cycling of Ethanol in Chronic Alcoholic Rats

Weight gain efficiency differences previously reported between alcohol-fed rats and their controls were investigated. Additionally, the futile cycling of ethanol proposed to explain such differences was studied by NMR spectroscopy. Male Sprague-Dawley rats were fed a nutritionally adequate diet containing 36% of the calories as alcohol, and their paired controls were fed an isocaloric diet for 1 f weeks to establish conditions of chronic alcohol feeding. Normalized metabolic efficiencies varied significantly during the initial 2-week period (6.86 ± 0.51 vs. 2.83 ± 0.18 g/kcal × 10⁻²) for control and alcohol-fed groups, respectively, and to a lesser extent over the entire feeding period (6.41 ± 0.78 vs. 4.60 ± 0.27 g/kcal × 10⁻²) for control and alcohol-fed groups, respectively. Alcohol-induced weight gain inefficiency in metabolism has previously been studied and explained by a variety of different biochemical and physiological mechanisms. One possible pathway of energy wastage may occur due to ethanol futile cycling from ethanol to acetaldehyde through the microsomal ethanol oxidation system pathway, and simultaneously from acetaldehyde to ethanol via the ADH pathway. This futile cycle represents a net loss of 6 ATP/cycle, corresponding to the loss of two reducing equivalents (NADH and NADPH). 1H NMR spectroscopy was used to test for this cycling in blood extracts after administration of 1,1-²H₂ ethanol. No futile cycling was detected either during the initial 2 weeks of feeding or after the entire feeding period.     

Anabolic effect of prostaglandins

Prostaglandins, particularly PGE₂, have been shown to stimulate bone formation in a number of circumstances. Endogenous prostaglandins may be important in heterotopic ossification and fracture healing. The major source of prostaglandins in bone is the inducible form of cyclooxygenase (COX)-2 and inhibition of COX-2 may impair bone formation. Recent studies using selective agonists for the prostaglandin EP2 and EP4 receptors, which stimulate cAMP in bone cells, have suggested that these might be used clinically to accelerate bone formation, particularly when used locally.     

Radical forequarter amputation with hemithoracectomy and free extended forearm flap: Technical and physiologic considerations

Background: A radical forequarter amputation with partial chest wall resection (one to four ribs) has been reported for benign and malignant lesions involving the shoulder and chest wall region. Concerns about reconstruction and postoperative pulmonary function have previously limited more extensive chest wall resections. The current report describes the first case in which a complete unilateral anterior and posterior chest wall resection and pneumonectomy (hemithoracectomy) accompany a forequarter amputation. A novel reconstructive technique used the full circumference of the forearm tissue with an intact ulna as a free osseomyocutaneous flap. Methods: In this case, a 21-year-old patient presented with an extensive recurrent desmoid tumor that involved the shoulder, brachial plexus, subclavian vein, and chest wall from the lateral sternal border to the midportion of the scapula and down to the eighth rib. The operative technique involved removal of the entire right hemithorax from the midline sternum to the transverse process posteriorly, down to the ninth rib inferiorly. Due to the absence of a rigid hemithorax, the uninvolved ipsilateral lung was also removed. The forearm flap was prepared before final separation of the specimen and division of the subclavian vessels. Results: Postoperatively, the patient maintained excellent oxygenation without atelectasis or fever and was extubated on the 15th postoperative day. As expected after pneumonectomy, significant decreases from preoperative to immediate postoperative values were noted for the vital capacity (VC) (from 4.87 L to 1.29 L), forced 1-s expiratory volume (FEV1) (from 3.77 L to 1.02 L), and inspiratory capacity (IC) (3.33 1 to 0.99 1). Rehabilitation included a specially designed external prosthesis to provide cosmesis and prevent scoliosis. By the 15th postoperative week the patient had returned to normal social and physical activities, with a gradual improvement in all respiratory parameters: VC 1.52 L, FEV1 1.29 L, IC 1.04 L. There has been no evidence of tumor recurrence at 1 year. Conclusions: This report provides evidence that a complete hemithoracectomy, pneumonectomy, and forequarter amputation can be safely performed for selective tumors involving the shoulder region with extensive chest wall invasion. Reconstruction may be achieved with an extended forearm osseomyocutaneous free flap with an excellent functional outcome. Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

Persistent Hypotension Associated with Hypermedullipinemia: A New Syndrome

A new syndrome is described in a patient with advanced renal insufficiency. This consists of severe and persistent hypotension causing weakness but associated with a clear mental status. Also present is evidence for decreased vascular reactivity. The hypotension was not orthostatic. The hypotension was associated with a circulating vasodepressor substance having the characteristics of medullipin I. The medullipin appears to have been derived from the remaining right kidney. Hypotension existed despite the presence of major prohypertensive mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia. It is likely that hypotension due to hypermedullipinemia is an entity occurring in the human being.