A series of N-mustard derivatives of 9-anilinoacridine was synthesized for antitumor and structure–activity relationship studies. The alkylating N-mustard residue was linked to the C-3′ or C-4′ position of the anilino ring with an O-ethylene (O–C2), O-butylene (O–C4), and methylene (C1) spacer. All of the new N-mustard derivatives exhibited significant cytotoxicity in inhibiting human lymphoblastic leukemic cells (CCRF–CEM) in culture. Of these agents, (3-(acridin-9-ylamino)-5-{2-[bis (2-chloroethyl)amino]ethoxy}phenyl)methanol (10) was subjected to antitumor studies, resulting in an approximately 100-fold more potent effect than its parent analogue 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) in inhibiting the growth of human lymphoblastic leukemic cells (CCRF–CEM) in vitro. This agent did not exhibit cross-resistance against vinblastine-resistant (CCRF–CEM/VBL) or Taxol-resistant (CCRF–CEM/Taxol) cells. Remarkably, the therapeutic effect of 10 at a dose as low as one tenth of the Taxol therapeutic dose [i.e., 1–2 mg/kg (Q3D × 7) or 3 mg/kg (Q4D × 5); intravenous injection] on nude mice bearing human breast carcinoma MX-1 xenografts resulted in complete tumor remission in two out of three mice. Furthermore, 10 yielded xenograft tumor suppression of 81–96% using human T-cell acute lymphoblastic leukemia CCRF–CEM, colon carcinoma HCT-116, and ovarian adenocarcinoma SK-OV-3 tumor models.

It has been recently observed that the dominant factor on network performance after a failure in a packet switched network is the transient or nonstationary congestion period triggered by the backlog of packets due to retransmission after a failure. Given this observation, we address the survivable network design problem for VP-based ATM networks by introducing the transient time threshold to clear backlog as one of the quality-of-service parameters and present a design framework. Through computational work on test networks, we observe that if this parameter is not incorporated, a network (where services do backlog traffic after a failure) may be under designed resulting in noticeably longer transient period than any acceptable threshold.

The utilization and distribution of radioactively labeled lipid emulsions were evaluated in Sprague-Dawley rats. Animals received one of three lipid emulsions. Group 1 received [14C]medium-chain-triglyceride (MCT) lipid emulsion, group 2 received a 75%:25% (vol:vol) admixture of [14C]MCT: unlabeled long-chain-triglyceride (LCT) lipid emulsion, and group 3 received only [14C]LCT. The radioactive dose appearing in expired carbon dioxide and various body tissues was monitored over a 24-h period. Results indicate that MCT is oxidized more rapidly and completely than in LCT; approximately 90% of the MCT is converted to carbon dioxide with in 24 h compared with 45% for LCT. When MCT and LCT are administered together, the metabolism of MCT is slowed but remains more rapid than that of LCT. Removal of MCT from the blood was more rapid than was removal of LCT, and tissue radioactivity was lower.

This study was conducted to assess the potential metabolic competitive interactions of intravenous medium-chain-triglyceride (MCT) and long-chain-triglyceride (LCT) lipid emulsions. To assess this competition increasing concentrations of LCT emulsion were added to an intravenous dose of MCT emulsion of 3.0 g/kg body wt up to a maximum dose of 3.0 g LCTs/kg body wt. Blood samples were assessed for competitive interactions by analyzing the following metabolites: glucose, insulin, lactate, pyruvate, ketones (acetoacetate, beta-hydroxybutyrate), elimination of triglycerides, and free fatty acids. Evaluation of the data showed a strong competitive interaction between the MCT and LCT emulsions. This competition was evident as soon as LCTs were added to the MCT infusions and appeared to favor LCTs for removal and metabolism over MCTs. This appears to indicate that there is a peripheral, strong affinity site for LCT removal and metabolism and a shared peripheral site and specific visceral site for MCT removal and metabolism.

The ability of soybean oil lipid emulsions to affect essential fatty acid deficiency (EFAD) and plasma fatty acid distribution was studied in neonatal pigs. The test animals were maintained on a fat-free diet prior to administration of lipid emulsion. Plasma and red blood cell (RBC) membrane levels of essential [linoleic (C-18:2 omega 6) and arachidonic (C-20:4 omega 6)] and nonessential [palmitic (C-16, palmitoleic (C-16:1 omega 7), stearic (C-18), and oleic (C-18:1 omega 9)] fatty acids and the triene:tetraene ratio [5,8,11-eicosatrienoic acid (C-20:3 omega 9):arachidonic acid (C-20:4 omega 6)] were monitored to ascertain the establishment of EFAD and its correction. Nonessential fatty acids were studied, as these components of lipid therapy have received little attention. Results indicate that soybean oil emulsions are effective in reversing fatty acid profiles found in EFAD, and both essential and nonessential fatty acids are under strict metabolic control.

Equine Veterinary JournalVolume 20, Issue s5 p. 17-18 The evolution of clinical nutrition in the critical care of the neonate R. COTTER, R. COTTER Clintec Nutrition Company, Baxter Healthcare Corporation, 1425 Lake Cook Road, Deerfield, Illinois 60015, USASearch for more papers by this author R. COTTER, R. COTTER Clintec Nutrition Company, Baxter Healthcare Corporation, 1425 Lake Cook Road, Deerfield, Illinois 60015, USASearch for more papers by this author First published: September 1988 https://doi.org/10.1111/j.2042-3306.1988.tb04629.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Andrew, G., Chan, G. and Schiff, D. (1976) Lipid metabolism in the neonate II. The effect of intralipid on bilirubin binding in vitro and in vivo. J. Pediat. 88, 279. 10.1016/S0022-3476(76)81000-1 CASPubMedWeb of Science®Google Scholar Bain, K. (1948) The incidence of breastfeeding in hospitals in the United States. Pediatrics 2, 313. CASPubMedWeb of Science®Google Scholar Drummond, W.H. (1985) Equine neonatology: Birth to adolescence in five years: 1980-85. Proceedings from the Veterinary Medicine Symposium "Equine neonatal intensive care and parenteral nutrition for large animal patients" hosted by Travenol Laboratories. pp 1–13. Google Scholar Fomon, S.J. (1974) In: Infant Nutrition. W.B. Saunders, Philadelphia. Google Scholar Greene, H.L., Hazlett, D. and DeMaree, R. (1976) Relationship between intralipid-induced hyperlipemia and pulmonary function. Am. J. Clin. Nutr. 29, 127. CASPubMedWeb of Science®Google Scholar Heird, W.C. and Winters, R.W. (1975) Total parenteral nutrition - the state of the art. J. Pediat. 86, 2–16. 10.1016/S0022-3476(75)80697-4 PubMedWeb of Science®Google Scholar Johnson, R.C. and Cotter, R. (1986) Metabolism of medium-chain lipid emulsion. Nutr. Int. 2, 150–158. CASGoogle Scholar Meyer, H.F. (1958) Infant feeding practices in hospital maternity nurseries. A survey of 1.904 hospitals involving 2,225.000 newborn infants. Pediatrics 21, 288. CASPubMedWeb of Science®Google Scholar Pereira, G.R. and Glassman, M. (1986) Parenteral nutrition in the neonate. In: Parenteral Nutrition. W.B. Saunders, Philadelphia. pp 702–720. Web of Science®Google Scholar Rivera, J. (1971) The frequency of use of various kinds of milk during infancy in middle and lower-income families. Am. J. Public Health 61, 277. 10.2105/AJPH.61.2.277 CASPubMedWeb of Science®Google Scholar Rombeau, J.L. and Caldwell, M.D. (1984) In: Enteral and Tube Feeding. W.B. Saunders, Philadelphia. Google Scholar Rombeau, J.L. and Caldwell, M.D. (1986) In: Parenteral Nutrition. W.B. Saunders, Philadelphia. Google Scholar Rudman, D. and Feller, A. (1986) Evidence for deficiencies of conditionally essential nutrients during total parenteral nutrition. J. Am. Col. Nutr. 5, 101–106. 10.1080/07315724.1986.10720117 CASPubMedWeb of Science®Google Scholar Salber, E.J. and Feinleib, M. (1966) Breast-feeding in Boston. Pediatrics 37, 299. CASPubMedWeb of Science®Google Scholar Truswell, A.S. (1985) ABC of nutrition. Infant feeding. Brit. Med. J. 291, 333–335. 10.1136/bmj.291.6491.333 CASPubMedWeb of Science®Google Scholar Wilmore, D.W. and Dudrick, S.J. (1968) Growth and development of an infant receiving all nutrients exclusively by vein. J. Am. med. Ass. 203, 860. CASPubMedWeb of Science®Google Scholar Volume20, Issues5September 1988Pages 17-18 ReferencesRelatedInformation

To evaluate how rapidly and to what extent a lipid emulsion rich in n-3 fatty acids could alter platelet function, six male juvenile African Green Monkeys (4-6 kg) were given a 6-hour IV continuous infusion of a 10% marine oil (MO) lipid emulsion (5 ml /kg/hr). Following a 21-day washout period, the same monkeys were given a similar infusion of a 10% soybean oil (SO) lipid emulsion (TRAVAMULSION®, Travenol Labs). Blood samples were collected pre-infusion, and at 6, 12, and 24 hours following initiation of infusion, upon which the following were measured: whole blood platelet aggregation and thromboxane B2 release following collagen activation, platelet count, and platelet total fatty acid composition (pre-infusion and 24 hrs only). Lipid Emulsion Fatty Acid Composition: mg/ml(% total F.A.) Both emulsions elicited comparable reductions in both platelet aggregation and thromboxane B2 release immediately following infusion (6 hr). Platelet aggregation response after MO was significantly less than that after SO at both 12 (pc.001) and 24 hrs (p<.001), and thromboxane B2 release was significantly less after MO vs SO at 24 hrs (p<.03). Platelet counts remained unchanged after both treatments. Platelet total fatty acid analyses revealed significant increases in % total F.A. for C20:5 [1.87(pre) vs 4.79(24hr); p<.005] and for C22:6 [1.09(pre) vs 3.15(24hr); p<.001] and significant decreases in % total F.A. for C18:2 [8.94(pre) vs 7.77(24hr); p<.05] and C20:4 [22.6(pre) vs 19.6(24hr) p<.05], following infusion of M0. Following infusion of SO, the % total F.A. change in C22:6 was the only one of significance [0.85(pre) vs 1.25(24hr); p<.05]. This was attributed to the C18:3 in the SO lipid emulsion. Whereas the IV infusion of an n-6 rich lipid emulsion has little effect upon platelet fatty acid composition and function, similar administration of an n-3 rich lipid emulsion markedly reduces platelet function and effects a significant increase in the n-3/n-6 fatty acid ratio of the platelets.

Two 20% lipid emulsions containing mixtures of long-(LCT) and medium-chain triglycerides (MCT) were compared with a 20% LCT lipid emulsion. Beagles were infused with emulsions containing either 100% LCT, 75% LCT-25% MCT, or 50% LCT-50% MCT. The emulsions were part of a total parenteral nutrition (TPN) regimen that included 10% dextrose and 5.5% amino acids. Basic nutritional parameters as well as elimination kinetics were monitored. Plasma linoleic acid, ketone, lactate, pyruvate, insulin, glucose, and carnitine were analyzed. The 75% LCT-25% MCT emulsion offers little advantage over 100% LCT as a metabolic substrate. The 50% LCT-50% MCT combination proved to be a potentially better caloric source due to rapid elimination kinetics, increased ketone production, lack of deposition, and no interference with linoleic acid metabolism.

The heavy ion linear accelerator of the Institut de Physique Nucleaire has been used to study the influence of the projectile charge state q i on secondary ion emission. Ions of Ne, Ar or Kr with a velocity of 1.16 MeV/u bombarded thin films of organic and inorganic solids. The experimental arrangement is described. The ion emission yield is strongly dependent on the charge state of the incident ion qi and of its atomic number (nature of the projectile). The emission yield between the three types of projectiles varies as q4eq where q eq is the equilibrium charge state within the material for each projectile.

Metabolic utilization of fat emulsions containing 20% lipid and 10% lipid were compared using beagles. The key parameter measured was elimination of the lipid from the bloodstream, which serves as an indication of the emulsion's availability for metabolism. Nonlinear kinetic analysis was used in this determination. Blood concentrations of free fatty acids, phospholipid, and cholesterol were also measured as additional ways of determining emulsion metabolism. The 10 and 20% emulsions appeared to be equivalent in elimination of the caloric substrate triglyceride from the blood stream. Results also showed an adaptation to emulsion infusion over time at both dosages administered (3 and 6 g/kg of body weight). This was indicated by increased elimination capacity and stabilization of each lipid class measured. However, blood concentrations of phospholipid and cholesterol indicate that the 20% emulsion provides a lesser lipid load for the amount of calories administered when compared to an emulsion containing 10% lipid.