RESEARCH Searle, by treatment of t h e methyl ester of estrone with an o r g a n i c metallic compound such as e t h y l lithide or ethyl magnesium bromide. A Birch type reduction t h e n follows. In revealing t h e new drug, company spokesmen point out it has been studied in more than 30 medical centers in the U. S. a n d E n g l a n d , for m a n y conditions which are benefited b y an increased protein balance. The d r u g has proved useful for: • Assisting recovery following major surgery. • Preparing patients for major surgery. • Improving nutritional state of patients with severe illness such as polio. • Aiding in the arrest: of the wasting of patients with cancer, leukemia, and Hodgkin's disease. • Strengthening of premature infants. But, the new drug has no known value in the actual prevention or cure of these diseases.
Cholesterol Plus . . . Fat transport a n d m e t a b olism must also b e understood by atherosclerosis r e searchers ATHEROSCLEROSIS STUDIES
must
go
a
great deal further than the cholesterol molecule alone. Those of us involved in this complex research must aim towards a greater understanding of the phenomena underlying triglyceride transport and metabolism," declares C. E. Anfinsen, Jr., of the National Heart Institute. "The abnormal pattern of hormonal interactions, so evident in diabetes, is almost certain to find its parallel in the case of atherosclerosis, a disease that i s so obviously linked with the metabolism o f fat." Anfinsen told the Federation of American Societies f o r Experimental Biology the secret of atherosclerosis (which causes 45% o f deaths in the U. S. today) lies in knowing the physiological control involving t h e destruction, production, and transport of lipoproteins in b o d y fluids. At least that's the indication from recent biochemical and statistical studies, b e explains. Present day investigation of atherogenic processes stems from the fact that lipids exist in animal tissues and fluids in t h e form of lipoprotein complexes. These make possible metabolism of lipids in a q u e o u s mediums. Although workers h a v e n o t yet characterized the cellular lipoprotein, t h e y have recog2136
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nized three major forms of circulating lipid: • Chylomicron—mostly neutral fat which contains small amounts of cholesterol, phospholipids, and protein. • Alpha lipoprotein—about 3 5 % lipid, believed to b e a single chain molecule terminating in aspartic acid. • Beta lipoprotein—a large molecule containing about 7 5 % fat. It is considered a single large p e p t i d e chain containing N-terminal glutamic acid. > Fats Get A r o u n d . M a n y workers today are engaged in fat transport studies, says Anfinsen. Some researchers think alpha a n d beta lipoproteins constitute two separate and distinct metabolic pools of circulating lipid that may mediate quite different physiological processes. Others, including t h e Heart Institute, are concerned over t h e mechanism involved in the regulation of fat transport. T h e institute began its mechanism studies shortly after independent workers revealed t h a t alimentary lipemia (blood fat) was rapidly "cleared" b y administration of heparin (a bloodclotting inhibitor) t o animals. This work b a s n o w evolved into a clear cut diagram of an enzyme system induced b y heparin—which character-istically digests the triglycerides of lipoproteins. In contrast to ordinary pancreatic lipase, this enzyme system is active only on lipoprotein-bound lipids—and so is called "lipoprotein lipase." This ' l i p a s e " rapidly attacks the triglyceride of chyle a n d low-density beta
lipoproteins. Also, it can attack ordinary triglyceride emulsions when these h a v e b e e n activated b y combination with the alpha lipoprotein fraction of plasma. F a t t y acids a n d glycerol are produced during t h e reaction, which requires presence of a fatty acid binder. Physiological tests show this binder to be serum albumin. T h e fact t h a t lipoprotein lipase is inactivated by protamine or t r e a t m e n t with a specific heparinase (isolated from a h e p a r i n degrading bacteria) is evidence that the lipase contains heparin or a heparinlike substance. A t the H e a r t Institute, the transport mechanism for lipids as unesterified fatty acids is visualized as being u n d e r hormonal control, conditioned b y t h e glucose level of t h e blood, says Anfinsen. This system is considered sensitive to protamine a n d other antiheparin agents. But, another t h o u g h t concerning fat transport revolves around the transport of lipoproteins. Such a mechanism might only be seen under circumstances where neither glucose nor fatty acid is a d e q u a t e to maintain t h e caloric r e quirements of t h e metabolizing tissues. • Diet C h a n g e s S o u g h t . In atherosclerosis, the altering of the body's cholesterol-lipid-lipoprotein metabolism plays a decisive role, says L. N . Katz, of Michael Reese Hospital. W i t h o u t an altered lipid metabolism, the-occurrence of clinically significant atherosclerosis would b e exceedingly rare. Changes in cholesterol-lipid-lipoprotein metabolism are frequently b r o u g h t about b y the individual's life-span pat-
Atherosclerosis research is t h e subject of conversation w i t h this triumvirate at the Atlantic City meeting of the F e d e r a t i o n of American Societies for Experimental Biology: Frederick J. Stare ( l e f t ) , of H a r v a r d ; L . N . Katz, of Michael Reese Hospital; C. B. Anfinsen, Jr., of National H e a r t I n s t i t u t e
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• Broil meat instead of frying it in deep fat. • Don't use gravies on meat. • Stop pouring sauces and dressings on vegetables and salads. • Eat fresh or cooked fruit, rather than pastries or pie a' la mode. In this way, the percentage of total calories obtained from fat can be reduced to a reasonable 25 to 30%. "This is not the complete answer to atherosclerosis," Katz emphasizes, "but it is a healthy step in the right direction."
• Facial tissues containing formald e h y d e compounds have caused skin disease in 6% of the patients studied by Samuel M. Peck of Mt. Sinai Hospital. The tissues are commercially identified as having "wet strength." In JAMA, April 7, Peck says that skin patch tests and contact tests on 50 patients showed that both melamineformaldehyde and urea-formaldehyde resins are capable of sensitization and play a role in contact dermatitis.
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tern of diet, particularly by the consumption of calories, cholesterol, and lipids. Continuous high intakes of these substances frequently overtax and may alter the body's limited regulatory functions, he says. Populations that consume relatively low amounts of calories, cholesterol, and lipids tend to have a low incidence of coronary atherosclerosis. Americans derive about 40 to 60% of their calories from lipids. Their intake of lipids, as well as of cholesterol, is excessive. People in the U. S. should increase their consumption of vitamins, minerals, and amino acids. This can be done without sacrificing food palatability. By way of specific suggestions, Katz urges Americans to:
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• A super alloy for use in aircraft and auto engines can be produced by a process developed at University of Michigan. By melting a nickel-base alloy, or one made up mainly of nickel, in a high vacuum, and pouring it in an atmosphere of argon, Richard A. Flinn gets a product of 40% higher tensile strength and two to 10 times the ductility of cobalt-base alloys. Improved properties result from exclusion of nitrogen, hydrogen, and oxygen of the air. The alloy is about half the price of cobalt-base alloys now used in jet engines and auto turbine. Flinn says the process may make gas turbine autos practical within two to five years.
