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Considerable attention has been focused in the effects of dietary parameters on carcinogenesis (Carroll & Khor, 1975). While total fat intake has been implicated in some types of cancer (i.g. breast, colon), not all studies support a positive association. Some epidemlologic studies in Western populations (Stemmerman et al, 1984; Willett et al, 1987) or even animal studies, have failed to show such correlations. It is clear however in animal experiments (Roebuck et al, 1981; Naus et al, 1983) that high fat intake was shown to increase carcinogenesis response. Kritchevsky et al, 1984 maintains that it is the total caloric intake which is important in the promotion of tumors rather than dietary fat per se. The issue while not resolved will be less confusing if the diet is described in terms of specific fats, rather than simply dietary fat.

This report confirmed earlier studies by other workers which suggested that collateral nerve sprouting in mammalian skeletal muscle is induced by factors released from denervated or atrophic muscle fibers. Crude lipid extracts of denervated but not of normal muscle were found to bring about histological evidence of significantly increased collateral nerve outgrowth when injected into normal muscles. Additional experiments indicated that separated non-polar and polar lipid fractions of muscle were less active. The injection of a chemically pure lipid, monlaurin, also caused significant sprouting.

A new family of surfactants, aminimides, has been screened forin vitro antimicrobial activity. These compounds are active against both bacteria and yeast, activity being a function of chain length. Maximum activity for acetimide and acrylimide amine derivatives was extablished with chain lengths of C14–C16. Homologous compounds with lower or higher chain lengths were less active. While showing low antimicrobial activity against gram negative bacteria, mixtures containing C12 and C16 gave good activity against gram negative strains without losing gram positive activity. Aminimides gave low acute LD50’s (200–400 mg/kg) when tested in mice by intraperitoneal injection.

A study was conducted to determine the effects of sorbic acid and several derivatives of fatty acids (amides, aminimides, and monoglycerides) upon toxigenic cultures of Aspergillus flavus and A. parasiticus. A synthetic medium was inoculated with spores, incubated for 48 h at 27°C, and then supplemented with sorbic acid and fatty acid derivatives. Cultures were then incubated for an additional 5 days. Aflatoxins were extracted, separated, and quantitated. Mycelial mats were dried, weighed, and analyzed for lipid and mineral content. Cerulenin (8 μg/ml) was the most effective fatty acid derivative examined, reducing mycelial growth by 37% and completely inhibiting extracellular accumulation of aflatoxins. Other derivatives, in decreasing order of effectiveness, included M-20 (an aminimide), lauribic, and lauricidin. Mycelia grown in the presence of fatty acid derivatives contained less phosphorus, potassium, magnesium, phosphatidyl ethanolamine, phosphatidyl serine, cholesterol, and triglycerides, but more cardiolipin, phosphatidyl choline, free fatty acids, fatty acid esters, and diglycerides. Levels of monoglycerides and cholesterol esters remained essentially unchanged. Inhibition by sorbic acid was nonspecific, affecting both mycelial growth and extracellular aflatoxin accumulation to approximately the same extent. Utilization of fatty acid derivatives for determining mechanisms of aflatoxin accumulation and lipid biosynthesis appears promising.

A sterile agar-meat was acidified with lactic acid and seeded with Staphylococcus aureus. Monolaurin (Lauricidin®), which is a GRAS emulsifier, caused both static and cidal effects on S. aureus 196E. When compared to potassium sorbate, Lauricidin® was slightly more active. The combination of sorbic acid and Lauricidin® (Lauribic™) gave a greater inhibitory effect than either of the substances alone. Inhibitory effects were greater on “anaerobic” than “aerobic” growth. These results indicate that monoglyceride emulsifiers like Lauricidin® alone or in combinations with other preservatives can be used in foods to create environments which are hostile to microorganisms.

Crude lipids extracted from Naja naja were separated by column, thin-layer and gas-liquid chromatography. Cholesterol was found to be the chief neutral lipid (10 per cent of total). Phosphatidyl choline (lecithin) represented 83 per cent of the total and was the only phospholipid detected. The fatty acid content of neutral lipids represented saturated acids, while the phospholipids had a predominance of unsaturated fatty acids.

Following the intravenous injection of a single dose of acetate-C 14 to women during early pregnancy, only negligible amounts of isotope could be detected in fetal brain cholesterol, but a significant incorporation of C 14 occurred in cholesterol isolated from the corpus luteum of pregnancy, fetal liver, and fetal adrenals. Neither cholesterol-C 14 synthesized in the fetal liver nor maternal plasma cholesterol-H 3 of dietary origin was taken up by the fetal brain in appreciable amounts. When glucose-C 14 was injected in the mother, the isotope was found in cholesterol isolated from the fetal brain and other fetal tissues but only negligible amounts were found in maternal tissues. The preferential utilization of glucose for the synthesis of fetal brain cholesterol emphasizes the significance of the "blood-brain barrier" which controls the movement of substances into and out of central nervous system tissue.

The structural relationships of 30 straight-chain fatty acids and derivatives and their bactericidal properties were studied with 8 gram-negative and 12 grampositive organisms. Chain length, unsaturation ( cis, trans ), and functional group were all variables considered in this study. Our data indicate that C 12 (lauric acid) is the most inhibitory saturated fatty acid against gram-positive organisms. Monoenoic acid (C 18:1 ) was more inhibitory than saturated fatty acid, but was less active than dienoic derivatives (C 18:2 ). Other unsaturated compounds were less active than C 18:2 . Alcohols and glyceryl esters were active only against gram-positive organisms. In general, esterification of the carboxyl group led to a compound which was less active; monoglycerides were the sole exception. Amine derivatives, contrary to results with fatty acids, esters, and amides, showed activity against both gram-positive and gram-negative organisms.

A broth dilution method was used to determine the minimal inhibitory concentration of a series of fatty acid esters of polyhydric alcohols against gram-negative and gram-positive organisms. Gram-negative organisms were not affected. Gram-positive organisms were inhibited as follows. Of the monoglycerol esters, monoglycerol laurate was the most active. Esters of polyglycerols (tri-, hexa-, and decaglycerol esters) were generally active when the fatty acid had chain lengths of 8 to 12 carbon atoms. Sucrose esters, when active, except for laurate, are more active than the free fatty acid. The spectrum of antimicrobial action of esters of polyhydric alcohols is narrower when compared with the free acids.

Dietary lipids, in particular unsaturated fat, promote the development of many experimental tumors. However, no mechanisms to fully explain these effects have been elucidated. Recent reports, which we summarize here, suggest a role for gap junction-mediated intercellular communication in the process of tumor promotion. We also review tumor-promoting effects of dietary fat on experimental, particularly mammary, carcinogenesis. Our main focus is to review recent data examining the inhibitory effects of unsaturated fatty acids on metabolic cooperation in Chinese hamster V79 cells. These data suggest that inhibition of junctional communication may be involved mechanistically in the promotion of tumors by high levels of dietary unsaturated fat. Finally, potential mechanisms by which unsaturated fatty acids inhibit metabolic cooperation are examined.

Aminimides are a new class of surface active agents which have antimicrobial activity. These bipolar compounds have activity against both gran-positive and yeast organisms. Their activity against gram-negative organisms is low or absent. The acyl derivatives tested showed maximum activity at chain lengths of C14 and C16. Fatty acid derivatives, shorter ( C16), were less active. Unsaturation was an important factor contributing to aminimide activity. Their low toxicity and wide spectrum of antimicrobial activity make aminimides ideal candidates for further investigation.

Monolaurin alone and monolaurin with tert-butylhydroxyanisole (BHA), methylparaben, or sorbic acid were tested for in vitro virucidal activity against 14 human RNA and DNA enveloped viruses in cell culture. At concentrations of 1% additive in the reaction mixture for 1 h at 23°C, all viruses were reduced in infectivity by >99.9%. Monolaurin with BHA was the most effective virucidal agent in that it removed all measurable infectivity from all of the viruses tested. The compounds acted similarly on all the viruses and reduced infectivity by disintegrating the virus envelope.

A new family of surfactants, aminimides, has been screened forin vitro antimicrobial activity. These compounds are active against both bacteria and yeast, activity being a function of chain length. Maximum activity for acetimide and acrylimide amine derivatives was extablished with chain lengths of C14–C16. Homologous compounds with lower or higher chain lengths were less active. While showing low antimicrobial activity against gram negative bacteria, mixtures containing C12 and C16 gave good activity against gram negative strains without losing gram positive activity. Aminimides gave low acute LD50’s (200–400 mg/kg) when tested in mice by intraperitoneal injection.

Twenty-four-hour urine was collected from normal and dystrophic mice and hamsters for catecholamine determinations. A new method of analysis was used whereby 3,4-dihydroxyphenylalanine (DOPA), dopamine (DA), norepinephrine (NE), and epinephrine (E) were measured simultaneously. The procedure is based on a combination of liquid-solid extraction, cation exchange chromatography, and controlled potential electrochemistry. The results of these experiments indicated that while DA levels were similar in both normal and pathological animal urine, DOPA levels decreased slightly in the dystrophic mouse but not the hamster, and NE and E levels in dystrophic groups were two and four times greater than normal in both species. The data supports the concept of biochemical alterations in tissue other than muscle. While not necessarily supportive to catecholamine abnormality as the primary cause of muscular dystrophy, the present data cast doubt that this disease is a primary muscle disease.

SummaryThree genetic groups of mice (DyDy, Dydy, and dydy) were studied at intervals of 6–14 wk. TCA intermediates were extracted, separated, and measured. Data indicate that mice with genetically induced muscular dystrophy (Strain 129) show alteration in several body tissues as well as in muscle itself. Of particular interest were changes measured in the brain of dystrophic mice. Support, but not proof, is given to the neurogenic concept of mouse muscular dystrophy.

Isozyme patterns of cholinesterase (ChE) from heart, tongue, and skeletal muscle of normal and dystrophic hamsters are presented. Two principal bands, bands 1 and 2, were evaluated. Band 1 migrates faster towards the anode than does band 2. While bands 1 and 2 stain for AChE and were found in control muscles, only band 2 was stained by a pseudocholinesterase (BuChE) and was decreased in samples from dystrophic hamsters. The decrease in BuChE was most pronounced in dystrophic heart muscle. The low level of BuChE measured for dystrophic animal tissue was similar to isozyme patterns found in embryonic tissue and in denervated muscle. BuChE obtained by acrylamide gel electrophoresis along with 16S AchE appears to be a useful biochemical marker of nerve-muscle interactions.

The incorporation of 1-(14)C-Acetate into tissue cholesterol of the baboon was measured. Using this indicator gray matter of the cerebrum indicated greater metabolic activity than did white matter.Other tissues besides neural tissue were examined. The peak of radioactivity occurred between 3 and 4 hr. The highest incorporation of radioactivity was measured in the adrenal gland. Liver, spleen and kidney values were of intermediate order.

The low molecular weight components of Elapidae venoms were investigated. The first separations of snake venom toxins by thin-layer chromatography (TLC) on silica gel were achieved. Sixteen Elapidae venoms were compared by starch gel electrophoresis and TLC. Almost three-quarters of the venom was dialyzable. The adsorption of toxins onto the larger protein molecules in snake venoms was demonstrated by measuring dialysis rates as well as showing that homogeneous electrophoretic bands yielded multiple spots by TLC. The feasibility of separating the low particle weight toxins of Elapidae venoms by silicic acid TLC and column chromatography was demonstrated. A low molecular weight toxic principle of Naja naja was isolated, partially characterized, and shown to be one of the most lethal materials isolated from biological sources (ld50 = 0·03 mg per kg).

Contrary to the limited effects of alkyl amides and their corresponding N -derivatives, alkyl amines affected both gram-positive and gram-negative organisms. As with other alkyl derivatives the most sensitive gram-negative bacteria were usually more resistant than the most resistant gram-positive bacteria. Compounds with a chain-length of 11 to 15 are most active. Although some of the general properties relating the activity of fatty acids to their antimicrobial action are similar to those of amine compounds, the amines are unique in that monounsaturation does not increase compound activity. The possible modes of action of these compounds are discussed.

Publisher Summary The potential of the adult brain for lipid metabolism has always been regarded as limited. Recently, the admission of newer evidence has challenged this static concept for neural metabolism. Studies with radioactive nutrients on the intact animal are difficult to interpret because of the protective mechanisms (blood-brain barrier) of the brain, which controls the movement of substances into and out of the neural tissue. Thus the unavailability of injected precursors to become incorporated into compounds of the central nervous system has been interpreted by early investigators as indicative of a limited metabolic potentiality. Through special techniques and experimental designs, recent studies have mitigated against this static metabolic picture for neural tissue, which now indicates extensive metabolic potentials. Pursuing the problems of cholesterol biosynthesis in various tissues by simultaneous use of selected 14 C- and 3 H-precursors, it has been previously reported that acetate was a poor choice for the study of the brain cholesterol formation. In this and similar studies, glucose is shown to be a better carbon source for brain cholesterol than acetate. It is of interest, therefore, to examine the contribution of a non-carbohydrate labeled substance and glucose as both became incorporated into the sterol of the developing mouse brain. Mice representing three age groups are simultaneously injected with acetate-2- 3 H and glucose-U- 14 C and the incorporation of these labeled nutrients into brain cholesterol was measured in this chapter.

During the past decade, our laboratory has been involved in studying the biosynthesis of brain cholesterol under various conditions. As a result of these studies, we feel that the hypothesis of metabolic stability of cholesterol in adult life is untenable. Our data suggest that there are several compartments of sterol metabolism ranging from extremely fast to metabolically very slow. It is our hypothesis that (a) brain function is more nearly associated with fast turnover compartments than with metabolically slow ones; (b) these compartments can be altered by a variety of stress conditions.

Publisher Summary This chapter discusses the effect of chemical and physical agents on brain cholesterol. The brain represents the largest repository of body cholesterol however relatively little is known about its metabolism and even less about its function and role within the central nervous system. It has been suggested that cholesterol turnover may be more rapid in some areas than in others. In view of new evidence that indicates both biosynthetic capacity and turnover ability of cholesterol in adult brain, studies dealing with the effect of chemical and physical agents on the constituent have become more rational. That the stability of brain cholesterol was so readily accepted in view of early experiments showing drug effect is difficult to comprehend. Drug stimulants and drug depressants may have their mechanism of action directly or indirectly on brain cholesterol. It is clear from the diversity of chemical structures which affect cholesterol metabolism in general and brain cholesterol in particular that further work will be necessary to relate the mechanisms of drug action on brain cholesterol and brain function.

Publisher Summary This chapter presents a critical review of brain cholesterol metabolism. Modern aspects of brain sterol metabolism are reviewed by Davison and Kabara. Consequently, for this review, the chapter emphasizes only the more recent concepts of brain cholesterol metabolism. To form a backdrop for the discussion of brain cholesterol metabolism, the anatomical and chemical changes taking place in the central nervous system (CNS) during growth and development are outlined in the chapter. Because sex, nutrition, precursor used, diurnal variation, etc., influence biosynthetic rates as measured, their influence should be considered in any developmental analysis of metabolic capacity within the CNS. Whole brain values obtained in the past from animals injected with a radioactive precursor did not reflect metabolism or changes in metabolism of anatomical areas, individual cells or organelles. Although accurate information is not available, conclusions based on such comparisons lead to statements in the literature which are very difficult to change, even in the face of new and more conclusive data.

Conclusions1. Various resorcinol derivatives of a non-toxic nature have been shown to be active against EEE virus under in vitro conditions. 2. Some factors affecting inactivation of EEE virus by 2,7-diiodotetraiodofluorescein have been presented and their importance in an in vitro study on compound-virus interaction stressed. 3. An in vitro screening technic has been demonstrated permitting the study of the effect of compound configuration on virus activity.