The finding of trypsin inhibitor in colostrum led to the hypothesis that the physiological role of the inhibitor is to protect the antibodies of colostrum from being digested and thus to facilitate their absorption (1). Some circumstantial evidence confirming this hypothesis has been accumulated (2, 3). For a direct experimental assault, insulin was chosen as the test protein, because its passage into the blood stream is reflected by the blood sugar level. (6) used blood plasma as a source of "antitrypsin," whereas Harned and Nash (7) used an extract from Ascaris. The quantities of the inhibitor present in such preparations were, however, much lower than those used now. The maximal positive effect reported was a temporary disappearance of glycosuria in depancreatized dogs, with (6) or without a significant (7) lowering of the blood sugar level. Early attempts to administer insulin through the gastrointestinal tract have been reviewed by Jensen (4). It is interesting to note that Murlin and Hawley (5) and Eaton and Murlin
The elimination of bile pigment during jaundice is, for practical purposes, unincreased by diuresis from water by mouth. Possibly, though, the flushing of the kidneys tends to lessen pigment accumulation within these organs and thus to diminish a serious potential source of trouble in long continued jaundice. Flood diuresis from intravenous injections of salt solution markedly increases the output of bile pigment. It is important to know the effect of variations in the urinary output on the elimination of bile salts, but methods for the purpose are not available at present. The passage of bile pigment into the kidney cells during jaundice is attested by the presence in the freshly voided urine of desquamated renal elements specifically stained, stippled, or granulated with bilirubin. Pigmentation of this sort is readily to be distinguished from the indiscriminate staining of cellular debris that occurs in icteric urines on standing. It has clinical significance, furnishing direct evidence on the degree of renal change.
The fatty acid composition of depot fat has been shown by several investigators to be resistant to change by dietary manipulation, a t least on a short-term basis.',' This would suggest that there are potent metabolic control systems responsible for its regulation. In an attempt to discover whether some of these controlling metabolic factors are disordered in obesity, studies have been carried out on fatty acid composition of the depot fat of obese or potentially obese experimental animals of several types, using gas-liquid chromatography. Marked changes in the distribution of fatty acids in depot fat have been observed and further studies have shown certain dynamic metabolic events associated with these changes.The experimental model initially chosen was the rat obese due to bilateral electrolytic lesions in the ventromedial nucleus of the hypothalamus.To summarize earlier ~o r k ,~-~ TABLE 1 shows that the composition of epididymal fat of lesioned rats differs from that of normal animals of the same age. There are significant and consistent changes in palmitic, palmitoleic, oleic and linoleic acids and it has been convenient to use the linoleic: palmitic ratio as an index of fatty acid changes. The success of the neurosurgical lesion appears to correlate with this ratio value. The greater the obesity ultimately attained by free fed animals the larger the alteration in fat composition, the ratio value varying inversely with total body fat.From the foregoing one might conclude that the change in fatty acid composition is simply a reflection of the total amount of body fat and not an index of metabolic abnormality. To determine whether a change in fatty acid composition would occur in the absence of weight gain, two animals were lesioned and maintained a t constant weight by dietary restriction. The upper portion of FIGURE 1 shows the weight curves for these two rats; below are plotted linoleic: palmitic ratios determined from serial epididymal fat pad biopsies. Just as in the free fed animal, the linoleic: palmitic ratio fell progressively in the first 10 days after lesioning, thereafter remaining constant. A third animal handled similarly was sacrificed after 20 days and the total body fat measured. The carcass fat was 22 per cent of dry weight, well within the
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