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229. Glycerol and serum cholesterol levels
FLAVOURING MA-I-IERS, SOLVENTS AND SWEETENERS
273
226. Toxicology of Quercus havardi tannin
The third paper by DoUahite and his colleagues describes the preliminary toxicological work on a hydrolysable tannin isolated from Q. havardi, whose polyhydro'xyphenol moiety consisted of gallic acid. When given to rabbits in daily oral doses of 4-12 g/kg appreciable quantities of tannin were absorbed as evidenced by the presence in the blood of 40-130 /zg/ml of the tannin. When the animals were examined after receiving the above doses for 5 days they showed severe haemorrhagic gastritis and numerous large gastric ulcers, kidneys with pale cortices and pale livers with areas of congestion. From the similarity of these effects to those of shin oak poisoning it is concluded that Q. havardi tannin is in part or wholly responsible for this condition. Pigeon, R. F., Camp, B. J. & Dollahite, J. W. (1962). Oral toxicity and polyhydroxyphenol moiety of tannin isolated from Quercus havardi (shin oak). Amer. J. vet. Res. 23, 1268. 227.~Xylitol and its effect on the intestine ~/, Although xylitol (I) is acceptable from the viewpoint of acute and chronic toxicity (Cited in F.C.T. 1963, 1, 109) it is not free from unwanted actions. Diarrhoea for example has occurred in both man and animals at high dose levels (e.g. 0.5 g/kg and above). This was thought to be due to the osmotic effect exerted by I. The present paper reports a study of " the relative stimulant effects of I and glucose (II) upon the intestine, in which Indian ink was administered into the stomachs of mice 30 rain after they were given single oral doses of I or II. After a further 40 rain the progress of the Indian ink particles along the intestine was measured and expressed in terms of the percentage of the length of the intestin~ they had traversed. At the 0.5 and 1 g/kg levels, I was found to be markedly more effective in increasing intestinal motility than equimolar amounts of II. This was probably due to the greater amount of II remaining in the intestine owing to the comparative slowness with which it is absorbed from the intestine. Czok, G. & Lang, K. (1963). Beeinflussung der Darmmotorik dutch Xylit. Klin. Wschr. 41, 241. 228. The fate of glycerol in man
In earlier studies (Eymer et al. Klin. Wschr. 1962, 40, 434) showed that glycerol (I) rapidly disappeared from the perfusion liquid when solutions of I were perfused through the isolated rat liver. It was therefore considered of interest to investigate the time course of the fate of I in man following administration of I via the parenteral and oral routes. In the first experiment of the present study 28 healthy starved volunteers were each given 10 g I and serial blood determinations of I were made. These showed that the peak concentration of I was attained 15"--25min after ingestion. Also when 3 g I was injected intravenously half the dose disappeared from the body after approximately 2 rain. This was similar to the values found by Fredrickson & Gordon (J. clin. lnvest. 1958, 37, 1504) for the biological half-life periods of palmitic acid and other fatty acids that are commonly present in natural fats. Schwarz, K., Bottermann, P., Claussen, G., Kopetz, K. & Eymer, K. P. (1962). Untersuchungen fiber die Resorption und die biologische Halbwertszeit yon Glycerin beim Menschen. Klin. Wschr. 40, 1183. 229. Glycerol and serum cholesterol levels
Orekhovich & Plotnikov (Arch. Biochem. Biophys. 1961, 93, 180) recently examined the effect of repeated high doses of glycerol (I) on rabbits. The investigation was prompted by their assumption that diets containing high amounts of animal fats give rise to atherosclerosis, and that the most important individual aetiologlcal factor was the high amounts
274
EMULSIFIERS AND STABILIZERS
of I liberated as a result of fat digestion in the gastro-intestinal tract. It was claimed that significant increases in rabbit serum cholesterol levels resulted from the daily administration into the stomach of 20 ml of 50 ~o I in physiological saline for 14 days. The present authors sought further evidence on this alleged effect by delivering into the stomachs of guinea-pigs and rabbits respectively 5 and 10 ml of 50Yo I in physiological saline. After 14-50 days dosage no consistent changes in either serum or red blood cell cholesterol levels were seen in either species that could be attributed to the ingestion of I. Evidence was obtained that I may give rise to anaemia when administered at the above dose levels. Ostwald, Rosemarie (1962). Glycerol intake, blood cholesterol level and anaemia in the guinea-pig and rabbit. Proc. Soc. exp. Biol., N. Y. 111, 632.
EMULSIFIERS AND STABILIZERS 230. Hypertensive effects of Polymers In a series of papers (Cited in F.C.T. 1963, 1, 111) the present authors have described the development of hypertension and glomerulonephritis following the parenteral administration of polyvinyl alcohol (I) and methylcellulose (II). The hypertensive effect of II only developed when drinking water containing sodium chloride (NaC1) was ingested simultaneously, but it was not known whether NaC1 administration is essential in the hypertension to which I gives rise. Nor was it known if NaCl affected the fluid intake. Rats were given daily subcutaneous injections of 1 or 5 ~o solutions of I or II respectively for 28 days. All developed hypertension when given NaCl in the drinking water, but only those receiving I did so in the absence of NaC1. Lesions were confined to the kidneys in rats receiving I but not drinking NaC1 solution. Addition of NaCl to the regimen caused in addition the appearance of hypertensive lesions of the heart, pancreatic and splenic arteries. Fluid intakes in the animals treated with I were raised irrespective of the ingestion of NaC1 solution, however those which received NaC1 showed from the outset a rapidly increasing fluid intake whereas in the absence of NaC1, fluid intakes increased only slowly starting at the third week. II failed to raise salt or fluid intakes. Both I and II caused haemoglobin levels to fall but only in those receiving I was a frank and progressive anaemic state produced. The anaemia was most severe when NaCI was ingested. Hall, C. E. & Hall, O. (1962). Comparison of macromolecular hypertension due to polyvinyl alcohol and methyl cellulose, in respect to the role of sodium chloride. Lab. Invest. 11,826.
231. Methylcellulose injections and macromolecular hypertension In their past work (Cited in F.C.T. 1963, 1, 111, and preceding abstract) the present authors have shown that hypertensive cardiovascular disease results from parenteral ad ministration of 2 ~o solutions of methylcellulose (I) to rats given 1 ~o sodium chloride (NaC1) to drink. A closer examination has now been made of the role of NaC1 in the aetiology of this condition. It was found that arterial hypertension, enlargement of the heart and kidneys and lesions in the arteries of various organs only occurred when I was administered to animals ingesting high amounts of salt. In the affected animals the authors considered that the incorporation of I within the kidney glomeruli and the resulting swelling of their linings that occurred led to reduction of filtration through the glomeruli. A state of sodium retention arose as a result in rats having a high salt intake. In support of this view it was observed that the onset and the rate at which the hypertensive state developed was
273
226. Toxicology of Quercus havardi tannin
The third paper by DoUahite and his colleagues describes the preliminary toxicological work on a hydrolysable tannin isolated from Q. havardi, whose polyhydro'xyphenol moiety consisted of gallic acid. When given to rabbits in daily oral doses of 4-12 g/kg appreciable quantities of tannin were absorbed as evidenced by the presence in the blood of 40-130 /zg/ml of the tannin. When the animals were examined after receiving the above doses for 5 days they showed severe haemorrhagic gastritis and numerous large gastric ulcers, kidneys with pale cortices and pale livers with areas of congestion. From the similarity of these effects to those of shin oak poisoning it is concluded that Q. havardi tannin is in part or wholly responsible for this condition. Pigeon, R. F., Camp, B. J. & Dollahite, J. W. (1962). Oral toxicity and polyhydroxyphenol moiety of tannin isolated from Quercus havardi (shin oak). Amer. J. vet. Res. 23, 1268. 227.~Xylitol and its effect on the intestine ~/, Although xylitol (I) is acceptable from the viewpoint of acute and chronic toxicity (Cited in F.C.T. 1963, 1, 109) it is not free from unwanted actions. Diarrhoea for example has occurred in both man and animals at high dose levels (e.g. 0.5 g/kg and above). This was thought to be due to the osmotic effect exerted by I. The present paper reports a study of " the relative stimulant effects of I and glucose (II) upon the intestine, in which Indian ink was administered into the stomachs of mice 30 rain after they were given single oral doses of I or II. After a further 40 rain the progress of the Indian ink particles along the intestine was measured and expressed in terms of the percentage of the length of the intestin~ they had traversed. At the 0.5 and 1 g/kg levels, I was found to be markedly more effective in increasing intestinal motility than equimolar amounts of II. This was probably due to the greater amount of II remaining in the intestine owing to the comparative slowness with which it is absorbed from the intestine. Czok, G. & Lang, K. (1963). Beeinflussung der Darmmotorik dutch Xylit. Klin. Wschr. 41, 241. 228. The fate of glycerol in man
In earlier studies (Eymer et al. Klin. Wschr. 1962, 40, 434) showed that glycerol (I) rapidly disappeared from the perfusion liquid when solutions of I were perfused through the isolated rat liver. It was therefore considered of interest to investigate the time course of the fate of I in man following administration of I via the parenteral and oral routes. In the first experiment of the present study 28 healthy starved volunteers were each given 10 g I and serial blood determinations of I were made. These showed that the peak concentration of I was attained 15"--25min after ingestion. Also when 3 g I was injected intravenously half the dose disappeared from the body after approximately 2 rain. This was similar to the values found by Fredrickson & Gordon (J. clin. lnvest. 1958, 37, 1504) for the biological half-life periods of palmitic acid and other fatty acids that are commonly present in natural fats. Schwarz, K., Bottermann, P., Claussen, G., Kopetz, K. & Eymer, K. P. (1962). Untersuchungen fiber die Resorption und die biologische Halbwertszeit yon Glycerin beim Menschen. Klin. Wschr. 40, 1183. 229. Glycerol and serum cholesterol levels
Orekhovich & Plotnikov (Arch. Biochem. Biophys. 1961, 93, 180) recently examined the effect of repeated high doses of glycerol (I) on rabbits. The investigation was prompted by their assumption that diets containing high amounts of animal fats give rise to atherosclerosis, and that the most important individual aetiologlcal factor was the high amounts
274
EMULSIFIERS AND STABILIZERS
of I liberated as a result of fat digestion in the gastro-intestinal tract. It was claimed that significant increases in rabbit serum cholesterol levels resulted from the daily administration into the stomach of 20 ml of 50 ~o I in physiological saline for 14 days. The present authors sought further evidence on this alleged effect by delivering into the stomachs of guinea-pigs and rabbits respectively 5 and 10 ml of 50Yo I in physiological saline. After 14-50 days dosage no consistent changes in either serum or red blood cell cholesterol levels were seen in either species that could be attributed to the ingestion of I. Evidence was obtained that I may give rise to anaemia when administered at the above dose levels. Ostwald, Rosemarie (1962). Glycerol intake, blood cholesterol level and anaemia in the guinea-pig and rabbit. Proc. Soc. exp. Biol., N. Y. 111, 632.
EMULSIFIERS AND STABILIZERS 230. Hypertensive effects of Polymers In a series of papers (Cited in F.C.T. 1963, 1, 111) the present authors have described the development of hypertension and glomerulonephritis following the parenteral administration of polyvinyl alcohol (I) and methylcellulose (II). The hypertensive effect of II only developed when drinking water containing sodium chloride (NaC1) was ingested simultaneously, but it was not known whether NaC1 administration is essential in the hypertension to which I gives rise. Nor was it known if NaCl affected the fluid intake. Rats were given daily subcutaneous injections of 1 or 5 ~o solutions of I or II respectively for 28 days. All developed hypertension when given NaCl in the drinking water, but only those receiving I did so in the absence of NaC1. Lesions were confined to the kidneys in rats receiving I but not drinking NaC1 solution. Addition of NaCl to the regimen caused in addition the appearance of hypertensive lesions of the heart, pancreatic and splenic arteries. Fluid intakes in the animals treated with I were raised irrespective of the ingestion of NaC1 solution, however those which received NaC1 showed from the outset a rapidly increasing fluid intake whereas in the absence of NaC1, fluid intakes increased only slowly starting at the third week. II failed to raise salt or fluid intakes. Both I and II caused haemoglobin levels to fall but only in those receiving I was a frank and progressive anaemic state produced. The anaemia was most severe when NaCI was ingested. Hall, C. E. & Hall, O. (1962). Comparison of macromolecular hypertension due to polyvinyl alcohol and methyl cellulose, in respect to the role of sodium chloride. Lab. Invest. 11,826.
231. Methylcellulose injections and macromolecular hypertension In their past work (Cited in F.C.T. 1963, 1, 111, and preceding abstract) the present authors have shown that hypertensive cardiovascular disease results from parenteral ad ministration of 2 ~o solutions of methylcellulose (I) to rats given 1 ~o sodium chloride (NaC1) to drink. A closer examination has now been made of the role of NaC1 in the aetiology of this condition. It was found that arterial hypertension, enlargement of the heart and kidneys and lesions in the arteries of various organs only occurred when I was administered to animals ingesting high amounts of salt. In the affected animals the authors considered that the incorporation of I within the kidney glomeruli and the resulting swelling of their linings that occurred led to reduction of filtration through the glomeruli. A state of sodium retention arose as a result in rats having a high salt intake. In support of this view it was observed that the onset and the rate at which the hypertensive state developed was