Joseph Leichter

Placental blood flow in rats fed alcohol before and during gestation

Abstract Female Sprague-Dawley rats were either given 20% alcohol in drinking water and solid diet ad libitum (alcohol group) or were pair-fed to the alcohol group (pair-fed group) or were given water and solid diet ad libitum (ad libitum group) for four weeks. They were then mated and the alcohol group was changed to 30% alcohol in water. On day 20 of gestation each rat was injected with 57Co-labeled microspheres into the left ventricle and radioactivity was determined in the placentas and kidneys. Cardiac output and blood flow to the placentas and kidneys was calculated. Fetuses and placentas were weighed, and the osmolality of the maternal plasma and water content of the muscle was determined. Cardiac output and blood flow to the kidneys did not differ among the three groups. Blood flow to the placenta, whether expressed as m1/min/g placenta or m1/min/placenta, or as % of cardiac output was significantly reduced in the alcohol group compared with the pair-fed and ad libitum groups, which did not differ from one another. Fetuses were significantly lighter and placentas were significantly heavier in the alcohol group than in the other two groups. Plasma osmolality was increased and muscle water was decreased about 7% in the alcohol group, indicating a moderate degree of dehydration. It is concluded that chronic alcohol consumption leads to a redistribution of blood, with less blood supplying the placentas. This may contribute to the growth retardation seen in fetal alcohol syndrome.

Effect of enteral nutritional products differing in carbohydrate and fat on indices of carbohydrate and lipid metabolism in patients with NIDDM

Non-insulin dependent diabetes mellitus (NIDDM) is associated with chronic hyperglycemia, which increases the risk of developing microvascular and macrovascular complications. Elevated triglyceride (TG) and VLDL cholesterol levels and low levels of HDL cholesterol have also been frequently reported in NIDDM patients. A diet high in complex carbohydrate and low in fat is typically recommended for management of NIDDM, however, this has recently been challenged by scientific reports of the benefits of dietary intakes high in monounsaturated fat. Thirty-two individuals with NIDDM were randomized to receive either Ensure with Fibre® (30% fat) or a high monounsaturated fatty acid product, Glucerna® (50% fat). These products were consumed for 28 days at 280% of daily energy intake. Post-treatment, dietary compliance was verified by a higher plasma TG 18:1 n-9 (p < 0.001) in the Glucerna® group and a higher plasma TG 18:2 n-6 (p < 0.001) in the Ensure with Fibre® group. The postprandial rise in blood glucose levels, determined by fingerprick samples, was significantly lower (p < 0.01) in the Glucerna® group. Trends of clinical interest were greater mean decreases in the Glucerna® group compared to the Ensure with Fibre® group in: fructosamine, 9.13 umol/L vs 0.14 umol/L; glucose, 1.61 mmol/L vs 0.63 mmol/L; and insulin, 46.0 pmol/L vs 12.6 pmol/L; respectively. However, overall, fasting plasma glucose, fructosamine, TG and cholesterol levels were not significantly different between groups. Thus, in these patients, the high monounsaturated fat diet and the standard diet were similar with regard to usual indicators of carbohydrate and lipid metabolism. A high monounsaturated fat diet appears to pose no risk to lipoprotein metabolism in NIDDM patients.

Plasma Amino Acids and Glucose Levels in the Rat Fetus and Dam after Chronic Maternal Alcohol Consumption

To evaluate the effect of chronic maternal alcohol consumption on plasma amino acid and glucose levels in both the fetus and the mother, female Sprague-Dawley rats were divided into 3 dietary treatment groups. Group 1 (alcohol) was fed ad libitum a stock diet plus 20% alcohol in drinking water for at least 4 weeks before mating and 30% alcohol during gestation. Group 2 was pair-fed the stock diet plus corn starch calorically equivalent to the amount of alcohol consumed by group 1 animals. Group 3 (control) received the stock diet and water ad libitum. On day 21 of gestation the fetuses of alcohol-treated dams weighed significantly less than those of the control and pair-fed groups. Fetal plasma glucose levels were significantly lower in the alcohol group when compared to those of the pair-fed and control groups, while the maternal glucose levels were similar in all three treatment groups. Plasma amino acid concentrations showed no corresponding trends in mother and fetus. Only proline was significantly reduced and alpha-amino-n-butyric acid elevated in the alcohol-treated dams when compared to the pair-fed and control rats. In the fetal plasma, only aspartic acid was significantly lower in the alcohol group when compared to the other two groups. A moderate degree of dehydration occurred in the alcohol-treated dams, but plasma albumin was within normal levels. It is concluded that the marked decrease in the concentration of plasma glucose in alcohol-exposed fetuses may be partially responsible for their retarded growth.

Histological Changes in the Placenta Induced by Maternal Alcohol Consumption in the Rat

To investigate the placental enlargement which accompanies maternal alcohol consumption during pregnancy, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On days 17, 18, 19 and 20 of gestation, placentas were removed for histological observation. On days 18-20, the placentas of alcohol-fed rats weighted significantly more than did those of controls, although there was no difference in weight on day 17. Giant cells in the basal zone were significantly increased in number and size in alcohol-fed rats compared to controls. Trophoblastic cells in the basal zone were significantly larger in the alcohol group than in the control groups except on day 17. The maternal blood channels in the labyrinth were wider and more filled with blood corpuscles in the alcohol group than in either control group. It is concluded that the increased weight of the placenta may be largely due to stagnated maternal blood cells in the labyrinthine blood channels and also to the increased number and size of giant cells and the enlarged trophoblastic cells in the basal zone.

Partial Purification and Some Properties of Pteroylpolyglutamate Hydrolase (Conjugase) from Chicken Pancreas

Summary A simple and rapid procedure for the purification of pteroylpolyglutamate hydrolase (conjugase) from chicken pancreas for the purpose of standardization of microbiological assays of folates has been developed. It yields a stable folate-free preparation in quantity. The purification steps included extraction of conjugase from crude lyophilized chicken pancreas in mer-captoethanol followed by DEAE-cellulose chromatography. The enzyme was further purified by absorption to alumina-C-γ-gel from which it was eluted with phosphate buffer, pH 6.5. The enzyme was concentrated by dialysis against 20 vol of 2 M sucrose, lyophilized, and vacuum-sealed. The purified conjugase exhibited two peaks on Sephadex G-75 chromatography corresponding to molecular weights of 50,000 and 25,000, respectively. The optimum

Method of ethanol administration as a confounding factor in studies of fetal alcohol syndrome

Female Sprague-Dawley rats were fed a complete liquid diet containing either 5.5% ethanol (mean daily intake of about 9g of ethanol per kg body weight) or an isocaloric amount of dextrose (control group), with additional water available ad libitum. The diets were fed for four weeks prior to and throughout pregnancy. On day 20 of gestation cardiac output and blood flow to the the placenta, heart, kidneys and uterus were measured and plasma osmolality and muscle dry weight were determined. No significant differences were seen between alcohol and control groups with respect to litter size, fetal weight, maternal cardiac output, blood flow to the placenta or other organs, plasma osmolality, or muscle dry weight. This contrasts with previous experiments in which a similar quantity of alcohol (as % calories) was offered in drinking water (equivalent to a mean daily ethanol intake of 10g/kg body weight). Under those conditions fetal weight was reduced, blood flow to the placenta was reduced, and plasma osmolality and muscle dry weight were increased, indicating a moderate degree of dehydration. It is concluded that the effect of ethanol ingestion is influenced by the mode of administration of the ethanol. Dehydration may be a confounding factor in studies of animal models of fetal alcohol syndrome, although it is not possible to rule out a differential metabolic response to alcohol, depending on the mode of administration.

Lactose tolerance in a jewish population

In order to investigate the possible effect of environment on lactose deficiency, lactose tolerance tests were performed on 32 healthy Jewish adults living in Western Canada. The results were compared with those obtained in Jewish communities in Israel. There were 20 males and 12 females, 20–47 years of age, with a mean of 27.2 years. The tests revealed that 22 (68.8%) of the subjects were lactose intolerant on the basis of a maximal blood glucose rise of less than 20 mg/100 ml above the fasting level after the lactose load. The mean maximum blood glucose rise was 4.1 mg/100 ml in the 22 lactose-intolerant subjects and 33.6 mg/100 ml in the 10 lactose-tolerant subjects. Gastrointestinal symptoms during the test were observed in 95.5% of the subjects with a low rise in blood glucose, and in 10% of those with a normal rise in blood glucose. There was no relationship between lactose tolerance and milk intake. The results suggest a high incidence of lactose intolerance among North American Jews, and are similar to findings in Jewish communities in Israel.

Lactose tolerance in a Slavic population

In order to gather data on the frequency of primary lactase deficiency in various population groups, lactose tolerance tests were performed on 38 healthy adults of Slavic origin who had recently left Eastern Europe and are presently living in Western Canada. Twenty-one of the subjects were born in Poland and 17 in Czechoslovakia. There were 16 males and 22 females, aged 17–65 years, with a mean of 29.8 years. The tests revealed that 9 (23.9%) of the 38 subjects were lactose intolerant on the basis of both criteria, showing a maximum rise in blood glucose of less than 20 mg/100 ml above the fasting blood glucose level after ingesting 50 g of lactose, and experiencing gastrointestinal symptoms during the test. The mean maximum rise in blood glucose was 39.1 mg/100 ml in the 29 lactose tolerant subjects and 7.3 mg/100 ml in the 9 lactose intolerant subjects. Gastrointestinal symptoms during the test were observed in all 9 subjects with a low rise in blood glucose, and no symptoms were produced in any of the 29 subjects with a significant rise in blood glucose (> 20 mg/100 ml). Most of the subjects consumed 1 cup of milk per day. In addition, they were irregularly consuming lactose-containing products such as ice cream, chocolate drinks, etc. The results suggest a relatively low frequency of lactose intolerance among Eastern Europeans of Slavic origin, and in this respect, they resemble Northern Europeans.

Lactose intolerance in Canadian West Coast Indians

Lactose tolerance tests were performed on 30 healthy Canadian West Coast Indians and 16 non-Indians of Northern European extraction. Among the Indians, there were 7 males and 23 females, aged 14–24 years, with only 1 above 20 years of age (mean 15.8 years). The non-Indians consisted of 3 males and 13 females, aged 15–26 years, with only 2 above 18 years of age (mean 17.4 years). The tests revealed that of the 30 Indians, 19 (63.3%) were lactose intolerant on the basis of maximal blood glucose rise of less than 20 mg/100 ml above the fasting level after the lactose load. Gastrointestinal symptoms during or after the test were observed in 68.4% of the subjects with a flat blood glucose curve and in 18.2% of those with normal curves. In contrast, of the 16 non-Indians, only 1 (6.3%) was lactose intolerant, and none experienced abdominal discomfort during or after the test. Milk consumption among most of the Indian subjects seems to be low by North American standards, as judged by their past milk-drinking habits. The results suggest a high incidence of lactose intolerance among West Coast Indians during adolescence.

Does dehydration contribute to retarded fetal growth in rats exposed to alcohol during gestation

An earlier study showed that pregnant rats given ethanol in drinking water exhibited a significant degree of dehydration. The objective of the present study was to determine whether dehydration alone contributes to fetal growth retardation in alcohol treated rats. Female Sprague-Dawley rats were divided into 4 dietary groups. Group 1 (alcohol) received 20% ethanol in drinking water for four weeks prior to mating and 30% alcohol in drinking water throughout pregnancy and a stock diet ad libitum. Group 2 (pair-fed) was given an amount of food equal to that consumed by the alcohol group with the alcohol isocalorically substituted by corn starch. Water was available ad libitum. Group 3 (pair-water) was given an amount of food and water equal to that consumed by the alcohol animals. Group 4 (ad libitum) was given food and water ad libitum. On day 21 of gestation body weights of the alcohol exposed fetuses were significantly lower than those of the other three treatment groups. The difference in fetal body weights between the pair-fed and pair-water groups was not significant. Placentas were significantly heavier in the alcohol group than in the pair-fed and pair-water groups. Maternal plasma osmolality was significantly higher in the alcohol treated rats when compared to the pair-fed and ad libitum controls but not the pair-water group. No significant differences were seen in fetal plasma osmolality among the four treatment groups. It is concluded that dehydration does not contribute significantly to retarded fetal growth in rats given alcohol in drinking water as the sole source of fluid prior to and during gestation.