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Biomedical subjects

S W Thenen

Publications and source records attributed to S W Thenen.

At least 19 recordsLinked to original sources
PubMed1991

Folate deficiency and an abnormal lymphocyte deoxyuridine suppression test in monkeys.

Cebus albifrons were fed folate-deficient diets in order to assess folate status at the cellular level with the deoxyuridine suppression test. Plasma and red blood cell folates were significantly lower at 2 months, compared to control values. Hematologic signs of megaloblastic anemia occurred after 6 months, with significantly lower hematocrit, hemoglobin and red blood cell number values and increased polymorphonuclear leukocyte lobe counts. Urinary formiminoglutamic acid excretion also was elevated significantly. Whole blood lymphocyte cultures exhibited abnormal deoxyuridine suppression of [3H]-thymidine incorporation into DNA with folate deficiency. Thus this deoxyuridine suppression test can be used in isolated whole blood lymphocytes of these nonhuman primates to document folate deficiency.

Animals↗
PubMed1989

Experimental maternal and neonatal folate status relationships in nonhuman primates.

The influence of maternal dietary folic acid intake on folate status was studied in Cebus albifrons monkeys by feeding 10 or 250 micrograms/100 kcal dietary folic acid during pregnancy and 4 wk postpartum. Maternal, infant, and nonpregnant hematologic indices; blood and liver folate concentrations; and urinary formiminoglutamic acid excretion all varied with dietary folate intake and pregnancy status as did milk folate concentration in lactating dams. Maternal folate status, determined by plasma, red blood cell, and milk folate concentrations, as well as urinary formiminoglutamic acid excretion, all were correlated significantly with liver folate concentrations in neonates (r = 0.740, r = 0.919, r = 0.936, and r = -0.851, respectively). Results in these primates showed that neonatal folate status was related significantly to the dietary folate intake and folate status of the mother during pregnancy and lactation.

Animals↗
PubMed1989

Megadose effects of vitamin C on vitamin B-12 status in the rat.

Effects of ascorbic acid ingestion on the severity of vitamin B-12 deficiency were investigated by feeding weanling rats experimental diets containing 0-100 micrograms of vitamin B-12 activity per kg of diet, with or without 6.0 mg of ascorbic acid per ml supplied in drinking water for 15 wk. This daily consumption of up to 150 mg of ascorbic acid did not impair growth, but did result in significantly higher concentrations of ascorbic acid in plasma, liver, adrenal glands and feces. When rats were fed diets deficient or marginally deficient in vitamin B-12, liver concentrations of vitamin B-12 were markedly lower than in liver of rats fed adequate vitamin B-12. Ascorbic acid ingestion raised values significantly in the vitamin B-12-deficient diet group. Urinary methylmalonic acid was significantly elevated in the deficient rats. However, it was significantly reduced to more normal values by ascorbic acid in rats with both low and marginal vitamin B-12 status, as defined by dietary and liver concentrations of vitamin B-12 activity. Although coprophagy was not prevented, rats showed no increased consumption of feces with the higher ascorbic acid content. Thus, the results of this research indicate that vitamin C ingestion partially protects rats from vitamin B-12 deficiency.

Adrenal Glands↗
PubMed1987

Intestinal absorption, liver uptake, and excretion of 3H-folic acid in folic acid-deficient, alcohol-consuming nonhuman primates.

Nonhuman primates fed folic acid-deficient diets +/- 30% kcal ethanol were used to determine alcohol effects on megaloblastic anemia development and folate bioavailability. Lower hemoglobin (Hb) and red blood cell (RBC) counts and higher mean corpuscular volume (MCV) occurred after 13 wk in alcohol-fed monkeys, later in controls. Plasma, RBC, and liver folate declined and urinary formiminoglutamic acid (FIGLU) was elevated in both groups with FIGLU increasing more among alcohol-fed monkeys at 38 wk. After 40 wk, the bioavailability of oral 3H-folic acid was investigated and showed increased fecal and reduced urinary tritium excretion in alcohol-fed monkeys compared with controls while plasma uptake and liver and whole body tritium retention were similar in both groups. These observations demonstrate that chronic alcohol consumption impairs folate coenzymes, accelerates appearance of hematologic indices of megaloblastic anemia, and causes possible malabsorption of enterohepatically circulated folates in folate deficiency even when other essential nutrients are provided.

Alcohol Drinking↗
PubMed1984

Influence of diet on glucose metabolism of soleus muscle in artificially-fed 15- and 20-day-old Zucker fatty rats.

The relationship between diet and soleus muscle insulin responsiveness was examined in lean and obese Zucker rat pups that were artificially fed high-fat and high-carbohydrate liquid diets from 10 to 20 d of age and compared to pups that suckled normally. Elevated plasma glucose and insulin concentrations were found in both lean and obese artificially-fed pups at 20 d as compared to dam-fed controls. Total glucose utilization in isolated soleus muscle was estimated from the sum of the rates of 14C-glucose oxidation and 14C-glucose incorporation into glycogen and varied with genotype, age and diet. In general, soleus muscle from artificially-fed obese pups showed a lower basal and insulin-stimulated total glucose utilization than lean pups, with a greater and earlier effect due to high carbohydrate feeding. These results suggest that early dietary modification can alter peripheral target tissue insulin responsiveness and accelerate the onset of the insulin-resistant state.

Animals↗
PubMed1984

Influence of diet on de novo lipogenesis in artificially-fed 15- and 20-day-old Zucker fatty rats.

Lean and obese Zucker rat pups were artificially fed high-fat and high-carbohydrate diets from 10-20 d of age to determine the effect of early diet composition on de novo lipogenesis and the development of obesity in the Zucker fatty rat. Amounts fed were the same as that consumed by suckling Zucker rat pups, which also were used as dam-fed controls. Lipogenic rates were measured by in vivo incorporation of tritium from 3H2O into total lipids and fatty acid and glyceride-glycerol fractions of liver, carcass and adipose tissue. Expressed on a per g tissue basis there was no difference in lipogenic rates between lean and obese pups in any tissues, even though pups accumulated a significantly higher percentage of carcass fat. High carbohydrate feeding accelerated growth and lipogenic rates in both lean and obese rats. Dam-fed pups had the lowest rates of lipogenesis and percentage of carcass fat. Thus, diet composition and method of feeding were important determinants of de novo lipogenic rates and body energy stores at this early age, but their influence was similar in lean and genetically obese animals.

Adipose Tissue↗
PubMed1982

Decreased insulin binding, glucose transport, and glucose metabolism in soleus muscle of rats fed a high fat diet.

The relationship between diet and insulin sensitivity was examined in isolated soleus muscle from 10-wk-old lean Zucker rats. Rats were fed either a high fat or high carbohydrate diet that had 67% of calories as fat or carbohydrate, respectively, for 10 days. Plasma insulin but not plasma glucose concentrations were significantly elevated in high-fat-fed rats, indicating that a state of insulin resistance existed. The mechanisms responsible for the insulin resistance were studied by measuring insulin binding, 2-deoxyglucose uptake, and glucose metabolism in soleus muscle. The soleus muscle from the high-fat-fed rats bound significantly less insulin than high carbohydrate control rats under equilibrium binding conditions. The 35% decrease in insulin binding at maximal insulin concentrations resulted from a decrease in insulin receptor number but no change in receptor affinity. Maximal insulin-stimulated 2-deoxyglucose uptake was reduced in soleus muscle from high-fat-fed rats when compared with high carbohydrate controls. A decrease in postmembrane basal and insulin-stimulated glucose utilization was produced by high rat feeding and varied depending upon the pathway involved. An estimate of glycolysis (3H2O) formation from [5-3H]glucose) and glucose oxidation (14CO2 production from 14C-glucose) demonstrated a greater decrease in basal and insulin-stimulated utilization than in [5-3H]glucose conversion to [3H]glycogen. These results suggest that multiple sites are responsible for the observed insulin resistance in soleus muscle after high fat feeding.

Animals↗
PubMed1982

Folacin content of supplemental foods for pregnancy.

Microbiological assay with Lactobacillus casei was made to determine total folacin content of foods allowed in the Special Supplemental Food Program (WIC) serving low-income pregnant women in the United States, who are at risk for folacin deficiency. Results of the assay showed that, when foods with a high nutrient density and Index of Nutritional Quality for folacin were selected, 69 percent of the folacin RDA for pregnancy could be provided in only 34 percent of the energy allowance. Thus the WIC program can contribute significant amounts of folacin to the diet of pregnant women.

Dairy Products↗
PubMed1981

Composition of rat milk from day 5 to 20 of lactation and milk intake of lean and preobese Zucker pups.

Milk composition and milk intake were measured in lean and preobese Zucker rat pups. Lactating dams were injected with 3H2O, which equilibrated with plasma water within 30 minutes. A constant specific activity of 3H was maintained by adding 3H2O to drinking water. Blood samples of 5 microliters were obtained from 1, 15 and 20-day-old suckling pups every 4 hours for a 24-hour period and the accumulation of tritium was used to calculate pups' milk intake. No diurnal variation in milk intake of pups was observed. Obese pups were identified at 5 weeks of age and showed no difference in milk intake compared to lean littermates at 10, 15 and 20 days of age. Milk intake of pups increased with age from 2.0 ml at day 10 to 15.8 ml by day 20. Food and water intake of dams also increased from day 10 to 20 of lactation. The protein and carbohydrate component of rat milk did not change significantly from day 5 to 20 of lactation; however, the fat component decreased significantly from 12.7% at day 5 to 4.2% at day 20.

Animals↗
PubMed1980

Influence of age and genetic background on in vivo fatty acid synthesis in obese (ob/ob) mice.

The relationship of developing obesity and hyperinsulinaemia to fatty acid synthesis in whole body and major tissues has been studied in two strains of genetically obese (ob/ob) mice using in vivo incorporation of 3H2O into fatty acids. Rates of fatty acid synthesis were not increased in pre-weaning C57BL/6J obese mice even though hyperinsulinaemia and obesity occurred. Post-weaning, rates of fatty acid synthesis increased to 5 weeks of age in adipose tissue, liver and carcass, the latter being the major site of synthesis. Synthesis then declined in carcass and adipose tissue, but remained unchanged in liver at 3 months. Increased fatty acid synthesis developed earlier in Imperial College obese mice as compared to the C57BL/6J strain and total rates of synthesis were 3--5 times greater. Adipose tissue was the major site of synthesis in Imperial College obese mice, while carcass was of only minor importance. Thus genetic background and age strongly affected rates of fatty acid synthesis and also the extent to which various tissues contributed.

Adipose Tissue↗
PubMed1980

Influence of thyroid hormone treatment on growth, body composition and metabolism during cold stress in genetically obese mice.

Pharmacologic doses of thyroid hormones were administered chronically in diets and acutely by injection to determine their metabolic effects on the development of obesity and the response to cold stress in genetically obese mice. Feeding a 0.1% thyroid powder (TP) diet for 6 weeks to weanling male mice resulted in a marked reduction in weight gain and high mortality in obese but not in non-obese mice. Diets containing 0.01 and 0.02% TP also produced enhanced effects in obese mice during a 13-week feeding period as indicated by reduced body weight, fat and protein and reduced blood glucose at ambient temperature. Both acute and chronic treatment with thyroid hormone produced similar effects in the cold (4 degrees). Blood glucose concentrations were reduced in both obese and non-obese mice, but blood free fatty acid values were unchanged due to hormone treatment. Neither acute nor chronic treatment with thyroid hormones prolonged survival of obese mice during cold exposure. These results suggest a normal or enhanced fat mobilization and utilization in response to exogenous thyroid hormone at ambient temperature. However, the defect in utilization of energy stores for thermogenesis during cold exposure was not ameliorated by this treatment.

Aging↗
PubMed1980

Early development of lipogenesis in genetically obese (ob/ob) mice.

This study was designed to sequence the earliest metabolic abnormalities associated with the development of obesity in the obese hyperglycemic mouse (C57BL/6J ob/ob). In situ lipogenesis was measured with 3H2O in fetuses at day 19 of gestation and in 5-, 10-, 15-, and 35-day-old mice. Preobese 15-day-old animals were identified on the basis of rectal hypothermia. The earliest increased accumulation of fatty acids was observed in the carcass of 15-day-old preobese animals (ob/ob) compared to their lean littermates (+/?) and known lean controls (+/+). The increased carcass lipogenesis in these animals was accompanied by an increase in plasma insulin concentration. Weaned 35-day-old obese animals showed a significant increase in hepatic and subcutaneous adipose tissue lipogenesis, plasma insulin, and glucose values when compared to their littermates (+/?). The results indicate that increased carcass lipogenesis, hyperinsulinemia, and hypothermia appear between days 10 and 15 and that these abnormalities precede the hyperglycemia and increased hepatic lipogenesis observed in the mature ob/ob mice.

Adipose Tissue↗
PubMed1980

Age-dependent development of insulin resistance of soleus muscle in genetically obese (ob/ob) mice.

The relationship between insulin binding and its biological effects was studied in soleus muscle of 3- to 15-wk-old genetically obese (ob/ob) mice. At 3 and 4 wk of age, soleus muscle from lean and obese mice bound similar amounts of insulin under equilibrium binding conditions. However, by 6 wk of age, insulin binding and total receptor concentration (Ro) were significantly decreased in soleus muscle from obese compared to lean mice. In addition lean and obese mice demonstrated an age-dependent decrease in insulin binding, Ro, and receptor affinity. At 4 wk of age, insulin-stimulated 2-deoxyglucose transport and glucose utilization were significantly lower in soleus muscle from obese mice and preceded alterations in insulin binding. The postmembrane decrease in insulin sensitivity was dissimilar for various pathways of glucose metabolism. Glucose conversion of glycogen, but not the glycolytic rate or glucose oxidation, remained sensitive to insulin stimulation. These data indicate that glucose transport and utilization rather than insulin binding may play the primary role in the development of insulin resistance of muscle in the obese diabetic syndrome.

Aging↗
PubMed1980

Effect of folic acid supplementation on pregnancy in the squirrel monkey (Saimiri sciureus).

Supplementation of squirrel monkeys with folic acid improved hematologic and folate status, maternal weight gain during pregnancy, and infant birth weight. Thus the folate content in the stock diet (1.4 microgram/g) did not meet the requirement for pregnancy. Low plasma vitamin B12 values suggest that vitamin B12 in the stock diet (22 ng/g) also was not adequate. Changes with folic acid supplementation are similar to those for human subjects, indicating that the squirrel monkey is an appropriate model for folic acid deficiency in pregnancy in man.

Animals↗
PubMed1979

Folacin deficiency and requirement in the squirrel monkey (Saimiri sciuresus).

Acute folacin deficiency was studied in eight young squirrel monkeys (Saimiri sciureus). Half of the animals were fed a semipurified deficient diet (no added folic acid) and half were fed a control diet (0.84 mg of added folic acid per kilogram of dry diet). Monkeys fed the deficient diet lost weight and suffered from diarrhea and dehydration leading to the death of one of the animals after 6 weeks. Folacin deficiency also was studied in six older animals fed diets containing varying levels of added folic acid. Monkeys fed diets containing 0.14 or 0.27 mg of added folic acid per kilogram of dry diet slowly developed alopecia, a scaly dermatitis, and a mild macrocytic anemia. When these animals were fed the deficient diet, they lost weight rapidly, the alopecia and dermatitis worsened, excretion of formiminoglutamic acid in the urine increased, and a severe megaloblastic anemia with profound intramedullary hemolysis developed. Deficient monkeys had low plasma and red blood cell folacin values but maintained normal plasma vitamin B12 values. Repletion of the animals fed the deficient diet with injections of folic acid reversed both the hematological and physical deterioration. The folacin requirement for maintenance of body weight in these animals was 28 micrograms of total folacin per kilogram of body weight per day. More than 75 micrograms of total folacin per kilogram of body weight/day may be needed to assure growth and normal hematological parameters and bone marrow cytology.

Animals↗
PubMed1979

Use of tritiated water for measurement of 24-hour milk intake in suckling lean and genetically obese (ob/ob) mice.

A non-invasive method has been developed for measuring milk intake of suckling mice under physiological conditions. This method was used to determine whether genetically obese (ob/ob) mice are hyperphagic at 10 and 15 days of age. Lactating dams were injected with tritiated water (3H2O), which equilibrated in body water within 30 minutes. A constant specific activity of 3H2O was maintained over a 24-hour period by provision of 3H2O in drinking water. Tritium accumulation in body water of pups was proportional to their milk intake. After 24 hours, pups were removed from the dam, weighed, and blood samples (less than 10 microliters) obtained for assay of plasma 3H content by liquid scintillation counting. Body water content was computed from body weight. The composition of mouse milk taken from dams on days 10 and 15 of lactation was analyzed both volumetrically and gravimetrically. Water content was 68 to 69%; lipid content was 20% on day 10, 17% on day 15. At 10 days, mean milk intake was 0.96 ml, independent of litter size. At 15 days, intake per pup tended to decrease, from 1.4 to 0.8 ml, with increasing litter size. Using this method we have established that under physiological conditions ob/ob mice, which were identified as such at 4 to 5 weeks of age, do not have increased milk consumption at either 10 or 15 days of age.

Animals↗