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Biomedical subjects

R M Russell

Publications and source records attributed to R M Russell.

At least 181 records · Page 10Linked to original sources

Protein energy malnutrition and taurine supplementation: effects on vitamin A nutritional status and electroretinogram of young rats.

The effect of protein energy malnutrition (PEM) on retinal function was investigated in weanling Long-Evans rats fed a low protein (4.2%) diet. After 8 wk, plasma retinol levels were lower in low protein (LP) and growth-restricted (GR) groups than in ad libitum controls (P less than 0.05); however, ocular vitamin A concentration remained normal. Plasma taurine concentration was lower only in the LP group, while retinal taurine was lower in both LP and GR groups than in control groups. The dark-adapted electroretinogram (ERG) became abnormal (e.g., depressed a and b waves, P less than 0.05) in both LP and GR groups but was corrected by ad libitum feeding of the control diet for an additional 8 wk. In a second study, weanling LP rats were supplemented with 0.4% taurine, 0.4% methionine or 0.4% glycine. Although taurine supplementation maintained plasma and retinal taurine stores, ERGs remained abnormal with retinal sensitivity significantly lower than in unsupplemented LP rats. Thus, PEM produced abnormal ERGs independent of ocular vitamin A concentration and retinal taurine levels. The high dietary taurine fed to protein-malnourished rats caused further impairment of visual function but was not detrimental to control or pair-fed rats.

Animals↗

Quantitation of the enterohepatic circulation of retinol in the rat.

Studies were done to determine whether vitamin A is reabsorbed in the enterohepatic circulation in forms that can be reutilized by the body for vision and reproduction. Micelles containing [11,12(n)-3H]retinol were administered orally to mesenteric lymph duct-cannulated rats. Lymph containing [3H]retinyl esters and small amounts of [3H]retinol and [3H]retinaldehyde was collected from these rats and an aliquot was injected into the jugular vein of a second group of mesenteric lymph duct-cannulated rats. The total radioactivity recovered in 24-h lymph collections from recipient rats was only 1.6% of that injected, and the [3H]retinyl esters, [3H]retinol and [3H]retinaldehyde recovered was only 0.9% of that injected. Thus, the amount of vitamin A recovered in the enterohepatic route in forms that can be reutilized by the body for vision and reproduction appears to be very small. Notable differences were observed in the composition of mesenteric lymph containing newly absorbed vitamin A and mesenteric lymph containing recycled vitamin A. In the former, 87% of the total lymph radioactivity was associated with retinyl esters, 5% with retinol, 3% with retinaldehyde and 5% with unidentified mostly nonpolar compounds. In the latter, only 41% of the total lymph radioactivity was associated with retinyl esters, 12% with retinol, 3% with retinaldehyde and 44% with unidentified mostly polar compounds.

Absorption↗

Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid.

Intestinal folic acid transport is a saturable process with a pH optimum of 5.5 to 6.0. Because of the possible effects of antacids and acid-lowering drugs on the pH of the proximal small intestine, the influence of these drugs on folic acid absorption was studied by using tritium-labeled pteroylmonoglutamic acid (PGA) in 30 subjects (21 women, nine men) of 56 to 89 years of age. Both cimetidine and an antacid containing aluminum and magnesium hydroxide reduced folate absorption from a liquid formula meal (p less than 0.01, p less than 0.001, respectively). Although ranitidine also caused a fall in folic acid absorption from the liquid meal, the change was not statistically significantly different from when PGA was given with the meal alone. Both histamine receptor antagonists tended to maintain a high intraluminal pH in the proximal small intestine after meals, which in part could explain the inhibition of folate absorption. However, neither drug was found to chemically interact with folic acid, and neither drug inhibited the dihydrofolate reductase. The antacid was found to precipitate folic acid at a pH of greater than 4.0, thus removing it from the aqueous phase. This appears to be the explanation for the lowered folate absorption in the presence of antacid. Although the effects of these drugs on reducing folic acid absorption were relatively small, such reductions could become clinically significant in chronic antacid or H2 receptor antagonist use or intensive antacid or H2 receptor antagonist use by individuals eating diets that are marginal in folate content.

Aged↗

Enterohepatic circulation of newly administered alpha-tocopherol in the rat.

We have measured the magnitude of the enterohepatic circulation of newly administered [3H]-alpha-tocopherol in rats. One group of animals (day-1 rats) was used to prepare [3H]-alpha-tocopherol-containing lymph. Another set of animals (day-2 rats) was divided into control and vitamin E supplemented (+E) groups, which were used to study the enterohepatic circulation of [3H]-alpha-tocopherol from day-1 rat lymph administered into the jugular vein of day-2 rats. Mesenteric lymph duct and common bile duct cannulations were performed. The enterohepatic circulation in day-2 rats of intrajugularly administered [3H]-alpha-tocopherol in chylomicrons was found to be 1.78 +/- 0.23% for control and 0.98 +/- 0.08% for +E rats (p less than 0.01). A considerable quantity (13.3 +/- 4.3% in control vs 19.2 +/- 4.7% in +E) of [3H]-radioactivity was recovered in bile over 24 h, of which pure [3H]-alpha-tocopherol was 3.17% in control and 1.04% in +E bile. More than 95% of [3H]-radioactivity recovered in day-2 control and +E bile was more polar than alpha-tocopherol shown by high performance liquid chromatography (HPLC). In contrast, more than 95% of [3H]-radioactivity appearing in day-2 lymph was unchanged alpha-tocopherol. Thus, the magnitude of enterohepatic circulation of alpha-tocopherol is very small in rats. Quantitation of the enterohepatic circulation of vitamin E under different physiological conditions remains to be investigated.

Animals↗

Severe hypervitaminosis A in siblings: evidence of variable tolerance to retinol intake.

A 2-year-old boy had signs and symptoms of chronic hypervitaminosis A. A course of increasing severity led to eventual death. A younger brother later had similar clinical features. Chicken liver spread containing up to 420 IU/g vitamin A was the likely source of intoxication. Markedly elevated circulating retinyl ester levels have persisted in the surviving sibling for 3 subsequent years despite severe restriction of vitamin A intake. A therapeutic trial of the carbohydrate-derived complexing agent 2-hydroxypropyl-beta-cyclodextrin was initiated. Circulating retinyl esters transiently increased during the infusion (from 407 to 4791 micrograms/dL), and urinary total vitamin A excretion, undetectable before infusion, increased to 23 micrograms/dL after infusion. The frequency of hypervitaminotic episodes has decreased somewhat in the 2 years since the infusion, probably related to dietary vitamin A restriction. The occurrence of this syndrome in two brothers, while a sister ingesting the same diet remains completely healthy, suggests an inherited variance in tolerance to vitamin A intake.

2-Hydroxypropyl-beta-cyclodextrin↗

Ascorbic acid, HDL, and total plasma cholesterol in the elderly.

The relationships between ascorbic acid (plasma and dietary) and plasma HDL cholesterol (HDL-C), total plasma cholesterol (T-C) and T-C:HDL-C ratio were examined in a population of 235 males and 445 females, age 60-98 years. Many known or suspected determinants of HDL-C and T-C, including age, sex, triceps skinfold thickness, fasting blood glucose, alcohol intake, and others, were considered as covariates due to their potential confounding or modifying effects on the relationships under study. The results show that plasma ascorbic acid is significantly (p less than 0.05) correlated with HDL-C (r = 0.09), T-C:HDL-C (r = 0.10), but not with T-C (r = 0.03). There is a strong age interaction with the largest effect of ascorbic acid in the youngest age group studied (60-69 years). The effects of dietary ascorbic acid are similar but slightly reduced in magnitude.

Aged↗

The short and long term effect of gastric partitioning surgery on serum protein levels.

The morbidly obese who undergo elective gastric partitioning surgery serve as models of surgical stress and subsequent severe protein calorie restriction. The short and long term effects of gastric partitioning surgery on circulating proteins and the specific micronutrients carried by the proteins were studied in 22 such patients (ages 23-56 years). Serum micronutrient values paralleled the levels of their carrier proteins. Mean concentrations of both short and long turnover proteins decreased significantly in the early postoperative period, whereas the acute phase reactant ceruloplasmin reached preoperative levels by the seventh postoperative day. Transthyretin and retinol binding protein remained depressed with long term reductions in protein and calorie intake, whereas ceruloplasmin and transferrin were somewhat less sensitive to prolonged protein-calorie restriction. Mean serum albumin, after an initial postoperative fall, rose to the baseline level by 1 month after surgery. Serum albumin levels remained within the normal range despite low protein and calorie intakes.

Adult↗

Vitamin requirements of the elderly.

In general, low dietary intakes can account for much of poor vitamin nutriture reported among various elderly populations. Despite problems in assessing vitamin nutriture in the elderly, the 1980 RDAs for thiamin, riboflavin, and ascorbic acid seem appropriate for those populations. However, RDAs for vitamin A and folate may be too high and the RDAs for vitamin D, vitamin B-6, and vitamin B-12 may be too low, due to specified age-related changes in the metabolism of these vitamins. For vitamin E, vitamin K, niacin, biotin, and pantothenic acid, the data is conflicting and/or insufficient to make a judgment about the appropriateness of the RDAs or to estimate safe and adequate daily intakes for the elderly.

Aged↗

Protein nutriture of a group of free-living elderly.

The adequacy of the protein intakes of elderly people without overt debilitating diseases was investigated on 691 free-living men and women divided into those aged 60-75 y and those greater than 75 y. In both age groups men and women had average protein intakes of 1.02-1.06 g/kg body weight, values well above the safe level of 0.75 g/kg recommended in a WHO/FAO/UNU report. Although plasma concentrations of albumin, prealbumin, and transferrin declined with age, these were not related to low intakes of protein by individual elderly people. Similarly, upper-arm muscle mass was not less in those elderly people at the lower end of the range of protein intakes. Thus in this population of overtly healthy elderly men and women, there was no evidence of protein deficiency in contrast to other surveys where elderly people with chronic diseases were included.

Age Factors↗

Folic acid malabsorption in atrophic gastritis. Possible compensation by bacterial folate synthesis.

Folic acid absorption was studied in 12 elderly subjects with atrophic gastritis and 10 elderly normal controls using tritium-labeled pteroylmonoglutamic acid. Two folic acid absorption tests were carried out on each subject with 120 ml of either water or 0.1 N HCl. Folic acid absorption was significantly lower in subjects with atrophic gastritis than in normal controls (31% vs. 51%, respectively; p less than 0.01). In subjects with atrophic gastritis, folic acid absorption rose significantly to 54% (p less than 0.001) when administered with acid, but did not change in normal controls (50%). Serum folate levels were normal in all subjects. Proximal small intestinal pH was higher in atrophic gastritis subjects than in normal controls (7.1 vs. 6.7, respectively; p less than 0.05), as were bacterial counts of small intestinal fluid (p less than 0.01). Bacteria cultured from the aspirates of subjects with atrophic gastritis were able to synthesize folate in vitro when incubated in a folate-free medium. Atrophic gastritis results in folic acid malabsorption but not in folate deficiency, possibly due to increased bacterial synthesis of folate in the small intestine.

Aged↗

Fundic atrophic gastritis in an elderly population. Effect on hemoglobin and several serum nutritional indicators.

The ratio of pepsinogen I to pepsinogen II in the circulation decreases progressively with increasing severity of atrophic gastritis of the fundic gland mucosa. Fasting blood was obtained from 359 free-living and institutionalized elderly people (age range, 60 to 99 years). A pepsinogen I/pepsinogen II ratio less than 2.9, indicating atrophic gastritis, was found in 113 (31.5%) subjects. The prevalence of atrophic gastritis increased significantly with advancing age (P less than .05). Within the atrophic gastritis group, 84 had a pepsinogen I level greater than or equal to 20 micrograms/L, indicating mild to moderate atrophic gastritis, and 29 had a pepsinogen I level less than 20 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. A significant increase in the prevalences of elevated serum gastrin levels (P less than .005), low serum vitamin B12 levels (P less than .005), circulating intrinsic factor antibody (P less than .005), and anemia (P less than .025) was observed with stepwise increases in severity of atrophic gastritis. Subjects with atrophic gastritis exhibited a lower mean serum vitamin B12 level (P less than .05) and a higher mean folate level (P less than .05), but no difference was detected in mean hemoglobin levels or serum levels of iron, ferritin, retinol or alpha-tocopherol. It is concluded that serum pepsinogen I and pepsinogen II levels can be used to determine the prevalence and severity of atrophic gastritis, that atrophic gastritis is common in an elderly population, and that atrophic gastritis is associated with vitamin B12 deficiency and anemia. Further, higher folate levels in atrophic gastritis may be related to an accumulation of 5-methyl tetrahydrofolate in serum due to vitamin B12 deficiency and/or greater folate synthesis by the intestinal flora resulting from bacterial overgrowth secondary to hypo- or achlorhydria.

Aged↗

Increased risk for vitamin A toxicity in severe hypertriglyceridemia.

A 48-year-old woman with malabsorption and type V hyperlipoproteinemia developed hypervitaminosis A with a total plasma vitamin A level of 871 micrograms/dL during therapy with an oral dosage of 18,000 retinol equivalents (60,000 IU) daily. Twelve percent of the total plasma retinol was found to be transported in the chylomicron-very low density lipoprotein (VLDL) fraction, which does not contain retinol-binding protein. For comparison, concentrations of retinyl esters and retinol were determined in nine patients with type V hyperlipoproteinemia and nine control subjects, none of whom were using vitamin A supplements. Both retinyl esters and retinol were significantly elevated in the group with hyperlipoproteinemia (p less than 0.0005 in both cases). Eight of these nine patients had retinol present in the chylomicron-VLDL fraction, whereas retinol was not detectable in this fraction in any of the nine normal controls. The data suggest that patients with severe hypertriglyceridemia associated with type V hyperlipoproteinemia are at increased risk for hypervitaminosis A.

Female↗

Determination of retinyl esters and retinol in serum or plasma by normal-phase liquid chromatography: method and applications.

Retinol and retinyl esters are measured in serum or plasma samples by gradient, normal-phase, adsorption "high-performance" liquid chromatography, with ultraviolet detection at 325 nm. The four major circulating retinyl esters in humans (esters of palmitate, stearate, oleate, and linoleate) are coeluted as a single peak. Retinyl acetate is included as an internal standard, to correct for variable recovery. Retinol values so measured correlated well (r = 0.88) with those by a widely used reversed-phase chromatographic technique (Clin Chem 1983;29:708-12). The mean retinol concentration was 570 (SEM 17) micrograms/L and the mean for retinyl esters was 33 (SEM 4) micrograms/L as determined in samples from 88 fasting young adults. Concentrations of retinol in plasma as low as 50 micrograms/L can be detected in 100-microL samples, as can 10 micrograms of retinyl esters per liter. Using this method, we measured absorption of low doses of vitamin A, which may provide a more physiological approach to assessment of fat malabsorption. Additionally, the procedure proved useful for quickly screening for vitamin A toxicity. Major advantages include small sample size, direct injection of the extract ed sample without evaporation, rapid elution pattern, co-elution of major retinyl esters as a single peak, and low limit of detection.

Adult↗