Maternal-neonatal serum vitamin A concentrations.

Prevention of neonatal vitamin A deficiency is related to the adequacy of maternal vitamin A stores. In this study we investigated maternal and cord serum vitamin A and retinol-binding protein (RBP) values in an Indian population including, for the first time, clinically vitamin A-deficient mothers. Twenty-eight maternal-neonatal pairs were selected from maternal cohorts of high socioeconomic status without clinical evidence of vitamin A deficiency (group I) and low socioeconomic status with conjunctival xerosis and Bitot's spots (group II). Maternal education, caloric and vitamin A intakes, weight, height, hemoglobin, and birth weight were significantly lower in group II. Serum vitamin A levels were significantly higher in group I mothers and newborns as were RBP levels in group I mothers. However, a significant difference between groups I and II in cord blood RBP was not observed. Upon correlation of maternal vitamin A levels with cord blood vitamin A levels, a logarithmic relationship was revealed, suggesting saturable transplacental transport of vitamin A.

Effect of Newcastle disease virus infection on vitamin A metabolism in chickens.

The effect of Newcastle disease virus (NDV, La Sota strain) infection on vitamin A metabolism was investigated in chickens maintained on normal or marginal vitamin A intake. NDV, a virus of the Paramyxoviridae family that primarily affects epithelial tissue, was administered at 4 wk of age. Plasma levels of retinol, retinol-binding protein and, to a lesser extent, transthyretin were found to be significantly lower during both the acute and postacute phases of infection in chickens fed a diet marginally deficient in vitamin A compared to noninfected birds fed the same diet, while vitamin A content in liver was unaffected. However, in chickens fed adequate vitamin A, NDV infection did not influence the parameters measured. Levels of retinol-binding protein in liver were significantly increased by inadequate vitamin A nutriture, but infection partly reduced this increase. The results suggest that the reduced vitamin A status in marginally vitamin A-deficient chickens infected with NDV can be attributed to a combination of a direct effect of the virus on retinol-binding protein metabolism in liver and an increased rate of utilization and catabolism of retinol and retinol-binding protein by extrahepatic tissues.

Use of retinol-binding protein and prealbumin as indicators of the response to nutrition therapy.

There is no single available measurement for evaluating the short-term response to nutrition therapy. The ideal parameter should have high sensitivity and specificity and should be unaffected by non-nutritional factors. A literature review suggested that plasma retinol-binding protein and prealbumin concentrations change earlier than albumin and transferrin levels and appear to correlate better with nitrogen balance during nutrition therapy. That conclusion was supported by our own findings in patients receiving total parenteral nutrition and following the transition to oral or enteral feedings. Although concentrations of these plasma proteins have been shown to be affected by stress and renal and hepatic disease, they appear to be more sensitive indicators of the adequacy of nutrition support than other more commonly used assessment parameters.

Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer.

In a nested case-control study the stored, frozen sera from 22 cases of cancer of the pancreas and 44 matched control subjects were assayed for retinol, retinol-binding protein, total carotenoids, beta-carotene, lycopene, vitamin E (alpha-tocopherol), and selenium. Prediagnostic serum levels of lycopene and Se were lower among cases than among matched control subjects. These differences remained after adjustment was made for possible confounding by smoking, educational level, and the other measured serum levels. Low levels of serum vitamin E appeared to have a protective effect but a chance association between vitamin E and cancer of the pancreas could not reasonably be excluded. The association between cancer of the pancreas and serum Se was significant when the data were analyzed as a whole but its effect was seen principally in men.

Comparison of the uptake and metabolism of retinol delivered to primary mouse keratinocytes either free or bound to rat serum retinol-binding protein.

Serum retinol-binding protein (RBP) is believed to be responsible for the transport of retinol from its storage site in the liver to vitamin A requiring target cells such as keratinocytes. We have used primary mouse keratinocytes as a model system to compare the uptake and metabolism of [3H] retinol delivered to them either free in solution or bound to RBP. RBP was purified from rat serum, loaded with [3H]retinol, and the [3H]retinol-RBP complex purified by affinity chromatography on human transthyretin-Sepharose. Keratinocytes incubated with either free [3H]retinol or [3H]retinol-RBP complex accumulated [3H]retinol in a time and temperature dependent manner. However, cells incubated with free [3H]retinol acquired 15- to 20-fold more ligand than if the retinol was delivered via RBP. The uptake of free [3H]retinol or [3H]retinol from RBP was not inhibited by excess unlabeled free retinol. The uptake of [3H]retinol from RBP was inhibited by high concentrations of holo-RBP, with half maximal inhibition occurring at 3 microM holo-RBP. However, no specific binding of 125I-labeled RBP to monolayers of keratinocytes or membranes prepared from them was found indicating the absence of a high affinity RBP receptor on keratinocytes. Surprisingly, 50% of the [3H]retinol delivered to the keratinocytes during a 30-min uptake period was released from them within 30-min irrespective of whether or not it was initially delivered to them as free [3H]retinol or bound to RBP. The remaining 50% was lost at a much slower rate, but only 20% remained 24-h after delivery. Studies on retinol metabolism demonstrated that 7%-12% of the total cell-associated [3H]retinol delivered during a 90-min uptake period was esterified (mostly as retinyl palmitate) whether or not it was given free in solution or bound to RBP. Additionally, [3H]retinol taken up by the keratinocytes during the initial 90-min incubation was not chased into a stable retinyl ester pool in a subsequent 9.5-h incubation, but instead, retinyl ester was lost from the cells with kinetics similar to those of total cell-associated radioactivity. These results suggest that a function of RBP is to protect cells from a rapid accumulation of the vitamin which occurs when it is delivered free in solution. However, the cellular fate and metabolism of retinol appears to be the same whether the vitamin is delivered free in solution or bound to RBP.

TSF, RBP and TBPA as nutritional indices in surgical patients with gynecological cancer.

The Authors investigated the usefulness of some biochemical markers of visceral protein synthesis (TSF, TBPA and RBP) in 24 patients affected with gynecological cancer and treated with Total Parenteral Nutrition in the perioperative period. The absence of an improving TSF and TBPA is related to increased morbidity and mortality.

Relationship of vitamin A and vitamin E intake to fasting plasma retinol, retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults: increased plasma retinyl esters among vitamin A-supplement users.

We studied the relationships of supplemental and total vitamin A and supplemental vitamin E intake with fasting plasma biochemical indicators of vitamin A and vitamin E nutritional status among 562 healthy elderly people (aged 60-98 y) and 194 healthy young adult (aged 19-59 y) volunteers. All subjects were nonsmokers. For the young adults, plasma retinol was significantly greater in males than in females (p less than 0.01); retinol was not related to supplemental vitamin A intake for either group. Fasting plasma retinyl esters demonstrated a significant increase with vitamin A supplement use. For supplemental vitamin A intakes of 5001-10,000 IU/d, a 2.5-fold increase over nonusers in fasting plasma retinyl esters was observed for elderly people (p less than 0.05) and a 1.5-fold increase for young adults (p greater than 0.20). For elderly people, greater fasting plasma retinyl esters were associated with long-term vitamin A supplement use (greater than 5 y) and biochemical evidence of liver damage. Elderly people who take vitamin A supplements may be at increased risk for vitamin A overload.

Retinol and retinyl esters in patients with alcoholic liver disease.

Liver retinoid levels and the retinyl esters were examined in liver biopsy specimens from 70 patients with alcoholic and nonalcoholic liver diseases. There was a wide variation in the liver retinoid levels. The liver retinoid level was statistically significantly lower in 15 patients with alcoholic liver disease and a depressed Normotest (NT) value of less than 65% compared with patients with alcoholic liver disease and a normal NT value of greater than 65% (P less than 0.01). The mean serum retinol level in patients with alcoholic cirrhosis was 0.68 +/- 0.38 mumol/l compared with 1.99 +/- 1.14 mumol/l in patients with alcoholic fatty liver (P less than 0.03). The relative amount of retinyl oleate was increased in the alcoholic fatty liver compared with the nonalcoholic fatty liver (P less than 0.001).

Nutritional status of patients with acquired immunodeficiency syndrome.

Nutritional status may be an important factor in the prognosis of morbidity and mortality. We assessed the nutritional status of individuals seropositive for human immunodeficiency virus (HIV) (as confirmed by Western blot) and of patients with AIDS, by determining the concentration in serum of total protein, albumin, prealbumin (transthyretin), and retinol-binding protein. HIV-seropositive individuals showed no significant difference from normal volunteers in values for prealbumin, albumin, and retinol-binding protein. Patients with AIDS showed significantly smaller prealbumin and albumin concentrations than did normal and HIV-positive individuals. There was no significant difference in the concentration of retinol-binding protein among the three groups. The concentration of total serum protein was significantly greater in HIV-positive individuals and in patients with AIDS than in normal individuals. Thus, the nutritional status of patients with AIDS may be a factor for morbidity and mortality.

Zinc status of children with sickle cell disease: relationship to poor growth.

We examined the zinc status of 80 children with sickle cell disease (SCD) and 44 disease-free sibling controls aged 3 to 18 years. For both patients and controls, variations in serum zinc by age, type of hemoglobinopathy, and growth status were measured. The mean serum zinc concentration of patients was significantly lower than for controls (77.8 +/- 9.9 vs. 82.2 +/- 9.8 micrograms/dl, mean +/- 1SD, P less than .05). Serum levels of alkaline phosphatase (AP) and retinol-binding protein (RBP), two zinc-dependent proteins, were also lower among patients (AP: 171 +/- 66 vs. 243 +/- 97 IU/L, P less than .001; RBP: 1.92 +/- .9 vs. 2.77 +/- .9 mg/dl, P less than .001). Patients greater than or equal to 12 years of age (n = 34) had significantly lower zinc levels than those less than 12 years (74.5 +/- 8.4 vs. 80.3 +/- 10.3 micrograms/dl, P less than .01), and children with homozygous SCD (Hb SS, n = 55) had a more pronounced deficiency than those with a variant hemoglobinopathy (76.3 +/- 8.9 vs. 81.5 +/- 11.5, micrograms/dl, P less than .05). Patients classified as having "poor" growth (height-for-age less than 5th percentile, n = 24) had a lower serum zinc level than those with "normal" growth (72.8 +/- 8.0 vs. 79.8 +/- 10.0 micrograms/dl, P less than .01). Dietary intake data, body mass index, and serum total protein and albumin levels were similar for patients and controls, suggesting that zinc deficiency in SCD does not relate to inadequate dietary intake. The origin of low serum zinc levels in children with SCD is more likely to relate to factors such as increased urinary zinc excretion, chronic intravascular hemolysis, and/or zinc malabsorption.

Immunoturbidimetric measurement of serum retinol-binding protein in renal and hepatic disease.

Serum retinol-binding protein (RBP), with a biological half-life of less than 12 h, is a useful indicator of liver or kidney dysfunction. An automated immunoturbidimetric assay for the measurement of RBP has been developed using the Cobas-BIO centrifugal analyser and commercially available materials. Serum samples with RBP concentrations as low as 3 mg/L were measured. Within-run and day-to-day imprecision were 3.7 and 5.7%, respectively. The reference range (mean +/- 2SD) for 51 adults was 17 to 61 mg/L. Slight haemolysis of serum (haemoglobin 10 g/L) resulted in an apparent 8% reduction of RBP with greater interference at higher haemoglobin concentrations. However, bilirubin in concentrations up to 0.15 g/L did not interfere with RBP measurements. There was good correlation between immunoturbidimetry and a commercial radial immunodiffusion method. Serum RBP concentrations were decreased in liver disease and increased in renal failure.

Serum prealbumin and retinol-binding protein concentrations in Japanese-type familial amyloid polyneuropathy.

Serum concentrations of prealbumin and retinol-binding protein were measured in 28 patients with Japanese-type familial amyloid polyneuropathy, 46 relatives and normal controls. Both the serum prealbumin and retinol-binding protein concentrations were significantly decreased in the patients when compared with normal controls. The mean serum levels of these proteins in the asymptomatic relatives were intermediate between controls and patients.

Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis.

In the last several years, five human plasma prealbumin (transthyretin) variants have been discovered in association with hereditary amyloidosis, a late-onset fatal disorder. We recently studied a patient of German descent with peripheral neuropathy and bowel dysfunction. Biopsied rectal tissue contained amyloid that stained with anti-human prealbumin. Amino acid sequence analysis of the patient's plasma prealbumin revealed both normal and variant prealbumin molecules, with the variant containing a tyrosine at position 77 instead of serine. We predicted a single nucleotide change in codon 77 of the variant prealbumin gene, which we then detected in the patient's DNA using the restriction enzyme SspI and a specifically tailored genomic prealbumin probe. DNA tests of other family members identified several gene carriers. This is the sixth prealbumin variant implicated in amyloidosis, and adds to the accumulating evidence that the prealbumin amyloidoses are more varied and prevalent than previously thought.

Novel aspects of vitamin A metabolism in the dog: distribution of lipoprotein retinyl esters in vitamin A-deprived and cholesterol-fed animals.

Retinyl ester concentrations in plasma from fasting humans, rabbits and rats are usually negligible. In contrast, plasma from fasting dogs contains appreciable amounts of retinyl esters, associated almost entirely with the low-density lipoproteins. This study was undertaken to gather additional information about the nature and origin of canine retinyl ester-containing lipoproteins. We examined the metabolism of endogenous lipoprotein retinyl esters in adult mongrel dogs with moderate vitamin A deficiency. Four animals were fed a diet of oatmeal and tuna fish that provided only 4% of the vitamin A contained in their control rations (15 vs. 367% of the canine recommended daily intake). There was an initial rapid decline in plasma retinyl esters. However, measurable concentrations persisted in plasma for up to 1 year of restricted vitamin A intake. Total plasma retinyl ester concentrations after 6 months of vitamin A deprivation, extrapolated from best-fit monoexponential decay curves for each animal, ranged from 11 to 89% of control, suggesting that there was sustained secretion of retinyl esters from endogenous stores. Density gradient ultracentrifugation of plasma from fasting vitamin A-deprived dogs showed retinyl esters in the very-low- and low-density lipoproteins. After fat and vitamin A feeding retinyl esters appeared among the very-low-, intermediate- and low-density lipoproteins, consistent with the suggestion that chylomicron retinyl esters are first taken up by the liver, and then resecreted as density less than 1.006-1.063 g/ml lipoproteins. Maximal incorporation of dietary retinyl esters into low-density lipoproteins was not reached until 24-48 h. Intermediate-density and beta-migrating low-density lipoprotein retinyl esters were increased markedly in fasting animals maintained on cholesterol- and saturated fat-enriched diets. These observations provide further evidence for the proposal that the canine liver secretes retinyl ester-containing particles, in amounts governed by dietary composition and vitamin A content. What selective advantage this unusual transport pathway might provide is not apparent.

Discriminant biochemical markers for evaluating the nutritional status of elderly patients in long-term care.

To determine the most discriminant serum markers of protein-energy status in elderly patients, we performed a discriminant analysis of 85 subjects grouped according to triceps skinfold and midarm circumference values as compared with reference percentiles. Results indicated that neither the classic serum indices of nutritional assessment nor retinol-binding protein can predict undernutrition. However, creatinine, urea, carotene, complement C3, and prealbumin included in a function enabled high discrimination between groups: 68% of subjects in 0-5th percentile for triceps skinfold and 75% of subjects in 0-5th percentile for midarm circumference are correctly predicted. Lower serum concentration was found in the lower anthropometric percentiles except for serum carotene, which showed an inverse relation not explained by diet. We found that nutritional alterations exist in hospitalized elderly patients. We emphasize the importance of considering several biochemical markers for detection of mal-nutrition and the pertinency of further exploration of serum carotene profiles in undernourished elderly patients.

Minerals in plasma and urine and gustatory function tests for salt in a group of healthy young men.

Detection threshold for salt (NaCl) and discrimination between two levels of NaCl concentration (0.6 and 0.7%) in foods, and their relation to some selected biochemical parameters in plasma and urine (Zn, Na, K, Mg, Ca, Se for plasma and urine, Cu and retinol binding protein for plasma) were investigated in 15 healthy male college students. No subject failed to discriminate the NaCl concentrations in more than 50% of the tests. The rate of correct discrimination (RCD) was not associated with plasma Zn (P-Zn), plasma retinol binding protein (P-RBP), urinary potassium (U-K) or urinary sodium (U-Na), which significantly correlated with RCD in our previous study, while the detection threshold was significantly correlated with urinary Ca-Mg ratio (U-Ca/Mg), urinary Ca (U-Ca), U-Na, and urinary Mg. In the stepwise multiple regression analysis, U-Ca/Mg, plasma Ca, plasma Na, and RCD were selected as significant independent variables. These indicate that the status of minerals such as Na, Ca, and Mg is related to the gustatory function. One possible explanation for the discrepancy between the present and previous results is the elevated P-Zn and P-RBP levels in the present subjects.

The effect of a synthetic polypeptide on the renal handling of protein in man.

Haemaccel is a synthetic polymer of partially degraded gelatin and a widely used plasma volume expander. The effect of a 17.5 g infusion of Haemaccel on protein excretion was investigated in four normal subjects. The urinary excretion of two low molecular weight proteins, retinol-binding protein and beta 2-microglobulin, increased 1000- and 500-fold respectively above the values found after administration of saline as a control. The urinary excretion of albumin did not change significantly (P greater than 0.5). In the hour after Haemaccel administration the excretion of the two low molecular weight proteins approached at least 50% of a predicted filtered load. This effect of Haemaccel may be due to inhibition of proximal tubular uptake or transport of the two proteins. Absence of any effect on albumin excretion suggests alternative mechanisms for its tubular reabsorption. Haemaccel may be a valuable new agent for the study of renal tubular protein metabolism.

Analysis of serum and urinary retinol binding protein in hepato-renal syndrome.

Retinol binding protein (RBP) was analyzed in the sera and urines of 5 patients with hepato-renal syndrome (HRS), 4 with acute tubular necrosis (ATN), 20 liver cirrhosis patients with normal kidney function (NKF), 14 chronic renal failure (CRF) patients, and 19 healthy adults. All renal failure patients had high mean urine RBP (URBP): HRS, 8 mg/L; ATN, 11 mg/L; CRF, 8 mg/L respectively; p less than 0.001 vs the rest. Those with ATN and CRF had high mean serum RPB (SRBP): 146 and 149 mg/L, respectively, p less than 0.001 compared to the other groups. In HRS, in spite of renal failure, SRBP was very low (mean = 12 mg/L). The cirrhotics with NKF averaged less than 50% of the SRBP values of the healthy controls (16 vs 41 mg/L RBP, p less than 0.001); their RBP excretion was normal (mean URBP of 0.1 vs 0.06 mg/L in the control group). RBP analyses before and during HRS in two patients showed a marked increase in urine RBP during HRS (35- and 600-fold respectively) with practically unchanged serum levels. Impaired hepatic production and/or release is proposed to explain the low serum RBP in HRS, and a renal tubular injury or dysfunction to account for its high excretion. The RBP urinary loss could further compromise an already abnormal RBP metabolism and its serum levels. This combination (of low serum and high urine RBP), in the context of renal failure occurring in alcoholic liver cirrhosis, could help in the recognition of HRS.

Vitamin A and D status of black South African women and their babies.

Knowledge of the vitamin D status of pregnant and lactating women in developing countries is very limited. An elective visit to the Transkei therefore provided us with the opportunity to study the relationship between the vitamin A and D status of dark-skinned mothers and babies resident in an environment of high sunshine exposure. 25-hydroxyvitamin D, retinol and retinol binding protein (RBP) were measured in serum samples collected from 43 black South African women and their babies, shortly after delivery. The results were compared with values obtained on sera from pregnant white and black women resident in the UK. The values for serum retinol in the Transkei mothers and babies were low. This accords with the poor nutrition and consequent high childhood mortality observed in this population. In contrast, the serum 25-OHD values were normal. This suggests that in these malnourished black South African mothers, normal vitamin D status is maintained by actinic synthesis.