Serum Concentrations Of Retinol-binding Protein Research Articles

MO128RETINOL BINDING PROTEIN (RBP) - NEW BIOMARKER OF KIDNEY INJURY IN MULTIPLE MYELOMA PATIENTS*

Abstract Background and Aims The aim of the study was to analyse the utility of retinol binding protein (RBP) in case of renal impairment in MM patients and investigate its relationship with acclaimed parameters of renal failure and markers of MM stages. Method We recruited 73 patients (35 women, 38 men, in age range of 29-90 years, mean 70 ± 10 years) with multiple myeloma (MM), including 6 (8%) with smoldering MM, 40 (55%) with International Staging System (ISS) stage I, 15 (21%) with ISS II and 12 (16%) with ISS III. The majority of patients (65, 89%) received at least one treatment scheme. Thirty patients (41%) received maintenance treatment at recruitment. Median eGFR based on serum creatinine (CKD-EPICr) equaled 67 (range 9 – 117) ml/min/1.73 m2. Results Significant correlation was observed between RBP and the ordered variable describing MM stage from smoldering myeloma to ISS III (R=0.36; p=0.002). There were no differences between patients in CR, PR, SD and PD at the time of samples’ collection. Patients who were on maintenance treatment at recruitment tended to have higher serum RBP (median 42.6 versus 37.7 mg/l), however, the difference was not statistically significant (p=0.068). The patients who received steroid treatment had significantly higher RBP concentrations. There were no such association with other medications. There was no association between RBP and the number of previous treatment lines (p=0.8). Serum RBP did not differ between men and women (p=0.7) and did not correlate with age (p=0.6). Significant correlations were found between RBP and serum creatinine, cystatin C and eGFR values calculated based on creatinine and/or cystatin C (Table 1). In multiple regression, serum creatinine or cystatin C and the treatment with steroids were associated with RBP independently of ISS stage (Table 2). Moreover, RBP correlated with β2-microglobulin, LDH, leukocyte count, α-klotho, FGF-23, GDF-15, uNGAL and uIGFBP-7, however, only the associations with β2-microglobulin and sTfR were independent of serum creatinine in multiple regression (Table 1). Baseline serum RBP concentration was significantly correlated with eGFR after a median of 19 months follow-up (range 1-24 months) (R=-0.35; p=0.003), however, the correlation was not independent of baseline serum creatinine ((beta ± SE: 0.06 ± 0.10; p=0.5). To the contrary, baseline serum cystatin C (beta ± SE: -0.36 ± 0.13; p=0.009) predicted final eGFR independently of baseline serum creatinine. Conclusion RBP may be useful marker in renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

Retinoids, anxiety and peripartum depressive symptoms among Chinese women: a prospective cohort study

BackgroundThe current study aimed to investigate whether serum RBP levels can be a key predictor of peripartum depression (PPD).MethodsThis was a prospective cohort study, conducted at a general teaching hospital in South China. Research participants were evaluated at three time points: the third trimester of pregnancy (T1), after delivery at week one (T2), and after delivery week six (T3) using a set of self-reported questionnaires and blood sample assays.ResultsA total of 156 subjects were included for data analysis. The prevalence of anxiety symptoms ranged from 32.69% to 36.53%. The prevalence of PPD was also high and ranged from 27.56% to 35.89%. In the third trimester, significant predictors of depressive symptoms include serum retinol-binding protein (RBP) concentrations and estradiol levels (P = 0.008 and 0.033, respectively). At one week after delivery, serum concentrations of RBP at T2 were still significant predictors of depressive symptoms (P = 0.020, and serum estradiol concentrations at T1 were a significant predictor (P = 0.010). The most stable predictor of depressive symptoms at T3 was anxiety symptoms, especially at T3 time point (P < 0.001). Serum RBP concentrations at T1 and T2 were still significant predictors of depressive symptoms at T3.ConclusionA high prevalence of anxiety and depressive symptoms tended to persist in Chinese women during the peripartum period. This study, which found the potential contribution of RBP to the occurrence of PPD, requires that large sample studies be conducted in future with a longer-term follow-up period, in order to confirm its results.

Influence of obesity on the serum concentration of retinol-binding protein 4 (RBP4) in young adults

ABSTRACT Introduction: Obesity is a chronic low-grade inflammation, in which macrophages play an important role in the maintenance of inflammation by producing pre-inflammatory and inflammatory substances such as retinol-binding protein 4 (RBP4), which acts as a trigger for adipose tissue inflammation and associated with obesity co-morbidities. Objective: This study evaluated the serum concentration of RBP4 and biomarkers of insulin resistance (IR) in young adult patients with normal weight, overweight and obese. Methods: A cross sectional study was conducted involving 149 subjects: 54 healthy individuals (32 women and 22 men), 27 overweight (17 women and 10 men) and 68 obese (41 women and 27 men). The anthropometric measures and the concentrations of RBP4, insulin, HbA1c and glucose were determined, in addition to the calculations for homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (IS). Results: overweight and obese patients showed significantly higher levels of glucose, HbA1c, insulin, and HOMA-IR (p 0.0001) when compared with the normal weight group. There was an increase in RBP4 proportional to the increase in body mass index (BMI); the obese group showed significantly higher levels (p < 0.05). Conclusion: This study suggests that RBP4 may play a key role in the development of inflammation and IR in young obese individuals, as it may promote significant disturbances in insulin metabolism and may contribute to the development of obesity-related co-morbidities. This parameter can represent a hope in the identification of new inflammatory and IR markers to assist in the diagnosis and follow-up of overweight and obese patients.

Effect of a clean stove intervention on inflammatory biomarkers in pregnant women in Ibadan, Nigeria: A randomized controlled study

BackgroundExposure to household air pollution (HAP) has been linked to systemic inflammation. We determined the impact of transition from traditional firewood/kerosene stove to bioethanol-burning stove on inflammatory biomarkers in pregnant Nigerian women. MethodsWomen (n=324), cooking with kerosene/firewood, were recruited during their first trimester of pregnancy from June 2013–October 2015 and were randomly allocated to either control (n=162) or intervention (n=162) group using web-based randomization. Controls continued to use their own firewood/kerosene stove, while intervention participants received bioethanol CleanCook stoves. Serum concentrations of retinol-binding protein (RBP), malondialdehyde (MDA), tumor necrosis factor alpha (TNF)-α, interleukin (IL)-6, and IL-8 were measured by ELISA. ResultsAfter excluding 53 women (loss of follow-up, untimely biomarker assessments, incorrect dates of enrollment), data from 271 women were included in analysis. Mean (SD) change in RBP, MDA, TNF-α, IL-6, and IL-8 between baseline and third trimester was −2.16 (4.47), −19.6 (46.4), 3.72 (37.2), 0.51 (14.4), and 13.2 (197), respectively, in intervention and −2.25 (4.30), −24.6 (43.6), 7.17 (32.6), −1.79, (11.4), and 31.3 (296) in control groups. None of these changes differed significantly between the two treatment arms. However, changes from baseline in TNF-α levels were significantly different between intervention and control groups in subset of women (n=99) using firewood before trial (−7.03 [32.9] vs. +12.4 [33.6]; 95% CI for group difference: −35.4 to −3.4, p=0.018). ConclusionsDecrease in TNF-α concentration from baseline to third trimesters in intervention group women could indicate reduced cardiovascular stress and prothrombotic effects from decreased HAP. Our findings suggest that ethanol-burning stoves may mitigate cardiovascular health risks.

Biofortified yellow cassava and vitamin A status of Kenyan children: a randomized controlled trial

Whereas conventional white cassava roots are devoid of provitamin A, biofortified yellow varieties are naturally rich in β-carotene, the primary provitamin A carotenoid. We assessed the effect of consuming yellow cassava on serum retinol concentration in Kenyan schoolchildren with marginal vitamin A status. We randomly allocated 342 children aged 5-13 y to receive daily, 6 d/wk, for 18.5 wk 1) white cassava and placebo supplement (control group), 2) provitamin A-rich cassava (mean content: 1460 μg β-carotene/d) and placebo supplement (yellow cassava group), and 3) white cassava and β-carotene supplement (1053 μg/d; β-carotene supplement group). The primary outcome was serum retinol concentration; prespecified secondary outcomes were hemoglobin concentration and serum concentrations of β-carotene, retinol-binding protein, and prealbumin. Groups were compared by using ANCOVA, adjusting for inflammation, baseline serum concentrations of retinol and β-carotene, and stratified design. The baseline prevalence of serum retinol concentration <0.7 μmol/L and inflammation was 27% and 24%, respectively. For children in the control, yellow cassava, and β-carotene supplement groups, the mean daily intake of cassava was 378, 371, and 378 g, respectively, and the total daily supply of provitamin A and vitamin A from diet and supplements was equivalent to 22, 220, and 175 μg retinol, respectively. Both yellow cassava and β-carotene supplementation increased serum retinol concentration by 0.04 μmol/L (95% CI: 0.00, 0.07 μmol/L); correspondingly, serum β-carotene concentration increased by 524% (448%, 608%) and 166% (134%, 202%). We found no effect on hemoglobin concentration or serum concentrations of retinol-binding protein and prealbumin. In our study population, consumption of yellow cassava led to modest gains in serum retinol concentration and a large increase in β-carotene concentration. It can be an efficacious, new approach to improve vitamin A status. This study was registered with clinicaltrials.gov as NCT01614483.

Association of Nutritional Status with Drug Sensitive and Drug Resistant Outcomes Among Pulmonary Tuberculosis Patients

The study established the association of nutritional status with drug sensitive and drug resistant outcomes among pulmonary tuberculosis (TB) patients. A hospital based prospective follow-up cohort study design. Two urban Directly Observed Treatment Short-course (DOTS) centers in Lucknow District of Uttar Pradesh, India. The newly diagnosed Acid-fast Bacilli (AFB) positive cases between the age group of 12 to 65 years were enrolled. The drug-susceptibility outcomes were assessed by mycobacterial culture and drugsusceptibility test. The assessment of nutritional status was performed by Body Mass Index (BMI), Mid-upperarm circumference (MUAC), 24-hour dietary recall method and measurement of serum concentration of retinolbinding protein (RBP) and zinc. A total of 185 newly diagnosed patients were recruited. Out of these, 14 patients were lost to follow up after treatment. The mean (±SD) age of the remaining 171 patients was 29 (±12) years. In the culture of 171 patients, 156 (91.2%) isolates were culture positive and subjected to drugsusceptibility test. Of these, 129 (82.6%) isolates were sensitive to all the drugs and 27 (17.3%) isolates were resistant to any drug. A significant difference was observed in serum RBP (p<0.0001) and zinc (p=0.005) at six month in drug sensitive and resistant patients. Among all the nutritional status parameters serum zinc (p=0.01) was significantly associated with drug resistant patients. Inadequate level of serum zinc was probably associated with drug resistance among new pulmonary TB patients.

Vitamin A deficiency associated with urinary retinol binding protein wasting in Dent’s disease

Three patients with Dent's disease presented with complaints of impaired night vision or xerophthalmia and were found to have severely decreased serum retinol concentrations. Retinol, bound to its carrier retinol-binding protein (RBP), is filtered at the glomerulus and reabsorbed at the proximal tubule. We hypothesized that urinary loss of retinol-RBP complex is responsible for decreased serum retinol. The study aim was to investigate vitamin A status and RBP in serum and urine of patients with genetically confirmed Dent's disease. Eight patients were studied, three boys had clinical vitamin A deficiency, three had asymptomatic deficiency, and two young men with Dent's disease and impaired renal function had normal retinol values. Serum RBP concentrations were low in patients with vitamin A deficiency and were correlated with vitamin A levels. Urinary RBP concentrations were increased in all patients (2,000-fold), regardless of vitamin A status. This was in contrast to patients with glomerular proteinuria who had only mildly increased urinary RBP with normal serum RBP and vitamin A, and patients with cystinosis with impaired renal function who had massive urinary RBP losses but without a decrease in serum RBP or vitamin A levels. Treatment with vitamin A supplements in patients with retinol deficiency resulted in rapid resolution of ocular symptoms and an increase in serum retinol concentrations. Vitamin A deficiency is common in patients with Dent's disease and preserved renal function. We therefore recommend screening these patients for retinol deficiency and treating them before visual symptoms develop.

Retinol‐Binding Protein in Serum and Urine of Hyperthyroid Cats before and after Treatment with Radioiodine

Retinol-binding protein (RBP) is suggested as a clinically useful marker of renal function in cats. Serum and urinary RBP concentrations in hyperthyroid (HT) cats differ from those in healthy (H) cats; radioiodine ((131)I) treatment influences serum and urinary RBP concentrations in HT cats. Ten HT and 8 H cats. RBP concentration was evaluated in feline serum and urine samples from a prospective study. There was a significant (P= .003) difference in the urinary RBP/creatinine (uRBP/c) ratios of H (-) and untreated HT (1.4 + or - 1.5 x 10(-2) microg/mg) cats. Serum total thyroxine concentration (1.8 + or - 1.9 microg/dL, 24 weeks) and uRBP/c (0.6 + or - 1.0 x 10(-2) microg/mg, 24 weeks) decreased significantly (P < .001) in HT cats at all time points after treatment with (131)I, and these variables were significantly correlated with one another (r= 0.42, P= .007). Serum RBP concentrations from HT cats (199 + or - 86 microg/L) did not differ significantly (P= .98) from those of H cats (174 + or - 60) and did not change after treatment with (131)I (182 + or - 124 microg/L, P= .80). The presence of urinary RBP in HT cats is a potential marker of tubular dysfunction that is correlated to thyroid status, although it is independent of circulating RBP concentrations. The decreased uRBP/c combined with the absence of changes in serum RBP after treatment suggests that the suspected tubular dysfunction was partly reversible with treatment of (131)I.

Serum Retinol-Binding Protein Concentration and Its Association with Components of the Uremic Metabolic Syndrome in Nondiabetic Patients with Chronic Kidney Disease Stage 5

Introduction: Chronic kidney disease (CKD) is associated with insulin resistance also in the absence of overt diabetes mellitus. The liver-derived transport protein retinol-binding protein (RBP) has recently been proposed as a novel adipokine involved in the metabolism of glucose. Although RBP is elevated in type 2 diabetics with mild CKD, its role in advanced CKD is not well studied. We hypothesized that altered RBP levels in CKD could be one factor contributing to the uremic insulin resistance. Patients and Methods: In a cross-sectional study, we evaluated 141 nondiabetic stage 5 CKD patients (GFR 6.8 ± 2.0 ml/min; 62% males, mean age 52 ± 11 years) close to the start of renal replacement therapy. We studied circulating RBP (RIA), retinol and metabolic markers. Body composition was also assessed using DEXA and patients were divided according to truncal fat mass above (obese) or below (lean) the sex-specific median. A fasting plasma glucose ≥6.1 mM was defined as impaired glucose tolerance (IGT). Results: Serum RBP levels were significantly elevated in CKD as compared to previous reports in non-renal patients. Whereas levels of RBP did not differ between lean and obese patients without IGT, they were lower in lean CKD patients with IGT (5.9 ± 2.9 μM) than in obese CKD patients with IGT (7.0 ± 2.9 μM; p < 0.05). While RBP did not correlate with truncal or total fat mass or biomarkers of inflammation, in univariate analysis, we found weak correlations with HbA1c% (rho = 0.17; p < 0.05), fasting serum triglycerides (rho = 0.20; p < 0.001) and fasting apolipoprotein (Apo) A1 (rho = 0.29; p < 0.001). RBP also correlated negatively with ApoB (rho = –0.29; p < 0.001). In multivariate analysis, RBP was a significant and independent predictor of both HbA1c% and ApoA1 levels. Finally, RBP was strongly correlated with serum retinol, and calculating a retinol/RBP index further strengthened the observed correlations with HOMA-IR and HbA1c%. Conclusions: RBP is elevated in nondiabetic stage 5 CKD and correlates weakly with HbA1c and ApoA1. As RBP is thought to induce insulin resistance and directly affect lipoprotein metabolism in other disease states, these findings may support a role for RBP in contributing to the uremic metabolic syndrome, putatively by altering ApoA1 metabolism, but further studies are needed to test this hypothesis.

Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes

Pregnancy is characterised by temporarily increased insulin resistance. Gestational diabetes occurs when pancreatic beta cell function is unable to compensate for this insulin resistance. Retinol-binding protein 4 (RBP4) could be related to insulin resistance. We hypothesised that RBP4 is elevated in gestational diabetes. Serum RBP4, transthyretin and retinol were cross-sectionally measured in 42 women with gestational diabetes and 45 pregnant controls. Of these, 20 women with and 22 without gestational diabetes were included in an additional longitudinal study. RBP4 was determined by enzyme immunometric assay (EIA) and western blot. Women with gestational diabetes had lower RBP4 EIA and western blot levels than controls (median 6.8 [interquartile range, 3.9-14.3] vs 11.3 [7.8-19.9] microg/ml, p < 0.001 and 25.1 [21.7-29.6] vs 26.6 [23.5-32.2] microg/ml, p = 0.026). Transthyretin and the RBP4:transthyretin molar ratio were comparable between the groups. Serum retinol was lower (p < 0.001) and the RBP4 Western blot level: retinol molar ratio was higher in women with gestational diabetes (p = 0.044). RBP4 was not associated with the glucose or homeostasis model assessment of insulin resistance (HOMA-IR), but in gestational diabetes the RBP4:retinol molar ratio correlated with blood glucose and negatively with 2 h post-load insulin. The RBP4:transthyretin ratio correlated with HOMA-IR and fasting insulin in controls. In women with gestational diabetes RBP4 EIA and western blot levels increased after delivery. Retinol increased in both groups, while transthyretin and the RBP4:transthyretin ratio were not altered after parturition. RBP4 measured by two different techniques is not elevated, but the RBP4:retinol molar ratio is higher and correlates with fasting blood glucose in women with gestational diabetes. Thus, the RBP4:retinol ratio and the RBP4:transthyretin ratio are more informative than RBP4 levels alone when assessing insulin-glucose homeostasis during pregnancy.

Effect of Lifestyle Changes on Serum Retinol Binding Protein in Obese Children: A Randomized Controlled Study

Recent studies in adults have suggested that obesity and insulin resistance are associated with elevated levels of serum retinol binding protein (RBP) and that a reduction in RBP improves insulin action. The potential role of RBP in insulin resistant obese children is unclear. In this study we measured serum RBP in obese and lean adolescents (n=18) matched for age (>14 yrs< 18 yrs) and maturity stage (≥Tanner IV) at baseline and after a 3–month, randomized and controlled lifestyle intervention (only in obese subjects; n = 12). Serum RBP was significantly higher in the obese group compared to the lean group (P=0.005) and showed correlations (all P< 0.05) with BMI (r=0.51), body fat (r=0.53), insulin (r= 0.70), HOMA-IR (r=0.65) and inflammatory factors (r for CRP=0.57; r for IL-6=0.49). Intervention reduced serum RBP levels by about 18% (P = 0.01) and was accompanied by reductions in insulin and HOMA-IR, fat mass and inflammatory factors. The data suggest that (i) alterations in RBP are evident early in the clinical course of obesity and are associated with obesity-related insulin resistance and sub-clinical inflammation in children; and (ii) the serum concentration of RBP is responsive to a simple lifestyle-based intervention in obese adolescents. Long-term studies are needed to better understand the role of RBP in the early development of CVD and diabetes in obese children.

Biochemical Indicators of Vitamin A Deficiency: Serum Retinol and Serum Retinol Binding Protein

Two biochemical indicators are currently recommended for determining whether vitamin A deficiency (VAD) is a public health problem: serum retinol and serum retinol-binding protein (RBP). After consideration of 40 data sets and the original rationale for previously proposed cut-offs, a cut-off for serum retinol concentration was proposed at <0.70 micro mol/L (20 micro g/dL) in > or =15% of the sampled population. This cut-off should be applied to a representative group of preschool age children (6-71 mo). Because measurement of low serum retinol concentrations requires high precision, analysis should be done by HPLC. For serum RBP, a cut-off cannot be reliably specified, because available data are too few and too variable. However, because serum RBP concentration correlates well with serum retinol concentration, it can be used to determine whether VAD is a public health problem in those populations for which the relationship between serum concentrations of retinol and RBP have been established. More efforts to establish a reliable cut-off for RBP is warranted, because analysis, in particular radial immunodiffusion (RID), is relatively simple and inexpensive. Whereas HPLC and RID analyses must be done in a laboratory, methods are being developed for assessing serum retinol and RBP under more remote conditions.

Endemic goiter with iodine sufficiency: a possible role for the consumption of pearl millet in the etiology of endemic goiter

Deficiencies of iodine, iron, and vitamin A are the 3 most common micronutrient deficiencies in developing countries, although control programs, when properly implemented, can be effective. We investigated these deficiencies and their possible interaction in preschool children in the southern Blue Nile area of Sudan. Goiter, signs of vitamin A deficiency, and biochemical markers of thyroid, vitamin A, and iron status were assessed in 984 children aged 1-6 y. The goiter rate was 22. 3%. The median urinary iodine concentration was 0.79 micromol/L and 19.3% of the children had a concentration >1.57 micromol/L. Although serum thyroxine and triiodothyronine concentrations were within reference ranges, the median thyrotropin concentration was 3.78 mIU/L and 44% of the children had thyrotropin concentrations above normal. The mean urinary thiocyanate concentration was high (259 +/- 121 micromol/L). The prevalences of Bitot spots and night blindness were 2.94% and 2.64%, respectively, and 32% of the subjects had serum retinol binding protein concentrations <15 mg/L. A significant positive correlation was observed between thyrotropin and retinol binding protein. Whereas 88% of the children had hemoglobin concentrations <1.86 mmol/L, only 13.5% had serum ferritin concentrations below the cutoff of 12 microg/L and 95% had serum transferrin concentrations above the cutoff of 2.50 g/L. Our results indicate that goiter is endemic in this region of Sudan despite iodine sufficiency and that both anemia and vitamin A deficiency are health problems in the area. Moreover, consumption of millet, vitamin A deficiency, and protein-energy malnutrition are possible etiologic factors in this endemic area.

Production of monoclonal antibodies and enzyme immunoassay to bovine retinol-binding protein and determination of retinol-binding protein serum levels and retinol concentrations in serum and liver in dairy cows before and after parturition

To study vitamin A transport in dairy cows and heifers around parturition, an enzyme immunoassay for bovine retinol binding protein (RBP) was developed and serum levels determined. Serum and liver concentrations of retinol were assayed by HPLC . Four weeks before expected calving the cows and heifers were divided into two groups each, and half of the animals received a protein supplementation during the dry period.The mean serum RBP concentration 4 weeks before calving was 42 mg l–1for the cows and 44 mg l–1for the heifers. The serum retinol concentrations were 0·53 mg l–1for the cows and 0·42 mg l–1for the heifers, and the liver retinol concentrations 0·30 mg l–1and 0·13 mg g–1, respectively. In the groups without protein supplementation there was a significant decrease in serum RBP at sampling 1 week before parturition compared to initial values. The measurement of serum RBP may prove useful in assessment of amino acid availability in dairy cows.

Evaluation of biochemical indicators of vitamin A status in breast-feeding and non-breast-feeding Indonesian women

Indicators of vitamin A status were evaluated in nonpregnant breast-feeding (n = 265) and nonpregnant non-breast-feeding (n = 49) Indonesian women. The concentration of vitamin A (not including provitamin A carotenoids) and fat in breast milk was 30% and 20% higher, respectively, for women with a breast-fed child 7-18 mo old than for women with an infant 3-6 mo old. The vitamin A content of milk fat was constant throughout lactation. Breast-milk vitamin A was most sensitive to changes in vitamin A status when expressed per volume. Sensitivity and specificity for detecting serum retinol concentrations < 0.70 mumol/L were < 75% for the concentration of breast-milk vitamin A and serum retinol binding protein (RBP). The modified-relative-dose-response (MRDR) method suffers from a relatively large intraindividual variation in the ratio of dehydroretinol to retinol because of vulnerability of the dehydroretinol concentration to laboratory errors and to variation in dosing and absorption. Within categories of dehydroretinol:retinol, serum retinol concentration was lower in breast-feeding women than in non-breast-feeding women. Thus, it may be necessary to use different cutoff values for the ratio and for serum retinol concentration. Serum retinol concentration, which was just above marginal (0.85 mumol/L), had the smallest within-person variation and was also the most sensitive indicator for detecting a difference between groups in change in vitamin A status postintervention, requiring only 19 subjects per group. Serum RBP concentration, breast-milk vitamin A expressed per volume or per gram milk fat, and the MRDR method required groups of 35, 36, 139, and 53 subjects, respectively.

Multiple retinoids alter liver bile salt-independent retinyl ester hydrolase activity, serum vitamin A and serum retinol-binding protein of rats

Liver bile salt-independent retinyl ester hydrolase (BSI-REH) has been suggested to play a significant role in the hydrolysis of chylomicron derived retinyl esters. Studies were conducted to investigate the individual effects of N-(4-hydroxyphenyl)retinamide (HPR), retinoic acid, 13- cis-retinoic acid, Acitretin and Temarotene on BSI-REH, serum retinol, and serum retinol-binding protein (RBP) concentrations. We have demonstrated that micromolar concentrations of HPR, retinoic acid, 13- cis-retinoic acid or Acitretin significantly reduced the in vitro hydrolysis of retinyl palmitate. In contrast, Temarotene stimulated retinyl palmitate hydrolysis by BSI-REH. Retinoic acid and 13- cis-retinoic acid produced transient, but significant, depressions of both serum retinol and RBP concentrations, when the individual retinoids were administered orally to rats. The duration of the depression was shorter than we previously observed with acute HPR administration. Furthermore, Acitretin appeared to function with bimodal activity, producing significant depressions of serum retinol at 2 h and 24 h. No effect of Acitretin or Temarotene on serum RBP concentration was observed. The alterations observed in BSI-REH activity, serum retinol and RBP concentrations provide evidence that these retinoids can alter liver retinyl ester hydrolysis, but the effects observed on serum retinol concentration can only be partially explained by the BSI-REH activity.

N-(4-Hydroxyphenyl)retinamide (Fenretinide) Induces Retinol-Binding Protein Secretion from Liver and Accumulation in the Kidneys in Rats

The chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (HPR) depresses serum retinol and retinol-binding protein (RBP) concentrations. To study long-term effects of HPR on serum proteins, rats were fed a control diet or a diet containing HPR (737 mumol/kg diet) for 14 d. Serum retinol and RBP of HPR-treated rats decreased to 42 and 41%, respectively, of initial concentrations. Transthyretin, albumin and transferrin did not differ between treatments. Previous studies found that HPR decreased secretion of the retinol-RBP complex into plasma. To investigate acute effects of HPR on RBP metabolism, vitamin A-deficient rats were injected with HPR (51 mumol/kg body wt), retinol (0.52 mumol/rat) or Tween carrier only. Liver RBP concentrations in HPR- and retinol-treated rats were 45 and 18%, respectively, of concentrations in Tween-treated rats, indicating rapid RBP secretion. Tween- and HPR-treated rats maintained relatively constant serum RBP concentrations, whereas retinol-replete rats had 12-fold higher serum RBP after 150 min. Rats treated with HPR and rats treated with retinol had 29- and eightfold higher kidney RBP concentrations, respectively, than Tween-treated rats, indicating rapid clearance of RBP from plasma. We conclude that HPR affects RBP metabolism by inducing secretion of liver RBP into the bloodstream and rapid RBP accumulation in the kidney.

Vitamin A absorption in cystic fibrosis: risk of hypervitaminosis A.

Vitamin A status was examined in nine adult cystic fibrosis patients and six adult control subjects, together with an assessment of their ability to absorb 10,000 IU of retinyl palmitate from a test meal, taken with appropriate pancreatic enzyme supplements. Median baseline values for plasma retinol and carotene, as well as median serum retinol binding protein concentrations, were significantly lower in cystic fibrosis patients than in control subjects. One cystic fibrosis patient had a raised fasting plasma retinyl ester concentration suggestive of chronic hypervitaminosis A, but no symptoms of toxicity. Measures of vitamin A absorption were also significantly lower in cystic fibrosis patients, although there was considerable overlap with control values. No correlation was observed between measures of baseline status and vitamin A absorption. Measurement of plasma retinyl esters may be an appropriate investigation in those patients considered to be at risk of chronic hypervitaminosis A.

The Effect of Glucocorticosteroids on Serum, Liver, and Lung Vitamin A and Retinyl Ester Concentrations

Vitamin A and its active metabolites are important factors in promoting normal respiratory epithelial differentiation and growth. Glucocorticoids, often used to treat chronic lung diseases in infancy and childhood, are known to increase serum retinol concentrations. To determine the effects of exogenous steroids on serum retinol and retinol-binding protein concentrations (as well as on liver and lung total vitamin A, retinol, and retinyl ester concentrations), 32 weanling Sprague-Dawley rats were divided into four equal experimental groups. Eight animals were vitamin A sufficient and received 7 days of intraperitoneal dexamethasone at 0.5 mg/kg/day (group SD), 8 were vitamin A sufficient and received placebo (group SP), 8 were made vitamin A deficient and subsequently received dexamethasone (group DD), and 8 were vitamin A deficient and received placebo (group DP). Dexamethasone increased serum retinol concentrations in the SD group (2.27 +/- 0.20 mumol/L) when compared with control (SP, 1.64 +/- 0.46 mumol/L, p less than 0.001) as well as with pretreatment baseline values (1.21 +/- 0.23 mumol/L, p less than 0.001). Lung total vitamin A, retinol, and individual retinyl esters were depleted by 56 +/- 19% in the SD group, whereas liver values were depleted by 36 +/- 23%. In the vitamin A-sufficient groups the relative percentages of four major retinyl esters (palmitate, stearate, oleate, and linoleate) did not change in either tissue after steroid exposure. The vitamin A-deficient groups had no detectable tissue vitamin A, and dexamethasone did not increase serum retinol concentrations in the DD group. Serum retinol-binding protein concentrations were significantly higher in both steroid-treated groups when compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)

Higher Serum Retinol-Binding Protein Concentration in Indonesian Neonates in Surabaya than Japanese Neonates in Kobe

The concentrations of serum retinol-binding protein (RBP), prealbumin (PA) and vitamin A of Indonesian neonates were compared with those of Japanese neonates. The mean serum concentrations of both PA and vitamin A did not differ significantly in Indonesian and Japanese neonates. Indonesian neonates had significantly higher serum RBP (2.75 +/- 0.87 mg/dl, mean +/- SD) than Japanese neonates (1.65 +/- 0.55 mg/dl, p less than 0.01). The molar ratio of vitamin A:RBP in Indonesian infants was significantly lower than in Japanese infants (p less than 0.02), and this in turn is indicative of increased concentrations of retinol-free RBP in the plasma of Indonesian neonates. The results suggest that RBP metabolism in Indonesian neonates differs from that in Japanese neonates.