UPTAKE, DISTRIBUTION, AND ESTERIFICATION OF RETINOL IN LIVER

Retinol is secreted by hepatocytes and is recycled to them by the R ˙ RBP ˙ TTR complex. Stellate cells, which have RBP receptors, are principal storage sites of retinol as esters.     

LIVER VITAMIN A MOBILIZATION DURING ZINC DEFICIENCY AND RESTRICTED FOOD INTAKE

Zinc-deficient rats, compared to pair-fed controls, had decreased plasma vitamin A and retinol-binding protein (RBP), with liver vitamin A normal and liver RBP depleted. The hypothesis was therefore advanced that synthesis of liver RBP declines in zinc deficiency as a result of the lower growth rate (i.e. food intake and utilization) of the deficient rats.     

Carence en vitamine A chez un groupe d’enfants sains âgés de 1 à 23 mois de la région de Blida,Algérie

The vitamin A deficiency (VAD) is considered as a major public health problem in the world. This phenomenon is still not well known in Algeria. The prevalence of this deficiency is calculated on a group of children in good health, not supplemented with vitamin A, from rural, semi-rural and urban environments in the Blida region (Algeria), aged 1 to 23 months and recruited in the pediatric services of Blida area, during the period of November 2007–April 2008. The sample is composed of 150 children (87 boys and 63 girls) who present a concentration of C-reactive protein (CRP) < 10 mg/L. The mean concentrations of serum retinol are 1.049 ± 0.422 μmol/L. The dosages of the serum retinol-binding protein (RBP) and prealbumin revealed the mean values of 0.024 ± 0.009 g/L and of 0.152 ± 0.039 g/L, respectively for RBP and prealbumin. The prevalence of serum retinol deficiency is 19%; this indicates the presence of a moderate VAD. The prevalence of carrier protein deficiency is 76% for the RBP and 10% for the prealbumin. To remedy the problem of vitamin A deficiency, it is advisable to implement a policy of nutritional education. The supplementation can be interesting only for the children whose nutritional status is defective or living in areas where the food products rich in vitamin A are rare.     

A CELL-SURFACE RECEPTOR FOR PLASMA RETINOL-BINDING PROTEIN ON PIGMENT EPITHELIUM AND INTESTINAL MUCOSAL CELLS

Retinol bound to its specific plasma carrier, retinol-binding protein (RBP) interacts with a specific cell-surface receptor where the retinol is detached and taken up by the cell, leaving apo-RBP behind.     

Retinoid Homeostasis and Beyond: How Retinol Binding Protein 4 Contributes to Health and Disease

Retinol binding protein 4 (RBP4) is the specific transport protein of the lipophilic vitamin A, retinol, in blood. Circulating RBP4 originates from the liver. It is secreted by hepatocytes after it has been loaded with retinol and binding to transthyretin (TTR). TTR association prevents renal filtration due to the formation of a higher molecular weight complex. In the circulation, RBP4 binds to specific membrane receptors, thereby delivering retinol to target cells, rendering liver-secreted RBP4 the major mechanism to distribute hepatic vitamin A stores to extrahepatic tissues. In particular, binding of RBP4 to ‘stimulated by retinoic acid 6’ (STRA6) is required to balance tissue retinoid responses in a highly homeostatic manner. Consequently, defects/mutations in RBP4 can cause a variety of conditions and diseases due to dysregulated retinoid homeostasis and cover embryonic development, vision, metabolism, and cardiovascular diseases. Aside from the effects related to retinol transport, non-canonical functions of RBP4 have also been reported. In this review, we summarize the current knowledge on the regulation and function of RBP4 in health and disease derived from murine models and human mutations.     

THE EFFECT OF ORAL CONTRACEPTIVE AGENTS ON PLASMA VITAMIN A IN THE HUMAN AND THE RAT

Women taking oral contraceptives have about a 50 percent higher than normal concentration of retinol in their plasma. This returns to normal levels in less than four months after they stop taking the contraceptive pill.     

Plasma 25(OH)D Concentrations and Gestational Diabetes Mellitus among Pregnant Women in Taiwan

Vitamin D’s function in the development of gestational diabetes mellitus (GDM) is not consistent in the literature. We examined the association between maternal plasma 25(OH)D concentration and GDM risk. A national cross-sectional study (1497 pregnant women) was conducted between 2017 and 2019 across Taiwan. Blood samples were drawn at recruitment to assess 25(OH)D concentrations, including vitamin D deficiency (VDD) (<20 ng/mL), insufficiency (<32 ng/mL), and sufficiency (≥32 ng/mL). GDM was detected from 24 to 28 weeks of gestation with the results extracted from the antenatal visit records. The prevalence of GDM was 2.9%. Logistic model analysis showed that 25(OH)D concentrations were not significantly associated with the risk of GDM (adjusted odds ratio (AOR) = 0.97, p = 0.144). However, subjects with VDD had a significantly greater risk of GDM (AOR = 2.26, p = 0.041), but not in those with vitamin D insufficiency (AOR = 1.20, p = 0.655). Furthermore, cubic piecewise spline regression was used to explore the relationship between five-unit intervals of 25(OH)D and the predicted probability of GDM. As the proportion of GDM increased for low 25(OH)D concentrations, it decreased at moderate concentrations and increased again at higher concentrations. These findings revealed a nonlinear relationship between 25(OH)D and GDM risk. VDD would be risky for GDM occurrence.     

急性时相反应对学龄前儿童维生素A营养评价指标的影响

【目的】评估急性时相反应对维生素A评价指标,包括血清视黄醇,视黄醇结合蛋白(retinol binding pro-tein,RBP),甲状腺素运载蛋白(transthyretin,TTR)以及RBP:TTR摩尔比值的影响。【方法】从重庆巴南地区随机抽取四所幼儿园中的350名学龄前儿童作为研究对象,利用HPLC法测定其血清视黄醇浓度,ELISA测定血清RBP浓度,免疫比浊法测定血清中TTR和C-反应蛋白(C-reaction protein,CRP)水平并对其相关性进行分析。【结果】边缘性维生素A缺乏(marginal vitamin A deficiency,MVAD)儿童的RBP水平明显低于维生素A正常(normal vitamin A,NVA)儿童(P<0.01)。维生素A缺乏(vitamin Adeficiency,VAD)儿童和MVAD儿童TTR值均显著低于NVA儿童(P<0.01)。MVAD儿童的RBP∶TTR摩尔比值显著低于NVA儿童(P<0.05)。RBP∶TTR摩尔比值在维生素A不足且伴感染的儿童中最低(P<0.05),而在正常维生素A状态不伴感染的儿童中最高(但差异不明显)。【结论】在伴感染的学龄前儿童中评价其维生素A营养状况时,RBP∶TTR摩尔比值有可能是一个有用的指标,但是还需要进一步的研究对其使用效度进行评价。     

Elevated Plasma Concentrations of Vitamin D-Binding Protein Are Associated with Lower High-Density Lipoprotein and Higher Fat Mass Index in Overweight and Obese Women

(1) Background: Observational studies have established that vitamin D-binding protein (DBP) and 25-hydroxyvitamin D₃ (25(OH)D) concentrations are the major factors affecting the bioavailability of 25(OH)D. It has also been shown that poor 25(OH)D bioavailability elevates the risk of obesity and its related cardio-metabolic disorders. However, the relationship between 25(OH)D and DBP concentrations with cardio-metabolic risk factors in overweight and obese cohorts has not been established. Consequently, we evaluated the association between DBP and 25(OH)D concentrations with lipid profile, blood pressure (BP), and body composition in overweight and obese women. (2) Methods: In this cross-sectional study of 236 overweight and obese women, DBP and 25(OH)D concentrations were measured using an enzyme-linked immunosorbent assay. Body composition was assessed via bioelectrical impedance analysis. Lipid profile and BP were assessed by an auto-analyzer and digital BP monitor, respectively. The associations were examined by multivariate logistic regression. (3) Results: The indicated showed an inverse relationship between DBP and high-density lipoprotein (HDL) (p = 0.010) concentrations (where individuals with higher DBP had lower HDL) which, after adjusting for possible cofounders, remained significant (p = 0.006). Moreover, DBP concentration was positively associated with fat mass index (FMI) after adjustment (p = 0.022). No significant relationships were observed among 25(OH)D and target variables. (4) Conclusions: In conclusion, lower concentrations of HDL and higher values of FMI are associated with higher concentrations of DBP in overweight and obese women. These findings present novel awareness regarding the association of DBP with some metabolic and body composition variables in overweight and obese women. However, a two-way causal relationship between DBP and target variables should be considered.     

PAPP-A、sFlt-1、TTR在妊娠期高血压疾病诊断中的价值

目的探讨妊娠相关蛋白A(PAPP-A)、可溶性血管内皮生长因子(sFlt-1)、中转甲状腺素蛋白(TTR)联合检测对于鉴别诊断妊娠期高血压疾病的临床价值。方法选取2018年1月至2019年12月在徐州医科大学附属沭阳医院确诊的妊娠期高血压疾病孕妇88例作为病例组,选取同期正常妊娠的孕妇120例作为对照组,检测两组孕妇于孕24~28周的PAPP-A、sFlt-1、TTR水平,并按照患者病情将病例组分为妊娠期高血压组、轻度子痫前期组、重度子痫前期组,采用受试者工作特征曲线(ROC)分析3项指标单独和联合检测鉴别诊断妊娠期高血压疾病的价值。结果病例组的PAPP-A水平显著高于对照组(t=2.254,P<0.05),病例组的sFlt-1、TTR水平显著低于对照组(t值分别为-3.226、-17.907,均P<0.05);妊娠期高血压组、轻度子痫前期组、重度子痫前期组患者的PAPP-A、sFlt-1、TTR水平比较差异均有统计学意义(F值分别为3.624、3.525、7.037,均P<0.05);PAPP-A、sFlt-1、TTR联合检测诊断妊娠期高血压疾病的灵敏度为97.15%、特异度为86.49%、漏诊率为2.85%、误诊率为13.51%,ROC曲线下面积AUC值为0.935。结论PAPP-A、sFlt-1、TTR这3项指标联合检测鉴别诊断妊娠期高血压疾病具有重要的临床价值。     

Vitamin D Deficiency in Pregnant Ukrainian Women: Effects of Alcohol Consumption on Vitamin D Status

Objective: Heavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women.

Methods: Women who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations.

Results: A high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20 ng/mL] or insufficient [25(OH)D ≥ 20 ng/mL and ≤30 ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability.

Conclusions: These data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.     

Impact of Vitamin A Supplementation on Pregnant Women and on Women Who Have Just Given Birth: A Systematic Review

Background: The aim of this review was to evaluate the impact of vitamin A supplementation on adult pregnant women and women who have just given birth in studies examining serum concentrations of vitamin A in breast milk and in maternal/child morbidity and mortality.

Methods: This review followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). In November 2014, an electronic search was independently performed by two authors on the Medline, Scopus, Web of Science, and LILACS databases on studies published from January 2004 to November 2014. The methodological quality of the studies was assessed in accordance with the Jadad scale, which determines the exclusion of studies with scores lower than 3.

Results: It was observed that when supplementation was provided only in the immediate postpartum period, it increased the liver stores of vitamin A. On the other hand, when supplementation was provided during pregnancy and puerperium5, the propensity for depleting the stores of vitamin A at the end of pregnancy decreased, the immune system improved, and cases of gestational night blindness decreased, but there were no changes in the outcomes at childbirth or in maternal, fetal, and child mortality. When supplementation was provided before and during pregnancy and in the immediate postpartum period, an additional improvement of lung function evaluated in preschool-aged children was found, but no significant changes in cognitive and motor development were noted.

Conclusions: Studies show the benefits of vitamin A supplementation, not just in the immediate postpartum period but, above all, when it is provided before and/or during pregnancy. Considering the positive repercussions observed, we suggest supplementation both in the gestational period and in the immediate postpartum period as a way to enhance the safety of mother–child care.     

危重患者抗氧化维生素血浆水平观察

目的了解危重患者体内抗氧化维生素水平。方法2002年5月～2003年2月间新华医院外科ICU收治的112例危重患者,采用高效液相法测定体内抗氧化维生素水平。结果112例危重患者抗氧化维生素水平明显低于正常对照组眼维生素A:(33.8±25.1)μg/dLvs(78.2±31.2)μg/dL,P=0.000;维生素E:穴6.5±4.4雪mg/Lvs(10.1±6.2)mg/L,P=0.000;β-胡萝卜素:(184±185)μg/Lvs(756±794)μg/L,P=0.000;维生素C:(5.0±4.2)mg/Lvs(6.7±3.9)mg/L,P=0.000演。危重患者中各维生素缺乏症发生率高于正常人,分别为维生素A:25.9%vs0%(P=0.000);维生素E:44.6%vs17.0%(P=0.000);β-胡萝卜素:46.4%vs12.8%(P=0.000);维生素C:62.5%vs31.2%(P=0.000)。危重患者中男性维生素A水平明显高于女性眼分别为(38.8±26.2)μg/dLvs(26.2±21.5)μg/dL,P=0.012演,且随年龄增长,维生素A水平显著降低(r=-0.234,P=0.015)。抽血日前禁食天数>7d组患者与≤7d组患者相比,各抗氧化维生素呈下降趋势,但无统计学差异。结论危重患者血浆维生素A、E和β-胡萝卜素水平明显低于正常人,且该人群中抗氧化维生素缺乏非常普遍。     

Plasma Vitamin A Homeostasis: The Relative Dose Response As A Measure Of Liver Vitamin A Reserves

Retinol levels in plasma of rats are constant and independent of dietary intake or liver stores above 10 μg per gram. If tissue needs of retinol are decreased by limiting protein intake or by feeding retinoic acid, plasma levels correspondingly decline. A single dose of newly supplied vitamin A leads to a short-term surge in plasma retinol level which may be a measure of liver reserves and vitamin A status.     

妊娠糖尿病患者补充维生素D3对孕妇免疫功能的作用

目的 探讨妊娠期糖尿病患者在孕期补充维生素D₃对提高孕妇免疫功能的作用。方法 本次研究所选取的研究对象是医院收治的妊娠期糖尿病患者,选取时间段为2018年3月—2020年6月,共有80例孕妇被纳入此次研究。根据奇偶分配原则,以接受常规治疗的 40例孕妇为对照组,以接受常规治疗联合维生素D₃治疗的40例孕妇为试验组。观察两组孕妇的治疗指标、免疫功能和妊娠结局变化。结果 干预前,孕妇的甲状腺激素、血钙、25(OH)D₃水平相比差异无统计学意义(P > 0.05),干预后孕妇的治疗指标有明显改善,但试验组更明显,差异有统计学意义(P < 0.05);干预前,两组孕妇的CD4⁺、CD8⁺、CD3⁺、CD4⁺/CD8⁺指标相比差异无统计学意义(P > 0.05),经过干预后,试验组的 CD8⁺T淋巴细胞比例同对照组比较低,其余各组免疫指标均有上升,试验组更明显,且差异有统计学意义(P...     

EFFECT OF VITAMIN A STATUS ON RETINOID-BINDING PROTEIN LEVELS IN RAT TISSUES

All organs of the rat have detectable levels of retinoid-binding proteins, some of which are altered in Vitamin A deficiency. The highest concentrations occur in reproductive organs.     

大鼠孕期、哺乳期维生素A水平对仔鼠细胞免疫功能的影响

目的　研究大鼠孕期、哺乳期维生素 A( Vit A)水平对仔鼠细胞免疫功能的影响。　方法　采用健康成年雌性SD大鼠 4 8只 ,按体重大小随机分成四组 ,均饲以 Vit A缺乏饲料。A组为 Vit A缺乏组 ,用吐温 - 80灌胃。B、C、D组剂量分别为 0 .63、3 .15、9.4 5 μmol/ kg.bw/ d维生素 A。　结果　A、D组仔鼠的胸腺及脾脏指数、足跖肿胀厚度、脾淋巴细胞增殖反应、IL- 2活性显著低于 C组 ( P<0 .0 5 )。　结论　大鼠孕期、哺乳期补充过量或缺乏 Vit A时 ,均使仔鼠细胞免疫功能降低。说明在孕期、哺乳期必须补充足量的 Vit A,并防止过量 ,才有利于子代免疫功能的增强     

Vitamin A metabolism: an update

Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years.     

Vitamin D Metabolite Ratio in Pregnant Women with Low Blood Vitamin D Concentrations Is Associated with Neonatal Anthropometric Data

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)₂D₃ to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D₃ to 25(OH)D) using data from the Japan Environment and Children’s Study at Chiba Regional Center. A total of 297 mother–neonate pairs were analyzed. Using liquid chromatography–tandem mass spectrometry, we measured 25(OH)D₂, 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.