Accounting for the influence of inflammation on retinol-binding protein in a population survey of Liberian preschool-age children

PubMed Central

Larson, Leila Margaret; Addo, O. Yaw; Sandalinas, Fanny; Faigao, Katherine; Kupka, Roland; Flores-Ayala, Rafael; Suchdev, Parminder S.

2016-01-01

Vitamin A deficiency (VAD) is an important contributor to child morbidity and mortality. The prevalence of VAD, measured by retinol-binding protein (RBP) or retinol, is overestimated in populations with a high prevalence of inflammation. We aimed to quantify and adjust for the effect of inflammation on VAD prevalence in a nationally representative survey of Liberian children 6 to 35 months of age. We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP <0.7 μmol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C-reactive protein (CRP) >5 mg/L or alpha1-acid glycoprotein (AGP) >1 g/)L; (3) multiplying each individual’s RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP – β1(lnCRPobs-lnCRPref) – β2(lnAGPobs-lnAGPref)). Corrected RBP was based on a regression model where reference lnCRP and lnAGP were set to the maximum of the lowest decile. The unadjusted prevalence of VAD was 24.7%. Children with elevated CRP and/or AGP had significantly lower RBP concentrations than their apparently healthy peers (geometric mean RBP 0.79 μmol/L (95% CI: 0.76, 0.82) vs. 0.95 μmol/L (95% CI: 0.92, 0.97), P <0.001). Using approaches 2–5 resulted in a prevalence of VAD of 11.6%, 14.3%, 13.5% and 7.3%, respectively. Depending on the approach, the VAD prevalence is reduced 10–17 percentage points when inflammation is taken into account. Further quantification of the influence of inflammation on biomarkers of vitamin A status from other national surveys is needed to compare and recommend the preferred adjustment approach across populations. PMID:26842430

Comparison of a fluorometric assay kit with high-performance liquid chromatography for the assessment of serum retinol concentration.

PubMed

Elom, Aglago Kouassivi; Imane, El Menchawy; Kaoutar, Benjeddou; Khalid, El Kari; Asmaa, El Hamdouchi; Mehdi, Azlaf; Noureddine, El Haloui; Hassan, Aguenaou

2015-06-01

Although high-performance liquid chromatography (HPLC) is the commonly used method for the analysis of retinol in biological samples, simple and rapid test kits are available. This study compared a rapid test kit (ICHECK Fluoro®) to HPLC for the assessment of serum retinol concentrations. For the analysis by HPLC, sample preparation included standard deproteinization and extraction phases. The analysis by ICHECK was performed by injecting serum into IEX reagent vials (n=89) and mixing manually for separation. After precipitation of the proteins, the vial was introduced into the chamber of the ICHECK Fluoro and analysed at 0 min (ICHECK0min) and 15 min later (ICHECK15min). Bland and Altman approach was applied to test the agreement between HPLC and ICHECK. Mean HPLC, ICHECK0min and ICHECK15min values were 421.2±106.0 µg/L, 423.1±118.3 µg/L and 413.2±107.6 µg/L, respectively. Retinol concentrations significantly decreased in the IEX solution over time (p<0.001). No significant proportional bias was observed between HPLC and ICHECK0min (r-0.038, p=0.73) and ICHECK15min (r=-0.024, p=0.82). Fixed biases (HPLC minus ICHECK) for ICHECK0min and ICHECK15min were respectively -1.9±23.1 µg/l (p=0.45) and 8.0±22.7 µg/l (p=0.002). ICHECK Fluoro may offer a reliable mean for assessing serum retinol for measurements performed with no significant time delay.

Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Friedmacher, Florian; Pes, Lara; Coyle, David; Doi, Takashi; Paradisi, Francesca; Puri, Prem

2016-04-01

Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP-dependent retinol transport in a nitrofen model of CDH. Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry. Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH. Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDH-associated PH by elevating serum and pulmonary retinol levels.

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Retinol-binding protein immunological test system....5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... the retinol-binding protein that binds and transports vitamin A in serum and urine. Measurement of...

High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

PubMed

Mondloch, Stephanie; Gannon, Bryan M; Davis, Christopher R; Chileshe, Justin; Kaliwile, Chisela; Masi, Cassim; Rios-Avila, Luisa; Gregory, Jesse F; Tanumihardjo, Sherry A

2015-08-01

Biomarkers of micronutrient status are needed to best define deficiencies and excesses of essential nutrients. We evaluated several supporting biomarkers of vitamin A status in Zambian children to determine whether any of the biomarkers were consistent with high liver retinol stores determined by using retinol isotope dilution (RID). A randomized, placebo-controlled, biofortified maize efficacy trial was conducted in 140 rural Zambian children from 4 villages. A series of biomarkers were investigated to better define the vitamin A status of these children. In addition to the assessment of total-body retinol stores (TBSs) by using RID, tests included analyses of serum carotenoids, retinyl esters, and pyridoxal-5'-phosphate (PLP) by using high-pressure liquid chromatography, retinol-binding protein by using ELISA, and alanine aminotransferase (ALT) activity by using a colorimetric assay. Children (n = 133) were analyzed quantitatively for TBSs by using RID. TBSs, retinyl esters, some carotenoids, and PLP differed by village site. Serum carotenoids were elevated above most nonintervened reference values for children. α-Carotene, β-carotene, and lutein values were >95th percentile from children in the US NHANES III, and 13% of children had hypercarotenemia (defined as total carotenoid concentration >3.7 μmol/L). Although only 2% of children had serum retinyl esters >10% of total retinol plus retinyl esters, 16% of children had >5% as esters, which was consistent with high liver retinol stores. Ratios of serum retinol to retinol-binding protein did not deviate from 1.0, which indicated full saturation. ALT activity was low, which was likely due to underlying vitamin B-6 deficiency, which was confirmed by very low serum PLP concentrations. The finding of hypervitaminosis A in Zambian children was supported by high circulating concentrations of carotenoids and mildly elevated serum retinyl esters. ALT-activity assays may be compromised with co-existing vitamin B-6

Serum retinol, alpha-tocopherol, and beta-carotene levels are not altered by excess ingestion of diacylglycerol-containing plant sterol esters.

PubMed

Saito, Shinichiro; Tomonobu, Kazuichi; Kudo, Naoto; Shiiba, Daisuke; Hase, Tadashi; Tokimitsu, Ichiro

2006-01-01

Diacylglycerol (DAG) suppresses the postprandial increase in serum triglycerides, and has antiobesity effects. On the other hand, plant sterol esters (PSE) lower serum cholesterol levels in hypercholesterolemia. Thus, DAG-containing PSE (PSE/DAG) would be expected to maintain an appropriate serum cholesterol level and decrease the risk of arteriosclerotic disorders. Several recent studies, however, report negative effects of PSE on serum fat-soluble (pro)vitamin levels. The objective of this study was to investigate the effect of PSE/DAG on serum retinol, beta-carotene, and alpha-tocopherol levels using a threefold excess of the effective dose obtained in our previous study. A randomized placebo-controlled double-blind parallel study was performed in healthy and mildly hypercholesterolemic subjects, in which the subjects ingested 1.2 g PSE/30 g DAG for 2 weeks in the form of mayonnaise-type products. Triacylglycerol (TAG) mayonnaise was used as a control. There were no subjective adverse effects or changes in serum retinol, alpha-tocopherol, and beta-carotene levels, abdominal symptoms, hematologic values, or blood biochemical values. Ingestion of a threefold excess of PSE/DAG for 2 weeks had no adverse effects compared to ingestion of conventional TAG mayonnaise. Copyright 2006 S. Karger AG, Basel.

[Vitamin A deficiency and the anthropometric nutritional status of urban and rural marginalized children in the state of Zulia, Venezuela].

PubMed

Amaya-Castellanos, Daisy; Viloria-Castejón, Haydée; Ortega, Pablo; Gómez, Gisela; Urrieta, Jesús R; Lobo, Pablo; Estévez, Jesús

2002-06-01

The present transversal study was carried out to estimate the prevalence of both vitamin A deficiency (VAD) and protein-energy malnutrition among children (24 to 85 months) from three urban slums (n = 173) in Maracaibo city, Zulia State, Venezuela and a rural slum area (n = 34), vieinal to Maracaibo, by measuring serum retinol and z score of anthropometric indices Height//Age (H//AZ); Weight//Age (W//AZ) and Weight//Height (W//HZ), compared to NCHS-WHO reference values. The Graffar's methodology adapted to Venezuela by Méndez Castellano (1986) confirmed the underprivileged socio-economic condition of the children population. For serum retinol analysis, peripheral venous blood was drawn and serum was treated according to the Bieri et al. (1979) technique and HPLC procedure. Values were recorded in microgram/dL. Statistical analysis was done by using Epi Info 2000, release 1.0 and SAS release 6.0 (1996) computer programs. The prevalence of VAD (serum retinol < 20 micrograms/dL) in the total children population (n = 207) was 22.2%, being higher in urban children than in rural children (22.5% vs 20.5%). No clinical signs of VAD were detected in the children. The nutritional status analysed by Z score of anthropometric indices revealed that 27.4% of children suffered from undernutrition (Z score = -2 to > -3 SD), being 15.4% stunted, 9.6% wasted and 2.6% with acute protein-energy malnutrition. Neither severe malnutrition nor overweight were detected. According with the H//AZ index, 54.6% of children had adequate nutrition. However 23% of them suffered from VAD. In children at risk of developing undernutrition (Z score = -1 to > -2 SD), 20.9% had VAD and of the stunted children, 21.9% presented VAD. With W//AZ, 60.3%, 29.9% and 9.1% of children were with adequate nutrition, at risk, or wasted respectively; of each group, 25.6%, 17.7% and 15%, respectively had serum retinol values below 20 micrograms/dL. The Z score of W//HZ indicator revealed that 87.4%, 10.4% and 2

Iron deficiency and anemia are associated with low retinol levels in children aged 1 to 5 years.

PubMed

Saraiva, Bárbara C A; Soares, Michele C C; Santos, Luana C dos; Pereira, Simone C L; Horta, Paula M

2014-01-01

To analyze the occurrence of anemia and iron deficiency in children aged 1 to 5 years and the association of these events and retinol deficiency. This was an observational analytic cross-sectional study conducted in Vitoria, ES, Brazil, between April and August of 2008, with healthy children aged 1 to 5 years (n=692) that lived in areas covered by primary healthcare services. Sociodemographic and economic conditions, dietary intake (energy, protein, iron, and vitamin A ingestion), anthropometric data (body mass index-for-age and height-for-age), and biochemical parameters (ferritin, hemoglobin, and retinol serum) were collected. The prevalence of anemia, iron deficiency, and retinol deficiency was 15.7%, 28.1%, and 24.7%, respectively. Univariate analysis showed a higher prevalence of anemia (PR: 4.62, 95% CI: 3.36, 6.34, p<0.001) and iron deficiency (PR: 4.51, 95% CI: 3.30, 6.17, p<0.001) among children with retinol deficiency. The same results were obtained after adjusting for socioeconomic and demographic conditions, dietary intake, and anthropometric variables. There was a positive association between ferritin vs. retinol serum (r=0.597; p<0.001) and hemoglobin vs. retinol serum (r=0.770; p<0.001). Anemia and iron deficiency were associated with low levels of serum retinol in children aged 1 to 5 years, and a positive correlation was verified between serum retinol and serum ferritin and hemoglobin levels. These results indicate the importance of initiatives encouraging the development of new treatments and further research regarding retinol deficiency. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Mathematical modeling of serum 13C-retinol in captive rhesus monkeys provides new insights on hypervitaminosis A.

PubMed

Escaron, Anne L; Green, Michael H; Howe, Julie A; Tanumihardjo, Sherry A

2009-10-01

Hypervitaminosis A is increasingly a public health concern, and thus noninvasive quantitative methods merit exploration. In this study, we applied the (13)C-retinol isotope dilution test to a nonhuman primate model with excessive liver stores. After baseline serum chemistries, rhesus macaques (Macaca mulatta; n = 16) were administered 3.5 mumol (13)C(2)-retinyl acetate. Blood was drawn at baseline, 5 h, and 2, 4, 7, 14, 21, and 28 d following the dose. Liver biopsies were collected 7 d before and 2 d after dosing (n = 4) and at 7, 14, and 28 d (n = 4/time) after dosing. Serum and liver were analyzed by HPLC and GC-combustion-isotope ratio MS for retinol and its enrichment, respectively. Model-based compartmental analysis was applied to serum data. Lactate dehydrogenase was elevated in 50% of the monkeys. Total body reserves (TBR) of vitamin A (VA) were calculated at 28 d. Predicted TBR (3.52 +/- 2.01 mmol VA) represented measured liver stores (4.56 +/- 1.38 mmol VA; P = 0.124). Predicted liver VA concentrations (13.3 +/- 9.7 micromol/g) were similar to measured liver VA concentrations (16.4 +/- 5.3 micromol/g). The kinetic models predict that 27-52% of extravascular VA is exchanging with serum in hypervitaminotic A monkeys. The test correctly diagnosed hypervitaminosis A in all monkeys, i.e. 100% sensitivity. Stable isotope techniques have important public health potential for the classification of VA status, including hypervitaminosis, because no other technique besides invasive liver biopsies, correctly identifies excessive liver VA stores.

The testis-specific VAD1.3/AEP1 interacts with β-actin and syntaxin 1 and directs peri-nuclear/Golgi expression with bipartite nucleus localization (BNL) sequence.

PubMed

Zuo, Yan; Gao, Jing; Yeung, William S B; Lee, Kai-Fai

2010-10-15

VAD1.3 (AEP1), a novel testis-specific gene, was first isolated from the testis of a retinol-treated vitamin-A-deficient (VAD) rat model. It is expressed at the acrosomal region of spermatids from postnatal day 25. VAD1.3 immunoreactivity is present in rat, human, monkey and porcine spermatids and spermatozoa, suggesting that VAD1.3 may play a role in acrosome formation. However, direct evidence on the detailed sub-cellular localization of the VAD1.3 protein in the acrosome and how VAD1.3 is involved in acrosome formation remains largely unknown. Here, we isolated and identified VAD1.3 interacting proteins by immunoprecipitation followed by mass spectrometry, and determined the functional motifs of VAD1.3 that were important for its specific sub-cellular location in vitro. We found that VAD1.3 bound to syntaxin 1 and β-actin proteins in vitro. Immunogold electron microscopic study localized VAD1.3 immunoreactivity to the acrosome membranes and matrix, and colocalized it with the β-actin protein. The full-length GFP-VAD (1-3601) and GFP-VAD (1-730) fusion proteins that contain the bipartite nucleus localization (BNL) signal were located in the peri-nucleus/Golgi of the transfected cells. In addition, the GFP signal colocalized with the endoplasmic reticulum marker and the syntaxin 1 protein in the transfected HeLa and GC-2spd cells. The C-terminal GFP-VAD (1770-3601) was expressed in the nucleus. Taken together, VAD1.3 interacts with β-actin and syntaxin 1 in vitro. The BNL signal may mediate the peri-nuclei localization of the protein that may interact with syntaxin 1 and β-actin for acrosome formation in spermatogenesis. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

[Study on anemia and vitamin A and vitamin D nutritional status of Chinese urban pregnant women in 2010-2012].

PubMed

Hu, Y C; Chen, J; Li, M; Wang, R; Li, W D; Yang, Y H; Yang, C; Yun, C F; Yang, L C; Yang, X G

2017-02-06

Objective: To evaluate the prevalence of anemia and the nutritional status of vitamins A and D by analyzing hemoglobin, serum retinol, and serum 25-hydroxyvitamin D levels in Chinese urban pregnant women during 2010-2012. Methods: Data were obtained from the China Nutrition and Health Survey in 2010-2012. Using multi-stage stratified sampling and population proportional stratified random sampling, 2 250 pregnant women from 34 metropolis and 41 middle-sized and small cities were included in this study. Information was collected using a questionnaire survey. The blood hemoglobin concentration was determined using the cyanmethemoglobin method, and anemia was determined using the World Health Organization guidelines combined with the elevation correction standard. The serum retinol level was determined using high-performance liquid chromatography, and vitamin A deficiency (VAD) was judged by the related standard recommended by the World Health Organization. The vitamin D level was determined using enzyme-linked immunosorbent assay and vitamin D deficiency was judged by the recommendation standards from the Institute of Medicine of The National Academies. The hemoglobin, serum retinol, and serum 25-hydroxyvitamin D levels were compared, along with differences in the prevalence of anemia, VAD, and the vitamin D deficiency rate (including deficiency and serious deficiency). Results: A total of 1 738 cases of hemoglobin level, 594 cases of serum retinol level, and 1 027 cases of serum 25-hydroxyvitamin D were available for analysis in this study. The overall blood hemoglobin level ( P (50) ( P (25)- P (75))) was 122.70 (114.00-131.10) g/L; 123.70 (115.21-132.00) g/L for metropolis and 122.01 (113.30-130.40) g/L for middle-sized and small cities. The blood hemoglobin level of metropolis residents was significantly higher than that of middle-sized and small city residents ( P= 0.027). The overall prevalence of anemia was 17.0% (295/1 738). The overall serum retinol level ( P

‘Dose-to-Mother’ Deuterium Oxide Dilution Technique: An Accurate Strategy to Measure Vitamin A Intake in Breastfed Infants

PubMed Central

Lopez-Teros, Veronica; Limon-Miro, Ana Teresa; Astiazaran-Garcia, Humberto; Tanumihardjo, Sherry A.; Tortoledo-Ortiz, Orlando; Valencia, Mauro E.

2017-01-01

In Mexico, infants (0–2 years old) show the highest prevalence of vitamin A deficiency (VAD), measured by serum retinol concentrations. Thus, we consider that low vitamin A (VA) intake through breast milk (BM) combined with poor weaning practices are the main factors that contribute to VAD in this group. We combined the assessment of VA status in lactating women using BM retinol and a stable isotope ‘dose-to-mother’ technique to measure BM production in women from urban and agricultural areas. Infants’ mean BM intake was 758 ± 185 mL, and no difference was observed between both areas (p = 0.067). Mean BM retinol concentration was 1.09 μmol/L, which was significantly lower for the agricultural area (p = 0.028). Based on BM retinol concentration, 57% of women were VAD; although this prevalence fell to 16% when based on fat content. Regardless of the VA biomarker used here, infants from the urban and agricultural areas cover only 66% and 49% of their dietary adequate intake from BM, respectively (p = 0.054). Our data indicate that VAD is still a public health concern in Mexico. Adopting both methods to assess VA transfer from the mother to the breastfed child offers an innovative approach towards the nutritional assessment of vulnerable groups. PMID:28230781

A novel high-throughput method for supported liquid extraction of retinol and alpha-tocopherol from human serum and simultaneous quantitation by liquid chromatography tandem mass spectrometry.

PubMed

Hinchliffe, Edward; Rudge, James; Reed, Paul

2016-07-01

Measurement of vitamin A (retinol) and E (alpha-tocopherol) in UK clinical laboratories is currently performed exclusively by high-performance liquid chromatography with ultraviolet detection. We investigated whether retinol and alpha-tocopherol could be measured simultaneously by liquid chromatography tandem mass spectrometry. Serum samples (100 μL) were extracted using Isolute + Supported Liquid Extraction plates. Chromatography was performed on a Phenomenex Kinetex Biphenyl 2.6 μm, 50 × 2.1 mm column, and liquid chromatography tandem mass spectrometry on a Waters Acquity TQD. Injection-to-injection time was 4.3 min. The assay was validated according to published guidelines. Patient samples were used to compare liquid chromatography tandem mass spectrometry and high-performance liquid chromatography with ultraviolet detection methods. For retinol and alpha-tocopherol, respectively, the assay was linear up to 6.0 and 80.0 μmol/L, and lower limit of quantification was 0.07 and 0.26 μmol/L. Intra and interassay imprecision were within desirable analytical specifications. Analysis of quality control material aligned to NIST SRM 968e, and relative spiked recovery from human serum, both yielded results within 15% of target values. Method comparison with high-performance liquid chromatography with ultraviolet detection methodology demonstrated a negative bias for retinol and alpha-tocopherol by the liquid chromatography tandem mass spectrometry method. Analysis of United Kingdom National External Quality Assurance Scheme samples yielded mean bias from the target value of +3.0% for retinol and -11.2% for alpha-tocopherol. We have developed a novel, high-throughput method for extraction of retinol and alpha-tocopherol from human serum followed by simultaneous quantitation by liquid chromatography tandem mass spectrometry. The method offers a rapid, sensitive, specific and cost-effective alternative to high-performance liquid chromatography with

Socioeconomic factors and vitamin a status of pregnant women in Calabar urban, southeastern Nigeria.

PubMed

Williams, Ima O; Essien, Essien U; Eka, Offiong U

2011-10-01

Vitamin A deficiency (VAD) is prevalent in developing countries. Socioeconomic status is increasingly being associated with nutritional status of individuals. Efforts to control or eliminate VAD must focus on socioeconomic factors and how to tackle them in the midst of other well recognized strategies. This research sought to determine the socioeconomic factors that may affect the serum retinol levels of pregnant women in Calabar, Nigeria. A total of 101 pregnant women in Calabar were studied for the effect of socioeconomic factors on the maternal vitamin A status using a structured household questionnaire and biochemical analytical techniques. The study revealed that a majority (82.2%) of the women studied were in their normal reproductive years (20-45 years), 63.4% had previous childbirth experience, 89.1% had formal education, 85% were employed, 85% lived in medium to large families (4 persons and above) while 62.3% were in the middle or high income class (over N50,000 per month). Among the women, only 35.6% had adequate vitamin A status while the rest had deficient (15.8%), low (32.7%) or very high (15.8%) levels. The results of the analysis of the influence of socioeconomic characteristics of the women on serum retinol status showed a positive relationship between serum retinol level and education (P < 0.05; F = 2.84) and between serum retinol level and parity (P < 0.05; F = 2.05). Serum retinol concentration was not affected by age, occupation, household size and other household characteristics used in the study. Increased maternal education and appropriate child spacing may be the key strategies for the elimination and control of vitamin A deficiency in developing countries.

Effect of vitamin A supplementation on the urinary retinol excretion in very low birth weight infants.

PubMed

Schmiedchen, Bettina; Longardt, Ann Carolin; Loui, Andrea; Bührer, Christoph; Raila, Jens; Schweigert, Florian J

2016-03-01

Despite high-dose vitamin A supplementation of very low birth weight infants (VLBW, <1500 g), their vitamin A status does not improve substantially. Unknown is the impact of urinary retinol excretion on the serum retinol concentration in these infants. Therefore, the effect of high-dose vitamin A supplementation on the urinary vitamin A excretion in VLBW infants was investigated. Sixty-three VLBW infants were treated with vitamin A (5000 IU intramuscular, 3 times/week for 4 weeks); 38 untreated infants were classified as control group. On days 3 and 28 of life, retinol, retinol-binding protein 4 (RBP4), glomerular filtration rate, proteinuria, and Tamm-Horsfall protein were quantified in urine. On day 3 of life, substantial retinol and RBP4 losses were found in both groups, which significantly decreased until day 28. Notwithstanding, the retinol excretion was higher (P < 0.01) under vitamin A supplementation as compared to infants of the control group. On day 28 of life, the urinary retinol concentrations were predictive for serum retinol concentrations in the vitamin A treated (P < 0.01), but not in the control group (P = 0.570). High urinary retinol excretion may limit the vitamin A supplementation efficacy in VLBW infants. Advanced age and thus postnatal kidney maturation seems to be an important contributor in the prevention of urinary retinol losses.

Longitudinal study of serum carotenoid, retinol, and tocopherol concentrations in relation to breast cancer risk among postmenopausal women12

PubMed Central

Kim, Mimi; Adams-Campbell, Lucile L; Caan, Bette J; Chlebowski, Rowan T; Neuhouser, Marian L; Shikany, James M; Rohan, Thomas E

2009-01-01

Background: Prospective studies have examined the association of serum and plasma carotenoids and micronutrients and breast cancer; however, to date, studies have only assessed exposure at one point in time. Objective: This study analyzed baseline and repeated serum measurements of carotenoids, retinol, and tocopherols to assess their associations with postmenopausal breast cancer risk. Design: Serum concentrations of α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, α-tocopherol, and γ-tocopherol were measured in a 6% sample of women in the Women's Health Initiative clinical trials at baseline and at years 1, 3, and 6 and in a 1% sample of women in the observational study at baseline and at year 3. The association of baseline compounds and breast cancer risk was estimated by Cox proportional hazards models. In addition, repeated measurements were analyzed as time-dependent covariates. Of 5450 women with baseline measurements, 190 incident cases of breast cancer were ascertained over a median of 8.0 y of follow-up. Results: After multivariable adjustment, risk of invasive breast cancer was inversely associated with baseline serum α-carotene concentrations (hazard ratio for highest compared with the lowest tertile: 0.55; 95% CI: 0.34, 0.90; P = 0.02) and positively associated with baseline lycopene (hazard ratio: 1.47; 95% CI: 0.98, 2.22; P = 0.06). Analysis of repeated measurements indicated that α-carotene and β-carotene were inversely associated with breast cancer and that γ-tocopherol was associated with increased risk. Conclusions: The present study, which was the first to assess repeated measurements of serum carotenoids and micronutrients in relation to breast cancer, adds to the evidence of an inverse association of specific carotenoids with breast cancer. The positive associations observed for lycopene and γ-tocopherol require confirmation. This trial was registered at clinicaltrials.gov as NCT00000611. PMID:19474140

Optimisation of the Sputnik-VAD design.

PubMed

Selishchev, Sergey V; Telyshev, Dmitry V

2016-10-10

Miniaturisation of VADs can offer important benefits, including less invasive implantation techniques and more versatility in patient selection. The aim of this work was to reduce the weight, size, and energy consumption of the Sputnik VAD. The second generation of the Sputnik VAD was developed with a set of changes in construction. The head pressure-flow rate (H-Q) and power consumption-flow rate curves for the Sputnik VADs were measured at different rotational speeds. Computational fluid dynamics (CFD) were used for operating condition simulation and the LVADs were compared under the simulated physiological conditions. The slope of the H-Q curves for the Sputnik 1 VAD remains almost invariable over the entire range of the measured flow rate, in contrast to the curves for the Sputnik 2 VAD, which become flat in the high flow-rate region. Despite the design modification, the operating rotor speed remained invariable. The preload sensitivity of the Sputnik VAD is higher than that of the other rotary blood pumps and amounts to 0.111 ± 0.0092 L min-1 mmHg-1. The power consumption for the Sputnik 2 VAD is lower over the entire speed range, except for at 5,000 rpm. The pump weight was reduced from 246 to 205 g, the pump length was decreased from 82 to 66 mm, and the pump diameter was decreased from 32 to 29 mm. The total energy consumption of the pump was reduced by 15%.

Mathematical Modeling of Serum 13C-Retinol in Captive Rhesus Monkeys Provides New Insights on Hypervitaminosis A1–3

PubMed Central

Escaron, Anne L.; Green, Michael H.; Howe, Julie A.; Tanumihardjo, Sherry A.

2009-01-01

Hypervitaminosis A is increasingly a public health concern, and thus noninvasive quantitative methods merit exploration. In this study, we applied the 13C-retinol isotope dilution test to a nonhuman primate model with excessive liver stores. After baseline serum chemistries, rhesus macaques (Macaca mulatta; n = 16) were administered 3.5 μmol 13C2-retinyl acetate. Blood was drawn at baseline, 5 h, and 2, 4, 7, 14, 21, and 28 d following the dose. Liver biopsies were collected 7 d before and 2 d after dosing (n = 4) and at 7, 14, and 28 d (n = 4/time) after dosing. Serum and liver were analyzed by HPLC and GC-combustion-isotope ratio MS for retinol and its enrichment, respectively. Model-based compartmental analysis was applied to serum data. Lactate dehydrogenase was elevated in 50% of the monkeys. Total body reserves (TBR) of vitamin A (VA) were calculated at 28 d. Predicted TBR (3.52 ± 2.01 mmol VA) represented measured liver stores (4.56 ± 1.38 mmol VA; P = 0.124). Predicted liver VA concentrations (13.3 ± 9.7 μmol/g) were similar to measured liver VA concentrations (16.4 ± 5.3 μmol/g). The kinetic models predict that 27–52% of extravascular VA is exchanging with serum in hypervitaminotic A monkeys. The test correctly diagnosed hypervitaminosis A in all monkeys, i.e. 100% sensitivity. Stable isotope techniques have important public health potential for the classification of VA status, including hypervitaminosis, because no other technique besides invasive liver biopsies, correctly identifies excessive liver VA stores. PMID:19710158

Effect of maternal vitamin A supplementation on retinol concentration in colostrum.

PubMed

Grilo, Evellyn C; Lima, Mayara S R; Cunha, Lahyana R F; Gurgel, Cristiane S S; Clemente, Heleni A; Dimenstein, Roberto

2015-01-01

To investigate the effect of vitamin A supplementation on the retinol concentration in colostrum under fasting and postprandial conditions. This was a quasi-experimental study, with before and after assessments, conducted with 33 patients treated at a public maternity hospital. Blood and colostrum samples were collected under fasting conditions in the immediate postpartum period. A second colostrum collection occurred two hours after the first meal of the day, at which time a mega dose of 200,000 IU of retinyl palmitate was administered. On the following day, the colostrum was collected again under fasting and postprandial conditions. Serum and colostrum retinol concentrations were determined by high performance liquid chromatography. The serum retinol concentration was 37.3 (16.8-62.2) μg/dL, indicating adequate nutritional status. The colostrum retinol concentration before supplementation was 46.8 (29.7-158.9) μg/dL in fasting and 67.3 (31.1-148.7) μg/dL in postprandial condition (p < 0.05), showing an increase of 43.8%. After supplementation, the values were 89.5 (32.9-264.2) μg/dL and 102.7 (37.3-378.3) μg/dL in fasting and postprandial conditions, respectively (p < 0.05), representing an increase of 14.7%. This study demonstrated that maternal supplementation with high doses of vitamin A in postpartum resulted in a significant increase of the retinol concentration in colostrum under fasting conditions, with an even greater increase after a meal. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Development of the NASA/Baylor VAD

NASA Technical Reports Server (NTRS)

Aber, G. S.; Akkerman, J. W.; Bozeman, R. J., Jr.; Saucler, D. R.; Bacak, J. W.; Svejkovsky, P. A.; Damm, G. A.; Mizuguchi, K.; Noon, G. P.; Nose, Y.

1994-01-01

A cooperative effort between the NASA/Johnson Space Center (JSC) and the Baylor College of Medicine (BCM) has been underway since 1988 to develop a long-term implantable Ventricular Assist Device (VAD). The VAD is intended to boost the cardiac output of patients with deteriorated cardiac function. For many of these patients, the best alternative is heart transplantation. Heart transplantation is a complex and expensive procedure and usually requires a long waiting period for a donor heart. The condition of the patient often deteriorates during this waiting period which complicates the pre and post-operative care. Because of these factors, the need for a long-term implantable VAD for use as a bridge-to-transplant device or as a permanent assist device has become the focus of much research. The need for a VAD has been estimated at 50,000 to 60,000 patients per year in the United States alone. A device which satisfies all the system performance and reliability requirements has yet to be achieved. However, the development of the NASA/Baylor VAD has progressed to a state in which commercial viability can being to be considered. The device is small, simple, efficient and reliable which meets all requirements for a totally implantable VAD.

Retinol esterification in bovine retinal pigment epithelium: reversibility of lecithin:retinol acyltransferase.

PubMed Central

Saari, J C; Bredberg, D L; Farrell, D F

1993-01-01

Esterification of all-trans-retinol is a key reaction of the vertebrate visual cycle, since it produces an insoluble, relatively non-toxic, form of the vitamin for storage and supplies substrate for the isomerization reaction. CoA-dependent and -independent pathways have been described for retinol esterification in retinal pigment epithelium (RPE). The CoA-independent reaction, catalysed by lecithin:retinol acyltransferase (LRAT) was examined in more detail in this study. Addition of retinol to RPE microsomes results in a burst of retinyl ester synthesis, followed by a rapid apparent cessation of the reaction. However, [3H]retinol, added when retinyl ester synthesis has apparently ceased, is rapidly incorporated into retinyl ester without a net increase in the amount of ester. The specific radioactivities of [3H]retinol and [3H]retinyl ester reach the same value. [14C]Palmitate from palmitoyl-CoA is incorporated into preexisting retinyl ester in the absence of net ester synthesis, too. These exchange reactions suggest that the reaction has reached equilibrium at the plateau of the progress curve and that only the accumulation of retinyl ester, and not its synthesis, has stopped during this phase of the reaction. Studies with geometrical isomers of retinol revealed that the rate of exchange of all-trans-retinol with all-trans-retinyl esters was about 6 times more rapid than exchange of 11-cis-retinol with 11-cis-retinyl ester. This is the first demonstration of the reversibility of LRAT and the first example of stereospecificity of retinyl ester synthesis in the visual system. Reversal of the LRAT reaction could contribute to the mobilization of 11-cis-retinol from 11-cis-retinyl ester pools. Images Figure 3 PMID:8489497

Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes

PubMed Central

2013-01-01

Background The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients deficiencies, such as retinol and vitamin D, which are especially important to immunity of the body and may influence pancreas β-cell function. However, the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes, immune and nutrition state are still uncertain. We are conducting a randomized controlled trial of vitamin A and/or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients. Methods/design This is a 2×2 factorial trial. We plan to enroll 400 active PTB patients with DM, and randomize them to VA (2000 IU daily retinol); VD (400 IU daily cholecalciferol); VAD (2000 IU daily retinol plus 400 IU cholecalciferol) or control (placebo) group. Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism, and the secondary outcome measure being immune and nutrition status of the subjects. Of the first 37 subjects enrolled: 8 have been randomized to VA, 10 to VD, 9 to VAD and 10 to control. To date, the sample is 97.3% Han Chinese and 91.9% female. The average fasting plasma glucose level is 12.19 mmol/L. Discussion This paper describes the design and rationale of a randomized clinical trial comparing VA and/or VD supplementation to active pulmonary TB patients with DM. Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition. This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active

Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes.

PubMed

Wang, Qiuzhen; Ma, Aiguo; Bygbjerg, Ib Christian; Han, Xiuxia; Liu, Yufeng; Zhao, Shanliang; Cai, Jing

2013-02-26

The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients deficiencies, such as retinol and vitamin D, which are especially important to immunity of the body and may influence pancreas β-cell function. However, the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes, immune and nutrition state are still uncertain. We are conducting a randomized controlled trial of vitamin A and/or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients. This is a 2×2 factorial trial. We plan to enroll 400 active PTB patients with DM, and randomize them to VA (2000 IU daily retinol); VD (400 IU daily cholecalciferol); VAD (2000 IU daily retinol plus 400 IU cholecalciferol) or control (placebo) group. Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism, and the secondary outcome measure being immune and nutrition status of the subjects. Of the first 37 subjects enrolled: 8 have been randomized to VA, 10 to VD, 9 to VAD and 10 to control. To date, the sample is 97.3% Han Chinese and 91.9% female. The average fasting plasma glucose level is 12.19 mmol/L. This paper describes the design and rationale of a randomized clinical trial comparing VA and/or VD supplementation to active pulmonary TB patients with DM. Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition. This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM. ChiCTR-TRC-12002546.

Kinetic studies of retinol addition radicals.

PubMed

El-Agamey, Ali; Fukuzumi, Shunichi; Naqvi, K Razi; McGarvey, David J

2011-03-07

Retinol neutral radicals (RS-retinol˙), generated from the reaction of retinol with 4-pyridylthiyl and 2-pyridylthiyl radicals in argon-saturated methanol, undergo β-elimination, which can be monitored via the slow secondary absorption rise at 380 nm attributed to the rearrangement of the unstable retinol neutral addition radicals to the more stable addition radicals. Rate constants for the β-elimination reactions (k(β)) of 4-PyrS-retinol˙ were measured at different temperatures and the Arrhenius equation for the reaction is described by log (k(β)/s(-1)) = (12.7 ± 0.2) - (54.3 ± 1.3)/θ, where θ = 2.3RT kJ mol(-1). The reactivities of retinol addition radicals (RS-retinol˙), generated from the reaction of retinol with various thiyl radicals, towards oxygen have also been investigated in methanol. In the presence of oxygen, the decay of RS-retinol˙ fits to biexponential kinetics and both observed rate constants for the RS-retinol˙ decay are oxygen-concentration dependent. This suggests that at least two thiyl addition radicals, formed from the reaction of RS˙ with retinol, undergo oxygen addition reactions. In light of the estimated rate constants for oxygen addition to RS-retinol˙ and RS-CAR˙ (CAR: carotenoid), the antioxidant-prooxidant properties of retinol are discussed.

Ventricular assist device elicits serum natural IgG that correlates with the development of primary graft dysfunction following heart transplantation.

PubMed

See, Sarah B; Clerkin, Kevin J; Kennel, Peter J; Zhang, Feifan; Weber, Matthew P; Rogers, Kortney J; Chatterjee, Debanjana; Vasilescu, Elena R; Vlad, George; Naka, Yoshifumi; Restaino, Susan W; Farr, Maryjane A; Topkara, Veli K; Colombo, Paolo C; Mancini, Donna M; Schulze, P Christian; Levin, Bruce; Zorn, Emmanuel

2017-08-01

Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome. IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant recipients, including 128 patients with VAD (VAD patients) and 78 patients without VAD (no-VAD patients). Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by enzyme-linked immunosorbent assay. No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared with no-VAD patients. This increase was likely due to the presence of the VAD, as revealed by lower serum IgG Nabs levels before implantation. Elevated pre-transplant IgG Nabs level was associated with development of primary graft dysfunction (PGD). Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with development of PGD suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The retinol esterifying enzyme LRAT supports cell signaling by retinol-binding protein and its receptor STRA6.

PubMed

Marwarha, Gurdeep; Berry, Daniel C; Croniger, Colleen M; Noy, Noa

2014-01-01

Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP). At some tissues, holo-RBP is recognized by a plasma membrane receptor termed STRA6, which serves a dual role: it mediates transport of retinol from RBP into cells, and it functions as a cytokine receptor that, on binding holo-RBP, activates JAK2/STAT5 signaling. As STAT target genes include SOCS3, an inhibitor of insulin receptor, holo-RBP suppresses insulin responses in STRA6-expressing cells. We have shown previously that the two functions of STRA6 are interdependent. These observations suggest factors that regulate STRA6-mediated retinol transport may also control STRA6-mediated cell signaling. One such factor is retinol metabolism, which enables cellular uptake of retinol by maintaining an inward-directed concentration gradient. We show here that lecithin:retinol acyl transferase (LRAT), which catalyzes esterification of retinol to its storage species retinyl esters, is necessary for activation of the STRA6/JAK2/STAT5 cascade by holo-RBP. In accordance, LRAT-null mice are protected from holo-RBP-induced suppression of insulin responses. Hence, STRA6 signaling, which requires STRA6-mediated retinol transport, is supported by LRAT-catalyzed retinol metabolism. The observations demonstrate that STRA6 regulates key cellular processes by coupling circulating holo-RBP levels and intracellular retinol metabolism to cell signaling.

Design, Synthesis, and Evaluation of Nonretinoid Retinol Binding Protein 4 Antagonists for the Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease

PubMed Central

2015-01-01

Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4–/– mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%. PMID:25210858

Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and Stargardt disease.

PubMed

Cioffi, Christopher L; Dobri, Nicoleta; Freeman, Emily E; Conlon, Michael P; Chen, Ping; Stafford, Douglas G; Schwarz, Daniel M C; Golden, Kathy C; Zhu, Lei; Kitchen, Douglas B; Barnes, Keith D; Racz, Boglarka; Qin, Qiong; Michelotti, Enrique; Cywin, Charles L; Martin, William H; Pearson, Paul G; Johnson, Graham; Petrukhin, Konstantin

2014-09-25

Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-) mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.

Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.

PubMed

Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

2014-12-01

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

PubMed

Chen, Yanmin; Lv, Ping; Du, Mengkai; Liang, Zhaoxia; Zhou, Menglin; Chen, Danqing

2017-07-01

Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal

PubMed Central

Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

2014-01-01

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a non­canonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided. PMID:25478840

Relationship between the Nutritional Status of Vitamin A per Trimester of Pregnancy with Maternal Anthropometry and Anemia after Roux-en-Y Gastric Bypass.

PubMed

Cruz, Sabrina; Matos, Andréa; da Cruz, Suelem Pereira; Pereira, Silvia; Saboya, Carlos; Ramalho, Andréa

2017-09-08

The aim of this study was to compare the nutritional status of vitamin A per trimester of pregnancy, as well as to assess its influence on pre-pregnancy BMI, total gestational weight gain (TGWG) and presence of anemia in women who had previously undergone Roux-en-Y gastric bypass (RYGB). An analytical, longitudinal and retrospective study comprising 30 pregnant women who had previously undergone RYGB was undertaken. In all trimesters of pregnancy, the serum concentrations of retinol, β-carotene, stages of vitamin A deficiency (VAD), night blindness (NB), anemia and anthropometric variables were assessed. VAD in pregnancy affected 90% of women, 86.7% developed NB and 82.8% had mild VAD. TGWG above/below the recommended range was related to the low serum concentrations of β-carotene ( p = 0.045) in the second trimester and women with TGWG above the recommended range showed 100% of inadequacy of this nutrient in the third trimester. Among the pregnant women with anemia, 90.9% had VAD and 86.4% had NB. This study highlights the importance of monitoring the nutritional status of vitamin A in prenatal care, due to its relationship with TGWG and the high percentage of VAD and NB found since the beginning of pregnancy. It also reaffirms the use of the cut-off <1.05 μmol/L for determining VAD.

Serum concentrations of lipids, vitamin d metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos.

PubMed

Crissey, Susan D; Ange, Kimberly D; Jacobsen, Krista L; Slifka, Kerri A; Bowen, Phyllis E; Stacewicz-Sapuntzakis, Maria; Langman, Craig B; Sadler, William; Kahn, Stephen; Ward, Ann

2003-01-01

Serum concentrations of several nutrients were measured in 12 captive wild felid species including caracal (Felis caracal), cheetah (Acinonyx jubatus), cougar (Felis concolor), fishing cat (Felis viverrinus), leopard (Panthera pardus), lion (Panthera leo), ocelot (Felis pardalis), pallas cat (Felis manul), sand cat (Felis margarita), serval (Felis serval), snow leopard (Panthera uncia) and tiger (Panthera tigris). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens and North Carolina Zoological Park). The nutritional composition of the diets at each institution met the probable dietary requirements for each species except for the pallas cat. Blood samples were collected from each animal (n = 69) and analyzed for lipids (total cholesterol, triacylglycerides, HDL cholesterol and LDL cholesterol), vitamin D metabolites [25-hydroxycholecalciferol (25(OH)D) and 1,25-dihydroxycholecalciferol (1,25(OH)(2)D)], vitamin A (retinol, retinyl stearate and retinyl palmitate), vitamin E (alpha- and gamma-tocopherol) and selected carotenoids. Species differences were found for all except triacylglycerides and 1,25(OH)(2)D. Genus differences were found for retinol, retinyl palmitate, retinyl stearate, gamma-tocopherol and beta-carotene. Circulating nutrient concentrations for many of the species in this study have not been reported previously and most have not been compared with the animals' dietary intakes. The large number of animals analyzed provides a substantial base for comparing the serum nutrient concentrations of healthy animals, for both wild and captive exotic species.

HPLC/UV quantitation of retinal, retinol, and retinyl esters in serum and tissues

PubMed Central

Kane, Maureen A.; Folias, Alexandra E.; Napoli, Joseph L.

2008-01-01

We report robust HPLC/UV methods for quantifying retinyl esters (RE), retinol (ROL) and retinal (RAL) applicable to diverse biological samples, with lower limits of detection of 0.7 pmol, 0.2 pmol, and 0.2 pmol, respectively, and linear ranges >3 orders of magnitude. These assays function well with small, complex biological samples (10–20 mg tissue). Coefficients of variation range from: intra-day, 5.9–10.0%; inter-day, 5.9–11.0%. Quantification of endogenous RE, ROL, and RAL in mouse serum and tissues (liver, kidney, adipose, muscle, spleen, testis, skin, brain, and brain regions) reveals utility. Ability to discriminate spatial concentrations of ROL and RE is illustrated with C57BL/6 mouse brain loci (hippocampus, cortex, olfactory bulb, thalamus, cerebellum, and striatum.) We also developed a method to distinguish isomeric forms of ROL to investigate precursors of retinoic acid. The ROL isomer assay has limits of detection between 3.5–4.5 pmol and a similar linear range and % CV as the ROL/RE and RAL assays. The assays described here provide for sensitive and rigorous quantification of endogenous RE, ROL, and RAL to elucidate retinoid homeostasis in disease states, such as Alzheimer’s disease, type 2 diabetes, obesity, and cancer. PMID:18410739

Newborn serum retinoic acid level is associated with variants of genes in the retinol metabolism pathway.

PubMed

Manolescu, Daniel C; El-Kares, Reyhan; Lakhal-Chaieb, Lajmi; Montpetit, Alexandre; Bhat, Pangala V; Goodyer, Paul

2010-06-01

Retinoic acid (RA) is a critical regulator of gene expression during embryonic development. In rodents, moderate maternal vitamin A deficiency leads to subtle morphogenetic defects and inactivation of RA pathway genes causes major disturbances of embryogenesis. In this study, we quantified RA in umbilical cord blood of 145 healthy full-term Caucasian infants from Montreal. Sixty seven percent of values were <10 nmol/L (84 were <0.07 nmol/L) and 33% had moderate or high levels. Variation in RA could not be explained by parallel variation in its precursor, retinol (ROL). However, we found that the (A) allele of the rs12591551 single nucleotide polymorphism (SNP) in the ALDH1A2 gene (ALDH1A2rs12591551(A)), occurring in 19% of newborns, was associated with 2.5-fold higher serum RA levels. ALDH1A2 encodes retinaldehyde dehydrogenase (RALDH) 2, which synthesizes RA in fetal tissues. We also found that homozygosity for the (A) allele of the rs12724719 SNP in the CRABP2 gene (CRABP2rs12724719(A/A)) was associated with 4.4-fold increase in umbilical cord serum RA. CRABP2 facilitates RA binding to its cognate receptor complex and transfer to the nucleus. We hypothesize that individual variation in RA pathway genes may account for subtle variations in RA-dependent human embryogenesis.

Mechanism underlying the suppressor activity of retinoic acid on IL4-induced IgE synthesis and its physiological implication.

PubMed

Seo, Goo-Young; Lee, Jeong-Min; Jang, Young-Saeng; Kang, Seung Goo; Yoon, Sung-Il; Ko, Hyun-Jeong; Lee, Geun-Shik; Park, Seok-Rae; Nagler, Cathryn R; Kim, Pyeung-Hyeun

2017-12-01

The present study extends an earlier report that retinoic acid (RA) down-regulates IgE Ab synthesis in vitro. Here, we show the suppressive activity of RA on IgE production in vivo and its underlying mechanisms. We found that RA down-regulated IgE class switching recombination (CSR) mainly through RA receptor α (RARα). Additionally, RA inhibited histone acetylation of germ-line ε (GL ε) promoter, leading to suppression of IgE CSR. Consistently, serum IgE levels were substantially elevated in vitamin A-deficient (VAD) mice and this was more dramatic in VAD-lecithin:retinol acyltransferase deficient (LRAT -/- ) mice. Further, serum mouse mast cell protease-1 (mMCP-1) level was elevated while frequency of intestinal regulatory T cells (Tregs) were diminished in VAD LRAT -/- mice, reflecting that deprivation of RA leads to allergic immune response. Taken together, our results reveal that RA has an IgE-repressive activity in vivo, which may ameliorate IgE-mediated allergic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin A nutritional status in high- and low-income postpartum women and its effect on colostrum and the requirements of the term newborn.

PubMed

Gurgel, Cristiane Santos Sânzio; Grilo, Evellyn C; Lira, Larissa Q; Assunção, Débora G F; Oliveira, Priscila G; Melo, Larisse R M de; de Medeiros, Silvia V; Pessanha, Luanna C; Dimenstein, Roberto; Lyra, Clélia O

To evaluate the vitamin A status in serum and colostrum of postpartum women with different socioeconomic status, comparing the colostrum retinol supply with the vitamin A requirement of the newborn. Cross-sectional study conducted with 424 postpartum women. Vitamin A maternal dietary intake was estimated using a food frequency questionnaire. Colostrum and serum retinol levels were measured by high performance liquid chromatography (HPLC). Serum retinol concentrations <20μg/dL were indicative of vitamin A deficiency (VAD). Vitamin A levels provided by colostrum <400μgRAE/day were considered as insufficient for term newborns. The mean maternal vitamin A intake during pregnancy was 872.2±639.2μgRAE/day in low-income women and 1169.2±695.2μgRAE/day for high-income women (p<0.005). The prevalence of vitamin A deficiency was 6.9% (n=18) in the low-income group and 3.7% (n=6) in the high-income group. The estimated mean retinol intake by infants of the high- and low-income mothers were 343.3μgRAE/day (85.8% AI) and 427.2μgRAE/day (106.8% AI), respectively. Serum vitamin A deficiency was considered a mild public health problem in both populations; however, newborns of low-income women were more likely to receive lower retinol levels through colostrum when compared with newborns of high-income mothers. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Maintenance therapy with alpha-interferon following first-line VAD in multiple myeloma.

PubMed

Kars, A; Celik, I; Kansu, E; Tekuzman, G; Ozişik, Y; Güler, N; Barişta, I; Güllü, I; Yalçin, S; Altundağ, K; Zengin, N; Türker, A; Hayran, M; Baltali, E; Firat, D

1997-08-01

The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first-line chemotherapy and to determine the efficacy of maintenance alpha-interferon (alpha-IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n=31), and those recruited after 1990 (n=33) were planned to be maintained with alpha-IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow-up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD-only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression-free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD-only group. VAD regimen was well tolerated and IFN-related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.

Serum retinol binding protein 4 in patients with familial partial lipodystrophy.

PubMed

Godoy-Matos, Amélio F; Moreira, Rodrigo O; MacDowell, Renata; Bendet, Izidro; Mory, Patrícia B; Moises, Regina S

2009-07-01

To determine Retinol Binding Protein 4 (RBP4) levels in patients with Familial Partial Lipodystrophy (FPLD). Ten patients with FPLD and a control group (9 patients) were selected to participate in the study. RBP4-log levels were lower in patients with FPLD in comparison to control group (1.52 +/- 0.32 vs 1.84+/-0.25, p=0.029). A statistical trend was observed between Waist-to-Hip Ratio and RBP4-log (r=-0.44, p=0.054). RBP4 levels are decreased in FPLD.

CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients.

PubMed

Skillbäck, Tobias; Delsing, Louise; Synnergren, Jane; Mattsson, Niklas; Janelidze, Shorena; Nägga, Katarina; Kilander, Lena; Hicks, Ryan; Wimo, Anders; Winblad, Bengt; Hansson, Oskar; Blennow, Kaj; Eriksdotter, Maria; Zetterberg, Henrik

2017-11-01

A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic Importance of Vitamins A, E and Retinol-binding Protein 4 in Renal Cell Carcinoma Patients.

PubMed

Sobotka, Roman; Čapoun, Otakar; Kalousová, Marta; Hanuš, Tomáš; Zima, Tomáš; Koštířová, Milada; Soukup, Viktor

2017-07-01

To assess the prognostic importance of serum levels of retinol, retinol-binding protein 4 (RBP4) and vitamin E at the time of diagnosis in patients with renal cell carcinoma (RCC). In this prospective study, in a cohort of 102 renal cell carcinoma patients, relationships between serum levels of the aforementioned markers and recurrence-free survival (RFS), overall survival (OS), as well as cancer-specific survival (CSS), were evaluated. The vitamin A and vitamin E levels were determined by high-performance liquid chromatography (HPLC), while the RBP4 level by enzyme-linked immunosorbent assay (ELISA). The median follow-up period was 39 months. Renal cell carcinoma recurred in 9 patients; 23 patients died with 12 of them from RCC. The preoperative vitamin E level was associated to RFS (p=0.02). We found a significant relationship between OS and the level of RBP4 (p=0.002), retinol (p=0.037) and vitamin E (p=0.007). The CSS period was significantly associated with the level of RBP4 (p=0.0001) and retinol (p=0.0003). Patients with an RBP4 level less than 21.0 mg/l at the time of diagnosis had a 13.5-times higher risk of death due to RCC progression; this risk was up to 7.7-times higher with vitamin A levels under 0.52 mg/l. Low levels of vitamin A, E and RBP4 at the time of RCC diagnosis are associated with a poorer prognosis after surgery. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Analysis and stability of retinol in plasma.

PubMed

Peng, Y M; Xu, M J; Alberts, D S

1987-01-01

A simple, precise, and specific high-performance liquid chromatography (HPLC) method was developed for the simultaneous measurement of retinol (ROH), 13-cis-retinoic acid (13-cRA), and 4-oxo-13-cRA. The average recovery of ROH from serum or plasma was 95%, and the precision of the assay was less than 5%. With this HPLC method, a series of studies was carried out to evaluate the stability of ROH in various matrices. ROH was stable under our HPLC assay conditions as well as in plasma- and in serum-enriched culture media; however, ROH was not stable in aqueous matrices. Serum or heparinized plasma may be routinely used for measurement of ROH concentrations, providing EDTA, oxalate, and citrate are not used as anticoagulants. Because of ROH stability, blood samples can be kept on ice in the dark for at least 24 hours prior to separation of plasma. In addition, plasma samples containing ROH can be stored for up to 1 year at -20 degrees C without loss of stability.

The relative dose response test based on retinol-binding protein 4 is not suitable to assess vitamin A status in very low birth weight infants.

PubMed

Schmiedchen, Bettina; Longardt, Ann Carolin; Bührer, Christoph; Raila, Jens; Loui, Andrea; Schweigert, Florian J

2014-01-01

The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants. © 2013 S. Karger AG, Basel.

Both HIV-infected and HIV-exposed uninfected children living in Brazil, Argentina and Mexico have similar rates of low concentrations of retinol, β-carotene and vitamin E

PubMed Central

Monteiro, Jacqueline P.; Freimanis-Hance, Laura; Faria, Lidiane B.; Mussi-Pinhata, Marisa M; Korelitz, James; Vannucchi, Hélio; Queiroz, Wladimir; Succi, Regina CM; Hazra, Rohan

2009-01-01

Our objective was to describe the prevalence of low concentrations of retinol, β-carotene, and vitamin E in a group of HIV-infected Latin American children and a comparison group of HIV-exposed, uninfected children. Our hypothesis was that the rates of low concentrations of these micronutrients would be higher in the HIV-infected group than those in the HIV-exposed, uninfected group. This was a cross-sectional substudy of a larger cohort study at clinical pediatric HIV centers in Latin America. Serum levels of micronutrients were measured in the first stored sample obtained after each child’s first birthday by high-performance liquid chromatography. Low concentrations of retinol, β-carotene and vitamin E were defined as serum levels below 0.70 μmol/L, 0.35 μmol/L and 18.0 μmol/L, respectively. The population for this analysis was 336 children (124 HIV-infected, 212 HIV-exposed, uninfected) aged ≥ 1 to < 4 years of age. Rates of low concentrations were 74% for retinol, 27% for β-carotene, and 89% for vitamin E. These rates were not affected by HIV status. Among the HIV-infected children those treated with antiretrovirals were less likely to have retinol deficiency, but no other HIV-related factors correlated with micronutrient low serum levels. Low concentrations of retinol, β-carotene and vitamin E are very common in children exposed to HIV living in Brazil, Argentina and Mexico, regardless of HIV-infection status. PMID:19917451

Improvement of anthropometric and biochemical, but not of vitamin A, status in adolescents who undergo Roux-en-Y gastric bypass: a 1-year follow up study.

PubMed

Silva, Jacqueline Souza; Chaves, Gabriela Villaça; Stenzel, Ana Paula; Pereira, Silvia Elaine; Saboya, Carlos José; Ramalho, Andréa

2017-02-01

The aim of this study was to describe anthropometric, biochemical, co-morbidity, and vitamin A nutritional status in severely obese adolescents before and 30, 180, and 365 days after Roux-en-Y gastric bypass (RYGB). Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Sixty-four adolescents (15-19 years old) with a body mass index≥40 kg/m 2 were enrolled in a prospective follow-up study. Vitamin A status was evaluated before surgery (T0), and 30 (T30), 180 (T180), and 365 (T365) days after surgery, applying biochemical and functional indicators. Anthropometric measures, lipid profile, glycemia, and basal insulin also were assessed. No patients were lost during follow-up. Before surgery, 26.6% of the sample group experienced vitamin A deficiency (VAD). Serum retinol levels dropped significantly 30 days after surgery and then returned to basal levels. There was a significant increase in the prevalence of β-carotene deficiency and night blindness throughout the postsurgery period. A significant reduction in blood glucose, insulin resistance, lipid profile, and anthropometric parameters was observed. The finding that oral daily supplementation with 5000 IU retinol acetate failed to reverse VAD and night blindness after RYGB is highly significant. We recommend assessment of VAD and night blindness in extremely obese adolescents before and after RYGB. We further recommend monitoring for an additional 180 days (for VAD) and 365 days (for night blindness) after surgery, with particular attention to daily supplementation needs. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

PubMed

Quinlan, Patrick; Horvath, Alexandra; Nordlund, Arto; Wallin, Anders; Svensson, Johan

2017-12-01

Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.

PubMed

Shirai, Tomomi; Shichi, Yuta; Sato, Miyuki; Tanioka, Yuri; Furusho, Tadasu; Ota, Toru; Tadokoro, Tadahiro; Suzuki, Tsukasa; Kobayashi, Ken-Ichi; Yamamoto, Yuji

2016-03-01

Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P < .01). In contrast, the renal retinol concentrations of GK rats increased by 70% (P < .01). However, expression of RARβ in the kidney, which was induced in a retinoic acid-dependent manner, was downregulated by 90% (P < .01) in GK rats. In conclusion, diabetes and obesity affected retinol metabolism differently, and the effects were different in different peripheral tissues. The impact of HFD may be limited to the storage of hepatic vitamin A as retinyl palmitate. In particular, our data indicate that renal retinoic acid production might represent an important target for the treatment of type 2 diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of VaD and AD prodromes: the Cache County Study.

PubMed

Hayden, K M; Warren, L H; Pieper, C F; Østbye, T; Tschanz, J T; Norton, M C; Breitner, J C S; Welsh-Bohmer, K A

2005-07-01

It is unclear whether vascular dementia (VaD) has a cognitive prodrome, akin to the mild cognitive impairment (MCI) prodrome to Alzheimer's dementia (AD). To evaluate whether VaD has a cognitive prodrome, and if it can be differentiated from prodromal AD, we examined neuropsychological test performance of participants in a nested case-control study within a population-based cohort aged 65 or older. Participants (n = 485) were identified from the Cache County Study, a large population-based study of aging and dementia. After an average of 3 years of follow-up, a total of 62 incident dementia cases were identified (14 VaD, 48 AD). We identified a number of neuropsychological tests (executive and memory) that discriminated between diagnosed VaD and AD cases. Multivariate analyses sought to differentiate between these same groups 3 years before clinical diagnosis. The Consortium to Establish a Registry for Alzheimer's Disease Word List Recognition Test correct recognition of foils (mean difference, 1.25; 95% confidence interval [CI], 0.42 to 2.07; p < 0.01), Logical Memory I (mean difference, 7.16; 95% CI, 0.78 to 13.55, p < 0.05), Logical Memory II delayed recall (mean difference, 8.67; 95% CI, 1.59 to 15.74, p < 0.05), and percent savings (mean difference, 51.07; 95% CI, 32.58 to 69.56, p < 0.0001) differentiated VaD from AD cases after adjustment for age, sex, education, and dementia severity. Three years before dementia diagnosis, word list recognition ("no" responses mean difference, 1.40; 95% CI, 0.64 to 2.17; p < 0.001, and "yes" responses mean difference, -1.14; 95% CI, -2.14 to -0.13; p < 0.03) discriminated between prodromal VaD and AD. These results suggest that VaD has a prodromal syndrome, the cognitive features of which are distinguishable from the cognitive prodrome of AD.

Photolysis of retinol in liposomes and its protection with tocopherol and oxybenzone.

PubMed

Young, A M; Gregoriadis, G

1996-03-01

In this work the stabilities of retinol in methanolic solutions and liposomal suspensions exposed to UV light were compared using absorbance spectroscopy and the ability of alpha-tocopherol and the sunscreen additive, oxybenzone, to reduce the rate of retinol decomposition assessed. Retinol in methanol decolorized almost completely within a few minutes of exposure to a 6 W 350 nm wavelength lamp. From the concentration dependence of the reaction rates it appears that retinol activated by light can decomposed either directly or after collision with a second retinol molecule. Several reaction products are formed. alpha-Tocopherol solutions were unaffected by 350 nm light but they did darken when irradiated with 250 nm wavelength light. Addition of alpha-tocopherol or removal of oxygen from the retinol in methanol solutions reduced only slightly the rates of retinol photolysis. When dispersed in water within liposomes made of equimolar egg phosphatidylcholine (PC) and cholesterol, up to six-fold increases in the decomposition rate of the retinol were observed. The reaction rate could be reduced but only slightly by increasing the ratio of PC to retinol. A mechanism that explains the concentration dependence of the retinol photolysis is that the reduction in reaction rate on diluting the retinol concentration within a given liposome was due to the prevention of the reaction between one light-activated retinol molecule with another within the same liposome. Incorporation of oxybenzone into the liposomes reduced the reaction rates. The results suggested that most of the protection in this case arises through the oxybenzone closet to the light source absorbing the light, thereby preventing it reaching retinol much further into the sample. Incorporation of alpha-tocopherol into the liposomes could also reduce substantially the photolysis rate of co-entrapped retinol. The mechanism of protection in this case appears to be via the tocopherol quenching activated retinol

Expression of Serum Retinol Binding Protein and Transthyretin within Mouse Gastric Ghrelin Cells

PubMed Central

Walker, Angela K.; Gong, Zhi; Park, Won-Mee

2013-01-01

Ghrelin is an orexigenic peptide hormone produced mainly by a distinct group of dispersed endocrine cells located within the gastric oxyntic mucosa. Besides secreted gene products derived from the preproghrelin gene, which include acyl-ghrelin, desacyl-ghrelin and obestatin, ghrelin cells also synthesize the secreted protein nesfatin-1. The main goal of the current study was to identify other proteins secreted from ghrelin cells. An initial gene chip screen using mRNAs derived from highly enriched pools of mouse gastric ghrelin cells demonstrated high levels of serum retinol-binding protein (RBP4) and transthyretin (TTR), both of which are known to circulate in the bloodstream bound to each other. This high expression was confirmed by quantitative RT-PCR using as template mRNA derived from the enriched gastric ghrelin cell pools and from two ghrelin-producing cell lines (SG-1 and PG-1). RBP4 protein also was shown to be secreted into the culture medium of ghrelin cell lines. Neither acute nor chronic caloric restriction had a significant effect on RBP4 mRNA levels within stomachs of C57BL/6J mice, although both manipulations significantly decreased stomach TTR mRNA levels. In vitro studies using PG-1 cells showed no effect on RBP4 release of octanoic acid, epinephrine or norepinephrine, all of which are known to act directly on ghrelin cells to stimulate ghrelin secretion. These data provide new insights into ghrelin cell physiology, and given the known functions of RBP4 and TTR, support an emerging role for the ghrelin cell in blood glucose handling and metabolism. PMID:23840311

Elevated Serum Triglyceride and Retinol-Binding Protein 4 Levels Associated with Fructose-Sweetened Beverages in Adolescents

PubMed Central

Chan, Te-Fu; Lin, Wei-Ting; Chen, Yi-Ling; Huang, Hsiao-Ling; Yang, Wei-Zeng; Lee, Chun-Ying; Chen, Meng-Hsueh; Wang, Tsu-Nai; Huang, Meng-Chuan; Chiu, Yu-Wen; Huang, Chun-Chi; Tsai, Sharon; Lin, Chih-Lung; Lee, Chien-Hung

2014-01-01

Background The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. Objectives This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. Methods We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r = 0.253 to 0.404), but not among non-drinkers. Conclusions High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4. PMID:24475021

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Retinol-binding protein immunological test system...

PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity.

PubMed

Mondul, Alison; Mancina, Rosellina M; Merlo, Andrea; Dongiovanni, Paola; Rametta, Raffaela; Montalcini, Tiziana; Valenti, Luca; Albanes, Demetrius; Romeo, Stefano

2015-08-01

Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2)) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations. © 2015 American Society for Nutrition.

Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines.

PubMed

Guo, X; Ruiz, A; Rando, R R; Bok, D; Gudas, L J

2000-11-01

When exogenous [(3)H]retinol (vitamin A) was added to culture medium, normal human epithelial cells from the oral cavity, skin, lung and breast took up and esterified essentially all of the [(3)H]retinol within a few hours. As shown by [(3)H]retinol pulse-chase experiments, normal epithelial cells then slowly hydrolyzed the [(3)H]retinyl esters to [(3)H]retinol, some of which was then oxidized to [(3)H]retinoic acid (RA) over a period of several days. In contrast, cultured normal human fibroblasts and human umbilical vein endothelial cells (HUVEC) did not esterify significant amounts of [(3)H]retinol; this lack of [(3)H]retinol esterification was correlated with a lack of expression of lecithin:retinol acyltransferase (LRAT) transcripts in normal fibroblast and HUVEC strains. These results indicate that normal, differentiated cell types differ in their ability to esterify retinol. Human carcinoma cells (neoplastically transformed epithelial cells) of the oral cavity, skin and breast did not esterify much [(3)H]retinol and showed greatly reduced LRAT expression. Transcripts of the neutral, bile salt-independent retinyl ester hydrolase and the bile salt-dependent retinyl ester hydrolase were undetectable in all of the normal cell types, including the epithelial cells. These experiments suggest that retinoid-deficiency in the tumor cells could develop because of the lack of retinyl esters, a storage form of retinol.

Ultra-Performance Liquid Chromatographic Determination of Tocopherols and Retinol in Human Plasma

PubMed Central

Bell, Edward C.; John, Mathew; Hughes, Rodney J.; Pham, Thu

2014-01-01

A rapid, selective and sensitive ultra-performance liquid chromatography method has been developed for the detection and quantification of tocopherols and retinol in human plasma. Alpha-tocopherol, gamma-tocopherol and retinol are assayed using fluorescence detection. Excitation/emission wavelengths are 295/330 nm and 325/470 nm for the analysis of both tocopherols and retinol, respectively. Retinol acetate is employed as the internal standard. The reversed-phase method incorporates gradient elution with a mobile phase consisting of methanol and acetonitrile. Separation of vitamin compounds is achieved using a bridged ethyl hybrid C18 column. The retention times for retinol, retinol acetate, gamma-tocopherol and alpha-tocopherol are 1.6, 1.8, 3.9 and 4.3 min, respectively. The limits of quantification for retinol, gamma-tocopherol and alpha-tocopherol were 0.02, 0.02 and 0.1 µg/mL, respectively. The assay method is suitable for the analysis of tocopherols and retinol in human plasma. The method may be applied following the ingestion of foods fortified with these fat-soluble vitamins. PMID:24170122

Association of Serum Retinol-Binding Protein 4 Concentration With Risk for and Prognosis of Amyotrophic Lateral Sclerosis.

PubMed

Rosenbohm, Angela; Nagel, Gabriele; Peter, Raphael S; Brehme, Torben; Koenig, Wolfgang; Dupuis, Luc; Rothenbacher, Dietrich; Ludolph, Albert C

2018-05-01

Knowledge about the metabolic states of patients with amyotrophic lateral sclerosis (ALS) may provide a therapeutic approach. To investigate the association between the onset and prognosis of ALS and serum retinol-binding protein 4 (RBP4) concentration as a biomarker for insulin resistance and vitamin A metabolism. Case-control design for risk factors of ALS; cohort design for prognostic factors within ALS cases. Between October 1, 2010, and June 30, 2014, a population-based case-control study with randomly selected controls was established based on the ALS Registry Swabia in southern Germany, with a target population of 8.4 million inhabitants. Response rates were 64.8% among the cases and 18.7% among the controls. The dates of analysis were April 2016 to May 2017. Serum samples were measured for RBP4. Information on covariates was assessed by an interview-based standardized questionnaire. Main outcomes and measures were adjusted odds ratios for risk of ALS associated with serum RBP4 concentration, as well as time to death associated with RBP4 concentration at baseline in ALS cases only. Conditional logistic regression was applied to calculate multivariable odds ratios for risk of ALS. Survival models were used in cases only to appraise their prognostic value. Data from 289 patients with ALS (mean [SD] age, 65.7 [10.5] years; 172 [59.5%] male) and 504 controls (mean [SD] age, 66.3 [9.8] years; 299 [59.3%] male) were included in the case-control study. Compared with controls, ALS cases were characterized by lower body mass index, less educational attainment, smoking, light occupational work intensity, and self-reported diabetes. The median serum RBP4 concentration was lower in ALS cases than in controls (54.0 vs 59.5 mg/L). In the multivariable model, increasing RBP4 concentration was associated with reduced odds for ALS (top vs bottom quartile odds ratio, 0.36; 95% CI, 0.22-0.59; P for trend <.001), which persisted after further adjustment for renal function and

Comparative study of the nutritional status of vitamin A in pregnant women and in women who became pregnant or did not after Roux-en-Y gastric bypass.

PubMed

Cruz, Sabrina; Machado, Suzana; Cruz, Suelem; Pereira, Sílvia; Saboya, Carlos; Ramalho, Andréa

2018-01-18

the changes in digestive physiology after Roux-en-Y gastric bypass (RYGB), as well as pregnancy, maximizes the risk of vitamin A deficiency (VAD) and both can result in harm to the mother and child health. to compare the nutritional status of vitamin A among women who became pregnant or did not after RYGB and in pregnant women who did not undergo surgery, and to assess the impact of VAD on the mother and child health. this is a cross-sectional study of the analytical type. The women were divided into: group 1 (G1) with 80 pregnant women; group 2 (G2) with 40 pregnant women who had previously undergone RYGB, both in their third trimester of pregnancy; and group 3 (G3) with 77 non-pregnant women who had previously undergone RYGB. Serum concentrations of retinol and β-carotene, night blindness (NB), gestational and neonatal intercurrences were investigated. The significance level adopted was p < 0.05. RYGB, per se,had a greater impact on the inadequacy of retinol, β-carotene, and on the increased percentage of NB when compared to non-surgical pregnant women. When surgery was associated with pregnancy, more than 75% of inadequacy of retinol and β-carotene was noted, as well as a higher percentage of individuals with NB. G2 also showed increased prevalence ratio for developing gestational and neonatal intercurrences, when compared to G1. RYGB provides greater negative impact on the nutritional status of vitamin A compared to pregnancy, and surgery associated with pregnancy can create even greater risks.

Ultra-performance liquid chromatographic determination of tocopherols and retinol in human plasma.

PubMed

Bell, Edward C; John, Mathew; Hughes, Rodney J; Pham, Thu

2014-10-01

A rapid, selective and sensitive ultra-performance liquid chromatography method has been developed for the detection and quantification of tocopherols and retinol in human plasma. Alpha-tocopherol, gamma-tocopherol and retinol are assayed using fluorescence detection. Excitation/emission wavelengths are 295/330 nm and 325/470 nm for the analysis of both tocopherols and retinol, respectively. Retinol acetate is employed as the internal standard. The reversed-phase method incorporates gradient elution with a mobile phase consisting of methanol and acetonitrile. Separation of vitamin compounds is achieved using a bridged ethyl hybrid C18 column. The retention times for retinol, retinol acetate, gamma-tocopherol and alpha-tocopherol are 1.6, 1.8, 3.9 and 4.3 min, respectively. The limits of quantification for retinol, gamma-tocopherol and alpha-tocopherol were 0.02, 0.02 and 0.1 µg/mL, respectively. The assay method is suitable for the analysis of tocopherols and retinol in human plasma. The method may be applied following the ingestion of foods fortified with these fat-soluble vitamins. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial.

PubMed

Baldwin, J Timothy; Mann, Douglas L

2010-11-01

Ventricular assist devices (VADs) are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent ("destination") therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, a National Heart, Lung, and Blood Institute (NHLBI) working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group's recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail, which will serve to test the hypothesis and inform the pivotal trial. Published by Elsevier Inc.

A non-retinoid antagonist of Retinol-Binding Protein 4 rescues phenotype in a model of Stargardt disease without inhibiting the visual cycle.

PubMed

Racz, Boglarka; Varadi, Andras; Kong, Jian; Allikmets, Rando; Pearson, Paul G; Johnson, Graham; Cioffi, Christopher L; Petrukhin, Konstantin

2018-06-05

A primary pathological defect in the heritable eye disorder Stargardt disease is excessive accumulation of cytotoxic lipofuscin bisretinoids in the retina. Age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) matches the age-dependent increase in the incidence of the atrophic (dry) form of age-related macular degeneration (AMD) and therefore may be one of several pathogenic factors contributing to AMD progression. Lipofuscin bisretinoid synthesis in the retina depends on the influx of serum retinol from the circulation into the RPE. Formation of the tertiary retinol-binding protein 4 (RBP4)-transthyretin-retinol complex in the serum is required for this influx. Herein, we report the pharmacological effects of the non-retinoid RBP4 antagonist, BPN-14136. BPN-14136 dosing in the Abca4-/- mouse model of increased lipofuscinogenesis significantly reduced serum RBP4 levels and inhibited bisretinoid synthesis, and this inhibition correlated with a partial reduction in visual cycle retinoids such as retinaldehydes serving as bisretinoid precursors. BPN-14136 administration at doses inducing maximal serum RBP4 reduction did not produce changes in the rate of the visual cycle, consistent with minimal changes in dark adaptation. Abca4-/- mice exhibited dysregulation of the complement system in the retina, and BPN-14136 administration normalized the retinal levels of proinflammatory complement cascade components such as complement factors D and H, C-reactive protein, and C3. We conclude that BPN-14136 has several beneficial characteristics, combining inhibition of bisretinoid synthesis and reduction in retinaldehydes with normalization of the retinal complement system. BPN-14136, or a similar compound, may be a promising drug candidate to manage Stargardt disease and dry AMD. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of routine prenatal supplementation on vitamin concentrations in maternal serum and breast milk.

PubMed

Sânzio Gurgel, Cristiane Santos; Alves de Araújo Pereira, Larisa; de Assis Costa, Aldiane; Adja da Silva Souza, Mayara; Araújo de Brito, Poliana; Miranda de Melo, Larisse Rayanne; Dimenstein, Roberto

2017-01-01

The aim of the present study was to assess the effect of multivitamin supplements and their different vitamin A sources on retinol concentrations in serum and colostrum milk of postpartum women. This was a retrospective cross-sectional study composed of healthy postpartum women attending two Brazilian private maternity wards (N = 100). According to the type of multivitamin taken during pregnancy, the women were assigned to one of four groups: control group (CG; n = 25), formulation 1 (F1; n = 25), formulation 2 (F2; n = 25), and formulation 3 (F3; n = 25). Blood and colostrum samples were collected under fasting conditions and retinol was analyzed by high-performance liquid chromatography. Dietary vitamin A was assessed using a food frequency questionnaire. Retinol concentrations <20 μg/dL (<0.70 μmol/L) in serum and <60 μg/dL (2.10 μmol/L) in colostrum were considered indicative of vitamin A deficiency. Of women in the control group, 12% (n = 3) presented serum retinol levels below the cut-off value for adequacy; this was not observed in the supplemented groups. Evaluating the retinol content in breast milk, supplemented groups F1 and F3 presented 4% (n = 1) of inadequacy cases, whereas F2 presented 40% (n = 10). The concentrations found in the F2 and F3 groups were statistically different (P < 0.05). The use of multivitamin supplements containing vitamin A during pregnancy prevents vitamin A deficiency regardless of the source administered. In breast milk, supplementation with β-carotene provided a lower concentration of vitamin A compared with retinol. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin.

PubMed

Rollman, O; Vahlquist, A

1986-04-01

The disposition of oral isotretinoin to the skin and the effects of the drug on the vitamin A levels in serum and skin were studied in 17 patients with nodulocystic acne. All patients received 0.5 mg/kg/day for 3 months and 8 patients continued treatment with 0.75 mg/kg/day for another 3 months. The parent drug, the major metabolite (4-oxo-isotretinoin), and 2 natural retinoids (retinol and dehydroretinol) were monitored in serum and biopsies of uninvolved skin, using adsorption high-pressure liquid chromatography. During the initial 3 months of treatment the mean isotretinoin level in the serum was 145 ng/ml and in the epidermis 73 ng/g. The corresponding values for 4-oxo-isotretinoin were 615 and 113 ng/g, respectively. Even at the highest dosage there was no progressive accumulation of isotretinoin in serum, epidermis, or subcutis. After discontinuation of therapy the drug disappeared from both serum and skin within 2-4 weeks. The serum transport of vitamin A, monitored by the concentrations of retinol, retinol-binding protein, and prealbumin (transthyretin), was not affected by the treatment. By contrast, the retinol level in the epidermis increased by an average of 53% (p less than 0.01) and the dehydroretinol level decreased by 79% (p less than 0.001) as a result of 3 months of treatment. Both changes were reversible. The results suggest that isotretinoin therapy interferes with the endogenous vitamin A metabolism in the skin.

Efficacy validation of synthesized retinol derivatives In vitro: stability, toxicity, and activity.

PubMed

Han, Hye-Sook; Kwon, Youn-Ja; Park, Myoung-Soon; Park, Si-Ho; Cho, So-Mi Kim; Rho, Young-Soy; Kim, Jin-Wou; Sin, Hong-Sig; Um, Soo-Jong

2003-08-15

Retinol (vitamin A) is used as an antiwrinkle agent in the cosmetics industry. However, its photo-instability makes it unsuitable for use in general cosmetic formulations. To improve the photo-stability of retinol, three derivatives (3, 4, and 5) were synthesized and their biological activities were analyzed. 1H NMR and HPLC analysis indicated that derivatives 3 and 5 were much more stable than retinol under our sunlight exposure conditions. When human adult fibroblasts were treated, the IC(50) of derivative 3 was 96 microM, which is similar to that of retinol, as determined by the MTT assay. Derivatives 4 and 5 were 2.5 and 8 times more toxic than retinol, respectively. At 1 microM treatment, like retinol, derivatives 3 and 4 were specifically active for RARalpha out of six retinoid receptors (RAR/RXRalpha, beta, gamma). Dose-dependent analysis confirmed that derivative 4 was as active as retinol and the other two derivatives were less active for RARalpha. The effect of our derivatives on the expression of collagenase, an indicator of wrinkle formation, was measured using the transient co-expression of c-Jun and RT-PCR in HaCaT cells. Collagenase promoter activity, which is increased by c-Jun expression, was reduced 42% by retinol treatment. The other derivatives inhibited collagenase promoter activity similarly. These results were further confirmed by RT-PCR analysis of the collagenase gene. Taken together, our results suggest that retinol derivative 3 is a promising antiwrinkle agent based on its higher photo-stability, lower RARalpha activity (possibly indicating reduced side effects), and similar effect on collagenase expression.

NHLBI’s Program for VAD Therapy for Moderately Advanced Heart Failure: The REVIVE-IT Pilot Trial

PubMed Central

Baldwin, J. Timothy; Mann, Douglas L.

2010-01-01

Background VADs are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent (“destination”) therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, an NHLBI working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Discussion and Recommendations Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group’s recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail which will serve to test the hypothesis and inform the pivotal trial. PMID:21055648

Terminal-group oxidation of retinol by mouse epidermis. Inhibition in vitro and in vivo.

PubMed Central

Connor, M J; Smit, M H

1987-01-01

Locally applied retinol is metabolized to retinoic acid in mouse epidermis in vivo. To characterize the oxidation system we investigated the ability of soluble extracts of hairless-mouse epidermis to convert retinol and retinal into retinoic acid. The extracts oxidized retinol to retinoic acid in two steps catalysed by two NAD+-dependent enzymes that were resolved on h.p.l.c. The first enzyme catalyses the reversible oxidation of retinol to retinal and is an alcohol dehydrogenase isoenzyme. The second enzyme oxidizes retinal to retinoic acid. Retinol oxidation by epidermal extracts was inhibited by the alcohol dehydrogenase inhibitor 4-methylpyrazole and by the polyene citral. The toxicity and relatively low potency at inhibiting the epidermal alcohol dehydrogenase isoenzyme curtailed the use of 4-methylpyrazole in vivo. However, citral significantly inhibited retinoic acid formation from retinol in the epidermis in vivo. The ability to inhibit the oxidation of retinol to retinoic acid in mouse epidermis provides a potential method to resolve the roles of retinol and retinoic acid in epithelial function. PMID:3663136

zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function

PubMed Central

Herzog, Christian; Yang, Cheng; Holmes, Alexandrea

2012-01-01

Cisplatin injury to renal tubular epithelial cells (RTEC) is accompanied by autophagy and caspase activation. However, autophagy gradually decreases during the course of cisplatin injury. The role of autophagy and the mechanism of its decrease during cisplatin injury are not well understood. This study demonstrated that autophagy proteins beclin-1, Atg5, and Atg12 were cleaved and degraded during the course of cisplatin injury in RTEC and the kidney. zVAD-fmk, a widely used pancaspase inhibitor, blocked cleavage of autophagy proteins suggesting that zVAD-fmk would promote the autophagy pathway. Unexpectedly, zVAD-fmk blocked clearance of the autophagosomal cargo, indicating lysosomal dysfunction. zVAD-fmk markedly inhibited cisplatin-induced lysosomal cathepsin B and calpain activities and therefore impaired autophagic flux. In a mouse model of cisplatin nephrotoxicity, zVAD-fmk impaired autophagic flux by blocking autophagosomal clearance as revealed by accumulation of key autophagic substrates p62 and LC3-II. Furthermore, zVAD-fmk worsened cisplatin-induced renal dysfunction. Chloroquine, a lysomotropic agent that is known to impair autophagic flux, also exacerbated cisplatin-induced decline in renal function. These findings demonstrate that impaired autophagic flux induced by zVAD-fmk or a lysomotropic agent worsened renal function in cisplatin acute kidney injury (AKI) and support a protective role of autophagy in AKI. These studies also highlight that the widely used antiapoptotic agent zVAD-fmk may be contraindicated as a therapeutic agent for preserving renal function in AKI. PMID:22896037

[Prevalence of vitamin a deficiency and anemia in children under five years of age in Peru].

PubMed

Pajuelo, Jaime; Miranda, Marianella; Zamora, Rosa

2015-01-01

To determine the prevalence of vitamin A deficiency (VAD) and nutritional anemia (NA) in children under five in Peru. Cross-sectional study with a stratified and multi-staged probabilistic sample conducted between November 2007 and April 2010.2,736 children were included for NA and 1,465 children for VAD. NA was defined as Hb<11 g/dL.VAD was identified by serum retinol levels <20 µg/dL. Sociodemographic variables related to the child and the mother were studied in addition to their participation in growth control and development programs, integrated nutrition program and supplementation with iron and vitamin A. Analysis of complex samples was performed, descriptive statistics and logistic regression with 95% confidence intervals and a significance level of p<0.05 were calculated. The prevalence of VAD was 11.7% (95% CI: 9.4 to 14.4). The highest prevalences were in children under five months (44.6%) and those living in rural areas (19.5%). The prevalence of NA was 33% (95% CI: 29.9 to 36.1) and was higher in children under 11 months (68.2%) and children of mothers aged 13-19 years old (55.4 %). VAD is a public health problem that remains, with the most affected children living in rural areas and in the jungle. The prevalence of NA shows a slight improvement. It is necessary to improve the efficiency and impact of programs that include supplementation of vitamin A and iron.

Alterations in chemically induced tissue injury related to all-trans-retinol pretreatment in rodents.

PubMed

Sauer, J M; Hooser, S B; Badger, D A; Baines, A; Sipes, I G

1995-01-01

Retinol (vitamin A) is an essential nutrient which has many physiological effects throughout the body. Our studies have demonstrated that retinol modulation of immune response, through alteration of macrophage and neutrophil function, can have dramatic effects on the toxicity of some compounds. Based on these studies, our current hypothesis for retinol potentiation of chemical-induced liver injury is that retinol administered to rats prior to the hepatotoxicant (CCl4 and AA in rats; and AA, APAP, and GalN in mice) primes the Kupffer cells to a more active state. This may occur in part as a result of increases in chemical mediators such as TNF from these Kupffer cells. Following hepatocyte damage by a toxicant, Kupffer cells are activated to release reactive oxygen species, immune mediators, and chemotactic factors which all serve to enhance the inflammatory response. This increased inflammatory response then results in increased injury to the already toxicant-damaged hepatocytes. In addition, retinol modulation of toxicant activation and detoxification may also make important contributions to the potentiation of some toxicants such as AA. Retinol protection of CCl4 hepatotoxicity in mice is more difficult to explain at this time but is possibly related to alterations in CCl4 metabolism in this species. Differences in response between pulmonary and liver macrophages (Kupffer cells) may explain the retinol protection from 1-NN pulmonary toxicity. Retinol may decrease the inflammatory response through downregulation of pulmonary macrophage function, thus resulting in decreased pulmonary injury. Finally, since retinol protection of cadmium toxicity in the liver and testis requires 7 days of retinol pretreatment, we suspect that retinol is inducing protective protein(s) in these organs. Aside from its normal biological role in rhe body, clinical medicine has found new uses for retinol in the treatment and prevention of some cancers, and in the treatment of certain

Soil-Transmitted Helminthiasis and Vitamin A Deficiency: Two Problems, One Policy.

PubMed

Strunz, Eric C; Suchdev, Parminder S; Addiss, David G

2016-01-01

Vitamin A deficiency (VAD) and soil-transmitted helminthiasis (STH) represent two widely prevalent and often overlapping global health problems. Approximately 75% of countries with moderate or severe VAD are coendemic for STH. We reviewed the literature on the complex relationship between STH and VAD. Treatment for STH significantly increases provitamin A (e.g., β-carotene) levels but is associated with minimal increases in preformed vitamin A (retinol). Interpretation of the data is complicated by variations in STH infection intensity and limitations of vitamin A biomarkers. Despite these challenges, increased coordination of STH and VAD interventions represents an important public health opportunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intestinal absorption of retinol and retinyl palmitate in the rat. Effects of tetrahydrolipstatin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandez, E.; Borgstroem, B.

1990-09-01

The aim of the present study was to characterize the intestinal absorption of retinol and retinyl palmitate in thoracic duct and bile duct fistulated rats and to investigate the effect of a simultaneously administered lipase inhibitor, tetrahydrolipstatin (THL). Absorption was determined as lymphatic recovery over a 24-hr period, including an initial 12-hr continuous intraduodenal infusion of either (11,12-3H)retinol or (11,12-3H)retinyl palmitate given in emulsified glyceryl trioleate or in mixed micellar solution of monoolein and oleic acid. From micellar dispersion, labeled retinol and retinyl palmitate were recovered in the lymph to 50-60% and both to the same extent. Administered in emulsifiedmore » form, labeled retinol from fed retinyl palmitate was recovered to 47%, but retinol from fed retinol to only 18%. THL (10(-4) M) in the infusate had no significant effect on the recovery of 14C-labeled oleic acid. The recovery of label from emulsified glyceryl tri(1-14C)oleate was significantly decreased at this concentration of THL (76.5% vs 19.6% recovery). When administered in emulsified form, retinol absorption was not significantly affected by THL at 10(-4) M, while retinyl palmitate absorption was very significantly decreased (5.0% compared to 47.8%). In the presence of THL, retinol absorption from retinyl palmitate in micellar solution was decreased (from 58% to 17%). Most of the retinol in the lymph extracts (72.2 to 91.3) was present as retinyl ester, regardless of the chemical and physical form of administration. Furthermore, THL did not induce any change in this pattern.« less

Effects on vitamin A deficiency in children of periodic high-dose supplements and of fortified oil promotion in a deficient area of the Philippines.

PubMed

Mason, John B; Ramirez, Maria A; Fernandez, Chona M; Pedro, Regina; Lloren, Tina; Saldanha, Lisa; Deitchler, Megan; Eisele, T

2011-09-01

Regular semi-annual distribution of high-dose (200,000 IU) vitamin A capsules (VACs) to children 1 - 5 years of age (previously identified as underweight), in Leyte Province, the Philippines, was compared to providing extra VACs to give three-monthly dosing, and to vitamin A-fortified cooking oil (VAFO) promotion (with continued VACs every 6 months). Serum retinol (SR) was measured at baseline and after 12 or 18 months (for VAFO). No sustained increase in SR was determined from the three-month VAC dosing regimen, and the prevalence of vitamin A deficiency (VAD) as assessed by SR (< 20 mcg / dL) remained around 30 % (in line with national survey estimates over the previous 15 years). The major difference found was that 18 months of VAFO (of which 9 months had sustained promotion) was associated with reducing the prevalence of VAD to < 10 %. The effective fortification and lack of effect of semi-annual VAC results are in line with previous studies; testing with dosing of VAC every three months is a new intervention. The results imply that promotion of fortified oil would reduce VAD in these conditions; whether it can replace or needs to be added to semi-annual VAC dosing remains to be determined. A phased changeover to reliance on fortified commodities (including oil) with careful monitoring of VAD trends is indicated.

Aptamer-Conjugated Calcium Phosphate Nanoparticles for Reducing Diabetes Risk via Retinol Binding Protein 4 Inhibition.

PubMed

Torabi, Raheleh; Ghourchian, Hedayatollah; Amanlou, Massoud; Pasalar, Parvin

2017-06-01

Inhibition of the binding of retinol to its carrier, retinol binding protein 4, is a new strategy for treating type 2 diabetes; for this purpose, we have provided an aptamer-functionalized multishell calcium phosphate nanoparticle. First, calcium phosphate nanoparticles were synthesized and conjugated to the aptamer. The cytotoxicity of nanoparticles releases the process of aptamer from nanoparticles and their inhibition function of binding retinol to retinol binding protein 4. After synthesizing and characterizing the multishell calcium phosphate nanoparticles and observing the noncytotoxicity of conjugate, the optimum time (48 hours) and the pH (7.4) for releasing the aptamer from the nanoparticles was determined. The half-maximum inhibitory concentration (IC 50 ) value for inhibition of retinol binding to retinol binding protein 4 was 210 femtomolar (fmol). The results revealed that the aptamer could prevent connection between retinol and retinol binding protein 4 at a very low IC 50 value (210 fmol) compared to other reported inhibitors. It seems that this aptamer could be used as an efficient candidate not only for decreasing the insulin resistance in type 2 diabetes, but also for inhibiting the other retinol binding protein 4-related diseases. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

The inhibition of human T cell proliferation by the caspase inhibitor z-VAD-FMK is mediated through oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajah, T.; Chow, S.C., E-mail: chow.sek.chuen@monash.edu

2014-07-15

The caspase inhibitor benzyloxycarbony (Cbz)-L-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) has recently been shown to inhibit T cell proliferation without blocking caspase-8 and caspase-3 activation in primary T cells. We showed in this study that z-VAD-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. The inhibition of anti-CD3-mediated T cell proliferation induced by z-VAD-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC) and L-cysteine, whereas D-cysteine which cannot be metabolised to GSH has no effect. These results suggest that the depletionmore » of intracellular GSH is the underlying cause of z-VAD-FMK-mediated inhibition of T cell activation and proliferation. The presence of exogenous GSH also attenuated the inhibition of anti-CD3-induced CD25 and CD69 expression mediated by z-VAD-FMK. However, none of the low molecular weight thiols were able to restore the caspase-inhibitory properties of z-VAD-FMK in activated T cells where caspase-8 and caspase-3 remain activated and processed into their respective subunits in the presence of the caspase inhibitor. This suggests that the inhibition of T cell proliferation can be uncoupled from the caspase-inhibitory properties of z-VAD-FMK. Taken together, the immunosuppressive effects in primary T cells mediated by z-VAD-FMK are due to oxidative stress via the depletion of GSH.« less

Contribution of cellular retinol-binding protein type 1 to retinol metabolism during mouse development.

PubMed

Matt, Nicolas; Schmidt, Carsten K; Dupé, Valérie; Dennefeld, Christine; Nau, Heinz; Chambon, Pierre; Mark, Manuel; Ghyselinck, Norbert B

2005-05-01

Within cells, retinol (ROL) is bound to cytoplasmic proteins (cellular retinol-binding proteins [CRBPs]), whose proposed function is to protect it from unspecific enzymes through channeling to retinoid-metabolizing pathways. We show that, during development, ROL and retinyl ester levels are decreased in CRBP type 1 (CRBP1) -deficient embryos and fetuses by 50% and 80%, respectively. The steady state level of retinoic acid (RA) is also decreased but to a lesser extent. However, CRBP1-null fetuses do not exhibit the abnormalities characteristic of a vitamin A-deficiency syndrome. Neither CRBP1 deficiency alters the expression patterns of RA-responding genes during development, nor does CRBP1 availability modify the expression of an RA-dependent gene in primary embryonic fibroblasts treated with ROL. Therefore, CRBP1 is required in prenatal life to maintain normal amounts of ROL and to ensure its efficient storage but seems of secondary importance for RA synthesis, at least under conditions of maternal vitamin A sufficiency. Copyright 2005 Wiley-Liss, Inc.

The additive effects of minoxidil and retinol on human hair growth in vitro.

PubMed

Yoo, Hyeon Gyeong; Chang, In-Young; Pyo, Hyun Keol; Kang, Yong Jung; Lee, Seung Ho; Kwon, Oh Sang; Cho, Kwang Hyun; Eun, Hee Chul; Kim, Kyu Han

2007-01-01

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

Purification and characterization of a novel cytosolic NADP(H)-dependent retinol oxidoreductase from rabbit liver.

PubMed

Huang, D Y; Ichikawa, Y

1997-03-07

Rabbit liver cytosol exhibits very high retinol dehydrogenase activity. At least two retinol dehydrogenases were demonstrated to exist in rabbit liver cytosol, and the major one, a cytosolic NADP(H)-dependent retinol dehydrogenase (systematic name: retinol oxidoreductase) was purified about 1795-fold to electrophoretic and column chromatographic homogeneity by a procedure involving column chromatography on AF-Red Toyopearl twice and then hydroxyapatite. Its molecular mass was estimated to be 34 kDa by SDS-PAGE, and 144 kDa by HPLC gel filtration, suggesting that it is a homo-tetramer. The enzyme uses free retinol and retinal, and their complexes with CRBP as substrates in vitro. The optimum pH values for retinol oxidation of free retinol and CRBP-retinol were 8.8-9.2 and 8.0-9.0, respectively, and those for retinal reduction of free retinal and retinal-CRBP were the same, 7.0-7.6. Km for free retinol and Vmax for retinal formation were 2.8 microM and 2893 nmol/min per mg protein at 37 degrees C (pH 9.0) and the corresponding values with retinol-CRBP as a substrate were 2.5 microM and 2428 nmol/min per mg protein at 37 degrees C (pH 8.6); Km for free retinal and Vmax for retinol formation were 6.5 microM and 4108 nmol/min per mg protein, and the corresponding values with retinal-CRBP as a substrate were 5.1 microM and 3067 nmol/min per mg protein at 37 degrees C, pH 7.4. NAD(H) was not effective as a cofactor. 4-Methylpyrazole was a weak inhibitor (IC50 = 28 mM) of the enzyme, and ethanol was neither a substrate nor an inhibitor of the enzyme. This enzyme exhibits relatively broad aldehyde reductase activity and some ketone reductase activity, the activity for aromatic substitutive aldehydes being especially high and effective. Whereas, except in the case of retinol, oxidative activity toward the corresponding alcohols was not detected. This novel cytosolic enzyme may play an important role in vivo in maintaining the homeostasis of retinal, the substrate of retinoic

Comparative studies of human and chicken retinol-binding proteins and prealbumins.

PubMed

Kopelman, M; Mokady, S; Cogan, U

1976-08-09

Microheterogeneity of retinol-binding proteins of human plasma and urine, and of chicken plasma was studied by polyacrylamide gel electrophoresis. All three protein systems were found microheterogenous. Incorporation of retinol into the protein preparations on the one hand, and depletion of these proteins from retinol on the other hand, enabled us to clarify the extent to which the presence or absence of the ligand affects the apparent heterogeneity. Upon electrophoresis, each of the native proteins displayed two pairs of protein zones. It appeared that within each pair the fast moving band corresponded to aporetinol-binding protein which upon binding of retinol was converted to a holoprotein with a slightly lower mobility. However, it did not seem that proteins of one pair were converted to proteins of the second pair upon binding of retinol, substantiating ghe microheterogenous character of this protein system. A rapid, two step procedure for isolation of prealbumins from plasma is described. The method which consists of DEAE-cellulose chromatography follwed by preparative electrophoresis was utilized to separate human and chicken prealbumins. Routine dodecyl sulphate electrophoresis resulted in partial dissociation of human prealbumin but in no dissociation of the chicken protein. More drastic treatments prior to electrophoresis were needed to effect complete disruption of both proteins into subunits.

Complex wound management in ventricular assist device (VAD) patients: the role of aggressive debridement and vascularized soft tissue coverage.

PubMed

Nelson, Jonas A; Shaked, Oren; Fischer, John P; Mirzabeigi, Michael N; Jandali, Shareef; Kovach, Stephen J; Low, David W; Acker, Michael A; Kanchwala, Suhail K

2014-12-01

Infections and complex wounds after ventricular assist device (VAD) placement can result in significant morbidity and mortality. The purpose of this study was to evaluate complex wound management in the VAD patient, and to describe a treatment protocol for these challenging and potentially mortal complications. A retrospective study was performed to examine all patients who underwent continuous flow, second-generation VAD placement at the Hospital of the University of Pennsylvania between March 2008 and April 2013. Overall, 150 VADs were placed, with 12 (8%) patients requiring 15 operative interventions by the plastic surgery services. The most common indication for operative intervention was a complicated wound with VAD exposure (5/12, 41.7%). All patients underwent aggressive operative debridement, and 11/12 (92%) underwent vascularized soft tissue coverage. Flaps commonly utilized included rectus abdominus myocutaneous (n = 4), rectus abdominus muscle (n = 4), pectoralis major (n = 3), and omentum (n = 3). Three patients experienced complications which required a return to the operating room, including 1 flap loss, 1 hematoma, and 1 wound dehiscence requiring further soft tissue coverage. Salvage was achieved, yet a 50% mortality rate in follow-up was noted. Complex wound management in VAD patients can be achieved with aggressive debridement and vascularized soft tissue coverage, most commonly utilizing well-vascularized rectus abdominus muscle or omental flaps. Plastic surgeons should be familiar with the armamentarium at their disposal when approaching these challenging cases as VAD wound complications stand to become an increasingly prevalent issue.

An in vivo confocal Raman study of the delivery of trans retinol to the skin.

PubMed

Pudney, Paul D A; Mélot, Mickaël; Caspers, Peter J; Van Der Pol, Andre; Puppels, Gerwin J

2007-08-01

The purpose of this study is to monitor in vivo the delivery of trans-retinol into human skin. Delivery to real systems, such as skin, can be extremely difficult to execute and is problematic to confirm and measure. So far, methods for studying the delivery of compounds through the skin are mostly ex vivo and so inherently influence the skin and may not translate directly to the in vivo situation. Raman spectroscopy is uniquely placed to be able to measure biological processes in vivo, and this paper shows that the trans-retinol penetration into the skin can successfully be measured in vivo using this technique. This study measured the volar forearm of volunteers treated with 0.3% trans-retinol in propylene glycol (PG)/ethanol and 0.3% trans-retinol in caprylic/capric acid triglyceride (MYRITOL318), an oil found in skin creams. Solutions were applied and then confocal Raman depth profiles were obtained of the stratum corneum (SC) and into the viable epidermis (VE) up to 10 hours after treatment. Remarkable differences between a penetrating and a nonpenetrating solution can clearly be observed. Treating with trans-retinol in PG/ethanol results in trans-retinol penetrating through the SC and into the VE. Its penetration was also observed to be highly correlated with the depth of penetration of the PG, which is well known as an efficient penetration enhancer. In contrast, while treating with trans-retinol in MYRITOL318, trans-retinol hardly penetrates at all. For the first time, the penetration of trans-retinol has been monitored directly after application of solutions, in vivo without skin excision. Here, the effect of two different solutions on the delivery of trans-retinol into the skin was measured very effectively in vivo by Raman spectroscopy.

Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study

PubMed Central

Epplein, Meira; Shvetsov, Yurii B; Wilkens, Lynne R; Franke, Adrian A; Cooney, Robert V; Le Marchand, Loïc; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2009-01-01

Introduction Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk. Methods From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals. Results Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings. Conclusions The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk. PMID:19619335

Color perception differentiates Alzheimer's Disease (AD) from Vascular Dementia (VaD) patients.

PubMed

Arnaoutoglou, N A; Arnaoutoglou, M; Nemtsas, P; Costa, V; Baloyannis, S J; Ebmeier, K P

2017-08-01

Alzheimer's Disease (AD) and Vascular Dementia (VaD) are the most common causes of dementia in older people. Both diseases appear to have similar clinical symptoms, such as deficits in attention and executive function, but specific cognitive domains are affected. Current cohort studies have shown a close relationship between αβ deposits and age-related macular degeneration (Johnson et al., 2002; Ratnayaka et al., 2015). Additionally, a close link between the thinning of the retinal nerve fiber (RNFL) and AD patients has been described, while it has been proposed that AD patients suffer from a non-specific type of color blindness (Pache et al., 2003). Our study included 103 individuals divided into three groups: A healthy control group (n = 35), AD (n = 32) according to DSM-IV-TR, NINCDS-ADRDA criteria, and VaD (n = 36) based on ΝΙΝDS-AIREN, as well as Magnetic Resonance Imaging (MRI) results. The severity of patient's cognitive impairment, was measured with the Mini-Mental State Examination (MMSE) and was classified according to the Reisberg global deterioration scale (GDS). Visual perception was examined using the Ishihara plates: "Ishihara Color Vision Test - 38 Plate." The three groups were not statistically different for demographic data (age, gender, and education). The Ishihara color blindness test has a sensitivity of 80.6% and a specificity of 87.5% to discriminate AD and VaD patients when an optimal (32.5) cut-off value of performance is used. Ishihara Color Vision Test - 38 Plate is a promising potential method as an easy and not time-consuming screening test for the differential diagnosis of dementia between AD and VaD.

Nitrofen increases total retinol levels in placenta during lung morphogenesis in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Pes, Lara; Friedmacher, Florian; Paradisi, Francesca; Puri, Prem

2014-10-01

It has been shown that pulmonary retinol level is decreased during lung morphogenesis in the nitrofen-induced PH in congenital diaphragmatic hernia (CDH). Placenta has a major role in the retinol homeostasis in fetal life. Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Placenta is the main fetal retinol store where retinol is stored in retinyl-ester formation. Trophoblasts have to produce its own retinol-binding protein (RBP) for retinol transport from placenta to fetus. Recently, we demonstrated that trophoblastic RBP expression is decreased in the nitrofen model of CDH. The aim of this study was to investigate the retinol transfer from mother to the placenta in nitrofen model of CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal placenta harvested on D21 and divided into two groups: control (n = 11) and nitrofen with CDH (n = 11). Retinoid levels in placenta were measured using HPLC. Immunohistochemistry was performed to evaluate trophoblastic expression of main RSP genes. Total retinol levels in the placenta were significantly increased in CDH placenta compared to control placenta. The retinyl-ester levels were significantly increased in CDH placenta compared to control placenta. Markedly, decreased immunoreactivity of retinoid signaling pathway was observed in trophoblast cells in CDH compared to control placenta. Increased placental retinol levels show that retinol is transferred from mother to placenta and stored in the placenta in nitrofen model of CDH during lung morphogenesis. Nitrofen may disturb the mobilization of retinol from placenta to fetal circulation causing PH in CDH.

Encapsulation and controlled release of retinol from silicone particles for topical delivery.

PubMed

Shields, C Wyatt; White, John P; Osta, Erica G; Patel, Jerishma; Rajkumar, Shashank; Kirby, Nickolas; Therrien, Jean-Philippe; Zauscher, Stefan

2018-05-28

Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI. We have developed a class of silicone particles that addresses these challenges for the encapsulation, protection and controlled release of retinol and other hydrophobic compounds. The particles are prepared by the sol-gel polymerization of silane monomers, which enables their rapid and facile synthesis at scale while maintaining a narrow size distribution (i.e., CV < 20%). We show that our particles can: (i) encapsulate retinol with high efficiency (>85%), (ii) protect retinol from degradation (yielding a half-life 9× greater than unencapsulated retinol) and (iii) slowly release retinol over several hours (at rates from 0.14 to 0.67 μg cm -2  s -1/2 ). To demonstrate that the controlled release of retinol from the particles can reduce irritation, we performed a double blind study on human subjects and found that formulations containing our particles were 12-23% less irritating than identical formulations containing Microsponge® particles (an industry standard by Amcol, Inc.). To show that the silicone particles can elicit a favorable biological response, similar to the Microsponge® particles, we applied both formulations to reconstructed human epidermal tissues and found an upregulation of keratin 19 (K19) and a downregulation of K10, indicating that the reduced irritation observed in the human study was not caused by reduced activity. We

Plasma concentrations of retinol in obese children and adolescents: relationship to metabolic syndrome components

PubMed Central

Teske, Márcia; Melges, Ana Paula B.; de Souza, Fabíola Isabel S.; Fonseca, Fernando Luiz A.; Sarni, Roseli Oselka S.

2014-01-01

Objective: To evaluate obese children and adolescents' retinol plasma levels and to correlate them with metabolic syndrome components. Methods: Cross-sectional study with 61 obese children and adolescents (body mass index Z score - ZBMI>+2). Pubertal development, arterial blood pressure, body weight and height for nutritional classification and waist circumference were obtained. A 15mL blood sample was collected (after a 12-hour fasting in a low luminosity room) for retinol determination (cut-off inadequate if <30µg/dL), lipid profile (HDL-c, LDL-c, and triglycerides), oral glucose tolerance test (fasting and 120 minutes) and for high sensitivity C-reactive protein. Spearman correlation and multiple linear regression were used in the statistical analysis. Results: Mean age was 10.7±2.7 years. There was a predominance of male gender 38/61 (62%) and pre-pubertal 35/61 (57%) subjects. The average plasmatic retinol was 48.5±18.6ug/dL. Retinol deficiency and severe obesity were observed in 6/61 (10%) and 36/61 (59%), respectively. Glucose level at 120 minutes was the independent and predictive variable of plasma retinol levels [β=-0.286 (95%CI -0.013 - -0.001)]. Conclusions: An independent and inverse association between plasma retinol levels and glucose tolerance was observed, suggesting an important contribution of this vitamin in the morbidities associated to obesity in children and adolescents. PMID:24676190

Effect of retinol on the hyperthermal response of normal tissue in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogers, M.A.; Marigold, J.C.L.; Hume, S.P.

The effect of prior administration of retinol, a membrane labilizer, on the in vivo hyperthermal response of lysosomes was investigated in the mouse spleen using a quantitative histochemical assay for the lysosomal enzyme acid phosphatase. A dose of retinol which had no effect when given alone enhanced the thermal response of the lysosome, causing an increase in lysosomal membrane permeability. In contrast, the same dose of retinol had no effect on the gross hyperthermal response of mouse intestine; a tissue which is relatively susceptible to hyperthermia. Thermal damage to intestine was assayed directly by crypt loss 1 day after treatmentmore » or assessed as thermal enhancement of x-ray damage by counting crypt microcolonies 4 days after a combined heat and x-ray treatment. Thus, although the hyperthermal response of the lysosome could be enhanced by the administration of retinol, thermal damage at a gross tissue level appeared to be unaffected, suggesting that lysosomal membrane injury is unlikely to be a primary event in hyperthermal cell killing.« less

Serum concentrations of micronutrient antioxidants in an adult Arab population.

PubMed

Abiaka, Clifford; Olusi, Samuel; Simbeye, Amos

2002-01-01

Serum concentrations of retinol, alpha-tocopherol, beta-carotene and lycopene were measured by reversed-phase high-performance liquid chromatography (r-P HPLC) in 260 randomly selected healthy adult Kuwaitis (159 men and 101 women) aged 18-63 years (mean 33.3 years) to established reference ranges of the micronutrient antioxidants. Total cholesterol concentrations were assayed by an enzymatic method to determine alpha-tocopherol: cholesterol ratios. The mean +/- SEM (micromol/L) for retinol, alpha-tocopherol, beta-carotene and lycopene were 1.76+/-0.02, 20.0+/-0.5, 0.52+/-0.03, 0.95+/-0.05, respectively. Compared to other populations, these data showed, on the whole, ordinary concentrations of beta-carotene, comparatively low concentrations of retinol and alpha-tocopherol and high concentrations of lycopene. Retinol concentrations were similar for both sexes, whereas alpha-tocopherol concentration was significantly (P < 0.0001) lower and the carotenoid levels (beta-carotene and lycopene) significantly higher (P < 0.0001) in women. Of the micronutrient antioxidants, alpha-tocopherol was most correlated with cholesterol (r = 0.492, P < 0.0001). beta-Carotene and lycopene were highly correlated with each other (r =0.744, P< 0.0001). Age was positively associated with beta-carotene (r = 0.214, P = 0.001) and lycopene (r = 239, P< 0.0001). Our data enabled us to establish a gender non-specific reference range for retinol and gender-specific reference ranges for alpha-tocopherol, beta-carotene and lycopene.

Serial changes in selected serum constituents in low birth weight infants on peripheral parenteral nutrition with different zinc and copper supplements.

PubMed

Lockitch, G; Pendray, M R; Godolphin, W J; Quigley, G

1985-07-01

One hundred and five infants of birth weight 2000 g or less who received peripherally administered parenteral nutrition for periods of three or more weeks, were randomly assigned to groups receiving different amounts of zinc and copper supplement. The blood concentrations of zinc, copper, retinol-binding protein, prealbumin, alkaline phosphatase and aspartate transaminase were followed weekly. Mean serum zinc, retinol-binding protein and prealbumin declined significantly over time while alkaline phosphatase rose. Only the group receiving the highest zinc supplement maintained a mean serum zinc concentration within the normal range at seven weeks. No difference in the protein or enzyme concentrations was found between the different zinc supplement groups. No difference was seen in serum copper or ceruloplasmin between copper dose groups although one intravenous supplement was double that of the other.

Computational Analysis of Intra-Ventricular Flow Pattern Under Partial and Full Support of BJUT-II VAD.

PubMed

Zhang, Qi; Gao, Bin; Chang, Yu

2017-02-27

BACKGROUND Partial support, as a novel support mode, has been widely applied in clinical practice and widely studied. However, the precise mechanism of partial support of LVAD in the intra-ventricular flow pattern is unclear. MATERIAL AND METHODS In this study, a patient-specific left ventricular geometric model was reconstructed based on CT data. The intra-ventricular flow pattern under 3 simulated conditions - "heart failure", "partial support", and "full support" - were simulated by using fluid-structure interaction (FSI). The blood flow pattern, wall shear stress (WSS), time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated to evaluate the hemodynamic effects. RESULTS The results demonstrate that the intra-ventricular flow pattern is significantly changed by the support level of BJUT-II VAD. The intra-ventricular vortex was enhanced under partial support and was eliminated under full support, and the high OSI and RRT regions changed from the septum wall to the cardiac apex. CONCLUSIONS In brief, the support level of the BJUT-II VAD has significant effects on the intra-ventricular flow pattern. The partial support mode of BJUT-II VAD can enhance the intra-ventricular vortex, while the distribution of high OSI and RRT moved from the septum wall to the cardiac apex. Hence, the partial support mode of BJUT-II VAD can provide more benefit for intra-ventricular flow pattern.

Circulating Retinol-Binding Protein-4 Concentration Might Reflect Insulin Resistance–Associated Iron Overload

PubMed Central

Fernández-Real, José Manuel; Moreno, José María; Ricart, Wifredo

2008-01-01

OBJECTIVES—The mechanisms behind the association between retinol-binding protein-4 (RBP4) and insulin resistance are not well understood. An interaction between iron and vitamin A status, of which RBP4 is a surrogate, has long been recognized. We hypothesized that iron-associated insulin resistance could be behind the impaired insulin action caused by RBP4. RESEARCH DESIGN AND METHODS—Serum ferritin and RBP4 concentration and insulin resistance were evaluated in a sample of middle-aged men (n = 132) and in a replication independent study. Serum RBP4 was also studied before and after iron depletion in patients with type 2 diabetes. Finally, the effect of iron on RBP4 release was evaluated in vitro in adipose tissue. RESULTS—A positive correlation between circulating RBP4 and log serum ferritin (r = 0.35 and r = 0.61, respectively; P < 0.0001) was observed in both independent studies. Serum RBP4 concentration was higher in men than women in parallel to increased ferritin levels. On multiple regression analyses to predict serum RBP4, log serum ferritin contributed significantly to RBP4 variance after controlling for BMI, age, and homeostasis model assessment value. Serum RBP4 concentration decreased after iron depletion in type 2 diabetic patients (percent mean difference −13.7 [95% CI −25.4 to −2.04]; P = 0.024). The iron donor lactoferrin led to increased dose-dependent adipose tissue release of RBP4 (2.4-fold, P = 0.005) and increased RBP4 expression, while apotransferrin and deferoxamine led to decreased RBP4 release. CONCLUSIONS—The relationship between circulating RBP4 and iron stores, both cross-sectional and after iron depletion, and in vitro findings suggest that iron could play a role in the RBP4–insulin resistance relationship. PMID:18426863

Retinol induces morphological alterations and proliferative focus formation through free radical-mediated activation of multiple signaling pathways.

PubMed

Gelain, Daniel Pens; Pasquali, Matheus Augusto de Bittencourt; Caregnato, Fernanda Freitas; Castro, Mauro Antonio Alves; Moreira, José Claudio Fonseca

2012-04-01

Toxicity of retinol (vitamin A) has been previously associated with apoptosis and/or cell malignant transformation. Thus, we investigated the pathways involved in the induction of proliferation, deformation and proliferative focus formation by retinol in cultured Sertoli cells of rats. Sertoli cells were isolated from immature rats and cultured. The cells were subjected to a 24-h treatment with different concentrations of retinol. Parameters of oxidative stress and cytotoxicity were analyzed. The effects of the p38 inhibitor SB203580 (10 μmol/L), the JNK inhibitor SP600125 (10 μmol/L), the Akt inhibitor LY294002 (10 μmol/L), the ERK inhibitor U0126 (10 μmol/L) the pan-PKC inhibitor Gö6983 (10 μmol/L) and the PKA inhibitor H89 (1 μmol/L) on morphological and proliferative/transformation-associated modifications were studied. Retinol (7 and 14 μmol/L) significantly increases the reactive species production in Sertoli cells. Inhibition of p38, JNK, ERK1/2, Akt, and PKA suppressed retinol-induced [(3)H]dT incorporation into the cells, while PKC inhibition had no effect. ERK1/2 and p38 inhibition also blocked retinol-induced proliferative focus formation in the cells, while Akt and JNK inhibition partially decreased focus formation. ERK1/2 and p38 inhibition hindered transformation-associated deformation in retinol-treated cells, while other treatments had no effect. Our results suggest that activation of multiple kinases is responsible for morphological and proliferative changes associated to malignancy development in Sertoli cells by retinol at the concentrations higher than physiological level.

The effect of retinol on the hyperthermal response of normal tissue in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogers, M.A.; Marigold, J.C.; Hume, S.P.

The effect of prior administration of retinol, a membrane labilizer, on the in vivo hyperthermal response of lysosomes was investigated in the mouse spleen using a quantitative histochemical assay for the lysosomal enzyme acid phosphatase. A dose of retinol which had no effect when given alone enhanced the thermal response of the lysosome, causing an increase in lysosomal membrane permeability. In contrast, the same dose of retinol had no effect on the gross hyperthermal response of mouse intestine; a tissue which is relatively susceptible to hyperthermia. Thermal damage to intestine was assayed directly by crypt loss 1 day after treatmentmore » or assessed as thermal enhancement of X-ray damage by counting crypt microcolonies 4 days after a combined heat and X-ray treatment. Thus, although the hyperthermal response of the lysosome could be enhanced by the administration of retinol, thermal damage at a gross tissue level appeared to be unaffected, suggesting that lysosomal membrane injury is unlikely to be a primary event in hyperthermal cell killing.« less

The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones

PubMed Central

Sato, Shinya; Frederiksen, Rikard; Cornwall, M. Carter; Kefalov, Vladimir J.

2017-01-01

Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones. PMID:28359344

Influence of Roux-en-Y Gastric Bypass on the Nutritional Status of Vitamin A in Pregnant Women: a Comparative Study.

PubMed

Machado, Suzana N; Pereira, Silvia; Saboya, Carlos; Saunders, Cláudia; Ramalho, Andréa

2016-01-01

The objective of the present study is to evaluate the nutritional status of vitamin A through biochemical and functional indicators of pregnant women who underwent Roux-en-Y gastric bypass (RYGB) surgery compared to pregnant women who did not undergo this surgery. The present study is a cross-sectional study of the analytical type with pregnant women paired by age and prepregnancy body mass index (BMI). Group 1 (G1) comprised 80 pregnant women without previous submission to RYGB and group 2 (G2) by 40 pregnant women who previously underwent this surgery. We used high-performance liquid chromatography with UV detector for quantification of retinol and β-carotene, and the functional evaluation of vitamin A deficiency (VAD) was performed through standardized interview validated for pregnant women. G1 mean age was 29.3 ± 5.3 and 30.8 ± 4.4 in G2. BMI mean prepregnancy found in G1 was 25.7 ± 3.2 and 26.8 ± 3.1 in G2, featuring overweight. Serum retinol and β-carotene means were significantly higher in G1 (1.8 ± 0.9; 87.4 ± 62.2) compared to G2 (0.99 ± 0.39; 22.7 ± 18.0), respectively (p < 0.001). Regarding the functional indicator for evaluation of VAD, approximately 75.0 % of pregnant women in G2 showed night blindness and 20.0 % in G1, and the percentage of pregnant women with this functional impairment was significantly higher in G2 compared to G1 with p < 0.001. Results show that pregnancy after RYGB can represent a high-risk situation for VAD. We recommend interdisciplinary monitoring added to the prenatal routine consultations and the conduction of studies addressed to the investigation of a safe and effective dose of oral supplementation of vitamin A to pregnant women undergoing RYGB.

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

PubMed Central

Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D.; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R.; Ceda, Gian Paolo; Ferrucci, Luigi

2015-01-01

Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = −0.29 ± 0.08, p

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women.

PubMed

Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R; Ceda, Gian Paolo; Ferrucci, Luigi

2015-08-05

In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998-2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. After adjustment for age, α-carotene (β ± SE = -0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = -0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = -1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = -0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the

Dietary and serum vitamins A and E and colorectal cancer risk in Chinese population: a case-control study.

PubMed

Luo, Hong; Fang, Yu-Jing; Lu, Min-Shan; Pan, Zhi-Zhong; Huang, Jing; Chen, Yu-Ming; Zhang, Cai-Xia

2018-05-24

The effect of vitamin A (VA) and vitamin E (VE) on colorectal cancer (CRC) risk is controversial. The aim of this study is to examine the association between serum concentrations and dietary intakes of VA and VE and the risk of CRC in Guangdong, China. A total of 535 cases and 552 sex and age-matched (5-year interval) controls were recruited during July 2010 to September 2014. Dietary information was assessed by face-to-face interviews using a validated food frequency questionnaire. Concentrations of VA and VE were measured by high-performance liquid chromatography. Multivariable logistic regression was used to estimate the odds ratios (ORs) and 95% confidence interval (CI) after adjusting for various potential confounders. A higher intake of VA and VE was found to be associated with 52 and 43% reduction in CRC risk. The ORs of the highest quartile compared with the lowest quartile intake were 0.48 (95% CI: 0.31, 0.73, Ptrend<0.01) for VA and 0.57 (95% CI: 0.37, 0.88, Ptrend<0.01) for VE. An inverse association was also found between serum retinol and CRC risk, with an adjusted OR (95% CI) of 0.28 (0.19-0.43) (Ptrend<0.01). However, no statistically significant association was found between serum α-tocopherol and CRC risk. Stratified analysis by sex showed that serum retinol and dietary VA and VE were inversely associated with CRC risk in both sexes. This study supported the hypothesis that lower serum levels of retinol and lower intakes of VA and VE were associated with the risk of CRC in a Chinese population.

Prevalence of anaemia, deficiencies of iron and vitamin A and their determinants in rural women and young children: a cross-sectional study in Kalalé district of northern Benin.

PubMed

Alaofè, Halimatou; Burney, Jennifer; Naylor, Rosamond; Taren, Douglas

2017-05-01

To identify the magnitude of anaemia and deficiencies of Fe (ID) and vitamin A (VAD) and their associated factors among rural women and children. Cross-sectional, comprising a household, health and nutrition survey and determination of Hb, biochemical (serum concentrations of ferritin, retinol, C-reactive protein and α1-acid glycoprotein) and anthropometric parameters. Multivariate logistic regression examined associations of various factors with anaemia and micronutrient deficiencies. Kalalé district, northern Benin. Mother-child pairs (n 767): non-pregnant women of reproductive age (15-49 years) and children 6-59 months old. In women, the overall prevalence of anaemia, ID, Fe-deficiency anaemia (IDA) and VAD was 47·7, 18·3, 11·3 and 17·7 %, respectively. A similar pattern for anaemia (82·4 %), ID (23·6 %) and IDA (21·2 %) was observed among children, while VAD was greater at 33·6 %. Greater risk of anaemia, ID and VAD was found for low maternal education, maternal farming activity, maternal health status, low food diversity, lack of fruits and vegetables consumption, low protein foods consumption, high infection, anthropometric deficits, large family size, poor sanitary conditions and low socio-economic status. Strong differences were also observed by ethnicity, women's group participation and source of information. Finally, age had a significant effect in children, with those aged 6-23 months having the highest risk for anaemia and those aged 12-23 months at risk for ID and IDA. Anaemia, ID and VAD were high among rural women and their children in northern Benin, although ID accounted for a small proportion of anaemia. Multicentre studies in various parts of the country are needed to substantiate the present results, so that appropriate and beneficial strategies for micronutrient supplementation and interventions to improve food diversity and quality can be planned.

Rod outer segment retinol formation is independent of Abca4, arrestin, rhodopsin kinase, and rhodopsin palmitylation.

PubMed

Blakeley, Lorie R; Chen, Chunhe; Chen, Ching-Kang; Chen, Jeannie; Crouch, Rosalie K; Travis, Gabriel H; Koutalos, Yiannis

2011-06-01

The reactive aldehyde all-trans retinal is released in rod photoreceptor outer segments by photoactivated rhodopsin and is eliminated through reduction to all-trans retinol. This study was undertaken to determine whether all-trans retinol formation depends on Abca4, arrestin, rhodopsin kinase, and the palmitylation of rhodopsin, all of which are factors that affect the release and sequestration of all-trans retinal. Experiments were performed in isolated retinas and single living rods derived from 129/sv wild-type mice and Abca4-, arrestin-, and rhodopsin kinase-deficient mice and in genetically modified mice containing unpalmitylated rhodopsin. Formation of all-trans retinol was measured by imaging its fluorescence and by HPLC of retina extracts. The release of all-trans retinal from photoactivated rhodopsin was measured in purified rod outer segment membranes according to the increase in tryptophan fluorescence. All experiments were performed at 37°C. The kinetics of all-trans retinol formation in the different types of genetically modified mice are in reasonable agreement with those in wild-type animals. The kinetics of all-trans retinol formation in 129/sv mice are similar to those in C57BL/6, although the latter are known to regenerate rhodopsin much more slowly. The release of all-trans retinal from rhodopsin in purified membranes is significantly faster than the formation of all-trans retinol in intact cells and is independent of the presence of the palmitate groups. The regeneration of rhodopsin and the recycling of its chromophore are not strongly coupled. Neither the activities of Abca4, rhodopsin kinase, and arrestin, nor the palmitylation of rhodopsin affects the formation of all-trans retinol.

The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

PubMed

Topper, Stephen R; Navitsky, Michael A; Medvitz, Richard B; Paterson, Eric G; Siedlecki, Christopher A; Slattery, Margaret J; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B

2014-03-01

We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro , a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s -1 , which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.

A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin.

PubMed

Kong, Rong; Cui, Yilei; Fisher, Gary J; Wang, Xiaojuan; Chen, Yinbei; Schneider, Louise M; Majmudar, Gopa

2016-03-01

All-trans retinol, a precursor of retinoic acid, is an effective anti-aging treatment widely used in skin care products. In comparison, topical retinoic acid is believed to provide even greater anti-aging effects; however, there is limited research directly comparing the effects of retinol and retinoic acid on skin. In this study, we compare the effects of retinol and retinoic acid on skin structure and expression of skin function-related genes and proteins. We also examine the effect of retinol treatment on skin appearance. Skin histology was examined by H&E staining and in vivo confocal microscopy. Expression levels of skin genes and proteins were analyzed using RT-PCR and immunohistochemistry. The efficacy of a retinol formulation in improving skin appearance was assessed using digital image-based wrinkle analysis. Four weeks of retinoic acid and retinol treatments both increased epidermal thickness, and upregulated genes for collagen type 1 (COL1A1), and collagen type 3 (COL3A1) with corresponding increases in procollagen I and procollagen III protein expression. Facial image analysis showed a significant reduction in facial wrinkles following 12 weeks of retinol application. The results of this study demonstrate that topical application of retinol significantly affects both cellular and molecular properties of the epidermis and dermis, as shown by skin biopsy and noninvasive imaging analyses. Although the magnitude tends to be smaller, retinol induces similar changes in skin histology, and gene and protein expression as compared to retinoic acid application. These results were confirmed by the significant facial anti-aging effect observed in the retinol efficacy clinical study. © 2015 Wiley Periodicals, Inc.

Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene.

PubMed

de Klerk, N H; Musk, A W; Ambrosini, G L; Eccles, J L; Hansen, J; Olsen, N; Watts, V L; Lund, H G; Pang, S C; Beilby, J; Hobbs, M S

1998-01-30

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

Serum Antioxidant Concentrations and Metabolic Syndrome Are Associated among U.S. Adolescents in Recent National Surveys123

PubMed Central

Beydoun, May A.; Canas, J. Atilio; Beydoun, Hind A.; Chen, Xiaoli; Shroff, Monal R.; Zonderman, Alan B.

2012-01-01

Specific micronutrients, including retinol, retinyl esters, carotenoids [α-carotene, β-carotene (cis+trans), β-cryptoxanthin, lutein+zeaxanthin, and total lycopene], vitamin E, and vitamin C have antiinflammatory and antioxidant effects, properties shown to reduce oxidative stress, a process that accompanies the pathogenesis of many chronic diseases. It is still largely unknown whether they are associated with the occurrence of metabolic syndrome (MetS) in the adolescent U.S. population. MetS was defined by the International Diabetes Federation (IDF) criteria. Other non-MetS outcomes relying on blood measurements were elevated HOMA-IR, C-reactive protein (CRP), and hyperuricemia. We tested associations between serum antioxidants and MetS outcomes among adolescents aged 12–19 y using cross-sectional data from NHANES 2001–2006 (n = 782–4285). IDF MetS prevalence was estimated at 7% among boys and 3% among girls. In adjusted models, adolescents with MetS had consistently lower carotenoid concentrations compared with their counterparts without MetS. Total carotenoids were also inversely related to HOMA-IR and CRP. Vitamin C was inversely related to uric acid level and MetS binary outcome. Retinol+retinyl esters exhibited an inverse relationship with CRP and a positive relationship with uric acid and HOMA-IR as well as MetS binary outcome. Vitamin E had no association with MetS, particularly after controlling for serum cholesterol and TG. In conclusion, among U.S. adolescents, serum carotenoid concentrations were inversely associated with MetS status, HOMA-IR, and CRP, whereas serum vitamin C was inversely related to MetS status and serum uric acid. Vitamin E had no consistent association with MetS, whereas retinol+retinyl esters had a positive relationship with HOMA-IR, uric acid, and MetS, while being inversely related to CRP. These associations need further study. PMID:22810988

No detectable carotenoid concentrations in serum of llamas and alpacas.

PubMed

Raila, J; Schweigert, F J; Stanitznig, A; Lambacher, B; Franz, S; Baldermann, S; Wittek, T

2017-08-01

Carotenoids are lipid-soluble pigments and important for a variety of physiological functions. They are major dietary vitamin A precursors and act as lipophilic antioxidants in a variety of tissues and are associated with important health benefits in humans and animals. All animals must acquire carotenoids from their diet, but to our knowledge, there are no studies investigating the intestinal carotenoid absorption and their blood concentrations in New World camelids. The present study aimed to assess the serum concentrations of selected carotenoids in llamas (n = 13) and alpacas (n = 27). Serum carotenoids as well as retinol (vitamin A) and α-tocopherol (vitamin E) were determined by high-performance liquid chromatography coupled with mass spectrometry and these were unable to detect any carotenoids (α- and β-carotene, α- and β-cryptoxanthin, lutein, zeaxanthin, lycopene) in the samples. The concentrations of retinol in alpacas (2.89 ± 1.13 μmol/l; mean ± SD) were higher (p = 0.024) than those found in llamas (2.05 ± 0.87 μmol/l); however, the concentrations of α-tocopherol were not significantly (p = 0.166) different (llamas: 3.98 ± 1.83 μmol/l; alpacas: 4.95 ± 2.14 μmol/l). The results show that both llamas and alpacas are not able to absorb intact carotenoids, but efficiently convert provitamin A carotenoids to retinol. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

A sensitive and specific method for measurement of multiple retinoids in human serum with UHPLC-MS/MS

PubMed Central

Arnold, Samuel L. M.; Amory, John K.; Walsh, Thomas J.; Isoherranen, Nina

2012-01-01

Retinol (vitamin A) circulates at 1–4 μM concentration and is easily measured in serum. However, retinol is biologically inactive. Its metabolite, retinoic acid (RA), is believed to be responsible for biological effects of vitamin A, and hence the measurement of retinol concentrations is of limited value. A UHPLC-MS/MS method using isotope-labeled internal standards was developed and validated for quantitative analysis of endogenous RA isomers and metabolites. The method was used to measure retinoids in serum samples from 20 healthy men. In the fed state, the measured concentrations were 3.1 ± 0.2 nM for atRA, 0.1 ± 0.02 nM for 9-cisRA, 5.3 ± 1.3 nM for 13-cisRA, 0.4 ± 0.4 nM for 9,13-dicisRA, and 17.2 ± 6.8 nM for 4oxo-13-cisRA. The concentrations of the retinoids were not significantly different when measured after an overnight fast (3.0 ± 0.1 nM for atRA, 0.09 ± 0.01nM for 9-cisRA, 3.9 ± 0.2 nM for 13-cisRA, 0.3 ± 0.1 nM for 9,13-dicisRA, and 11.9 ± 1.6 nM for 4oxo-13-cisRA). 11-cisRA and 4OH-RA were not detected in human serum. The high sensitivity of the MS/MS method combined with the UHPLC separation power allowed detection of endogenous 9-cisRA and 4oxo-atRA for the first time in human serum. PMID:22192917

Vitamin A deficiency and hepatic retinol levels in sea otters, Enhydra lutris.

PubMed

St Leger, Judy A; Righton, Alison L; Nilson, Erika M; Fascetti, Andrea J; Miller, Melissa A; Tuomi, Pamela A; Goertz, Caroline E C; Puschner, Birgit

2011-03-01

Vitamin A deficiency has rarely been reported in captive or free-ranging wildlife species. Necropsy findings in two captively housed southern sea otters (Enhydra lutris nereis) included irregular thickening of the calvaria characterized by diffuse hyperostoses on the internal surface. One animal also had moderate squamous metaplasia of the seromucinous glands of the nose. There was no measurable retinol in the liver of either sea otter. For comparison, hepatic retinol concentration was determined for 23 deceased free-ranging southern and northern (Enhydra lutris kenyoni) sea otters from California and Alaska. Free-ranging otters were found to have similar hepatic retinol concentrations (316 +/- 245 mg/kg wet weight) regardless of their location and subspecies. All of these values were significantly higher than the levels in the affected animals. Consumption of a diet with very low vitamin A concentrations and noncompliance in daily supplementation are hypothesized as the causes of vitamin A deficiency in these two sea otters.

Distribution of vitamins A (retinol) and E (α-tocopherol) in polar bear kidney: Implications for biomarker studies.

PubMed

Bechshøft, T Ø; Jakobsen, J; Sonne, C; Dietz, R

2011-08-15

Vitamins A and E content of inner organs, among these the kidneys, are increasingly being used as an indicator of adverse effects caused to the organism by e.g. environmental contaminants. In general, only a renal sub sample is used for analyses, and it is thus essential to know which part of the organ to sample in order to get a representative value for this important biomarker. The aim here was to assess the distribution of vitamins A (retinol) and E (α-tocopherol) within the polar bear multireniculate kidney (i.e. polar vs. medial position) and also within the cortex vs. medulla of each separate renculi. The results showed no significant difference between the medial and polar renculi with regards to either retinol (p=0.44) or α-tocopherol (p=0.75). There were, however, significant differences between cortex and medulla for both vitamins (retinol, p=0.0003; α-tocopherol, p<0.0001). The kidney cortex contained higher values of both vitamins than the medulla; on average 29% more retinol and 57% more α-tocopherol. Mean concentrations in the medulla was 2.7 mg/kg for retinol and 116 mg/kg for α-tocopherol, and in the cortex 3.5 mg/kg for retinol and 182 mg/kg for α-tocopherol. These results clearly indicate that one should take precautions when analyzing retinol and α-tocopherol in polar bear kidneys. Prior to analysis, the renculi should be separated into medulla and cortex. The results indicated no significant differences between renculi from different parts of the kidney. Copyright © 2011 Elsevier B.V. All rights reserved.

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

DOE PAGES

Chen, Yanling; Reese, David H.; Kelly, Gregory M.

2016-09-29

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), whichmore » controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. In conclusion, the surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

PubMed Central

Chen, Yanling; Reese, David H.

2016-01-01

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), which controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. The surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the observed effect of

Corexit-EC9527A Disrupts Retinol Signaling and Neuronal Differentiation in P19 Embryonal Pluripotent Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yanling; Reese, David H.; Kelly, Gregory M.

Corexit-EC9500A and Corexit-EC9527A are two chemical dispersants that have been used to remediate the impact of the 2010 Deepwater Horizon oil spill. Both dispersants are composed primarily of organic solvents and surfactants and act by emulsifying the crude oil to facilitate biodegradation. The potential adverse effect of the Corexit chemicals on mammalian embryonic development remains largely unknown. Retinol (vitamin A) signaling, mediated by all-trans retinoic acid (RA), is essential for neural tube formation and the development of many organs in the embryo. The physiological levels of RA in cells and tissues are maintained by the retinol signaling pathway (RSP), whichmore » controls the biosynthesis of RA from dietary retinol and the catabolism of RA to polar metabolites for removal. RA is a potent activating ligand for the RAR/RXR nuclear receptors. Through RA and the receptors, the RSP modulates the expression of many developmental genes; interference with the RSP is potentially teratogenic. In this study the mouse P19 embryonal pluripotent cell, which contains a functional RSP, was used to evaluate the effects of the Corexit dispersants on retinol signaling and associated neuronal differentiation. The results showed that Corexit-EC9500A was more cytotoxic than Corexit-EC9527A to P19 cells. At non-cytotoxic doses, Corexit-EC9527A inhibited retinol-induced expression of the Hoxa1 gene, which encodes a transcription factor for the regulation of body patterning in the embryo. Such inhibition was seen in the retinol- and retinal- induced, but not RA-induced, Hoxa1 up-regulation, indicating that the Corexit chemicals primarily inhibit RA biosynthesis from retinal. In addition, Corexit-EC9527A suppressed retinol-induced P19 cell differentiation into neuronal cells, indicating potential neurotoxic effect of the chemicals under the tested conditions. In conclusion, the surfactant ingredient, dioctyl sodium sulfosuccinate (DOSS), may be a major contributor to the

Discovery and biological relevance of 3,4-didehydroretinol (vitamin A2) in small indigenous fish species and its potential as a dietary source for addressing vitamin A deficiency.

PubMed

La Frano, Michael R; Cai, Yimeng; Burri, Betty J; Thilsted, Shakuntala H

2018-05-01

Discovered in the late 1920s, 3,4-didehydroretinol (DROL, vitamin A 2 ) plays a significant biological role in freshwater fish. The functions of this vitamin have been investigated but to a far lesser extent than those of retinol (ROL, vitamin A 1 ). A recent study indicating all-trans DROL has 119-127% vitamin A biological activity compared to that of all-trans ROL suggests the significance of DROL for addressing vitamin A deficiency (VAD) in comparison to ROL may be currently overlooked. Freshwater fish such as small indigenous fish species (SIS), with high DROL content can be a promising dietary source for reducing VAD in areas where SIS are readily available and consumed. In this paper, the discovery and biological relevance of DROL are reviewed and furthermore, the vast potential of production and consumption of DROL-rich SIS in food-based strategies to combat VAD in Bangladesh and other developing countries with high prevalence of VAD is highlighted.

Existing and emerging technologies for measuring stable isotope labelled retinol in biological samples: isotope dilution analysis of body retinol stores.

PubMed

Preston, Tom

2014-01-01

This paper discusses some of the recent improvements in instrumentation used for stable isotope tracer measurements in the context of measuring retinol stores, in vivo. Tracer costs, together with concerns that larger tracer doses may perturb the parameter under study, demand that ever more sensitive mass spectrometric techniques are developed. GCMS is the most widely used technique. It has high sensitivity in terms of sample amount and uses high resolution GC, yet its ability to detect low isotope ratios is limited by background noise. LCMSMS may become more accessible for tracer studies. Its ability to measure low level stable isotope tracers may prove superior to GCMS, but it is isotope ratio MS (IRMS) that has been designed specifically for low level stable isotope analysis through accurate analysis of tracer:tracee ratios (the tracee being the unlabelled species). Compound-specific isotope analysis, where GC is interfaced to IRMS, is gaining popularity. Here, individual 13C-labelled compounds are separated by GC, combusted to CO2 and transferred on-line for ratiometric analysis by IRMS at the ppm level. However, commercially-available 13C-labelled retinol tracers are 2 - 4 times more expensive than deuterated tracers. For 2H-labelled compounds, GC-pyrolysis-IRMS has now become more generally available as an operating mode on the same IRMS instrument. Here, individual compounds are separated by GC and pyrolysed to H2 at high temperature for analysis by IRMS. It is predicted that GC-pyrolysis-IRMS will facilitate low level tracer procedures to measure body retinol stores, as has been accomplished in the case of fatty acids and amino acids. Sample size requirements for GC-P-IRMS may exceed those of GCMS, but this paper discusses sample preparation procedures and predicts improvements, particularly in the efficiency of sample introduction.

Comparisons among Equations Used for Retinol Isotope Dilution in the Assessment of Total Body Stores and Total Liver Reserves.

PubMed

Gannon, Bryan M; Tanumihardjo, Sherry A

2015-05-01

Vitamin A plays an essential role in animal biology and has negative effects associated with both hypo- and hypervitaminosis A. Many notable interventions are being done globally to eliminate vitamin A deficiency, including supplementation, fortification, and biofortification. At the same time, it is important to monitor vitamin A status in nations where preformed vitamin A intake is high because of consumption of animal source foods (e.g., liver, dairy, eggs), fortified foods (e.g., milk, cereals, oil, sugar, margarine), or vitamin supplements (e.g., one-a-day multivitamins) to ensure the population does not reach hypervitaminosis A. To accurately assess population status and evaluate interventions aimed at improving vitamin A status, accurate assessment methods are needed. The primary storage site of vitamin A is the liver; however, routinely obtaining liver samples from humans is impractical and unethical. Isotope dilution using deuterium- or (13)C-labeled retinol is currently the most sensitive indirect biomarker of vitamin A status across a wide range of liver reserves. The major drawback to its application is the increased technicality in sample analysis and data calculations when compared to less sensitive methodology, such as serum retinol concentrations and dose response tests. Two main equations have emerged for calculating vitamin A body pool size or liver concentrations from isotope dilution data: the "Olson equation" and the "mass balance equation." Different applications of these equations can lead to confusion and lack of consistency if the underlying principles and assumptions used are not clarified. The purpose of this focused review is to describe the evolution of the equations used in retinol stable-isotope work and the assumptions appropriate to different applications of the test. Ultimately, the 2 main equations are shown to be fundamentally the same and differ only in assumptions made for each specific research application. © 2015 American

Retinol Binding Protein 4 in children with Inflammatory Bowel Disease: a negative correlation with the disease activity.

PubMed

Roma, E; Krini, M; Hantzi, E; Sakka, S; Panayiotou, I; Margeli, A; Papassotiriou, I; Kanaka-Gantenbein, C

2012-10-01

Retinol Binding Protein-4 (RBP-4), the action of which was initially thought to be only the transport of vitamin A, is a major circulating adipocytokine involved in the inflammation. We evaluated the serum RBP-4 levels in children with inflammatory bowel disease (IBD) and correlated them with transthyretin (TTR), inflammation markers, disease activity, and body mass index (BMI). In 41 children of mean age 11.9 ± 3.6 years (range 5-17.7 y) with IBD (19 with Crohn's disease (CD) and 22 with Ulcerative colitis (UC) serum RBP-4, TTR, Amyloid A (SAA), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), disease activity and BMI were prospectively determined and compared with those of 42 matched controls. No difference in the RBP-4 and TTR serum levels, between patients and controls as well as between active and remission state of the disease was noticed. A negative correlation of serum RBP-4 with the disease activity, SAA and ESR and a positive correlation with TTR was found, but no significant correlation with CRP or BMI was found. Inflammation markers were significantly increased in patients compared to controls and had a positive correlation with the disease activity. RBP-4 negatively correlated with disease activity of children with IBD probably indicating a protective anti-inflammatory mechanism of action in addition to transport of vitamin A.

Characterization of human short chain dehydrogenase/reductase SDR16C family members related to retinol dehydrogenase 10.

PubMed

Adams, Mark K; Lee, Seung-Ah; Belyaeva, Olga V; Wu, Lizhi; Kedishvili, Natalia Y

2017-10-01

All-trans-retinoic acid (RA) is a bioactive derivative of vitamin A that serves as an activating ligand for nuclear transcription factors, retinoic acid receptors. RA biosynthesis is initiated by the enzymes that oxidize retinol to retinaldehyde. It is well established that retinol dehydrogenase 10 (RDH10, SDR16C4), which belongs to the 16C family of the short chain dehydrogenase/reductase (SDR) superfamily of proteins, is the major enzyme responsible for the oxidation of retinol to retinaldehyde for RA biosynthesis during embryogenesis. However, several lines of evidence point towards the existence of additional retinol dehydrogenases that contribute to RA biosynthesis in vivo. In close proximity to RDH10 gene on human chromosome 8 are located two genes that are phylogenetically related to RDH10. The predicted protein products of these genes, retinol dehydrogenase epidermal 2 (RDHE2, SDR16C5) and retinol dehydrogenase epidermal 2-similar (RDHE2S, SDR16C6), share 59% and 56% sequence similarity with RDH10, respectively. Previously, we showed that the single ortholog of the human RDHE2 and RDHE2S in frogs, Xenopus laevis rdhe2, oxidizes retinol to retinaldehyde and is essential for frog embryonic development. In this study, we explored the potential of each of the two human proteins to contribute to RA biosynthesis. The results of this study demonstrate that human RDHE2 exhibits a relatively low but reproducible activity when expressed in either HepG2 or HEK293 cells. Expression of the native RDHE2 is downregulated in the presence of elevated levels of RA. On the other hand, the protein encoded by the human RDHE2S gene is unstable when expressed in HEK293 cells. RDHE2S protein produced in Sf9 cells is stable but has no detectable catalytic activity towards retinol. We conclude that the human RDHE2S does not contribute to RA biosynthesis, whereas the low-activity RA-sensitive human RDHE2 may have a role in adjusting the cellular levels of RA in accord with

Sitagliptin down-regulates retinol-binding protein 4 and reduces insulin resistance in gestational diabetes mellitus: a randomized and double-blind trial.

PubMed

Sun, Xia; Zhang, Zhendong; Ning, Hui; Sun, Hong; Ji, Xianghong

2017-06-01

Gestational diabetes mellitus (GDM) is a condition that affects increasing number of pregnant women worldwide. Sitagliptin was reported to alleviate symptoms of type 2 diabetes mellitus by reducing serum levels of retinol-binding protein 4 (RBP-4). We investigated the effectiveness of sitagliptin on insulin sensitivity parameters in GDM patients. Pregnant GDM women in the 2nd trimester were recruited for this study. Participants were then assigned randomly to sitagliptin treatment group or placebo treatment group, and administered sitagliptin or placebo daily for 16 weeks. Glucose and insulin profiles, as well as serum RBP-4 level, were measured at both baseline and end of the study. After 16 weeks of treatment, participants in the STL group exhibited significantly improved levels of fasting plasma glucose and serum insulin, homeostasis model of assessment of β cell function (HOMA-β) and insulin resistance (HOMA-IR), compared with those in the placebo group. Serum levels of RBP-4 were also markedly decreased in the sitagliptin treatment group, and more importantly it was positively correlated with improved insulin resistance parameters. Our study supports a potentially promising role of sitagliptin in improving insulin resistance by decreasing RBP-4 in GDM-affected women.

Determination of vitamin A (retinol) in infant formula and adult nutritionals by liquid chromatography: First Action 2011.15.

PubMed

DeVries, Jonathan W; Silvera, Karlene R; McSherry, Elliot; Dowell, Dawn

2012-01-01

During the "Standards Development and International Harmonization: AOAC INTERNATIONAL Mid-Year Meeting," held on June 29, 2011, an Expert Review Panel (ERP) reviewed the method for the "Determination of Vitamins A (Retinol) and E (alpha-Tocopherol) in Foods by Liquid Chromatography: Collaborative Study," published by Jonathan W. DeVries and Karlene R. Silvera in J. AOAC Int. in 2002. After evaluation of the original validation data, an ERP agreed in June 2011 that the method meets standard method performance requirements (SMPRs) for vitamin A, as articulated by the Stakeholder Panel on Infant Formula and Adult Nutritionals. The ERP granted the method First Action status, applicable to determining vitamin A in ready-to-eat infant and adult nutritional formula. In an effort to achieve Final Action status, it was recommended that additional information be generated for different types of infant and adult nutritional formula matrixes at varied concentration levels as indicated in the vitamin A (retinol) SMPR. Existing AOAC LC methods are suited for specific vitamin A analytical applications. The original method differs from existing methods in that it can be used to assay samples in all nine sectors of the food matrix. One sector of the food matrix was powdered infant formula and gave support for the First Action approval for vitamin A in infant and adult nutritional formula. In this method, standards and test samples are saponified in basic ethanol-water solution, neutralized, and diluted, converting fats to fatty acids and retinol esters to retinol. Retinol is quantitated by an LC method, using UV detection at 313 or 328 nm for retinol. Vitamin concentration is calculated by comparison of the peak heights or peak areas of retinol in test samples with those of standards.

No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene.

PubMed

Ambrosini, G L; Bremner, A P; Reid, A; Mackerras, D; Alfonso, H; Olsen, N J; Musk, A W; de Klerk, N H

2013-04-01

Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men. There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007. The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture. Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97). This study observed no increases in fracture risk after long

Concentration of carotenoids, retinol and alpha-tocopherol in plasma of six microchiroptera species.

PubMed

Müller, Kerstin; Voigt, Christian C; Raila, Jens; Hurtienne, Andrea; Vater, Marianne; Brunnberg, Leo; Schweigert, Florian J

2007-07-01

To adequately feed species in captivity it is necessary to know their nutritional habits and their natural availability of specific nutrients. Such essential nutrients are vitamin A, vitamin E and selected carotenoids as vitamin-A-precursors. Because their blood plasma concentration are valid biomarkers of nutritional status of dietary intake, we determined the concentrations of carotenoids, retinol and alpha-tocopherol by HPLC as well as the transport proteins for retinol, the retinol-binding protein (RBP) and transthyretin (TTR) immunologically in the plasma of six species of microchiroptera from free-ranging animals and compared it in one species (Carollia perspicillata) to a group held in captivity. Plasma concentrations of the investigated components were generally much lower compared to most other mammals. Within the bats, differences were observed for all components. As in other species retinol, RBP and TTR were present but no retinyl esters could be detected. Plasma of the insectivorous bat species Molossus molossus contained carotenoids. Within the group of carotenoids, beta-carotene was dominant and only traces of lutein were present. Phyllostomus hastatus revealed the highest alpha-tocopherol concentration. No differences in the plasma content of the investigated compounds were found between a group of Carollia perspicillata kept in captivity for 20 years and free-ranging individuals from a population in Central America. No sex related differences were obvious. In conclusion, nutritional biomarkers in bats were highly variable due to dietary and possible species-specific differences.

Retinol and α-Tocopherol in the Breast Milk of Women after a High-Risk Pregnancy.

PubMed

Sámano, Reyna; Martínez-Rojano, Hugo; Hernández, Rosa M; Ramírez, Cristina; Flores Quijano, María E; Espíndola-Polis, José M; Veruete, Daniela

2017-01-01

There is scant information about whether, after a high-risk pregnancy, breast milk provides enough vitamins for assuring satisfactory bodily reserves in newborns. To comparatively evaluate, in women with high-risk and normal pregnancy, the concentration of retinol and α-tocopherol in breast milk. This cross-sectional, analytical study was evaluated with reverse-phase high-performance liquid chromatography (HPLC). Informed consent was signed by 95 mothers with a high-risk pregnancy and 32 mothers with a normal pregnancy. From the mothers with a high-risk pregnancy were obtained: 23 samples of colostrum, 24 of transitional milk, and 48 of mature milk. From the normal pregnancy group, 32 mature milk samples were collected. Pregestational Body Mass Index (BMI) and the gestational weight gain were noted. Models of logistic regression were constructed to identify the variables related to a low concentration of either retinol or α-tocopherol in breast milk. The concentration of retinol and α-tocopherol in mature milk was 60 (interquartile range (IQR), 41-90) and 276 (103-450) μg/dL, respectively, for the high-risk pregnancy group, and 76 (65-91) and 673 (454-866) µg/dL, respectively, for the normal pregnancy group ( p = 0.001). The concentration of retinol and α-tocopherol was similar in the subgroups of mothers with different disorders during gestation. A clear correlation was found between a greater pregestational weight and a lower concentration of retinol ( Rho = -0.280, p = 0.006), and between α-tocopherol and retinol in all cases ( Rho = 0.463, p = 0.001). Among women having a high-risk pregnancy, those delivering prematurely rather than carrying their pregnancy to term had a reduced concentration of retinol (54 (37-78) vs. 70 (49-106) µg/dL; p = 0.002) and a tendency to a lower concentration of α-tocopherol in breast milk (185 (75-410) vs. 339 (160-500) µg/dL; p = 0.053). Compared to mothers with a normal pregnancy, those with a high-risk pregnancy

Retinol Binding Protein 4 in Relation to Diet, Inflammation, Immunity, and Cardiovascular Diseases12

PubMed Central

Zabetian-Targhi, Fateme; Mahmoudi, Mohammad J; Rezaei, Nima; Mahmoudi, Maryam

2015-01-01

Retinol binding protein 4 (RBP4), previously called retinol binding protein (RBP), is considered a specific carrier of retinol in the blood. It is also an adipokine that has been implicated in the pathophysiology of insulin resistance. RBP4 seems to be correlated with cardiometabolic markers in inflammatory chronic diseases, including obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases (CVDs). It has recently been suggested that inflammation produced by RBP4 induces insulin resistance and CVD. The clinical relevance of this hypothesis is discussed in this review. Knowledge concerning the association of RBP4 with inflammation markers, oxidative stress, and CVDs as well as concerning the role of diet and antioxidants in decreasing RBP4 concentrations are discussed. Special attention is given to methodologies used in previously published studies and covariates that should be controlled when planning new studies on this adipokine. PMID:26567199

A double-blind randomized study comparing the association of Retinol and LR2412 with tretinoin 0.025% in photoaged skin.

PubMed

Bouloc, Anne; Vergnanini, Andre Luiz; Issa, Maria Claudia

2015-03-01

Topical tretinoin is considered the gold standard to treat photoaged skin, but it is associated with side effects and only available upon prescription. To compare the efficacy, tolerance, and perception of a fixed proprietary combination (Retinol 0.2%/LR2412 2%) vs. tretinoin 0.025% cream in women with photoaged skin. In this randomized, parallel, double-blind, controlled clinical study, women applied to the entire face for 3 months in the morning a SPF 50 sunscreen and in the evening either the association of Retinol 0.2%/LR2412 2% or tretinoin 0.025%. Clinical and instrumental parameters were assessed at days 0, 28, 56, and 84. Subject perception of the efficacy, tolerance and cosmeticity of the tested products were assessed at days 28, 56, and 84. A total of 120 women (60 to Retinol 0.2%/LR2412 2% cream and 60 to tretinoin 0.025% cream) were included in the study. Both products improved considerably wrinkles, mottled pigmentation, pores, and global photodamage. No statistically significant differences were noted between Retinol 0.2%/LR2412 2% cream and tretinoin 0.025% cream. Adverse effects were mostly graded mild. Overall, Retinol 0.2%/LR2412 2% cream was better tolerated than tretinoin 0.025% cream. At all visits, subject perception of the association of Retinol 0.2%/LR2412 2% was either comparable to or better than tretinoin 0.025% cream. The treatment outcome of Retinol 0.2%/LR2412 2% cream does not differ from the one of tretinoin 0.025% cream. Clinical results were not statistically different. Furthermore, Retinol 0.2%/LR2412 2% cream is better tolerated and better perceived by women used to rejuvenation procedures. © 2015 The Authors Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.

The Role of Lecithin: Retinol Acyltransferase (LRAT)-Mediated Esterification of Vitamin A in Regulating Human Breast Cancer Cell Proliferation and Differentiation

DTIC Science & Technology

2007-04-01

involved in thetranscriptional regulation of the human LRAT gene. 15. SUBJECT TERMS Breast cancer, lecithin : Retinol Acyltransferase (LRAT...R.R., Nanus, D.M., Scherr, D.S., and Gudas, L.J. 2004. Reduced lecithin : retinol acyltransferase expression correlates with increased pathologic...Solubilization and partial characterization of lecithin -retinol acyltransferase from rat liver. J Nutr Biochem 2: 503-511. Isogai, M., Chiantore, M.V., Haque

Molecular characterization of an aldo-keto reductase from Marivirga tractuosa that converts retinal to retinol.

PubMed

Hong, Seung-Hye; Nam, Hyun-Koo; Kim, Kyoung-Rok; Kim, Seon-Won; Oh, Deok-Kun

2014-01-01

A recombinant aldo-keto reductase (AKR) from Marivirga tractuosa was purified with a specific activity of 0.32unitml(-1) for all-trans-retinal with a 72kDa dimer. The enzyme had substrate specificity for aldehydes but not for alcohols, carbonyls, or monosaccharides. The enzyme turnover was the highest for benzaldehyde (kcat=446min(-1)), whereas the affinity and catalytic efficiency were the highest for all-trans-retinal (Km=48μM, kcat/Km=427mM(-1)min(-1)) among the tested substrates. The optimal reaction conditions for the production of all-trans-retinol from all-trans-retinal by M. tractuosa AKR were pH 7.5, 30°C, 5% (v/v) methanol, 1% (w/v) hydroquinone, 10mM NADPH, 1710mgl(-1) all-trans-retinal, and 3unitml(-1) enzyme. Under these optimized conditions, the enzyme produced 1090mgml(-1) all-trans-retinol, with a conversion yield of 64% (w/w) and a volumetric productivity of 818mgl(-1)h(-1). AKR from M. tractuosa showed no activity for all-trans-retinol using NADP(+) as a cofactor, whereas human AKR exhibited activity. When the cofactor-binding residues (Ala158, Lys212, and Gln270) of M. tractuosa AKR were changed to the corresponding residues of human AKR (Ser160, Pro212, and Glu272), the A158S and Q270E variants exhibited activity for all-trans-retinol. Thus, amino acids at positions 158 and 270 of M. tractuosa AKR are determinant residues of the activity for all-trans-retinol. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

The temporal requirement for vitamin A in the developing eye: mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina.

PubMed

See, Angela Wai-Man; Clagett-Dame, Margaret

2009-01-01

Mammalian eye development requires vitamin A (retinol, ROL). The role of vitamin A at specific times during eye development was studied in rat fetuses made vitamin A deficient (VAD) after embryonic day (E) 10.5 (late VAD). The optic fissure does not close in late VAD embryos, and severe folding and collapse of the retina is observed at E18.5. Pitx2, a gene required for normal optic fissure closure, is dramatically downregulated in the periocular mesenchyme in late VAD embryos, and dissolution of the basal lamina does not occur at the optic fissure margin. The addition of ROL to late VAD embryos by E12.5 restores Pitx2 expression, supports dissolution of the basal lamina, and prevents coloboma, whereas supplementation at E13.5 does not. Surprisingly, ROL given as late as E13.5 completely prevents folding of the retina despite the presence of an open fetal fissure, showing that coloboma and retinal folding represent distinct VAD-dependent defects. Retinal folding due to VAD is preceded by an overall reduction in the percentage of cyclin D1 positive cells in the developing retina, (initially resulting in retinal thinning), as well as a dramatic reduction in the cell adhesion-related molecules, N-cadherin and beta-catenin. Reduction of retinal cell number combined with a loss of the normal cell-cell adhesion proteins may contribute to the collapse and folding of the retina that occurs in late VAD fetuses.

Studying the effectiveness of penetration enhancers to deliver retinol through the stratum cornum by in vivo confocal Raman spectroscopy.

PubMed

Mélot, Mickaël; Pudney, Paul D A; Williamson, Ann-Marie; Caspers, Peter J; Van Der Pol, Andre; Puppels, Gerwin J

2009-08-19

The purpose of this study is to monitor in vivo the effect of chemical penetration enhancers on the delivery of trans-retinol into human skin. Chemical penetration enhancers reversibly alter barrier properties of the SC by disruption of the membrane structures or maximising drug solubility with the skin. So far, most of permeation or penetration experiments are performed in vitro. Raman spectroscopy is uniquely placed to be able to measure biological processes in vivo and this paper shows for the first time that the effect of penetration enhancer on the delivery of trans-retinol can successfully be measured in vivo using this technique. Here, the volar forearm of volunteers was treated with four formulations. One formulation is a highly effective model delivery system identified from ex vivo experiments: trans-retinol in Propylene Glycol (PG)/ethanol, with PG being a well-known and efficient penetration enhancer. The other three formulations are based on 0.3% trans-retinol in Caprylic/Capric Acid Triglyceride (MYRITOL 318), an oil commonly used in skin creams but in two of them a specific penetration enhancer is added. One contains a lipid extractor, Triton X 100, whereas another formulation contains a lipid fluidiser, Oleic Acid. Solutions were applied once and measurements were performed up to 6 h after treatment. Remarkable differences in the delivery of trans-retinol between formulation with or without penetration enhancer can clearly be seen. Moreover, the type of penetration enhancer is also shown to influence the delivery. While using the Oleic Acid, which is a lipid fluidiser, a better delivery of trans-retinol in the skin can be detected. For the first time, the effect of penetration enhancer on the delivery of trans-retinol has been monitored, non invasively in vivo, with time.

Retinoids, carotenoids, and tocopherols in breast adipose tissue and serum of benign breast disease and breast cancer patients

USDA-ARS?s Scientific Manuscript database

Various retinoic acid (RA) isomers (all-trans, 13-cis, 11-cis, and 9-cis) as well as retinol, carotenoids, and tocopherol concentrations were determined in both serum and breast adipose tissue of 22 benign breast disease patients and 52 breast cancer patients categorized into 4 stages by malignancy....

Vitamin A (retinol and retinyl esters), alpha-tocopherol and lipid levels in plasma of captive wild mammals and birds.

PubMed

Schweigert, F J; Uehlein-Harrell, S; von Hegel, G; Wiesner, H

1991-02-01

Vitamin A (retinol and retinyl esters), vitamin E and lipids were determined in a wide variety of wild mammals and birds held in captivity. In mammals plasma levels of vitamin A were generally below 500 ng/ml and those of vitamin E were highly variable (0.1-2 micrograms/ml). In primates, vitamin E levels were 3 to 8 micrograms/ml. Whereas in Marsupialia, Chiroptera, primates, Rodentia, Proboscidea, Sirenia, Perissodactyla and Artiodactyla only retinol was found, retinyl esters (basically retinol palmitate/oleate) represented 10 to 50% of the total plasma vitamin A in some birds of the order Ciconiiformes and Falconiformes. Retinol levels in birds were higher compared to mammals (500-2,000 ng/ml). The same was true for lipids as well as for vitamin E levels (1-26 micrograms/ml) in the plasma of birds.

Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Rohit B.; Wang, Qingde; Khillan, Jaspal S., E-mail: khillan@pitt.edu

Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibitmore » mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.« less

Retinol and α-Tocopherol in the Breast Milk of Women after a High-Risk Pregnancy

PubMed Central

Sámano, Reyna; Martínez-Rojano, Hugo; Hernández, Rosa M.; Ramírez, Cristina; Flores Quijano, María E.; Espíndola-Polis, José M.; Veruete, Daniela

2017-01-01

Background: There is scant information about whether, after a high-risk pregnancy, breast milk provides enough vitamins for assuring satisfactory bodily reserves in newborns. Objective: To comparatively evaluate, in women with high-risk and normal pregnancy, the concentration of retinol and α-tocopherol in breast milk. Methods: This cross-sectional, analytical study was evaluated with reverse-phase high-performance liquid chromatography (HPLC). Informed consent was signed by 95 mothers with a high-risk pregnancy and 32 mothers with a normal pregnancy. From the mothers with a high-risk pregnancy were obtained: 23 samples of colostrum, 24 of transitional milk, and 48 of mature milk. From the normal pregnancy group, 32 mature milk samples were collected. Pregestational Body Mass Index (BMI) and the gestational weight gain were noted. Models of logistic regression were constructed to identify the variables related to a low concentration of either retinol or α-tocopherol in breast milk. Results: The concentration of retinol and α-tocopherol in mature milk was 60 (interquartile range (IQR), 41–90) and 276 (103–450) μg/dL, respectively, for the high-risk pregnancy group, and 76 (65–91) and 673 (454–866) µg/dL, respectively, for the normal pregnancy group (p = 0.001). The concentration of retinol and α-tocopherol was similar in the subgroups of mothers with different disorders during gestation. A clear correlation was found between a greater pregestational weight and a lower concentration of retinol (Rho = –0.280, p = 0.006), and between α-tocopherol and retinol in all cases (Rho = 0.463, p = 0.001). Among women having a high-risk pregnancy, those delivering prematurely rather than carrying their pregnancy to term had a reduced concentration of retinol (54 (37–78) vs. 70 (49–106) µg/dL; p = 0.002) and a tendency to a lower concentration of α-tocopherol in breast milk (185 (75–410) vs. 339 (160–500) µg/dL; p = 0.053). Compared to mothers with a

cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration

PubMed Central

Sato, Shinya

2016-01-01

Key points This study explores the nature of the cis retinol that Müller cells in the retina provide to cones for the regeneration of their visual pigment.We report that the retina visual cycle provides cones exclusively with 11‐cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11‐cis‐specific cellular retinaldehyde binding protein (CRALBP) present in Müller cells.Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark‐adapt in the retina following a bleach and to use exogenous 9‐cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone‐specific and pigment‐independent.Our results show that the retina produces 11‐cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods. Abstract Chromophore supply by the retinal Müller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase‐1, the putative all‐trans retinol isomerase in Müller cells, appears to be 9‐cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11‐cis retinal. Here, we used the different absorption spectra of 9‐cis and 11‐cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark‐adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark‐adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11‐cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a

Serum transferrin as a prognostic indicator of spontaneous closure and mortality in gastrointestinal cutaneous fistulas.

PubMed Central

Kuvshinoff, B W; Brodish, R J; McFadden, D W; Fischer, J E

1993-01-01

OBJECTIVE: This study determined whether there are any laboratory or other features that will enable prediction of spontaneous closure in patients with gastrointestinal cutaneous fistulas. SUMMARY BACKGROUND DATA: Although the anatomic criteria for spontaneous closure of gastrointestinal cutaneous fistulas have been presented by several authors, less than 50% of such fistulas tend to close, even in the most recent series. METHODS: A group of patients with gastrointestinal cutaneous fistulas with anatomical features favorable to study were investigated with respect to a series of parameters including the usual demographic parameters, plus fistula output, number of blood transfusions, presence of sepsis, as well as metabolic parameters including serum transferrin, retinol-binding protein, thyroxin-binding prealbumin, and serum albumin. RESULTS: Of 79 patients with 116 fistulas, 16 (20.3%) died. Causes of death were uncontrolled sepsis in eight patients and cancer in five patients. Postoperative fistulas constituted 80% of the group. The presence of local sepsis, systemic sepsis, remote sepsis (such as pneumonia or line sepsis), the number of fistulas, fistula output, and the number of blood transfusions were not predictive of spontaneous closure, whereas serum transferrin was predictive of spontaneous closure. Serum transferrin, retinol-binding protein, and thyroxin-binding prealbumin were predictive of mortality. CONCLUSIONS: Serum transferrin does not appear to be an entirely independent variable, but seems to identify those patients with significant remote sepsis, systemic sepsis, and neoplasia in whom these processes are clinically significant. The results, if confirmed, and provided that nutritional needs are met, suggest that short-turnover proteins, particularly serum transferrin, might be useful in predicting which patients with gastrointestinal cutaneous fistulas should undergo surgery despite anatomic criteria favorable for spontaneous closure. PMID:8507110

Disposable cartridge extraction of retinol and alpha-tocopherol from fatty samples.

PubMed

Bourgeois, C F; Ciba, N

1988-01-01

A new approach is proposed for liquid/solid extraction of retinol and alpha-tocopherol from samples, using a disposable kieselguhr cartridge. The substitution of the mixture methanol-ethanol-n-butanol (4 + 3 + 1) for methanol in the alkaline hydrolysis solution makes it now possible to process fatty samples. Methanol is necessary to solubilize the antioxidant ascorbic acid, and a linear chain alcohol such as n-butanol is necessary to reduce the size of soap micelles so that they can penetrate into the kieselguhr pores. In comparisons of the proposed method with conventional methods on mineral premixes and fatty feedstuffs, recovery and accuracy are at least as good by the proposed method. Advantages are increased rate of determinations and the ability to hydrolyze and extract retinol and alpha-tocopherol together from the same sample.

Retinol Binding Protein-4 Levels and Non-alcoholic Fatty Liver Disease: A community-based cross-sectional study.

PubMed

Chen, Xuechen; Shen, Tianran; Li, Qing; Chen, Xu; Li, Yanping; Li, Dan; Chen, Gengdong; Ling, Wenhua; Chen, Yu-Ming

2017-03-23

Previous reports on the association between retinol binding protein 4 (RBP4) and nonalcoholic fatty liver disease (NAFLD) were controversial. This study aimed to investigate the association between the serum RBP4 levels and occurrence of NAFLD in Chinese population. In total, 2938 participants aged 40-75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of RBP4 and the presence of NAFLD were determined. Patients with NAFLD had significantly higher concentrations of RBP4 (37.9 ± 6.8 μg/ml) than did non-NAFLD controls (35.0 ± 6.7 μg/ml) (P < 0.001). The odds ratios (ORs) of NAFLD for the highest (vs. lowest) quartile of RBP4 were 1.884 (95% CI: 1.391, 2.551) for females (P < 0.001), and 2.107 (95% CI: 1.357, 3.273) for male participants (P < 0.01) after adjusting for related factors. The serum RBP4 levels were positively associated with the prevalence of NAFLD in middle-aged and elderly Chinese people, and Homeostatic model assessment-insulin resistance (HOMA-IR), trunk fat, the waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) might be implicated in the pathogenesis of RBP4 in NAFLD.

Vitamin A and retinol intakes and the risk of fractures among participants of the Women's Health Initiative Observational Study123

PubMed Central

Ritenbaugh, Cheryl; Wactawski-Wende, Jean; Snetselaar, Linda G; Chen, Zhao

2009-01-01

Background: Excessive intakes of vitamin A have been shown to have adverse skeletal effects in animals. High vitamin A intake may lead to an increased risk of fracture in humans. Objective: The objective was to evaluate the relation between total vitamin A and retinol intakes and the risk of incident total and hip fracture in postmenopausal women. Design: A total of 75,747 women from the Women's Health Initiative Observational Study participated. The risk of hip and total fractures was determined using Cox proportional hazards models according to different intakes of vitamin A and retinol. Results: In the analysis adjusted for some covariates (age; protein, vitamin D, vitamin K, calcium, caffeine, and alcohol intakes; body mass index; hormone therapy use; smoking; metabolic equivalents hours per week; ethnicity; and region of clinical center), the association between vitamin A intake and the risk of fracture was not statistically significant. Analyses for retinol showed similar trends. When the interaction term was analyzed as categorical, the highest intake of retinol with vitamin D was significant (P = 0.033). Women with lower vitamin D intake (≤11 μg/d) in the highest quintile of intake of both vitamin A (hazard ratio: 1.19; 95% CI: 1.04, 1.37; P for trend: 0.022) and retinol (hazard ratio: 1.15; 95% CI: 1.03, 1.29; P for trend: 0.056) had a modest increased risk of total fracture. Conclusions: No association between vitamin A or retinol intake and the risk of hip or total fractures was observed in postmenopausal women. Only a modest increase in total fracture risk with high vitamin A and retinol intakes was observed in the low vitamin D–intake group. PMID:19056568

Antioxidant Vitamin Status in the Serum and Amniotic Fluid of Women with Premature Rupture of the Fetal Membranes.

NASA Astrophysics Data System (ADS)

Barrett, Bridget M.

The purpose of this study was to examine the status of antioxidant vitamins in women with premature rupture of the fetal membranes. Specimens of blood and amniotic fluid were obtained from 80 pregnant subjects included both smokers and non-smokers during the third trimester. The concentrations of ascorbic acid (ASA), beta -carotene, retinol and alpha -tocopherol in serum and amniotic fluid were determined. The experimental group consisted of those subjects with PROM while the control subjects were those with normal pregnancy. No statistical differences were found between the PROM and control groups in retinol and vitamin E concentrations in amniotic fluid and serum. Serum ASA concentrations of PROM subjects were not different from controls, but the PROM subjects had significantly lower amniotic fluid ASA concentrations. However, in a study with fewer subjects a lower serum ASA concentration in the PROM subjects was observed. The ratio of amniotic fluid ASA concentration to ASA serum concentration was significantly lower in PROM patients than in controls in both studies. This suggests that low levels of ASA in the amniotic fluid, but not in serum is better associated with PROM. A low amniotic fluid concentration of ASA may reflect an inefficient transfer and/or increased fetal utilization. Alterations in ASA concentration in the amniotic fluid may affect the integrity of the chorioamnion leading to PROM. beta -Carotene was not found in the amniotic fluid. Serum beta-carotene levels were significantly lower in the PROM group compared to the control group. Low concentrations of beta-carotene in maternal serum in smokers not only associated with poor maternal outcome (PROM) but also compromised the fetal outcome (decreased birth weight). Maintenance of adequate serum beta-carotene concentration and amniotic fluid ASA in smokers may result in better maternal and fetal outcome. This study demonstrated that nutrition is an important factor in the prevention of PROM.

Serum concentrations of vitamin A and oxidative stress in critically ill patients with sepsis.

PubMed

Ribeiro Nogueira, C; Ramalho, A; Lameu, E; Da Silva Franca, C A; David, C; Accioly, E

2009-01-01

Sepsis is one of the main causes of mortality in patients in Intensive Care Units. As a result of the systemic inflammatory response and of the decrease of the aerobic metabolism in sepsis, the oxidative stress occurs. Vitamin A is recognized by the favorable effect that it exerts on the immune response to infections and antioxidant action. To bring new elements for reviewing of the nutritional support addressed to critically ill patients with sepsis, with emphasis to vitamin A. Critically ill patients with sepsis had circulating concentrations of retinol, beta-carotene, thiobarbituric acid-reactive substances (TBARS) and C-reactive protein (CRP) measured in Medicosurgical Intensive Care Unit in the city of Rio de Janeiro, Brazil. The patients were divided into two groups: patients who were receiving nutritional support and those without support. At the act of the patient's admission, APACHE II score was calculated. 46 patients were studied (with diet n = 24 and without diet n = 22). Reduced levels of retinol and beta-carotene were found in 65.2% and 73.9% of the patients, respectively. Among the patients who presented lower concentrations of CRP it was found higher beta-carotene inadequacy (64.8%) and 50% of retinol inadequacy. There was no significant difference as regards retinol, TBARS and APACHE II levels among the patients with and without nutritional support. However, higher levels of CRP (p = 0.001) and lower levels of serum beta-carotene (p = 0.047) were found in patients without nutritional support. Septic patients presented an important inadequacy of retinol and beta-carotene. The present study bring elements to the elaboration/review of the nutritional protocol directed to the group studied, especially as regards vitamin A intake.

Beyond the VAD: Human Factors Engineering for Mechanically Assisted Circulation in the 21st Century.

PubMed

Throckmorton, Amy L; Patel-Raman, Sonna M; Fox, Carson S; Bass, Ellen J

2016-06-01

Thousands of ventricular assist devices (VADs) currently provide circulatory support to patients worldwide, and dozens of heart pump designs for adults and pediatric patients are under various stages of development in preparation for translation to clinical use. The successful bench-to-bedside development of a VAD involves a structured evaluation of possible system states, including human interaction with the device and auxiliary component usage in the hospital or home environment. In this study, we review the literature and present the current landscape of preclinical design and assessment, decision support tools and procedures, and patient-centered therapy. Gaps of knowledge are identified. The study findings support the need for more attention to user-centered design approaches for medical devices, such as mechanical circulatory assist systems, that specifically involve detailed qualitative and quantitative assessments of human-device interaction to mitigate risk and failure. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Modulation of radiochemoimmunotherapy-induced B16 melanoma cell death by the pan-caspase inhibitor zVAD-fmk induces anti-tumor immunity in a HMGB1-, nucleotide- and T-cell-dependent manner

PubMed Central

Werthmöller, N; Frey, B; Wunderlich, R; Fietkau, R; Gaipl, U S

2015-01-01

One prerequisite that radiotherapy (RT) and chemotherapy (CT) result in anti-tumor immune responses is triggering of immunogenic cell death forms such as necroptosis. The latter is inducible by inhibition of apoptosis with the pan-caspase inhibitor zVAD-fmk. The design of multimodal therapies that overcome melanoma's resistance to apoptosis is a big challenge of oncoimmunology. As hints exist that immune stimulation by hyperthermia (HT) augments the efficacy of melanoma therapies and that tumors can be sensitized for RT with zVAD-fmk, we asked whether combinations of RT with dacarbazine (DTIC) and/or HT induce immunogenic melanoma cell death and how this is especially influenced by zVAD-fmk. Necroptosis was inducible in poorly immunogenic B16-F10 melanoma cells and zVAD-fmk generally increased melanoma cell necrosis concomitantly with the release of HMGB1. Supernatants (SNs) of melanoma cells whose cell death was modulated with zVAD-fmk induced an upregulation of the activation markers CD86 and MHCII on macrophages. The same was seen on dendritic cells (DCs), but only when zVAD-fmk was added to multimodal tumor treatments including DTIC. DCs of MyD88 KO mice and DCs incubated with SNs containing apyrase did not increase the expression of these activation markers on their surface. The in vivo experiments revealed that zVAD-fmk decreases the tumor growth significantly and results in a significantly reduced tumor infiltration of Tregs when added to multimodal treatment of the tumor with RT, DTIC and HT. Further, a significantly increased DC and CD8+ T-cell infiltration into the tumor and in the draining lymph nodes was induced, as well as an increased expression of IFNγ by CD8+ T cells. However, zVAD-fmk did not further reduce tumor growth in MyD88 KO mice, mice treated with apyrase or RAG KO mice. We conclude that HMGB1, nucleotides and CD8+ T cells mediate zVAD-fmk induced anti-melanoma immune reactions in multimodal therapy settings. PMID:25973681

Comparison of the ligand binding properties of two homologous rat apocellular retinol-binding proteins expressed in Escherichia coli.

PubMed

Levin, M S; Locke, B; Yang, N C; Li, E; Gordon, J I

1988-11-25

Cellular retinol-binding protein (CRBP) and cellular retinol-binding protein II (CRBP II) are 132-residue cytosolic proteins which have 56% amino acid sequence identity and bind all-trans-retinol as their endogenous ligand. They belong to a family of cytoplasmic proteins which have evolved to bind distinct hydrophobic ligands. Their patterns of tissue-specific and developmental regulation are distinct. We have compared the ligand binding properties of rat apo-CRBP and apo-CRBP II that have been expressed in Escherichia coli. Several observations indicate that the E. coli-derived apoproteins are structurally similar to the native rat proteins: they co-migrate on isoelectric focusing gels; and when complexed with all-trans-retinol, their absorption and excitation/emission spectra are nearly identical to those of the authentic rat holoproteins. Comparative lifetime and acrylamide quenching studies suggest that there are differences in the conformations of apo-CRBP and apo-CRBP II. The interaction of E. coli-derived apo-CRBP and apo-CRBP II with a variety of retinoids was analyzed using spectroscopic techniques. Both apoproteins formed high affinity complexes with all-trans-retinol (K'd approximately 10 nM). In direct binding assays, all-trans-retinal bound to both apoproteins (K'd approximately 50 nM for CRBP; K'd approximately 90 nM for CRBP II). However, all-trans-retinal could displace all-trans-retinol bound to CRBP II but not to CRBP. These observations suggests that there is a specific yet distinct interaction between these two proteins and all-trans-retinal. Apo-CRBP and apo-CRBP II did not demonstrate significant binding to either retinoic acid or methyl retinoate, an uncharged derivative of all-trans-retinoic acid. This indicates that the carboxymethyl group of methyl retinoate cannot be sterically accommodated in their binding pockets and that failure to bind retinoic acid probably is not simply due to the negative charge of its C-15 carboxylate group

In vitro and in vivo percutaneous absorption of retinol from cosmetic formulations: Significance of the skin reservoir and prediction of systemic absorption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yourick, Jeffrey J.; Jung, Connie T.; Bronaugh, Robert L.

2008-08-15

The percutaneous absorption of retinol (Vitamin A) from cosmetic formulations was studied to predict systemic absorption and to understand the significance of the skin reservoir in in vitro absorption studies. Viable skin from fuzzy rat or human subjects was assembled in flow-through diffusion cells for in vitro absorption studies. In vivo absorption studies using fuzzy rats were performed in glass metabolism cages for collection of urine, feces, and body content. Retinol (0.3%) formulations (hydroalcoholic gel and oil-in-water emulsion) containing {sup 3}H-retinol were applied and absorption was measured at 24 or 72 h. All percentages reported are % of applied dose.more » In vitro studies using human skin and the gel and emulsion vehicles found 0.3 and 1.3% retinol, respectively, in receptor fluid at 24 h. Levels of absorption in the receptor fluid increased over 72 h with the gel and emulsion vehicles. Using the gel vehicle, in vitro rat skin studies found 23% in skin and 6% in receptor fluid at 24 h, while 72-h studies found 18% in skin and 13% in receptor fluid. Thus, significant amounts of retinol remained in rat skin at 24 h and decreased over 72 h, with proportional increases in receptor fluid. In vivo rat studies with the gel found 4% systemic absorption of retinol after 24 h and systemic absorption did not increase at 72 h. Retinol remaining in rat skin after in vivo application was 18% and 13% of the applied dermal dose after 24 and 72 h, respectively. Similar observations were made with the oil-in water emulsion vehicle in the rat. Retinol formed a reservoir in rat skin both in vivo and in vitro. Little additional retinol was bioavailable after 24 h. Comparison of these in vitro and in vivo results for absorption through rat skin indicates that the 24-h in vitro receptor fluid value accurately estimated 24-h in vivo systemic absorption. Therefore, the best single estimate of retinol systemic absorption from in vitro human skin studies is the 24-h

Innovative approaches to vitamin A assessment.

PubMed

Craft, N E

2001-05-01

The health and sight of millions of children are compromised each year as a consequence of vitamin A (VA) deficiency. Serum retinol is the most commonly used indicator of VA status. Unfortunately, its use is impractical for national surveys because it involves collection of venous blood, centrifugation and frozen storage before analysis. To make VA assessment more practical, we have developed approaches incorporating dried blood spots (DBS) or portable instrumentation. DBS have been used as a sample matrix to screen neonates for many biochemical compounds. Until recently, it was not thought that VA was stable in DBS. However, we demonstrated that the measure of DBS retinol correlates well with serum retinol in both healthy adults (r(2) = 0.88-0.90) and compromised populations (r(2) = 0.73-0.84). Compared with serum retinol, the sensitivity and specificity of detecting VA deficiency by DBS retinol range from 73 to 93% and from 90 to 100%, respectively. Although few data are available, retinol binding protein (RBP) can also be measured in DBS. RBP has been used as a surrogate marker for serum retinol. Correlations coefficients (r(2)) between serum RBP and serum retinol range from 0.4 to 0.8. In addition, work has been done to develop portable instrumentation to measure VA status in the field. A fluorometer has been optimized for VA fluorescence and is linear into the deficient range for the direct fluorimetric measurement of serum holo-RBP. Progress is being made to use the instrument to directly measure holo-RBP in a drop of whole blood.

Disruption of Retinol (Vitamin A) Signaling by Phthalate Esters: SAR and Mechanism Studies.

PubMed

Chen, Yanling; Reese, David H

2016-01-01

A spectrum of reproductive system anomalies (cryptorchidism, hypospadias, dysgenesis of Wolffian duct-derived tissues and prostate, and reduced sperm production) in male rats exposed in utero to phthalate esters (PEs) are thought to be caused by PE inhibition of fetal testosterone production. Recently, dibutyl and dipentyl phthalate (DBuP, DPnP) were shown to disrupt the retinol signaling pathway (RSP) in mouse pluripotent P19 embryonal carcinoma cells in vitro. The RSP regulates the synthesis and cellular levels of retinoic acid (RA), the active metabolite of retinol (vitamin A). In this new study, a total of 26 di- and mono-esters were screened to identify additional phthalate structures that disrupt the RSP and explore their mechanisms of action. The most potent PEs, those causing > 50% inhibition, contained aryl and cycloalkane groups or C4-C6 alkyl ester chains and were the same PEs reported to cause malformations in utero. They shared similar lipid solubility; logP values were between 4 and 6 and, except for PEs with butyl and phenyl groups, were stable for prolonged periods in culture. Mono- and cognate di-esters varied in ability to disrupt the RSP; e.g., DEHP was inactive but its monoester was active while DBuP was active yet its monoester was inactive. DBuP and dibenzyl phthalate both disrupted the synthesis of RA from retinol but not the ability of RA to activate gene transcription. Both PEs also disrupted the RSP in C3H10T1/2 multipotent mesenchymal stem cells. Based on this in vitro study showing that some PEs disrupt retinol signaling and previous in vivo studies that vitamin A/RA deficiency and PEs both cause strikingly similar anomalies in the male rat reproductive system, we propose that PE-mediated inhibition of testosterone and RA synthesis in utero are both causes of malformations in male rat offspring.

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

PubMed

Talsma, Elise F; Brouwer, Inge D; Verhoef, Hans; Mbera, Gloria N K; Mwangi, Alice M; Demir, Ayşe Y; Maziya-Dixon, Busie; Boy, Erick; Zimmermann, Michael B; Melse-Boonstra, Alida

2016-01-01

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

An immunohistochemical study of retinol-binding protein (RBP) in livers of free-living polar bears (Ursus maritimus) from east Greenland.

PubMed

Heier, Annabelle; Sonne, Christian; Gröne, Andrea; Leifsson, Pall S; Dietz, Rune; Born, Erik W; Bacciarini, Luca N

2005-09-01

From 1999 to 2002 samples from 114 free-ranging polar bears (Ursus maritimus) were collected in the municipality of Scoresby Sound, East Greenland, to detect levels of organochlorines and potential histopathologic changes. Livers of 16 female polar bears from this group were evaluated histologically and analyzed for hepatic retinol-binding protein by immunohistochemistry. Retinol-binding protein is the main transport protein for retinol, an important vitamin A metabolite in the polar bear. Only mild pathologic changes were noted on histologic evaluation of the livers. Small lymphocytic or lymphohistiocytic infiltrates were present in all the livers. Small lipid granulomas, mild periportal fibrosis, and bile duct proliferation were found in several cases. Immunohistochemistry for retinol-binding protein of hepatic tissue from free-ranging polar bears showed no distinct difference in staining intensity by a number of criteria: age, season (fasting and nonfasting), or lactation status. The staining was diffuse to finely stippled in the cytoplasm and showed very little variation among the animals. Because of the lack of macroscopic changes and the absence of severe histologic liver lesions, these polar bears were assumed to be healthy. The diffuse cytoplasmic retinol-binding protein staining in hepatocytes of free-ranging polar bears varies markedly from the prominent granular, less intense staining of captive polar bears investigated previously.

A Polymorphism in the Retinol Binding Protein 4 Gene is Not Associated with Gestational Diabetes Mellitus in Several Different Ethnic Groups

PubMed Central

Urschitz, Johann; Sultan, Omar; Ward, Kenneth

2011-01-01

Objective Various Asian and Pacifific Islander groups have higher prevalence rates of type 2 diabetes and gestational diabetes. This increased incidence is likely to include genetic factors. Single nucleotide polymorphisms in the retinol binding protein 4 gene have been linked to the occurrence of type 2 diabetes. Hypothesizing a link between retinol binding protein 4 and gestational diabetes, we performed a candidate gene study to look for an association between an important retinol binding protein gene polymorphism (rs3758539) and gestational diabetes. Study Design Blood was collected from Caucasian, Asian, and Pacific Islander women diagnosed with gestational diabetes and from ethnically matched non-diabetic controls. DNA was extracted and real time PCR technology (TaqMan, Applied Biosystems) used to screen for the rs3758539 single nucleotide polymorphism located 5′ of exon 1 of the retinol binding protein 4 gene. Results Genotype and allele frequencies in the controls and gestational diabetes cases were tested using chi-square contingency tests. Genotype frequencies were in Hardy-Weinberg equilibrium. There was no association between the rs3758539 retinol binding protein 4 single nucleotide polymorphism and gestational diabetes in the Caucasian, Filipino, or Pacific Islander groups. Conclusion Interestingly, the rs3758539 retinol binding protein 4 single nucleotide polymorphism was not found to be associated with gestational diabetes. The absence of association suggests that gestational and type 2 diabetes may have more divergent molecular pathophysiology than previously suspected. PMID:21886308

Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

PubMed

Gessner, D K; Most, E; Schlegel, G; Kupczyk, K; Schwarz, F J; Eder, K

2015-12-01

This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, Holstein cows received daily from 3 weeks ante-partum to 14 weeks post-partum either 172 g of a CLA-free rumen-protected control fat (control group, n = 20) or the same amount of a rumen-protected CLA fat, supplying 4.3 g of cis-9, trans-11 CLA and 3.8 g of trans-10, cis-12 CLA per d (CLA group, n = 20). Milk samples (collected at weeks 1, 3, 5, 8 and 11 of lactation) were analysed for retinol, α- and γ-tocopherol concentrations. Milk of cows supplemented with CLA had higher concentrations of retinol (+34%), α-tocopherol (+44%) and γ-tocopherol (+21%) than milk of control cows (p < 0.05). The daily output of these vitamins via milk was also greater in cows of the CLA group than in cows of the control group (+36, 50 and 24% for retinol, α-tocopherol and γ-tocopherol, respectively, p < 0.05). In agreement with higher concentrations of tocopherols, concentrations of thiobarbituric acid-reactive substances, determined in milk of week 5, were lower in cows of the CLA group than in control cows, indicative of a lower susceptibility of milk lipids to peroxidation. Plasma concentrations of retinol and α-tocopherol, determined at 1 and 5 weeks post-partum, were not different between the two groups of cows. In conclusion, this study shows that supplementing dairy cows with a moderate amount of CLA causes an increase of the concentrations of vitamins A and E in the milk and results in an increased output of those vitamins via milk. These effects might be beneficial with respect to the nutritional value of dairy products and the susceptibility of milk fat to oxidative deterioration. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

A simultaneous quantitative method for vitamins A, D and E in human serum using liquid chromatography-tandem mass spectrometry.

PubMed

Albahrani, Ali A; Rotarou, Victor; Roche, Peter J; Greaves, Ronda F

2016-05-01

Non-classical roles of fat-soluble vitamins (FSVs) in many pathologies including cancer have been identified. There is also evidence of hormonal interactions between two of these vitamins, A and D. As a result of this enhanced clinical association with disease, translational clinical research and laboratory requests for FSV measurement has significantly increased. However there are still gaps in the analytical methods available for the measurement of these vitamins. This study aimed to develop a method for simultaneous quantification of 25-hydroxyvitamin-D2 (25-OHD2), 25-hydroxyvitamin-D3 (25-OHD3) and its 3-epimer (epi-25-OHD3), retinol and α-tocopherol in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The procedure was developed and validated across two LC-MS/MS platforms, using commercial calibrators referenced to certified reference materials, controls, and deuterated internal standards. The samples were prepared by liquid-liquid extraction prior to injection and LC separation (using a Pursuit-PFP column) on two Agilent MS/MS systems (6410 and 6490) in electrospray ionisation positive mode with multiple reaction monitoring. Identification and quantification of 25-OHD3 from its 3-epimer as well as 25-OHD2, retinol and α-tocopherol were achieved. The dynamic ranges were 4-160 nmol/L for 25-OHD2 and epi-25-OHD3, 4-200 nmol/L for 25-OHD3, 0.1-4.0μmol/L for retinol and 4-70μmol/L for α-tocopherol with correlation (r(2)) of 0.997-0.998. Based on participation in an external quality assurance program, the overall performance of the simultaneous methods were: imprecision (CV%) and inaccuracy (average bias) 3.0% and 3.2 nmol/L, respectively, for 25-OHD3; 5.0% and 0.04μmol/L, respectively, for retinol; and 4.7% and 0.2μmol/L, respectively, for α-tocopherol. In summary, two simple LC-MS/MS methods were successfully developed and validated for the simultaneous quantification of the three vitamin D metabolites (25-OHD2, 25-OHD3 and 3

Updating the Evidence on the Association between Serum Cholesterol and Risk of Late-Life Dementia: Review and Meta-Analysis.

PubMed

Anstey, Kaarin J; Ashby-Mitchell, Kimberly; Peters, Ruth

2017-01-01

Cohort studies have reported that midlife high total serum cholesterol (TC) is associated with increased risk of Alzheimer's disease (AD) in late-life but findings have been based on few studies and previous reviews have been limited by a lack of compatible data. We synthesized all high quality data from cohort studies reporting on the association between total serum cholesterol measured and late-life cognitive outcomes including Alzheimer's disease (AD), vascular dementia (VaD), any dementia, mild cognitive impairment (MCI), and cognitive decline. The literature was searched up to October 2016 using a registered protocol. Thirty-four articles meeting study criteria were identified. Seventeen studies published from 1996 to 2014, including 23,338 participants were included in meta-analyses. Relative risk of developing AD for adults with high TC in midlife was 2.14 (95% CI 1.33-3.44) compared with normal cholesterol. Individual studies that could not be pooled also reported high TC in midlife increased the risk of MCI and cognitive decline in late-life. High TC in late-life was not associated with MCI, AD, VaD, any dementia, or cognitive decline. Late-life measured HDL cholesterol and triglycerides were not associated with increased risk of VaD, and HDL was not associated with risk of MCI, AD, or any dementia. There were insufficient data to examine other cholesterol sub-fractions, sex differences, or APOE interactions. Significant gaps in the literature regarding TC and late-life dementia remain. Evidence suggests that high midlife TC increases risk of late-life AD, and may correlate with the onset of AD pathology.

Biochemical Properties of Purified Human Retinol Dehydrogenase 12 (RDH12): Catalytic Efficiency toward Retinoids and C9 Aldehydes and Effects of Cellular Retinol-Binding Protein Type I (CRBPI) and Cellular Retinaldehyde-Binding Protein (CRALBP) on the Oxidation and Reduction of Retinoids†

PubMed Central

Belyaeva, Olga V.; Korkina, Olga V.; Stetsenko, Anton V.; Kim, Tom; Nelson, Peter S.; Kedishvili, Natalia Y.

2008-01-01

Retinol dehydrogenase 12 (RDH12) is a novel member of the short-chain dehydrogenase/reductase superfamily of proteins that was recently linked to Leber’s congenital amaurosis 3 (LCA). We report the first biochemical characterization of purified human RDH12 and analysis of its expression in human tissues. RDH12 exhibits ~2000-fold lower Km values for NADP+ and NADPH than for NAD+ and NADH and recognizes both retinoids and lipid peroxidation products (C9 aldehydes) as substrates. The kcat values of RDH12 for retinaldehydes and C9 aldehydes are similar, but the Km values are, in general, lower for retinoids. The enzyme exhibits the highest catalytic efficiency for all-trans-retinal (kcat/Km ~900 min−1 μM−1), followed by 11-cis-retinal (450 min−1 mM−1) and 9-cis-retinal (100 min−1 mM−1). Analysis of RDH12 activity toward retinoids in the presence of cellular retinol-binding protein (CRBP) type I or cellular retinaldehyde-binding protein (CRALBP) suggests that RDH12 utilizes the unbound forms of all-trans- and 11-cis-retinoids. As a result, the widely expressed CRBPI, which binds all-trans-retinol with much higher affinity than all-trans-retinaldehyde, restricts the oxidation of all-trans-retinol by RDH12, but has little effect on the reduction of all-trans-retinaldehyde, and CRALBP inhibits the reduction of 11-cis-retinal stronger than the oxidation of 11-cis-retinol, in accord with its higher affinity for 11-cis-retinal. Together, the tissue distribution of RDH12 and its catalytic properties suggest that, in most tissues, RDH12 primarily contributes to the reduction of all-trans-retinaldehyde; however, at saturating concentrations of peroxidic aldehydes in the cells undergoing oxidative stress, for example, photoreceptors, RDH12 might also play a role in detoxification of lipid peroxidation products. PMID:15865448

Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status.

PubMed

Ribaya-Mercado, J D; Solon, F S; Solon, M A; Cabal-Barza, M A; Perfecto, C S; Tang, G; Solon, J A; Fjeld, C R; Russell, R M

2000-08-01

It is important to understand the factors affecting strategies to improve the vitamin A status of populations. We reported previously that a 3-d deuterated-retinol-dilution (DRD) procedure might be used to indicate total body stores of vitamin A. We studied the ability of 3-d DRD to detect changes in the body pool size of vitamin A and the effect of vitamin A status on the bioconversion of plant carotenoids to vitamin A. Two separate, unrelated studies were conducted in 7-13-y-old children with poor or marginal serum retinol concentrations (0.32-0.93 micromol/L) by feeding them controlled diets daily for 5 d/wk for 12 wk, after treatment with an anthelmintic drug. In school 1 (n = 27), lunch and 2 snacks that were provided at school contained 2258 retinol equivalents/d (mostly from orange fruit and vegetables) and 5.3 MJ/d from 33 g fat, 37 g protein, and 209 g carbohydrates; in school 2 (n = 25), 2 snacks provided 2.5 MJ/d from 9.4 g fat, 9.6 g protein, and 119 g carbohydrates, but no carotenes. In school 1, mean serum beta-carotene increased from 0.12 to 0.62 micromol/L (P = 0.0001) and serum retinol increased from 0.68 to 1. 06 micromol/L (P = 0.0001). In school 2, serum beta-carotene increased from 0.06 to 0.11 micromol/L (P = 0.0001) and serum retinol increased from 0.66 to 0.86 micromol/L (P = 0.0001). In school 1, but not school 2, improvement in serum retinol varied inversely with baseline retinol (r = -0.38, P = 0.048). In both schools, 3-d DRD showed reductions in the ratio of serum deuterated to nondeuterated retinol (D:H retinol) postintervention, denoting improvements in vitamin A status; the higher D:H retinol (ie, the poorer the status) at baseline, the greater the reduction in D:H retinol postintervention (school 1: r = -0.99, P = 0.0001; school 2: r = -0.89, P = 0.0001). Three-day DRD can detect changes in the body pool size of vitamin A, although a predictive equation to quantitate total body stores of vitamin A with the use of 3-d data needs to

Effect of vitamin supplementation on breast milk concentrations of retinol, carotenoids, and tocopherols in HIV-infected Tanzanian women

PubMed Central

Webb, Aimee L.; Aboud, Said; Furtado, Jeremy; Murrin, Clare; Campos, Hannia; Fawzi, Wafaie W.; Villamor, Eduardo

2011-01-01

Background The effect of daily prenatal and postnatal vitamin supplementation on concentrations of breast milk nutrients is not well characterized in HIV-infected women. Objective We examined the impact of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, carotenoids, and tocopherols during the first year post-partum among 626 HIV-infected Tanzanian women. Design We conducted a randomized, double-blind, placebo controlled trial. Women were assigned to one of four daily oral supplements: vitamin A + β-carotene (VA+BC); multivitamins (B, C, E (MV)); MV+VA+BC; or placebo. Concentrations of breast milk nutrients were determined by HPLC at birth and every 3 mo thereafter. Results Supplementation with VA+BC increased concentrations of retinol, β-carotene, and α-carotene at delivery by 4799, 1791, and 84 nmol/L, respectively, compared to no VA+BC (all p<0.0001). MV supplementation did not increase concentrations of α-tocopherol or δ-tocopherol at delivery but significantly decreased concentrations of breast milk γ-tocopherol and retinol. Although concentrations of all nutrients decreased significantly by 3 months postpartum, retinol, α-carotene, and β-carotene concentrations were significantly higher among those receiving VA+BC at 3, 6, and 12 mo compared to no VA+BC. Alpha tocopherol was significantly higher, while γ-tocopherol concentrations were significantly lower, among women receiving MV compared to no MV at 3, 6, and 12 mo post-partum. Conclusions Sustained supplementation of HIV-infected breastfeeding mothers with MV could be a safe and effective intervention to improve vitamin E concentrations in breast milk. VA+BC supplementation increases concentrations of breast milk retinol but it is not recommended in HIV-infected mothers due to the elevated risk of vertical transmission. PMID:17940544

Effect of vitamin supplementation on breast milk concentrations of retinol, carotenoids and tocopherols in HIV-infected Tanzanian women.

PubMed

Webb, A L; Aboud, S; Furtado, J; Murrin, C; Campos, H; Fawzi, W W; Villamor, E

2009-03-01

The effect of daily prenatal and postnatal vitamin supplementation on concentrations of breast milk nutrients is not well characterized in HIV-infected women. We examined the impact of vitamin supplementation during pregnancy and lactation on breast milk concentrations of retinol, carotenoids and tocopherols during the first year postpartum among 626 HIV-infected Tanzanian women. We conducted a randomized, double-blind, placebo-controlled trial. Women were assigned to one of four daily oral supplements: vitamin A+beta-carotene (VA+BC); multivitamins (MV; B, C and E); MV+VA+BC or placebo. Concentrations of breast milk nutrients were determined by high-performance liquid chromatography at birth and every 3 months thereafter. Supplementation with VA+BC increased concentrations of retinol, beta-carotene and alpha-carotene at delivery by 4799, 1791 and 84 nmol l(-1), respectively, compared to no VA+BC (all P<0.0001). MV supplementation did not increase concentrations of alpha-tocopherol or delta-tocopherol at delivery but significantly decreased concentrations of breast milk gamma-tocopherol and retinol. Although concentrations of all nutrients decreased significantly by 3 months postpartum, retinol, alpha-carotene and beta-carotene concentrations were significantly higher among those receiving VA+BC at 3, 6 and 12 months compared to no VA+BC. alpha-Tocopherol was significantly higher, while gamma-tocopherol concentrations were significantly lower, among women receiving MV compared to no MV at 3, 6 and 12 months postpartum. Sustained supplementation of HIV-infected breastfeeding mothers with MV could be a safe and effective intervention to improve vitamin E concentrations in breast milk. VA+BC supplementation increases concentrations of breast milk retinol but it is not recommended in HIV-infected mothers due to the elevated risk of vertical transmission.

Nitrofen interferes with trophoblastic expression of retinol-binding protein and transthyretin during lung morphogenesis in the nitrofen-induced congenital diaphragmatic hernia model.

PubMed

Kutasy, Balazs; Gosemann, Jan H; Doi, Takashi; Fujiwara, Naho; Friedmacher, Florian; Puri, Prem

2012-02-01

Retinoids play a key role in lung development. Retinoid signaling pathway has been shown to be disrupted in the nitrofen model of congenital diaphragmatic hernia (CDH) but the exact mechanism is not clearly understood. Retinol-binding protein (RBP) and transthyretin (TTR) are transport proteins for delivery of retinol to the tissues via circulation. Previous studies have shown that pulmonary retinol levels are decreased during lung morphogenesis in the nitrofen CDH model. In human newborns with CDH, both retinol and RBP levels are decreased. It has been reported that maternal RBP does not cross the placenta and the fetus produces its own RBP by trophoblast. RBP and TTR synthesized in the fetus are essential for retinol transport to the developing organs including lung morphogenesis. We hypothesized that nitrofen interferes with the trophoblastic expression of RBP and TTR during lung morphogenesis and designed this study to examine the trophoblastic expression of RBP and TTR, and the total level of RBP and TTR in the lung in the nitrofen model of CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs and placenta harvested on D21 and divided into two groups: control (n = 8) and nitrofen with CDH (n = 8). Total lung RBP and TTR levels using protein extraction were compared with enzyme linked immunoassay (ELISA). Immunohistochemistry was performed to evaluate trophoblastic RBP and TTR expression. Total protein levels of lung RBP and TTR were significantly lower in CDH (0.26 ± 0.003 and 6.4 ± 0.5 μg/mL) compared with controls (0.4 ± 0.001 and 9.9 ± 1.6 μg/mL, p < 0.05). In the control group, immunohistochemical staining showed strong immunoreactivity of RBP and TTR in the trophoblast compared to CDH group. Decreased trophoblast expression of retinol transport proteins suggest that nitrofen may interfere with the fetal retinol transport resulting in reduced pulmonary RBP and TTR levels and causing pulmonary

Vitamin A Deficiency Due to Selective Eating as a Cause of Blindness in a High-Income Setting.

PubMed

Martini, Silvia; Rizzello, Angela; Corsini, Ilaria; Romanin, Benedetta; Fiorentino, Michelangelo; Grandi, Sara; Bergamaschi, Rosalba

2018-04-01

Vitamin A is a fat-soluble micronutrient involved in the regulation of several physiologic functions, such as visual acuity, epithelial tissue integrity, immune response, and gene expression, thus playing a crucial role in childhood growth and development. Although vitamin A deficiency (VAD) in resource-limited settings is still an actual issue and represents the leading cause of preventable childhood blindness, its occurrence in high-income countries is rare, although possibly underdiagnosed because of its nonspecific early manifestations. A good awareness of VAD symptoms and risk factors could aid its early diagnosis, which is fundamental to undertake a prompt treatment and to prevent ocular complications. Nevertheless, the role of restrictive dietary habits, increasingly common in developed countries, is often overlooked in infants and children. We present a case of VAD with permanent ocular sequelae in a 5-year-old girl from a high-income country. In the case described, VAD ensued from a highly restricted diet, mainly limited to oat milk, which had been followed for more than 2 years. This child presented with ocular symptoms, opportunistic infection, anemia, poor growth, and a diffuse squamous metaplasia of the bladder; after commencing retinol supplementation, a gradual healing of clinical VAD manifestations occurred, with the exception of the ocular sequelae, which resulted in irreversible visual loss. Copyright © 2018 by the American Academy of Pediatrics.

Identification of compounds that modulate retinol signaling using a cell-based qHTS assay

PubMed Central

Chen, Yanling; Sakamuru, Srilatha; Huang, Ruili; Reese, David H.; Xia, Menghang

2016-01-01

In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling. PMID:26820057

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

PubMed Central

Schleinitz, Dorit

2015-01-01

Adipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the “protective” allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed. PMID:26859657

13-cis-retinoic acid competitively inhibits 3 alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands?

PubMed

Karlsson, Teresa; Vahlquist, Anders; Kedishvili, Natalia; Törmä, Hans

2003-03-28

Retinol dehydrogenase-4 (RoDH-4) converts retinol and 13-cis-retinol to corresponding aldehydes in human liver and skin in the presence of NAD(+). RoDH-4 also converts 3 alpha-androstanediol and androsterone into dihydrotestosterone and androstanedione, which may stimulate sebum secretion. This oxidative 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity of RoDH-4 is competitively inhibited by retinol and 13-cis-retinol. Here, we further examine the substrate specificity of RoDH-4 and the inhibition of its 3 alpha-HSD activity by retinoids. Recombinant RoDH-4 oxidized 3,4-didehydroretinol-a major form of vitamin A in the skin-to its corresponding aldehyde. 13-cis-retinoic acid (isotretinoin), 3,4-didehydroretinoic acid, and 3,4-didehydroretinol, but not all-trans-retinoic acid or the synthetic retinoids acitretin and adapalene, were potent competitive inhibitors of the oxidative 3 alpha-HSD activity of RoDH-4, i.e., reduced the formation of dihydrotestosterone and androstandione in vitro. Extrapolated to the in vivo situation, this effect might explain the unique sebosuppressive effect of isotretinoin when treating acne.

[Nutritional evaluation, micronutrient deficiencies and anemia among female adolescents in an urban and a rural zone from Zulia state, Venezuela].

PubMed

Ortega, Pablo; Leal, Jorymar; Amaya, Daysi; Chávez, Carlos

2010-03-01

Female adolescents in reproductive age are a susceptible group to anemia and micronutrient deficiencies. The objective of this study was to know the nutritional, anthropometric and dietetic status, the prevalence of anemia, depletion of iron deposits (FeD) and Vitamin A deficiency (VAD) in female adolescents. Seventy-eight not pregnant female adolescents (15.9 +/- 1.1 years old), from an urban and a periurban zone of Maracaibo, and a rural zone near this city, without infectious and inflammatory processes, were analyzed. Anemia in adolescents was considered when Hb < 120 g/L; FeD: ferritin < 12 microg/L; VAD serum retinol <20 microg/dL; risk of VAD (RVAD) 20-30 microg/dL. The data were analyzed with the SAS program and expressed as Means +/- Standard Deviations, statistical significance was considered when p < 0.05. The percentage of caloric and protean adjustment in all groups was below the daily requirements. Adolescents from the rural zone showed significant lower values of weight (p = 0.0024), height (p = 0.0027), body mass index BMI (p = 0.0487), fatty area (p = 0.0183), MCV (p = 0.0241), MCH (p = 0.0488), MHCC (p = 0.0228), and the highest prevalence of anemia (66.67%), anemia+FeD (33.33%), and anemia+FeD+RVAD (5.56%), with respect to adolescents from the urban zone. Although, anemic adolescents from the rural zone showed a non significant decrease of the iron percentage adjustment. Iron requirements are increased during adolescence, reaching a maximum at the peak of growth and remaining almost as high in girls after menarche, to replace menstrual losses. The low iron status among adolescents from the rural zone determine that this is a high risk group to anemia and FeD and they require prevention, control and suplementation strategies.

Procedure for the determination of retinol and alpha-tocopherol in poultry tissues using capillary gas chromatography with solvent venting injection.

PubMed

Maraschiello, C; García Regueiro, J A

1998-08-28

A procedure designed for the determination of retinol (vitamin A) and alpha-tocopherol (vitamin E) in poultry tissues has been developed. The procedure involves lipid extraction, saponification, solid-phase clean-up and capillary gas chromatography (cGC). Retinol and alpha-tocopherol were determined separately by cGC-flame ionisation detection using a fused-silica open tubular capillary column, 30 m x 0.25 mm I.D. coated with 5% phenylmethylsilicone and with a film thickness of 0.25 micron. Solvent extraction followed by saponification were sufficient to provide a purified extract which was directly analyzed for retinol by cGC in the solvent venting mode. However, in order to accurately determine alpha-tocopherol by cGC, further purification of the extract by solid-phase extraction was necessary. A silica SPE column was used to remove interfering cholesterol from the extract. alpha-Tocopherol was analyzed in its derivatized form. Absolute and relative recoveries for both vitamins from spiked samples were evaluated. Absolute and relative recoveries ranging from 80 to 95% were obtained for both compounds. 5 alpha-Cholestane and alpha-tocopheryl acetate were used as internal standards. Poultry muscle meat and liver tissue were analyzed for their retinol and alpha-tocopherol content and the peaks detected by cGC were confirmed by cGC-mass spectrometry.

Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice*

PubMed Central

Sahu, Bhubanananda; Sun, Wenyu; Perusek, Lindsay; Parmar, Vipulkumar; Le, Yun-Zheng; Griswold, Michael D.; Palczewski, Krzysztof; Maeda, Akiko

2015-01-01

Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5−/−Rdh11−/− mice as compared with Rdh5−/− mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5−/− and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision. PMID:26391396

Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene.

PubMed

Huang, Peiwu; Ren, Xiaohu; Huang, Zhijun; Yang, Xifei; Hong, Wenxu; Zhang, Yanfang; Zhang, Hang; Liu, Wei; Huang, Haiyan; Huang, Xinfeng; Wu, Desheng; Yang, Linqing; Tang, Haiyan; Zhou, Li; Li, Xuan; Liu, Jianjun

2014-08-17

Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease. Copyright © 2014. Published by Elsevier Ireland Ltd.

Retinol, α-tocopherol, and selected minerals in breast milk of lactating women with full-term infants in South Korea

PubMed Central

Kim, Hyesook; Jung, Byung-Mun; Lee, Bum-Noh; Kim, Yun-Je

2017-01-01

BACKGROUND/OBJECTIVES This study was performed to measure fat-soluble vitamins and minerals in breast milk of Korean lactating mothers who exclusively breastfed their babies. SUBJECTS/METHODS Breast milk samples were collected from 334 mothers. Concentrations of retinol and α-tocopherol were analyzed by high performance liquid chromatography ultraviolet spectrometry while concentrations of minerals were measured by inductively coupled plasma optical emission spectrometry. RESULTS Retinol and α-tocopherol contents of breast milk were 39.58 ± 19.64 µg/dL and 0.23 ± 0.13 mg/dL, respectively. Average sodium, potassium, calcium, phosphorus, and magnesium levels in breast milk were 11.11 ± 5.16, 38.56 ± 9.01, 27.87 ± 6.10, 13.56 ± 3.30, and 3.05 ± 0.65 mg/dL, respectively. Contents of trace elements such as iron, zinc, copper, and manganese were 40.26 ± 46.21, 98.40 ± 62.47, 24.09 ± 9.03, and 0.90 ± 1.63 µg/dL, respectively. Fat-soluble vitamin concentration was positively correlated with total fat in milk samples, but no significant differences were observed in levels of retinol, α-tocopherol, or minerals based on whether or not lactating women were taking dietary supplements. CONCLUSIONS Micronutrient contents of breast milk samples from Korean lactating women were comparable to those of other nations. Retinol and α-tocopherol levels were correlated and also with total fat in breast milk. PMID:28194267

Involvement of retinol dehydrogenase 10 in embryonic patterning and rescue of its loss of function by maternal retinaldehyde treatment

PubMed Central

Rhinn, Muriel; Schuhbaur, Brigitte; Niederreither, Karen; Dollé, Pascal

2011-01-01

Retinoic acid (RA), an active vitamin A metabolite, is a key signaling molecule in vertebrate embryos. Morphogenetic RA gradients are thought to be set up by tissue-specific actions of retinaldehyde dehydrogenases (RALDHs) and catabolizing enzymes. According to the species, two enzymatic pathways (β-carotene cleavage and retinol oxidation) generate retinaldehyde, the substrate of RALDHs. Placental species depend on maternal retinol transferred to the embryo. The retinol-to-retinaldehyde conversion was thought to be achieved by several redundant enzymes; however, a random mutagenesis screen identified retinol dehydrogenase 10 [Rdh10Trex allele; Sandell LL, et al. (2007) Genes Dev 21:1113–1124] as responsible for a homozygous lethal phenotype with features of RA deficiency. We report here the production and characterization of unique murine Rdh10 loss-of-function alleles generated by gene targeting. We show that although Rdh10−/− mutants die at an earlier stage than Rdh10Trex mutants, their molecular patterning defects do not reflect a complete state of RA deficiency. Furthermore, we were able to correct most developmental abnormalities by administering retinaldehyde to pregnant mothers, thereby obtaining viable Rdh10−/− mutants. This demonstrates the rescue of an embryonic lethal phenotype by simple maternal administration of the missing retinoid compound. These results underscore the importance of maternal retinoids in preventing congenital birth defects, and lead to a revised model of the importance of RDH10 and RALDHs in controlling embryonic RA distribution. PMID:21930923

Retinol values in the plasma of the Arabian camel (Camelus dromedarius) and the influence of aflatoxicosis.

PubMed

Abbas, T A; Ali, B H

2001-08-01

The normal values are reported of the concentration of vitamin A (retinol) in the plasma of 44 male and female adult camels (Camelus dromedarius) in the United Arab Emirates. The concentrations of the vitamin in the plasma of eight camels of both sexes afflicted with aflatoxicosis were also determined. The mean concentration (+/-SD) of the vitamin in healthy camels was 460.1 +/- 49.3 ng/L. Sex had no significant effect on the concentration of the vitamin. Camels with aflatoxicosis had a mean concentration of retinol in the plasma of 243.4 +/- 32.3 ng/L. The concentrations of aflatoxins in the liver and ruminal contents of these animals were 18.2 +/- 1.3 and 243.4 microg/kg, respectively.

Risk factors for vitamin A deficiency in rural areas of the Philippines.

PubMed

Rosen, D S; Sloan, N L; del Rosario, A; de la Paz, T C

1994-04-01

A survey of vitamin A deficiency was conducted in January and February 1991 on the island of Mindanao in the Philippines. Demographic, serum retinol, conjunctival impression cytology (CIC), anthropometric, and dietary data were collected from 248 preschool children in five randomly selected rural communities on the outskirts of Davao City. Twenty-nine per cent [95 per cent confidence interval (CI) 23-35 per cent] of preschool children had serum retinol levels below 20 micrograms/dl. Nearly 6 per cent (95 per cent CI 3-9 per cent) had serum retinol levels below 10 micrograms/dl. Thirty-two per cent (95 per cent CI 25-38 per cent) had abnormal CIC findings. The correlation between serum retinol and CIC results was poor. Recent history of diarrheal disease, reported night blindness, maternal education less than 9 years, and infrequent consumption of eggs, mangoes, and liver were associated with increased risk of vitamin A deficiency.

Comparison of methods of assessing vitamin A status in children.

PubMed

Makdani, D; Sowell, A L; Nelson, J D; Apgar, J; Gunter, E W; Hegar, A; Potts, W; Rao, D; Wilcox, A; Smith, J C

1996-10-01

A study of children (2-8 years; n = 613) in Belize, Central America, was conducted to determine what proportion of the children might be at risk of vitamin A (vit A) deficiency. The data provide an opportunity to compare results of three methods of assessing vit A status in a population which was not severely malnourished. Serum retinyl ester concentrations were also determined; their relevance to one of the tests, the relative dose response (RDR) test, is discussed. The three methods of assessing vit A status were: RDR test, fasting serum retinol concentration, and conjunctival impression cytology (CIC). Retinol-binding protein (RBP), serum retinyl esters and serum zinc concentrations were also determined. Inadequate vit A status was indicated for 17% of subjects by the RDR test (14% cutoff), for 24% by fasting serum retinol concentration (< 0.87 mumol/L), and for 49% by "abnormal" CIC score. Retinyl esters constituted 24% of serum retinoids at the time (5 hours after a retinyl palmitate dose) at which the second blood sample is taken for the RDR test. Regression tree analyses (CART) indicated ethnicity was a predictor of RDR score; ethnicity, stunting and age were predictors of fasting serum retinol concentration; ethnicity and stunting were predictors of 0-hour retinyl ester concentration. The three indices of vit A status did not identify the same individuals nor indicate the same percentage of the population to be at risk for vit A deficiency. Increased concentrations of retinyl esters at 5 hours compared to those at 0 hours suggest that insufficient retinol may have been taken up by the liver at 5 hours to release all accumulated retinol-binding protein (RBP) in deficient individuals; prevalence of vit A deficiency might therefore be underestimated by the RDR test. The selection of ethnicity as a predictor of RDR score and of 0-hour retinol and retinyl ester concentrations suggests that factors other than vit A status affect vit A metabolism and may affect

Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF-AICR systematic review of published prospective studies.

PubMed

Abar, Leila; Vieira, Ana Rita; Aune, Dagfinn; Stevens, Christophe; Vingeliene, Snieguole; Navarro Rosenblatt, Deborah A; Chan, Doris; Greenwood, Darren C; Norat, Teresa

2016-08-01

Carotenoids and retinol are considered biomarkers of fruits and vegetables intake, and are of much interest because of their anti-inflammatory and antioxidant properties; however, there is inconsistent evidence regarding their protective effects against lung cancer. We conducted a meta-analysis of prospective studies of blood concentrations of carotenoids and retinol, and lung cancer risk. We identified relevant prospective studies published up to December 2014 by searching the PubMed and several other databases. We calculated summary estimates of lung cancer risk for the highest compared with lowest carotenoid and retinol concentrations and dose-response meta-analyses using random effects models. We used fractional polynomial models to assess potential nonlinear relationships. Seventeen prospective studies (18 publications) including 3603 cases and 458,434 participants were included in the meta-analysis. Blood concentrations of α-carotene, β-carotene, total carotenoids, and retinol were significantly inversely associated with lung cancer risk or mortality. The summary relative risk were 0.66 (95% confidence interval [CI]: 0.55-0.80) per 5 μg/100 mL of α-carotene (studies [n] = 5), 0.84 (95% CI: 0.76-0.94) per 20 μg/100 mL of β-carotene (n = 9), 0.66 (95% CI: 0.54-0.81) per 100 μg/100 mL of total carotenoids (n = 4), and 0.81 (95% CI: 0.73-0.90) per 70 μg/100 mL of retinol (n = 8). In stratified analysis by sex, the significant inverse associations for β-carotene and retinol were observed only in men and not in women. Nonlinear associations were observed for β-carotene, β-cryptoxanthin, and lycopene, with stronger associations observed at lower concentrations. There were not enough data to conduct stratified analyses by smoking. In conclusion, higher blood concentrations of several carotenoids and retinol are associated with reduced lung cancer risk. Further studies in never and former smokers are needed to rule out confounding by smoking

Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins*

PubMed Central

Golczak, Marcin; Kiser, Philip D.; Sears, Avery E.; Lodowski, David T.; Blaner, William S.; Palczewski, Krzysztof

2012-01-01

Lecithin:retinol acyltransferase-like proteins, also referred to as HRAS-like tumor suppressors, comprise a vertebrate subfamily of papain-like or NlpC/P60 thiol proteases that function as phospholipid-metabolizing enzymes. HRAS-like tumor suppressor 3, a representative member of this group, plays a key role in regulating triglyceride accumulation and energy expenditure in adipocytes and therefore constitutes a novel pharmacological target for treatment of metabolic disorders causing obesity. Here, we delineate a catalytic mechanism common to lecithin:retinol acyltransferase-like proteins and provide evidence for their alternative robust lipid-dependent acyltransferase enzymatic activity. We also determined high resolution crystal structures of HRAS-like tumor suppressor 2 and 3 to gain insight into their active site architecture. Based on this structural analysis, two conformational states of the catalytic Cys-113 were identified that differ in reactivity and thus could define the catalytic properties of these two proteins. Finally, these structures provide a model for the topology of these enzymes and allow identification of the protein-lipid bilayer interface. This study contributes to the enzymatic and structural understanding of HRAS-like tumor suppressor enzymes. PMID:22605381

A simple and robust quantitative analysis of retinol and retinyl palmitate using a liquid chromatographic isocratic method.

PubMed

Yokota, Satoshi; Oshio, Shigeru

2018-04-01

Vitamin A is a vital nutritional substances that regulates biological activities including development, but is also associated with disease onset. The extent of vitamin A intake influences the retinoid content in the liver, the most important organ for the storage of vitamin A. Measurement of endogenous retinoid in biological samples is important to understand retinoid homeostasis. Here we present a reliable, highly sensitive, and robust method for the quantification of retinol and retinyl palmitate using a reverse-phase HPLC/UV isocratic method. We determined the impact of chronic dietary vitamin A on retinoid levels in livers of mice fed an AIN-93G semi-purified diet (4 IU/g) compared with an excess vitamin A diet (1000 IU/g) over a period from birth to 10 weeks of age. Coefficients of variation for intra-assays for both retinoids were less than 5%, suggesting a higher reproducibility than any other HPLC/UV gradient method. Limits of detection and quantification for retinol were 0.08 pmol, and 0.27 pmol, respectively, which are remarkably higher than previous results. Supplementation with higher doses of vitamin A over the study period significantly increased liver retinol and retinyl palmitate concentrations in adult mice. The assays described here provide a sensitive and rigorous quantification of endogenous retinol and retinyl palmitate, which can be used to help determine retinoid homeostasis in disease states, such as toxic hepatitis and liver cancer. Copyright © 2017. Published by Elsevier B.V.

Vitamin A status of Filipino preschool children given a massive oral dose.

PubMed

Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I

1996-12-01

The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (< 20 microg/dl) levels were significantly lower one and six months after supplementation. All follow-up serum retinol levels of children with deficient and low values at baseline were significantly lower (p < 0.001) than those with normal values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

[Nutritional value of daily diets prepared in several regions of the country. Part VI. Value of retinol, beta-carotene and vitamin E].

PubMed

Nadolna, I; Okolska, G; Kunachowicz, H

1992-01-01

Determinations of retinol, beta-carotene and vitamin E were carried out in daily diets of manual and mental workers with medium incomes. The diets were prepared on the basis of the analysis of the Central Statistical Office in 1986 under laboratory conditions in five regions of Poland (Warszawa, Lublin, Olsztyn, Poznań, Wrocław). It was found that these diets contained respectively: vitamin A (retinol and beta-carotene) 844 and 859 micrograms, retinol 466 and 496 micrograms, beta-carotene 2267 and 2167 micrograms and vitamin E 4.82 and 5.12 mg per day. In relation to the realization of daily recommended dietary allowances by these diets, for vitamin A were met respectively 102 and 104% and for vitamin E 58 and 61%. There were considerable differences in the content of beta-carotene and vitamin E between diets prepared in all five regions of Poland.

Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression.

PubMed

Fulan, Hu; Changxing, Jiang; Baina, Wang Yi; Wencui, Zhang; Chunqing, Lin; Fan, Wang; Dandan, Li; Dianjun, Sun; Tong, Wang; Da, Pang; Yashuang, Zhao

2011-10-01

To comprehensively summarize the associations between retinol, vitamins A, C, and E and breast cancer, and quantitatively estimate their dose-response relationships. We searched PubMed, Embase, and Cochrane databases (from January 1982 to 15 March 2011) and the references of the relevant articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals, and comparable categories of vitamins. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer. Overall, 51 studies met the inclusion criteria. Comparing the highest with the lowest intake, total vitamin A intake reduced the breast cancer risk by 17% (pooled OR = 0.83, 95% CI: 0.78-0.88). Further subgroup analysis based on study design did not change the significant reduction. Although the dietary vitamin A, dietary vitamin E, and total vitamin E intake all reduced breast cancer risk significantly when data from all studies were pooled, the results became nonsignificant when data from cohort studies were pooled. The significant association between total retinol intake and breast cancer in all studies became nonsignificant in case-control studies but remain significant in cohort studies. No significant dose-response relationship was observed in the higher intake of these vitamins with reduced breast cancer risk. Our results indicate that both the total intake of vitamin A and retinol could reduce breast cancer risk. However, associations between other vitamins and breast cancer seem to be limited.

Childhood vitamin A status and the risk of otitis media.

PubMed

Durand, A M; Sabino, H; Masga, R; Sabino, M; Olopai, F; Abraham, I

1997-10-01

It has been suggested that vitamin A deficiency may predispose to otitis media. We conducted a prospective, observational study of 200 children, ages 3 to 5 years, on the island of Saipan in the Commonwealth of the Northern Mariana Islands. Baseline measurements of serum retinol concentrations were obtained from the children, and incidence of otitis media was determined during the following year by review of medical records. The sera were also tested for concentration of other carotenoids (beta-carotene, alpha-carotene, lutein and zeaxanthin, beta-cryptoxanthin, lycopene), and alpha-tocopherol and baseline concentrations of these compounds were also examined for relationship to incidence of otitis media. Serum retinol concentrations of the children ranged from 13 to 58 microg/dl. Episodes of otitis media occurred in 22% of children during the follow-up period. Children with low serum retinol concentrations did not have an excess of episodes of otitis media (chi square for trend, 0.438; P = 0.508 for children grouped by serum retinol concentration; mean serum retinol concentrations were 29.1 and 28.6 microg/dl, respectively, for children who had and did not have a subsequent episode of otitis media). Controlling for potential confounding variables (duration of breast feeding, smoking in the household, illness or live virus vaccination in the 2 weeks before serum collection, day-care attendance) did not substantially alter this finding. Baseline serum concentrations of the other carotenoids and alpha-tocopherol also demonstrated no relation to incidence of otitis media. In the range of serum vitamin concentrations found in this population, the status of vitamin A and related compounds in children appeared to have no effect on the incidence of otitis media.

[Correlation of retinol binding protein 4 with 
metabolic indexes of glucose and 
lipid, bile cholesterol saturation index].

PubMed

Wang, Wen; Li, Nianfeng

2015-06-01

To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
 A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
 The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both P<0.01). There was no significant difference in the serum total bile acid (TBA), serum triglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4

Serum Carotenoid Concentrations in Postmenopausal Women from the United States with and without Osteoporosis

PubMed Central

Yang, Zhifang; Zhang, Zhumin; Penniston, Kristina L.; Binkley, Neil; Tanumihardjo, Sherry A.

2009-01-01

Antioxidant defenses may be compromised in osteoporotic women. Little is known about fruit and vegetable or carotenoid consumption among postmenopausal women. The primary carotenoids in human serum are α- and β-carotene, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. This study investigated the interrelationships among serum carotenoid concentrations, fruit and vegetable intake, and osteoporosis in postmenopausal women (n = 59, 62.7 ± 8.8 y). Bone density was assessed by dual energy x-ray absorptiometry and osteoporosis diagnosis was based upon T-scores. Serum samples (n = 53) and 3-day diet records (n = 49) were analyzed. Logistic regression analyzed differences between carotenoids after adjusting for serum retinol; supplement usage; milk, yogurt, fruit, and vegetable intake; and BMI. Pearson statistics correlated carotenoids with specific fruit or vegetable intake. Serum lycopene concentrations were lower in the osteoporosis group than controls (p = 0.03). β-Cryptoxanthin intake was higher in the osteoporosis group (p = 0.0046). Total fruit and vegetable intakes were correlated with serum lycopene and β-cryptoxanthin (p = 0.03, 0.006, respectively). Serum α-carotene concentration was associated with carrot intake, and zeaxanthin and β-cryptoxanthin with lettuce intake. Carotenoids that may have beneficial skeletal effects are lower in women with osteoporosis. Research is needed to identify potential protective mechanisms or utilization of carotenoids during osteoporosis. PMID:19003732

The Effects of an Oil and Wheat Flour Fortification Program on Pre-School Children and Women of Reproductive Age Living in Côte d’Ivoire, a Malaria-Endemic Area

PubMed Central

Rohner, Fabian; Raso, Giovanna; Aké-Tano, Sassor Odile P.; Tschannen, Andreas B.; Mascie-Taylor, Christopher Guy Nicholas; Northrop-Clewes, Christine A.

2016-01-01

Anemia and micronutrient deficiencies are widespread in sub-Saharan Africa, but the impact of food fortification is still debated. The objective of this study was to estimate the iron and vitamin A status of preschool children (PSC) and women of reproductive age (WRA) in households consuming fortified oil and wheat flour. The survey was cross-sectional in a rural and an urban area. Data on demographics, socioeconomic status, and fortified foods were collected at households. Hemoglobin (Hb), retinol binding protein (RBP), ferritin, soluble transferrin receptors (sTfR), subclinical inflammation, and Plasmodium spp. infection data were collected. In PSC, vitamin A deficiency (VAD) was prevalent, but for each 1 mg retinol equivalents (RE)/kg of oil consumed, RBP increased by 0.37 μmol/L (p = 0.03). In WRA, there was no significant VAD in the population (0.7%). Anemia was found in 92.2% of rural and 56.3% of urban PSC (p < 0.001). PSC with access to adequately fortified flour had Hb concentrations 15.7 g/L higher than those who did not (p < 0.001). Hb levels increased by +0.238 g/L per mg/kg increase in iron fortification levels (p < 0.001). The national program fortifying vegetable oil with vitamin A and wheat flour with iron and folic acid may have contributed to improved micronutrient status of PSC from two areas in Côte d’Ivoire. PMID:26959060

Identification of V122I (Val122Ile) transthyretin cardiac amyloidosis (ATTR) using serum retinol-binding protein 4 (RBP4) and a clinical prediction model

PubMed Central

Arvanitis, Marios; Koch, Clarissa M; Chan, Gloria G.; Arancivia, Celia M.T.; LaValley, Michael; Jacobson, Daniel; Berk, John L.; Connors, Lawreen H.; Ruberg, Frederick L.

2017-01-01

Importance Transthyretin amyloid cardiomyopathy (ATTR) is an under-recognized cause of heart failure (HF) in the elderly, owing in part to difficulty in diagnosis. ATTR can result from mutant TTR protein with one of the most common mutations in the United States, V122I, present in 3.43% of African Americans. Objective To determine whether serum retinol-binding protein 4 (RBP4), an endogenous TTR ligand, could be used as a diagnostic test for ATTR V122I amyloidosis. Design Combined prospective and retrospective cohort study Setting Tertiary care referral center Participants Fifty prospectively genotyped African American patients over age 60 years with non-amyloid HF and cardiac wall thickening, and a comparator cohort of biopsy proven ATTR V122I amyloidosis patients (n=25) comprised the development cohort. Twenty-seven prospectively genotyped African American patients and 9 ATTR V122I amyloidosis patients comprised the validation cohort. Main Outcomes and Measures Circulating RBP4, TTR, B-type natriuretic peptide (BNP) and troponin I (TnI) concentrations, electrocardiography (ECG), echocardiography, and clinical characteristics were assessed in all patients. Receiver operating characteristic (ROC) analysis was performed to identify optimal thresholds for ATTR V122I amyloidosis identification. A clinical prediction rule was developed using penalized logistic regression, evaluated using ROC analysis and validated in an independent cohort of cases and controls. Results Age, gender, BNP and TnI were similar between ATTR V122I amyloidosis patients and controls. Serum RBP4 concentration was lower in patients with ATTR V122I amyloidosis compared to non-amyloid controls (31.5 vs. 49.4 ug/ml, p < 0.001) and the difference persisted after controlling for potential confounding parameters. Left ventricular ejection fraction (LVEF) was lower in ATTR V122I amyloidosis (40% vs. 57%, p<0.001), while interventricular septal diameter (IVSd) was higher (16 vs. 14 mm, p<0.001). ROC

Effect of Lipid Peroxidation Products on the Activity of Human Retinol Dehydrogenase 12 (RDH12) and Retinoid Metabolism

PubMed Central

Lee, Seung-Ah; Belyaeva, Olga V.; Kedishvili, Natalia Y.

2008-01-01

SUMMARY Mutations in human Retinol Dehydrogenase 12 (RDH12) are known to cause photoreceptor cell death but the physiological function of RDH12 in photoreceptors remains poorly understood. In vitro, RDH12 recognizes both retinoids and medium-chain aldehydes as substrates. Our previous study suggested that RDH12 protects cells against toxic levels of retinaldehyde and retinoic acid [Lee et al., J. Biol. Chem. 282 (2007) 35621–35628]. Here, we investigated whether RDH12 can also protect cells against highly reactive medium-chain aldehydes. Analysis of cell survival demonstrated that RDH12 was protective against nonanal but not against 4-hydroxynonenal. At high concentrations, nonanal inhibited the activity of RDH12 towards retinaldehyde, suggesting that nonanal was metabolized by RDH12. 4-Hydroxynonenal did not inhibit the RDH12 retinaldehyde reductase activity, but it strongly inhibited the activities of lecithin:retinol acyl transferase and aldehyde dehydrogenase, resulting in decreased levels of retinyl esters and retinoic acid and accumulation of unesterified retinol. Thus, the results of this study showed that RDH12 is more effective in protection against retinaldehyde than against medium-chain aldehydes, and that medium-chain aldehydes, especially 4-hydroxynonenal, severely disrupt cellular retinoid homeostasis. Together, these findings provide a new insight into the effects of lipid peroxidation products and the impact of oxidative stress on retinoid metabolism. PMID:18396173

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction.

PubMed

Hamamura, Kengo; Matsunaga, Naoya; Ikeda, Eriko; Kondo, Hideaki; Ikeyama, Hisako; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Yoshida, Yuya; Matsuda, Masaki; Yasuda, Kaori; Doi, Atsushi; Yokota, Yoshifumi; Amamoto, Toshiaki; Aramaki, Hironori; Irino, Yasuhiro; Koyanagi, Satoru; Ohdo, Shigehiro

2016-03-04

Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-β1 (TGF-β1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-β1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Friedmacher, Florian; Pes, Lara; Paradisi, Francesca; Puri, Prem

2014-06-01

The retinol signaling pathway is disrupted in congenital diaphragmatic hernia (CDH). Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Nitrofen interferes with the retinol-binding protein (RBP) transfer pathway in CDH. However, in RBP knockout mice, retinol has been shown to be present. In this model, increased uptake of maternal dietary retinyl ester (RE) bounded in low-dense-lipoprotein (LDL) through low-density-lipoprotein-receptor 1 (LRP1) and increased activity of RE hydrolysis by lipoprotein-lipase (LPL) have been found. The aim of this study was to investigate the RE transfer pathway in the nitrofen CDH model. Pregnant rats were treated with nitrofen or vehicle on gestational day (D9) and sacrificed on D21. Immunohistochemistry was performed to evaluate LRP1 and LPL protein expression. Serum LDL levels were measured by ELISA. Pulmonary and serum retinoid levels were measured using HPLC. Markedly increased trophoblastic and pulmonary LRP1 and LPL immunoreactivity were observed in CDH compared to controls. Significantly increased serum LDL and RE levels were observed in CDH compared to controls. The increased uptake of dietary retinoids at the maternal-fetal barrier in the nitrofen CDH model suggests that the RE transfer pathway may be the main source of retinol in this model. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative genomic and phylogenetic analysis of short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity.

PubMed

Belyaeva, Olga V; Kedishvili, Natalia Y

2006-12-01

Human short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity (RODH-like enzymes) are thought to contribute to the oxidation of retinol for retinoic acid biosynthesis and to the metabolism of androgenic and neuroactive 3alpha-hydroxysteroids. Here, we investigated the phylogeny and orthology of these proteins to understand better their origins and physiological roles. Phylogenetic and genomic analysis showed that two proteins (11-cis-RDH and RDHL) are highly conserved, and their orthologs can be identified in the lower taxa, such as amphibians and fish. Two other proteins (RODH-4 and 3alpha-HSD) are significantly less conserved. Orthologs for 3alpha-HSD are present in all mammals analyzed, whereas orthologs for RODH-4 can be identified in some mammalian species but not in others due to species-specific gene duplications. Understanding the evolution and divergence of RODH-like enzymes in various vertebrate species should facilitate further investigation of their in vivo functions using animal models.

Orally ingested (13)C(2)-retinol is incorporated into hepatic retinyl esters in a nonhuman primate (Macaca mulatta) model of hypervitaminosis A.

PubMed

Escaron, Anne L; Tanumihardjo, Sherry A

2010-02-01

The mechanism responsible for the metabolism of vitamin A during hypervitaminosis is largely unknown. This study investigated hepatic (13)C-retinol uptake in hypervitaminotic A rhesus monkeys. We hypothesized that individual retinyl esters would be enriched in (13)C after a physiologic dose of (13)C(2)-retinyl acetate, thus suggesting de novo in vivo hepatic retinol esterification. Male rhesus macaques (n = 16; 11.8 +/- 2.9 y) each received 3.5 micromol 14, 15-(13)C(2)-retinyl acetate. Blood was drawn at baseline and 5 h and 2, 4, 7, 14, 21, and 28 d after administration. Liver biopsies were collected 7 d before and 2 d after dose administration (n = 4) and at 7, 14, and 28 d after dose administration (n = 4 per time point). (13)C enrichments of retinol and retinyl esters HPLC-purified from liver samples were measured by using gas chromatography-combustion-isotope ratio mass spectrometry. (13)C enrichment of total vitamin A and individual retinyl esters were significantly greater 2 d after dose administration compared with baseline levels. In contrast, the concentration of isolated retinyl esters did not always increase 2 d after treatment. Given that the liver biopsy site differed between monkeys, these data suggest that the accumulation of hepatic retinyl esters is a dynamic process that is better represented by combining analytical techniques. This sensitive methodology can be used to characterize vitamin A trafficking after physiologic doses of (13)C-retinol. In this nonhuman primate model of hypervitaminosis A, hepatic retinyl esters continued to accumulate with high liver stores.

Orally Ingested 13C2-Retinol is Incorporated into Hepatic Retinyl Esters in a Nonhuman Primate (Macaca mulatta) Model of Hypervitaminosis A

PubMed Central

Escaron, Anne L; Tanumihardjo, Sherry A

2010-01-01

The mechanism responsible for the metabolism of vitamin A during hypervitaminosis is largely unknown. This study investigated hepatic 13C-retinol uptake in hypervitaminotic A rhesus monkeys. We hypothesized that individual retinyl esters would be enriched in 13C after a physiologic dose of 13C2-retinyl acetate, thus suggesting de novo in vivo hepatic retinol esterification. Male rhesus macaques (n = 16; 11.8 ± 2.9 y) each received 3.5 µmol 14, 15-13C2-retinyl acetate. Blood was drawn at baseline and 5 h and 2, 4, 7, 14, 21, and 28 d after administration. Liver biopsies were collected 7 d before and 2 d after dose administration (n = 4) and at 7, 14, and 28 d after dose administration (n = 4 per time point). 13C enrichments of retinol and retinyl esters HPLC-purified from liver samples were measured by using gas chromatography–combustion–isotope ratio mass spectrometry. 13C enrichment of total vitamin A and individual retinyl esters were significantly greater 2 d after dose administration compared with baseline levels. In contrast, the concentration of isolated retinyl esters did not always increase 2 d after treatment. Given that the liver biopsy site differed between monkeys, these data suggest that the accumulation of hepatic retinyl esters is a dynamic process that is better represented by combining analytical techniques. This sensitive methodology can be used to characterize vitamin A trafficking after physiologic doses of 13C-retinol. In this nonhuman primate model of hypervitaminosis A, hepatic retinyl esters continued to accumulate with high liver stores. PMID:20158952

Coenzyme Q10, carotenoid, tocopherol, and retinol levels in cord plasma from multiethnic subjects in Hawaii

PubMed Central

Franke, AA; Lai, J.F.; Morrison, C.M.; Pagano, I.; Li, X; Halm, B.M.; Soon, R.; Custer, L.J.

2015-01-01

Coenzyme Q10 (Q10), carotenoids, tocopherols, and retinol are the major circulating lipid-phase micronutrients (LPM) known to help mitigate oxidative damage and prevent chronic diseases. However, the functions of these compounds in newborns are little understood. This is due, in part, to the paucity of studies reporting their concentrations in this population. We measured Q10, carotenoids, tocopherols, and retinol in cord plasma from 100 multiethnic subjects living in Hawaii using HPLC with diode array and electrochemical detection. Appropriate internal standards were used including, for the first time, custom designed oxidized (UN10) and reduced (UL10) Q10 analogues. These compounds reflected the oxidation of UL10 to UN10 that occurred during sample processing and analysis and thus permitted accurate adjustments of natively circulating Q10 levels. All LPM measured were much lower in cord than in peripheral plasma. Cord plasma levels of total carotenoids, tocopherols, and retinol were approximately 10-fold, 3- to 5-fold and 1.5- to 3-fold lower than those in children or women. Cord plasma levels of total Q10 (TQ10; median, 113 ng/mL) were approximately 2-fold or 7- to 9-fold lower than peripheral plasma levels of neonates or children and adults, respectively. In contrast, the UN10/TQ10 ratio was substantially higher in cord (24%) than in peripheral plasma of children (3 – 4%) or adults (9%). Among the 5 ethnic groups in our cohort, no differences were observed in the levels of UN10, UL10, or TQ10. However, significant differences in many of the LPM were observed between ethnicities. More research is needed to explain these phenomena. PMID:23829202

Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32.

PubMed Central

Slee, E A; Zhu, H; Chow, S C; MacFarlane, M; Nicholson, D W; Cohen, G M

1996-01-01

Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases. PMID:8670109

Decidual β-carotene-15,15'-oxygenase-1 and 2 (BCMO1,2) expression is increased in nitrofen model of congenital diaphragmatic hernia.

PubMed

Takahashi, Hiromizu; Kutasy, Balazs; Pes, Lara; Paradisi, Francesca; Puri, Prem

2015-01-01

Retinoids are essential for fetal and lung development. Beta-carotene(BC) is the main dietary retinoid source and beta-carotene-15,15'-oxygenase-1 and 2 (Bcmo1,2) is the primary enzyme generating retinoid from BC in adult mammalian tissues. Placenta has a major role in the retinol homeostasis in fetal life: Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. It has been recently shown that BC can be converted to retinol by Bcmo1,2 in placenta for retinol transfer and moreover, BC can cross the placenta intact. The placental Bcmo1,2 expression is tightly controlled by placental retinol level. In severe retinol deficiency it has been shown that placental Bcmo1,2 expression are increased for generating retinol from dietary maternal BC even when the main retinol transfer is blocked. In recent years, low pulmonary retinol levels and disrupted retinoid signaling pathway have been implicated in the pathogenesis of pulmonary hypoplasia and congenital diaphragmatic hernia (CDH) in the nitrofen model of CDH. Recently, it has been demonstrated that the main retinol transfer in the placenta is blocked in the nitrofen model of CDH causing increased placental and decreased serum retinol level. The aim of our study was to determine maternal and fetal β-carotene levels and to investigate the hypothesis that placental expression of BCMO1 and BCMO2 is altered in nitrofen-exposed rat fetuses with CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Maternal and fetal serum, placenta, liver and left lungs were harvested on D21 and divided into two groups: control (n = 8) and nitrofen with CDH (n = 8). Immunochistochemistry was performed to evaluate trophoblasts by cytokeratin expression and placental Bcmo1,2 expression. Expression levels of Bcmo1,2 genes in fetal lungs and liver were determined using RT-PCR and immunohistochemistry. BC level was measured using HPLC. Markedly increased decidual Bcmo1

Vitamin A-Deficient Diet Accelerated Atherogenesis in Apolipoprotein E−/− Mice and Dietary β-Carotene Prevents This Consequence

PubMed Central

Relevy, Noa Zolberg; Harats, Dror; Harari, Ayelet; Ben-Amotz, Ami; Bitzur, Rafael; Rühl, Ralph; Shaish, Aviv

2015-01-01

Vitamin A is involved in regulation of glucose concentrations, lipid metabolism, and inflammation, which are major risk factors for atherogenesis. However, the effect of vitamin A deficiency on atherogenesis has not been investigated. Therefore, the objective of the current study was to examine whether vitamin A deficiency accelerates atherogenesis in apolipoprotein E-deficient mice (apoE−/−). ApoE−/− mice were allocated into the following groups: control, fed vitamin A-containing chow diet; BC, fed chow diet fortified with Dunaliella powder containing βc isomers; VAD, fed vitamin A-deficient diet; and VAD-BC group, fed vitamin A-deficient diet fortified with a Dunaliella powder. Following 15 weeks of treatment, liver retinol concentration had decreased significantly in the VAD group to about 30% that of control group. Vitamin A-deficient diet significantly increased both plasma cholesterol concentrations and the atherosclerotic lesion area at the aortic sinus (+61%) compared to the control group. Dietary βc fortification inhibited the elevation in plasma cholesterol and retarded atherogenesis in mice fed the vitamin A-deficient diet. The results imply that dietary vitamin A deficiency should be examined as a risk factor for atherosclerosis and that dietary βc, as a sole source of retinoids, can compensate for vitamin A deficiency. PMID:25802864

Consumption of vitamin A by breastfeeding children in rural Kenya.

PubMed

Ettyang, Grace; Oloo, Aggrey; van Marken Lichtenbelt, Wauter; Saris, Wim

2004-09-01

Vitamin A deficiency remains a significant health risk in developing countries, affecting infants and children in particular. To counter child malnutrition, mothers are encouraged to breastfeed to ensure that their children receive adequate macro- and micronutrients, including vitamin A. However, this assumes that the mother has sufficient vitamin A intake to provide enough vitamin A to her child. This study investigates maternal and infant intakes of locally available foods of high vitamin A content in a rural agricultural community in Kenya. The study aims to establish the community risk for vitamin A deficiency and to assess whether breast milk is adequate to maintain and build retinol reserves of the breastfed infant. The study assesses 62 mother-child pairs and employs several methods to support its objectives, including the Helen Keller International food-frequency survey, maternal and infant anthropometric measurements, and maternal breast-milk and blood samples to determine breast-milk and serum retinol levels. We found that mothers with marginal (< 0.700 micromol/l) serum retinol and breast-milk deficient (< 1.05 micromol/l) in retinol accounted for 45.2% and 77.4%, of our sample, respectively. A significant (p < 0.05) proportion (40.3%) of mothers had breast milk deficient in retinol and marginal levels of serum retinol. The risk of vitamin A deficiency in breastfed infants older than six months was high, because 89.5% of them did not consume foods high in vitamin A content three times weekly. The primary source of vitamin A for infants younger than six months was breast-milk deficient in retinol vitamin A. This study suggests that in this rural community, breastfed infants may not receive appropriate foods with high vitamin A content and that although exclusive breastfeeding is advocated, most breast milk is deficient in retinol, further heightening the risk of vitamin A deficiency.

Concentrations of retinoids in early pregnancy and in newborns and their mothers.

PubMed

Berggren Söderlund, Maria; Fex, Göran A; Nilsson-Ehle, Peter

2005-03-01

Retinoids are vital for embryonic development; both excesses and deficiencies of vitamin A are known to give similar patterns of birth defects. Concentrations of retinol in newborns and in pregnant women have been investigated, but concentrations of the biologically active metabolite all-trans retinoic acid and its isomer 13-cis retinoic acid have not. We measured serum concentrations of these retinoid derivatives in newborns and their mothers and in women in the first trimester of pregnancy, when embryonic differentiation (organogenesis) takes place. In this descriptive study, 10 newborns from normal deliveries and their mothers and 16 healthy women in their first trimester of pregnancy were studied. Seventeen healthy women served as control subjects. all-trans and 13-cis Retinoic acid and retinol concentrations were measured by HPLC. The newborns had significantly lower retinol concentrations (1.0 micromol/L) than did their mothers (1.7 micromol/L; P = 0.013). Serum all-trans retinoic acid was also significantly lower in the newborns (3.4 nmol/L) than in their mothers (5.8 nmol/L; P = 0.008). In addition, serum concentrations of 13-cis retinoic acid were significantly lower in the newborns (2.0 nmol/L) than in their mothers (2.6 nmol/L; P = 0.005). The serum concentrations of all-trans retinoic acid and retinol did not correlate in any group. Retinol concentrations do not accurately reflect the concentrations of the biologically active derivative all-trans retinoic acid.

Subclinical inflammation influences the association between vitamin A- and iron status among schoolchildren in Ghana

PubMed Central

Abizari, Abdul-Razak; Azupogo, Fusta; Brouwer, Inge D.

2017-01-01

Background and objective In resource-poor settings, micronutrient deficiencies such as vitamin A deficiency may co-exist with iron-deficiency. In this study we assessed the iron and vitamin A status of schoolchildren and the association between vitamin A and iron status. Methods A cross-sectional design using the baseline data of a dietary intervention trial conducted among randomly selected 5–12 years old schoolchildren (n = 224) from 2 rural schools in northern Ghana. Hemoglobin (Hb), serum ferritin (SF) and serum transferrin receptor (sTfR) concentrations were used as measures of iron status. Retinol binding protein (RBP) was used as a measure of vitamin A status. Subclinical inflammation (SCI) was measured using C-reactive protein (CRP) and α1-acid glycoprotein (AGP) concentrations. We examined the cross-sectional association between vitamin A and iron status biomarkers with multiple linear regressions. Results The proportions of schoolchildren with anemia (WHO criteria), iron-deficiency (ID, SF <15μg/l and/or sTfR >8.5mg/l) and iron-deficiency anemia (IDA, concurrent anemia and ID) were 63.8%, 68.3% and 46.4% respectively. Low or marginal vitamin A status (0.70 μmol/l ≤ RBP < 1.05μmol/l) was present in 48.2% while 37.5% of the schoolchildren had vitamin A deficiency (VAD, RBP <0.70 μmol/l). The prevalence of SCI as well as concurrent VAD and ID were 48.7% and 25% respectively. RBP was associated with Hb (β = 7.2, P = 0.05) but not SF (β = 20.7, P = 0.33) and sTfR concentration (β = 12.0, P = 0.63). In the presence of SCI, RBP was not associated with hemoglobin status but a significant positive association was observed among children without SCI. Conclusions The study shows that RBP is significantly associated with Hb concentration but not with SF and sTfR. The observed relationship between RBP and Hb is only significant in the absence of SCI. PMID:28152069

The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo

PubMed Central

2011-01-01

Background The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring. Methods Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. Results We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials. Conclusions RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs. PMID:22040120

All-trans retinol, vitamin D and other hydrophobic compounds bind in the axial pore of the five-stranded coiled-coil domain of cartilage oligomeric matrix protein.

PubMed Central

Guo, Y; Bozic, D; Malashkevich, V N; Kammerer, R A; Schulthess, T; Engel, J

1998-01-01

The potential storage and delivery function of cartilage oligomeric matrix protein (COMP) for cell signaling molecules was explored by binding hydrophobic compounds to the recombinant five-stranded coiled-coil domain of COMP. Complex formation with benzene, cyclohexane, vitamin D3 and elaidic acid was demonstrated through increases in denaturation temperatures of 2-10 degreesC. For all-trans retinol and all-trans retinoic acid, an equilibrium dissociation constant KD = 0.6 microM was evaluated by fluorescence titration. Binding of benzene and all-trans retinol into the hydrophobic axial pore of the COMP coiled-coil domain was proven by the X-ray crystal structures of the corresponding complexes at 0.25 and 0.27 nm resolution, respectively. Benzene binds with its plane perpendicular to the pore axis. The binding site is between the two internal rings formed by Leu37 and Thr40 pointing into the pore of the COMP coiled-coil domain. The retinol beta-ionone ring is positioned in a hydrophobic environment near Thr40, and the 1.1 nm long isoprene tail follows a completely hydrophobic region of the pore. Its terminal hydroxyl group complexes with a ring of the five side chains of Gln54. A mutant in which Gln54 is replaced by Ile binds all-trans retinol with affinity similar to the wild-type, demonstrating that hydrophobic interactions are predominant. PMID:9736606

Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition.

PubMed

Perrotta, Silverio; Nobili, Bruno; Rossi, Francesca; Criscuolo, Maria; Iolascon, Achille; Di Pinto, Daniela; Passaro, Irene; Cennamo, Lucia; Oliva, Adriana; Della Ragione, Fulvio

2002-03-15

Vitamin A is a pivotal biochemical factor required for normal proliferation and differentiation as well as for specialized functions, such as vision. The dietary intake of 1500 IU/day is recommended in the first year of life. Here, we report the case of an infant who had been given 62 000 IU/day for 80 days. The infant showed several clinical signs of retinol intoxication, including severe anemia and thrombocytopenia. Bone marrow showed a remarkably reduced number of erythroid and megakaryocytic cells. The interruption of vitamin A treatment was immediately followed by clinical and biochemical recovery. To clarify whether the effects of retinol are due to a direct action on bone marrow cell proliferation, we investigated the activity of retinol (both the drug and the pure molecule) on the growth of K-562, a multipotent hematopoietic cell line, and on bone marrow mesenchymal stem cells. We observed that vitamin A strongly inhibited the proliferation of the cells at concentrations similar to those reached in vivo. Subsequent biochemical analyses of the cell cycle suggested that the effect was mediated by the up-regulation of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1). These are the first findings to demonstrate that infant hypervitaminosis A causes a severe anemia and thrombocytopenia and that this is probably due to the direct effect of the molecule on the growth of all bone marrow cellular components. Our data also suggest potential bone marrow functional alterations after excessive vitamin A intake because of emerging social habits.

Five-year follow-up of a food-based vitamin A intervention in Tanzania.

PubMed

Kidala, D; Greiner, T; Gebre-Medhin, M

2000-12-01

: To evaluate the long-term effects of a horticultural and nutrition education intervention in rural Tanzania. : A quasi-experimental post-test design was used. : The research was carried out in 10 villages in Singida region, Tanzania. : Mothers and their children aged 6-71 months (n = 236) from an experimental (Ilongero) and control (Ihanja) area were interviewed regarding knowledge and practices related to vitamin A nutrition. Intake of vitamin A-rich foods by the children during the 7 days prior to the interview was recorded. Stools were examined for helminths and serum samples were analysed for retinol and C-reactive protein (CRP) (n = 146) for the children aged 12-71 months. : Knowledge and practices were more favourable to vitamin A intake in the experimental area than in the control area, and an increased frequency of intake of green leaves was associated with higher serum retinol values. The experimental area had lower mean serum retinol levels (13.7 microg dl(-1), n = 75) than the control area (19.3 microg dl(-1), n = 71). One likely confounder was the higher helminth infestation in the experimental area (n = 75, 79%) than in the control area (n = 71, 49%) (P < 0.001). Children with helminths (n = 94) had a lower mean serum retinol level than those without (n = 52) (12.3 +/- 5 vs. 24 +/- 10 microg dl(-1); P = 0.001). : Food-based vitamin A programmes can make sustainable improvements in knowledge and dietary practices but these may not necessarily be reflected in increases in serum retinol. Programme implementation and evaluation should take confounders into consideration as, in this case, helminth infestation.

Cancer of the cervix uteri and vitamin A.

PubMed Central

Harris, R. W.; Forman, D.; Doll, R.; Vessey, M. P.; Wald, N. J.

1986-01-01

The concentrations of retinol and beta carotene were measured in serum samples taken from 113 women with cervical cancer, 32 with invasive and 81 with pre-invasive disease, and compared with those from 226 age-matched control women. There was little difference in serum retinol levels between women with cancer of the cervix, at any stage, and the control women, after adjusting for potential confounding factors. Serum beta carotene concentrations were likewise similar in women with invasive disease and the controls. However mean beta carotene levels were significantly reduced in women with pre-invasive disease compared to the controls (221.3 cf. 291.6 micrograms l-1, P less than 0.05). This reduction was more evident amongst women with a diagnosis of carcinoma-in-situ (mean 213.1 micrograms l-1 than amongst those with severe dysplasia (mean 228.7 micrograms l-1. There is a negative trend between beta carotene and risk of pre-invasive disease which is of borderline significance. These data have also been used to investigate the effects of smoking and oral contraceptive usage on the serum levels of retinol and beta carotene. Both habits tend to increase retinol and decrease beta carotene concentrations. PMID:3718822

β-carotene and retinol contents in the meat of herbivorous ungulates with a special reference to their public health importance.

PubMed

Darwish, Wageh Sobhy; Ikenaka, Yoshinori; Morshdy, Alaa Eldin; Eldesoky, Kamal Ibrahim; Nakayama, Shouta; Mizukawa, Hazuki; Ishizuka, Mayumi

2016-02-01

The aim of this study was to estimate total carotenoids, β-carotene and retinol concentrations in the livers and muscles of some ungulates (cattle, buffalo, sheep, goats and horses) in comparison with the Wistar rats as a control. Cattle and horses had the highest contents of total carotenoids and β-carotene. Unexpectedly, sheep was the highest accumulator of retinol with a mean concentration of 203 ± 23.34 µg/g, while the least accumulator was buffalo, having a mean value of 58.28 ± 13.77 µg/g. Livers had higher contents of the examined phytochemicals than muscles. Consumption of these tissues may provide human with some needs from these important phytochemicals, though ingestion of livers, especially that of the sheep, is not advisable for the pregnant women.

Vitamin A-fortified cooking oil reduces vitamin A deficiency in infants, young children and women: results from a programme evaluation in Indonesia.

PubMed

Sandjaja; Jus'at, Idrus; Jahari, Abas B; Ifrad; Htet, Min Kyaw; Tilden, Robert L; Soekarjo, Damayanti; Utomo, Budi; Moench-Pfanner, Regina; Soekirman; Korenromp, Eline L

2015-10-01

To assess oil consumption, vitamin A intake and retinol status before and a year after the fortification of unbranded palm oil with retinyl palmitate. Pre-post evaluation between two surveys. Twenty-four villages in West Java. Poor households were randomly sampled. Serum retinol (adjusted for subclinical infection) was analysed in cross-sectional samples of lactating mothers (baseline n 324/endline n 349), their infants aged 6-11 months (n 318/n 335) and children aged 12-59 months (n 469/477), and cohorts of children aged 5-9 years (n 186) and women aged 15-29 years (n 171), alongside food and oil consumption from dietary recall. Fortified oil improved vitamin A intakes, contributing on average 26 %, 40 %, 38 %, 29 % and 35 % of the daily Recommended Nutrient Intake for children aged 12-23 months, 24-59 months, 5-9 years, lactating and non-lactating women, respectively. Serum retinol was 2-19 % higher at endline than baseline (P<0·001 in infants aged 6-11 months, children aged 5-9 years, lactating and non-lactating women; non-significant in children aged 12-23 months; P=0·057 in children aged 24-59 months). Retinol in breast milk averaged 20·5 μg/dl at baseline and 32·5 μg/dl at endline (P<0·01). Deficiency prevalence (serum retinol <20 μg/dl) was 6·5-18 % across groups at baseline, and 0·6-6 % at endline (P≤0·011). In multivariate regressions adjusting for socio-economic differences, vitamin A intake from fortified oil predicted improved retinol status for children aged 6-59 months (P=0·003) and 5-9 years (P=0·03). Although this evaluation without a comparison group cannot prove causality, retinyl contents in oil, Recommended Nutrient Intake contributions and relationships between vitamin intake and serum retinol provide strong plausibility of oil fortification impacting vitamin A status in Indonesian women and children.

Vitamin D status and vascular dementia due to cerebral small vessel disease in the elderly Asian Indian population.

PubMed

Prabhakar, Puttachandra; Chandra, Sadanandavalli Retnaswami; Supriya, Manjunath; Issac, Thomas Gregor; Prasad, Chandrajit; Christopher, Rita

2015-12-15

Vitamin D plays vital roles in human health and recent studies have shown its beneficial effect on brain functioning. The present study was designed to evaluate the association of vitamin D with vascular dementia (VaD) due to cerebral small vessel disease (SVD) in Asian Indian population. 140 VaD patients aged ≥ 60 years with neuroimaging evidence of SVD, and 132 age and gender-matched controls, were investigated. Vitamin D status was estimated by measuring serum 25-hydroxy vitamin D. Logistic regression model revealed that deficient levels of vitamin D (<12 ng/ml) were associated with 2.2-fold increase in odds of VaD after adjustment with covariates. Hypertension was independently associated with 11.3-fold increased odds of VaD. In hypertensives with vitamin D deficiency and insufficiency (12-20 ng/ml), the odds were increased to 31.6-fold and 14.4-fold, respectively. However, in hypertensives with vitamin D sufficiency (>20 ng/ml), the odds of VaD were increased by 3.8-fold only. Pearson correlation showed that serum vitamin D was inversely associated with systolic and diastolic blood pressure (r=-0.401 and -0.411, p<0.01, respectively) in vitamin D-deficient subjects. Since the combined presence of hypertension and vitamin D deficiency increases the probability of developing VaD, screening for vitamin D status in addition to regular monitoring of blood pressure, could reduce the risk of VaD associated with cerebral SVD in the elderly Asian Indian subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

An Open Label Clinical Trial to Evaluate the Efficacy and Tolerance of a Retinol and Vitamin C Facial Regimen in Women With Mild-to-Moderate Hyperpigmentation and Photodamaged Facial Skin.

PubMed

Herndon, James H; Jiang, Lily I; Kononov, Tatiana; Fox, Theresa

2016-04-01

A 12-week open-label, single-center clinical usage trial was conducted to determine the effectiveness of a dual product regimen consisting of a 0.5% retinol treatment and an anti-aging moisturizer with 30% vitamin C in women with mild to moderate hyperpigmented and photodamaged facial skin. Clinical grading of several efficacy parameters, tolerability evaluations, subject self-assessment questionnaires, and digital photography were completed at baseline and at weeks 4, 8, and 12. A total of 44 women completed the study. Effective ingredients incorporated into the 0.5% retinol treatment included encapsulated retinol for a retinol concentration of 0.5%, bakuchiol, and Ophiopogon japonicus root extract. The anti-aging moisturizer with 30% vitamin C contained 30% vitamin C in the form of tetrahexyldecyl ascorbate (THD ascorbate), alpha-tocopheryl acetate (vitamin E) and ubiquinone (coenzyme Q10). The facial regimen produced a statistically significant decrease (improvement) in clinical grading scores for all parameters assessed at weeks 8 and 12 when compared with baseline scores. In addition, the majority of these parameters were improved at week 4. The test regimen was well-perceived by the subjects for various inquiries regarding facial skin condition, product efficacy, and product attributes. Several tolerability parameters were assessed with no statistically significant increase except for dryness. A statistically significant increase in clinical grading scores for dryness on the face occurred at weeks 4 and 8 when compared to baseline scores. The increase in dryness is expected when introducing a retinol product to a facial regimen and the dryness did not persist to the week 12 time point.

Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures.

PubMed

Silvaroli, Josie A; Arne, Jason M; Chelstowska, Sylwia; Kiser, Philip D; Banerjee, Surajit; Golczak, Marcin

2016-04-15

Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo- and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included α-helix II and hairpin turns between β-strands βC-βD and βE-βF as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Role of Vitamin A Metabolism in IIH: Results from the Idiopathic Intracranial Hypertension Treatment Trial

PubMed Central

Libien, J; Kupersmith, MJ; Blaner, W; McDermott, MP; Gao, S; Liu, Y; Corbett, J; Wall, M

2017-01-01

Introduction Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF. Methods Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months. Results At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33 nM) and controls (median 5.04 nM, p = 0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p = 0.02) and CSF ATRA (p = 0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r = −0.44, p = 0.006) and the change in CSF retinol (r = −0.61, p = 0.02). Conclusion Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging *

PubMed Central

Afornali, Alessandro; de Vecchi, Rodrigo; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; de Oliveira, Luciana Lima; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

2013-01-01

BACKGROUND The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. PMID:24474102

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging.

PubMed

Afornali, Alessandro; Vecchi, Rodrigo de; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; Oliveira, Luciana Lima de; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

2013-01-01

The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.

Assessing the Safety of Vitamin A Delivered Through Large-Scale Intervention Programs: Workshop Report on Setting the Research Agenda.

PubMed

Tanumihardjo, Sherry A; Mokhtar, Najat; Haskell, Marjorie J; Brown, Kenneth H

2016-06-01

Vitamin A (VA) deficiency (VAD) is still a concern in many parts of the world, and multiple intervention strategies are being implemented to reduce the prevalence of VAD and associated morbidity and mortality. Because some individuals within a population may be exposed to multiple VA interventions, concerns have been raised about the possible risk of hypervitaminosis A. A consultative meeting was held in Vienna, Austria, in March 2014 to (1) review current knowledge concerning the safety and effectiveness of large-scale programs to control VAD, (2) develop a related research agenda, and (3) review current available methods to assess VA status and risk of hypervitaminosis A. Multiple countries were represented and shared their experiences using a variety of assessment methods, including retinol isotope dilution (RID) techniques. Discussion included next steps to refine assessment methodology, investigate RID limitations under different conditions, and review programmatic approaches to ensure VA adequacy and avoid excessive intakes. Fortification programs have resulted in adequate VA status in Guatemala, Zambia, and parts of Cameroon. Dietary patterns in several countries revealed that some people may consume excessive preformed VA from fortified foods. Additional studies are needed to compare biomarkers of tissue damage to RID methods during hypervitaminosis A and to determine what other biomarkers can be used to assess excessive preformed VA intake. © The Author(s) 2016.

Vitamin A status and nutritional intake of carotenoids of preschool children in Ijaye Orile community in Nigeria.

PubMed

Oso, O O; Abiodun, P O; Omotade, O O; Oyewole, D

2003-02-01

This study was carried out to determine the vitamin A status and nutritional intake of carotenoids of 213 children between the ages of 6 months and 6 years in a rural community in Nigeria. There were 109 males and 104 females. A total of 57 (26.8 per cent) children were deficient in serum retinol levels (< 10 microg/dl) while 102 (47.9 per cent) had low levels (10-19 microg/dl). The highest prevalence of serum retinol deficiency was in the 6-12 months age group, most of whom were breastfeeding and there was poor correlation between duration of breastfeeding and serum retinol levels. The prevalence of night-blindness was 1.5 per cent; however, none of the children had xerophthalmia. Chronically malnourished children had lower mean serum retinol levels than well nourished children. There was a high consumption of carotenoid-containing food, but despite this there was a high prevalence of vitamin A deficiency. We therefore suggest that measures to combat vitamin A deficiency should include vitamin A supplementation on a short-term basis. On a long-term basis parents should be educated on the importance of the consumption of locally available sources of provitamin A and pre-formed vitamin A rich foods, and the avoidance of overcooking. Parents should also be encouraged to grow more beta-carotene containing foods.

Promotion of Orange-Fleshed Sweet Potato Increased Vitamin A Intakes and Reduced the Odds of Low Retinol-Binding Protein among Postpartum Kenyan Women.

PubMed

Girard, Amy Webb; Grant, Frederick; Watkinson, Michelle; Okuku, Haile Selassie; Wanjala, Rose; Cole, Donald; Levin, Carol; Low, Jan

2017-05-01

Background: Orange-fleshed sweet potato (OFSP) improves vitamin A (VA) status of young children; research with pregnant and lactating women is limited. Objective: We examined the effectiveness of the Mama SASHA (Sweetpotato Action for Security and Health in Africa) program to improve nutrition knowledge, diets, and nutritional status of pregnant and lactating women (PLW) in Western Kenya. Methods: Eight health facilities were allocated to the Mama SASHA intervention or comparison arms. PLW in intervention facilities received enhanced nutrition counseling at health clinics, were linked with community-based maternal support groups, and received vouchers for OFSP vine cuttings. Control PLW received clinic-based nutrition counseling only. A total of 505 women in early and midpregnancy, attending their first antenatal care visit, and with no previous engagement in project activities were enrolled from the 8 facilities. Nutrition and health-seeking knowledge, food security, dietary patterns, and anthropometric measurements were collected at 4 time points at ≤9 mo postpartum. VA intakes were assessed with multipass 24-h recalls in a subsample of 206 mothers at 8-10 mo postpartum. VA status was assessed by using serum retinol-binding protein (RBP). Impacts were estimated with multilevel mixed models adjusted for clustering and differences at enrollment. Results: At enrollment, 22.9% of women had RBP <1.17 μmol/L. By 9 mo postpartum, intervention women had significantly higher intakes of VA [adjusted difference = 297.0 retinol activity equivalent (RAE) units; 95% CI: 82, 513 RAE units; P = 0.01; n = 206], greater consumption of VA-rich fruit and vegetables in the previous 7 d (difference-in-difference estimate: 0.40 d; 95% CI: 0.23, 0.56 d; P < 0.01), and a 45% reduction in the odds of RBP <1.17 μmol/L (OR: 0.55; 95% CI: 0.33, 0.92; P = 0.01). Conclusion: Promotion of OFSP to PLW through health services is a feasible strategy to improve women's nutrition knowledge, VA

Giardiasis and Poor Vitamin A Status among Aboriginal School Children in Rural Malaysia

PubMed Central

Al-Mekhlafi, Hesham M.; Surin, Johari; Sallam, Atiya A.; Abdullah, Ariffin W.; Mahdy, Mohammed A. K.

2010-01-01

A cross-sectional study was carried out on 241 primary schoolchildren in Pahang, Malaysia to update their vitamin A status and to investigate the association of poor vitamin A status with their health and socioeconomic factors. All children were screened for intestinal parasitic infections. Blood samples were collected and vitamin A status was assessed. Socioeconomic data were collected by using pre-tested questionnaires. The results showed that 66 (27.4%) children had low serum retinol levels (< 0.70 μmol/L). Giardiasis and severe ascariasis were significantly associated with low serum retinol levels (P = 0.004 and P = 0.018, respectively). Logistic regression confirmed the significant association of giardiasis with low serum retinol (odds ratio = 2.7, 95% confidence interval = 1.3–5.5). In conclusion, vitamin A deficiency is still a public health problem in rural Malaysia. Vitamin A supplementation and treatment of intestinal parasitic infections should be distributed periodically to these children to improve their health and nutritional status. PMID:20810815

Breast-feeding, dietary intakes and their associations with subclinical vitamin A deficiency in children in Anhui Province, China.

PubMed

Zhang, Yewu; Tao, Fangbiao; Yin, Huiping; Zhu, Xiaoming; Ji, Guoping; Kong, Shenghua; Song, Qinhua; Chen, Jianhua; Chu, Chengzhi; Li, Zhu

2007-07-01

This study aimed to explore the associations between breast-feeding, dietary intakes and other related factors and subclinical vitamin A deficiency (SVAD) in children aged 0-5 years in an area in China where mild vitamin A deficiency (VAD) is found. Data were from a population-based cross-sectional study with 1052 children aged 0-5 years. SVAD cases were identified by the indicator of serum retinolVAD in an area with mild SVAD.

Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.

PubMed

Tso, P; Lee, T; DeMichele, S J

2001-08-01

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

PubMed Central

Jenab, M; Riboli, E; Ferrari, P; Friesen, M; Sabate, J; Norat, T; Slimani, N; Tjønneland, A; Olsen, A; Overvad, K; Boutron-Ruault, M-C; Clavel-Chapelon, F; Boeing, H; Schulz, M; Linseisen, J; Nagel, G; Trichopoulou, A; Naska, A; Oikonomou, E; Berrino, F; Panico, S; Palli, D; Sacerdote, C; Tumino, R; Peeters, P H; Numans, M E; Bueno-de-Mesquita, H B; Büchner, F L; Lund, E; Pera, G; Chirlaque, M D; Sánchez, M-J; Arriola, L; Barricarte, A; Quirós, J R; Johansson, I; Johansson, A; Berglund, G; Bingham, S; Khaw, K-T; Allen, N; Key, T; Carneiro, F; Save, V; Giudice, G Del; Plebani, M; Kaaks, R; Gonzalez, C A

2006-01-01

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and α- and γ-tocopherol, with the risk of gastric adenocarcinoma in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and α-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma β-cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30–0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22–0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33–0.93, Ptrend=0.005) and lipid-unadjusted α-tocopherol (OR=0.59, 95% CI=0.37–0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted α-tocopherol (OR=0.26, 95% CI=0.11–0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and α-tocopherol are associated with reduced risk

Binding of human serum proteins to titanium dioxide particles in vitro.

PubMed

Zaqout, Mazen S K; Sumizawa, Tomoyuki; Igisu, Hideki; Higashi, Toshiaki; Myojo, Toshihiko

2011-01-01

To determine the capacity of human serum proteins to bind to titanium dioxide (TiO(2)) particles of different polymorphs and sizes. TiO(2) particles were mixed with diluted human serum, purified human serum albumin (HSA) or purified human serum gamma-globulin (HGG) solutions. After incubation at 37°C for 1 h, the particles were sedimented by centrifugation, and proteins in the supernatant, as well as those bound to the particles, were analyzed. The total protein concentration in the supernatant was lowered by TiO(2), whereas the albumin/globulin ratio was elevated by the particles. Incubation with TiO(2) also lowered the immunoglobulin, pre-albumin, beta2-microglobulin, ceruloplasmin and retinol-binding protein levels, but not ferritin levels, in the supernatant. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), proteins in the supernatant, especially HGG, were observed to decrease, while those released from the particles (after adding 1% SDS and heating) increased, depending on the dose of TiO(2). Purified HGG and HSA were also bound to TiO(2), although the former appeared to have a higher affinity. All the proteins tested showed the highest binding potency to the amorphous particles (<50 nm) and the lowest to the rutile particles (<5,000 nm), while binding to anatase particles was intermediate. The affinity to the larger anatase was higher than that to smaller anatase particles in most cases. Human serum proteins, including the two major components, HSA and HGG, are bound by TiO(2) particles. The polymorph of the particles seems to be important for determining the binding capacity of the particles and it may affect distribution of the particles in the body.

Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

PubMed

El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

2016-09-01

Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus.

PubMed

Saito, Tomoyuki; Murata, Miho; Otani, Taeko; Tamemoto, Hiroyuki; Kawakami, Masanobu; Ishikawa, San-E

2012-01-01

The goal of the study was to examine the association of subcutaneous and visceral fat mass with serum concentrations of adipokines in 130 subjects with type 2 diabetes mellitus. The levels of serum high sensitivity C-reactive protein (HS-CRP), adiponectin, high-molecular-weight (HMW) adiponectin, interleukin-18, and retinol-binding protein 4 were measured. Percentage body fat was determined by dual energy X-ray absorptiometry, and subcutaneous and visceral fat areas were measured by abdominal CT. HS-CRP had significant positive correlations with percentage body fat and subcutaneous fat area, and a particularly significant positive correlation with visceral fat area. Serum adiponectin had a negative correlation with the subcutaneous and visceral fat areas, with the strongest correlation with the visceral fat area. Similar results were obtained for HMW adiponectin. Serum adiponectin had a negative correlation with visceral fat area in subjects with a visceral fat area < 100 cm², but not in those with a visceral fat area ≥ 100 cm². In contrast, serum HS-CRP showed a positive correlation with visceral fat area in subjects with visceral fat area ≥ 100 cm², but not in those with a visceral fat area < 100 cm². These findings indicate that an increased visceral fat area is associated with inflammatory changes, and that inflammatory reactions may alter the functional properties of visceral fat in type 2 diabetes mellitus.

Biomarkers of Nutrition for Development (BOND)—Vitamin A Review1234

PubMed Central

Tanumihardjo, Sherry A; Russell, Robert M; Stephensen, Charles B; Craft, Neal E; Haskell, Marjorie J; Lietz, Georg; Schulze, Kerry; Raiten, Daniel J

2016-01-01

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-informed advice to anyone with an interest in the role of nutrition in health. The BOND program provides information with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect, which will be especially useful for readers who want to assess nutrient status. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutritional status at the individual and population levels. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, folate, zinc, iron, vitamin A, and vitamin B-12. This review of vitamin A is the current article in this series. Although the vitamin was discovered >100 y ago, vitamin A status assessment is not trivial. Serum retinol concentrations are under homeostatic control due in part to vitamin A’s use in the body for growth and cellular differentiation and because of its toxic properties at high concentrations. Furthermore, serum retinol concentrations are depressed during infection and inflammation because retinol-binding protein (RBP) is a negative acute-phase reactant, which makes status assessment challenging. Thus, this review describes the clinical and functional indicators related to eye health and biochemical biomarkers of vitamin A status (i.e., serum retinol, RBP, breast-milk retinol, dose-response tests, isotope dilution methodology, and serum retinyl esters). These biomarkers are then related to liver vitamin A concentrations, which are usually considered the gold standard for vitamin A status. With regard to biomarkers, future research questions and gaps in our current understanding as well as limitations of the methods are described. PMID:27511929

Serum Nutritional Biomarkers and Their Associations with Sleep among US Adults in Recent National Surveys

PubMed Central

Beydoun, May A.; Gamaldo, Alyssa A.; Canas, Jose A.; Beydoun, Hind A.; Shah, Mauli T.; McNeely, Jessica M.; Zonderman, Alan B.

2014-01-01

Background The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear. Methods Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2005–2006 were used. We selected 2,459 adults aged 20–85, with complete data on key variables. Five sleep measures were constructed as primary outcomes: (A) Sleep duration; (B) Sleep disorder; (C) Three factors obtained from factor analysis of 15 items and labeled as “Poor sleep-related daytime dysfunction” (Factor 1), “Sleepiness” (Factor 2) and “Sleep disturbance” (Factor 3). Main exposures were serum concentrations of key nutrients, namely retinol, retinyl esters, carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene), folate, vitamin B-12, total homocysteine (tHcy), vitamin C, 25-hydroxyvitamin D (25(OH)D) and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models. Results Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OH)D and sleepiness (as well as insomnia), and between folate and sleep disturbance. Serum total carotenoids concentration was linked to higher odds of short sleep duration (i.e. 5–6 h per night) compared to normal sleep duration (7–8 h per night). Conclusions A few of the selected serum nutritional biomarkers were associated with sleep quantity and quality. Longitudinal studies are needed to ascertain temporality and assess putative causal relationships. PMID:25137304

[The influence of age and sex on fat- and water-soluble vitamins sufficiency of adulthood].

PubMed

Beketova, N A; Spiricheva, T V; Pereverzeva, O G; Kosheleva, O V; Brzhesinskaia, O A; Kharitonchik, L A; Kodentsova, V M; Spirichev, V B

2009-01-01

Serum concentrations of vitamins A, B2, B6, C, E and beta-carotene were determined in 174 healthy individuals ages 22-59 years. It was been shown that only 11% of examined men and 24% of women were well provided with all vitamins-antioxidants and beta-carotene. 38% cent of women and 67% cent of men had the combined insufficiency of 2-3 antioxidants (more often of vitamin C, B2 and beta-carotene). Men presented significantly higher serum retinol concentrations and lower concentrations of vitamin C and beta-carotene--than women. Serum concentrations of retinol for women and tocopherols for both men and women increased by 0.3% and 0.4% per year, respectively.

Evaluation of insulin-like growth factor (IGF-1) and retinol binding protein (RBP-4) levels in patients with newly diagnosed pancreatic adenocarcinoma (PDAC).

PubMed

Wlodarczyk, Barbara; Gasiorowska, Anita; Borkowska, Anna; Malecka-Panas, Ewa

The elevation of insulin-like growth factor 1 (IGF-1) and adipokine retinol-binding protein 4 (RBP-4) is known to be associated with the risk of many cancers. The aim of this study was to evaluate the serum concentrations of IGF-1 and RBP-4 in patients with PDAC and chronic pancreatitis (CP). The study included 43 patients with PDAC, 39 patients with CP and 10 controls. The concentrations of IGF-1 and RBP-4 were obtained using the ELISA method (Corgenix UK Ltd R&D Systems). The study protocol was approved by the Bioethics Committee at the Medical University of Lodz. In PDAC patients the serum IGF-1 level was significantly higher than in patients with CP (107.79 ± 66.40 ng/ml vs 89.91 ± 74.06 ng/ml; P < 0.05). Patients with both CP and diabetes mellitus (DM) were noted to have a significantly lower level of IGF-1 compared with those who only had CP (51.33 ± 24.30 ng/ml vs 108.42 ± 82.39 ng/ml; P = 0.01). The same result was obtained for men with and without DM (58.05 ± 32.44 ng/ml vs 98.79 ± 79.47 ng/ml, P = 0.05). As regards the serum level of RBP-4, the PDAC and CP groups were not significantly different from each other. Diabetes accompanying PDAC does not influence the level of IGF-1 as opposed to diabetes in the course of CP. The IGF-1 level can be useful for early diagnosis of PDAC. High concentration of RBP-4 is not specific to pancreatic cancer, so it does not appear to be a useful biomarker for PDAC. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis

PubMed Central

Kimura, Yayoi; Yanagimachi, Masakatsu; Ino, Yoko; Aketagawa, Mao; Matsuo, Michie; Okayama, Akiko; Shimizu, Hiroyuki; Oba, Kunihiro; Morioka, Ichiro; Imagawa, Tomoyuki; Kaneko, Tetsuji; Yokota, Shumpei; Hirano, Hisashi; Mori, Masaaki

2017-01-01

Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features. PMID:28262744

Determination of carotenoids and all-trans-retinol in fish eggs by liquid chromatography-electrospray ionization-tandem mass spectrometry.

PubMed

Li, Hongxia; Tyndale, Sélène T; Heath, Daniel D; Letcher, Robert J

2005-02-25

A novel method was developed for the combined determination of carotenoids and retinoids in fish eggs, which incorporates prior analyte isolation using liquid-liquid partitioning to minimize analyte degradation, and fraction analysis using high-performance liquid chromatography-electrospray (positive)-quadrupole mass spectrometry (LC-ESI(+)-MS; SIM or MRM modes). Eggs from Chinook salmon (Oncorhynchus tshawytscha) were used as the model fish egg matrix. The methodology was assessed and validated for beta-carotene, lutein, zeaxanthin, and beta-cryptoxanthin (molecular ion radicals [M](+)), canthaxanthin and astaxanthin ([M+Na](+) adducts) and all-trans-retinol ([(M+H)-H(2)O](+)). Using replicate egg samples (n=5) spiked with beta-cryptoxanthin and beta-carotene before and after extraction, matrix-sourced ESI(+) enhancement was observed as evidenced by comparable %matrix effect and %process efficiency values for beta-cryptoxanthin and beta-carotene of 114-119%. In aquaculture-raised eggs from adult Chinook salmon astaxanthin, all-trans-retinol, lutein and canthaxanthin were identified and determined at concentrations of 4.12, 1.06, 0.12 and 0.45 microg/g (egg wet weight), respectively. To our knowledge, this is the first report on a method for LC-MS determination of carotenoids and retinoids in a fish egg matrix, and the first carotenoid-specific determination in any fish egg sample.

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older.

PubMed

Majerczyk, M; Kocełak, P; Choręza, P; Arabzada, H; Owczarek, A J; Bożentowicz-Wikarek, M; Brzozowska, A; Szybalska, A; Puzianowska-Kuźnicka, M; Grodzicki, T; Więcek, A; Olszanecka-Glinianowicz, M; Chudek, J

2018-03-09

Elevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older. The study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured. Nutritional status (BMI/waist circumference) and treatment with statins and fibrates were evaluated. Glomerular filtration rate (eGFR), de Ritis ratio, and fatty liver index (FLI), as well as HOMA-IR were calculated. Our study revealed a strong relationship between components of MS and RBP4 in both sexes: plasma RBP4 levels were increased in men by at least 3×, and in women by at least 4×. Hypertriglyceridemia was most strongly associated with elevated plasma RBP4 levels. Multivariate, sex-adjusted regression analysis demonstrated that chronic kidney disease [OR 1.86 (95% CI 1.78-1.94)], hypertriglyceridemia [OR 1.52 (1.24-1.87)], hypertension [OR 1.15 (1.12-1.19)], low serum HDL cholesterol [OR 0.94 (0.92-0.97)], and age > 80 years [OR 0.86 (0.81-0.90)] were each independently associated with RBP4 concentration (all p < 0.001). In Caucasians 65 years and older, RBP4 serum levels are associated with a number of components of MS, independent of sex and kidney function. Hypertriglyceridemia as a component of MS is most significantly related to RBP4 concentration.

Thermometric sensing of peroxide in organic media. Application to monitor the stability of RBP-retinol-HRP complex.

PubMed

Ramanathan, K; Jönsson, B R; Danielsson, B

2000-08-01

The stability of horseradish peroxidase (HRP) in aqueous and organic solvents is applied to develop a simple thermometric procedure to detect the binding of retinoic acid-HRP conjugate to retinol binding protein (RBP). Butanone peroxide (BP) in organic phase and hydrogen peroxide in aqueous phase is detected thermometrically on a HRP column, immobilized by cross-linking with glutaraldehyde on controlled pore glass (CPG). Acetone, acetonitrile, methanol, and 2-butanol are used for detection of BP, in the flow injection analysis (FIA) mode. A linear range between 1 and 50 mM BP is obtained in all the organic solvents with a precision of 5-7% (CV%). The magnitude and nature of the thermometric response is significantly different in each organic solvent. The stability of HRP in the organic phase is used to study the stability of a retinoic acid-HRP conjugate bound to immobilized RBP. The response of HRP (to 20 mM BP) in the retinoic acid-HRP conjugate is used as an indicator of the stability of the RBP-retinoic acid-HRP complex, after challenges with various organic/aqueous solvents. Both immobilized HRP and RBP are stable at least for 6 months. The effect of o-phenylene diamine on the thermometric response of HRP is also investigated. A scheme for the design of a thermometric retinol (vitamin A) biosensor is proposed.

No drive line, no seal, no bearing and no wear: magnetics for impeller suspension and flow assessment in a new VAD.

PubMed

Huber, Christoph H; Tozzi, Piergiorgio; Hurni, Michel; von Segesser, Ludwig K

2004-06-01

The new magnetically suspended axial pump is free of seals, bearings, mechanical friction and wear. In the absence of a drive shaft or flow meter, pump flow assessment is made with an algorithm based on currents required for impeller rotation and stabilization. The aim of this study is to validate pump performance, algorithm-based flow and effective flow. A series of bovine experiments was realized after equipment with pressure transducers, continuous-cardiac-output-catheter, intracardiac ultrasound (AcuNav) over 6 h. Pump implantation was through a median sternotomy (LV-->VAD-->calibrated transonic-flow-probe-->aorta). A transonic-HT311-flow-probe was fixed onto the outflow cannula for flow comparison. Animals were electively sacrificed and at necropsy systematic pump inspection and renal embolus score was realized. Observation period was 340+/-62.4 min. The axial pump generated a mean arterial pressure of 58.8+/-14.3 mmHg (max 117 mmHg) running at a speed of 6591.3+/-1395.4 rev./min (min 5000/max 8500 rev./min) and generating 2.5+/-1.0 l/min (min 1.4/max 6.0 l/min) of flow. Correlation between the results of the pump flow algorithm and measured pump flow was linear (y=1.0339x, R2=0.9357). VAD explants were free of macroscopic thrombi. Renal embolus score was 0+/-0. The magnetically suspended axial flow pump provides excellent left ventricular support. The pump flow algorithm used is accurate and reliable. Therefore, there is no need for direct flow measurement.

Risk of zinc, iodine and other micronutrient deficiencies among school children in North East Thailand.

PubMed

Thurlow, R A; Winichagoon, P; Pongcharoen, T; Gowachirapant, S; Boonpraderm, A; Manger, M S; Bailey, K B; Wasantwisut, E; Gibson, R S

2006-05-01

Micronutrient deficiencies during childhood can contribute to impairments in growth, immune competence, and mental and physical development, and the coexistence of several such deficiencies can adversely affect the efficacy of single micronutrient interventions. To assess the prevalence of zinc and iodine deficiency and their interrelationships with vitamin A deficiency and anemia and associations with socio-economic status, hemoglobin type, and anthropometry in a cross-sectional study. A total of 10 primary schools in North East Thailand. Non-fasting venipuncture blood samples and casual urine samples were collected from 567 children aged 6-13 years. Anthropometric measures and serum zinc, albumin, C-reactive protein and urinary iodine, are reported here and integrated with published data on vitamin A, anemia, and socio-economic status. Of the children, 57% had low serum zinc and 83% had urinary iodine levels below the 100 microg/l cutoff. Suboptimal serum zinc and urinary iodine concentrations may result from low intakes of zinc and iodized salt. Significant risk factors for low serum zinc were serum retinol <1.05 micromol/l and being male. Those for urinary iodine <100 microg/l were height-for-age score>median and being female. For serum retinol <1.05 micromol/l, risk factors were low hemoglobin, low serum zinc, and <9 years, and for low hemoglobin indicative of anemia risk factors were <9 years, AE hemoglobinopathy, and serum retinol <1.05 micromol/l. Of the children, 60% were at risk of two or more coexisting micronutrient deficiencies, most commonly suboptimal urinary iodine and low serum zinc. The findings emphasize the need for multimicronutrient interventions in North East Thailand.

Depletion of serum carotenoid and other fat-soluble vitamin concentrations following obesity surgery.

PubMed

Granado-Lorencio, Fernando; Simal-Antón, Alberto; Blanco-Navarro, Inmaculada; González-Dominguez, Teresa; Pérez-Sacristán, Belén

2011-10-01

Obesity constitutes a growing health problem, and surgical treatment of severe obesity is increasingly used. Nutrient deficiencies are common following bariatric surgery and the evidence indicates a progressive increase in the incidence and severity of the deficiency of certain vitamins and related clinical conditions. Because of the potential role of carotenoids in disease prevention, our aim was to assess the carotenoid status in candidates for obesity surgery and the time-course changes following two bariatric procedures. Seventy-five candidates for bariatric surgery (17 men, 58 women; age 43 ± 10 years) and a total of 362 serum samples after obesity surgery (i.e., Roux-en-Y gastric bypass (n = 187) and biliopancreatic diversion (n = 175)) were consecutively collected and assessed. Retinol, α- and γ-tocopherol, 25-OH-vitamin D3, lutein, zeaxanthin, α- and β-cryptoxanthin, lycopene (trans and cis), α- and β-carotene (trans and cis) were analyzed by high-performance liquid chromatography. Mean serum levels of carotenoids in candidates for obesity surgery were within the reference values reported in controls and seasonal variations were present in several analytes. After surgery, and regardless of the type of intervention, all serum carotenoids dropped following first-order kinetics. Cis/trans ratio of lycopene and β-carotene did not change after surgery, over the time or between surgical procedures. On a long-term, serum carotenoids were at or below fifth percentile of reference groups. The chronic low levels of carotenoids in these patients compromise their availability to tissues, constituting an additional risk factor for other clinical conditions. Dietary advice on carotenoid-rich, fortified foods or supplements should be also evaluated in these patients.

Evaluation of anti-wrinkle effects of a novel cosmetic containing retinol using the guideline of the Japan Cosmetic Industry Association.

PubMed

Kawada, Akira; Konishi, Natsuko; Momma, Tomoyuki; Oiso, Naoki; Kawara, Shigeru

2009-11-01

Retinol is known to be effective in the treatment of sallowness, wrinkling, red blotchiness and hyperpigmented spots in aging skin. In this study, we have evaluated the anti-wrinkle effects of a new cosmetic containing retinol. An open study was performed in 30 healthy Japanese women who had wrinkles at the corners of the eyes. The tested lotion, Retin-OX+ (RoC SA, Colombes, France), was applied on wrinkles of one side of the face for 8 weeks, and not on the other site as a control. Anti-wrinkle effects were evaluated by two methods: (i) doctors' observation and photos based on the guideline of the Japan Cosmetic Industry Association; and (ii) the Robo Skin Analyzer. This lotion showed marked and moderate improvement in 34% of the subjects with a significant difference as compared with the control sites (P < 0.05). Moreover, the length and area decreased in the applied site more than the control site with a significant difference (P < 0.01). All the patients completed the study without significant adverse reactions. The tested lotion was well tolerated and may be an optional preparation for the treatment of wrinkles at the corner of the eyes.

A randomized, double-blind, controlled comparative trial of the anti-aging properties of non-prescription tri-retinol 1.1% vs. prescription tretinoin 0.025%.

PubMed

Ho, Elizabeth T; Trookman, Nathan S; Sperber, Brian R; Rizer, Ronald L; Spindler, Ralph; Sonti, Sujatha; Gotz, Vincent; Mehta, Rahul

2012-01-01

Vitamin A and its derivatives (commonly termed retinoids) are widely used in topical anti-aging products. Certain retinoids such as retinol and its esters are available without a prescription, while others such as tretinoin are available only via prescription. A randomized, double-blind, controlled clinical study was conducted to compare the efficacy and tolerability of a tri-retinol 1.1% gradual release cream vs. tretinoin 0.025% cream in females with mild-to-moderate facial photodamage. Subjects applied the test product to the entire face in the evening after cleansing in a progressively increasing frequency starting twice weekly for the first week, followed by three times weekly during the second week and then daily as tolerated for the third week and beyond. Treatment was continued for a total of three months. Clinical evaluations and standardized digital photographs were performed at baseline and after four, eight, and 12 weeks of treatment. Self-assessment questionnaires were completed by the subjects at four, eight, and 12 weeks to assess perceived efficacy of the test products. Thirty-four subjects (16: tri-retinol and 18: tretinoin) completed the study. Both test products significantly improved signs of photodamage, including fine and coarse periocular wrinkles, skin firmness, skin tone, mottled pigmentation, tactile roughness, overall photodamage and global photodamage improvement. There were no significant differences in efficacy between the two products for these assessments. The adverse effects (which were graded as mild or less) were those typically seen with topical retinoids. Subjects reported >93 percent overall satisfaction with both products at weeks 8 and 12.

[Effects of vitamin A supplementation on nutritional status of iron in healthy adults].

PubMed

Li, Zuwen; Fan, Ping; Deng, Gangbo; Du, Zhen; Shao, Zewei; Wang, Zhixu

2012-05-01

To investigate the effect of vitamin A (VA) supplementation on the nutritional status of iron in healthy adults. One hundred and fifteen healthy adults were recruited and divided randomly into four groups, with 28 or 29 adults in each group. VA supplements with different doses of retinyl acetate in capsules were given for 4-month. The equivalent doses of supplemented retinyl acetate were 600 microg/d, 400 microg/d, 200 microg/d and 0 microg/d (control) of retinol, respectively. The capsules were administered orally by double blind method. During the experiment, the subjects kept their usual dietary pattern but avoided high VA or pre-VA carotenoids foods from their diets. A 24-h dietary recall was carried out monthly on every subject. Before and after the intervention, the fast blood samples were collected from each subject, and were determined for hemoglobin concentration, levels of serum retinol, iron, ferrtin and transferrtin receptor. Total 108 subjects finished the experiment, with 27, 28, 27 and 26 persons left in group A, B, C and D, respectively. The subjects from each group had similar dietary intakes of energy nutrients, VA and iron (both were P > 0.05) during the experimental period. The serum retinol concentration of subjects from group A increased from 1.63 +/- 0.55 micromol/L of baseline to 1.93 +/-0.52 micromol/L at the end of the experiment (P < 0.05). The elevated value of serum retinol for group B and C were 0.29 micromol/L and 0.14 micromol/L (both were P < 0.05). There was no difference before and after the experiment for control group D (P > 0.05). There was no significant difference on Hb concentration before and after the experiment as well as between groups (all were P > 0.05). In subjects of group A, serum iron concentration increased (P < 0.05) and serum ferrtin and transferrtin receptor concentration decreased significantly (both were P < 0.05) after VA supplement intervention. No such changes were observed in group B and C (P < 0.05). It

[Determination of serum or plasma alpha-tocopherol by high performance liquid chromatography: optimization of operative models].

PubMed

Jezequel-Cuer, M; Le Moël, G; Mounié, J; Peynet, J; Le Bizec, C; Vernet, M H; Artur, Y; Laschi-Loquerie, A; Troupel, S

1995-01-01

A previous multicentric study set up by the Société française de biologie clinique has emphasized the usefulness of a standardized procedure for the determination by high performance liquid chromatography of alpha-tocopherol in serum or plasma. In our study, we have tested every step of the different published procedures: internal standard adduct, lipoprotein denaturation and vitamin extraction. Reproducibility of results was improved by the use of tocol as an internal standard when compared to retinol or alpha-tocopherol acetates. Lipoprotein denaturation was more efficient with ethanol addition than with methanol and when the ethanol/water ratio was > or = 0.7. Use of n-hexane or n-heptane gave the same recovery of alpha-tocopherol. When organic solvent/water ratio was > or = 1, n-hexane enabled to efficiently extract, in a one-step procedure, the alpha-tocopherol from both normo and hyperlipidemic sera. Performances of the selected procedure were: detection limit: 0.5 microM--linear range: 750 microM--within run coefficient of variation: 2.03%--day to day: 4.76%. Finally, this pluricentric study allows us to propose an optimised procedure for the determination of alpha-tocopherol in serum or plasma.

Retinoic Acid Is Present in the Postnatal Rat Olfactory Organ and Persists in Vitamin A–Depleted Neural Tissue1–3

PubMed Central

Asson-Batres, Mary Ann; Smith, W. Bradford; Clark, Gale

2009-01-01

Vitamin A (VA), all-trans-retinol (at-ROL), and its derivative, all-trans-retinoic acid (at-RA), are required for neuron development. The effects of these retinoids are dependent upon the nutritional status of the rat and tissue-specific dynamics of retinoid access and utilization. The purpose of this study was to determine the status of at-ROL and at-RA in the peripheral olfactory organ of postnatal rats fed a normal diet and rats fed a VA-deficient (VAD) diet. Extracted retinoids were analyzed by HPLC. Resolved sample peaks were identified by comparing their elution times and spectra with those of authentic standards. Mean at-RA and at-ROL concentrations of 23 pmol/g olfactory tissue and 0.13 nmol/g, respectively, were recovered from olfactory tissue. The ratio of at-RA:at-ROL in olfactory was ∼2 times that in testis and 200 times that in liver. at-ROL was depleted from the liver and olfactory organ of rats fed a VAD diet from birth to 70 d of age. Surprisingly, at-RA was still present in olfactory tissue from these rats. At 90 d of age, the VAD rats were frankly deficient and at-RA was no longer detectable in olfactory tissue. The comparatively high ratio of at-RA:at-ROL in the peripheral olfactory organ and the persistence of at-RA in at-ROL-depleted tissues strongly suggests that maintenance of local stores of at-RA is functionally relevant in this tissue. PMID:19403718

Antiaging action of retinol: from molecular to clinical.

PubMed

Bellemère, G; Stamatas, G N; Bruère, V; Bertin, C; Issachar, N; Oddos, T

2009-01-01

The antiaging efficacy of retinol (ROL) has been explored mainly clinically in photoprotected skin sites and for high doses of ROL (0.4-1.6%). The objective of the study was to demonstrate the antiaging action of a low and tolerable dose of ROL (0.1%) ex vivo by measuring the expression of cellular retinoic-acid-binding protein II (CRABP2) and heparin-binding epidermal growth factor (HBEGF) by a histological evaluation of the epidermis and in vivo by assessing major aging signs and performing three-dimensional profilometry and digital imaging during a 9-month double-blind placebo-controlled study involving 48 volunteers. Finally, epidermal cell proliferation was evaluated using tryptophan fluorescence spectroscopy. Our results demonstrate that 0.1% ROL induced CRABP2 and HBEGF gene expression and increased keratinocyte proliferation and epidermal thickness. In human volunteers, topical application of a ROL-containing product improved all major aging signs assessed in our study (wrinkles under the eyes, fine lines and tone evenness). Moreover, tryptophan fluorescence increased in the active-agent-treated group and not in the placebo-treated group, indicating that cell proliferation was accelerated in vivo. These data demonstrate that a product containing a low dose (0.1%) of ROL promotes keratinocyte proliferation ex vivo and in vivo, induces epidermal thickening ex vivo and alleviates skin aging signs, without any significant adverse reaction. Copyright 2009 S. Karger AG, Basel.

Simultaneous determination of carotenoids, tocopherols, retinol and cholesterol in ovine lyophilised samples of milk, meat, and liver and in unprocessed/raw samples of fat.

PubMed

Bertolín, J R; Joy, M; Rufino-Moya, P J; Lobón, S; Blanco, M

2018-08-15

An accurate, fast, economic and simple method to determine carotenoids, tocopherols, retinol and cholesterol in lyophilised samples of ovine milk, muscle and liver and raw samples of fat, which are difficult to lyophilise, is sought. Those analytes have been studied in animal tissues to trace forage feeding and unhealthy contents. The sample treatment consisted of mild overnight saponification, liquid-liquid extraction, evaporation with vacuum evaporator and redissolution. The quantification of the different analytes was performed by the use of ultra-high performance liquid chromatography with diode-array detector for carotenoids, retinol and cholesterol and fluorescence detector for tocopherols. The retention times of the analytes were short and the resolution between analytes was very high. The limits of detection and quantification were very low. This method is suitable for all the matrices and analytes and could be adapted to other animal species with minor changes. Copyright © 2018 Elsevier Ltd. All rights reserved.

A randomized, double-blind, split-face study comparing the efficacy and tolerability of three retinol-based products vs. three tretinoin-based products in subjects with moderate to severe facial photodamage.

PubMed

Babcock, Michael; Mehta, Rahul C; Makino, Elizabeth T

2015-01-01

Retinol, has been shown to improve the appearance of photodamaged skin when applied topically, and is generally considered to be approximately ten times less potent than tretinoin. To assess this theory, three cosmetic formulations containing 0.25%, 0.5%, and 1.0% retinol were developed to correspond to the three commonly prescribed concentrations of tretinoin (0.025%, 0.05%, and 0.1%). A randomized, double-blind, split-face comparison study was conducted to compare the three concentrations retinol (Ret) including 0.25%, 0.5%, and 1.0%, against the respective three strengths of tretinoin (Tret) 0.025%, 0.05%, and 0.1% in subjects with moderate to severe facial photodamage. Subjects were randomized into three groups: Group 1 (Ret 0.25% vs. Tret 0.025%); Group 2 (Ret 0.5% vs. Tret 0.05%); and Group 3 (Ret 1.0% vs. Tret 0.1%). Within each group, subjects were randomized to apply Ret on one half of the face (left or right) and Tret on the other facial side, for a duration of twelve weeks. Clinical evaluations for efficacy and tolerability, as well as standardized digital photographs were conducted at baseline and at weeks 4, 8, and 12. Sixty-five subjects completed the twelve-week study (Group 1: n=24, Group 2: n=20, and Group 3: n=21). At week 12 in all treatment groups, both Ret and Tret produced statistically significant improvements from baseline in all efficacy parameters, including overall photodamage, fine lines/wrinkles, coarse lines/wrinkles, skin tone brightness, mottled pigmentation, and tactile roughness (all P<0.001). There were no significant differences in efficacy between Ret and Tret in these efficacy parameters. Results from this comparison study suggest that this sustained-release retinol complex containing multiple agents for optimal irritation control provides comparable improvements to tretinoin in the appearance of photodamage.

Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study.

PubMed

Liu, Gang; Ding, Ming; Chiuve, Stephanie E; Rimm, Eric B; Franks, Paul W; Meigs, James B; Hu, Frank B; Sun, Qi

2016-11-01

To examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus. Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid-binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance. These data suggest that higher levels of fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus. © 2016 American Heart Association, Inc.

Combined effects of retinol, ascorbic acid and α-tocopherol on diurnal variations in rectal temperature of Black Harco pullets subjected to heat stress

NASA Astrophysics Data System (ADS)

Sinkalu, Victor Olusegun; Ayo, Joseph Olusegun

2018-01-01

The experiment was performed with the aim of determining the effect of co-administration of antioxidant vitamins, retinol, ascorbic acid and α-tocopherol on rectal temperature (RT) fluctuations in pullets during the hot-dry season in Nigeria. Forty-eight Black Harco pullets, aged 16 weeks and weighing 1.5 ± 0.03 kg were divided by simple random sampling into two groups, consisting of 28 treated and 20 control Black Harco pullets. The RTs of 28 treated and 20 control Black Harco pullets were measured hourly for 3 days, 3 days apart, from 06:00 to 19:00 h (GMT + 1) with a standard clinical thermometer. The treated pullets were administered individually with the vitamins orally in water, while the control pullets were given only water. The lowest hourly RT of 40.9 ± 0.04 °C was obtained in treated pullets at 06:00 h, while the highest value of 41.1 ± 0.01 °C was recorded from 17:00 to 19:00 h ( P < 0.001). In control pullets, the RT rose significantly from 41.0 ± 0.03 °C at 06:00 h to the maximum value of 41.6 ± 0.04 °C at 15:00 h ( P < 0.001). The pullets co-administered with retinol, ascorbic acid and α-tocopherol had consistently lower RT values than those of control pullets, especially during the hot hours of the day, from 13:00 to 17:00 h. It is concluded that co-administration of retinol, ascorbic acid and α-tocopherol, by preventing a rise in body temperature, ameliorated heat stress, and may enhance productivity of pullets reared under unfavourable, thermal environment conditions.

Mineral and vitamin status in elderly persons from Northwest Spain consuming an Atlantic variant of the Mediterranean diet.

PubMed

Vaquero, M Pilar; Sánchez-Muniz, Francisco J; Carbajal, Angeles; García-Linares, M Carmen; García-Fernández, M Camino; García-Arias, M Trinidad

2004-01-01

To assess dietary intake and serum mineral and vitamin levels in elderly people from Northwest Spain consuming a Mediterranean diet, rich in vegetables, fruit, meat, fish, olive oil, dairy products and moderate in wine. Cross-sectional observational study in four retirement homes. Forty-five men and 65 women participated. Dietary intake and serum calcium, magnesium, iron, retinol, alpha-tocopherol, albumin, cholesterol, glucose and hematological parameters were determined. Mean consumption of fruit plus vegetables was 600 g/day. Men consumed significantly more legumes, fruit, meat, and alcoholic beverages, but fewer vegetables than women. Women presented higher carbohydrate and lower alcohol energy contributions. Men consumed significantly more thiamin, niacin equivalents, riboflavin, retinol equivalents and iron. Vitamin D intake was 2.2 +/- 1.2 microg/day and folate intake was 204 +/- 47 microg/day without gender differences. Prevalence of anemia was 6.7% and that of high ferritin, 1.8%. Serum cholesterol and retinol were higher in women. Mean serum alpha-tocopherol/cholesterol ratio in the whole population was 6.3 +/- 2.3 mmol/mol without gender differences. This elderly population consumes an Atlantic-Mediterranean diet that appears, according to biochemical and hematological parameters, appropriate. However, more fatty fish and leafy green vegetables and the inclusion of fortified foods in the diet might optimize micronutrient status. Copyright 2004 S. Karger AG, Basel

Diethylnitrosamine-induced hepatocarcinogenesis is suppressed in lecithin:retinol acyltransferase-deficient mice primarily through retinoid actions immediately after carcinogen administration.

PubMed

Shirakami, Yohei; Gottesman, Max E; Blaner, William S

2012-02-01

Loss of retinoid-containing lipid droplets upon hepatic stellate cell (HSC) activation is one of the first events in the development of liver disease leading to hepatocellular carcinoma. Although retinoid stores are progressively lost from HSCs during the development of hepatic disease, how this affects hepatocarcinogenesis is unclear. To investigate this, we used diethylnitrosamine (DEN) to induce hepatic tumorigenesis in matched wild-type (WT) and lecithin:retinol acyltransferase (LRAT) knockout (KO) mice, which lack stored retinoid and HSC lipid droplets. Male 15-day-old WT or Lrat KO mice were given intraperitoneal injections of DEN (25 mg/kg body wt). Eight months later, Lrat KO mice showed significantly less liver tumor development compared with WT mice, characterized by less liver tumor incidence and smaller tumor size. Two days after DEN injection, lower serum levels of alanine aminotransferase and decreased hepatic levels of cyclin D1 were observed in Lrat KO mice. Lrat KO mice also exhibited increased levels of retinoic acid-responsive genes, including p21, lower levels of cytochrome P450 enzymes required for DEN bioactivation and higher levels of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), both before and after DEN treatment. Our results indicate that Lrat KO mice are less susceptible to DEN-induced hepatocarcinogenesis due to increased retinoid signaling and higher expression of p21, which is accompanied by altered hepatic levels of DEN-activating enzymes and MGMT in Lrat KO mice also contribute to decreased cancer initiation and suppressed liver tumor development.

Vitamin A deficiency and inflammatory markers among preschool children in the Republic of the Marshall Islands.

PubMed

Maqsood, Maria; Dancheck, Barbara; Gamble, Mary V; Palafox, Neal A; Ricks, Michelle O; Briand, Kennar; Semba, Richard D

2004-12-08

The exclusion of individuals with elevated acute phase proteins has been advocated in order to improve prevalence estimates of vitamin A deficiency in surveys, but it is unclear whether this will lead to sampling bias. The purpose of the study was to determine whether the exclusion of individuals with elevated acute phase proteins is associated with sampling bias and to characterize inflammation in children with night blindness. In a survey in the Republic of the Marshall Islands involving 281 children, aged 1-5 years, serum retinol, C-reactive protein (CRP), and alpha1-acid glycoprotein (AGP) were measured. Of 281 children, 24 (8.5%) had night blindness and 165 (58.7%) had serum retinol < 0.70 micromol/L. Of 248 children with AGP and CRP measurements, 123 (49.6%) had elevated acute phase proteins (CRP > mg/L and/or AGP > 1000 mg/L). Among children with and without night blindness, the proportion with serum retinol < 0.70 micromol/L was 79.2% and 56.8% (P = 0.03) and with anemia was 58.3% and 35.7% (P = 0.029), respectively. The proportion of children with serum retinol < 0.70 micromol/L was 52.0% after excluding children with elevated acute phase proteins. Among children with and without elevated acute phase proteins, mean age was 2.8 vs 3.2 years (P = 0.016), the proportion of boys was 43.1% vs. 54.3% (P = 0.075), with no hospitalizations in the last year was 11.0% vs 23.6% (P = 0.024), and with anemia was 43.8% vs 31.7% (P = 0.05), respectively. Exclusion of children with inflammation in this survey of vitamin A deficiency does not improve prevalence estimates for vitamin A deficiency and instead leads to sampling bias for variables such as age, gender, anemia, and hospitalization history.

Vitamin A intake, serum vitamin D and bone mineral density: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2011).

PubMed

Joo, Nam-Seok; Yang, Sung-Won; Song, Byeng Chun; Yeum, Kyung-Jin

2015-03-10

The association of high vitamin A intake and low bone mineral density (BMD) is still controversial. To determine the association of dietary vitamin A intake and serum 25-hydroxyvitamin D (25(OH)D) concentration with BMD, a total of 6481 subjects (2907 men and 3574 women) aged ≥50 years from the Korean National Health and Nutrition Examination Survey (2008-2011) were divided into groups according to dietary vitamin A intake (tertiles) and serum 25(OH)D (<50, 50-75, >75 nmol/L), and evaluated for BMD after adjusting for relevant variables. Mean dietary vitamin A intakes were 737 and 600 μg RE (Retinol Equivalents) in men and women, respectively. Total hip and femoral neck BMD in men and lumbar spine BMD in women were both positively correlated with dietary vitamin A intake in subjects with serum 25(OH)D >75 nmol/L. Among men with serum 25(OH)D <50 nmol/L, both the top (mean 1353 μg RE) and bottom (mean 218 μg RE) tertiles of dietary vitamin A intake had lower BMD than the middle group (mean 577 μg RE). In this population, BMD was the highest among men and women with serum 25(OH)D = 50-75 nmol/L and that there were no differences in BMD by vitamin A intake in these vitamin D adequate groups. This cross-sectional study indicates that vitamin A intake does not affect bone mineral density as long as the serum 25(OH)D concentration is maintained in the moderate level of 50-75 nmol/L.

Phylogeny of lion tamarins (Leontopithecus spp) based on interphotoreceptor retinol binding protein intron sequences.

PubMed

Mundy, N I; Kelly, J

2001-05-01

The evolutionary relationships of the lion tamarins (Leontopithecus) were investigated using nuclear interphotoreceptor retinol binding protein (IRBP) intron sequences. Phylogenetic reconstructions strongly support the monophyly of the genus, and a sister relationship between the golden lion tamarin, Leontopithecus rosalia, and the black lion tamarin, L. chrysopygus, to the exclusion of the golden-headed lion tamarin, L. chrysomelas. The most parsimonious evolutionary reconstruction suggests that the ancestral lion tamarin and the common ancestor of L. rosalia and L. chrysopygus had predominantly black coats. This reconstruction is not consistent with a theory of orthogenetic evolution of coat color that was based on coat color evolution in marmosets and tamarins. An alternative reconstruction that is consistent with metachromism requires that ancestral lion tamarins had agouti hairs. Copyright 2001 Wiley-Liss, Inc.

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors.

PubMed

Alicke, Marie; Boakye-Appiah, Justice K; Abdul-Jalil, Inusah; Henze, Andrea; van der Giet, Markus; Schulze, Matthias B; Schweigert, Florian J; Mockenhaupt, Frank P; Bedu-Addo, George; Danquah, Ina

2017-01-01

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4-15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38-52%), for malnutrition 50% (43-57%) and for CRFs 16% (11-21%). Infectious diseases and malnutrition frequently co-existed (28%; 21-34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2-9%) or with malnutrition (7%; 3-11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted.

Serum vitamin E, C and A status of the drug addicts undergoing detoxification: influence of drug habit, sexual practice and lifestyle factors.

PubMed

Nazrul Islam, S K; Jahangir Hossain, K; Ahsan, M

2001-11-01

The study was carried out on the hypothesis that drug addicts would have reduced vitamin E, C and A status which could be influenced by drug habit, sexual practice and lifestyle factors. Serum concentrations of Vitamin E, C and A of male drug addicts and cohort controls were analysed, and influence of drug habit, sexual practice and lifestyle factors of the addicts on the vitamin status was assessed. The study was conducted among 253 drug addicts who sought detoxification voluntarily during the period of June 1997 to July 1998 at the Central Drug Addiction Treatment Hospital, Dhaka, and 100 cohort control men. Research instruments were questionnaire and blood specimens. HPLC and spectrophotometric methods were used to determine the vitamin levels in sera of drug addicts. alpha-Tocopherol (12.60+/-3.73 compared with 16.3+/-3.37 micromol/l; t=8.6, P=0.05), ascorbic acid (21.59+/-10.5 compared with 38.3+/-13.62 micromol/l; t=10.93, P=0.003) and retinol (1.15+/-0.39 compared with 1.33+/-0.30 micromol/l; t=5.28, P=0.048) in the drug addicts were significantly low as compared to those in the cohort controls. Use of multiple illicit drugs for a longer period of time did result in reduced levels of these vitamins. A significant reduction in retinol concentration was noted among the multiple drug users (F(2,250)=3.23, P=0.041). Duration of addiction had a significant linear correlation with the level of reduction in retinol (F(2,250)=3.23, P=0.041) and alpha-tocopherol (F(2,250)=3.06, P=0.049). Apart from having a significant negative correlation between number of sexual partners and retinol level (F(3,247)=2.65, P=0.049), sexual practice did not have any influence on the vitamin status of the addicts. Occupation did have a significant effect on the ascorbic acid level (F(4,248)=2.46, P=0.046), but other socioeconomic factors like income, age etc did not influence the vitamin E, C and A levels. Body mass index had a positive linear correlation with the vitamins, but it was

Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort.

PubMed

Bakker, Marije F; Peeters, Petra Hm; Klaasen, Veronique M; Bueno-de-Mesquita, H Bas; Jansen, Eugene Hjm; Ros, Martine M; Travier, Noémie; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Rinaldi, Sabina; Romieu, Isabelle; Brennan, Paul; Boutron-Ruault, Marie-Christine; Perquier, Florence; Cadeau, Claire; Boeing, Heiner; Aleksandrova, Krasimira; Kaaks, Rudolf; Kühn, Tilman; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Vineis, Paolo; Krogh, Vittorio; Panico, Salvatore; Masala, Giovanna; Tumino, Rosario; Weiderpass, Elisabete; Skeie, Guri; Lund, Eiliv; Quirós, J Ramón; Ardanaz, Eva; Navarro, Carmen; Amiano, Pilar; Sánchez, María-José; Buckland, Genevieve; Ericson, Ulrika; Sonestedt, Emily; Johansson, Matthias; Sund, Malin; Travis, Ruth C; Key, Timothy J; Khaw, Kay-Tee; Wareham, Nick; Riboli, Elio; van Gils, Carla H

2016-02-01

Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity. This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer. In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided. In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution). Our results indicate that higher concentrations of plasma �

Immunohistochemical study of retinol-binding protein in livers of polar bears (Thalarctos maritimus).

PubMed

Heier, A; Gröne, A; Völlm, J; Kübber-Heiss, A; Bacciarini, L N

2003-03-01

Liver tumors of unknown cause have frequently been described in polar bears. Concurrent decrease of vitamin A levels and chronic liver disease are associated with hepatic carcinogenesis in humans. More than 90% of the body's vitamin A is stored in the liver, where it is bound to an intracellular retinol-binding protein (RBP). Therefore, in this retrospective study, RBP was assessed by immunohistochemistry in liver sections of 11 polar bears. Two of these polar bears had hepatocellular carcinoma, four showed other chronic liver changes, and five had normal livers. In normal livers, the cytoplasm stained diffusely positive with intensely staining cytoplasmic granules. RBP staining was evaluated and the abundance of diffuse cytoplasmic staining and intracytoplasmic large granules was determined. All cases with pathologic liver changes had markedly decreased staining intensities for RBP compared with normal livers. The findings of this study suggest that in polar bears, as in humans, vitamin A metabolism may play a role in hepatic carcinogenesis.

Ada Compiler Validation Summary Report: Certificate Number: 901129W1. 11096 Verdix Corporation, VADS Sequent Balance DYNIX 3.0, VAda-110-2323, Version 6.0, Sequent Balance 8000, DYNIX Version 3.0 (Host & Target).

DTIC Science & Technology

1991-08-01

90-09-25- VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 901129W1.11096 Verdix Corporation VADS Sequent Balance DYNIX 3.0, VAda-1lO...8000, DYNIX Version 3.0 Target Computer System: Sequent Balance 8000, DYNIX Version 3.0 Customer Agreement Number: 90-09-25- VRX See Section 3.1 for any

Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment ofmore » learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good

Redox proteomic analysis of serum from aortic anerurysm patients: insights on oxidation of specific protein target.

PubMed

Spadaccio, Cristiano; Coccia, Raffaella; Perluigi, Marzia; Pupo, Gilda; Schininà, Maria Eugenia; Giorgi, Alessandra; Blarzino, Carla; Nappi, Francesco; Sutherland, Fraser W; Chello, Massimo; Di Domenico, Fabio

2016-06-21

oxidative stress is undoubtedly one of the main players in abdominal aortic aneurysm (AAA) pathophysiology. Recent studies in AAA patients reported an increase in the indices of oxidative damage at the tissue level and in biological fluids coupled with the loss of counter-regulatory mechanisms of protection from oxidative stress. We recently reported, in a proteomic analysis of AAA patient sera, changes in the expression of several proteins exerting important modulatory activities on cellular proliferation, differentiation and response to damage. This study aimed to explore the involvement of protein oxidation, at peripheral levels, in AAA. a redox proteomic approach was used to investigate total and specific protein carbonylation and protein-bound 4-hydroxy-2-nonenal (HNE) in the serum of AAA patients compared with age-matched controls. our results show increased oxidative damage to protein as indexed by the total carbonyl levels and total protein-bound HNE. By redox proteomics we identified specific carbonylation of three serum proteins: serum retinol-binding protein, vitamin D-binding protein and fibrinogen α-chain HNE. We also identified increased protein-bound HNE levels for hemopexin, IgK chain C region and IgK chain V-III region SIE. In addition we found a high correlation between specific protein carbonylation and protein-bound HNE and the aortic diameter. Moreover the analysis of serum proteins with antioxidant activity demonstrates the oxidation of albumin together with the overexpression of transferrin, haptoglobin and HSPs 90, 70, 60 and 32. this study support the involvement of oxidative stress in the pathogenesis of AAA and might provide a further degree of knowledge in the cause-effect role of oxidative stress shedding new light on the molecular candidates involved in the disease.

Retinol Improves In Vitro Differentiation of Pre-Pubertal Mouse Spermatogonial Stem Cells into Sperm during the First Wave of Spermatogenesis

PubMed Central

Arkoun, Brahim; Dumont, Ludovic; Milazzo, Jean-Pierre; Way, Agathe; Bironneau, Amandine; Wils, Julien; Macé, Bertrand; Rives, Nathalie

2015-01-01

Testicular tissue freezing has been proposed for fertility preservation in pre-pubertal boys. Thawed frozen testicular tissue must undergo a maturation process to restore sperm production. The purpose of the current study was to evaluate the ability of retinol to improve the in vitro differentiation of pre-pubertal mouse spermatogonial stem cells into sperm. Testes from pre-pubertal mice, aged 2.5 and 6.5 days post-partum, were cultured on agarose gel at a gas-liquid interphase for 34, 38 and 60 days (D) and for 16, 30 and 36 D respectively. Assessment of basal medium (BM) supplemented with retinol (RE) alone, FSH/LH alone or a combination of both, was performed. Stereological analyses and tissue lesion scoring were performed at the culture time points indicated above. Sperm production was quantified at D30 and D34 after mechanical dissection of the testicular tissues. FSH/LH significantly increased the percentage of round spermatids at D30 and D38, when compared to BM alone. However, RE significantly increased the percentages of round but also elongated spermatids at D30 and D34. Moreover, RE significantly increased the number of spermatozoa per milligram of tissue at D30 and D34 when compared to BM. Therefore, RE improved the in vitro production of spermatids and spermatozoa from pre-pubertal SSCs during the first wave of spermatogenesis. The use of RE could be a useful tool for in vitro spermatogenesis from pre-pubertal human testicular tissue. PMID:25714609

Black synthetic quartz glass layer for optical fiber cross-talk reduction fabricated by VAD method

NASA Astrophysics Data System (ADS)

Kobayashi, Soichi; Fukuda, Kaoru; Onishi, Gen; Fujii, Yusuke

2016-09-01

In this report the new black-glass fiber-preform fabricated by the vapor-phase axial deposition (VAD) method to realize high-resolution optical bundle fibers is discussed with the Energy Dispersive X-ray (EDX) analysis and the transmittance spectrum measurement. The black glass consists of SiO2, GeO2, Bi2O3 and Al2O3. Firstly, the rod-shaped soot of SiO2 and GeO2 is prepared by blowing SiCl4 and GeCl4 into the oxyhydrogen burner. Then the soot is dipped into the solution of the Bi and Al compounds. After drying the soot with Bi and Al penetrated, the soot is consolidated into the glass preform by heating with the carbon heater at 1650 degrees Celsius. The diameter of the obtained preform is 10.5 mm and the black glass layer thickness is 2.6 mm located at the periphery. The Bi concentration distribution shows the content of several wt% in the black glass layer. The black glass preform is drawn into the black optical fiber being expected to make a clear image because of no light leaking from the neighboring optical fibers as compared to the conventional fiber endoscope.

A Simple Plasma Retinol Isotope Ratio Method for Estimating β-Carotene Relative Bioefficacy in Humans: Validation with the Use of Model-Based Compartmental Analysis.

PubMed

Ford, Jennifer Lynn; Green, Joanne Balmer; Lietz, Georg; Oxley, Anthony; Green, Michael H

2017-09-01

Background: Provitamin A carotenoids are an important source of dietary vitamin A for many populations. Thus, accurate and simple methods for estimating carotenoid bioefficacy are needed to evaluate the vitamin A value of test solutions and plant sources. β-Carotene bioefficacy is often estimated from the ratio of the areas under plasma isotope response curves after subjects ingest labeled β-carotene and a labeled retinyl acetate reference dose [isotope reference method (IRM)], but to our knowledge, the method has not yet been evaluated for accuracy. Objectives: Our objectives were to develop and test a physiologically based compartmental model that includes both absorptive and postabsorptive β-carotene bioconversion and to use the model to evaluate the accuracy of the IRM and a simple plasma retinol isotope ratio [(RIR), labeled β-carotene-derived retinol/labeled reference-dose-derived retinol in one plasma sample] for estimating relative bioefficacy. Methods: We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to develop and apply a model that provided known values for β-carotene bioefficacy. Theoretical data for 10 subjects were generated by the model and used to determine bioefficacy by RIR and IRM; predictions were compared with known values. We also applied RIR and IRM to previously published data. Results: Plasma RIR accurately predicted β-carotene relative bioefficacy at 14 d or later. IRM also accurately predicted bioefficacy by 14 d, except that, when there was substantial postabsorptive bioconversion, IRM underestimated bioefficacy. Based on our model, 1-d predictions of relative bioefficacy include absorptive plus a portion of early postabsorptive conversion. Conclusion: The plasma RIR is a simple tracer method that accurately predicts β-carotene relative bioefficacy based on analysis of one blood sample obtained at ≥14 d after co-ingestion of labeled β-carotene and retinyl acetate. The method also provides

RNA-sequencing and pathway analysis reveal alteration of hepatic steroid biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow (Gobiocypris rarus).

PubMed

Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Huang, Maoxian; Fan, Mingzhen; Liu, Min

2017-07-01

Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse effects of TBT on reproduction and lipogenesis are observed in fishes, the underlying mechanisms, especially in livers, are still scarce and inconclusive. Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially expressed genes were identified, enrichment analysis and validation by quantitative real-time PCR were conducted. The results showed that TBT up-regulated the profile of hepatic genes in the steroid biosynthesis pathway and down-regulated the profile of hepatic genes in the retinol metabolism pathway. In the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of cholesterol, which could affect the bioavailability of steroid hormones. More important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays essential roles in both reproduction and lipogenesis. The results of two pathways offered new mechanisms underlying the toxicology of TBT and represented a starting point from which detailed mechanistic links should be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

Retinol as a micronutrients related to cervical local immunity: The expression of tumor necrosis factor-alpha specifically stimulated with E6 epitope of human papillomavirus type-16 and ratio of CD4+/CD8+ T cell in natural history of cervical cancer

NASA Astrophysics Data System (ADS)

Utami, T. W.; Aziz, M. F.; Ibrahim, F.; Andrijono

2017-08-01

Retinol is one of the antioxidant micronutrients that plays essential roles in the immune system, by preventing the persistence of modulating CD4+ and CD8+ T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-α) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF-α induces carcinogenesis. The ratio of CD4+ cells to CD8+ T cells and adequate TNF-α production in acute HPV infection are key points for clearance. The aim of this research is to analyze the sufficiency level of retinol deposit, the expression of TNF-α, and the ratio of CD4+: CD8+ T cells in a normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group. The sufficiency level of retinol deposit was analyzed from peripheral blood using the ELISA method. The cervico-vaginal secretions, which were incubated for 24 hours, were stimulated specifically by E6 epitope HPV type-16, measuring TNF-α expression semi-quantitatively by the ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method. The sufficient level of retinol deposit in a normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF-α in normal cervix group was 10%, while for cervical cancer it was 75% (OR 27.00; p < 0.001). There was no expression in clearance and persistent HPV subclinical infection groups. A high ratio of CD4+: CD8+ T cells in the normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There was no high ratio of CD4+: CD8+ T cells in clearance (OR 1.22) and persistent (OR 0.95) HPV subclinical infection groups. This study was able to prove that the normal cervix group has the highest retinol deposit sufficiency level and the cervical cancer group has the highest TNF-α expression (OR 27; p < 0.001). The lowest of retinol deposit sufficiency

Vitamin A deficiency and inflammatory markers among preschool children in the Republic of the Marshall Islands

PubMed Central

Maqsood, Maria; Dancheck, Barbara; Gamble, Mary V; Palafox, Neal A; Ricks, Michelle O; Briand, Kennar; Semba, Richard D

2004-01-01

Background The exclusion of individuals with elevated acute phase proteins has been advocated in order to improve prevalence estimates of vitamin A deficiency in surveys, but it is unclear whether this will lead to sampling bias. The purpose of the study was to determine whether the exclusion of individuals with elevated acute phase proteins is associated with sampling bias and to characterize inflammation in children with night blindness. Methods In a survey in the Republic of the Marshall Islands involving 281 children, aged 1–5 years, serum retinol, C-reactive protein (CRP), and α1-acid glycoprotein (AGP) were measured. Results Of 281 children, 24 (8.5%) had night blindness and 165 (58.7%) had serum retinol <0.70 μmol/L. Of 248 children with AGP and CRP measurements, 123 (49.6%) had elevated acute phase proteins (CRP >5 mg/L and/or AGP >1000 mg/L). Among children with and without night blindness, the proportion with serum retinol <0.70 μmol/L was 79.2% and 56.8% (P = 0.03) and with anemia was 58.3% and 35.7% (P = 0.029), respectively. The proportion of children with serum retinol <0.70 μmol/L was 52.0% after excluding children with elevated acute phase proteins. Among children with and without elevated acute phase proteins, mean age was 2.8 vs 3.2 years (P = 0.016), the proportion of boys was 43.1% vs. 54.3% (P = 0.075), with no hospitalizations in the last year was 11.0% vs 23.6% (P = 0.024), and with anemia was 43.8% vs 31.7% (P = 0.05), respectively. Conclusions Exclusion of children with inflammation in this survey of vitamin A deficiency does not improve prevalence estimates for vitamin A deficiency and instead leads to sampling bias for variables such as age, gender, anemia, and hospitalization history. PMID:15588289

/sup 3/H-retinol derived photopigment in chick pineal membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallingford, J.; Zatz, M.

Pineal glands display a day-night rhythm in the synthesis and secretion of melatonin. Dispersed chick pinealocytes retain their ability to respond to light in vitro for at least a week. Pinealocytes incubated overnight with /sup 3/H-retinol in the dark incorporate radioactivity predominantly into retinyl esters. To identify the chick pineal photopigment, SDS-PAGE was performed on radiolabelled preparations of pinealocytes and (intraocularly injected) rat retina. When intact cells or membrane preparations of cultured cells were incubated with NaCNBH/sub 3/, in the dark, a single radioactive peak with an apparent molecular weight of 32,000 daltons was observed. Rat retina preparations revealed amore » major peak at approximately 40,000 daltons. Protease inhibitors were present in the workup, and radioactivity corresponding to the smaller peak from pineal was not observed in retina. There was no radioactive peak when NaCNBH/sub 3/ was omitted. When samples were boiled in SDS the radioactivity shifted to the origin. These data suggest a protein in pinealocyte membranes which binds retinoid via a Schiff's base. Exposure to light of deoxycholate solubilized pineal membranes reduced the radioactivity associated with the protein. These findings raise the possibility that this protein is the pinealocyte's photopigment. Photopigments smaller than those observed in mammals have been reported in invertebrates.« less

Levels of selected minerals, nitric oxide, and vitamins in aborted Sakis sheep raised under semitropical conditions

PubMed Central

Aypak, Serap Unubol

2010-01-01

The serum levels of calcium, phosphorus, magnesium, copper, zinc and iron and of nitric oxide, retinol, and β-carotene were determined in Sakiz ewes that had experienced an abortion and in healthy controls. Ten healthy and 25 aborted Sakiz sheep were selected from Afyon zone in western Turkey. Their ages ranged between 2 and 4 years weighing between 40 and 60 kg at the time of experiment. All of the abortions occurred in October. The concentrations of retinol, β-carotene, phosphorus, and zinc were significantly lower and those of calcium and nitric oxide were increased in aborted ewes relative to healthy controls. The serum levels of iron, copper, and magnesium were not significantly different among the two groups. In conclusion, abortion is an important problem in commercially important species of ruminants in many regions in the tropics including of western Turkey. Deficiencies of retinol, β-carotene, phosphorus and zinc, and the increase of calcium and nitric oxide concentration may play an important role in the etiology of abortion in ewes. Prophylactic measures such as vitamin and mineral supplementation may be of help to prevent or reduce the incidence of abortion in sheep. PMID:21076941

Determination of water-soluble and fat-soluble vitamins in tears and blood serum of infants and parents by liquid chromatography/mass spectrometry.

PubMed

Khaksari, Maryam; Mazzoleni, Lynn R; Ruan, Chunhai; Kennedy, Robert T; Minerick, Adrienne R

2017-02-01

Tears serve as a viable diagnostic fluid with advantages including less invasive sample to collect and less complex to prepare for analysis. Several water-soluble and fat-soluble vitamins were detected and quantified in human tears and compared with blood serum levels. Samples from 15 family pairs, each pair consisting of a four-month-old infant and one parent were analyzed; vitamin concentrations were compared between tears and blood serum for individual subjects, between infants and parents, and against self-reported dietary intakes. Water-soluble vitamins B 1 , B 2 , B 3 (nicotinamide), B 5 , B 9 and fat-soluble vitamin E (α-tocopherol) were routinely detected in tears and blood serum while fat-soluble vitamin A (retinol) was detected only in blood serum. Water-soluble vitamin concentrations measured in tears and blood serum of single subjects were comparable, while higher concentrations were measured in infants compared to their parents. Fat-soluble vitamin E concentrations were lower in tears than blood serum with no significant difference between infants and parents. Serum vitamin A concentrations were higher in parents than infants. Population trends were compiled and quantified using a cross correlation factor. Strong positive correlations were found between tear and blood serum concentrations of vitamin E from infants and parents and vitamin B 3 concentrations from parents, while slight positive correlations were detected for infants B 3 and parents B 1 and B 2 concentrations. Correlations between infants and parents were found for the concentrations of B 1 , B 2 , B 3 , and E in tears, and the concentrations of B 2, A, and E in blood serum. Stronger vitamin concentration correlations were found between infants and parents for the breast-fed infants, while no significant difference was observed between breast-fed and bottle-fed infants. This work is the first to demonstrate simultaneous vitamin A, B, and E detection and to quantify correlations between

Effect of administration of 200,000 IU of vitamin A to women within 24 hrs after delivery on response to PPV administered to the newborn.

PubMed

Bhaskaram, P; Balakrishna, N

1998-03-01

To explore the effect of maternal supplementation of vitamin A on the immune response to oral polio vaccine in breastfed infants. Randomized controlled trial. Hospital based. One hundred mothers having uncomplicated deliveries randomly received either 200,000 IU vitamin A orally (Experimental) or placebo (Control). All the newborns were given a dose of oral polio vaccine within 72 hours after birth and were breastfed. Type specific neutralizing antibodies to polio viruses in test sera diluted from 1:4 to 1:512 and serum retinol levels were determined from the cord blood and at the age of 6 weeks. Breast milk retinol levels were determined at 3, 10, 30, 45 and 90 days of lactation. Seroconversion to OPV and geometric means of antibody titers to the three types of polio viruses were comparable between the groups of infants belonging to the experimental and control mothers. Breast milk retinol levels were significantly higher in the experimental group upto 45-90 days of lactation. Majority of the infants at birth had serum retinol levels < 15 micrograms/dl which improved significantly by 6 weeks irrespective of the maternal supplementation status. Maternal vitamin A supplementation soon after delivery improves vitamin A intakes of breastfed infants during the first 3 months and has no interference with the seroconversion to a neonatal dose of OPV. OPV administered to newborn in turn has no adverse effect on the vitamin A status of the breastfed infants.

Vitamin A in human nutrition.

PubMed

Sklan, D

1987-01-01

Vitamin A, an unsaturated 20 carbon cyclic alcohol, has a variety of physiological functions including a role in vision, reproduction, growth and maintenance of epithelial and bone structures. The main sources of vitamin A are from preformed vitamin A in animal foods or from -carotene in green plants. Carotene is cleaved in the intestinal mucosa to retinol, which is transported in chylomicrons mainly to the liver which is the major storage site of vitamin A, where stores are mainly of retinyl palmitate. Utilization of vitamin A appears to be a highly regulated process; retinol is transported in the serum bound to a specific binding protein. There also may be some control of the level of retinol in cells possibly through membrane receptors or of excretion from the cell. Intracellular cytosolic retinol binding proteins transport retinol to the nucleus where specific receptors for retinol have been found. Intracellular binding proteins for retinoic acid and retinal, metabolites of retinol have also been found, and an interstitial protein transporting retinol is present in the eye. Vitamin A deficiency causes cessation of growth, night blindness, and renders the organism more susceptible to infection, and vitamin A supplementation has been shown to enhance immune response. Epidemiological studies have shown low vitamin A and carotene to be correlated with incidence of cancer. Excess vitamin A intake results in hypervitaminosis with severe detrimental effects. Vitamin A requirements appear to be met in most developed countries although in the populations at greatest risk, newborns and pregnant and nursing women, cases of deficiency are observed. However, in large areas of the world vitamin A deficiency is endemic, causing widespread blindness and mortality.

Adolescent health in rural Ghana: A cross-sectional study on the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors

PubMed Central

Alicke, Marie; Boakye-Appiah, Justice K.; Abdul-Jalil, Inusah; Henze, Andrea; van der Giet, Markus; Schulze, Matthias B.; Schweigert, Florian J.; Mockenhaupt, Frank P.; Bedu-Addo, George

2017-01-01

In sub-Saharan Africa, infectious diseases and malnutrition constitute the main health problems in children, while adolescents and adults are increasingly facing cardio-metabolic conditions. Among adolescents as the largest population group in this region, we investigated the co-occurrence of infectious diseases, malnutrition and cardio-metabolic risk factors (CRFs), and evaluated demographic, socio-economic and medical risk factors for these entities. In a cross-sectional study among 188 adolescents in rural Ghana, malarial infection, common infectious diseases and Body Mass Index were assessed. We measured ferritin, C-reactive protein, retinol, fasting glucose and blood pressure. Socio-demographic data were documented. We analyzed the proportions (95% confidence interval, CI) and the co-occurrence of infectious diseases (malaria, other common diseases), malnutrition (underweight, stunting, iron deficiency, vitamin A deficiency [VAD]), and CRFs (overweight, obesity, impaired fasting glucose, hypertension). In logistic regression, odds ratios (OR) and 95% CIs were calculated for the associations with socio-demographic factors. In this Ghanaian population (age range, 14.4–15.5 years; males, 50%), the proportions were for infectious diseases 45% (95% CI: 38–52%), for malnutrition 50% (43–57%) and for CRFs 16% (11–21%). Infectious diseases and malnutrition frequently co-existed (28%; 21–34%). Specifically, VAD increased the odds of non-malarial infectious diseases 3-fold (95% CI: 1.03, 10.19). Overlap of CRFs with infectious diseases (6%; 2–9%) or with malnutrition (7%; 3–11%) was also present. Male gender and low socio-economic status increased the odds of infectious diseases and malnutrition, respectively. Malarial infection, chronic malnutrition and VAD remain the predominant health problems among these Ghanaian adolescents. Investigating the relationships with evolving CRFs is warranted. PMID:28727775

[Changes in vitamin A intake following the social marketing of red palm oil among children and women in Burkina Faso].

PubMed

Zagré, No l-Marie; Delisle, Hélène; Tarini, Ann; Delpeuch, Francis

2002-01-01

This paper focuses on changes in vitamin A (VA) intakes as part of the evaluation of a pilot project on social marketing of red palm oil (RPO) as a VA supplement for mothers and children in central-north Burkina Faso. The objectives of the 30-month project are to demonstrate the feasibility and effectiveness of introducing RPO in non-consuming areas. RPO is collected from women in the South-West region and it is sold in project sites by village volunteers. RPO is promoted by community workers trained in persuasive communication and social marketing. The target population is free to buy and consume RPO. Evaluation design includes data collected at onset, then 12 and 24 months later, from the same sample of 210 mothers and their children randomly selected in seven project sites. Children were 1 to 3 years old at onset. Blood samples were collected at baseline from mothers and children for serum retinol determination by HPLC. VA intakes are estimated by a semi-quantitative food frequency questionnaire, using the conventional beta-carotene to retinol conversion factors and the newly revised lower factors. VA deficiency is a major public health problem in the area: 64% of mothers and 85% of children had serum retinol concentrations < 0,70 mumol/l at baseline. VA came mainly from plant foods, particularly fruits and dark green vegetables which provided more than 90% of the dietary VA at onset of the project. Mean vitamin A intakes are low. We found 138 106 mug ER for the children and 302 +/- 235 microg ER for the mothers with conventional factors and 64 +/- 58 microg ER and 133 +/- 162 microg ER, respectively, with the revised factors. One year later, one third of respondents had consumed RPO in the previous week, and it supplied around 56% of the VA intake of children and 67% of mothers (36% and 46% respectively for the whole group). VA intakes were significantly increased at 510 +/- 493 microg ER and 801 +/- 913 microg ER for the children and their mothers respectively

Hawaii cohort study of serum micronutrient concentrations and clearance of incident oncogenic human papillomavirus infection of the cervix.

PubMed

Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Franke, Adrian A; Bertram, Cathy Cramer; Kessel, Bruce; Bernice, Marge; Sunoo, Christian; Ning, Lily; Easa, David; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y

2007-06-15

The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (serum levels of alpha-tocopherol and total-tocopherol, but significant trends in these associations were limited to infections lasting 120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.

Ada Compiler Validation Summary Report: Certificate Number: 901129W1. 11097 Verdix Corporation, VADS Sun-4= 68k, Sun OS 4.0, VAda-110-40125, Version 6.0, Sun-4/260 (Host) to MVME 147 (Motorola 68030) (Target)

DTIC Science & Technology

1991-08-01

VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 901129W1.11097 Verdix Corporation VADS Sun-4 => 63K, Sun OS 4.0, VAda-110-40125...68030) (bare machine) Customer Agreement Number: 90-09-25- VRX See Section 3.1 for any additional information about the testing environment. As a

Functions of Intracellular Retinoid Binding-Proteins.

PubMed

Napoli, Joseph L

Multiple binding and transport proteins facilitate many aspects of retinoid biology through effects on retinoid transport, cellular uptake, metabolism, and nuclear delivery. These include the serum retinol binding protein sRBP (aka Rbp4), the plasma membrane sRBP receptor Stra6, and the intracellular retinoid binding-proteins such as cellular retinol-binding proteins (CRBP) and cellular retinoic acid binding-proteins (CRABP). sRBP transports the highly lipophilic retinol through an aqueous medium. The major intracellular retinol-binding protein, CRBP1, likely enhances efficient retinoid use by providing a sink to facilitate retinol uptake from sRBP through the plasma membrane or via Stra6, delivering retinol or retinal to select enzymes that generate retinyl esters or retinoic acid, and protecting retinol/retinal from excess catabolism or opportunistic metabolism. Intracellular retinoic acid binding-proteins (CRABP1 and 2, and FABP5) seem to have more diverse functions distinctive to each, such as directing retinoic acid to catabolism, delivering retinoic acid to specific nuclear receptors, and generating non-canonical actions. Gene ablation of intracellular retinoid binding-proteins does not cause embryonic lethality or gross morphological defects. Metabolic and functional defects manifested in knockouts of CRBP1, CRBP2 and CRBP3, however, illustrate their essentiality to health, and in the case of CRBP2, to survival during limited dietary vitamin A. Future studies should continue to address the specific molecular interactions that occur between retinoid binding-proteins and their targets and their precise physiologic contributions to retinoid homeostasis and function.

IRF5 haplotypes demonstrate diverse serological associations which predict serum interferon alpha activity and explain the majority of the genetic association with systemic lupus erythematosus

PubMed Central

Niewold, Timothy B; Kelly, Jennifer A; Kariuki, Silvia N; Franek, Beverly S; Kumar, Akaash A; Kaufman, Kenneth M; Thomas, Kenaz; Walker, Daniel; Kamp, Stan; Frost, Jacqueline M; Wong, Andrew K; Merrill, Joan T; Alarcón-Riquelme, Marta E; Tikly, Mohammed; Ramsey-Goldman, Rosalind; Reveille, John D; Petri, Michelle A; Edberg, Jeffrey C; Kimberly, Robert P; Alarcón, Graciela S; Kamen, Diane L; Gilkeson, Gary S; Vyse, Timothy J; James, Judith A; Gaffney, Patrick M; Moser, Kathy L; Crow, Mary K; Harley, John B

2012-01-01

Objective High serum interferon α (IFNα) activity is a heritable risk factor for systemic lupus erythematosus (SLE). Auto-antibodies found in SLE form immune complexes which can stimulate IFNα production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5. Genetic variation in IRF5 is associated with SLE susceptibility; however, it is unclear how IRF5 functional genetic elements contribute to human disease. Methods 1034 patients with SLE and 989 controls of European ancestry, 555 patients with SLE and 679 controls of African–American ancestry, and 73 patients with SLE of South African ancestry were genotyped at IRF5 polymorphisms, which define major haplotypes. Serum IFNα activity was measured using a functional assay. Results In European ancestry subjects, anti-double-stranded DNA (dsDNA) and anti-Ro antibodies were each associated with different haplotypes characterised by a different combination of functional genetic elements (OR > 2.56, p >003C; 1.9×10−14 for both). These IRF5 haplotype-auto-antibody associations strongly predicted higher serum IFNα in patients with SLE and explained > 70% of the genetic risk of SLE due to IRF5. In African–American patients with SLE a similar relationship between serology and IFNα was observed, although the previously described European ancestry-risk haplotype was present at admixture proportions in African–American subjects and absent in African patients with SLE. Conclusions The authors define a novel risk haplotype of IRF5 that is associated with anti-dsDNA antibodies and show that risk of SLE due to IRF5 genotype is largely dependent upon particular auto-antibodies. This suggests that auto-antibodies are directly pathogenic in human SLE, resulting in increased IFNα in cooperation with particular combinations of IRF5 functional genetic elements. SLE is a systemic autoimmune disorder affecting multiple organ systems including the skin, musculoskeletal, renal and

Ada Compiler Validation Summary Report. Certificate Number: 900726W1. 11017, Verdix Corporation VADS IBM RISC System/6000, AIX 3.1, VAda-110-7171, Version 6.0 IBM RISC System/6000 Model 530 = IBM RISC System/6000 Model 530

DTIC Science & Technology

1991-01-22

Customer Agreement Number: 90-05-29- VRX See Section 3.1 for any additional information about the testing environment. As a result of this validation...22 January 1991 90-05-29- VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 900726W1.11017 Verdix Corporation VADS IBM RISC System/6000

Preparation and value assignment of standard reference material 968e fat-soluble vitamins, carotenoids, and cholesterol in human serum.

PubMed

Thomas, Jeanice B; Duewer, David L; Mugenya, Isaac O; Phinney, Karen W; Sander, Lane C; Sharpless, Katherine E; Sniegoski, Lorna T; Tai, Susan S; Welch, Michael J; Yen, James H

2012-01-01

Standard Reference Material 968e Fat-Soluble Vitamins, Carotenoids, and Cholesterol in Human Serum provides certified values for total retinol, γ- and α-tocopherol, total lutein, total zeaxanthin, total β-cryptoxanthin, total β-carotene, 25-hydroxyvitamin D(3), and cholesterol. Reference and information values are also reported for nine additional compounds including total α-cryptoxanthin, trans- and total lycopene, total α-carotene, trans-β-carotene, and coenzyme Q(10). The certified values for the fat-soluble vitamins and carotenoids in SRM 968e were based on the agreement of results from the means of two liquid chromatographic methods used at the National Institute of Standards and Technology (NIST) and from the median of results of an interlaboratory comparison exercise among institutions that participate in the NIST Micronutrients Measurement Quality Assurance Program. The assigned values for cholesterol and 25-hydroxyvitamin D(3) in the SRM are the means of results obtained using the NIST reference method based upon gas chromatography-isotope dilution mass spectrometry and liquid chromatography-isotope dilution tandem mass spectrometry, respectively. SRM 968e is currently one of two available health-related NIST reference materials with concentration values assigned for selected fat-soluble vitamins, carotenoids, and cholesterol in human serum matrix. This SRM is used extensively by laboratories worldwide primarily to validate methods for determining these analytes in human serum and plasma and for assigning values to in-house control materials. The value assignment of the analytes in this SRM will help support measurement accuracy and traceability for laboratories performing health-related measurements in the clinical and nutritional communities.

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

PubMed

Hemanth Kumar, Boyina; Arun Reddy, Ravula; Mahesh Kumar, Jerald; Dinesh Kumar, B; Diwan, Prakash V

2017-01-01

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

Association of Thr420Lys polymorphism in DBP gene with fat-soluble vitamins and low radial bone mineral density in postmenopausal Thai women.

PubMed

Chupeerach, Chaowanee; Tungtrongchitr, Anchalee; Phonrat, Benjaluck; Schweigert, Florian J; Tungtrongchitr, Rungsunn; Preutthipan, Sangchai

2012-02-01

To investigate the genetic markers for osteoporosis bone mineral density by the genotyping of rs7041, rs4588 and rs1352845 in the DBP gene with either bone mineral density or serum 25-hydroxycholecalciferol, retinol and α-tocopherol, among 365 postmenopausal Thai women. The DBP genotypes were analyzed by a PCR restriction fragment-length polymorphism method. Serum 25-hydroxycholecalciferol was assessed using a commercial chemiluminescent immunoassay. Serum retinol and α-tocopherol were measured by reverse-phase high-performance liquid chromatography. After adjustment for age >50 years, elder Thai subjects with low BMI (≤25 kg/m(2)) and carrying the rs4588 CC genotype had a higher risk of radial bone mineral density osteoporosis (odds ratio: 6.29; p = 0.048). The rs1352845 genotype also had a statistical association with total hip bone mineral density; however, it disappeared after adjustment for age and BMI. No association was found in fat-soluble vitamins with bone mineral density. DBP genotypes may influence the osteoporosis bone mineral density in postmenopausal Thai women.

Vitamin A deficiency and xerophthalmia in western Yemen.

PubMed

Rosen, D S; al Sharif, Z; Bashir, M; al Shabooti, A; Pizzarello, L D

1996-01-01

To determine the prevalence of xerophthalmia and the extent of vitamin A deficiency in western Yemen. A stratified cluster sample of children aged 1-5 years with clinical examination for signs of xerophthalmia as well as blood serum survey. The 18 districts of western Yemen, of which 10 clusters were chosen at random. All children aged 1-5 years resident in the cluster sites (n = 2438). Clinical signs of xerophthalmia, a history of night blindness, serum retinol levels in a random sample of clinically normal children (n =338) in addition to all children with xerophthalmia. Night blindness was found in 0.5% of the children, Bitot's spots in 1.7%, corneal ulceration in 0.04% and corneal scars in 0.04% Of the subsample, 7.2% (95% confidence interval [c.i.] 4.4-10.0%) had serum retinol values below 10 micrograms/dl; 63.0% (95% c.i. 57.6- 68.4%) had values below 20 micrograms/dl. Xerophthalmia and vitamin A deficiency are public health problems in western Yemen.

Retinol-Binding Protein 4 and Lipids Prospectively Measured During Early to Mid-Pregnancy in Relation to Preeclampsia and Preterm Birth Risk.

PubMed

Mendola, Pauline; Ghassabian, Akhgar; Mills, James L; Zhang, Cuilin; Tsai, Michael Y; Liu, Aiyi; Yeung, Edwina H

2017-06-01

Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women. © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2017. This work is written by (a) US Government employees(s) and is in the public domain in the US.

Ada Compiler Validation Summary Report: Certificate Number: 891116W1.10194, Verdix Corporation, VADS VMS-MIL-STD-1750A, V6.0, MP, DEC MicroVAX III Host and Tektronix 1750A Emulator (Ethernet Download), v1.00-00 Target

DTIC Science & Technology

1989-11-16

VRX Ada COMPILER VALIDATION SUMMARY REPORT; Certificate Number: 891116W1.10194 Verdix Corporation VADS VMS->MIL-STD-1750A, V6.0, MP DEC MicroVAX III...1.10 Customer Agreement Number: 89-08-30- VRX This report has been reviewed and i- approved. Ada Validation Facility Steven P. Wilson Technical

Serum carotenoid interactions in premenopausal women reveal α-carotene is negatively impacted by body fat.

PubMed

Nuss, Emily Taylor; Valentine, Ashley R; Zhang, Zhumin; Lai, HuiChuan Jennifer; Tanumihardjo, Sherry A

2017-01-01

Increasing body mass indices (BMIs) across the globe reflect pandemic shifts towards habitual positive energy imbalances. Excess body fat in individuals is often associated with high-energy and high-fat diets scanty in fresh produce. Carotenoids are fat-soluble pigments plentiful in many fruits and vegetables. They are well-known for provitamin A and antioxidant functions, but little research has been done related to carotenoid-body mass interactions. Serum carotenoids were analyzed relative to body fat to determine correlations between major serum carotenoids, retinol, BMI, fat mass, and lean mass. Healthy women ( n = 76), 19-50 years old, were categorized into two comparison groups determined by percent body fat measured by air displacement plethysomography (BOD POD®), i.e. <31% and ≥31% fat mass. Anthropometric and three-day diet records were completed for BMI and nutrient intake calculations, respectively. Serum α-carotene concentrations were strongly inversely associated with all measures of body composition ( P < 0.001 α-carotene) controlling for dietary intake and age, while β-carotene, lutein, and lycopene were not ( P > 0.05). Dietary intake between groups did not differ, including carrot consumption (a high dietary source of α-carotene). These results confirm previous carotenoid-health research and propose the need for further investigation of potential protective roles that α-carotene may perform for optimal health. Serum α-carotene may provide a deeper and clinically relevant purpose, beyond previous suggestions for its use as a biomarker for fruit and vegetable consumption, in that α-carotene may be a biomarker for chronic disease risk frequently linked with obesity. Impact statement Carotenoids are important pigments in fruit and vegetables and found in human serum. This study isolated a negative relationship between serum α-carotene and body fatness. As humans begin to live over a century, determining biomarkers of ultimate

Association of serum retinoic acid with hepatic steatosis and liver injury in nonalcoholic fatty liver disease.

PubMed

Liu, Yan; Chen, Hongen; Wang, Jingjing; Zhou, Wenjing; Sun, Ruifang; Xia, Min

2015-07-01

Retinoic acid (RA), an active metabolite of vitamin A (retinol), has been implicated in the regulation of lipid metabolism and hepatic steatosis in animal models. However, the relation between RA and liver histology in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is unknown. This study aimed at examining the association of RA with NAFLD and NASH in Chinese subjects. Serum RA concentration was determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38 patients with NASH. The associations of RA with adiposity, serum glucose, lipid profiles, and markers of liver damage were studied. Moreover, both mRNA and protein levels of retinoic X receptor α (RXRα) in the liver were analyzed in subjects with different degrees of hepatic steatosis. Serum RA concentrations in patients with NAFLD (1.42 ± 0.47 ng/mL) and NASH (1.14 ± 0.26 ng/mL) were significantly lower than those in control subjects (2.70 ± 0.52 ng/mL) (P < 0.01). Furthermore, serum RA concentrations were significantly different between subjects with normal glucose tolerance and those with type 2 diabetes in control [2.87 ± 0.52 (n = 28) vs. 2.32 ± 0.44 ng/mL (n = 13)], NAFLD [1.61 ± 0.37 (n = 29) vs. 1.28 ± 0.41 ng/mL (n = 16)], and NASH [1.35 ± 0.34 (n = 24) vs. 1.07 ± 0.29 ng/mL (n = 14)] groups. In human liver tissue, RXRα mRNA expression was inversely correlated with the exacerbation of hepatic steatosis. Both serum RA concentrations and RXRα mRNA levels were inversely correlated with intrahepatic triglyceride content (r = -0.700, P < 0.001, and r = -0.611, P = 0.002, respectively). Compared with grade 0 severity, the concentration of RXRα protein was lower in more severe grades in patients with NAFLD. These results show that circulating RA concentrations were lower in subjects with NAFLD and were associated with hepatic lipid metabolism and insulin resistance. This trial was registered at clinicaltrials.gov as NCT01940263. © 2015

Factors associated with serum retinol, x-tocopherol, carotenoids, and selenium in Hispanics with problems of HIV, chornis hepatitis, chronic hepatitis C, and drug use

USDA-ARS?s Scientific Manuscript database

The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C inf...

Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35-74 Years) General Population: A Cross-Sectional Study in Six European Countries.

PubMed

Stuetz, Wolfgang; Weber, Daniela; Dollé, Martijn E T; Jansen, Eugène; Grubeck-Loebenstein, Beatrix; Fiegl, Simone; Toussaint, Olivier; Bernhardt, Juergen; Gonos, Efstathios S; Franceschi, Claudio; Sikora, Ewa; Moreno-Villanueva, María; Breusing, Nicolle; Grune, Tilman; Bürkle, Alexander

2016-09-30

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene ( r = -0.248), α-tocopherol ( r = 0.208), α-carotene ( r = -0.112), and β-cryptoxanthin ( r = 0.125; all p < 0.001). Age was inversely associated with lycopene (-6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m²)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (-4.8% vs. -3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene.

Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck™ FLUORO) with high-performance liquid chromatography (HPLC).

PubMed

Raila, Jens; Kawashima, Chiho; Sauerwein, Helga; Hülsmann, Nadine; Knorr, Christoph; Myamoto, Akio; Schweigert, Florian J

2017-05-10

Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC). The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP). Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r 2  = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison. With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle.

Background and design of the profiling biobehavioral responses to mechanical support in advanced heart failure study.

PubMed

Lee, Christopher S; Mudd, James O; Gelow, Jill M; Nguyen, Thuan; Hiatt, Shirin O; Green, Jennifer K; Denfeld, Quin E; Bidwell, Julie T; Grady, Kathleen L

2014-01-01

Unexplained heterogeneity in response to ventricular assist device (VAD) implantation for the management of advanced heart failure impedes our ability to predict favorable outcomes, provide adequate patient and family education, and personalize monitoring and symptom management strategies. The purpose of this article was to describe the background and the design of a study entitled "Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure" (PREMISE). PREMISE is a prospective cohort study designed to (1) identify common and distinct trajectories of change in physical and psychological symptom burden; (2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction; and (3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Latent growth mixture modeling, including parallel process and cross-classification modeling, will be used to address the study aims and will entail identifying trajectories, quantifying associations between trajectories and both clinical and quality-of-life outcomes, and identifying predictors of favorable symptom and biomarker responses to VAD implantation. Research findings from the PREMISE study will be used to enhance shared patient and provider decision making and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation.

Expression of proteins in serum, synovial fluid, synovial membrane, and articular cartilage samples obtained from dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament disease and dogs without stifle joint arthritis.

PubMed

Garner, Bridget C; Kuroki, Keiichi; Stoker, Aaron M; Cook, Cristi R; Cook, James L

2013-03-01

To identify proteins with differential expression between healthy dogs and dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament (CCL) disease. Serum and synovial fluid samples obtained from dogs with stifle joint osteoarthritis before (n = 10) and after (8) surgery and control dogs without osteoarthritis (9) and archived synovial membrane and articular cartilage samples obtained from dogs with stifle joint osteoarthritis (5) and dogs without arthritis (5). Serum and synovial fluid samples were analyzed via liquid chromatography-tandem mass spectrometry; results were compared against a nonredundant protein database. Expression of complement component 3 in archived tissue samples was determined via immunohistochemical methods. No proteins had significantly different expression between serum samples of control dogs versus those of dogs with stifle joint osteoarthritis. Eleven proteins (complement component 3 precursor, complement factor I precursor, apolipoprotein B-100 precursor, serum paraoxonase and arylesterase 1, zinc-alpha-2-glycoprotein precursor, serum amyloid A, transthyretin precursor, retinol-binding protein 4 precursor, alpha-2-macroglobulin precursor, angiotensinogen precursor, and fibronectin 1 isoform 1 preproprotein) had significantly different expression (> 2.0-fold) between synovial fluid samples obtained before surgery from dogs with stifle joint osteoarthritis versus those obtained from control dogs. Complement component 3 was strongly expressed in all (5/5) synovial membrane samples of dogs with stifle joint osteoarthritis and weakly expressed in 3 of 5 synovial membrane samples of dogs without stifle joint arthritis. Findings suggested that the complement system and proteins involved in lipid and cholesterol metabolism may have a role in stifle joint osteoarthritis, CCL disease, or both.

Physiological and Microfluorometric Studies of Reduction and Clearance of Retinal in Bleached Rod Photoreceptors

PubMed Central

Tsina, Efthymia; Chen, Chunhe; Koutalos, Yiannis; Ala-Laurila, Petri; Tsacopoulos, Marco; Wiggert, Barbara; Crouch, Rosalie K.; Cornwall, M. Carter

2004-01-01

The visual cycle comprises a sequence of reactions that regenerate the visual pigment in photoreceptors during dark adaptation, starting with the reduction of all-trans retinal to all-trans retinol and its clearance from photoreceptors. We have followed the reduction of retinal and clearance of retinol within bleached outer segments of red rods isolated from salamander retina by measuring its intrinsic fluorescence. Following exposure to a bright light (bleach), increasing fluorescence intensity was observed to propagate along the outer segments in a direction from the proximal region adjacent to the inner segment toward the distal tip. Peak retinol fluorescence was achieved after ∼30 min, after which it declined very slowly. Clearance of retinol fluorescence is considerably accelerated by the presence of the exogenous lipophilic substances IRBP (interphotoreceptor retinoid binding protein) and serum albumin. We have used simultaneous fluorometric and electrophysiological measurements to compare the rate of reduction of all-trans retinal to all-trans retinol to the rate of recovery of flash response amplitude in these cells in the presence and absence of IRBP. We find that flash response recovery in rods is modestly accelerated in the presence of extracellular IRBP. These results suggest such substances may participate in the clearance of retinoids from rod photoreceptors, and that this clearance, at least in rods, may facilitate dark adaptation by accelerating the clearance of photoproducts of bleaching. PMID:15452202

Factors associated with the nutritional status of children less than 5 years of age

PubMed Central

Miglioli, Teresa Cristina; Fonseca, Vania Matos; Gomes, Saint Clair; da Silva, Katia Silveira; de Lira, Pedro Israel Cabral; Batista, Malaquias

2015-01-01

OBJECTIVE To analyze if the nutritional status of children aged less than five years is related to the biological conditions of their mothers, environmental and socioeconomic factors, and access to health services and social programs. METHODS This cross-sectional population-based study analyzed 664 mothers and 790 children using canonical correlation analysis. Dependent variables were characteristics of the children (weight/age, height/age, BMI/age, hemoglobin, and retinol serum levels). Independent variables were those related to the mothers’ nutritional status (BMI, hemoglobin, and retinol serum levels), age, environmental and socioeconomic factors and access to health service and social programs. A < 0.05 significance level was adopted to select the interpreted canonical functions (CF) and ± 0.40 as canonical load value of the analyzed variables. RESULTS Three canonical functions were selected, concentrating 89.9% of the variability of the relationship among the groups. In the first canonical function, weight/age (-0.73) and height/age (-0.99) of the children were directly related to the mother’s height (-0.82), prenatal appointments (-0.43), geographical area of the residence (-0.41), and household income per capita (-0.42). Inverse relationship between the variables related to the children and people/room (0.44) showed that the larger the number of people/room, the poorer their nutritional status. Rural residents were found to have the worse nutritional conditions. In the second canonical function, the BMI of the mother (-0.48) was related to BMI/age and retinol of the children, indicating that as women gained weight so did their children. Underweight women tended to have children with vitamin A deficiency. In the third canonical function, hemoglobin (-0.72) and retinol serum levels (-0.40) of the children were directly related to the mother’s hemoglobin levels (-0.43). CONCLUSIONS Mothers and children were associated concerning anemia, vitamin A

Carotene-rich plant foods ingested with minimal dietary fat enhance the total-body vitamin A pool size in Filipino schoolchildren as assessed by stable-isotope-dilution methodology.

PubMed

Ribaya-Mercado, Judy D; Maramag, Cherry C; Tengco, Lorena W; Dolnikowski, Gregory G; Blumberg, Jeffrey B; Solon, Florentino S

2007-04-01

Strategies for improving the vitamin A status of vulnerable populations are needed. We studied the influence of the amounts of dietary fat on the effectiveness of carotene-rich plant foods in improving vitamin A status. Schoolchildren aged 9-12 y were fed standardized meals 3 times/d, 5 d/wk, for 9 wk. The meals provided 4.2 mg provitamin A carotenoids/d (mainly beta-carotene) from yellow and green leafy vegetables [carrots, pechay (bok choy), squash, and kangkong (swamp cabbage)] and 7, 15, or 29 g fat/d (2.4, 5, or 10 g fat/meal) in groups A, B, and C (n = 39, 39, and 38, respectively). Other self-selected foods eaten were recorded daily. Before and after the intervention, total-body vitamin A pool sizes and liver vitamin A concentrations were measured with the deuterated-retinol-dilution method; serum retinol and carotenoid concentrations were measured by HPLC. Similar increases in mean serum beta-carotene (5-fold), alpha-carotene (19-fold), and beta-cryptoxanthin (2-fold) concentrations; total-body vitamin A pool size (2-fold); and liver vitamin A (2-fold) concentrations were observed after 9 wk in the 3 study groups; mean serum retinol concentrations did not change significantly. The total daily beta-carotene intake from study meals plus self-selected foods was similar between the 3 groups and was 14 times the usual intake; total fat intake was 0.9, 1.4, or 2.0 times the usual intake in groups A, B, and C, respectively. The overall prevalence of low liver vitamin A (<0.07 mumol/g) decreased from 35% to 7%. Carotene-rich yellow and green leafy vegetables, when ingested with minimal fat, enhance serum carotenoids and the total-body vitamin A pool size and can restore low liver vitamin A concentrations to normal concentrations.

Correlations between conceptal concentrations of all-trans-retinoic acid and dysmorphogenesis after microinjections of all-trans-retinoic acid, 13-cis-retinoic acid, all-trans-retinoyl-beta-glucuronide, or retinol in cultured whole rat embryos.

PubMed

Kraft, J C; Juchau, M R

1992-01-01

Retinol (4,000 ng/ml), all-trans-retinoyl-beta-glucuronide (4,000 ng/ml), and 13-cis-retinoic acid (1,500 ng/ml) each produced dysmorphogenic effects qualitatively similar to those elicited by 250 ng/ml of all-trans-retinoic acid after microinjections of the respective individual retinoids into the amniotic cavities of cultured whole rat embryos. Subsequent HPLC analyses of the cultured whole conceptuses, embryos proper, yolk sacs, and culture media (24 hr after microinjections) indicated that conceptal biotransformation of each of the retinoids had occurred during the culture period. All-trans-retinoic acid was present in the embryos proper at quantitatively similar concentrations (20-100 nM) after microinjections of the selected quantities of each of the microinjected retinoids: retinol, all-trans-retinoyl-beta-glucuronide, 13-cis-retinoic acid, or all-trans-retinoic acid. The results suggested that all-trans-retinoic acid acted as an ultimate dysmorphogen for the retinoids tested with respect to the anomalies monitored in the embryo culture system.

Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35–74 Years) General Population: A Cross-Sectional Study in Six European Countries

PubMed Central

Stuetz, Wolfgang; Weber, Daniela; Dollé, Martijn E. T.; Jansen, Eugène; Grubeck-Loebenstein, Beatrix; Fiegl, Simone; Toussaint, Olivier; Bernhardt, Juergen; Gonos, Efstathios S.; Franceschi, Claudio; Sikora, Ewa; Moreno-Villanueva, María; Breusing, Nicolle; Grune, Tilman; Bürkle, Alexander

2016-01-01

Blood micronutrient status may change with age. We analyzed plasma carotenoids, α-/γ-tocopherol, and retinol and their associations with age, demographic characteristics, and dietary habits (assessed by a short food frequency questionnaire) in a cross-sectional study of 2118 women and men (age-stratified from 35 to 74 years) of the general population from six European countries. Higher age was associated with lower lycopene and α-/β-carotene and higher β-cryptoxanthin, lutein, zeaxanthin, α-/γ-tocopherol, and retinol levels. Significant correlations with age were observed for lycopene (r = −0.248), α-tocopherol (r = 0.208), α-carotene (r = −0.112), and β-cryptoxanthin (r = 0.125; all p < 0.001). Age was inversely associated with lycopene (−6.5% per five-year age increase) and this association remained in the multiple regression model with the significant predictors (covariables) being country, season, cholesterol, gender, smoking status, body mass index (BMI (kg/m2)), and dietary habits. The positive association of α-tocopherol with age remained when all covariates including cholesterol and use of vitamin supplements were included (1.7% vs. 2.4% per five-year age increase). The association of higher β-cryptoxanthin with higher age was no longer statistically significant after adjustment for fruit consumption, whereas the inverse association of α-carotene with age remained in the fully adjusted multivariable model (−4.8% vs. −3.8% per five-year age increase). We conclude from our study that age is an independent predictor of plasma lycopene, α-tocopherol, and α-carotene. PMID:27706032

Fusion protein of retinol-binding protein and albumin domain III reduces liver fibrosis

PubMed Central

Lee, Hongsik; Jeong, Hyeyeun; Park, Sangeun; Yoo, Wonbaek; Choi, Soyoung; Choi, Kyungmin; Lee, Min-Goo; Lee, Mihwa; Cha, DaeRyong; Kim, Young-Sik; Han, Jeeyoung; Kim, Wonkon; Park, Sun-Hwa; Oh, Junseo

2015-01-01

Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell-targeting, retinol-binding protein–albumin domain III fusion protein (referred to as R-III), inactivate cultured HSCs. Here, we investigated the mechanism of action of albumin/R-III in HSCs and examined the anti-fibrotic potential of R-III in vivo. R-III treatment and albumin expression downregulated retinoic acid (RA) signaling which was involved in HSC activation. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti-fibrotic effect of R-III and albumin, respectively. R-III uptake into cultured HSCs was significantly decreased by siRNA-STRA6, and injected R-III was localized predominantly in HSCs in liver. Importantly, R-III administration reduced CCl4- and bile duct ligation-induced liver fibrosis. R-III also exhibited a preventive effect against CCl4-inducd liver fibrosis. These findings suggest that the anti-fibrotic effect of albumin/R-III is, at least in part, mediated by downregulation of RA signaling and that R-III is a good candidate as a novel anti-fibrotic drug. PMID:25864124

Comparison of a New Multiplex Immunoassay for Measurement of Ferritin, Soluble Transferrin Receptor, Retinol-Binding Protein, C-Reactive Protein and α1-Acid-glycoprotein Concentrations against a Widely-Used s-ELISA Method

PubMed Central

Henderson, Amanda M.; Samson, Kaitlyn L. I.; Aljaadi, Abeer M.; Devlin, Angela M.; Becquey, Elodie; Wirth, James P.

2018-01-01

Recently, a multiplex ELISA (Quansys Biosciences) was developed that measures ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), C-reactive protein (CRP), α1-acid glycoprotein (AGP), thyroglobulin, and histidine-rich protein 2. Our primary aim was to conduct a method-comparison study to compare five biomarkers (ferritin, sTfR, RBP, CRP, and AGP) measured with the Quansys assay and a widely-used s-ELISA (VitMin Lab, Willstaett, Germany) with use of serum samples from 180 women and children from Burkina Faso, Cambodia, and Malaysia. Bias and concordance were used to describe the agreement in values measured by the two methods. We observed poor overall agreement between the methods, both with regard to biomarker concentrations and deficiency prevalence estimates. Several measurements were outside of the limit of detection with use of the Quansys ELISA (total n = 42 for ferritin, n = 2 for sTfR, n = 0 for AGP, n = 5 for CRP, n = 22 for RBP), limiting our ability to interpret assay findings. Although the Quansys ELISA has great potential to simplify laboratory analysis of key nutritional and inflammation biomarkers, there are some weaknesses in the procedures. Overall, we found poor comparability of results between methods. Besides addressing procedural issues, additional validation of the Quansys against a gold standard method is warranted for future research. PMID:29393894

Vitamin A deficiency among children in a periurban South African settlement.

PubMed

Coutsoudis, A; Mametja, D; Jinabhai, C C; Coovadia, H M

1993-06-01

Preschool children (aged 3-6 y) who were living in an informal settlement within metropolitan Durban, South Africa, were assessed for vitamin A status. The serum retinol concentration of 169 children tested was 0.73 +/- 0.26 mumol/L (mean +/- SD). Nine children (5%) had vitamin A deficiency (< 0.35 mumol/L) and 75 children (44%) had low vitamin A concentrations (< 0.70 mumol/L). Conjunctival impression cytology (CIC) in 185 children revealed that 18% had poor vitamin A status as defined by two abnormal conjunctival specimens. The CIC test was a feasible and reproducible method; however, it correlated poorly with the traditionally accepted serum retinol threshold of deficiency in this population where overt vitamin A deficiency is not prevalent. This survey demonstrated that regardless of the measurement tool, there is a prevalence of subclinical vitamin A deficiency in this typical periurban informal settlement and accordingly we suggest that these children should be targeted for vitamin A-intervention strategies.

Oxidant and antioxidant status in children with subacute sclerosing panencephalitis.

PubMed

Caksen, Hüseyin; Ozkan, Mustafa; Cemek, Mustafa; Cemek, Fatma

2014-11-01

We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid levels and malondialdehyde and reduced glutathione concentrations on erythrocyte and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta-carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid reduced glutathione concentrations were decreased; however, erythrocyte and cerebrospinal fluid malondialdehyde levels were increased in the patients. Cerebrospinal fluid malondialdehyde levels were different between clinical stages of the disease (P < .05). Higher cerebrospinal fluid malondialdehyde level was associated with the more severe clinical stage. A positive correlation was found between cerebrospinal fluid malondialdehyde level and clinical stages (r = 0.42; P < .05) and between erythrocyte malondialdehyde level and clinical stages (r = 0.40; P < .05). Our findings showed presence of oxidative damage in subacute sclerosing panencephalitis and that antioxidants were increased as defense mechanisms of the organism against oxidative damage. © The Author(s) 2013.

[Influence of vegetarian diet on serum values of homocysteine and total antioxidant status in children].

PubMed

Chełchowska, Magdalena; Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Ołtarzewski, Mariusz; Laskowska-Klita, Teresa

2010-09-01

The vegetarian diet may play a preventive role in the development of chronic diseases such as coronary heart and cardiovascular disease. However increase of homocysteine (Hcy) concentration in peoples avoiding animal products may contribute to an increased atherosclerotic risk in these subjects. Recent evidence has suggested that role of hyperhomocysteinemia in atherogenesis is associated with process of autooxidation, which can promote the production of hydroxyl radicals, resulting in oxidative modification of low density lipoprotein and endothelium injury. The oxidant-antioxidant imbalance depends not only on the amount of enhanced free oxygen species but also insufficiency of antioxidant defence system. Total antioxidant status (TAS) expresses capacity for scavenging of free radicals minimizes oxidative damage. The aim of this study was to asses concentrations of homocysteine and total antioxidant status in serum of children on vegetarian and omnivorous diet. We also studied levels of vitamin A (retinol) and vitamin E (alpha-tocopherol) particular components of TAS. The study included 35 children, aged 5-16 who had been referred to Institute of Mother and Child for dietary consultation. From those, 17 were lacto-ovo-vegetarians and 18 omnivores. Dietary constituents were analyzed using the nutritional programme Dietetyk2 and completed with supplementation data. Concentration of homocysteine was estimated in serum with fluorescence polarization immunoassay and TAS by colorimetric method. Levels of vitamin A and E were determined using high-pressure liquid chromatography (HPLC). The mean concentration of homocysteine was similar in both studied groups (vegetarians: 6.13 +/- 1.01 micromol/l vs. omnivores: 5.45 +/- 0.98 micromol/l). In vegetarian children serum level of TAS was significantly lower (1.21 +/- 0.06 mmol/I) as compared to those in non-vegetarian ones (1.30 +/- 0.05 mmol/l, p < 0.0001), but remained within the physiological range (1.16-1.40 mmol/l). The

Molecular Mechanism of Wide Photoabsorption Spectral Shifts of Color Variants of Human Cellular Retinol Binding Protein II.

PubMed

Cheng, Cheng; Kamiya, Motoshi; Uchida, Yoshihiro; Hayashi, Shigehiko

2015-10-21

Color variants of human cellular retinol binding protein II (hCRBPII) created by protein engineering were recently shown to exhibit anomalously wide photoabsorption spectral shifts over ∼200 nm across the visible region. The remarkable phenomenon provides a unique opportunity to gain insight into the molecular basis of the color tuning of retinal binding proteins for understanding of color vision as well as for engineering of novel color variants of retinal binding photoreceptor proteins employed in optogenetics. Here, we report a theoretical investigation of the molecular mechanism underlying the anomalously wide spectral shifts of the color variants of hCRBPII. Computational modeling of the color variants with hybrid molecular simulations of free energy geometry optimization succeeded in reproducing the experimentally observed wide spectral shifts, and revealed that protein flexibility, through which the active site structure of the protein and bound water molecules is altered by remote mutations, plays a significant role in inducing the large spectral shifts.

Malnutrition and xerophthalmia in rural communities of Ethiopia.

PubMed

Haidar, J; Demissie, T

1999-10-01

To determine the level of malnutrition and xerophthalmia in pre-school children. Non-randomised community based study. Four different administrative regions: Harari, Tigray, Southern Nation Nationalities and people region (SNNPR) and Oromiya, with different eco-zones, were studied from May to June 1996. Fifteen thousand and eighty seven children, aged between six and 71 months, examined for clinical symptoms and signs of xerophthalmia. Anthropometry and blood samples were taken from every 20 children (n = 634) of same age, for serum retinol and nutritional determination. INTERVENTION MEASURES: Disease targeted approach of vitamin A supplementation was employed in the regions. The overall prevalence rates of night blindness and Bitot's spots exceeded WHO cut-off point for xerophthalmia as a public health problem, with higher prevalence rates in males (53%) than females (26%). The proportion of children with deficient serum retinol concentrations (SRC), and Bitot's spot were observed to be higher in Oromiya and Harari regions followed by Tigray, than SNNPR administrative regions. Most of the affected children were aged between 36 and 72 months. The greatest low SRC was also observed in the same age group of children in all regions. There was higher prevalence rate of stunting (60.1%) than wasting (12.2%) with an additional (8.8%) of children both stunted and wasted. The proportion of stunted children was high in Tigray followed by Oromiya, SNNPR and Harari regions. The high level of stunting and Bitot's spot, together with the low level of serum retinol concentrations found in these regions, indicates the need to strengthen this intervention strategy further with universal vitamin A capsule distribution, nutrition education and promotion of horticulture activities.

AdA Compiler Validation Summary Report: Certificate Number: 910920W1. 11211 Verdix Corporation, VADS Sun4 SunOS= 68020/30 ARTX, VAda-110-40120, Version 6.0, SPAECstation 2 (Host) to Motorola MVME147 (Target)

DTIC Science & Technology

1991-09-20

SunOS Release 4.1.1) Target Computer System: Motorola MVME147 (Motorola 68030 Bare Board) Customer Agreement Number: 91-07-16- VRX See section 3.1 for...AVF-VSR-504.0292 18 February 1992 91-07-1 6- VRX Ada COMPILER VALIDATION SUMMARY REPORT: Certificate Number: 910920W1.11211 VERDIX Corporation VADS...SunOS Release 4.1.1) Target Computer System: Motorola MVME147 (Motorola 68030 Bare Board) Customer Agreement Number: 91-07-16- VRX See section 3.1 for

Effect of African leafy vegetables on the micronutrient status of mildly deficient farm-school children in South Africa: a randomized controlled study.

PubMed

van der Hoeven, Marinka; Faber, Mieke; Osei, Jennifer; Kruger, Annamarie; Smuts, Cornelius M

2016-04-01

A randomized controlled trial was conducted to assess the effect of African leafy vegetable (ALV) consumption on Fe, Zn and vitamin A status in children. Children were randomly allocated to receive either a 300 g cooked ALV dish and school meal starch (n 86) or the normal school meal (n 81) five times per week for three months. ALV in the dish consisted mainly of Amaranthus cruentus (at least 80 %) and the remainder of Cleome gynandra, Cucurbita maxima or Vigna unguiculata. Nutrient content and consumer acceptance of the ALV dish were also determined. North West Province, South Africa. Grade R to grade 4 children (6-12 years old) of two farm schools. The ALV dish contributed 11·6-15·8 mg Fe and 1·4-3·7 mg Zn. At baseline, prevalence of deficiencies in the intervention group was 16·0 %, 16·3 %, 7·0 % and 75·6 %, respectively, for anaemia (Hb<11·5 g/dl), Fe (serum ferritin<15 µg/l), vitamin A (serum retinol<20 μg/dl) and Zn (serum Zn<65 μg/dl); and in the control group 10·5 %, 18·5 %, 2·5 % and 75·3 %, respectively. No significant estimated intervention effect was found. This randomized controlled trial showed that ALV were unable to improve serum retinol, serum ferritin or Hb if there are only mild deficiencies present. Furthermore, despite the low Zn status in the study population, ALV consumption did not improve serum Zn concentrations either.

Determining appropriate nutritional interventions for South African children living in informal urban settlements.

PubMed

Coutsoudis, A; Jinabhai, C C; Coovadia, H M; Mametja, L D

1994-09-01

Rapid urbanisation in South Africa has led to the creation of informal shack settlements where the health status of children is in jeopardy; it needs to be monitored so that appropriate intervention strategies can be formulated. Accordingly, the nutritional status of 190 children (3-6 years of age) living in Besters, a typical urban shack settlement north of Durban, was assessed anthropometrically. In addition the following biochemical values were determined: vitamins A and E, calcium, magnesium, phosphorus, albumin, haemoglobin, serum iron and ferritin and percentage of transferrin saturation. Malnutrition was evident in 13% of the children who were underweight (below the National Center for Health Statistics (NCHS) third weight-for-age percentile) and 27% who were stunted (below the NCHS third height-for-age percentile). Concentrations of albumin, calcium, magnesium, phosphorus and vitamin E were close to normal, with no more than 10% of the sample having values outside the normal range. However, 44% of the children had low serum retinol levels (< 20 micrograms/dl) and 21% of the children had anaemia (haemoglobin < 11 micrograms/dl). Significant positive correlations were found between serum retinol and all biochemical indicators of iron status except serum ferritin. This study highlights the fact that nutrient deficiencies are interrelated, particularly protein energy malnutrition and poor vitamin A and iron status. A broad multifaceted comprehensive health intervention programme is therefore required.

Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia.

PubMed

Manickavasagar, Baheerathi; McArdle, Andrew J; Yadav, Pallavi; Shaw, Vanessa; Dixon, Marjorie; Blomhoff, Rune; Connor, Graeme O'; Rees, Lesley; Ledermann, Sarah; Van't Hoff, William; Shroff, Rukshana

2015-02-01

Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia. We studied the relationship between vitamin A intake, serum retinoid levels, and serum calcium in 105 children with CKD stages 2-5 on dialysis and posttransplant. Serum retinoid measures included retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA) and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary. Twenty-five children were in CKD 2-3, 35 in CKD 4-5, 23 on dialysis and 22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake (RNI) value. Children receiving supplemental feeds compared with diet alone had higher vitamin A intake (p = 0.02) and higher serum ROH (p < 0.001). Notably, increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m(2) fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in ROH. RBP4 levels were increased in CKD 3-5 and dialysis patients. The lowest ratios of ROH:RBP4 were seen in dialysis compared with CKD 2-3 (p = 0.03), suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA were associated with serum calcium. On multivariable analysis RBP4 levels and alfacalcidol dose were significant predictors of serum calcium (model R (2) 32 %) in dialysis patients. Hypervitaminosis A is seen in early CKD, with highest levels in children on supplemental feeds compared with diet alone. Serum retinoid levels significantly predict hypercalcemia.

Randomized controlled trial of zinc and vitamin A as co-adjuvants for the treatment of pulmonary tuberculosis.

PubMed

Lawson, Lovett; Thacher, Tom D; Yassin, Mohammed A; Onuoha, Ndubusi A; Usman, Auwal; Emenyonu, Nnamdi E; Shenkin, Alan; Davies, Peter D O; Cuevas, Luis E

2010-12-01

To assess the efficacy of weekly zinc or zinc plus retinol as adjuncts for the treatment of pulmonary tuberculosis.   Double-blind, randomized, placebo-controlled trial in 350 patients >15 years old with smear-positive tuberculosis in Nigeria (ISRCTN36636609). In addition to antituberculous treatment, patients were randomly allocated to weekly supplements of zinc (90 mg), zinc plus retinol (5000 IU) or placebos for 6 months. Primary outcomes were time to sputum smear conversion and resolution of radiographic abnormalities. After 8 weeks of treatment, 68% had achieved sputum smear conversion, and the median conversion time was 6.5 weeks. Hazard ratios (HR, 95%CI) for sputum conversion relative to the placebo group were not significant for zinc (1.07, 0.92-1.29) or zinc plus retinol (0.89, 0.76-1.07). Significant predictors of time to sputum conversion were lung abnormality score, sputum smear grade, age and serum C-reactive protein. HIV co-infection and gender were not independent predictors of time to sputum conversion. There were no significant differences between supplement groups in clinical, radiological or laboratory outcomes at 2 months or 6 months. There were 9, 9 and 2 deaths in patients receiving zinc, zinc plus retinol or placebos, respectively. Mortality in those who received zinc (HR 1.71, 0.88-3.58) or zinc plus retinol (HR 1.54, 0.78-3.26) did not differ significantly from those who received placebos. Most deaths occurred in patients co-infected with HIV.   Supplementation with zinc or zinc plus retinol did not lead to better outcomes than placebos, and caution is warranted regarding routine micronutrient supplementation, particularly in patients co-infected with HIV. © 2010 Blackwell Publishing Ltd.

Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease.

PubMed

Kaukonen, Maria; Woods, Sean; Ahonen, Saija; Lemberg, Seppo; Hellman, Maarit; Hytönen, Marjo K; Permi, Perttu; Glaser, Tom; Lohi, Hannes

2018-05-29

Maternally skewed transmission of traits has been associated with genomic imprinting and oocyte-derived mRNA. We report canine congenital eye malformations, caused by an amino acid deletion (K12del) near the N terminus of retinol-binding protein (RBP4). The disease is only expressed when both dam and offspring are deletion homozygotes. RBP carries vitamin A (retinol) from hepatic stores to peripheral tissues, including the placenta and developing eye, where it is required to synthesize retinoic acid. Gestational vitamin A deficiency is a known risk factor for ocular birth defects. The K12del mutation disrupts RBP folding in vivo, decreasing its secretion from hepatocytes to serum. The maternal penetrance effect arises from an impairment in the sequential transfer of retinol across the placenta, via RBP encoded by maternal and fetal genomes. Our results demonstrate a mode of recessive maternal inheritance, with a physiological basis, and they extend previous observations on dominant-negative RBP4 alleles in humans. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Vitamin A toxicity in wild-caught African green vervet monkeys (Chlorocebus aethiops) after 2 years in captivity.

PubMed

Mills, Jordan P; Tanumihardjo, Sherry A

2006-10-01

Primate lab diets typically contain high vitamin A concentrations when compared with human recommended intakes. In this study, we analyzed the vitamin A contents of liver and serum from 13 adult female African green vervet monkeys (Chlorocebus aethiops). These monkeys were wild-caught and held in captivity for 2 y, during which time they consumed a standard primate diet. Liver vitamin A concentration (mean +/- 1 standard deviation) was 14.6 +/- 2.3 micromol retinol/g liver; subtoxicity in humans is defined as at least 1 micromol/g liver. The serum retinol concentration (0.93 +/- 0.21 microM) was not elevated. Hypertrophy and hyperplasia of hepatic stellate cells were present which, in conjunction with elevated hepatic vitamin A concentrations, are evidence of toxicity. Although the ramifications of chronically toxic vitamin A status in experimental monkeys have not been defined, this state may influence nonhuman primate research outcomes and confound data interpretation. The validity of bone mineral research using nonhuman primates is of greatest concern, in light of the association between vitamin A toxicity and compromised bone health.

Serum sickness

MedlinePlus

Drug allergy - serum sickness; Allergic reaction - serum sickness; Allergy - serum sickness ... Unlike other drug allergies , which occur very soon after receiving the medicine, serum sickness develops 7 to 21 days after the first exposure ...

Computational Fluid Dynamics (CFD) study of the 4th generation prototype of a continuous flow Ventricular Assist Device (VAD).

PubMed

Song, Xinwei; Wood, Houston G; Olsen, Don

2004-04-01

The continuous flow ventricular assist device (VAD) is a miniature centrifugal pump, fully suspended by magnetic bearings, which is being developed for implantation in humans. The CF4 model is the first actual prototype of the final design product. The overall performances of blood flow in CF4 have been simulated using computational fluid dynamics (CFD) software: CFX, which is commercially available from ANSYS Inc. The flow regions modeled in CF4 include the inlet elbow, the five-blade impeller, the clearance gap below the impeller, and the exit volute. According to different needs from patients, a wide range of flow rates and revolutions per minute (RPM) have been studied. The flow rate-pressure curves are given. The streamlines in the flow field are drawn to detect stagnation points and vortices that could lead to thrombosis. The stress is calculated in the fluid field to estimate potential hemolysis. The stress is elevated to the decreased size of the blood flow paths through the smaller pump, but is still within the safe range. The thermal study on the pump, the blood and the surrounding tissue shows the temperature rise due to magnetoelectric heat sources and thermal dissipation is insignificant. CFD simulation proved valuable to demonstrate and to improve the performance of fluid flow in the design of a small size pump.

Visfatin and retinol-binding protein 4 concentrations in lean, glucose-tolerant women with PCOS.

PubMed

Yildiz, Bulent O; Bozdag, Gurkan; Otegen, Umit; Harmanci, Ayla; Boynukalin, Kubra; Vural, Zehra; Kirazli, Serafettin; Yarali, Hakan

2010-01-01

Since insulin resistance is accepted to be a common feature of polycystic ovary syndrome (PCOS), the exact molecular mechanism(s) involved in glucose and lipid metabolism have been under investigation in the syndrome. Recently, two novel adipokines, namely visfatin and retinol-binding protein 4 (RBP4), have been suggested to play a role in insulin resistance and diabetes. This study sought to determine whether plasma concentrations of visfatin and RBP4 are altered in PCOS by comparing a total of 27 lean, normal glucose-tolerant PCOS patients with 19 age- and body mass index-matched healthy controls. The mean plasma visfatin concentrations were higher in PCOS patients than those in healthy subjects (37.9+/-18.2 versus 19.8+/-17.5, P<0.01), while RBP4 concentrations were similar between the two. Both adipokines were correlated with each other in the whole (r=0.50, P<0.01) and in PCOS (r=0.52, P<0.01) groups but not in controls. The results suggest that lean, glucose-tolerant women with PCOS have increased circulating visfatin and unaltered RBP4 concentrations compared with healthy lean women. In order to clarify overlapping effects and their potential contribution to the pathophysiology of PCOS, further studies are needed. Copyright (c) 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

[Functional reserves of humans in North condition and its providing of fat-soluble vitamins].

PubMed

Boĭko, E R; Potolitsyna, N N; Boĭko, S G; Larina, V E; Zelenov, V A

2008-01-01

It was been examined 810 healthy peoples inhabited in Russian European North. It was been shown that more than 35% of examined person from different group have lowered serum level of retinol and alpha-tocopherol. Described that alpha-tocopherol deficits occur more often and proposed that it cased as a result of free radical oxidation typical for North inhabitances.

Vitamin A deficiency, iron deficiency, and anemia among preschool children in the Republic of the Marshall Islands.

PubMed

Palafox, Neal A; Gamble, Mary V; Dancheck, Barbara; Ricks, Michelle O; Briand, Kennar; Semba, Richard D

2003-05-01

We investigated the co-occurrence of vitamin A deficiency, iron deficiency, and anemia among young children in the Republic of the Marshall Islands. Hemoglobin, serum retinol, and serum ferritin were assessed in the Republic of the Marshall Islands Vitamin A Deficiency Study, a community-based survey that involved 919 children ages 1 to 5 y. The proportion of children with vitamin A deficiency (serum retinol concentrations < 0.70 microM/L) was 59.9%. The prevalences of anemia (hemoglobin < 110 g/L), iron deficiency (serum ferritin < 12 microg/L), and iron deficiency anemia (iron deficiency and anemia) were 36.4%, 53.5%, and 23.8%, respectively. The proportion of children who had co-occurrence of vitamin A and iron deficiencies was 33.2%. The mean ages of children with and without vitamin A deficiency were 3.2 +/- 1.4 and 2.9 +/- 1.5 y, respectively (P = 0.01), and the mean ages of those with and without iron deficiency were 2.7 +/- 1.3 and 3.5 +/- 1.4 y, respectively (P < 0.0001). Children in the Republic of the Marshall Islands, ages 1 to 5 y, are at high risk of anemia, vitamin A deficiency, and iron deficiency, and one-third of these children had the co-occurrence of vitamin A and iron deficiencies. Further investigation is needed to identify risk factors and evaluate interventions to address vitamin A and iron deficiencies among children.

Carotenoid status among preschool children with vitamin A deficiency in the Republic of the Marshall Islands.

PubMed

Gamble, Mary V; Palafox, Neal A; Dancheck, Barbara; Ricks, Michelle O; Briand, Kennar; Semba, Richard D

2004-01-01

Although carotenoids are known to be important dietary sources of vitamin A, there have been few epidemiological studies that have characterized the serum concentrations of major dietary carotenoids among preschool children with vitamin A deficiency. We conducted a population-based, cross-sectional study of serum pro-vitamin A carotenoids (alpha -carotene, beta-carotene, beta-cryptoxanthin), non-provitamin A carotenoids (lutein/zeaxanthin, and lycopene), and retinol among 278 children, aged 1-5 y, in the Republic of the Marshall Islands. Vitamin A deficiency was defined as serum retinol <0.70 micromol/L. Geometric mean serum concentrations of carotenoids among children with and without vitamin A deficiency were 0.003 vs 0.006 micromol/L for alpha-carotene (P = 0.0017), 0.011 vs 0.023 micromol/L for beta-carotene (P <0.0001), 0.023 vs 0.034 micromol/L for beta-cryptoxanthin (P = 0.0075), 0.007 vs 0.012 micromol/L for lycopene (P = 0.037), 0.044 vs 0.052 micromol/L for lutein/zeaxanthin (P = 0.2), and 0.045 vs 0.074 micromol/L for total provitamin A carotenoids (P <0.0001) respectively. In a multivariate analysis adjusting for sex, age (Odds Ratio [O.R.] 1.44, 95% confidence interval [C.I.] 1.16-1.78), and serum provitamin A carotenoids (O.R. 0.49, 95% C.I. 0.34-0.71) were associated with vitamin A deficiency, but serum non-provitamin A carotenoids were not associated with vitamin A deficiency (O.R. 0.93, 95% C.I. 0.67-1.28). Preschool children with vitamin A deficiency in the Republic of the Marshall Islands have extremely low serum concentrations of provitamin A carotenoids and interventions are needed to improve the dietary intake of provitamin A carotenoids among Marshallese children.

Retinol Promotes In Vitro Growth of Proximal Colon Organoids through a Retinoic Acid-Independent Mechanism

PubMed Central

Nibe, Yoichi; Akiyama, Shintaro; Matsumoto, Yuka; Nozaki, Kengo; Fukuda, Masayoshi; Hayashi, Ayumi; Mizutani, Tomohiro; Oshima, Shigeru; Watanabe, Mamoru; Nakamura, Tetsuya

2016-01-01

Retinol (ROL), the alcohol form of vitamin A, is known to control cell fate decision of various types of stem cells in the form of its active metabolite, retinoic acid (RA). However, little is known about whether ROL has regulatory effects on colonic stem cells. We examined in this study the effect of ROL on the growth of murine normal colonic cells cultured as organoids. As genes involved in RA synthesis from ROL were differentially expressed along the length of the colon, we tested the effect of ROL on proximal and distal colon organoids separately. We found that organoid forming efficiency and the expression level of Lgr5, a marker gene for colonic stem cells were significantly enhanced by ROL in the proximal colon organoids, but not in the distal ones. Interestingly, neither retinaldehyde (RAL), an intermediate product of the ROL-RA pathway, nor RA exhibited growth promoting effects on the proximal colon organoids, suggesting that ROL-dependent growth enhancement in organoids involves an RA-independent mechanism. This was confirmed by the observation that an inhibitor for RA-mediated gene transcription did not abrogate the effect of ROL on organoids. This novel role of ROL in stem cell maintenance in the proximal colon provides insights into the mechanism of region-specific regulation for colonic stem cell maintenance. PMID:27564706

Chronic ovine evaluation of a totally implantable electrical left ventricular assist system.

PubMed

Ramasamy, N; Chen, H; Miller, P J; Jassawalla, J S; Greene, B A; Ocampo, A; Siegel, L C; Oyer, P E; Portner, P M

1989-01-01

The totally implantable Novacor left ventricular assist system (LVAS) comprises a pump/drive unit (VAD), electronic control and power subsystem (ECP), variable volume compensator (VVC), and belt skin transformer (BST). The system is now undergoing chronic in vivo evaluation. Cumulative animal testing of VAD, VVC, and BST subsystems are 12.1, 4.9, and 43 years, respectively. The longest implants were 279 days for the VAD, 767 days for the VVC, and 1,148 days for the BST. A chronic implant of the total system was electively terminated at 260 days. The LVAS was powered via the BST. Continuously monitored hemodynamic and pump parameters have demonstrated normal hemodynamics and LVAS operation. Periodic VVC determinations suggest a 0.8 ml/day diffusive gas loss. Tether-free operation has been demonstrated with an Ag-Zn battery backpack. The animal was healthy and free of infection as indicated by routine hematologic, biochemical and serum enzyme determinations. Hemolysis is minimal (plasma free hemoglobin less than 5 mg%). Pump output ranged from 7 to 8 L/min. Severe valve calcification was the reason for elective termination at 260 days. This preclinical in vivo experience, and in vitro reliability studies, demonstrate efficacy of the total system.

Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial123456

PubMed Central

Gannon, Bryan; Kaliwile, Chisela; Arscott, Sara A; Schmaelzle, Samantha; Chileshe, Justin; Kalungwana, Ngándwe; Mosonda, Mofu; Pixley, Kevin; Masi, Cassim; Tanumihardjo, Sherry A

2014-01-01

Background: Biofortification is a strategy to relieve vitamin A (VA) deficiency. Biofortified maize contains enhanced provitamin A concentrations and has been bioefficacious in animal and small human studies. Objective: The study sought to determine changes in total body reserves (TBRs) of vitamin A with consumption of biofortified maize. Design: A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired 13C-retinol isotope dilution test, a sensitive biomarker for VA status, was used to measure TBRs before and after a 90-d intervention. Treatments were white maize with placebo oil (VA−), orange maize with placebo (orange), and white maize with VA in oil [400 μg retinol activity equivalents (RAEs) in 214 μL daily] (VA+). Results: In total, 133 children completed the trial and were analyzed for TBRs (n = 44 or 45/group). Change in TBR residuals were not normally distributed (P < 0.0001); median changes (95% CI) were as follows: VA−, 13 (−19, 44) μmol; orange, 84 (21, 146) μmol; and VA+, 98 (24, 171) μmol. Nonparametric analysis showed no statistical difference between VA+ and orange (P = 0.34); both were higher than VA− (P = 0.0034). Median (95% CI) calculated liver reserves at baseline were 1.04 (0.97, 1.12) μmol/g liver, with 59% >1 μmol/g, the subtoxicity cutoff; none were <0.1 μmol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 μg β-carotene equivalents/1 μg retinol by using the middle 3 quintiles of change in TBRs from each group. Serum retinol did not change in response to intervention (P = 0.16) but was reduced with elevated C-reactive protein (P = 0.0029) and α-1-acid glycoprotein (P = 0.0023) at baseline. Conclusions: β-Carotene from maize was efficacious when consumed as a staple food in this population and could avoid the potential for hypervitaminosis A that was observed with the use of preformed VA from supplementation and fortification. Use of

Biofortified orange maize is as efficacious as a vitamin A supplement in Zambian children even in the presence of high liver reserves of vitamin A: a community-based, randomized placebo-controlled trial.

PubMed

Gannon, Bryan; Kaliwile, Chisela; Arscott, Sara A; Schmaelzle, Samantha; Chileshe, Justin; Kalungwana, Ngándwe; Mosonda, Mofu; Pixley, Kevin; Masi, Cassim; Tanumihardjo, Sherry A

2014-12-01

Biofortification is a strategy to relieve vitamin A (VA) deficiency. Biofortified maize contains enhanced provitamin A concentrations and has been bioefficacious in animal and small human studies. The study sought to determine changes in total body reserves (TBRs) of vitamin A with consumption of biofortified maize. A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired (13)C-retinol isotope dilution test, a sensitive biomarker for VA status, was used to measure TBRs before and after a 90-d intervention. Treatments were white maize with placebo oil (VA-), orange maize with placebo (orange), and white maize with VA in oil [400 μg retinol activity equivalents (RAEs) in 214 μL daily] (VA+). In total, 133 children completed the trial and were analyzed for TBRs (n = 44 or 45/group). Change in TBR residuals were not normally distributed (P < 0.0001); median changes (95% CI) were as follows: VA-, 13 (-19, 44) μmol; orange, 84 (21, 146) μmol; and VA+, 98 (24, 171) μmol. Nonparametric analysis showed no statistical difference between VA+ and orange (P = 0.34); both were higher than VA- (P = 0.0034). Median (95% CI) calculated liver reserves at baseline were 1.04 (0.97, 1.12) μmol/g liver, with 59% >1 μmol/g, the subtoxicity cutoff; none were <0.1 μmol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 μg β-carotene equivalents/1 μg retinol by using the middle 3 quintiles of change in TBRs from each group. Serum retinol did not change in response to intervention (P = 0.16) but was reduced with elevated C-reactive protein (P = 0.0029) and α-1-acid glycoprotein (P = 0.0023) at baseline. β-Carotene from maize was efficacious when consumed as a staple food in this population and could avoid the potential for hypervitaminosis A that was observed with the use of preformed VA from supplementation and fortification. Use of more sensitive methods other than serum retinol alone, such

Multinutrient-fortified juices improve vitamin D and vitamin E status in children: a randomized controlled trial.

PubMed

Economos, Christina D; Moore, Carolyn E; Hyatt, Raymond R; Kuder, Julia; Chen, Tai; Meydani, Simin Nikbin; Meydani, Mohsen; Klein, Ellen; Biancuzzo, Rachael M; Holick, Michael F

2014-05-01

Provision of fortified juices may provide a convenient method to maintain and increase blood fat-soluble vitamins. To determine whether children consuming orange juice fortified with calcium and combinations of vitamins D, E, and A could increase serum 25-hydroxyvitamin D [25(OH)D], α-tocopherol, and retinol levels. A 12-week randomized, double-blind, controlled trial. One hundred eighty participants (aged 8.04±1.42 years) were recruited at Tufts (n=70) and Boston University (n=110) during 2005-2006. Of those recruited, 176 children were randomized into three groups: CaD (700 mg calcium+200 IU vitamin D), CaDEA (700 mg calcium+200 IU vitamin D+12 IU vitamin E+2,000 IU vitamin A as beta carotene), or Ca (700 mg calcium). Children consumed two 240-mL glasses of CaD, CaDEA, or Ca fortified orange juice daily for 12 weeks. Serum 25(OH)D, α-tocopherol, and retinol concentrations. Changes in 25(OH)D, α-tocopherol, retinol, and parathyroid hormone concentrations were examined. Covariates included sex, age, race/ethnicity, body mass index, and baseline 25(OH)D, α-tocopherol, retinol, or parathyroid hormone levels. Multivariate models and repeated measures analysis of variance tested for group differences with pre-post measures (n=141). Baseline 25(OH)D was 68.4±27.7 nmol/L (27.4±11.10 ng/mL) ), with 21.7% of participants having inadequate 25(OH)D (<50 nmol/L [20.03 ng/mL]). The CaD group's 25(OH)D increase was greater than that of the Ca group (12.7 nmol/L [5.09 ng/mL], 95% CI 1.3 to 24.1; P=0.029). The CaDEA group's increase in α-tocopherol concentration was greater than that in the Ca or CaD groups (3.79 μmol/L [0.16 μg/mL], 95% CI 2.5 to 5.1 and 3.09 μmol/L [0.13 μg/mL], 95% CI -1.8 to 4.3), respectively (P<0.0001). Retinol levels did not change, and body weight remained as expected for growth. Daily consumption of orange juice providing 200 IU vitamin D and 12 IU vitamin E increased 25(OH)D and α-tocopherol concentrations in young children within 12 weeks

De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH-Mediated Ovarian Follicular Cell Differentiation and Female Fertility

PubMed Central

Kawai, Tomoko; Yanaka, Noriyuki; Richards, JoAnne S.

2016-01-01

Retinoic acid (RA) is the active form of vitamin A and is synthesized from retinol by two key enzymes, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). As the physiological precursor of RA, retinol impacts female reproductive functions and fertility. The expression of Adh1 and Adh5 as well as Aldh1a1 and Aldh1a7 are significantly increased in the ovaries of mice treated with equine chorionic gonadotropin/FSH. The RA receptor is expressed and localized in granulosa cells and is activated by endogenous RA as indicated by LacZ expression in granulosa cells of RA-responsive transgene-LacZ transgenic mice (RA reporter mice). Coinjection of the ADH inhibitor, 4-methylpyrazole, with equine chorionic gonadotropin significantly decreases the number and developmental competence of oocytes ovulated in response to human chorionic gonadotropin/LH as compared with controls. Injections of RA completely reverse the effects of the inhibitor of ovulation and oocyte development. When mice were fed a retinol-free, vitamin A-deficient diet that significantly reduced the serum levels of retinol, the expression of the LH receptor (Lhcgr) was significantly lower in the ovaries of the vitamin A-deficient mice, and injections of human chorionic gonadotropin failed to induce genes controlling ovulation. These results indicate that ovarian de novo biosynthesis of RA is required for the follicular expression of Lhcgr in granulosa cells and their ability to respond to the ovulatory LH surge. PMID:27022678

Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.

PubMed

Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V; Chavali, Venkata R M; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G Bhanuprakash; Sieving, Paul A; Ayyagari, Radha

2012-01-01

Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th) decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.

Exome Analysis Identified a Novel Mutation in the RBP4 Gene in a Consanguineous Pedigree with Retinal Dystrophy and Developmental Abnormalities

PubMed Central

Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V.; Chavali, Venkata R. M.; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G. Bhanuprakash; Sieving, Paul A.; Ayyagari, Radha

2012-01-01

Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism. PMID:23189188

Comparative Hepatoprotective Effect of Vitamins A and E Against Gasoline Vapor Toxicity in Male and Female Rats

PubMed Central

Uboh, Friday Effiong; Ebong, Patrick E.; Umoh, Ime B.

2009-01-01

Background Plasma alanine transferase(ALT), aspartate transferase(AST), α-glutamyl transferase(GGT), and alkaline phosphatase(ALP) activities are known biomarkers in assessing hepatic functional integrity. A remarkable rise in the activities of these enzymes normally signifies hepatotoxicity of chemical agent(s) in the biological system. Exposure to 17.8 cm3h-1m-3 of PMS blend unleaded gasoline vapors (UGV) for 6 hr/day, 5 days/week for 20 weeks have been reported to cause hepatotoxicity in rats. Methods In this study, the comparative hepatoprotective effect of vitamins A (retinol) and E (α-tocopherol) against UGV-induced toxicity was assessed in male and female rats. Retinol and α-tocopherol at prophylactic dosage (400 and 200 IU/kg/day, respectively) were separately administered orally to the test rats concomitant with exposure to UGV in the last two weeks of the experiment. Results The results of this study indicated that exposure to UGV caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in male and female rats. Oral administration of prophylactic doses of retinol and α-tocopherol produced a significant decrease (P < 0.05) in the activities of these parameters in male and female test rats, compared with the non-treated test rats; but insignificant increase(P ≥ 0.05), compared with the control. However, the hepatoprotective effect of α-tocopherol was observed to be more potent than that of retinol. Conclusions The result of this study demonstrated that the hepatoprotective potency of α-tocopherol against gasoline vapors toxicity was higher than that of retinol in male and female rats, although the female gender of the animal model responded to treatment with both vitamins better than the males. Hence, the work suggested the beneficial effects of both vitamins against hepatotoxicity in individuals frequently exposed to gasoline vapors. PMID:27956974

Studies on the apoptotic activity of natural and synthetic retinoids: discovery of a new class of synthetic terphenyls that potently support cell growth and inhibit apoptosis in neuronal and HL-60 cells.

PubMed

Simoni, Daniele; Giannini, Giuseppe; Roberti, Marinella; Rondanin, Riccardo; Baruchello, Riccardo; Rossi, Marcello; Grisolia, Giuseppina; Invidiata, Francesco Paolo; Aiello, Stefania; Marino, Silvia; Cavallini, Sabrina; Siniscalchi, Anna; Gebbia, Nicola; Crosta, Lucia; Grimaudo, Stefania; Abbadessa, Vincenzo; Di Cristina, Antonietta; Tolomeo, Manlio

2005-06-30

New terphenyl derivatives have been synthesized and tested for their effect on cell survival in serum-free cultures. These compounds protected HL60 cells from death and supported their growth with an activity higher than that of the natural 14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic activity on neuronal cells, proving them as possible candidates for the treatment of neurodegenerative and ischemic diseases.

A skincare containing retinol adenosine and hyaluronic acid optimises the benefits from a type A botulinum toxin injection.

PubMed

Ascher, Benjamin; Fanchon, Chantal; Kanoun-Copy, Leila; Bouloc, Anne; Benech, Florence

2012-10-01

A monocentre double-blind two parallel group clinical study was conducted to assess whether a new skincare regimen containing retinol, adenosine and hyaluronic acid, applied after the injection of botulinum toxin A to the glabellar area, provided a beneficial effect. Standardised photographs acquired using LifeViz cameras and zoomed pictures of the glabella and of the crow's feet areas were analysed with automatic well-defined procedures. Perceived efficacy and tolerance were also analysed by comparison between the two groups. A beneficial effect versus placebo-treated group was proven in the group having topically applied the new skincare regimen for 2 months following botulinum toxin A injection with no touch up after 1 month. 3D image analysis showed more rapid results on D10 and enhanced efficacy on M2. Moreover, a beneficial effect independent of injection was measured in the crow's feet area, and analysis of the self-evaluation questionnaire showed enhanced efficacy perceived by the volunteers. A specially developed skincare regimen applied immediately after botulinum toxin A injection completes the beneficial effect of the injection on the glabellar area and offers clinical benefits in fine lines, wrinkles and smoothness on the whole face.

Serum factors and clinical characteristics associated with serum E-Screen activity

PubMed Central

Wang, Jue; Trentham-Dietz, Amy; Hemming, Jocelyn D. C.; Hedman, Curtis J.; Sprague, Brian L.

2013-01-01

Background The E-Screen bioassay can measure the mitogenicity of human serum and thus may be useful as a biomarker in epidemiologic studies of breast cancer. While the assay’s MCF-7 cells are known to proliferate in response to estrogen, the specific determinants of variation in E-Screen activity in human serum samples are poorly understood. We sought to identify serum molecules and patient characteristics associated with serum E-Screen activity among postmenopausal women. Methods Postmenopausal women (N=219) aged 55–70 with no history of postmenopausal hormone use or breast cancer completed a questionnaire and provided a blood sample. Serum was analyzed for E-Screen activity and a variety of molecules including sex hormones, growth factors, and environmental chemicals. Stepwise selection procedures were used to identify correlates of E-Screen activity. Results Serum samples from all women had detectable E-Screen activity, with a median estradiol equivalents value of 0.027 ng/mL and interquartile range of 0.018–0.036 ng/mL. In the final multivariable-adjusted model, serum E-Screen activity was positively associated with serum estradiol, estrone, IGFBP-3, and testosterone levels (p<0.05), as well as body mass index (p=0.03). Serum E-Screen activity was lower among women with higher SHBG (p<0.0001) and progesterone levels (p=0.03). Conclusion Serum E-Screen activity varies according to levels of endogenous estrogens and other serum molecules. Obesity appears to confer additional serum mitogenicity beyond its impact on the measured hormones and growth factors. Impact By capturing mitogenicity due to a variety of patient and serum factors, the E-Screen may provide advantages for use as a biomarker in breast cancer studies. PMID:23588007

Prenatal vitamin A deficiency impairs adaptive immune responses to pentavalent rotavirus vaccine (RotaTeq®) in a neonatal gnotobiotic pig model.

PubMed

Kandasamy, Sukumar; Chattha, Kuldeep S; Vlasova, Anastasia N; Saif, Linda J

2014-02-07

Vitamin A deficiency (VAD) is associated with increased childhood mortality and morbidity in impoverished Asian and African countries, but the impact of VAD on rotavirus (RV) vaccine or infection is poorly understood. We assessed effects of gestational and dietary induced pre- and post-natal VAD and vitamin A supplementation on immune responses to a pentavalent rotavirus vaccine, RotaTeq(®) in a neonatal gnotobiotic pig model. Vaccine efficacy was assessed against virulent G1P[8] human rotavirus (HRV) challenge. VAD and vitamin A sufficient (VAS) piglets were derived from dietary VAD and VAS sows, respectively. VAD piglets had significantly lower levels of hepatic vitamin A compared to that of VAS piglets. RotaTeq(®)-vaccinated VAD piglets had 350-fold higher fecal virus shedding titers compared to vaccinated VAS piglets post-challenge. Only 25% of vaccinated non-vitamin A supplemented VAD piglets were protected against diarrhea compared with 100% protection rate in vaccinated non-supplemented VAS piglets post-challenge. Intestinal HRV specific immune responses were compromised in VAD piglets. Vaccinated VAD piglets had significantly lower ileal HRV IgG antibody secreting cell (ASC) responses (pre-challenge) and duodenal HRV IgA ASC responses (post-challenge) compared to vaccinated VAS piglets. Also, intestinal HRV IgA antibody titers were 11-fold lower in vaccinated VAD compared to vaccinated VAS piglets post-challenge. Persistently elevated levels of IL-8, a pro-inflammatory mediator, and lower IL-10 responses (anti-inflammatory) in vaccinated VAD compared to VAS piglets suggest more severe inflammatory responses in VAD piglets post-challenge. Moreover higher IFN-γ responses pre-challenge were observed in VAD compared to VAS piglets. The impaired vaccine-specific intestinal antibody responses and decreased immunoregulatory cytokine responses coincided with reduced protective efficacy of the RV vaccine against virulent HRV challenge in VAD piglets. In

Small quantities of carotenoid-rich tropical green leafy-vegetables indigenous to Africa maintain vitamin A status in Mongolian gerbils (Meriones unguiculatus)

PubMed Central

Ejoh, Richard A.; Dever, Joseph T.; Mills, Jordan P.; Tanumihardjo, Sherry A.

2015-01-01

Leafy vegetables are important sources of provitamin A carotenoids. Information on their ability to provide vitamin A is often misleading because of the methodology used to assess bioefficacy. Mongolian gerbils were used to evaluate the bioefficacy of provitamin A carotenoids in tropical leafy vegetables (i.e. Solanium nigrum, Moringa oleifera, Vernonia calvoana, and Hibiscus cannabinus) that are indigenous to Africa. Gerbils (n = 67) were vitamin A-depleted for 5 weeks. After a baseline kill (n = 7), the gerbils were weight-matched and assigned to 6 treatment groups (n = 10/group; 4 vegetable groups; negative and positive controls). For 4 weeks, the treatments included 35 nmol vitamin A (theoretical concentrations based on 100% bioefficacy) in the form of vegetables or retinyl acetate. In addition to their diets, the control and vegetable groups received daily doses of oil, while the vitamin A group received retinyl acetate in oil matched to prior day intake. Serum and livers were analysed for vitamin A using HPLC. Serum retinol concentrations did not differ among groups, but total liver vitamin A of the vitamin A and vegetable groups were higher than that of the negative control group (P < 0·0001). Liver β-carotene 15,15′-monooxygenase-1 expression levels were determined for two vegetable groups and were similar to the positive and negative controls. Conversion factors for the different leafy vegetables were between 1·9 and 2·3 μg β-carotene equivalents to 1 μg retinol. Small quantities of these vegetables maintained vitamin A status in gerbils through efficient bioconversion of β-carotene to retinol. PMID:20412609

Retinol Dehydrogenase-10 Regulates Pancreas Organogenesis and Endocrine Cell Differentiation via Paracrine Retinoic Acid Signaling.

PubMed

Arregi, Igor; Climent, Maria; Iliev, Dobromir; Strasser, Jürgen; Gouignard, Nadège; Johansson, Jenny K; Singh, Tania; Mazur, Magdalena; Semb, Henrik; Artner, Isabella; Minichiello, Liliana; Pera, Edgar M

2016-12-01

Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here, we show that retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme. Rdh10 null mutant mouse embryos exhibited dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Conditional disruption of Rdh10 from the endoderm caused increased mortality, reduced body weight, and lowered blood glucose levels after birth. Endodermal Rdh10 deficiency led to a smaller dorsal pancreas with a reduced density of early glucagon + and insulin + cells. During the secondary transition, the reduction of Neurogenin3 + endocrine progenitors in the mutant dorsal pancreas accounted for fewer α- and β-cells. Changes in the expression of α- and β-cell-specific transcription factors indicated that Rdh10 might also participate in the terminal differentiation of endocrine cells. Together, our results highlight the importance of both mesenchymal and epithelial Rdh10 for pancreogenesis and the first wave of endocrine cell differentiation. We further propose a model in which the Rdh10-expressing exocrine tissue acts as an essential source of RA signals in the second wave of endocrine cell differentiation.

Thyroid Hormones, Retinol and Clinical Parameters in Relation to Mercury and Organohalogen Contaminants in Great Blue Heron (Ardea herodias) Nestlings from the St. Lawrence River, Québec, Canada.

PubMed

Champoux, Louise; Boily, Monique; Fitzgerald, Guy

2017-02-01

The exposure and effects of persistent environmental contaminants were investigated in great blue heron (Ardea herodias) nestlings sampled in 2001, 2002, 2006, and 2007 in freshwater and estuarine heronries along the St. Lawrence River, Québec (Canada). Biomarkers (retinoids, thyroid hormones, and clinical parameters) and contaminants (organochlorine contaminants, polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), and mercury (Hg)) were analyzed in blood, and Hg was analyzed in feathers (generally 9 nestlings per colony and 4 colonies per year). Feather Hg and most contaminants detected in blood were found in higher concentrations in birds from freshwater than estuarine colonies more distant from the pollution sources. Among freshwater colonies, Ile aux Hérons showed the highest levels of contaminants, with mean Hg concentrations of 8.4 and 0.55 mg/kg in feathers and plasma, respectively, and plasma ΣBFRs of 19.6 ng/g ww. The highest mean ΣPCBs, 56.5 ng/g ww, was measured at Grande Ile in 2001. The levels of contaminants in heron nestlings were generally below critical thresholds for adverse effects observed on reproduction or survival. Retinol, dehydroretinol (DROH), and thyroid hormone concentrations differed significantly among colonies. Retinol concentrations were negatively related to ΣPCBs, whereas DROH concentrations were negatively related to Hg and total and free triiodothyronine (T 3 ) concentrations were negatively related to ΣBFRs. These results indicate that contaminants from the St. Lawrence River could impair the development and fitness of great blue heron nestlings and emphasize the need for more research on the great blue heron population to assess their health and nutritional status.

Effects of regular exercise on obesity and type 2 diabete mellitus in Korean children: improvements glycemic control and serum adipokines level

PubMed Central

Lee, Sung Soo; Kang, Sunghwun

2015-01-01

[Purpose] The aim of the study was to clarify the effects of regular exercise on lipid profiles and serum adipokines in Korean children. [Subjects and Methods] Subjects were divided into controls (n=10), children who were obese (n=10), and children with type 2 diabetes mellitus (n=10). Maximal oxygen uptake (VO2max), body composition, lipid profiles, glucagon, insulin and adipokines (leptin, resistin, visfatin and retinol binding protein 4) were measured before to and after a 12-week exercise program. [Results] Body weight, body mass index, and percentage body fat were significantly higher in the obese and diabetes groups compared with the control group. Total cholesterol, triglycerides, low-density lipoprotein cholesterol and glycemic control levels were significantly decreased after the exercise program in the obese and diabetes groups, while high-density lipoprotein cholesterol levels were significantly increased. Adipokines were higher in the obese and diabetes groups compared with the control group prior to the exercise program, and were significantly lower following completion. [Conclusion] These results suggest that regular exercise has positive effects on obesity and type 2 diabetes mellitus in Korean children by improving glycemic control and reducing body weight, thereby lowering cardiovascular risk factors and adipokine levels. PMID:26180345

Effect of low vitamin A diets with high-moisture or dry corn on marbling and adipose tissue fatty acid composition of beef steers.

PubMed

Gorocica-Buenfil, M A; Fluharty, F L; Bohn, T; Schwartz, S J; Loerch, S C

2007-12-01

Angus-cross steers (n = 165; 295 +/- 16 kg of BW) were used evaluate the effect of low vitamin A diets with high-moisture corn (HMC) or dry corn (DC) on marbling and fatty acid composition. Steers were allotted to 24 pens (7 steers/pen), such that each pen had the same average initial BW. Treatments were randomly allotted to the pens. The experiment had a completely randomized design, with a 2 x 2 factorial arrangement of treatments: low vitamin A (Lo, no supplemental vitamin A) and HMC (LoHMC); LoDC; high vitamin A (Hi, supplemented with 2,200 IU of vitamin A/kg of DM) and HMC (HiHMC); and HiDC. Diets contained 76% corn, 10% corn silage, 11% protein supplement, and 3% soybean oil (DM basis). Samples of feed ingredients were collected for carotenoid analysis. Blood samples were collected for serum retinol determination. Steers were slaughtered after 145 d on feed. Carcass characteristics and LM composition were determined. Samples from the s.c. fat depot were analyzed for fatty acid composition. High-moisture corn had a greater vitamin A content, based on its carotenoid content, than DC (614 vs. 366 IU/kg of DM, P < 0.01). No vitamin A x corn type interactions were detected for feedlot performance, carcass characteristics, or serum, s.c. fat, or liver retinol concentration. Average daily gain, DMI, and G:F were not affected by vitamin A (P > 0.05). Marbling score and USDA quality grade were greater (P < 0.05) in Lo vs. Hi steers. Hot carcass weight, backfat, and yield grade were not affected by the treatments (P > 0.05). Vitamin A and corn type did not affect LM composition (DM, ash, CP, or ether-extractable fat, P > 0.05). Vitamin A supplementation increased (P < 0.06) serum retinol on d 112 and 145 and increased (P < 0.01) liver retinol at slaughter (Lo = 38.7 vs. Hi = 102.9 mug/g). The s.c. fat retinol concentrations were less (P < 0.01) for Lo (0.8 mug/g) than for Hi (1.4 mug/g) at slaughter. Cell diameter of adipocytes in the i.m. depot was not affected by

Perioperative management of two patients with left ventricular assist devices presenting for noncardiac surgery in the prone position.

PubMed

Chacon, M Megan; Hattrup, Emily A; Shillcutt, Sasha K

2014-03-15

Ventricular assist devices (VADs) provide mechanical circulatory support for patients with advanced heart failure. Patients with VADs are presenting for noncardiac surgery with increasing frequency. Understanding anesthetic management of patients with VADs is timely and necessary for perioperative physicians. We present 2 patients supported by left VADs who required intraoperative prone positioning, and how transesophageal echocardiography and VAD variables can be used to guide management.

Corona-directed nucleic acid delivery into hepatic stellate cells for liver fibrosis therapy.

PubMed

Zhang, Zhengping; Wang, Chunming; Zha, Yinhe; Hu, Wei; Gao, Zhongfei; Zang, Yuhui; Chen, Jiangning; Zhang, Junfeng; Dong, Lei

2015-03-24

Strategies to modify nanoparticles with biological ligands for targeted drug delivery in vivo have been widely studied but met with limited clinical success. A possible reason is that, in the blood circulation, serum proteins could rapidly form a layer of protein "corona" on the vehicle surface, which might block the modified ligands and hamper their targeting functions. We speculate that strategies for drug delivery can be designed based upon elegant control of the corona formation on the vehicle surfaces. In this study, we demonstrate a retinol-conjugated polyetherimine (RcP) nanoparticle system that selectively recruited the retinol binding protein 4 (RBP) in its corona components. RBP was found to bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to hepatic stellate cells (HSC), which play essential roles in the progression of hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles effectively suppressed the expression of type I collagen (collagen I), and consequently ameliorated hepatic fibrosis. Such findings suggest that this delivery system, designed to exploit the power of corona proteins, can serve as a promising tool for targeted delivery of therapeutic agents for the treatment of hepatic fibrosis.

Establishing a reliable multiple reaction monitoring-based method for the quantification of obesity-associated comorbidities in serum and adipose tissue requires intensive clinical validation.

PubMed

Oberbach, Andreas; Schlichting, Nadine; Neuhaus, Jochen; Kullnick, Yvonne; Lehmann, Stefanie; Heinrich, Marco; Dietrich, Arne; Mohr, Friedrich Wilhelm; von Bergen, Martin; Baumann, Sven

2014-12-05

Multiple reaction monitoring (MRM)-based mass spectrometric quantification of peptides and their corresponding proteins has been successfully applied for biomarker validation in serum. The option of multiplexing offers the chance to analyze various proteins in parallel, which is especially important in obesity research. Here, biomarkers that reflect multiple comorbidities and allow monitoring of therapy outcomes are required. Besides the suitability of established MRM assays for serum protein quantification, it is also feasible for analysis of tissues secreting the markers of interest. Surprisingly, studies comparing MRM data sets with established methods are rare, and therefore the biological and clinical value of most analytes remains questionable. A MRM method using nano-UPLC-MS/MS for the quantification of obesity related surrogate markers for several comorbidities in serum, plasma, visceral and subcutaneous adipose tissue was established. Proteotypic peptides for complement C3, adiponectin, angiotensinogen, and plasma retinol binding protein (RBP4) were quantified using isotopic dilution analysis and compared to the standard ELISA method. MRM method variabilities were mainly below 10%. The comparison with other MS-based approaches showed a good correlation. However, large differences in absolute quantification for complement C3 and adiponectin were obtained compared to ELISA, while less marked differences were observed for angiotensinogen and RBP4. The verification of MRM in obesity was performed to discriminate first lean and obese phenotype and second to monitor excessive weight loss after gastric bypass surgery in a seven-month follow-up. The presented MRM assay was able to discriminate obese phenotype from lean and monitor weight loss related changes of surrogate markers. However, inclusion of additional biomarkers was necessary to interpret the MRM data on obesity phenotype properly. In summary, the development of disease-related MRMs should include a

Analyte stability during the total testing process: studies of vitamins A, D and E by LC-MS/MS.

PubMed

Albahrani, Ali A; Rotarou, Victor; Roche, Peter J; Greaves, Ronda F

2016-10-01

There are limited evidence based studies demonstrating the stability of fat-soluble vitamins (FSV) measured in blood. This study aimed to examine the effects of light, temperature and time on vitamins A, D and E throughout the total testing process. Four experiments were conducted. Three investigated the sample matrix, of whole blood, serum and the extracted sample, against the variables of temperature and light; and the fourth experiment investigated the sample during the extraction process against the variable of light. All samples were analysed via our simultaneous FSV method using liquid chromatography-tandem mass spectrometry technology. The allowable clinical percentage change was calculated based on biological variation and desirable method imprecision for each analyte. The total change limit was ±7.3% for 25-OH-vitamin D3, ±11.8% for retinol and ±10.8% for α-tocopherol. Vitamins D and E were stable in the investigated conditions (concentration changes <4%) in the pre-analytical and analytical stages. Vitamin A showed photosensitivity in times >48 h with concentration changes of -6.8% (blood) and -6.5% (serum), both are within the allowable clinical percentage change. By contrast, the extracted retinol sample demonstrated a concentration change of -18.4% after 48 h of light exposure. However, vitamin A in the serum and extracted solution was stable for one month when stored at -20°C. Blood samples for vitamins D and E analyses can be processed in normal laboratory conditions of lighting and temperature. The required conditions for vitamin A analysis are similar when performed within 48 h. For longer-term storage, serum and vitamin A extracts should be stored at -20°C.

Binding of perlecan to transthyretin in vitro.

PubMed Central

Smeland, S; Kolset, S O; Lyon, M; Norum, K R; Blomhoff, R

1997-01-01

Transthyretin is one of two specific proteins involved in the transport of thyroid hormones in plasma; it possesses two binding sites for serum retinol-binding protein. In the present study we demonstrate that transthyretin also interacts in vitro with [35S]sulphate-labelled material from the medium of HepG2 cells. By using the same strategy as for purifying serum retinol-binding protein, [35S]sulphate-labelled medium was specifically eluted from a transthyretin-affinity column. Ion-exchange chromatography showed that the material was highly polyanionic, and its size and alkali susceptibility suggested that it was a proteoglycan. Structural analyses with chondroitinase ABC lyase and nitrous acid revealed that approx. 20% was chondroitin sulphate and 80% heparan sulphate. Immunoprecipitation showed that the [35S]sulphate-labelled material contained perlecan. Further analysis by binding studies revealed specific and saturable binding of 125I-transthyretin to perlecan-enriched Matrigel. Because inhibition of sulphation by treating HepG2 cells with sodium chlorate increased the affinity of the perlecan for transthyretin, and [3H]heparin was not retained by the transthyretin affinity column, the binding is probably mediated by the core protein and is not a protein-glycosaminoglycan interaction. Because perlecan is released from transthyretin in water, the binding might be due to hydrophobic interactions. PMID:9307034

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

PubMed Central

James, D R; Owen, G; Campbell, I A; Goodchild, M C

1992-01-01

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. PMID:1612491

Influence of carotene-rich vegetable meals on the prevalence of anaemia and iron deficiency in Filipino schoolchildren.

PubMed

Maramag, C C; Ribaya-Mercado, J D; Rayco-Solon, P; Solon, J A A; Tengco, L W; Blumberg, J B; Solon, F S

2010-05-01

To determine the effects of eating carotene-rich green and yellow vegetables on the prevalence of anaemia, iron deficiency and iron-deficiency anaemia in schoolchildren. Schoolchildren (n=104), aged 9-12 years, received standardized meals containing 4.2 mg of provitamin A carotenoids/day (mainly beta-carotene) from yellow and green leafy vegetables and at least 7 g dietary fat/day. The meals were provided three times/day, 5 days/week, for 9 weeks at school. Before and after the dietary intervention, total-body vitamin A pool size was assessed by using the deuterated-retinol-dilution method; serum retinol and beta-carotene concentrations were measured by high-performance liquid chromatography; and whole blood haemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations were measured by using a photometer and a hematofluorometer, respectively. After 9 weeks, the mean total-body vitamin A pool size increased twofold (95% confidence interval (CI): -0.11, -0.07 micromol retinol; P<0.001), and serum beta-carotene concentration increased fivefold (95% CI: -0.97, -0.79 micromol/l; P<0.001). Blood Hb (95% CI: -1.02, -0.52 g per 100 ml; P<0.001) and ZnPP increased (95% CI: -11.82, -4.57 microol/mol haem; P<0.001). The prevalence of anaemia (Hb<11.5 g per 100 ml) decreased from 12.5 to 1.9% (P<0.001). There were no significant changes in the prevalence of iron deficiency or iron-deficiency anaemia. Ingestion of carotene-rich yellow and green leafy vegetables improves the total-body vitamin A pool size and Hb concentration, and decreases anaemia rates in Filipino schoolchildren, with no effect on iron deficiency or iron-deficiency anaemia rates.

Ventricular assist devices as bridge to heart transplantation: impact on post-transplant infections.

PubMed

Héquet, Delphine; Kralidis, Georg; Carrel, Thierry; Cusini, Alexia; Garzoni, Christian; Hullin, Roger; Meylan, Pascal R; Mohacsi, Paul; Mueller, Nicolas J; Ruschitzka, Frank; Tozzi, Piergiorgio; van Delden, Christian; Weisser, Maja; Wilhelm, Markus J; Pascual, Manuel; Manuel, Oriol

2016-07-08

Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients. Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant. Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post-transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p < 0.001), but presence of a VAD was not (HR 0.94, [95 % CI 0.38-2.32], p = 0.89, for continuous-flow devices, and HR 0.45 [0.15 - 1.34], p = 0.15, for other devices). Risk for post-transplant viral and all fungal infections was not increased in patients with VAD. One-year survival was 82.9 % (29/35) in the VAD group and 82.1 % (69/84) in the non-VAD group. All 6 patients in the VAD group that died after transplant had a history of pre-transplant VAD infection. In this nationwide cohort of heart transplant recipients, the presence of VAD at the time of transplant had no influence on the development of post-transplant infections.

Computational analysis of pediatric ventricular assist device implantation to decrease cerebral particulate embolization.

PubMed

Nguyen, ThuyTien; Argueta-Morales, I Ricardo; Guimond, Stephen; Clark, William; Ceballos, Andres; Osorio, Ruben; Divo, Eduardo A; De Campli, William M; Kassab, Alain J

2016-01-01

Stroke is the most devastating complication after ventricular assist device (VAD) implantation with a 19% incidence and 65% mortality in the pediatric population. Current pediatric VAD technology and anticoagulation strategies alone are suboptimal. VAD implantation assisted by computational methods (CFD) may contribute reducing the risk of cerebral embolization. Representative three-dimensional aortic arch models of an infant and a child were generated. An 8 mm VAD outflow-graft (VAD-OG) anastomosed to the aorta was rendered and CFD was applied to study blood flow patterns. Particle tracks, originating in the VAD, were computed with a Lagrangian phase model and the percentage of particles entering the cerebral vessels was calculated. Eight implantation configurations (infant = 5 and child = 3) and 5 particle sizes (0.5, 1, 2, 3, and 4 mm) were considered. For the infant model, percentage of particles entering the cerebral vessels ranged from 15% for a VAD-OG anastomosed at 90° to the aorta, to 31% for 30° VAD-OG anastomosis (overall percentages: X(2) = 10,852, p < 0.0001). For the child model, cerebral embolization ranged from 9% for the 30° VAD-OG anastomosis to 15% for the 60° anastomosis (overall percentages: χ(2) = 10,323, p < 0.0001). Using detailed CFD calculations, we demonstrate that the risk of stroke depends significantly on the VAD implantation geometry. In turn, the risk probably depends on patient-specific anatomy. CFD can be used to optimize VAD implantation geometry to minimize stroke risk.

Single-center experience of the bridge-to-bridge strategy using the Nipro paracorporeal ventricular assist device.

PubMed

Yoshitake, Shuichi; Kinoshita, Osamu; Nawata, Kan; Hoshino, Yasuhiro; Itoda, Yoshifumi; Kimura, Mitsutoshi; Yamauchi, Haruo; Ono, Minoru

2018-06-25

Currently, we use the Nipro paracorporeal VAD (p-VAD) for initial short-term ventricular support, as a bridge to decision (BTD) or a bridge to candidacy (BTC) treatment, in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 and 2 patients. However, it is possible that compared to patients with primary implantable-VADs (P-iVAD), the bridge-to-bridge (BTB) patients are more likely to develop complications. This retrospective study used data from 24 consecutive BTB patients who were initially implanted with Nipro p-VAD as BTD or BTC treatments between April 2011 and March 2016, and subsequently underwent conversion to an i-VAD. The data from 72 patients who underwent a primary i-VAD (P-iVAD) procedure were used for comparison. Between the two groups, there was no significant difference in the incidence of infectious events (p = 0.72) or stroke (p = 0.44). Orthotropic heart transplantation was performed in 6 of the 24 patients in the BTB group and in 21 of the 72 patients in the P-iVAD group. The 1- and 2-year survival rates were 95.8% and 95.8% in the BTB group and 91% and 85.8% in the P-iVAD group; these values were not significantly different between groups (p = 0.91). Based on these results we conclude that BTB using Nipro p-VAD is a reasonable strategy for treating patients with severe decompensated end-stage heart failure.

Relation of serum molindone levels to serum prolactin levels and antipsychotic response.

PubMed

Pandurangi, A K; Narasimhachari, N; Blackard, W G; Landa, B S

1989-10-01

The antipsychotic drug molindone is considered to be atypical in its mode of action and to have mild side effects. Currently no data are available on the range of serum levels of this drug during treatment. By means of a high performance liquid chromatographic technique, serum molindone levels were measured in 14 psychotic patients receiving a wide range of doses of this drug. Molindone levels as high as 350 ng/mL were obtained and were not associated with any toxic effects. Significant relations were noted between the serum level of the drug and both serum prolactin level and treatment response. The authors suggest that molindone may have a range of serum levels consistent with therapeutic benefit. Serum molindone and prolactin levels might help assess resistance to molindone treatment.

β-Carotene in Golden Rice is as good as β-carotene in oil at providing vitamin A to children.

PubMed

Tang, Guangwen; Hu, Yuming; Yin, Shi-an; Wang, Yin; Dallal, Gerard E; Grusak, Michael A; Russell, Robert M

2012-09-01

Golden Rice (GR) has been genetically engineered to be rich in β-carotene for use as a source of vitamin A. The objective was to compare the vitamin A value of β-carotene in GR and in spinach with that of pure β-carotene in oil when consumed by children. Children (n = 68; age 6-8 y) were randomly assigned to consume GR or spinach (both grown in a nutrient solution containing 23 atom% ²H₂O) or [²H₈]β-carotene in an oil capsule. The GR and spinach β-carotene were enriched with deuterium (²H) with the highest abundance molecular mass (M) at M(β-C)+²H₁₀. [¹³C₁₀]Retinyl acetate in an oil capsule was administered as a reference dose. Serum samples collected from subjects were analyzed by using gas chromatography electron-capture negative chemical ionization mass spectrometry for the enrichments of labeled retinol: M(retinol)+4 (from [²H₈]β-carotene in oil), M(retinol)+5 (from GR or spinach [²H₁₀]β-carotene), and M(retinol)+10 (from [¹³C₁₀]retinyl acetate). Using the response to the dose of [¹³C₁₀]retinyl acetate (0.5 mg) as a reference, our results (with the use of AUC of molar enrichment at days 1, 3, 7, 14, and 21 after the labeled doses) showed that the conversions of pure β-carotene (0.5 mg), GR β-carotene (0.6 mg), and spinach β-carotene (1.4 mg) to retinol were 2.0, 2.3, and 7.5 to 1 by weight, respectively. The β-carotene in GR is as effective as pure β-carotene in oil and better than that in spinach at providing vitamin A to children. A bowl of ~100 to 150 g cooked GR (50 g dry weight) can provide ~60% of the Chinese Recommended Nutrient Intake of vitamin A for 6-8-y-old children.

The Hepatoprotective Effect of Vitamin A against Gasoline Vapor Toxicity in Rats

PubMed Central

Uboh, Friday E.; Ekaidem, Itemobong S.; Ebong, Patrick E.; Umoh, Ime B.

2009-01-01

Background Changes in the activities of plasma alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) are used to assess the functional state of the liver. Significant increase in the activities of these enzymes commonly indicates the hepatotoxicity of chemical agent(s) in the body. Exposure of male and female rats to 17.8 cm3h-1m-3 of Premium Motor Spirit (PMS) blend unleaded gasoline (UG) vapors for 6 hr/day, 5 days/week for 20 weeks have been observed to cause hepatotoxicity. In this study, the potential hepatoprotective effect of vitamin A (retinol) against gasoline vapours-induced toxicity was investigated in male and female rats. Methods Retinol (400 IU/kg/day) was orally administered to the test rats concomitant with the gasoline vapor exposure in the last two weeks of the experiment. Results The results obtained from this study showed that exposure to gasoline vapors caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in both male and female rats. The treatment of the male and female test rats with vitamin A produced a significant decrease (P < 0.05) in the activities of these parameters, compared with the test rats without treatment; but insignificant increase(P ≥ 0.05), compared with the control. Conclusions The result of this study demonstrates the beneficial effects of retinol, at prophylactic dosage, against gasoline vapours hepatotoxicity in male and female rats, thereby suggesting that retinol may be used to prevent hepatotoxicity in individuals frequently exposed to gasoline vapours. PMID:27933127

Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection

PubMed Central

Odaka, Akito; Toshida, Hiroshi; Ohta, Toshihiko; Tabuchi, Nobuhito; Koike, Daisuke; Suto, Chikako; Murakami, Akira

2012-01-01

Purpose We examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected. Materials and methods After alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops. Results The fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells. Conclusion It is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes. PMID:23055683

Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

PubMed

Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

2013-09-01

In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

Treatment of mild to moderate acne with a fixed combination of hydroxypinacolone retinoate, retinol glycospheres and papain glycospheres.

PubMed

Veraldi, S; Barbareschi, M; Guanziroli, E; Bettoli, V; Minghetti, S; Capitanio, B; Sinagra, J L; Sedona, P; Schianchi, R

2015-04-01

A fixed combination of 0.1% hydroxypinacolone retinoate (synthetic esther of 9-cis-retinoic acid), 1% retinol in glycospheres and 2% papain in glycospheres in aqueous gel has been recently introduced into the Italian market in order to reduce the incidence and severity of irritant contact dermatitis caused by topical retinoids, without compromising their efficacy. Primary objectives of this sponsor-free, pilot, open, multicenter study were to evaluate the efficacy and tolerability of this gel in patients with comedonal-papular, mild to moderate acne of the face. Ninety-eight Caucasian patients (28 males and 70 females), with an age ranging from 15 to 40 years, were treated with the gel once daily for 12 weeks. Acne severity and treatment efficacy were evaluated by means of the Global Acne Grading System (GAGS) and lesions count. Ninety-four patients were considered evaluable. A 41% mean reduction in the GAGS score was observed; a 40.8% mean reduction of total lesions was recorded; 15.3% of patients experienced mild to moderate local side effects (dryness, peeling, erythema, burning). No patients stopped the treatment because of these side effects. This study, based on a high number of evaluable patients, demonstrates that this fixed combination is an effective and safe option for the treatment of comedonal-papular, mild to moderate acne of the face. A controlled clinical study is necessary to confirm these data.

Magnetic suspension of the rotor of a ventricular assist device of mixed flow type.

PubMed

Horikawa, Oswaldo; de Andrade, Aron José Pazin; da Silva, Isaías; Bock, Eduardo Guy Perpetuo

2008-04-01

This work presents results of preliminary studies concerning application of magnetic bearing in a ventricular assist device (VAD) being developed by Dante Pazzanese Institute of Cardiology-IDPC (São Paulo, Brazil). The VAD-IDPC has a novel architecture that distinguishes from other known VADs. In this, the rotor has a conical geometry with spiral impellers, showing characteristics that are intermediate between a centrifugal VAD and an axial VAD. The effectiveness of this new type of blood pumping principle was showed by tests and by using it in heart surgery for external blood circulation. However, the developed VAD uses a combination of ball bearings and mechanical seals, limiting the life for some 10 h, making impossible its long-term use or its use as an implantable VAD. As a part of development of an implantable VAD, this work aims at the replacement of ball bearings by a magnetic bearing. The most important magnetic bearing principles are studied and the magnetic bearing developed by Escola Politécnica of São Paulo University (EPUSP-MB) is elected because of its very simple architecture. Besides presenting the principle of the EPUSP-MB, this work presents one possible alternative for applying the EPUSP-MB in the IDPC-VAD.

Serum antioxidant levels and nutritional status in early and advanced stage lung cancer patients.

PubMed

Klarod, Kultida; Hongsprabhas, Pranithi; Khampitak, Tueanjit; Wirasorn, Kosin; Kiertiburanakul, Sasisopin; Tangrassameeprasert, Roongpet; Daduang, Jureerut; Yongvanit, Puangrat; Boonsiri, Patcharee

2011-01-01

Malnutrition frequently occurs in lung cancer patients. We aimed to determine nutritional status and antioxidant and mineral levels in Thai patients with lung cancer. A prospective study with matched case-control was conducted. Nutritional status was assessed by body mass index (BMI) and subjective global assessment (SGA). Eastern Cooperative Oncology Group (ECOG) performance status was used to assess the performance. The serum antioxidant and mineral levels were determined. Forty-nine patients with a mean age of 58.8 (range, 35-82) who were first diagnosed with lung cancer were enrolled. They were compared with 60 healthy controls, and levels of retinol, α-tocopherol, β-carotene, lycopene, β-cryptoxanthin, selenium, and zinc were lower (P < 0.05). However, peroxidase activity was higher (P = 0.002) in patients. Selenium levels were higher in early stage compared to advanced stage patients (P = 0.041). Overweight patients had higher selenium levels (0.04 mg/L) than normal BMI patients (β = 0.04, P = 0.035). Patients with SGA class C had lower selenium levels (0.03 mg/L) than those with class A (β = -0.03, P = 0.035). The poorer ECOG performance patients had significantly lower β-carotene (β = -0.192, P = 0.003) and selenium (β = -0.031, P = 0.011) levels compared with those with good ECOG performance status. Significantly lower levels of antioxidants and selenium were found in lung cancer patients compared to healthy controls. Levels of some antioxidants and minerals differed among categories of BMI, SGA categories, or ECOG performance status. These findings may be helpful for further studies, such as the effect of nutritional supplementation on clinical outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

[Antineoplastic treatment impact on nutritional status in patients with breast cancer].

PubMed

Monroy Cisneros, Karina; Astiazarán García, Humberto; Esparza Romero, Julián; Guevara Torres, Alfonso Genaro; Valencia Juillerat, Mauro E; Méndez Estrada, Rosa Olivia; Tortoledo Ortiz, Orlando; Pacheco Moreno, Bertha Isabel

2014-10-01

Breast cancer is the most commonly diagnosed malignancy in women in Mexico and also has the highest mortality. Although treatment has improved significantly, it can affect the nutritional status of the recipients. The aim of this study was to assess the impact of the initial phase of antineoplastic therapy on the nutritional status in patients with breast cancer. Forty subjects with primary diagnosed of invasive breast cancer were studied in a before and after intervention (six month apart) using a quasi-experimental design. Basal and six month after intervention measurements included were anthropometry, body composition by dual X-ray absorptiometry (DEXA), diet by 24-hour recall and food frequency questionnaire, as well as serum -carotene and retinol. The therapy effect was analyzed using repeated measurements mixed linear regression. Lean tissue decreased after the studied period (p=0.032). Addicionally, there was an interaction between weight, BMI and body fat parameters with menopausal status, increasing in these variables due to therapy only premenopausal patients (p=0.005, 0.006 and 0.001, respectively). Decreased serum retinol (p=0.049) despite the improvement in -carotene status (p=0.03). In general there was an increase the consumption of vegetables food products whilst a decrease in animal foods. The breast cancer antineoplastic treatment had a negative effect on weight and body fat, especially in young women. Although there were some positive dietary changes, vegetables consumption remained insufficient, which was also reflected in serum biomarkers. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Circulating retinol binding protein 4 levels in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

PubMed

Zhou, Zhongwei; Chen, Hongmei; Ju, Huixiang; Sun, Mingzhong

2017-09-20

Retinol binding protein 4 (RBP4) is implicated in obesity, insulin resistance and type 2 diabetes mellitus that are closely associated with nonalcoholic fatty liver disease (NAFLD). However, recent investigations regarding circulating RBP4 levels in NAFLD are conflicting. This meta-analysis is to determine whether NAFLD, non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) patients have altered RBP4 levels. We performed a systematic search in PubMed, EMBASE and The Cochrane Library up until 18 March 2017, and 12 studies comprising a total of 4247 participants (2271 NAFLD patients and 1976 controls) were included in the meta-analysis. There were no significant differences of circulating RBP4 levels in the following comparisons: (1) NAFLD patients vs controls (standardized mean differences [SMD]: 0.08; 95% CI: -0.21, 0.38); (2) NASH patients vs controls (SMD: -0.49; 95% CI: -1.09, 0.12); (3) SS patients vs controls (SMD: -0.72; 95% CI: -1.64, 0.20) and (4) NASH vs SS patients (SMD: -0.04; 95% CI: -0.32, 0.24). The results remained essentially unchanged in the comparisons between NAFLD patients and controls after excluding single individual study or bariatric studies (n = 2). No significant publication bias was detected. However, there was significant heterogeneity among studies and the subgroup and meta-regression analyses did not find the potential sources. Circulating RBP4 levels may not be associated with NAFLD. Further prospective cohort studies are required to confirm these findings.

Outcomes of ventricular assist device implantation in children and young adults: the Melbourne experience.

PubMed

Shi, William Y; Marasco, Silvana F; Saxena, Pankaj; d'Udekem, Yves; Yong, Matthew S; Mitnovetski, Sergei; Brizard, Christian P; McGiffin, David C; Weintraub, Robert G; Konstantinov, Igor E

2016-12-01

We evaluated our experience with ventricular assist device (VAD) implantation in children and young adults. A total of 64 patients underwent VAD implantation in two centres. The mean age was 15 ± 7.2 years. Thirty-five (55%) patients were under 18 years of age. Devices implanted included the Thoratec Paracorporeal in 30 (47%) patients, Berlin Heart EXCOR in 11 (17%) and VentrAssist in 14 (22%). The diagnosis was cardiomyopathy in 53, congenital heart disease in 11, and graft failure in four patients. There were 10 (16%) in-hospital deaths. Mortality was higher in patients <18 years of age (26% compared with 3.4% for those ≥18 years, P = 0.02). The use of extracorporeal membrane oxygenation prior to VAD implantation was associated with higher mortality (P = 0.006). Seventeen (27%) patients experienced stroke. Nine patients (14%) required change of VAD because of thrombosis. Transplantation was performed in 44 patients after a mean of 131 ± 141 days on VAD, 11 patients died without transplantation and three patients currently await transplantation. The VAD was explanted in six patients because of recovery. Overall survival from VAD implantation was 69% and 61% at 5 and 10 years, respectively. The 5-year post-transplant survival for those bridged with VAD support was 91% and was comparable with a cohort of patients who did not receive a pre-transplant VAD. Children requiring pre-transplant VAD support have a higher mortality and morbidity compared with young adults. Survival after heart transplantation those supported with VADs was similar to patients of similar age who did not require pre-transplant support. © 2015 Royal Australasian College of Surgeons.

Cost-Effectiveness of Ventricular Assist Device Destination Therapy for Advanced Heart Failure in Duchenne Muscular Dystrophy.

PubMed

Magnetta, Defne A; Kang, JaHyun; Wearden, Peter D; Smith, Kenneth J; Feingold, Brian

2018-05-17

Destination ventricular assist device therapy (DT-VAD) is well accepted in select adults with medically refractory heart failure (HF) who are not transplant candidates; however, its use in younger patients with progressive diseases is unclear. We sought to evaluate the cost-effectiveness of DT-VAD in Duchenne muscular dystrophy (DMD) patients with advanced HF. We created a Markov-state transition model (5-year horizon) to compare survival, costs, and quality of life (QOL) between medical management and DT-VAD in DMD with advanced HF. Model input parameters were derived from the literature. We used sensitivity analyses to explore uncertainty around model assumptions. DT-VAD had higher costs ($435,602 vs. $125,696), survival (3.13 vs. 0.60 years), and quality-adjusted survival (1.99 vs. 0.26 years) than medical management. The incremental cost-effectiveness ratio (ICER) for DT-VAD was $179,086 per quality-adjusted life year (QALY). In sensitivity analyses that were widely varied to account for uncertainty in model assumptions, the DT-VAD strategy generally remained more costly and effective than medical management. Only when VAD implantation costs were <$113,142 did the DT-VAD strategy fall below the $100,000/QALY willingness-to-pay threshold commonly considered to be "cost-effective." In this exploratory analysis, DT-VAD for patients with DMD and advanced HF exceeded societal expectations for cost-effectiveness but had an ICER similar to the accepted practice of DT-VAD in adult HF patients. While more experience and research in this population is needed, our analysis suggests that DT-VAD for advanced HF in DMD should not be dismissed solely based on cost.

Application of isotope dilution technique in vitamin A nutrition.

PubMed

Wasantwisut, Emorn

2002-09-01

The isotope dilution technique involving deuterated retinol has been developed to quantitatively estimate total body reserves of vitamin A in humans. The technique provided good estimates in comparison to hepatic vitamin A concentrations in Bangladeshi surgical patients. Kinetic studies in the United States, Bangladesh, and Guatemala indicated the mean equilibration time of 17 to 20 days irrespective of the size of hepatic reserves. Due to the controversy surrounding the efficacy of a carotene-rich diet on improvement of vitamin A status, the isotope dilution technique was proposed to pursue this research question further (IAEA's coordinated research program). In the Philippines, schoolchildren with low serum retinol concentrations showed significant improvement in total body vitamin A stores following intake of carotene-rich foods (orange fruits and vegetables), using a three-day deuterated-retinol-dilution procedure. When Chinese kindergarten children were fed green and yellow vegetables during the winter, their total body vitamin A stores were sustained as compared to a steady decline of vitamin A stores in the control children. Likewise, daily consumption of purified beta-carotene or diet rich in provitamin A carotenoids were shown to prevent a loss in total body vitamin A stores among Thai lactating women during the rice-planting season. These studies demonstrate potentials of the isotope dilution technique to evaluate the impact of provitamin A carotenoid intervention programs.

Effects and mechanisms of vitamin A and vitamin E on the levels of serum leptin and other related cytokines in rats with rheumatoid arthritis

PubMed Central

XIONG, RI-BO; LI, QING; WAN, WEI-REN; GUO, JIN-QIANG; LUO, BING-DE; GAN, LU

2014-01-01

Leptin has been identified as an important cytokine in the inflammatory networks of rheumatoid arthritis (RA). Higher serum leptin levels may accelerate the development of RA. This study aimed to examine the effects of vitamin A (VitA) and vitamin E (VitE) on the levels of leptin and other related experimental and clinical indices, and to explore the mechanisms of these effects through the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway in rats with collagen-induced arthritis (CIA). CIA model rats were established by the intradermal injection of bovine type II collagen emulsified in incomplete Freund’s adjuvant, followed by a booster intradermal injection. Four weeks later, the CIA model rats were treated with 42.86 μg retinol equivalents/kg body weight (b.w.) VitA or 200 mg/kg b.w. VitE for four weeks. The levels of leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, IL-4, C-reactive protein (CRP) and rheumatic factor were measured by ELISA using commercial kits, and the erythrocyte sedimentation rate (ESR) was determined. In addition, the expression levels of phosphorylated (p)-STAT1, p-STAT3 and leptin in the synovium were evaluated by western blot analysis. The results indicated that VitA and VitE significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR and significantly increased the levels of IL-10 compared with those of the model group. Furthermore, significantly reduced p-STAT3 protein expression levels were observed in the VitA and VitE groups. In conclusion, VitA and VitE reduced the levels of serum leptin protein and other cytokines. Furthermore, VitA and VitE also reduced the p-STAT3 protein levels. The present study may provide a novel approach for the treatment of RA. PMID:25009608

Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: efficacy of a nutrition intervention.

PubMed

Bertolaso, Chiara; Groleau, Veronique; Schall, Joan I; Maqbool, Asim; Mascarenhas, Maria; Latham, Norma E; Dougherty, Kelly A; Stallings, Virginia A

2014-04-01

The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI). Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (α-tocopherol, α-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire. A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 μg/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or α-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months. Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.

Evidence for Leydig cell dysfunction in rats with seminiferous tubule damage.

PubMed

Rich, K A; Kerr, J B; de Kretser, D M

1979-02-01

To study the effects of seminiferous tubule damage on Leydig cell function and morphology, rats were treated by fetal irradiation (to induce Sertoli cell-only syndrome, SCO), 3 months administration of hydroxyurea (HU), or chronic feeding of a vitamin A-deficient diet (VAD). Leydig cell function was assessed by the measurement of serum LH and testosterone and the response of serum testosterone to hCG stimulation, while morphology was studied by electron microscopy after perfusion fixation. Serum LH was significantly elevated in each experimental group, while basal serum testosterone was significantly lower only in SCO rats. In all treatment groups, the serum testosterone response to hCG was significantly decreased when measureed as the area under the response curve. Despite a decreased response to hCG, the Leydig cells were larger than normal and showed striking increases in quantities of smooth endoplasmic reticulum, mitochondria and Golgi complex. Leydig cell dysfunction has been demonstrated in animals with varying degrees of seminiferous tubule damage, but paradoxically the cytological features of the Leydig cells were indicative of hypertrophy.

Serum HSP70

PubMed Central

Dutta, Sudhir K.; Girotra, Mohit; Singla, Montish; Dutta, Anand; Stephen, F. Otis; Nair, Padmanabhan P.; Merchant, Nipun B.

2014-01-01

Objectives Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer. Methods Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls. Results The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively. Conclusions Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer. PMID:22158074

An Estimate of Attributable Cases of Alzheimer Disease and Vascular Dementia due to Modifiable Risk Factors: The Impact of Primary Prevention in Europe and in Italy.

PubMed

Mayer, Flavia; Di Pucchio, Alessandra; Lacorte, Eleonora; Bacigalupo, Ilaria; Marzolini, Fabrizio; Ferrante, Gianluigi; Minardi, Valentina; Masocco, Maria; Canevelli, Marco; Di Fiandra, Teresa; Vanacore, Nicola

2018-01-01

Up to 53.7% of all cases of dementia are assumed to be due to Alzheimer disease (AD), while 15.8% are considered to be due to vascular dementia (VaD). In Europe, about 3 million cases of AD could be due to 7 potentially modifiable risk factors: diabetes, midlife hypertension and/or obesity, physical inactivity, depression, smoking, and low educational level. To estimate the number of VaD cases in Europe and the number of AD and VaD cases in Italy attributable to these 7 potentially modifiable risk factors. Assuming the nonindependence of the 7 risk factors, the adjusted combined population attributable risk (PAR) was estimated for AD and VaD. In Europe, adjusted combined PAR was 31.4% for AD and 37.8% for VaD. The total number of attributable cases was 3,033,000 for AD and 873,000 for VaD. In Italy, assuming a 20% reduction of the prevalence of each risk factor, adjusted combined PAR decreased from 45.2 to 38.9% for AD and from 53.1 to 46.6% for VaD, implying a 6.4 and 6.5% reduction in the prevalence of AD and VaD, respectively. A relevant reduction of AD and VaD cases in Europe and Italy could be obtained through primary prevention.

How the factoid of wind turbines causing 'vibroacoustic disease' came to be 'irrefutably demonstrated'.

PubMed

Chapman, Simon; St George, Alexis

2013-06-01

In recent years, claims have proliferated in cyberspace that wind turbines cause a large variety of symptoms and diseases. One of these, "vibroacoustic disease" (VAD) is frequently mentioned. The aim of this study is to examine the quality of the evidence on how VAD came to be associated with wind turbine exposure by wind farm opponents. Searches of the web (Google advanced) and major research databases for papers on VAD and wind turbines. Self-citation analysis of research papers on VAD. Google returned 24,700 hits for VAD and wind turbines. Thirty-five research papers on VAD were found, none reporting any association between VAD and wind turbines. Of the 35 papers, 34 had a first author from a single Portuguese research group. Seventy-four per cent of citations to these papers were self-citations by the group. Median self-citation rates in science are around 7%. Two unpublished case reports presented at conferences were found asserting that VAD was "irrefutably demonstrated" to be caused by wind turbines. The quality of these reports was abject. VAD has received virtually no scientific recognition beyond the group who coined and promoted the concept. There is no evidence of even rudimentary quality that vibroacoustic disease is associated with or caused by wind turbines. The claim that wind turbines cause VAD is a factoid that has gone 'viral' in cyberspace and may be contributing to nocebo effects among those living near turbines. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

PubMed

Jeurnink, Suzanne M; Ros, Martine M; Leenders, Max; van Duijnhoven, Franzel J B; Siersema, Peter D; Jansen, Eugene H J M; van Gils, Carla H; Bakker, Marije F; Overvad, Kim; Roswall, Nina; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Racine, Antoine; Cadeau, Claire; Grote, Verena; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Valanou, Elisavet; Palli, Domenico; Krogh, Vittorio; Vineis, Paolo; Tumino, Rosario; Mattiello, Amalia; Weiderpass, Elisabete; Skeie, Guri; Castaño, José María Huerta; Duell, Eric J; Barricarte, Aurelio; Molina-Montes, Esther; Argüelles, Marcial; Dorronsoro, Mire; Johansen, Dorthe; Lindkvist, Björn; Sund, Malin; Crowe, Francesca L; Khaw, Kay-Tee; Jenab, Mazda; Fedirko, Veronika; Riboli, E; Bueno-de-Mesquita, H B

2015-03-15

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted. © 2014 UICC.

Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice.

PubMed

Sasaki, Rie; Nishimura, Natsumi; Hoshino, Hiromi; Isa, Yasuka; Kadowaki, Maho; Ichi, Takahito; Tanaka, Akihito; Nishiumi, Shin; Fukuda, Itsuko; Ashida, Hitoshi; Horio, Fumihiko; Tsuda, Takanori

2007-12-03

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines.

Influence of dietary spices on the in vivo absorption of ingested β-carotene in experimental rats.

PubMed

Veda, Supriya; Srinivasan, Krishnapura

2011-05-01

Animal studies were conducted to evaluate the influence of dietary spice compounds, piperine, capsaicin and ginger, on the absorption of orally administered β-carotene and its conversion to vitamin A. In rats maintained on these spice-containing diets for 8 weeks, concentrations of β-carotene and retinol were determined in the serum, liver and intestine 4 h after a single oral administration of β-carotene. β-Carotene concentration was significantly increased in the serum, liver and intestine of piperine- and ginger-fed rats, suggesting improved absorption of β-carotene. However, retinol concentration was not significantly changed in these animals, suggesting that the bioconversion of β-carotene to vitamin A was not similarly influenced. Between the two enzymes involved in the bioconversion of β-carotene to vitamin A, the activity of intestinal and hepatic β-carotene 15,15'-dioxygenase was either unaffected or lowered by these spice treatments. The activity of intestinal and hepatic retinal reductase was unaffected by the dietary spices. Activities of these two enzymes involved in the bioconversion of β-carotene to retinal were inhibited by the test spices in vitro, thus corroborating with the in vivo observation. Although the bioconversion of β-carotene was not promoted, increased absorption and tissue levels of β-carotene by the dietary spices may contribute to a higher antioxidant protection.

THE NATURE OF SERUM ANTITRYPSIN

PubMed Central

Jobling, James W.; Petersen, William

1914-01-01

1. The ferment-inhibiting action of the serum is due to the presence of compounds of the unsaturated fatty acids. 2. These fatty acid compounds may be removed from the serum by means of chloroform or ether. 3. Soaps prepared by saponifying the chloroform or ether extracts inhibit the action of trypsin. 4. The anti-enzyme action of the serum can be removed by filtering acid serum through kaolin, and can in part be restored by extracting the kaolin. 5. The decrease in strength of anti-enzyme in old sera is probably due to the action of the serum lipase. 6. Iodin, potassium iodide, or hydrogen peroxide remove the inhibiting action of the serum. 7. Soaps of the unsaturated fatty acids lose their ferment-inhibiting action when heated with serum at 70° C. PMID:19867786

Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial.

PubMed

Colgate, E Ross; Haque, Rashidul; Dickson, Dorothy M; Carmolli, Marya P; Mychaleckyj, Josyf C; Nayak, Uma; Qadri, Firdausi; Alam, Masud; Walsh, Mary Claire; Diehl, Sean A; Zaman, K; Petri, William A; Kirkpatrick, Beth D

2016-09-01

Rotavirus is the world's leading cause of childhood diarrheal death. Despite successes, oral rotavirus vaccines are less effective in developing countries. In an urban slum of Dhaka, we performed active diarrhea surveillance to evaluate monovalent G1P[8] rotavirus vaccine (RV1) efficacy and understand variables contributing to risk of rotavirus diarrhea (RVD). We performed a randomized controlled trial of monovalent oral rotavirus vaccine (RV1). Seven hundred healthy infants received RV1 or no RV1 (1:1) using delayed dosing (10 and 17 weeks) and were followed for 1 year. Intensive diarrhea surveillance was performed. The primary outcome was ≥1 episode of RVD. Nutritional, socioeconomic, and immunologic factors were assessed by logistic regression best-subsets analysis for association with risk of RVD and interactions with vaccine arm. Incidence of all RVD was 38.3 cases per 100 person-years. Per-protocol RV1 efficacy was 73.5% (95% confidence interval [CI], 45.8%-87.0%) against severe RVD and 51% (95% CI, 33.8%-63.7%) against all RVD. Serum zinc level (odds ratio [OR], 0.77; P = .002) and lack of rotavirus immunoglobulin A (IgA) seroconversion (OR, 1.95; P = .018) were associated with risk of RVD, independent of vaccination status. Water treatment and exclusive breastfeeding were of borderline significance. Factors not associated with RVD included height for age at 10 weeks, vitamin D, retinol binding protein, maternal education, household income, and sex. In an urban slum with high incidence of RVD, the efficacy of RV1 against severe RVD was higher than anticipated in the setting of delayed dosing. Lower serum zinc level and lack of IgA seroconversion were associated with increased risk of RVD independent of vaccination. NCT01375647. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Vitamin A status of the minority ethnic group of Karen hill tribe children aged 1-6 years in Northern Thailand.

PubMed

Tienboon, Prasong; Wangpakapattanawong, Prasit

2007-01-01

Vitamin A deficiency (VAD) is the most common cause of childhood blindness in the developing world. It is estimated that by giving adequate vitamin A, in vitamin A deficient populations, child mortality from measles can be reduced by 50%, and mortality from diarrheal disease by 40%. Overall mortality in children 6-59 months of age can be reduced by 23%. This paper reported results from a study of vitamin A status and malnutrition of the minority ethnic group of Karen hill tribe children aged 1-6 years in the north of Thailand. All children aged 1-6 years (N = 158; 83 boys, 75 girls) from the three Karen villages (Mae Hae Tai, Mae Yot, Mae Raek) of Mae Chaem district in the north of Thailand were studied. The Karen is the largest mountain ethnic minority ("hill tribe") group in Thailand. All children were examined by a qualified medical doctor and were assessed for their vitamin A intakes using 24 hours dietary recall. Thai food composition table from Ministry of Health, Thailand were used as references. The results were compared with the Thai Recommended Dietary Allowances. Children aged 1-3 years and 4-6 years were separately analysed due to the differences in Thai Recommended Dietary Allowances between the two age groups. A whole blood of 300 microL was obtained by "fingerstick" for determination of serum vitamin A. Community or village's vitamin A status was assessed by using Simplified Dietary Assessment (SDA) method and Helen Keller International (HKI) food frequency method. Descriptive statistics were used to analyse the data. All families of the study boys and girls had income lower than the Thailand poverty line (US $ 1,000/year). On average, 63% of children from Mae Hae Tai village, 1.5% of children from Mae Yot village and none of children from Mae Raek village had serum vitamin A<0.7 micromol/L which indicated VAD. All boys and only girls from Mae Raek village consumed vitamin A more than the Thai RDA but girls from Mae Hae Tai village and Mae Yot

Valproic acid downregulates RBP4 and elicits hypervitaminosis A-teratogenesis--a kinetic analysis on retinol/retinoic acid homeostatic system.

PubMed

Chuang, Chao-Ming; Chang, Chi-Huang; Wang, Hui-Er; Chen, Kuan-Chou; Peng, Chiung-Chi; Hsieh, Chiu-Lan; Peng, Robert Y

2012-01-01

Valproic acid (VPA) is an antiepileptic and anti-migraine prophylactic drug. VPA exhibits two severe side effects, namely acute liver toxicity and teratogenicity. These side effects are usually seen at the genetic and somatic levels. The cited action mechanisms involve inhibition of histone deacetylase, hypofolatenemia, hyperhomocysteinemia, and reactive oxidative stress. The proteomic information associated with VPA teratogenicity is still unavailable. We hypothesized that proteomic analysis might help us identify functional proteins that could be relevantly affected by VPA, and this phenomenon could be very sensitive in early embryonic stage, resulting in VPA teratogenicity. Proteomic analysis on the chicken embryos at Hamburger and Hamilton (HH) stage 28 showed that there were significant downregulations of ovotransferrins, carbonic anhydrase-2, retinol binding protein-4 (RBP4), NADH cytochrome b5 reductase 2 (CYB5R2), apolipoprotein A1, and protein SET, together with upregulation of 60S ribosomal protein L22. Among these, RBP4 was the most significantly downregulated (-32%). Kinetic analysis suggested that this situation could trigger hypervitaminosis A (+39.3%), a condition that has been well known to induce teratogenesis.. This is the first report showing that VPA dowregulates RBP4. Our finding not only has led to a possible mechanism of VPA teratogenesis, but also has initiated new preventive strategies for avoiding VPA teratogeneis.

Valproic Acid Downregulates RBP4 and Elicits Hypervitaminosis A-Teratogenesis—A Kinetic Analysis on Retinol/Retinoic Acid Homeostatic System

PubMed Central

Chuang, Chao-Ming; Chang, Chi-Huang; Wang, Hui-Er; Chen, Kuan-Chou; Peng, Chiung-Chi; Hsieh, Chiu-Lan; Peng, Robert Y.

2012-01-01

Background Valproic acid (VPA) is an antiepileptic and anti-migraine prophylactic drug. VPA exhibits two severe side effects, namely acute liver toxicity and teratogenicity. These side effects are usually seen at the genetic and somatic levels. The cited action mechanisms involve inhibition of histone deacetylase, hypofolatenemia, hyperhomocysteinemia, and reactive oxidative stress. The proteomic information associated with VPA teratogenicity is still unavailable. We hypothesized that proteomic analysis might help us identify functional proteins that could be relevantly affected by VPA, and this phenomenon could be very sensitive in early embryonic stage, resulting in VPA teratogenicity. Methodology/Principal Findings Proteomic analysis on the chicken embryos at Hamburger and Hamilton (HH) stage 28 showed that there were significant downregulations of ovotransferrins, carbonic anhydrase-2, retinol binding protein-4 (RBP4), NADH cytochrome b5 reductase 2 (CYB5R2), apolipoprotein A1, and protein SET, together with upregulation of 60S ribosomal protein L22. Among these, RBP4 was the most significantly downregulated (−32%). Kinetic analysis suggested that this situation could trigger hypervitaminosis A (+39.3%), a condition that has been well known to induce teratogenesis.. Conclusions/Significance This is the first report showing that VPA dowregulates RBP4. Our finding not only has led to a possible mechanism of VPA teratogenesis, but also has initiated new preventive strategies for avoiding VPA teratogeneis. PMID:23028466

The Application of a Three-Step Proteome Analysis for Identification of New Biomarkers of Pancreatic Cancer

PubMed Central

Abulaizi, Mayinuer; Tomonaga, Takeshi; Satoh, Mamoru; Sogawa, Kazuyuki; Matsushita, Kazuyuki; Kodera, Yoshio; Obul, Jurat; Takano, Shigetsugu; Yoshitomi, Hideyuki; Miyazaki, Masaru; Nomura, Fumio

2011-01-01

We searched for novel tumor markers of pancreatic cancer by three-step serum proteome analysis. Twelve serum abundant proteins were depleted using immunoaffinity columns followed by fractionation by reverse-phase high-performance liquid chromatography. Proteins in each fraction were separated by two-dimensional gel electrophoresis. Then the gel was stained by Coomassie Brilliant Blue. Protein spots in which the expression levels were significantly different between cancer and normal control were identified by LC-MS/MS. One hundred and two spots were upregulated, and 84 spots were downregulated in serum samples obtained from patients with pancreatic cancers, and 58 proteins were identified by mass spectrometry. These candidate proteins were validated using western blot analysis and enzyme-linked immunosorbent assay (ELISA). As a result of these validation process, we could confirm that the serum levels of apolipoprotein A-IV, vitamin D-binding protein, plasma retinol-binding protein 4, and tetranectin were significantly decreased in patients with pancreatic cancer. PMID:22091389

Talking with caregivers of children living in the community with ventricular assist devices.

PubMed

Petruik, Courtney; Mack, Cheryl; Conway, Jennifer; Buchholz, Holger; van Manen, Michael

2017-11-01

A VAD is a mechanical pump used to support the functioning of a failing heart. As a pediatric therapy, a VAD is used as a temporary solution for poor heart function, a bridge to transplantation or recovery, or a destination therapy. The goal of this qualitative study was to explore the perspectives of family and professional caregivers of children who are supported by VADs in outpatient settings. Semi-structured interviews were conducted with 22 caregivers of school-aged children discharged home on VAD support. Interviews were transcribed, and data were analyzed using qualitative content analysis. Caregivers identified issues facing children on VAD support in the contexts of home, school, and other childhood places including being physically connected to a device; experiencing changes; living a medical life; negotiating restrictions; cost of care; family, kinship, and community; and, present and future living. While a child with a VAD may have much in common with other medically complex children, the technological complications and risks of living with a VAD are uniquely identified by caregivers as an issue, especially when considering the way that children with a VAD are connected to their device-implanted yet exterior, mobile yet restricted, and autonomous yet dependent. © 2017 The Authors. Pediatric Transplantation Published by Wiley Periodicals, Inc.

Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo.

PubMed

Shao, Y; He, T; Fisher, G J; Voorhees, J J; Quan, T

2017-02-01

Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin

Combined Measurement of 6 Fat-Soluble Vitamins and 26 Water-Soluble Functional Vitamin Markers and Amino Acids in 50 μL of Serum or Plasma by High-Throughput Mass Spectrometry.

PubMed

Midttun, Øivind; McCann, Adrian; Aarseth, Ove; Krokeide, Marit; Kvalheim, Gry; Meyer, Klaus; Ueland, Per M

2016-11-01

Targeted metabolic profiling characterized by complementary platforms, multiplexing and low volume consumption are increasingly used for studies using biobank material. Using liquid-liquid extraction, we developed a sample workup suitable for quantification of 6 fat- and 26 water-soluble biomarkers. 50 μL of serum/plasma was mixed with dithioerythritol, ethanol, and isooctane/chloroform. The organic layer was used for analysis of the fat-soluble vitamins all-trans retinol (A), 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, α-tocopherol (E), γ-tocopherol (E), and phylloquinone (K1) by LC-MS/MS. The remaining aqueous fraction was mixed with ethanol, water, pyridine, and methylchloroformate (in toluene) to derivatize the water-soluble biomarkers. The resulting toluene layer was used for GC-MS/MS analysis of alanine, α-ketoglutarate, asparagine, aspartic acid, cystathionine, total cysteine, glutamic acid, glutamine, glycine, histidine, total homocysteine, isoleucine, kynurenine, leucine, lysine, methionine, methylmalonic acid, ornithine, phenylalanine, proline, sarcosine, serine, threonine, tryptophan, tyrosine, and valine. Isotope-labeled internal standards were used for all analytes. Chromatographic run times for the LC-MS/MS and GC-MS/MS were 4.5 and 11 min, respectively. The limits of detection (LOD) for the low-concentration analytes (25-hydroxyvitamin D2, 25-hydroxyvitamin D3, and phylloquinone) were 25, 17, and 0.33 nM, respectively, while all other analytes demonstrated sensitivity significantly lower than endogenous concentrations. Recoveries ranged from 85.5-109.9% and within- and between-day coefficients of variance (CVs) were 0.7-9.4% and 1.1-17.5%, respectively. This low-volume, high-throughput multianalyte assay is currently in use in our laboratory for quantification of 32 serum/plasma biomarkers in epidemiological studies.

Serum laminin in malaria.

PubMed Central

Wenisch, C; Graninger, W; Viravan, C; Looareesuwan, S; Parschalk, B; Wernsdorfer, W

1994-01-01

AIM--To determine serum laminin concentrations in patients with uncomplicated Plasmodium falciparum malaria. METHODS--An enzyme linked immunosorbent assay (ELISA) was used to determine serum laminin concentrations in 54 patients with acute uncomplicated P falciparum malaria during and after treatment, and in 17 control subjects in Bangkok, Thailand. RESULTS--Raised concentrations of soluble laminin were observed in patients (mean (SD) concentration 628 (225) ng/ml), compared with normal controls (490 (116) ng/ml), during the acute phase of the disease. During treatment, serum laminin concentrations decreased and returned to normal within three days. Serum laminin concentrations were correlated with parasite counts before treatment, and with the serum concentration of soluble intercellular adhesion molecule-1 (ICAM-1), soluble E-selectin, and soluble tumour necrosis factor receptor at 55 kilodaltons. CONCLUSIONS--These findings are compatible with an increased production or release of laminin in P falciparum malaria, which could indicate a role for the subendothelial basement membrane in the pathogenesis of the disease. PMID:7525659

Serum Creatinine: Not So Simple!

PubMed

Delanaye, Pierre; Cavalier, Etienne; Pottel, Hans

2017-01-01

Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range). © 2017 S. Karger AG, Basel.

Detection of Serum microRNAs From Department of Defense Serum Repository

PubMed Central

Woeller, Collynn F.; Thatcher, Thomas H.; Van Twisk, Daniel; Pollock, Stephen J.; Croasdell, Amanda; Kim, Nina; Hopke, Philip K.; Xia, Xiaoyan; Thakar, Juilee; Mallon, COL Timothy M.; Utell, Mark J.; Phipps, Richard P.

2017-01-01

Objective The aim of this study was to investigate whether serum samples from the Department of Defense Serum Repository (DoDSR) are of sufficient quality to detect microRNAs (miRNAs), cytokines, immunoglobulin E (IgE), and polycyclic aromatic hydrocarbons (PAHs). Methods MiRNAs were isolated and quantified by polymerase chain reaction (PCR) array. Cytokines and chemokines related to inflammation were measured using multiplex immunoassays. Cotinine and IgE were detected by enzyme-linked immunoassay (ELISA) and PAHs were detected by Liquid Chromatography/Mass Spectroscopy. Results We detected miRNAs, cytokines, IgE, and PAHs with high sensitivity. Eleven of 30 samples tested positive for cotinine suggesting tobacco exposure. Significant associations between serum cotinine, cytokine, IgE, PAHs, and miRNA were discovered. Conclusion We successfully quantified over 200 potential biomarkers of occupational exposure from DoDSR samples. The stored serum samples were not affected by hemolysis and represent a powerful tool for biomarker discovery and analysis in retrospective studies. PMID:27501106

Frequency and topography of small cerebrovascular lesions in vascular and in mixed dementia: a post-mortem 7-tesla magnetic resonance imaging study with neuropathological correlates.

PubMed

De Reuck, Jacques; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Maurage, Claude-Alain; Cordonnier, Charlotte; Pasquier, Florence; Leys, Didier; Bordet, Regis

2017-01-01

Introduction: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD. Material and methods: Based on neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11 as controls. Three coronal sections of a cerebral hemisphere and a horizontal section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI examination. The mean values and topographic distribution of white matter changes (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical microinfarcts (CoMIs) were determined and compared between the different groups. Results: Compared to the controls, both VaD and MixD brains had significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of VaD, while were mainly present in the occipital lobe of MixD. White matter changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were significantly increased in the corona radiata and putamen of VaD patients. Conclusions: The present post-mortem MRI study shows clear differences in the distribution and the types of cerebrovascular lesions on high-field MRI, confirming that VaD and MixD are different diseases. .

Passive control of a biventricular assist device with compliant inflow cannulae.

PubMed

Gregory, Shaun David; Pearcy, Mark John; Timms, Daniel

2012-08-01

Rotary ventricular assist device (VAD) support of the cardiovascular system is susceptible to suction events due to the limited preload sensitivity of these devices. This may be of particular concern with rotary biventricular support (BiVAD) where the native, flow balancing Starling response is diminished in both ventricles. The reliability of sensor and sensorless-based control systems which aim to control VAD flow based on preload has limitations, and, thus, an alternative solution is desired. This study introduces a compliant inflow cannula (CIC) which could improve the preload sensitivity of a rotary VAD by passively altering VAD flow depending on preload. To evaluate the design, both the CIC and a standard rigid inflow cannula were inserted into a mock circulation loop to enable biventricular heart failure support using configurations of atrial and ventricular inflow, and arterial outflow cannulation. A range of left (LVAD) and right VAD (RVAD) rotational speeds were tested as well as step changes in systemic/pulmonary vascular resistance to alter relative preloads, with resulting flow rates recorded. Simulated suction events were observed, particularly at higher VAD speeds, during support with the rigid inflow cannula, while the CIC prevented suction events under all circumstances. The compliant section passively restricted its internal diameter as preload was reduced, which increased the VAD circuit resistance and thus reduced VAD flow. Therefore, a CIC could potentially be used as a passive control system to prevent suction events in rotary left, right, and biventricular support. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Excess Costs Associated with Possible Misdiagnosis of Alzheimer’s Disease Among Patients with Vascular Dementia in a UK CPRD Population

PubMed Central

Happich, Michael; Kirson, Noam Y.; Desai, Urvi; King, Sarah; Birnbaum, Howard G.; Reed, Catherine; Belger, Mark; Lenox-Smith, Alan; Price, David

2016-01-01

Background: Prior diagnosis of Alzheimer’s disease (AD) among patients later diagnosed with vascular dementia (VaD) has been associated with excess costs, suggesting potential benefits of earlier rule-out of AD diagnosis. Objective: To investigate whether prior diagnosis with AD among patients with VaD is associated with excess costs in the UK. Methods: Patients with a final VaD diagnosis, continuous data visibility for≥6 months prior to index date, and linkage to Hospital Episode Statistics data were retrospectively selected from de-identified Clinical Practice Research Datalink data. Patients with AD diagnosis before a final VaD diagnosis were matched to similar patients with no prior AD diagnosis using propensity score methods. Annual excess healthcare costs were calculated for 5 years post-index, stratified by time to final diagnosis. Results: Of 9,311 patients with VaD, 508 (6%) had prior AD diagnosis with a median time to VaD diagnosis exceeding 2 years from index date. Over the entire follow-up period, patients with prior AD diagnosis had accumulated healthcare costs that were approximately GBP2,000 higher than those for matched counterparts (mostly due to higher hospitalization costs). Cost differentials peaked particularly in the period including the final VaD diagnosis, with excess costs quickly declining thereafter. Conclusion: Potential misdiagnosis of AD among UK patients with VaD resulted in substantial excess costs. The decline in excess costs following a final VaD diagnosis suggests potential benefits from earlier rule-out of AD. PMID:27163798

Retinoic acid reverses the airway hyperresponsiveness but not the parenchymal defect that is associated with vitamin A deficiency.

PubMed

McGowan, Stephen E; Holmes, Amey Jo; Smith, Jennifer

2004-02-01

Airway hyperresponsiveness (AHR) is influenced by structural components of the bronchial wall, including the smooth muscle and connective tissue elements and the neuromuscular function. AHR is also influenced by parenchymally derived tethering forces on the bronchial wall, which maintain airway caliber by producing outward radial traction. Our previous work has shown that vitamin A-deficient (VAD) rats exhibit cholinergic hyperresponsiveness and a decrease in the expression and function of the muscarinic-2 receptors (M2R). We hypothesized that if decreases in radial traction from airway or parenchymal structures contributed to the VAD-related increase in AHR, then the radial traction would normalize more slowly than VAD-related alterations in neurotransmitter signaling. Rats remained vitamin A sufficient (VAS) or were rendered VAD and then maintained on the VAD diet in the presence or absence of supplementation with all-trans retinoic acid (RA). VAD was associated with an approximately twofold increase in respiratory resistance and elastance compared with VAS rats. Exposure to RA for 12 days but not 4 days restored resistance and elastance to control (VAS) levels. In VAD rats, AHR was accompanied by decreases in bronchial M2R gene expression and function, which were restored after 12 days of RA supplementation. Subepithelial bronchial elastic fibers were decreased by approximately 50% in VAD rats and were significantly restored by RA. The increase in AHR that is associated with VAD is accompanied by decreases in M2R expression and function that can be restored by RA and a reduction in airway elastic fibers that can be partially restored by RA.

Serum-converted platelet lysate can substitute for fetal bovine serum in human mesenchymal stromal cell cultures.

PubMed

Mojica-Henshaw, Mariluz P; Jacobson, Pam; Morris, Julie; Kelley, Linda; Pierce, Jan; Boyer, Michael; Reems, Jo-Anna

2013-12-01

Fetal bovine serum (FBS) is commonly used as a serum supplement for culturing human mesenchymal stromal cells (hMSCs). However, human cells grown in FBS, especially for extended periods, risk potential exposure to bovine immunogenic proteins and infectious agents. To address this issue, we investigated the ability of a novel human platelet serum supplement to substitute for FBS in hMSC cultures. Platelet lysate-serum (PL-serum) was converted from platelet lysate-plasma (PL-plasma) that was manufactured from pooled platelet-rich plasma (PRP) apheresis units. Growth factor levels and the number of residual intact platelets in PL-serum and PL-plasma were compared with enzyme-linked immunosorbent assays and flow cytometry, respectively. Proliferation responses of hMSCs cultured in PL-serum, PL-plasma, or FBS were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the immunophenotype of harvested hMSCs was evaluated by flow cytometry and tri-lineage differentiation potential was evaluated by assessing adipogenic, osteogenic and chondrogenic development. Selected growth factor levels in PL-serum were not significantly different from PL-plasma (P > 0.05). hMSC cultures supplemented with PL-serum had comparable growth kinetics to PL-plasma, and hMSC yields were consistently greater than with FBS. hMSCs harvested from cultures supplemented with PL-serum, PL-plasma or FBS had similar cell surface phenotypes and maintained tri-lineage differentiation potential. PL-serum, similar to PL-plasma, can substitute for FBS in hMSC cultures. Use of PL-serum, in contrast to PL-plasma, has an added advantage of not requiring addition of a xenogeneic source of heparin, providing a completely xeno-free culture medium. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh.

PubMed

Ahmed, A M S; Soares Magalhaes, R J; Long, K Z; Ahmed, T; Alam, Md A; Hossain, Md I; Islam, Md M; Mahfuz, M; Mondal, D; Haque, R; Mamun, A A

2016-08-01

To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate-to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children. © 2016 John Wiley & Sons Ltd.

The vicious cycle of vitamin a deficiency: A review.

PubMed

Wiseman, Elina Manusevich; Bar-El Dadon, Shimrit; Reifen, Ram

2017-11-22

Vitamin A deficiency (VAD) is a serious and widespread public health problem and the leading cause of preventable blindness in young children. It is also associated with increased rates of death from severe infections, especially in developing countries. Over the past 35 years, researchers have examined the numerous activities of vitamin A in different tissues of the human body. VAD can lead to a series of ocular symptoms, anemia, and weak resistance to infection, which can increase the severity of infectious diseases and the risk of death. Cell development, vision, growth, and normal metabolism are among the vital processes that are insufficiently supported in the presence of VAD. VAD leads to impaired tissue function especially during the developmental periods of infancy, childhood, pregnancy, and lactation. We describe a multidirectional model of VAD that demonstrates how VAD can have progressive, negative effects on vital processes of the human body throughout the life cycle. This model starts with impaired intake and its link to decreased absorption and digestion and includes outcomes such as malnutrition, inflammation, and improper growth processes, including possible mechanisms. Together, these clinical and biochemical manifestations contribute to the vicious cycle of VAD.

The pharmacotherapy implications of ventricular assist device in the patient with end-stage heart failure.

PubMed

Von Ruden, Serena A S; Murray, Margaret A; Grice, Jennifer L; Proebstle, Amy K; Kopacek, Karen J

2012-04-01

Advances in mechanical circulatory support, such as the use of ventricular assist devices (VADs), have become a means for prolonging survival in end-stage heart failure (HF). VADs decrease the symptoms of HF and improve quality of life by replacing some of the work of a failing heart. They unload the ventricle to provide improved cardiac output and end-organ perfusion, resulting in improvement in cardiorenal syndromes and New York Heart Association functional class rating. VADs are currently used asa bridge to heart transplantation, a bridge to recovery of cardiac function, or as destination therapy. Complications of VAD include bleeding, infections, arrhythmias, multiple organ failure, right ventricular failure, and neurological dysfunction. Patients with VAD have unique pharmacotherapeutic requirements in terms of anticoagulation, appropriate antibiotic selection, and continuation of HF medications. Pharmacists in acute care and community settings are well prepared to care for the patient with VAD. These patients require thorough counseling and follow-up with regard to prevention and treatment of infections, appropriate levels of anticoagulation, and maintenance of fluid balance. A basic understanding of this unique therapy can assist pharmacists in attending to the needs of patients with VAD.

Plasma Homocysteine, Serum Folic Acid, Serum Vitamin B12, Serum Vitamin B6, MTHFR, and Risk of Normal-Tension Glaucoma.

PubMed

Li, Jinmiao; Xu, Fan; Zeng, Rui; Gong, Haijun; Lan, Yuqing

2016-02-01

This meta-analysis aims to comprehensively evaluate the association between total homocysteine (tHcy) levels, serum folic acid, vitamin B12, vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, and risk of normal-tension glaucoma (NTG). A systematic search of the EMBASE and PubMed databases was performed to evaluate plasma tHcy levels, serum folic acid, B vitamins' mean difference, and odds ratios of MTHFR C677T genotype between cases and controls. A total of 7 studies including 458 cases and 555 controls meeting the inclusion criteria were involved in this meta-analysis. There were 4 studies for tHcy (149 cases and 148 controls), 2 studies for vitamin B6, vitamin B12, and folate (90 cases and 82 controls), and 4 studies for MTHFR (343 cases and 449 controls). Overall, the mean plasma tHcy levels, serum folic acids, vitamin B12, and vitamin B6 levels were 1.16 μmol/L [95% confidence interval (CI), -0.13, 2.45], -0.62 μmol/L (95% CI, -1.98, 0.74), 5.81 μmol/L (95% CI, -3.53, 15.14), and -16.79 μmol/L (95% CI, -86.09, 52.51). MTHFR TT genotype was found to be unrelated to NTG risk (odds ratio=1.08; 95% CI, 0.69, 1.69). NTG is not associated with elevated plasma tHcy, serum folic acid, serum vitamin B12, serum vitamin B6, and MTHFR C677T genotype.

Lecithin retinol acyltransferase and its S175R mutant have a similar secondary structure content and maximum insertion pressure but different enzyme activities.

PubMed

Bussières, Sylvain; Cantin, Line; Salesse, Christian

2011-11-01

Recent work on Lecithin:retinol acyltransferase (LRAT) allowed to gather a large amount of information on its secondary structure, enzymatic properties and membrane binding. A truncated form of LRAT (tLRAT) as well as its S175R mutant leading to retinis pigmentosa, a severe form of retinal dystrophy, were studied to understand the role of this mutation on the dysfunction of this protein. Consistently with previous reports, the S175R-tLRAT mutant was shown to lack enzyme activity. However, very similar secondary structures probed by circular dichroism have been obtained with the S175R-tLRAT mutant and tLRAT. Moreover, similar values of maximum insertion pressure of the S175R-tLRAT mutant and tLRAT have been obtained using Langmuir monolayers, thus suggesting that the S175R mutation has no effect on the membrane binding properties of tLRAT. These findings leave open the possibility that the loss of enzymatic activity associated with the S175R mutant is related to loss of an essential nucleophile near the active site, or alternatively, to steric obstruction of the active site that impedes substrate binding. Copyright © 2011 Elsevier Ltd. All rights reserved.

Human NRDRB1, an alternatively spliced isoform of NADP(H)-dependent retinol dehydrogenase/reductase enhanced enzymatic activity of benzil.

PubMed

Yan, Yinxia; Song, Xuhong; Liu, Gefei; Su, Zhongjing; Du, Yongming; Sui, Xuxia; Chang, Xiaolan; Huang, Dongyang

2012-01-01

Human NRDRB1, a 226 amino acid alternatively spliced isoform of the NADP(H)- dependent retinol dehydrogenase/reductase (NRDR), lacks the complete coding region of exon 3, but preserves all the important functional motifs for NRDR catalytic activity. Nevertheless, its tissue distribution and physiological function remain to be elucidated. Expression of NRDRB1 and NRDR in cells and tissues was analyzed by semi-quantitative polymerase chain reaction (PCR) and western blot. NRDRB1 was expressed as a His(6) fusion protein and subjected to kinetics assays. Recombinant NRDRB1 had 1.2 to 8.6 fold higher k(cat)/K(m) values than recombinant NRDR, depending on the substrate. NRDRB1 catalyzed the NADPH-dependent reduction of α-dicarbonyl compounds, such as isatin, 9,10-phenanthrenequinone, and especially benzil. The significantly high catalytic activity and the relatively high expression in human liver of NRDRB1 conferred cellular resistance to benzil-induced cell toxicity and over-expression of NRDRB1 in low expressing Ec109 cells significantly enhanced cell tolerance toward benzil. Based on its substrate specificity, catalytic activity and relatively high expression in human liver tissue, our results suggest that NRDRB1, an alternatively spliced isoform of NRDR in vivo functions better than NRDR as a dicarbonyl reductase for xenobiotics containing reactive carbonyls. Our study is the first reporting this phenomenon of the enzymes involved in biochemical reactions. Copyright © 2012 S. Karger AG, Basel.

Correlation of serum androgens and pituitary hormone levels with serum PSA less than 2.5 ng/ml.

PubMed

Sofikerim, Mustafa; Oruç, Ozgür; Eskicorapci, Sadettin; Guliyev, Fuat; Ozen, Haluk

2007-07-27

The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone) and serum prostate specific antigen (PSA) levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer. Prior to digital rectal examination, serum was obtained from all patients between 8.30-10:00 AM for hormone and PSA concentrations. The study was performed on 210 male patients >40 years of age visiting our urology outpatient clinics. PSA was correlated to age (r = 0.23, p = 0.019), but there none between serum testosterone and age. No significant correlation was noted between testosterone or free testosterone and serum PSA levels, and none between serum FSH or LH and PSA. In age specific reference groups (41-49; 50-59; 60-69 years), we found no significant correlation between PSA and hormone concentrations. In this population of eugonadal men with serum PSA values less than 2.5 ng/ml, serum androgens and pituitary hormones do not appear to correlate with serum PSA.

Suitability of ultra-high performance liquid chromatography for the determination of fat-soluble nutritional status (vitamins A, E, D, and individual carotenoids).

PubMed

Granado-Lorencio, F; Herrero-Barbudo, C; Blanco-Navarro, I; Pérez-Sacristán, B

2010-06-01

Our aim was to assess the suitability of ultra-high performance liquid chromatography (UHPLC) for the simultaneous determination of biomarkers of vitamins A (retinol, retinyl esters), E (alpha- and gamma-tocopherol), D (25-OH-vitamin D), and the major carotenoids in human serum to be used in clinical practice. UHPLC analysis was performed on HSS T3 column (2.1 x 100 mm; 1.8 microm) using gradient elution and UV-VIS detection. The system allows the simultaneous determination of retinol, retinyl palmitate, 25-OH-vitamin D, alpha- and gamma-tocopherol, lutein plus zeaxanthin, alpha-carotene, beta-carotene, alpha- and beta-cryptoxanthin and lycopene. The method showed a good linearity over the physiological range with an adequate accuracy in samples from quality control programs. Suitability of the method in clinical practice was tested by analyzing samples (n = 286) from patients. In conclusion, UHPLC constitutes a reliable approach for nutrient/biomarker profiling allowing the rapid, simultaneous and low-cost determination of vitamins A, E, and D (including vitamers and ester forms) and the major carotenoids in clinical practice.

Graph theoretical analysis of EEG effective connectivity in vascular dementia patients during a visual oddball task.

PubMed

Wang, Chao; Xu, Jin; Zhao, Songzhen; Lou, Wutao

2016-01-01

The study was dedicated to investigating the change in information processing in brain networks of vascular dementia (VaD) patients during the process of decision making. EEG was recorded from 18 VaD patients and 19 healthy controls when subjects were performing a visual oddball task. The whole task was divided into several stages by using global field power analysis. In the stage related to the decision-making process, graph theoretical analysis was applied to the binary directed network derived from EEG signals at nine electrodes in the frontal, central, and parietal regions in δ (0.5-3.5Hz), θ (4-7Hz), α1 (8-10Hz), α2 (11-13Hz), and β (14-30Hz) frequency bands based on directed transfer function. A weakened outgoing information flow, a decrease in out-degree, and an increase in in-degree were found in the parietal region in VaD patients, compared to healthy controls. In VaD patients, the parietal region may also lose its hub status in brain networks. In addition, the clustering coefficient was significantly lower in VaD patients. Impairment might be present in the parietal region or its connections with other regions, and it may serve as one of the causes for cognitive decline in VaD patients. The brain networks of VaD patients were significantly altered toward random networks. The present study extended our understanding of VaD from the perspective of brain functional networks, and it provided possible interpretations for cognitive deficits in VaD patients. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Vibroacoustic disease: biological effects of infrasound and low-frequency noise explained by mechanotransduction cellular signalling.

PubMed

Alves-Pereira, Mariana; Castelo Branco, Nuno A A

2007-01-01

At present, infrasound (0-20 Hz) and low-frequency noise (20-500 Hz) (ILFN, 0-500 Hz) are agents of disease that go unchecked. Vibroacoustic disease (VAD) is a whole-body pathology that develops in individuals excessively exposed to ILFN. VAD has been diagnosed within several professional groups employed within the aeronautical industry, and in other heavy industries. However, given the ubiquitous nature of ILFN and the absence of legislation concerning ILFN, VAD is increasingly being diagnosed among members of the general population, including children. VAD is associated with the abnormal growth of extra-cellular matrices (collagen and elastin), in the absence of an inflammatory process. In VAD, the end-product of collagen and elastin growth is reinforcement of structural integrity. This is seen in blood vessels, cardiac structures, trachea, lung, and kidney of both VAD patients and ILFN-exposed animals. VAD is, essentially, a mechanotransduction disease. Inter- and intra-cellular communication is achieved through both biochemical and mechanotranduction signalling. When the structural components of tissue are altered, as is seen in ILFN-exposed specimens, the mechanically mediated signalling is, at best, impaired. Common medical diagnostic tests, such as EKG, EEG, as well as many blood chemistry analyses, are based on the mal-function of biochemical signalling processes. VAD patients typically present normal values for these tests. However, when echocardiography, brain MRI or histological studies are performed, where structural changes can be identified, all consistently show significant changes in VAD patients and ILFN-exposed animals. Frequency-specific effects are not yet known, valid dose-responses have been difficult to identify, and large-scale epidemiological studies are still lacking.

Ethical analysis of withdrawing ventricular assist device support.

PubMed

Mueller, Paul S; Swetz, Keith M; Freeman, Monica R; Carter, Kari A; Crowley, Mary Eliot; Severson, Cathy J Anderson; Park, Soon J; Sulmasy, Daniel P

2010-09-01

To describe a series of patients with heart failure supported with a ventricular assist device (VAD) who requested (or whose surrogates requested) withdrawal of VAD support and the legal and ethical aspects pertaining to these requests. We retrospectively reviewed the medical records of patients at Mayo Clinic, Rochester, MN, from March 1, 2003, through January 31, 2009, who requested (or whose surrogates requested) withdrawal of VAD support and for whom the requests were fulfilled. We then explored the legal and ethical permissibility of carrying out such requests. The median age of the 14 patients identified (13 men, 1 woman) was 57 years. Requests were made by 2 patients and 12 surrogates. None of the patients' available advance directives mentioned the VAD. For 11 patients, multidisciplinary care conferences were held before withdrawal of VAD support. Only 1 patient had an ethics consultation. All 14 patients died within 1 day of withdrawal of VAD support. Patients have the right to refuse or request the withdrawal of any unwanted treatment, and we argue that this right extends to VAD support. We also argue that the cause of death in these cases is the underlying heart disease, not assisted suicide or euthanasia. Therefore, patients with heart failure supported with VADs or their surrogates may request withdrawal of this treatment. In our view, carrying out such requests is permissible in accordance with the principles that apply to withdrawing other life-sustaining treatments.

Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos.

PubMed

Crissey, S; Ange, K; Slifka, K; Bowen, P; Stacewicz-Sapuntzakis, M; Langman, C; Sadler, W; Ward, A

2001-01-01

Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them.

Resource Utilization in Pediatric Patients Supported With Ventricular Assist Devices in the United States: A Multicenter Study From the Pediatric Interagency Registry for Mechanically Assisted Circulatory Support and the Pediatric Health Information System.

PubMed

Rossano, Joseph W; Cantor, Ryan S; Dai, Dingwei; Shamszad, Pirouz; Huang, Yuan-Shung; Hall, Matthew; Lin, Kimberly Y; Edens, R Erik; Parrino, P Eugene; Kirklin, James K

2018-06-01

Few data exist on resource utilization with pediatric ventricular assist devices (VADs). We tested the hypothesis that device type and adverse events are associated with increased resource utilization in pediatric patients supported with VADs. The Pediatric Interagency Registry for Mechanically Assisted Circulatory Support, a national registry of VADs in patients <19 years old, and the Pediatric Health Information System, an administrative database, were merged. Univariate analysis was performed assessing the association of all factors with the total cost and length of stay first. Significant variables ( P <0.05) were subjected to multivariable analysis. The study included 142 patients from 19 centers with VAD implants from October 2012 to June 2016. The median age was 9 years (interquartile range [IQR] 2-15), 84 (59%) supported with a continuous-flow VAD. Overall median hospital costs were $750 000 (IQR $539 000 to $1 100 000) with a median hospital length of stay of 81 days (IQR 54-128). On multivariable analysis, device type and postoperative complications were not associated with resource utilization. Factors associated with increased costs included patient age, lower-volume VAD center, being intubated, being on extracorporeal membrane oxygenation, number of complex chronic medical conditions, and length of stay. Among continuous-flow VAD patients, discharge to home before transplant versus remaining hospitalized was associated with lower hospital costs (median $600 000 [IQR $400 000 to $820 000] versus median $680 000 [IQR $500 000 to $970 000], P =0.03). VADs in pediatric patients are associated with high resource utilization. Increased resource utilization was associated with lower-volume VAD centers, disease severity at VAD implantation, and the presence of complex chronic medical conditions. Further study is needed to develop cost-effective strategies in this complex population. © 2018 The Authors. Published on behalf of the American Heart

Increased Serum Alkaline Phosphatase and Serum Phosphate as Predictors of Mortality after Stroke

PubMed Central

S, Pratibha; JB, Agadi

2014-01-01

Context: Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. Aims: To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Materials and Methods: Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Results: Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged. PMID:25300293

Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke.

PubMed

S, Pratibha; S, Praveen-Kumar; Jb, Agadi

2014-08-01

Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged.

Effect of Ramadan fasting on serum heat shock protein 70 and serum lipid profile.

PubMed

Zare, A; Hajhashemi, M; Hassan, Z M; Zarrin, S; Pourpak, Z; Moin, M; Salarilak, S; Masudi, S; Shahabi, S

2011-07-01

Ramadan, the holy month for the Islamic world, is a period every year when food and fluid intake is restricted to the pre-sunrise and post-sunset hours. The aim of this study was to evaluate the effect of Ramadan fasting on the serum concentration of heat shock protein 70 (HSP70) and serum lipid profile in healthy men. A total of 32 male volunteers with a mean age of 28.5 (range 23-37) years were selected for the study. Blood samples were obtained one day prior to Ramadan and on the 3rd and 25th days of fasting. Serum HSP70, triglyceride (TG), cholesterol (Chol), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), LDL/HDL and Chol/HDL ratios were investigated. It was observed that the mean concentrations of serum HSP70 and HDL on the 25th day of Ramadan were significantly higher than those recorded one day before Ramadan and on the 3rd day of Ramadan, and the levels on the 3rd day of Ramadan was significantly higher than those recorded one day before Ramadan. Mean concentrations of serum TG, Chol, LDL, and LDL/HDL and Chol/HDL ratios on the 25th day of Ramadan were significantly lower than those recorded one day before Ramadan and on the 3rd day of Ramadan, and the levels found on the 3rd day of Ramadan were also significantly lower than those recorded one day before Ramadan. Ramadan fasting increases serum HSP70 and improves serum lipid profile.

Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

PubMed

You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

2013-01-01

Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

Male mice are susceptible to high fat diet-induced hyperglycaemia and display increased circulatory retinol binding protein 4 (RBP4) levels and its expression in visceral adipose depots.

PubMed

Asha, G V; Raja Gopal Reddy, M; Mahesh, M; Vajreswari, A; Jeyakumar, S M

2016-01-01

Vitamin A and its metabolites are known to modulate adipose tissue development and its associated complications. Here, we assessed the vitamin A status and its metabolic pathway gene expression in relation to sexual dimorphism by employing 35 days old C57BL/6J male and female mice, which were fed either stock or high fat (HF) diet for 26 weeks. HF diet feeding increased body weight/weight gain and white adipose tissue (WAT) of visceral and subcutaneous regions, however, increase in vitamin A levels observed only in subcutaneous WAT. Further, the expression of most of the vitamin A metabolic pathway genes showed no sexual dimorphism. The observed HF diet-induced hyperglycaemia in male corroborates with increased retinol binding protein 4 (RBP4) levels in plasma and its expression in visceral adipose depots. In conclusion, the male mice are susceptible to high fat diet-induced hyperglycaemia and display higher plasma RBP4 levels, possibly due to its over-expression in visceral adipose depots.

Study on the correlation of vertebral artery dominance, basilar artery curvature and posterior circulation infarction.

PubMed

Zhu, Wei; Wang, Ya-Fang; Dong, Xiao-Feng; Feng, Hong-Xuan; Zhao, He-Qing; Liu, Chun-Feng

2016-09-01

Vertebral artery dominance (VAD), which is a common congenital variation of vertebral artery, may be associated with an increased risk of cerebral posterior circulation infarction (PCI). The aims of this study were to investigate the correlation of VAD with incidence and laterality of PCI, and oblige the correlation of VAD and basilar artery (BA) curvature. Incidence of separate territory infarction in posterior circulation and incidence of BA curvature were compared between 78 VAD patients and 68 controls. VA dominance, laterality of BA curvature and separate territory infarction, and their directional relationships were observed in VAD group. The incidence of BA curvature in VAD group was significantly higher than that in controls (P = 0.000). 89.7 % (35/39) of patients had an opposite directional relationship between dominant VA and BA curvature. The total incidence of PCI in VAD group was significantly higher than that in controls (P = 0.001). The incidences of posterior inferior cerebellar artery (PICA) and BA territory infarction were both significantly higher than those in controls [11.5 % (9/78) vs. 1.5 % (1/68), P = 0.016; 20.5 % (16/78) vs. 7.4 % (5/68), P = 0.024]. No differences were found in superior cerebellar artery and posterior cerebral artery territory infarction between two groups. 77.8 % (7/9) of PICA infarction were on the opposite side of dominant VA. 75.0 % (12/16) of BA infarction were on the side of dominant VA. The incidence of PCI in BA curvature patients was significantly higher than that in BA straight patients. The incidence of BA curvature is higher in VAD patients, and BA usually bends to the opposite side of dominant VA. The incidence of PCI is higher in VAD patients, especially in PICA infarction and BA infarction patients.

The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats.

PubMed

Cao, Yanjing; Liang, Lizhen; Xu, Jian; Wu, Jiali; Yan, Yongxing; Lin, Ping; Chen, Qiang; Zheng, Fengming; Wang, Qin; Ren, Qian; Gou, Zengmei; Du, Yifeng

2016-05-01

Flavonoids have been shown to improve cognitive function and delay the dementia progression. However, the underlying mechanisms remain elusive. In the present study, we examined the effect of Scutellaria baicalensis stem-leaf total flavonoids (SSTFs) extracted from S. baicalensis Georgi on spatial learning and memory in a vascular dementia (VaD) rat model and explored its molecular mechanisms. The VaD rats were developed by permanent bilateral occlusion of the common carotid artery. Seven days after recovery, the VaD rats were treated with either 50 or 100 mg/kg of SSTF for 60 days. The spatial learning and memory was evaluated in the Morris water maze (MWM) test. The tau hyperphosphorylation and the levels of the related protein kinases or phosphatases were examined by western blot analysis. In VaD rats, SSTF treatment at 100 mg/kg significantly reduced the escape latency in training trial in MWM test. In the probe trial, SSTF treatment increased the searching time and travel distance in the target quadrant. SSTF treatment inhibited the tau phosphorylation in both cortex and hippocampus in VaD rats. Meanwhile, SSTF reduced the activity of glycogen synthase kinase 3β and cyclin-dependent kinase 5 in VaD rats. In contrast, SSTF treatment increased the level of the protein phosphatase 2A subunit B in VaD rats. SSTF treatment significantly improved the spatial cognition in VaD rats. Our results suggest that SSTF may alleviate tau-hyperphosphorylation-induced neurotoxicity through coordinating the activity of kinases and phosphatase after a stroke. SSTF may be developed into promising novel therapeutics for VaD. © The Author 2016. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Alzheimer disease with cerebrovascular disease and vascular dementia: clinical features and course compared with Alzheimer disease.

PubMed

Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Deramecourt, V; Lebert, F; Amouyel, P; Pasquier, F

2009-02-01

Vascular dementia (VaD) and Alzheimer disease with cerebrovascular disease (AD+CVD) are the leading causes of dementia after Alzheimer disease alone (AD). Little is known about the progression of either VaD or AD+CVD. The aim of this study was to compare demographic features, cognitive decline and survival of patients with VaD, AD+CVD and AD alone attending a memory clinic. This study included 970 patients who were followed at the Lille-Bailleul memory clinic, France. Cognitive functions were measured with the Mini Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). Survival rate was analysed with a left-truncated Cox model. Analyses were adjusted for age, sex, education, hypertension, diabetes and baseline MMSE and DRS. Of 970 patients, 141 had VaD, 663 AD alone and 166 AD+CVD. The latter were significantly older than AD or VaD patients at onset (71 (SD 7) vs 69 (9) and 68 (9) years, p = 0.01) and at first visit (75 (6) vs 73 (8) and 72 (8) years, p = 0.0002). Baseline MMSE and DRS evaluations were highest for VaD compared with AD alone or AD+CVD patients (p<0.006). Cognitive decline during follow-up was slowest for VaD, intermediate for AD+CVD and fastest for AD alone (p = 0.03). After adjustment, compared with AD patients, mortality risk was similar for those with VaD (relative mortality risk (RR) = 0.7 (0.5 to 1.1)) and tended to be lower for AD+CVD (RR = 0.7 (0.5 to 1.0)). The shorter the delay between first symptoms and first visit, the longer patients survived. This clinical cohort study shows that patients with VaD, AD+CVD and AD present different characteristics at baseline and during follow-up, and underlines the need to distinguish between them.

Bone mineral density, serum albumin and serum magnesium.

PubMed

Saito, Noboru; Tabata, Naoto; Saito, Saburou; Andou, Yoshihisa; Onaga, Yukiko; Iwamitsu, Akihiro; Sakamoto, Morihide; Hori, Tuyoshi; Sayama, Harumi; Kawakita, Toshiko

2004-12-01

This study explores clinical and laboratory abnormalities that contribute to the prevalence of bone fractures in frail and control elderly patients, to ascertain factors that relate to bone strength and fragility. Patients were selected as free from renal failure and not taking supplements or medications that affect their magnesium status, and categorized according to their underlying diseases, sex and age, and evaluated by tests of bone strength. Findings, differentiating elderly patients on the basis of their magnesium, calcium, serum albumin, body mass, bone mineral density and their fracture occurrence were tabulated. Evidence is presented of low magnesium and albumin serum levels, especially in women with low bone density, as well as of low calcium and trace minerals.

Computational Approach for Developing Blood Pump

NASA Technical Reports Server (NTRS)

Kwak, Dochan

2002-01-01

This viewgraph presentation provides an overview of the computational approach to developing a ventricular assist device (VAD) which utilizes NASA aerospace technology. The VAD is used as a temporary support to sick ventricles for those who suffer from late stage congestive heart failure (CHF). The need for donor hearts is much greater than their availability, and the VAD is seen as a bridge-to-transplant. The computational issues confronting the design of a more advanced, reliable VAD include the modelling of viscous incompressible flow. A computational approach provides the possibility of quantifying the flow characteristics, which is especially valuable for analyzing compact design with highly sensitive operating conditions. Computational fluid dynamics (CFD) and rocket engine technology has been applied to modify the design of a VAD which enabled human transplantation. The computing requirement for this project is still large, however, and the unsteady analysis of the entire system from natural heart to aorta involves several hundred revolutions of the impeller. Further study is needed to assess the impact of mechanical VADs on the human body

Hydrodynamic endurance test of the prosthetic valve used in the various types of the ventricular assist device.

PubMed

Nitta, S; Yambe, T; Katahira, Y; Sonobe, T; Saijoh, Y; Naganuma, S; Akiho, H; Kakinuma, Y; Tanaka, M; Miura, M

1991-12-01

To evaluate the various basic designs of the pump chambers used in the ventricular assist devices (VADs), hydrodynamic endurance test was performed from the viewpoint of the durability of the prosthetic valves used in the VAD. For the hydrodynamic analysis, we designed three basic types of pump (sac type, diaphragm type, and pusher plate type) using the same material and having the same capacity and shape. Prosthetic valves in these VADs were tested from the standpoint of the water hammer effect, which affects the valve durability, to determine which pump design would be most durable as a prosthetic valve in the VAD. The water-hammer phenomenon was evaluated using the maximum pressure gradient (MPG) across the prosthetic valve in the moc circulatory loop. Maximum pump output was recorded when we used the diaphragm type model, and minimum MPG in the commonly used driving condition of the VAD were recorded when we used the sac type model. The results suggest that the sac type VAD model is the most durable design for the prosthetic value.

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population.

PubMed

Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-12-01

Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important.A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects.The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB).We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population.

Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population

PubMed Central

Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

2016-01-01

Abstract Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important. A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects. The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB). We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population. PMID:27977609

Combination Superficial Peels With Salicylic Acid and Post-Peel Retinoids.

PubMed

Kligman, Douglas E; Draelos, Zoe D

2016-04-01

Salicylic acid (SA) and retinoids, tretinoin (all-trans retinoic acid [ATRA]), and retinol (all-trans retinol) are widely used as topical agents for the improvement of photodamage and acne vulgaris. They can be used in daily take-home products or as part of an in-office procedure, combining the benefits of a keratolytic (SA) and a retinoid. The objective of this research was to compare the efficacy for ameliorating photodamage of topical tretinoin (0.25%) and retinol (0.25%) to baseline and with each other when applied after a 30% salicylic acid peel on human facial skin. Twenty female subjects received a full face 30% SA peel followed by the overnight application of tretinoin to a 1 randomized half-face and retinol to the opposite side (split-face study). The identical procedure was repeated at week 2. Double-blinded subject and investigator assessments of the results were captured at weeks 2 and 4. By investigator evaluation, both peeling regimens were effective in improving photodamage parameters compared to baseline. (ATRA P-values at week 4 were: P=.00008 texture, P=.00013 roughness, P=.00221 pores, P=.00098 dryness, P=.02770 erythema, and P=.00008 overall appearance. Retinol P-values at week 4 were: P=.00019 texture, P=.00053 roughness, P=.00221 pores, P=.00147 dryness, P=.02770 erythema, and P=.0043 overall appearance.) By subject self-assessment compared with baseline, both tretinoin and retinol were effective in improving overall appearance (ATRA P=.0229 and retinol P=.0190). By investigator evaluation comparing tretinoin with retinol, tretinoin was slightly better than retinol at week 4 in improving texture P=.00506, roughness P=.01171, and overall appearance P=.00506. By subject self-assessment comparing tretinoin with retinol, there was no difference in overall appearance (ATRA P=.2367 and retinol P=.3613). Either topical tretinoin (0.25%) or retinol (0.25%) can be used safely and effectively when applied in office immediately after SA peeling to

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

PubMed

Verras, Christos G; Christou, Georgios A; Simos, Yannis V; Ayiomamitis, George D; Melidonis, Andreas J; Kiortsis, Dimitrios N

2017-07-01

The elucidation of the changes of fetuin-A in the context of bariatric surgery. Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

Vitamin a derivatives labelled with 131I — Potential agents for liver scientigraphy

NASA Astrophysics Data System (ADS)

Kadeřávek, J.; Kozempel, J.; Štícha, M.; Petrášek, J.; Jirsa, M.; Taimr, P.; Lešetický, L.

2006-01-01

Two retinol derivatives, 4-[(131I)-4-iodobenzoyloxy]retinol propionate and 4-[(131I)-3-iodobenzylcarbamoyl]retinol propionate, were synthesized and their biodistribution in rats was studied in vivo by the whole body scintigraphy.

Association between serum soluble CD30 and serum creatinine before and after renal transplantation.

PubMed

López-Hoyos, M; San Segundo, D; Benito, M J; Fernández-Fresnedo, G; Ruiz, J C; Rodrigo, E; Gómez-Alamillo, C; Benito, A; Arias, M

2008-11-01

There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr (r = .454; P = .013). Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.

Association of serum calcium with serum sex steroid hormones in men in NHANES III.

PubMed

Van Hemelrijck, Mieke; Michaelsson, Karl; Nelson, William G; Kanarek, Norma; Dobs, Adrian; Platz, Elizabeth A; Rohrmann, Sabine

2013-12-01

Bone is a positive regulator of male fertility, which indicates a link between regulation of bone remodeling and reproduction or more specifically a link between calcium and androgens. This possibly suggests how calcium is linked to prostate cancer development through its link with the reproductive system. We studied serum calcium and sex steroid hormones in the Third National Health and Nutrition Examination Survey (NHANES III). Serum calcium and sex steroid hormones were measured for 1262 men in NHANES III. We calculated multivariable-adjusted geometric means of serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide (AAG), and sex hormone binding globulin (SHBG) by categories of calcium (lowest 5% [<1.16 mmol/L], mid 90%, top 5% [≥1.30 mmol/L]). Levels of total and free testosterone, total estradiol or AAG did not differ across categories of serum calcium. Adjusted SHBG concentrations were 36.4 for the bottom 5%, 34.2 for the mid 90% and 38.9 nmol/L for the top 5% of serum calcium (Ptrend = 0.006), free estradiol levels were 0.88, 0.92 and 0.80 pg/ml (Ptrend = 0.048). This link between calcium and sex steroid hormones, in particular the U-shaped pattern with SHBG, may, in part, explain why observational studies have found a link between serum calcium and risk of prostate cancer.

[Hepatic fibrosis and portal hypertension in chronic vitamin A poisoning].

PubMed

Verneau, A; Rosenbaum, J; Zafrani, E S; Roudot-Thoraval, F; Leclercq, M; Dhumeaux, D

1984-02-01

The authors report the case of a 36-year-old man who was hospitalized for portal hypertension. The patient had been receiving 200 millions units of vitamin A for ten years duration as treatment of psoriasis. There were no extrahepatic signs of hypervitaminosis A and the serum concentration of vitamin A was low. Microscopic examination of a liver specimen showed: a) spontaneous fluorescence due to vitamin A accumulation in sinusoidal cells; b) portal, periportal and perisinusoidal fibrosis; c) hyperplasia and hypertrophy of Ito cells. Hepatic vitamin A concentration was markedly increased. Hemodynamic study showed increased wedged hepatic venous pressure. Low serum concentration of retinol binding protein, which could be due to severe denutrition, explained the low serum vitamin A. This case report emphasizes that severe hepatic injury due to chronic hypervitaminosis A may be observed in the absence of extrahepatic signs of vitamin A intoxication and increase in serum vitamin A concentration. In such cases, histologic examination of a liver specimen and determination of hepatic vitamin A concentration are the only means of diagnosis.

Direct /sup 125/I-radioligand assays for serum progesterone compared with assays involving extraction of serum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ratcliffe, W.A.; Corrie, J.E.; Dalziel, A.H.

1982-06-01

Researchers compared two direct radioimmunoassays for progesterone in 50 microL of unextracted serum or plasma with assays involving extraction of serum. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11 alpha hemisuccinyl conjugate and the radioligand /sup 125/I-labeled progesterone 11 alpha-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r greatermore » than 0.96) with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. Researchers conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum.« less

Direct /sup 125/I-radioligand assays for serum progesterone compared with assays involving extraction of serum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ratcliffe, W.A.; Corrie, J.E.T.; Dalziel, A.H.

1982-06-01

Two direct radioimmunoassays for progesterone in 50 ..mu..L of unextracted serum or plasma with assays involving extraction of serum were compared. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11..cap alpha..-hemisuccinyl conjugate and the radioligand /sup 125/I-labeled progesterone 11..cap alpha..-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r > 0.96)more » with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. We conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum.« less

Fractionation of canine serum magnesium.

PubMed

Schenck, Patricia A

2005-06-01

Serum total magnesium (tMg) consists of 3 fractions: ionized magnesium (iMg), protein-bound magnesium (pbMg), and complexed magnesium (cMg). Serum iMg may be measured by an ion-selective electrode, but determination of pbMg and cMg has not been attempted in dogs. The objectives of this study were to assess the validity of a micropartition system to fractionate serum tMg and to establish reference intervals for pbMg, cMg, and iMg in clinically normal dogs using this method. Serum samples from 10 clinically healthy dogs were fractionated using a micropartition system (Centrifree YM-30, Amicon Corp, Lexington, MA, USA). Serum tMg and iMg were measured in whole serum, and tMg was also measured in the ultrafiltrate. Concentration of cMg was obtained by the subtraction of iMg from tMg concentrations of the ultrafiltrate. Protein-bound Mg was calculated by subtracting the tMg concentration of the ultrafiltrate from the tMg concentration of whole serum. Results for pbMg and cMg using the micropartition system showed good reproducibility. Determination of tMg and iMg had acceptable inter- and intra-assay precision. Concentrations of iMg, cMg, and pbMg were 0.50 +/- 0.05 mmol/L, 0.05 +/- 0.04 mmol/L, and 0.24 +/- 0.04 mmol/L, representing 63%, 6%, and 31% of the tMg concentration, respectively. The micropartition system was a reproducible means to accurately assess cMg and pbMg concentrations in dogs.

[Serum glycosaminoglycans in Graves' disease patients].

PubMed

Winsz-Szczotka, Katarzyna B; Olczyk, Krystyna Z; Koźma, Ewa M; Komosińska-Vassev, Katarzyna B; Wisowski, Grzegorz R; Marcisz, Czesław

2006-01-01

The aim of the study was to determine the blood serum sulfated glycosaminoglycans (GAGs) and hyaluronic acid (HA) concentration of Graves' disease patients before treatment and after attainment of the euthyroid state. The study was carried out on the blood serum obtained from 17 patients with newly recognised Graves' disease and from the same patients after attainment of the euthyroid state. Graves' patients had not any clinical symptoms neither of ophthalmopathy nor pretibial myxedema. GAGs were isolated from the blood serum by the multistage extraction and purification using papaine hydrolysis, alkali elimination, as well as cetylpyridium chloride binding. Total amount of GAGs was quantified by the hexuronic acids assay. HA content in obtained GAGs sample was evaluated by the ELISA method. Increased serum concentration of sulfated GAGs in non-treated Graves' disease patients was found. Similarly, serum HA level in untreated patients was significantly elevated. The attainment of euthyroid state was accompanied by the decreased serum sulfated GAGs level and by normalization of serum HA concentration. In conclusion, the results obtained demonstrate that the alterations of GAGs metabolism connected with Graves' disease can lead to systemic changes of the extracellular matrix properties.

High pulmonary vascular resistance in addition to low right ventricular stroke work index effectively predicts biventricular assist device requirement.

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro; Kinoshita, Osamu; Nawata, Kan; Ono, Minoru

2016-03-01

Although the right ventricular stroke work index (RVSWI) is a good index for RV function, a low RVSWI is not necessarily an indicator for the need for a right ventricular assist device at the time of left VAD implantation. We here aimed to determine a more precise indicator for the need for a biventricular assist device (BiVAD). In total, 116 patients (mean age, 38 ± 14 years), who underwent hemodynamic assessments preoperatively including 12 BiVAD patients, and had been followed at our institute from 2003 to 2015, were included. Multivariate logistic regression analysis indicated that RVSWI and pulmonary vascular resistance (PVR) were independent predictors of BiVAD requirement (P < 0.05 for both). In addition, all patients were classified into 4 groups: (1) normal (RVSWI > 5 g/m, PVR < 3.7 WU), (2) pulmonary hypertension (RVSWI > 5, PVR > 3.7), (3) RV failure (RVSWI < 5, PVR < 3.7), and (4) both pulmonary hypertension and RV failure (RVSWI < 5, PVR > 3.7), and examined. Most of the patients in Group 4 (75 %), with acutely depressed hemodynamics and inflammatory responses in the myocardium, required BiVAD. Overall, patients with BiVAD had a worse survival rate as compared with those with LVAD alone. In conclusion, high PVR in addition to low RVSWI effectively predicts BiVAD requirement.

Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer

PubMed Central

Arellano-Garcia, Martha E.; Li, Roger; Liu, Xiaojun; Xie, Yongming; Yan, Xiaofei; Loo, Joseph A.; Hu, Shen

2010-01-01

Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B). We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients. PMID:20957082

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients.

PubMed

Morote, Juan; Comas, Imma; Ferrer, Roser; Planas, Jacques; Celma, Anna; Regis, Lucas

2017-10-22

Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists. Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients "on LH-RH agonists", 303 "off LH-RH agonist" in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion "no LH-RH agonist" who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on "LH-RH agonists" and 19 "off LH-RH agonists", serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS). The area under the curve (AUC) to distinguish patients "on versus off LH-RH agonists" was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients "on LH-RH agonists" was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients "on versus off LH-RH agonists" was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method. Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients "on versus off LH-RH agonists". The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.

Microgels for long-term storage of vitamins for extended spaceflight

NASA Astrophysics Data System (ADS)

Schroeder, R.

2018-02-01

Biocompatible materials that can encapsulate large amounts of nutrients while protecting them from degrading environmental influences are highly desired for extended manned spaceflight. In this study, alkaline-degradable microgels based on poly(N-vinylcaprolactam) (PVCL) were prepared and analysed with their regard to stabilise retinol which acts as a model vitamin (vitamin A1). It was investigated whether the secondary crosslinking of the particles with a polyphenol can prevent the isomerisation of biologically active all-trans retinol to biologically inactive cis-trans retinol. Both loading with retinol and secondary crosslinking of the particles was performed at room temperature to prevent an early degradation of the vitamin. This study showed that PVCL microgels drastically improve the water solubility of hydrophobic retinol. Additionally, it is demonstrated that the highly crosslinked microgel particles in aqueous solution can be utilised to greatly retard the light- and temperature-induced isomerisation process of retinol by a factor of almost 100 compared to pure retinol stored in ethanol. The use of microgels offers various advantages over other drug delivery systems as they exhibit enhanced biocompatibility and superior aqueous solubility.

Serum ferritin: Past, present and future.

PubMed

Wang, Wei; Knovich, Mary Ann; Coffman, Lan G; Torti, Frank M; Torti, Suzy V

2010-08-01

Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases. In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool. Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer. Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights. Copyright 2010 Elsevier B.V. All rights reserved.

Techniques for measuring vitamin A activity from β-carotene.

PubMed

Tang, Guangwen

2012-11-01

Dietary β-carotene is the most important precursor of vitamin A. However, the determination of the efficiency of in vivo conversion of β-carotene to vitamin A requires sensitive and safe techniques. It presents the following challenges: 1) circulating β-carotene concentration cannot be altered by eating a meal containing ≤6 mg β-carotene; 2) because retinol concentrations are homeostatically controlled, the conversion of β-carotene into vitamin A cannot be estimated accurately in well-nourished humans by assessing changes in serum retinol after supplementation with β-carotene. In the past half-century, techniques using radioisotopes of β-carotene and vitamin A, depletion-repletion with vitamin A and β-carotene supplements, measurement of postprandial chylomicron fractions after consumption of a β-carotene dose, and finally, stable isotopes as tracers to follow the absorption and conversion of β-carotene in humans have been developed. The reported values for β-carotene to vitamin A conversion showed a wide variation from 2 μg β-carotene to 1 μg retinol (for synthetic pure β-carotene in oil) and 28 μg β-carotene to 1 μg retinol (for β-carotene from vegetables). In recent years, a stable isotope reference method (IRM) was developed that used labeled synthetic β-carotene. The IRM method provided evidence that the conversion of β-carotene to vitamin A is likely dose dependent. With the development of intrinsically labeled plant foods harvested from a hydroponic system with heavy water, vitamin A activity of stable isotope-labeled biosynthetic β-carotene from various foods consumed by humans was studied. The efficacy of plant foods rich in β-carotene, such as natural (spinach, carrots, spirulina), hybrid (high-β-carotene yellow maize), and bioengineered (Golden Rice) foods, to provide vitamin A has shown promising results. The results from these studies will be of practical importance in recommendations for the use of pure β-carotene and foods

ACTION OF SERUM ON FIBROBLASTS IN VITRO

PubMed Central

Carrel, Alexis; Ebeling, Albert H.

1923-01-01

It may be concluded that, under the conditions of the experiments: 1. The duration of life of fibroblasts is not altered by the presence of 7 per cent serum in a medium composed of fibrin and Tyrode solution, but is slightly decreased when the concentration of the serum reaches 25 per cent. 2. Fibroblasts cultivated in serum or in Tyrode solution are only in a condition of survival; they do not build up new protoplasm from the serum proteins and their mass does not increase. 3. When embryonic tissue juice is added to the medium, the tissues increase in mass. But the rate of growth is the same in media containing 0 per cent and 10 per cent serum. In 25 per cent serum, however, the rate of growth slightly decreases. Even in the presence of embryonic tissue juice, serum does not increase the rate of growth of connective tissue. 4. The nitrogenous compounds contained in serum are not used as food material by fibroblasts growing in vitro. PMID:19868757

Epidemiology and Microbiology of First Ventricular Assist Device Infection and Their Effect on Outcomes

PubMed Central

Guzman, Merilda Blanco; Vader, Justin; Olsen, Margaret; Dubberke, Erik R

2017-01-01

Abstract Background Left ventricular assist devices (VADs) are life-saving for patients with end stage heart failure but their benefits are limited due to infectious complications. Large studies looking at the site of infection and microbiology on outcomes are not available. Methods We conducted a single center retrospective cohort study of patients who underwent VAD implantation from 2009 to 2015. VAD infections were defined according to the criteria by the International Society for Heart and Lung Transplantation (ISHLT). Only the first VAD infection was included. Patients were followed until transplant, death or end of study. Descriptive statistics were performed. Time to event data was analyzed using Kaplan Meier and Cox Proportional Hazards. Results A total of 451 patients had a VAD placed during the study period. Median duration of follow up was 293 days (IQR-503) in patients without infection and 585 days (IQR 577) in those with VAD infection. 175 patients (38.8%) had at least 1 VAD infection, 29.1% involved the endovascular space and 70.9% involved local VAD infection. Median survival time was 1,430 days with local infection, 592 days with endovascular infection and 661 days in patients without infection (P < 0.001, Figure). The most common endovascular infection involved the pump/cannula (52.9%) and the most common local infection involved the superficial driveline (61.3%). Of the infections with a single identifiable organism, 74.5% were Gram-positives, 19.6 % were Gram-negatives and 5.2% were candida species. The predominant microorganisms were Staphylococcus aureus (35.9%), S. epidermidis (8.5%), Pseudomonas aeruginosa (7.8%) and Enterococcus faecalis (6.5%). There was no difference in mortality when Gram-positive, Gram-negative and Candida infections were compared. Conclusion Patients who survive the early post-VAD period frequently develop infectious complications. Patients with endovascular infections had significantly decreased survival

Evaluation of the need for chest X-rays in the management of asymptomatic, intraluminal vascular access device occlusion in childhood cancer.

PubMed

Stammers, David; Connolly, Bairbre; Brandão, Leonardo R; Zupanec, Sue; Gupta, Sumit

2017-07-01

Venous access device (VAD) occlusion from intraluminal thrombus is a common complication during childhood cancer treatment. Current practice at many institutions is to assess VAD position with a chest X-ray (CXR) prior to intraluminal administration of tissue plasminogen activator (tPA). We aimed to determine the utility of this practice. A retrospective chart review of children with newly diagnosed cancer with a VAD, treated at The Hospital for Sick Children between 2010 and 2011, was performed. Episodes of line occlusion were identified both by reviewing patient CXRs for indication and identifying tPA doses dispensed. These episodes were reviewed to determine whether CXR findings resulted in management other than tPA. Cases in which the X-ray resulted in a change in management were further reviewed to determine whether administration of tPA could have resulted in potential patient harm. A total of 330 patients with newly diagnosed cancer with VADs were identified. Eighty-five (25.8%) patients experienced 123 episodes of VAD occlusion. VAD occlusions occurred more frequently in patients with tunneled external central venous lines (16/39, 41.5%) and peripherally inserted central catheters (PICC) (27/73, 37.0%) versus PORT (42/216, 19.4%; P = 0.001). There were nine (8.1%) episodes of VAD occlusion evaluated with a CXR in which the findings led to a change in management other than administering tPA. In each case, multiple specialists independently concluded that administration of tPA would have been unlikely to cause patient harm. Routine CXRs prior to the administration of tPA for asymptomatic VAD occlusion can safely be omitted. © 2016 Wiley Periodicals, Inc.

Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity.

PubMed

Tristão, Vivian Regina; Pessoa, Edson A; Nakamichi, Renata; Reis, Luciana A; Batista, Marcelo Costa; Durão Junior, Marcelino de Souza; Monte, Júlio Cesar Martins

2016-01-01

Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury.

[Serum sclerostin levels and metabolic bone diseases].

PubMed

Yamauchi, Mika; Sugimoto, Toshitsugu

2013-06-01

Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

Depression and anxiety levels of the mothers of children and adolescents with left ventricular assist devices.

PubMed

Ozbaran, Burcu; Kose, Sezen; Yagdi, Tahir; Engin, Cagatay; Erermis, Serpil; Yazici, Kemal Utku; Noyan, Aysin; Ozbaran, Mustafa

2012-11-01

VADs have been used to provide treatment for end-stage heart failure. Parents may feel overwhelmed with the VAD regimes responsibility and be affected from this process beside children. In this study, we aimed to evaluate the depressive and anxiety symptoms of mothers of the first eight children equipped with a VAD in Turkey. The mothers of eight pediatric patients living with VADs were filled BDI and STAI at first month of VAD implantation (E.I) and secondly six months after their first evaluation (E.II). In E.I, the BDI mean score of mothers was 20.87, in E.II 14.37. STAI-S mean score was 53.37 in E.I and 43.62 in E.II. The Wilcoxon nonparametric-paired t-test revealed significant difference between baseline and end-point STAI-S scores (Z: -2.035; p: 0.042), and for BDI scores (Z, -1.965; p, 0.049). Prolonged usage of VAD may increase distress in parents. Psychiatric evaluation and support of the primary caregiver is important for the well-being of the pediatric patients. © 2012 John Wiley & Sons A/S.