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Schindler, Rainer, Tanja Fielenbach, and Gerhard Rave. "A comparative study on the effects of oral amiodarone and trimeprazine, two in vitro retinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats." British Journal of Nutrition 94, no. 5 (November 2005): 675–83. http://dx.doi.org/10.1079/bjn20051495.
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Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P<0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P<0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P<0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended.
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Kim, Youngnam. "Recommended Intake and Dietary Intake of Vitamin A for Koreans by Unit of Retinol Activity Equivalent." Korean Journal of Community Nutrition 21, no. 4 (2016): 344. http://dx.doi.org/10.5720/kjcn.2016.21.4.344.
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Amoussa-Hounkpatin, Waliou, Claire Mouquet-Rivier, Adéchola Pierre Polycarpe Kayodé, Joseph Djidjoho Hounhouigan, and Sylvie Avallone. "Effect of a multi-step preparation of amaranth and palm nut sauces on their carotenoid content and retinol activity equivalent values." International Journal of Food Science & Technology 48, no. 1 (September 11, 2012): 204–10. http://dx.doi.org/10.1111/j.1365-2621.2012.03178.x.
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Meng, Goh Yong, Razif Abas, Nurmawati Syakroni, Nur Izah Abdul Razak, Nurul Huda Mohd Nor, Siti Fadziyah Mohamad Asri, Safuraa Salihan, Nurul Hayati Mohamad Zainal, Suryati Mohd Thani, and Azmah Saat. "Evaluation and Determinants of Secondary Metabolites and its Antioxidant Activities of Various Fractions from Albizia myriophylla Bark." Proceedings 61, no. 1 (October 30, 2020): 7. http://dx.doi.org/10.3390/iecn2020-07004.
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Albizia myriophylla (ABZ) is a plant used in Thailand and Peninsular Malaysia for the treatment of diabetes mellitus type II. The antioxidant activities of ABZ have been suggested as one of the mechanisms for the observed beneficial effects. Hence, this study examined the phenolic, flavonoid, and saponin contents and antioxidant activity from methanol extract (ME) and its derived fractions hexane (HE), chloroform (CE), ethyl acetate (EAE), butanol (BE), and aqueous fraction of the bark of ABZ (AE). Amongst the extracts, EAE showed the highest total phenolic content of about 0.77 mg of gallic acid equivalent/g of extract (mg GAE/mg). However, the highest flavonoid content was detected in HE at 1.04 µg retinol equivalent ((RE)/g extract), while the saponin content was highest in CE at 1.1 µg diosgenin equivalent ((DE)/g extract). In 1,1-diphenyl-2-picrylhidrazyl (DPPH) radical scavenging test, EAE at 100 µg/mL had the highest percentage of inhibition of about 72.55%. 2-2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS radical scavenging test) showed BE had the highest percentage of inhibition at 100 µg/mL at 82.91%. Ferric reducing antioxidant power elucidated BE as having the highest percentage of inhibition which was 86.04% followed closely by ME at 85.90%. Thus, the different extracts of ABZ displayed various antioxidant capacity with probable free radical scavenging activity, which may be useful for the treatment of chronic inflammatory related metabolic diseases, such as diabetes and obesity.
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Record, Ian R., Ivor E. Dreosti, and Jennifer K. McInerney. "Changes in plasma antioxidant status following consumption of diets high or low in fruit and vegetables or following dietary supplementation with an antioxidant mixture." British Journal of Nutrition 85, no. 4 (April 2001): 459–64. http://dx.doi.org/10.1079/bjn2000292.
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The aim of the present study was to examine the effect of consumption of a high-fruit and vegetable diet, or a spray-dried extract of selected fruits and vegetables of high antioxidant content, on indices of antioxidant status of individuals consuming a background diet with minimal antioxidant intake. Plasma antioxidant concentrations were determined in twenty-five men following a 2-week depletion period during which they consumed self-selected low-antioxidant diets (less than three servings of fruit and vegetables with no tea, coffee, red wine or fruit juice). Following this period the volunteers consumed either a self-selected diet containing five to seven servings of fruit and vegetables/d, or 30 g of a spray-dried supplement designed to provide the equivalent antioxidant activity of five to seven servings of fruit and vegetables for 2 weeks in a crossover trial. Following consumption of a high-antioxidant diet for 2 weeks, plasma concentrations of ascorbic acid, α- and β-carotene and lutein+zeaxanthin were all significantly increased (P<0.05) over the depletion period. However, concentrations of lycopene, retinol and tocopherol were not affected. Consumption of the supplement also raised the concentrations of these same antioxidants in plasma. Despite the increases in the concentrations of measured antioxidant nutrients, the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid-equivalent antioxidant capacity of plasma, as estimated by inhibition of metmyoglobin activity, was not significantly affected by any of the dietary treatments.
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Hemalatha, N., J. Naveen, and V. Baskaran. "Medicinal Plants as Sources of Retina Protective Carotenoids (Lutein, β-carotene) and their Radical Scavenging Property." Indian Journal of Nutrition and Dietetics 56, no. 4 (October 1, 2019): 365. http://dx.doi.org/10.21048/ijnd.2019.56.4.23709.
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The study assesses the Retinol Activity Equivalent (RAE), lutein and zeaxanthin, total polyphenols and antioxidant potential of medicinal plants. Amongst plants, the highest levels (mg/100 g dry weight) of β-carotene and lutein + zeaxanthin were detected in Centella asiatica, (197.5) and V. aroma (894.6). Interestingly, V. aroma (871, 85), Acacia concinna (587, 65), Centella asiatica (404, 198), Oxalis corniculata (501, 196) and Tinospara cordifolia (417, 120) are rich in β-carotene and lutein + zeaxanthin. The RAE (RAE/100 g dry wt.) is higher in A. citratus (9.5), B. diffusa (13.0), C. asiatica (16.5) and V. negundo (10.1) respectively. Total polyphenols were higher in R. officinalis (10.26 mg/g) and B. diffusa (8.07 mg/g). Among plants, R. officinalis, P. amboinicus and B. diffusa, showed highest free-radical scavenging (98%) radical reducing power (73.61%) and inhibition of the peroxidation (33.4%). To conclude, plants having higher levels of RAE and lutein + zeaxanthin can ameliorate vitamin-A deficiency and age-related macular degeneration.
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Luo, Hanqi, Kevin W. Dodd, Charles D. Arnold, and Reina Engle-Stone. "A New Statistical Method for Estimating Usual Intakes of Nearly-Daily Consumed Foods and Nutrients Through Use of Only One 24-hour Dietary Recall." Journal of Nutrition 149, no. 9 (June 7, 2019): 1667–73. http://dx.doi.org/10.1093/jn/nxz070.
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ABSTRACT Background To estimate usual intake distributions of dietary components, collection of nonconsecutive repeated 24-h dietary recalls is recommended, but resource limitations sometimes restrict data collection to single-day dietary data per person. Objectives We developed a new statistical method, the NCI 1-d method, which uses single-day dietary data and an external within-person to between-person variance ratio to estimate population distributions of usual intake of nearly-daily consumed foods and nutrients. Methods We used NHANES 2011–2014 data for men (n = 4938 and n = 4293 for the first and second 24-h recalls) to compare nutrient intake distributions of vitamin A, magnesium, folate, and vitamin E generated by the 1-d method (with use of only the first recall per person) with those from the NCI amount-only method (with use of all days of dietary intake per person). The within-person to between-person variance ratio from the amount-only model was used as the unbiased “external” estimate for the 1-d method. We also examined the effect of mis-specification of variance ratios on usual intake distributions. Results The amount-only and 1-d methods estimated statistically equivalent median (25p, 75p): 647 (459, 890) compared with 648 (461, 886) µg retinol activity equivalents/d, 338 (268, 420) compared with 334 (266, 417) mg magnesium/d, 595 (458, 762) compared with 589 (456, 758) µg dietary folate equivalents/d, and 9.7 (7.3, 12.6) compared with 9.6 (7.3, 12.7) mg vitamin E/d. As the external variance ratios increased from 25% to 200% of the unbiased ratios, the prevalence of inadequate intake ranged from 53% to 43% for vitamin A, 57% to 55% for magnesium, 16% to 2% for folate, and 70% to 73% for vitamin E. Conclusions The 1-d method is a viable statistical method for estimating usual intakes of nearly-daily consumed dietary components when the variance ratio is unbiased. Results are sensitive to variance ratio selection, so researchers should still collect replicate data where possible.
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Martínez-Sánchez, Ascensión, María Elena López-Cañavate, Josefa Guirao-Martínez, María José Roca, and Encarna Aguayo. "Aloe vera Flowers, a Byproduct with Great Potential and Wide Application, Depending on Maturity Stage." Foods 9, no. 11 (October 26, 2020): 1542. http://dx.doi.org/10.3390/foods9111542.
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Flowers of Aloe vera are a byproduct providing a valuable source of bioactive compounds with different functions for health benefits. The characterization in amino acids, organic acids, sugars, trigonelline, volatiles compounds, fatty acids, total phenolic, carotenoids, vitamin C content, and antioxidant capacity of Aloe flowers (Aloe barbadensis Miller) has been studied at three maturity stages (I: immature; II: mature; III: mature, with flowers buds opened). Immature flowers presented the highest content in phenyl alanine, tyrosine, citric acid, trigonelline, carotenoids, retinol activity equivalent, vitamin C, and total phenolic and antioxidant capacity. As the flower develops, the content of these compounds decreases. Aloe vera flowers presented an important content in fatty acids, and the principal concentration was identified in polyunsaturated unsaturated fatty acids (PUFAs) as α-linolenic acid, and linoleic acid, with a ratio close to one. The main saturated fatty acid was palmitic acid, followed by stearic acid. Maturity stage III showed the lowest fatty acid content. The bioactive compounds found in Aloe vera flowers have potential applications in the cosmetic, pharmaceutical, nutraceutical, and food industries. Depending on the compound of interest, it could be worthwhile harvesting flowers at maturity stage I, thereby reducing the energy consumption of flowers from the plant and thus favoring plant development. This is an example of a circular economy for Aloe vera producers, generating economic and business opportunities and thus providing environmental and social benefits.
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Menezes Filho, Antonio Carlos Pereira de, Josemar Gonçalves de Oliveira Filho, Marcela Christofoli, and Castro Frederico de Sousa. "Atividade Antioxidante, Conteúdo de Fenólicos Totais, Carotenoides e Provitamina A em Extratos Vegetais do Cerrado Goiano." UNICIÊNCIAS 22, no. 1 (September 6, 2018): 28. http://dx.doi.org/10.17921/1415-5141.2018v22n1p28-32.
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Diferentes grupos vegetais encontrados no bioma Cerrado vêm sendo amplamente estudados quanto as suas possíveis características químicas, apresentando dentre essas biocompostos de interesse para a indústria de alimentos, como na produção de barras de cereais nutritivas e em condimentos alimentares capazes de inibir ações de radicais livres causadores de patologias. No entanto, ainda pouco se sabe sobre a grande variedade destes compostos bioativos, que compõem as características químicas das espécies rasteiras, arbustivas e arbóreas, que coabitam nas mais diversas variantes deste bioma. A descoberta dos efeitos deletérios dos radicais livres sobre as células, agindo como causadores de doenças, impulsionando a busca por novos compostos bioativos na área de alimentos, que a cada ano cresce com a produção de novos produtos alimentícios, com características mais saudáveis, permitindo a prevenção e minimizando os danos oxidativos sobre as células. O presente trabalho teve como objetivo avaliar a atividade antioxidante pela captura do radical DPPH, conteúdos de fenólicos totais pelo reagente de Folin-Ciocalteau, carotenoides, provitamina A em equivalente de Retinol por métodos espectrofotométricos UV-Vis dos extratos etanólicos foliares das espécies botânicas: Byrsonima coccolobifolia (Kunth.), Dimorphandra mollis (Benth.), Hymenaea stignocarpa (Mart. ex Hayne), Solanum lycocarpum (St. Hil.) e Cardiopetalum calophyllum (Schlecht.). Os resultados demonstraram a presença de atividade antioxidante pelo método de sequestro do radical DPPH, expressivos conteúdos de fenólicos totais, teores de β-caroteno, presença de licopeno, exceto nas espécies Dimorphandra mollis e Hymenaea stignocarpa, presença de baixos teores de provitamina A.Palavras-chave: Folhas. DPPH. Licopeno.AbstractDifferent vegetable groups found in the Cerrado biome have been widely studied as to their possible chemical characteristics, presenting among them biocomposites of interest for the food industry, as in the production of nutritious cereal bars and in food condiments capable of inhibiting actions of free radicals causing pathologies. But little is known about the great variety of these bioactive compounds that make up the chemical characteristics of the shrub, shrub and tree species that cohabit in the most diverse variants of this biome. The discovery of the deleterious effects of free radicals on cells, acting as cause of disease, driving the search for new bioactive compounds in the area of food that grows every year with the production of new food products with healthier characteristics allowing prevention and minimizing the oxidative damage on cells. The objective of the present work was to evaluate the antioxidant activity by capturing DPPH radical, total phenolic contents by Folin-Ciocalteau reagent, carotenoids, provitamin A in Retinol equivalent by UV-Vis spectrophotometric methods of the foliar ethanolic extracts of botanical species: Byrsonima Coccolobifolia (Kunth.), Dimorphandra mollis (Benth.), Hymenaea stignocarpa (Mart. ex Hayne), Solanum lycocarpum (St. Hil.) and Cardiopetalum calophyllum (Schlecht.). The results showed the presence of antioxidant activity by the DPPH radical sequestration method, expressive total phenolic content, β-carotene content, lycopene content, except for Dimorphandra mollis and Hymenaea stignocarpa species, with low levels of provitamin A.Keywords: Sheets. DPPH. Lycopene.
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Aragaw, Habtamu Seyoum, Donatus Nohr, and Daniel Callo-Concha. "Nutritional potential of underutilized edible plant species in coffee agroforestry systems of Yayu, southwestern Ethiopia." Agroforestry Systems 95, no. 6 (April 23, 2021): 1047–59. http://dx.doi.org/10.1007/s10457-021-00626-6.
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AbstractEthiopia is confronted with the paradox of hosting hundreds of edible plants and having high food and nutritional insecurity. Meals are mainly made up of staples and often lack of protein and micronutrients. Therefore, a large section of the population, particularly children and women, are malnourished. We hypothesize that wild edible plant species can contribute to fulfil the micronutrient demands of local people. Hence, we assessed the nutritional potential of underutilized edible plant species growing in understories of coffee agroforestry systems of southwestern Ethiopia. An ethnobotanical household survey (n = 300) documented the edible existing plants; and a promising subset of them (n = 12) was analysed for nutrient and antinutritional factor content in the lab. All 12 species, except fruits, have higher calcium, iron and zinc contents compared to regularly cultivated crops. Vitamin C was high in Syzygium guineense (330.72 mg/100 g edible parts or EP) and Rubus apetalus (294.19 mg/100 g). Beta-carotene ranged from 9.2 to 75 µg retinol activity equivalent (RAE) /100 g 25 among all species, but was exceptionally high in Rubus apetalus (161.7 µg RAE/100 g). Concerning the antinutritional factors, phytate content varied from 31.06 to 601.65 µg/100 g, being lower in Dioscorea prehensilis (31.06 µg/100 g) and D. alata (90.17 µg/100 g) compared to Carissa spinarum (601.65 µg/100 g) and Solanum nigrum (536.48 µg/100 g). Thus, we conclude that the assessed underutilized species are potential sources of dietary nutrients locally needed, and are notable Amaranthus graecizans, Portulaca oleracea and Dioscorea cayenensis as providers of Ca, Fe and Zn, and the fruit Rubus apetalus of provitamin A.
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Hotz, Christine, Justin Chileshe, Ward Siamusantu, Uma Palaniappan, and Emmanuel Kafwembe. "Vitamin A intake and infection are associated with plasma retinol among pre-school children in rural Zambia." Public Health Nutrition 15, no. 9 (March 23, 2012): 1688–96. http://dx.doi.org/10.1017/s1368980012000924.
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AbstractObjectiveTo determine the prevalence of vitamin A deficiency, infection and adequacy of vitamin A intakes among Zambian children, and the contribution of dietary vitamin A and infection to vitamin A status.DesignA cross-sectional survey of vitamin A intakes by the 24 h recall method, vitamin A status by plasma retinol and the modified relative dose-response test, and infection by acute-phase proteins.SettingRural communities in Central and Eastern Provinces of Zambia.SubjectsChildren 2–5 years of age.ResultsThe prevalence of vitamin A deficiency was 56 % by plasma retinol, 48 % with infection-adjusted plasma retinol and 22 % by the modified relative dose-response test. The majority of children (61 %) had a current infection. Vitamin A intakes were relatively high (331 to 585 μg retinol activity equivalents/d in the harvest/early post-harvest and late post-harvest seasons, respectively) and the prevalence of inadequate intakes was <1 % when compared with the Estimated Average Requirement (210 and 275 μg retinol activity equivalents/d for children aged 1–3 and 4–8 years, respectively). Elevated α-1-acid glycoprotein was negatively associated with plasma retinol (P< 0·0 0 1) and vitamin A intake was positively associated with plasma retinol (P< 0·05), but only when estimated assuming a 26:1 retinol equivalence for provitamin A from green and yellow vegetables.ConclusionsInfection and vitamin A intakes were significant determinants of plasma retinol. We cannot conclude which indicator more accurately represents the true vitamin A status of the population. Reasons for the persistent high prevalence of vitamin A deficiency in the presence of adequate vitamin A intakes are unclear, but the high rates of infection may play a role.
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Reiter, Chad E. N., Lakshman Sandirasegarane, Ellen B. Wolpert, Marianne Klinger, Ian A. Simpson, Alistair J. Barber, David A. Antonetti, Mark Kester, and Thomas W. Gardner. "Characterization of insulin signaling in rat retina in vivo and ex vivo." American Journal of Physiology-Endocrinology and Metabolism 285, no. 4 (October 2003): E763—E774. http://dx.doi.org/10.1152/ajpendo.00507.2002.
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Insulin receptor (IR) signaling cascades have been studied in many tissues, but retinal insulin action has received little attention. Retinal IR signaling and activity were investigated in vivo in rats that were freely fed, fasted, or injected with insulin by phosphotyrosine immunoblotting and by measuring kinase activity. A retina explant system was utilized to investigate the IR signaling cascade, and immunohistochemistry was used to determine which retinal cell layers respond to insulin. Basal IR activity in the retina was equivalent to that in brain and significantly greater than that of liver, and it remained constant between freely fed and fasted rats. Furthermore, IR signaling increased in the retina after portal vein administration of supraphysiological doses of insulin. Ex vivo retinas responded to 10 nM insulin with IR β-subunit (IRβ) and IR substrate-2 (IRS-2) tyrosine phosphorylation and AktSer473 phosphorylation. The retina expresses mRNA for all three Akt isoforms as determined by in situ hybridization, and insulin specifically increases Akt-1 kinase activity. Phospho-AktSer473 immunoreactivity increases in retinal nuclear cell layers with insulin treatment. These results demonstrate that the retinal IR signaling cascade to Akt-1 possesses constitutive activity, and that exogenous insulin further stimulates this prosurvival pathway. These findings may have implications in understanding normal and dysfunctional retinal physiology.
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Kongsbak, Katja, Shakuntala H. Thilsted, and Mohammed A. Wahed. "Effect of consumption of the nutrient-dense, freshwater small fishAmblypharyngodon molaon biochemical indicators of vitamin A status in Bangladeshi children: a randomised, controlled study of efficacy." British Journal of Nutrition 99, no. 3 (March 2008): 581–97. http://dx.doi.org/10.1017/s000711450781912x.
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In Bangladesh, some commonly consumed, indigenous, freshwater small fish species (eaten whole with bone, head and eyes) such as mola (Amblypharyngodon mola) are nutrient-dense, containing preformed vitamin A as retinol and especially 3,4-dehydroretinol. The objective of the present randomised, controlled efficacy study was to evaluate the effects of mola on biochemical indicators of vitamin A status. Children (n196), aged 3–7 years, with serum retinol 0·36–0·75 μmol/l, were randomly allocated to one of three treatment groups to receive a daily test meal (6 d/week for 9 weeks) of rice and vegetable curry (no vitamin A)ad libitumand 50 g fish curry consisting of: (1) mola, 600 retinol activity equivalents (RAE) (using 40 % biological activity of 3,4-dehydroretinol isomers) (experimental group,n66); (2) rui (Labeo rohita), a large fish (no vitamin A), with added retinyl palmitate, 600 RAE (positive control group,n65); or (3) rui, 0 RAE (negative control group,n65). The nutrient compositions of the dishes were analysed. After 9 weeks, no significant treatment effects were observed for serum retinol (P = 0·52) and retinol-binding protein (P = 0·81) in the experimental group compared with the negative control, whereas the positive control improved significantly (P < 0·001). The present results do not suggest conversion of the large amount of 3,4-dehydroretinol in mola curry to retinol. Further research on the functional effect of mola in humans is needed. Mola is a nutrient-dense animal-source food, rich in haem Fe, Zn and especially Ca, thus consumption of mola in Bangladesh should continue to be encouraged.
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Helms, J. A., C. H. Kim, G. Eichele, and C. Thaller. "Retinoic acid signaling is required during early chick limb development." Development 122, no. 5 (May 1, 1996): 1385–94. http://dx.doi.org/10.1242/dev.122.5.1385.
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In the chick limb bud, the zone of polarizing activity controls limb patterning along the anteroposterior and proximodistal axes. Since retinoic acid can induce ectopic polarizing activity, we examined whether this molecule plays a role in the establishment of the endogenous zone of polarizing activity. Grafts of wing bud mesenchyme treated with physiologic doses of retinoic acid had weak polarizing activity but inclusion of a retinoic acid-exposed apical ectodermal ridge or of prospective wing bud ectoderm evoked strong polarizing activity. Likewise, polarizing activity of prospective wing mesenchyme was markedly enhanced by co-grafting either a retinoic acid-exposed apical ectodermal ridge or ectoderm from the wing region. This equivalence of ectoderm-mesenchyme interactions required for the establishment of polarizing activity in retinoic acid-treated wing buds and in prospective wing tissue, suggests a role of retinoic acid in the establishment of the zone of polarizing activity. We found that prospective wing bud tissue is a high-point of retinoic acid synthesis. Furthermore, retinoid receptor-specific antagonists blocked limb morphogenesis and down-regulated a polarizing signal, sonic hedgehog. Limb agenesis was reversed when antagonist-exposed wing buds were treated with retinoic acid. Our results demonstrate a role of retinoic acid in the establishment of the endogenous zone of polarizing activity.
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Deminice, Thalia Manfrin Martins, Ivan Savioli Ferraz, Jacqueline Pontes Monteiro, Alceu Afonso Jordão, Lívia Maria Cordeiro Simões Ambrósio, and Carlos Alberto Nogueira-de-Almeida. "Vitamin A intake of Brazilian mothers and retinol concentrations in maternal blood, human milk, and the umbilical cord." Journal of International Medical Research 46, no. 4 (February 13, 2018): 1555–69. http://dx.doi.org/10.1177/0300060518757155.
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Objectives To analyse intake of vitamin A (VA) and retinol concentrations in maternal blood, breast milk (BM), and the umbilical cord (UC) of newborns, and to determine the associations among these variables. Methods We performed a cross-sectional, epidemiological study of 180 mother–newborn dyads. Maternal and UC blood samples and BM were collected. VA intake by the mother over 30 days was assessed using a questionnaire. Results Mean retinol concentrations in maternal serum, the UC, and BM were 0.65 ± 0.27, 0.36 ± 0.18, and 2.95 ± 2.70 µmol/L, respectively. Retinol concentrations <0.70 µmol/L were found in 57.2% of maternal blood samples and in 94.9% of UC samples. A total of 27.9% of BM samples showed retinol concentrations <1.05 µmol/L. Mean VA intake by the mothers was 1041.33 ± 1187.86 µg retinol activity equivalents/day and was inadequate (<550 µg retinol activity equivalents/day) in 44.7%. Conclusions High proportions of insufficient retinol concentrations were observed in the UC, maternal blood, and BM. A high percentage of pregnant women had inadequate VA intake. Mothers with insufficient serum retinol concentrations had newborns with lower retinol concentrations in the UC. Higher retinol concentrations were observed in maternal blood and the UC with a higher VA intake.
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Ford, Jennifer Lynn, Joanne Balmer Green, Marjorie J. Haskell, Shaikh M. Ahmad, Dora Inés Mazariegos Cordero, Anthony Oxley, Reina Engle-Stone, Georg Lietz, and Michael H. Green. "Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries." Journal of Nutrition 150, no. 2 (September 18, 2019): 411–18. http://dx.doi.org/10.1093/jn/nxz225.
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ABSTRACT Background Model-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans. Objectives We applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines. Methods Children ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data. Results Model-predicted TBS was 198, 533, and 1062 μmol for the Bangladeshi (age, 9–17 mo), Filipino (12–18 mo), and Guatemalan children (35–65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2–3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 μg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively). Conclusions By collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).
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Kim, Giraud, Cho, and Driskell. "Vitamin A Inadequacy Observed in a Group of 2- to 6-Year-Old Children Living in Kwangju, Republic of Korea." International Journal for Vitamin and Nutrition Research 77, no. 5 (September 1, 2007): 311–19. http://dx.doi.org/10.1024/0300-9831.77.5.311.
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Dietary intakes and plasma concentrations of retinol and carotenoids were estimated in assessing the vitamin A status of young children in Kwangju, Republic of Korea. Three consecutive 24-hour food recalls and fasting blood samples were obtained from 123 healthy children (58 boys, 65 girls), aged 2–6 years. The daily vitamin A intake (mean ± SD) was 355.9 ± 178.1 μg retinol equivalents or 239.0 ± 111.2 μg retinol activity equivalents. Provitamin A carotenoid intakes were 1211.2 ± 840.0 μg/day β-carotene, 234.6 ± 231.7 μg/day α-carotene, and 149.1 ± 160.7 μg/day β-cryptoxanthin. Approximately 15–26% of subjects consumed < Korean Estimated Average Requirements (EAR) for vitamin A; whereas, 57–64% consumed < EAR for vitamin A for USA/Canadians. The mean plasma retinol concentration was 1.108 ± 0.244 μmol/L. There were no significant correlations between intakes and plasma concentrations of retinol and carotenoids. Only 2.4% of children were vitamin A-deficient based on having plasma retinol concentrations < 0.70 μmol/L. Plasma retinol concentrations of 42.3% of subjects were 0.70– < 1.05 μmol/L, which is considered indicative of potentially suboptimal vitamin A status. Therefore, some children may be at risk of inadequate vitamin A status in Kwangju, Republic of Korea.
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Wagner, M., B. Han, and T. M. Jessell. "Regional differences in retinoid release from embryonic neural tissue detected by an in vitro reporter assay." Development 116, no. 1 (September 1, 1992): 55–66. http://dx.doi.org/10.1242/dev.116.1.55.
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Retinoic acid and related retinoids have been suggested to contribute to the pattern of cell differentiation during vertebrate embryonic development. To identify cell groups that release morphogenetically active retinoids, we have developed a reporter assay that makes use of a retinoic acid inducible response element (RARE) to drive lacZ or luciferase reporter genes in stably transfected cell lines. This reporter gene assay allows detection of retinoids released from embryonic tissues over a range equivalent to that induced by femtomole amounts of retinoic acid. We have used this assay first to determine whether the floor plate, a cell group that has polarizing properties in neural tube and limb bud differentiation, is a local source of retinoids within the spinal cord. We have also examined whether the effects of exogenously administered retinoic acid on anteroposterior patterning of cells in the developing central nervous system correlate with differences in retinoid release from anterior and posterior neural tissue. We find that the release of morphogenetically active retinoids from the floor plate is only about 1.5-fold that of the dorsal spinal cord, which does not have neural tube or limb polarizing activity. These results suggest that the spatial distribution of retinoid release from spinal cord tissues differs from that of the neural and limb polarizing activity. This assay has also shown that retinoids are released from the embryonic spinal cord at much greater levels than from the forebrain. This result, together with previous observations that the development of forebrain structures is suppressed by low concentrations of retinoic acid, suggest that the normal development of forebrain structures is dependent on the maintenance of low concentrations of retinoids in anterior regions of the embryonic axis. This assay has also provided initial evidence that other embryonic tissues with polarizing properties in vivo release retinoids in vitro.
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Miller, WH Jr, A. Jakubowski, WP Tong, VA Miller, JR Rigas, F. Benedetti, GM Gill, JA Truglia, E. Ulm, and M. Shirley. "9-cis retinoic acid induces complete remission but does not reverse clinically acquired retinoid resistance in acute promyelocytic leukemia." Blood 85, no. 11 (June 1, 1995): 3021–27. http://dx.doi.org/10.1182/blood.v85.11.3021.bloodjournal85113021.
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9-cis retinoic acid (RA) is a high-affinity ligand for both retinoic acid receptors (RARs) and retinoid “X” receptors (RXRs). Although all-trans RA does not bind to RXRs, RAR/RXR heterodimers or RXR/RXR homodimers bind to specific DNA response elements and modulate proliferation and differentiation of normal and malignant cells. Because the development of clinical resistance to all-trans RA has been associated with a progressive decrease in plasma drug concentrations, we evaluated the ability of 9-cis RA to induce in vitro cytodifferentiation in subclones of a retinoid-sensitive and resistant APL cell line (NB4) and in short-term cultures of fresh leukemic cells aspirated from patients. We also evaluated the clinical activity and pharmacokinetics of 9-cis RA (LGD 1057) in patients with APL who were previously treated with all-trans RA. In vitro tests of both retinoid-sensitive NB4 cells, as well as samples of fresh cells from 11 patients with APL, showed relatively equivalent degrees of sensitivity to both 9-cis RA and all-trans RA at concentrations ranging from 10(-6) to 10(-8) mol/L; however, no substantial cytodifferentiation was observed using either drug alone or in combination (10(-6) mol/L of each) in retinoid-resistant NB4 cells. Seven patients with APL who had previously relapsed from a remission induced by all-trans RA were treated with 9-cis RA at daily oral doses ranging from 30 to 230 mg/m2. Pharmacokinetic studies showed that the mean terminal plasma half-life of 9-cis RA (1.3 hours) changed very little after several weeks of dosing, although the mean change per dose level in area under the plasma concentration x time curves and peak plasma concentrations showed a decrease by 49% and 45%, respectively. Peak plasma concentrations equaled or exceeded concentrations that were effective against retinoid-sensitive cells in vitro. Despite these favorable pharmacokinetic results, only one of the seven patients achieved complete remission, corroborating in vitro studies of blasts from three of the nonresponders that showed a relatively equivalent degree of resistance to both retinoids. Our results suggest that while 9-cis RA may not induce its own catabolism to the same degree as all-trans RA, this feature does not appear to overcome clinically acquired resistance to all-trans RA in APL. Nonetheless, the drug can induce complete remissions in patients with APL and may be useful for extended therapy in other diseases. Future studies should address the use of lower doses in patients who have not previously received retinoid therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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Olmedilla-Alonso, Begoña, Elena Rodríguez-Rodríguez, Beatriz Beltrán-de-Miguel, and Rocío Estévez-Santiago. "Dietary β-Cryptoxanthin and α-Carotene Have Greater Apparent Bioavailability Than β-Carotene in Subjects from Countries with Different Dietary Patterns." Nutrients 12, no. 9 (August 29, 2020): 2639. http://dx.doi.org/10.3390/nu12092639.
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β-carotene, α-carotene and β-cryptoxanthin are greater contributors to vitamin A intake than retinol in the human diet for most people around the world. Their contribution depends on several factors, including bioavailability and capacity of conversion into retinol. There is an increasing body of research showing that the use of retinol activity equivalents or retinol equivalents could lead to the underestimation of the contribution of β-cryptoxanthin and of α-carotene. The aim is to assess their apparent bioavailability by comparing concentrations in blood to their dietary intakes and identifying the major food contributors to their dietary intake. Dietary intake (3-day 24-h records) and serum concentrations (by HPLC) were calculated in normolipemic subjects with adequate retinol status (≥1.1 µmol/L) from our studies (n = 633) and apparent bioavailability calculated from 22 other studies (n = 29,700). Apparent bioavailability was calculated as the ratio of concentration in the blood to carotenoid intake. Apparent bioavailabilities for α-carotene and β-cryptoxanthin were compared to those for β-carotene. Eating comparable amounts of α-carotene, β-cryptoxanthin and β-carotene foods resulted in 55% greater α-carotene (95% CI 35, 90) and 686% higher β-cryptoxanthin (95% CI 556, 1016) concentrations than β-carotene in blood. This suggests differences in the apparent bioavailability of α-carotene and β-cryptoxanthin and even larger differences with β-cryptoxanthin, greater than that of β-carotene. Four fruits (tomato, orange, tangerine, red pepper) and two vegetables (carrot, spinach) are the main contributors to their dietary intake (>50%) in Europeans.
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Hoon, M. A., J. K. Northup, R. F. Margolskee, and N. J. P. Ryba. "Functional expression of the taste specific G-protein, α-gustducin." Biochemical Journal 309, no. 2 (July 15, 1995): 629–36. http://dx.doi.org/10.1042/bj3090629.
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The taste-specific G-protein alpha-subunit, alpha-gustducin, was expressed using a baculovirus based system. alpha-Gustducin was demonstrated to be myristoylated and was also palmitoylated in insect larval cells. Recombinant alpha-gustducin was purified to homogeneity. Neither receptors nor effectors that interact with gustducin in taste are known. However, alpha-gustducin has a close structural similarity to the visual G-protein, alpha-transducin. Therefore alpha-gustducin was reconstituted with components of the visual system to determine the degree of its functional similarity with alpha-transducin. Despite the fact that the sequences of alpha-gustducin and alpha-transducin share only 80% identity with each other, the interactions and functions of these two proteins were quantitatively identical. These included the interaction with receptor, bovine rhodopsin, with effector, bovine retinal cyclic GMP-phosphodiesterase, and with bovine brain and retinal G-protein beta gamma-heterodimers; receptor-catalysed GDP-GTP exchange and the intrinsic GTPase activity of alpha-gustducin and alpha-transducin were also identical. Gi alpha which is 70% identical with alpha-transducin interacts with different receptor and effector proteins and has very different guanine-nucleotide binding properties. Therefore, the functional equivalence of alpha-gustducin and alpha-transducin suggest that taste buds are likely to contain receptor and effector proteins that share many properties with their retinal equivalents.
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SILVA, RAQUEL B., EDVALDO V. SILVA-JÚNIOR, LAÍS C. RODRIGUES, LAISE H. C. ANDRADE, SUZENE I. DA SILVA, WOLFGANG HARAND, and ANTONIO F. M. OLIVEIRA. "A comparative study of nutritional composition and potential use of some underutilized tropical fruits of Arecaceae." Anais da Academia Brasileira de Ciências 87, no. 3 (July 28, 2015): 1701–9. http://dx.doi.org/10.1590/0001-3765201520140166.
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In this study, pulp and kernel of fruits from six Arecaceae species were subjected to proximate analysis, fatty acid composition and total carotenoid content analysis. The species with the highest carbohydrate, lipid and protein values were Ptychosperma macarthurii(70.1 g/100 g in the kernel), Syagrus cearensis(40.6 g/100 g in the kernel), andS. coronata(20.6 g/100 g in the pulp). The ash content ranged from 0.61 to 7.51 g/100 g. Lauric, palmitic, and oleic acids were the major fatty acids identified. The total carotenoid contents and retinol activity equivalents were highest in the Pinanga kuhlii (180.3 µg/g) andAcrocomia intumescens (138.0 µg/g) pulp oils. Retinol activity equivalents varied between the investigated species (456 to 1515 μg RAE/100 g). Native species such as A. intumescens, S. coronata, and S. cearensis are good sources of fresh food for the underserved populations that inhabit poorly developed areas such as the semi-arid region of Brazil. P. macarthurii, an exotic species, is an excellent source of ash and carotenoids, demonstrating its potential both as a food source and as bioactive compounds. Pulp and kernel ofA. intumescens,could be a good alternative feedstock for soap and biodiesel production, respectively.
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Nana, CP, ID Brouwer, NM Zagré, FJ Kok, and AS Traoré. "Impact of promotion of mango and liver as sources of vitamin A for young children: a pilot study in Burkina Faso." Public Health Nutrition 9, no. 6 (September 2006): 808–13. http://dx.doi.org/10.1079/phn2005911.
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AbstractObjectiveTo assess the effectiveness of a behaviour change approach, with or without financial support, in improving vitamin A (VA) intake and serum retinol concentration through mango and liver consumption by children.DesignA parallel design (no control area) was used to assess changes in VA intake and serum retinol over a 15-week period.Setting and subjectsA pilot study was implemented in the Department of Kokologho, a rural area in central west Burkina Faso. One hundred and fifty children aged 2–3 years were randomly selected and assigned to two treatment groups: PA$$ (promotional activities and financial support) and PA (promotional activities).ResultsThe intervention significantly increased (P<0.001) total VA intake by 56% in PA$$ and by 50% in PA. VA intake from liver increased significantly (P<0.001) from 12.7±23.5 to 155.3±56.3 μg retinol activity equivalents (RAE) in PA$$ and from 21.6±29.7 to 135.3±44.9 μg RAE in PA. Changes in VA intake from liver were significantly higher (P=0.004) in PA$$ compared with PA. Mean serum retinol concentration increased significantly by 26% (P<0.001) in PA$$ and 30% (P<0.001) in PA. Changes in serum retinol concentration (0.13 μmol l−1 in PA$$ vs. 0.17 μmol l−1 and in PA) did not differ significantly (P=0.455) between groups over the intervention.ConclusionPromotional activities on mango and liver intake effectively increased VA intake and serum retinol concentrations. Although an additional beneficial effect of financial support on liver intake was observed, this did not translate into a further increase in serum retinol concentration.
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Zmijewski, Michal A., Rajesh K. Sharma, and Andrzej T. Slominski. "Expression of molecular equivalent of hypothalamic–pituitary–adrenal axis in adult retinal pigment epithelium." Journal of Endocrinology 193, no. 1 (April 2007): 157–69. http://dx.doi.org/10.1677/joe.1.06927.
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We have investigated expression of molecular elements of the hypothalamic–pituitary–adrenal (HPA) axis in the human retinal pigment epithelium (RPE) cells. The presence of corticotropin-releasing factor (CRF); urocortins I, II and III; CRF receptor type 1 (CRFR1); POMC and prohormone convertases 1 and 2 (PC1 and PC2) mRNAs were shown by RT-PCR; the protein products were detected by ELISA, western blot or immunocytochemical methods in an ARPE-19 cell line derived from an adult human donor. CRFR2 was below the level of detectability. The CRFR1 was functional as evidenced by CRF stimulation of cAMP and inositol triphosphate production as well as by ligand induction of transcriptional activity of inducible cis-elements cAMP responsive element (CRE), activator protein 1 responsive element (AP-1) and POMC promoter) in ARPE-19 using luciferase reporter assay. Immunoreactivities representative of CRF, pre-urocortin, CRFR1 receptor and ACTH were also detected in mouse retina by in situ immunocytochemistry. Finally, using RT-PCR, we detected expression of genes encoding four key enzymes participating in steroids synthesis (CYP11A1, CYP11B1, CYP17 and CYP21A2) and showed transformation of progesterone into cortisol-immunoreactivity in cultured ARPE-19 cells. Therefore, we suggest that ocular tissue expresses CRF-driven signalling system that follows organisational structure of the HPA axis.
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Zagré, NM, F. Delpeuch, P. Traissac, and H. Delisle. "Red palm oil as a source of vitamin A for mothers and children: impact of a pilot project in Burkina Faso." Public Health Nutrition 6, no. 8 (December 2003): 733–42. http://dx.doi.org/10.1079/phn2003502.
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AbstractObjective:To demonstrate the effectiveness of the commercial introduction of red palm oil (RPO) as a source of vitamin A (VA) for mothers and children in a non-consuming area, as a dietary diversification strategy.Design:A pre–post intervention design (no control area) was used to assess changes in VA intake and status over a 24-month pilot project.Setting and subjects:The pilot project involved RPO promotion in 10 villages and an urban area in east-central Burkina Faso, targeting approximately 10?000 women and children aged < 5 years. A random sample of 210 mother–child (12–36-months-old) pairs was selected in seven out of the 11 pilot sites for the evaluation.Results:After 24 months, RPO was reportedly consumed by nearly 45% of mothers and children in the previous week. VA intake increased from 235 ± 23 μg retinol activity equivalents (RAE) to 655 ± 144 μg RAE in mothers (41 to 120% of safe intake level), and from 164 ± 14 μg RAE to 514 ± 77 μg RAE in children (36 to 97%). Rates of serum retinol < 0.70 μmoll−1 decreased from 61.8 ± 8.0% to 28.2 ± 11.0% in mothers, and from 84.5 ± 6.4% to 66.9 ± 11.2% in children. Those with a lower initial concentration of serum retinol showed a higher serum retinol response adjusted for VA intake.Conclusions:Commercial distribution of RPO was effective in reducing VA deficiency in the pilot sites. While it is promising as part of a national strategy, additional public health and food-based measures are needed to control VA malnutrition, which remained high in the RPO project area
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Gliem, Martin, Johannes Birtel, Philipp Herrmann, Rolf Fimmers, Moritz Berger, Christoph Coch, Almut Wingen, Frank G. Holz, and Peter Charbel Issa. "Aflibercept for choroidal neovascularizations secondary to pseudoxanthoma elasticum: a prospective study." Graefe's Archive for Clinical and Experimental Ophthalmology 258, no. 2 (December 20, 2019): 311–18. http://dx.doi.org/10.1007/s00417-019-04551-4.
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Abstract Purpose To evaluate the use of 2 mg intravitreal aflibercept for treatment of choroidal neovascularization (CNV) secondary to angioid streaks in patients with pseudoxanthoma elasticum (PXE). Methods In this 12-month prospective, open-label, uncontrolled, non-randomized interventional clinical trial, 15 PXE patients with CNV (mean age: 53 years, range 22–65) received one initial intravitreal injection of 2 mg aflibercept. Further injections were based on CNV activity at monthly examinations. The primary endpoint was change of best corrected visual acuity (BCVA) after 12 months. Secondary outcomes were change of central retinal thickness (CRT), leakage from CNV, retinal sensitivity, and vision-related quality of life. Results BCVA improved from 75.0 ± 10.8 (± SD, Snellen equivalent 20/32) to 79.3 ± 7.3 ETDRS letters (20/32) at final visit (p = 0.083). CRT decreased from 317 ± 81 to 279 ± 51 μm (p = 0.004). Retinal sensitivity on microperimetry changed from 17.8 ± 4.5 to 18.5 ± 4.3 dB (p = 0.103) and vision-related quality of life from a VQF-25 score of 80.7 ± 10.4 to 83.5 ± 14.5 (p = 0.554). The mean number of injections was 6.7 ± 2.6, and 5 participants had persistent or reactivated CNV activity at final visit. The observed adverse events were comparable with studies on aflibercept for other indications. Conclusion The results of this study indicate that intravitreal aflibercept is a treatment option for CNV secondary to PXE.
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Suzuki, D. A., and E. L. Keller. "The role of the posterior vermis of monkey cerebellum in smooth-pursuit eye movement control. II. Target velocity-related Purkinje cell activity." Journal of Neurophysiology 59, no. 1 (January 1, 1988): 19–40. http://dx.doi.org/10.1152/jn.1988.59.1.19.
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1. Purkinje cell activity was recorded from lobules VI and VII of the cerebellar vermis during the performance of visuooculomotor tasks designed to dissociate the signals related to head, smooth-pursuit eye, and retinal image movements. Task-related modulations in the simple spike discharge rates of 157 cells were observed in three alert monkeys. 2. Of 65 Purkinje cells that were completely tested for all three signals, all exhibited smooth-pursuit eye movement-related activity. An additional vestibular or visual response was observed in 17 and 11% of the cells, respectively. Eye, head, and retinal image velocity signals were all recorded in the same unit in 52% of the Purkinje cells. The responses of 5% of the fully tested cells were associated with changes in the direction of eye, head, and retinal image movement. 3. The observed sensorioculomotor responses were direction selective in 98% of the Purkinje cells. For the Purkinje cells that were fully tested, 60% of the cells exhibited peak discharge rates for ipsilateral and 40% for contralateral eye velocity. Of these Purkinje cells, 45% exhibited eye, head, and retinal image velocity signals with equivalent direction preferences. 4. Of 42 Purkinje cells tested, 88% demonstrated some kinds of interactive responses during combined eye and sensory stimulation. The interaction of eye and head velocity signals has been discussed in a companion paper (38). The modulation in discharge rate observed during tracking in the presence of a random dot background pattern could be predicted from the dissociated responses to smooth pursuit in the dark and to movements of the background pattern during suppression of eye movements. 5. The sensitivity to smooth-pursuit eye velocity averaged 1.4 times the sensitivity to head velocity. In 80% of the Purkinje cells, however, the sensitivity to eye velocity exceeded the sensitivity to head velocity by an average of only 10%. The sensitivity to smooth-pursuit eye velocity averaged 1.6 times the sensitivity to retinal image velocity. 6. An increase in Purkinje cell discharge rate was observed during the open-loop period of the initiation of smooth-pursuit eye movements. This open-loop response was consistent with the presence of a visual signal during ocular pursuit, since these cells were also shown to be responsive to a dissociated retinal image velocity signal. Furthermore, the magnitude of the open-loop response indicated an enhancement of the sensitivity to retinal image velocity when visual information became behaviorally significant.(ABSTRACT TRUNCATED AT 400 WORDS)
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Afolami, Ibukun, Martin N. Mwangi, Folake Samuel, Erick Boy, Paul Ilona, Elise F. Talsma, Edith Feskens, and Alida Melse-Boonstra. "Daily consumption of pro-vitamin A biofortified (yellow) cassava improves serum retinol concentrations in preschool children in Nigeria: a randomized controlled trial." American Journal of Clinical Nutrition 113, no. 1 (November 12, 2020): 221–31. http://dx.doi.org/10.1093/ajcn/nqaa290.
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ABSTRACT Background Vitamin A deficiency is a public health problem in sub-Saharan Africa. Pro-vitamin A biofortified (yellow) cassava has the potential to contribute significantly to improve vitamin A status, especially in populations that are difficult to reach with other strategies. Objectives The study aimed at determining the efficacy of biofortified cassava to improve vitamin A status of Nigerian preschool children. Methods An open-label randomized controlled trial was conducted in southwestern Nigeria. In total, 176 preschool children (aged 3–5 y) were randomized into 2 parallel arms comprising an experimental group (n = 88), fed foods prepared from biofortified (yellow) cassava, and a control group (n = 88), fed foods prepared from white cassava, twice a day, 6 d a week for 93 d. Results A total of 159 children completed the trial (yellow cassava group, n = 80; white cassava group, n = 79). Children consumed 221 and 74 µg/d retinol activity equivalents from intervention foods in the yellow and white cassava groups, respectively. The treatment effect on serum retinol concentrations at the end of the feeding trial was 0.06 µmol/L (95% CI: 0.004, 0.124 µmol/L), after adjustment for baseline retinol concentrations, inflammation, and asymptomatic malaria status. No significant treatment effects were detected for serum β-carotene (adjusted effect: 3.9%; 95% CI: −0.6%, 8.6%) and gut permeability (adjusted effect: 0.002; 95% CI: −0.089, 0.092), but a significant effect was detected for hemoglobin concentrations (adjusted effect: 3.08 g/L; 95% CI: 0.38, 5.78 g/L). Conclusions Daily consumption of β-carotene from biofortified cassava improved serum retinol and hemoglobin concentrations modestly in Nigerian preschool children. This study was registered with clinicaltrials.gov as NCT02627222.
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Raife, TJ, EM Demetroulis, and SR Lentz. "Regulation of thrombomodulin expression by all-trans retinoic acid and tumor necrosis factor-alpha: differential responses in keratinocytes and endothelial cells." Blood 88, no. 6 (September 15, 1996): 2043–49. http://dx.doi.org/10.1182/blood.v88.6.2043.bloodjournal8862043.
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Thrombomodulin is a cell-surface anticoagulant glycoprotein expressed by vascular endothelial cells and epidermal keratinocytes. Thrombomodulin expression in endothelial cells is regulated by retinoic acid and tumor necrosis factor-alpha (TNF), agents that also modulate epidermal differentiation. We examined thrombomodulin function and regulation of thrombomodulin expression by all-trans retinoic acid (ATRA) and TNF in human keratinocytes and endothelial cells. Untreated keratinocytes and endothelial cells expressed thrombomodulin of comparable activity and apparent thrombin affinity. Incubation of keratinocytes with 10 mumol/L ATRA for 24 hours increased thrombomodulin activity 5.4 +/- 0.9-fold (mean +/- SE), with equivalent increases observed in thrombomodulin protein (5.5 +/- 2.1-fold) and mRNA (4.2 +/- 1.2-fold). Incubation of keratinocytes with 1.0 nmol/L TNF markedly increased expression of keratinocyte transglutaminase, but had no effect on thrombomodulin activity, protein, or mRNA. In endothelial cells, ATRA produced a small increase in thrombomodulin activity (1.9 +/- 0.1-fold), and incubation with TNF for 24 hours decreased thrombomodulin activity 83% +/- 7%. The activity profile of keratinocyte thrombomodulin exhibited a distinct maximum near 1.0 mmol/L Ca2+. These results demonstrate that keratinocyte thrombomodulin is regulated by retinoids and Ca2+, but not by TNF, and that regulation of thrombomodulin expression differs in keratinocytes and endothelial cells.
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Engle-Stone, Reina, Jody Miller, Ame Stormer, Dolly Reario, Mario Capanzana, Carl Cabanilla, Jennifer Ford, Georg Lietz, and Marjorie Haskell. "Development of a Screening Tool to Estimate Vitamin A Intake and Comparison with Detailed Dietary Assessment Methods." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 182. http://dx.doi.org/10.1093/cdn/nzaa043_033.
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Abstract Objectives We aimed to develop and validate a tool to estimate vitamin A (VA) intake and identify children at risk of intake above the tolerable upper intake level (UL). Methods We developed, pilot-tested, and refined a screening tool to estimate VA intake among Filipino children 12–18 mo of age. Data were entered into tablets with pre-loaded food composition data to calculate VA intake immediately. The screening tool was used to identify children likely to have “adequate” (one group: 200–500 µg retinol activity equivalents, RAE/d) or “high” (two groups: >600 µg retinol/d) intake. Interviewers administered four 24-h recalls, one 12-h observed weighed record with 12-h recall, and a 30-d supplement questionnaire. Breastmilk intake and VA concentration were measured among breastfeeding children. We compared the screening tool and detailed dietary assessment (DDA) results for primary VA sources, group mean usual intake, and prevalence of intakes above the UL. Results Major VA sources were similar between methods: fortified milk powders, multivitamin supplements, and breastmilk; contributions from intervention programs (e.g., micronutrient powders, fortified staple foods) were low. Mean usual retinol intakes for the high groups (n = 47 and 39, respectively) were 1218 and 1313 µg/d by screening tool vs. 1096 and 931 by DDA; 70 and 77% had usual intake above 600 µg/d. In the adequate group (n = 37), mean total VA intake was 375 and 559 µg RAE/d by screening and DDA, respectively. Conclusions This screening tool provides a reasonably good rapid estimate of VA intake among Filipino children and can be useful for identifying groups with adequate to excessive intakes. Funding Sources Bill & Melinda Gates Foundation.
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Lee, Young-Jin, Letetia C. Jones, Nikolai A. Timchenko, Danilo Perrotti, Daniel G. Tenen, and Scott C. Kogan. "CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities." Blood 108, no. 7 (October 1, 2006): 2416–19. http://dx.doi.org/10.1182/blood-2006-02-003582.
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Abstract CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis. Dysregulation of these proteins likely contributes to the pathogenesis of myeloid disorders characterized by a block in granulopoiesis. In one such disease, acute promyelocytic leukemia (APL), a promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion protein is expressed as a result of a t(15;17) chromosomal translocation. Treatment of PML-RARα leukemic cells with all-trans retinoic acid (ATRA) causes them to differentiate into mature neutrophils, an effect thought to be mediated by C/EBPs. In this study, we assess the potential for cooperativity between increased C/EBP activity and ATRA therapy. We demonstrate that although both C/EBPα and C/EBPϵ can significantly prolong survival in a mouse model of APL, they are not functionally equivalent in this capacity. We also show that forced expression of C/EBPα or C/EBPϵ in combination with ATRA treatment has a synergistic effect on survival of leukemic mice compared with either therapy alone.
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Doyon, Christian, Réjean Fortin, and Philip A. Spear. "Retinoic acid hydroxylation and teratogenesis in lake sturgeon (Acipenser fulvescens) from the St. Lawrence River and Abitibi region, Quebec." Canadian Journal of Fisheries and Aquatic Sciences 56, no. 8 (August 1, 1999): 1428–36. http://dx.doi.org/10.1139/f99-086.
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All-trans-retinoic acid (RA) is an extremely active form of vitamin A; however, excessive or insufficient concentrations elicit anomalies including those associated with limb and craniofacial development. Lake sturgeon (Acipenser fulvescens) from the St. Lawrence River and tributaries were estimated to have a 2.9% incidence of fin and craniofacial malformations. Among larvae raised in artificial streams, a greater incidence of fin malformations (6.3%; p < 0.001) occurred in St. Lawrence River sturgeon compared with larvae from the Abitibi region. To test the hypothesis that the differences in rate of malformations may be associated with metabolic imbalances of RA, cytochrome P-450 dependent conversion to 4-hydroxyretinoic acid (4-OH-RA) was investigated. Optimal assay conditions are described for in vitro 4-OH-RA production in liver microsomes. Enzyme activity tended to decrease with increasing age and gonadal development in fish collected from Abitibi, but no statistically significant effects of sex, age, length, or gonadal development were discerned. The rate of 4-OH-RA formation was 3.5-fold greater (p < 0.0001) in the St. Lawrence sturgeon while the concentrations of cytochrome P-450 inducing PCBs (expressed as dioxin toxic equivalents) were 20-fold greater in a composite liver sample of the St. Lawrence sturgeon. Liver retinoid concentrations were negatively correlated (p < 0.0001) with RA hydroxylation rate. These results are consistent with the possibility that cytochrome P-450 dependent RA metabolism increased by chemical contaminants is associated with developmental anomalies in the St. Lawrence sturgeon.
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Tian, Ning, Thomas N. Hwang, and David R. Copenhagen. "Analysis of Excitatory and Inhibitory Spontaneous Synaptic Activity in Mouse Retinal Ganglion Cells." Journal of Neurophysiology 80, no. 3 (September 1, 1998): 1327–40. http://dx.doi.org/10.1152/jn.1998.80.3.1327.
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Tian, Ning, Thomas N. Hwang, and David R. Copenhagen. Analysis of excitatory and inhibitory spontaneous synaptic activity in mouse retinal ganglion cells. J. Neurophysiol. 80: 1327–1340, 1998. Spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs) were identified and characterized with whole cell and perforated patch voltage-clamp recordings in adult mouse retinal ganglion cells. Pharmacological dissection revealed that all cells were driven by spontaneous synaptic inputs mediated by glutamate and γ-aminobutyric acid-A (GABAA) receptors. One-half (7/14) of the cells also received glycinergic spontaneous synaptic inputs. Both GABAA and glycine receptor–mediated sIPSCs had rise times (10–90%) of <1 ms. The decay times of the GABAA receptor–mediated sIPSCs were comparable with those of the glycine receptor–mediated sIPSCs. The average decay time constant for monoexponentially fitted sIPSCs was 63.2 ± 74.1 ms (mean ± SD, n = 3278). Glutamate receptor–mediated sEPSCs had an average rise time of 0.50 ± 0.20 ms ( n = 109) and an average monoexponential decay time constant of 5.9 ± 8.6 ms ( n = 2705). Slightly more than two-thirds of the spontaneous synaptic events were monoexponential (68% for sIPSCs and 76% for sEPSCs). The remainder of the events was biexponential. The amplitudes of the spontaneous synaptic events were not correlated with rise times, suggesting that the electrotonic filtering properties of the neurons and/or differences in the spatial location of synaptic inputs could not account for the difference between the decay time constants of the glutamate and GABAA/glycine receptor–mediated spontaneous synaptic events. The amplitudes of sEPSCs were similar to those recorded in tetrodotoxin (TTX), consistent with the events measured in control saline being the response to the release of a single quantum of transmitter. The range of the sIPSC amplitudes in control saline was wider than that recorded in TTX, consistent with some sIPSCs being evoked by presynaptic spikes having an average quantal size greater than one. The rates of sIPSCs and sEPSCs were determined under equivalent conditions by recording with perforated patch electrodes at potentials at which both types of event could be identified. Two groups of ganglion cell were observed; one group had an average sEPSCs/sIPSCs frequency ratio of 0.96 ± 0.77 ( n = 28) and another group had an average ratio of 6.63 ± 0.82 ( n = 7). These findings suggest that a subset of cells is driven much more strongly by excitatory synaptic inputs. We propose that this subset of cells could be off ganglion cells, consistent with the higher frequency of spontaneous action potentials found in off ganglion cells in other studies.
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Michikawa, Takehiro, Shin Yamazaki, Makiko Sekiyama, Tatsuo Kuroda, Shoji F. Nakayama, Tomohiko Isobe, Yayoi Kobayashi, et al. "Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children’s Study." British Journal of Nutrition 122, no. 11 (November 4, 2019): 1295–302. http://dx.doi.org/10.1017/s0007114519002204.
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AbstractThe pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case–control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011–2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 μg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 μg/d). When we restricted to mothers with a prepregnancy BMI of 18·5–24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.
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Hurez, Vincent, Michel D. Kazatchkine, Tchavdar Vassilev, Sheela Ramanathan, Anastas Pashov, Bertrand Basuyaux, Yvonne de Kozak, Blanche Bellon, and Srini V. Kaveri. "Pooled Normal Human Polyspecific IgM Contains Neutralizing Anti-Idiotypes to IgG Autoantibodies of Autoimmune Patients and Protects From Experimental Autoimmune Disease." Blood 90, no. 10 (November 15, 1997): 4004–13. http://dx.doi.org/10.1182/blood.v90.10.4004.
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Abstract Normal human serum contains IgM antibodies that regulate the natural autoantibody activity of IgG in autologous serum. In the present study, we show that pooled normal human IgM (IVIgM) purified from plasma of more than 2,500 healthy donors and processed in a similar fashion to that of therapeutic preparations of pooled normal human IgG (IVIg) suppresses activity of IgG autoantibodies purified from the serum of patients with autoimmune diseases in vitro. The inhibitory effect of IVIgM was greater or equivalent to that of IVIg on a molar basis. We show that IVIgM contains anti-idiotypic antibodies directed against idiotypic determinants of autoantibodies, in particular by showing that Sepharose-bound IVIgM selectively retained F(ab′)2 fragments of IgG autoantibodies. The infusion of (Lewis × Brown-Norway) F1 rats with IVIgM protected the animals against experimental autoimmune uveitis induced by immunization with the soluble retinal S antigen, as evidenced by clinical scoring and histopathological analysis. The present findings provide a rationale for considering pooled IgM for immunomodulation of autoimmune disease.
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Xuefu, Liu, Zhao Gang, Tan Huisong, and Lu Fangjun. "Lithium Abundance and Activity for 57 Rs Cvn Systems." International Astronomical Union Colloquium 137 (1993): 657. http://dx.doi.org/10.1017/s0252921100018583.
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AbstractHigh-resolution (0.145A/diode, high signal-to-noise (> 100) Reticon spectra of 57 RS CVn systems, which were observed with the coudé spectrographs of the McDonald 2.1m telescope and Yunnan lm telescope, were used to analyse a correlation between Li abundance and chromospere activity. Li abundances of 57 RS CVn stars, which include 76 detected components have been determined through the determination of equivalent widths of Li doublet (6707.761A + 6707.912A) and Kuruz’s model atmosphere. The model metal abundance and line analysis of 10 RS CVn stars were determined from the present spectral lines data. The main results are the following: 1, Lithium abunances of 76 RS CVn components for 57 RS CVn systems are obviously reduced with the the effective temperatures gradually decreasing. 2, Li abundance has staistically decreasing trend in RS CVn stars with the rotational velocities vsini increasing. 2, The position of 168 RS CVn stars in the (U-B, B-V) Figure show that they can be devided into two groups. The most of them seem to be not poor-metal stars. Li abundances of these stars seem to have no obious correlations with their stellar chromosphery activity levels, but 7 RS CVn systems, in which cool component is more active show that the more active component has a lower Li abundance.
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Argyropoulou, O., E. Aissopou, A. Argyris, A. Goules, C. Mavragani, N. Tentolouris, P. Sfikakis, P. Vlachoyiannopoulos, A. Tzioufas, and A. Protogerou. "POS0807 RETINAL VESSEL CALIBERS AS A NON-INVASIVE BIOMARKER OF INFLAMMATORY BURDEN IN PRIMARY SYSTEMIC VASCULITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 656.1–656. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1950.
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Background:Primary Systemic Vasculitides (PSV) constitute a heterogeneous group of rare and potentially life-threatening autoimmune diseases, characterized by a varying degree of inflammatory response, leading to local or generalized vascular disease. Vessel involvement accounts for the micro- and macrovascular complications of the disease, along with the classic risk factors including, among others age and chronic use of steroids (1). Early identification of high-risk patients for cardiovascular disease (CVD) development and the contribution of inflammation towards this adverse outcome are still unmet needs. Alterations of retinal microcirculation have been independently associated with increased CVD risk in the general population (2). The potential changes of retinal vasculature and their association with disease activity and the magnitude of inflammation have not been studied in PSV so far.Objectives:To explore the effect of disease activity and inflammation on retinal microcirculation in PSV, classified according to vessel size as large, medium or small vessel vasculitides (LVV, MVV or SVV respectively), and polymyalgia rheumatica (PMR) without vasculitis.Methods:Fifty-nine patients, 43 with active disease [30 active vasculitis (12 LVV, 4 MVV, 14 SVV) and 13 PMR] and 16 with chronic inactive disease (13 vasculitis, 3 PMR) were studied. All patients were matched at 1:1 ratio with 59 controls, without underlying autoimmune/autoinflammatory disorder, neoplasia or infection, according to age, gender, CVD history, BMI, smoking, arterial hypertension, dyslipidemia, diabetes mellitus and treatment related to comorbidities. A total of 32 rheumatoid arthritis (RA) patients with mild to moderate inflammatory component as defined by standard of care acute phase reactants (ESR and CRP) and 16 chronic RA patients with normal ESR and CRP levels, matched 1:1 according to all the above parameters with 32 active and 16 inactive vasculitis/PMR patients respectively, served as disease controls. Digital retinal images were obtained and retinal vessel calibers were measured with a validated software to determine central retinal arteriolar and venular equivalents ratio (CRAE and CRVE respectively). For 16 patients with active vasculitis/PMR, retinal examination was performed in two time points (baseline and ≤ 6 months later).Results:In the overall population, patients with active Vasculitis/PMR had increased CRVE (213.8±21.7 vs 201.3±17.1, p<0.001) and CRAE (180.0±19.2 vs 164.1±17.5 p<0.001) compared to healthy controls. Separating patients according to disease type, we found that in LVV, MVV and PMR, CRAE (p≤0.05) and CRVE (p<0.05) were increased compared to control group, while in SVV only CRAE was increased (p<0.001). Interestingly, chronic patients with disease in remission displayed higher CRAE compared to matched controls (179.8±17.2 vs 169.1±11.1, p=0.006). After immunosuppressive treatment for ≤ 6 months CRVE and to a lesser extent CRAE were reduced (p=0.048 and 0.149 respectively) with a stronger statistical significance found in the Vasculitis group (p=0.026 and 0.069 respectively). Pearson’s linear correlation coefficient in active disease state (at baseline examination) revealed positive bivariate correlation only between CRVE with ESR and CRP. Patients with Vasculitis/PMR had also increased CRAE when compared to RA patients in both active and inactive disease status (182.8±19.4 vs 170.1±18.4, p<0.001 and 179.8±17.2 vs 166.3±17.9, p=0.005 respectively).Conclusion:Systemic inflammation alters retinal microcirculation in both a reversible (venules) and irreversible (arterioles) way, independently of PSV form. Thus, common disease specific pathogenetic mechanisms related to inflammation may be implicated in vascular remodeling. Sequential follow-up of PSV patients will address whether retinal vessel calibers may serve as a biomarker of disease activity and CVD development.References:[1]Argyropoulou OD et al. Curr Opin Rheumatol 2017.[2]Shaohua G et al. Current Atherosclerosis reports 2020.Disclosure of Interests:None declared
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Samuels, Ivy S., Brent A. Bell, Ariane Pereira, Joseph Saxon, and Neal S. Peachey. "Early retinal pigment epithelium dysfunction is concomitant with hyperglycemia in mouse models of type 1 and type 2 diabetes." Journal of Neurophysiology 113, no. 4 (February 15, 2015): 1085–99. http://dx.doi.org/10.1152/jn.00761.2014.
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In the diabetic retina, cellular changes in the retinal pigment epithelium (RPE) and neurons occur before vision loss or diabetic retinopathy can be identified clinically. The precise etiologies of retinal pathology are poorly defined, and it remains unclear if the onset and progression of cellular dysfunction differ between type 1 and type 2 diabetes. Three mouse models were used to compare the time course of RPE involvement in type 1 and type 2 diabetes. C57BL/6J mice injected with streptozotocin (STZ mice) modeled type 1 diabetes, whereas Lepr db/db mice on both BKS and B6.BKS background strains modeled type 2 diabetes. Electroretinogram (ERG)-based techniques were used to measure light-evoked responses of the RPE (direct current-coupled ERG, dc-ERG) and the neural retina (a-wave, b-wave). Following onset of hyperglycemia, a-wave and b-wave amplitudes of STZ mice declined progressively and by equivalent degrees. Components of the dc-ERG were also altered, with the largest reduction seen in the c-wave. Lepr db/db mice on the BKS strain (BKS.Lepr) displayed sustained hyperglycemia and a small increase in insulin, whereas Lepr db/db mice on the B6.BKS background (B6.BKS.Lepr) were transiently hyperglycemic and displayed severe hyperinsulinemia. BKS.Lepr mice exhibited sustained reductions in the dc-ERG c-wave, fast oscillation, and off response that were not attributable to reduced photoreceptor activity; B6.BKS.Lepr mice displayed transient reductions in the c-wave and fast oscillation that correlated with hyperglycemia and magnitude of photoreceptor activity. In summary, all mouse models displayed altered RPE function concomitant with the onset of hyperglycemia. These results suggest that RPE function is directly reduced by elevated blood glucose levels. That RPE dysfunction was reversible and mitigated in hyperinsulinemic B6.BKS.Lepr mice provides insight into the underlying mechanism.
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MITRA, PRATIP, and ROBERT F. MILLER. "Normal and rebound impulse firing in retinal ganglion cells." Visual Neuroscience 24, no. 1 (January 2007): 79–90. http://dx.doi.org/10.1017/s0952523807070101.
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Given that the action potential output of retinal ganglion cells (RGCs) determines the nature of the visual information that is transmitted from the retina, an understanding of their intrinsic impulse firing characteristics is critical for an appreciation of the overall processing of visual information. Recordings from RGCs within an isolated whole-mount retina preparation showed that their normal impulse firing from the resting membrane potential (RMP) was linearly correlated in its frequency with the stimulus intensity. In addition to describing the relationship between the magnitude of the current injection and the resulting impulse frequency (F/I relationship), we have characterized the properties of individual action potentials when they are elicited from the RMP. In contrast, hyperpolarizing below the RMP revealed that RGCs displayed a time dependent anomalous rectification, manifested by the appearance of a depolarizing sag in their voltage response. When an adequate period of hyperpolarization was terminated, a fast phasic period of “rebound excitation” was observed, characterized by a brief phasic burst of impulse activity. When compared to equivalent action potential firing evoked by depolarizing from the RMP, rebound spiking was associated with a lower threshold and shorter latency for impulse activation as well as a prominent, phasic, burst-like doublet, or triplet of impulses. The rebound action potential had a more positive voltage overshoot and displayed a higher peak rate of rise in its upstroke than those correspondingly generated by depolarizing current pulses from the RMP. Blocking sodium spikes with TTX confirmed that the preceding hyperpolarization led to the recruitment and subsequent generation of a transient depolarizing voltage overshoot, which we have termed the net depolarizing overshoot (NDO). We propose that the NDO boosts the generation of sodium spikes by triggering rebound spikes on its upstroke and crest, thus accounting for the observed voltage dependent change in the firing pattern of RGCs.
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Gallemore, R. P., E. Hernandez, R. Tayyanipour, S. Fujii, and R. H. Steinberg. "Basolateral membrane Cl- and K+ conductances of the dark-adapted chick retinal pigment epithelium." Journal of Neurophysiology 70, no. 4 (October 1, 1993): 1656–68. http://dx.doi.org/10.1152/jn.1993.70.4.1656.
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1. We characterized the basolateral membrane Cl- and K+ conductances of the dark-adapted chick neural retina-retinal pigment epithelium (RPE)-choroid preparation. Conventional microelectrodes were used to measure apical (V(ap)) and basolateral (Vba) membrane voltage, and double-barreled Cl- and K+ selective microelectrodes were used to follow the time course and magnitude of ion concentration changes outside the basolateral (basal) membrane. 2. In response to a fivefold decrease in basal [Cl-]o, Vba rapidly depolarized by 6.4 +/- 0.7 (SE) mV, and the apparent resistance of the basolateral membrane (Rba) increased. The Cl- channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) suppressed the Vba depolarization by 40% and blocked the Rba increase. Estimates of the relative Cl- conductance (transference number, TCl) from the DIDS-sensitive component of the Cl- diffusion potential gave an average value for TCl of 0.22 +/- 0.03. 3. Further evidence for a Cl- conductance was obtained by measuring changes in intracellular Cl- activity (aCli) induced by transtissue current. Depolarizing Vba elevated aiCl, whereas hyperpolarizing Vba had the opposite effect, consistent with conductive Cl- movement across the basal membrane. TCl estimated from these data averaged 0.23 +/- 0.02. 4. In response to a sixfold increase in basal [K+]o, Vba depolarized 6.1 +/- 0.8 mV. The amplitude of this K+ diffusion potential was inhibited 44 and 67% by 5 and 10 mM Ba2+, respectively. TK was estimated to be 0.61 +/- 0.05. 5. The rapid c-wave membrane hyperpolarizations in response to the light-evoked decrease in subretinal [K+]o were used to calculate the equivalent resistances of the apical membrane (R(ap)), basolateral membrane (Rba), and the paracellular shunt pathway (Rs). They were 152 +/- 10, 615 +/- 38, and 138 +/- 7 omega.cm2 (n = 11 tissues), respectively. From these data the equivalent electromotive force for the basal (Eba) and apical (Eap) membranes were estimated to be -45 +/- 2 and -77 +/- 1 mV, respectively. This estimate of Eba is in the range of that predicted from our estimates of TCl and TK, indicating that, in the dark-adapted chick retina, the resting conductance of the basal membrane can largely be accounted for by the Cl- and K+ conductances described here.
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da Fonseca, María, and Inés Samengo. "Statistical Properties of Color Matching Functions." Neural Computation 33, no. 9 (August 19, 2021): 2578–601. http://dx.doi.org/10.1162/neco_a_01421.
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Abstract In trichromats, color vision entails the projection of an infinite-dimensional space (the one containing all possible electromagnetic power spectra) onto the three-dimensional space that modulates the activity of the three types of cones. This drastic reduction in dimensionality gives rise to metamerism, that is, the perceptual chromatic equivalence between two different light spectra. The classes of equivalence of metamerism are revealed by color-matching experiments in which observers adjust the intensity of three monochromatic light beams of three preset wavelengths (the primaries) to produce a mixture that is perceptually equal to a given monochromatic target stimulus. Here we use the linear relation between the color matching functions and the absorption probabilities of each type of cone to find particularly useful triplets of primaries. As a second goal, we also derive an analytical description of the trial-to-trial variability and the correlations of color matching functions stemming from Poissonian noise in photon capture. We analyze how the statistical properties of the responses to color-matching experiments vary with the retinal composition and the wavelengths of peak absorption probability, and compare them with experimental data on subject-to-subject variability obtained previously.
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Garcia, Ada L., Corinna Koebnick, Peter C. Dagnelie, Carola Strassner, Ibrahim Elmadfa, Norbert Katz, Claus Leitzmann, and Ingrid Hoffmann. "Long-term strict raw food diet is associated with favourable plasma β-carotene and low plasma lycopene concentrations in Germans." British Journal of Nutrition 99, no. 6 (June 2008): 1293–300. http://dx.doi.org/10.1017/s0007114507868486.
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Dietary carotenoids are associated with a reduced risk of chronic diseases. Raw food diets are predominantly plant-based diets that are practised with the intention of preventing chronic diseases by virtue of their high content of beneficial nutritive substances such as carotenoids. However, the benefit of a long-term adherence to these diets is controversial since little is known about their adequacy. Therefore, we investigated vitamin A and carotenoid status and related food sources in raw food diet adherents in Germany. Dietary vitamin A, carotenoid intake, plasma retinol and plasma carotenoids were determined in 198 (ninety-two male and 106 female) strict raw food diet adherents in a cross-sectional study. Raw food diet adherents consumed on average 95 weight% of their total food intake as raw food (approximately 1800 g/d), mainly fruits. Raw food diet adherents had an intake of 1301 retinol activity equivalents/d and 16·7 mg/d carotenoids. Plasma vitamin A status was normal in 82 % of the subjects ( ≥ 1·05 μmol/l) and 63 % had β-carotene concentrations associated with chronic disease prevention ( ≥ 0·88 μmol/l). In 77 % of subjects the lycopene status was below the reference values for average healthy populations ( < 0·45 μmol/l). Fat contained in fruits, vegetables and nuts and oil consumption was a significant dietary determinant of plasma carotenoid concentrations (β-carotene r 0·284; P < 0·05; lycopene r 0·168; P = 0·024). Long-term raw food diet adherents showed normal vitamin A status and achieve favourable plasma β-carotene concentrations as recommended for chronic disease prevention, but showed low plasma lycopene levels. Plasma carotenoids in raw food adherents are predicted mainly by fat intake.
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Coleman, P. A., and R. F. Miller. "Measurement of passive membrane parameters with whole-cell recording from neurons in the intact amphibian retina." Journal of Neurophysiology 61, no. 1 (January 1, 1989): 218–30. http://dx.doi.org/10.1152/jn.1989.61.1.218.
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1. Whole-cell recordings have been obtained from intact, photoactive retinal neurons using patch-clamp electrodes in the amphibian superfused retina eyecup preparation. 2. After removal of the vitreous humor from the surface of the retina, using a collagenase with low tryptic activity, high-resistance seals (1-10 G omega) could be formed between the patch pipette and the cell membrane by applying mild suction to the pipette. Additional suction broke the membrane patch and provided continuity between the low-resistance pipette and the interior of the neuron. 3. Measurements of input resistance and time constant were obtained from bipolar, amacrine, and ganglion cells. Assuming the membrane capacitance was 1 microF/cm2, time constant data were used to derive the specific membrane resistance. The average specific membrane resistance for the inner retinal neurons in our sample was 68,000 omega.cm2. 4. Analysis of the charging curve induced by a brief current pulse applied to the soma was used to analyze the average electrotonic length of dendrites. The charging curves of some ganglion cells were well represented by a single exponential, suggesting that they were essentially isopotential. 5. The voltage decay along an equivalent cylinder model of a ganglion cell was calculated, using the experimentally obtained values of membrane resistance to compute decay of steady-state voltages along the dendritic tree. The calculations indicate that with the high membrane resistance values implied by this study, the electrotonic length of dendritic cables were short, and there may be relatively little attenuation of the synaptic potentials irrespective of their location along the dendritic tree.
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Chandra, Rosita D., Chandra A. Siswanti, Monika N. U. Prihastyanti, Heriyanto, Leenawaty Limantara, and Tatas H. P. Brotosudarmo. "Evaluating Provitamin A Carotenoids and Polar Metabolite Compositions during the Ripening Stages of the Agung Semeru Banana (Musa paradisiaca L. AAB)." International Journal of Food Science 2020 (May 12, 2020): 1–9. http://dx.doi.org/10.1155/2020/8503923.
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Banana cultivars that are rich in provitamin A carotenoids and other nutrients may offer a potential food source to help alleviate vitamin A deficiencies, particularly in developing countries. The local plantain type banana, Agung Semeru (Musa paradisiaca L.), was investigated, in order to analyse the changes in the compositions of the provitamin A carotenoids and metabolite compounds, including the amino acids, organic acids, and sugars, during the ripening stage as this banana is widely processed for food products in either the unripe, ripe, or overripe stages. The bananas that had reached the desired ripening stages were subjected to high-performance liquid chromatography (HPLC) analysis, and the results indicated that the total provitamin A carotenoid concentrations ranged between 4748.83 μg/100 g dry weight (dw) and 7330.40 μg/100 g dw, with the highest level of vitamin A activity at 457.33±5.18 μg retinol activity equivalents (RAE)/100 g dw. Compared to the Cavendish variety, which is consumed worldwide, the Agung Semeru banana had vitamin A activity that was 40 to 90 times higher, dependent on the stage of ripening. The breakdown of the starch during the ripening stages resulted in an increase of its sugar compounds, such as sucrose, fructose, and glucose, as well as its dominant organic acids, such as malic acid, oxalic acid, and citric acid, which were observed using gas chromatography-mass spectrometry (GC-MS) during the ripening stages. The findings of this study show that the Agung Semeru banana is a promising fruit that could be widely produced as a nutritional and energy food resource, due to its high levels of vitamin A activity and sugars.
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Laforest, L., C. W. Brown, G. Poleo, J. Geraudie, M. Tada, M. Ekker, and M. A. Akimenko. "Involvement of the sonic hedgehog, patched 1 and bmp2 genes in patterning of the zebrafish dermal fin rays." Development 125, no. 21 (November 1, 1998): 4175–84. http://dx.doi.org/10.1242/dev.125.21.4175.
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The signaling molecule encoded by Sonic hedgehog (shh) participates in the patterning of several embryonic structures including limbs. During early fin development in zebrafish, a subset of cells in the posterior margin of pectoral fin buds express shh. We have shown that regulation of shh in pectoral fin buds is consistent with a role in mediating the activity of a structure analogous to the zone of polarizing activity (ZPA) (Akimenko and Ekker (1995) Dev. Biol. 170, 243–247). During growth of the bony rays of both paired and unpaired fins, and during fin regeneration, there does not seem to be a region equivalent to the ZPA and one would predict that shh would play a different role, if any, during these processes specific to fish fins. We have examined the expression of shh in the developing fins of 4-week old larvae and in regenerating fins of adults. A subset of cells in the basal layer of the epidermis in close proximity to the newly formed dermal bone structures of the fin rays, the lepidotrichia, express shh, and ptc1 which is thought to encode the receptor of the SHH signal. The expression domain of ptc1 is broader than that of shh and adjacent blastemal cells releasing the dermal bone matrix also express ptc1. Further observations indicate that the bmp2 gene, in addition to being expressed in the same cells of the basal layer of the epidermis as shh, is also expressed in a subset of the ptc1-expressing cells of the blastema. Amputations of caudal fins immediately after the first branching point of the lepidotrichia, and global administration of all-trans-retinoic acid, two procedures known to cause fusion of adjacent rays, result in a transient decrease in the expression of shh, ptc1 and bmp2. The effects of retinoic acid on shh expression occur within minutes after the onset of treatment suggesting direct regulation of shh by retinoic acid. These observations suggest a role for shh, ptc1 and bmp2 in patterning of the dermoskeleton of developing and regenerating teleost fins.
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Kitareewan, S., L. T. Burka, K. B. Tomer, C. E. Parker, L. J. Deterding, R. D. Stevens, B. M. Forman, et al. "Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR." Molecular Biology of the Cell 7, no. 8 (August 1996): 1153–66. http://dx.doi.org/10.1091/mbc.7.8.1153.
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RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways.
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Fohlmeister, J. F., and R. F. Miller. "Mechanisms by Which Cell Geometry Controls Repetitive Impulse Firing in Retinal Ganglion Cells." Journal of Neurophysiology 78, no. 4 (October 1, 1997): 1948–64. http://dx.doi.org/10.1152/jn.1997.78.4.1948.
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Fohlmeister, J. F. and R. F. Miller. Mechanisms by which cell geometry controls repetitive impulse firing in retinal ganglion cells. J. Neurophysiol. 78: 1948–1964, 1997. Models for generating repetitive impulse activity were developed based on multicompartmental representations of ganglion cell morphology in the amphibian retina. Each model includes five nonlinear ion channels and one linear (leakage) channel. Compartmental distribution of ion channel type and density was designed to simulate whole cell recording experiments carried out in the intact retina-eyecup preparation. Correspondence between the model and physiology emphasized channel-specific details in the impulse waveform, based on phase plot analysis, frequency versus current (F/I) properties, and interspike trajectories for current injected into the soma, as well as the ability to conduct impulses in both orthodromic and antidromic directions. Two general types of model are developed, including equivalent cylinder representations and more realistic compartmentalizations of dendritic morphology. These multicompartmental models include representations for dendritic trees, soma, axon hillock, a thin axonal segment, and axon distal to thin segment. A large number of compartments (≤800) representing a single neuron were employed to ensure that maximum voltage differences between neighboring compartments during the steepest rates of change of membrane potential were acceptably small. Leakage conductance varied from 3 to 8 μS/cm2. The results establish that intercompartmental currents, due to inhomogeneous morphology, dominate membrane currents in the interspike intervals and thus play a major role in determining the impulse spacing and the information carried by impulse trains. Variations in input resistance are far less important than the degree to which ion channels are present in the dendritic compartments for the regulation of F/I properties. Cell geometry, including the thin axonal segment, places significant constraints on the location of ion channels required to support impulse initiation and propagation in both the ortho- and antidromic directions. The site of impulse initiation varies greatly and depends on the stimulus magnitude. Models that conform to physiological constraints also show irregular firing, particularly for near threshold stimulation of the soma, due to multiple sites of impulse initiation. Such behavior could represent an asset to the cells for conveying information under conditions of low contrast stimulation. Multiple spike initiation zones also can provide retinal ganglion cells with a variety of response characteristics, including spike doublets, depending on the level of cell activation. Increasing the diameter of the dendritic equivalent cylinder reduces the impulse frequency (F/I) response. Over a restricted range of ion channel densities in the dendritic tree, phase locking between dendritic membrane oscillations and somatic spiking can occur with dendritic stimulation, and mathematical chaos can be demonstrated when sufficiently thin dendritic processes are present. We conclude that cell morphology is the primary factor in determining firing patterns and the impulse frequency response of a given cell and that differences in channel density distribution across a population of cells plays, at most, a secondary role in this function. This conclusion applies to both synaptic activation and electrode stimulation of the soma.
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Koréissi-Dembélé, Yara, Esmee L. Doets, Nadia Fanou-Fogny, Paul JM Hulshof, Diego Moretti, and Inge D. Brouwer. "Comparing intake estimations based on food composition data with chemical analysis in Malian women." Public Health Nutrition 20, no. 8 (February 8, 2017): 1351–61. http://dx.doi.org/10.1017/s1368980017000015.
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AbstractObjectiveFood composition databases are essential for estimating nutrient intakes in food consumption surveys. The present study aimed to evaluate the Mali food composition database (TACAM) for assessing intakes of energy and selected nutrients at population level.DesignWeighed food records and duplicate portions of all foods consumed during one day were collected. Intakes of energy, protein, fat, available carbohydrates, dietary fibre, Ca, Fe, Zn and vitamin A were assessed by: (i) estimating the nutrient intake from weighed food records based on an adjusted TACAM (a-TACAM); and (ii) chemical analysis of the duplicate portions. Agreement between the two methods was determined using the Wilcoxon signed-rank test and Bland–Altman plots.SettingBamako, Mali.SubjectsApparently healthy non-pregnant, non-lactating women (n36) aged 15–36 years.ResultsCorrelation coefficients between estimated and analysed values ranged from 0·38 to 0·61. At population level, mean estimated and analysed nutrient intakes differed significantly for carbohydrates (203·0v. 243·5 g/d), Fe (9·9v. 22·8 mg/d) and vitamin A (356v. 246 µg retinol activity equivalents). At individual level, all estimated and analysed nutrient intakes differed significantly; the differences tended to increase with higher intakes.ConclusionsThe a-TACAM is sufficiently acceptable for measuring average intakes of macronutrients, Ca and Zn at population level in low-intake populations, but not for carbohydrate, vitamin A and Fe intakes, and nutrient densities.
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Jaeschke, H., and A. Farhood. "Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver." American Journal of Physiology-Gastrointestinal and Liver Physiology 260, no. 3 (March 1, 1991): G355—G362. http://dx.doi.org/10.1152/ajpgi.1991.260.3.g355.
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The hypothesis that Kupffer cells and infiltrating neutrophils generate reactive oxygen in the hepatic sinusoids and may contribute to ischemia-reperfusion injury in the liver was investigated in a model of partial no-flow ischemia and reperfusion in male Fischer rats in vivo. During the reperfusion period of 60 min, plasma concentrations of glutathione disulfide (GSSG; index of oxidant stress) increased from 1.62 +/- 0.20 microM glutathione (GSH) equivalents to maximal values of 11.82 +/- 1.45 (45 min ischemia), 24.19 +/- 2.35 (60 min ischemia), and 70.20 +/- 7.8 (120 min ischemia). The basal tissue GSSG content in the postischemic lobes (0.19 +/- 0.02 nmol GSH eq/mg protein) increased by 50-100%. Although the number of neutrophils in liver and lung increased by 3- to 10-fold during reperfusion, there was no positive correlation between the number of neutrophils and the GSSG concentrations measured in plasma or tissue. However, activation of Kupffer cells with high doses of retinol or with Propionibacterium acnes significantly enhanced plasma GSSG levels, while inactivation of Kupffer cells with methyl palmitate or gadolinium chloride significantly attenuated the increase of plasma GSSG. Inactivation of Kupffer cells protected the liver significantly against ischemia-reperfusion injury. It is concluded that Kupffer cells are the predominant source of reactive oxygen formed during the initial reperfusion period and that Kupffer cell activity (including reactive oxygen formation) contributes to reperfusion injury in the liver in vivo.
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Dokucu, M. E., S. L. Zipursky, and R. L. Cagan. "Atonal, rough and the resolution of proneural clusters in the developing Drosophila retina." Development 122, no. 12 (December 1, 1996): 4139–47. http://dx.doi.org/10.1242/dev.122.12.4139.
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In the developing Drosophila retina, the proneural gene for photoreceptor neurons is atonal, a basic helix-loop-helix transcription factor. Using atonal as a marker for proneural maturation, we examine the stepwise resolution of proneural clusters during the initiation of ommatidial differentiation in the developing eye disc. In addition, evidence is provided that atonal is negatively regulated by rough, a homeobox-containing transcription factor expressed exclusively in the retina. This interaction leads to the refinement of proneural clusters to specify R8, the first neuron to emerge in the retinal neuroepithelium. Ectopic expression of atonal or removal of rough results in the transformation of a discrete ‘equivalence group’ of cells into R8s. In addition, ectopic expression of rough blocks atonal expression and proneural cluster formation within the morphogenetic furrow. Thus, rough provides retina-specific regulation to the more general atonal-mediated proneural differentiation pathway. The opposing roles of atonal and rough are not mediated through the Notch pathway, as their expression remains complementary when Notch activity is reduced. These observations suggest that homeobox-containing genes can provide tissue-specific regulation to bHLH factors.