Studies on the riboflavin, pantothenic acid, nicotinic acid and choline requirements of young Embden geese

USGS Publications Warehouse

Serafin, J.A.

1981-01-01

Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.

Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

PubMed

Ishii, Kiyoko; Komaki, Hirofumi; Ohkuma, Aya; Nishino, Ichizo; Nonaka, Ikuya; Sasaki, Masayuki

2010-09-01

We report an adolescent case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by intermittent nausea and depressive state as early symptoms. At the age of 12 years and 11 months, the patient experienced intermittent nausea and vomiting, and depressive state. She was on medication for depression for 5 months but it was ineffective. Brain magnetic resonance imaging showed disseminated high-intensity areas in the periventricular white matter and in the splenium of the corpus callosum on T2-weighted images and fluid-attenuated inversion-recovery images. Progressive muscle weakness occurred and blood creatine kinase level was found to be elevated. The muscle biopsy revealed lipid storage myopathy. Urine organic acid analysis and mutation analysis of the ETFDH gene confirmed the diagnosis of MADD. With oral supplements of riboflavin and l-carnitine, in addition to a high-calorie and reduced-fat diet, her clinical symptoms improved dramatically. Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. Copyright 2009 Elsevier B.V. All rights reserved.

Involvement of riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of riboflavin in mice.

PubMed

Yao, Yoshiaki; Yonezawa, Atsushi; Yoshimatsu, Hiroki; Omura, Tomohiro; Masuda, Satohiro; Matsubara, Kazuo

2013-08-15

Riboflavin (vitamin B2) acts as an intermediary during various biochemical oxidation-reduction reactions in the liver. Hepatic riboflavin homeostasis is suggested to be maintained through its transporter(s). Riboflavin transporters, RFVT2/Slc52a2 and RFVT3/Slc52a3, have been identified in rodents. However, the role of each RFVT in the hepatic homeostasis of riboflavin has not yet been fully clarified. In this study, we assessed the contribution of each RFVT to riboflavin uptake into the liver using in vitro and in vivo studies. The uptake of riboflavin by mouse primary hepatocytes increased in a time-dependent and a concentration-dependent manner. Riboflavin transport was independent of extracellular Na(+). However, the uptake decreased slightly along with the extracellular pH increases. Real-time PCR analysis revealed that the mRNA level of Slc52a2, or coding for mouse (m)RFVT2, in the mouse liver was 10 times higher than that of Slc52a3 (coding for mRFVT3). The uptake of riboflavin at pH 7.4 by primary hepatocytes was significantly decreased by the transfection of Slc52a2-small interfering RNA (siRNA), but not Slc52a3-siRNA. Furthermore, we also confirmed the contribution of riboflavin transporters in vivo. The riboflavin concentrations in plasma, but not in the liver, were significantly decreased in mice fed on a riboflavin-deficient diet for 8 weeks. The expression of Slc52a2 mRNA was significantly upregulated by riboflavin deprivation. These results strongly suggest that mRFVT2 was involved in hepatic riboflavin homeostasis. © 2013 Elsevier B.V. All rights reserved.

Mitochondrial oxidative metabolism during respiratory infection in riboflavin deficient mice.

PubMed

Brijlal, S; Lakshmi, A V; Bamji, M S

1999-12-01

Studies in children and mice have shown that respiratory infection alters riboflavin metabolism, resulting in increased urinary loss of this vitamin. This could be due to mobilization of riboflavin from the liver to blood because liver Flavin adenine dinucleotide (FAD) levels were lowered in the mice during infection. To understand the functional implications of lowered hepatic FAD levels during respiratory infection, flavoprotein functions such as oxidative phosphorylation and beta-oxidation of the liver mitochondria were examined during infection in mice. Weanling mice were fed either riboflavin-restricted or control diet for 18 days and then injected with a sublethal dose of Klebsiella pneumoniae. During infection, the state 3 respiratory rate with palmitoyl-L-carnitine and glutamate were significantly lowered (27-29%) in the riboflavin-restricted group, whereas in the control group 10% reduction was observed with palmitoyl-L-carnitine as substrate. A 22% reduction in the respiratory control ratio with palmitoyl-L-carnitine as substrate was observed during infection in the riboflavin-restricted group. The beta-oxidation of palmitoyl-L-carnitine was significantly lowered (29%) in the riboflavin-restricted infected group. The results of the study suggest that the effects of infection on vital physiologic functions were more pronounced in the riboflavin-restricted mice than in the control mice. (c) Elsevier Science Inc. 1999.

Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency.

PubMed

Cornelius, Nanna; Frerman, Frank E; Corydon, Thomas J; Palmfeldt, Johan; Bross, Peter; Gregersen, Niels; Olsen, Rikke K J

2012-08-01

Riboflavin-responsive forms of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) have been known for years, but with presumed defects in the formation of the flavin adenine dinucleotide (FAD) co-factor rather than genetic defects of electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). It was only recently established that a number of RR-MADD patients carry genetic defects in ETF-QO and that the well-documented clinical efficacy of riboflavin treatment may be based on a chaperone effect that can compensate for inherited folding defects of ETF-QO. In the present study, we investigate the molecular mechanisms and the genotype-phenotype relationships for the riboflavin responsiveness in MADD, using a human HEK-293 cell expression system. We studied the influence of riboflavin and temperature on the steady-state level and the activity of variant ETF-QO proteins identified in patients with RR-MADD, or non- and partially responsive MADD. Our results showed that variant ETF-QO proteins associated with non- and partially responsive MADD caused severe misfolding of ETF-QO variant proteins when cultured in media with supplemented concentrations of riboflavin. In contrast, variant ETF-QO proteins associated with RR-MADD caused milder folding defects when cultured at the same conditions. Decreased thermal stability of the variants showed that FAD does not completely correct the structural defects induced by the variation. This may cause leakage of electrons and increased reactive oxygen species, as reflected by increased amounts of cellular peroxide production in HEK-293 cells expressing the variant ETF-QO proteins. Finally, we found indications of prolonged association of variant ETF-QO protein with the Hsp60 chaperonin in the mitochondrial matrix, supporting indications of folding defects in the variant ETF-QO proteins.

Effects of methodological variation on assessment of riboflavin status using the erythrocyte glutathione reductase activation coefficient assay.

PubMed

Hill, Marilyn H E; Bradley, Angela; Mushtaq, Sohail; Williams, Elizabeth A; Powers, Hilary J

2009-07-01

Riboflavin status is usually measured as the in vitro stimulation with flavin adenine dinucleotide of the erythrocyte enzyme glutathione reductase, and expressed as an erythrocyte glutathione reductase activation coefficient (EGRAC). This method is used for the National Diet and Nutrition Surveys (NDNS) of the UK. In the period between the 1990 and 2003 surveys of UK adults, the estimated prevalence of riboflavin deficiency, expressed as an EGRAC value > or = 1.30, increased from 2 to 46 % in males and from 1 to 34 % in females. We hypothesised that subtle but important differences in the detail of the methodology between the two NDNS accounted for this difference. We carried out an evaluation of the performance of the methods used in the two NDNS and compared against an 'in-house' method, using blood samples collected from a riboflavin intervention study. Results indicated that the method used for the 1990 NDNS gave a significantly lower mean EGRAC value than both the 2003 NDNS method and the 'in-house' method (P < 0.0001). The key differences between the methods relate to the concentration of FAD used in the assay and the duration of the period of incubation of FAD with enzyme. The details of the EGRAC method should be standardised for use in different laboratories and over time. Additionally, it is proposed that consideration be given to re-evaluating the basis of the EGRAC threshold for riboflavin deficiency.

Inhibition of riboflavin metabolism in rat tissues by chlorpromazine, imipramine, and amitriptyline.

PubMed

Pinto, J; Huang, Y P; Rivlin, R S

1981-05-01

Prompted by recognition of the similar structures of riboflavin (vitamin B(2)), phenothiazine drugs, and tricyclic antidepressants, our studies sought to determine effects of drugs of these two types upon the conversion of riboflavin into its active coenzyme derivative, flavin adenine dinucleotide (FAD) in rat tissues. Chlorpromazine, a phenothiazine derivative, and imipramine and amitriptyline, both tricyclic antidepressants, each inhibited the incorporation of [(14)C]riboflavin into [(14)C]FAD in liver, cerebrum, cerebellum, and heart. A variety of psychoactive drugs structurally unrelated to riboflavin were ineffective. Chlorpromazine, imipramine, and amitriptyline in vitro inhibited hepatic flavokinase, the first of two enzymes in the conversion of riboflavin to FAD. Evidence was obtained that chlorpromazine administration for a 3- or 7-wk period at doses comparable on a weight basis to those used clinically has significant effects upon riboflavin metabolism in the animal as a whole: (a) the activity coefficient of erythrocyte glutathione reductase, an FAD-containing enzyme used as an index of riboflavin status physiologically, was elevated, a finding compatible with a deficiency state, (b) the urinary excretion of riboflavin was more than twice that of age- and sex-matched pair-fed control rats, and (c) after administration of chlorpromazine for a 7-wk period, tissue levels of flavin mononucleotide and FAD were significantly lower than those of pair-fed littermates, despite consumption of a diet estimated to contain 30 times the recommended dietary allowance. The present study suggests that certain psychotropic drugs interfere with riboflavin metabolism at least in part by inhibiting the conversion of riboflavin to its coenzyme derivatives, and that as a consequence of such inhibition, the overall utilization of the vitamin is impaired.

Riboflavin Responsive Mitochondrial Dysfunction in Neurodegenerative Diseases

PubMed Central

Udhayabanu, Tamilarasan; Manole, Andreea; Rajeshwari, Mohan; Varalakshmi, Perumal; Houlden, Henry; Ashokkumar, Balasubramaniem

2017-01-01

Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on biologically active flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN), which are derived from the dietary component riboflavin, a water soluble vitamin. Riboflavin regulates the structure and function of flavoenzymes through its cofactors FMN and FAD and, thus, protects the cells from oxidative stress and apoptosis. Hence, it is not surprising that any disturbance in riboflavin metabolism and absorption of this vitamin may have consequences on cellular FAD and FMN levels, resulting in mitochondrial dysfunction by reduced energy levels, leading to riboflavin associated disorders, like cataracts, neurodegenerative and cardiovascular diseases, etc. Furthermore, mutations in either nuclear or mitochondrial DNA encoding for flavoenzymes and flavin transporters significantly contribute to the development of various neurological disorders. Moreover, recent studies have evidenced that riboflavin supplementation remarkably improved the clinical symptoms, as well as the biochemical abnormalities, in patients with neuronopathies, like Brown-Vialetto-Van-Laere syndrome (BVVLS) and Fazio-Londe disease. This review presents an updated outlook on the cellular and molecular mechanisms of neurodegenerative disorders in which riboflavin deficiency leads to dysfunction in mitochondrial energy metabolism, and also highlights the significance of riboflavin supplementation in aforementioned disease conditions. Thus, the outcome of this critical assessment may exemplify a new avenue to enhance the understanding of possible mechanisms in the progression of neurodegenerative diseases and may provide new rational approaches of disease surveillance and treatment. PMID:28475111

Pyridoxal-5'-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients.

PubMed

Molina-López, Jorge; Florea, Daniela; Quintero-Osso, Bartolomé; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Del Pozo, Elena Planells

2016-06-01

Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of pyridoxal-5'-phosphate decreasing their body reserves. This study was designed to assess the nutritional pyridoxal-5'-phosphate status in critical care patients with systemic inflammatory response syndrome, comparing them with a group of healthy people, and studying it's association with factors involved in the pyridoxine and other B vitamins metabolism, as the total antioxidant capacity and Hcy as cardiovascular risk biomarker. Prospective, multicentre, comparative, observational and analytic study. One hundred and three critically ill patients from different hospitals, and eighty four healthy subjects from Granada, Spain, all with informed consent. Data from daily nutritional assessment, ICU severity scores, clinical and nutritional parameters, antioxidant status and homocysteine levels was taken at admission and at the seventh day of the ICU stay. Thiamine, riboflavin, pyridoxine and folate status proved deficient in a large number of patients, being significantly lower in comparison with control group, and significantly decreased at 7th day of ICU stay. Higher homocysteine was observed in patients compared with control group (p < 0.05) where 31.5 and 26.8 percent of subjects presented hyperhomocysteinemia at initial and final of study, respectively. Antioxidant status was lower than control group in two periods analysed, and decreased at 7th day of ICU stay (p < 0.05) being associated with PLP deficiency. PLP deficiency was also correlated with hyperhomocysteinemia at two times measured (r. -0.73, p < 0.001; r. -0.69, p < 0.001, respectively), showing at day 7 an odds ratio of 6.62 in our multivariate model. Critically ill patients with SIRS show deficient B vitamin and low antioxidant statuses. Despite association found between PLP deficiency and low antioxidant status in critically ill patients, PLP deficiency was only associated with hyperhomocysteinemia regardless of antioxidant, riboflavin, cobalamine, and folate statuses in critically ill patients with SIRS at seventh day of ICU stay. PLP deficient patients presented about six times more risk of cardiovascular disease than non deficients. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

FAD-induced in vitro activation of glutathione reductase in the lens of B2 deficient rats.

PubMed

Ono, S; Hirano, H

1984-04-01

We studied the FAD-induced in vitro stimulation of lenticular glutathione reductase in riboflavin-deficient rats. The stimulatory effect of FAD on lenticular glutathione reductase in rats fed a B2-deficient diet for 4 weeks was remarkably higher than in paired control rats fed a B2-supplemented basal diet and control rats had ad libitum access to a B2-supplemented basal diet. The in vitro FAD stimulation effect on rat lenticular glutathione reductase represents a sensitive indicator of the B2 deficient status.

Pathophysiology of motor dysfunction in a childhood motor neuron disease caused by mutations in the riboflavin transporter.

PubMed

Menezes, Manoj P; Farrar, Michelle A; Webster, Richard; Antony, Jayne; O'Brien, Katherine; Ouvrier, Robert; Kiernan, Matthew C; Burns, Joshua; Vucic, Steve

2016-01-01

Brown-Vialetto-Van Laere (BVVL) syndrome is a progressive motor and sensory neuronopathy secondary to mutations in SLC52A2 encoding the riboflavin transporter type 2 (RFVT2). The phenotype is characterized by early childhood onset hearing loss and sensory ataxia followed by progressive upper limb weakness, optic atrophy, bulbar weakness and respiratory failure. To gain further insight into disease pathophysiology and response to riboflavin supplementation, the present study investigated whether axonal ion channel or membrane abnormalities were a feature of BVVL. Axonal excitability studies and clinical assessments were prospectively undertaken on six patients with BVVL secondary to riboflavin transporter deficiency type 2 (age range 10-21 years) at baseline and after 12 months of riboflavin (1000 mg daily) therapy. At baseline, depolarizing and hyperpolarizing threshold electrotonus was 'fanned out' and superexcitability was increased, while the resting current-threshold gradient and refractoriness were significantly reduced in BVVL patients when compared to controls. Mathematical modeling suggested that functional alterations of myelin underlay these findings with an increase in myelin permeability. Riboflavin therapy resulted in partial normalization of the axonal excitability findings, paralleled by maintenance of muscle strength. The present study established that abnormalities in myelin permeability at the paranode was a feature of BVVL and were partially normalized with riboflavin therapy. This study reveals a novel pathophysiological process for motor nerve dysfunction in BVVL. It also indicates that nerve excitability studies may be further developed in larger cohorts as a potential biomarker to identify treatment response for BVVL patients. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

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

Dutta, P.; Siegel, L.; Pinto, J.

This laboratory has previously demonstrated that imipramine (IM) and amitriptyline (AM), inhibit the conversion of riboflavin to its coenzymic derivatives. Several other laboratories have shown that dietary riboflavin deficiency is protective against malarial infection. In the present investigation, the authors determined whether IM and AM exert antimalarial effects similar to that of riboflavin deficiency, as they have hypothesized. In addition, they evaluated whether these drugs, like other antimalarial agents, increase the hemolytic response to ferriprotoporphyrin IX (FP). The growth of P. falciparum (FCR3) in the absence or presence of these drugs (80 ..mu..M) was measured by incubating parasitized erythrocytes formore » 48 h in RPMI 1640 medium. Parasitemia was determined by counting erythrocyte smears and monitoring (/sup 3/H)hypoxanthine uptake. With no drug, parasitemia was 20.3 +/- 5.3%, whereas in the presence of IM and AM, parasitemia was reduced to 7.3 +/- 0.8% and 13.6 +/- 2.8%, respectively. The uptake of (/sup 3/H)hypoxanthine was reduced to 47 +/- 3.6% and 54 +/- 2.9% of control by IM and AM, respectively. Assays of hemolysis were conducted by incubating 0.5% RBC suspension in NaCl-Tris buffer for 3 h at 37/sup 0/C with variable concentrations of drugs and/or FP (1-7 ..mu..M). Both drugs at 10 to 100 ..mu..M significantly enhanced hemolysis induced by FP. No hemolysis by these drugs was detected in the absence of FP. It is concluded that the tricyclic antidepressants, IM and AM, possess substantial antimalarial properties, thereby supporting the hypothesis that drugs which interfere with riboflavin metabolism should also provide protection against malaria.« less

Etiology of Anemia Among Infants, School-Aged Children, and Young Non-Pregnant Women in Different Settings of South-Central Côte d'Ivoire

PubMed Central

Righetti, Aurélie A.; Koua, Ahou-Yah G.; Adiossan, Lukas G.; Glinz, Dominik; Hurrell, Richard F.; N'Goran, Eliézer K.; Niamké, Sébastien; Wegmüller, Rita; Utzinger, Jürg

2012-01-01

Anemia affects one-quarter of the world's population, but its etiology remains poorly understood. We determined the prevalence of anemia and studied underlying risk factors in infants (6–23 months), young school-aged children (6–8 years), and young non-pregnant women (15–25 years) in south-central Côte d'Ivoire. Blood, stool, and urine samples were subjected to standardized, quality-controlled methods. We found high prevalence of anemia, malaria, inflammation, and deficiencies of iron, riboflavin, and vitamin A but low prevalence and intensities of soil-transmitted helminth and schistosome infections. Multivariate regression analysis revealed significant associations between anemia and Plasmodium falciparum for infants, inflammation for school-aged children, and cellular iron deficiency for both school-aged children and non-pregnant women. Women with riboflavin deficiency had significantly lower odds of anemia. Our findings call for interventions to protect infants from malaria, improved intake of dietary iron, better access to health care, and health education. PMID:22848097

Genetics Home Reference: riboflavin transporter deficiency neuronopathy

MedlinePlus

... Epub 2004 Dec 15. Citation on PubMed Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib ... JR, Megarbane A, Urtizberea JA, Hernandez DG, Foley AR, Arepalli S, Pandraud A, Simón-Sánchez J, Clayton P, ...

Physical and intellectual development in Philippine children fed five different dietary staples.

PubMed

Guzman, V B; Guthrie, H A; Guthrie, G M

1976-11-01

Assessments of dietary intake, intelligence, physical growth, and clinical signs of malnutrition were made on 600 children from five Philippine communities. Five boys and five girls each at ages 8,9, and 10 from poor and less poor families drawn from town and rural schools in each community were examined. Dietary staples were rice, fish, corn, coconuts, and sweet potatoes, respectively, at the five sites. Analyses of variance indicated marked differences among communities in nutrient intake based on 24-hr recall, in intellectual and anthropometric measures and in clinical signs of malnutrition. There were few significant F ratios for urban-rural residence, socioeconomic status, sec, or age. There were positive correlations of approximately 0.20 between intake of calories and carbohydrates and intelligence; between calories and carbohydrates and anthropometric measures; and between intelligence and anthropometric measures. Clinical signs in the eye and on the skin showed low correlations of about-0.20 with dietary intake of protein, fat, thiamin, and riboflavin but not with vitamin A. In all communities energy intake was low reflecting limited fat consumption. Where rice or corn was the staple, thiamin and riboflavin were also frequent deficiencies; with fish, ascorbic acid; with sweet potatoes and coconuts, calcium, riboflavin, and thiamin. A very high incidence of eye changes, suggestive of a vitamin A deficiency, was found even where vitamin A intake seemed adequate.

Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency.

PubMed

Olsen, Rikke K J; Koňaříková, Eliška; Giancaspero, Teresa A; Mosegaard, Signe; Boczonadi, Veronika; Mataković, Lavinija; Veauville-Merllié, Alice; Terrile, Caterina; Schwarzmayr, Thomas; Haack, Tobias B; Auranen, Mari; Leone, Piero; Galluccio, Michele; Imbard, Apolline; Gutierrez-Rios, Purificacion; Palmfeldt, Johan; Graf, Elisabeth; Vianey-Saban, Christine; Oppenheim, Marcus; Schiff, Manuel; Pichard, Samia; Rigal, Odile; Pyle, Angela; Chinnery, Patrick F; Konstantopoulou, Vassiliki; Möslinger, Dorothea; Feichtinger, René G; Talim, Beril; Topaloglu, Haluk; Coskun, Turgay; Gucer, Safak; Botta, Annalisa; Pegoraro, Elena; Malena, Adriana; Vergani, Lodovica; Mazzà, Daniela; Zollino, Marcella; Ghezzi, Daniele; Acquaviva, Cecile; Tyni, Tiina; Boneh, Avihu; Meitinger, Thomas; Strom, Tim M; Gregersen, Niels; Mayr, Johannes A; Horvath, Rita; Barile, Maria; Prokisch, Holger

2016-06-02

Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Vitamins and oral contraceptive use.

PubMed

Wynn, V

1975-03-08

Reports concerning the interaction between steroidal contraceptives (the combined pill) and vitamins indicate that in users the mean serum-vitamin-A level is raised and the mean serum-vitamin-B2 (riboflavine), vitamin-B6 (pyridoxine), vitamine-C, folic-acid, and vitamin-B12 levels are reduced. Other vitamins have been insufficiently studied for comment. Biochemical evidence of co-enzyme deficiency has been reported for vitamin B2, vitamin B6, and folic acid. Clinical effects due to vitamin deficiency have been described for vitamin B6--namely, depression and impaired glucose tolerance. Folic-acid deficiency with megaloblastic anaemia has been reported in only 21 cases.

Biofortification of riboflavin and folate in idli batter, based on fermented cereal and pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655.

PubMed

Chandrasekar Rajendran, S C; Chamlagain, B; Kariluoto, S; Piironen, V; Saris, P E J

2017-06-01

Lactococcus lactis N8 and Saccharomyces boulardii SAA655 were investigated for their ability to synthesize B-vitamins (riboflavin and folate) and their functional role as microbial starters in idli fermentation. In this study, ultra-high performance liquid chromatography and microbiological assay were used to determine the total riboflavin and folate content respectively. Increased levels of folate were evident in both L. lactis N8 and S. boulardii SAA655 cultivated medium. Enhanced riboflavin levels were found only in S. boulardii SAA655 grown medium, whereas decreased riboflavin level was found in L. lactis N8 cultivated medium. To evaluate the functional role of microbial starter strains, L. lactis N8 and S. boulardii SAA655 were incorporated individually and in combination into idli batter, composed of wet grounded rice and black gram. For the experiments, naturally fermented idli batter was considered as control. The results indicated that natural idli fermentation did not enhance the riboflavin level and depleted folate levels by half. In comparison with control, L. lactis N8 and S. boulardii SAA655 incorporated idli batter (individually and in combination) increased riboflavin and folate levels by 40-90%. Apart from compensating the folate loss caused by natural fermentation, S. boulardii SAA655 fermented idli batter individually and in combination with L. lactis N8 also showed the highest leavening character. Moreover, the microbial starter incorporation did not significantly influence the pH of idli batter. Incorporation of L. lactis N8 and S. boulardii SAA655 can evidently enhance the functional and technological characteristics of idli batter. UN General Assembly declared 2016 the International Year of pulses emphasizing the importance of legumes as staple food. Furthermore, this is the first experimental report of in situ biofortifcation of riboflavin and folate using microbes in pulse based fermented staple food. The current study suggests possible avenues for research towards an economical strategy to reduce B-vitamin deficiency among the consuming population. © 2017 The Society for Applied Microbiology.

The relationship between maternal nutritional status and spontaneous abortion.

PubMed

Neela, J; Raman, L

1997-01-01

The incidence of pregnancy wastage is high among poor women. Though the aetiology of spontaneous abortion is multifactorial, nutritional deficiency is considered to be an important contributory factor. A case-control study was conducted to assess the relationship between maternal vitamin status and spontaneous abortion. The incidence of anaemia (15%), and riboflavin (84%) and folate deficiency (24.5%) were similar among the cases and controls. Vitamin A levels were higher in the study group compared to those in controls. The results suggest that various nutrient deficiencies have no correlation with the occurrence of spontaneous abortion. The role of increased vitamin A levels needs to be studied further.

Feeding the vegan infant and child.

PubMed

Truesdell, D D; Acosta, P B

1985-07-01

Nutrients that may be deficient in diets of vegetarian infants and preschoolers and that affect growth and development are energy, protein, calcium, iron, zinc, riboflavin, and vitamins B-12 and D. Reasons for these nutrient deficiencies include: limited volumetric capacity of the stomach of infants, toddlers, and preschoolers; low-caloric-density foods eaten by vegans; limited food choices; and restriction of number of meals and snacks eaten by vegan children. Suggestions are made for meeting the energy and nutrient needs of infants and children within the food ways of their families.

The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives.

PubMed

Bosch, Annet M; Stroek, Kevin; Abeling, Nico G; Waterham, Hans R; Ijlst, Lodewijk; Wanders, Ronald J A

2012-10-29

The Brown-Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months.

The Brown-Vialetto-Van Laere and Fazio Londe syndrome revisited: natural history, genetics, treatment and future perspectives

PubMed Central

2012-01-01

The Brown-Vialetto-Van Laere syndrome is a rare neurological disorder which may present at all ages with sensorineural deafness, bulbar palsy and respiratory compromise. Fazio-Londe syndrome is considered to be the same disease entity. Recently it was demonstrated that in some patients the disease is caused by mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter. In these patients riboflavin deficiency is the cause of the BVVL/FL syndrome and supplementation of riboflavin proved a life saving treatment. Mutations in the SLC52A2 gene and the SLC52A1 (GPR172B) gene, coding for human riboflavin transporters hRFT3 and hRFT1 have been associated with the BVVL syndrome as well. We performed a review of the literature, with emphasis on the natural history and the effects of treatment in these patients. A total of 35 publications were traced reporting on the clinical presentation of 74 patients who presented before age 18. The most prevalent symptoms were bulbar palsy, hearing loss, facial weakness and respiratory compromise. Death was reported in 28 of the 61 untreated patients, with a very low survival in patients presenting before age 4. All 13 patients who were treated with riboflavin survived, with a strong clinical improvement after days to months of treatment in eight patients. Three patients demonstrated a stable clinical course and treatment was stopped early in two patients. Abnormalities in plasma flavin levels and/or plasma acylcarnitine profiles were observed in some but not in all patients, and also patients with normal plasma flavin levels and acylcarnitine profiles demonstrated a striking clinical improvement on riboflavin supplementation. It is now clear that proper diagnosis requires mutation analysis of all three transporter genes and treatment should be started immediately without first awaiting results of molecular analysis. Clinical improvement may be rapid or gradual over a period of more than 12 months. PMID:23107375

Vitamin B-12 in breast milk and diet, and riboflavin in breastmilk, are very low in Kenyan lactating women, although vitamin B-6 is sufficient.

USDA-ARS?s Scientific Manuscript database

Background: Breastmilk B-vitamin concentrations can fluctuate with maternal intake. Low maternal intake of B-vitamins may result in low B-vitamin breastmilk concentrations and consequently B-vitamin deficiency in their infants because infants 0–6 months are recommended to be exclusively breastfed. T...

Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure: An Observational Study.

PubMed

McKeag, Nicholas A; McKinley, Michelle C; Harbinson, Mark T; McGinty, Ann; Neville, Charlotte E; Woodside, Jayne V; McKeown, Pascal P

Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status. The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure. Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion. More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration <50 nmol/L) was observed in 75.6% of patients. Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.

Effect of iodine status and other nutritional factors on psychomotor and cognitive performance of Filipino schoolchildren.

PubMed

Amarra, Ma Sofia V; Bongga, Demetria C; Peñano-Ho, Leticia; Cruz, Federico B; Solis, José S; Barrios, Erniel B

2007-03-01

Until 1998, iodine deficiency was a public health problem in the Philippines. A law entitled "An Act Promoting Salt Iodization Nationwide" (ASIN) has been passed and implemented by the government to eliminate iodine deficiency. The contribution of salt iodization, as well as dietary, health, and environmental factors, to improving the intellectual performance of Filipino schoolchildren remains to be determined. The objectives of the study were to determine the relationship between iodine status and levels of psychomotor and cognitive performance in first-grade children aged 6 to 10 years, and to examine the extent to which dietary, biochemical, health, and environmental factors contribute to children's mental performance. Two hundred ninety children in six classroom sections from a public school in Manila were examined by measurement of urinary iodine excretion (UIE) and thyroid palpation. The median UIE level for each section was determined. Sixty-five children classified as iodine deficient (UIE < 90 microg/L with grade 1 goiter, n = 34) and non-iodine deficient (UIE > 100 microg/L without goiter, n = 31) were given psychomotor and cognitive function tests (Bender-Gestalt and Raven's Colored Progressive Matrices). Scores from the two tests were used to determine each child's general ability percentile rank. Other variables examined were dietary intake (% RDA of nutrients ingested based on two nonconsecutive 24-hour recalls); deficiencies in iron, vitamin A, and selenium; parasitic infection; coliform contamination of drinking water; household use of iodized salt; illness in the past 2 weeks; and wasting and stunting. Children whose general ability scores were at or above the 50th percentile had higher UIE levels, but the relationship was not significant. Children from sections with higher median UIE levels had higher percentile ranks for general ability (p = .002). Backward logistic regression showed that the variance in deficient and adequate mental performance was explained by dietary intakes that met > or = 80% of the RDA for energy, protein, thiamin, and riboflavin; the use of iodized salt; child's iodine status; and stunting (R2 = .520, p = .0016). Higher class median UIE was associated with better psychomotor and cognitive performance in children who were tested. Factors that contributed to better performance include higher intakes of energy, protein, thiamin, and riboflavin; household use of iodized salt; normal iodine status; and absence of stunting or chronic malnutrition. Salt iodization, accompanied by adequate intakes of energy, protein, and foods rich in thiamin and riboflavin, can contribute to improved mental performance in Filipino schoolchildren. Longer-term factors that can contribute to improved performance are achievement of normal iodine status and elimination of protein-energy malnutrition.

Drug-nutrient interaction.

PubMed

Matsui, M S; Rozovski, S J

1982-01-01

The effect of certain drugs on nutrient metabolism is discussed. Antituberculotic drugs such as INH and cycloserine interfere with vitamin B6 metabolism and may produce a secondary niacin deficiency. Oral contraceptives interfere with the metabolism of folic acid and ascorbic acid, and in cases of deficient nutrition, they also seem to interfere with riboflavin. Anticonvulsants can act as folate antagonists and precipitate folic acid deficiency. Therefore, in some cases, supplementation with folate has been recommended simultaneously with anticonvulsant therapy. Cholestyramine therapy has been associated with malabsorption of vitamins; several reports suggest that cholestyramine affects absorption of the fat-soluble vitamins K and D and, in addition, may alter water-soluble vitamins, including folic acid. The study of the interaction of drugs and nutrients is an area that deserves a greater attention in the future, especially in groups where nutrient deficiencies may be prevalent.

SLC52A3, A Brown–Vialetto–van Laere syndrome candidate gene is essential for mouse development, but dispensable for motor neuron differentiation

PubMed Central

Intoh, Atsushi; Suzuki, Naoki; Koszka, Kathryn; Eggan, Kevin

2016-01-01

Riboflavin, also known as vitamin B2, is essential for cellular reduction-oxidation reactions, but is not readily synthesized by mammalian cells. It has been proposed that riboflavin absorption occurs through solute carrier family 52 members (SLC52) A1, A2 and A3. These transporters are also candidate genes for the childhood onset-neural degenerative syndrome Brown–Vialetto–Van Laere (BVVL). Although riboflavin is an essential nutrient, why mutations in its transporters result in a neural cell-specific disorder remains unclear. Here, we provide evidence that Slc52a3 is the mouse ortholog of SLC52A3 and show that Slc52a3 deficiency results in early embryonic lethality. Loss of mutant embryos was associated with both defects in placental formation and increased rates of apoptosis in embryonic cells. In contrast, Slc52a3 −/− embryonic stem cell lines could be readily established and differentiated into motor neurons, suggesting that this transporter is dispensable for neural differentiation and short-term maintenance. Consistent with this finding, examination of Slc52a3 gene products in adult tissues revealed expression in the testis and intestine but little or none in the brain and spinal cord. Our results suggest that BVVL patients with SCL52A3 mutations may be good candidates for riboflavin replacement therapy and suggests that either the mutations these individuals carry are hypomorphic, or that in these cases alternative transporters act during human embryogenesis to allow full-term development. PMID:26976849

[Influence wheat bran on organism vitamin (experiment on rats)].

PubMed

Beketova, N A; Kodentsova, V M; Vrzhesinskaia, O A; Kosheleva, O V; Pereverzeva, O G; Isaeva, V A; Pozdniakov, A L

2011-01-01

The inclusion of wheat bran (at a dose of 2,3 and 4,6% of the dry weight) in the semi-synthetic diet of rats under combined deficiency of vitamins (20 and 50% of the adequate level) did not have a significant effect on vitamins C, B1 and B2 liver levels, riboflavin blood plasma level, and thiamine and riboflavin urinary excretion. The consumption of bran in high dose has been accompanied by a decrease of retinol blood plasma level on 19-28% but it has no effect on liver retinol palmitate content. Bran intake in both doses resulted in a deterioration of rats sufficiency with vitamin E, which had been confirmed by a simultaneous significant decrease of blood plasma alpha-tocopherol concentration on 31-40%, and its liver level on 23-43%. The results obtained indicate the advisability of vitamin E enrichment of diets with a high content of dietary fiber.

Histoplasma capsulatum Depends on De Novo Vitamin Biosynthesis for Intraphagosomal Proliferation

PubMed Central

Garfoot, Andrew L.; Zemska, Olga

2014-01-01

During infection of the mammalian host, Histoplasma capsulatum yeasts survive and reside within macrophages of the immune system. Whereas some intracellular pathogens escape into the host cytosol, Histoplasma yeasts remain within the macrophage phagosome. This intracellular Histoplasma-containing compartment imposes nutritional challenges for yeast growth and replication. We identified and annotated vitamin synthesis pathways encoded in the Histoplasma genome and confirmed by growth in minimal medium that Histoplasma yeasts can synthesize all essential vitamins with the exception of thiamine. Riboflavin, pantothenate, and biotin auxotrophs of Histoplasma were generated to probe whether these vitamins are available to intracellular yeasts. Disruption of the RIB2 gene (riboflavin biosynthesis) prevented growth and proliferation of yeasts in macrophages and severely attenuated Histoplasma virulence in a murine model of respiratory histoplasmosis. Rib2-deficient yeasts were not cleared from lung tissue but persisted, consistent with functional survival mechanisms but inability to replicate in vivo. In addition, depletion of Pan6 (pantothenate biosynthesis) but not Bio2 function (biotin synthesis) also impaired Histoplasma virulence. These results indicate that the Histoplasma-containing phagosome is limiting for riboflavin and pantothenate and that Histoplasma virulence requires de novo synthesis of these cofactor precursors. Since mammalian hosts do not rely on vitamin synthesis but instead acquire essential vitamins through diet, vitamin synthesis pathways represent druggable targets for therapeutics. PMID:24191299

From Cholesterogenesis to Steroidogenesis: Role of Riboflavin and Flavoenzymes in the Biosynthesis of Vitamin D12

PubMed Central

Pinto, John T.; Cooper, Arthur J. L.

2014-01-01

Flavin-dependent monooxygenases and oxidoreductases are located at critical branch points in the biosynthesis and metabolism of cholesterol and vitamin D. These flavoproteins function as obligatory intermediates that accept 2 electrons from NAD(P)H with subsequent 1-electron transfers to a variety of cytochrome P450 (CYP) heme proteins within the mitochondria matrix (type I) and the (microsomal) endoplasmic reticulum (type II). The mode of electron transfer in these systems differs slightly in the number and form of the flavin prosthetic moiety. In the type I mitochondrial system, FAD-adrenodoxin reductase interfaces with adrenodoxin before electron transfer to CYP heme proteins. In the microsomal type II system, a diflavin (FAD/FMN)-dependent cytochrome P450 oxidoreductase [NAD(P)H-cytochrome P450 reductase (CPR)] donates electrons to a multitude of heme oxygenases. Both flavoenzyme complexes exhibit a commonality of function with all CYP enzymes and are crucial for maintaining a balance of cholesterol and vitamin D metabolites. Deficits in riboflavin availability, imbalances in the intracellular ratio of FAD to FMN, and mutations that affect flavin binding domains and/or interactions with client proteins result in marked structural alterations within the skeletal and central nervous systems similar to those of disorders (inborn errors) in the biosynthetic pathways that lead to cholesterol, steroid hormones, and vitamin D and their metabolites. Studies of riboflavin deficiency during embryonic development demonstrate congenital malformations similar to those associated with genetic alterations of the flavoenzymes in these pathways. Overall, a deeper understanding of the role of riboflavin in these pathways may prove essential to targeted therapeutic designs aimed at cholesterol and vitamin D metabolism. PMID:24618756

Defective remethylation of homocysteine is related to decreased synthesis of coenzymes B2 in thyroidectomized rats.

PubMed

Ayav, A; Alberto, J M; Barbe, F; Brunaud, L; Gerard, P; Merten, M; Gueant, J L

2005-02-01

We investigated the influence of hypothyroidism on homocysteine metabolism in rats, focusing on a hypothetical deficient synthesis of FAD by riboflavin kinases. Animals were allocated in control group (n = 7), thyroidectomized rats (n = 6), rats with diet deficient in vitamin B2, B9, B12, choline and methionine (n = 7), thyroidectomized rats with deficient diet (n = 9). Homocysteine was decreased in operated rats (2.6 +/- 1.01 vs. 4.05 +/- 1.0 mumol/L, P = 0.02) and increased in deficient diet rats (29.56 +/- 4.52 vs. 4.05 +/- 1.0 micromol/L, P = 0.001), when compared to control group. Erythrocyte-Glutathione-Reductase-Activation-Coefficient (index of FAD deficiency) was increased in thyroidectomized or deficient diet rats (P = 0.004 for both). Methylenetetrahydrofolate-reductase and methionine-synthase activities were decreased in thyroidectomized rats but not in those subjected to deficient diet. Cystathionine-beta-synthase was increased only in operated rats. Taken together, these results showed a defective re-methylation in surgical hypothyroidism, which was due in part to a defective synthesis of vitamin B2 coenzymes. This defective pathway was overcompensated by the increased Cystathionine-beta-synthase activity.

The study of riboflavin requirement in broiler chickens.

PubMed

Olkowski, A A; Classen, H L

1998-01-01

Riboflavin status indices in tissues (brain, liver, heart) and blood plasma, and performance parameters were studied in male and female broiler chickens in response to a wide range of dietary supplementation of riboflavin in order to establish the requirement for riboflavin in fast growing modern broilers. The birds fed riboflavin supplemented diets were increasing their body weight at a higher rate than those fed the unsupplemented diet, but this was apparent only during the first stage of growth (days 1 to 21). Supplementation of 2 mg riboflavin per kg was sufficient to support the maximum growth rate. Feed consumption was not affected by different levels of dietary supplementation of riboflavin. The supplementation of riboflavin in the diet increased (p < 0.001) plasma riboflavin level, but the magnitude of response decreased with age. The main component in the tissues was FAD, followed by FMN and riboflavin. Overall, the dietary riboflavin supplementation had highly significant (p < 0.001) effects on tissue FAD, FMN, and riboflavin status, but the effect of supplementation was clearly pronounced only at days 7 and 14, and thereafter the status of FAD, FMN, and riboflavin in the tissues did not differ between unsupplemented and supplemented birds. Neither FAD, FMN, and riboflavin nor GSSG-RED activity correlate with the level of supplementation. Saturation levels of riboflavin in the blood plasma and tissues, corresponded with dietary riboflavin levels of supplementation at 1 to 2 mg per kg. Based on the performance and biochemical data, the dietary requirement of riboflavin for fast growing broilers should be set at a level of 5 mg/kg. The currently recommended allowance of 3.6 mg riboflavin per kg of ration is not sufficient for modern breeds of broiler chickens.

Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing

PubMed Central

Porter, Kirsty; Hoey, Leane; Hughes, Catherine F.; Ward, Mary; McNulty, Helene

2016-01-01

The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis. Deficient or low status of these B-vitamins alone or in combination with genetic polymorphisms, including the common MTHFR 677 C → T polymorphism, could contribute to greater disease risk in ageing by causing perturbations in one carbon metabolism. Moreover, interventions with the relevant B-vitamins to optimise status may have beneficial effects in preventing degenerative diseases. The precise mechanisms are unknown but many have been proposed involving the role of folate and the related B-vitamins as co-factors for one-carbon transfer reactions, which are fundamental for DNA and RNA biosynthesis and the maintenance of methylation reactions. This review will examine the evidence linking folate and related B-vitamins with health and disease in ageing, associated mechanisms and public health implications. PMID:27854316

Identification of the First Riboflavin Catabolic Gene Cluster Isolated from Microbacterium maritypicum G10*

PubMed Central

Xu, Hui; Chakrabarty, Yindrila; Philmus, Benjamin; Mehta, Angad P.; Bhandari, Dhananjay; Hohmann, Hans-Peter; Begley, Tadhg P.

2016-01-01

Riboflavin is a common cofactor, and its biosynthetic pathway is well characterized. However, its catabolic pathway, despite intriguing hints in a few distinct organisms, has never been established. This article describes the isolation of a Microbacterium maritypicum riboflavin catabolic strain, and the cloning of the riboflavin catabolic genes. RcaA, RcaB, RcaD, and RcaE were overexpressed and biochemically characterized as riboflavin kinase, riboflavin reductase, ribokinase, and riboflavin hydrolase, respectively. Based on these activities, a pathway for riboflavin catabolism is proposed. PMID:27590337

FAD Regulates CRYPTOCHROME Protein Stability and Circadian Clock in Mice.

PubMed

Hirano, Arisa; Braas, Daniel; Fu, Ying-Hui; Ptáček, Louis J

2017-04-11

The circadian clock generates biological rhythms of metabolic and physiological processes, including the sleep-wake cycle. We previously identified a missense mutation in the flavin adenine dinucleotide (FAD) binding pocket of CRYPTOCHROME2 (CRY2), a clock protein that causes human advanced sleep phase. This prompted us to examine the role of FAD as a mediator of the clock and metabolism. FAD stabilized CRY proteins, leading to increased protein levels. In contrast, knockdown of Riboflavin kinase (Rfk), an FAD biosynthetic enzyme, enhanced CRY degradation. RFK protein levels and FAD concentrations oscillate in the nucleus, suggesting that they are subject to circadian control. Knockdown of Rfk combined with a riboflavin-deficient diet altered the CRY levels in mouse liver and the expression profiles of clock and clock-controlled genes (especially those related to metabolism including glucose homeostasis). We conclude that light-independent mechanisms of FAD regulate CRY and contribute to proper circadian oscillation of metabolic genes in mammals. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Malnutrition and skin disease in Far East prisoners-of-war in World War II.

PubMed

Creamer, D

2018-05-31

During the Second World War, thousands of captured British and Commonwealth troops were interned in prisoner-of-war (POW) camps in the Far East. Imprisonment was extremely harsh, and prisoners developed multiple pathologies induced by physical hardship, tropical infections and starvation. Immediately after the war, several POW doctors published their clinical experiences, including reports of skin disease caused by malnutrition. The most notable deficiency dermatoses seen in Far East POWs were ariboflavinosis (vitamin B2 or riboflavin deficiency) and pellagra (vitamin B3 or niacin deficiency). A lack of vitamin B2 produces a striking inflammatory disorder of scrotal skin. Reports of pellagra in POWs documented a novel widespread eruption, developing into exfoliative dermatitis, in addition to the usual photosensitive dermatosis. A review of the literature from 70 years ago provides a reminder of the skin's response to malnutrition. © 2018 British Association of Dermatologists.

Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier.

PubMed

Kubo, Yoshiyuki; Yahata, Shizuka; Miki, Satoshi; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

2017-02-01

Riboflavin (vitamin B 2 ) supply to the retina across the inner blood-retinal barrier (BRB) was investigated. In rats, the apparent influx permeability clearance of [ 3 H]riboflavin (62.8 μL/(min·g retina)) was much higher than that of a non-permeable paracellular marker, suggesting the facilitative influx transport of riboflavin across the BRB. The retinal uptake index (RUI) of [ 3 H]riboflavin was 59.0%, and significantly reduced by flavin adenine dinucleotide (FAD), but not by l-ascorbic acid, suggesting the substrate specificity of riboflavin transport. TR-iBRB2 cells, an in vitro model of the inner BRB, showed a temperature- and concentration-dependent [ 3 H]riboflavin uptake with a K m of 113 nM, suggesting that the influx transport of riboflavin across the inner BRB involves a carrier-mediated process. [ 3 H]Riboflavin uptake by TR-iBRB2 cells was slightly altered by Na + - and Cl - -free buffers, suggesting that riboflavin transport at the inner BRB is preferentially Na + - and Cl - -independent. [ 3 H]Riboflavin uptake by TR-iBRB2 cells was significantly reduced by riboflavin analogues while the uptake remained unchanged by other vitamins. The function and inhibition profile suggested the involvement of riboflavin transporters (SLC52A/RFVT) in riboflavin transport at the inner BRB, and this is supported by expression and knockdown analysis of rRFVT2 (Slc52a2) and rRFVT3 (Slc52a3) in TR-iBRB2 cells. Copyright © 2016. Published by Elsevier Ltd.

Laboratory measurement of the absorption coefficient of riboflavin for ultraviolet light (365 nm).

PubMed

Iseli, Hans Peter; Popp, Max; Seiler, Theo; Spoerl, Eberhard; Mrochen, Michael

2011-03-01

Corneal cross-linking (CXL) is an increasingly used treatment technique for stabilizing the cornea in keratoconus. Cross-linking (polymerization) between collagen fibrils is induced by riboflavin (vitamin B2) and ultraviolet light (365 nm). Although reported to reach a constant value at higher riboflavin concentrations, the Lambert-Beer law predicts a linear increase in the absorption coefficient. This work was carried out to determine absorption behavior at different riboflavin concentrations and to further investigate the purported plateau absorption coefficient value of riboflavin and to identify possible bleaching effects. The Lambert-Beer law was used to calculate the absorption coefficient at various riboflavin concentrations. The following investigated concentrations of riboflavin solutions were prepared using a mixture of 0.5% riboflavin and 20% Dextran T500 dissolved in 0.9% sodium chloride solution: 0%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.08%, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5%, and were investigated with and without aperture plate implementation. An additional test series measured the transmitted power at selected riboflavin concentrations over time. In diluted solutions, a linear correlation exists between the absorption coefficient and riboflavin concentration. The absorption coefficient reaches a plateau, but this occurs at a higher riboflavin concentration (0.1%) than previously reported (just above 0.04%). Transmitted light power increases over time, indicating a bleaching effect of riboflavin. The riboflavin concentration can be effectively varied as a treatment parameter in a considerably broader range than previously thought. Copyright 2011, SLACK Incorporated.

Cross-sectional dietary deficiencies among a prison population in Papua New Guinea.

PubMed

Gould, Camilla; Tousignant, Benoit; Brian, Garry; McKay, Robert; Gibson, Rosalind; Bailey, Karl; Venn, Bernard J

2013-04-22

To investigate the dietary adequacy of prisoners of Beon Prison, Madang, Papua New Guinea in response to a report of possible nutritional deficiency. We undertook an observational, cross-sectional study. All 254 male inmates (May 2010) were eligible to answer a validated interview-based questionnaire; to have a comprehensive dietary assessment; and to provide blood for biochemical analysis (α-tocopherol, β-carotene, lutein, thiamin, riboflavin, niacin, folate, homocysteine, zinc, ferritin, and vitamins A, B12 and C). Prison guards were invited to participate as a comparison group. 148 male prisoners (58.3%) and 13 male prison guards participated. Prison rations consisted of white rice fortified with thiamin, niacin, and iron, tinned tuna, tinned corned beef, water crackers, and black tea, with occasional intakes of fruit and vegetables. Some prisoners received supplementary food from weekend visitors. From assessment of the prisoners dietary data, median intakes of calcium (137 mg), potassium (677 mg), magnesium (182 mg), riboflavin (0.308 mg), vitamin A (54.1 μg), vitamin E (1.68 mg), vitamin C (5.7 mg) and folate (76.4 μg) were found to be below estimated average requirements (EAR). The prisoners diets are likely lacking in several micronutrients and recommendations for dietary change have been made to the prison authorities. Ongoing vigilance is required in prisons to ensure the basic human right of access to a nutritionally adequate diet is being observed.

Mutagenicity of the potent rat hepatocarcinogen 6BT to the liver of transgenic (lacI) rats: consideration of a reduced mutation assay protocol.

PubMed

Lefevre, P A; Tinwell, H; Ashby, J

1997-01-01

6-(p-dimethylaminophenylazo)benzothiazole (6BT) is an unusually potent rat hepatocarcinogen, producing large malignant liver tumours after only 2-3 months of dietary administration in a riboflavin-deficient diet. This azocarcinogen has been evaluated in a Big Blue F344 transgenic rat (lacI) gene mutation assay. In a reproduction of the early stages of the carcinogenesis bioassay of this agent, rats were maintained on a riboflavin-deficient diet and were given 10 consecutive daily doses of 6BT (10 mg/kg) by oral gavage. The animals were killed and the livers examined 11 days after the final dose. The livers of 6BT-treated rats showed evidence of hepatocellular hypertrophy in centrolobular areas, with some indication of an increased incidence of mitotic figures. An approximately 10-fold increase in the mutation frequency of DNA isolated from an aliquot of the combined liver homogenates of 6BT-treated rats was observed over that obtained from an equivalent aliquot from control animals. Examination of DNA samples isolated from the livers of individual animals confirmed that 6BT was mutagenic in Big Blue rat livers. These data extend the sensitivity of this transgenic assay to include azo hepatocarcinogens. The determination of mutation frequencies using pooled tissue samples represented a major resource-saving adaptation of the assay protocol in the present study; the general advantages and disadvantages of this practice are discussed.

The superfamily keeps growing: Identification in trypanosomatids of RibJ, the first riboflavin transporter family in protists.

PubMed

Balcazar, Darío E; Vanrell, María Cristina; Romano, Patricia S; Pereira, Claudio A; Goldbaum, Fernando A; Bonomi, Hernán R; Carrillo, Carolina

2017-04-01

Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors. While metazoans obtain riboflavin from the diet through RFVT/SLC52 transporters, the riboflavin transport mechanisms in trypanosomatids still remain unknown. Here, we show that riboflavin is imported with high affinity in Trypanosoma cruzi, Trypanosoma brucei, Leishmania (Leishmania) mexicana, Crithidia fasciculata and Phytomonas Jma using radiolabeled riboflavin transport assays. The vitamin is incorporated through a saturable carrier-mediated process. Effective competitive uptake occurs with riboflavin analogs roseoflavin, lumiflavin and lumichrome, and co-factor derivatives FMN and FAD. Moreover, important biological processes evaluated in T. cruzi (i.e. proliferation, metacyclogenesis and amastigote replication) are dependent on riboflavin availability. In addition, the riboflavin competitive analogs were found to interfere with parasite physiology on riboflavin-dependent processes. By means of bioinformatics analyses we identified a novel family of riboflavin transporters (RibJ) in trypanosomatids. Two RibJ members, TcRibJ and TbRibJ from T. cruzi and T. brucei respectively, were functionally characterized using homologous and/or heterologous expression systems. The RibJ family represents the first riboflavin transporters found in protists and the third eukaryotic family known to date. The essentiality of riboflavin for trypanosomatids, and the structural/biochemical differences that RFVT/SLC52 and RibJ present, make the riboflavin transporter -and its downstream metabolism- a potential trypanocidal drug target.

The superfamily keeps growing: Identification in trypanosomatids of RibJ, the first riboflavin transporter family in protists

PubMed Central

Balcazar, Darío E.; Vanrell, María Cristina; Romano, Patricia S.; Pereira, Claudio A.; Goldbaum, Fernando A.; Bonomi, Hernán R.; Carrillo, Carolina

2017-01-01

Background Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors. While metazoans obtain riboflavin from the diet through RFVT/SLC52 transporters, the riboflavin transport mechanisms in trypanosomatids still remain unknown. Methodology/Principal findings Here, we show that riboflavin is imported with high affinity in Trypanosoma cruzi, Trypanosoma brucei, Leishmania (Leishmania) mexicana, Crithidia fasciculata and Phytomonas Jma using radiolabeled riboflavin transport assays. The vitamin is incorporated through a saturable carrier-mediated process. Effective competitive uptake occurs with riboflavin analogs roseoflavin, lumiflavin and lumichrome, and co-factor derivatives FMN and FAD. Moreover, important biological processes evaluated in T. cruzi (i.e. proliferation, metacyclogenesis and amastigote replication) are dependent on riboflavin availability. In addition, the riboflavin competitive analogs were found to interfere with parasite physiology on riboflavin-dependent processes. By means of bioinformatics analyses we identified a novel family of riboflavin transporters (RibJ) in trypanosomatids. Two RibJ members, TcRibJ and TbRibJ from T. cruzi and T. brucei respectively, were functionally characterized using homologous and/or heterologous expression systems. Conclusions/Significance The RibJ family represents the first riboflavin transporters found in protists and the third eukaryotic family known to date. The essentiality of riboflavin for trypanosomatids, and the structural/biochemical differences that RFVT/SLC52 and RibJ present, make the riboflavin transporter -and its downstream metabolism- a potential trypanocidal drug target. PMID:28406895

Genetic Control of Biosynthesis and Transport of Riboflavin and Flavin Nucleotides and Construction of Robust Biotechnological Producers†

PubMed Central

Abbas, Charles A.; Sibirny, Andriy A.

2011-01-01

Summary: Riboflavin [7,8-dimethyl-10-(1′-d-ribityl)isoalloxazine, vitamin B2] is an obligatory component of human and animal diets, as it serves as the precursor of flavin coenzymes, flavin mononucleotide, and flavin adenine dinucleotide, which are involved in oxidative metabolism and other processes. Commercially produced riboflavin is used in agriculture, medicine, and the food industry. Riboflavin synthesis starts from GTP and ribulose-5-phosphate and proceeds through pyrimidine and pteridine intermediates. Flavin nucleotides are synthesized in two consecutive reactions from riboflavin. Some microorganisms and all animal cells are capable of riboflavin uptake, whereas many microorganisms have distinct systems for riboflavin excretion to the medium. Regulation of riboflavin synthesis in bacteria occurs by repression at the transcriptional level by flavin mononucleotide, which binds to nascent noncoding mRNA and blocks further transcription (named the riboswitch). In flavinogenic molds, riboflavin overproduction starts at the stationary phase and is accompanied by derepression of enzymes involved in riboflavin synthesis, sporulation, and mycelial lysis. In flavinogenic yeasts, transcriptional repression of riboflavin synthesis is exerted by iron ions and not by flavins. The putative transcription factor encoded by SEF1 is somehow involved in this regulation. Most commercial riboflavin is currently produced or was produced earlier by microbial synthesis using special selected strains of Bacillus subtilis, Ashbya gossypii, and Candida famata. Whereas earlier RF overproducers were isolated by classical selection, current producers of riboflavin and flavin nucleotides have been developed using modern approaches of metabolic engineering that involve overexpression of structural and regulatory genes of the RF biosynthetic pathway as well as genes involved in the overproduction of the purine precursor of riboflavin, GTP. PMID:21646432

Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers.

PubMed

Abbas, Charles A; Sibirny, Andriy A

2011-06-01

Riboflavin [7,8-dimethyl-10-(1'-d-ribityl)isoalloxazine, vitamin B₂] is an obligatory component of human and animal diets, as it serves as the precursor of flavin coenzymes, flavin mononucleotide, and flavin adenine dinucleotide, which are involved in oxidative metabolism and other processes. Commercially produced riboflavin is used in agriculture, medicine, and the food industry. Riboflavin synthesis starts from GTP and ribulose-5-phosphate and proceeds through pyrimidine and pteridine intermediates. Flavin nucleotides are synthesized in two consecutive reactions from riboflavin. Some microorganisms and all animal cells are capable of riboflavin uptake, whereas many microorganisms have distinct systems for riboflavin excretion to the medium. Regulation of riboflavin synthesis in bacteria occurs by repression at the transcriptional level by flavin mononucleotide, which binds to nascent noncoding mRNA and blocks further transcription (named the riboswitch). In flavinogenic molds, riboflavin overproduction starts at the stationary phase and is accompanied by derepression of enzymes involved in riboflavin synthesis, sporulation, and mycelial lysis. In flavinogenic yeasts, transcriptional repression of riboflavin synthesis is exerted by iron ions and not by flavins. The putative transcription factor encoded by SEF1 is somehow involved in this regulation. Most commercial riboflavin is currently produced or was produced earlier by microbial synthesis using special selected strains of Bacillus subtilis, Ashbya gossypii, and Candida famata. Whereas earlier RF overproducers were isolated by classical selection, current producers of riboflavin and flavin nucleotides have been developed using modern approaches of metabolic engineering that involve overexpression of structural and regulatory genes of the RF biosynthetic pathway as well as genes involved in the overproduction of the purine precursor of riboflavin, GTP.

Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome.

PubMed

Haack, Tobias B; Makowski, Christine; Yao, Yoshiaki; Graf, Elisabeth; Hempel, Maja; Wieland, Thomas; Tauer, Ulrike; Ahting, Uwe; Mayr, Johannes A; Freisinger, Peter; Yoshimatsu, Hiroki; Inui, Ken; Strom, Tim M; Meitinger, Thomas; Yonezawa, Atsushi; Prokisch, Holger

2012-11-01

Brown-Vialetto-Van Laere syndrome (BVVLS [MIM 211530]) is a rare neurological disorder characterized by infancy onset sensorineural deafness and ponto-bulbar palsy. Mutations in SLC52A3 (formerly C20orf54), coding for riboflavin transporter 2 (hRFT2), have been identified as the molecular genetic correlate in several individuals with BVVLS. Exome sequencing of just one single case revealed that compound heterozygosity for two pathogenic mutations in the SLC52A2 gene coding for riboflavin transporter 3 (hRFT3), another member of the riboflavin transporter family, is also associated with BVVLS. Overexpression studies confirmed that the gene products of both mutant alleles have reduced riboflavin transport activities. While mutations in SLC52A3 cause decreased plasma riboflavin levels, concordant with a role of SLC52A3 in riboflavin uptake from food, the SLC52A2-mutant individual had normal plasma riboflavin concentrations, a finding in line with a postulated function of SLC52A2 in riboflavin uptake from blood into target cells. Our results contribute to the understanding of human riboflavin metabolism and underscore its role in the pathogenesis of BVVLS, thereby providing a rational basis for a high-dose riboflavin treatment.

Blue light induced free radicals from riboflavin in degradation of crystal violet by microbial viability evaluation.

PubMed

Liang, Ji-Yuan; Yuann, Jeu-Ming P; Hsie, Zong-Jhe; Huang, Shiuh-Tsuen; Chen, Chiing-Chang

2017-09-01

Crystal violet (CV) is applied in daily use mainly as a commercial dye and antimicrobial agent. Waste water containing CV may affect aquatic ecosystems. Riboflavin, also known as vitamin B 2 , is non-toxic and an essential vitamin required for the functions of the human body. Riboflavin is photosensitive to UV and visible light in terms of generating reactive oxygen species. This study investigated the potential application of blue light on riboflavin, so as to come up with an effective way of degrading CV during its treatment. Photosensitivity of CV leading to degradation in the presence of riboflavin was investigated by light intensity, exposure time, and irradiation dosage. The degradation of CV during riboflavin photolysis treatment was studied by a UV/vis spectrometry and chromatography. The effects of CV degradation on microbial viability are relevant when considering the influences on the ecosystem. This study proved that riboflavin photochemical treatment with blue light degrades CV dye by ROS formation. The riboflavin photolysis-treated CV solution appeared to be transparent during conformational transformations of the CV that was rearranged by free radical species generated from riboflavin photolysis. After riboflavin photolysis, colony-forming units (CFUs) were determined for each CV solution. CFU preservation was 85.2% for the CV dissolved riboflavin solution treated with blue light irradiation at 2.0mW/cm 2 for 120min. Degradation of CV by riboflavin photochemical procedures can greatly reduce antimicrobial ability and serve as an environmental friendly waste water treatment method. Our results presented here concerning riboflavin photolysis in degradation of CV provide a novel technique, and a simple and safe practice for environmental decontamination processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells.

PubMed

Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

2012-08-15

Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of a riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with K(m) and V(max) values of 19 ± 3 μM and 0.235 ± 0.012 pmol/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca(++)/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-riboflavin. Apical and baso-lateral uptake of [3H]-riboflavin clearly indicates that a riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to a riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. The blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Inadequate Riboflavin Intake and Anemia Risk in a Chinese Population: Five-Year Follow Up of the Jiangsu Nutrition Study

PubMed Central

Shi, Zumin; Zhen, Shiqi; Wittert, Gary A.; Yuan, Baojun; Zuo, Hui; Taylor, Anne W.

2014-01-01

Objectives Riboflavin (vitamin B2) has been shown in animal studies to affect the absorption and metabolism of iron. Cross-sectional population studies show a relationship between riboflavin intake and anemia but prospective population studies are limited. The aim of the study was to determine the relationship between riboflavin intake and the risk of anemia in a Chinese cohort. Method The study used data from 1253 Chinese men and women who participated in two waves of the Jiangsu Nutrition Study (JIN), five years apart, in 2002 and 2007. Riboflavin intake and hemoglobin (Hb) were quantitatively assessed together with dietary patterns, lifestyle, socio-demographic and health-related factors. Results At baseline, 97.2% of participants had inadequate riboflavin intake (below the estimate average requirement). Riboflavin intake was positively associated with anemia at baseline, but low riboflavin intake was associated with an increased risk of anemia at follow-up among those anemic at baseline. In the multivariate model, adjusting for demographic and lifestyle factors and dietary patterns, the relative risk and 95% confidence interval for anemia at follow-up, across quartiles of riboflavin intake were: 1, 0.82(0.54–1.23), 0.56(0.34–0.93), 0.52(0.28–0.98) (p for trend 0.021). There was a significant interaction between riboflavin and iron intake; when riboflavin intake was low, a high iron intake was associated with a lower probability of anemia at follow-up. This association disappeared when riboflavin intake was high. Conclusion Inadequate riboflavin intake is common and increases the risk of anemia in Chinese adults. Given the interaction with iron intake correcting inadequate riboflavin intake may be a priority in the prevention of anemia, and population based measurement and intervention trials are required. PMID:24533156

Carrier-mediated transport of riboflavin in the rat colon.

PubMed

Yuasa, H; Hirobe, M; Tomei, S; Watanabe, J

2000-03-01

Carriers involved in riboflavin transport have generally been presumed to be localized in the upper small intestine. However, using a closed loop technique, we found that in the rat colon the absorption of riboflavin could be significantly reduced by raising the concentration from 0.1 to 200 microM and by adding lumiflavin, an analogue of riboflavin. These results suggest that saturable transport by the carrier that is specific for riboflavin and analogues may also be involved in riboflavin absorption in the colon. At the lower concentration of 0.1 microM, carrier-mediated transport was suggested to prevail, compared with passive transport, both in the colon and the small intestine. Furthermore, carrier-mediated transport in the colon was comparable with that in the small intestine. This study is the first to suggest carrier-mediated riboflavin transport in the colon. Although the riboflavin transport system in the colon needs to be subjected to more detailed investigation of its transport functions and role in riboflavin absorption after oral administration, it would be of interest to explore potential use of this carrier as a system for drug delivery.

Quantitative analysis of corneal stromal riboflavin concentration without epithelial removal.

PubMed

Rubinfeld, Roy S; Stulting, R Doyle; Gum, Glenwood G; Talamo, Jonathan H

2018-02-01

To compare the corneal stromal riboflavin concentration and distribution using 2 transepithelial corneal crosslinking (CXL) systems. Absorption Systems, San Diego, California, USA. Experimental study. The stromal riboflavin concentration of 2 transepithelial CXL systems was compared in rabbit eyes in vivo. The systems were the Paracel/Vibex Xtra, comprising riboflavin 0.25% solution containing TRIS and ethylenediaminetetraacetic acid and an isotonic solution of riboflavin 0.25%, (Group 1) and the CXLO system (Group 2). Manufacturers' Instructions For Use were followed. The intensity of riboflavin fluorescence by slitlamp observation 10, 15, and 20 minutes after instillation was graded on a scale of 0 to 5. The animals were humanely killed and the corneal stromal samples analyzed with liquid chromatography and mass spectrometry. The mean riboflavin fluorescence intensity grades in Group 1 (4 eyes) were 3.8, 4.8, and 4.8 at 10, 15, and 20 minutes, respectively. The mean grades in Group 2 (3 eyes) were 2.0, 2.3, and 2.0, respectively. The riboflavin distribution was uniform in Group 1 but not in Group 2. The mean riboflavin concentration by liquid chromatography and mass spectrometry was 27.0 μg/g stromal tissue in Group 1 and 6.7 μg/g in Group 2. A stromal riboflavin concentration theoretically adequate for CXL, 15 μg/g, was achieved in all eyes in Group 1 and no eyes in Group 2. Slitlamp grading correlated well with liquid chromatography and mass spectrometry concentration (R 2  = 0.940). The system used in Group 1 produced corneal riboflavin concentrations that were theoretically adequate for effective transepithelial CXL (≥15 μg/g), while the system in Group 2 did not. Slitlamp grading successfully estimated the corneal riboflavin concentration and can be used to ensure an adequate concentration of riboflavin in the cornea for transepithelial CXL. Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Prophylaxis of migraine headaches with riboflavin: A systematic review.

PubMed

Thompson, D F; Saluja, H S

2017-08-01

Migraine headache is a relatively common, debilitating condition that costs our healthcare system over 78 billion dollars per year. Riboflavin has been advocated as a safe, effective prophylactic therapy for the prevention of migraines. The purpose of this study was to provide a systematic review of the current role of riboflavin in the prophylaxis of migraine headache. A MEDLINE literature search inclusive of the dates 1966-2016 was performed using the search terms: riboflavin and migraine disorders. Excerpta Medica was searched from 1980 to 2016 using the search terms: riboflavin and migraine. Additionally, Web of Science was searched using the terms riboflavin and migraine inclusive of 1945-2016. Bibliographies of all relevant papers were reviewed for additional citations. We utilized the PRISMA guidelines to select English language, human, clinical trials of riboflavin as a single entity or in combination, review articles, and supporting pharmacokinetic and pharmacogenomic data assessing the efficacy and mechanism of riboflavin therapy in the prophylactic treatment of migraine headache. A total of 11 clinical trials reveal a mixed effect of riboflavin in the prophylaxis of migraine headache. Five clinical trials show a consistent positive therapeutic effect in adults; four clinical trials show a mixed effect in paediatric and adolescent patients, and two clinical trials of combination therapy have not shown benefit. Adverse reactions with riboflavin have generally been mild. Riboflavin is well tolerated, inexpensive and has demonstrated efficacy in the reduction of adult patient's migraine headache frequency. Additional data are needed, however, to resolve questions involving pharmacokinetic issues and pharmacogenomic implications of therapy. © 2017 John Wiley & Sons Ltd.

Electrochemical Characterization of Riboflavin-Enhanced Reduction of Trinitrotoluene

PubMed Central

Sumner, James J.; Chu, Kevin

2011-01-01

There is great interest in understanding trinitrotoluene (TNT) and dinitrotoluene (DNT) contamination, detection and remediation in the environment due to TNT’s negative health effects and security implications. Numerous publications have focused on detecting TNT in groundwater using multiple techniques, including electrochemistry. The main degradation pathway of nitrotoluenes in the environment is reduction, frequently with biological and/or photolytic assistance. Riboflavin has also been noted to aid in TNT remediation in soils and groundwater when exposed to light. This report indicates that adding riboflavin to a TNT or DNT solution enhances redox currents in electrochemical experiments. Here AC voltammetry was performed and peak currents compared with and without riboflavin present. Results indicated that TNT, DNT and riboflavin could be detected using AC voltammetry on modified gold electrodes and the addition of riboflavin affected redox peaks of TNT and DNT. Poised potential experiments indicated that it is possible to enhance reduction of TNT in the presence of riboflavin and light. These results were dramatic enough to explain long term enhancement of bioremediation in environments containing high levels of riboflavin and enhance the limit of detection in electrochemically-based nitrotoluene sensing. PMID:22346674

Blue light induced free radicals from riboflavin on E. coli DNA damage.

PubMed

Liang, Ji-Yuan; Yuann, Jeu-Ming P; Cheng, Chien-Wei; Jian, Hong-Lin; Lin, Chin-Chang; Chen, Liang-Yu

2013-02-05

The micronutrients in many cellular processes, riboflavin (vitamin B(2)), FMN, and FAD are photo-sensitive to UV and visible light to generate reactive oxygen species (ROS). The riboflavin photochemical treatment with UV light has been applied for the inactivation of microorganisms to serve as an effective and safe technology. Ultra-violet or high-intensity radiation is, however, considered as a highly risky practice. This study was working on the application of visible LED lights to riboflavin photochemical reactions to development an effective antimicrobial treatment. The photosensitization of bacterial genome with riboflavin was investigated in vitro and in vivo by light quality and irradiation dosage. The riboflavin photochemical treatment with blue LED light was proved to be able to inactivate E. coli by damaging nucleic acids with ROS generated. Riboflavin is capable of intercalating between the bases of bacterial DNA or RNA and absorbs lights in the visible regions. LED light illumination could be a more accessible and safe practice for riboflavin photochemical treatments to achieve hygienic requirements in vitro. Copyright © 2013 Elsevier B.V. All rights reserved.

Medium-mediated effects increase cell killing in a human keratinocyte cell line exposed to solar-simulated radiation.

PubMed

Maguire, Alanna; Morrissey, Brian; Walsh, James E; Lyng, Fiona M

2011-01-01

The objective of this study was to investigate whether cell culture medium is a biologically relevant exposure medium that can be employed in non-ionising photobiological investigations. The effect of solar-simulated irradiation on cell culture medium and its ability to elicit cell death was studied. The role of reactive oxygen species (ROS), cell secreted factors, and the contribution of individual components of the medium were investigated. Cell death was found to be primarily mediated through the formation of ROS via riboflavin photosensitisation and degradation in the cell culture medium. Phenol red was found to significantly reduce the cell killing ability of riboflavin. Exposures in riboflavin-free medium resulted in significantly increased cell survival compared to identical exposures in riboflavin containing medium. This study has shown that solar radiation toxicity is augmented by cell culture medium due to the presence of riboflavin. Results suggest that exposures performed in phenol red-free medium may serve to increase phototoxic effects if riboflavin is present. Riboflavin-free media is recommended for solar radiation investigations to eliminate concerns regarding riboflavin photosensitisation and nutrient deprivation.

A directed-overflow and damage-control N -glycosidase in riboflavin biosynthesis

DOE PAGES

Frelin, Océane; Huang, Lili; Hasnain, Ghulam; ...

2015-02-15

Plants and bacteria synthesize the essential human micronutrient riboflavin (vitamin B2) via the same multistep pathway. The early intermediates of this pathway are notoriously reactive, and may be overproduced in vivo because riboflavin biosynthesis enzymes lack feedback controls. Here we demonstrate disposal of riboflavin intermediates by COG3236 (DUF1768), a protein of previously unknown function that is fused to two different riboflavin pathway enzymes in plants and bacteria (RIBR and RibA, respectively). We present cheminformatic, biochemical, genetic, and genomic evidence to show that: (i) plant and bacterial COG3236 proteins cleave the N-glycosidic bond of the first two intermediates of riboflavin biosynthesis,more » yielding relatively innocuous products; (ii) certain COG3236 proteins are in a multienzyme riboflavin biosynthesis complex that gives them privileged access to riboflavin intermediates; and (iii) COG3236 action in Arabidopsis thaliana and Escherichia coli helps maintain flavin levels. We find COG3236 proteins thus illustrate two emerging principles in chemical biology: directed overflow metabolism, in which excess flux is diverted out of a pathway, and the pre-emption of damage from reactive metabolites.« less

Riboflavin-mediated RDX transformation in the presence of Shewanella putrefaciens CN32 and lepidocrocite.

PubMed

Bae, Sungjun; Lee, Yoonhwa; Kwon, Man Jae; Lee, Woojin

2014-06-15

The potential of riboflavin for the reductive degradation of a cyclic nitramine, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), was investigated in the presence of lepidocrocite and/or Shewanella putrefaciens CN32. RDX reduction by CN32 alone or CN32 with lepidocrocite was insignificant, while 110 μM RDX was completely reduced by CN32 with riboflavin in 78 h. The transformation products identified included nitroso metabolites, formaldehyde, and ammonium, indicating the ring cleavage of RDX. UV and visible light analysis revealed that riboflavin was microbially reduced by CN32, and that the reduced riboflavin was linked to the complete degradation of RDX. In the presence of both CN32 and lepidocrocite (γ-FeOOH), 100 μM-riboflavin increased the rate and extent of Fe(II) production as well as RDX reduction. An abiotic study also showed that Fe(II)-riboflavin complex, and Fe(II) adsorbed on lepidocrocite, reduced RDX by 48% and 21%, respectively. The findings in this study suggest that riboflavin-mediated RDX degradation pathways in subsurface environments are diverse and complex. However, riboflavin, either from bacteria or exogenous sources, can significantly increase RDX degradation. This will provide a sustainable clean-up option for explosive-contaminated subsurface environments. Copyright © 2014 Elsevier B.V. All rights reserved.

Ultraviolet A: Visible spectral absorbance of the human cornea after transepithelial soaking with dextran-enriched and dextran-free riboflavin 0.1% ophthalmic solutions.

PubMed

Lombardo, Marco; Micali, Norberto; Villari, Valentina; Serrao, Sebastiano; Pucci, Giuseppe; Barberi, Riccardo; Lombardo, Giuseppe

2015-10-01

To evaluate the stromal concentration of 2 commercially available transepithelial riboflavin 0.1% solutions in human donor corneas with the use of spectrophotometry. University of Calabria, Rende, Italy. Experimental study. The absorbance spectra of 12 corneal tissues were measured in the 330 to 700 nm wavelength range using a purpose-designed spectrophotometry setup before and after transepithelial corneal soaking with a 15% dextran-enriched riboflavin 0.1% solution (n = 6) or a hypotonic dextran-free riboflavin 0.1% solution (n = 6). Both ophthalmic solutions contained ethylenediaminetetraacetic acid and trometamol as enhancers. In addition, 4 deepithelialized corneal tissues underwent stromal soaking with a 20% dextran-enriched riboflavin 0.1% solution and were used as controls. All the riboflavin solutions were applied topically for 30 minutes. The stromal concentration of riboflavin was quantified by analysis of absorbance spectra of the cornea collected before and after application of each solution. The mean stromal riboflavin concentration was 0.012% ± 0.003% (SD), 0.0005% ± 0.0003% (P < .001), and 0.004% ± 0.001% (P < .01) in tissues soaked with 20% dextran-enriched, 15% dextran-enriched, and hypotonic dextran-free solutions, respectively. The difference of stromal riboflavin concentration between the 2 transepithelial solutions was statistically significant (P < .01). Dextran-enriched solutions required complete corneal deepithelialization to permit effective stromal soaking with riboflavin. Nevertheless, riboflavin in hypotonic dextran-free solution with enhancers permeates across stroma through an intact epithelium. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Construction and fed-batch cultivation of Candida famata with enhanced riboflavin production.

PubMed

Dmytruk, Kostyantyn; Lyzak, Oleksy; Yatsyshyn, Valentyna; Kluz, Maciej; Sibirny, Vladimir; Puchalski, Czeslaw; Sibirny, Andriy

2014-02-20

Riboflavin (vitamin B2) is an essential nutrition component serving as a precursor of coenzymes FMN and FAD that are involved mostly in reactions of oxidative metabolism. Riboflavin is produced in commercial scale and is used in feed and food industries, and in medicine. The yeast Candida famata (Candida flareri) belongs to the group of so called "flavinogenic yeasts" which overproduce riboflavin under iron limitation. Three genes SEF1, RIB1 and RIB7 coding for a putative transcription factor, GTP cyclohydrolase II and riboflavin synthase, respectively were simultaneously overexpressed in the background of a non-reverting riboflavin producing mutant AF-4, obtained earlier in our laboratory using methods of classical selection (Dmytruk et al. (2011), Metabolic Engineering 13, 82-88). Cultivation conditions of the constructed strain were optimized for shake-flasks and bioreactor cultivations. The constructed strain accumulated up to 16.4g/L of riboflavin in optimized medium in a 7L laboratory bioreactor during fed-batch fermentation. Copyright © 2013 Elsevier B.V. All rights reserved.

21 CFR 582.5697 - Riboflavin-5-phosphate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5697 Riboflavin-5-phosphate. (a) Product. Riboflavin-5-phosphate. (b) Conditions of use...

21 CFR 582.5697 - Riboflavin-5-phosphate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5697 Riboflavin-5-phosphate. (a) Product. Riboflavin-5-phosphate. (b) Conditions of use...

21 CFR 582.5697 - Riboflavin-5-phosphate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements 1 § 582.5697 Riboflavin-5-phosphate. (a) Product. Riboflavin-5-phosphate. (b) Conditions of use...

Clinical, pathological and functional characterization of riboflavin-responsive neuropathy

PubMed Central

Manole, Andreea; Jaunmuktane, Zane; Hargreaves, Iain; Ludtmann, Marthe H R; Salpietro, Vincenzo; Bello, Oscar D; Pope, Simon; Pandraud, Amelie; Horga, Alejandro; Scalco, Renata S; Li, Abi; Ashokkumar, Balasubramaniem; Lourenço, Charles M; Heales, Simon; Horvath, Rita; Chinnery, Patrick F; Toro, Camilo; Singleton, Andrew B; Jacques, Thomas S; Abramov, Andrey Y; Muntoni, Francesco; Hanna, Michael G; Reilly, Mary M; Revesz, Tamas; Kullmann, Dimitri M

2017-01-01

Abstract Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column–medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy. PMID:29053833

Clinical, pathological and functional characterization of riboflavin-responsive neuropathy.

PubMed

Manole, Andreea; Jaunmuktane, Zane; Hargreaves, Iain; Ludtmann, Marthe H R; Salpietro, Vincenzo; Bello, Oscar D; Pope, Simon; Pandraud, Amelie; Horga, Alejandro; Scalco, Renata S; Li, Abi; Ashokkumar, Balasubramaniem; Lourenço, Charles M; Heales, Simon; Horvath, Rita; Chinnery, Patrick F; Toro, Camilo; Singleton, Andrew B; Jacques, Thomas S; Abramov, Andrey Y; Muntoni, Francesco; Hanna, Michael G; Reilly, Mary M; Revesz, Tamas; Kullmann, Dimitri M; Jepson, James E C; Houlden, Henry

2017-11-01

Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Comparison of Changes in Central Corneal Thickness During Corneal Collagen Cross-Linking, Using Isotonic Riboflavin Solutions With and Without Dextran, in the Treatment of Progressive Keratoconus.

PubMed

Zaheer, Naima; Khan, Wajid Ali; Khan, Shama; Khan, M Abdul Moqeet

2018-03-01

To compare intraoperative changes in central corneal thickness (CCT) during corneal cross-linking, using 2 different isotonic riboflavin solutions either with dextran or with hydroxy propyl methylcellulose, in the treatment of progressive keratoconus. In this retrospective study, we analyzed records of corneal thickness measurements, taken during various steps of cross-linking. Cross-linking was performed using either isotonic riboflavin with dextran (group A) or isotonic riboflavin with hydroxy propyl methylcellulose (without dextran) (group B). CCT measurements were recorded before and after epithelial removal, after saturation with respective isotonic riboflavin solution, after use of hypotonic riboflavin in selected cases, and after ultraviolet A (UV-A) application. A mixed-way analysis of variance was conducted on CCT readings within each group and between both groups, and p < 0.05 was considered significant. In group A (100 cases), after saturation with isotonic riboflavin, CCT was decreased by a mean of 51.4 μm (12.1%). In 64%, CCT was <400 μm and additional hypotonic riboflavin was used. After UV-A irradiation, CCT was decreased by a mean of 46.7 μm (11.4%). In group B (100 cases), after saturation with isotonic riboflavin, CCT was increased by a mean of 109.4 μm (26.1%). After UV-A exposure, CCT was increased by a mean of 59.2 μm (11.2%). There was a substantial main effect for time on CCT during corneal cross-linking (CXL), p < 0.001, within both groups. The main effect comparing CCT readings between groups A and B was also significant, p < 0.001. During cross-linking, isotonic riboflavin with dextran causes a significant decrease in corneal thickness, whereas dextran-free isotonic riboflavin causes a significant increase in corneal thickness, thus facilitating the procedure.

Medium composition influence on Biotin and Riboflavin production by newly isolated Candida sp

PubMed Central

Suzuki, Gaby Tiemi; Macedo, Juliana Alves; Macedo, Gabriela Alves

2011-01-01

Complex B vitamins as Biotin and Riboflavin are required by living organisms, not only for growth but also for metabolite production, and the feed market classifies them as growth promoters. Since Brazil will soon be one of the world’s biggest animal protein producers, feed production is a large consumer of vitamins and micronutrients. The industry requires 10 mg riboflavin/0.2 mg biotin per kilogram of feed; a ratio of 40 ~ 50:1. Although few studies have been conducted specifically on riboflavin production using factorial design and surface response method as an optimization strategy, it is a common practice in biotechnology with many research reports available. However, there are no reports on the use of statistical design for biotin production. This study set out to evaluate medium composition influence on biotin and riboflavin production using a statistical design. There are no studies relating biotin and riboflavin production by Candida sp LEB 130. In this preliminary study to improve the simultaneous production of biotin and riboflavin, the maximum riboflavin/biotin ratio of 8.3 μg/mL was achieved with medium component concentrations of: sucrose 30 g/L, KH2PO4 2 g/L, MgSO4 1 g/L and ZnSO4 0.5mL/L. PMID:24031727

Medium composition influence on Biotin and Riboflavin production by newly isolated Candida sp.

PubMed

Suzuki, Gaby Tiemi; Macedo, Juliana Alves; Macedo, Gabriela Alves

2011-07-01

Complex B vitamins as Biotin and Riboflavin are required by living organisms, not only for growth but also for metabolite production, and the feed market classifies them as growth promoters. Since Brazil will soon be one of the world's biggest animal protein producers, feed production is a large consumer of vitamins and micronutrients. The industry requires 10 mg riboflavin/0.2 mg biotin per kilogram of feed; a ratio of 40 ~ 50:1. Although few studies have been conducted specifically on riboflavin production using factorial design and surface response method as an optimization strategy, it is a common practice in biotechnology with many research reports available. However, there are no reports on the use of statistical design for biotin production. This study set out to evaluate medium composition influence on biotin and riboflavin production using a statistical design. There are no studies relating biotin and riboflavin production by Candida sp LEB 130. In this preliminary study to improve the simultaneous production of biotin and riboflavin, the maximum riboflavin/biotin ratio of 8.3 μg/mL was achieved with medium component concentrations of: sucrose 30 g/L, KH2PO4 2 g/L, MgSO4 1 g/L and ZnSO4 0.5mL/L.

Quadratic nonlinear optics to assess the morphology of riboflavin doped chitosan for eco-friendly lithography

NASA Astrophysics Data System (ADS)

Ray, Cédric; Caillau, Mathieu; Jonin, Christian; Benichou, Emmanuel; Moulin, Christophe; Salmon, Estelle; Maldonado, Melissa E.; Gomes, Anderson S. L.; Monnier, Virginie; Laurenceau, Emmanuelle; Leclercq, Jean-Louis; Chevolot, Yann; Delair, Thierry; Brevet, Pierre-François

2018-06-01

We report the use of the Second Harmonic Generation response from a riboflavin doped chitosan film as a characterization method of the film morphology. This film is of particular interest in the development of new and bio-sourced material for eco-friendly UV lithography. The method allows us to determine how riboflavin is distributed as a function of film depth in the sample. This possibility is of importance in order to have a better understanding of the riboflavin influence in chitosan films during the lithography process. On the contrary, linear optical techniques provide no information beyond the mere confirmation of the riboflavin presence.

The protective effect of salicylic acid on lysozyme against riboflavin-mediated photooxidation

NASA Astrophysics Data System (ADS)

Li, Kun; Wang, Hongbao; Cheng, Lingli; Zhu, Hui; Wang, Mei; Wang, Shi-Long

2011-06-01

As a metabolite of aspirin in vivo, salicylic acid was proved to protect lysozyme from riboflavin-mediated photooxidation in this study. The antioxidative properties of salicylic acid were further studied by using time-resolved laser flash photolysis of 355 nm. It can quench the triplet state of riboflavin via electron transfer from salicylic acid to the triplet state of riboflavin with a reaction constant of 2.25 × 10 9 M -1 s -1. Mechanism of antioxidant activities of salicylic acid on lysozyme oxidation was discussed. Salicylic acid can serve as a potential antioxidant to quench the triplet state of riboflavin and reduce oxidative pressure.

Integrated whole-genome and transcriptome sequence analysis reveals the genetic characteristics of a riboflavin-overproducing Bacillus subtilis.

PubMed

Wang, Guanglu; Shi, Ting; Chen, Tao; Wang, Xiaoyue; Wang, Yongcheng; Liu, Dingyu; Guo, Jiaxin; Fu, Jing; Feng, Lili; Wang, Zhiwen; Zhao, Xueming

2018-06-02

Commercial riboflavin production with Bacillus subtilis has been developed by combining rational and classical strain development for almost two decades, but how an improved riboflavin producer can be created rationally is still not completely understood. In this study, we demonstrate the combined use of integrated genomic and transcriptomic analysis of the genetic basis for riboflavin over-production in B. subtilis. This methodology succeeded in discerning the positive mutations in the mutagenesis derived riboflavin producer B. subtilis 24/pMX45 through whole-genome sequencing and transcriptome sequencing. These included RibC (G199D), ribD + (G+39A), PurA (P242L), CcpN(A44S), YvrH (R222Q) and two nonsense mutations YhcF (R90*) and YwaA (Q68*). Reintroducing these specific mutations into the wild-type strain recovered the riboflavin overproduction phenotype and subsequent metabolic engineering greatly improved riboflavin production, achieving an up to 3.4-fold increase of the riboflavin titer over the sequenced producer. A novel mutation, YvrH (R222Q), involved in a typical two-component regulatory system deregulated the purine de novo synthesis pathway and increased the pool of intracellular purine metabolites, which in turn increased riboflavin production. Taken together, we present a case study of combining genome and transcriptome analysis to elucidate the genetic underpinnings of a complex cellular property, which enabled the transfer of beneficial mutations to engineer a reference strain into an overproducer. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Riboflavin Has Neuroprotective Potential: Focus on Parkinson’s Disease and Migraine

PubMed Central

Marashly, Eyad T.; Bohlega, Saeed A.

2017-01-01

With the huge negative impact of neurological disorders on patient’s life and society resources, the discovery of neuroprotective agents is critical and cost-effective. Neuroprotective agents can prevent and/or modify the course of neurological disorders. Despite being underestimated, riboflavin offers neuroprotective mechanisms. Significant pathogenesis-related mechanisms are shared by, but not restricted to, Parkinson’s disease (PD) and migraine headache. Those pathogenesis-related mechanisms can be tackled through riboflavin proposed neuroprotective mechanisms. In fact, it has been found that riboflavin ameliorates oxidative stress, mitochondrial dysfunction, neuroinflammation, and glutamate excitotoxicity; all of which take part in the pathogenesis of PD, migraine headache, and other neurological disorders. In addition, riboflavin-dependent enzymes have essential roles in pyridoxine activation, tryptophan-kynurenine pathway, and homocysteine metabolism. Indeed, pyridoxal phosphate, the active form of pyridoxine, has been found to have independent neuroprotective potential. Also, the produced kynurenines influence glutamate receptors and its consequent excitotoxicity. In addition, methylenetetrahydrofolate reductase requires riboflavin to ensure normal folate cycle influencing the methylation cycle and consequently homocysteine levels which have its own negative neurovascular consequences if accumulated. In conclusion, riboflavin is a potential neuroprotective agent affecting a wide range of neurological disorders exemplified by PD, a disorder of neurodegeneration, and migraine headache, a disorder of pain. In this article, we will emphasize the role of riboflavin in neuroprotection elaborating on its proposed neuroprotective mechanisms in opposite to the pathogenesis-related mechanisms involved in two common neurological disorders, PD and migraine headache, as well as, we encourage the clinical evaluation of riboflavin in PD and migraine headache patients in the future. PMID:28775706

Effect of Acidity of a Medium on Riboflavin Photodestruction

NASA Astrophysics Data System (ADS)

Astanov, S. Kh.; Turdiev, M.; Sharipov, M. Z.; Kurtaliev, É. N.; Nizomov, N. N.

2016-03-01

Effect of acidity of a medium on the spectroscopic characteristics of riboflavin aqueous solutions is investigated by the method of fluorescent and absorption spectroscopy. Significant deformation of the electronic spectra of riboflavin aqueous solutions irradiated with unfiltered light of a PRK-2 lamp is observed. It is established that riboflavin photostability in an acid medium is about twice as much as the photostability in a neutral medium, which is caused by the formation of a protonated species.

Biosynthesis of riboflavin: an unusual riboflavin synthase of Methanobacterium thermoautotrophicum.

PubMed Central

Eberhardt, S; Korn, S; Lottspeich, F; Bacher, A

1997-01-01

Riboflavin synthase was purified by a factor of about 1,500 from cell extract of Methanobacterium thermoautotrophicum. The enzyme had a specific activity of about 2,700 nmol mg(-1) h(-1) at 65 degrees C, which is relatively low compared to those of riboflavin synthases of eubacteria and yeast. Amino acid sequences obtained after proteolytic cleavage had no similarity with known riboflavin synthases. The gene coding for riboflavin synthase (designated ribC) was subsequently cloned by marker rescue with a ribC mutant of Escherichia coli. The ribC gene of M. thermoautotrophicum specifies a protein of 153 amino acid residues. The predicted amino acid sequence agrees with the information gleaned from Edman degradation of the isolated protein and shows 67% identity with the sequence predicted for the unannotated reading frame MJ1184 of Methanococcus jannaschii. The ribC gene is adjacent to a cluster of four genes with similarity to the genes cbiMNQO of Salmonella typhimurium, which form part of the cob operon (this operon contains most of the genes involved in the biosynthesis of vitamin B12). The amino acid sequence predicted by the ribC gene of M. thermoautotrophicum shows no similarity whatsoever to the sequences of riboflavin synthases of eubacteria and yeast. Most notably, the M. thermoautotrophicum protein does not show the internal sequence homology characteristic of eubacterial and yeast riboflavin synthases. The protein of M. thermoautotrophicum can be expressed efficiently in a recombinant E. coli strain. The specific activity of the purified, recombinant protein is 1,900 nmol mg(-1) h(-1) at 65 degrees C. In contrast to riboflavin synthases from eubacteria and fungi, the methanobacterial enzyme has an absolute requirement for magnesium ions. The 5' phosphate of 6,7-dimethyl-8-ribityllumazine does not act as a substrate. The findings suggest that riboflavin synthase has evolved independently in eubacteria and methanobacteria. PMID:9139911

Increased riboflavin production from activated bleaching earth by a mutant strain of Ashbya gossypii.

PubMed

Tajima, Satoshi; Itoh, Yoko; Sugimoto, Takashi; Kato, Tatsuya; Park, Enoch Y

2009-10-01

The production of riboflavin from vegetable oil was increased using a mutant strain of Ashbya gossypii. This mutant was generated by treating the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Riboflavin production was 10-fold higher in the mutant compared to the wild-type strain. The specific intracellular catalase activity after 3 d of culture was 6-fold higher in the mutant than in the wild-type strain. For the mutant, riboflavin production in the presence of 40 mM hydrogen peroxide was 16% less than that in the absence of hydrogen peroxide, whereas it was 56% less for the wild-type strain. The isocitrate lyase (ICL) activity of the mutant was 0.26 mU/mg of protein during the active riboflavin production phase, which was 2.6-fold higher than the wild-type strain. These data indicate that the mutant utilizes the carbon flux from the TCA cycle to the glyoxylate cycle more efficiently than the wild-type strain, resulting in enhanced riboflavin production. This novel mutant has the potential to be of use for industrial-scale riboflavin production from waste-activated bleaching earth (ABE), thereby transforming a useless material into a valuable bioproduct.

Comparison of Corneal Riboflavin Gradients Using Dextran and HPMC Solutions.

PubMed

Ehmke, Tobias; Seiler, Theo G; Fischinger, Isaak; Ripken, Tammo; Heisterkamp, Alexander; Frueh, Beatrice E

2016-12-01

To determine the riboflavin concentration gradient in the anterior corneal stroma when using hydroxypropyl methylcellulose (HPMC) or dextran as the carrier agent. Four different groups of porcine corneas (5 each) were compared regarding the riboflavin concentration in the anterior stroma. Prior to all experiments, stable hydration conditions were established for the corresponding solution. The dextran groups were treated with 0.1% riboflavin in 20% dextran for 10 and 30 minutes and the HPMC groups with 0.1% riboflavin in 1.1% HPMC for 10 and 30 minutes. After imbibition, nonlinear microscopy and consecutive image analysis were used to determine two-photon fluorescence intensities. To determine the riboflavin concentration, corneas were saturated and measured a second time by two-photon microscopy. With this measurement, a proper correction for absorption and scattering could be performed. Ultraviolet-A (UVA) transmission was measured after the application time for each group. Riboflavin concentration decreased with increasing depth and increased with longer application times in all groups. Comparing the dextran for 30 minutes and HPMC for 10 minutes groups, a significantly higher stromal riboflavin concentration was found within the most anterior 70 µm in the dextran group for 30 minutes, whereas deeper than 260 µm HPMC-assisted imbibition for 10 minutes yielded higher concentrations. In dextran-treated corneas, values obtained from pachymetry were substantially reduced, whereas HPMC-assisted imbibition led to a decent swelling. UVA transmission values were higher in dextran-assisted imbibition than in HPMC-assisted imbibition. Stromal riboflavin gradients are similar when applied in dextran for 30 minutes and HPMC for 10 minutes. When using HPMC solutions, a shallower cross-linked volume is expected due to a higher corneal hydration. [J Refract Surg. 2016;32(12):798-802.]. Copyright 2016, SLACK Incorporated.

Probiotic abilities of riboflavin-overproducing Lactobacillus strains: a novel promising application of probiotics.

PubMed

Arena, Mattia P; Russo, Pasquale; Capozzi, Vittorio; López, Paloma; Fiocco, Daniela; Spano, Giuseppe

2014-09-01

The probiotic potential of Lactobacillus plantarum and Lactobacillus fermentum strains, capable of overproducing riboflavin, was investigated. The riboflavin production was quantified in co-cultures of lactobacilli and human intestinal epithelial cells, and the riboflavin overproduction ability was confirmed. When milk and yogurt were used as carrier matrices, L. plantarum and L. fermentum strains displayed a significant ability to survive through simulated gastrointestinal transit. Adhesion was studied on both biotic and abiotic surfaces. Both strains adhered strongly on Caco-2 cells, negatively influenced the adhesion of Escherichia coli O157:H7, and strongly inhibited the growth of three reference pathogenic microbial strains. Resistance to major antibiotics and potential hemolytic activity were assayed. Overall, this study reveals that these Lactobacillus stains are endowed with promising probiotic properties and thus are candidates for the development of novel functional food which would be both enriched in riboflavin and induce additional health benefits, including a potential in situ riboflavin production, once the microorganisms colonize the host intestine.

Triazine-Carbon Nanotubes: New Platforms for the Design of Flavin Receptors.

PubMed

Lucío, María Isabel; Pichler, Federica; Ramírez, José Ramón; de la Hoz, Antonio; Sánchez-Migallón, Ana; Hadad, Caroline; Quintana, Mildred; Giulani, Angela; Bracamonte, Maria Victoria; Fierro, Jose L G; Tavagnacco, Claudio; Herrero, María Antonia; Prato, Maurizio; Vázquez, Ester

2016-06-20

The synthesis of functionalised carbon nanotubes as receptors for riboflavin (RBF) is reported. Carbon nanotubes, both single-walled and multi-walled, have been functionalised with 1,3,5-triazines and p-tolyl chains by aryl radical addition under microwave irradiation and the derivatives have been fully characterised by using a range of techniques. The interactions between riboflavin and the hybrids were analysed by using fluorescence and UV/Vis spectroscopic techniques. The results show that the attached functional groups minimise the π-π stacking interactions between riboflavin and the nanotube walls. Comparison of p-tolyl groups with the triazine groups shows that the latter have stronger interactions with riboflavin because of the presence of hydrogen bonds. Moreover, the triazine derivatives follow the Stern-Volmer relationship and show a high association constant with riboflavin. In this way, artificial receptors in catalytic processes could be designed through specific control of the interaction between functionalised carbon nanotubes and riboflavin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Riboflavin uptake transporter Slc52a2 (RFVT2) is upregulated in the mouse mammary gland during lactation.

PubMed

Wu, Alex Man Lai; Dedina, Liana; Dalvi, Pooja; Yang, Mingdong; Leon-Cheon, John; Earl, Brian; Harper, Patricia A; Ito, Shinya

2016-04-01

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second (SLC52A2) and third (SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction ofSlc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk. Copyright © 2016 the American Physiological Society.

21 CFR 73.450 - Riboflavin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... additive mixtures for coloring foods. (b) Specifications. Riboflavin shall meet the specifications given in... may be safely used for the coloring of foods generally, in amounts consistent with good manufacturing... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Riboflavin. 73.450 Section 73.450 Food and Drugs...

21 CFR 73.450 - Riboflavin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... additive mixtures for coloring foods. (b) Specifications. Riboflavin shall meet the specifications given in... may be safely used for the coloring of foods generally, in amounts consistent with good manufacturing... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Riboflavin. 73.450 Section 73.450 Food and Drugs...

Ultrafast Excited-state Deactivation of Flavins Bound to Dodecin*

PubMed Central

Staudt, Heike; Oesterhelt, Dieter; Grininger, Martin; Wachtveitl, Josef

2012-01-01

Dodecins, a group of flavin-binding proteins with a dodecameric quaternary structure, are able to incorporate two flavins within each of their six identical binding pockets building an aromatic tetrade with two tryptophan residues. Dodecin from the archaeal Halobacterium salinarum is a riboflavin storage device. We demonstrate that unwanted side reactions induced by reactive riboflavin species and degradation of riboflavin are avoided by ultrafast depopulation of the reactive excited state of riboflavin. Intriguingly, in this process, the staggered riboflavin dimers do not interact in ground and photoexcited states. Rather, within the tetrade assembly, each riboflavin is kept under the control of the respective adjacent tryptophan, which suggests that the stacked arrangement is a matter of optimizing the flavin load. We further identify an electron transfer in combination with a proton transfer as a central element of the effective excited state depopulation mechanism. Structural and functional comparisons of the archaeal dodecin with bacterial homologs reveal diverging evolution. Bacterial dodecins bind the flavin FMN instead of riboflavin and exhibit a clearly different binding pocket design with inverse incorporations of flavin dimers. The different adoption of flavin changes photochemical properties, making bacterial dodecin a comparably less efficient quencher of flavins. This supports a functional role different for bacterial and archaeal dodecins. PMID:22451648

Riboflavin accumulation and characterization of cDNAs encoding lumazine synthase and riboflavin synthase in bitter melon (Momordica charantia).

PubMed

Tuan, Pham Anh; Kim, Jae Kwang; Lee, Sanghyun; Chae, Soo Cheon; Park, Sang Un

2012-12-05

Riboflavin (vitamin B2) is the universal precursor of the coenzymes flavin mononucleotide and flavin adenine dinucleotide--cofactors that are essential for the activity of a wide variety of metabolic enzymes in animals, plants, and microbes. Using the RACE PCR approach, cDNAs encoding lumazine synthase (McLS) and riboflavin synthase (McRS), which catalyze the last two steps in the riboflavin biosynthetic pathway, were cloned from bitter melon (Momordica charantia), a popular vegetable crop in Asia. Amino acid sequence alignments indicated that McLS and McRS share high sequence identity with other orthologous genes and carry an N-terminal extension, which is reported to be a plastid-targeting sequence. Organ expression analysis using quantitative real-time RT PCR showed that McLS and McRS were constitutively expressed in M. charantia, with the strongest expression levels observed during the last stage of fruit ripening (stage 6). This correlated with the highest level of riboflavin content, which was detected during ripening stage 6 by HPLC analysis. McLS and McRS were highly expressed in the young leaves and flowers, whereas roots exhibited the highest accumulation of riboflavin. The cloning and characterization of McLS and McRS from M. charantia may aid the metabolic engineering of vitamin B2 in crops.

Effect of Ultraviolet Light Irradiation Combined with Riboflavin on Different Bacterial Pathogens from Ocular Surface Infection.

PubMed

Shen, Jing; Liang, Qingfeng; Su, Guanyu; Zhang, Yang; Wang, Zhiqun; Liang, Hong; Baudouin, Christophe; Labbé, Antoine

2017-01-01

In order to study Staphylococcus epidermis and Staphylococcus aureus in vitro viability after the exposure to ultraviolet (UV) light and riboflavin, twelve strains of Staphylococcus epidermis and twelve strains of Staphylococcus aureus were isolated from patients with bacterial keratitis. The growth situation of Staphylococcus epidermidis and Staphylococcus aureus under different experimental conditions was qualitatively observed. The number of colonies surviving bacteria was counted under different UV light power and different exposure time. The experiment showed that there was no inhibition effect on the growth of bacteria using riboflavin alone. In UV alone group and UV-riboflavin group, inhibition effect on the bacteria growth was found. The UV-riboflavin combination had better inhibition effect on bacteria than UV irradiation alone. The amount of bacteria in the UV-riboflavin group was decreased by 99.1%~99.5% and 54.8%~64.6% in the UV alone group, when the UV light power was 10.052 mW/cm 2 and the irradiation time was 30 min. Moreover, with the increase of the UV power or irradiation time, the survival rates of bacteria were rapidly reduced. Compared with Staphylococcus aureus , Staphylococcus epidermis was more easily to be killed under the action of UV light combined with riboflavin.

Characterization of particle deformation during compression measured by confocal laser scanning microscopy.

PubMed

Guo, H X; Heinämäki, J; Yliruusi, J

1999-09-20

Direct compression of riboflavin sodium phosphate tablets was studied by confocal laser scanning microscopy (CLSM). The technique is non-invasive and generates three-dimensional (3D) images. Tablets of 1% riboflavin sodium phosphate with two grades of microcrystalline cellulose (MCC) were individually compressed at compression forces of 1.0 and 26.8 kN. The behaviour and deformation of drug particles on the upper and lower surfaces of the tablets were studied under compression forces. Even at the lower compression force, distinct recrystallized areas in the riboflavin sodium phosphate particles were observed in both Avicel PH-101 and Avicel PH-102 tablets. At the higher compression force, the recrystallization of riboflavin sodium phosphate was more extensive on the upper surface of the Avicel PH-102 tablet than the Avicel PH-101 tablet. The plastic deformation properties of both MCC grades reduced the fragmentation of riboflavin sodium phosphate particles. When compressed with MCC, riboflavin sodium phosphate behaved as a plastic material. The riboflavin sodium phosphate particles were more tightly bound on the upper surface of the tablet than on the lower surface, and this could also be clearly distinguished by CLSM. Drug deformation could not be visualized by other techniques. Confocal laser scanning microscopy provides valuable information on the internal mechanisms of direct compression of tablets.

Comparison of Riboflavin and Toluidine Blue O as Photosensitizers for Photoactivated Disinfection on Endodontic and Periodontal Pathogens In Vitro.

PubMed

Nielsen, Henrik Krarup; Garcia, Javier; Væth, Michael; Schlafer, Sebastian

2015-01-01

Photoactivated disinfection has a strong local antimicrobial effect. In the field of dentistry it is an emerging adjunct to mechanical debridement during endodontic and periodontal treatment. In the present study, we investigate the effect of photoactivated disinfection using riboflavin as a photosensitizer and blue LED light for activation, and compare it to photoactivated disinfection with the widely used combination of toluidine blue O and red light. Riboflavin is highly biocompatible and can be activated with LED lamps at hand in the dental office. To date, no reports are available on the antimicrobial effect of photoactivated disinfection using riboflavin/blue light on oral microorganisms. Planktonic cultures of eight organisms frequently isolated from periodontal and/or endodontic lesions (Aggregatibacter actinomycetemcomitans, Candida albicans, Enterococcus faecalis, Escherischia coli, Lactobacillus paracasei, Porphyromonas gingivalis, Prevotella intermedia and Propionibacterium acnes) were subjected to photoactivated disinfection with riboflavin/blue light and toluidine blue O/red light, and survival rates were determined by CFU counts. Within the limited irradiation time of one minute, photoactivated disinfection with riboflavin/blue light only resulted in minor reductions in CFU counts, whereas full kills were achieved for all organisms when using toluidine blue O/red light. The black pigmented anaerobes P. gingivalis and P. intermedia were eradicated completely by riboflavin/blue light, but also by blue light treatment alone, suggesting that endogenous chromophores acted as photosensitizers in these bacteria. On the basis of our results, riboflavin cannot be recommended as a photosensitizer used for photoactivated disinfection of periodontal or endodontic infections.

Riboflavin as adjuvant with cisplatin: study in mouse skin cancer model.

PubMed

Salman, Maria; Naseem, Imrana

2015-01-01

Cisplatin used in treatment of solid tumor induces oxidative stress which leads to hepatotoxicity and nephrotoxicity. New strategies are therefore needed to combat toxicity and optimize its therapeutic potential. Riboflavin (VitaminB2) under photoillumination works as an anti proliferative agent and induces apoptosis. These properties of riboflavin have been exploited to mitigate cisplatin induced toxicities. 9,10-dimethylbenz(a)anthracene /12-O-tetradecanoylphorbol-13-acetate  were used to induce skin tumor in Swiss albino mice. The tumor induced mice were treated with cisplatin, riboflavin as well as their combination under photo illumination. In comparison to tumor control group the cisplatin and riboflavin treated groups showed a compromised level of antioxidant enzymes, functional markers and a higher degree of lipid peroxidation. However these parameters tended towards normal in the combination treated group. The results from histopathology indicate that apoptosis was favored mode of cell death and that necrosis was reduced in combination treated groups. Our findings indicate that combination of cisplatin with riboflavin under photo illumination synergizes its anti cancer activity towards cancer cells and attenuates the cisplatin induced toxicities.

Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection.

PubMed

Flieger, Miroslav; Bandouchova, Hana; Cerny, Jan; Chudíčková, Milada; Kolarik, Miroslav; Kovacova, Veronika; Martínková, Natália; Novák, Petr; Šebesta, Ondřej; Stodůlková, Eva; Pikula, Jiri

2016-09-13

Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml(-1), indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats' primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay.

Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection

PubMed Central

Flieger, Miroslav; Bandouchova, Hana; Cerny, Jan; Chudíčková, Milada; Kolarik, Miroslav; Kovacova, Veronika; Martínková, Natália; Novák, Petr; Šebesta, Ondřej; Stodůlková, Eva; Pikula, Jiri

2016-01-01

Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml−1, indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats’ primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay. PMID:27620349

Efficacy of multiple micronutrient supplementation for improving anemia, micronutrient status, growth, and morbidity of Peruvian infants.

PubMed

López de Romaña, Guillermo; Cusirramos, Sandra; López de Romaña, Daniel; Gross, Rainer

2005-03-01

Anemia, micronutrient deficiencies, and growth faltering are still common in Peru. The study objective was to determine the efficacy of different micronutrient supplements in preventing growth failure, anemia, and micronutrient deficiencies in Peruvian infants. Three hundred and thirteen infants aged 6 to 12 mo participated in a double-blind, masked, controlled trial in which they were randomly assigned to receive either a daily dose of iron (DI), a daily dose of multiple micronutrients (DMM), a weekly dose of multiple micronutrients, or a placebo (P) for 6 mo. None of the supplements tested prevented growth faltering or the morbidities common during infancy. Anemia and plasma homocysteine concentrations fell significantly in all groups during the study, but the mean change of plasma homocysteine during the trial period was significantly smaller in the DI group than in other groups, and the increase in hemoglobin concentrations was smaller in the P group than the micronutrient treatment groups. Plasma ferritin concentrations decreased least in the groups taking daily micronutrient supplements containing iron (DI and DMM). There were no significant differences among groups in mean final values or changes in plasma zinc, retinol, tocopherol, or riboflavin. Although the DMM intervention was the most efficacious for preventing anemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this group still remained anemic, zinc deficient, and iron deficient, respectively, at the end of the study. Further research thus should investigate whether higher doses of iron and zinc, together with infection control measures, are more efficacious.

A dynamic metabolic flux analysis of ABE (acetone-butanol-ethanol) fermentation by Clostridium acetobutylicum ATCC 824, with riboflavin as a by-product.

PubMed

Zhao, Xinhe; Kasbi, Mayssa; Chen, Jingkui; Peres, Sabine; Jolicoeur, Mario

2017-12-01

The present study reveals that supplementing sodium acetate (NaAc) strongly stimulates riboflavin production in acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum ATCC 824 with xylose as carbon source. Riboflavin production increased from undetectable concentrations to ∼0.2 g L -1 (0.53 mM) when supplementing 60 mM NaAc. Of interest, solvents production and biomass yield were also promoted with fivefold acetone, 2.6-fold butanol, and 2.4-fold biomass adding NaAc. A kinetic metabolic model, developed to simulate ABE biosystem, with riboflavin production, revealed from a dynamic metabolic flux analysis (dMFA) simultaneous increase of riboflavin (ribA) and GTP (precursor of riboflavin) (PurM) synthesis flux rates under NaAc supplementation. The model includes 23 fluxes, 24 metabolites, and 72 kinetic parameters. It also suggested that NaAc condition has first stimulated the accumulation of intracellular metabolite intermediates during the acidogenic phase, which have then fed the solventogenic phase leading to increased ABE production. In addition, NaAc resulted in higher intracellular levels of NADH during the whole culture. Moreover, lower GTP-to-adenosine phosphates (ATP, ADP, AMP) ratio under NaAc supplemented condition suggests that GTP may have a minor role in the cell energetic metabolism compared to its contribution to riboflavin synthesis. © 2017 Wiley Periodicals, Inc.

Comparison of four types of diet using clinical, laboratory and psychological studies

PubMed Central

Lockie, Andrew H.; Carlson, Eleanor; Kipps, Michael; Thomson, James

1985-01-01

Thirty-seven people of different dietary habits—vegans, ovolactovegetarians, whole-food omnivores and average omnivores—were studied using nine-day weighed food intakes, clinical and laboratory assessments, standard psychology questionnaires, measurements of urinary cortisol and catecholamine levels and questionnaires on life-style and health factors. The vegan diet most clearly approximated current thinking on diet, as expressed in the NACNE Report, but was deficient in vitamin D, riboflavin, and vitamin B12. Cholesterol levels were significantly higher in both diet and serum in all groups compared with the vegans. There was no significant difference in social background, money spent on food, exercise, smoking, stress levels or psychological parameters between groups. PMID:2993600

The Analysis of Riboflavin in Urine Using Fluorescence

NASA Astrophysics Data System (ADS)

Henderleiter, Julie A.; Hyslop, Richard M.

1996-06-01

To become functional as scientists, chemistry students must integrate concepts learned in their classes and apply them to novel, "real life" situations. The laboratory provides an important place for the students to practice integrating concepts. This laboratory experiment, designed for undergraduate biochemistry students, requires each student to determine the amount of riboflavin excreted by his/her body following oral administration of riboflavin contained in a multi-vitamin tablet. The experimental procedure describes a protocol for the analysis of riboflavin concentration in urine using a fluorometric assay. The students must draw upon their knowledge of solution preparation, construction of a standard curve, and back-calculation procedures to determine the concentration of riboflavin in their urine. Students need to combine knowledge from general and analytical chemistry with that learned in biochemistry to complete this analysis, thus providing an opportunity to integrate knowledge while answering a novel question.

Thiamin and riboflavin vitamers in human milk: effects of lipid-based nutrient supplementation and stage of lactation on vitamer secretion and contributions to total vitamin content

USDA-ARS?s Scientific Manuscript database

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main...

Excess Vitamin Intake before Starvation does not Affect Body Mass, Organ Mass, or Blood Variables but Affects Urinary Excretion of Riboflavin in Starving Rats.

PubMed

Moriya, Aya; Fukuwatari, Tsutomu; Shibata, Katsumi

2013-01-01

B-vitamins are important for producing energy from amino acids, fatty acids, and glucose. The aim of this study was to elucidate the effects of excess vitamin intake before starvation on body mass, organ mass, blood, and biological variables as well as on urinary excretion of riboflavin in rats. Adult rats were fed two types of diets, one with a low vitamin content (minimum vitamin diet for optimum growth) and one with a sufficient amount of vitamins (excess vitamin diet). Body mass, organ mass, and blood variables were not affected by excess vitamin intake before starvation. Interestingly, urinary riboflavin excretion showed a different pattern. Urine riboflavin in the excess vitamin intake group declined gradually during starvation, whereas it increased in the low vitamin intake group. Excess vitamin intake before starvation does not affect body mass, organ mass, or blood variables but does affect the urinary excretion of riboflavin in starving rats.

Influence of foliar riboflavin applications to vineyard on grape amino acid content.

PubMed

González-Santamaría, Rosario; Ruiz-González, Rubén; Nonell, Santi; Garde-Cerdán, Teresa; Pérez-Álvarez, Eva P

2018-02-01

Nitrogen is an important element for grapevine and winemaking, which affects plant development, grape juice fermentation and has a potential effect in modulating wine quality. The aim was to study the influence of foliar applications of riboflavin (vitamin B2) to vineyard on grape nitrogen composition. This vitamin has a reported capacity to protect different plant species, but its application to favor grape and grape juice quality had not previously been studied. This work reports the oenological properties and the effect on amino acid concentration of grape juices obtained from grapes treated with riboflavin at two different doses compared to control. Results showed that probable alcohol, malic acid, color intensity and hue had significant differences when the riboflavin treatments were applied. Most of the amino acids presented the highest concentrations when the lowest riboflavin dose was used. These results are promising in terms of fermentation development and grape juice nitrogen composition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isolation and partial characterisation of human riboflavin carrier protein and the estimation of its levels during human pregnancy.

PubMed

Natraj, U; George, S; Kadam, P

1988-06-01

Human cord serum contains protein(s) capable of binding to [14C]-riboflavin. Riboflavin-bound protein cross-reacts with anti-serum to chicken riboflavin carrier protein (cRCP). The carrier protein was isolated using affinity chromatography on a riboflavin AH Sepharose column. Bulk isolation and purification was also attempted by a combination of ion exchange, gel filtration and gel permeation chromatography on HPLC. The protein so isolated had a molecular weight of 36,000 +/- 2,000 daltons with an isoelectric point of 4.1. The levels of RCP in maternal serum during pregnancy were monitored using a sensitive heterologous radioimmunoassay system, using cRCP as standard and anti serum to cRCP. The levels of the protein increased after 4 months and remained significantly elevated up to 8 months. Although the level of the protein in the maternal serum remained low until 4 months, its level in amniotic fluid was elevated 2-3-fold as compared to that in serum.

Alternative Electron-Transfer Channels Ensure Ultrafast Deactivation of Light-Induced Excited States in Riboflavin Binding Protein.

PubMed

Zanetti-Polzi, Laura; Aschi, Massimiliano; Amadei, Andrea; Daidone, Isabella

2017-07-20

Flavoproteins, containing flavin chromophores, are enzymes capable of transferring electrons at very high speeds. The ultrafast photoinduced electron-transfer (ET) kinetics of riboflavin binding protein to the excited riboflavin was studied by femtosecond spectroscopy and found to occur within a few hundred femtoseconds [ Zhong and Zewail, Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 11867-11872 ]. This ultrafast kinetics was attributed to the presence of two aromatic rings that could transfer the electron to riboflavin: the side chains of tryptophan 156 and tyrosine 75. However, the underlying ET mechanism remained unclear. Here, using a hybrid quantum mechanical-molecular dynamics approach, we perform ET dynamics simulations taking into account the motion of the protein and the solvent upon ET. This approach reveals that ET occurs via a major reaction channel involving tyrosine 75 (83%) and a minor one involving tryptophan 156 (17%). We also show that the protein environment is designed to ensure the fast quenching of the riboflavin excited state.

[Effects of excess vitamin B1 or vitamin B2 on growth and urinary excretion of water-soluble vitamins in weaning rats].

PubMed

Fukuwatari, Tsutomu; Kuzuya, Mako; Satoh, Shiori; Shibata, Katsumi

2009-04-01

To determine the tolerable upper intake levels of vitamin B(1) and vitamin B(2) in humans, we investigated the effects of excess thiamin or riboflavin administration on body weight gain, food intake, tissue weights, and urinary excretion of B-group vitamins in weaning rats. The weaning rats were freely fed ordinary diet containing 0.0006% thiamin-HCl or the same diet with 0.006%, 0.03%, 0.18% or 1.0% thiamin-HCl for 30 days, or the diet containing 0.0006% riboflavin or the same diet with 0.1%, 0.5 or 1.0% riboflavin for 22 days. Mild diarrhea was seen only in the rats fed with 1.0% thiamin-HCl diet. Excess thiamin-HCl or riboflavin did not affect body weight gains, food intake or tissue weights. The urinary excretions of water-soluble vitamins also did not differ among the diets. These results clearly showed that feeding a diet containing up to 1.0% thiamin-HCl or 1.0% riboflavin did not induce apparent adverse effects, and the no-observed-adverse-effect-levels (NOAELs) for thiamin-HCl and riboflavin in rats might be 1.0% in diet, corresponding to 900 mg/kg body weight/day.

Persistent Epithelial Defects and Corneal Opacity After Collagen Cross-Linking With Substitution of Dextran (T-500) With Dextran Sulfate in Compounded Topical Riboflavin.

PubMed

Höllhumer, Roland; Watson, Stephanie; Beckingsale, Peter

2017-03-01

Collagen cross-linking (CXL) is a commonly performed procedure to prevent the progression of keratoconus. Riboflavin is an essential part of the procedure, which facilitates both the cross-linking process and protection of intraocular structures. Dextran can be added to riboflavin to create an isotonic solution. This case report highlights the importance of compounding riboflavin with the correct dextran solution. A retrospective case series. Six eyes of 4 male patients with keratoconus aged from 20 to 38 years underwent CXL with substitution of 20% dextran (T-500) with 20% dextran sulfate in a compounded riboflavin 0.1% solution. Postoperatively, persistent corneal epithelial defects, stromal haze, and then scarring occurred. Corneal transplantation was performed for visual rehabilitation but was complicated by graft rejection followed by failure (n = 1 eye), dehiscence (n = 4), cataract (n = 2), post-laser ablation haze (n = 1), and steroid-induced glaucoma (n = 2). The visual outcome was <6/18 in all 6 cases because of irregular astigmatism and stromal haze. Thinning, vascularization, and scarring of the residual host tissue were noted. Substitution of dextran (T-500) with dextran sulfate in riboflavin solutions during CXL results in loss of vision from permanent corneal opacity. Residual host changes may compromise the results of corneal transplantation.

The influence of vitamin B2 intake on the activation coefficient of erythrocyte glutation reductase in the elderly.

PubMed

López-Sobaler, A M; Ortega, R M; Quintas, M E; Navarro, A R; Aparicio, A; Gomez-Rodriguez, N; Cocho, M; Requejo, A M

2002-01-01

To evaluate the influence of dietetic vitamin B2 on the activation coefficient of erythrocyte glutation reductase (alpha-EGR) of a group of elderly people. The study subjects were 133, independently-living elderly people, between 65 and 90 years of age. A dietetic study was performed using a 7-day food record. Riboflavin status was measured by determining the alpha-EGR. Some 23.9% of subjects had riboflavin intakes lower than those recommended. At the biochemical level, 9.8% of subjects (7.7% of men and of 10.6% women) showed alpha-EGR>1.2. Those subjects with riboflavin intakes below 90% of those recommended showed significantly higher alpha-EGR levels (1.15+/-0.16), an indication of a poorer riboflavin status at the biochemical level. Those with greater intakes showed lower alpha-EGR values (1.05+/-0.10). Furthermore, the mean consumption of dairy products (an important source of this vitamin) by subjects is insuficiente (341.1+/-159.8 g/day, 2.1+/-1 servings/day). The data show that those with riboflavin intakes below those recommended took 204.7+/-89.4 g/day of milk products (1.3+/-0.5 servings/day) compared to the 384+/-153.1 g/day (2.4+/-1 servings/day) (p<0.001) consumed by those with higher riboflavin intakes. Although the mean riboflavin intake is acceptable, there remain some insufficiencies that require attention. It would seem advisable to recommend the elderly increase their intake of milk products. This would be especially important for subjects who take less than two rations per day.

Severe sensory neuropathy in patients with adult-onset multiple acyl-CoA dehydrogenase deficiency.

PubMed

Wang, Zhaoxia; Hong, Daojun; Zhang, Wei; Li, Wurong; Shi, Xin; Zhao, Danhua; Yang, Xu; Lv, He; Yuan, Yun

2016-02-01

Multiple Acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation. Most patients with late-onset MADD are clinically characterized by lipid storage myopathy with dramatic responsiveness to riboflavin treatment. Abnormalities of peripheral neuropathy have rarely been reported in patients with late-onset MADD. We describe six patients who presented with proximal limb weakness and loss of sensation in the distal limbs. Muscle biopsy revealed typical myopathological patterns of lipid storage myopathy and blood acylcarnitine profiles showed a combined elevation of multiple acylcarnitines supporting the diagnosis of MADD. However, nerve conduction investigations and sural nerve biopsies in these patients indicated severe axonal sensory neuropathy. Causative ETFDH gene mutations were found in all six cases. No other causative gene mutations were identified in mitochondrial DNA and genes associated with hereditary neuropathies through next-generation-sequencing panel. Late-onset patients with ETFDH mutations can present with proximal muscle weakness and distal sensory neuropathy, which might be a new phenotypic variation, but the precise underlying pathogenesis remains to be elucidated. Copyright © 2015. Published by Elsevier B.V.

Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells.

PubMed

Pincikova, Terezia; Paquin-Proulx, Dominic; Moll, Markus; Flodström-Tullberg, Malin; Hjelte, Lena; Sandberg, Johan K

2018-05-01

Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points. MAIT cells are a large, recently described subset of T cells that recognize microbial riboflavin metabolites presented by the highly evolutionarily conserved MR1 molecules. The MAIT cell deficiency was specific; other T-cell subsets were intact. Even though this is only one unique case, the findings lend significant support to the emerging role of MAIT cells in mucosal immune defense and suggest that MAIT cells may significantly modify the clinical phenotype of respiratory diseases. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

A novel mutation in ETFDH manifesting as severe neonatal-onset multiple acyl-CoA dehydrogenase deficiency.

PubMed

van der Westhuizen, Francois H; Smuts, Izelle; Honey, Engela; Louw, Roan; Schoonen, Maryke; Jonck, Lindi-Maryn; Dercksen, Marli

2018-01-15

Neonatal-onset multiple acyl-CoA dehydrogenase deficiency (MADD type I) is an autosomal recessive disorder of the electron transfer flavoprotein function characterized by a severe clinical and biochemical phenotype, including congenital abnormalities with unresponsiveness to riboflavin treatment as distinguishing features. From a retrospective study, relying mainly on metabolic data, we have identified a novel mutation, c.1067G>A (p.Gly356Glu) in exon 8 of ETFDH, in three South African Caucasian MADD patients with the index patient presenting the hallmark features of type I MADD and two patients with compound heterozygous (c.1067G>A+c.1448C>T) mutations presenting with MADD type III. SDS-PAGE western blot confirmed the significant effect of this mutation on ETFDH structural instability. The identification of this novel mutation in three families originating from the South African Afrikaner population is significant to direct screening and strategies for this disease, which amongst the organic acidemias routinely screened for, is relatively frequently observed in this population group. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparative analysis of single cell and droplet-based FACS for improving production phenotypes: Riboflavin overproduction in Yarrowia lipolytica.

PubMed

Wagner, James M; Liu, Leqian; Yuan, Shuo-Fu; Venkataraman, Maya V; Abate, Adam R; Alper, Hal S

2018-04-23

Evolutionary approaches to strain engineering inherently require the identification of suitable selection techniques for the product and phenotype of interest. In this work, we undertake a comparative analysis of two related but functionally distinct methods of high-throughput screening: traditional single cell fluorescence activated cell sorting (single cell FACS) and microdroplet-enabled FACS (droplet FACS) using water/oil/water (w/o/w) emulsions. To do so, we first engineer and evolve the non-conventional yeast Yarrowia lipolytica for high extracellular production of riboflavin (vitamin B2), an innately fluorescent product. Following mutagenesis and adaptive evolution, a direct parity-matched comparison of these two selection strategies was conducted. Both single cell FACS and droplet FACS led to significant increases in total riboflavin titer (32 and 54 fold relative to the parental PO1f strain, respectively). However, single cell FACS favored intracellular riboflavin accumulation (with only 70% of total riboflavin secreted) compared with droplet FACS that favored extracellular product accumulation (with 90% of total riboflavin secreted). We find that for the test case of riboflavin, the extent of secretion and total production were highly correlated. The resulting differences in production modes and levels clearly demonstrate the significant impact that selection approaches can exert on final evolutionary outcomes in strain engineering. Moreover, we note that these results provide a cautionary tale when intracellular read-outs of product concentration (including signals from biosensors) are used as surrogates for total production of potentially secreted products. In this regard, these results demonstrate that extracellular production is best assayed through an encapsulation technique when performing high throughput screening. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Photochemical eradication of methicillin-resistant Staphylococcus aureus by blue light activation of riboflavin.

PubMed

Makdoumi, Karim; Goodrich, Ray; Bäckman, Anders

2017-08-01

To compare elimination of methicillin-resistant Staphylococcus aureus (MRSA) by exposure of blue light alone and with riboflavin. A reference strain of MRSA was cultured and diluted in PBS with and without riboflavin (0.01%). Fifteen microlitre was added on a microscope slide, creating a fluid layer with a thickness of around 400 microns. Both of the bacterial suspensions were exposed to blue light, and the effect between exposure with and without riboflavin was compared. Evaluation involved two different wavelengths (412 and 450 nm) of blue light with a lower (5.4 J/cm 2 ) and higher dose (approximately 28.5 J/cm 2 ). The effect of 412 nm light was also evaluated for a thicker fluid layer (1.17 mm). After exposure, colony-forming units (CFUs) were determined for each solution. All measurements were repeated eight times. The reductions in bacteria were similar for both wavelengths. With riboflavin, a statistically significant elimination was observed for both 412 and 450 nm (p < 0.001). At both dosages, the mean reduction was more pronounced with the presence of riboflavin than without it. Using the higher dose, CFU reduction was 99% and 98%, respectively, for 412 and 450 nm light. The bactericidal efficacy was high also in the deeper fluid layer (93%, higher dose). Riboflavin enhanced the antibacterial effect on the exposed MRSA strain of blue light for both 412 and 450 nm blue light. This indicates that blue light could be considered for possible implementation in deep corneal infections. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Protective effects of riboflavin and selenium on brain microsomal Ca2+-ATPase and oxidative damage caused by glyceryl trinitrate in a rat headache model.

PubMed

Nazıroğlu, Mustafa; Çelik, Ömer; Uğuz, Abdulhadi Cihangir; Bütün, Ayşe

2015-03-01

Migraine headaches are considered to be associated with increased mitochondrial energy metabolism. Mitochondrial oxidative stress is also important in migraine headache pathophysiology although riboflavin and selenium (Se) induced a modulator role on mitochondrial oxidative stress in the brain. The current study aimed to determine the effects of Se with/without riboflavin on the microsomal membrane Ca(2+)-ATPase (MMCA), lipid peroxidation, antioxidant, and electroencephalography (EEG) values in glyceryl trinitrate (GTN)-induced brain injury rats. Thirty-two rats were randomly divided into four groups. The first group was used as the control, and the second group was the GTN group. Se and Se plus oral riboflavin were administered to rats constituting the third and fourth groups for 10 days prior to GTN administration. The second, third, and fourth groups received GTN to induce headache. Ten hours after the administration of GTN, the EEG records and brain cortex samples were obtained for all groups. Brain cortex microsomes were obtained from the brain samples. The brain and microsomal lipid peroxidation levels were higher in the GTN group compared to the control group, whereas they were decreased by selenium and selenium + riboflavin treatments. Vitamin A, vitamin C, vitamin E, and reduced glutathione (GSH) concentrations of the brain and MMCA, GSH and glutathione peroxidase values of microsomes were decreased by the GTN administration, although the values and β-carotene concentrations were increased by Se and Se + riboflavin treatments. There was no significant change in EEG records of the four groups. In conclusion, Se with/without riboflavin administration protected against GTN-induced brain oxidative toxicity by inhibiting free radicals and the modulation of MMCA activity and supporting the antioxidant redox system.

Inactivation of Orientia tsutsugamushi in red blood cells, plasma, and platelets with riboflavin and light, as demonstrated in an animal model.

PubMed

Rentas, Francisco; Harman, Ronald; Gomez, Charlotte; Salata, Jeanne; Childs, Joseph; Silva, Tonya; Lippert, Lloyd; Montgomery, Joshua; Richards, Allen; Chan, Chye; Jiang, Ju; Reddy, Heather; Li, John; Goodrich, Raymond

2007-02-01

Treatment of blood products with riboflavin and light has been used to reduce the number of certain pathogens. Orientia (formerly Rickettsia) tsutsugamushi, the scrub typhus agent, is an obligate intracellular bacterium that grows free in the cytoplasm of infected cells. This study evaluated the capability of riboflavin and light to inactivate O. tsutsugamushi in red blood cells (RBCs), platelets (PLTs), and plasma, as measured by mouse infectivity. A total of 108 mice, equally divided into groups receiving RBCs, plasma, and PLTs, received untreated products infected with 10(0) to 10(5) organisms. Eighteen mice received products infected with 10(5) organisms and were subsequently treated with riboflavin and light. Mice were monitored daily for up to 17 days for signs and symptoms of infection (e.g., lethargy, labored breathing, rough coat) and killed upon appearance of symptoms or on Day 17 after infection. Real-time polymerase chain reaction (PCR) on blood and Giemsa stains from peritoneal exudates were performed. A total of 102 of 108 mice receiving the untreated products developed signs and symptoms of infection and had positive PCR and Giemsa stain results. None of the 18 animals receiving riboflavin and light-treated blood products exhibited signs or symptoms of infection, nor was infection observed by PCR testing or Giemsa staining. Riboflavin and light are effective in reducing O. tsutsugamushi. Mice injected with blood products inoculated with 10(5) organisms and treated with riboflavin and light did not experience any signs or symptoms of infection, 17 days after inoculation. A 5-log reduction of this organism in blood was achieved as assayed in an animal model.

In vitro analysis of riboflavin-modified, experimental, two-step etch-and-rinse dentin adhesive: Fourier transform infrared spectroscopy and micro-Raman studies.

PubMed

Daood, Umer; Swee Heng, Chan; Neo Chiew Lian, Jennifer; Fawzy, Amr S

2015-06-26

To modify two-step experimental etch-and-rinse dentin adhesive with different concentrations of riboflavin and to study its effect on the bond strength, degree of conversion, along with resin infiltration within the demineralized dentin substrate, an experimental adhesive-system was modified with different concentrations of riboflavin (m/m, 0, 1%, 3%, 5% and 10%). Dentin surfaces were etched with 37% phosphoric acid, bonded with respective adhesives, restored with restorative composite-resin, and sectioned into resin-dentin slabs and beams to be stored for 24 h or 9 months in artificial saliva. Micro-tensile bond testing was performed with scanning electron microscopy to analyse the failure of debonded beams. The degree of conversion was evaluated with Fourier transform infrared spectroscopy (FTIR) at different time points along with micro-Raman spectroscopy analysis. Data was analyzed with one-way and two-way analysis of variance followed by Tukey's for pair-wise comparison. Modification with 1% and 3% riboflavin increased the micro-tensile bond strength compared to the control at 24 h and 9-month storage with no significant differences in degree of conversion (P<0.05). The most predominant failure mode was the mixed fracture among all specimens except 10% riboflavin-modified adhesive specimens where cohesive failure was predominant. Raman analysis revealed that 1% and 3% riboflavin adhesives specimens showed relatively higher resin infiltration. The incorporation of riboflavin in the experimental two-step etch-and-rinse adhesive at 3% (m/m) improved the immediate bond strengths and bond durability after 9-month storage in artificial saliva without adversely affecting the degree of conversion of the adhesive monomers and resin infiltration.

Phenol and terpene quenching of singlet- and triplet-excited states of riboflavin in relation to light-struck flavor formation in beer.

PubMed

Cardoso, Daniel R; Olsen, Karsten; Møller, Jens K S; Skibsted, Leif H

2006-07-26

Phenolic compounds present in beer were shown by fluorescence spectroscopy and laser flash photolysis to deactivate both singlet- and triplet-excited states of riboflavin with bimolecular rate constants close to the diffusion control ranging from 2.8x10(9) to 1.1x10(10) M-1 s-1 and from 1.1x10(9) to 2.6x10(9) M-1 s-1, respectively. Enthalpies of activation were low (up to 33.2 kJ mol-1), and entropies of activation were positive, ranging from 17 to 92 J mol-1 K-1, as derived from temperature dependence, indicating a compensation effect. From a Stern-Volmer analysis of the singlet-excited riboflavin quenching by phenols it was found that high amounts of phenolic compounds (>0.3 M) would be needed to hinder triplet-excited riboflavin generation. On the other hand, a phenolic content of 0.36 mM is likely to quench 90% of the triplet-excited state. Phenol photodegradation was found to be complex, and using ESI-MS analysis it was not possible to identify specific photooxidation products of the phenolic compounds; only the photoproducts of riboflavin could be detected and structurally assigned. The rate of reaction of triplet-excited riboflavin with phenolic compounds in acetonitrile/citrate buffer (pH 4.6, 10 mM) is 550 times faster than the reaction with iso-alpha-acids from hops, indicating that triplet-excited quenchers such as phenols may be involved in the early steps in light-struck flavor formation in beer through radical formation. Terpenes present in herb-flavored beers were found to be nonreactive toward singlet- and triplet-excited-state riboflavin, and any protection depends on other mechanisms.

In vitro analysis of riboflavin-modified, experimental, two-step etch-and-rinse dentin adhesive: Fourier transform infrared spectroscopy and micro-Raman studies

PubMed Central

Daood, Umer; Swee Heng, Chan; Neo Chiew Lian, Jennifer; Fawzy, Amr S

2015-01-01

To modify two-step experimental etch-and-rinse dentin adhesive with different concentrations of riboflavin and to study its effect on the bond strength, degree of conversion, along with resin infiltration within the demineralized dentin substrate, an experimental adhesive-system was modified with different concentrations of riboflavin (m/m, 0, 1%, 3%, 5% and 10%). Dentin surfaces were etched with 37% phosphoric acid, bonded with respective adhesives, restored with restorative composite–resin, and sectioned into resin–dentin slabs and beams to be stored for 24 h or 9 months in artificial saliva. Micro-tensile bond testing was performed with scanning electron microscopy to analyse the failure of debonded beams. The degree of conversion was evaluated with Fourier transform infrared spectroscopy (FTIR) at different time points along with micro-Raman spectroscopy analysis. Data was analyzed with one-way and two-way analysis of variance followed by Tukey's for pair-wise comparison. Modification with 1% and 3% riboflavin increased the micro-tensile bond strength compared to the control at 24 h and 9-month storage with no significant differences in degree of conversion (P<0.05). The most predominant failure mode was the mixed fracture among all specimens except 10% riboflavin-modified adhesive specimens where cohesive failure was predominant. Raman analysis revealed that 1% and 3% riboflavin adhesives specimens showed relatively higher resin infiltration. The incorporation of riboflavin in the experimental two-step etch-and-rinse adhesive at 3% (m/m) improved the immediate bond strengths and bond durability after 9-month storage in artificial saliva without adversely affecting the degree of conversion of the adhesive monomers and resin infiltration. PMID:25257880

Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines.

PubMed

Mal, Pinky; Dutta, Kallol; Bandyopadhyay, Debasish; Basu, Anirban; Khan, Rajni; Bishayi, Biswadev

2013-03-01

To determine alternate therapeutic measures to combat Staphylococcus aureus induced arthritis. Thus, azithromycin was combined with riboflavin, which may combat the ROS production and inflammation. An in vivo model of S. aureus infection-induced arthritis was set up by infecting mice with 5 × 10⁶ bacterial cell/mouse. S. aureus was administered intravenously. Azithromycin and riboflavin was injected intraperitoneally at a single dose of 100 and 20 mg/kg body, respectively. The mice were sacrificed at 3, 9, 15 days post infection (dpi). TNF-α, IFN-γ, IL-6 and IL-10 from serum and SOD, catalase and reduced glutathione concentration were observed in hepatic, cardiac, renal and splenic tissue. CFU was found very prominent in spleen and joints and reduced in blood at 3 and 9 dpi. However, treatment with azithromycin and riboflavin completely eradicated the bacteria from blood and spleen. TNF-α, IFN-γ, IL-6, and MCP-1 were induced due to infection which were downregulated by treatment with azithromycin and riboflavin. Infected mice were also found to have altered antioxidant status, measured in terms of reduced glutathione and anti-oxidant enzymes such as SOD and catalase. These changes were found to be ameliorated when the animals were co-treated with azithromycin and riboflavin.

Atomic Force Microscopy Probing of Receptor–Nanoparticle Interactions for Riboflavin Receptor Targeted Gold–Dendrimer Nanocomposites

PubMed Central

2015-01-01

Riboflavin receptors are overexpressed in malignant cells from certain human breast and prostate cancers, and they constitute a group of potential surface markers important for cancer targeted delivery of therapeutic agents and imaging molecules. Here we report on the fabrication and atomic force microscopy (AFM) characterization of a core–shell nanocomposite consisting of a gold nanoparticle (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We designed this nanocomposite for potential applications such as a cancer targeted imaging material based on its surface plasmon resonance properties conferred by AuNP. We employed AFM as a technique for probing the binding interaction between the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled precise measurement of the AuNP height distribution before (13.5 nm) and after chemisorption of riboflavin-conjugated dendrimer (AuNP–dendrimer; 20.5 nm). Binding of RfBP to the AuNP–dendrimer caused a height increase to 26.7 nm, which decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand, supporting interaction of AuNP–dendrimer and its target protein. In summary, physical determination of size distribution by AFM imaging can serve as a quantitative approach to monitor and characterize the nanoscale interaction between a dendrimer-covered AuNP and target protein molecules in vitro. PMID:24571134

Genome-wide RNA-seq of iPSC-derived motor neurons indicates selective cytoskeletal perturbation in Brown–Vialetto disease that is partially rescued by riboflavin

PubMed Central

Rizzo, Federica; Ramirez, Agnese; Compagnucci, Claudia; Salani, Sabrina; Melzi, Valentina; Bordoni, Andreina; Fortunato, Francesco; Niceforo, Alessia; Bresolin, Nereo; Comi, Giacomo P.; Bertini, Enrico; Nizzardo, Monica; Corti, Stefania

2017-01-01

Riboflavin is essential in numerous cellular oxidation/reduction reactions but is not synthesized by mammalian cells. Riboflavin absorption occurs through the human riboflavin transporters RFVT1 and RFVT3 in the intestine and RFVT2 in the brain. Mutations in these genes are causative for the Brown–Vialetto–Van Laere (BVVL), childhood-onset syndrome characterized by a variety of cranial nerve palsies as well as by spinal cord motor neuron (MN) degeneration. Why mutations in RFVTs result in a neural cell–selective disorder is unclear. As a novel tool to gain insights into the pathomechanisms underlying the disease, we generated MNs from induced pluripotent stem cells (iPSCs) derived from BVVL patients as an in vitro disease model. BVVL-MNs explained a reduction in axon elongation, partially improved by riboflavin supplementation. RNA sequencing profiles and protein studies of the cytoskeletal structures showed a perturbation in the neurofilament composition in BVVL-MNs. Furthermore, exploring the autophagy–lysosome pathway, we observed a reduced autophagic/mitophagic flux in patient MNs. These features represent emerging pathogenetic mechanisms in BVVL-associated neurodegeneration, partially rescued by riboflavin supplementation. Our data showed that this therapeutic strategy could have some limits in rescuing all of the disease features, suggesting the need to develop complementary novel therapeutic strategies. PMID:28382968

Force spectroscopy of multivalent binding of riboflavin-conjugated dendrimers to riboflavin binding protein.

PubMed

Leistra, Abigail N; Han, Jong Hyun; Tang, Shengzhuang; Orr, Bradford G; Banaszak Holl, Mark M; Choi, Seok Ki; Sinniah, Kumar

2015-05-07

Putative riboflavin receptors are considered as biomarkers due to their overexpression in breast and prostate cancers. Hence, these receptors can be potentially exploited for use in targeted drug delivery systems where dendrimer nanoparticles with multivalent ligand attachments can lead to greater specificity in cellular interactions. In this study, the single molecule force spectroscopy technique was used to assess the physical strength of multivalent interactions by employing a riboflavin (RF)-conjugated generation 5 PAMAM dendrimer G5(RF)n nanoparticle. By varying the average RF ligand valency (n = 0, 3, 5), the rupture force was measured between G5(RF)n and the riboflavin binding protein (RFBP). The rupture force increased when the valency of RF increased. We observed at the higher valency (n = 5) three binding events that increased in rupture force with increasing loading rate. Assuming a single energy barrier, the Bell-Evans model was used to determine the kinetic off-rate and barrier width for all binding interactions. The analysis of our results appears to indicate that multivalent interactions are resulting in changes to rupture force and kinetic off-rates.

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia.

PubMed

Cınar, Yasin; Cingü, Abdullah Kürşat; Sahin, Alparslan; Türkcü, Fatih Mehmet; Yüksel, Harun; Caca, Ihsan

2014-03-01

Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases. The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation. Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea. Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.

Remarkable motor recovery after riboflavin therapy in adult-onset Brown—Vialetto—Van Laere syndrome

PubMed Central

Bashford, James A; Chowdhury, Fahmida A; Shaw, Chris E

2017-01-01

The clinical diagnosis of Brown—Vialetto—Van Laere syndrome in this woman with rapidly progressive pontobulbar palsy led to empirical high-dose oral riboflavin (1200 mg/day) therapy. This resulted in a dramatic improvement in her motor function from being anarthric, dysphagic, tetraparetic and in ventilatory failure to living independently with mild dysarthria and distal limb weakness. DNA sequencing of the SLC52A3 gene found compound heterozygous C-terminus mutations, V413A1/D461Y, consistent with recent reports of mutations within the riboflavin transporter genes (SLC52A2 and SLC52A3) in this condition. Early diagnosis and empirical riboflavin therapy can lead to major motor recovery in this condition, that can be sustained with long-term maintenance therapy. PMID:27777325

Biofunctionalized Zinc Oxide Field Effect Transistors for Selective Sensing of Riboflavin with Current Modulation

PubMed Central

Hagen, Joshua A.; Kim, Sang N.; Bayraktaroglu, Burhan; Leedy, Kevin; Chávez, Jorge L.; Kelley-Loughnane, Nancy; Naik, Rajesh R.; Stone, Morley O.

2011-01-01

Zinc oxide field effect transistors (ZnO-FET), covalently functionalized with single stranded DNA aptamers, provide a highly selective platform for label-free small molecule sensing. The nanostructured surface morphology of ZnO provides high sensitivity and room temperature deposition allows for a wide array of substrate types. Herein we demonstrate the selective detection of riboflavin down to the pM level in aqueous solution using the negative electrical current response of the ZnO-FET by covalently attaching a riboflavin binding aptamer to the surface. The response of the biofunctionalized ZnO-FET was tuned by attaching a redox tag (ferrocene) to the 3′ terminus of the aptamer, resulting in positive current modulation upon exposure to riboflavin down to pM levels. PMID:22163977

Riboflavin

MedlinePlus

... and nails, to slow aging, for canker sores, multiple sclerosis, memory loss including Alzheimer's disease, high blood pressure, ... the risk of liver cancer in older people. Multiple sclerosis. Early research shows that taking riboflavin by mouth ...

On the nature of solvatochromic effect: The riboflavin absorption spectrum as a case study

NASA Astrophysics Data System (ADS)

Daidone, Isabella; Amadei, Andrea; Aschi, Massimiliano; Zanetti-Polzi, Laura

2018-03-01

We present here the calculation of the absorption spectrum of riboflavin in acetonitrile and dimethyl sulfoxide using a hybrid quantum/classical approach, namely the perturbed matrix method, based on quantum mechanical calculations and molecular dynamics simulations. The calculated spectra are compared to the absorption spectrum of riboflavin previously calculated in water and to the experimental spectra obtained in all three solvents. The experimentally observed variations in the absorption spectra upon change of the solvent environment are well reproduced by the calculated spectra. In addition, the nature of the excited states of riboflavin interacting with different solvents is investigated, showing that environment effects determine a recombination of the gas-phase electronic states and that such a recombination is strongly affected by the polarity of the solvent inducing significant changes in the absorption spectra.

The role of riboflavin in decolourisation of Congo red and bioelectricity production using Shewanella oneidensis-MR1 under MFC and non-MFC conditions.

PubMed

Gomaa, Ola M; Fapetu, Segun; Kyazze, Godfrey; Keshavarz, Tajalli

2017-03-01

Dissimilatory metal reducing bacteria can exchange electrons extracellularly and hold great promise for their use in simultaneous wastewater treatment and electricity production. This study investigated the role of riboflavin, an electron carrier, in the decolourisation of Congo red in microbial fuel cells (MFCs) using Shewanella oneidensis MR-1 as a model organism. The contribution of the membrane-bound protein MtrC to the decolourisation process was also investigated. Within the range of riboflavin concentrations tested, 20 µM was found to be the best with >95% of the dye (initial concentration 200 mg/L) decolourised in MFCs within 50 h compared to 90% in the case where no riboflavin was added. The corresponding maximum power density was 45 mW/m 2 . There was no significant difference in the overall decolourisation efficiencies of Shewanela oneidensis MR-1 ΔMtrC mutants compared to the wild type. However, in terms of power production the mutant produced more power (P max 76 mW/m 2 ) compared to the wild type (P max 46 mW/m 2 ) which was attributed to higher levels of riboflavin secreted in solution. Decolourisation efficiencies in non-MFC systems (anaerobic bottles) were similar to those under MFC systems indicating that electricity generation in MFCs does not impair dye decolourisation efficiencies. The results suggest that riboflavin enhances both decolourisation of dyes and simultaneous electricity production in MFCs.

[Effects of riboflavin combined with photosensitization on reduction of Gram-positive and Gram-negative indicating germs in plasma and P-selectin expression of apheresis platelet concentrates].

PubMed

Zhou, Xue-Yin; Xiong, Wen; Kong, Ling-Kui

2010-08-01

This study was purposed to confirm the practical efficacy of reducing indicating germs suspended in plasma by riboflavin and photosensitized inactivation and to evaluate its influence on activation of apheresis platelet concentrates. The synergistic effects of riboflavin combined with ultraviolet irradiation on inactivation of germs were investigated by using Escherichia Coli (E. coli) and Staphylococcus Aureus (S. aureus) as Gram⁻ and Gram(+) indicating germs, respectively. The activation status of apheresis-platelet concentrates treated with riboflavin combined with ultraviolet irradiation was detected by flow cytometry. The results showed that when 50 μmol/L of riboflavin was combined with 6.2 J/ml of ultraviolet irradiation, the T/E ratios reached 1.42 for E. coli and 1.68 for S. Aureus, and reduction of E. Coli and S. Aureus were 3.87 Logs and 3.82 Logs respectively; the CD62p expression level on germ-inactivated platelets stored at 22 degrees C for 0 and 5 days were 4.92% and 36.18% respectively, which slightly increased as compared with controls (3.94% and 32.03)% (p < 0.05). It is concluded that combination of riboflavin with ultraviolet irradiation displays well synergistic effects which can reduce E. Coli and S. Aureus counts, but no significantly influence on platelets. The partial activation of liquid platelets mainly presents metabolism damage during storage, which is found at an acceptable level.

Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes.

PubMed

Matern, Andreas; Pedrolli, Danielle; Großhennig, Stephanie; Johansson, Jörgen; Mack, Matthias

2016-12-01

The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B 2 ), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. Lmo1329 generates the cofactors flavin mononucleotide (FMN) and FAD, whereas Lmo0728 produces FAD only. The combined activities of Lmo1329 and Lmo0728 are responsible for the intracellular formation of the toxic cofactor analogs roseoflavin mononucleotide (RoFMN), roseoflavin adenine dinucleotide (RoFAD), 8-demethyl-8-aminoriboflavin mononucleotide (AFMN), and 8-demethyl-8-aminoriboflavin adenine dinucleotide (AFAD). In vivo reporter gene assays and in vitro transcription/translation experiments show that the L. monocytogenes FMN riboswitch Rli96, which controls expression of the riboflavin transport gene lmo1945, is negatively affected by riboflavin/FMN and RoF/RoFMN but not by AF/AFMN. Treatment of L. monocytogenes with RoF or AF leads to drastically reduced FMN/FAD levels. We suggest that the reduced flavin cofactor levels in combination with concomitant synthesis of inactive cofactor analogs (RoFMN, RoFAD, AFMN, and AFAD) explain why RoF and AF contribute to antibiotic activity in L. monocytogenes IMPORTANCE: The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are small molecules which are produced by Streptomyces davawensis and Streptomyces cinnabarinus RoF and AF were reported to have antibacterial activity, and we studied how these compounds are metabolized by the human bacterial pathogen Listeria monocytogenes We found that the L. monocytogenes protein Lmo1945 mediates uptake of AF and RoF and that the combined activities of the enzymes Lmo1329 and Lmo0728 are responsible for the conversion of AF and RoF to toxic cofactor analogs. Comparative studies with RoF and AF (a weaker antibiotic) suggest that the reduction in FMN/FAD levels and the formation of inactive FMN/FAD analogs explain to a large extent the antibiotic activity of AF and RoF. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bacterial Production, Characterization and Protein Modeling of a Novel Monofuctional Isoform of FAD Synthase in Humans: An Emergency Protein?

PubMed

Leone, Piero; Galluccio, Michele; Barbiroli, Alberto; Eberini, Ivano; Tolomeo, Maria; Vrenna, Flavia; Gianazza, Elisabetta; Iametti, Stefania; Bonomi, Francesco; Indiveri, Cesare; Barile, Maria

2018-01-06

FAD synthase (FADS, EC 2.7.7.2) is the last essential enzyme involved in the pathway of biosynthesis of Flavin cofactors starting from Riboflavin (Rf). Alternative splicing of the human FLAD1 gene generates different isoforms of the enzyme FAD synthase. Besides the well characterized isoform 1 and 2, other FADS isoforms with different catalytic domains have been detected, which are splice variants. We report the characterization of one of these novel isoforms, a 320 amino acid protein, consisting of the sole C-terminal 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductase domain (named FADS6). This isoform has been previously detected in Riboflavin-Responsive (RR-MADD) and Non-responsive Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) patients with frameshift mutations of FLAD1 gene. To functionally characterize the hFADS6, it has been over-expressed in Escherichia coli and purified with a yield of 25 mg·L -1 of cell culture. The protein has a monomeric form, it binds FAD and is able to catalyze FAD synthesis (k cat about 2.8 min -1 ), as well as FAD pyrophosphorolysis in a strictly Mg 2+ -dependent manner. The synthesis of FAD is inhibited by HgCl₂. The enzyme lacks the ability to hydrolyze FAD. It behaves similarly to PAPS. Combining threading and ab-initio strategy a 3D structural model for such isoform has been built. The relevance to human physio-pathology of this FADS isoform is discussed.

Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis.

PubMed

Smuts, Cornelius M; Lombard, Carl J; Benadé, A J Spinnler; Dhansay, Muhammad A; Berger, Jacques; Hop, Le Thi; López de Romaña, Guillermo; Untoro, Juliawati; Karyadi, Elvina; Erhardt, Jürgen; Gross, Rainer

2005-03-01

Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.

Cloning and characterization of a riboflavin-binding hexamerin from the larval fat body of a lepidopteran stored grain pest, Corcyra cephalonica.

PubMed

Rao, V Venkat; Ningshen, Thuirei Jacob; Chaitanya, R K; Senthilkumaran, B; Dutta-Gupta, Aparna

2016-01-01

In the present study, a riboflavin-binding hexamerin (RbHex) was cloned and characterized from the larval fat body of Corcyra cephalonica. The complete cDNA (2121bp) encodes a 706-amino acid protein with a molecular mass ~82kDa. Expression of RbHex 82 was predominant in fat body among larval tissues. Further, it is prominently expressed during the last instar larval development. Homology modeling and docking studies predicted riboflavin binding site of the hexamerin. Spectrofluorimetric analysis further confirmed riboflavin release from the hexamerin fraction. Quantitative RT-PCR studies demonstrated hormonal regulation of RbHex 82. 20-Hydroxyecdysone (20HE) had a stimulatory effect on its transcription whereas JH alone did not show any effect. However, JH in the presence of 20HE maintains the RbHex 82 expression which indicates the JH's role as a status quo factor. This study is the first to report the characterization of riboflavin-binding hexamerin in a lepidopteran pest. Further, the possibility of RbHex 82 as a pest control target is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.

PubMed

Stops, Frances; Fell, John T; Collett, John H; Martini, Luigi G

2008-02-28

Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.

Riboflavin and migraine: the bridge over troubled mitochondria.

PubMed

Colombo, Bruno; Saraceno, Lorenzo; Comi, Giancarlo

2014-05-01

Brain energy metabolism has been found to be disturbed in migraine. A mitochondrial defect may reduce the threshold for migraine attacks both increasing neuronal excitability and leading migrainous brain to a hyper-responsiveness to triggering stimuli. Riboflavin, a major co-factor in oxidative metabolism, may overcome this impairment. RCT studies in adult confirmed that riboflavin is safe and probably effective in migraine prophylaxis, based on level B evidence. Improving brain energy metabolism may reduce the susceptibility to migraine when brain energy demand increases due to both physiological and biopsychological factors.

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2

PubMed Central

Foley, A. Reghan; Menezes, Manoj P.; Pandraud, Amelie; Gonzalez, Michael A.; Al-Odaib, Ahmad; Abrams, Alexander J.; Sugano, Kumiko; Yonezawa, Atsushi; Manzur, Adnan Y.; Burns, Joshua; Hughes, Imelda; McCullagh, B. Gary; Jungbluth, Heinz; Lim, Ming J.; Lin, Jean-Pierre; Megarbane, Andre; Urtizberea, J. Andoni; Shah, Ayaz H.; Antony, Jayne; Webster, Richard; Broomfield, Alexander; Ng, Joanne; Mathew, Ann A.; O’Byrne, James J.; Forman, Eva; Scoto, Mariacristina; Prasad, Manish; O’Brien, Katherine; Olpin, Simon; Oppenheim, Marcus; Hargreaves, Iain; Land, John M.; Wang, Min X.; Carpenter, Kevin; Horvath, Rita; Straub, Volker; Lek, Monkol; Gold, Wendy; Farrell, Michael O.; Brandner, Sebastian; Phadke, Rahul; Matsubara, Kazuo; McGarvey, Michael L.; Scherer, Steven S.; Baxter, Peter S.; King, Mary D.; Clayton, Peter; Rahman, Shamima; Reilly, Mary M.; Ouvrier, Robert A.; Christodoulou, John; Züchner, Stephan; Muntoni, Francesco

2014-01-01

Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms. PMID:24253200

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2.

PubMed

Foley, A Reghan; Menezes, Manoj P; Pandraud, Amelie; Gonzalez, Michael A; Al-Odaib, Ahmad; Abrams, Alexander J; Sugano, Kumiko; Yonezawa, Atsushi; Manzur, Adnan Y; Burns, Joshua; Hughes, Imelda; McCullagh, B Gary; Jungbluth, Heinz; Lim, Ming J; Lin, Jean-Pierre; Megarbane, Andre; Urtizberea, J Andoni; Shah, Ayaz H; Antony, Jayne; Webster, Richard; Broomfield, Alexander; Ng, Joanne; Mathew, Ann A; O'Byrne, James J; Forman, Eva; Scoto, Mariacristina; Prasad, Manish; O'Brien, Katherine; Olpin, Simon; Oppenheim, Marcus; Hargreaves, Iain; Land, John M; Wang, Min X; Carpenter, Kevin; Horvath, Rita; Straub, Volker; Lek, Monkol; Gold, Wendy; Farrell, Michael O; Brandner, Sebastian; Phadke, Rahul; Matsubara, Kazuo; McGarvey, Michael L; Scherer, Steven S; Baxter, Peter S; King, Mary D; Clayton, Peter; Rahman, Shamima; Reilly, Mary M; Ouvrier, Robert A; Christodoulou, John; Züchner, Stephan; Muntoni, Francesco; Houlden, Henry

2014-01-01

Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.

Crystallographic and kinetic study of riboflavin synthase from Brucella abortus, a chemotherapeutic target with an enhanced intrinsic flexibility

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

Serer, María I.; Bonomi, Hernán R.; Guimarães, Beatriz G.

This work reports crystal structures of trimeric riboflavin synthase from the pathogen B. abortus both as the apo protein and in complex with several ligands of interest. It is shown that ligand binding drives the assembly of the unique active site of the trimer, and these findings are complemented by a detailed kinetic study on this enzyme, in which marked inhibition by substrate and product was observed. Riboflavin synthase (RS) catalyzes the last step of riboflavin biosynthesis in microorganisms and plants, which corresponds to the dismutation of two molecules of 6,7-dimethyl-8-ribityllumazine to yield one molecule of riboflavin and one moleculemore » of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. Owing to the absence of this enzyme in animals and the fact that most pathogenic bacteria show a strict dependence on riboflavin biosynthesis, RS has been proposed as a potential target for antimicrobial drug development. Eubacterial, fungal and plant RSs assemble as homotrimers lacking C{sub 3} symmetry. Each monomer can bind two substrate molecules, yet there is only one active site for the whole enzyme, which is located at the interface between two neighbouring chains. This work reports the crystallographic structure of RS from the pathogenic bacterium Brucella abortus (the aetiological agent of the disease brucellosis) in its apo form, in complex with riboflavin and in complex with two different product analogues, being the first time that the structure of an intact RS trimer with bound ligands has been solved. These crystal models support the hypothesis of enhanced flexibility in the particle and also highlight the role of the ligands in assembling the unique active site. Kinetic and binding studies were also performed to complement these findings. The structural and biochemical information generated may be useful for the rational design of novel RS inhibitors with antimicrobial activity.« less

Absorption and emission spectroscopic characterisation of 8-amino-riboflavin

NASA Astrophysics Data System (ADS)

Tyagi, A.; Zirak, P.; Penzkofer, A.; Mathes, T.; Hegemann, P.; Mack, M.; Ghisla, S.

2009-10-01

The flavin dye 8-amino-8-demethyl- D-riboflavin (AF) in the solvents water, DMSO, methanol, and chloroform/DMSO was studied by absorption and fluorescence spectroscopy. The first absorption band is red-shifted compared to riboflavin, and blue-shifted compared to roseoflavin (8-dimethylamino-8-demethyl-D-riboflavin). The fluorescence quantum yield of AF in the studied solvents varies between 20% and 50%. The fluorescence lifetimes were found to be in the 2-5 ns range. AF is well soluble in DMSO, weakly soluble in water and methanol, and practically insoluble in chloroform. The limited solubility causes AF aggregation, which was seen in differences between measured absorption spectra and fluorescence excitation spectra. Light scattering in the dye absorption region is discussed and approximate absorption cross-section spectra are determined from the combined measurement of transmission and fluorescence excitation spectra. The photo-stability of AF was studied by prolonged light exposure. The photo-degradation routes of AF are discussed.

Characterization of mitochondrial proteome in a severe case of ETF-QO deficiency.

PubMed

Rocha, H; Ferreira, R; Carvalho, J; Vitorino, R; Santa, C; Lopes, L; Gregersen, N; Vilarinho, L; Amado, F

2011-12-10

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a mitochondrial fatty acid oxidation disorder caused by mutations that affect electron transfer flavoprotein (ETF) or ETF:ubiquinone oxidoreductase (ETF-QO) or even due to unidentified disturbances of riboflavin metabolism. Besides all the available data on the molecular basis of FAO disorders, including MADD, the pathophysiological mechanisms underlying clinical phenotype development, namely at the mitochondrial level, are poorly understood. In order to contribute to the elucidation of these mechanisms, we isolated mitochondria from cultured fibroblasts, from a patient with a severe MADD presentation due to ETF-QO deficiency, characterize its mitochondrial proteome and compare it with normal controls. The used approach (2-DE-MS/MS) allowed the positive identification of 287 proteins in both patient and controls, presenting 35 of the significant differences in their relative abundance. Among the differentially expressed are proteins associated to binding/folding functions, mitochondrial antioxidant enzymes as well as proteins associated to apoptotic events. The overexpression of chaperones like Hsp60 or mitochondrial Grp75, antioxidant enzymes and apoptotic proteins reflects the mitochondrial response to a complete absence of ETF-QO. Our study provides a global perspective of the mitochondrial proteome plasticity in a severe case of MADD and highlights the main molecular pathways involved in its pathogenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease.

PubMed

Johnson, Janel O; Gibbs, J Raphael; Megarbane, Andre; Urtizberea, J Andoni; Hernandez, Dena G; Foley, A Reghan; Arepalli, Sampath; Pandraud, Amelie; Simón-Sánchez, Javier; Clayton, Peter; Reilly, Mary M; Muntoni, Francesco; Abramzon, Yevgeniya; Houlden, Henry; Singleton, Andrew B

2012-09-01

Brown-Vialetto-Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly C20orf54), one of three known riboflavin transporter genes, have recently been shown to underlie a number of severe cases of Brown-Vialetto-Van Laere syndrome; however, cases and families with this disease exist that do not appear to be caused by SLC52A3 mutations. We used a combination of linkage and exome sequencing to identify the disease causing mutation in an extended Lebanese Brown-Vialetto-Van Laere kindred, whose affected members were negative for SLC52A3 mutations. We identified a novel mutation in a second member of the riboflavin transporter gene family (gene symbol: SLC52A2) as the cause of disease in this family. The same mutation was identified in one additional subject, from 44 screened. Within this group of 44 patients, we also identified two additional cases with SLC52A3 mutations, but none with mutations in the remaining member of this gene family, SLC52A1. We believe this strongly supports the notion that defective riboflavin transport plays an important role in Brown-Vialetto-Van Laere syndrome. Initial work has indicated that patients with SLC52A3 defects respond to riboflavin treatment clinically and biochemically. Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results.

SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown-Vialetto-Van Laere Syndrome in an Indian patient: First genetically proven case with mutations in two riboflavin transporters

PubMed Central

Udhayabanu, Tamilarasan; Subramanian, Veedamali S; Teafatiller, Trevor; Gowda, Vykuntaraju K; Raghavan, Varun S; Varalakshmi, Perumal; Said, Hamid M; Ashokkumar, Balasubramaniem

2017-01-01

Background Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by bulbar palsies and sensorineural deafness, is mainly associated with defective riboflavin transporters encoded by the SLC52A2 and SLC52A3 genes. Methods Here we present a 16-year-old BVVLS patient belonging to a five generation consanguineous family from Indian ethnicity with two homozygous missense mutations viz., c.421C>A [p.P141T] in SLC52A2 and c.62A>G [p.N21S] in SLC52A3. Results Functional characterization based on 3H-riboflavin uptake assay and live-cell confocal imaging revealed that the effect of mutation c.421C>A [p.P141T] identified in SLC52A2 had a slight reduction in riboflavin uptake; on the other hand, the c.62A>G [p.N21S] identified in SLC52A3 showed a drastic reduction in riboflavin uptake, which appeared to be due to impaired trafficking and membrane targeting of the hRFVT-3 protein. Conclusions This is the first report presenting mutations in both riboflavin transporters hRFVT-2 and hRFVT-3 in the same BVVLS patient. Also, c.62A>G [p.N21S] in SLC52A3 appears to contribute more to the disease phenotype in this patient than c.421C>A [p.P141T] in SLC52A2. PMID:27702554

Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease

PubMed Central

Johnson, Janel O.; Gibbs, J. Raphael; Megarbane, Andre; Urtizberea, J. Andoni; Hernandez, Dena G.; Foley, A. Reghan; Arepalli, Sampath; Pandraud, Amelie; Simón-Sánchez, Javier; Clayton, Peter; Reilly, Mary M.; Muntoni, Francesco; Abramzon, Yevgeniya; Houlden, Henry

2012-01-01

Brown–Vialetto–Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly C20orf54), one of three known riboflavin transporter genes, have recently been shown to underlie a number of severe cases of Brown–Vialetto–Van Laere syndrome; however, cases and families with this disease exist that do not appear to be caused by SLC52A3 mutations. We used a combination of linkage and exome sequencing to identify the disease causing mutation in an extended Lebanese Brown–Vialetto–Van Laere kindred, whose affected members were negative for SLC52A3 mutations. We identified a novel mutation in a second member of the riboflavin transporter gene family (gene symbol: SLC52A2) as the cause of disease in this family. The same mutation was identified in one additional subject, from 44 screened. Within this group of 44 patients, we also identified two additional cases with SLC52A3 mutations, but none with mutations in the remaining member of this gene family, SLC52A1. We believe this strongly supports the notion that defective riboflavin transport plays an important role in Brown–Vialetto–Van Laere syndrome. Initial work has indicated that patients with SLC52A3 defects respond to riboflavin treatment clinically and biochemically. Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results. PMID:22740598

Thiamin and Riboflavin in Human Milk: Effects of Lipid-Based Nutrient Supplementation and Stage of Lactation on Vitamer Secretion and Contributions to Total Vitamin Content

PubMed Central

Hampel, Daniela; Shahab-Ferdows, Setareh; Adair, Linda S.; Bentley, Margaret E.; Flax, Valerie L.; Jamieson, Denise J.; Ellington, Sascha R.; Tegha, Gerald; Chasela, Charles S.; Kamwendo, Debbie; Allen, Lindsay H.

2016-01-01

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer’s contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9–4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151μg/L (TMP), 13.3 versus 10.5μg/L (free thiamin, p<0.05 for both, suggesting an up-regulated active mechanism for TMP and free thiamin accumulation at early stages of lactation. Free riboflavin was consistently and significantly increased with LNS (range: 14.8–19.6μg/L (LNS) versus 5.0–7.4μg/L (control), p<0.001), shifting FAD:riboflavin relative amounts from 92–94:6–8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The continuous presence of FAD in breast milk suggests an active transport and secretion system for this vitamer or possibly formation of this co-enymatic form in the mammary gland. PMID:26886782

Dietary modifications to improve micronutrient status of Indian children and adolescents with type 1 diabetes.

PubMed

Parthasarathy, Lavanya S; Chiplonkar, Shashi A; Khadilkar, Anuradha V; Khadilkar, Vaman V

2015-01-01

Diet plays a crucial role for maintaining normal growth and development while optimizing glycemic control in children with diabetes. Dietary restrictions, in a diabetic child's diet may lead to micronutrient deficiencies. To examine dietary nutritional deficiencies of Asian Indian children with Type 1 diabetes mellitus and develop micronutrient-rich recipes suitable for them. Anthropometry, diet (3-day recall) of 70 children with diabetes (24 boys) was recorded. Daily nutrient intakes and nutrient content of recipes were estimated using CDIET version 2.0. Mean intake amongst children for energy was 79% of Indian Recommended Dietary Allowance (RDA), protein was 105% RDA, but fat intakes were high (143% RDA). Mean intakes of riboflavin, β carotene, zinc, iron were less than 50%, and thiamin and calcium were around 60% RDA suggesting a possible multiple micronutrient deficiency. Based on popularly consumed snacks, 20 healthy recipes were devised that can be incorporated in children's diet. Mean energy content of new recipes was similar to routine snacks (281±28 kcal/100 g vs 306±27 kcal/100 g cooked weight). However, the mean vitamin and mineral content of new recipes was significantly higher (p<0.01). There was a five-fold increase in total mineral content (zinc, calcium and iron) and twofold increase in total vitamin content (β carotene, vitamin C, vitamin B-1, B-2, and B-3) in new recipes compared with the routine snacks. Multiple dietary micronutrient deficiencies are observed in diabetic children. Addition of newly developed recipes in their everyday diet may help to enhance micronutrient intakes without increasing their energy load.

[Optimization of riboflavin sodium phosphate loading to calcium alginate floating microspheres by response surface methodology].

PubMed

Zhang, An-yang; Fan, Tian-yuan

2009-12-18

To investigate the preparation, optimization and in vitro properties of riboflavin sodium phosphate floating microspheres. The floating microspheres composed of riboflavin sodium phosphate and calcium alginate were prepared using ion gelatin-oven drying method. The properties of the microspheres were investigated, including the buoyancy, release, appearance and entrapment efficiency. The formulation was optimized by response surface methodology (RSM). The optimized microspheres were round. The entrapment efficiency was 57.49%. All the microspheres could float on the artificial gastric juice over 8 hours. The release of the drug from the microspheres complied with Fick's diffusion.

Pichia guilliermondii

NASA Astrophysics Data System (ADS)

Sibirny, Andriy A.; Boretsky, Yuriy R.

Pichia guilliermondii (asporogenous strains of this species are designated as Candida guilliermondii ) is the model organism of a group so named “ flavinogenic yeasts ” capable of riboflavin oversynthesis during starvation for iron. Besides, some strains of this species efficiently convert xylose to xylitol, an anti-caries sweetener. However, there are also pathogenic C. guilliermondii strains. This species has been used for studying enzymology of riboflavin synthesis due to overproduction of participating enzymes and intermediates under iron-limiting conditions as well as for identification of genes of negative and positive action involved in such a regulation. Besides, P. guilliermondii was used for identification and studying the properties of the systems for active transport of riboflavin in the cell (riboflavin permease) and out of the cell (riboflavin “ excretase ” ). The genetic line of P. guilliermondii with high fertility has been selected and the methods of classic genetics (hybridization and analysis of meiotic segregation) have been developed. More recently, tools for molecular genetic studies of P. guilliermondii have been developed which include collection of host strains, vectors with recessive and dominant markers, several transformation protocols including that for gene knock out. Recently, the genome of this yeast species was sequenced and become publicly available ( http://www.broad.mit.edu )

Spectrophotometric determination of ternary mixtures of thiamin, riboflavin and pyridoxal in pharmaceutical and human plasma by least-squares support vector machines.

PubMed

Niazi, Ali; Zolgharnein, Javad; Afiuni-Zadeh, Somaie

2007-11-01

Ternary mixtures of thiamin, riboflavin and pyridoxal have been simultaneously determined in synthetic and real samples by applications of spectrophotometric and least-squares support vector machines. The calibration graphs were linear in the ranges of 1.0 - 20.0, 1.0 - 10.0 and 1.0 - 20.0 microg ml(-1) with detection limits of 0.6, 0.5 and 0.7 microg ml(-1) for thiamin, riboflavin and pyridoxal, respectively. The experimental calibration matrix was designed with 21 mixtures of these chemicals. The concentrations were varied between calibration graph concentrations of vitamins. The simultaneous determination of these vitamin mixtures by using spectrophotometric methods is a difficult problem, due to spectral interferences. The partial least squares (PLS) modeling and least-squares support vector machines were used for the multivariate calibration of the spectrophotometric data. An excellent model was built using LS-SVM, with low prediction errors and superior performance in relation to PLS. The root mean square errors of prediction (RMSEP) for thiamin, riboflavin and pyridoxal with PLS and LS-SVM were 0.6926, 0.3755, 0.4322 and 0.0421, 0.0318, 0.0457, respectively. The proposed method was satisfactorily applied to the rapid simultaneous determination of thiamin, riboflavin and pyridoxal in commercial pharmaceutical preparations and human plasma samples.

Finding the Needle in the Haystack-the Use of Microfluidic Droplet Technology to Identify Vitamin-Secreting Lactic Acid Bacteria.

PubMed

Chen, Jun; Vestergaard, Mike; Jensen, Thomas Glasdam; Shen, Jing; Dufva, Martin; Solem, Christian; Jensen, Peter Ruhdal

2017-05-30

Efficient screening technologies aim to reduce both the time and the cost required for identifying rare mutants possessing a phenotype of interest in a mutagenized population. In this study, we combined a mild mutagenesis strategy with high-throughput screening based on microfluidic droplet technology to identify Lactococcus lactis variants secreting vitamin B 2 (riboflavin). Initially, we used a roseoflavin-resistant mutant of L. lactis strain MG1363, JC017, which secreted low levels of riboflavin. By using fluorescence-activated droplet sorting, several mutants that secreted riboflavin more efficiently than JC017 were readily isolated from the mutagenesis library. The screening was highly efficient, and candidates with as few as 1.6 mutations per million base pairs (Mbp) were isolated. The genetic characterization revealed that riboflavin production was triggered by mutations inhibiting purine biosynthesis, which is surprising since the purine nucleotide GTP is a riboflavin precursor. Purine starvation in the mutants induced overexpression of the riboflavin biosynthesis cluster ribABGH When the purine starvation was relieved by purine supplementation in the growth medium, the outcome was an immediate downregulation of the riboflavin biosynthesis cluster and a reduction in riboflavin production. Finally, by applying the new isolates in milk fermentation, the riboflavin content of milk (0.99 mg/liter) was improved to 2.81 mg/liter, compared with 0.66 mg/liter and 1.51 mg/liter by using the wild-type strain and the original roseoflavin-resistant mutant JC017, respectively. The results obtained demonstrate how powerful classical mutagenesis can be when combined with droplet-based microfluidic screening technology for obtaining microorganisms with useful attributes. IMPORTANCE The food industry prefers to use classical approaches, e.g., random mutagenesis followed by screening, to improve microorganisms used in food production, as the use of recombinant DNA technologies is still not widely accepted. Although modern automated screening platforms are widely accessible, screening remains as a bottleneck in strain development, especially when a mild mutagenesis approach is applied to reduce the chance of accumulating unintended mutations, which may cause unwanted phenotypic changes. Here, we incorporate a droplet-based high-throughput screening method into the strain development process and readily capture L. lactis variants with more efficient vitamin secretion from low-error-rate mutagenesis libraries. This study shows that useful mutants showing strong phenotypes but without extensive mutations can be identified with efficient screening technologies. It is therefore possible to avoid accumulating detrimental mutations while enriching beneficial ones through iterative mutagenesis screening. Due to the low mutation rates, the genetic determinants are also readily identified. Copyright © 2017 Chen et al.

Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

PubMed Central

Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

2015-01-01

Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking.

PubMed

Labate, Cristina; Lombardo, Marco; Lombardo, Giuseppe; De Santo, Maria Penelope

2017-01-01

The purpose of this study was to investigate the biomechanical stiffening effect induced by nanoplatform-based transepithelial riboflavin/UV-A cross-linking protocol using atomic force microscopy (AFM). Twelve eye bank donor human sclerocorneal tissues were investigated using a commercial atomic force microscope operated in force spectroscopy mode. Four specimens underwent transepithelial corneal cross-linking using a hypotonic solution of 0.1% riboflavin with biodegradable polymeric nanoparticles of 2-hydroxypropyl-β-cyclodextrin plus enhancers (trometamol and ethylenediaminetetraacetic acid) and UV-A irradiation with a 10 mW/cm2 device for 9 minutes. After treatment, the corneal epithelium was removed using the Amoils brush, and the Young's modulus of the most anterior stroma was quantified as a function of scan rate by AFM. The results were compared with those collected from four specimens that underwent conventional riboflavin/UV-A corneal cross-linking and four untreated specimens. The average Young's modulus of the most anterior stroma after the nanoplatform-based transepithelial and conventional riboflavin/UV-A corneal cross-linking treatments was 2.5 times (P < 0.001) and 1.7 times (P < 0.001) greater than untreated controls respectively. The anterior stromal stiffness was significantly different between the two corneal cross-linking procedures (P < 0.001). The indentation depth decreased after corneal cross-linking treatments, ranging from an average of 2.4 ± 0.3 μm in untreated samples to an average of 1.2 ± 0.1 μm and 1.8 ± 0.1 μm after nanoplatform-based transepithelial and conventional cross-linking, respectively. The present nanotechnology-based transepithelial riboflavin/UV-A corneal cross-linking was effective to improve the biomechanical strength of the most anterior stroma of the human cornea.

SLC52A2 [p.P141T] and SLC52A3 [p.N21S] causing Brown-Vialetto-Van Laere Syndrome in an Indian patient: First genetically proven case with mutations in two riboflavin transporters.

PubMed

Udhayabanu, Tamilarasan; Subramanian, Veedamali S; Teafatiller, Trevor; Gowda, Vykuntaraju K; Raghavan, Varun S; Varalakshmi, Perumal; Said, Hamid M; Ashokkumar, Balasubramaniem

2016-11-01

Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by bulbar palsies and sensorineural deafness, is mainly associated with defective riboflavin transporters encoded by the SLC52A2 and SLC52A3 genes. Here we present a 16-year-old BVVLS patient belonging to a five generation consanguineous family from Indian ethnicity with two homozygous missense mutations viz., c.421C>A [p.P141T] in SLC52A2 and c.62A>G [p.N21S] in SLC52A3. Functional characterization based on 3 H-riboflavin uptake assay and live-cell confocal imaging revealed that the effect of mutation c.421C>A [p.P141T] identified in SLC52A2 had a slight reduction in riboflavin uptake; on the other hand, the c.62A>G [p.N21S] identified in SLC52A3 showed a drastic reduction in riboflavin uptake, which appeared to be due to impaired trafficking and membrane targeting of the hRFVT-3 protein. This is the first report presenting mutations in both riboflavin transporters hRFVT-2 and hRFVT-3 in the same BVVLS patient. Also, c.62A>G [p.N21S] in SLC52A3 appears to contribute more to the disease phenotype in this patient than c.421C>A [p.P141T] in SLC52A2. Copyright © 2016 Elsevier B.V. All rights reserved.

Riboflavin Is an Active Redox Cofactor in the Na+-pumping NADH:Quinone Oxidoreductase (Na+-NQR) from Vibrio cholerae*

PubMed Central

Juárez, Oscar; Nilges, Mark J.; Gillespie, Portia; Cotton, Jennifer; Barquera, Blanca

2008-01-01

Here we present new evidence that riboflavin is present as one of four flavins in Na+-NQR. In particular, we present conclusive evidence that the source of the neutral radical is not one of the FMNs and that riboflavin is the center that gives rise to the neutral flavosemiquinone. The riboflavin is a bona fide redox cofactor and is likely to be the last redox carrier of the enzyme, from which electrons are donated to quinone. We have constructed a double mutant that lacks both covalently bound FMN cofactors (NqrB-T236Y/NqrC-T225Y) and have studied this mutant together with the two single mutants (NqrB-T236Y and NqrC-T225Y) and a mutant that lacks the noncovalently bound FAD in NqrF (NqrF-S246A). The double mutant contains riboflavin and FAD in a 0.6:1 ratio, as the only flavins in the enzyme; noncovalently bound flavins were detected. In the oxidized form, the double mutant exhibits an EPR signal consistent with a neutral flavosemiquinone radical, which is abolished on reduction of the enzyme. The same radical can be observed in the FAD deletion mutant. Furthermore, when the oxidized enzyme reacts with ubiquinol (the reduced form of the usual electron acceptor) in a process that reverses the physiological direction of the electron flow, a single kinetic phase is observed. The kinetic difference spectrum of this process is consistent with one-electron reduction of a neutral flavosemiquinone. The presence of riboflavin in the role of a redox cofactor is thus far unique to Na+-NQR. PMID:18832377

21 CFR 582.5695 - Riboflavin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Riboflavin. 582.5695 Section 582.5695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

21 CFR 582.5695 - Riboflavin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Riboflavin. 582.5695 Section 582.5695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

21 CFR 73.450 - Riboflavin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.450 Riboflavin. (a) Identity. (1) The color additive... practice; except that it may not be used to color foods for which standards of identity have been...

21 CFR 73.450 - Riboflavin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.450 Riboflavin. (a) Identity. (1) The color additive... practice; except that it may not be used to color foods for which standards of identity have been...

21 CFR 73.450 - Riboflavin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.450 Riboflavin. (a) Identity. (1) The color additive... practice; except that it may not be used to color foods for which standards of identity have been...

21 CFR 582.5695 - Riboflavin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Riboflavin. 582.5695 Section 582.5695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

21 CFR 582.5695 - Riboflavin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Riboflavin. 582.5695 Section 582.5695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

21 CFR 582.5695 - Riboflavin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Riboflavin. 582.5695 Section 582.5695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary Supplements...

Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52.

PubMed

Yonezawa, Atsushi; Inui, Ken-ichi

2013-01-01

Riboflavin, a water-soluble vitamin also known as vitamin B2, is essential for normal cellular functions. Riboflavin transporters play important roles in its homeostasis. Recently, three novel riboflavin transporters were identified, and designated as RFT1, RFT2 and RFT3. Because the RFTs did not show similarity to other SLC transporters, and RFT1 and RFT3 are similar in sequence and function, they were assigned into a new SLC family, SLC52. Subsequently, RFT1/GPR172B, RFT3/GPR172A and RFT2/C20orf54 were renamed as RFVT1/SLC52A1, RFVT2/SLC52A2 and RFVT3/SLC52A3, respectively. In this review, we summarize recent findings on the cloning, nomenclature, functional characterization and genetic diseases of RFVT1/SLC52A1, RFVT2/SLC52A2 and RFVT3/SLC52A3. Copyright © 2012 Elsevier Ltd. All rights reserved.

Remarkable motor recovery after riboflavin therapy in adult-onset Brown-Vialetto-Van Laere syndrome.

PubMed

Bashford, James A; Chowdhury, Fahmida A; Shaw, Chris E

2017-01-01

The clinical diagnosis of Brown-Vialetto-Van Laere syndrome in this woman with rapidly progressive pontobulbar palsy led to empirical high-dose oral riboflavin (1200 mg/day) therapy. This resulted in a dramatic improvement in her motor function from being anarthric, dysphagic, tetraparetic and in ventilatory failure to living independently with mild dysarthria and distal limb weakness. DNA sequencing of the SLC52A3 gene found compound heterozygous C-terminus mutations, V413A1/D461Y, consistent with recent reports of mutations within the riboflavin transporter genes (SLC52A2 and SLC52A3) in this condition. Early diagnosis and empirical riboflavin therapy can lead to major motor recovery in this condition, that can be sustained with long-term maintenance therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Photo-dynamics of roseoflavin and riboflavin in aqueous and organic solvents

NASA Astrophysics Data System (ADS)

Zirak, P.; Penzkofer, A.; Mathes, T.; Hegemann, P.

2009-03-01

Roseoflavin (8-dimethylamino-8-demethyl- D-riboflavin) and riboflavin in aqueous and organic solvents are studied by optical absorption spectroscopy, fluorescence spectroscopy, and fluorescence decay kinetics. Solvent polarity dependent absorption shifts are observed. The fluorescence quantum yields are solvent dependent. For roseoflavin the fluorescence decay shows a bi-exponential dependence (ps to sub-ps time constant, and 100 ps to a few ns time constant). The roseoflavin photo-dynamics is explained in terms of fast intra-molecular charge transfer (diabatic electron transfer) from the dimethylamino electron donor group to the pteridin carbonyl electron acceptor followed by intra-molecular charge recombination. The fast fluorescence component is due to direct locally-excited-state emission, and the slow fluorescence component is due to delayed locally-excited-state emission and charge transfer state emission. The fluorescence decay of riboflavin is mono-exponential. The S 1-state potential energy surface is determined by vibronic relaxation and solvation dynamics due to excited-state dipole moment changes (adiabatic optical electron transfer).

Mixomics analysis of Bacillus subtilis: effect of oxygen availability on riboflavin production.

PubMed

Hu, Junlang; Lei, Pan; Mohsin, Ali; Liu, Xiaoyun; Huang, Mingzhi; Li, Liang; Hu, Jianhua; Hang, Haifeng; Zhuang, Yingping; Guo, Meijin

2017-09-12

Riboflavin, an intermediate of primary metabolism, is one kind of important food additive with high economic value. The microbial cell factory Bacillus subtilis has already been proven to possess significant importance for the food industry and have become one of the most widely used riboflavin-producing strains. In the practical fermentation processes, a sharp decrease in riboflavin production is encountered along with a decrease in the dissolved oxygen (DO) tension. Influence of this oxygen availability on riboflavin biosynthesis through carbon central metabolic pathways in B. subtilis is unknown so far. Therefore the unveiled effective metabolic pathways were still an unaccomplished task till present research work. In this paper, the microscopic regulation mechanisms of B. subtilis grown under different dissolved oxygen tensions were studied by integrating 13 C metabolic flux analysis, metabolomics and transcriptomics. It was revealed that the glucose metabolic flux through pentose phosphate (PP) pathway was lower as being confirmed by smaller pool sizes of metabolites in PP pathway and lower expression amount of ykgB at transcriptional level. The latter encodes 6-phosphogluconolactonase (6-PGL) under low DO tension. In response to low DO tension in broth, the glucose metabolic flux through Embden-Meyerhof-Parnas (EMP) pathway was higher and the gene, alsS, encoding for acetolactate synthase was significantly activated that may result due to lower ATP concentration and higher NADH/NAD + ratio. Moreover, ResE, a membrane-anchored protein that is capable of oxygen regulated phosphorylase activity, and ResD, a regulatory protein that can be phosphorylated and dephosphorylated by ResE, were considered as DO tension sensor and transcriptional regulator respectively. This study shows that integration of transcriptomics, 13 C metabolic flux analysis and metabolomics analysis provides a comprehensive understanding of biosynthesized riboflavin's regulatory mechanisms in B. subtilis grown under different dissolved oxygen tension conditions. The two-component system, ResD-ResE, was considered as the signal receiver of DO tension and gene regulator that led to differences between biomass and riboflavin production after triggering the shifts in gene expression, metabolic flux distributions and metabolite pool sizes.

Theoretical modeling of the absorption spectrum of aqueous riboflavin

NASA Astrophysics Data System (ADS)

Zanetti-Polzi, Laura; Aschi, Massimiliano; Daidone, Isabella; Amadei, Andrea

2017-02-01

In this study we report the modeling of the absorption spectrum of riboflavin in water using a hybrid quantum/classical mechanical approach, the MD-PMM methodology. By means of MD-PMM calculations, with which the effect of riboflavin internal motions and of solvent interactions on the spectroscopic properties can be explicitly taken into account, we obtain an absorption spectrum in very good agreement with the experimental spectrum. In particular, the calculated peak maxima show a consistent improvement with respect to previous computational approaches. Moreover, the calculations show that the interaction with the environment may cause a relevant recombination of the gas-phase electronic states.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

PubMed

Wang, Li-Dong; Zhou, Fu-You; Li, Xue-Min; Sun, Liang-Dan; Song, Xin; Jin, Yan; Li, Jiang-Man; Kong, Guo-Qiang; Qi, Hong; Cui, Juan; Zhang, Lian-Qun; Yang, Jie-Zhi; Li, Ji-Lin; Li, Xing-Chuan; Ren, Jing-Li; Liu, Zhi-Cai; Gao, Wen-Jun; Yuan, Ling; Wei, Wu; Zhang, Yan-Rui; Wang, Wei-Peng; Sheyhidin, Ilyar; Li, Feng; Chen, Bao-Ping; Ren, Shu-Wei; Liu, Bin; Li, Dan; Ku, Jian-Wei; Fan, Zong-Min; Zhou, Sheng-Li; Guo, Zhi-Gang; Zhao, Xue-Ke; Liu, Na; Ai, Yong-Hong; Shen, Fang-Fang; Cui, Wen-Yan; Song, Shuang; Guo, Tao; Huang, Jing; Yuan, Chao; Huang, Jia; Wu, Yue; Yue, Wen-Bin; Feng, Chang-Wei; Li, Hong-Lei; Wang, Yan; Tian, Jin-Ya; Lu, Yue; Yuan, Yi; Zhu, Wen-Liang; Liu, Min; Fu, Wen-Jing; Yang, Xia; Wang, Han-Jing; Han, Suo-Li; Chen, Jie; Han, Min; Wang, Hai-Yan; Zhang, Peng; Li, Xiu-Min; Dong, Jin-Cheng; Xing, Guo-Lan; Wang, Ran; Guo, Ming; Chang, Zhi-Wei; Liu, Hai-Lin; Guo, Li; Yuan, Zhi-Qing; Liu, Hai; Lu, Qin; Yang, Liu-Qin; Zhu, Fu-Guo; Yang, Xiu-Feng; Feng, Xiao-Shan; Wang, Zhou; Li, Yin; Gao, She-Gan; Qige, Qirenwang; Bai, Long-Tang; Yang, Wen-Jun; Lei, Guang-Yan; Shen, Zhong-Ying; Chen, Long-Qi; Li, En-Min; Xu, Li-Yan; Wu, Zhi-Yong; Cao, Wei-Ke; Wang, Jian-Po; Bao, Zhi-Qin; Chen, Ji-Li; Ding, Guang-Cheng; Zhuang, Xiang; Zhou, Ying-Fa; Zheng, Hou-Feng; Zhang, Zheng; Zuo, Xian-Bo; Dong, Zi-Ming; Fan, Dong-Mei; He, Xin; Wang, Jin; Zhou, Qi; Zhang, Qin-Xian; Jiao, Xin-Ying; Lian, Shi-Yong; Ji, Ai-Fang; Lu, Xiao-Mei; Wang, Jin-Sheng; Chang, Fu-Bao; Lu, Chang-Dong; Chen, Zhi-Guo; Miao, Jian-Jun; Fan, Zeng-Lin; Lin, Ruo-Bai; Liu, Tai-Jiang; Wei, Jin-Chang; Kong, Qing-Peng; Lan, Yu; Fan, Yu-Jing; Gao, Fu-Sheng; Wang, Tian-Yun; Xie, Dong; Chen, Shu-Qing; Yang, Wan-Cai; Hong, Jun-Yan; Wang, Liang; Qiu, Song-Liang; Cai, Zhi-Ming; Zhang, Xue-Jun

2010-09-01

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

Washout of water-soluble vitamins and of homocysteine during haemodialysis: effect of high-flux and low-flux dialyser membranes.

PubMed

Heinz, Judith; Domröse, Ute; Westphal, Sabine; Luley, Claus; Neumann, Klaus H; Dierkes, Jutta

2008-10-01

Vitamin deficiencies are common in patients with end-stage renal disease (ESRD) owing to dietary restrictions, drug-nutrient interactions, changes in metabolism, and vitamin losses during dialysis. The present study investigated the levels of serum and red blood cell (RBC) folate, plasma pyridoxal-5'-phosphate (PLP), serum cobalamin, blood thiamine, blood riboflavin, and plasma homocysteine (tHcy) before and after haemodialysis treatment. Vitamin and tHcy blood concentrations were measured in 30 patients with ESRD before and after dialysis session either with low-flux (n = 15) or high-flux (n = 15) dialysers. After the dialysis procedure, significantly lower concentrations of serum folate (37%), plasma PLP (35%), blood thiamine (6%) and blood riboflavin (7%) were observed. No significant changes were found for serum cobalamin or for RBC folate. There were no differences in the washout of water-soluble vitamins between treatments with low-flux and high-flux membranes. Furthermore, a 41% lower concentration in tHcy was observed. The percentage decrease in tHcy was significantly greater in the patients treated with high-flux dialysers (48% vs 37%; P < 0.01). The percentage change during dialysis was significantly inversely related to the molecular weight of the vitamins measured (r =-0.867, P < 0.01). This study showed significantly lower blood or serum levels of various water-soluble vitamins after dialysis, independently of the dialyser membrane. The monitoring of the vitamin status is essential in patients treated with high-flux dialysers as well as in patients treated with low-flux dialysers.

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., or isolated from natural sources. (b) The ingredient meets the specifications of the Food Chemicals... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Riboflavin. 184.1695 Section 184.1695 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

Effect of photoactivated riboflavin on the biodegradation-resistance of root-dentin collagen.

PubMed

Priyadarshini, Balasankar Meera; Lu, Thong Beng; Fawzy, Amr S

2017-12-01

This study was conducted to evaluate the effect of UVA-activated 1% riboflavin solution on structural integrity; mechanical properties and stability; and collagenase-mediated collagen solubilisation resistance of demineralized root dentin collagen matrix. Root dentin specimens demineralized with 17% EDTA for 7days were treated with 1% RF for 1min followed by UVA photo-activation at intensity 7mW/cm 2 for 1min. Control specimens were completely devoid of riboflavin and/or UVA treatments. Specimens were challenged with bacterial collagenase type-I solution for different time-periods at 37°C. Collagen solubilisation resistance was evaluated in terms of hydroxyproline (HYP) liberation. Mechanical characterization of dentin specimens before and after 24h of exposure to collagenase solution was done in terms of apparent-elastic modulus (E appr ) and ultimate tensile strength (UTS). Variations in dentin collagen-network structure with exposure time in collagenase were visualized by TEM. Crosslinking dentin with UVA-activated riboflavin significantly decreased HYP release and increased E appr and UTS compared to control specimens with storage time in collagenase. Moreover, crosslinked specimens showed higher structural resistance to collagenase effect reflected from dense, well-formed collagen fibrils-network with characteristic collagen cross-banding. UVA-activated riboflavin treatment increased collagenase-mediated collagen degradation resistance and enhanced mechanical stability against collagenase challenges of root dentin after EDTA demineralization. Copyright © 2017 Elsevier B.V. All rights reserved.

An Inexpensive Device for Capillary Electrophoresis with Fluorescence Detection

ERIC Educational Resources Information Center

Anderson, Greg; Thompson, Jonathan E.; Shurrush, Khriesto

2006-01-01

We describe an inexpensive device for performing capillary electrophoresis (CE) separations with fluorescence detection. As a demonstration of the device's utility we have determined the mass of riboflavin in a commercially available dietary supplement. The device allows for separation of riboflavin in [asymptotically equivalent to] 100 s with a…

21 CFR 582.5697 - Riboflavin-5-phosphate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Riboflavin-5-phosphate. 582.5697 Section 582.5697 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

21 CFR 582.5697 - Riboflavin-5-phosphate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Riboflavin-5-phosphate. 582.5697 Section 582.5697 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Nutrients and/or Dietary...

Drug-food and drug-nutrient interactions.

PubMed

Roe, D A

1985-07-01

This article analyzes the modifying effects on absorption rates, disposition, and therapeutic effects when drugs interact with both nutrient and non-nutrient food and beverage components. A classification of drug-nutrient interactions is presented and a profile of risk factors is developed. Drug absorption can be affected by food components through changes in gastric emptying time, filling of the gastrointestinal tract, adsorption of drug onto food components, interaction of drug with a food substance, changes in splanchnic blood flow, and bile release. Drugs may be metabolized faster when patients are on high protein-low carbohydrate diets. Adverse drug reactions can be precipitated by intake with specific foods or alcoholic beverages. In addition, certain drugs can produce nutritional toxicity or deficiencies. For example, the vitamin B6 requirements of oral contraceptive (OC) users are increased over those of nonusers; however, the subclinical deficiencies of folacin, riboflavin, and vitamins B12 and C that were associated with pre-1974 OCs have been lessened by recent reductions in OC's estrogen content. The major risk factor for drug-nutrient and drug-alcohol incompatibilities is lack of awareness on the part of the patient of the circumstances in which such a reaction is likely to occur. Patients with diagnoses of depression, anxiety-depression, phobic anxiety, Hodgkin's disease, tuberculosis, bacterial enteritis, giadiasis, trichomonal vaginitis, dermatophytosis, and alcoholism are at greatest risk. High-risk groups for drug-induced nutritional deficiencies are the elderly, alcoholics, pregnant women, epileptics, and cancer patients.

Spectroscopic and thermodynamic study of charge transfer complex formation between cloxacillin sodium and riboflavin in aqueous ethanol media of varying composition

NASA Astrophysics Data System (ADS)

Roy, Dalim Kumar; Saha, Avijit; Mukherjee, Asok K.

2006-03-01

Cloxacillin sodium has been shown to form a charge transfer complex of 2:1 stoichiometry with riboflavin (Vitamin B 2) in aqueous ethanol medium. The enthalpy and entropy of formation of this complex have been determined by estimating the formation constant spectrophotometrically at five different temperatures in pure water medium. Pronounced effect of dielectric constant of the medium on the magnitude of K has been observed by determining K in aqueous ethanol mixtures of varying composition. This has been rationalized in terms of ionic dissociation of the cloxacillin sodium (D -Na +), hydrolysis of the anion D - and complexation of the free acid, DH with riboflavin.

The role of light, temperature and wine bottle colour on pigment enhancement in white wine.

PubMed

Dias, Daniel A; Smith, Trevor A; Ghiggino, Kenneth P; Scollary, Geoffrey R

2012-12-15

Pigmentation enhancement in a Chardonnay wine with high flavan-3-ol concentration was examined by irradiating the wine under controlled conditions. Heating the wine in darkness required temperatures in excess of 50°C before enhanced pigmentation became apparent. It was found that ultraviolet and, to a lesser extent, low wavelength visible light contributed to pigment production. The development of pigmentation depended on wine bottle glass colour: Flint>Arctic Blue>French Green>Antique Green. This is in agreement with the transmission characteristics of the bottles with even the darkest (Antique Green) allowing the transmission of some ultraviolet light. Riboflavin, when added to the wine, degraded rapidly when exposed to radiation <400 nm. The degradation of riboflavin and the onset of colour development depended on the actual amounts as well as the ratio of riboflavin to flavan-3-ol, suggesting that a complex series of reactions are occurring. A degradation product of riboflavin may be contributing to the increase in absorbance in the visible region observed during light exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Case of Brown-Vialetto-Van Laere Syndrome Due To a Novel Mutation in SLC52A3 Gene: Clinical Course and Response to Riboflavin.

PubMed

Thulasi, Venkatraman; Veerapandiyan, Aravindhan; Pletcher, Beth A; Tong, Chun M; Ming, Xue

2017-01-01

Brown-Vialetto-Van Laere syndrome is a rare disorder characterized by motor, sensory, and cranial neuronopathies, associated with mutations in SLC52A2 and SLC52A3 genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. The authors describe the clinical course of a 6-year-old girl with Brown-Vialetto-Van Laere syndrome and a novel homozygous mutation c.1156T>C in the SLC52A3 gene, who presented at the age of 2.5 years with progressive brain stem dysfunction including ptosis, facial weakness, hearing loss, dysphagia, anarthria with bilateral vocal cord paralysis, and ataxic gait. She subsequently developed respiratory failure requiring tracheostomy and worsening dysphagia necessitating a gastrostomy. Following riboflavin supplementation, resolution of facial diplegia and ataxia, improvements in ptosis, and bulbar function including vocalization and respiration were noted. However, her sensorineural hearing loss remained unchanged. Similar to other cases of Brown-Vialetto-Van Laere syndrome, our patient responded favorably to early riboflavin supplementation with significant but not complete neurologic recovery.

Candida famata (Debaryomyces hansenii)

NASA Astrophysics Data System (ADS)

Sibirny, Andriy A.; Voronovsky, Andriy Y.

Debaryomyces hansenii (teleomorph of asporogenous strains known as Candida famata ) belongs to the group of so named ‘ flavinogenic yeasts ’ capable of riboflavin oversynthesis during starvation for iron. Some strains of C. famata belong to the most flavinogenic organisms known (accumulate 20 mg of riboflavin in 1 ml of the medium) and were used for industrial production of riboflavin in USA for long time. Many strains of D. hansenii are characterized by high salt tolerance and are used for ageing of cheeses whereas some others are able to convert xylose to xylitol, anti-caries sweetener. Transformation system has been developed for D. hansenii. It includes collection of host recipient strains, vectors with complementation and dominant markers and several transformation protocols based on protoplasting and electroporation. Besides, methods of multicopy gene insertion and insertional mutagenesis have been developed and several strong constitutive and regulatable promoters have been cloned. All structural genes of riboflavin synthesis and some regulatory genes involved in this process have been identified. Genome of D. hansenii has been sequenced in the frame of French National program ‘Genolevure’ and is opened for public access

Determination of Vitamin C, b-carotene and Riboflavin Contents in Five Green Vegetables Organically and Conventionally Grown.

PubMed

Ismail, Amin; Cheah, Sook Fun

2003-03-01

As consumer interest in organically grown vegetables is increasing in Malaysia, there is a need to answer whether the vegetables are more nutritious than those conventionally grown. This study investigates commercially available vegetables grown organically and conventionally, purchased from retailers to analyse β-carotene, vitamin C and riboflavin contents. Five types of green vegetables were selected, namely Chinese mustard (sawi) (Brassica juncea), Chinese kale (kai-lan) (Brassica alboglabra), lettuce (daun salad) (Lactuca sativa), spinach (bayam putih) (Amaranthus viridis) and swamp cabbage (kangkung) (Ipomoea aquatica). For vitamin analysis, a reverse-phase high performance liquid chromatography was used to identify and quantify β -carotene, vitamin C and riboflavin. The findings showed that not all of the organically grown vegetables were higher in vitamins than that conventionally grown. This study found that only swamp cabbage grown organically was highest in β -carotene, vitamin C and riboflavin contents among the entire samples studied. The various nutrients in organically grown vegetables need to be analysed for the generation of a database on nutritional value which is important for future research.

Assessment of Rose Bengal vs. Riboflavin Photodynamic Therapy for Inhibition of Fungal Keratitis Isolates

PubMed Central

Arboleda, Alejandro; Miller, Darlene; Cabot, Florence; Taneja, Mukesh; Aguilar, Mariela C.; Alawa, Karam; Amescua, Guillermo; Yoo, Sonia H.; Parel, Jean-Marie

2014-01-01

Purpose To compare the in vitro effect of rose bengal and riboflavin as photosensitizing agents for photodynamic therapy (PDT) on fungal isolates that are common causes of fungal keratitis Design Experimental study Methods Three isolates (Fusarium solani, Aspergillus fumigatus, Candida albicans) recovered from patients with confirmed fungal keratitis were used in the experiments. Isolates were grown on Sabouraud-Dextrose agar, swabbed and prepared in suspension, and one milliliter aliquots were inoculated onto test plates in triplicate. Test plates were separated into 5 groups: Group 1 - no treatment, Group 2 - 0.1% rose bengal alone, Group 3 - 518 nm irradiation alone, Group 4 - riboflavin PDT (riboflavin + 375 nm irradiation), and Group 5 - rose bengal PDT (rose bengal + 518 nm irradiation). Irradiation was performed over a circular area using either a green LED array (peak wavelength: 518 nm) or a UV-A LED array (peak wavelength: 375 nm). Test plates were irradiated with an energy density of 5.4 J/cm2. Later, plates were placed in a 30° C incubator and observed for growth. Results Rose bengal-mediated PDT successfully inhibited the growth of all three fungal isolates in the irradiated area. All other groups exhibited unrestricted growth throughout the plate. Conclusions Rose bengal-mediated PDT successfully inhibited the growth of three types of fungi. No other experimental groups, including riboflavin-mediated PDT, had any inhibitory effect on the isolates. The results might be useful for the treatment of patients suffering from corneal infection. PMID:24792103

A novel mechanism of UV-A and riboflavin-mediated corneal cross-linking through induction of tissue transglutaminases.

PubMed

Kopsachilis, Nikolaos; Tsaousis, Konstantinos T; Tsinopoulos, Ioannis T; Kruse, Friedrich E; Welge-Luessen, Ulrich

2013-07-01

Collagen cross-linking using UV-A irradiation combined with the photosensitizer riboflavin is a new technique for treating progressive keratoconus. The purposes of this study were to examine whether primary human corneal keratocytes (HCKs) are capable of expressing and secreting fibronectin and tissue transglutaminase (tTgase), an enzyme cross-linking extracellular matrix protein, and to examine whether fibronectin and tTgase are increased after the treatment of HCK cells with UV-A irradiation combined with riboflavin (RFUV-A), thus providing another possible physiological mechanism of the cross-linking pathway. Cell cultures established from HCKs were treated with 0.025% riboflavin solution and UV-A (370 nm) irradiance 3 mW/cm2 for 30 minutes. Induction of fibronectin and tTgase was investigated by immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis. Cell viability was quantified by a microscopic live-dead assay. External tTgase activity was measured by the ability to form polymerized fibronectin and the incorporation of biotinylated cadaverine into fibronectin. Treatment of cultured HCK cells with RFUV-A increased the fibronectin and tTgase messenger RNA and protein levels. This effect was not observed in cells treated with riboflavin or UV-A radiation alone. Incorporation of biotinylated cadaverine was significantly increased when HCK cells were treated with RFUV-A. The enzymes tTgase and fibronectin are expressed by RFUV-A treatment in cultured HCK cells. This mechanism provides more information about the physiology of corneal cross-linking.

Hydrogen peroxide generation in a model paediatric parenteral amino acid solution.

PubMed

Brawley, V; Bhatia, J; Karp, W B

1993-12-01

1. Parenteral amino acid solutions undergo photooxidation, which may be an important factor in total parenteral nutrition-associated hepatic dysfunction. Light-exposed parenteral solutions containing amino acids, in addition to vitamins and trace minerals, generate free radicals, which, in turn, may contribute to this type of injury. This study examined the characteristics of H2O2 production in a parenteral amino acid solution modelled on a commercially available paediatric parenteral amino acid solution. 2. The solution was exposed to light in the presence of riboflavin-5'-monophosphate (riboflavin), and peroxide formation in the presence and absence of catalase (H2O2 formation) was assayed using potassium iodide/molybdate. 3. Peak H2O2 production occurred at a light intensity of 8 microW cm-2 nm-1 in the 425-475 nm waveband and was linear to 2 h of light exposure. H2O2 production reached 500 mumol/l at 24 h. 4. H2O2 was directly related to a riboflavin concentration of up to 20 mumol/l and was maximal at 30 mumol/l. 5. H2O2 production was greatest in the amino acid/riboflavin solution at a pH of between 5 and 6. 6. Under the conditions of light exposure intensity, light exposure time, riboflavin concentration and pH found during the administration of parenteral nutrition in neonatal intensive care units, net H2O2 production occurs in solutions modelled on a paediatric parenteral amino acid preparation.

Photoactivated riboflavin treatment of infectious keratitis using collagen cross-linking technology.

PubMed

Price, Marianne O; Tenkman, Lawrence R; Schrier, Amilia; Fairchild, Kelly M; Trokel, Stephen L; Price, Francis W

2012-10-01

To evaluate riboflavin/ultraviolet-A (UVA) as an adjunct treatment for infectious keratitis. This prospective, dual-center, interventional case series included cases of infectious keratitis that were treated by instilling riboflavin 0.1% solution for 30 minutes to saturate the cornea, followed by exposure to 365-nm UVA light (3 mW/cm(2)) for 15 to 45 minutes, with continued instillation of riboflavin. Eyes continued on standard antibiotic treatment. The primary outcome measures were the times to resolution of the infiltrate and the epithelial defect. Forty patients aged 14 to 86 years were enrolled. Seven (18%) eyes had a previous keratoplasty. Bacterial species were identified in 24 eyes, fungal in 7, protozoan in 2, viral in 1, and no organism in 6. The maximum infiltrate diameter ranged from 1 to 12 mm and the epithelial defect diameter was 0 to 8 mm before treatment. In 6 cases (2 bacterial, 3 fungal, and 1 without growth), the keratitis did not resolve successfully and the eye received a penetrating keratoplasty (PK). In 1 eye with prior PK, the infection resolved following treatment, but a regraft was required to address perforation of the PK incision. Riboflavin/UVA should be avoided in eyes with prior herpes simplex but otherwise posed no obvious safety risk in this series and appeared to be most effective when the infection depth was limited. The success rate was higher for bacterial infections than fungal infections. Randomized studies against antibiotics alone are needed to further evaluate efficacy. Copyright 2012, SLACK Incorporated.

Effect of flour extraction rate and baking on thiamine and riboflavin content and antioxidant capacity of traditional rye bread.

PubMed

Martinez-Villaluenga, C; Michalska, A; Frias, J; Piskula, M K; Vidal-Valverde, C; Zieliński, H

2009-01-01

The effect of rye flour extraction rates and baking on thiamine and riboflavin content, and antioxidant capacity of traditional rye bread were studied and compared with white wheat flour. The content of thiamine was higher (10.9%) in rye dough formulated with dark rye flour (F-100%; extraction rate of 100%) than in rye dough formulated with brown rye flour (F-92%; extraction rate of 92%) that was similar to dough made with wheat flour. The riboflavin content in rye dough made from flour F-100% was also higher (16%) than in dough formulated with flour F-92%, and both provided larger riboflavin content than wheat dough. Baking led to reductions in thiamine of 56% for wheat bread and of 20% for both rye breads; however, this process caused only a 10% decrease in riboflavin for wheat bread and a 30% decrease for rye breads. Trolox equivalent antioxidant capacity, peroxyl radical scavenging capacity, DPPH radical scavenging activity, and Folin-Ciocalteu reducing capacity were higher in rye than in wheat dough and bread. Baking process produced slight changes in antioxidant activity, except for Superoxide Dismutase-like activity where a sharp decrease was observed. Our findings showed that rye breads are an important source of B vitamins and rye breads formulated with dark and brown flours showed better antioxidant properties than wheat bread. Therefore, rye breads should be more widely recommended in human nutrition.

The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma.

PubMed

Hayes, Sally; Kamma-Lorger, Christina S; Boote, Craig; Young, Robert D; Quantock, Andrew J; Rost, Anika; Khatib, Yasmeen; Harris, Jonathan; Yagi, Naoto; Terrill, Nicholas; Meek, Keith M

2013-01-01

To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour. One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm(2)) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm(2)). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques. Corneal thickness decreased significantly following riboflavin application (p<0.01) and also to a lesser extent after UVA exposure (p<0.05). With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01), all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion. It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen.

The Effect of Riboflavin/UVA Collagen Cross-linking Therapy on the Structure and Hydrodynamic Behaviour of the Ungulate and Rabbit Corneal Stroma

PubMed Central

Hayes, Sally; Kamma-Lorger, Christina S.; Boote, Craig; Young, Robert D.; Quantock, Andrew J.; Rost, Anika; Khatib, Yasmeen; Harris, Jonathan; Yagi, Naoto; Terrill, Nicholas; Meek, Keith M.

2013-01-01

Purpose To examine the effect of riboflavin/UVA corneal crosslinking on stromal ultrastructure and hydrodynamic behaviour. Methods One hundred and seventeen enucleated ungulate eyes (112 pig and 5 sheep) and 3 pairs of rabbit eyes, with corneal epithelium removed, were divided into four treatment groups: Group 1 (28 pig, 2 sheep and 3 rabbits) were untreated; Group 2 (24 pig) were exposed to UVA light (3.04 mW/cm2) for 30 minutes and Group 3 (29 pig) and Group 4 (31 pig, 3 sheep and 3 rabbits) had riboflavin eye drops applied to the corneal surface every 5 minutes for 35 minutes. Five minutes after the initial riboflavin instillation, the corneas in Group 4 experienced a 30 minute exposure to UVA light (3.04 mW/cm2). X-ray scattering was used to obtain measurements of collagen interfibrillar spacing, spatial order, fibril diameter, D-periodicity and intermolecular spacing throughout the whole tissue thickness and as a function of tissue depth in the treated and untreated corneas. The effect of each treatment on the hydrodynamic behaviour of the cornea (its ability to swell in saline solution) and its resistance to enzymatic digestion were assessed using in vitro laboratory techniques. Results Corneal thickness decreased significantly following riboflavin application (p<0.01) and also to a lesser extent after UVA exposure (p<0.05). With the exception of the spatial order factor, which was higher in Group 4 than Group 1 (p<0.01), all other measured collagen parameters were unaltered by cross-linking, even within the most anterior 300 microns of the cornea. The cross-linking treatment had no effect on the hydrodynamic behaviour of the cornea but did cause a significant increase in its resistance to enzymatic digestion. Conclusions It seems likely that cross-links formed during riboflavin/UVA therapy occur predominantly at the collagen fibril surface and in the protein network surrounding the collagen. PMID:23349690

Comparison of dietary histories and seven-day food records in a nutritional assessment of older adults.

PubMed

Mahalko, J R; Johnson, L K; Gallagher, S K; Milne, D B

1985-09-01

Dietary histories and seven-day food records were obtained for 54 apparently healthy older adults. The two dietary methods correlated for most nutrients, but mean differences were significant for several nutrients. Intakes below recommended levels occurred most frequently for energy, calcium, and zinc. Biochemical evidence of thiamin and riboflavin deficiency was unexpectedly frequent. Using food records, dietary iron correlated with serum ferritin. Using dietary histories, dietary protein correlated with serum albumin, and dietary zinc correlated with plasma zinc. Using either dietary method, plasma ascorbate was associated positively with both dietary ascorbate and ascorbate supplements, and negatively with cigarette smoking. Use of thiamin- or folate-containing supplements was associated with improved biochemical status for the respective vitamin. Though neither dietary histories nor food records give precise intake data for individuals, either method may be useful for epidemiologic studies with appropriate sample sizes.

Covalent Immobilization of (-)-Riboflavin on Polymer Functionalized Silica Particles: Application in the Photocatalytic E→Z Isomerization of Polarized Alkenes.

PubMed

Metternich, Jan B; Sagebiel, Sven; Lückener, Anne; Lamping, Sebastian; Ravoo, Bart Jan; Gilmour, Ryan

2018-03-20

The covalent immobilization of the biomimetic, photo-organocatalyst (-)-riboflavin on silica micro- and nanoparticles via atom transfer radical polymerization (ATRP) is disclosed. Given the effectiveness of (-)-riboflavin as a versatile, environmentally benign photocatalyst, an immobilization strategy based on acrylate-linker modification of the catalyst core and controlled polymerization on initiator pre-functionalized silica particles has been developed. Validation of this approach is demonstrated in the E→Z isomerization of a benchmark cinnamonitrile (Z/E up to 88:12) with 0.97 mol % catalyst loading. Characterization of the immobilized photocatalyst supports covalent embedding of the catalyst in the polymeric brushes on the silica particle surface. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of high power LED-based UVA emission system and a photosensitive substance for clinical application in corneal radiation

NASA Astrophysics Data System (ADS)

Mota, Alessandro D.; Cestari, André M.; de Oliveira, André O.; Oliveira, Anselmo G.; Terruggi, Cristina H. B.; Rossi, Giuliano; Castro, Jarbas C.; Ligabô, João. P. B.; Ortega, Tiago A.; Rosa, Tiago

2015-09-01

This work presents an innovative cross-linking procedure to keratoconus treatment, a corneal disease. It includes the development of an ultraviolet controlled emission portable device based on LED source and a new formulation of a photosensitive drug called riboflavin. Thus new formulation improves drug administration by its transepithelial property. The UV reaction with riboflavin in corneal tissue leads to a modification of corneal collagen fibers, turning them more rigid and dense, and consequently restraining the advance of the disease. We present the control procedures to maintain UV output power stable up to 45mw/cm2, the optical architecture that leads to a homogeneous UV spot and the new formulation of Riboflavin.

Multiple Acyl-CoA Dehydrogenation Deficiency (Glutaric Aciduria Type II) with a Novel Mutation of Electron Transfer Flavoprotein-Dehydrogenase in a Cat.

PubMed

Wakitani, Shoichi; Torisu, Shidow; Yoshino, Taiki; Hattanda, Kazuhisa; Yamato, Osamu; Tasaki, Ryuji; Fujita, Haruo; Nishino, Koichiro

2014-01-01

Multiple acyl-CoA dehydrogenation deficiency (MADD; also known as glutaric aciduria type II) is a human autosomal recessive disease classified as one of the mitochondrial fatty-acid oxidation disorders. MADD is caused by a defect in the electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH) molecule, but as yet, inherited MADD has not been reported in animals. Here we present the first report of MADD in a cat. The affected animal presented with symptoms characteristic of MADD including hypoglycemia, hyperammonemia, vomiting, diagnostic organic aciduria, and accumulation of medium- and long-chain fatty acids in plasma. Treatment with riboflavin and L-carnitine ameliorated the symptoms. To detect the gene mutation responsible for MADD in this case, we determined the complete cDNA sequences of feline ETFα, ETFβ, and ETFDH. Finally, we identified the feline patient-specific mutation, c.692T>G (p.F231C) in ETFDH. The affected animal only carries mutant alleles of ETFDH. p.F231 in feline ETFDH is completely conserved in eukaryotes, and is located on the apical surface of ETFDH, receiving electrons from ETF. This study thus identified the mutation strongly suspected to have been the cause of MADD in this cat.

Reprint of: Nutrition in the Management of Cirrhosis and its Neurological Complications☆

PubMed Central

Bémeur, Chantal; Butterworth, Roger F.

2015-01-01

Malnutrition is a common feature of chronic liver diseases that is often associated with a poor prognosis including worsening of clinical outcome, neuropsychiatric complications as well as outcome following liver transplantation. Nutritional assessment in patients with cirrhosis is challenging owing to confounding factors related to liver failure. The objectives of nutritional intervention in cirrhotic patients are the support of liver regeneration, the prevention or correction of specific nutritional deficiencies and the prevention and/or treatment of the complications of liver disease per se and of liver transplantation. Nutritional recommendations target the optimal supply of adequate substrates related to requirements linked to energy, protein, carbohydrates, lipids, vitamins and minerals. Some issues relating to malnutrition in chronic liver disease remain to be addressed including the development of an appropriate well-validated nutritional assessment tool, the identification of mechanistic targets or therapy for sarcopenia, the development of nutritional recommendations for obese cirrhotic patients and liver-transplant recipients and the elucidation of the roles of vitamin A hepatotoxicity, as well as the impact of deficiencies in riboflavin and zinc on clinical outcomes. Early identification and treatment of malnutrition in chronic liver disease has the potential to lead to better disease outcome as well as prevention of the complications of chronic liver disease and improved transplant outcomes. PMID:26041952

Very low adequacy of micronutrient intakes by young children and women in rural Bangladesh is primarily explained by low food intake and limited diversity.

PubMed

Arsenault, Joanne E; Yakes, Elizabeth A; Islam, M Munirul; Hossain, Mohammad B; Ahmed, Tahmeed; Hotz, Christine; Lewis, Bess; Rahman, Ahmed Shafiqur; Jamil, Kazi M; Brown, Kenneth H

2013-02-01

Documentation of micronutrient intake inadequacies among developing country populations is important for planning interventions to control micronutrient deficiencies. The objective of this study was to quantify micronutrient intakes by young children and their primary female caregivers in rural Bangladesh. We measured 24-h dietary intakes on 2 nonconsecutive days in a representative sample of 480 children (ages 24-48 mo) and women in 2 subdistricts of northern Bangladesh by using 12-h weighed food records and subsequent 12-h recall in homes. We calculated the probability of adequacy (PA) of usual intakes of 11 micronutrients and an overall mean PA, and evaluated dietary diversity by counting the total number of 9 food groups consumed. The overall adequacy of micronutrient intakes was compared to dietary diversity scores using correlation and multivariate regression analyses. The overall mean prevalence of adequacy of micronutrient intakes for children was 43% and for women was 26%. For children, the prevalence of adequate intakes for each of the 11 micronutrients ranged from a mean of 0 for calcium to 95% for vitamin B-6 and was <50% for iron, calcium, riboflavin, folate, and vitamin B-12. For women, mean or median adequacy was <50% for all nutrients except vitamin B-6 and niacin and was <1% for calcium, vitamin A, riboflavin, folate, and vitamin B-12. The mean PA (MPA) was correlated with energy intake and dietary diversity, and multivariate models including these variables explained 71-76% of the variance in MPA. The degree of micronutrient inadequacy among young children and women in rural Bangladesh is alarming and is primarily explained by diets low in energy and little diversity of foods.

Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the positive effects of lipid-based nutrient supplements on breast-milk B vitamins.

PubMed

Allen, Lindsay H; Hampel, Daniela; Shahab-Ferdows, Setareh; York, Emily R; Adair, Linda S; Flax, Valerie L; Tegha, Gerald; Chasela, Charles S; Kamwendo, Debbie; Jamieson, Denise J; Bentley, Margaret E

2015-12-01

Little information is available on B vitamin concentrations in human milk or on how they are affected by maternal B vitamin deficiencies, antiretroviral therapy, or maternal supplementation. The objective was to evaluate the effects of antiretroviral therapy and/or lipid-based nutrient supplements (LNSs) on B vitamin concentrations in breast milk from HIV-infected women in Malawi. Breast milk was collected from 537 women recruited within the Breastfeeding, Antiretrovirals, and Nutrition study at 2 or 6 wk and 24 wk postpartum. Women were assigned to receive antiretrovirals and LNSs, antiretrovirals only, LNSs only, or a control. Antiretrovirals and LNSs were given to the mothers from weeks 0 to 28. The antiretrovirals were zidovudine/lamivudine and nelfinavir or lopinavir/ritonavir. LNSs provided 93-118% of the Recommended Dietary Allowances of thiamin, riboflavin, niacin, pyridoxine, and vitamin B-12. Infants were exclusively breastfed. LNSs increased milk concentrations of all vitamins except thiamin, whereas antiretrovirals lowered concentrations of nicotinamide, pyridoxal, and vitamin B-12. Although antiretrovirals alone had no significant effect on riboflavin concentrations, they negatively affected the LNS-induced increase in this vitamin. Thiamin was not influenced by the study interventions. Concentrations of all B vitamins were much lower than usually accepted values. All B vitamins were low in milk, and all but thiamin were increased by maternal supplementation with LNSs. Antiretrovirals alone decreased concentrations of some B vitamins in milk. When LNS was given in addition to antiretrovirals, the negative effect of antiretrovirals offset the positive effect of LNSs for all vitamins except thiamin. This trial was registered at clinicaltrials.gov as NCT00164762. © 2015 American Society for Nutrition.

The effectiveness of riboflavin and ultraviolet light pathogen reduction technology in eliminating Trypanosoma cruzi from leukoreduced whole blood.

PubMed

Jimenez-Marco, Teresa; Cancino-Faure, Beatriz; Girona-Llobera, Enrique; Alcover, M Magdalena; Riera, Cristina; Fisa, Roser

2017-06-01

The parasitic Chagas disease is caused by the protozoan Trypanosoma cruzi, which is mainly transmitted by insect vectors. Other infection routes, both in endemic and in nonendemic areas, include organ and marrow transplantation, congenital transmission, and blood transfusion. Asymptomatic chronic chagasic individuals may have a low and transient parasitemia in peripheral blood and, consequently, they can unknowingly transmit the disease via blood transfusion. Riboflavin and ultraviolet (UV) light pathogen reduction is a method to reduce pathogen transfusion transmission risk based on damage to the pathogen nucleic acids. In this study, we tested the effectiveness of this technology for the elimination of T. cruzi parasites in artificially contaminated whole blood units (WBUs) and thus for decreasing the risk of T. cruzi transfusion transmission. The contaminated WBUs were leukoreduced by filtration and treated with riboflavin and UV light. The level of pathogen reduction was quantified by a real-time polymerase chain reaction (qPCR) and a real-time reverse transcription-polymerase chain reaction (RT-qPCR) as a viability assay. The RNA (cDNA) quantification of the parasites showed a more than 99% reduction of viable T. cruzi parasites after leukoreduction and a complete reduction (100%) after the riboflavin and UV light treatment. Riboflavin and UV light treatment and leukoreduction used in conjunction appears to eliminate significant amounts of viable T. cruzi in whole blood. Both strategies could complement other blood bank measures already implemented to prevent the transmission of T. cruzi via blood transfusion. © 2017 AABB.

Effect of oxygen on the per‐cell extracellular electron transfer rate of Shewanella oneidensis MR‐1 explored in bioelectrochemical systems

PubMed Central

Lu, Mengqian; Chan, Shirley; Babanova, Sofia

2016-01-01

ABSTRACT Extracellular electron transfer (EET) is a mechanism that enables microbes to respire solid‐phase electron acceptors. These EET reactions most often occur in the absence of oxygen, since oxygen can act as a competitive electron acceptor for many facultative microbes. However, for Shewanella oneidensis MR‐1, oxygen may increase biomass development, which could result in an overall increase in EET activity. Here, we studied the effect of oxygen on S. oneidensis MR‐1 EET rates using bioelectrochemical systems (BESs). We utilized optically accessible BESs to monitor real‐time biomass growth, and studied the per‐cell EET rate as a function of oxygen and riboflavin concentrations in BESs of different design and operational conditions. Our results show that oxygen exposure promotes biomass development on the electrode, but significantly impairs per‐cell EET rates even though current production does not always decrease with oxygen exposure. Additionally, our results indicated that oxygen can affect the role of riboflavin in EET. Under anaerobic conditions, both current density and per‐cell EET rate increase with the riboflavin concentration. However, as the dissolved oxygen (DO) value increased to 0.42 mg/L, riboflavin showed very limited enhancement on per‐cell EET rate and current generation. Since it is known that oxygen can promote flavins secretion in S. oneidensis, the role of riboflavin may change under anaerobic and aerobic conditions. Biotechnol. Bioeng. 2017;114: 96–105. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:27399911

Shewanella secretes flavins that mediate extracellular electron transfer

PubMed Central

Marsili, Enrico; Baron, Daniel B.; Shikhare, Indraneel D.; Coursolle, Dan; Gralnick, Jeffrey A.; Bond, Daniel R.

2008-01-01

Bacteria able to transfer electrons to metals are key agents in biogeochemical metal cycling, subsurface bioremediation, and corrosion processes. More recently, these bacteria have gained attention as the transfer of electrons from the cell surface to conductive materials can be used in multiple applications. In this work, we adapted electrochemical techniques to probe intact biofilms of Shewanella oneidensis MR-1 and Shewanella sp. MR-4 grown by using a poised electrode as an electron acceptor. This approach detected redox-active molecules within biofilms, which were involved in electron transfer to the electrode. A combination of methods identified a mixture of riboflavin and riboflavin-5′-phosphate in supernatants from biofilm reactors, with riboflavin representing the dominant component during sustained incubations (>72 h). Removal of riboflavin from biofilms reduced the rate of electron transfer to electrodes by >70%, consistent with a role as a soluble redox shuttle carrying electrons from the cell surface to external acceptors. Differential pulse voltammetry and cyclic voltammetry revealed a layer of flavins adsorbed to electrodes, even after soluble components were removed, especially in older biofilms. Riboflavin adsorbed quickly to other surfaces of geochemical interest, such as Fe(III) and Mn(IV) oxy(hydr)oxides. This in situ demonstration of flavin production, and sequestration at surfaces, requires the paradigm of soluble redox shuttles in geochemistry to be adjusted to include binding and modification of surfaces. Moreover, the known ability of isoalloxazine rings to act as metal chelators, along with their electron shuttling capacity, suggests that extracellular respiration of minerals by Shewanella is more complex than originally conceived. PMID:18316736

Ultra-performance liquid chromatography tandem mass-spectrometry (uplc-ms/ms) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk

USDA-ARS?s Scientific Manuscript database

A novel, rapid and sensitive Ultra Performance Liquid-Chromatography tandem Mass-Spectrometry (UPLC-MS/MS) method for the simultaneous determination of several B-vitamins in human milk was developed. Resolution by retention time or multiple reaction monitoring (MRM) for thiamin, riboflavin, flavin a...

Characterization of Rabbit Corneas Subjected to Stromal Stiffening by the Açaí Extract (Euterpe oleracea).

PubMed

Bersanetti, Patrícia A; Bueno, Tatiane L N; Morandim-Giannetti, Andreia de A; Nogueira, Regina F; Matos, Jivaldo R; Schor, Paulo

2017-04-01

In this study, we characterized rabbit corneas subjected to corneal cross-linking (CXL) with açaí extract compared with a riboflavin photo-stimulated procedure. The corneas of the slaughterhouse rabbits were divided into three groups: control, consisting of untreated corneal samples; riboflavin/UVA, where corneas were treated with 0.1% riboflavin photo-stimulated at 365 nm as the standard protocol; and açaí, where the samples were subjected to 4% açaí extract for 0.5-2 h. After the CXL procedure, corneas of the three groups were characterized by analyzing their elastic modulus and thermal denaturation profile. The elastic modulus at 3% strain showed an approximately threefold increase in the riboflavin/UVA group and 10.5 times in the corneas treated with 4% açaí extract for 2 h, compared with the control group (p < 0.01). The denaturation temperature values of the two groups of crosslinked corneas increased significantly (p < 0.05) and were more pronounced in the açaí group. The açaí extract was effective in promoting CXL in rabbit corneas as characterized by the different techniques.

Association of riboflavin, caffeine, and sodium salicylate in aqueous solution

NASA Astrophysics Data System (ADS)

Baranovskii, S. F.; Bolotin, P. A.

2007-03-01

We have used UV and visible spectrophotometry to study self-association of aromatic riboflavin molecules (RFN, vitamin B2, 7,8-dimethyl-10-N-(1'-D-ribityl)isoalloxazine) in aqueous solution (pH 6.86) at T = 298 K, using a dimer model. We have determined the equilibrium dimerization constant for riboflavin, KdB = 125 ± 40 M-1. We have studied heteroassociation in the system of molecules of 7,8-dimethyl-10-ribitylisoalloxazine with 1,3,7-trimethylxanthine (caffeine) and sodium salicylate (NAS) in aqueous solution (pH 6.86; T = 298 K). We have determined the heteroassociation constants for RFN-NAS and RFN-caffeine molecules in the absence and in the presence of urea in solutions using a modified Benesi-Hildebrand equation: 25 ± 4, 17 ± 3, and 74 ± 11, 53 ± 7 M-1 respectively. We have determined the dimerization constants for NAS (2.7 ± 0.5 M-1) and caffeine (17.0 ± 1.5 M-1). We conclude that heteroassociation of the aromatic molecules leads to a lower effective riboflavin concentration in solution, and the presence of urea in mixed solutions leads to an decrease in the complexation constants for the RFN-NAS and RFN-caffeine systems.

Localization and Function of the Membrane-bound Riboflavin in the Na+-translocating NADH:Quinone Oxidoreductase (Na+-NQR) from Vibrio cholerae*

PubMed Central

Casutt, Marco S.; Huber, Tamara; Brunisholz, René; Tao, Minli; Fritz, Günter; Steuber, Julia

2010-01-01

The sodium ion-translocating NADH:quinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae is a respiratory membrane protein complex that couples the oxidation of NADH to the transport of Na+ across the bacterial membrane. The Na+-NQR comprises the six subunits NqrABCDEF, but the stoichiometry and arrangement of these subunits are unknown. Redox-active cofactors are FAD and a 2Fe-2S cluster on NqrF, covalently attached FMNs on NqrB and NqrC, and riboflavin and ubiquinone-8 with unknown localization in the complex. By analyzing the cofactor content and NADH oxidation activity of subcomplexes of the Na+-NQR lacking individual subunits, the riboflavin cofactor was unequivocally assigned to the membrane-bound NqrB subunit. Quantitative analysis of the N-terminal amino acids of the holo-complex revealed that NqrB is present in a single copy in the holo-complex. It is concluded that the hydrophobic NqrB harbors one riboflavin in addition to its covalently attached FMN. The catalytic role of two flavins in subunit NqrB during the reduction of ubiquinone to ubiquinol by the Na+-NQR is discussed. PMID:20558724

Simultaneous Determination of Pyridoxine and Riboflavin in Energy Drinks by High-Performance Liquid Chromatography with Fluorescence Detection

ERIC Educational Resources Information Center

Martí-Andre´s, P.; Escuder-Gilabert, L.; Martín-Biosca, Y.; Sagrado, S.; Medina-Herna´ndez, M.J.

2015-01-01

Energy drinks, as familiar consumer products, have been widely used in laboratory courses to help promote student interest, as well as to connect lecture concepts with laboratory work. Energy drinks contain B vitamins: pyridoxine (vitamin B6) and riboflavin (vitamin B2) of which amounts are high enough to be of concern. In this work, a fast and…

Damage threshold in adult rabbit eyes after scleral cross-linking by riboflavin/blue light application.

PubMed

Iseli, Hans Peter; Körber, Nicole; Karl, Anett; Koch, Christian; Schuldt, Carsten; Penk, Anja; Liu, Qing; Huster, Daniel; Käs, Josef; Reichenbach, Andreas; Wiedemann, Peter; Francke, Mike

2015-10-01

Several scleral cross-linking (SXL) methods were suggested to increase the biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye elongation in progressive myopia. In addition to scleral cross-linking and biomechanical effects caused by riboflavin and light irradiation such a treatment might induce tissue damage, dependent on the light intensity used. Therefore, we characterized the damage threshold and mechanical stiffening effect in rabbit eyes after application of riboflavin combined with various blue light intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5 %) and varying blue light (450 ± 50 nm) dosages from 18 to 780 J/cm(2) (15 to 650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were detected by means of light microscopy, electron microscopy and immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological changes in ocular tissues; the damage threshold was defined by the light intensities which induced cellular degeneration and/or massive collagen structure changes. At such high dosages, we observed alterations of the collagen structure in scleral tissue, as well as pigment aggregation, internal hemorrhages, and collapsed blood vessels. Additionally, photoreceptor degenerations associated with microglia activation and macroglia cell reactivity in the retina were detected. These pathological alterations were locally restricted to the treated areas. Pigmentation of rabbit eyes did not change the damage threshold after a treatment with riboflavin and blue light but seems to influence the vulnerability for blue light irradiations. Increased biomechanical stiffness of scleral tissue could be achieved with blue light intensities below the characterized damage threshold. We conclude that riboflavin and blue light application increased the biomechanical stiffness of scleral tissue at blue light energy levels below the damage threshold. Therefore, applied blue light intensities below the characterized damage threshold might define a therapeutic blue light tolerance range. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous determination of riboflavin and pyridoxine by UHPLC/LC-MS in UK commercial infant meal food products.

PubMed

Zand, Nazanin; Chowdhry, Babur Z; Pullen, Frank S; Snowden, Martin J; Tetteh, John

2012-12-15

An assay for the simultaneous quantitative determination of riboflavin and pyridoxine in eight different complementary infant meal products has been developed in order to (1) estimate the daily intake of these vitamins from commercial infant food consumption, and (2) ascertain their nutritional suitability relative to dietary guidelines for the 6-9 months age group. The method involves mild hydrolysis of the foods, an extraction of the supernatant by centrifugation followed by quantitative determination using ultra-high performance liquid chromatography. Separation of the two water soluble vitamins is achieved within one minute and the resultant sample is also LC-MS compatible. Despite wide individual differences between brands (p=6.5e-12), no significant differences were observed in the level of pyridoxine between the meat and vegetable-based varieties (p=0.7) per 100g of commercial infant food. Riboflavin was not detected in any of the samples where the detection limit was below 0.07 μg/mL. In terms of the Reference Nutrient Intake (RNI) of pyridoxine for 6-9 months old infants, the complementary infant meal products analysed herein provided less than 15% of the RNI values with mean (SD) values of 12.87 (± 4.46)% and 13.88 (± 4.97)% for the meat- and vegetable-based recipes, respectively. The estimated total daily intake of riboflavin and pyridoxine from the consumption of commercial complementary food was found to be satisfactory and in accordance with the Dietary Reference Values (DRVs). The intake of both riboflavin and pyridoxine was estimated to be mainly derived from the consumption of formula milk which could be a cause of concern if the quality of an infant's milk diet is compromised by an inadequate or lack of supplemented milk intake. The results of this study suggest that the selected commercial complementary infant foods in the UK market may not contain the minimum levels of riboflavin and pyridoxine required for the labelling declaration of the micronutrient content of such products as recommended by Commission Directive 2006/125/EC. Copyright © 2012 Elsevier Ltd. All rights reserved.

Treatment Results of Corneal Collagen Cross-Linking Combined with Riboflavin and 440 Nm Blue Light for Bacterial Corneal Ulcer in Rabbits.

PubMed

Wei, Shufang; Zhang, Cuiying; Zhang, Shaoru; Xu, Yanyun; Mu, Guoying

2017-10-01

To study the treatment effect of corneal collagen cross-linking (CXL) combined with 440 nm blue light and riboflavin on bacterial corneal ulcer using animal experiments. A total of 21 New Zealand white rabbits that developed Staphylococcus aureus corneal ulcer were randomly divided into three groups. Seven rabbits were used as blank control groups; seven rabbits were treated with CXL combined with riboflavin and 440 nm blue light; and seven rabbits were treated with CXL combined with riboflavin and 370 nm ultraviolet A light. Necrotic tissues or secretions from the ulcer surface, eye secretions, conjunctival hyperemia, hypopyon, corneal infiltration, and pathological changes of the cornea were all observed. The 1st, 3th, and 7th day after CXL treatment, a statistically significant difference was found among the inflammation scores of the three groups. The scores of 440 and 370 groups decreased gradually, significantly lower than that of the control group. Bacterial cultures of 440 and 370 groups turned to be negative while that of the control group remained positive. After 1 day of CXL treatment, pathology pictures of the three groups all showed loss of corneal epithelia with many inflammatory cells in deep stroma. After 7 days of CXL treatment, abscess formed in almost all corneal area in the control group, while in 440 and 370 groups, multilayer healing of corneal epithelia, neovascularization, and many inflammatory cells within ulcers and proliferation of a small amount of fibroblast were seen. CXL combined with riboflavin and 440 nm blue light is effective in treating S. aureus corneal ulcer.

Dose-dependent collagen cross-linking of rabbit scleral tissue by blue light and riboflavin treatment probed by dynamic shear rheology.

PubMed

Schuldt, Carsten; Karl, Anett; Körber, Nicole; Koch, Christian; Liu, Qing; Fritsch, Anatol W; Reichenbach, Andreas; Wiedemann, Peter; Käs, Josef A; Francke, Mike; Iseli, Hans Peter

2015-08-01

To determine the visco-elastic properties of isolated rabbit scleral tissue and dose-dependent biomechanical and morphological changes after collagen cross-linking by riboflavin/blue light treatment. Scleral patches from 87 adult albino rabbit eyes were examined by dynamic shear rheology. Scleral patches were treated by riboflavin and different intensities of blue light (450 nm), and the impact on the visco-elastic properties was determined by various rheological test regimes. The relative elastic modulus was calculated from non-treated and corresponding treated scleral patches, and treatments with different blue light intensities were compared. Shear rheology enables us to study the material properties of scleral tissue within physiological relevant parameters. Cross-linking treatment increased the viscous as well as the elastic modulus and changed the ratio of the elastic versus viscous proportion in scleral tissue. Constant riboflavin application combined with different blue light intensities from 12 mW/cm(2) up to 100 mW/cm(2) increased the relative elastic modulus of scleral tissue by factors up to 1.8. Further enhancement of the applied light intensity caused a decline of the relative elastic modulus. This might be due to destructive changes of the collagen bundle structure at larger light intensities, as observed by histological examination. Collagen cross-linking by riboflavin/blue light application increases the biomechanical stiffness of the sclera in a dose-dependent manner up to certain light intensities. Therefore, this treatment might be a suitable therapeutic approach to stabilize the biomechanical properties of scleral tissue in cases of pathological eye expansion. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Separation and preconcentration of riboflavin from human plasma using polythionine coated magnetite/hydroxyapatite nanocomposite prior to analysis by surfactant-enhanced fluorimetry

NASA Astrophysics Data System (ADS)

Farzin, Leila; Shamsipur, Mojtaba

2017-09-01

The exploration of novel adsorption properties of conductive polymers based on hybridization with biocompatible nanomaterials receives an increasing interest. In this regard, hydroxyapatite (HA) bioceramic is of critical importance mainly owing to its facile synthesis, high surface area, economic and low toxicity in biological environments. In this work, we first prepared and characterized a magnetite/hydroxyapatite (Fe3O4/HA) nanocomposite using the bio-waste chicken eggshell via an attractive green way that involved low cost and irrespective of toxicity. Then, polythionine as a novel class of conductive polymers was in situ coated on the synthesized magnetic bioceramic for the separation and preconcentration of riboflavin (vitamin B2) in human plasma before its fluorimetric determination. Considering the putative role of riboflavin in protecting against cancer and cardiovascular diseases, it is essential to evaluate this vitamin in biological fluids. The described method possesses a linear range of 0.75-262.5 μg L- 1 (R2 = 0.9985) and a detection limit of 0.20 μg L- 1 (signal-to-noise ratio of 3). The relative standard deviations (RSDs) for single-sorbent repeatability and sorbent-to-sorbent reproducibility were less than 4.0% and 7.6% (n = 5), respectively. The respective enrichment factor and extraction recovery of the method found to be 35.7 and 98.4%. The analytical performance of method for riboflavin was characterized by good consistency of the results with those obtained by the enzyme-linked immunosorbent assay (ELISA) conventional method (p-value of < 0.05). The optimized protocol intended for control determinations of riboflavin in human subjects and is addressed to clinical laboratories.

Main-chain optically active riboflavin polymer for asymmetric catalysis and its vapochromic behavior.

PubMed

Iida, Hiroki; Iwahana, Soichiro; Mizoguchi, Tomohisa; Yashima, Eiji

2012-09-12

A novel optically active polymer consisting of riboflavin units as the main chain (poly-1) was prepared from naturally occurring riboflavin (vitamin B(2)) in three steps. The riboflavin residues of poly-1 were converted to 5-ethylriboflavinium cations (giving poly-2), which could be reversibly transformed into the corresponding 4a-hydroxyriboflavins (giving poly-2OH) through hydroxylation/dehydroxylation reactions. This reversible structural change was accompanied by a visible color change along with significant changes in the absorption and circular dichroism (CD) spectra. The nuclear Overhauser effect spectroscopy (NOESY) and CD spectra of poly-2 revealed a supramolecularly twisted helical structure with excess one-handedness through face-to-face stacking of the intermolecular riboflavinium units, as evidenced by the apparent NOE correlations between the interstrand riboflavin units and intense Cotton effects induced in the flavinium chromophore regions. The hydroxylation of poly-2 at the 4a-position proceeded in a diastereoselective fashion via chirality transfer from the induced supramolecular helical chirality assisted by the ribityl pendants, resulting in a 83:17 diastereomeric mixture of poly-2OH. The diastereoselectivity of poly-2 was remarkably higher than that of the corresponding monomeric model (64.5:35.5), indicating amplification of the chirality resulting from the supramolecular chirality induced in the stacked poly-2 backbones. The optically active poly-2 efficiently catalyzed the asymmetric organocatalytic oxidation of sulfides with hydrogen peroxide, yielding optically active sulfoxides with up to 60% enantiomeric excess (ee), whose enantioselectivity was higher than that catalyzed by the monomeric counterpart (30% ee). In addition, upon exposure to primary and secondary amines, poly-2 exhibited unique high-speed vapochromic behavior arising from the formation of 4a-amine adducts in the film.

Hydrosoluble vitamins.

PubMed

Chawla, Jasvinder; Kvarnberg, David

2014-01-01

The hydrosoluble vitamins are a group of organic substances that are required by humans in small amounts to prevent disorders of metabolism. Significant progress has been made in our understanding of the biochemical, physiologic and nutritional aspects of the water-soluble vitamins. Deficiency of these particular vitamins, most commonly due to inadequate nutrition, can result in disorders of the nervous system. Many of these disorders have been successfully prevented in developed countries; however, they are still common in developing countries. Of the hydrosoluble vitamins, the nervous system depends the most on vitamins B and C (ascorbic acid) for proper functioning. The B group vitamins include thiamin (vitamin B1), riboflavin (vitamin B2), niacin or niacinamide (vitamin B3), pantothenic acid (vitamin B5), pyridoxine or pyridoxal (vitamin B6) and cobalamin (vitamin B12). Clinical findings depend upon the deficiency of the underlying vitamin; generally, deficiency symptoms are seen from a combination rather than an isolated vitamin deficiency. True hereditary metabolic disorders and serious deficiency-associated diseases are rare and in general limited to particular geographic regions and high-risk groups. Their recognition is truly important as that determines the appropriate therapeutic management. The general availability of vitamins to practically everyone and several national health programs have saved many lives and prevented complications. However, there has been some apprehension for several decades about how harmless generous dosages of these vitamins are. Overt overdosages can cause vitamin toxicity affecting various body systems including the nervous system. Systemically, vitamin toxicity is associated with nonspecific symptoms, such as nausea, vomiting, diarrhea, and skin rash which are common with any acute or chronic vitamin overdose. At a national level, recommended daily allowances for vitamins become policy statements. Nutrition policy has far reaching implications in the food industry, in agriculture, and in food provision programs. Overall, water-soluble vitamins are complex molecular structures and even today, many areas of vitamin biochemistry still need to be explored. Many readers might be of the opinion that the classic forms of nutritional deficiency diseases have faded into the background of interesting history. This has caused their diverse symptoms to be neglected by most modern physicians since vitamin enrichment of many foods automatically erases them from their consideration in differential diagnosis. Vitamin B12 and folic acid deficiencies are discussed in other chapters. © 2014 Elsevier B.V. All rights reserved.

The Effects of Caloric Density of the Food on Running Endurance and General Condition of Rats and Hamsters Restricted in Food Intake or Fed Ad Libitum

DTIC Science & Technology

1975-08-01

I.U.; alpha-tocopherol, 80; menadione , 0.30; thiamine.HCl, 6.0; riboflavin, 5.0; pyridoxine.HCl, 3.0; nlacin, 30; Ca-pantothenate, 16; choline (as...alpha-tocopherol, 100; menadione , 0.30; thiamine.HCl, 10.0; riboflavin, 6.0; pyridoxine.HCl, 5.0; niacin, 40; Ca-pantorher.ate, 40; choline, 705

Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin.

PubMed

Jin, Bei; Zhou, Xiaosong; Li, Xiangzhong; Lin, Weiqin; Chen, Guangbin; Qiu, Riji

2016-03-15

A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32-40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes.

Effect of oral contraceptive agents on nutrients: II. Vitamins.

PubMed

Prasad, A S; Oberleas, D; Moghissi, K S; Stryker, J C; Lei, K Y

1975-04-01

Clinical, biochemical and nutritional data were collected from a large population of women using oral contraceptive agents. Higher incidence of abnormal clinical signs related to malnutrition were observed in the lower (B) as compared to the higher (A) socioeconomic groups, and also in the nonsupplemented groups as compared to the supplemented groups in the B subjects. As a rule the intake of oral contraceptive agent subjects of vitamin A, C, B6 and folic acid did not differ from that of the controls As expected, subjects from the supplemented groups had higher intake of vitamin A, C, B6, thiamin, riboflavin and folic acid, and A groups had higher intake of vitamin C, B6, riboflavin and folic acid. Increased plasma vitamin A and decreased carotene levels were observed in oral contraceptive agent users. In general oral contraceptive agents had little or no effect on plasma ascorbic acid. Urinary excretion of both thiamin and riboflavin in subjects using oral contraceptive agents were lower in A groups. Erythrocyte folate and plasma pyridoxal phosphate was decreased in A groups due to oral contraceptive agents. Subjects who took supplements had higher levels of plasma vitamin A, ascorbic acid and folate. But urinary thiamin and riboflavin were higher only in group A subjects who took supplements.

Observation of oscillatory surface reactions of riboflavin, trolox, and singlet oxygen using single carbon nanotube fluorescence spectroscopy.

PubMed

Sen, Fatih; Boghossian, Ardemis A; Sen, Selda; Ulissi, Zachary W; Zhang, Jingqing; Strano, Michael S

2012-12-21

Single-molecule fluorescent microscopy allows semiconducting single-walled carbon nanotubes (SWCNTs) to detect the adsorption and desorption of single adsorbate molecules as a stochastic modulation of emission intensity. In this study, we identify and assign the signature of the complex decomposition and reaction pathways of riboflavin in the presence of the free radical scavenger Trolox using DNA-wrapped SWCNT sensors dispersed onto an aminopropyltriethoxysilane (APTES) coated surface. SWCNT emission is quenched by riboflavin-induced reactive oxygen species (ROS), but increases upon the adsorption of Trolox, which functions as a reductive brightening agent. Riboflavin has two parallel reaction pathways, a Trolox oxidizer and a photosensitizer for singlet oxygen and superoxide generation. The resulting reaction network can be detected in real time in the vicinity of a single SWCNT and can be completely described using elementary reactions and kinetic rate constants measured independently. The reaction mechanism results in an oscillatory fluorescence response from each SWCNT, allowing for the simultaneous detection of multiple reactants. A series-parallel kinetic model is shown to describe the critical points of these oscillations, with partition coefficients on the order of 10(-6)-10(-4) for the reactive oxygen and excited state species. These results highlight the potential for SWCNTs to characterize complex reaction networks at the nanometer scale.

Measuring Binding Affinity of Protein-Ligand Interaction Using Spectrophotometry: Binding of Neutral Red to Riboflavin-Binding Protein

ERIC Educational Resources Information Center

Chenprakhon, Pirom; Sucharitakul, Jeerus; Panijpan, Bhinyo; Chaiyen, Pimchai

2010-01-01

The dissociation constant, K[subscript d], of the binding of riboflavin-binding protein (RP) with neutral red (NR) can be determined by titrating RP to a fixed concentration of NR. Upon adding RP to the NR solution, the maximum absorption peak of NR shifts to 545 nm from 450 nm for the free NR. The change of the absorption can be used to determine…

Investigations of blue light-induced reactive oxygen species from flavin mononucleotide on inactivation of E. coli.

PubMed

Liang, Ji-Yuan; Cheng, Chien-Wei; Yu, Chin-Hao; Chen, Liang-Yü

2015-02-01

The micronutrients in many cellular processes, riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) are photo-sensitive to UV and visible light for generating reactive oxygen species (ROS). Produced from phosphorylation of riboflavin, FMN is more water-soluble and rapidly transformed into free riboflavin after ingestion. This study investigated the application of visible blue light with FMN to development of an effective antimicrobial treatment. The photosensitization of bacterial viability with FMN was investigated by light quality, intensity, time, and irradiation dosage. The blue light-induced photochemical reaction with FMN could inactivate Escherichiacoli by the generated ROS in damaging nucleic acids, which was validated. This novel photodynamic technique could be a safe practice for photo-induced inactivation of environmental microorganism to achieve hygienic requirements in food processing. Copyright © 2015 Elsevier B.V. All rights reserved.

Riboflavin transporter 3 involvement in infantile Brown-Vialetto-Van Laere disease: two novel mutations.

PubMed

Ciccolella, Marianna; Corti, Stefania; Catteruccia, Michela; Petrini, Stefania; Tozzi, Giulia; Rizza, Teresa; Carrozzo, Rosalba; Nizzardo, Monica; Bordoni, Andreina; Ronchi, Dario; D'Amico, Adele; Rizzo, Cristiano; Comi, Giacomo Pietro; Bertini, Enrico

2013-02-01

Brown-Vialetto-Van Laere (BVVL) syndrome is a rare disorder characterised by progressive pontobulbar palsy and sensorineural deafness. Causative mutations in genes encoding human riboflavin transporter 2 (hRFT2) and 3 (hRFT3) have been identified in BVVL patients. We report the clinical and molecular features of a severe BVVL patient in whom screening of SLC52A3/hRFT2 was negative. Sequence analysis identified two novel compound heterozygous mutations in SLC52A2/hRFT3, namely c.155C>T and c.1255G>A, leading to the amino acid changes p.S52F and p.G419S, respectively. Functional studies show that these defects impair the gene expression of the corresponding transporter, resulting in a significant reduction of riboflavin transport. These findings support the pathogenetic role of SLC52A2/hRFT3 in BVVL with important clinical and therapeutic implications.

Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle

PubMed Central

Wolfe, Lynne A.; He, Miao; Vockley, Jerry; Payne, Nicole; Rhead, William; Hoppel, Charles; Spector, Elaine; Gernert, Kim; Gibson, K. Michael

2014-01-01

We describe a 22-year-old male who developed severe hypoglycemia and lethargy during an acute illness at 4 months of age and subsequently grew and developed normally. At age 4 years he developed recurrent vomiting with mild hyperammonemia and dehydration requiring frequent hospitalizations. Glutaric aciduria Type II was suspected based upon biochemical findings and managed with cornstarch, carnitine and riboflavin supplements. He did not experience metabolic crises between ages 4-12 years. He experienced recurrent vomiting, mild hyperammonemia, and generalized weakness associated with acute illnesses and growth spurts. At age 18 years, he developed exercise intolerance and proximal muscle weakness leading to the identification of multiple acyl-CoAdehydrogenase and complex II/III deficiencies in both skeletal muscle and liver. Subsequent molecular characterization of the ETFDH gene revealed novel heterozygous mutations, p.G274X:c.820 G>T (exon 7) and p.P534L: c.1601 C>T (exon 12), the latter within the iron sulfur-cluster and predicted to affect ubiquinone reductase activity of ETFDH and the docking of ETF to ETFDH. Our case supports the concept of a structural interaction between ETFDH and other enzyme partners, and suggests that the conformational change upon ETF binding to ETFDH may play a key role in linking ETFDH to II/III super-complex formation. PMID:21088898

Novel ETF dehydrogenase mutations in a patient with mild glutaric aciduria type II and complex II-III deficiency in liver and muscle.

PubMed

Wolfe, Lynne A; He, Miao; Vockley, Jerry; Payne, Nicole; Rhead, William; Hoppel, Charles; Spector, Elaine; Gernert, Kim; Gibson, K Michael

2010-12-01

We describe a 22-year-old male who developed severe hypoglycemia and lethargy during an acute illness at 4 months of age and subsequently grew and developed normally. At age 4 years he developed recurrent vomiting with mild hyperammonemia and dehydration requiring frequent hospitalizations. Glutaric aciduria Type II was suspected based upon biochemical findings and managed with cornstarch, carnitine and riboflavin supplements. He did not experience metabolic crises between ages 4-12 years. He experienced recurrent vomiting, mild hyperammonemia, and generalized weakness associated with acute illnesses and growth spurts. At age 18 years, he developed exercise intolerance and proximal muscle weakness leading to the identification of multiple acyl-CoA dehydrogenase and complex II/III deficiencies in both skeletal muscle and liver. Subsequent molecular characterization of the ETFDH gene revealed novel heterozygous mutations, p.G274X:c.820 G > T (exon 7) and p.P534L: c.1601 C > T (exon 12), the latter within the iron sulfur-cluster and predicted to affect ubiquinone reductase activity of ETFDH and the docking of ETF to ETFDH. Our case supports the concept of a structural interaction between ETFDH and other enzyme partners, and suggests that the conformational change upon ETF binding to ETFDH may play a key role in linking ETFDH to II/III super-complex formation.

Nutritional status of preschool children in informal settlement areas near Bloemfontein, South Africa.

PubMed

Dannhauser, A; Bester, C; Joubert, G; Badenhorst, P; Slabber, M; Badenhorst, A; Du Toit, E; Barnard, H; Botha, P; Nogabe, L

2000-09-01

To determine the nutritional status and household resources of preschool children. A cross-sectional survey. : Two informal settlement areas, Joe Slovo (JS) and JB Mafora (JBM) in Mangaung, near Bloemfontein, South Africa. Preschool children (<72 months) of a randomly selected sample of households in JS (experimental) (n = 162) and JBM (control) (n = 186) were included. Standard methods were used to obtain household and care-giver particulars, weight and height measurements, blood and stool samples, and 24-hour dietary recalls. Breast-feeding and dietary intake in the two areas were nearly similar; breast-feeding was continued for 12 months and longer. Although the children's total protein intake was sufficient, their energy intake was low. A low median intake of micronutrients prevailed, including iron, zinc, calcium, niacin, riboflavin, thiamine and vitamins C, B6, A and D. The prevalence of being underweight (JS = 19.8%; JBM = 18.8%), stunted (JS = 29%; JBM = 21. 5%) and wasted (JS = 6.5%; JBM = 3.7%) were fairly similar in both areas, as well as the prevalence of marginal vitamin A deficiency, anaemia, iron deficiency and parasite infestations. No significant associations could be found between household and nutritional status indicators, probably due to the small number of well-nourished children and the generally poor household situation of the participants. The generally poor nutritional status and environmental conditions emphasize the urgency of intervention for these children.

Dietary Intake of Minerals, Vitamins, and Trace Elements Among Geriatric Population in India.

PubMed

Gupta, Aakriti; Khenduja, Preetika; Pandey, Ravindra Mohan; Sati, Hem Chandra; Sofi, Nighat Yaseen; Kapil, Umesh

2017-11-01

The geriatric population is at a high risk of developing deficiencies of essential micronutrients such as minerals, vitamins, and trace elements and their related deficiency signs and symptoms. Scarce data is available on the dietary intake of essential micronutrients among geriatric subjects in India. Hence, to fill the gap in the existing knowledge, a community-based cross-sectional study was conducted during 2015-2016 in District Nainital, Uttarakhand State, India. A total of 255 geriatric subjects were enrolled from 30 clusters (villages) identified by using population proportionate to size sampling methodology. Data were collected on sociodemographic profile and dietary intake of essential micronutrients (24-h dietary recall, food frequency questionnaire) from all the geriatric subjects. A high percentage of geriatric subjects did not consume the recommended daily intake for essential micronutrients such as energy (78%), protein (78%), calcium (51%), thiamine (33%), riboflavin (64%), niacin (88%), vitamin C (42%), iron (72%), folic acid (72%), magnesium (48%), zinc (98%), copper (81%) and chromium (89%) adequately. Food groups rich in essential micronutrients such as pulses, green leafy vegetables, roots and tubers, other vegetables, fruits, nonvegetarian food items, and milk and milk products were consumed irregularly by the subjects. The overall intake of energy and essential micronutrients was inadequate among the geriatric population in India, possibly due to poor quality and quantity of the diet consumed.

B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans.

PubMed

Majchrzak, D; Singer, I; Männer, M; Rust, P; Genser, D; Wagner, K-H; Elmadfa, I

2006-01-01

A vegetarian diet is considered to promote health and longevity and reduce the risk of cardiovascular diseases and cancer. However, a vegetarian diet may be deficient in some nutrients. Exclusion of animal products in vegetarian diets may affect the status of certain B-vitamins, and further cause the rise of plasma homocysteine concentration. The nutritional status of various B-vitamins (B(1), B(2), B(6), B(12), folic acid) and the concentration of homocysteine in blood plasma of omnivores (n = 40), vegetarians (n = 36) and vegans (n = 42) in Austria was evaluated. The evaluation was done using the functional parameters erythrocyte transketolase (ETK), glutathione reductase (EGR) and glutamic oxaloacetic transaminase (EGOT) activation coefficients. Enzyme activity was measured photometrically. The quantity of vitamins B(1), B(2) and B(6) in urine and the concentrations of vitamin B(6) and homocysteine in plasma were determined by HPLC methods with fluorescence detection. Plasma concentration of vitamin B(12) and folic acid were measured with radioimmunoassay. Most of the subjects showed a satisfying vitamin B(1) status. Vegans presented a significantly lower mean plasma vitamin B(12) concentration than omnivores and vegetarians and deficiency in 2.4% of the volunteers but the highest mean value of plasma folate among the investigated groups. A deficient status of folate was found in 18% of omnivores and in approximately 10% of vegans and vegetarians. The status of riboflavin is considered to be deficient in about 10% of omnivores and vegetarians and in over 30% of vegans. According to the activation coefficient of GOT, approximately one third of all subjects showed vitamin B(6) deficiency. Elevated homocysteine concentration in plasma was observed in 66% of the vegans and about 45-50% of the omnivores and vegetarians. Vegan subjects had significantly higher mean plasma homocysteine levels than omnivores. Thiamin and folate need not be a problem in a well-planned vegan diet. Vitamins B(12) and B(2) may need attention in the strict vegan diet, especially regarding elevated homocysteine levels in plasma. Pyridoxine status appeared to be independent of the diet. Copyright 2006 S. Karger AG, Basel.

Apparent ruminal synthesis of B vitamins in lactating dairy cows fed diets with different forage-to-concentrate ratios.

PubMed

Seck, M; Linton, J A Voelker; Allen, M S; Castagnino, D S; Chouinard, P Y; Girard, C L

2017-03-01

Effects of the forage-to-concentrate ratio on apparent ruminal synthesis of thiamine, riboflavin, niacin, vitamin B 6 , folates, and vitamin B 12 were evaluated in an experiment using 14 ruminally and duodenally cannulated Holstein cows. The experiment was a crossover design with two 15-d treatment periods and a 14-d preliminary period in which cows were fed a diet intermediate in composition between the treatment diets. Treatments were diets containing low-forage (44.8% forage, 32.8% starch, 24.4% neutral detergent fiber) or high-forage (61.4% forage, 22.5% starch, 30.7% neutral detergent fiber) concentrations. Both diets were formulated with different proportions of the same ingredients. Concentrations of B vitamins were analyzed in feed and duodenal digesta. Apparent ruminal synthesis of each B vitamin was calculated as the duodenal flow minus the intake. The high-forage diet had the highest concentrations of riboflavin, niacin, vitamin B 6 , and folates, whereas the low-forage diet had the highest thiamine concentration. Vitamin B 12 in the diets was under the level of detection. Consequently, despite a reduction in dry matter intake when the cows were fed the high-forage diet, increasing dietary forage concentration increased or tended to increase intakes of riboflavin, niacin, and vitamin B 6 but reduced thiamine and folate intakes. Increasing dietary forage concentration reduced apparent ruminal degradation of thiamine and apparent ruminal synthesis of riboflavin, niacin, and folates and increased ruminal degradation of vitamin B 6 , but had no effect on ruminal synthesis of vitamin B 12 . As a consequence, increasing the forage-to-concentrate ratio had no effect on the amounts of thiamine, riboflavin, and vitamin B 12 reaching the small intestine but decreased the amounts of niacin, vitamin B 6 , and folates available for absorption. Apparent ruminal syntheses of riboflavin, niacin, folates, and vitamin B 12 were correlated positively with the amount of starch digested in the rumen and duodenal flow of microbial N, whereas these correlations were negative for thiamine. Apparent ruminal syntheses of thiamine and vitamin B 6 were negatively correlated with their respective intakes, whereas folate intake was positively correlated with its synthesis in the rumen. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Nutritional deficiency and arsenical manifestations: a perspective study in an arsenic-endemic region of West Bengal, India.

PubMed

Deb, Debasree; Biswas, Anirban; Ghose, Aloke; Das, Arabinda; Majumdar, Kunal K; Guha Mazumder, Debendra N

2013-09-01

To assess whether nutritional deficiency increases susceptibility to arsenic-related health effects. Assessment of nutrition was based on a 24 h recall method of all dietary constituents. Epidemiological cross-sectional study was conducted in an arsenic endemic area of West Bengal with groundwater arsenic contamination. The study was composed of two groups – Group 1 (cases, n 108) exhibiting skin lesions and Group 2 (exposed controls, n 100) not exhibiting skin lesions – age- and sex-matched and having similar arsenic exposure through drinking water and arsenic levels in urine and hair. Both groups belonged to low socio-economic strata (Group 1 significantly poorer, P<0·01) and had low BMI (prevalence of BMI<18·5 kg/m2: in 38% in Group 1 and 27% in Group 2). Energy intake was below the Recommended Daily Allowance (set by the Indian Council of Medical Research) in males and females in both groups. Increased risk of arsenical skin lesions was found for those in the lowest quintile of protein intake (v. highest quintile: OR=4·60, 95% CI 1·36, 15·50 in males; OR=5·62, 95% CI 1·19, 34·57 in females). Significantly lower intakes of energy, protein, thiamin, niacin, Mg, Zn and choline were observed in both males and females of Group 1 compared with Group 2. Significantly lower intakes of carbohydrate, riboflavin, niacin and Cu were also observed in female cases with skin lesions compared with non-cases. Deficiencies of Zn, Mg and Cu, in addition to protein, B vitamins and choline, are found to be associated with arsenical skin lesions in West Bengal.

Hydrodynamic chronoamperometry for probing kinetics of anaerobic microbial metabolism--case study of Faecalibacterium prausnitzii.

PubMed

Prévoteau, Antonin; Geirnaert, Annelies; Arends, Jan B A; Lannebère, Sylvain; Van de Wiele, Tom; Rabaey, Korneel

2015-07-01

Monitoring in vitro the metabolic activity of microorganisms aids bioprocesses and enables better understanding of microbial metabolism. Redox mediators can be used for this purpose via different electrochemical techniques that are either complex or only provide non-continuous data. Hydrodynamic chronoamperometry using a rotating disc electrode (RDE) can alleviate these issues but was seldom used and is poorly characterized. The kinetics of Faecalibacterium prausnitzii A2-165, a beneficial gut microbe, were determined using a RDE with riboflavin as redox probe. This butyrate producer anaerobically ferments glucose and reduces riboflavin whose continuous monitoring on a RDE provided highly accurate kinetic measurements of its metabolism, even at low cell densities. The metabolic reaction rate increased linearly over a broad range of cell concentrations (9 × 10(4) to 5 × 10(7) cells.mL(-1)). Apparent Michaelis-Menten kinetics was observed with respect to riboflavin (KM = 6 μM; kcat = 5.3 × 10(5) s(-1), at 37 °C) and glucose (KM = 6 μM; kcat = 2.4 × 10(5) s(-1)). The short temporal resolution allows continuous monitoring of fast cellular events such as kinetics inhibition with butyrate. Furthermore, we detected for the first time riboflavin reduction by another potential probiotic, Butyricicoccus pullicaecorum. The ability of the RDE for fast, accurate, simple and continuous measurements makes it an ad hoc tool for assessing bioprocesses at high resolution.

Intraoperative Optical Coherence Tomography Using the RESCAN 700: Preliminary Results in Collagen Crosslinking.

PubMed

Pahuja, Natasha; Shetty, Rohit; Jayadev, Chaitra; Nuijts, Rudy; Hedge, Bharath; Arora, Vishal

2015-01-01

To compare the penetration of riboflavin using a microscope-integrated real time spectral domain optical coherence tomography (ZEISS OPMI LUMERA 700 and ZEISS RESCAN 700) in keratoconus patients undergoing accelerated collagen crosslinking (ACXL) between epithelium on (epi-on) and epithelium off (epi-off). Intraoperative images were obtained during each of the procedures. Seven keratoconus patients underwent epi-on ACXL and four underwent epi-off ACXL. A software tool was developed using Microsoft.NET and Open Computer Vision (OpenCV) libraries for image analysis. Pre- and postprocedure images were analyzed for changes in the corneal hyperreflectance pattern as a measure of the depth of riboflavin penetration. The mean corneal hyperreflectance in the epi-on group was 12.97 ± 1.49 gray scale units (GSU) before instillation of riboflavin and 14.46 ± 2.09 GSU after AXCL (P = 0.019) while in the epi-off group it was 11.43 ± 2.68 GSU and 16.98 ± 8.49 GSU, respectively (P = 0.002). The average depth of the band of hyperreflectance in the epi-on group was 149.39 ± 15.63 microns and in the epi-off group it was 191.04 ± 32.18 microns. This novel in vivo, real time imaging study demonstrates riboflavin penetration during epi-on and epi-off ACXL.

The effect of riboflavin/UVA cross-linking on anti-degeneration and promoting angiogenic capability of decellularized liver matrix.

PubMed

Xiang, Junxi; Liu, Peng; Zheng, Xinglong; Dong, Dinghui; Fan, Shujuan; Dong, Jian; Zhang, Xufeng; Liu, Xuemin; Wang, Bo; Lv, Yi

2017-10-01

Weak mechanical property and unstable degradation rate limited the application of decellularized liver matrix in tissue engineering. The aim of this study was to explore a new method for improving the mechanical properties, anti-degeneration and angiogenic capability of decellularized liver matrix. This was achieved by a novel approach using riboflavin/ultraviolet A treatment to induce collagen cross-linking of decellularized matrix. Histological staining and scanning electron microscope showed that the diameter of cross-linked fibers significantly increased compared with the control group. The average peak load and Young's modulus of decellularized matrix were obviously improved after cross-linking. Then we implanted the modified matrix into the rat hepatic injury model to test the anti-degeneration and angiogenic capability of riboflavin/UVA cross-linked decellularized liver scaffolds in vivo. The results indicated that cross-linked scaffolds degrade more slowly than those in the control group. In the experiment group, average microvessel density in the implanted matrix was higher than that in the control group since the first week after implantation. In conclusion, we initiated the method to improve the biomechanical properties of decellularized liver scaffolds by riboflavin/UVA cross-linking, and more importantly, its improvement on anti-degeneration and angiogenesis was identified. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2662-2669, 2017. © 2017 Wiley Periodicals, Inc.

Corneal Resistance to Keratolysis After Collagen Crosslinking With Rose Bengal and Green Light.

PubMed

Fadlallah, Ali; Zhu, Hong; Arafat, Samer; Kochevar, Irene; Melki, Samir; Ciolino, Joseph B

2016-12-01

The purpose of this study was to evaluate the resistance to degradation by collagenase A of corneas that have been crosslinked with Rose Bengal and green light (RGX). The ex vivo crosslinking procedure was performed on enucleated rabbit corneas. Corneas were deepithelialized after applying 30% alcohol. Corneas were stained with Rose Bengal (RB, 0.1%) for 2 minutes and then exposed to green light (532 nm) at 0.25 W/cm2 for times to deliver doses of 50, 100, 150, or 200 J/cm2 (n = 5 per group). Five corneas were pretreated with riboflavin solution (0.1% riboflavin) for 15 minutes and irradiated with ultraviolet A (UVA) light (370 nm, 3 mW/cm2) for 30 minutes. Five corneas underwent only de-epithelialization and were otherwise untreated. Five corneas were stained with RB without light exposure. The central corneas of each group was removed with a 8.5-mm trephine and incubated at 37°C in 0.3% collagenase A solution. Time to dissolution of each cornea was compared across treatments. Corneas treated with RGX were treated with light fluences of 50, 100, 150, and 200 J/cm2; these corneas dissolved completely at 8.3 ± 1.2, 11.1 ± 1.4, 12.4 ± 1.7, and 15.7 ± 1.8 hours, respectively. Corneas treated by riboflavin and UVA light dissolved at 15.7 ± 1.7 hours, and nontreated corneas dissolved at 6.1 ± 1.3 hours. Corneas treated with only RB (no green light) dissolved at 9.3 ± 1.7 hours. Compared with the untreated corneas, all of the RB groups and the riboflavin-UVA-treated group of corneas degraded statistically significantly slower than untreated corneas (P < 0.05). Crosslinking with RGX increased corneal resistance to digestion by collagenase comparable to that produced by riboflavin and UVA treatment.

Identification and Characterization of the Missing Pyrimidine Reductase in the Plant Riboflavin Biosynthesis Pathway1[W][OA

PubMed Central

Hasnain, Ghulam; Frelin, Océane; Roje, Sanja; Ellens, Kenneth W.; Ali, Kashif; Guan, Jiahn-Chou; Garrett, Timothy J.; de Crécy-Lagard, Valérie; Gregory, Jesse F.; McCarty, Donald R.; Hanson, Andrew D.

2013-01-01

Riboflavin (vitamin B2) is the precursor of the flavin coenzymes flavin mononucleotide and flavin adenine dinucleotide. In Escherichia coli and other bacteria, sequential deamination and reduction steps in riboflavin biosynthesis are catalyzed by RibD, a bifunctional protein with distinct pyrimidine deaminase and reductase domains. Plants have two diverged RibD homologs, PyrD and PyrR; PyrR proteins have an extra carboxyl-terminal domain (COG3236) of unknown function. Arabidopsis (Arabidopsis thaliana) PyrD (encoded by At4g20960) is known to be a monofunctional pyrimidine deaminase, but no pyrimidine reductase has been identified. Bioinformatic analyses indicated that plant PyrR proteins have a catalytically competent reductase domain but lack essential zinc-binding residues in the deaminase domain, and that the Arabidopsis PyrR gene (At3g47390) is coexpressed with riboflavin synthesis genes. These observations imply that PyrR is a pyrimidine reductase without deaminase activity. Consistent with this inference, Arabidopsis or maize (Zea mays) PyrR (At3g47390 or GRMZM2G090068) restored riboflavin prototrophy to an E. coli ribD deletant strain when coexpressed with the corresponding PyrD protein (At4g20960 or GRMZM2G320099) but not when expressed alone; the COG3236 domain was unnecessary for complementing activity. Furthermore, recombinant maize PyrR mediated NAD(P)H-dependent pyrimidine reduction in vitro. Import assays with pea (Pisum sativum) chloroplasts showed that PyrR and PyrD are taken up and proteolytically processed. Ablation of the maize PyrR gene caused early seed lethality. These data argue that PyrR is the missing plant pyrimidine reductase, that it is plastid localized, and that it is essential. The role of the COG3236 domain remains mysterious; no evidence was obtained for the possibility that it catalyzes the dephosphorylation that follows pyrimidine reduction. PMID:23150645

Biofunctionalized Zinc Oxide Field Effect Transistors for Selective Sensing of Riboflavin With Current Modulation

DTIC Science & Technology

2011-06-27

ZnO-FET was tuned by attaching a redox tag ( ferrocene ) to the 3’ terminus of the aptamer, resulting in positive current modulation upon exposure to...flexibility in aptamer detection systems can be added by attaching redox molecules, such as ferrocene or methylene blue, to the 3’ end of the DNA...AGA TCG TTC C-3’. Ferrocene terminated riboflavin aptamers were purchased from Friz BioChem (Germany) and HPLC purification with the following sequence

SERS study of riboflavin on green-synthesized silver nanoparticles prepared by reduction using different flavonoids: What is the role of flavonoid used?

NASA Astrophysics Data System (ADS)

Švecová, Marie; Ulbrich, Pavel; Dendisová, Marcela; Matějka, Pavel

2018-04-01

Spectroscopy of surface-enhanced Raman scattering (SERS) is nowadays widely used in the field of bio-science and medicine. These applications require new enhancing substrates with special properties. They should be non-toxic, environmentally friendly and (bio-) compatible with examined samples. Flavonoids are natural antioxidants with many positive effects on human health. Simultaneously, they can be used as reducing agent in preparation procedure of plasmonic enhancing substrate for SERS spectroscopy. The best amplifiers of Raman vibrational spectroscopic signal are generally silver nanoparticles (AgNPs). In this study, several flavonoids (forming a logical set) were used as reducing agent in AgNPs preparation procedures. Reactivity of 10 structurally arranged flavonoids (namely flavone, chrysin, apigenin, luteolin, tricetin, 3-hydroxyflavone, galangin, kaempferol, quercetin and myricetin) was compared and SERS-activity of prepared AgNPs was tested using model analyte riboflavin. Riboflavin was detected down to concentration 10-9 mol/l.

Mutations in riboflavin transporter present with severe sensory loss and deafness in childhood.

PubMed

Srour, Myriam; Putorti, Maria Lisa; Schwartzentruber, Jeremy; Bolduc, Véronique; Shevell, Michael Israel; Poulin, Chantal; O'ferrall, Erin; Buhas, Daniela; Majewski, Jacek; Brais, Bernard

2014-11-01

We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood-onset recessive sensory loss associated with deafness and variable optic atrophy. Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals. WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown-Vialetto-Van-Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement. Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability. © 2014 Wiley Periodicals, Inc.

A synthetic microbial consortium of Shewanella and Bacillus for enhanced generation of bioelectricity.

PubMed

Liu, Ting; Yu, Yang-Yang; Chen, Tao; Chen, Wei Ning

2017-03-01

In this study, a synthetic microbial consortium containing exoelectrogen Shewanella oneidensis MR-1 and riboflavin-producing strain, Bacillus subtilis RH33, was rationally designed and successfully constructed, enabling a stable, multiple cycles of microbial fuel cells (MFCs) operation for more than 500 h. The maximum power density of MFCs with this synthetic microbial consortium was 277.4 mW/m 2 , which was 4.9 times of that with MR-1 (56.9 mW/m 2 ) and 40.2 times of RH33 (6.9 mW/m 2 ), separately. At the same time, the Coulombic efficiency of the synthetic microbial consortium (5.6%) was higher than MR-1 (4.1%) and RH33 (2.3%). Regardless the high concentration of riboflavin produced by RH33, the power density of RH33 was rather low. The low bioelectricity generation can be ascribed to the low efficiency of RH33 in utilizing riboflavin for extracellular electron transfer (EET). In the synthetic microbial consortium of MR-1 and RH33, it was found that both mediated and direct electron transfer efficiencies were enhanced. By exchanging the anolyte of MR-1 and RH33, it was confirmed that the improved MFC performance with the synthetic microbial consortium was because MR-1 could efficiently utilize the high concentration of riboflavin produced by RH33. Biotechnol. Bioeng. 2017;114: 526-532. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hydrodynamic chronoamperometry for probing kinetics of anaerobic microbial metabolism - case study of Faecalibacterium prausnitzii

NASA Astrophysics Data System (ADS)

Prévoteau, Antonin; Geirnaert, Annelies; Arends, Jan B. A.; Lannebère, Sylvain; van de Wiele, Tom; Rabaey, Korneel

2015-07-01

Monitoring in vitro the metabolic activity of microorganisms aids bioprocesses and enables better understanding of microbial metabolism. Redox mediators can be used for this purpose via different electrochemical techniques that are either complex or only provide non-continuous data. Hydrodynamic chronoamperometry using a rotating disc electrode (RDE) can alleviate these issues but was seldom used and is poorly characterized. The kinetics of Faecalibacterium prausnitzii A2-165, a beneficial gut microbe, were determined using a RDE with riboflavin as redox probe. This butyrate producer anaerobically ferments glucose and reduces riboflavin whose continuous monitoring on a RDE provided highly accurate kinetic measurements of its metabolism, even at low cell densities. The metabolic reaction rate increased linearly over a broad range of cell concentrations (9 × 104 to 5 × 107 cells.mL-1). Apparent Michaelis-Menten kinetics was observed with respect to riboflavin (KM = 6 μM kcat = 5.3×105 s-1, at 37 °C) and glucose (KM = 6 μM kcat = 2.4 × 105 s-1). The short temporal resolution allows continuous monitoring of fast cellular events such as kinetics inhibition with butyrate. Furthermore, we detected for the first time riboflavin reduction by another potential probiotic, Butyricicoccus pullicaecorum. The ability of the RDE for fast, accurate, simple and continuous measurements makes it an ad hoc tool for assessing bioprocesses at high resolution.

Whole blood treated with riboflavin and ultraviolet light: quality assessment of all blood components produced by the buffy coat method.

PubMed

Schubert, Peter; Culibrk, Brankica; Karwal, Simrath; Serrano, Katherine; Levin, Elena; Bu, Daniel; Bhakta, Varsha; Sheffield, William P; Goodrich, Raymond P; Devine, Dana V

2015-04-01

Pathogen inactivation (PI) technologies are currently licensed for use with platelet (PLT) and plasma components. Treatment of whole blood (WB) would be of benefit to the blood banking community by saving time and costs compared to individual component treatment. However, no paired, pool-and-split study directly assessing the impact of WB PI on the subsequently produced components has yet been reported. In a "pool-and-split" study, WB either was treated with riboflavin and ultraviolet (UV) light or was kept untreated as control. The buffy coat (BC) method produced plasma, PLT, and red blood cell (RBC) components. PLT units arising from the untreated WB study arm were treated with riboflavin and UV light on day of production and compared to PLT concentrates (PCs) produced from the treated WB units. A panel of common in vitro variables for the three types of components was used to monitor quality throughout their respective storage periods. PCs derived from the WB PI treatment were of significantly better quality than treated PLT components for most variables. RBCs produced from the WB treatment deteriorated earlier during storage than untreated units. Plasma components showed a 3% to 44% loss in activity for several clotting factors. Treatment of WB with riboflavin and UV before production of components by the BC method shows a negative impact on all three blood components. PLT units produced from PI-treated WB exhibited less damage compared to PLT component treatment. © 2014 AABB.

The APSES protein Sok2 is a positive regulator of sporulation in Ashbya gossypii.

PubMed

Wasserstrom, Lisa; Dünkler, Alexander; Walther, Andrea; Wendland, Jürgen

2017-12-01

Ashbya gossypii is a homothallic, flavinogenic, filamentous ascomycete that starts overproduction of riboflavin and fragments its mycelium quantitatively into spore producing sporangia at the end of a growth phase. Mating is not required for sporulation and the standard homothallic laboratory strain is a MATa strain. Here we show that ectopic expression of Saccharomyces cerevisiae MATα2 in A. gossypii completely suppresses sporulation, inhibits riboflavin overproduction and downregulates among others AgSOK2. AgSok2 belongs to a fungal-specific group of (APSES) transcription factors. Deletion of AgSOK2 strongly reduces riboflavin production and blocks sporulation. The initiator of meiosis, AgIME1, is a transcription factor essential for sporulation. We characterized the AgIME1 promoter region required for complementation of the Agime1 mutant. Reporter assays with AgIME1 promoter fragments fused to lacZ showed that AgSok2 does not control AgIME1 transcription. However, global transcriptome analysis identified two other essential regulators of sporulation, AgIME2 and AgNDT80, as potential targets of AgSok2. Our data suggest that sporulation and riboflavin production in A. gossypii are under mating type locus and nutritional control. Sok2, a target of the cAMP/protein kinase A pathway, serves as a central positive regulator to promote sporulation. This contrasts Saccharomyces cerevisiae where Sok2 is a repressor of IME1 transcription. © 2017 John Wiley & Sons Ltd.

An Aromatic Cap Seals the Substrate Binding Site in an ECF-Type S Subunit for Riboflavin

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

Karpowich, Nathan K.; Song, Jinmei; Wang, Da-Neng

2016-06-13

ECF transporters are a family of active membrane transporters for essential micronutrients, such as vitamins and trace metals. Found exclusively in archaea and bacteria, these transporters are composed of four subunits: an integral membrane substrate-binding subunit (EcfS), a transmembrane coupling subunit (EcfT), and two ATP-binding cassette ATPases (EcfA and EcfA'). We have characterized the structural basis of substrate binding by the EcfS subunit for riboflavin from Thermotoga maritima, TmRibU. TmRibU binds riboflavin with high affinity, and the protein–substrate complex is exceptionally stable in solution. The crystal structure of riboflavin-bound TmRibU reveals an electronegative binding pocket at the extracellular surface inmore » which the substrate is completely buried. Analysis of the intermolecular contacts indicates that nearly every available substrate hydrogen bond is satisfied. A conserved aromatic residue at the extracellular end of TM5, Tyr130, caps the binding site to generate a substrate-bound, occluded state, and non-conservative mutation of Tyr130 reduces the stability of this conformation. Using a novel fluorescence binding assay, we find that an aromatic residue at this position is essential for high-affinity substrate binding. Comparison with other S subunit structures suggests that TM5 and Loop5-6 contain a dynamic, conserved motif that plays a key role in gating substrate entry and release by S subunits of ECF transporters.« less

Fluorescence spectroscopy for non-invasive measurement of mechanical stiffness after photo-crosslinking of rabbit cornea

NASA Astrophysics Data System (ADS)

Williams, Maura; Lewis, William; Ortega-Martinez, Antonio; Franco, Walfre

2017-02-01

Background and Objectives: Keratoconus is a disease characterized by progressive steepening and thinning of the cornea, altering visual acuity and sometimes potentiating the need for corneal transplant if the disease progresses.1-3 Corneal crosslinking, a procedure that uses topical riboflavin and UV light to increase the stiffness of the cornea through the creation of collagen crosslinks was recently approved by the FDA for use in the U.S. The objective of the present study was to investigate whether endogenous collagen fluorescence changes following treatment can be correlated to alterations in the stiffness of the cornea, thereby guiding treatment parameters. Study Design and Results: 78 ex-vivo rabbit eyes divided into three groups: riboflavin solution plus UV irradiation, dextran solution plus UV irradiation, and riboflavin solution only. An additional group of eyes received no treatment. The epithelium was removed from each sample and topical riboflavin was applied. Eyes were irradiated with a 365 nm black ray UV lamp for various treatment times, ranging from half the clinical treatment time to three times the length. Mechanical testing was performed to determine the force/displacement relationship for the various treatment times. Fluorescence spectral changes following treatment corresponded with changes in stiffness. In particular, a decrease in the value of fluorescence intensity at 290/340 nm excitation/emission wavelengths corresponded to an increase in corneal stiffness following treatment. It may be possible to use fluorescence spectral changes of endogenous corneal crosslinks to evaluate mechanical stiffness changes non-invasively.

Childhood malnutrition and parasitic helminth interactions.

PubMed

Papier, Keren; Williams, Gail M; Luceres-Catubig, Ruby; Ahmed, Faruk; Olveda, Remigio M; McManus, Donald P; Chy, Delia; Chau, Thao N P; Gray, Darren J; Ross, Allen G P

2014-07-15

There is evidence to support that nutritional deficiency can reduce the body's immune function, thereby decreasing resistance to disease and increasing susceptibility to intestinal parasites. A cross-sectional survey was carried out on 693 school-aged children from 5 schistosomiasis-endemic villages in Northern Samar, the Philippines. Data on dietary intake, nutritional status, and intestinal parasitic infection were collected. The prevalence of stunting, thinness, and wasting was 49.2%, 27.8%, and 59.7% of all children. The proportion of children infected with Schistosoma japonicum (15.6%, P = .03) and hookworm (22.0%, P = .05) were significantly lower among children who met the recommended energy and nutrient intake (RENI) for total calories. The percentage of children infected with Trichuris trichiura was highest among children who did not meet the RENI for energy (74.1%, P = .04), iron (73.4%, P = .01), thiamine (74.0%, P = .00), and riboflavin (73.3%, P = .01). Susceptibility to having 1 or more parasitic infections was significantly associated with poor intake of energy (P = .04), thiamine (P = .02), and riboflavin (P = .01).The proportion of stunted children was significantly higher among children who did not meet the RENI for energy (68.9%, P = .002), protein (54.0%, P = .004), or niacin (30.8%, P = .02) and for those infected with hookworm (31.8%, P = .0002). After adjusting for potential confounders, protein intake less than the RENI (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.03-2.14), and hookworm infection (OR, 1.77; 95% CI, 1.22-2.55) were the major predictors of stunting. The results support the hypothesis that poor nutrient intake may increase susceptibility to parasitic diseases and together they negatively affect childhood nutritional status. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Do Chinese Children Get Enough Micronutrients?

PubMed Central

Wang, Huijun; Wang, Dantong; Ouyang, Yifei; Huang, Feifei; Ding, Gangqiang; Zhang, Bing

2017-01-01

The aim of this study was to examine usual daily micronutrient intake of Chinese children based on data from the 2011 China Health and Nutrition Survey. We analyzed data from 4 to 17-year-old participants, who provided dietary data on three consecutive days combined with the household weighing method in 2011. Usual daily intake of each nutrient was estimated using a mixed effects model based on the China Food Composition published in 2009. The means, medians and percentages below Estimated Average Requirements (EAR) were reported for selected micronutrients, including calcium, sodium, potassium, iron, zinc, selenium, vitamin A, thiamine, riboflavin and vitamin C. For sodium and potassium, the means and the distribution of intakes were compared to the Adequate Intake (AI) level. The average usual daily intakes of all micronutrients increase with age, and the intakes of boys were found to be higher than girls in the same age group. The average calcium intake increased from 272 mg/day in 4–6 years to 391 mg/day in 14–17 years, but the percentage of inadequate calcium intake remained very high (>96%). The prevalence of inadequacy of calcium was the highest among the mineral nutrients reported in this study. As the requirements of micronutrients increased with age, the percentage of subjects with inadequate intake increased in the 11–17 years age groups. Among 14–17 years group, the percentages of study participants with dietary intakes of calcium, iron, zinc, selenium, vitamin A, thiamine, riboflavin and vitamin C below the EAR were 96.8%, 18.8%, 37.6%, 72.8%, 36.8%, 91.8%. 85.9% and 75.5%, respectively. Among 11–13 years group, the percentages of study participants with dietary intakes of iron, zinc and vitamin A below the EAR were 23.5%, 41.5%, and 41.6%, respectively. Thus, micronutrient deficiency is a problem in Chinese children. Nutrition education and intervention programs are needed to address these nutritional gaps. PMID:28420205

The ultrastructure of rabbit sclera after scleral crosslinking with riboflavin and blue light of different intensities.

PubMed

Karl, Anett; Makarov, Felix N; Koch, Christian; Körber, Nicole; Schuldt, Carsten; Krüger, Martin; Reichenbach, Andreas; Wiedemann, Peter; Bringmann, Andreas; Iseli, Hans Peter; Francke, Mike

2016-08-01

We aimed to determine the ultrastructural changes of collagen fibrils and cells in the rabbit sclera after scleral crosslinking using riboflavin and blue light of different intensities. Scleral crosslinking is known to increase scleral stiffness and may inhibit the axial elongation of progressive myopic eyes. The equatorial parts of the sclera of one eye of six adult albino rabbits were treated with topical riboflavin solution (0.5 %) followed by irradiation with blue light (200, 400, 650 mW/cm(2)) for 20 min. After 3 weeks, the ultrastructure of scleral cells and the abundance of small- (10-100 nm) and large-diameter (>100 nm) collagen fibrils in fibril bundles of different scleral layers were examined with electron microscopy. In the scleral stroma of control eyes, the thickness of collagen fibrils showed a bimodal distribution. The abundance of small-diameter collagen fibrils decreased from the inner towards the outer sclera, while the amount of large-diameter fibrils and the scleral collagen content did not differ between different stroma layers. Treatment with riboflavin and blue light at 200 mW/cm(2) did not induce ultrastructural changes of cells and collagen fibrils in the scleral stroma. Treatment with blue light of higher intensities induced scleral cell activation in a scleral layer-dependent manner. In addition, outer scleral layers contained phagocytes that engulfed collagen fibrils and erythrocytes. Blue light of the highest intensity induced a reduction of the scleral collagen content, a decreased abundance of large-diameter collagen fibrils, and an increased amount of small-diameter fibrils in the whole scleral stroma. The data indicate that in rabbits, scleral crosslinking with riboflavin and blue light of 200 mW/cm(2) for 20 min is relatively safe and does not induce ultrastructural alterations of scleral cells and of the collagen composition of the scleral stroma. Irradiation with blue light of intensities between 200 and 400 mW/cm(2) induces scleral cell activation, which may contribute to scleral scarring and stiffening. Higher intensities cause scleritis.

Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

PubMed

Finch, Anthony J; Benson, Jamie M; Donnelly, Patrick E; Torzilli, Peter A

2017-06-01

Objective Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers. Materials UV-visible spectroscopy was performed on each major component of cartilage in solution, on bovine synovial fluid, and on four photosensitizers, riboflavin, Irgacure 2959, quinine, and riboflavin-5'-phosphate. Molar extinction and absorption coefficients were calculated at wavelengths of maximum absorbance and 365 nm. Intact articular cartilage was also examined. Results The individual major biochemical components of cartilage, Irgacure 2959, and quinine did not exhibit a significant absorption at 365 nm. Riboflavin and riboflavin-5'-phosphate were more effectual light absorbers at 365 nm, compared with the individual native species. Intact cartilage absorbed a significantly greater amount of UV light in comparison with the native species. Conclusion Our results indicate that none of the individual native species in cartilage will interfere with the absorption of UV light at 365 nm by these commonly used photoinitiators. Intact cartilage slices exhibited significant light absorption at 365 nm, while also having distinct absorbance peaks at wavelengths less than 300 nm. Determining the UV absorptive properties of the biomolecules native to articular cartilage and synovial fluid will aid in optimizing scaffolding procedures to ensure sufficient scaffold polymerization at a minimum UV intensity.

Photocrosslinked Tyramine-Substituted Hyaluronate Hydrogels with Tunable Mechanical Properties Improve Immediate Tissue‐Hydrogel Interfacial Strength in Articular Cartilage

PubMed Central

Donnelly, Patrick E.; Chen, Tony; Finch, Anthony; Brial, Caroline; Maher, Suzanne A.; Torzilli, Peter A.

2017-01-01

Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self‐crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5–16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press‐fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage. PMID:28134036

The B Vitamins Nicotinamide (B3) and Riboflavin (B2) Stimulate Metamorphosis in Larvae of the Deposit-Feeding Polychaete Capitella teleta: Implications for a Sensory Ligand-Gated Ion Channel

PubMed Central

Burns, Robert T.; Pechenik, Jan A.; Biggers, William J.; Scavo, Gia; Lehman, Christopher

2014-01-01

Marine sediments can contain B vitamins, presumably incorporated from settled, decaying phytoplankton and microorganisms associated with decomposition. Because B vitamins may be advantageous for the energetically intensive processes of metamorphosis, post-metamorphic growth, and reproduction, we tested several B vitamins to determine if they would stimulate larvae of the deposit-feeding polychaete Capitella teleta to settle and metamorphose. Nicotinamide and riboflavin individually stimulated larvae of C. teleta to settle and metamorphose, generally within 1–2 hours at nicotinamide concentrations as low as 3 µM and riboflavin concentrations as low as 50 µM. More than 80% of the larvae metamorphosed within 30 minutes at a nicotinamide concentration of 7 µM. The pyridine channel agonist pyrazinecarboxamide also stimulated metamorphosis at very low concentrations. In contrast, neither lumichrome, thiamine HCl, pyridoxine HCl, nor vitamin B12 stimulated larvae of C. teleta to metamorphose at concentrations as high as 500 µM. Larvae also did not metamorphose in response to either nicotinamide or pyrazinecarboxamide in calcium-free seawater or with the addition of 4-acetylpyridine, a competitive inhibitor of the pyridine receptor. Together, these results suggest that larvae of C. teleta are responding to nicotinamide and riboflavin via a chemosensory pyridine receptor similar to that previously reported to be present on crayfish chela and involved with food recognition. Our data are the first to implicate B vitamins as possible natural chemical settlement cues for marine invertebrate larvae. PMID:25390040

Riboflavin-ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells.

PubMed

Tormey, Christopher A; Santhanakrishnan, Manjula; Smith, Nicole H; Liu, Jingchun; Marschner, Susanne; Goodrich, Raymond P; Hendrickson, Jeanne E

2016-04-01

Ultraviolet (UV) illumination/pathogen reduction effectively inactivates white blood cells (WBCs) in whole blood. Given that cotransfused WBCs may impact recipient immune responses, we hypothesized that pathogen reduction of whole blood may alter responses to RBC antigens. Transgenic mice expressing a model (HOD) antigen, authentic human (hGPA or KEL) antigens, or natural fluorescence (uGFP) on their RBCs were utilized as blood donors. Recipients were transfused with fresh whole blood to which riboflavin had been added or fresh whole blood treated by UV illumination/pathogen reduction treatment after the addition of riboflavin. Posttransfusion RBC recovery, survival, and alloimmunization were measured by flow cytometry. UV illumination/pathogen reduction treatment did not alter RBC antigen expression, and recipients of treated syngeneic RBCs had persistently negative direct antiglobulin tests. Greater than 75% of treated and untreated syngeneic RBCs were recovered 24 hours posttransfusion in all experiments, although alterations in the long-term posttransfusion survival of treated RBCs were observed. Treated and untreated KEL RBCs induced similar recipient alloimmune responses, with all recipients making anti-KEL glycoprotein immunoglobulins (p > 0.05). Alloimmune responses to treated HOD or hGPA RBCs were no different from untreated RBCs (p > 0.05). Pathogen inactivation treatment of fresh whole murine blood with riboflavin and UV illumination does not impact the rate or magnitude of RBC alloimmunization to three distinct RBC antigens. Further, UV illumination/pathogen reduction appears safe from an immunohematologic standpoint, with no immunogenic neoantigens detected on treated murine RBCs. Future studies with fresh and stored human RBCs are warranted to confirm these findings. © 2015 AABB.

Rapid determination of the various native forms of vitamin B6 and B2 in cow's milk using ultra-high performance liquid chromatography.

PubMed

Schmidt, A; Schreiner, M G; Mayer, H K

2017-06-02

As the formation of pyridoxal phosphate, the active cofactor of vitamin B 6 , is dependent on riboflavin 5-phosphate, we propose a fast and simple ultra-high performance liquid chromatography method for the simultaneous determination of the native B 6 vitamers pyridoxal, pyridoxine, pyridoxamine, their mono phosphorus esters and 4-pyridoxic acid as well as vitamin B 2 as riboflavin and its phosphorus ester riboflavin 5-phosphate in milk. Separation was achieved under 6.0min by reversed-phase and pH gradient elution. Sample preparation was optimized regarding various acids and pH levels. Changes in those parameters led to significant deviations of sample matrix breakdown efficiency. The optimized method was then validated regarding specificity, accuracy, precision, linearity, range, detection and quantification limits. As the method performed satisfactory, is was used to study commercial liquid cow's milk (n=31), regarding effects of the employed preservation technique (pasteurization, extended shelf-life, ultra-high temperature) on the composition and content of B 6 and B 2 vitamers. In cow's milk, vitamin B 6 mostly consists of pyridoxal and its phosphate ester, with pyridoxal phosphate being the bulk component. The catabolite of the vitamin B 6 metabolism, 4-pyridoxic acid was present in significant amounts in all studied samples, with up to 2.69μmolL -1 . Vitamin B 2 was present as riboflavin and its phosphate ester up to 12.86μmolL -1 . Copyright © 2017 Elsevier B.V. All rights reserved.

Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

PubMed Central

Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

2014-01-01

Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

A Case of Brown-Vialetto-Van Laere Syndrome Due To a Novel Mutation in SLC52A3 Gene

PubMed Central

Thulasi, Venkatraman; Veerapandiyan, Aravindhan; Pletcher, Beth A.; Tong, Chun M.

2017-01-01

Brown-Vialetto-Van Laere syndrome is a rare disorder characterized by motor, sensory, and cranial neuronopathies, associated with mutations in SLC52A2 and SLC52A3 genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. The authors describe the clinical course of a 6-year-old girl with Brown-Vialetto-Van Laere syndrome and a novel homozygous mutation c.1156T>C in the SLC52A3 gene, who presented at the age of 2.5 years with progressive brain stem dysfunction including ptosis, facial weakness, hearing loss, dysphagia, anarthria with bilateral vocal cord paralysis, and ataxic gait. She subsequently developed respiratory failure requiring tracheostomy and worsening dysphagia necessitating a gastrostomy. Following riboflavin supplementation, resolution of facial diplegia and ataxia, improvements in ptosis, and bulbar function including vocalization and respiration were noted. However, her sensorineural hearing loss remained unchanged. Similar to other cases of Brown-Vialetto-Van Laere syndrome, our patient responded favorably to early riboflavin supplementation with significant but not complete neurologic recovery. PMID:28856173

Complete genome sequence of Lactobacillus plantarum LZ227, a potential probiotic strain producing B-group vitamins.

PubMed

Li, Ping; Zhou, Qingqing; Gu, Qing

2016-09-20

B-group vitamins play an important role in human metabolism, whose deficiencies are associated with a variety of disorders and diseases. Certain microorganisms such as Lactic acid bacteria (LAB) have been shown to have capacities for B-group vitamin production and thus could potentially replace chemically synthesized vitamins for food fortification. A potential probiotic strain named Lactobacillus plantarum LZ227, which was isolated from raw cow milk in this study, exhibits the ability to produce B-group vitamins. Complete genome sequencing of LZ227 was performed to gain insights into the genetic elements involved in B-group vitamin production. The genome of LZ227 contains a circular 3,131,750-bp chromosome, three circular plasmids and two predicted linear plasmids. LZ227 also contains gene clusters for biosynthesis of both riboflavin and folate. This genome sequence provides a basis for further elucidation of its molecular genetics and probiotic functions, and will facilitate its applications as starter cultures in food industry. Copyright © 2016 Elsevier B.V. All rights reserved.

[Epidemiology and risk factors of the oral carcinoma].

PubMed

Podlodowska, Justyna; Szumiło, Justyna; Podlodowski, Wiktor; Starosławska, Elzbieta; Burdan, Franciszek

2012-02-01

Oral cancer is the eleventh most common malignancy in the world, with squamous cell carcinoma being a predominant histologic type. The highest incidence is observed in India, Australia, Brazil, France and South Africa. In Europe the most affected regions are France, French-language cantons of Switzerland, northern Italy and countries of the Middle-East Europe. In most regions cancer is much more common in man. Oral cancer accounts for 1.34% of all registered malignant tumors in Poland in 2008. Etiology of the oral squamous cell carcinoma is complex. The most important risk factors, especially in well-developed countries are tobacco smoking and alcohol exposure. Alcohol promotes cancer development not only administered as a stimulant but also as a component of mouthwashes. Betel chewing, human papilloma virus infection, deficiency of vitamin A, riboflavin and iron, poor mouth hygiene and immunosuppressive therapy are also associated with higher incidence of oral carcinoma. More recently, relation between individual increased susceptibility to oral cancer and some genes polymorphisms, especially those encoding cytokines and enzymes engaged in alcohol metabolism has been found.

Establishing Corneal Cross-Linking With Riboflavin and UV-A in the Mouse Cornea In Vivo: Biomechanical Analysis.

PubMed

Hammer, Arthur; Kling, Sabine; Boldi, Marc-Olivier; Richoz, Olivier; Tabibian, David; Randleman, J Bradley; Hafezi, Farhad

2015-10-01

To establish corneal cross-linking (CXL) with riboflavin and UV-A in in the mouse cornea in vivo and to develop tools to measure the biomechanical changes observed. A total of 55 male C57BL/6 wild-type mice (aged 5 weeks) were divided into 14 groups. Standard CXL parameters were adapted to the anatomy of the mouse cornea, and riboflavin concentration (0.1%-0.5%) and fluence series (0.09-5.4 J/cm²) were performed on the assumption of the endothelial damage thresholds. Untreated and riboflavin only corneas were used as controls. Animals were killed at 30 minutes and at 1 month after CXL. Corneas were harvested. Two-dimensional (2D) biomechanical testing was performed using a customized corneal holder in a commercially available stress-strain extensometer/indenter. Both elastic and viscoelastic analyses were performed. Statistical inference was performed using t-tests and specific mathematical models fitted to the experimental stress-strain and stress-relaxation data. Adjusted P values by the method of Benjamini and Hochberg are reported. For all CXL treatment groups, stress-relaxation showed significant differences (P < 0.0001) after 120 seconds of constant strain application, with cross-linked corneas maintaining a higher stress (441 ± 40 kPa) when compared with controls (337 ± 39 kPa). Stress-strain analysis confirmed these findings but was less sensitive to CXL-induced changes: at 0.5% of strain, cross-linked corneas remained at higher stress (778 ± 111 kPa) when compared with controls (659 ± 121 kPa). Cross-linking was induced in the mouse cornea in vivo, and its biomechanical effect successfully measured. This could create opportunities to study molecular pathways of CXL in transgenic mice.

Customized Corneal Cross-Linking-A Mathematical Model.

PubMed

Caruso, Ciro; Epstein, Robert L; Ostacolo, Carmine; Pacente, Luigi; Troisi, Salvatore; Barbaro, Gaetano

2017-05-01

To improve the safety, reproducibility, and depth of effect of corneal cross-linking with the ultraviolet A (UV-A) exposure time and fluence customized according to the corneal thickness. Twelve human corneas were used for the experimental protocol. They were soaked using a transepithelial (EPI-ON) technique using riboflavin with the permeation enhancer vitamin E-tocopheryl polyethylene glycol succinate. The corneas were then placed on microscope slides and irradiated at 3 mW/cm for 30 minutes. The UV-A output parameters were measured to build a new equation describing the time-dependent loss of endothelial protection induced by riboflavin during cross-linking, as well as a pachymetry-dependent and exposure time-dependent prescription for input UV-A fluence. The proposed equation was used to establish graphs prescribing the maximum UV-A fluence input versus exposure time that always maintains corneal endothelium exposure below toxicity limits. Analysis modifying the Lambert-Beer law for riboflavin oxidation leads to graphs of the maximum safe level of UV-A radiation fluence versus the time applied and thickness of the treated cornea. These graphs prescribe UV-A fluence levels below 1.8 mW/cm for corneas of thickness 540 μm down to 1.2 mW/cm for corneas of thickness 350 μm. Irradiation times are typically below 15 minutes. The experimental and mathematical analyses establish the basis for graphs that prescribe maximum safe fluence and UV-A exposure time for corneas of different thicknesses. Because this clinically tested protocol specifies a corneal surface clear of shielding riboflavin on the corneal surface during UV-A irradiation, it allows for shorter UV-A irradiation time and lower fluence than in the Dresden protocol.

[Dietary status of preschool children from day-care kindergartens in six cites of China].

PubMed

Yin, Shian; Su, Yixiang; Liu, Qipei; Zhang, Maoyu

2002-10-01

In order to highlight nutrients of potential concern on deficiency for the age groups under study, the dietary status of preschool children were studied in the kindergartens of Beijing, Shanghai, Guangzhou, Chengdu, Changsha and Dalian in 1998-1999. All the children who regularly attended the kindergarten, who were in the age range of 3-6 year old and generally health were considered eligible for enrollment in this study. The final results included a total of 1170 children, with 583 boys and 587 girls. Food weighing method was used in consecutive three-day dietary survey by recording breakfast, lunch and afternoon refreshments in kindergarten. Questionnaire form was applied to record the other food consumption outside of the kindergarten. Nutrient intakes of per child were calculated according to the Chinese Food composition Table. The average energy, protein, iron, selenium, vitamin A, vitamin E, thiamin, riboflavin, and nicotinic acid intakes were adequate in each group. The dietary energy provided by fat was near to the high marginal (30%), which indicated that more fat intake should be avoided in these children. The ratio of energy provided by each meal per day was lower in the breakfast and higher in the dinner and foods consumed at home. The average ratio of calcium to phosphorus for 3-6 years was 0.63. A deficiency of calcium is rather common, and the intake of calcium accounted for only 61.6% of the recommended nutrient intake(RNI). Salt intake was relatively higher than that of adequate intake recommended by Chinese Nutritional Society. The zinc intake reached 62.9% of RNIs. Vitamin C intakes from each age of groups did not meet their RNI. The present study indicates that the deficiencies of some trace nutrients in the diets for preschool children in day-care kindergartens is probably related to that the body weight and height of preschool children have not achieved a "satisfactory" level.

Bioengineered riboflavin in nanotechnology.

PubMed

Beztsinna, N; Solé, M; Taib, N; Bestel, I

2016-02-01

Riboflavin (RF) is an essential water-soluble vitamin with unique biological and physicochemical properties such as transporterspecific cell internalization, implication in redox reactions, fluorescence and photosensitizing. Due to these features RF attracted researchers in various fields from targeted drug delivery and tissue engineering to optoelectronics and biosensors. In this review we will give a brief reminder of RF chemistry, its optical, photosensitizing properties, RF transporter systems and its role in pathologies. We will point a special attention on the recent findings concerning RF applications in nanotechnologies such as RF functionalized nanoparticles, polymers, biomolecules, carbon nanotubes, hydrogels and implants for tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biotechnological production of vitamin B2-enriched bread and pasta.

PubMed

Capozzi, Vittorio; Menga, Valeria; Digesu, Anna Maria; De Vita, Pasquale; van Sinderen, Douwe; Cattivelli, Luigi; Fares, Clara; Spano, Giuseppe

2011-07-27

Lactic acid bacteria (LAB) were obtained from durum wheat flour samples and screened for roseoflavin-resistant variants to isolate natural riboflavin-overproducing strains. Two riboflavin-overproducing strains of Lactobacillus plantarum isolated as described above were used for the preparation of bread (by means of sourdough fermentation) and pasta (using a prefermentation step) to enhance their vitamin B2 content. Pasta was produced from a monovarietal semolina obtained from the durum wheat cultivar PR22D89 and, for experimental purposes, from a commercial remilled semolina. Several samples were collected during the pasta-making process (dough, extruded, dried, and cooked pasta) and tested for their riboflavin content by a high-performance liquid chromatography method. The applied approaches resulted in a considerable increase of vitamin B2 content (about 2- and 3-fold increases in pasta and bread, respectively), thus representing a convenient and efficient food-grade biotechnological application for the production of vitamin B2-enriched bread and pasta. This methodology may be extended to a wide range of cereal-based foods, feed, and beverages. Additionally, this work exemplifies the production of a functional food by a novel biotechnological exploitation of LAB in pasta-making.

[Assessment of the impact of vitamin and dietary fiber content in the diet on the characteristics of protective colon microbiota populations of rats].

PubMed

Markova, Yu M; Sheveleva, S A

2015-01-01

The content of lactobacilli and enterobacteria in the experiment in rats with varying levels of vitamins and dietary fiber was studied. The study was performed on 48 male weanling Wistar rats randomized into 8 groups, with the creation of vitamin deficiency (30 d.) and its further compensation (5 d.). Vitamin content in the semisynthetic diet in rats of the control group N 1 corresponded to 100% of a daily adequate intake. In the similar composition of the diet of the control group N 2 wheat bran was added in amount of 5% of the weight of the diet. In groups N 3–8 rats received a diet with the reduced amount of vitamin mixture by 5 times (20% of the adequate intake) and the total exclusion of tocopherol, thiamine and riboflavin from the mixture. The wheat bran (5% of diet mass) was added to the diets in Groups N 4, 6, 8. At the stage of compensation of deficiency rats were fed with the diets with increased content of vitamin mixture: Group 5–6 to 80% 7–8 to 200% (100 and 220% of the adequate intake, respectively), and the groups N 3–4 continued to receive deficient diet with or without wheat bran until the end of the experiment. After 35 days rats were anesthetized with ether, decapitated, necropsied and the cecum segments were selected for quantitative microbiological analysis of its contents. It has been shown that the addition of wheat bran to vitamin deficient diet lead to the reduction of the manifestation of physical sign of hypovitaminosis. It also eliminated the differences in the integrated index of growth and development of rats in comparison with the group without vitamin deficiency. It was found that the vitamin deficiency in the diet, regardless of the presence or absence of wheat bran, led to a significant reduction of the number of lactobacilli in the intestinal contents, but almost did not affect the number of normal and opportunistic pathogenic enterobacteria. The compensation of deficiency during 5 days lead to the increased number of lactobacilli, but the physiological levels and levels in control animals it reached only in rats received 220% of the vitamins with the addition of wheat bran. In the lactobacilli population in all rats received different doses of vitamins (including reduced to 20%), regardless of the presence of wheat bran, prevailing culturable representatives were 3 kinds of Lactobacillus spp. – acidophilus, fermentum, paracasei. These species showed stable presence in the intestine even in conditions of prolonged vitamin deficiency (35 days). L. acidophilus was the dominated lactoflora representative in all rats, its’ content was average 91.7% of all culturable lactobacilli. With less constancy and in lower amounts were detected L. plantarum and representatives of coccal flora (Leuconostoc lactis, Lactococcus lactis).

Immobilization of Growth Factors to Collagen Surfaces Using Pulsed Visible Light.

PubMed

Fernandes-Cunha, Gabriella M; Lee, Hyun Jong; Kumar, Alisha; Kreymerman, Alexander; Heilshorn, Sarah; Myung, David

2017-10-09

In the treatment of traumatic injuries, burns, and ulcers of the eye, inadequate epithelial tissue healing remains a major challenge. Wound healing is a complex process involving the temporal and spatial interplay between cells and their extracellular milieu. It can be impaired by a variety of causes including infection, poor circulation, loss of critical cells, and/or proteins, and a deficiency in normal neural signaling (e.g., neurotrophic ulcers). Ocular anatomy is particularly vulnerable to lasting morbidity from delayed healing, whether it be scarring or perforation of the cornea, destruction of the conjunctival mucous membrane, or cicatricial changes to the eyelids and surrounding skin. Therefore, there is a major clinical need for new modalities for controlling and accelerating wound healing, particularly in the eye. Collagen matrices have long been explored as scaffolds to support cell growth as both two-dimensional coatings and substrates, as well as three-dimensional matrices. Meanwhile, the immobilization of growth factors to various substrates has also been extensively studied as a way to promote enhanced cellular adhesion and proliferation. Herein we present a new strategy for photochemically immobilizing growth factors to collagen using riboflavin as a photosensitizer and exposure to visible light (∼458 nm). Epidermal growth factor (EGF) was successfully bound to collagen-coated surfaces as well as directly to endogenous collagen from porcine corneas. The initial concentration of riboflavin and EGF as well as the blue light exposure time were keys to the successful binding of growth factors to these surfaces. The photocrosslinking reaction increased EGF residence time on collagen surfaces over 7 days. EGF activity was maintained after the photocrosslinking reaction with a short duration of pulsed blue light exposure. Bound EGF accelerated in vitro corneal epithelial cell proliferation and migration and maintained normal cell phenotype. Additionally, the treated surfaces were cytocompatible, and the photocrosslinking reaction was proven to be safe, preserving nearly 100% cell viability. These results suggest that this general approach is safe and versatile may be used for targeting and immobilizing bioactive factors onto collagen matrices in a variety of applications, including in the presence of live, seeded cells or in vivo onto endogenous extracellular matrix collagen.

Usual Vitamin Intakes by Mexican Populations.

PubMed

Pedroza-Tobías, Andrea; Hernández-Barrera, Lucía; López-Olmedo, Nancy; García-Guerra, Armando; Rodríguez-Ramírez, Sonia; Ramírez-Silva, Ivonne; Villalpando, Salvador; Carriquiry, Alicia; Rivera, Juan A

2016-09-01

In the past several years, the consumption of high-energy, nutrient-poor foods has increased globally. Dietary intake data collected by the National Health and Nutrition Survey (ENSANUT) 2012 provide information to assess the quality of the Mexican diet and to guide food and nutrition policy. The aim was to describe the usual intake and the prevalence of inadequate intakes of vitamins for the overall Mexican population and by subgroups defined by sex, age, region, urban or rural areas, and socioeconomic status (SES). ENSANUT 2012 is a cross-sectional probabilistic survey representative of the Mexican population. Dietary information was collected by using the 24-h recall automated multiple-pass method (n = 10,096) with a repeated measurement on a subsample (n = 889) to permit adjustment for intraindividual variability with the use of the Iowa State University method. Mean usual intakes and the prevalence of inadequate intakes of thiamin, riboflavin, niacin, folate, and vitamins A, D, E, C, B-6, and B-12 were calculated for children aged 1-4 y (CH1-4y), children aged 5-11 y (CH5-11y), adolescents aged 12-19 y, and adults aged ≥20 y. In all of the age groups, prevalences of inadequate intakes of vitamins D and E were the highest (77-99% of adults and adolescents and 53-95% of CH5-11y and CH1-4y) and those of folate and vitamin A were intermediate (47-70% of adults and adolescents, 15-23% of CH5-11y and 8-13% of CH1-4y), whereas those of thiamin, riboflavin, niacin, and vitamins B-6, B-12, and C were the lowest (0-37% of adults, 1-27% of adolescents, and 0-2.4% of CH5-11y and CH1-4y). With few exceptions, the highest prevalences of inadequate intakes for vitamins were observed in the poorest populations (rural South region and the lowest tertile of SES). The intake of vitamins among Mexicans is inadequate overall. Information collected by ENSANUT can help target food assistance programs and develop strategies to prevent vitamin deficiencies. © 2016 American Society for Nutrition.

[Estimation of vitamin status of moscow student according to data on vitamins intake and their levels in blood].

PubMed

Beketova, N A; Kodentsova, V M; Vrzhesinskaya, O A; Kosheleva, O V; Pereverzeva, O G; Solntseva, T N; Pogozheva, A V; Khanferyan, R A; Berketova, L V; Lipatova, L P

Supply with vitamins C, A, E and B2 of 61 high school students (38 girls and 23 boys, aged 18–22 years, body mass index – 23.0±0.6 kg/m2) by means of determination of blood plasma concentration of ascorbic acid, retinol and carotenoids, tocopherols and riboflavin has been investigated in the period from May to September. All students were well supplied with vitamin C (only 2 boys had a reduced level of ascorbic acid) and vitamin A. Decreased level of carotenoids was more common in boys (48 versus 24% in girls). 20% of the students were insufficiently supplied with vitamin E, 38% – with vitamin B2. 39% of students (50% girls and 22% boys) were adequately provided with all studied vitamins. 5% of the students had a combined deficiency of 3 vitamins, 20% – 2 vitamins. Student’s sufficiency with vitamins B2, C, A, E, carotenoids did not depend on the season. Diet intake of vitamins C, A, carotenoids and vitamin B2 has been calculated basing on the data on the frequency of food consumption during the previous month. Reduced consumption relatively to the Russia RDA of vitamins В2, C and А took place in 63, 54 and 46% of the students respectively. The lack of vitamin B2 in the diet was most pronounced, the value of probabilistic risk corresponded to the average level in 34% of students. Average probabilistic risk of inadequate intake of vitamin A was present in 17% of students, vitamin C – 6%. Coincidence of the results of vitamin C and A status assessment obtained by calculation of vitamin diet intake and by biochemical methods (concentration of vitamins in the blood plasma) was 94 and 83%. These methods are interchangeable if you select the value of the average probability of risk failure intake of these vitamins as a criterion. Proportion of coinciding results of the estimation of vitamin B2 status was 56%. Special well-designed studies on larger sample surveyed are needed for the final output of the interchangeability of methods to assess riboflavin status.

Pharmaceutical Approval Update.

PubMed

Kaufman, Michele B

2016-08-01

Venetoclax (Venclexta) for chronic lymphocytic leukemia; riboflavin 5'-phosphate solutions (Photrexa Viscous and Photrexa) for progressive keratoconus; and pimavanserin (Nuplazid) for Parkinson's disease psychosis.

Singlet Oxygen Generation by UVA Light Exposure of Endogenous Photosensitizers

PubMed Central

Baier, Jürgen; Maisch, Tim; Maier, Max; Engel, Eva; Landthaler, Michael; Bäumler, Wolfgang

2006-01-01

UVA light (320–400 nm) has been shown to produce deleterious biological effects in tissue due to the generation of singlet oxygen by substances like flavins or urocanic acid. Riboflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), β-nicotinamide adenine dinucleotide (NAD), and β-nicotinamide adenine dinucleotide phosphate (NADP), urocanic acid, or cholesterol in solution were excited at 355 nm. Singlet oxygen was directly detected by time-resolved measurement of its luminescence at 1270 nm. NAD, NADP, and cholesterol showed no luminescence signal possibly due to the very low absorption coefficient at 355 nm. Singlet oxygen luminescence of urocanic acid was clearly detected but the signal was too weak to quantify a quantum yield. The quantum yield of singlet oxygen was precisely determined for riboflavin (ΦΔ = 0.54 ± 0.07), FMN (ΦΔ = 0.51 ± 0.07), and FAD (ΦΔ = 0.07 ± 0.02). In aerated solution, riboflavin and FMN generate more singlet oxygen than exogenous photosensitizers such as Photofrin, which are applied in photodynamic therapy to kill cancer cells. With decreasing oxygen concentration, the quantum yield of singlet oxygen generation decreased, which must be considered when assessing the role of singlet oxygen at low oxygen concentrations (inside tissue). PMID:16751234

Potential apoptotic effect of ultraviolet-A irradiation during cross-linking: a study on ex vivo cultivated limbal epithelial cells.

PubMed

Matalia, Himanshu; Shetty, Rohit; Dhamodaran, Kamesh; Subramani, Murali; Arokiaraj, Vincent; Das, Debashish

2012-10-01

To study the effects of ultraviolet-A (UV-A) irradiation, in the presence or absence of riboflavin, on ex vivo cultured limbal epithelial cells (LECs). The study was carried out in a super specialty ophthalmic hospital. Ex vivo cultured LECs were grown on denuded amniotic membranes and exposed to similar levels of UV-A radiation used during corneal cross-linking (CXL), in the presence or absence of the photosensitiser, riboflavin. These cells were then used for extraction of RNA, cDNA conversion, and antibody staining. Quantitative PCR and immunofluorescence staining were performed to evaluate the apoptotic state of treated and non-treated LECs. Statistical analyses were evaluated using a Student's t test. We found that bcl-2, an antiapoptotic gene, was downregulated, whereas, bax, a proapoptotic gene, was upregulated. After LECs were exposed to UV-A radiation, a significant upregulation of both caspase 3 and caspase 9 was observed in treated cells when compared with untreated LECs. These results indicate that exposure of LECs to UV-A dosages similar to those used in the CXL procedure promotes the expression of genes known to promote apoptosis. In the presence of riboflavin, the damage caused by UV-A treatment was marginalised, but not totally blocked.

An overview on the identification of MAIT cell antigens.

PubMed

Kjer-Nielsen, Lars; Corbett, Alexandra J; Chen, Zhenjun; Liu, Ligong; Mak, Jeffrey Y W; Godfrey, Dale I; Rossjohn, Jamie; Fairlie, David P; McCluskey, James; Eckle, Sidonia B G

2018-04-14

Mucosal Associated Invariant T (MAIT) cells are restricted by the monomorphic MHC class I-like molecule, MHC-related protein-1 (MR1). Until 2012, the origin of the MAIT cell antigens (Ags) was unknown, although it was established that MAIT cells could be activated by a broad range of bacteria and yeasts, possibly suggesting a conserved Ag. Using a combination of protein chemistry, mass spectrometry, cellular biology, structural biology and chemistry, we discovered MAIT cell ligands derived from folic acid (vitamin B9) and from an intermediate in the microbial biosynthesis of riboflavin (vitamin B2). While the folate derivative 6-formylpterin (6-FP) generally inhibited MAIT cell activation, two riboflavin pathway derivatives, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), were potent MAIT cell agonists. Other intermediates and derivatives of riboflavin synthesis displayed weak or no MAIT cell activation. Collectively, these studies revealed that in addition to peptide and lipid-based Ags, small molecule natural product metabolites are also ligands that can activate T cells expressing αβ T cell receptors, and here we recount this discovery. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Oxygen suppresses light-driven anodic current generation by a mixed phototrophic culture.

PubMed

Darus, Libertus; Ledezma, Pablo; Keller, Jürg; Freguia, Stefano

2014-12-02

This paper describes the detrimental effect of photosynthetically evolved oxygen on anodic current generation in the presence of riboflavin upon illumination of a mixed phototrophic culture enriched from a freshwater pond at +0.6 V vs standard hydrogen electrode. In the presence of riboflavin, the phototrophic biomass in the anodic compartment produced an electrical current in response to light/dark cycles (12 h/12 h) over 12 months of operation, generating a maximum current density of 17.5 mA x m(-2) during the dark phase, whereas a much lower current of approximately 2 mA x m(-2) was generated during illumination. We found that the low current generation under light exposure was caused by high rates of reoxidation of reduced riboflavin by oxygen produced during photosynthesis. Quantification of biomass by fluorescence in situ hybridization images suggested that green algae were predominant in both the anode-based biofilm (55.1%) and the anolyte suspension (87.9%) with the remaining biovolume accounted for by bacteria. Genus-level sequencing analysis revealed that bacteria were dominated by cyanobacterium Leptolyngbia (∼35%), while the prevailing algae were Dictyosphaerium, Coelastrum, and Auxenochlorella. This study offers a key comprehension of mediator sensitivity to reoxidation by dissolved oxygen for improvement of microbial solar cell performance.

The sequential injection system with adsorptive stripping voltammetric detection.

PubMed

Kubiak, W W; Latonen, R M; Ivaska, A

2001-03-16

Two sequential injection systems have been developed for adsorptive stripping voltammetric measurement. One is for substances adsorbing at mercury, e.g. riboflavin. In this case, a simple arrangement with only sample aspiration is needed. Reproducibility was 3% and detection limit 0.07 muM. The measuring system was applied to determination of riboflavin in vitamin pills and to study the photodegradation process of riboflavin in aqueous solutions. In the second case, metal ions were determined. They have to be complexed before deposition on the mercury surface. Thus, both the sample and the ligand have to be aspirated in the system. In this case, the reproducibility was approximately 6% and the detection limit <0.1 ppm for cadmium, lead and copper when complexation with oxine was used. Dimethylglyoxime was used in determination of nickel and cobalt and nioxime complexes were used in determination of nickel and copper. With these complexing agents, the reproducibility was the same as with oxine, but the metals could be determined at concentrations lower than 0.01 ppm. Application of two ligands in a SIA system with AdSV detection was also studied. Simultaneous determination of copper, lead, cadmium and cobalt was possible by using oxine and dimethylglyoxime. Copper and nickel were simultaneously determined by using dimethylglyoxime and nioxime.

A major integral protein of the plant plasma membrane binds flavin.

PubMed

Lorenz, Astrid; Kaldenhoff, Ralf; Hertel, Rainer

2003-05-01

Abundant flavin binding sites have been found in membranes of plants and fungi. With flavin mononucleotide-agarose affinity columns, riboflavin-binding activity from microsomes of Cucurbita pepoL. hypocotyls was purified and identified as a specific PIP1-homologous protein of the aquaporin family. Sequences such as gi|2149955 in Phaseolus vulgaris, PIP1b of Arabidopsis thaliana, and NtAQP1 of tobacco are closely related. The identification as a riboflavin-binding protein was confirmed by binding tests with an extract of Escherichia coli cells expressing the tobacco NtAQP1 as well as leaves of transgenic tobacco plants that overexpress NtAQP1 or were inhibited in PIP1 expression by antisense constructs. When binding was assayed in the presence of dithionite, the reduced flavin formed a relatively stable association with the protein. Upon dilution under oxidizing conditions, the adduct was resolved, and free flavin reappeared with a half time of about 30 min. Such an association can also be induced photochemically, with oxidized flavin by blue light at 450 nm, in the presence of an electron donor. Several criteria, localization in the plasma membrane, high abundance, affinity to roseoflavin, and photochemistry, argue for a role of the riboflavin-binding protein PIP1 as a photoreceptor.

Photodynamic antimicrobial therapy to inhibit pseudomonas aeruginosa of corneal isolates (Conference Presentation)

NASA Astrophysics Data System (ADS)

Durkee, Heather A.; Relhan, Nidhi; Arboleda, Alejandro; Halili, Francisco; De Freitas, Carolina; Alawa, Karam; Aguilar, Mariela C.; Amescua, Guillermo; Miller, Darlene; Parel, Jean-Marie

2016-03-01

Keratitis associated with Pseudomonas aeruginosa is difficult to manage. Treatment includes antibiotic eye drops, however, some strains of Pseudomonas aeruginosa are resistant. Current research efforts are focused on finding alternative and adjunct therapies to treat multi-drug resistant bacteria. One promising alternate technique is photodynamic therapy (PDT). The purpose of this study was to evaluate the effect of riboflavin- and rose bengal-mediated PDT on Pseudomonas aeruginosa keratitis isolates in vitro. Two isolates (S+U- and S-U+) of Pseudomonas aeruginosa were derived from keratitis patients and exposed to five experimental groups: (1) Control (dark, UV-A irradiation, 525nm irradiation); (2) 0.1% riboflavin (dark, UV-A irradiation); and (3) 0.1% rose bengal, (4) 0.05% rose bengal and (5) 0.01% rose bengal (dark, 525nm irradiation). Three days after treatment, in dark conditions of all concentration of riboflavin and rose bengal showed no inhibition in both S+U- and S-U+ strains of Pseudomonas aeruginosa. In 0.1% and 0.05% rose bengal irradiated groups, for both S+U- and S-U+ strains, there was complete inhibition of bacterial growth in the central 50mm zone corresponding to the diameter of the green light source. These in vitro results suggest that rose bengal photodynamic therapy may be an effective adjunct treatment for Pseudomonas aeruginosa keratitis.

Energy Metabolism Impairment in Migraine.

PubMed

Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

2018-06-22

Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of forage family on apparent ruminal synthesis of B vitamins in lactating dairy cows.

PubMed

Castagnino, D S; Seck, M; Beaudet, V; Kammes, K L; Linton, J A Voelker; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

2016-03-01

Effects of forage family (legume vs. grass) on apparent ruminal synthesis (ARS) and postruminal supply of B vitamins were evaluated in 2 experiments. Diets containing either alfalfa (AL) or orchardgrass (OG) silages as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. Experiment 1 compared diets containing AL and OG [~23% forage neutral detergent fiber (NDF) and ~27% total NDF] offered to 8 cows in two 15-d treatment periods. Experiment 2 compared diets containing AL and OG (~25% forage NDF and ~30% total NDF) offered to 13 cows in two 18-d treatment periods. Thiamin, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were analyzed in feeds and duodenal digesta. Apparent ruminal synthesis was calculated as the duodenal flow of each vitamin minus its intake. Forage family affected B vitamin intakes, duodenal flow, and ARS. In both experiments, AL diets increased vitamin B6 and decreased folate intakes. In experiment 1, riboflavin and niacin intakes were greater with the OG diet, whereas in experiment 2 thiamin intake was greater but riboflavin intake was smaller with the OG diet. In spite of the low contribution of either silage to the dietary folate content, folate intake was greater with OG diets than AL due to the difference in soybean meal contribution between diets. Niacin and folate ARS were not affected by the forage family. Duodenal microbial nitrogen flow was positively correlated with ARS of riboflavin, niacin, vitamin B6, folates, and vitamin B12, but tended to be negatively correlated with thiamin ARS. Apparent ruminal synthesis of folates and vitamin B12 appear to be related to microbial biomass activity. Changes in nutrient composition of the diets likely affected the microbial population in the rumen and their B vitamin metabolism. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A rapid solid-phase extraction fluorometric method for thiamine and riboflavin in salmonid eggs

USGS Publications Warehouse

Zajicek, James L.; Tillitt, Donald E.; Brown, Scott B.; Brown, Lisa R.; Honeyfield, Dale C.; Fitzsimons, John D.

2005-01-01

A new method has been developed and successfully applied to the selective measurement of thiamine (nonphosphorylated), total thiamine (sum of thiamine, thiamine monophosphate [TMP], thiamine diphosphate [TDP], and thiamine triphosphate [TTP]), and potentially interfering riboflavin in acidic (2% trichloroacetic acid) extracts of selected salmonid and walleye egg samples. Acidic extracts of eggs were applied directly to end-capped C18, reversed-phase solid-phase extraction (SPE) columns and separated into three fractions by elution with mixtures of PO4 buffer (pH 2), methanol (10%), and acetonitrile (20%). All thiamine compounds recovered in the first two fractions were oxidized to their corresponding thiochromes with alkaline potassium hexacyanoferrate, and we measured the thiochrome fluorescence (excitation at 360 nm, emission at 460 nm) in a 96-well microplate reader. Riboflavin, recovered in third fraction (eluted with pH 2, 20% acetonitrile), was analyzed directly by measuring the fluorescence of this fraction (excitation at 450 nm, emission at 530 nm). Significant portions of the phosphate esters of thiamine (TMP, TDP, and presumably TTP), when present at low concentrations (< 10 nmol of total -thiamine per gram of egg), were not retained by the 100-mg SPE column, and were collected directly during sample loading and in a subsequent phosphoric acid rinse as fraction 1. Free thiamine (nonphosphorylated) and remaining portions of the TDP and TMP were then eluted in the second fraction with 10% methanol/PO4 buffer, whereas the un-ionized, relatively nonpolar riboflavin was eluted in the third fraction with 20% acetonitrile. This new method uses a traditional sample homogenization of egg tissue to extract thiamine compounds into 2% trichlororacetic acid solution; an inexpensive, commercially available SPE column; small amounts of sample (0.5-1 g); microliter volumes of solvents per sample; a traditional, relatively nonhazardous, oxidation of thiamine compounds to fluorescent thiochromes; and an ultraviolet-visible-wavelength-filter fluorometer for the measurements. ?? Copyright by the American Fisheries Society 2005.

Vitamin profile of cooked foods: how healthy is the practice of ready-to-eat foods?

PubMed

Agte, Vaishali; Tarwadi, Kirtan; Mengale, Sangeeta; Hinge, Ashwini; Chiplonkar, Shashi

2002-05-01

During recent years importance of B complex vitamins, beta-carotene and vitamin C has been realised in terms of their antioxidative and anticarcinogenic properties. Fruits and vegetables are the rich sources of these vitamins. However, there are considerable cooking losses of vitamins, and information on vitamin contents of cooked foods is essential for assessing the adequacy of vitamin intakes. Secondly, there is a growing trend to consume ready-to-eat foods such as stuffed pancakes (samosa, patties), pastries, French fries; replacing traditional foods for lunch or dinner like roti, vegetable curry, bread, non-vegetarian items. Ready-to-eat foods are considered to give empty calories rather than a balanced diet. A study was undertaken to estimate ascorbic acid, folic acid, riboflavin, thiamine and beta-carotene of 263 cooked food samples and 260 meals representing dietary patterns of Asia, Africa, Europe, USA and Latin America by spectrophotometry and photoflurometry. A broad range of beta-carotene (84-2038 mcg%), riboflavin (0.01-0.48 mg%), thiamine (0.04-0.36 mg%), vitamin C (1-28 mg%) and folate (26-111 mcg%) was observed in individual foods. Bakery products and sweets were found to be poor sources and green leafy vegetables and fruits were good sources of these five vitamins. The differences between ready-to-eat foods and meals consumed during lunch or dinner were prominent for beta-carotene, ascorbic acid, riboflavin and folic acid (P < 0.05). The cooking losses were 34.6, 30, 52.2, 45.9 and 32.2% in case of ascorbic acid, thiamine, riboflavin, beta-carotene and folic acid respectively. Irrespective of whether it is ready-to-eat or a lunch/dinner food item, the contribution of vegetables in the preparations was found to make a marked impact on the vitamin profile. While results justify the concept of a food pyramid, emphasis needs to be given to types of fruits and vegetables rich in vitamins; preferably in their uncooked form, rather than considering their total consumption.

Particle length of silages affects apparent ruminal synthesis of B vitamins in lactating dairy cows.

PubMed

Castagnino, D S; Kammes, K L; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

2016-08-01

Effects of particle length of silages on apparent ruminal synthesis (ARS) and postruminal supply of B vitamins were evaluated in 2 feeding trials. Diets containing alfalfa (trial 1) or orchardgrass (trial 2) silages, chopped to either 19mm (long cut, LC) or 10mm (short cut, SC) theoretical particle length, as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. Forages chopped to a theoretical particle length of 19 and 10mm had mean particles sizes of 14.1 and 8.1mm, respectively, in trial 1, and 15.3 and 11.3mm, respectively, in trial 2. Trial 1 was conducted with 13 multiparous cows in two 19-d treatment periods; both diets contained approximately 20% forage neutral detergent fiber (NDF), 25% total NDF, and forage-to-concentrate ratios were approximately 47:53. Trial 2 was conducted with 15 cows in two 18-d treatment periods; both diets contained approximately 23% forage NDF, 28% total NDF, and had a forage-to-concentrate ratio of 50:50. Thiamine, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were measured in feed and duodenal content. Daily ARS was calculated as the duodenal flow minus the intake. In trial 1, daily intake of individual B vitamins was increased with the LC diet, but ARS of thiamine, riboflavin, vitamin B6, and folates was reduced. In trial 2, except for folates, intakes of the other B vitamins were decreased with the LC diets, whereas ARS of riboflavin, niacin, and vitamin B6 was increased. Daily ARS of thiamine, riboflavin, niacin, and vitamin B6 were correlated negatively with their intake, suggesting that ruminal bacteria reduced their synthesis when dietary supply increased. Microbial activity could have also reduced degradation of thiamine, riboflavin, and niacin, which is supported by (1) the negative correlation between ARS of these vitamins and ruminal pH or microbial N duodenal flow; and (2) the positive correlation between ARS and ruminal concentrations of volatile fatty acids. Folate ARS followed the opposite correlation pattern. Nevertheless, in spite of differences in intake and ARS, with both forages, decreasing particle length of silages had limited effects on the amounts of B vitamins reaching the sites of absorption in the small intestine of dairy cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Mutually Exclusive Alterations in Secondary Metabolism Are Critical for the Uptake of Insoluble Iron Compounds by Arabidopsis and Medicago truncatula1[C][W

PubMed Central

Rodríguez-Celma, Jorge; Lin, Wen-Dar; Fu, Guin-Mau; Abadía, Javier; López-Millán, Ana-Flor; Schmidt, Wolfgang

2013-01-01

The generally low bioavailability of iron in aerobic soil systems forced plants to evolve sophisticated genetic strategies to improve the acquisition of iron from sparingly soluble and immobile iron pools. To distinguish between conserved and species-dependent components of such strategies, we analyzed iron deficiency-induced changes in the transcriptome of two model species, Arabidopsis (Arabidopsis thaliana) and Medicago truncatula. Transcriptional profiling by RNA sequencing revealed a massive up-regulation of genes coding for enzymes involved in riboflavin biosynthesis in M. truncatula and phenylpropanoid synthesis in Arabidopsis upon iron deficiency. Coexpression and promoter analysis indicated that the synthesis of flavins and phenylpropanoids is tightly linked to and putatively coregulated with other genes encoding proteins involved in iron uptake. We further provide evidence that the production and secretion of phenolic compounds is critical for the uptake of iron from sources with low bioavailability but dispensable under conditions where iron is readily available. In Arabidopsis, homozygous mutations in the Fe(II)- and 2-oxoglutarate-dependent dioxygenase family gene F6′H1 and defects in the expression of PLEIOTROPIC DRUG RESISTANCE9, encoding a putative efflux transporter for products from the phenylpropanoid pathway, compromised iron uptake from an iron source of low bioavailability. Both mutants were partially rescued when grown alongside wild-type Arabidopsis or M. truncatula seedlings, presumably by secreted phenolics and flavins. We concluded that production and secretion of compounds that facilitate the uptake of iron is an essential but poorly understood aspect of the reduction-based iron acquisition strategy, which is likely to contribute substantially to the efficiency of iron uptake in natural conditions. PMID:23735511

Effect of supplementation with a lipid-based nutrient supplement on the micronutrient status of children aged 6-18 months living in the rural region of Intibucá, Honduras.

PubMed

Siega-Riz, Anna M; Estrada Del Campo, Yaniré; Kinlaw, Alan; Reinhart, Gregory A; Allen, Lindsay H; Shahab-Ferdows, Setareh; Heck, Jeff; Suchindran, Chirayath M; Bentley, Margaret E

2014-05-01

Lipid-based nutrient supplements (LNS) have been effective in the treatment of acute malnutrition among children. We evaluated the use of LNS supplementation for improving the micronutrient status of young children. A 12-month randomised controlled trial was conducted among children aged 6-18 months living in Intibucá, Honduras. Communities (n = 18) were randomised into clusters matched by poverty indicators (9 intervention, n = 160 and 9 controls, n = 140). Intervention participants received LNS. All children received food vouchers and nutrition education. Primary outcomes included measures of micronutrient status: at baseline, 6 and 12 months' blood were collected for assessment of folate, iron, zinc, riboflavin, and vitamin B12 status; haemoglobin was measured every 3 months; and dietary and anthropometry collected monthly. Longitudinal analyses were based on intent to treat and LNS adherence. Generalised estimating equations were used in the estimation of generalised linear regression models specified for the data. At 6-month follow-up, children in the intervention group had a lower proportion classified as deficient for B12 (43.6%) compared with the control (67.7%; P = 0.03). The intervention group had a higher mean concentration for folate at 6 months (P = 0.06), and improvements continued through 12 months for folate (P = 0.002) and vitamin A deficiency (P = 0.03). This pattern of results, with improved significance, remained in subanalysis based on LNS adherence. These data demonstrate that LNS improved select micronutrient status in young non-malnourished Honduran children. © 2014 John Wiley & Sons Ltd.

Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease.

PubMed

Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

2012-11-01

MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease

PubMed Central

Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Álvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

2012-01-01

BACKGROUND AND PURPOSE MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. EXPERIMENTAL APPROACH We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. KEY RESULTS According to our results, supplementation with riboflavin or coenzyme Q10 effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. CONCLUSIONS AND IMPLICATIONS Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. PMID:22747838

[Effect of vitamin sufficiency on adaptation syndrome in growing rats].

PubMed

Sidorova, Iu S; Beketova, N A; Vrzhesinskaia, O A; Kodentsova, V M; Kosheleva, O V; Zorin, S N; Selifanov, A V; Mazo, V K

2014-01-01

The influence of vitamin supply of growing male -Wistar rats (n=21) with an initial body weight 53,5±0,9 g on their resistance to a single distress induced by the electric shock has been investigated. Control rats within 21 days received a complete semisynthetic diet,providingadequate amounts of vitamins. Combined vitamin deficiency in experimental rats was caused by 5-fold decrease of vitamin mixture amount in the feed and the total vitamin E exclusion from the mixture. On the 21st day, one day before the end of the experiment, both groups of rats were subjected to stress impact (electrocutaneous irritation on paws, 0,4 mA for 8 sec) and then animals were placed in metabolic cages to collect urine. By the end of the experiment, the animals with the combined vitamin deficiency lag behind in growth. Vitamin B2, A, B1 and E liver content decreased in experimental rats by 1,6, 2,3, 4,4 and 15 fold accordingly. Retinol plasma concentration was significantly reduced by 18%, α-tocopherol level - by 5 fold, urinary excretionof riboflavin and 4-pyridoxic acid (vitamin B6 metabolite) was significantly reduced by 6,5 and 2,46 times accordingly. MDA blood plasma concentration and the urinary ratio of oxidized and not oxidized form of 8-hydroxy-2'-deoxy-guanosine did not differ in both groups of rats. Urinary excretion of stress biomarker corticosterone in rats with combined vitamin deficit was 2,5-fold higher than in control rats. Thus, reducing of vitamins supply resulted in an increase of urine corticosterone in stressed rats, that characterized the intensity of general adaptation syndrome. This fact shows the importance of optimal sufficiency with vitamins in nonspecific (general) resistance to stress.

Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking: Ultrastructural studies

PubMed Central

Almubrad, Turki; Paladini, Iacopo; Mencucci, Rita

2013-01-01

Purpose Study to investigate the effects of collagen cross-linking on the ultrastructural organization of the corneal stroma in the human keratoconus cornea (KC). Methods Three normal, three keratoconus (KC1, KC2, KC3), and three cross-linked keratoconus (CXL1, CXL2, CXL3) corneas were analyzed. The KC corneas were treated with a riboflavin-ultraviolet A (UVA) treatment (CXL) method described by Wollensak et al. Penetrating keratoplasty (PKP) was performed 6 months after treatment. All samples were processed for electron microscopy. Results The riboflavin-UVA-treated CXL corneal stroma showed interlacing lamellae in the anterior stroma followed by well-organized parallel running lamellae. The lamellae contained uniformly distributed collagen fibrils (CFs) decorated with normal proteoglycans (PGs). The CF diameter and interfibrillar spacing in the CXL cornea were significantly increased compared to those in the KC cornea. The PG area in the CXL corneas were significantly smaller than the PGs in the KC cornea. The epithelium and Bowman’s layer were also normal. On rare occasions, a thick basement membrane and collagenous pannus were also observed. Conclusions Corneal cross-linking leads to modifications of the cornea stroma. The KC corneal structure showed a modification in the CF diameter, interfibrillar spacing, and PG area. This resulted in a more uniform distribution of collagen fibrils, a key feature for corneal transparency. PMID:23878503

Coenzyme Recognition and Gene Regulation by a Flavin Mononucleotide Riboswitch

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

Serganov, A.; Huang, L; Patel, D

2009-01-01

The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches also known as RFN elements, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B2) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains.more » FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg{sup 2+}-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.« less

Studies on the biosynthesis of vitamin B sub 2 and vitamin B sub 12

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

Chen, H.C.

1988-01-01

Feeding experiments with Ashbya gossypii followed by NMR analysis of the resulting riboflavin showed incorporation of deuterium from D-(2-{sup 2}H)ribose at C-2{prime} and from D-(1-{sup 2}H)ribose in the pro-R position at C-1{prime} of the ribityl side chain. The results rule out an Amadori rearrangement mechanism for the reduction of the ribosylamino to the ribitylamino linkage and point to formation of a Schiff base that is reduced stereospecifically opposite to the face from which the oxygen has departed. As prerequisite for the analysis, the {sup 1}H NMR signals for the pro-R and pro-S hydrogens at C-1{prime} of riboflavin and its tetraacetatemore » were assigned with the aid of synthetic stereospecifically deuteriated samples. Feeding experiments with Propionibacterium shermianii followed by NMR analysis of the resulting vitamin B{sub 12} showed: (1) 5-methylbenzimidazole (5MBI) incorporated and only one regioisomer (B6-demethylcyanocobalamin)formed. (2) 8-demethylriboflavin incorporated and the same regioisomer was obtained as 5MBI experiment. (3) (1{prime}-{sup 13}C, 5-{sup 15}N)riboflavin incorporated and {sup 13}C-NMR showed that {sup 13}C at the B2 position of cyanocobalamin coupled to both adjacent nitrogen-15 atoms at about the same ratio.« less

Delivery of Riboflavin-5'-Monophosphate Into the Cornea: Can Liposomes Provide Any Enhancement Effects?

PubMed

Kandzija, Neva; Khutoryanskiy, Vitaliy V

2017-10-01

Keratoconus is a progressive condition caused by the thinning of the cornea, which eventually deforms the front surface of the eye into a cone shape leading to ghosting, multiple images, glare, and several other vision problems. Currently, keratoconus is treated with UV-induced riboflavin (Rb)-mediated collagen cross-linking, which requires a physical removal of the corneal epithelium under topical anesthesia. This study reports the penetration of Rb and its more water-soluble form, riboflavin-5'-monophosphate (RbP), into the bovine cornea ex vivo. Using ex vivo bovine corneal tissues and 0.8 mg/mL drug solutions in phosphate buffer, it was established that RbP penetration into the cornea within 3 h of diffusion experiment was greater (17.3 ± 0.8 μg) compared with Rb (10.4 ± 4.2 μg). In the cornea, RbP was found to convert to Rb, which is mediated with enzymes present in this tissue. Several formulations including the conventional and propylene glycol-containing liposomes with encapsulated RbP have been developed, and their effect on the drug penetration into the bovine cornea was evaluated. Encapsulation of RbP into the liposomes did not provide any statistically significant improvement in the penetration of RbP into the cornea. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Photodynamic inactivation assisted by localized surface plasmon resonance of silver nanoparticles: In vitro evaluation on Escherichia coli and Streptococcus mutans.

PubMed

Ribeiro, Martha S; de Melo, Luciana S A; Farooq, Sajid; Baptista, Alessandra; Kato, Ilka T; Núñez, Silvia C; de Araujo, Renato E

2018-06-01

Localized surface plasmon resonance (LSPR) of gold nanoparticles has been reported to increase the antimicrobial effect of the photodynamic therapy. Although silver nanoparticles (AgNPs) are an efficient growth inhibitor of microorganisms, no studies exploring LSPR of AgNPs to enhance the photodynamic inactivation (PDI) have been related. In this work, we described the LSPR phenomenon of AgNP sand investigated its interaction with riboflavin, a natural photosensitizer. We evaluated the use of AgNPs coated with pectin (p-AgNP) in riboflavin (Rb)-mediated PDI of Escherichia coli (Gram- bacteria) and Streptococcus mutans (Gram + bacteria) using a blue light-emitting diode (λ = 455 ± 20 nm) of optical power 200 mW. Irradiance was 90 mW/cm 2 and radiant exposure varied according to the time exposure. Uptake of Rb and p-AgNP by the cells was evaluated by measuring the supernatant absorption spectra of the samples. We observed that LSPR of p-AgNPs was able to enhance the riboflavin photodynamic action on S. mutans but not on E. coli, probably due to the lower uptake of Rb by E. coli. Taken together, our results provide insights to explore the use of the LPRS promoted by silver nanostructures to optimize antimicrobial PDI protocols. Copyright © 2018 Elsevier B.V. All rights reserved.

[Evaluation of the dietary intake of vitamins and minerals in the daily food rations by the students of the Rzeszów University].

PubMed

Gil, Marian; Głodek, Elzbieta; Rudy, Mariusz

2012-01-01

To function properly the human body needs, from a nutritional point of view, the supply of a wide variety of nutrients. In this respect, in addition to essential nutrients, vitamins and minerals play an important role. Particular attention should be paid to the nutrition of studying youth as in their diet there are observed many irregularities arising from the specific nature of student life. The aim of the study was to identify and assess the level of intake of selected vitamins and minerals in a group of students with consideration of gender. The study included the group of 200 persons studying at the Faculty of Biology and Agriculture at the University of Rzeszów. The assessment of intake was made using the method of immediate recording of products and beverages consumed by students within three successive days. Using the Tables of Nutritional Value of Foods and Dishes there was calculated the average daily intake of minerals (sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, copper, manganese) and vitamins (A, D, E, thiamine, riboflavin, niacin, vitamin B6, folates and vitamin B12). It was found that the nutrition of women had seriously deficient intake of vitamin D (49%), folates (54%), thiamine and niacin. In terms of mineral intake in women there was diagnosed insufficient contribution of iron (46%), potassium (51.4%), calcium (55.4%) and magnesium (71.6%) in the diet. In the group of men deficiencies were found in the case of vitamin D (79.4%), foliates (71.6%) and vitamin C (76.0%). The excess of manganese (210.0%), phosphorus (198.9%), sodium (170.2%) in the diet and deficiency of potassium (65.5%), calcium (67.0%) and magnesium (73.9%) were found. The diet of men to a greater extent fulfils the need for vitamins and minerals. The results of the study show the necessity of education in order to foster healthy nutritional habits and to increase the share of natural sources of vitamins and minerals in the diet to prevent the occurrence of adverse effects related to their insufficient consumption.

Exome sequencing results in successful riboflavin treatment of a rapidly progressive neurological condition

PubMed Central

Petrovski, Slavé; Shashi, Vandana; Petrou, Steven; Schoch, Kelly; McSweeney, Keisha Melodi; Dhindsa, Ryan S.; Krueger, Brian; Crimian, Rebecca; Case, Laura E.; Khalid, Roha; El-Dairi, Maysantoine A.; Jiang, Yong-Hui; Mikati, Mohamad A.; Goldstein, David B.

2015-01-01

Genetically targeted therapies for rare Mendelian conditions are improving patient outcomes. Here, we present the case of a 20-mo-old female suffering from a rapidly progressing neurological disorder. Although diagnosed initially with a possible autoimmune condition, analysis of the child's exome resulted in a diagnosis of Brown–Vialetto–Van Laere syndrome 2 (BVVLS2). This new diagnosis led to a change in the therapy plan from steroids and precautionary chemotherapy to high-dose riboflavin. Improvements were reported quickly, including in motor strength after 1 mo. In this case, the correct diagnosis and appropriate treatment would have been unlikely in the absence of exome sequencing and careful interpretation. This experience adds to a growing list of examples that emphasize the importance of early genome-wide diagnostics. PMID:27148561

Extracellular Electron Transport-Mediated Fe(III) Reduction by a Community of Alkaliphilic Bacteria That Use Flavins as Electron Shuttles

PubMed Central

Fuller, Samuel J.; McMillan, Duncan G. G.; Renz, Marc B.; Schmidt, Martin

2014-01-01

The biochemical and molecular mechanisms used by alkaliphilic bacterial communities to reduce metals in the environment are currently unknown. We demonstrate that an alkaliphilic (pH > 9) consortium dominated by Tissierella, Clostridium, and Alkaliphilus spp. is capable of using iron (Fe3+) as a final electron acceptor under anaerobic conditions. Iron reduction is associated with the production of a freely diffusible species that, upon rudimentary purification and subsequent spectroscopic, high-performance liquid chromatography, and electrochemical analysis, has been identified as a flavin species displaying properties indistinguishable from those of riboflavin. Due to the link between iron reduction and the onset of flavin production, it is likely that riboflavin has an import role in extracellular metal reduction by this alkaliphilic community. PMID:24141133

Study of energy transfer between riboflavin (vitamin B2) and AgNPs

NASA Astrophysics Data System (ADS)

Mokashi, Vidya V.; Walekar, Laxman S.; Anbhule, Prashant V.; Lee, Sang Hak; Patil, Shivajirao R.; Kolekar, Govind B.

2014-03-01

Here, we report the studies on the interaction and formation of nanobiocomplex between silver nanoparticle (AgNPs) and vitamin B2, i.e., riboflavin (RF). The binding study of AgNP to RF was studied by fluorescence, UV-Vis, and TEM techniques. AgNPs were prepared by reducing AgNO3 with trisodium citrate. Prepared nanoparticles size obtained at 20 nm having surface Plasmon resonance band at 426 nm. The absorbance band of RF at 264, 374, and 444 nm changes significantly in the presence of AgNPs suggests that there is change in the chemical environment surrounding AgNPs. A fluorescence spectral change for a solution of RF upon the addition of AgNPs and rapid quenching is suggestive of a rapid adsorption of RF on AgNPs.

Riboflavin

MedlinePlus

... 23193625 . Mason JB. Vitamins, trace minerals, and other micronutrients. In: Goldman L, Schafer AI, eds. Goldman-Cecil ... Saunders; 2016:chap 218. Salwen MJ. Vitamins and trace elements. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

Tryptophan

MedlinePlus

... and serotonin. Serotonin is thought to produce healthy sleep and a stable mood. In order for tryptophan in the diet to be changed into niacin, the body needs to have enough: Iron Riboflavin Vitamin B6

Thiamine

MedlinePlus

... B vitamins, and found in many vitamin B complex products. Vitamin B complexes generally include vitamin B1 (thiamine), vitamin B2 (riboflavin), ... is required by our bodies to properly use carbohydrates. It also helps maintain proper nerve function.

Vitamins and Minerals

MedlinePlus

... The water-soluble vitamins — C and the B-complex vitamins (such as vitamins B6, B12, niacin, riboflavin, ... day, as well as the right balance of carbohydrates, proteins, fats, and calories. Whole or unprocessed foods — ...

Photo-degradation behaviour of roseoflavin in some aqueous solutions

NASA Astrophysics Data System (ADS)

Tyagi, A.; Penzkofer, A.; Mathes, T.; Hegemann, P.

2010-03-01

An absorption and emission spectroscopic characterization of roseoflavin (8-dimethylamino-8-demethyl-riboflavin, RoF) in aqueous solutions was carried out. The studies were concentrated on roseoflavin in pH 8 phosphate buffer. Absorption cross-section spectra, fluorescence excitation spectra, fluorescence quantum distributions, fluorescence quantum yields and fluorescence lifetimes were determined. The fluorescence of RoF is quenched by photo-induced intra-molecular charge-transfer at room temperature. The photo-degradation of RoF in un-buffered water, in Tris-HCl buffer, and in phosphate buffer was studied. Phosphate buffer and to a smaller extent Tris buffer catalyse the RoF photo-degradation. Photo-excitation of the primary photoproduct, 8-methylamino-riboflavin (8-MNH-RF), enhanced the RoF degradation by triplet 8-MNH-RF - singlet RoF excitation transfer with subsequent triplet-state RoF degradation.

The effect of riboflavin-UV-A treatment on corneal limbal epithelial cells--a study on human cadaver eyes.

PubMed

Vimalin, Jeyalatha; Gupta, Nidhi; Jambulingam, Malathi; Padmanabhan, Prema; Madhavan, Hajib N

2012-09-01

To determine the effect of riboflavin-UV-A treatment on the corneal limbal epithelial cells during a corneal collagen cross-linking (CXL) procedure. Thirty freshly enucleated human cadaveric eyeballs were subjected to a CXL procedure, mimicking the clinical protocol. During the UV-A exposure, one half of the limbus (sector A) was left unprotected, whereas the other half (sector B) was covered by a metal shield. Limbal biopsies from both sectors before and after the procedure were analyzed. Each strip of tissue was divided into 3 segments, for cell count of viable cells, for cultivation on human amniotic membrane (HAM), and for stem cell and differentiated corneal epithelial cell marker studies using reverse transcriptase-polymerase chain reaction. Compared with the cell count before CXL, there was a statistically significant drop in the mean number of viable cells after CXL in sector A but not in sector B. Biopsies from both sectors before CXL and from sector B after CXL showed good growth on HAM. Biopsies from sector A after CXL showed no growth on HAM. The putative stem cell marker ABCG2 was absent in all samples and p63 was absent in 3 of 10 samples taken from sector A after CXL. All markers were present in all samples from sector B after CXL. Riboflavin-UV-A treatment can result in damage to limbal epithelial cells, particularly the stem cells. Covering the limbal region with a metal shield effectively prevents this damage.

Oxidative stress protection and glutathione metabolism in response to hydrogen peroxide and menadione in riboflavinogenic fungus Ashbya gossypii.

PubMed

Kavitha, S; Chandra, T S

2014-11-01

Ashbya gossypii is a plant pathogen and a natural overproducer of riboflavin and is used for industrial riboflavin production. A few literature reports depict a link between riboflavin overproduction and stress in this fungus. However, the stress protection mechanisms and glutathione metabolism are not much explored in A. gossypii. In the present study, an increase in the activity of catalase and superoxide dismutase was observed in response to hydrogen peroxide and menadione. The lipid peroxide and membrane lipid peroxide levels were increased by H2O2 and menadione, indicating oxidative damage. The glutathione metabolism was altered with a significant increase in oxidized glutathione (GSSG), glutathione peroxidase (GPX), glutathione S transferase (GST), and glutathione reductase (GR) and a decrease in reduced glutathione (GSH) levels in the presence of H2O2 and menadione. Expression of the genes involved in stress mechanism was analyzed in response to the stressors by semiquantitative RT-PCR. The messenger RNA (mRNA) levels of CTT1, SOD1, GSH1, YAP1, and RIB3 were increased by H2O2 and menadione, indicating the effect of stress at the transcriptional level. A preliminary bioinformatics study for the presence of stress response elements (STRE)/Yap response elements (YRE) depicted that the glutathione metabolic genes, stress genes, and the RIB genes hosted either STRE/YRE, which may enable induction of these genes during stress.

The absorption characteristics of the human cornea in ultraviolet-a crosslinking.

PubMed

Koppen, Carina; Gobin, Laure; Tassignon, Marie-José

2010-03-01

With respect to the safety of ultraviolet-A (UVA) crosslinking for the corneal endothelium, an absorption coefficient is used that has been calculated in riboflavin soaked porcine corneas. We aim to validate this value for clinical use by measuring the absorption coefficient for UVA 365 nm in postmortem human corneas after instilling riboflavin on the corneal surface. Corneal thickness was measured in nine pairs of human donor eyes of which one eye was subjected to manual removal of the epithelium, whereas the epithelium of the fellow eye was left intact. Both eyes were instilled with riboflavin 0.1% in dextran 20% on the intact globe. After 20 min, the corneas were rinsed, and a corneoscleral button was trephined. The transmission of the cornea for UVA 365 nm was measured by transillumination, which allows calculation of the absorption coefficient. Measurement of average corneal thickness was 658.5 +/- 51.5 microm when the epithelium was removed, and 758.3 +/- 98.8 microm without epithelial removal. The average transmittance for UVA 365 nm was 12.89 +/- 4.10% with epithelial debridement and 28.52 +/- 4.39% without (P<0.05). The resultant average absorption coefficient is 32 +/- 5 cm when the epithelium is removed and 17 +/- 2 cm when it is left intact (P<0.05). Our results show an absorption coefficient for human corneas that is much lower than the values reported in the literature. This finding may be relevant when considering endothelial safety of the clinical crosslinking treatment.

Preparation and evaluation of sustained drug release from pluronic polyol rectal suppositories.

PubMed

Anderson, D; Amomo, M M

2001-01-01

Suppository dosage forms offer several advantages in drug delivery and can be compounded in a pharmacy setting for the needs of the individual patient. In this study, we have examined the use of Pluronic polyols in the development of sustained-release rectal suppository formulations. Solid and liquid Pluronic poyols (Pluronic L61, F68, L101, and F108) were combined in a weight ratio ranging from 80:20 (solid to liquid) to 70:30 to prepare the bases. The release behavior of a model drug, riboflavin, from the suppositories wee evaluated by means of the United Stated Pharmacopeia Basket Dissolution Method. When compared with the control Polybase suppository, which released 50% of the drug (t50) in about 7.23 minutes, Pluronic F68/L61 suppositories at an 80:20 weight ratio exhibited a t50 of 86.5 minutes (1.44 hours). Riboflavin release from suppositories made with Pluronic F108/L101 was even further delayed. The t50 of riboflavin from Pluronic F108/L101 suppositories at an 80:20 weight ratio, for instance, was 274.4 minutes (4.6 hours). The results of this study show that by choosing specific combinations of Pluronic polyols and weight ratios, compounding pharmacists can prepare sustained-release suppository formulations that can deliver drugs within minutes to hours. This flexibility of compounding sustained-release suppositories is beneficial, especially for the management of chronic pain in cancer patients.

Determination of B-complex vitamins in pharmaceutical formulations by surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Junior, Benedito Roberto Alvarenga; Soares, Frederico Luis Felipe; Ardila, Jorge Armando; Durango, Luis Guillermo Cuadrado; Forim, Moacir Rossi; Carneiro, Renato Lajarim

2018-01-01

The aim of this work was to quantify B-complex vitamins in pharmaceutical samples by surface enhanced Raman spectroscopy technique using gold colloid substrate. Synthesis of gold nanoparticles was performed according to an adapted Turkevich method. Initial essays were able to suggest the orientation of molecules on gold nanoparticles surface. Central Composite design was performed to obtain the highest SERS signal for nicotinamide and riboflavin. The evaluated parameters in the experimental design were volume of AuNPs, concentration of vitamins and sodium chloride concentration. The best condition for nicotinamide was NaCl 2.3 × 10- 3 mol L- 1 and 700 μL of AuNPs colloid and this same condition showed to be adequate to quantify thiamine. The experimental design for riboflavin shows the best condition at NaCl 1.15 × 10- 2 mol L- 1 and 2.8 mL of AuNPs colloid. It was possible to quantify thiamine and nicotinamide in presence of others vitamins and excipients in two solid multivitamin formulations using the standard addition procedure. The standard addition curve presented a R2 higher than 0.96 for both nicotinamide and thiamine, at orders of magnitude 10- 7 and 10- 8 mol L- 1, respectively. The nicotinamide content in a cosmetic gel sample was also quantified by direct analysis presenting R2 0.98. The t-student test presented no significant difference regarding HPLC method. Despite the experimental design performed for riboflavin, it was not possible its quantification in the commercial samples.

[Proposed neotype Streptomyces ruber (Krainsky, 1914) Waksman et Henrici, 1948].

PubMed

Kuznetsov, V D; Filippova, S N; Poltorak, V A

1987-01-01

Culture 78 was proposed as a neotype of Streptomyces ruber. It was isolated from the soils of the Baikal region and was closest, in its taxonomic properties, to the original description of the species [13] whose representative had been lost. Cultures from different microbial collections designated as S. ruber were shown to be unlike the original description. The neotype had the following taxononic properties: the cell wall of type I; spiral sporophores with extended spirals having 2-3 coils; oval spores with a smooth envelope; greyish pink aerial and dark-red substrate mycelia; a red pigment not passing into the medium; slow gelatin liquefaction and milk peptonization; weak starch hydrolysis; assimilation of glucose, xylose, rammose, fructose, and inositol; weak growth on arabinose, raffinose and mannitol, but not on sucrose; no formation of melanoid pigments; synthesis of riboflavin and prodigiosin pigments; inhibition of Gram-positive bacterial and acid-resistant mycobacterial growth; no inhibition of yeast and fungal growth. The culture was sensitive to streptomycin, neomycin, gentamycin, monomycin, tetracycline,erythromycin, oleandomycin, lincomycin, ristomycin, levomycetin, polymyxin and fusidin, but resistant in penicillin. The population was composed of six variants [3]: main, faded, asporogenic red, asporogenic yellow, asporogenic white and nocardia-like. The latter two were not capable of riboflavin and prodigiosin formation. The asporogenic yellow variant was a monosynthetic organism: it formed riboflavin, but could not synthesize prodigiosin. The neotype of S. ruber 78 is deposited withthe national Collection of Microorganisms (the reference number is VKM A-611).

Electron transfer mediators accelerated the microbiologically influence corrosion against carbon steel by nitrate reducing Pseudomonas aeruginosa biofilm.

PubMed

Jia, Ru; Yang, Dongqing; Xu, Dake; Gu, Tingyue

2017-12-01

Electron transfer is a rate-limiting step in microbiologically influenced corrosion (MIC) caused by microbes that utilize extracellular electrons. Cross-cell wall electron transfer is necessary to transport the electrons released from extracellular iron oxidation into the cytoplasm of cells. Electron transfer mediators were found to accelerate the MIC caused by sulfate reducing bacteria. However, there is no publication in the literature showing the effect of electron transfer mediators on MIC caused by nitrate reducing bacteria (NRB). This work demonstrated that the corrosion of anaerobic Pseudomonas aeruginosa (PAO1) grown as a nitrate reducing bacterium biofilm on C1018 carbon steel was enhanced by two electron transfer mediators, riboflavin and flavin adenine dinucleotide (FAD) separately during a 7-day incubation period. The addition of either 10ppm (w/w) (26.6μM) riboflavin or 10ppm (12.7μM) FAD did not increase planktonic cell counts, but they increased the maximum pit depth on carbon steel coupons considerably from 17.5μm to 24.4μm and 25.0μm, respectively. Riboflavin and FAD also increased the specific weight loss of carbon steel from 2.06mg/cm 2 to 2.34mg/cm 2 and 2.61mg/cm 2 , respectively. Linear polarization resistance, electrochemical impedance spectroscopy and potentiodynamic polarization curves all corroborated the pitting and weight loss data. Copyright © 2017 Elsevier B.V. All rights reserved.

Blue light induced reactive oxygen species from flavin mononucleotide and flavin adenine dinucleotide on lethality of HeLa cells.

PubMed

Yang, Ming-Yeh; Chang, Chih-Jui; Chen, Liang-Yü

2017-08-01

Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm). Under blue light irradiation at 3.744J/cm 2 (=0.52mW/cm 2 irradiated for 2h), the minimal lethal dose is 3.125μM and the median lethal doses (LD 50 ) for FMN and FAD are 6.5μM and 7.2μM, respectively. Individual exposure to visible blue light irradiation or riboflavin photosensitizers does not produce cytotoxicity and no side effects are observed in this study. The western blotting results also show that an intrinsic apoptosis pathway is activated by the ROS during photolysis of riboflavin analogues. Blue light triggers the cytotoxicity of riboflavins on HeLa cells in vitro. Based on these results, this is a feasible and efficient of PDT with an intrinsic photosensitizer for cancer research. Copyright © 2017 Elsevier B.V. All rights reserved.

Palate morphogenesis in mouse embryos after x-irradiation

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

Callas, Gerald; Walker, Bruce E.

1963-01-01

The development of cleft palate was investigated by irradiating pregnant female C57BL and A/Jax mice on the 11 1/3 day of gestation with 300-r, whole-body doses and examining the fetuses at subsequent intervals. When palate stage was compared with chronological age, morphological rating, or embryonic weight, it was obvious that intermediate stages of palate closure persisted in x-irradiated embryos long after such stages had been passed in normal embryos. Thus, movement of the palatine shelves from the sagittal to the horizontal plane was retarded by x irradiation. Measurements of head and palate did not show any consistent disproportionality of palatemore » growth in the xirradiated embryos except that which resulted from retardation of shelf movement. X irradiation affected A/Jax strain litters more severely than C57BL strain litters according to cleft palate frequency and average palate stage at 18 1/3 days postconception. Cleft palate was seen in 73.1% of strain C57BL fetuses and in 99.5% of A/Jax fetuses. A variety of malformations other than cleft palate were also observed in the offspring of treated mice. Morphologic analysis of cleft palate development after xray treatment gave essentially the same results as comparable analyses of cleft palates produced by cortisone, hypervitaminosis A, and riboflavin deficiency. (TCO)« less

New biotechnological applications for Ashbya gossypii: Challenges and perspectives

PubMed Central

2017-01-01

ABSTRACT The filamentous fungus Ashbya gossypii has long been considered a paradigm of the White Biotechnology in what concerns riboflavin production. Its industrial relevance led to the development of a significant molecular and in silico modeling toolbox for its manipulation. This, together with the increasing knowledge of its genome and metabolism has helped designing effective metabolic engineering strategies for optimizing riboflavin production, but also for developing new A. gossypii strains for novel biotechnological applications, such as production of recombinant proteins, single cell oils (SCOs), and flavour compounds. With the recent availability of its genome-scale metabolic model, the exploration of the full biotechnological potential of A. gossypii is now in the spotlight. Here, we will discuss some of the challenges that these emerging A. gossypii applications still need to overcome to become economically attractive and will present future perspectives for these and other possible biotechnological applications for A. gossypii. PMID:27791453

Evaluating the Effects of Riboflavin/UV-A and Rose-Bengal/Green Light Cross-Linking of the Rabbit Cornea by Noncontact Optical Coherence Elastography

PubMed Central

Singh, Manmohan; Li, Jiasong; Han, Zhaolong; Vantipalli, Srilatha; Liu, Chih-Hao; Wu, Chen; Raghunathan, Raksha; Aglyamov, Salavat R.; Twa, Michael D.; Larin, Kirill V.

2016-01-01

Purpose The purpose of this study was to use noncontact optical coherence elastography (OCE) to evaluate and compare changes in biomechanical properties that occurred in rabbit cornea in situ after corneal collagen cross-linking by either of two techniques: ultraviolet-A (UV-A)/riboflavin or rose-Bengal/green light. Methods Low-amplitude (≤10 μm) elastic waves were induced in mature rabbit corneas by a focused air pulse. Elastic wave propagation was imaged by a phase-stabilized swept source OCE (PhS-SSOCE) system. Corneas were then cross-linked by either of two methods: UV-A/riboflavin (UV-CXL) or rose-Bengal/green light (RGX). Phase velocities of the elastic waves were fitted to a previously developed modified Rayleigh-Lamb frequency equation to obtain the viscoelasticity of the corneas before and after the cross-linking treatments. Micro-scale depth-resolved phase velocity distribution revealed the depth-wise heterogeneity of both cross-linking techniques. Results Under standard treatment settings, UV-CXL significantly increased the stiffness of the corneas by ∼47% (P < 0.05), but RGX did not produce statistically significant increases. The shear viscosities were unaffected by either cross-linking technique. The depth-wise phase velocities showed that UV-CXL affected the anterior ∼34% of the corneas, whereas RGX affected only the anterior ∼16% of the corneas. Conclusions UV-CXL significantly strengthens the cornea, whereas RGX does not, and the effects of cross-linking by UV-CXL reach deeper into the cornea than cross-linking effects of RGX under similar conditions. PMID:27409461

Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown–Vialetto–Van Laere syndrome

PubMed Central

Nalini, Atchayaram; Pandraud, Amelie; Mok, Kin; Houlden, Henry

2013-01-01

Introduction Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown–Vialetto–Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio–Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively). Methods and results We describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10. Conclusions These data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors. PMID:24139842

Phototoxic Effect of Topical Fluoroquinolones Administered Before Corneal Crosslinking in a Murine Model.

PubMed

Reviglio, Victor E; Osaba, Matias; Sambuelli, Gabriela; Kuo, Irene C

2017-03-01

Corneal crosslinking by UV light (UV-CXL) has become a popular treatment for keratoconus and corneal ectasia. Fluoroquinolones (FQs), commonly administered topically before UV-CXL, are known to be phototoxic to the skin and lens. The purpose of this study was to investigate phototoxic effects of topical FQ treatment on murine corneas before UV-CXL, in which the corneal epithelium was kept intact. Murine corneas were treated with various antibiotics with or without riboflavin before UV-CXL. At 24 h, the animals were sacrificed, and the corneas were analyzed for histologic evidence of inflammation and apoptosis and for expression of apoptosis markers BAX and caspases 3 and 9 and for expression of matrix metalloproteinase 9 (MMP-9). Spectrofluorometric analysis was performed. Corneas treated with topical FQ with or without riboflavin before UV-CXL showed mild corneal stromal inflammation, apoptosis by both terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased expression of BAX gene and caspases 3 and 9 by densitometric analysis. Untreated corneas, corneas treated with azithromycin before UV-CXL, and corneas undergoing UV-CXL without any antibiotic or riboflavin pretreatment showed normal histology, no staining for apoptosis, and no increased production of apoptosis markers by polymerase chain reaction. The phototoxic effects of FQs on the cornea may lead surgeons to consider another antibiotic class for prophylaxis against infectious keratitis in UV-CXL. These effects, along with the known cytotoxic effects of FQs independent of UV radiation, may contribute to some of the complications of corneal UV-CXL. Dosage studies may be warranted.

UV cross-linking of donor corneas confers resistance to keratolysis.

PubMed

Arafat, Samer N; Robert, Marie-Claude; Shukla, Anita N; Dohlman, Claes H; Chodosh, James; Ciolino, Joseph B

2014-09-01

The aim of this study was to develop a modified ex vivo corneal cross-linking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. Ex vivo cross-linking of human corneas was performed using Barron artificial anterior chambers. The corneas were deepithelialized, pretreated with riboflavin solution (0.1% riboflavin/20% dextran), and irradiated with ultraviolet A (UV-A) light (λ = 370 nm, irradiance = 3 mW/cm) for various durations. The combined effect of UV-A and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37°C with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. Deepithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 ± 0.6 hours. Cross-linked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 ± 2.6 hours (P < 0.0001). The corneal tissues' resistance to collagenase increased with longer UV-A exposure, reaching a plateau at 30 minutes. Cross-linking both the anterior and posterior corneas did not provide added resistance when compared with cross-linking the anterior corneas only (P > 0.05). γ-irradiated corneas dissolved as readily as deepithelialized controls regardless of whether they were further cross-linked (5.6 ± 1.2 hours) or not (6.1 ± 0.6 hours) (P = 0.43). Collagen cross-linking of the deepithelialized anterior corneal surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A.

Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products.

PubMed

Keil, Shawn D; Saakadze, Natia; Bowen, Richard; Newman, James L; Karatela, Sulaiman; Gordy, Paul; Marschner, Susanne; Roback, John; Hillyer, Christopher D

2015-04-01

Two studies were performed to test the effectiveness of riboflavin and ultraviolet (UV) light treatment (Mirasol PRT, Terumo BCT) against murine cytomegalovirus (MCMV). The first study utilized immune-compromised mice to measure the reduction of cell-free MCMV. A second study used a murine model to evaluate the ability of Mirasol PRT to prevent transfusion-transmitted (TT)-MCMV infection. Human plasma was inoculated with MCMV and then treated with Mirasol PRT. The viral titer was measured using an infectious dose 50% assay in nude mice. Mice were euthanized on Day 10 posttransfusion, and their spleens were tested for the presence of MCMV DNA using polymerase chain reaction (PCR). Mirasol PRT was also evaluated to determine its effectiveness in preventing TT-MCMV in platelets (PLTs) stored in PLT additive solution. PLTs were inoculated with either cell-associated MCMV or cell-free MCMV and then treated with Mirasol PRT. Mice were transfused with treated or untreated product and were euthanized 14 days posttransfusion. Blood and spleens were assayed for MCMV DNA by real-time-PCR. Using nude mice to titer MCMV, a modest 2.1-log reduction was observed in plasma products after Mirasol PRT treatment. TT-MCMV was not observed in the mouse transfusion model when either cell-free or cell-associated MCMV was treated with Mirasol PRT; MCMV transmission was uniformly observed in mice transfused with untreated PLTs. These results suggest that using riboflavin and UV light treatment may be able to reduce the occurrence of transmission of human CMV from infectious PLTs and plasma units. © 2014 AABB.

Madras motor neuron disease (MMND) is distinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome.

PubMed

Nalini, Atchayaram; Pandraud, Amelie; Mok, Kin; Houlden, Henry

2013-11-15

Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. There is a considerable overlap in the phenotype of MMND with Brown-Vialetto-Van Laere syndrome (BVVL) Boltshauser syndrome, Nathalie syndrome and Fazio-Londe syndrome. Recently a number of BVVL cases and families have been described with mutations in two riboflavin transporter genes SLC52A2 and SLC52A3 (solute carrier family 52, riboflavin transporter, member 2 and 3 respectively). We describe six families and four sporadic MMND cases that have been clinically characterized in detail with history, examination, imaging and electrophysiological investigations. We sequenced the SLC52A1, SLC52A2 and SLC52A3 in affected probands and sporadic individuals from the MMND series as well as the C9ORF72 expansion. No genetic defects were identified and the C9ORF72 repeats were all less than 10. These data suggest that MMND is a distinct clinical subgroup of childhood onset MND patients where the known genetic defects are so far negative. The clinico-genetic features of MMND in comparison with the BVVL group of childhood motor neuron diseases suggest that these diseases are likely to share a common defective biological pathway that may be a combination of genetic and environmental factors. © 2013 Published by Elsevier B.V.

Determination of B-complex vitamins in pharmaceutical formulations by surface-enhanced Raman spectroscopy.

PubMed

Junior, Benedito Roberto Alvarenga; Soares, Frederico Luis Felipe; Ardila, Jorge Armando; Durango, Luis Guillermo Cuadrado; Forim, Moacir Rossi; Carneiro, Renato Lajarim

2018-01-05

The aim of this work was to quantify B-complex vitamins in pharmaceutical samples by surface enhanced Raman spectroscopy technique using gold colloid substrate. Synthesis of gold nanoparticles was performed according to an adapted Turkevich method. Initial essays were able to suggest the orientation of molecules on gold nanoparticles surface. Central Composite design was performed to obtain the highest SERS signal for nicotinamide and riboflavin. The evaluated parameters in the experimental design were volume of AuNPs, concentration of vitamins and sodium chloride concentration. The best condition for nicotinamide was NaCl 2.3×10 -3 molL -1 and 700μL of AuNPs colloid and this same condition showed to be adequate to quantify thiamine. The experimental design for riboflavin shows the best condition at NaCl 1.15×10 -2 molL -1 and 2.8mL of AuNPs colloid. It was possible to quantify thiamine and nicotinamide in presence of others vitamins and excipients in two solid multivitamin formulations using the standard addition procedure. The standard addition curve presented a R 2 higher than 0.96 for both nicotinamide and thiamine, at orders of magnitude 10 -7 and 10 -8 molL -1 , respectively. The nicotinamide content in a cosmetic gel sample was also quantified by direct analysis presenting R 2 0.98. The t-student test presented no significant difference regarding HPLC method. Despite the experimental design performed for riboflavin, it was not possible its quantification in the commercial samples. Copyright © 2017 Elsevier B.V. All rights reserved.

The comparative safety of genipin versus UVA-riboflavin crosslinking of rabbit corneas

PubMed Central

Song, Wenjing; Tang, Yun; Qiao, Jing; Li, Haili; Rong, Bei; Yang, Songlin; Wu, Yuan

2017-01-01

Purpose To investigate, after 24 h, the safety of genipin or ultraviolet A (UVA)-riboflavin crosslinking of keratocytes and endothelial cells. Methods Fifteen New Zealand white rabbits were selected and divided into a PBS group (five rabbits), a 0.2% genipin crosslinking (GP-CXL) group (five rabbits), and a UVA-riboflavin crosslinking (UVA-CXL) group (five rabbits). In the GP-CXL and PBS groups, 0.2% genipin or PBS was applied to the corneal surface of the right eyes. In the UVA-CXL group, a clinical crosslinking procedure was used. Before and after surgery, the operated eyes of each group were characterized with confocal microscopy, and the corneal buttons were excised for endothelium staining and electron microscopy. Results The corneal endothelial cell density of the GP-CXL, UVA-CLX, and PBS groups changed. There was a statistically significant difference in thickness and changes in corneal endothelial cell density between the UVA-CXL group and the PBS group (p<0.05), and between the UVA-CXL group and the GP-CXL group (p<0.05), but no statistically significant difference between the GP-CXL group and the PBS group. Confocal microscopy, transmission electron microscopy, and hematoxylin and eosin staining showed that there was keratocyte apoptosis in the anterior and middle stroma and endothelial cell damage in the UVA-CXL group. In the GP-CXL group, only active keratocytes were found and minimal endothelial cell damage. Conclusions Treatment of rabbit corneas with 0.2% genipin showed minimal toxicity toward keratocytes and endothelial cells. Genipin is safer than UVA-CXL for crosslinking of thin corneas. PMID:28761323

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure

PubMed Central

Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Mahon, Sari B.; Kim, Sonia; Ryu, Justine H.; Werdich, Andreas; Januzzi, James L.; Boss, Gerry R.; Rockwood, Gary A.; MacRae, Calum A.; Brenner, Matthew; Gerszten, Robert E.; Peterson, Randall T.

2013-01-01

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.—Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. PMID:23345455

Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria.

PubMed

Makdoumi, Karim; Bäckman, Anders

2016-09-01

To evaluate the bactericidal effect of clinical ultraviolet A (UVA) settings used in photoactivated chromophore for infectious keratitis (PACK)-collagen cross-linking (CXL) in antibiotic-resistant and non-resistant bacterial strains. Well-characterized bacterial strains from clinical isolates, without and with antibiotic resistance, were studied in a pairwise comparison. The evaluated pathogens were Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacteria were dispersed in PBS and diluted to a concentration of approximately 4 × 10 5 /ml. Riboflavin was added to a concentration of 0.01%. By spreading the solution on a microscope slide, a fluid film layer, with a thickness of around 400 mm, was formed and UVA exposure followed. Eight separate exposures were made for each strain (n = 8). The degree of elimination in resistant and non-resistant pathogens was compared. The bactericidal efficacy of exposure differed between the tested microorganisms, and the mean elimination ranged between 60 and 92%, being most extensive in both of the evaluated Pseudomonas strains and least in the E. faecalis strains. Similar reductions were seen in antibiotic-resistant and non-resistant strains, with the exception of S. aureus, in which the resistant strain metchicillin-resistant Staphylococcus aureus (MRSA) was eradicated in a greater extent than the non-resistant strain (P = 0.030). UVA-riboflavin settings used in PACK-CXL are effective in reducing both antibiotic-resistant and non-resistant bacteria. Antibiotic resistance does not appear to be protective against the photooxidative exposure. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

Effect of fasting on the urinary excretion of water-soluble vitamins in humans and rats.

PubMed

Fukuwatari, Tsutomu; Yoshida, Erina; Takahashi, Kei; Shibata, Katsumi

2010-01-01

Recent studies showed that the urinary excretion of the water-soluble vitamins can be useful as a nutritional index. To determine how fasting affects urinary excretion of water-soluble vitamins, a human study and an animal experiment were conducted. In the human study, the 24-h urinary excretion of water-soluble vitamins in 12 healthy Japanese adults fasting for a day was measured. One-day fasting drastically decreased urinary thiamin content to 30%, and increased urinary riboflavin content by 3-fold. Other water-soluble vitamin contents did not show significant change by fasting. To further investigate the alterations of water-soluble vitamin status by starvation, rats were starved for 3 d, and water-soluble vitamin contents in the liver, blood and urine were measured during starvation. Urinary excretion of thiamin, riboflavin, vitamin B(6) metabolite 4-pyridoxic acid, nicotinamide metabolites and folate decreased during starvation, but that of vitamin B(12), pantothenic acid and biotin did not. As for blood vitamin levels, only blood vitamin B(1), plasma PLP and plasma folate levels decreased with starvation. All water-soluble vitamin contents in the liver decreased during starvation, whereas vitamin concentrations in the liver did not decrease. Starvation decreased only concentrations of vitamin B(12) and folate in the skeletal muscle. These results suggest that water-soluble vitamins were released from the liver, and supplied to the peripheral tissues to maintain vitamin nutrition. Our human study also suggested that the effect of fasting should be taken into consideration for subjects showing low urinary thiamin and high urinary riboflavin.

Bioremediation of chromium by the yeast Pichia guilliermondii: toxicity and accumulation of Cr (III) and Cr (VI) and the influence of riboflavin on Cr tolerance.

PubMed

Ksheminska, Helena; Jaglarz, Anita; Fedorovych, Daria; Babyak, Lyubov; Yanovych, Dmytro; Kaszycki, Pawel; Koloczek, Henryk

2003-01-01

A comparative study has been made on the sensitivity of the yeast Pichia guilliermondii to Cr (III) and Cr (VI) as well as on the Cr uptake potential at growth-inhibitory concentrations of chromium. The strains used in the study were either isolated from natural sources or obtained from a laboratory strain collection. The results show that most of the natural strains were more tolerant to chromium and were able to grow in the presence of 5 mM Cr (III) or 0.5 mM Cr (VI), that is at concentrations which substantially inhibited the growth of laboratory strains. The cellular Cr content after treatment was similar for both strain types and ranged from 1.2-4.0 mg/g d.w. and 0.4-0.9 mg/g d.w., for Cr (III) and Cr (VI) forms, respectively, however, in one case of a natural strain it reached the value of 10 mg Cr (III)/g dry mass. Natural-source strains were grouped into four groups based on the yeasts' differential response to Cr (III) and Cr (VI). Hexavalent Cr-resistant mutants of a P. giuilliermondii laboratory strain, which revealed markedly changed capabilities of chromium accumulation, were obtained by means of UV-induced mutagenesis. Cr (VI) treatment triggered oversynthesis of riboflavin and the addition of exogenous riboflavin increased P. guilliermondii resistance to both Cr (III) and Cr (VI). Electrophoretic protein profiles revealed the induction and/or suppression of several proteins in response to toxic Cr (VI) levels.

Plasma Riboflavin and Vitamin B-6, but Not Homocysteine, Folate, or Vitamin B-12, Are Inversely Associated with Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition-Varese Cohort.

PubMed

Agnoli, Claudia; Grioni, Sara; Krogh, Vittorio; Pala, Valeria; Allione, Alessandra; Matullo, Giuseppe; Di Gaetano, Cornelia; Tagliabue, Giovanna; Pedraglio, Samuele; Garrone, Giulia; Cancarini, Ilaria; Cavalleri, Adalberto; Sieri, Sabina

2016-06-01

One-carbon metabolism-important for DNA stability and integrity-may play a role in breast carcinogenesis. However, epidemiologic studies addressing this issue have yielded inconsistent results. We prospectively investigated associations between breast cancer and plasma folate, riboflavin, vitamin B-6, vitamin B-12, and homocysteine in women recruited to the Varese (Italy) cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We performed a nested case-control study on women aged 35-65 y at recruitment with a median body mass index of 25.3 kg/m(2) who gave blood samples in 1987-1992 and again in 1993-1998. Breast cancer cases identified by 31 December 2009 were individually matched to controls. RRs of breast cancer (and subtypes defined by hormone receptor status) with 95% CIs were estimated by unconditional logistic regression, controlling for matching factors and breast cancer risk factors. After a median of 14.9 y, 276 breast cancer cases were identified and matched to 276 controls. Increasing plasma vitamin B-6 was associated with decreased risk of overall (RR: 0.78; 95% CI: 0.63, 0.96 for 1-SD increase), premenopausal (RR: 0.66; 95% CI: 0.48, 0.92 for 1-SD increase), estrogen receptor-positive (RR: 0.79; 95% CI: 0.63, 1.00 for 1-SD increase), and progesterone receptor-positive (RR: 0.72; 95% CI: 0.55, 0.95 for 1-SD increase) breast cancers. Increased plasma vitamin B-6 was also associated with decreased breast cancer risk in alcohol consumers (≥7 g/d) compared with consumption of <7 g/d or nonconsumption (RR: 0.71; 95% CI: 0.51, 0.99). High plasma riboflavin was associated with significantly lower risk in premenopausal women (RR: 0.45; 95% CI: 0.21, 0.94; highest compared with the lowest quartile, P trend = 0.021). Plasma homocysteine, folate, and vitamin B-12 were not associated with breast cancer risk. High plasma vitamin B-6 and riboflavin may lower breast cancer risk, especially in premenopausal women. Additional research is necessary to further explore these associations. © 2016 American Society for Nutrition.

What role does measuring medication compliance play in evaluating the efficacy of naltrexone?

PubMed

Baros, Alicia M; Latham, Patricia K; Moak, Darlene H; Voronin, Konstantin; Anton, Raymond F

2007-04-01

Compliance with medication in pharmacotherapy trials of alcoholism has been shown to be equal to, or more, important than in other areas of medicine. Research has suggested that naltrexone's effectiveness can be greatly influenced by the compliance of participants in clinical trials. Presently, we compare 2 compliance measurement methods [urine riboflavin and medication event monitoring system (MEMS)] used simultaneously to evaluate naltrexone's efficacy and the impact of compliance on the size of observable treatment effects. One hundred and thirty-seven of 160 randomized alcoholic patients completed 12-weeks (84 days) of naltrexone or placebo and cognitive behavioral therapy (CBT) or motivational enhancement therapy (MET). Urine riboflavin was determined during study weeks 2, 6, and 12. The MEMS provided a detailed computerized record of when a participant opened their medication bottle throughout the trial. Baseline predictors of MEMS (80% openings) and urine riboflavin (>or=1,500 ng/mL by fluorimetry) compliance were examined. The effects of the treatments in the compliant participants defined by one, the other, or both methods were compared and contrasted with a previously reported intent-to-treat analysis where compliance was not taken into account. Age was predictive of compliance. 105 participants were deemed compliant via urine riboflavin criteria, 87 via MEMS, and 77 when both criteria were met, with no significant differences between treatment groups. The most compliant participants showed a significant medication by therapy interaction. Those treated with naltrexone/CBT showed more abstinence days (p<0.03), less heavy drinking days (p<0.03) and less total drinks (p<0.03) than the other groups. The effect size of this interaction increased from about 0.2 in the intent-to-treat analysis, to about 0.4 to 0.5 in the compliant group analyses, with little difference between compliance measurement methods. Compliance measurement does appear to influence the evaluation of the efficacy of naltrexone within the context of CBT. Treatment effect sizes approximately doubled in the most compliant individuals. Measuring compliance by either of 2 distinct methods provides approximately similar results. As compliance with naltrexone within the context of CBT has such a large impact of treatment outcome, methods of enhancing compliance during treatment should be given the utmost attention.

Intestinal absorption of water-soluble vitamins in health and disease.

PubMed

Said, Hamid M

2011-08-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. © The Authors Journal compilation © 2011 Biochemical Society

Factors influencing zinc status of apparently healthy indians.

PubMed

Agte, Vaishali V; Chiplonkar, Shashi A; Tarwadi, Kirtan V

2005-10-01

To identify dietary, environmental and socio-economic factors associated with mild zinc deficiency, three zinc status indices; erythrocyte membrane zinc (RBCMZn), plasma zinc and super oxide dismutase (SOD) were assessed in free living and apparently healthy Indian population. Dietary patterns of 232 men and 223 women (20-65 yr) from rural, industrial and urban regions of Western India were evaluated by food frequency questionnaire. RBCMZn was estimated using atomic absorption spectrometry, hemoglobin and serum ceruloplasmin by spectrophotometer. On a sub sample (48 men and 51 women) plasma zinc and SOD were also assessed. Mean RBCMZn was 0.5 +/- 0.1 micromols/g protein with 46% individuals showing zinc deficiency. Mean plasma zinc was 0.98 +/- 0.12 microg/mL with 25% men and 2.5% women having values below normal range. Mean SOD was 0.97 +/- 0.1 (u/mL cells). A significant positive correlation was observed between intakes of green leafy vegetables, other vegetables and milk products with RBCMZn status (p < 0.05). But these were not correlated with plasma zinc (p > 0.2). Cereal and legume intakes were negatively correlated with RBCMZn (p < 0.05) but positively correlated with plasma zinc (p < 0.05) and not correlated with SOD (p > 0.2). Fruit and other vegetable intake were positively correlated with SOD (p < 0.05) alone. Logistic regression analyses revealed that RBCMZn was positively associated with intakes of beta-carotene, zinc and environmental conditions and negatively associated with family size (p < 0.05). Plasma zinc indicated positive association with zinc, thiamin and riboflavin intakes (p < 0.05) and SOD showed negative association with iron and family size. RBCMZn was a more sensitive indicator of long-term zinc status than plasma zinc and SOD. Prominent determinants of zinc status were intakes of beta-carotene and zinc along with environmental conditions and family size.

Intestinal absorption of water-soluble vitamins in health and disease

PubMed Central

Said, Hamid M.

2014-01-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. PMID:21749321

Health and nutrition and the role of the family.

PubMed

Galvez Tan, J Z

1990-01-01

Certain socioeconomic factors weakened families and socioeconomic development in the Philippines. 34% of pregnant mothers in 1982 had anemia and by 1987 it increased to 45%. 70.4% of children 6-12 months old and 38.7% of those 12 months were also deficient in iron. Moreover, 12.4% of pregnant women in 1987 had a goiter for a total of 223,200 pregnancies of which likely resulted in spontaneous abortions, fetal death, or cretinism. 20% of newborns weighed 2.5 kg in 1990 so 324,000 newborns began their lives malnourished. Breast feeding fell from 87% in 1983 to 80% in 1984. 17.7% of children 6 years old were malnourished and 67% of them had stunted growth. 23% of elementary school students also were malnourished. Family daily energy intake decreased from the already inadequate level of 1808 calories in 1982 to 1753 in 1987. Similar falls in dietary intakes included protein, carbohydrates, calcium, ascorbic acid, and riboflavin. In 1989, 50% of families were poor thereby limiting their access to health, education, and food. Even though fertility fell from 6.3 in 1970 to 4.5 in 1984, it still was too high. Infant mortality in 1990 stood at 652 which meant that 250 babies died each day. In addition, 70 1-4 year old children died each day. Yet most of these deaths could have been prevented. Pneumonia was responsible for 40% of these child deaths. Other leading causes of death included diarrhea, measles, nutritional deficiencies, and bronchitis. The government has chosen primary health care (PHC) as the means to better the health status of the population, but is had no official policy and PHC committees largely are inactive. The government must seriously implement PHC throughout the Philippines and place health at the top of its list. Cooperation and coordination among all levels of government and nongovernmental organizations must begin.

Light Barrier for Non-Foil Packaging

DTIC Science & Technology

2010-12-16

packaging to reduce light-induced changes continues (Tung et al 2001). Lipid oxidation chemistry PRINTPACK Inc. Atlanta, Ga Item No. 0010 Final...complete protection against UV and visible light (i.e. opacity) is advisable. Photosensitizers particularly (e.g. flavonoids , riboflavin —especially for

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific...

Analyzing B-vitamins in Human Milk: Methodological Approaches.

PubMed

Hampel, Daniela; Allen, Lindsay H

2016-01-01

According to the World Health Organization (WHO), infants should be exclusively breastfed for the first six months of life. However, there is insufficient information about the concentration of nutrients in human milk. For some nutrients, including B-vitamins, maternal intake affects their concentration in human milk but the extent to which inadequate maternal diets affect milk B-vitamin content is poorly documented. Little is known about infant requirements for B-vitamins; recommendations are generally set as Adequate Intakes (AI) calculated on the basis of the mean volume of milk (0.78 L/day) consumed by infants exclusively fed with human milk from well-nourished mothers during the first six months, and the concentration of each vitamin in milk based on reported values. Methods used for analyzing B-vitamins, commonly microbiological, radioisotope dilution or more recently chromatographic, coupled with UV, fluorometric and MS detection, have rarely been validated for the complex human milk matrix. Thus the validity, accuracy, and sensitivity of analytical methods is important for understanding infant requirements for these nutrients, the maternal intakes needed to support adequate concentrations in breast milk. This review summarizes current knowledge on methods used for analyzing the B-vitamins thiamin, riboflavin, niacin, vitamin B-6 and pantothenic acid, vitamin B-12, folate, biotin, and choline in human milk, their chemical and physical properties, the different forms and changes in concentration during lactation, and the effects of deficiency on the infant.

The "trophic" value of foods.

PubMed

Williams, R J; Heffley, J D; Yew, M L; Bode, C W

1973-03-01

Foods must furnish (i) calories, which can readily be measured, and (ii) raw materials necessary for the building and maintenance of metabolic machinery which makes possible fuel utilization. We have called this "beyond-calorie" quality of food its "trophic" value. This concept has more unity than appears on the surface, and is capable of approximate measurement by biological testing as our experiments show. The trophic value of a food cannot be ascertained from food composition tables because only a smattering of the necessary information is commonly furnished. A food cannot support life if it is missing, or deficient with respect to, any one of the necessary nutrients. A tabulation which includes only a few nutrients-e.g., calcium, thiamin, riboflavin, niacin, phosphorus, and iron-can be woefully misleading, especially if these individual nutrients have been added by way of fortification. THE MEASUREMENT WE HAVE APPLIED TO A NUMBER OF FOODS IS POTENTIALLY VALUABLE FOR COMPARING SIMILAR FOOD PRODUCTS: two grains, two breads, two milk products, or for comparison of the same food grown, processed, or preserved in different ways. By using essentially this method we have found that barnyard eggs are somewhat superior to battery eggs, but that whether they are fertile or infertile makes no difference. We are of the opinion that extensive biological testing of many commercial food products is highly desirable to help promote human health and better internal environments for our cells and tissues.

Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines.

PubMed

Dias, Joana; Leeansyah, Edwin; Sandberg, Johan K

2017-07-03

Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway. The ability of MAIT cells to exhibit microbe-specific functional specialization has not been thoroughly investigated. Here, we found that MAIT cell responses against Escherichia coli and Candida albicans displayed microbe-specific polyfunctional response profiles, antigen sensitivity, and response magnitudes. MAIT cell effector responses against E. coli and C. albicans displayed differential MR1 dependency and TCR β-chain bias, consistent with possible divergent antigen subspecificities between these bacterial and fungal organisms. Finally, although the MAIT cell immunoproteome was overall relatively homogenous and consistent with an effector memory-like profile, it still revealed diversity in a set of natural killer cell-associated receptors. Among these, CD56, CD84, and CD94 defined a subset with higher expression of the transcription factors promyelocytic leukemia zinc finger (PLZF), eomesodermin, and T-bet and enhanced capacity to respond to IL-12 and IL-18 stimulation. Thus, the conserved and innate-like MAIT cells harbor multiple layers of functional heterogeneity as they respond to bacterial or fungal organisms or innate cytokines and adapt their antimicrobial response patterns in a stimulus-specific manner.

Kinetic mechanism and quaternary structure of Aminobacter aminovorans NADH:flavin oxidoreductase: an unusual flavin reductase with bound flavin.

PubMed

Russell, Thomas R; Demeler, Borries; Tu, Shiao-Chun

2004-02-17

The homodimeric NADH:flavin oxidoreductase from Aminobacter aminovorans is an NADH-specific flavin reductase herein designated FRD(Aa). FRD(Aa) was characterized with respect to purification yields, thermal stability, isoelectric point, molar absorption coefficient, and effects of phosphate buffer strength and pH on activity. Evidence from this work favors the classification of FRD(Aa) as a flavin cofactor-utilizing class I flavin reductase. The isolated native FRD(Aa) contained about 0.5 bound riboflavin-5'-phosphate (FMN) per enzyme monomer, but one bound flavin cofactor per monomer was obtainable in the presence of excess FMN or riboflavin. In addition, FRD(Aa) holoenzyme also utilized FMN, riboflavin, or FAD as a substrate. Steady-state kinetic results of substrate titrations, dead-end inhibition by AMP and lumichrome, and product inhibition by NAD(+) indicated an ordered sequential mechanism with NADH as the first binding substrate and reduced FMN as the first leaving product. This is contrary to the ping-pong mechanism shown by other class I flavin reductases. The FMN bound to the native FRD(Aa) can be fully reduced by NADH and subsequently reoxidized by oxygen. No NADH binding was detected using 90 microM FRD(Aa) apoenzyme and 300 microM NADH. All results favor the interpretation that the bound FMN was a cofactor rather than a substrate. It is highly unusual that a flavin reductase using a sequential mechanism would require a flavin cofactor to facilitate redox exchange between NADH and a flavin substrate. FRD(Aa) exhibited a monomer-dimer equilibrium with a K(d) of 2.7 microM. Similarities and differences between FRD(Aa) and certain flavin reductases are discussed.

Transport and Stability of Biological Molecules in Surfactant-Alginate Composite Hydrogels

PubMed Central

Stoppel, Whitney L.; White, Joseph C.; Horava, Sarena D.; Bhatia, Surita R.; Roberts, Susan C.

2013-01-01

Obstructed transport of biological molecules can result in improper release of pharmaceuticals or biologics from biomedical devices. Recent studies have shown that nonionic surfactants, such as Pluronic® F68 (F68), positively alter biomaterial properties, such as mesh size and microcapsule diameter. To further understand the effect of F68 (incorporated at concentrations well above the critical micelle concentration (CMC)) in traditional biomaterials, the transport properties of BSA and riboflavin were investigated in F68-alginate composite hydrogels. Results indicate that small molecule transport (represented by riboflavin) was not significantly hindered by F68 in homogeneously crosslinked hydrogels (up to an 11% decrease in loading capacity and 14% increase in effective diffusion coefficient, Deff), while protein transport in homogeneously crosslinked hydrogels (represented by BSA) was significantly affected (up to a 43% decrease in loading capacity and 40% increase in Deff). For inhomogeneously crosslinked hydrogels (CaCl2 or BaCl2 gelation), the Deff increased up to 50% and 83% for small molecule and proteins, respectively. Variation in the alginate gelation method was shown to affect transport through measurable changes in swelling ratio (30% decrease) and observable changes in crosslinking structure as well as up to a 3.6 and 11.8-fold difference in Deff for riboflavin and BSA, respectively. The change in protein transport properties is a product of mesh size restrictions (10–25 nm estimated by mechanical properties) and BSA-F68 interaction (DLS). Taken as a whole, these results show that incorporation of a nonionic surfactant at concentrations above the CMC can affect device functionality by impeding the transport of large biological molecules. PMID:21798381

The effect of standard and high-fluence corneal cross-linking (CXL) on cornea and limbus.

PubMed

Richoz, Olivier; Tabibian, David; Hammer, Arthur; Majo, François; Nicolas, Michael; Hafezi, Farhad

2014-07-22

When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross-linking with UV-A and riboflavin (CXL) must be applied eccentrically to the periphery of the lower cornea, partly irradiating the corneal limbus. Here, we investigated the effect of standard and double-standard fluence corneal cross-linking with riboflavin and UV-A (CXL) on cornea and corneal limbus in the rabbit eye in vivo. Epithelium-off CXL was performed in male New Zealand White rabbits with two irradiation diameters (7 mm central cornea, 13 mm cornea and limbus), using standard fluence (5.4 J/cm(2)) and double-standard fluence (10.8 J/cm(2)) settings. Controls were subjected to epithelial removal and riboflavin instillation, but were not irradiated with UV-A. Following CXL, animals were examined daily until complete closure of the epithelium, and at 7, 14, 21, and 28 days. Animals were killed and a corneoscleral button was excised and processed for light microscopy and immunohistochemistry. For both irradiation diameters and fluences tested, no signs of endothelial damage or limbal vessel thrombosis were observed, and time to re-epithelialization was similar to untreated controls. Histological and immunohistochemical analysis revealed no differences in the p63 putative stem cell marker expression pattern. Even when using fluence twice as high as the one used in current clinical CXL settings, circumferential UV-A irradiation of the corneal limbus does not alter the regenerative capacity of the limbal epithelial cells, and the expression pattern of the putative stem cell marker p63 remains unchanged. This suggests that eccentric CXL may be performed safely in PMD. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

In vivo viability of stored red blood cells derived from riboflavin plus ultraviolet light-treated whole blood.

PubMed

Cancelas, Jose A; Rugg, Neeta; Fletcher, Dana; Pratt, P Gayle; Worsham, D Nicole; Dunn, Susan K; Marschner, Susanne; Reddy, Heather L; Goodrich, Raymond P

2011-07-01

A novel system using ultraviolet (UV) light and riboflavin (Mirasol System, CaridianBCT Biotechnologies) to fragment nucleic acids has been developed to treat whole blood (WB), aiming at the reduction of potential pathogen load and white blood cell inactivation. We evaluated stored red blood cell (RBC) metabolic status and viability, in vitro and in vivo, of riboflavin/UV light-treated WB (IMPROVE study). The study compared recovery and survival of RBCs obtained from nonleukoreduced WB treated using three different UV light energies (22, 33, or 44 J/mL(RBC)). After treatment, WB from 12 subjects was separated into components and tested at the beginning and end of component storage. After 42 days of storage, an aliquot of RBCs was radiolabeled and autologously reinfused into subjects for analysis of 24-hour recovery and survival of RBCs. Eleven subjects completed the in vivo study. No device-related adverse events were observed. By Day 42 of storage, a significant change in the concentrations of sodium and potassium was observed. Five subjects had a 24-hour RBC recovery of 75% or more with no significant differences among the energy groups. RBC t(1/2) was 24 ± 9 days for the combined three groups. Significant correlations between 24-hour RBC recovery and survival, hemolysis, adenosine triphosphate (ATP), and CO(2) levels were observed. This study shows that key RBC quality variables, hemolysis, and ATP concentration may be predictive of their 24-hour recovery and t(1/2) survival. These variables will now be used to assess modifications to the system including storage duration, storage temperature, and appropriate energy dose for treatment. © 2011 American Association of Blood Banks.

The crystal structure of the bifunctional deaminase/reductase RibD of the riboflavin biosynthetic pathway in Escherichia coli: implications for the reductive mechanism.

PubMed

Stenmark, Pål; Moche, Martin; Gurmu, Daniel; Nordlund, Pär

2007-10-12

We have determined the crystal structure of the bi-functional deaminase/reductase enzyme from Escherichia coli (EcRibD) that catalyzes two consecutive reactions during riboflavin biosynthesis. The polypeptide chain of EcRibD is folded into two domains where the 3D structure of the N-terminal domain (1-145) is similar to cytosine deaminase and the C-terminal domain (146-367) is similar to dihydrofolate reductase. We showed that EcRibD is dimeric and compared our structure to tetrameric RibG, an ortholog from Bacillus subtilis (BsRibG). We have also determined the structure of EcRibD in two binary complexes with the oxidized cofactor (NADP(+)) and with the substrate analogue ribose-5-phosphate (RP5) and superposed these two in order to mimic the ternary complex. Based on this superposition we propose that the invariant Asp200 initiates the reductive reaction by abstracting a proton from the bound substrate and that the pro-R proton from C4 of the cofactor is transferred to C1 of the substrate. A highly flexible loop is found in the reductase active site (159-173) that appears to control cofactor and substrate binding to the reductase active site and was therefore compared to the corresponding Met20 loop of E. coli dihydrofolate reductase (EcDHFR). Lys152, identified by comparing substrate analogue (RP5) coordination in the reductase active site of EcRibD with the homologous reductase from Methanocaldococcus jannaschii (MjaRED), is invariant among bacterial RibD enzymes and could contribute to the various pathways taken during riboflavin biosynthesis in bacteria and yeast.

The single NqrB and NqrC subunits in the Na(+)-translocating NADH: quinone oxidoreductase (Na(+)-NQR) from Vibrio cholerae each carry one covalently attached FMN.

PubMed

Casutt, Marco S; Schlosser, Andreas; Buckel, Wolfgang; Steuber, Julia

2012-10-01

The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is the prototype of a novel class of flavoproteins carrying a riboflavin phosphate bound to serine or threonine by a phosphodiester bond to the ribityl side chain. This membrane-bound, respiratory complex also contains one non-covalently bound FAD, one non-covalently bound riboflavin, ubiquinone-8 and a [2Fe-2S] cluster. Here, we report the quantitative analysis of the full set of flavin cofactors in the Na(+)-NQR and characterize the mode of linkage of the riboflavin phosphate to the membrane-bound NqrB and NqrC subunits. Release of the flavin by β-elimination and analysis of the cofactor demonstrates that the phosphate group is attached at the 5'-position of the ribityl as in authentic FMN and that the Na(+)-NQR contains approximately 1.7mol covalently bound FMN per mol non-covalently bound FAD. Therefore, each of the single NqrB and NqrC subunits in the Na(+)-NQR carries a single FMN. Elimination of the phosphodiester bond yields a dehydro-2-aminobutyrate residue, which is modified with β-mercaptoethanol by Michael addition. Proteolytic digestion followed by mass determination of peptide fragments reveals exclusive modification of threonine residues, which carry FMN in the native enzyme. The described reactions allow quantification and localization of the covalently attached FMNs in the Na(+)-NQR and in related proteins belonging to the Rhodobacter nitrogen fixation (RNF) family of enzymes. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

Assessment of UVA-Riboflavin Corneal Cross-Linking Using Small Amplitude Oscillatory Shear Measurements.

PubMed

Aslanides, Ioannis M; Dessi, Claudia; Georgoudis, Panagiotis; Charalambidis, Georgios; Vlassopoulos, Dimitris; Coutsolelos, Athanassios G; Kymionis, George; Mukherjee, Achyut; Kitsopoulos, Theofanis N

2016-04-01

The effect of ultraviolet (UV)-riboflavin cross-linking (CXL) has been measured primarily using the strip extensometry technique. We propose a simple and reliable methodology for the assessment of CXL treatment by using an established rheologic protocol based on small amplitude oscillatory shear (SAOS) measurements. It provides information on the average cross-link density and the elastic modulus of treated cornea samples. Three fresh postmortem porcine corneas were used to study the feasibility of the technique, one serving as control and two receiving corneal collagen cross-linking treatment. Subsequently, five pairs of fresh postmortem porcine corneas received corneal collagen cross-linking treatment with riboflavin and UVA-irradiation (370 nm; irradiance of 3 mW/cm2) for 30 minutes (Dresden protocol); the contralateral porcine corneas were used as control samples. After the treatment, the linear viscoelastic moduli of the corneal samples were measured using SAOS measurements and the average cross-linking densities extracted. For all cases investigated, the dynamic moduli of the cross-linked corneas were higher compared to those of the corresponding control samples. The increase of the elastic modulus of the treated samples was between 122% and 1750%. The difference was statistically significant for all tested samples (P = 0.018, 2-tailed t-test). We report a simple and accurate methodology for quantifying the effects of cross-linking on porcine corneas treated with the Dresden protocol by means of SAOS measurements in the linear regime. The measured dynamic moduli, elastic and viscous modulus, represent the energy storage and energy dissipation, respectively. Hence, they provide a means to assess the changing physical properties of the cross-linked collagen networks after CXL treatment.

Physical Stability, Autoxidation, and Photosensitized Oxidation of ω-3 Oils in Nanoemulsions Prepared with Natural and Synthetic Surfactants.

PubMed

Uluata, Sibel; McClements, D Julian; Decker, Eric A

2015-10-28

The food industry is interested in the utilization of nanoemulsions stabilized by natural emulsifiers, but little research has been conducted to determine the oxidative stability of such emulsions. In this study, two natural (lecithin and quillaja saponin) and two synthetic (Tween 80 and sodium dodecyl sulfate) surfactants were used to fabricate omega-3 nanoemulsion using high pressure homogenization (microfluidization). Initially, all the nanoemulsions contained small (d from 45 to 89 nm) and anionic (ζ-potential from -8 to -65 mV) lipid droplets (pH 7). The effect of pH, ionic strength, and temperature on the physical stability of the nanoemulsion system was examined. Nanoemulsion stabilized with Tween 80, quillaja saponin, or sodium dodecyl sulfate (SDS) exhibited no major changes in particle size or visible creaming in the pH range of 3 to 8. All nanoemulsions were relatively stable to salt addition (0 to 500 mM NaCl, pH 7.0). Nanoemulsions stabilized with SDS and quillaja saponin were stable to heating (30 to 90 °C). The impact of surfactant type on lipid oxidation was determined in the presence and absence of the singlet oxygen photosensitizers, riboflavin, and rose bengal. Riboflavin and rose bengal accelerated lipid oxidation when compare to samples without photosensitizers. Lipid hydroperoxide formation followed the order Tween 80 > SDS > lecithin > quillaja saponin, and propanal formation followed the order lecithin > Tween 80 > SDS > quillaja saponin at 37 °C for autoxidation. The same order of oxidative stability was observed in the presence of photosensitized oxidation promoted by riboflavin. Quillaja saponin consistently produced the most oxidatively stable emulsions, which could be due to its high free radical scavenging capacity.

Exploiting automatic on-line renewable molecularly imprinted solid-phase extraction in lab-on-valve format as front end to liquid chromatography: application to the determination of riboflavin in foodstuffs.

PubMed

Oliveira, Hugo M; Segundo, Marcela A; Lima, José L F C; Miró, Manuel; Cerdà, Victor

2010-05-01

In the present work, it is proposed, for the first time, an on-line automatic renewable molecularly imprinted solid-phase extraction (MISPE) protocol for sample preparation prior to liquid chromatographic analysis. The automatic microscale procedure was based on the bead injection (BI) concept under the lab-on-valve (LOV) format, using a multisyringe burette as propulsion unit for handling solutions and suspensions. A high precision on handling the suspensions containing irregularly shaped molecularly imprinted polymer (MIP) particles was attained, enabling the use of commercial MIP as renewable sorbent. The features of the proposed BI-LOV manifold also allowed a strict control of the different steps within the extraction protocol, which are essential for promoting selective interactions in the cavities of the MIP. By using this on-line method, it was possible to extract and quantify riboflavin from different foodstuff samples in the range between 0.450 and 5.00 mg L(-1) after processing 1,000 microL of sample (infant milk, pig liver extract, and energy drink) without any prior treatment. For milk samples, LOD and LOQ values were 0.05 and 0.17 mg L(-1), respectively. The method was successfully applied to the analysis of two certified reference materials (NIST 1846 and BCR 487) with high precision (RSD < 5.5%). Considering the downscale and simplification of the sample preparation protocol and the simultaneous performance of extraction and chromatographic assays, a cost-effective and enhanced throughput (six determinations per hour) methodology for determination of riboflavin in foodstuff samples is deployed here.

Photo, thermal and chemical degradation of riboflavin

PubMed Central

Kazi, Sadia Hafeez; Ahmed, Sofia; Anwar, Zubair; Ahmad, Iqbal

2014-01-01

Summary Riboflavin (RF), also known as vitamin B2, belongs to the class of water-soluble vitamins and is widely present in a variety of food products. It is sensitive to light and high temperature, and therefore, needs a consideration of these factors for its stability in food products and pharmaceutical preparations. A number of other factors have also been identified that affect the stability of RF. These factors include radiation source, its intensity and wavelength, pH, presence of oxygen, buffer concentration and ionic strength, solvent polarity and viscosity, and use of stabilizers and complexing agents. A detailed review of the literature in this field has been made and all those factors that affect the photo, thermal and chemical degradation of RF have been discussed. RF undergoes degradation through several mechanisms and an understanding of the mode of photo- and thermal degradation of RF may help in the stabilization of the vitamin. A general scheme for the photodegradation of RF is presented. PMID:25246959

[Photosensitization and photoprotection by some drugs, metabolites and other compounds].

PubMed

Lozovskaia, E L; Makareeva, E N; Makedonov, I U

1997-01-01

Photosensitizing and photoprotecting efficiency of about a hundred of compounds, mainly drugs, was studied. The method based on chemiluminescence occurred along with photooxidation of glycyltryptophan under irradiation in UVB range in solution was used for testing. As a measure of photosensitizing efficiency the concentration of photosensitizer which induced two-fold increase of chemiluminescence intensity was chosen. The most effective photosensitizers are riboflavin, FAD, furagin, psoralene, vicasol, benzobarbital, mydocalm, angelicyn, furadonin, ethacridin, diazolin, folic acid. With regard to pharmacological doses of drugs in organism more dangerous sensitizers (in descending order) are p-aminosalicylic acid, furagin, riboflavin, benzobarbital, thiopental, chloramphenicol, nicodin, mydocalm, furadonin, oxolonic acid, furazolidone, psoralene, nicotinamide and diazolin. Photoprotecting effect was described by the concentration at which chemiluminescence intensity decreased twice. The most effective photoprotectors are etamsilat, quercetin, ftivazid, chlorpromazine, diprazine, thioridazine, aminophenazone, oxaphenamide. Concentration dependence for some of these drugs (etamsilat, chlorpromazine, diprazine, thioridazine) is non-monotonous: they inhibit photooxidation in low concentration (about 10(-7)-10(-6) M), but at higher concentrations (10(-5)-10(-4) M) photosensitization dominates over photoprotection.

Photo-induced degradation of some flavins in aqueous solution

NASA Astrophysics Data System (ADS)

Holzer, W.; Shirdel, J.; Zirak, P.; Penzkofer, A.; Hegemann, P.; Deutzmann, R.; Hochmuth, E.

2005-01-01

The blue-light induced photo-degradation of FMN, FAD, riboflavin, lumiflavin, and lumichrome in aqueous solution at pH 8 is studied by measurement of absorption coefficient spectral changes due to continuous excitation at 428 nm. The quantum yields of photo-degradation determined are ϕD(riboflavin, pH 8) ≈ 7.8 × 10 -3, ϕD(FMN, pH 5.6) ≈ 7.3 × 10 -3, ϕD(FMN, pH 8) ≈ 4.6 × 10 -3, ϕD(FAD, pH 8) ≈ 3.7 × 10 -4, ϕD(lumichrome, pH 8) ≈ 1.8 × 10 -4, and ϕD(lumiflavin, pH 8) ⩽ 1.1 × 10 -5. In a mass-spectroscopic analysis, the photo-products of FMN dissolved in water (solution pH is 5.6) were identified to be lumichrome and the lumiflavin derivatives dihydroxymethyllumiflavin, formyllumiflavin, and lumiflavin-hydroxy-acetaldehyde. An absorption and emission spectroscopic characterisation of the primary photoproducts of FMN at pH 8 is carried out.

Effect of different drying methods on concentrations of several phytochemicals in herbal preparation of 8 medicinal plants leaves.

PubMed

Mahanom, H; Azizah, A; Dzulkifly, M

1999-12-01

The effect of oven drying at 50ᵒC ± 1ᵒC for 9 hour, 70ᵒC ± 1ᵒC for 5 hour and freeze drying on retention of chlorophyll, riboflavin, niacin, ascorbic acid and carotenoids in herbal preparation consisting of 8 medicinal plants was evaluated. The medicinal plants selected were leaves of Apium graveolens (saderi), Averrhoa bilimbi (belimbing buluh), Centella asiatica (pegaga), Mentha arvensis (pudina), Psidium guajava (jambu batu), Sauropus androgynous (cekor manis), Solanum nigrum (terung meranti) and Polygonum minus (kesum ). Results revealed that both type and conditions of the drying treatments affected retention of all phytochemicals analysed. Herbal preparation developed using oven drying was found to have inferior phytochemicals content compared to that obtained by freeze dryer. Nevertheless, the herbal preparation developed using all treatments still retain appreciable amount of phytochemicals studied, especially carotenoids, ascorbic acid, niacin and riboflavin and thus have potential for commercial purposes.

Molecular characterization of an unauthorized genetically modified Bacillus subtilis production strain identified in a vitamin B2 feed additive.

PubMed

Paracchini, Valentina; Petrillo, Mauro; Reiting, Ralf; Angers-Loustau, Alexandre; Wahler, Daniela; Stolz, Andrea; Schönig, Birgit; Matthies, Anastasia; Bendiek, Joachim; Meinel, Dominik M; Pecoraro, Sven; Busch, Ulrich; Patak, Alex; Kreysa, Joachim; Grohmann, Lutz

2017-09-01

Many food and feed additives result from fermentation of genetically modified (GM) microorganisms. For vitamin B2 (riboflavin), GM Bacillus subtilis production strains have been developed and are often used. The presence of neither the GM strain nor its recombinant DNA is allowed for fermentation products placed on the EU market as food or feed additive. A vitamin B 2 product (80% feed grade) imported from China was analysed. Viable B. subtilis cells were identified and DNAs of two bacterial isolates (LHL and LGL) were subjected to three whole genome sequencing (WGS) runs with different devices (MiSeq, 454 or HiSeq system). WGS data revealed the integration of a chloramphenicol resistance gene, the deletion of the endogenous riboflavin (rib) operon and presence of four putative plasmids harbouring rib operons. Event- and construct-specific real-time PCR methods for detection of the GM strain and its putative plasmids in food and feed products have been developed. Copyright © 2017 Elsevier Ltd. All rights reserved.

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or available for inspection at the... at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal... the Federal Food, Drug, and Cosmetic Act (the Act) or with regulations promulgated under section 412(a...

21 CFR 184.1695 - Riboflavin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or available for inspection at the... at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal_register/code_of_federal... the Federal Food, Drug, and Cosmetic Act (the Act) or with regulations promulgated under section 412(a...

Electrochemically Active Soluble Mediators from Shewanella oneidensis: Relevance to Microbial Fuel Cells and Extracellular Electron Transfer

DTIC Science & Technology

2008-05-01

A second approach is the use of soluble mediators such as, quinones, phenazines , and riboflavin, which are able to shuttle electrons from the cell...done using the equivalent graphite felt or graphite felt coated with platinum nanoparticles . Fuel cell chambers were separated using a gas-permeable

Nutritional significance and acceptance of solar-dried foods of rural Leyte Philippines

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

Swanson, M.A.

1987-01-01

Training in solar dryer construction and food preservation was provided to villagers in three barangays in rural Leyte, Philippines. A 24 hour dietary recall assessed dietary status of the women prior to the solar dried food intervention. Nutrients of greatest dietary concern were thiamine, vitamin A, riboflavin, iron and energy.

21 CFR 184.1697 - Riboflavin-5′-phosphate (sodium).

Code of Federal Regulations, 2010 CFR

2010-04-01

... food with no limitation other than current good manufacturing practice. The affirmation of this... following current good manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in § 170.3(o)(20) of this chapter. (2) The ingredient is used in milk products, as...

21 CFR 184.1697 - Riboflavin-5′-phosphate (sodium).

Code of Federal Regulations, 2012 CFR

2012-04-01

... food with no limitation other than current good manufacturing practice. The affirmation of this... following current good manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in § 170.3(o)(20) of this chapter. (2) The ingredient is used in milk products, as...

21 CFR 184.1697 - Riboflavin-5′-phosphate (sodium).

Code of Federal Regulations, 2011 CFR

2011-04-01

... food with no limitation other than current good manufacturing practice. The affirmation of this... following current good manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in § 170.3(o)(20) of this chapter. (2) The ingredient is used in milk products, as...

21 CFR 184.1697 - Riboflavin-5′-phosphate (sodium).

Code of Federal Regulations, 2013 CFR

2013-04-01

... food with no limitation other than current good manufacturing practice. The affirmation of this... following current good manufacturing practice conditions of use: (1) The ingredient is used as a nutrient supplement as defined in § 170.3(o)(20) of this chapter. (2) The ingredient is used in milk products, as...

A history of the isolation and identification of vitamin B(6)

USDA-ARS?s Scientific Manuscript database

In the 1930s, Rudolf Peters showed that young rats kept on a semi-synthetic diet with added thiamin and riboflavin but no other supplement developed 'rat acrodynia', a condition characterized by severe cutaneous lesions. In 1934, Paul György showed that the factor which cured 'rat acrodynia' was vit...

Maternal one-carbon nutrient intake and cancer risk in offspring

USDA-ARS?s Scientific Manuscript database

Dietary intake of one-carbon nutrients, particularly folate, vitamin B2 (riboflavin), vitamin B6, vitamin B12, and choline have been linked to the risk of cancers of the colon and breast in both human and animal studies. More recently, experimental and epidemiological data have emerged to suggest t...

[Nutritional value of daily diets prepared in several regions of the country. Part V. Value of group b vitamins].

PubMed

Nadolna, I; Wiśniewska, W; Kunachowicz, H

1991-01-01

Studies of the content of group B vitamins: thiamin, riboflavin, niacin and vitamin b6 in daily diets of manual and mental workers with medium income were carried on. The diets were prepared for five regions of the country (Warszawa, Lublin, Olsztyn, Poznań, Wrocław) under laboratory conditions. These diets contained respectively: thiamin 1.17 and 1.11 mg, riboflavin 1.48 and 1.55 mg; niacin 11.3 and 10.2 mg and vitamin B6 1.50 and 1.21 mg per day. According to the studies the realization of daily requirements by these diets for thiamin were met 82 and 98%, for niacin 62 and 65%, and for vitamin B6 79 and 64%. The comparison of the presently studied diets with the ones from 1973, 1980 and 1981 showed that the content of niacin and vitamin B6 intakes systematically decrease. There were no considerable differences in the contents of group B vitamins between diets prepared in all five regions of Poland.

Flavins contained in yeast extract are exploited for anodic electron transfer by Lactococcus lactis.

PubMed

Masuda, Masaki; Freguia, Stefano; Wang, Yung-Fu; Tsujimura, Seiya; Kano, Kenji

2010-06-01

Cyclic voltammograms of yeast extract-containing medium exhibit a clear redox peak around -0.4V vs. Ag|AgCl. Fermentative bacterium Lactococcus lactis was hereby shown to exploit this redox compound for extracellular electron transfer towards a graphite anode using glucose as an electron donor. High performance liquid chromatography revealed that this may be a flavin-type compound. The ability of L. lactis to exploit exogenous flavins for anodic glucose oxidation was confirmed by tests where flavin-type compounds were supplied to the bacterium in well defined media. Based on its mid-point potential, riboflavin can be regarded as a near-optimal mediator for microbially catalyzed anodic electron transfer. Riboflavin derivative flavin mononucleotide (FMN) was also exploited by L. lactis as a redox shuttle, unlike flavin adenine dinucleotide (FAD), possibly due to the absence of a specific transporter for the latter. The use of yeast extract in microbial fuel cell media is herein discouraged based on the related unwanted artificial addition of redox mediators which may distort experimental results. Copyright 2009 Elsevier B.V. All rights reserved.

B-vitamins, carotenoids and α-/γ-tocopherol in raw and roasted nuts.

PubMed

Stuetz, Wolfgang; Schlörmann, Wiebke; Glei, Michael

2017-04-15

The concentrations of B-vitamins, carotenoids and tocopherols in nuts may differ between species and might be influenced by roasting. Thiamine, riboflavin, pyridoxine, lutein, zeaxanthin, β-carotene and α-/γ-tocopherol were determined in different varieties of raw and roasted nuts using HPLC (fluorescence/UV-vis detection). The analysis revealed remarkable concentrations of thiamine and pyridoxine in pistachios (57%, 79% of the recommended daily intake/100g (RDI), respectively) and riboflavin in almonds (119% of the RDI). Pistachios were rich in lutein/zeaxanthin and contained highest β-carotene levels among nuts. Almonds and hazelnuts were abundant in α-tocopherol (>4-fold the RDI for tocopherol equivalents) while pistachios and walnuts were rich in γ-tocopherol. Roasting had a diminishing effect on thiamine, carotenoids and tocopherols especially in almonds and walnuts. Nuts could make a valuable contribution to a healthy diet in regard to B-vitamins, lutein/zeaxanthin and tocopherols. A reduction in micronutrient content by roasting is reliant on the nut variety and specific micronutrient. Copyright © 2016 Elsevier Ltd. All rights reserved.

Site-specific detection of radicals on α-lactalbumin after a riboflavin-sensitized reaction, detected by immuno-spin trapping, ESR, and MS.

PubMed

Dalsgaard, Trine K; Triquigneaux, Mathilde; Deterding, Leesa; Summers, Fiona; Ranguelova, Kalina; Mortensen, Grith; Mason, Ronald P

2013-01-16

Free radicals and other oxidation products were characterized on α-lactalbumin with electron spin resonance (ESR), immuno-spin trapping, and mass spectrometry (MS) after riboflavin-mediated oxidation. Radicals were detected using the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in immuno-spin trapping with both enzyme-linked immunosorbent assay (ELISA) and Western blotting and further characterized with mass spectrometry. A DMPO-trapped radical was identified at His68 and another at one of the tyrosine residues, Tyr50 or Tyr36, respectively, generated by a type II or I mechanism. Not all tyrosyl radicals were trapped, as the secondary oxidation product, 3,4-dihydroxyphenylalanine (DOPA), was detected by mass spectrometry at Tyr18 and Tyr50. A further oxidation of DOPA resulted in the DOPA o-semiquinone radical, which was characterized by ESR. Both surface exposure and the neighboring residues in the local environment of the tertiary structure of α-lactalbumin seem to play a role in the generation of DMPO trapped radicals and secondary oxidation products.

Corneal Cross-Linking Has No Effect on Matrix Metalloproteinase 9 and 13 Levels During Fungal Keratitis on the Early Stage.

PubMed

Kalkanci, Ayse; Bilgihan, Kamil; Ozdemir, Huseyin Baran; Yar Saglam, Atiye Seda; Karakurt, Funda; Erdogan, Merve

2018-04-01

The aim of our study was to investigate matrix metalloproteinases, MMP-9 and MMP-13 levels, in the rabbit model of Fusarium and Candida keratitis treated by corneal cross-linking (PACK-CXL). Rabbit corneas were inoculated with fungal inoculum for keratitis. Each group divided into four subgroups, including un-treated group, PACK-CXL group, voriconazole group and PACK-CXL plus voriconazole group. PACK-CXL was applied with 0.25% riboflavin in accelerated Dresden protocol, and 0.1% voriconazole drops were administered. All corneal buttons excised at tenth day after ophthalmological examination. Fungal cell counts and Scheiber scores were determined in all groups. Corneal tissue MMP mRNA levels were evaluated quantitative reverse transcriptase PCR. The difference in MMP-9 and MMP-13 levels at all groups was not statistically significant (p > 0.05). PACK-CXL with 0.25% riboflavin either alone or combined with antifungal drops was unable to provide decline in inflammatory findings in both macroscopic and microscopic levels similar to medical antifungal treatment.

Sustained therapeutic response to riboflavin in a child with a progressive neurological condition, diagnosed by whole-exome sequencing

PubMed Central

Shashi, Vandana; Petrovski, Slavé; Schoch, Kelly; Crimian, Rebecca; Case, Laura E.; Khalid, Roha; El-Dairi, Maysantoine A.; Jiang, Yong-Hui; Mikati, Mohamad A.; Goldstein, David B.

2015-01-01

One of the most promising outcomes of whole-exome sequencing (WES) is the alteration of medical management following an accurate diagnosis in patients with previously unresolved disorders. Although case reports of targeted therapies resulting from WES have been published, there are few reports with long-term follow-up that confirm a sustained therapeutic response. Following a diagnosis by WES of Brown–Vialetto–Van Laere Syndrome 2 (BVVLS2), high-dose riboflavin therapy was instituted in a 20-mo-old child. An immediate clinical response with stabilization of signs and symptoms was noted over the first 2–4 wk. Subsequent clinical follow-up over the following 8 mo demonstrates not just stabilization, but continuing and sustained improvements in all manifestations of this usually fatal condition, which generally includes worsening motor weakness, sensory ataxia, hearing, and vision impairments. This case emphasizes that early application of WES can transform patient care, enabling therapy that in addition to being lifesaving can sometimes reverse the disabling disease processes in a progressive condition. PMID:27148562

Development and in vitro evaluation of expandable gastroretentive dosage forms based on compressed collagen sponges.

PubMed

Gröning, R; Cloer, C; Müller, R S

2006-07-01

The objective of this study was to develop and evaluate new collagen gastroretentive dosage forms (GRDFs) which expand in the stomach after contact with gastric fluids. The GRDFs should remain in the stomach for a prolonged period of time due to their size. The dosage forms were prepared from collagen sponges. The sponges were manufactured by freeze-drying a riboflavin-containing collagen solution. A computer controlled material supply was constructed to transport precompressed collagen into a tablet machine. A second type of tablet was manufactured by combining compressed collagen sponges with hydrophilic matrix layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or aciclovir were developed. In vitro experiments were performed with both types of dosage forms. The collagen tablets expand within a few minutes after contact with artificial gastric juice and form a drug delivery system with a size of 8 mm x 18 mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the release of aciclovir or captopril can be controlled by the composition of the sustained release layer.

Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering.

PubMed

Heo, Jiseung; Koh, Rachel H; Shim, Whuisu; Kim, Hwan D; Yim, Hyun-Gu; Hwang, Nathaniel S

2016-04-01

A meniscus tear is a common knee injury, but its regeneration remains a clinical challenge. Recently, collagen-based scaffolds have been applied in meniscus tissue engineering. Despite its prevalence, application of natural collagen scaffold in clinical setting is limited due to its extremely low stiffness and rapid degradation. The purpose of the present study was to increase the mechanical properties and delay degradation rate of a collagen-based scaffold by photo-crosslinking using riboflavin (RF) and UV exposure. RF is a biocompatible vitamin B2 that showed minimal cytotoxicity compared to conventionally utilized photo-initiator. Furthermore, collagen photo-crosslinking with RF improved mechanical properties and delayed enzyme-triggered degradation of collagen scaffolds. RF-induced photo-crosslinked collagen scaffolds encapsulated with fibrochondrocytes resulted in reduced scaffold contraction and enhanced gene expression levels for the collagen II and aggrecan. Additionally, hyaluronic acid (HA) incorporation into photo-crosslinked collagen scaffold showed an increase in its retention. Based on these results, we demonstrate that photo-crosslinked collagen-HA hydrogels can be potentially applied in the scaffold-based meniscus tissue engineering.

Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin

PubMed Central

Jankowitsch, Frank; Schwarz, Julia; Rückert, Christian; Gust, Bertolt; Szczepanowski, Rafael; Blom, Jochen; Pelzer, Stefan; Kalinowski, Jörn

2012-01-01

Streptomyces davawensis JCM 4913 synthesizes the antibiotic roseoflavin, a structural riboflavin (vitamin B2) analog. Here, we report the 9,466,619-bp linear chromosome of S. davawensis JCM 4913 and a 89,331-bp linear plasmid. The sequence has an average G+C content of 70.58% and contains six rRNA operons (16S-23S-5S) and 69 tRNA genes. The 8,616 predicted protein-coding sequences include 32 clusters coding for secondary metabolites, several of which are unique to S. davawensis. The chromosome contains long terminal inverted repeats of 33,255 bp each and atypical telomeres. Sequence analysis with regard to riboflavin biosynthesis revealed three different patterns of gene organization in Streptomyces species. Heterologous expression of a set of genes present on a subgenomic fragment of S. davawensis resulted in the production of roseoflavin by the host Streptomyces coelicolor M1152. Phylogenetic analysis revealed that S. davawensis is a close relative of Streptomyces cinnabarinus, and much to our surprise, we found that the latter bacterium is a roseoflavin producer as well. PMID:23043000

Dual-Targeting Small-Molecule Inhibitors of the Staphylococcus aureus FMN Riboswitch Disrupt Riboflavin Homeostasis in an Infectious Setting.

PubMed

Wang, Hao; Mann, Paul A; Xiao, Li; Gill, Charles; Galgoci, Andrew M; Howe, John A; Villafania, Artjohn; Barbieri, Christopher M; Malinverni, Juliana C; Sher, Xinwei; Mayhood, Todd; McCurry, Megan D; Murgolo, Nicholas; Flattery, Amy; Mack, Matthias; Roemer, Terry

2017-05-18

Riboswitches are bacterial-specific, broadly conserved, non-coding RNA structural elements that control gene expression of numerous metabolic pathways and transport functions essential for cell growth. As such, riboswitch inhibitors represent a new class of potential antibacterial agents. Recently, we identified ribocil-C, a highly selective inhibitor of the flavin mononucleotide (FMN) riboswitch that controls expression of de novo riboflavin (RF, vitamin B2) biosynthesis in Escherichia coli. Here, we provide a mechanistic characterization of the antibacterial effects of ribocil-C as well as of roseoflavin (RoF), an antimetabolite analog of RF, among medically significant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. We provide genetic, biophysical, computational, biochemical, and pharmacological evidence that ribocil-C and RoF specifically inhibit dual FMN riboswitches, separately controlling RF biosynthesis and uptake processes essential for MRSA growth and pathogenesis. Such a dual-targeting mechanism is specifically required to develop broad-spectrum Gram-positive antibacterial agents targeting RF metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of copper(II) the activity of glutathione peroxidase in patients with head and neck cancer.

PubMed

Malinowska, Katarzyna; Morawiec-Sztandera, Alina; Majsterek, Ireneusz; Kaczmarczyk, Dariusz

2016-11-20

Head and neck squamous cell carcinoma (HNSCC) accounts for about 6% of all malignant cancers. In the epidemiology of oral cavity neoplasm, important risk factors include: tobacco smoking, alcohol abuse, bad oral hygiene, papilloma virus infection, riboflavin and iron deficiency. The objective of the investigation was a synthesis of Cu(II) complex and the evaluation of antioxidative enzymatic barrier in red blood cells of patients with head and neck tumor as well as in the control group. For the investigation conduction, a consent of Bioethics Committee number RNN/142/09/KB was obtained. Blood for the examination was obtained from the patients of the Dapartment of Head and Neck Neoplasms Surgery Medical University of Łódź. The experiment was conducted on the group of 40 patients with HNSCC and 40 healthy people, using spectrophotometric method, glutathione peroxidase was marked. The investigation was conducted on the hemolysate obtained from the patients that were divided into two groups - a study group (1 and 2), which consisted of patients diagnosed with head and neck cancer and a control group (1 and 2) - healthy people. A significant statistical result for GPX occurred in control-1 and study-1 group with complex compound Cu(II) (p<0,001). Presented research prove, that complex compound Cis-dichlorobis(N1-hydroxymethyl-3methylpyrazole-κN2)copper (II) has an impact on the activity of the antioxidative GPX enzyme.

Vitamins in Heart Failure: Friend or Enemy?

PubMed

Georgiopoulos, George; Chrysohoou, Christina; Vogiatzi, Georgia; Magkas, Nikolaos; Bournelis, Ippokratis; Bampali, Sofia; Gruson, Damien; Tousoulis, Dimitris

2017-01-01

The failing heart is characterized by a depleted metabolic energy reserve and the upregulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. The objective of the present study was to evaluate all available information on vitamins supplementation in patients with chronic HF for possible beneficial effect on metabolic, inotropic, chronotropic and hemodynamic indices. We searched MEDLINE via Pubmed by using the following terms: "chronic heart failure" OR "cardiomyopathy" AND "vitamins", "vitamin A", "B complex vitamins", "vitamin C", "ascorbic acid", "vitamin D", "retinol", "vitamin E", "thiamine", "riboflavin", "niacin", "pyridoxine", "cobalamin", "folate", "pantothenic acid", "biotin", "tocopherol" and combinations of them. Data regarding supplementation of micronutrients in HF for most vitamins were sparse, and the inference about cardiovascular outcomes was obscured by the heterogeneity of studies, high inherent morbidity, and mortality of this group of high-risk patients, limited sample sizes in certain studies, unclear design and lack of head to head comparisons. Most vitamins in human trials failed to offer survival, or robust beneficial effect. Mostly indirect favorable evidence is derived from patients with deficiencies of certain micronutrients rather than their ad hoc supplementation. While vitamins and micronutrients are promising compounds for optimizing myocardial metabolism and homeostasis in HF, additional randomized clinical trials of larger scale are warranted to demonstrate the benefits of their supplementation in this high risk group of patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Major contribution of the Ehrlich pathway for 2-phenylethanol/rose flavor production in Ashbya gossypii.

PubMed

Ravasio, Davide; Wendland, Jürgen; Walther, Andrea

2014-09-01

Aroma alcohols of fermented food and beverages are derived from fungal amino acids catabolism via the Ehrlich pathway. This linear pathway consists of three enzymatic reactions to form fusel alcohols. Regulation of some of the enzymes occurs on the transcriptional level via Aro80. The riboflavin overproducer Ashbya gossypii produces strong fruity flavours in contrast to its much less aromatic relative Eremothecium cymbalariae. Genome comparisons indicated that A. gossypii harbors genes for aromatic amino acid catabolism (ARO8a, ARO8b, ARO10, and ARO80) while E. cymbalariae only encodes ARO8a and thus lacks major components of aromatic amino acid catabolism. Volatile compound (VOC) analysis showed that both Eremothecium species produce large amounts of isoamyl alcohol while A. gossypii also produces high levels of 2-phenylethanol. Deletion of the A. gossypii ARO-genes did not confer any growth deficiencies. However, A. gossypii ARO-mutants (except Agaro8a) were strongly impaired in aroma production, particularly in the production of the rose flavour 2-phenylethanol. Conversely, overexpression of ARO80 via the AgTEF1 promoter resulted in 50% increase in VOC production. Together these data indicate that A. gossypii is a very potent flavour producer and that amongst the non-Saccharomyces biodiversity strains can be identified that could provide positive sensory properties to fermented beverages. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

High-concentrate diets based on forages harvested at different maturity stages affect ruminal synthesis of B vitamins in lactating dairy cows.

PubMed

Castagnino, D S; Kammes, K L; Allen, M S; Gervais, R; Chouinard, P Y; Girard, C L

2017-04-01

Effects of plant maturity on apparent ruminal synthesis and post-ruminal supply of B vitamins were evaluated in two feeding trials. Diets containing alfalfa (Trial 1) or orchardgrass (Trial 2) silages harvested either (1) early cut, less mature (EC) or (2) late cut, more mature (LC) as the sole forage were offered to ruminally and duodenally cannulated lactating Holstein cows in crossover design experiments. In Trial 1, conducted with 16 cows (569±43 kg of empty BW (ruminal content removed) and 43.7±8.6 kg/day of 3.5% fat-corrected milk yield; mean±SD) in two 17-day treatment periods, both diets provided ~22% forage NDF and 27% total NDF, and the forage-to-concentrate ratios were 53 : 47 and 42 : 58 for EC and LC, respectively. In Trial 2, conducted with 13 cows (588±55 kg of empty BW and 43.7±7.7 kg/day of 3.5% fat-corrected milk yield; mean±SD) in two 18-day treatment periods, both diets provided ~25% forage NDF and 31% total NDF; the forage-to-concentrate ratios were 58 : 42 and 46 : 54 for EC and LC, respectively. Thiamin, riboflavin, niacin, vitamin B6, folates and vitamin B12 were measured in feed and duodenal content. Apparent ruminal synthesis was calculated as the duodenal flow minus the intake. Diets based on EC alfalfa decreased the amounts of thiamin, niacin and folates reaching the duodenum, whereas diets based on EC orchardgrass increased riboflavin duodenal flow. Daily apparent ruminal synthesis of thiamin, riboflavin, niacin and vitamin B6 were correlated negatively with their intake, suggesting a microbial regulation of their concentration in the rumen. Vitamin B12 apparent ruminal synthesis was correlated negatively with total volatile fatty acids concentration, but positively with ruminal pH and microbial N duodenal flow.

Corneal biomechanical properties from two-dimensional corneal flap extensiometry: application to UV-riboflavin cross-linking.

PubMed

Kling, Sabine; Ginis, Harilaos; Marcos, Susana

2012-07-27

Corneal biomechanical properties are usually measured by strip extensiometry or inflation methods. We developed a two-dimensional (2D) flap extensiometry technique, combining the advantages of both methods, and applied it to measure the effect of UV-Riboflavin cross-linking (CXL). Corneal flaps (13 pig/8 rabbit) from the de-epithelialized anterior stroma (96 μm) were mounted on a custom chamber, consisting of a BK7 lens, a reflective retina, and two reservoirs (filled with Riboflavin and silicone oil). Stretching the corneal flap during five pressure increase/decrease cycles (0-30 mm Hg) changed the refractive power of the system, whose Zernike aberrations were monitored with a ray-tracing aberrometer. Porcine flaps were used to test the system. Rabbits were treated with CXL unilaterally in vivo following standard clinical procedures. Flaps were measured 1 month postoperatively. An analytical model allowed estimating Young's modulus from the change in surface (strain) and pressure (stress). Confocal microscopy examination was performed before, and at different times after CXL. Flap curvature changed with increased function of IOP in pig flaps (23.4 × 10⁻³ D/mm Hg). In rabbit flaps curvature changed significantly less in 1 month post CXL (P = 0.026) than in untreated corneas [17.0 vs. 6.36 millidiopter (mD)/mm Hg]. Young's modulus was 2.29 megapascals (MPa) in porcine corneas, 1.98 MPa in untreated rabbit corneas, and 4.83 MPa in 1 month post CXL rabbit corneas. At the same time, highly reflective structures were observed in the rabbit midstroma after treatment. 2D flap extensiometry allows estimating corneal elasticity in vitro. The measurements are spatially resolved in depth, minimize the effects of corneal hydration, and preserve the integrity of the cornea. The method proved the efficacy of CXL in increasing corneal rigidity after 1 month in rabbits.

Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion.

PubMed

Feys, H B; Van Aelst, B; Devreese, K; Devloo, R; Coene, J; Vandekerckhove, P; Compernolle, V

2014-05-01

Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF-PRT). Activity and antigen of plasma components were determined following RF-PRT in the presence or absence of dissolved molecular oxygen. Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23 ± 8% and 29 ± 9% (n = 24), respectively, which corroborates with a mean decrease of 25% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF-PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3·1 ± 0·8 vs. 1·6 ± 0·5 nmol/mg protein) following RF-PRT, but not in the absence of dissolved molecular oxygen (1·8 ± 0·4 nmol/mg). RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process. © 2013 International Society of Blood Transfusion.

Photochemical inactivation of lymphocytes by riboflavin with visible light for TA-GVHD prevention.

PubMed

Mo, Qin; Huang, Yuwen; Wang, Li; Cheng, Zhenzhen; Wu, Xiaofei; Jia, Yao; Wang, Xun; Zhang, Bo

2017-09-01

Transfusion-associated graft-versus-host disease (TA-GVHD) is a life-threatening complication caused by the input of a number of immunocompetent allogeneic lymphocytes. This study focus on the photochemical effects of riboflavin excited by visible light (RB+L) treatment on human lymphocytes, to study the feasibility of using RB+L treatment to prevent adverse immune reactions caused by transfused lymphocytes. 100μM riboflavin was added to lymphocyte suspensions. After exposure to 400-580nm visible light with a total energy of 40J/mL, cells were cultured and the ability of proliferation and cytokine secretion were assayed upon stimuli. Meanwhile, lymphocytes were also treated by gamma-irradiation as parallel to testify the inactivation effect of RB+L. Results showed that γ-irradiation and RB+L treated cells showed a decline in cell viability. After stimulation of phytohemagglutinin (PHA) or anti-CD3 together with anti-CD28, proliferative ability of RB+L treated cells was strongly inhibited when compared to untreated cells. The inhibitive rates of proliferation in RB+L group were also higher than those of cells treated by γ-irradiation. Results of CFSE assays also illustrated hardly any cell division of RB+L and γ-irradiation treated lymphocytes. Besides low level productions of IL-4 and IL-12, cytokine production of TNF-α, IFN-γ and IL-10 by incubation with PHA or IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γ stimulated by anti-CD3 plus anti-CD28 were suppressed after treatment of RB+L significantly. It was suggested that RB+L/γ-irradiation treatment induced cell apoptosis. These results indicated that RB+L treatment functionally inactivated lymphocytes by inhibiting cell proliferation and cytokine production. RB+L might be an alternative for TA-GVHD prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Vitamins B2 and B6 as determinants of kynurenines and related markers of interferon-γ-mediated immune activation in the community-based Hordaland Health Study.

PubMed

Theofylaktopoulou, Despoina; Ulvik, Arve; Midttun, Øivind; Ueland, Per Magne; Vollset, Stein Emil; Nygård, Ottar; Hustad, Steinar; Tell, Grethe S; Eussen, Simone J P M

2014-10-14

Vitamins B2 and B6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of vitamins B2 and B6 as determinants of kynurenines and two markers of interferon-γ-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of vitamins B2 and B6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of vitamins B2 and B6 was assessed using a validated FFQ. Associations were investigated using partial Spearman's correlations, generalised additive models, and segmented or multiple linear regression. The B2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The vitamin B6 vitamer, pyridoxal 5'-phosphate (PLP), was positively associated with most kynurenines at PLP concentrations < 39·3-47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations < 18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by vitamin status. Future studies on B-vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-vitamins status and tryptophan metabolism.

21 CFR 184.1697 - Riboflavin-5′-phosphate (sodium).

Code of Federal Regulations, 2014 CFR

2014-04-01

... limitation other than current good manufacturing practice. The affirmation of this ingredient as generally recognized as safe (GRAS) as a direct human food ingredient is based upon the following current good... § 170.3(o)(20) of this chapter. (2) The ingredient is used in milk products, as defined in § 170.3(n)(31...

GREEN AND CONTROLLED SYNTHESIS OF GOLD AND PLATINUM NANOMATERIALS USING VITAMIN B2: DENSITY-ASSISTED SELF-ASSEMBLY OF NANOSPHERES, WIRES AND RODS

EPA Science Inventory

For the first time, we report density-assisted self-assembly and efficient synthesis of gold (Au) and platinum (Pt) nanospheres, nanowires and nanorods using vitamin B₂ (riboflavin) without employing any special capping or dispersing agent at room temperature; this env...

Determinants of health and nutritional status of rural Nigerian women.

PubMed

Ene-Obong, H N; Enugu, G I; Uwaegbute, A C

2001-12-01

This study was undertaken to determine the effects of socioeconomic and cultural factors on the health and nutritional status of 300 women of childbearing age in two rural farming communities in Enugu State, Nigeria. The women were engaged in farming, trading, and teaching. A cross-sectional survey was conducted using both qualitative and quantitative data-collection methods. The study involved focus-group discussions (FGDs), interviews using a questionnaire, measurement of food/nutrient intake, assessment of activity patterns, anthropometry, and observations of clinical signs of malnutrition. The better-educated women had higher incomes than those with little or no education. Poor education was mainly attributed to lack of monetary support by parents (34%), marriage while in school (27%), and sex discrimination (21%). The teachers had significantly (p < 0.05) better health status, health and nutrition knowledge, food habits, nutrient intake, and self-concept, and adhered less to detrimental cultural practices. However, none of the women met their iron, riboflavin and niacin requirements. More cases of chronic energy deficiency were observed among the farmers (16%) and traders (13%) than among the teachers (5%). Generally, the women worked long hours with reported working hours (6-7 hours) being lower than the observed working hours (11 hours) for the traders and teachers. Income had a significant (p < 0.05) positive correlation with all nutritional variables, except vitamin C, age-at-marriage (r = 0.719), and nutrition knowledge (r = 0.601). Age-at-marriage had a positive correlation with body mass index (BMI) and all nutritional variables but was significant (p < 0.05) for protein (r = 0.362), calcium (r = 0.358), iron (r = 0.362), riboflavin (r = 0.364), and vitamin C (r = 0.476). Workload was negatively correlated with protein intake (r = 0.346; p < 0.05). Meal frequencies for more than 70% of the farmers and petty traders and 42% of the teachers were dependent on the availability of food in the household. Food taboos had no effect on their nutrient intake, since only 5-11% of women adhered to taboos. Although most women gave their children and husbands preference in food distribution, not much difference was found in the amount of food consumed by these women. The ratio of wife's portion to husband's was 1:1.4 for the farmers, 1:1.3 for the traders, and 1:1.2 for the teachers. FGDs revealed that sex discrimination in education prevailed where resources were limited. The results of the study suggest that the basic determinants of health and nutritional status of women are socioeconomic and cultural, education having a mediating or modifying influence on cultural practices.

Microbiology of Fresh Comminuted Turkey Meat

DTIC Science & Technology

1976-04-12

823 Reprinted from J. Milk Food Technol. Vol. 39. No. 12. Pages 823-829 (December. 1976) Cooyright 1976, International Association of Milk , Food, and...most probable number (MPN) method (13). niacin, and riboflavin (29). Canadian officials have proposed microbial standards The literature contains...onto Mueller-Hinton agar plates containing 5% various retail markets in the San Francisco Bay Area. They were defibrinated sheep blood. Representative

Effect of amino acids and vitamins on laccase production by the bird's nest fungus Cyathus bulleri.

PubMed

Dhawan, Shikha; Kuhad, Ramesh Chander

2002-08-01

Various amino acids, their analogues and vitamins have shown stimulatory as well as inhibitory effects on laccase production by Cyathus bulleri. DL-methionine, DL-tryptophan, glycine and DL-valine stimulated laccase production, while L-cysteine monohydrochloride completely inhibited the enzyme production. Among vitamins tested biotin, riboflavin and pyridoxine hydrochloride were found to induce laccase production.

DEVELOPMENT OF EVALUATION OF A QUANTITATIVE VIDEO-FLUORESCENCE IMAGING SYSTEM AND FLUORESCENT TRACER FOR MEASURING TRANSFER OF PESTICIDE RESIDUES FROM SURFACES TO HANDS WITH REPEATED CONTACTS

EPA Science Inventory

A video imaging system and the associated quantification methods have been developed for measurement of the transfers of a fluorescent tracer from surfaces to hands. The highly fluorescent compound riboflavin (Vitamin B2), which is also water soluble and non-toxic, was chosen as...

21 CFR 104.47 - Frozen “heat and serve” dinner.

Code of Federal Regulations, 2013 CFR

2013-04-01

... § 104.5(b), shall contain at least the following three components: (1) One or more sources of protein... selected so that one or more of the listed protein sources of paragraph (a)(1) of this section, excluding... 150.00 520.0 Thiamine, mg .05 .2 Riboflavin, mg .06 .2 Niacin, mg .99 3.4 Pantothenic acid, mg .32 1.1...

21 CFR 104.47 - Frozen “heat and serve” dinner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... § 104.5(b), shall contain at least the following three components: (1) One or more sources of protein... selected so that one or more of the listed protein sources of paragraph (a)(1) of this section, excluding... 150.00 520.0 Thiamine, mg .05 .2 Riboflavin, mg .06 .2 Niacin, mg .99 3.4 Pantothenic acid, mg .32 1.1...

21 CFR 104.47 - Frozen “heat and serve” dinner.

Code of Federal Regulations, 2011 CFR

2011-04-01

... § 104.5(b), shall contain at least the following three components: (1) One or more sources of protein... selected so that one or more of the listed protein sources of paragraph (a)(1) of this section, excluding... 150.00 520.0 Thiamine, mg .05 .2 Riboflavin, mg .06 .2 Niacin, mg .99 3.4 Pantothenic acid, mg .32 1.1...

21 CFR 104.47 - Frozen “heat and serve” dinner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... § 104.5(b), shall contain at least the following three components: (1) One or more sources of protein... selected so that one or more of the listed protein sources of paragraph (a)(1) of this section, excluding... 150.00 520.0 Thiamine, mg .05 .2 Riboflavin, mg .06 .2 Niacin, mg .99 3.4 Pantothenic acid, mg .32 1.1...

21 CFR 104.47 - Frozen “heat and serve” dinner.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 104.5(b), shall contain at least the following three components: (1) One or more sources of protein... selected so that one or more of the listed protein sources of paragraph (a)(1) of this section, excluding... 150.00 520.0 Thiamine, mg .05 .2 Riboflavin, mg .06 .2 Niacin, mg .99 3.4 Pantothenic acid, mg .32 1.1...

Surface-enhanced Raman scattering (SERS) of riboflavin on nanostructured Ag surfaces: The role of excitation wavelength, plasmon resonance and molecular resonance

NASA Astrophysics Data System (ADS)

Šubr, Martin; Kuzminova, Anna; Kylián, Ondřej; Procházka, Marek

2018-05-01

Optimization of surface-enhanced Raman scattering (SERS)-based sensors for (bio)analytical applications has received much attention in recent years. For optimum sensitivity, both the nanostructure fabrication process and the choice of the excitation wavelength used with respect to the specific analyte studied are of crucial importance. In this contribution, detailed SERS intensity profiles were measured using gradient nanostructures with the localized surface-plasmon resonance (LSPR) condition varying across the sample length and using riboflavin as the model biomolecule. Three different excitation wavelengths (633 nm, 515 nm and 488 nm) corresponding to non-resonance, pre-resonance and resonance excitation with respect to the studied molecule, respectively, were tested. Results were interpreted in terms of a superposition of the enhancement provided by the electromagnetic mechanism and intrinsic properties of the SERS probe molecule. The first effect was dictated mainly by the degree of spectral overlap between the LSPR band, the excitation wavelength along with the scattering cross-section of the nanostructures, while the latter was influenced by the position of the molecular resonance with respect to the excitation wavelength. Our experimental findings contribute to a better understanding of the SERS enhancement mechanism.

Nonlinear optical collagen cross-linking and mechanical stiffening: a possible photodynamic therapeutic approach to treating corneal ectasia

PubMed Central

Chai, Dongyul; Juhasz, Tibor; Brown, Donald J.

2013-01-01

Abstract. In this study we test the hypothesis that nonlinear optical (NLO) multiphoton photoactivation of riboflavin using a focused femtosecond (FS) laser light can be used to induce cross-linking (CXL) and mechanically stiffen collagen as a potential clinical therapy for the treatment of keratoconus and corneal ectasia. Riboflavin-soaked, compressed collagen hydrogels are cross-linked using a FS laser tuned to 760 nm and set to either 100 mW (NLO CXL I) or 150 mW (NLO CXL II) of laser power. FS pulses are focused into the hydrogel using a 0.75 NA objective lens, and the hydrogel is three-dimensionally scanned. Measurement of hydrogel stiffness by indentation testing show that the calculated elastic modulus (E) values are significantly increased over twofold following NLO CXL I and II compared with baseline values (P<0.05). Additionally, no significant differences are detected between NLO CXL and single photon, UVA CXL (P>0.05). This data suggests that NLO CXL has a comparable effect to conventional UVA CXL in mechanically stiffening collagen and may provide a safe and effective approach to localize CXL at different regions and depths within the cornea. PMID:23515869

Recent advances in bulbar syndromes: genetic causes and disease mechanisms.

PubMed

Manole, Andreea; Fratta, Pietro; Houlden, Henry

2014-10-01

With advances in next-generation gene sequencing, progress in deep phenotyping and a greater understanding of the pathogenesis of motor neuron disease, our knowledge of the progressive bulbar syndromes has significantly increased in recent years. This group of heterogeneous conditions, in which the primary disorder is focused around degeneration of the lower cranial nerves, can occur in children or adults and form a spectrum of severity, based around the common feature of bulbar dysfunction. Early genetic diagnosis may allow treatment in some bulbar syndromes. Brown-Vialetto-Van Laere and Fazio-Londe syndromes are the most recent childhood forms of progressive bulbar palsy to be genetically defined. The clinical phenotype of this group of childhood disorders was first reported over 120 years ago. Recently, it was demonstrated that in a third of these patients Brown-Vialetto-Van Laere is caused by mutations in the SLC52A2 and SLC52A3 genes, both of which encode riboflavin transporters. Importantly, supplementation of riboflavin can lead to significant clinical improvement if started early in the disease process. Here, we outline the clinical features, management and an update on the disease mechanisms and genetic causes of the progressive bulbar syndromes.

Nutritional and food protection against epidemic emerging neuropathy. Epidemiological findings in the unique disease-free urban area of Cuba.

PubMed

Barnouin, J; Verdura Barrios, T; Chassagne, M; Pérez Cristiá, R; Arnaud, J; Fleites Mestre, P; Montoya, M E; Favier, A

2001-09-01

A survey was conducted through the SECUBA (SEguridad alimentaria en CUba y Buena Alimentación) research program in Cuban healthy smokers living in Guantánamo and in Havana. The aim of the survey was to investigate biological and nutritional factors connected with the occurrence of zero epidemic neuropathy (EN) observed in Guantánamo urban area since the disease emerged in Cuba. Blood riboflavin status and carotenoid and selenium concentrations were higher in Guantánamo than in Havana smokers. Food dietary quantities of plantain banana, pepper (Capsicum spp.), bovine meat and milk products were higher in Guantánamo. Inversely, foods rich in cholesterol, especially eggs, were more consumed in Havana. Through riboflavin, carotenoid and selenium contents and specific antioxidants substances (indoleamines, capsaicin), the foods more consumed in Guantánamo could be considered as EN protective factors. Disease protective effects could be exerted via enhancement of defence mechanisms against free radical damage and related mechanisms focused on redox recycling of glutathione and local protection from carotenoids. Finally, the results of the present study should help Cuba, through a better EN control, to improve long-term food safety and define healthier dietary habits.

Redox reaction characteristics of riboflavin: a fluorescence spectroelectrochemical analysis and density functional theory calculation.

PubMed

Chen, Wei; Chen, Jie-Jie; Lu, Rui; Qian, Chen; Li, Wen-Wei; Yu, Han-Qing

2014-08-01

Riboflavin (RF), the primary redox active component of flavin, is involved in many redox processes in biogeochemical systems. Despite of its wide distribution and important roles in environmental remediation, its redox behaviors and reaction mechanisms in hydrophobic sites remain unclear yet. In this study, spectroelectrochemical analysis and density functional theory (DFT) calculation were integrated to explore the redox behaviors of RF in dimethyl sulfoxide (DMSO), which was used to create a hydrophobic environment. Specifically, cyclic voltafluorometry (CVF) and derivative cyclic voltafluorometry (DCVF) were employed to track the RF concentration changing profiles. It was found that the reduction contained a series of proton-coupled electron transfers dependent of potential driving force. In addition to the electron transfer-chemical reaction-electron transfer process, a disproportionation (DISP1) process was also identified to be involved in the reduction. The redox potential and free energy of each step obtained from the DFT calculations further confirmed the mechanisms proposed based on the experimental results. The combination of experimental and theoretical approaches yields a deep insight into the characteristics of RF in environmental remediation and better understanding about the proton-coupled electron transfer mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Photoinduced collagen cross-linking: a new approach to venous insufficiency.

PubMed

Frullini, Alessandro; Manetti, Leonardo; Di Cicco, Emiliano; Fortuna, Damiano

2011-08-01

What little research has been done on methods of venous valve function recovery with radiofrequency has had disappointing results. Valvuloplasty has some supporters, but the majority of physicians do not consider it a valid therapeutic option. To test a new method of treating varicose veins based on their collagen structure. This procedure it is not a thermal treatment, but it is fast, with significant shrinking and preservation of the endothelium. In the laboratory, we subjected greater saphenous vein specimens to irradiation with a blue light-emitting diode generated (wavelength 450-480 nm) while a riboflavin solution (vitamin B2) was administered. The riboflavin acts as a cross-linking agent, and the blue light as the activator. In this photo-induced reaction, oxygen singlet is produced with oxidative deamination, forming new covalent bonds between collagen fibrils and water. In venous specimens, we demonstrated fast and significant shrinkaged without histologic evidence of endothelial damage and with evident change in mechanical properties of varicose veins. Photochemically induced collagen cross-linking to restructure varicose veins is only a research field but may become an important tool for recovery of vein diameter and valve function. © 2011 by the American Society for Dermatologic Surgery, Inc.

Effect of gamma irradiation on the thiamine, riboflavin and vitamin B 6 content in two varieties of Brazilian beans

NASA Astrophysics Data System (ADS)

Villavicencio, A. L. C. H. A. L. C. H.; Mancini-Filho, J. J.; Delincée, H. H.; Bognár, A. A.

2000-03-01

The effect of 60Co gamma rays on the content of several B-vitamins in two varieties of Brazilian beans has been studied. Carioca ( Phaseolus vulgaris L. var. Carioca) and Macaçar beans ( Vigna unguiculata L. Walp, var. Macaçar) were irradiated at doses of 0, 0.5, 1.0, 2.5, 5.0 and 10 kGy, and subsequently stored at ambient temperature for 6 months. The content of vitamin B 1, B 2 and B 6 was analysed by HPLC. In addition, the optimum cooking time was established for each dose and bean variety. A taste panel evaluated sensory properties. Only slight changes were measured for thiamine and riboflavin, whereas a dose-dependent decrease was noted for pyridoxine, which, however, was significant only at the highest doses of 5 and 10 kGy. Cooking time was considerably reduced with increasing radiation dose, but accompanied by a loss of the sensory quality. However, at the disinfestation dose up to 1 kGy, acceptable ratings were obtained for the sensory evaluation. In conclusion, for insect disinfestation of Brazilian beans radiation processing is a promising technology.

The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity.

PubMed

Capel, I D; Jenner, M; Williams, D C; Donaldson, D; Nath, A

1981-08-01

A clinical study was undertaken to determine whether oral contraceptives (OCs) affect the activity of the enzyme glutathione peroxidase. OC users recruited for the study were volunteers attending the Redhill Family Planning Clinic in England. Their demographic characteristics were noted. Pre- and postmenopausal comparative subjects were also used. The laboratory procedures involved in the study are described. Findings are tabulated. The average erythrocyte glutathione peroxidase levels of women using OCs for more than 7 months were significantly higher than those of the pre- and postmenopausal subjects. These levels increased progressively with duration of OC use. These levels did not fluctuate with the menstrual cycle in either OC or non-OC users. Levels of erythrocyte selenium and plasma pyridoxal were not significantly altered by OC use. Riboflavin status, however, as estimated by glutathione reductase activity was substantially lower in OC users and was lowest in women who had used OCs for the longest amount of time. Riboflavin status was found to be directly correlated with erythrocyte glutathione peroxidase levels. These findings may be important because selenium is currently believed to offer protective benefits against carcinogenesis, especially breast cancer. All the OCs studied produced the same effects.

A comparison of food pattern, macro- and some micronutrients density of the diet across different socio-economic zones of Tehran

PubMed Central

Abdollahi, Morteza; Salehi, Forouzan; Kalantari, Naser; Asadilari, Mohsen; Khoshfetrat, Mohammad Reza; Ajami, Marjan

2016-01-01

Background: The consumption of low quality foods is common in low socioeconomic areas; and according to epidemiological studies, the density of nutrients often proves the quality of diet. This study aimed to compare the density of macronutrients and micronutrients in various parts of Tehran. Methods: This was a cross-sectional study performed from September to December 2007 in all the 22 districts of the municipality of Tehran including 1,807 households. Experienced interviewers completed a 24-hour recall questionnaire. To estimate the nutrient densities, nutrient intake (grams or milligrams) was calculated per 1,000 kcal energy intake. To calculate the density of energy intake, energy intake (kcal) was divided by 100 g of foodstuff. The 22 districts of Tehran were divided into five zones of north, center, east, west and south. ANOVA and Tukey tests were used. Results: The highest density of protein and fat intake was observed in the north of Tehran, while carbohydrate density was highest in the west, east and south zones, and energy density was highest in the south zone (p<0.05). Calcium and vitamin C had the highest density in the north of Tehran, and vitamin A and riboflavin had the highest density in the north and center of Tehran, and the lowest level in the south of Tehran (p<0.05). Conclusion: Despite the high density of energy in the south of Tehran, a deficiency of micronutrient intake was obvious, reflecting the importance of the impact of socioeconomic factors. PMID:27390710

Folic acid is a potent chemoattractant of free-living amoebae in a new and amazing species of protist, Vahlkampfia sp.

PubMed

Maeda, Yasuo; Mayanagi, Taira; Amagai, Aiko

2009-03-01

Folic acid (folate; vitamin Bc) is well recognized as essential for the proper metabolism of the essential amino acid methionine as well as for the synthesis of adenine and thymine. A folate deficiency has been Implicated in a wide variety of disorders from Alzheimer's disease to depression and neural tube defects. In the cellular slime molds, including Dictyostelium, vegetative growth-phase cells are known to chemotactically move toward folate that is secreted by bacterial food sources such as Escherichia coli. Intracellular folate signal transductlon, including G proteins, Ca(2+)channels, and the PIP3 pathway, has been reported in D. discoideum. To our surprise, the genuine chemoattractant(s) of free-living protozoan amoebae have remained to be determined, possibly because of lack of a pertinent method for assaying chemotaxis. We recently isolated a primitive free-living amoeba from the soil of Costa Rica and identified it as a new species of the genus Vahlkampfia belonging to Subclass Gymnamoebia, which includes Entamoeba and Acanthamoeba. The amoebae can grow and multiply quite rapidly, engulfing nearby bacteria such as E. coli. Importantly, we have demonstrated here using a quite simple but finely designed chemotaxis assay that the Vahlkampfia amoebae exhibit chemotaxis toward higher folate concentrations. Riboflavin and cyanocobalamin were also found to serve as positive chemoattractants. Among these chemoattractants, folate is of particular importance because its function seems to be evolutionarily conserved as a potent chemoattractant of amoeboid cells in a wide range of organisms as well as in the Protista and cellular slime molds.

By their genes ye shall know them: genomic signatures of predatory bacteria

PubMed Central

Pasternak, Zohar; Pietrokovski, Shmuel; Rotem, Or; Gophna, Uri; Lurie-Weinberger, Mor N; Jurkevitch, Edouard

2013-01-01

Predatory bacteria are taxonomically disparate, exhibit diverse predatory strategies and are widely distributed in varied environments. To date, their predatory phenotypes cannot be discerned in genome sequence data thereby limiting our understanding of bacterial predation, and of its impact in nature. Here, we define the ‘predatome,' that is, sets of protein families that reflect the phenotypes of predatory bacteria. The proteomes of all sequenced 11 predatory bacteria, including two de novo sequenced genomes, and 19 non-predatory bacteria from across the phylogenetic and ecological landscapes were compared. Protein families discriminating between the two groups were identified and quantified, demonstrating that differences in the proteomes of predatory and non-predatory bacteria are large and significant. This analysis allows predictions to be made, as we show by confirming from genome data an over-looked bacterial predator. The predatome exhibits deficiencies in riboflavin and amino acids biosynthesis, suggesting that predators obtain them from their prey. In contrast, these genomes are highly enriched in adhesins, proteases and particular metabolic proteins, used for binding to, processing and consuming prey, respectively. Strikingly, predators and non-predators differ in isoprenoid biosynthesis: predators use the mevalonate pathway, whereas non-predators, like almost all bacteria, use the DOXP pathway. By defining predatory signatures in bacterial genomes, the predatory potential they encode can be uncovered, filling an essential gap for measuring bacterial predation in nature. Moreover, we suggest that full-genome proteomic comparisons are applicable to other ecological interactions between microbes, and provide a convenient and rational tool for the functional classification of bacteria. PMID:23190728

Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency

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

Xia, Chuanwu; Panda, Satya P.; Marohnic, Christopher C.

2012-03-15

NADPH-cytochrome P450 oxidoreductase (CYPOR) is essential for electron donation to microsomal cytochrome P450-mediated monooxygenation in such diverse physiological processes as drug metabolism (approximately 85-90% of therapeutic drugs), steroid biosynthesis, and bioactive metabolite production (vitamin D and retinoic acid metabolites). Expressed by a single gene, CYPOR's role with these multiple redox partners renders it a model for understanding protein-protein interactions at the structural level. Polymorphisms in human CYPOR have been shown to lead to defects in bone development and steroidogenesis, resulting in sexual dimorphisms, the severity of which differs significantly depending on the degree of CYPOR impairment. The atomic structure ofmore » human CYPOR is presented, with structures of two naturally occurring missense mutations, V492E and R457H. The overall structures of these CYPOR variants are similar to wild type. However, in both variants, local disruption of H bonding and salt bridging, involving the FAD pyrophosphate moiety, leads to weaker FAD binding, unstable protein, and loss of catalytic activity, which can be rescued by cofactor addition. The modes of polypeptide unfolding in these two variants differ significantly, as revealed by limited trypsin digestion: V492E is less stable but unfolds locally and gradually, whereas R457H is more stable but unfolds globally. FAD addition to either variant prevents trypsin digestion, supporting the role of the cofactor in conferring stability to CYPOR structure. Thus, CYPOR dysfunction in patients harboring these particular mutations may possibly be prevented by riboflavin therapy in utero, if predicted prenatally, or rescued postnatally in less severe cases.« less

Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif.

PubMed

Er, Tze-Kiong; Chen, Chih-Chieh; Liu, Yen-Yi; Chang, Hui-Chiu; Chien, Yin-Hsiu; Chang, Jan-Gowth; Hwang, Jenn-Kang; Jong, Yuh-Jyh

2011-10-21

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disease caused by the defects in the mitochondrial electron transfer system and the metabolism of fatty acids. Recently, mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene, encoding electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) have been reported to be the major causes of riboflavin-responsive MADD. To date, no studies have been performed to explore the functional impact of these mutations or their mechanism of disrupting enzyme activity. High resolution melting (HRM) analysis and sequencing of the entire ETFDH gene revealed a novel mutation (p.Phe128Ser) and the hotspot mutation (p.Ala84Thr) from a patient with MADD. According to the predicted 3D structure of ETF:QO, the two mutations are located within the flavin adenine dinucleotide (FAD) binding domain; however, the two residues do not have direct interactions with the FAD ligand. Using molecular dynamics (MD) simulations and normal mode analysis (NMA), we found that the p.Ala84Thr and p.Phe128Ser mutations are most likely to alter the protein structure near the FAD binding site as well as disrupt the stability of the FAD binding required for the activation of ETF:QO. Intriguingly, NMA revealed that several reported disease-causing mutations in the ETF:QO protein show highly correlated motions with the FAD-binding site. Based on the present findings, we conclude that the changes made to the amino acids in ETF:QO are likely to influence the FAD-binding stability.

Computational analysis of a novel mutation in ETFDH gene highlights its long-range effects on the FAD-binding motif

PubMed Central

2011-01-01

Background Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an autosomal recessive disease caused by the defects in the mitochondrial electron transfer system and the metabolism of fatty acids. Recently, mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene, encoding electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) have been reported to be the major causes of riboflavin-responsive MADD. To date, no studies have been performed to explore the functional impact of these mutations or their mechanism of disrupting enzyme activity. Results High resolution melting (HRM) analysis and sequencing of the entire ETFDH gene revealed a novel mutation (p.Phe128Ser) and the hotspot mutation (p.Ala84Thr) from a patient with MADD. According to the predicted 3D structure of ETF:QO, the two mutations are located within the flavin adenine dinucleotide (FAD) binding domain; however, the two residues do not have direct interactions with the FAD ligand. Using molecular dynamics (MD) simulations and normal mode analysis (NMA), we found that the p.Ala84Thr and p.Phe128Ser mutations are most likely to alter the protein structure near the FAD binding site as well as disrupt the stability of the FAD binding required for the activation of ETF:QO. Intriguingly, NMA revealed that several reported disease-causing mutations in the ETF:QO protein show highly correlated motions with the FAD-binding site. Conclusions Based on the present findings, we conclude that the changes made to the amino acids in ETF:QO are likely to influence the FAD-binding stability. PMID:22013910

What Does It Cost to Improve Household Diets in Nepal? Using the Cost of the Diet Method to Model Lowest Cost Dietary Changes.

PubMed

Biehl, Erin; Klemm, Rolf D W; Manohar, Swetha; Webb, Patrick; Gauchan, Devendra; West, Keith P

2016-07-03

In Nepal, limited availability and affordability of nutritious foods contribute to malnutrition. To identify nutrient deficiencies in commonly consumed diets and model lowest cost changes that could improve diet quality in 3 agroecological zones of Nepal. In August to September 2014, we collected market price and women's food frequency data from 3 representative villages in Nepal's mountains (Mahat Gaun, Jumla, n = 181 households), hills (Sitapur, Arghakhanchi, n = 166), and terai (Saigaun, Banke, n = 232) and verified local diets during women's group discussions. Using the Cost of the Diet method, we compared models of the most nutritious version of a commonly consumed diet given locally available foods ("common diet") with the cheapest possible diet meeting nutrient requirements, including foods not currently available ("optimal diet"). The household common diet lacks sufficient vitamin B12, riboflavin, and calcium in the mountains; B6, B12, calcium, and iron in the hills; vitamin A, calcium, and iron in the terai. Adding fish to the mountain and hill diets and increasing dark green leafy vegetable consumption in all zones yielded nutritional adequacy. Optimal diets are more expensive than the common diet in the mountains and hills but less expensive in the terai. The modeled lowest cost diet commonly eaten in 3 Nepalese communities lacks key nutrients. Policies and interventions that increase market availability and consumption of vitamin B12- and calcium-rich fish and dark green leafy vegetables could improve local diets, particularly in the mountains and hills. © The Author(s) 2016.

19F NMR ligand perturbation studies on 6,7-bis(trifluoromethyl)-8-ribityllumazine-7-hydrates and the lumazine synthase complex of Bacillus subtilis. Site-directed mutagenesis changes the mechanism and the stereoselectivity of the catalyzed haloform-type reaction.

PubMed

Scheuring, J; Kugelbrey, K; Weinkauf, S; Cushman, M; Bacher, A; Fischer, M

2001-06-01

The riboflavin synthase/lumazine synthase complex of Bacillus subtilis catalyzes the last two steps in riboflavin biosynthesis. The protein comprises a capsid of 60 beta subunits with lumazine synthase activity and a core of three alpha subunits with riboflavin synthase activity. The beta subunits catalyze the formation of 6,7-dimethyl-8-ribityllumazine (3) from 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione (1) and 3,4-dihydroxy-2-butanone 4-phosphate (2). Complexes of recombinant lumazine synthase (beta(60) capsids) with 6-trifluoromethyl-7-oxo-8-ribityllumazine (10) as well as 7S- or 7R-6,7-bistrifluoromethyl-8-ribityllumazine hydrate (11) were studied by (19)F NMR spectroscopy. Despite the large molecular weight of approximately 960 kDa of the protein, spectra with separated signals of free and bound ligand could be obtained. An unusually large shift difference of 8 ppm was observed between the 7-trifluoromethyl signals of free and bound ligand for epimer B of 11 and the enzyme. The signal is sensitive to the replacement of amino acid residues F22 and H88. Lumazine synthase catalyzes the elimination of the 7-trifluoromethyl group of R-diastereomer epimer A in a haloform-like reaction. The elimination reaction is also catalyzed by F22 mutants. The H88R mutant displays an opposite stereoselectivity for epimer B and a greatly enhanced reaction rate. From a model of the epimers in the active site of the protein, the main function of the side chain of F22 seems to be to keep the substrate ring in the correct position. H88 is in a position suited to act as proton acceptor in both the physiological as well as the haloform reaction. A different mechanism of the haloform-reaction is proposed in the case of the H88R mutant, initiated by hydrogen bonding of the 7-trifluorormethyl group and the guanidinium group of the arginine residue.

Clinical results with two different pharmaceutical preparations of riboflavin in corneal cross-linking: an 18-month follow up.

PubMed

Hashemi, Hassan; Seyedian, Mohammad Amin; Miraftab, Mohammad; Bahrmandy, Hooman; Sabzevari, Araz; Asgari, Soheila

2015-01-24

Comparison of long-term clinical results of two different pharmaceutical formulations used in corneal cross-linking (CXL) in keratoconus patients. Sixty eyes of 60 keratoconus patients underwent CXL in two groups. We used riboflavin preparations from Sina Darou, Iran in group A, and Streuli Pharma, Switzerland in group B. Here we made inter-group comparison of changes in vision, refraction, Pentacam indices, corneal biomechanical indices, and endothelial cell count (ECC) 18 months after CXL. Since four patients were lost to follow-up, 56 eyes (28 eyes in each group) were compared. Mean improvement in uncorrected visual acuity (UCVA) was 0.31 ± 0.65 LogMAR (P=0.014) in group A and 0.24 ± 0.62 LogMAR (P=0.082) in group B. Best corrected visual acuity (BCVA) remained quite unchanged in both groups (P=0.774). Mean spherical refractive error reduced by 0.45 ± 1.15 diopter (D) (P=0.041) in group A and 0.27 ± 1.73 D (P=0.458) in group B (P=0.655). Cylinder error and spherical equivalent had a similar trend without any change. Max-K (P=0.006) and mean-K (P=0.044) decreased significantly more in group A compared to group B. The reduction in CCT was significantly more in group A than group B (P=0.004). Q-value was quite unchanged in both groups (P=0.704). The inter-group difference in CH reduction was borderline significant statistically (P=0.057). Changes in corneal resistance factor and endothelial cell count were not significantly different between two groups (P=0.117 and P=0.229). Clinical results of CXL with the domestic preparation of riboflavin are similar to that achieved with the Swiss made product in some aspects, and it is the preferred brand in some other aspects. This study will continue to report longer follow-up results. IRCT201212034333N2.

Evaluating the Toxicity/Fixation Balance for Corneal Cross-Linking With Sodium Hydroxymethylglycinate (SMG) and Riboflavin-UVA (CXL) in an Ex Vivo Rabbit Model Using Confocal Laser Scanning Fluorescence Microscopy.

PubMed

Kim, Su-Young; Babar, Natasha; Munteanu, Emilia Laura; Takaoka, Anna; Zyablitskaya, Mariya; Nagasaki, Takayuki; Trokel, Stephen L; Paik, David C

2016-04-01

To develop methods to delineate the relationship between endothelial cell toxicity and tissue fixation (toxicity/fixation) using sodium hydroxymethylglycinate (SMG), a formaldehyde releaser, and riboflavin-UVA photochemical corneal cross-linking (CXL) for therapeutic tissue cross-linking of the cornea. Eleven fresh cadaveric rabbit heads were used for ex vivo corneal cross-linking simulation. After epithelial debridement, the tissue was exposed to 1/4 max (9.8 mM) or 1/3 max (13 mM) SMG at pH 8.5 for 30 minutes or riboflavin-UVA (CXL). The contralateral cornea served as a paired control. Postexposure, cross-linking efficacy was determined by thermal denaturation temperature (Tm) and endothelial damage was assessed using calcein AM and ethidium homodimer staining (The Live/Dead Kit). Confocal laser scanning fluorescence microscopy was used to generate live/dead cell counts using a standardized algorithm. The ΔTm after CXL, 1/3 SMG, and 1/4 SMG was 2.2 ± 0.9°C, 1.3 ± 0.5°C, and 1.1 ± 0.5°C, respectively. Endothelial cell damage was expressed as the percent of dead cells/live + dead cells counted per high-power field. The values were 3 ± 1.7% (control) and 8.9 ± 11.1% (CXL) (P = 0.390); 1 ± 0.2% (control) and 19.5 ± 32.2% (1/3 max SMG) (P = 0.426); and 2.7 ± 2.4% (control) and 2.8 ± 2.2% (1/4 max SMG) (P = 0.938). The values for endothelial toxicity were then indexed over the shift in Tm to yield a toxicity/fixation index. The values were as follows: 2.7 for CXL, 14 for 1/3 max, and 0.1 for 1/4 max. Quarter max (1/4 max = 9.8 mM) SMG effectively cross-linked tissue and was nontoxic to endothelial cells. Thus, SMG is potentially a compound that could achieve both desired effects.

Chondrogenically primed tonsil-derived mesenchymal stem cells encapsulated in riboflavin-induced photocrosslinking collagen-hyaluronic acid hydrogel for meniscus tissue repairs.

PubMed

Koh, Rachel H; Jin, Yinji; Kang, Byung-Jae; Hwang, Nathaniel S

2017-04-15

Current meniscus tissue repairing strategies involve partial or total meniscectomy, followed by allograft transplantation or synthetic material implantation. However, allografts and synthetic implants have major drawbacks such as the limited supply of grafts and lack of integration into host tissue, respectively. In this study, we investigated the effects of conditioned medium (CM) from meniscal fibrochondrocytes and TGF-β3 on tonsil-derived mesenchymal stem cells (T-MSCs) for meniscus tissue engineering. CM-expanded T-MSCs were encapsulated in riboflavin-induced photocrosslinked collagen-hyaluronic acid (COL-RF-HA) hydrogels and cultured in chondrogenic medium containing TGF-β3. In vitro results indicate that CM-expanded cells followed by TGF-β3 exposure stimulated the expression of fibrocartilage-related genes (COL2, SOX9, ACAN, COL1) and production of extracellular matrix components. Histological assessment of in vitro and subcutaneously implanted in vivo constructs demonstrated that CM-expanded cells followed by TGF-β3 exposure resulted in highest cell proliferation, GAG accumulation, and collagen deposition. Furthermore, when implanted into meniscus defect model, CM treatment amplified the potential of TGF-β3 and induced complete regeneration. Conditioned medium derived from chondrocytes have been reported to effectively prime mesenchymal stem cells toward chondrogenic lineage. Type I collagen is the main component of meniscus extracellular matrix and hyaluronic acid is known to promote meniscus regeneration. In this manuscript, we investigated the effects of conditioned medium (CM) and transforming growth factor-β3 (TGF-β3) on tonsil-derived mesenchymal stem cells (T-MSCs) encapsulated in riboflavin-induced photocrosslinked collagen-hyaluronic acid (COL-RF-HA) hydrogel. We employed a novel source of conditioned medium, derived from meniscal fibrochondrocytes. Our in vitro and in vivo results collectively illustrate that CM-expanded cells followed by TGF-β3 exposure have the best potential for meniscus regeneration. This manuscript highlights a novel stem cell commitment strategy combined with biomaterials designs for meniscus regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome

PubMed Central

Mills, Philippa B.; Camuzeaux, Stephane S.M.; Footitt, Emma J.; Mills, Kevin A.; Gissen, Paul; Fisher, Laura; Das, Krishna B.; Varadkar, Sophia M.; Zuberi, Sameer; McWilliam, Robert; Stödberg, Tommy; Plecko, Barbara; Baumgartner, Matthias R.; Maier, Oliver; Calvert, Sophie; Riney, Kate; Wolf, Nicole I.; Livingston, John H.; Bala, Pronab; Morel, Chantal F.; Feillet, François; Raimondi, Francesco; Del Giudice, Ennio; Chong, W. Kling; Pitt, Matthew

2014-01-01

The first described patients with pyridox(am)ine 5’-phosphate oxidase deficiency all had neonatal onset seizures that did not respond to treatment with pyridoxine but responded to treatment with pyridoxal 5’-phosphate. Our data suggest, however, that the clinical spectrum of pyridox(am)ine 5’-phosphate oxidase deficiency is much broader than has been reported in the literature. Sequencing of the PNPO gene was undertaken for a cohort of 82 individuals who had shown a reduction in frequency and severity of seizures in response to pyridoxine or pyridoxal 5’-phosphate. Novel sequence changes were studied using a new cell-free expression system and a mass spectrometry-based assay for pyridoxamine phosphate oxidase. Three groups of patients with PNPO mutations that had reduced enzyme activity were identified: (i) patients with neonatal onset seizures responding to pyridoxal 5’-phosphate (n = 6); (ii) a patient with infantile spasms (onset 5 months) responsive to pyridoxal 5’-phosphate (n = 1); and (iii) patients with seizures starting under 3 months of age responding to pyridoxine (n = 8). Data suggest that certain genotypes (R225H/C and D33V) are more likely to result in seizures that to respond to treatment with pyridoxine. Other mutations seem to be associated with infertility, miscarriage and prematurity. However, the situation is clearly complex with the same combination of mutations being seen in patients who responded and did not respond to pyridoxine. It is possible that pyridoxine responsiveness in PNPO deficiency is affected by prematurity and age at the time of the therapeutic trial. Other additional factors that are likely to influence treatment response and outcome include riboflavin status and how well the foetus has been supplied with vitamin B6 by the mother. For some patients there was a worsening of symptoms on changing from pyridoxine to pyridoxal 5’-phosphate. Many of the mutations in PNPO affected residues involved in binding flavin mononucleotide or pyridoxal 5’-phosphate and many of them showed residual enzyme activity. One sequence change (R116Q), predicted to affect flavin mononucleotide binding and binding of the two PNPO dimers, and with high residual activity was found in Groups (ii) and (iii). This sequence change has been reported in the 1000 Genomes project suggesting it could be a polymorphism but alternatively it could be a common mutation, perhaps responsible for the susceptibility locus for genetic generalized epilepsy on 17q21.32 (close to rs72823592). We believe the reduction in PNPO activity and B6-responsive epilepsy in the patients reported here indicates that it contributes to the pathogenesis of epilepsy. PMID:24645144

Improving Joint Function Using Photochemical Hydrogels for Articular Surface Repair

DTIC Science & Technology

2013-10-01

riboflavin and blue light in hypoxic conditions. Control gels were not photochemically crosslinked . New cartilage matrix was formed in vivo in mice after 4...Sections were probed with AlexaFluor 568- conjugated secondary antibodies and counterstained with DAPI for cell nuclei. All samples were processed at...calcium deposits demonstrated with von Kossa stains; 2) A degradable form of photochemically crosslinked PEG norbomene gel was formulated and growth

Comparative Thermal Degradation Patterns of Natural Yellow Colorants Used in Foods.

PubMed

Giménez, Pedro J; Fernández-López, José A; Angosto, José M; Obón, José M

2015-12-01

There is a great interest in natural yellow colorants due to warnings issued about certain yellow food colorings of synthetic origin. However, no comparative studies have been reported of their thermal stability. For this reason, the thermal stabilities of six natural yellow colorants used in foods--lutein, riboflavin, curcumin, ß-carotene, gardenia yellow and Opuntia betaxanthins--were studied in simple solutions over a temperature range 30-90 °C. Spectral properties and visual color were investigated during 6 h of heat treatment. Visual color was monitored from the CIEL*a*b* parameters. The remaining absorbance at maximum wavelength and the total color difference were used to quantify color degradation. The rate of color degradation increased as the temperature rose. The results showed that the thermal degradation of the colorants followed a first-order reaction kinetics. The reaction rate constants and half-life periods were determined as being central to understanding the color degradation kinetics. The temperature-dependent degradation was adequately modeled on the Arrhenius equation. Activation energies ranged from 3.2 kJmol(-1) (lutein) to 43.7 kJmol(-1) (Opuntia betaxanthins). ß-carotene and lutein exhibited high thermal stability, while betaxanthins and riboflavin degraded rapidly as temperature increased. Gardenia yellow and curcumin were in an intermediate position.

Immunocontraceptive efficacy of synthetic peptides corresponding to major antigenic determinants of chicken riboflavin carrier protein in the female rats.

PubMed

Subramanian, S; Karande, A A; Adiga, P R

2000-09-01

Earlier studies have demonstrated that antibodies directed towards the N-terminal (residues 10-17) and C-terminal (residues 200-207) regions on chicken riboflavin carrier protein (RCP; 219 AA) are effective in pregnancy termination in rodents and sub-human primates. In the present study, the immunocontraceptive potential of three additional immunodominant sequences comprising of residues 33-49, 64 83 and 130-147 (CYA, CED and CGE peptides, respectively) of chicken RCP was investigated. The three antigenic peptides were synthesized by using Fmoc chemistry. Oligoclonal antibodies were generated in rabbits. Bioneutralizing capacity of these peptides was assessed by passive and active immunoneutralization studies. All the three peptides-specific antisera recognized their cognate epitopes on native RCP. When the affinity purified peptide IgG were administered on three consecutive days to pregnant rats (on days 10, 11 and 12), it was observed that the rats injected with CED and CGE-IgG failed to deliver any pups whereas the animals which received CYA IgG delivered normal pups. Active immunization of fertile female rats with CED or CGE peptide conferred protection from pregnancy. These results demonstrate the presence of two additional stretches in chicken RCP which can serve as mini-vaccines.

MAIT cells: new guardians of the liver.

PubMed

Kurioka, Ayako; Walker, Lucy J; Klenerman, Paul; Willberg, Christian B

2016-08-01

The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases.

MAIT cells: new guardians of the liver

PubMed Central

Kurioka, Ayako; Walker, Lucy J; Klenerman, Paul; Willberg, Christian B

2016-01-01

The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases. PMID:27588203

Extracellular Electron Transfer Is a Bottleneck in the Microbiologically Influenced Corrosion of C1018 Carbon Steel by the Biofilm of Sulfate-Reducing Bacterium Desulfovibrio vulgaris.

PubMed

Li, Huabing; Xu, Dake; Li, Yingchao; Feng, Hao; Liu, Zhiyong; Li, Xiaogang; Gu, Tingyue; Yang, Ke

2015-01-01

Carbon steels are widely used in the oil and gas industry from downhole tubing to transport trunk lines. Microbes form biofilms, some of which cause the so-called microbiologically influenced corrosion (MIC) of carbon steels. MIC by sulfate reducing bacteria (SRB) is often a leading cause in MIC failures. Electrogenic SRB sessile cells harvest extracellular electrons from elemental iron oxidation for energy production in their metabolism. A previous study suggested that electron mediators riboflavin and flavin adenine dinucleotide (FAD) both accelerated the MIC of 304 stainless steel by the Desulfovibrio vulgaris biofilm that is a corrosive SRB biofilm. Compared with stainless steels, carbon steels are usually far more prone to SRB attacks because SRB biofilms form much denser biofilms on carbon steel surfaces with a sessile cell density that is two orders of magnitude higher. In this work, C1018 carbon steel coupons were used in tests of MIC by D. vulgaris with and without an electron mediator. Experimental weight loss and pit depth data conclusively confirmed that both riboflavin and FAD were able to accelerate D. vulgaris attack against the carbon steel considerably. It has important implications in MIC failure analysis and MIC mitigation in the oil and gas industry.

Stability of hydrophilic vitamins mixtures in the presence of electrolytes and trace elements for parenteral nutrition: a nuclear magnetic resonance spectroscopy investigation.

PubMed

Uccello-Barretta, Gloria; Balzano, Federica; Aiello, Federica; Falugiani, Niccolò; Desideri, Ielizza

2015-03-25

In total parenteral nutrition (TPN), especially in the case of preterm infants, simultaneous administration of vitamins and trace elements is still a problematic issue: guidelines put in evidence the lack of specific documentation. In this work NMR spectroscopy was applied to the study of vitamins (pyridoxine hydrochloride, thiamine nitrate, riboflavin-5'-phosphate and nicotinamide) stability in presence of salts and trace elements. Vitamins in D2O were first analyzed by (1)H NMR spectroscopy in absence of salts and trace elements; changes in chemical shifts or in diffusion coefficients, measured by NMR DOSY technique, were analyzed. The effects of salts and trace elements on single vitamins and on their admixtures were then investigated by performing quantitative analyses during 48h. Selected vitamins are subject to intermolecular interactions. No degradative effects were observed in presence of salts and trace elements. Only riboflavin-5'-phosphate is subject to precipitation in presence of divalent cations; however, at low concentration and in presence of other vitamins this effect was not observed. Solutions analyzed, in the condition of this study, are stable for at least 48h and vitamins and trace elements can be administered together in TPN. Copyright © 2014 Elsevier B.V. All rights reserved.

In Situ Molecular Imaging of the Biofilm and Its Matrix.

PubMed

Ding, Yuanzhao; Zhou, Yufan; Yao, Juan; Szymanski, Craig; Fredrickson, James; Shi, Liang; Cao, Bin; Zhu, Zihua; Yu, Xiao-Ying

2016-11-15

Molecular mapping of live biofilms at submicrometer resolution presents a grand challenge. Here, we present the first chemical mapping results of biofilm extracellular polymeric substance (EPS) in biofilms using correlative imaging between super resolution fluorescence microscopy and liquid time-of-flight secondary ion mass spectrometry (TOF-SIMS). Shewanella oneidensis is used as a model organism. Heavy metal chromate (Cr 2 O 7 2- ) anions consisting of chromium Cr(VI) was used as a model environmental stressor to treat the biofilms. Of particular interest, biologically relevant water clusters have been first observed in the biofilms. Characteristic fragments of biofilm matrix components such as proteins, polysaccharides, and lipids can be spatially imaged. Furthermore, characteristic fatty acids (e.g., palmitic acid), quinolone signal, and riboflavin fragments were found to respond after the biofilm is treated with Cr(VI), leading to biofilm dispersal. Significant changes in water clusters and quorum sensing signals indicative of intercellular communication in the aqueous environment were observed, suggesting that they might result in fatty acid synthesis and inhibition of riboflavin production. The Cr(VI) reduction seems to follow the Mtr pathway leading to Cr(III) formation. Our approach potentially opens a new avenue for mechanistic insight of microbial community processes and communications using in situ imaging mass spectrometry and super resolution optical microscopy.

Recovery of Elemental Tellurium Nanoparticles by the Reduction of Tellurium Oxyanions in a Methanogenic Microbial Consortium.

PubMed

Ramos-Ruiz, Adriana; Field, Jim A; Wilkening, Jean V; Sierra-Alvarez, Reyes

2016-02-02

This research focuses on the microbial recovery of elemental tellurium (Te(0)) from aqueous streams containing soluble tellurium oxyanions, tellurate (Te(VI)), and tellurite (Te(IV)). An anaerobic mixed microbial culture occurring in methanogenic granular sludge was able to biocatalyze the reduction of both Te oxyanions to produce Te(0) nanoparticles (NPs) in sulfur-free medium. Te(IV) reduction was seven times faster than that of Te(VI), such that Te(IV) did not accumulate to a great extent during Te(VI) reduction. Endogenous substrates in the granular sludge provided the electron equivalents required to reduce Te oxyanions; however, the reduction rates were modestly increased with an exogenous electron donor such as H2. The effect of four redox mediators (anthraquinone-2,6-disulfonate, hydroxocobalamin, riboflavin, and lawsone) was also tested. Riboflavin increased the rate of Te(IV) reduction eleven-fold and also enhanced the fraction Te recovered as extracellular Te(0) NPs from 21% to 64%. Lawsone increased the rate of Te(VI) reduction five-fold, and the fraction of Te recovered as extracellular material increased from 49% to 83%. The redox mediators and electron donors also impacted the morphologies and localization of Te(0) NPs, suggesting that NP production can be tailored for a particular application.

Surface-enhanced Raman scattering (SERS) of riboflavin on nanostructured Ag surfaces: The role of excitation wavelength, plasmon resonance and molecular resonance.

PubMed

Šubr, Martin; Kuzminova, Anna; Kylián, Ondřej; Procházka, Marek

2018-05-15

Optimization of surface-enhanced Raman scattering (SERS)-based sensors for (bio)analytical applications has received much attention in recent years. For optimum sensitivity, both the nanostructure fabrication process and the choice of the excitation wavelength used with respect to the specific analyte studied are of crucial importance. In this contribution, detailed SERS intensity profiles were measured using gradient nanostructures with the localized surface-plasmon resonance (LSPR) condition varying across the sample length and using riboflavin as the model biomolecule. Three different excitation wavelengths (633 nm, 515 nm and 488 nm) corresponding to non-resonance, pre-resonance and resonance excitation with respect to the studied molecule, respectively, were tested. Results were interpreted in terms of a superposition of the enhancement provided by the electromagnetic mechanism and intrinsic properties of the SERS probe molecule. The first effect was dictated mainly by the degree of spectral overlap between the LSPR band, the excitation wavelength along with the scattering cross-section of the nanostructures, while the latter was influenced by the position of the molecular resonance with respect to the excitation wavelength. Our experimental findings contribute to a better understanding of the SERS enhancement mechanism. Copyright © 2018. Published by Elsevier B.V.

Preventive role of lens antioxidant defense mechanism against riboflavin-mediated sunlight damaging of lens crystallins.

PubMed

Anbaraki, Afrooz; Khoshaman, Kazem; Ghasemi, Younes; Yousefi, Reza

2016-10-01

The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. Copyright © 2016 Elsevier B.V. All rights reserved.

Consumption of ready-to-eat cereals (RTEC) among Malaysian children and association with socio-demographics and nutrient intakes - findings from the MyBreakfast study.

PubMed

Mohd Nasir, Mohd Taib; Nurliyana, Abdul Razak; Norimah, A Karim; Jan Mohamed, Hamid Jan B; Tan, Sue Yee; Appukutty, Mahenderan; Hopkins, Sinead; Thielecke, Frank; Ong, Moi Kim; Ning, Celia; Tee, E Siong

2017-01-01

Background : The association between different types of breakfast meals and nutrient intakes has been studied to a lesser extent. Objective : This study compared nutrient intakes at breakfast and throughout the day between Malaysian children who consumed ready-to-eat cereals (RTEC) and those who did not. Methods : Anthropometric and dietary data for 1955 children aged 6-12 years from the MyBreakfast study were used in the analysis. Results : Overall, 18% of the children consumed RTEC at breakfast on at least one of the recall days. RTEC consumption was associated with younger age, urban areas, higher income and education level of parents. Among consumers, RTEC contributed 10% and 15% to daily intakes of calcium and iron respectively and ≥20% to daily intakes of vitamin C, thiamin, riboflavin and niacin. RTEC consumers had significantly higher mean intakes of vitamin C, thiamin, riboflavin, niacin, calcium, iron and sugar but lower intakes of fat and sodium than non-RTEC consumers at breakfast and for the total day. Conclusion : Consumption of fortified RTEC at breakfast was associated with lower fat and sodium intakes and higher intakes of several micronutrients both at breakfast and for the total day. However, total sugar intakes appeared to be higher.

Extracellular Electron Transfer Is a Bottleneck in the Microbiologically Influenced Corrosion of C1018 Carbon Steel by the Biofilm of Sulfate-Reducing Bacterium Desulfovibrio vulgaris

PubMed Central

Li, Yingchao; Feng, Hao; Liu, Zhiyong; Li, Xiaogang; Gu, Tingyue; Yang, Ke

2015-01-01

Carbon steels are widely used in the oil and gas industry from downhole tubing to transport trunk lines. Microbes form biofilms, some of which cause the so-called microbiologically influenced corrosion (MIC) of carbon steels. MIC by sulfate reducing bacteria (SRB) is often a leading cause in MIC failures. Electrogenic SRB sessile cells harvest extracellular electrons from elemental iron oxidation for energy production in their metabolism. A previous study suggested that electron mediators riboflavin and flavin adenine dinucleotide (FAD) both accelerated the MIC of 304 stainless steel by the Desulfovibrio vulgaris biofilm that is a corrosive SRB biofilm. Compared with stainless steels, carbon steels are usually far more prone to SRB attacks because SRB biofilms form much denser biofilms on carbon steel surfaces with a sessile cell density that is two orders of magnitude higher. In this work, C1018 carbon steel coupons were used in tests of MIC by D. vulgaris with and without an electron mediator. Experimental weight loss and pit depth data conclusively confirmed that both riboflavin and FAD were able to accelerate D. vulgaris attack against the carbon steel considerably. It has important implications in MIC failure analysis and MIC mitigation in the oil and gas industry. PMID:26308855

Effectiveness of a flow-based device using riboflavin photochemistry in damaging blood-borne viral nucleic acids.

PubMed

Zhu, Liguo; Tong, Hongli; Wang, Shufang; Yu, Yang; Liu, Zhong; Li, Changqing; Wang, Deqing

2018-05-03

Effectiveness of a flow-based treatment device using riboflavin photochemistry was demonstrated by cytopathic effect method using indicator viruses. However, inactivation efficacy against real blood-borne viruses needs to be evaluated, especially at nucleic acid level. Special plasma samples with varying concentrations of blood-borne virus were selected using a strict blood selection procedure and were treated with device treatment (DT). Nucleic acid test (NAT) using polymerase chain reaction fluorescence method was used to detect virus copies. The NAT value of 4325 in plasma with high Hepatitis B Virus (HBV) concentrations decreased to 1330 with DT. After 100-fold dilution, the NAT value was below the NAT detection limits with DT compared with 23.0 that without DT. The NAT value of 61.9 in plasma with medium HBV concentrations decreased to 37.8 with DT, and after 10-fold dilution, the NAT value was below the NAT detection limits with DT compared with below 20 that without DT. The Ct values of plasma with low concentrations of blood-borne viruses were below the NAT detection limits with DT. There was a dose effect with DT which was effective in blood-borne viruses damaging nucleic acids to a level below the NAT detection limits. Copyright © 2018 Elsevier B.V. All rights reserved.

Recovery of Elemental Tellurium Nanoparticles by the Reduction of Tellurium Oxyanions in a Methanogenic Microbial Consortium

PubMed Central

Ramos-Ruiz, Adriana; Field, Jim A.; Wilkening, Jean V.; Sierra-Alvarez, Reyes

2016-01-01

This research focuses on the microbial recovery of elemental tellurium (Te0) from aqueous streams containing soluble tellurium oxyanions, tellurate (TeVI) and tellurite (TeIV). An anaerobic mixed microbial culture occurring in methanogenic granular sludge was able to biocatalyze the reduction of both Te oxyanions to produce Te0 nanoparticles (NPs) in sulfur-free medium. TeIV reduction was 7-fold faster than that of TeVI, such that TeIV did not accumulate to a great extent during TeVI reduction. Endogenous substrates in the granular sludge provided the electron equivalents required to reduce Te oxyanions; however, the reduction rates were modestly increased with an exogenous electron donor such as H2. The effect of four redox mediators (anthraquinone-2,6-disulfonate, hydroxocobalamin, riboflavin, and lawsone) was also tested. Riboflavin increased the rate of TeIV reduction by 11-fold and also enhanced the fraction Te recovered as extracellular Te0 NPs from 21% to 64%. Lawsone increased the rate of TeVI reduction by 5-fold and the fraction of Te recovered as extracellular material increased from 49% to 83%. The redox mediators and electron donors also impacted the morphologies and localization of Te0 NPs, suggesting that NP production can be tailored for a particular application. PMID:26735010

Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection.

PubMed

Hühner, Jens; Ingles-Prieto, Álvaro; Neusüß, Christian; Lämmerhofer, Michael; Janovjak, Harald

2015-02-01

Cultured mammalian cells essential are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are critical for cellular redox reactions and sense light in naturally occurring photoreceptors and optogenetic tools. Here, we quantified flavin contents of commonly used mammalian cell lines. We first compared three procedures for extraction of free and noncovalently protein-bound flavins and verified extraction using fluorescence spectroscopy. For separation, two CE methods with different BGEs were established, and detection was performed by LED-induced fluorescence with limit of detections (LODs 0.5-3.8 nM). We found that riboflavin (RF), FMN, and FAD contents varied significantly between cell lines. RF (3.1-14 amol/cell) and FAD (2.2-17.0 amol/cell) were the predominant flavins, while FMN (0.46-3.4 amol/cell) was found at markedly lower levels. Observed flavin contents agree with those previously extracted from mammalian tissues, yet reduced forms of RF were detected that were not described previously. Quantification of flavins in mammalian cell lines will allow a better understanding of cellular redox reactions and optogenetic tools. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial.

PubMed

Torsvik, Ingrid Kristin; Ueland, Per Magne; Markestad, Trond; Midttun, Øivind; Bjørke Monsen, Anne-Lise

2015-12-18

Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months. Levels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month. Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03). The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency. ClinicalTrials.gov, number NCT01201005.

Nutritional and environmental studies on an ocean-going oil tanker. 4. The diet of seamen

PubMed Central

Eddy, T. P.; Wheeler, Erica F.; Stock, Anne L.

1971-01-01

Eddy, T. P., Wheeler, Erica F., and Stock, Anne L. (1971).Brit. J. industr. Med.,28, 342-352. Nutritional and environmental studies on an ocean-going oil tanker. 4. The diet of seamen. Previous reports by Collins and his colleagues (1971a, b) and Eddy, Stock, and Wheeler (1971) have described energy and nutrient balances measured during a voyage of the oil tanker S.S. Esso Newcastle to the Persian Gulf in July and August 1967. This study of the diet of seamen during the voyage describes inter-relationships of the energy-yielding constituents of the diet, particularly the relationship of alcohol to other constituents, and vitamin intakes. For the whole ship's crew the percentages of energy derived from the main constituents were from protein 12%, fat 35%, carbohydrate 40%, and alcohol 13%. The intakes of six subjects studied in detail showed relatively little variation in protein, 13·9 ± 0·4 Joules%; but greater variation in fat (33·0 ± 1·6%), carbohydrate (42·7 ± 1·4%), and alcohol (10·4 ± 1·3%). There were high negative correlations, r=-0·75, between energy percentages derived from alcohol and those derived from protein and fat respectively. Flour purchased for the ship in a foreign port was deficient in thiamine and niacin. There was a negative correlation between energy and thiamine intake, and with unfortified white flour thiamine intake would fall below the recommended allowance at intakes above 14·5 MJ (3500 kcal). The unwitting substitution of unfortified flours in place of fortified British flour is a potential cause of deficiency. The estimated intake of riboflavine decreased when fresh milk supplies were exhausted following the 10th day out, and would have fallen below the recommended intake of 0·5 mg/1000 kcal (4·186 MJ) but for the consumption of beer. The intake of ascorbic acid was not affected by the duration of the voyage. It averaged 70mg/man/day and was derived chiefly from citrus fruits and potatoes. The Statutory Scale of Provisions issued under the Merchant Shipping Act. 1906, is out of date and a new scale should be drawn up. PMID:5171426

Permeation of superoxide anion through the bilayer of vesicles of a synthetic amphiphile.

PubMed

Gomes, L F; Cuccovia, I M; Chaimovich, H; Barbieri, D H; Politi, M J

1993-10-10

Large unilamellar vesicles, prepared with dioctadecyldimethylammonium chloride, entrap nitroblue tetrazolium. Addition of solid KO2, or production of superoxide anion by riboflavin photolysis, to nitroblue tetrazolium-containing dioctadecyldimethylammonium vesicles results in the formation of monoformazan above the phase-transition temperature of the bilayer. Below the phase-transition temperature the yield of monoformazan is negligible. These results demonstrate that superoxide anion permeates vesicles above the phase-transition temperature of the bilayer.

Primary Hemostatic Capacity of Whole Blood: A Comprehensive Analysis of Pathogen Reduction and Refrigeration Effects Over Time

DTIC Science & Technology

2013-01-01

reduction and refrigeration is intriguing and suggests that PRT WB may complement the beneficial effects of the antifibrinolytic, tranexamic acid in...and ABBREVIATIONS: aPTT = activated partial thromboplastin time; ASPI = arachidonic acid agonist; COL = collagen; GPIba = glycoprotein Ib alpha; K...riboflavin and ultraviolet (UV) light to damage the nucleic acids of white blood cells (WBCs), parasites, bacteria, and viruses, is being consid- ered

Genetic associations with micronutrient levels identified in immune and gastrointestinal networks.

PubMed

Morine, Melissa J; Monteiro, Jacqueline Pontes; Wise, Carolyn; Teitel, Candee; Pence, Lisa; Williams, Anna; Ning, Baitang; McCabe-Sellers, Beverly; Champagne, Catherine; Turner, Jerome; Shelby, Beatrice; Bogle, Margaret; Beger, Richard D; Priami, Corrado; Kaput, Jim

2014-07-01

The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physiological processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6-14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_PC1 levels were significantly associated with (1) single-nucleotide polymorphisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune functions, as identified in a global network of metabolic/protein-protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene-nutrient interactions. The systems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions.

Animal source foods have a positive impact on the primary school test scores of Kenyan schoolchildren in a cluster-randomised, controlled feeding intervention trial.

PubMed

Hulett, Judie L; Weiss, Robert E; Bwibo, Nimrod O; Galal, Osman M; Drorbaugh, Natalie; Neumann, Charlotte G

2014-03-14

Micronutrient deficiencies and suboptimal energy intake are widespread in rural Kenya, with detrimental effects on child growth and development. Sporadic school feeding programmes rarely include animal source foods (ASF). In the present study, a cluster-randomised feeding trial was undertaken to determine the impact of snacks containing ASF on district-wide, end-term standardised school test scores and nutrient intake. A total of twelve primary schools were randomly assigned to one of three isoenergetic feeding groups (a local plant-based stew (githeri) with meat, githeri plus whole milk or githeri with added oil) or a control group receiving no intervention feeding. After the initial term that served as baseline, children were fed at school for five consecutive terms over two school years from 1999 to 2001. Longitudinal analysis was used controlling for average energy intake, school attendance, and baseline socio-economic status, age, sex and maternal literacy. Children in the Meat group showed significantly greater improvements in test scores than those in all the other groups, and the Milk group showed significantly greater improvements in test scores than the Plain Githeri (githeri+oil) and Control groups. Compared with the Control group, the Meat group showed significant improvements in test scores in Arithmetic, English, Kiembu, Kiswahili and Geography. The Milk group showed significant improvements compared with the Control group in test scores in English, Kiswahili, Geography and Science. Folate, Fe, available Fe, energy per body weight, vitamin B₁₂, Zn and riboflavin intake were significant contributors to the change in test scores. The greater improvements in test scores of children receiving ASF indicate improved academic performance, which can result in greater academic achievement.

A systematic review of the nutritional adequacy of the diet in the Central Andes.

PubMed

Berti, Peter R; Fallu, Cynthia; Cruz Agudo, Yesmina

2014-11-01

To examine dietary adequacy in the Andean area, including macro- and micronutrient intakes, with a particular focus on rural communities; to highlight nutrition priorities in the Andes; and to identify opportunities for improvement. A comprehensive literature search was conducted, identifying published and grey literature in English and Spanish related to diet in the central Andean countries of Bolivia, Colombia, Ecuador, and Peru. Articles reporting data from dietary surveys or nutrition interventions were included. Thirty-four papers or reports published in 1969-2011 were included in the final review. The mean and variation in intakes by sex and age group of all presented nutrients were collated and the mean of means were calculated. Thiamin, niacin, and vitamin C intakes were usually adequate. Intakes of most other micronutrients, including iron, zinc, vitamin A, riboflavin, vitamin B12, folate, and zinc were low, likely resulting in high levels of inadequacy. Energy intakes were lower than requirements, but it is unlikely to be a common problem, rather, this result was probably due to the known tendency of most dietary survey tools to underreport intake. However, energy from fat intakes was very low, usually less than 20% of the total, and in some settings, less than 10%. The inadequate intake of some micronutrients is common in many developing countries, but the extremely low intake of dietary fat found in the central Andes is not. Increased consumption of animal-source foods would increase fat intakes, while addressing micronutrient deficiencies; however, the impact on the fragile ecosystem of the Andes needs considering. Indigenous crops, such as lupine bean, quinoa, and amaranth are also rich in fat or micronutrients.

The potential contribution of yellow cassava to dietary nutrient adequacy of primary-school children in Eastern Kenya; the use of linear programming.

PubMed

Talsma, Elise F; Borgonjen-van den Berg, Karin J; Melse-Boonstra, Alida; Mayer, Eva V; Verhoef, Hans; Demir, Ayşe Y; Ferguson, Elaine L; Kok, Frans J; Brouwer, Inge D

2018-02-01

Introduction of biofortified cassava as school lunch can increase vitamin A intake, but may increase risk of other deficiencies due to poor nutrient profile of cassava. We assessed the potential effect of introducing a yellow cassava-based school lunch combined with additional food-based recommendations (FBR) on vitamin A and overall nutrient adequacy using Optifood (linear programming tool). Cross-sectional study to assess dietary intakes (24 h recall) and derive model parameters (list of foods consumed, median serving sizes, food and food (sub)group frequency distributions, food cost). Three scenarios were modelled, namely daily diet including: (i) no school lunch; (ii) standard 5d school lunch with maize/beans; and (iii) 5d school lunch with yellow cassava. Each scenario and scenario 3 with additional FBR were assessed on overall nutrient adequacy using recommended nutrient intakes (RNI). Eastern Kenya. Primary-school children (n 150) aged 7-9 years. Best food pattern of yellow cassava-based lunch scenario achieved 100 % RNI for six nutrients compared with no lunch (three nutrients) or standard lunch (five nutrients) scenario. FBR with yellow cassava and including small dried fish improved nutrient adequacy, but could not ensure adequate intake of fat (52 % of average requirement), riboflavin (50 % RNI), folate (59 % RNI) and vitamin A (49 % RNI). Introduction of yellow cassava-based school lunch complemented with FBR potentially improved vitamin A adequacy, but alternative interventions are needed to ensure dietary adequacy. Optifood is useful to assess potential contribution of a biofortified crop to nutrient adequacy and to develop additional FBR to address remaining nutrient gaps.

Low energy availability and low body fat of female gymnasts before an international competition.

PubMed

Silva, M R G; Paiva, T

2015-01-01

The purpose of the present study was to evaluate dietary intake and body composition of elite rhythmic gymnastics (RG) athletes prior to a competition event. Sixty-seven rhythmic gymnasts (18.7 ± 2.9 years old) of high performance level, with 36.6 ± 7.6 h of training/week were evaluated in order to collect training and competition data, medical and gynaecological history, detailed dietary intake and body composition before an international competition. The majority of the participants (n = 40; 59.7%) had already menstruated, but age of menarche was delayed (15.3 ± 1.3 years) and all revealed menstrual irregularities. Gymnasts' body mass (48.4 ± 4.9 kg) and body mass index (BMI; 17.4 ± 1.1 kg/m(2)) were below the normal for age, and height (1.66 ± 0.05 m) was normal or even slightly above normal for age. Body fat was 9.0 ± 2.0% with no significant differences between age strata. Gymnasts exhibited low energy availability (EA; 31.5 ± 11.9 kcal/kg fat-free mass (FFM)/day). The average carbohydrate and protein intakes were 5.1 ± 2.3 g/kg/day and 1.6 ± 04 g/kg/day, which correspond to 51.4 ± 7.2% and 16.9 ± 3.4% of total energy intakes, respectively; average fat contribution was 33.0 ± 5.3%. Low intakes of pantothenic acid, folate and vitamins D, E and K and of minerals, including calcium, iron and magnesium were reported. Intakes of thiamine, riboflavin, niacin, vitamins A, B-6, B-12, C and manganese and zinc were above-adequate (P < 0.05). Low EA, low body fat and micronutrient deficiencies are common among RG.

Nutritional requirements during lactation. Towards European alignment of reference values: the EURRECA network.

PubMed

Hall Moran, Victoria; Lowe, Nicola; Crossland, Nicola; Berti, Cristiana; Cetin, Irene; Hermoso, Maria; Koletzko, Berthold; Dykes, Fiona

2010-10-01

There is considerable variation in reference values for micronutrient intake during lactation across Europe. The European Micronutrients Recommendations Aligned project aims to harmonize dietary recommendations throughout Europe. Recommended nutrient intakes during lactation are based on limited data and are often extrapolated from known secretion of the nutrient in milk with adjustments for bioavailability, so that differences between values can be partly ascribed to differences in methodological approaches and how these approaches were applied. Few studies have considered the impact of lactation on the mother's nutritional status. Rather, focus has been placed on the influence of maternal nutritional status on the composition of her breast milk. Most common nutritional deficits in breast milk are the result of maternal deficiencies of the water-soluble vitamins, thiamine, riboflavin and vitamins B6 and B12. Other than maternal vitamin A status, which to some extent is reflected in breast milk, concentrations of fat-soluble vitamins and most minerals in breast milk are less affected by maternal status. Factors relating to suboptimal maternal nutritional status during lactation include maternal age, diet and lifestyle factors and spacing of consecutive births. Recent research is providing new knowledge on the micronutrient requirements of lactating women. Identifying needs for research and improving understanding of the differences in values that have been derived by various committees and groups across Europe will enhance transparency and facilitate the application of dietary recommendations in policy-making decision and their translation into recommendations for lactating women. Given the wide variation in breastfeeding practices across Europe, making nutritional recommendations for lactating women is complex and challenging. Thus, it is crucial to first examine the cultural practices within and across European populations and to assess its relevance before making recommendations. © 2010 Blackwell Publishing Ltd.

Nutritional situation of Beijing residents.

PubMed

Zhao, X H

1992-01-01

Beijing is the capital of China with the population of 10.32 million in 1990 and the area of 1687.8 km2. It is the economic and cultural center of the country. Since the founding of new China, the development of Beijing city has been very fast. The gross national product (GNP) of Beijing in 1988 is 2.78 times the average GNP of the whole country. The sanitary institution has increased 71 times from 1949 to 1989. The prevalence of infectious diseases decreased significantly. The infant mortality is 11.6 per thousand approaching the figure of developed countries. The main food products increased rapidly. The grain, meat and egg increased from 100.7 kg and 0.48 kg per capita per year in 1949 to 217.1 kg and 20.17 kg in 1988 respectively. The food consumption of residents have been increasing consistently with the increasing of food production in Beijing. The food available in Beijing is well both in quantity and in quality. The results of the nutritional survey in 1985 showed that the daily average energy intake was 2549 kcal per capita. The average protein intake was 70g per person per day. The fat intake as the percentage of the total energy was 25.7. The average nutrients intake of Beijing residents meets the Chinese RDA basically. The nutritional status of people living in the city is good in general. But there are still some nutritional problem exist. Zn and Fe deficiencies anemia are common in infants and children along with the decreasing rate of breast feeding. Riboflavin, Zn and Ca intakes are inadequate in a lot of adults and the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Reinventing the Wheel and Making It Round Again: Evolutionary Convergence in Buchnera–Serratia Symbiotic Consortia between the Distantly Related Lachninae Aphids Tuberolachnus salignus and Cinara cedri

PubMed Central

Manzano-Marín, Alejandro; Simon, Jean-Christophe; Latorre, Amparo

2016-01-01

Virtually all aphids (Aphididae) harbor Buchnera aphidicola as an obligate endosymbiont to compensate nutritional deficiencies arising from their phloem diet. Many species within the Lachninae subfamily seem to be consistently associated also with Serratia symbiotica. We have previously shown that both Cinara (Cinara) cedri and Cinara (Cupressobium) tujafilina (Lachninae: Eulachnini tribe) have indeed established co-obligate associations with both Buchnera and S. symbiotica. However, while Buchnera genomes of both Cinara species are similar, genome degradation differs greatly between the two S. symbiotica strains. To gain insight into the essentiality and degree of integration of S. symbiotica within the Lachninae, we sequenced the genome of both Buchnera and S. symbiotica endosymbionts from the distantly related aphid Tuberolachnus salignus (Lachninae: Tuberolachnini tribe). We found a striking level of similarity between the endosymbiotic system of this aphid and that of C. cedri. In both aphid hosts, S. symbiotica possesses a highly reduced genome and is found exclusively intracellularly inside bacteriocytes. Interestingly, T. salignus’ endosymbionts present the same tryptophan biosynthetic metabolic complementation as C. cedri’s, which is not present in C. tujafilina’s. Moreover, we corroborate the riboflavin-biosynthetic-role take-over/rescue by S. symbiotica in T. salignus, and therefore, provide further evidence for the previously proposed establishment of a secondary co-obligate endosymbiont in the common ancestor of the Lachninae aphids. Finally, we propose that the putative convergent split of the tryptophan biosynthetic role between Buchnera and S. symbiotica could be behind the establishment of S. symbiotica as an obligate intracellular symbiont and the triggering of further genome degradation. PMID:27190007

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation.

PubMed

Hampel, Daniela; Shahab-Ferdows, Setareh; Islam, M Munirul; Peerson, Janet M; Allen, Lindsay H

2017-04-01

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18-26 y) in Dhaka, Bangladesh, at 2-4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800-0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14-18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2-4 h postdosing, with 0.1-6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026.

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation1234

PubMed Central

Shahab-Ferdows, Setareh; Peerson, Janet M; Allen, Lindsay H

2017-01-01

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations. Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations. Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18–26 y) in Dhaka, Bangladesh, at 2–4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800–0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample. Results: Significant but small differences (14–18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2–4 h postdosing, with 0.1–6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake. Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026. PMID:28202638

Vision Restoration with a Collagen Cross-linked Boston Keratoprosthesis Unit

DTIC Science & Technology

2017-09-01

Tissue Bank International, the tissue bank used for this study changed their company name to KeraLink International. The name was changed to better...solution to KeraLink International, and Dr. Joseph Ciolino traveled to the tissue bank to train staff on the Cross-Linking procedure. KeraLink is now... tissue by collagen-crosslinking the cornea graft ex vivo using vitamin B2 (riboflavin) and ultraviolet light. The overall objective of this study is

In Situ Dechlorination of Solvents in Saturated Soils

DTIC Science & Technology

1996-05-01

riboflavin 0.025 nicotinic acid 0.025 DL-calcium pantothenate 0.025 vitamin B12 0.025 p-aminobenzoic acid 0.025 lipoic acid 0.025 yeast extract...contaminated core materials collected from the Coast Guard Air Station in Traverse City, MI. Four fatty acids and three alcohols were tested for their...EXTRACT CONCENTRATIONS Vitamin/Yeast Extract Concentration (mg/L) d-biotin 0.01 folic acid 0.01 pyridoxine hydrochloride 0.05 thiamin hydrochloride 0.025

Consumption of ready-to-eat cereals (RTEC) among Malaysian children and association with socio-demographics and nutrient intakes – findings from the MyBreakfast study

PubMed Central

Mohd Nasir, Mohd Taib; Nurliyana, Abdul Razak; Norimah, A. Karim; Jan Mohamed, Hamid Jan B.; Tan, Sue Yee; Appukutty, Mahenderan; Hopkins, Sinead; Thielecke, Frank; Ong, Moi Kim; Ning, Celia; Tee, E. Siong

2017-01-01

ABSTRACT Background: The association between different types of breakfast meals and nutrient intakes has been studied to a lesser extent. Objective: This study compared nutrient intakes at breakfast and throughout the day between Malaysian children who consumed ready-to-eat cereals (RTEC) and those who did not. Methods: Anthropometric and dietary data for 1955 children aged 6–12 years from the MyBreakfast study were used in the analysis. Results: Overall, 18% of the children consumed RTEC at breakfast on at least one of the recall days. RTEC consumption was associated with younger age, urban areas, higher income and education level of parents. Among consumers, RTEC contributed 10% and 15% to daily intakes of calcium and iron respectively and ≥20% to daily intakes of vitamin C, thiamin, riboflavin and niacin. RTEC consumers had significantly higher mean intakes of vitamin C, thiamin, riboflavin, niacin, calcium, iron and sugar but lower intakes of fat and sodium than non-RTEC consumers at breakfast and for the total day. Conclusion: Consumption of fortified RTEC at breakfast was associated with lower fat and sodium intakes and higher intakes of several micronutrients both at breakfast and for the total day. However, total sugar intakes appeared to be higher. PMID:28469545

Stability of Alprazolam, Atropine Sulfate, Glutamine, Levofloxacin, Metoprolol Tartrate, Nitrofurantoin, Ondansetron Hydrochloride, Oxandrolone, Pregabaline, and Riboflavin in SyrSpend SF pH4 Oral Suspensions.

PubMed

Ferreira, Anderson O; Polonini, Hudson C; Loures da Silva, Sharlene; Cerqueira de Melo, Victor Augusto; de Andrade, Laura; Brandão, Marcos Antônio Fernandes

2017-01-01

The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): alprazolam 1.0 mg/mL, atropine sulfate 0.1 mg/mL, glutamine 250.0 mg/mL, levofloxacin 50.0 mg/mL, metoprolol tartrate 10.0 mg/mL, nitrofurantoin 2.0 mg/mL, ondansetron hydrochloride 0.8 mg/mL, oxandrolone 3.0 mg/mL, pregabaline 20.0 mg/mL, riboflavin 10.0 mg/mL. All suspensions were stored at both controlled refrigeration (2°C to 8°C) and controlled room temperature (20°C to 25°C). Stability was assessed by measuring the percent recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions with regard to both temperatures. This suggests that the vehicle is stable for compounding active pharmaceutical ingredients from different pharmacological classes. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf extracts

PubMed Central

2012-01-01

Background Plants play a significant role in maintaining human health and improving the quality of human life. They serve humans well as valuable components of food, as well as in cosmetics, dyes, and medicines. In fact, many plant extracts prepared from plants have been shown to exert biological activity in vitro and in vivo. The present study explored antioxidant and antigenotoxic effects of Daphne gnidium leaf extracts. Methods The genotoxic potential of petroleum ether, chloroform, ethyl acetate, methanol and total oligomer flavonoid (TOF) enriched extracts from leaves of Daphne gnidium, was assessed using Escherichia coli PQ37. Likewise, the antigenotoxicity of the same extracts was tested using the “SOS chromotest test”. Antioxidant activities were studied using non enzymatic and enzymatic method: NBT/Riboflavine and xantine oxidase. Results None of the different extracts produced a genotoxic effect, except TOF extract at the lowest tested dose. Our results showed that D. gnidium leaf extracts possess an antigenotoxic effect against the nitrofurantoin a mutagen of reference. Ethyl acetate and TOF extracts were the most effective in inhibiting xanthine oxidase activity. While, methanol extract was the most potent superoxide scavenger when tested with the NBT/Riboflavine assay. Conclusions The present study has demonstrated that D. gnidium leaf extract possess antioxidant and antigenotoxic effects. These activities could be ascribed to compounds like polyphenols and flavonoid. Further studies are required to isolate the active molecules. PMID:22974481

Epitope mapping and evaluation of specificity of T-helper sites in four major antigenic peptides of chicken riboflavin carrier protein in outbred rats.

PubMed

Subramanian, Sarada; Andal, S; Karande, Anjali A; Radhakantha Adiga, P

2003-11-07

This paper reviews our studies on synthetic peptides spanning the major antigenic determinants of the chicken riboflavin carrier protein (RCP; 219 AA). These determinants are composed of residues 4-24 (YGC), 64-83 (CED), 130-147 (GEN), and 200-219 (HAC) and function as minivaccines in terms of eliciting anti-peptide antibodies which recognize the native protein and are particularly promising contraceptive vaccine candidates. We have used 15-residue synthetic peptides to define short sequences involved in interaction with antibody and with T-cells. We have mapped the boundaries of T-cell epitopes of these peptides in outbred rats by immunizing the animals with each peptide and assaying the popliteal lymph node cell proliferation against a series of overlapping synthetic 15-mers covering the entire length of the individual peptides. The peptides YGC, GEN, and HAC harboured a single T-cell epitope each whereas the peptide CED exhibited bimodal response possessing two epitopes, one at N-terminus and the other at the C-terminus. These studies provide insight into the way in which an immunogen is viewed by the immune system. In addition, preferential T-cell helper function for B cells recognizing unique determinants on the same molecule was demonstrated. This information helps in exploiting synthetic peptides in the construction of designer immunogens which have potential as candidate vaccines.

Effect of sodium metabisulfite on hydrogen peroxide production in light-exposed pediatric parenteral amino acid solutions.

PubMed

Brawley, V; Bhatia, J; Karp, W B

1998-06-15

The effect of sodium metabisulfite (MBS) on hydrogen peroxide (HP) production in model and commercial amino acid solutions exposed to phototherapy light was studied. Model and commercial pediatric amino acid solutions were prepared such that the amino acid concentration was 1%. MBS concentration, riboflavin concentration, and duration of exposure to phototherapy light were varied to determine the effect on HP production. Control solutions were kept in the dark. HP production was assayed in the model amino acid solutions by using potassium iodide in the presence of ammonium molybdate. In all experiments, HP production was measured at 360 nm in the presence and absence of catalase. In light-exposed solutions, HP production increased linearly for several hours and reached a plateau by eight hours. A mean maximum of 940 microM was produced (data pooled for all solutions). No detectable HP was generated in the solutions kept in the dark. After two hours of light exposure, it was necessary to add at least 10 times more MBS than is typically found in commercial total parenteral nutrient solutions to scavenge all the HP produced. An average of up to 940 microM of HP was produced in model and commercial pediatric parenteral 1% amino acid solutions in the presence of phototherapy light and clinically relevant concentrations of riboflavin and MBS. Light exposure decreased the antioxidant effect of MBS.

Effect of Nicotinamide on the Photolysis of Riboflavin in Aqueous Solution

PubMed Central

Ahmad, Iqbal; Ahmed, Sofia; Sheraz, Muhammad Ali; Anwar, Zubair; Qadeer, Kiran; Noor, Adnan; Evstigneev, Maxim P.

2016-01-01

The photolysis of riboflavin (RF) in aqueous solution in the presence of nicotinamide (NA) by visible light has been studied in the pH range 1.0–12.0 and the various photoproducts have been identified as known compounds. RF has been determined in degraded solutions by a specific multicomponent spectrometric method in the presence of its photoproducts and NA. The second-order rate constants (k2) for the bimolecular interaction of RF and NA range from 0.54 (pH 1.0) to 9.66 M–1 min–1 (pH 12.0). The log k2–pH profile for the photolysis reaction follows a sigmoid curve showing a gradual increase in the rate of pH due to a change in the ionization behavior of the molecule. The lower rate in the acid region is probably due to protonation of the molecule since the cationic form of RF is less susceptible to photolysis than the neutral form. Similarly, a slowing of the rate in the alkaline region is due to anion formation of the molecule. NA is involved as an electron acceptor during the sequence of reactions and thus enhances the rate of photolysis of RF. Absorption and fluorescence measurements did not provide evidence for the complex formation between the two compounds under the present conditions. PMID:27222605

Impact of Pre-Pregnancy BMI on B Vitamin and Inflammatory Status in Early Pregnancy: An Observational Cohort Study

PubMed Central

Bjørke-Monsen, Anne-Lise; Ulvik, Arve; Nilsen, Roy M.; Midttun, Øivind; Roth, Christine; Magnus, Per; Stoltenberg, Camilla; Vollset, Stein Emil; Reichborn-Kjennerud, Ted; Ueland, Per Magne

2016-01-01

Maternal nutrition and inflammation have been suggested as mediators in the development of various adverse pregnancy outcomes associated with maternal obesity. We have investigated the relation between pre-pregnancy BMI, B vitamin status, and inflammatory markers in a group of healthy pregnant women. Cobalamin, folate, pyridoxal 5′-phosphate, and riboflavin; and the metabolic markers homocysteine, methylmalonic acid, and 3-hydroxykynurenine/xanthurenic acid ratio (HK/XA); and markers of cellular inflammation, neopterin and kynurenine/tryptophan ratio (KTR) were determined in pregnancy week 18 and related to pre-pregnancy body mass index (BMI), in 2797 women from the Norwegian Mother and Child Cohort Study (MoBa). Pre-pregnancy BMI was inversely related to folate, cobalamin, pyridoxal 5′-phosphate (PLP), and riboflavin (p < 0.001), and associated with increased neopterin and KTR levels (p < 0.001). Inflammation seemed to be an independent predictor of low vitamin B6 status, as verified by low PLP and high HK/XA ratio. A high pre-pregnancy BMI is a risk factor for low B vitamin status and increased cellular inflammation. As an optimal micronutrient status is vital for normal fetal development, the observed lower B vitamin levels may contribute to adverse pregnancy outcomes associated with maternal obesity and B vitamin status should be assessed in women with high BMI before they get pregnant. PMID:27916904

Genomic diversity and immunomodulatory activity of Lactobacillus plantarum isolated from dairy products.

PubMed

Zago, M; Scaltriti, E; Bonvini, B; Fornasari, M E; Penna, G; Massimiliano, L; Carminati, D; Rescigno, M; Giraffa, G

2017-08-24

In this study, we aimed to investigate some functional characteristics and the immunomodulatory properties of three strains of Lactobacillus plantarum of dairy origin which, in a previous screening, showed to be candidate probiotics. Genome sequencing and comparative genomics, which confirmed the presence of genes involved in folate and riboflavin production and in the immune response of dendritic cells (DCs), prompted us to investigate the ability of the three strains to accumulate the two vitamins and their immunomodulation properties. The ability of the three strains to release antioxidant components in milk was also investigated. Small amounts of folate and riboflavin were produced by the three strains, while they showed a good antioxidant capacity in milk with FRAP method. The immune response experiments well correlated with the presence of candidate genes influencing in DCs cytokine response to L. plantarum. Specifically, the amounts of secreted cytokins by DCs after stimulation with cells of Lp790, Lp813 and Lp998 resulted pro-inflammatory whereas stimulation with culture supernatants (postbiotics) inhibited the release of interleukin (IL)-12p70 and increased the release of the anti-inflammatory IL-10 cytokine. This study adds further evidence on the importance of L. plantarum in human health. Understanding how probiotics (or postbiotics) work in preclinical models can allow a rational choice of the different strains for clinical and/or commercial use.

Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial

PubMed Central

Ciliberto, Heather; Ciliberto, Michael; Briend, Andreé; Ashorn, Per; Bier, Dennis; Manary, Mark

2005-01-01

Objective To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Design Prospective, double blind, placebo controlled trial randomised by household. Setting 8 villages in rural southern Malawi. Participants 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Intervention Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. Main outcome measures The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. Results 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Conclusions Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor. PMID:15851401

In Situ Molecular Imaging of the Biofilm and Its Matrix

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

Ding, Yuanzhao; Zhou, Yufan; Yao, Juan

2016-11-15

Molecular mapping of live biofilms at submicron resolution presents a grand challenge. Here, we present the first chemical mapping results of biofilm extracellular polymeric sub-stance (EPS) components in biofilms using correlative imaging be-tween super resolution florescence microscopy and liquid time-of-flight secondary ion mass spectrometry (ToF-SIMS). Shewanella oneidensis is used as a model organism. Heavy metal anions chro-mate (Cr2O72-) consisting of chromium Cr (VI) was a model envi-ronmental stressor used to treat the biofilms. Of particular interest, biologically relevant water clusters have been first observed in the biofilms. Characteristic fragments of biofilm matrix components such as proteins, polysaccharides, and lipids canmore » be spatially im-aged. Furthermore, characteristic fatty acids (e.g., palmitic acid), quinolone signal, and riboflavin fragments are found to respond af-ter the biofilm is treated with Cr (VI), leading to biofilm dispersion. Significant changes in water clusters and quorum sensing signals indicative of intercellular communication in the aqueous environ-ment are observed, suggesting that they might result in fatty acid synthesis and inhibit riboflavin production. The Cr (VI) reduction seems to follow the Mtr pathway leading to Cr (III) formation. Our approach potentially opens a new avenue for mechanistic insight of microbial community processes and communications using in situ imaging mass spectrometry and superresolution optical micros-copy.« less

Ion-pair cloud-point extraction: a new method for the determination of water-soluble vitamins in plasma and urine.

PubMed

Heydari, Rouhollah; Elyasi, Najmeh S

2014-10-01

A novel, simple, and effective ion-pair cloud-point extraction coupled with a gradient high-performance liquid chromatography method was developed for determination of thiamine (vitamin B1 ), niacinamide (vitamin B3 ), pyridoxine (vitamin B6 ), and riboflavin (vitamin B2 ) in plasma and urine samples. The extraction and separation of vitamins were achieved based on an ion-pair formation approach between these ionizable analytes and 1-heptanesulfonic acid sodium salt as an ion-pairing agent. Influential variables on the ion-pair cloud-point extraction efficiency, such as the ion-pairing agent concentration, ionic strength, pH, volume of Triton X-100, extraction temperature, and incubation time have been fully evaluated and optimized. Water-soluble vitamins were successfully extracted by 1-heptanesulfonic acid sodium salt (0.2% w/v) as ion-pairing agent with Triton X-100 (4% w/v) as surfactant phase at 50°C for 10 min. The calibration curves showed good linearity (r(2) > 0.9916) and precision in the concentration ranges of 1-50 μg/mL for thiamine and niacinamide, 5-100 μg/mL for pyridoxine, and 0.5-20 μg/mL for riboflavin. The recoveries were in the range of 78.0-88.0% with relative standard deviations ranging from 6.2 to 8.2%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Role of Shewanella oneidensis MR-1 Outer Surface Structures in Extracellular Electron Transfer

DTIC Science & Technology

2010-01-01

Supernatants from the wells of the air-exposed VBSA that had been in operation for 220 h were harvested and planktonic cells were removed via...prepilins. In some bacteria, such as Pseudomonas aerugino- sa and Vibrio cholerae, PilD plays a dual role and processes type IVand T2SS prepilins [38 – 41... harvested from the VBSA at the times indicated by arrows in Fig. 4 (100 h data not shown). Fig. 6. Presence of riboflavin in cell-free supernatants

Treatment of platelets with riboflavin and ultraviolet light mediates complement activation and suppresses monocyte interleukin-12 production in whole blood.

PubMed

Loh, Y S; Dean, M M; Johnson, L; Marks, D C

2015-11-01

Pathogen inactivation (PI) and storage may alter the immunomodulatory capacity of platelets (PLTs). The aim of this study was to examine the effect of PI (Riboflavin and ultraviolet light treatment) and storage on the capacity of PLTs to induce cytokine responses in recipient inflammatory cells. A pool and split design was used to prepare untreated and PI-treated buffy coat-derived platelet concentrates (PCs). Samples were taken on days 2 and 7 postcollection and incubated with ABO/RhD-matched fresh whole blood for 6 h with or without lipopolysaccharide (LPS). The intracellular production of IP-10, MCP-1, MIP-1α, IL-8, IL-6, IL-10, IL-12, TNF-α and MIP-1β in monocytes and neutrophils was assessed using flow cytometry. Complement proteins in PLT supernatants were measured using a cytometric bead array. PLTs and PLT supernatant (both untreated and PI-treated) resulted in modulation of intracellular MIP-1β and IL-12 production in monocytes. Compared to untreated PLTs, PI-treated PLTs resulted in significantly lower LPS-induced monocyte IL-12 production (day 7). The concentration of C3a and C5a (and their desArg forms) was significantly increased in PLT supernatants following PI. PI results in decreased LPS-induced monocyte IL-12 production and increased complement activation. The association between platelet-induced complement activation and IL-12 production warrants further investigation. © 2015 International Society of Blood Transfusion.

Microwave high performance liquid chromatography with UV-visible detection. Application to vitamins determination.

PubMed

Terol, Amanda; Maestre, Salvador E; Prats, Soledad; Todolí, José L

2012-05-07

The present work describes the first attempt to use microwave reversed phase high performance liquid chromatography (MW-HPLC) to carry out the separation of organic compounds. Biotin and riboflavin were selected for the characterization of the new separation technique. Additional vitamins (nicotinamide, pyridoxine and thiamine) were used as reference compounds. In order to perform the separation, a chromatographic column was placed inside a domestic microwave oven in a hanging position. The column particular location was an extremely critical point, since it precluded the actual power absorbed by the sample. In order to avoid magnetron damage, a heat well (i.e., water vessels) was used. Vitamins were detected using a UV-VIS detector. Results obtained showed that the application of microwave radiation, even at low power levels, gave rise to a significant modification in the characteristics of the chromatograms. It was found that retention times for biotin and riboflavin shortened as the power increased. Furthermore, the peak shape also changed, with the modification being more significant for the former vitamin than for the latter one. Furthermore, sensitivity also increased as the column was exposed to the action of microwave. Comparatively speaking, MW-HPLC was more efficient in terms of compound separation than when performed at room temperature or thermostatted at 45 °C HPLC. This was likely due to the combined action of a moderate and quick heating of the mobile phase with an increase in the analytes diffusivity caused by the radiation.

Need for multivitamin use in the postoperative period of gastric bypass.

PubMed

Colossi, Fernanda G; Casagrande, Daniela S; Chatkin, Raquel; Moretto, Myriam; Barhouch, Anália S; Repetto, Giuseppe; Padoin, Alexandre V; Mottin, Cláudio C

2008-02-01

Based on the reduced gastric volume and the malabsorption produced by Roux-en-Y gastric bypass (RYGBP) and diet therapy, it is essential in the postoperative period to obtain and maintain an adequate nutritional state, with the aim of preventing malnutrition and seeking a healthy life. It is observed that patients have difficulty in understanding the new food choices that must considered, as they have eating habits that are very divergent from those currently proposed. There is often the need for vitamin and mineral replacement after laboratory tests. This study calculated and evaluated the 24-h eating records of 210 patients, collected in the course of nutritional visits in follow-ups of the first, third, sixth, ninth, 12th, 18th, and 24th months postoperative. It was possible to observe an increase in the consumption of nutrients in the course of the study period, but it was not regular and significant for all the nutrients. Also, it is noted that the minimal requirements for vitamin A, vitamin C, calcium, iron and B-complex vitamins (except for cyanocobalamin and riboflavin) were not attained. The nutrients in which satisfactory results were obtained were total proteins of high biological value: cyanocobalamin and riboflavin. This study demonstrated the concern for nutrient supplementation in the postoperative period of RYGBP. Thus, the routine use of multivitamins is deemed necessary after the first month postoperatively, with its maintenance preferably for the rest of the patient's life, without abandoning periodic clinical and laboratory follow-up.

Mapping three guanine oxidation products along DNA following exposure to three types of reactive oxygen species.

PubMed

Matter, Brock; Seiler, Christopher L; Murphy, Kristopher; Ming, Xun; Zhao, Jianwei; Lindgren, Bruce; Jones, Roger; Tretyakova, Natalia

2018-06-01

Reactive oxygen and nitrogen species generated during respiration, inflammation, and immune response can damage cellular DNA, contributing to aging, cancer, and neurodegeneration. The ability of oxidized DNA bases to interfere with DNA replication and transcription is strongly influenced by their chemical structures and locations within the genome. In the present work, we examined the influence of local DNA sequence context, DNA secondary structure, and oxidant identity on the efficiency and the chemistry of guanine oxidation in the context of the Kras protooncogene. A novel isotope labeling strategy developed in our laboratory was used to accurately map the formation of 2,2-diamino-4-[(2-deoxy-β-D-erythropentofuranosyl)amino]- 5(2 H)-oxazolone (Z), 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG), and 8-nitroguanine (8-NO 2 -G) lesions along DNA duplexes following photooxidation in the presence of riboflavin, treatment with nitrosoperoxycarbonate, and oxidation in the presence of hydroxyl radicals. Riboflavin-mediated photooxidation preferentially induced OG lesions at 5' guanines within GG repeats, while treatment with nitrosoperoxycarbonate targeted 3'-guanines within GG and AG dinucleotides. Little sequence selectivity was observed following hydroxyl radical-mediated oxidation. However, Z and 8-NO 2 -G adducts were overproduced at duplex ends, irrespective of oxidant identity. Overall, our results indicate that the patterns of Z, OG, and 8-NO 2 -G adduct formation in the genome are distinct and are influenced by oxidant identity and the secondary structure of DNA. Copyright © 2018 Elsevier Inc. All rights reserved.

Spectrofluorimetric determination of some water-soluble vitamins.

PubMed

Mohamed, Abdel-Maaboud I; Mohamed, Horria A; Abdel-Latif, Niveen M; Mohamed, Marwa R

2011-01-01

Two simple and sensitive spectrofluorimetric methods were developed for determination of three water-soluble vitamins (B1, B2, and B6) in mixtures in the presence of cyanocobalamin. The first one was for thiamine determination, which depends on the oxidation of thiamine HCl to thiochrome by iodine in an alkaline medium. The method was applied accurately to determine thiamine in binary, ternary, and quaternary mixtures with pyridoxine HCl, riboflavin, and cyanocobalamin without interference. In the second method, riboflavin and pyridoxine HCl were determined fluorimetrically in acetate buffer, pH 6. The three water-soluble vitamins (B1, B2, and B6) were determined spectrofluorimetrically in binary, ternary, and quaternary mixtures in the presence of cyanocobalamin. All variables were studied in order to optimize the reaction conditions. Linear relationship was obeyed for all studied vitamins by the proposed methods at their corresponding lambda(exc) or lambda(em). The linear calibration curves were obtained from 10 to 500 ng/mL; the correlation ranged from 0.9991 to 0.9999. The suggested procedures were applied to the analysis of the investigated vitamins in their laboratory-prepared mixtures and pharmaceutical dosage forms from different manufacturers. The RSD range was 0.46-1.02%, which indicates good precision. No interference was observed from common pharmaceutical additives. Good recoveries (97.6 +/- 0.7-101.2 +/- 0.8%) were obtained. Statistical comparison of the results with reported methods shows excellent agreement and indicates no significant difference in accuracy and precision.

Synthesis, characterization, thermal and antimicrobial studies of diabetic drug models: Complexes of vanadyl(II) sulfate with ascorbic acid (vitamin C), riboflavin (vitamin B2) and nicotinamide (vitamin B3)

NASA Astrophysics Data System (ADS)

Refat, Moamen S.

2010-04-01

The oxovanadium(II) complexes of the different vitamins like ascorbic acid (vitamin C; Vit. C), riboflavin (vitamin B2; Vit. B2) and nicotinamide (vitamin B3; Vit. B3) were synthesized and characterized by elemental analysis, molar conductance, IR, electronic, magnetic measurements, thermal studies, XRD and SEM. Conductance measurements indicated that the vanadyl(II) complexes of Vit. B2 and Vit. B3 are 1:2 electrolytes except for [VO(Vit. C) 2(H 2O) 2] complex is non-electrolyte. IR data show that Vit. B2 is bidentate ligand against azomethine nitrogen of pyrazine ring and C dbnd O of pyrimidine-2,4-dione but Vit. B3 and Vit. C acts as a monodentate ligand through pyridine nitrogen and hydroxo oxygen of furan ring, respectively. Electronic spectral measurements indicated that all VO(II) complexes have a square-pyramidal geometry. Magnetic measurements for the new vanadyl(II) complexes are in a good agreement with the proposed formula. Thermal analyses (TG/DSC) of the studied complexes show that the decomposition process takes place in more than two steps. XRD refer that VO(II) complexes have an amorphous behavior. The surface morphology of the complexes was studied by SEM. The antimicrobial activities of the ligands and its complexes indicate that the vanadyl(II) complexes possess high antibacterial and antifungal activities towards the bacterial species and the fungal species than start ligands.

Tapioca starch graft copolymers and Dome Matrix® modules II. Effect of modules assemblage on riboflavin release kinetics.

PubMed

Casas, Marta; Strusi, Orazio Luca; Jiménez-Castellanos, M Rosa; Colombo, Paolo

2011-01-01

This paper studies the Riboflavin release from systems made of assembled modules of Dome Matrix® technology using tapioca starch-ethylmethacrylate (TSEMA) and tapioca hydroxypropylstarch-ethylmethacrylate (THSEMA) graft copolymers produced by two different drying methods. Two different shape modules were manufactured for this study, i.e., female and male modules, in order to facilitate their assemblage in "void configuration", a system with an internal void space. Drug release studies on void configurations based on THSEMA show faster releases than TSEMA; HPMC systems used as a comparative reference showed intermediate release. Moreover, using void configurations made with one module of TSEMA and the other of THSEMA is possible to average the drug release, without difference between the drying methods used for the polymers. With respect to the floatation characteristics, all the void configurations floated immediately and, due to the mass center of the system, the floatation position of the system was always axial with the female module up and the male down. The drug release studies performed with a sinker to force the immersion of the systems in the medium did not show differences with respect to the dissolution test without a sinker. The combination of floatation capability of the assembled modules and the prolonged drug release provided with the graft copolymers make these assembled modules candidates as controlled release gastro-retentive dosage forms. Copyright © 2010 Elsevier B.V. All rights reserved.

Pathogen reduction of blood components.

PubMed

Solheim, Bjarte G

2008-08-01

Thanks to many blood safety interventions introduced in developed countries the risk of transfusion transmitted infections has become exceedingly small in these countries. However, emerging pathogens still represent a serious challenge, as demonstrated by West Nile virus in the US and more recently by Chikungunya virus in the Indian Ocean. In addition bacterial contamination, particularly in platelets, and protozoa transmitted by blood components still represent sizeable risks in developed countries. In developing countries the risk of all transfusion transmitted infections is still high due to insufficient funding and organisation of the health service. Pathogen reduction of pooled plasma products has virtually eliminated the risk of transfusion transmitted infections, without compromising the quality of the products significantly. Pathogen reduction of blood components has been much more challenging. Solvent detergent treatment which has been so successfully applied for plasma products dissolves cell membranes, and can, therefore, only be applied for plasma and not for cellular blood components. Targeting of nucleic acids has been another method for pathogen inactivation of plasma and the only approach possible for cellular blood products. As documented in more than 15 year's track record, solvent detergent treatment of pooled plasma can yield high quality plasma. The increased risk for contamination by unknown viruses due to pooling is out weighed by elimination of TRALI, significant reduction in allergic reactions and standardisation of the product. Recently, a promising method for solvent detergent treatment of single donor plasma units has been published. Methylene blue light treatment of single donor plasma units has a similar long track record as pooled solvent detergent treated plasma; but the method is less well documented and affects coagulation factor activity more. Psoralen light treated plasma has only recently been introduced (CE marked in Europe, but not licensed by the FDA), while the method of Riboflavin light treatment of plasma still is under development. In addition to pathogen reduction the methods, however, result in some reduction of coagulation factor activity. For platelets only Psoralen and Riboflavin light treatment have been implemented. Both are CE marked products in Europe but only approved for clinical trials in the USA. The methods affect platelet activity, but result in clinically acceptable platelets with only slightly reduced CCI and increased demand for platelet transfusions. Pathogen reduction of red blood cells with FRALE (S-303) or INACTINE (PEN110) has so far resulted in the formation of antibodies against neo-epitopes on red blood cells. A promising method for Riboflavin treatment of red blood cells is under development. This manuscript reviews the current experience and discusses future trends.

Photothermal Techniques Used to Evaluate Quality in Dairy Products.

NASA Astrophysics Data System (ADS)

López-Romero, E.; Balderas-López, J. A.

2017-01-01

Photothermal systems were used to quantify thermal and optical properties of commercial and natural dairy products. Thermal diffusivity and light absorption coefficient were analyzed. It was found that water content easily alters thermal properties in samples of milk. In addition, all samples showed strong light absorptions at 405 nm, 980 nm and 488 nm, evidencing presence of proteins, fat and vitamins (riboflavin), respectively. Therefore, it was shown that thermo-physical properties measured in this work could be used as complementary parameters for quality evaluation of dairy products.

Dynamic OCT measurement of corneal deformation by an air puff in normal and cross-linked corneas

PubMed Central

Dorronsoro, Carlos; Pascual, Daniel; Pérez-Merino, Pablo; Kling, Sabine; Marcos, Susana

2012-01-01

A new technique is presented for the non-invasive imaging of the dynamic response of the cornea to an air puff inducing a deformation. A spectral OCT instrument combined with an air tonometer in a non-collinear configuration was used to image the corneal deformation over full corneal cross-sections, as well as to obtain high speed measurements of the temporal evolution of the corneal apex. The entire deformation process can be dynamically visualized. A quantitative analysis allows direct extraction of several deformation parameters, such as amplitude, diameter and volume of the maximum deformation, as well as duration and speed of the increasing deformation period and the recovery period. The potential of the technique is demonstrated on porcine corneas in vitro under constant IOP for several conditions (untreated, after riboflavin instillation and under cross-linking with ultraviolet light), as well as on human corneas in vivo. The new technique has proved very sensitive to detect differences in the deformation parameters across conditions. We have confirmed non-invasively that Riboflavin and UV-cross-linking induce changes in the corneal biomechanical properties. Those differences appear to be the result of changes in constituent properties of the cornea, and not a consequence of changes in corneal thickness, geometry or IOP. These measurements are a first step for the estimation of the biomechanical properties of corneal tissue, at an individual level and in vivo, to improve diagnosis and prognosis of diseases and treatments involving changes in the biomechanical properties of the cornea. PMID:22435096

Fibrinogen, Riboflavin, and UVA to Immobilize a Corneal Flap—Conditions for Tissue Adhesion

PubMed Central

Littlechild, Stacy L.; Brummer, Gage; Zhang, Yuntao; Conrad, Gary W.

2012-01-01

Purpose. Laser-assisted in situ keratomileus (LASIK) creates a permanent flap that remains non-attached to the underlying laser-modified stroma. This lack of permanent adhesion is a liability. To immobilize a corneal flap, a protocol using fibrinogen (FIB), riboflavin (RF), and ultraviolet (UVA) light (FIB+RF+UVA) was devised to re-adhere the flap to the stroma. Methods. A model flap was created using rabbit (Oryctolagus cuniculus) and shark (Squalus acanthias) corneas. Solutions containing FIB and RF were applied between corneal strips as glue. Experimental corneas were irradiated with long wavelength (365 nm) UVA. To quantify adhesive strength between corneal strips, the glue-tissue interface was subjected to a constant force while a digital force gauge recorded peak tension. Results. In the presence of FIB, substantive non-covalent interactions occurred between rabbit corneal strips. Adhesiveness was augmented if RF and UVA also were applied, suggesting formation of covalent bonds. Additionally, exposing both sides of rabbit corneas to UVA generated more adhesion than exposure from one side, suggesting that RF in the FIB solution catalyzes formation of covalent bonds at only the interface between stromal molecules and FIB closest to the UVA. In contrast, in the presence of FIB, shark corneal strips interacted non-covalently more substantively than those of rabbits, and adhesion was not augmented by applying RF+UVA, from either or both sides. Residual RF could be rinsed away within 1 hour. Conclusions. Glue solution containing FIB and RF, together with UVA treatment, may aid immobilization of a corneal flap, potentially reducing risk of flap dislodgement. PMID:22589434

A case control study of nutritional factors and cervical dysplasia.

PubMed

Liu, T; Soong, S J; Wilson, N P; Craig, C B; Cole, P; Macaluso, M; Butterworth, C E

1993-01-01

The association of nutritional factors with cervical dysplasia was examined through a case-control study. Analysis was conducted in 257 cases and 133 controls confirmed both by cytological examination and colposcopic findings. A 24-h dietary recall questionnaire was used to assess nutritional intake. Various risk factors (including age at first intercourse, number of sexual partners, parity, cigarette smoking, oral contraceptive use, human papillomavirus type 16 infection, and age and race) were adjusted for their potential confounding effects. While analyses were also performed to adjust for total calories, results were not changed significantly. Among the nutrients examined, vitamin A intake showed a significantly increased risk at the lowest quartile compared to the highest quartile, with an odds ratio of 2.2 (95% confidence interval, 1.2-4.2). A significant trend of increasing risk was also observed with lower intake of vitamin A (P = 0.05). Riboflavin showed increased risk at the two lower quartiles of intake with a trend test P value of 0.04. Increased risk was also found for lower intakes of vitamin C compared to the highest intake level. For folate, increased risk was found in the second highest quartile compared with the highest quartile with an odds ratio of 2.0 (95% confidence interval, 1.0-3.8). The calcium:phosphorus ratio showed an increased risk at the lowest level (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). Insufficient intake of vitamin A, riboflavin, ascorbate, and folate is associated with an increased risk of cervical dysplasia.

Nutritional quality of lunches consumed by Korean workers: Comparison between institutional and commercial lunches

PubMed Central

Kim, Won Gyoung; Choi, Injoo

2016-01-01

BACKGROUND/OBJECTIVES The nutritional quality of lunches is an important factor related to workers' health. This study examined the nutritional quality of Korean workers' lunches with a focus on comparing institutional and commercial lunches. SUBJECTS/METHODS The data from a 1-day, 24-hour dietary recall from the 5th Korea National Health and Nutrition Examination Survey (2010-2012) were analyzed. A total of 2,192 subjects aged 19 to 64 years, who had consumed lunches served by institutional or commercial food service vendors, were included for analysis. The nutritional quality of the lunches of the institutional lunch group (n=626) and the commercial lunch group (n=1,566) was compared in terms of the number of servings, food groups, nutrient intake, Nutrient Adequacy Ratio (NAR), and Mean Adequacy Ratio (MAR). RESULTS The NAR and MAR were significantly higher in the institutional lunches than in the commercial lunches, but more than half of workers in both groups obtained over 65% of their energy from carbohydrate. The average sodium intake from the lunches exceeded the daily intake goal (2,000 mg) in both groups. More than half of workers in both groups presented less than one-third of their respective recommended daily intake of riboflavin and calcium. With the exception of riboflavin, the nutrient intake from lunches accounted for more than 35% of the daily nutrient intake. CONCLUSIONS The overall nutritional quality of institutional lunches was higher than that of commercial lunches. However, institutional lunches had room for improvement in terms of nutritional quality. PMID:27909558

MTHFR 677TT genotype and disease risk: is there a modulating role for B-vitamins?

PubMed

Reilly, R; McNulty, H; Pentieva, K; Strain, J J; Ward, M

2014-02-01

Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme which requires riboflavin as its co-factor. A common polymorphism (677C→T) in the MTHFR gene results in reduced MTHFR activity in vivo which in turn leads to impaired folate metabolism and elevated homocysteine concentrations. Homozygosity for this polymorphism (TT genotype) is associated with an increased risk of a number of conditions including heart disease and stroke, but there is considerable variability in the extent of excess risk in various reports. The present review will explore the evidence which supports a role for this polymorphism as a risk factor for a number of adverse health outcomes, and the potential modulating roles for B-vitamins in alleviating disease risk. The evidence is convincing in the case which links this polymorphism with hypertension and hypertensive disorders of pregnancy, particularly preeclampsia. Furthermore, elevated blood pressure was found to be highly responsive to riboflavin intervention specifically in individuals with the MTHFR 677TT genotype. Future intervention studies targeted at these genetically predisposed individuals are required to further investigate this novel gene-nutrient interaction. This polymorphism has also been associated with an increased risk of neural tube defects (NTD) and other adverse pregnancy outcomes; however, the evidence in this area has been inconsistent. Preliminary evidence has suggested that there may be a much greater need for women with the MTHFR 677TT genotype to adhere to the specific recommendation of commencing folic acid prior to conception for the prevention of NTD, but this requires further investigation.

[Complications and postoperative therapeutic strategies in cross-linking].

PubMed

Kohlhaas, M

2017-08-01

The reduced corneal mechanical stability in keratoconus and similar collagen diseases can lead to a progressive and irregular corneal shape and decrease of visual acuity. A progression of keratectatic diseases can be shown with corneal topography. Keratoconus can be treated by photo-oxidative cross-linking of the corneal collagen. In order to achieve a high absorption of irradiation energy in the cornea, riboflavin at a concentration of 0.1% and UVA light at a wavelength of 370 nm corresponding to the relative maximum absorption of riboflavin (vitamin B2) are used. Evidence for corneal cross-linking are the increase of biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibers. The currently available data demonstrate that the therapeutic cross-linking procedure is safe when respecting the important theoretical and clinical parameters and that a progression of the keratoconus can be avoided. In 80% of cases an average levelling of the curvature of approximately 2 dpt can be achieved, which leads not only to stabilization but also to an increase in visual acuity of approximately 1.2 lines. In a Cochrane review from 2015 publications about complications and results were reviewed. Complication rates ranged from 1-10% depending on the initial situation, comorbidities and stage of the keratoconus. The most important complications are early epithelial wound healing problems as well as extremely rare perforations. Corneal cross-linking is a well-established and safe procedure but is not free of complications.

Reduced MHC Alloimmunization and Partial Tolerance Protection With Pathogen Reduction Of Whole Blood

PubMed Central

Jackman, Rachael P.; Muench, Marcus O.; Inglis, Heather; Heitman, John W.; Marschner, Susanne; Goodrich, Raymond P.; Norris, Philip J.

2017-01-01

BACKGROUND Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We have previously shown that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and UV light (UV+R) can prevent alloimmunization in mice. A similar pathogen reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light. We sought to determine the effectiveness of this treatment in prevention of alloimmunization. STUDY DESIGN AND METHODS BALB/c mice were transfused with untreated or UV+R treated allogeneic C57Bl/6 whole blood with or without leukoreduction. Mice were evaluated for donor specific antibodies and ex vivo splenocyte cytokine responses, as well as for changes in the frequency of regulatory T (Treg) cells. RESULTS UV+R treatment blocked cytokine priming and reduced anti-MHC alloantibody responses to transfused whole blood. Leukoreduction reduced alloantibody levels in both the untreated and UV+R groups. Mice transfused with UV+R treated whole blood had reduced alloantibody and cytokine responses when subsequently transfused with untreated blood from the same donor type. This reduction in responses was not associated with increased Treg cells. CONCLUSIONS Pathogen reduction of whole blood with UV+R significantly reduces, but does not eliminate the alloimmune response. Exposure to UV+R treated whole blood transfusion does appear to induce tolerance to alloantigens resulting in reduced anti-MHC alloantibody and cytokine responses to subsequent exposures to the same alloantigens. This tolerance does not appear to be driven by an increase in Treg cells. PMID:27859333

Riboflavin and ultraviolet light reduce the infectivity of Babesia microti in whole blood.

PubMed

Tonnetti, Laura; Thorp, Aaron M; Reddy, Heather L; Keil, Shawn D; Goodrich, Raymond P; Leiby, David A

2013-04-01

Babesia microti is the parasite most frequently transmitted by blood transfusion in the United States. Previous work demonstrated the efficacy of riboflavin (RB) and ultraviolet (UV) light to inactivate B.microti in apheresis plasma and platelet units. In this study we investigated the effectiveness of RB and UV light to reduce the levels of B.microti in whole blood (WB). WB units were spiked with B. microti-infected hamster blood. Spearman-Karber methods were used to calculate infectivity of each sample in terms of hamster infectious dose 50% (HID50 ) value. After RB addition, the units were illuminated with 80 J/mLRBC UV light. Two samples were collected: one before illumination and one after illumination. The samples were serially diluted and dilutions injected into a group of five naive hamsters. Four weeks postinoculation (PI), blood was collected from the animals and evaluated by microscopic observation. One pilot study showed a good dose response in the animals and demonstrated that sample infectivity could be calculated in terms of an HID50 . Three additional replicates were performed in the same manner as the pilot study, but with fewer dilutions. Infectivity values were consistent between the experiments and were used to calculate log reduction. The posttreatment reduction of B. microti for all the experiments was more than 5 log. The data collected indicate that use of RB and UV is able to decrease the parasite load in WB units thus reducing the risk of transfusion-transmitted B. microti from blood components containing B. microti-infected RBCs. © 2012 American Association of Blood Banks.

Micronutrient supplementation improves physical performance measures in Asian Indian school-age children.

PubMed

Vaz, Mario; Pauline, Maria; Unni, Uma S; Parikh, Panam; Thomas, Tinku; Bharathi, A V; Avadhany, Sandhya; Muthayya, Sumithra; Mehra, Ruchika; Kurpad, Anura V

2011-11-01

Micronutrients are important in physical work capacity and therefore performance. The impact of a multi-micronutrient-fortified nutritional beverage on physical performance measures among clinically healthy school-age children was assessed in a double-blind (for test and placebo groups), placebo-controlled, randomized trial in children aged between 7 and 10.5 y (n = 300). The participants with height- and weight-for-age Z-scores between 0 and ≥ -3 were randomized to 1 of 3 study arms: fortified choco-malt beverage powder (F), matched energy equivalent unfortified placebo (U), and untreated control (C). Participants in the F and C groups were given 40 g fortified (19 key vitamins and minerals) and unfortified choco-malt beverage, respectively, daily for 120 d. Primary efficacy outcomes included endurance and aerobic capacity using a 20-m shuttle test and step test. Other physical performance measures included speed (40-m sprint), visual reaction time, maximal hand grip, and forearm static endurance. Micronutrient status included thiamin, riboflavin, folate, niacin, iron, pyridoxal phosphate, and vitamins B-12 and C. All measurements were made at baseline and the end of the intervention. There was a within-subject increase in aerobic capacity and whole body endurance (P < 0.05) accompanied by a significant improvement in the status of iron thiamin, riboflavin, pyridoxal phosphate, folate, and vitamins C and B-12 in the F group compared to the within-subject changes in the other 2 groups (P < 0.05). The study suggests that multiple micronutrient supplementation in similar populations may be beneficial in improving micronutrient status and enhancing aerobic capacity and endurance in children.

Behavior in the open field predicts the number of KCl-induced cortical spreading depressions in rats.

PubMed

Bogdanov, Volodymyr Borysovych; Bogdanova, Olena Viktorivna; Koulchitsky, Stanislav Vladimirovich; Chauvel, Virginie; Multon, Sylvie; Makarchuk, Mykola Yukhymovych; Brennan, Kevin Christopher; Renshaw, Perry Franklin; Schoenen, Jean

2013-01-01

Anxiety disorders are known to be comorbid with migraine, and cortical spreading depression (CSD) is the most likely cause of the migraine aura. To search for possible correlations between susceptibility to CSD and anxiety we used the open field test in male Sprague-Dawley rats chronically treated with the preventive anti-migraine drugs valproate or riboflavin. Animals avoiding the central area of the open field chamber and those with less exploratory activity (i.e. rearing) were considered more anxious. After 4 weeks of treatment CSDs were elicited by application of 1M KCl over the occipital cortex and the number of CSDs occurring over a 2h period was compared to the previously assessed open field behavior. Higher anxiety-like behavior was significantly correlated with a higher frequency of KCl-induced CSDs. In saline-treated animals, fewer rearings were found in animals with more frequent CSDs (R=-1.00). The duration of ambulatory episodes in the open field center correlated negatively with number of CSDs in the valproate group (R=-0.83; p<0.005) and in riboflavin treated group (R=-0.69; p<0.05) as well as total time spent in the open field center in both groups (R=-0.75; p<0.05 and R=-0.58; p<0.1 respectively). These results suggest that anxiety symptoms are associated with susceptibility to CSD and might explain why it can be an aggravating factor in migraine with aura. Copyright © 2012 Elsevier B.V. All rights reserved.

Evolutionary divergence of chloroplast FAD synthetase proteins

PubMed Central

2010-01-01

Background Flavin adenine dinucleotide synthetases (FADSs) - a group of bifunctional enzymes that carry out the dual functions of riboflavin phosphorylation to produce flavin mononucleotide (FMN) and its subsequent adenylation to generate FAD in most prokaryotes - were studied in plants in terms of sequence, structure and evolutionary history. Results Using a variety of bioinformatics methods we have found that FADS enzymes localized to the chloroplasts, which we term as plant-like FADS proteins, are distributed across a variety of green plant lineages and constitute a divergent protein family clearly of cyanobacterial origin. The C-terminal module of these enzymes does not contain the typical riboflavin kinase active site sequence, while the N-terminal module is broadly conserved. These results agree with a previous work reported by Sandoval et al. in 2008. Furthermore, our observations and preliminary experimental results indicate that the C-terminus of plant-like FADS proteins may contain a catalytic activity, but different to that of their prokaryotic counterparts. In fact, homology models predict that plant-specific conserved residues constitute a distinct active site in the C-terminus. Conclusions A structure-based sequence alignment and an in-depth evolutionary survey of FADS proteins, thought to be crucial in plant metabolism, are reported, which will be essential for the correct annotation of plant genomes and further structural and functional studies. This work is a contribution to our understanding of the evolutionary history of plant-like FADS enzymes, which constitute a new family of FADS proteins whose C-terminal module might be involved in a distinct catalytic activity. PMID:20955574

Fibrinogen, Riboflavin, and UVA to Immobilize a Corneal Flap – Molecular Mechanisms

PubMed Central

Littlechild, Stacy L.; Zhang, Yuntao; Tomich, John M.; Conrad, Gary W.

2012-01-01

Purpose. Tissue glue containing fibrinogen (FIB) and riboflavin (RF), upon exposure to long wavelength ultraviolet light (UVA, 365 nM) has been proposed potentially to solve long-standing problems presented by corneal wound and epithelial ingrowth side-effects from laser-assisted in situ keratomileuis (LASIK). Data presented in a previous study demonstrated an ability of FIB + RF + UVA to adhere two stromal surfaces; however, to our knowledge no molecular mechanisms have been proposed to account for interactions occurring between corneal extracellular matrix (ECM) and tissue glue molecules. Here, we document several covalent and noncovalent interactions between these classes of macromolecules. Methods. SDS-PAGE and Western blot techniques were used to identify covalent interactions between tissue glue molecules and corneal ECM molecules in either the presence or absence of RF and UVA, in vitro and ex vivo. Surface plasmon resonance (SPR) was used to characterize noncovalent interactions, and obtain ka, kd, and KD binding affinity values. Results. SDS-PAGE and Western blot analyses indicated that covalent interactions occurred between neighboring FIB molecules, as well as between FIB and collagen type I (Coll-I) proteins (in vitro and ex vivo). These interactions occurred only in the presence of RF and UVA. SPR data demonstrated the ability of FIB to bind noncovalently to corneal stroma molecules, Coll-I, decorin, dermatan sulfate, and corneal basement membrane molecules, laminin and heparan sulfate – only in the presence of Zn2+. Conclusions. Covalent and (zinc-mediated) noncovalent mechanisms involving FIB and stromal ECM molecules contribute to the adhesion created by FIB + RF + UVA. PMID:22879413

Structural and Kinetic Properties of Lumazine Synthase Isoenzymes in the Order Rhizobiales

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

Klinke,S.; Zylberman, V.; Bonomi, H.

6, 7-Dimethyl-8-ribityllumazine synthase (lumazine synthase; LS) catalyzes the penultimate step in the biosynthesis of riboflavin in plants and microorganisms. This protein is known to exhibit different quaternary assemblies between species, existing as free pentamers, decamers (dimers of pentamers) and icosahedrally arranged dodecamers of pentamers. A phylogenetic analysis on eubacterial, fungal and plant LSs allowed us to classify them into two categories: Type I LSs (pentameric or icosahedral) and Type II LSs (decameric). The Rhizobiales represent an order of ?-proteobacteria that includes, among others, the genera Mesorhizobium, Agrobacterium and Brucella. Here, we present structural and kinetic studies on several LSs frommore » Rhizobiales. Interestingly, Mesorhizobium and Brucella encode both a Type-I LS and a Type-II LS called RibH1 and RibH2, respectively. We show that Type II LSs appear to be almost inactive, whereas Type I LSs present a highly variable catalytic activity according to the genus. Additionally, we have solved four RibH1/RibH2 crystallographic structures from the genera Mesorhizobium and Brucella. The relationship between the active-site architecture and catalytic properties in these isoenzymes is discussed, and a model that describes the enzymatic behavior is proposed. Furthermore, sequence alignment studies allowed us to extend our results to the genus Agrobacterium. Our results suggest that the selective pressure controlling the riboflavin pathway favored the evolution of catalysts with low reaction rates, since the excess of flavins in the intracellular pool in Rhizobiales could act as a negative factor when these bacteria are exposed to oxidative or nitrosative stress.« less

Dietary intake of the water-soluble vitamins B1, B2, B6, B12 and C in 10 countries in the European Prospective Investigation into Cancer and Nutrition.

PubMed

Olsen, A; Halkjaer, J; van Gils, C H; Buijsse, B; Verhagen, H; Jenab, M; Boutron-Ruault, M C; Ericson, U; Ocké, M C; Peeters, P H M; Touvier, M; Niravong, M; Waaseth, M; Skeie, G; Khaw, K T; Travis, R; Ferrari, P; Sanchez, M J; Agudo, A; Overvad, K; Linseisen, J; Weikert, C; Sacerdote, C; Evangelista, A; Zylis, D; Tsiotas, K; Manjer, J; van Guelpen, B; Riboli, E; Slimani, N; Bingham, S

2009-11-01

To describe the intake of vitamins thiamine (B1), riboflavin (B2), B6 (pyridoxine), B12 (cobalamine) and C (ascorbic acid) and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Between 1995 and 2000, 36 034 persons aged between 35 and 74 years were administered a standardized 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes of the four B vitamins and vitamin C were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age and weighted by season and day of recall. Intake of B vitamins did not vary considerably between centres, except in the UK health-conscious cohort, in which substantially higher intakes of thiamine and lower intakes of vitamin B12 were reported compared with other centres. Overall, meat was the most important contributor to the B vitamins in all centres except in the UK health-conscious group. Vitamin C showed a clear geographical gradient, with higher intakes in the southern centres as compared with the northern ones; this was more pronounced in men than in women. Vegetables and fruits were major contributors to vitamin C in all centres, but juices and potatoes were also important sources in the northern centres. This study showed no major differences across centres in the mean intakes of B vitamins (thiamine, riboflavin, B6, B12), whereas a tendency towards a north-south gradient was observed for vitamin C.

Protective effects of B vitamins and antioxidants on the risk of arsenic-related skin lesions in Bangladesh.

PubMed

Zablotska, Lydia B; Chen, Yu; Graziano, Joseph H; Parvez, Faruque; van Geen, Alexander; Howe, Geoffrey R; Ahsan, Habibul

2008-08-01

An estimated 25-40 million of the 127 million people of Bangladesh have been exposed to high levels of naturally occurring arsenic from drinking groundwater. The mitigating effects of diet on arsenic-related premalignant skin lesions are largely unknown. The purpose of this study was to clarify the effects of the vitamin B group (thiamin, riboflavin, niacin, pyridoxine, and cobalamin) and antioxidants (vitamins A, C, and E) on arsenic-related skin lesions. We performed a cross-sectional study using baseline data from the Health Effects of Arsenic Longitudinal Study (HEALS), 2000-2002, with individual-level, time-weighted measures of arsenic exposure from drinking water. A total of 14,828 individuals meeting a set of eligibility criteria were identified among 65,876 users of all 5,996 tube wells in the 25-km(2) area of Araihazar, Bangladesh; 11,746 were recruited into the study. This analysis is based on 10,628 subjects (90.5%) with nonmissing dietary data. Skin lesions were identified according to a structured clinical protocol during screening and confirmed with further clinical review. Riboflavin, pyridoxine, folic acid, and vitamins A, C, and E significantly modified risk of arsenic-related skin lesions. The deleterious effect of ingested arsenic, at a given exposure level, was significantly reduced (ranging from 46% reduction for pyridoxine to 68% for vitamin C) for persons in the highest quintiles of vitamin intake. Intakes of B-vitamins and antioxidants, at doses greater than the current recommended daily amounts for the country, may reduce the risk of arsenic-related skin lesions in Bangladesh.

Transient corneal endothelial changes following accelerated collagen cross-linking for the treatment of progressive keratoconus.

PubMed

Cingü, Abdullah Kürşat; Sogutlu-Sari, Esin; Cınar, Yasin; Sahin, Muhammed; Türkçü, Fatih Mehmet; Yüksel, Harun; Sahin, Alparslan; Caça, Ihsan

2014-06-01

To evaluate the corneal endothelial changes following accelerated collagen cross-linking (CXL) for the treatment of progressive keratoconus. Thirty-six consecutive progressive keratoconus patients who received accelerated CXL treatment were enrolled in the study. Following de-epithelization, isoosmolar 0.1% riboflavin solution without dextran was instilled every 3 min throughout the 30 min of soaking time before the 5 min of 18 mW/cm(2) UVA irradiation and every 2 min during the UVA irradiation. Corneal specular microscopy was performed on both treated and fellow eyes of each patient preoperatively, in the first week, and in the first, third and sixth month postoperatively. There were significant differences in endothelial cell density (ECD), percentages of hexagonality (6A) and coefficient of variation of endothelial cell area (CV) in the first week and first month postoperatively in the treated eyes when compared to their preoperative values and also to the first week and first month ECD, 6A and CV values of the non-operative eyes. ECD returned to the preoperative values at sixth month whereas 6A and CV returned to the preoperative values at third month. Our results suggested that there may be transient changes in human corneal endothelium following accelerated UVA/riboflavin CXL. Resolution of these changes during the follow-up may indicate a safe recovery. However, the treatment guidelines for accelerated CXL including irradiance level and soaking time should be clearly established to minimize the toxic effects of the treatment.

Topological, chemical and electro-optical characteristics of riboflavin-doped artificial and natural DNA thin films

NASA Astrophysics Data System (ADS)

Gnapareddy, Bramaramba; Dugasani, Sreekantha Reddy; Son, Junyoung; Park, Sung Ha

2018-02-01

DNA is considered as a useful building bio-material, and it serves as an efficient template to align functionalized nanomaterials. Riboflavin (RF)-doped synthetic double-crossover DNA (DX-DNA) lattices and natural salmon DNA (SDNA) thin films were constructed using substrate-assisted growth and drop-casting methods, respectively, and their topological, chemical and electro-optical characteristics were evaluated. The critical doping concentrations of RF ([RF]C, approx. 5 mM) at given concentrations of DX-DNA and SDNA were obtained by observing the phase transition (from crystalline to amorphous structures) of DX-DNA and precipitation of SDNA in solution above [RF]C. [RF]C are verified by analysing the atomic force microscopy images for DX-DNA and current, absorbance and photoluminescence (PL) for SDNA. We study the physical characteristics of RF-embedded SDNA thin films, using the Fourier transform infrared spectrum to understand the interaction between the RF and DNA molecules, current to evaluate the conductance, absorption to understand the RF binding to the DNA and PL to analyse the energy transfer between the RF and DNA. The current and UV absorption band of SDNA thin films decrease up to [RF]C followed by an increase above [RF]C. By contrast, the PL intensity illustrates the reverse trend, as compared to the current and UV absorption behaviour as a function of the varying [RF]. Owing to the intense PL characteristic of RF, the DNA lattices and thin films with RF might offer immense potential to develop efficient bio-sensors and useful bio-photonic devices.

Topological, chemical and electro-optical characteristics of riboflavin-doped artificial and natural DNA thin films

PubMed Central

Gnapareddy, Bramaramba; Son, Junyoung

2018-01-01

DNA is considered as a useful building bio-material, and it serves as an efficient template to align functionalized nanomaterials. Riboflavin (RF)-doped synthetic double-crossover DNA (DX-DNA) lattices and natural salmon DNA (SDNA) thin films were constructed using substrate-assisted growth and drop-casting methods, respectively, and their topological, chemical and electro-optical characteristics were evaluated. The critical doping concentrations of RF ([RF]C, approx. 5 mM) at given concentrations of DX-DNA and SDNA were obtained by observing the phase transition (from crystalline to amorphous structures) of DX-DNA and precipitation of SDNA in solution above [RF]C. [RF]C are verified by analysing the atomic force microscopy images for DX-DNA and current, absorbance and photoluminescence (PL) for SDNA. We study the physical characteristics of RF-embedded SDNA thin films, using the Fourier transform infrared spectrum to understand the interaction between the RF and DNA molecules, current to evaluate the conductance, absorption to understand the RF binding to the DNA and PL to analyse the energy transfer between the RF and DNA. The current and UV absorption band of SDNA thin films decrease up to [RF]C followed by an increase above [RF]C. By contrast, the PL intensity illustrates the reverse trend, as compared to the current and UV absorption behaviour as a function of the varying [RF]. Owing to the intense PL characteristic of RF, the DNA lattices and thin films with RF might offer immense potential to develop efficient bio-sensors and useful bio-photonic devices. PMID:29515837

Design and evaluation of capillary coupled with optical fiber light-emitting diode induced fluorescence detection for capillary electrophoresis.

PubMed

Ji, Hongyun; Li, Meng; Guo, Lihong; Yuan, Hongyan; Wang, Chunling; Xiao, Dan

2013-09-01

A new detector, capillary coupled with optical fiber LED-induced fluorescence detector (CCOF-LED-IFD, using CCOF for short), is introduced for CE. The strategy of the present work was that the optical fiber and separation capillary were, in the parallel direction, fastened in a fixation capillary with larger inner diameter. By employing larger inner diameter, the fixation capillary allowed the large diameter of the optical fiber to be inserted into it. By transmitting an enhanced excitation light through the optical fiber, the detection sensitivity was improved. The advantages of the CCOF-CE system were validated by the detection of riboflavin, and the results were compared to those obtained by the in-capillary common optical fiber LED-induced fluorescence detector (IC-COF-LED-IFD, using COF for short). The LODs of CCOF-CE and COF-CE were 0.29 nM and 11.0 nM (S/N = 3), respectively. The intraday (n = 6) repeatability and interday (n = 6) reproducibility of migration time and corresponding peak area for both types of CE were all less than 1.10 and 3.30%, respectively. The accuracy of the proposed method was judged by employing standard addition method, and recoveries obtained were in the range of 98.0-102.4%. The results indicated that the sensitivity of the proposed system was largely improved, and that its reproducibility and accuracy were satisfactory. The proposed system was successfully applied to separate and determine riboflavin in real sample. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationships among Socioeconomic Status, Dietary Intake, and Stress in Breastfeeding Women.

PubMed

Aubuchon-Endsley, Nicki L; Kennedy, Tay S; Gilchrist, Megan; Thomas, David G; Grant, Stephanie

2015-06-01

As breastfeeding duration increases, it is important to understand diets of breastfeeding women and other factors salient to maternal/offspring health, including stress. It is important to further consider sociodemographic factors, given their associations with nutritional deficiencies and perceived stress. We cross-sectionally compared breastfeeding women's dietary intakes from a food frequency questionnaire (assessing from pregnancy through 3 months postpartum) with Estimated Average Requirements (EARs). We hypothesized that dietary intake was related to sociodemographic variables and parenting stress. We examined a cohort of predominately breastfeeding women. Food frequency questionnaire results were compared with EARs, the Parenting Stress Index: Short Form, and a demographic questionnaire. Participants included 101 women (of 289 recruited) who breastfed singleton, full-term infants for the first 3 months while using <28 oz formula/wk. The study included community recruitment in rural Oklahoma from 2008 to 2012. Mean and standard deviation or frequencies were reported. One-sample t tests compared EARs with mean dietary intakes over the past 12 months. Pearson correlations and one-way analyses of variance explored relationships among dietary, sociodemographic, and stress variables. Twenty-two percent of women did not meet EAR minimum energy recommendations and >40% did not meet protein recommendations. Despite widespread supplement use, some consumed less than the EAR for vitamin E (35%), calcium (22%), and vitamin C (19%). Carbohydrate consumption was positively related to the difficult child scale (r=0.19; P=0.05). Dietary riboflavin (r=-0.19; P=0.05) and vitamin D intake (r=-0.19; P=0.05) were negatively related to the parent-child dysfunction scale. Despite efforts to enhance education and counseling regarding adequate perinatal nutrition-related practices, even well-educated women may not meet EARs. This poor dietary intake may be associated with parenting stress and have potential long-term implications for child health. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

[The vitamin status of pregnant women in Moscow: effect of multivitamin-mineral supplements].

PubMed

Beketova, N A; Sokolnikov, A A; Kodentsova, V M; Pereverzeva, O G; Vrzhesinskaya, O A; Kosheleva, O V; Gmoshinskaya, M V

2016-01-01

Examination of the vitamin status of 102 pregnant women (19-41 years old) from Moscow (gestational age 6-38 weeks) in winter and spring 2015 has been conducted. The lack of vitamin B2 (blood serum level of riboflavin <5 ng/ml), D (25(OH)D level <30 ng/ml) and β-carotene (<20 mg/dL) occurred in 49-66% of pregnant women. The percentage of persons with reduced serum levels of vitamin B6 (<4.8 mg/l), folic acid (<3 mg/l), vitamin A (<30 mg/dL), and E (<0.8 mg/dl) was insignificant and amounted 6-8%. All of the women had an adequate supply with vitamins C (>0.4 mg/dL) and B12 (>150 ng/L). The frequency of the combined deficiency of two vitamins was 29%, of three vitamins - 21%, four - 10%, five - 5%. Only 8% of women were sufficiently supplied with all 8 studied vitamins and β-carotene. A positive correlation (p<0.001) between the concentration of vitamin E and gestation term occurred. β-Carotene blood serum level raised with increasing gestation term in women receiving multivitamin-mineral supplements (VMS) and directly correlated (p<0.05) with vitamin E serum level. In 63 women who were not taking VMS, blood serum level of vitamins A, D, C, B2, B6, B12, folic acid and β-carotene was lower, and the frequency of inadequate supply, on the contrary, was significantly higher, compared to 39 women receiving VMS. Blood serum concentration of vitamins C, A, D, B6 and folic acid in women who were not taking VMS was significantly reduced (p<0.05) with increasing gestation term, whereas in women consuming VMS vitamin blood serum level was maintained at a constant level. The data obtained demonstrate advisability of VMS intake during pregnancy to maintain vitamin status of pregnant women at a satisfactory level and to reduce the risk of birth defects in infants.

Inadequate Dietary Intake in Patients with Thalassemia

PubMed Central

Fung, Ellen B.; Xu, Yan; Trachtenberg, Felicia; Odame, Isaac; Kwiatkowski, Janet L.; Neufeld, Ellis J.; Thompson, Alexis A.; Boudreaux, Jeanne; Quinn, Charles T.; Vichinsky, Elliott P.

2012-01-01

Background Patients with thalassemia have low circulating levels of many nutrients, but the contribution of dietary intake has not been assessed. Objective Assess dietary intake in a large contemporary sample of patients with thalassemia. Design Prospective, longitudinal cohort study using a validated food frequency questionnaire Participants 221 patients (19.7±11.3 yrs, 106 female) categorized into three age groups: young children (3–7.9 y), older children/adolescents (8–18.9 yr), and adult (≥ 19 yr). 78.8% β-thalassemia; 90% chronically transfused. Setting 10 hematology outpatient clinics in the United States and Canada. Main outcome measures Comparison of intake with U.S. Dietary Reference Intakes, and correlation with serum 25-OH vitamin D and total body iron stores. Statistical Analyses Performed Intake was defined as inadequate if less than the estimated average requirement (EAR). Chi-square, Fisher’s exact and Student’s t-test were utilized to compare intake between age categories and logistic regression analysis to test the relationship between intake and outcomes, controlling for age, gender and race. Results Over 30% of patients consumed inadequate levels of vitamin A, D, E, K, folate, calcium, and magnesium. The only nutrients for which >90% of patients consumed adequate amounts were riboflavin, vitamin B12 and selenium. Dietary inadequacy increased with increasing age group (p<0.01) for vitamins A, C, E, B6, folate, thiamin, calcium, magnesium and zinc. Over half the sample took additional supplements of calcium and vitamin D, although circulating levels of 25-OH vitamin D remained insufficient in 61% of patients. Dietary iron intake was not related to total body iron stores. Conclusion Patients with thalassemia have reduced intake of many key nutrients. These preliminary findings of dietary inadequacy is concerning and supports the need for nutritional monitoring to determine which patients are at greatest risk for nutritional deficiency. Future research should focus on the effect of dietary quality and nutritional status on health outcomes in thalassemia. PMID:22551675

Complete genome sequence of Lactobacillus heilongjiangensis DSM 28069(T): Insight into its probiotic potential.

PubMed

Zheng, Beiwen; Jiang, Xiawei; Cheng, Hong; Xu, Zemin; Li, Ang; Hu, Xinjun; Xiao, Yonghong

2015-12-20

Lactobacillus heilongjiangensis DSM 28069(T) is a potential probiotic isolated from traditional Chinese pickle. Here we report the complete genome sequence of this strain. The complete genome is 2,790,548bp with the GC content of 37.5% and devoid of plasmids. Sets of genes involved in the biosynthesis of riboflavin and folate were identified in the genome, which revealed its potential application in biotechnological industry. The genome sequence of L. heilongjiangensis DSM 28069(T) now provides the fundamental information for future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

The nature of multiphoton fluorescence from red blood cells

NASA Astrophysics Data System (ADS)

Saytashev, Ilyas; Murphy, Michael; Osseiran, Sam; Spence, Dana M.; Evans, Conor L.; Dantus, Marcos

2016-03-01

We report on the nature of multiphoton excited fluorescence observed from human erythrocytes (red blood cells RBC's) and their "ghosts" following 800nm sub-15 fs excitation. The detected optical signal is assigned as two-photon excited fluorescence from hemoglobin. Our findings are supported by wavelength-resolved fluorescence lifetime decay measurements using time-correlated single photon counting system from RBC's, their ghosts as well as in vitro samples of various fluorophores including riboflavin, NADH, NAD(P)H, hemoglobin. We find that low-energy and short-duration pulses allow two-photon imaging of RBC's, but longer more intense pulses lead to their destruction.

[Influence of hypocaloric diet with addition of a vitamin-mineral complex on status of patients with obesity 1st and 2nd degrees].

PubMed

Sharafetdinov, Kh Kh; Plotnikova, O A; Zykina, V V; Mal'tsev, G Iu; Sokol'nikov, A A; Kaganov, B S

2011-01-01

Addition of a vitamin-mineral complex (VMC) to a standard hypocaloric diet leads to a positive dynamics of antropometric characteristics in patients with obesity 1st and 2nd degrees which is comparable to effectiveness of standard dietotherapy (dietary treatment) traditionally used in complex treatment of obesity. Addition of 1,8 mg of vitamin B2 as part of VMC to a hypocaloric diet is shown to be inadequate in eradication of marginal provision of riboflavin when using diets reduced in calories.

New Methods for the Analysis of Water-Soluble Vitamins in Infant Formula and Adult/Pediatric Nutritionals.

PubMed

Martin, Frederic; Giménez, Ester Campos; Konings, Erik

2016-01-01

Water-soluble vitamins (WSVs) are a group of organic compounds which are essential micronutrients. WSVs could be divided between the B complex group and vitamin C (l-ascorbic acid). Within the B complex group, eight vitamins are recognized: vitamins B1 (thiamin), B2 (riboflavin), B3 (niacin or niacinamide), B5 (pantothenic acid), B6 (pyridoxine, pyridoxal, or pyridoxamine), B7 (biotin), B9 (folic acid), and B12 (various cobalamins). This paper reviews the new methods for the analysis of these vitamins, with a focus on infant formula and adult nutritionals.

Atlantic salmon (Salmo salar) require increased dietary levels of B-vitamins when fed diets with high inclusion of plant based ingredients

PubMed Central

Lock, Erik-Jan; Olsvik, Pål Asgeir; Hamre, Kristin; Espe, Marit; Torstensen, Bente Elisabeth; Silva, Joana; Hansen, Ann-Cecilie; Waagbø, Rune; Johansen, Johan S.; Sanden, Monica; Sissener, Nini H.

2016-01-01

Aiming to re-evaluate current recommendations for nutrient supplementations when Atlantic salmon are fed diets based on plant ingredients, two regression experiments, with parr and post-smolt, were conducted. A control diet was included to evaluate if ingredients supplied sufficient nutrients without any added nutrient package (NP). The nutrient package consisted of vitamins B, C, E, minerals, cholesterol, methionine, taurine and histidine. This paper focus on B-vitamins. In parr, growth, health and welfare parameters responded on NP additions, but this was not observed in the seawater stage. During three months of feeding, parr tripled their weight. Parr given diets added the NP above NRC (2011) showed improved protein retention, and reduced liver and viscera indices. Post-smolt fed the same diets during five months showed a doubling of weight, but did not respond to the variation in NP to the same extent as parr. Significant regressions were obtained in body compartments for several of the B-vitamins in the premix. Whole body biotin concentration was unaffected by micronutrient premix level, and mRNA expression of the enzymes dependent of biotin showed only weak increases with increased biotin. Muscle thiamine plateaued at a diet level similar to NRC (2011) recommendation in freshwater, and showed stable values independent on premix addition in seawater. The mRNA expression of the enzyme G6PDH (glucose-6-phosphate dehydrogenase) is sensitive to thiamine availability; results did not indicate any need to add thiamine above levels recommended for fish in general. Niacin showed a steady increase in whole body concentrations as feed niacin increased. Muscle riboflavin peaked at a diet level of 12.4 mg kg−1. Sufficient riboflavin is important to avoid e.g., development of cataract. Cataract was not registered to be any problem, neither in fresh- nor in seawater. Cobalamin (B 12) in muscle and liver was saturated at 0.17 mg kg−1 diet. Muscle pyridoxine showed a dose-dependent level in muscle, and peaked around 10 mg kg −1 diet. White muscle ASAT (asparagine amino transferase) activity steadily increased, with indications of stable values when dietary pyridoxine was around 10–16 mg kg −1 diet. Pantothenic acid increased in gill tissue up to a level of 5.5 mg kg −1 soft gill tissue; at a dietary level of 22 mg kg−1. Improved performance, and coverage of metabolic need for niacin was at a dietary level of 66 mg kg −1, riboflavin 10–12 mg kg−1, pyridoxine 10 mg kg−1 and panthotenic acid 22 mg kg−1. Based on these results, recommended B-vitamin supplementation in plant based diets for Atlantic salmon should be adjusted. PMID:27703849

Structural characterization of ribT from Bacillus subtilis reveals it as a GCN5-related N-acetyltransferase.

PubMed

Srivastava, Ritika; Kaur, Amanpreet; Sharma, Charu; Karthikeyan, Subramanian

2018-04-01

In bacteria, biosynthesis of riboflavin occurs through a series of enzymatic steps starting with one molecule of GTP and two molecules of ribulose-5-phosphate. In Bacillus subtilis (B. subtilis) the genes (ribD/G, ribE, ribA, ribH and ribT) which are involved in riboflavin biosynthesis are organized in an operon referred as rib operon. All the genes of rib operon are characterized functionally except for ribT. The ribT gene with unknown function is found at the distal terminal of rib operon and annotated as a putative N-acetyltransferase. Here, we report the crystal structure of ribT from B. subtilis (bribT) complexed with coenzyme A (CoA) at 2.1 Å resolution determined by single wavelength anomalous dispersion method. Our structural study reveals that bribT is a member of GCN5-related N-acetyltransferase (GNAT) superfamily and contains all the four conserved structural motifs that have been in other members of GNAT superfamily. The members of GNAT family transfers the acetyl group from acetyl coenzyme A (AcCoA) to a variety of substrates. Moreover, the structural analysis reveals that the residues Glu-67 and Ser-107 are suitably positioned to act as a catalytic base and catalytic acid respectively suggesting that the catalysis by bribT may follow a direct transfer mechanism. Surprisingly, the mutation of a non-conserved amino acid residue Cys-112 to alanine or serine affected the binding of AcCoA to bribT, indicating a possible role of Cys-112 in the catalysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Corneal cross-linking in 9 horses with ulcerative keratitis

PubMed Central

2013-01-01

Background Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting. Results Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4–26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis. Conclusions CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species. PMID:23803176

Bioavailability of Cu, Zn and Mn from Mineral Chelates or Blends of Inorganic Salts in Growing Turkeys Fed with Supplemental Riboflavin and/or Pyridoxine.

PubMed

Salami, S A; Oluwatosin, O O; Oso, A O; Fafiolu, A O; Sogunle, O M; Jegede, A V; Bello, F A; Pirgozliev, V

2016-09-01

An 84-day feeding trial was conducted in growing turkeys to measure the bioavailability of Cu, Zn and Mn from a commercial mineral chelate and corresponding inorganic salts in composite feeds containing supplemental riboflavin (B2) and/or pyridoxine (B6). A total of 320, 28-day-old British United Turkeys (BUT) were assigned to eight dietary treatments in a 2 × 4 factorial arrangement comprising two trace mineral sources: chelated trace mineral blend (CTMB) and its corresponding inorganic trace minerals blend (ITMB) fed solely or with supplements of vitamin B2 (8 ppm) or B6 (7 ppm) or 8 ppm B2 + 7 ppm B6. Each treatment was replicated four times with 10 turkeys each. It was observed that turkeys fed with diets supplemented solely with ITMB elicited higher (P < 0.05) Zn excretion than their counterparts fed with diets containing ITMB with supplements of vitamins B2 and/or B6. Manganese retention was lower (P < 0.05) in turkeys fed with diets supplemented solely with ITMB than those fed with diets containing vitamins B2 and/or B6 additives. Combination of CTMB or ITMB with B6 improved (P < 0.05) the concentration of Mn in the liver and Cu in the bone. It was concluded that the minerals in CTMB were more available to the animals than ITMB. Furthermore, vitamins B2 and/or B6 supplementation improved the bioavailability of the inorganic Cu, Zn and Mn in growing turkeys and tended to reduce the concentration of these trace elements in birds' excreta.

Comparison of the effects of dietary factors in the management and prophylaxis of migraine

PubMed Central

Zencirci, Beyazit

2010-01-01

Migraine is defined as a disorder characterized by intermittent headache episodes, accompanied with nausea, photophobia and/or phonophobia. Pharmacological therapy is in accordance with the severity of pain and may include acute, prophylactic and most commonly both approaches. The aim of the acute therapy is stopping or alleviating the attack or progression of the pain and, in case of a migraine attack that has started, lessening the pain. Preventive therapy aims to reduce attack frequency and severity. This study was designed to evaluate the effect of dietary factors in the management and prophylaxis of migraine in cases diagnosed as having migraine disorder according to the 2003-IHS criteria. Fifty consecutive Turkish patients (13 men, 37 women) with diagnosis of migraine were randomly divided into two groups for treatment protocols with the written approval of the ethics committee. The cases in the first group (K) were treated with metoprolol, vitamin B2 (riboflavin), and naproxen sodium just at the aura or at the beginning of the attacks. The cases in the second group (D) were also supplied with a comprehensive dietary list arranged by our algology clinic in addition to the same medication protocol. There were no demographic differences between the cases (P > 0.05). VAS scores were lower in group D than group K (P < 0.01), and also the migraine attack frequencies and monthly amounts of analgesic consumed amounts were also statistically significantly less. It was concluded that beta-blocker and riboflavin therapy supplemented with a convenient diet with appropriate alternatives in patients with migraine disorder was associated with statistically significant decreases in headache frequency, intensity, duration and medication intake. PMID:21197315

Greenhouse gas emissions of realistic dietary choices in Denmark: the carbon footprint and nutritional value of dairy products

PubMed Central

Werner, Louise Bruun; Flysjö, Anna; Tholstrup, Tine

2014-01-01

Background Dairy products are important in a healthy diet due to their high nutritional value; they are, however, associated with relatively large greenhouse gas emissions (GHGE) per kg product. When discussing the need to reduce the GHGE caused by the food system, it is crucial to consider the nutritional value of alternative food choices. Objective The objective of this study was to elucidate the role of dairy products in overall nutrition and to clarify the effects of dietary choices on GHGE, and to combine nutritional value and GHGE data. Methods We created eight dietary scenarios with different quantity of dairy products using data from the Danish National Dietary Survey (1995–2006). Nutrient composition and GHGE data for 71 highly consumed foods were used to estimate GHGE and nutritional status for each dietary scenario. An index was used to estimate nutrient density in relation to nutritional recommendation and climate impact for solid food items; high index values were those with the highest nutrient density scores in relation to the GHGE. Results The high-dairy scenario resulted in 27% higher protein, 13% higher vitamin D; 55% higher calcium; 48% higher riboflavin; and 18% higher selenium than the non-dairy scenario. There was a significant correlation between changes in calcium and changes in vitamin D, selenium, and riboflavin content (P=0.0001) throughout all of the diets. The estimated GHGE for the dietary scenario with average-dairy consumption was 4,631 g CO2e/day. Conclusions When optimizing a diet with regard to sustainability, it is crucial to account for the nutritional value and not solely focus on impact per kg product. Excluding dairy products from the diet does not necessarily mitigate climate change but in contrast may have nutritional consequences. PMID:24959114

Greenhouse gas emissions of realistic dietary choices in Denmark: the carbon footprint and nutritional value of dairy products.

PubMed

Werner, Louise Bruun; Flysjö, Anna; Tholstrup, Tine

2014-01-01

Dairy products are important in a healthy diet due to their high nutritional value; they are, however, associated with relatively large greenhouse gas emissions (GHGE) per kg product. When discussing the need to reduce the GHGE caused by the food system, it is crucial to consider the nutritional value of alternative food choices. The objective of this study was to elucidate the role of dairy products in overall nutrition and to clarify the effects of dietary choices on GHGE, and to combine nutritional value and GHGE data. We created eight dietary scenarios with different quantity of dairy products using data from the Danish National Dietary Survey (1995-2006). Nutrient composition and GHGE data for 71 highly consumed foods were used to estimate GHGE and nutritional status for each dietary scenario. An index was used to estimate nutrient density in relation to nutritional recommendation and climate impact for solid food items; high index values were those with the highest nutrient density scores in relation to the GHGE. The high-dairy scenario resulted in 27% higher protein, 13% higher vitamin D; 55% higher calcium; 48% higher riboflavin; and 18% higher selenium than the non-dairy scenario. There was a significant correlation between changes in calcium and changes in vitamin D, selenium, and riboflavin content (P=0.0001) throughout all of the diets. The estimated GHGE for the dietary scenario with average-dairy consumption was 4,631 g CO2e/day. When optimizing a diet with regard to sustainability, it is crucial to account for the nutritional value and not solely focus on impact per kg product. Excluding dairy products from the diet does not necessarily mitigate climate change but in contrast may have nutritional consequences.

A comparison of food and nutrient intake between instant noodle consumers and non-instant noodle consumers in Korean adults

PubMed Central

Park, Juyeon; Lee, Jung-Sug; Jang, Young Ai; Chung, Hae Rang

2011-01-01

Instant noodles are widely consumed in Asian countries. The Korean population consumed the largest quantity of instant noodles in the world in 2008. However, few studies have investigated the relationship between instant noodles and nutritional status in Koreans. The objective of this study was to examine the association between instant noodle consumption and food and nutrient intake in Korean adults. We used dietary data of 6,440 subjects aged 20 years and older who participated in the Korean National Health and Nutrition Examination Survey III. The average age of the instant noodle consumers (INC) was 36.2 and that of the non-instant noodle consumers (non-INC) was 44.9; men consumed more instant noodles than women (P < 0.001). With the exception of cereals and grain products, legumes, seaweeds, eggs, and milk and dairy products, INC consumed significantly fewer potatoes and starches, sugars, seeds and nuts, vegetables, mushrooms, fruits, seasonings, beverages, meats, fishes, and oils and fats compared with those in the non-INC group. The INC group showed significantly higher nutrient intake of energy, fat, sodium, thiamine, and riboflavin; however, the INC group showed a significantly lower intake of protein, calcium, phosphorus, iron, potassium, vitamin A, niacin, and vitamin C compared with those in the non-INC group. This study revealed that consuming instant noodles may lead to excessive intake of energy, fats, and sodium but may also cause increased intake of thiamine and riboflavin. Therefore, nutritional education helping adults to choose a balanced meal while consuming instant noodles should be implemented. Additionally, instant noodle manufacturers should consider nutritional aspects when developing new products. PMID:22125682

A comparison of food and nutrient intake between instant noodle consumers and non-instant noodle consumers in Korean adults.

PubMed

Park, Juyeon; Lee, Jung-Sug; Jang, Young Ai; Chung, Hae Rang; Kim, Jeongseon

2011-10-01

Instant noodles are widely consumed in Asian countries. The Korean population consumed the largest quantity of instant noodles in the world in 2008. However, few studies have investigated the relationship between instant noodles and nutritional status in Koreans. The objective of this study was to examine the association between instant noodle consumption and food and nutrient intake in Korean adults. We used dietary data of 6,440 subjects aged 20 years and older who participated in the Korean National Health and Nutrition Examination Survey III. The average age of the instant noodle consumers (INC) was 36.2 and that of the non-instant noodle consumers (non-INC) was 44.9; men consumed more instant noodles than women (P < 0.001). With the exception of cereals and grain products, legumes, seaweeds, eggs, and milk and dairy products, INC consumed significantly fewer potatoes and starches, sugars, seeds and nuts, vegetables, mushrooms, fruits, seasonings, beverages, meats, fishes, and oils and fats compared with those in the non-INC group. The INC group showed significantly higher nutrient intake of energy, fat, sodium, thiamine, and riboflavin; however, the INC group showed a significantly lower intake of protein, calcium, phosphorus, iron, potassium, vitamin A, niacin, and vitamin C compared with those in the non-INC group. This study revealed that consuming instant noodles may lead to excessive intake of energy, fats, and sodium but may also cause increased intake of thiamine and riboflavin. Therefore, nutritional education helping adults to choose a balanced meal while consuming instant noodles should be implemented. Additionally, instant noodle manufacturers should consider nutritional aspects when developing new products.

Treatment of whole blood with riboflavin plus ultraviolet light, an alternative to gamma irradiation in the prevention of transfusion-associated graft-versus-host disease?

PubMed

Fast, Loren D; Nevola, Martha; Tavares, Jennifer; Reddy, Heather L; Goodrich, Ray P; Marschner, Susanne

2013-02-01

Exposure of blood products to gamma irradiation is currently the standard of care in the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). Regulatory, technical, and clinical challenges associated with the use of gamma irradiators are driving efforts to develop alternatives. Pathogen reduction methods were initially developed to reduce the risk of microbial transmission by blood components. Through modifications of nucleic acids, these technologies interfere with the replication of both pathogens and white blood cells (WBCs). To date, systems for pathogen and WBC inactivation of products containing red blood cells are less well established than those for platelets and plasma. In this study, the in vitro and in vivo function of WBCs present in whole blood after exposure to riboflavin plus ultraviolet light (Rb-UV) was examined and compared to responses of WBCs obtained from untreated or gamma-irradiated blood by measuring proliferation, cytokine production, activation, and antigen presentation and xenogeneic (X-)GVHD responses in an in vivo mouse model. In vitro studies demonstrated that treatment of whole blood with Rb-UV was as effective as gamma irradiation in preventing WBC proliferation, but was more effective in preventing antigen presentation, cytokine production, and T-cell activation. Consistent with in vitro findings, treatment with Rb-UV was as effective as gamma irradiation in preventing X-GVHD, a mouse model for TA-GVHD. The ability to effectively inactivate WBCs in fresh whole blood using Rb-UV, prior to separation into components, provides the transfusion medicine community with a potential alternative to gamma irradiation. © 2012 American Association of Blood Banks.

Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis.

PubMed

Qadri, Syed M; Chen, Deborah; Schubert, Peter; Perruzza, Darian L; Bhakta, Varsha; Devine, Dana V; Sheffield, William P

2017-03-01

Pathogen reduction treatment using riboflavin and ultraviolet light illumination (Mirasol) effectively reduces the risk of transfusion-transmitted infections. This treatment is currently licensed for only platelets and plasma products, while its application to whole blood (WB) to generate pathogen-inactivated red blood cells (RBCs) is under development. RBC storage lesion, constituting numerous morphologic and biochemical changes, influences RBC quality and limits shelf life. Stored RBCs further show enhanced susceptibility to RBC programmed cell death (eryptosis) characterized by increased cytosolic Ca 2+ -provoked membrane phosphatidylserine (PS) externalization. Using a "pool-and-split" approach, we examined multiple variables of RBC storage lesion and eryptosis in RBC units, derived from Mirasol-treated or untreated WB, after 4 to 42 days of storage, under blood bank conditions. In comparison to untreated RBC units, Mirasol treatment significantly altered membrane microvesiculation, supernatant hemoglobin, osmotic fragility, and intracellular adenosine triphosphate levels but did not influence membrane CD47 expression and 2,3-diphosphoglycerate levels. Mirasol-treated RBCs showed significantly higher PS exposure after 42, but not after not more than 21, days of storage, which was accompanied by enhanced cytosolic Ca 2+ activity, ceramide abundance, and oxidative stress, but not p38 kinase activation. Mirasol treatment significantly augmented PS exposure, Ca 2+ entry, and protein kinase C activation after energy depletion, a pathophysiologic cell stressor. Mirasol-treated RBCs were, however, more resistant to cell shrinkage. Prolonged storage of Mirasol-treated RBCs significantly increases the proportion of eryptotic RBCs, while even short-term storage enhances the susceptibility of RBCs to stress-induced eryptosis, which could reduce posttransfusion RBC recovery in patients. © 2016 AABB.

Detoxification and decolorization of a simulated textile dye mixture by phytoremediation using Petunia grandiflora and, Gailardia grandiflora: a plant-plant consortial strategy.

PubMed

Watharkar, Anuprita D; Jadhav, Jyoti P

2014-05-01

In vitro grown Petunia grandiflora and Gaillardia grandiflora plantlets showed 76 percent and 62 percent American Dye Manufacturers Institute value (color) removal from a simulated dyes mixture within 36h respectively whereas their consortium gave 94 percent decolorization. P. grandiflora, G. grandiflora and their consortium could reduce BOD by 44 percent, 31 percent and, 69 percent and COD by 58 percent, 37 percent and 73 percent respectively. Individually, root cells of P. grandiflora showed 74 and 24 percent induction in the activities of veratryl alcohol oxidase and laccase respectively; whereas G. grandiflora root cells showed 379 percent, 142 percent and 77 percent induction in the activities of tyrosinase, riboflavin reductase and lignin peroxidase respectively. In the consortium set, entirely a different enzymatic pattern was observed, where P. grandiflora root cells showed 231 percent, 12 percent and 65 percent induction in the activities of veratryl alcohol oxidase, laccase and 2, 6-dichlorophenol-indophenol reductase respectively, while G. grandiflora root cells gave 300 percent, 160 percent, 79 percent and 55 percent inductions in the activities of lignin peroxidase, riboflavin reductase, tyrosinase and laccase respectively. Because of the synergistic effect of the enzymes from both the plants, the consortium was found to be more effective for the degradation of dyes from the mixture. Preferential dye removal was confirmed by analyzing metabolites of treated dye mixture using UV-vis spectroscopy, FTIR and biotransformation was visualized using HPTLC. Metabolites formed after the degradation of dyes revealed the reduced cytogenotoxicity on Allium cepa roots cells when compared with untreated dye mixture solution. Phytotoxicity study exhibited the less toxic nature of the metabolites. Copyright © 2014 Elsevier Inc. All rights reserved.

Sculpting with light: Light/matter interactions in biocompatible polymers

NASA Astrophysics Data System (ADS)

Applegate, Matthew B.

When light interacts with matter either the light or the material can be changed. This dissertation focuses on light/matter interaction in silk fibroin and its utility for biomedical applications. Silk, a natural biocompatible, biodegradable polymer, has a large 3-photon absorption cross-section which allows modest peak intensity light to cause significant multiphoton absorption. This absorption allows voids to be formed with three dimensional control within soft, transparent silk hydrogels. A theoretical model of the void formation process is developed to allow the size of the voids to be predicted for a range of laser and sample parameters. Arbitrary 3D patterns are created in silk gels that allow cells to penetrate into the bulk of the gel both in vitro and in vivo. To explore how silk can be used to alter light, the creation of step-index optical waveguides, formed by encapsulating a silk film within a silk hydrogel, is described. These waveguides allow light to be delivered to targets through several centimeters of highly scattering biological tissue. Finally, the interaction of light with riboflavin is used to photocrosslink silk to form solid structures, rather than voids. The mechanism of crosslinking to be driven by radicalized tyrosine residues resulting in the formation of dityrosine bonds which lead to the gelation of a liquid silk solution. Riboflavin is a versatile photoinitiator and can be used to crosslink collagen as well as silk, which allows silk to be crosslinked directly to corneal collagen. When applied to the eye, an artificial corneal layer is formed which has the potential to treat various corneal diseases and allow for risk-free laser vision correction. These studies show the versatility of light-based processing of silk for a wide variety of medical applications.

Transepithelial corneal collagen cross-linking in keratoconus.

PubMed

Leccisotti, Antonio; Islam, Tahmina

2010-12-01

To evaluate the clinical effects of transepithelial corneal cross-linking (CXL) on keratoconic eyes pre-treated with substances enhancing epithelial permeability. Prospective, consecutive, single-masked, paired-eye study on 51 patients. The eye with more severe keratoconus was treated; the fellow eye served as the control. Gentamicin, benzalkonium chloride, and ethylenediaminetetraacetic acid were instilled for 3 hours, then oxybuprocaine for 30 minutes. Riboflavin 0.1% in 20% dextran T500 and oxybuprocaine were instilled for 30 minutes. Finally, ultraviolet A irradiation to the central 7.5 mm of the cornea was applied for 30 minutes, while riboflavin was instilled every 5 minutes. Mean corrected distance visual acuity improved by 0.036 logMAR after CXL and worsened by 0.039 logMAR in the control eyes (P<.05). Safety index was 1.05 after CXL and 0.96 in the control group. Mean spherical equivalent refraction decreased by 0.35 D (less myopic) after CXL and increased by 0.83 diopters (D) in the control eyes (P<.05). Mean apex curvature on tangential videokeratography increased by 0.51 D after CXL and by 1.61 D in the control eyes (P=.16). Mean average simulated keratometry decreased by 0.10 D after CXL and increased by 0.88 D in the control eyes (P<.05). Mean index of surface variance increased (worsened) by 0.9 after CXL and 5.3 in the control eyes (P<.05). Mean endothelial cell density was unchanged. A limited but favorable effect of transepithelial CXL was noted on keratoconic eyes, without complications. The effect appears to be less pronounced than described in the literature after CXL with de-epithelialization. Copyright 2010, SLACK Incorporated.

Dietary intake in Head Start vs non-Head Start preschool-aged children: results from the 1999-2004 National Health and Nutrition Examination Survey.

PubMed

Bucholz, Emily M; Desai, Mayur M; Rosenthal, Marjorie S

2011-07-01

To determine whether dietary intakes of children enrolled in Head Start programs differ from those of children not attending preschool or children in non-Head Start programs. Using data from the 1999-2004 National Health and Nutrition Examination Survey, low-income, 3- to 5-year-old children were categorized into one of four preschool groups: Head Start (n=184), non-Head Start (n=189), past preschool (n=193), and no preschool (n=384). Total nutrient intakes were calculated using 24-hour parental recalls. Mean macronutrient and micronutrient intakes were compared across groups and the percentage of children not meeting Recommended Dietary Allowances (RDAs) were calculated. Multivariate logistic regression was used to evaluate the relationship between preschool group and likelihood of not meeting dietary guidelines. Many children did not meet the RDA for folate (20.5%), vitamin A (39.7%), vitamin E (79.7%), calcium (40.2%), iron (28.8%), and potassium (90.8%). Compared with the other preschool groups, Head Start children had lower mean protein, saturated fat, riboflavin, calcium, and phosphorous intakes. The greatest differences in intake were observed between Head Start participants and no-preschool children. Multivariate analyses demonstrated an association between Head Start and inadequate intake of protein, thiamin, riboflavin, niacin, calcium, and selenium. Compared with other low-income children, those in Head Start programs appear to be at greater risk for not meeting the RDA for several key vitamins and minerals. These differences in diet quality may present an opportunity for Head Start programs to enhance nutrition in this student population. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.