Auswahl der wissenschaftlichen Literatur zum Thema „Vitamin C loss“

ABSTRACT Background: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. Objective: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. Design: This prospective cohort study followed 65,521 women in the Nurses’ Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. Results: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of β-carotene and β-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for β-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for β-cryptoxanthin. In comparison with women with folate intake 200–399 μg/d, very low folate intake (<200 μg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. Conclusion: Higher intakes of β-carotene, β-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk.

The antioxidant effects of vitamins C and E on cryptorchidism-induced oxidative stress were investigated in male Sprague-Dawley rats. Forty rats (200–250 g) were randomly divided in a blinded fashion into five groups (). Group 1 was sham operated and treated with vehicle (corn-oil, 10 mL/kg). Groups 2, 3, 4, and 5 were rendered unilaterally cryptorchid and treated with vehicle (10 mL/kg), vitamin E solution (75 mg/kg), vitamin C solution (1.25 g/kg), and combination of vitamin E (75 mg/kg) and vitamin C (1.25 g/kg) solutions, respectively. Germ cell count, superoxide dismutase (SOD), total protein (TP), and testicular weight (TW) were lower, but malondialdhyde (MDA) was higher in the cryptorchid rats than the sham-operated rats. When administered separately, vitamins C and E increased germ cell count, SOD, TP, and TW but did not reduce MDA in the cryptorchid rats when compared to the vehicle-treated cryptorchid rats. However, there was no significant difference in these parameters between vehicle-treated and combined vitamins C- and E-treated rats. This suggests that vitamins E and C alleviate the germ cell loss and oxidative stress in cryptorchidism when administered separately but not when combined in rats.

Global market is flooded with vitamin-enriched foods, mainly beverages. Major vitamins for enriching beverages are the antioxidant vitamins A, C and E. Ascorbic acid is readily oxidized and lost during storage of the beverages, at rates depending on the conditions of storage. This fact is of great importance for the consumer who must know how to store beverages and when to consume them in order to get the maximum benefit of added vitamin C. The objective of this paper was to determine the amount of ascorbic acid lost in beverages applying different preservation methods and storage condition. Beverage was made in laboratory conditions with synthetic L-ascorbic acid added according to the national legislations. After 30 days of storage at 4-8oC ascorbic acid overall loss was from 81.01% to 90.27% in thermally pasteurized samples and from 97.83 % to almost complete loss in samples preserved with sodium benzoate.

Vitamin E was identified as a lipophilic compound essential to maintain rat pregnancy. Low vitamin E intake during early pregnancy associates with congenital malformations and embryonic loss in animals and with miscarriage and intrauterine growth restriction in humans. Vitamin E protects cell membranes from lipoperoxidation and exerts non-antioxidant activities. Its function can be restored by vitamin C; thus, intake and circulating levels of both micronutrients are frequently analyzed together. Although substantial vitamin E inadequacy was reported worldwide, its consumption in Latin America (LatAm) is mostly unknown. Using data from the Latin American Study of Nutrition and Health (Estudio Latinoamericano de Nutrición y Salud, ELANS), we evaluated vitamin E and C intake in women of reproductive age (WRA) from eight LatAm countries and identified their main food sources. Two non-consecutive 24-h dietary recalls in 3704 women aged from 15 to 49 years and living in urban locations showed low average intake of vitamin E (7.9 mg/day vs. estimated average requirement (EAR) of 12 mg/day) and adequate overall vitamin C consumption (95.5 mg/day vs. EAR of 60 mg/day). The mean regional inadequacy was 89.6% for vitamin E and 36.3% for vitamin C. The primary food sources of vitamin E were fats and oils, as well as vegetables. Vitamin C intake was explained mainly by the consumption of fruit juices, fruits, and vegetables. Combined deficient intake of both vitamins was observed in 33.7% of LatAm women. Although the implications of low antioxidant vitamins’ consumption in WRA are still unclear, the combined deficient intake of both vitamins observed in one-third of ELANS participants underscores the need for further research on this topic.

Abstract. Fruits and vegetables are rich in vitamin C with antioxidant properties which are known to influence bone quality. This study evaluated whether vitamin C (1000 mg/L) added to drinking water reverses the bone loss in ovariectomized rats. Ninety-day-old female Sprague-Dawley rats were randomly assigned to either sham (n = 14) or ovariecotmized groups (n = 28). Sixty days after ovariectomy, the treatments were sham, ovariectomy (OVX), OVX + vitamin C (22 mg oral intake daily) for 60 days. Urine was collected for deoxypyridinoline (DPD) evaluation, rats were sacrificed, and antioxidant capacity, osteopontin, alkaline phosphatase (ALP), and bone specific tartrate resistant acid phosphatase (TRAP) were evaluated in the plasma. Right femur and 5th lumbar were evaluated for bone density, strength, ash, Ca, and Mg concentrations. Antioxidant capacity, ALP activity, osteopontin decreased (p-value < 0.05), while TRAP and urinary DPD increased (p-value < 0.05) with ovariectomy. In contrast, vitamin C increased (p-value < 0.05) antioxidant capacity, ALP activity, osteopontin concentration and reduced (p-value < 0.05) TRAP and urinary DPD excretion, respectively. Ovariectomy reduced (p-value < 0.05) bone quality, bone ash, Ca and Mg concentrations. Vitamin C increased (p-value < 0.05) femoral density without affecting (p-value > 0.1) femoral strength, ash, or Ca, and Mg concentrations, while it increased (p-value < 0.05) the 5th lumbar density, ash, and Ca and Mg concentrations. In conclusion, vitamin C increased bone quality and antioxidant capacity in ovariectomized rats.

Objetivo: Conocer las percepciones sobre cambios en la actividad física y el consumo de frutas ricas en vitamina C durante la pandemia por el COVID 19, en estudiantes de una universidad privada de Lima. Diseño: Es un estudio cualitativo con un diseño de investigación fenomenológica. La fenomenología es un estudio que busca comprender experiencias vividas por el individuo (17,18,19).

Memoria para optar al título de Químico<br>El objetivo de este estudio fue evaluar el efecto de la materia orgánica soluble y la materia orgánica coloidal de dos biosólidos obtenidos por distintos procesos, sobre la biodisponibilidad de cobre, plomo, cadmio, níquel y niveles de glutatión oxidado (GSSG) y reducido (GSH), ácido ascórbico (AA) y ácido dehidroascórbico (ADHA) en plantas de tomate (Lycopersicon esculentum L.). El estudio involucró el cultivo hidropónico de plantas bajo condiciones controladas y el análisis de elementos mediante espectroscopía de absorción atómica, emisión atómica y espectroscopía molecular. El análisis de las formas de glutatión, ácido ascórbico y ácido dehidroascórbico se llevó a cabo por electroforesis capilar de zona (ECZ), para lo cual se optimizaron las condiciones de análisis y pretratamiento de las muestras de tejido vegetal. Las conclusiones de este estudio fueron: La electroforesis capilar es una técnica apropiada para el estudio de las formas oxidada y reducida de ácido ascórbico. Fue posible establecer un método para la cuantificación de ácido ascórbico y por diferencia el ácido dehidroascórbico, bajo condiciones de electromigración en zonas, detección directa por absorción UV, modo de polaridad normal y electrolito de alta fuerza iónica. La Tris [2-carboxietil] fosfina (TCEP) fue efectivo como reductor del ácido dehidroascórbico en la matriz ácida constituida por MPA 2%. La aplicación de una concentración de 1 mM por 24 horas a temperatura ambiente reduce el ADHA produciendo cantidades cuantificables de ácido ascórbico. El efecto reductor es independiente de la presencia de AA en la muestra. La materia orgánica soluble modifica la biodisponibilidad de los metales pesados en solución, efecto que depende de cada elemento y se manifiesta en un cambio en la concentración de los elementos en la parte aérea y raíz de la planta. A nivel foliar la MOS disminuye la concentración de cobre y cadmio, incrementa la de plomo y no presenta efecto sobre níquel. A nivel de la raíz, el comportamiento es distinto, cobre, plomo y níquel disminuyen su concentración respecto de un tratamiento solo con metal y cadmio la incrementa. La asociación de materia orgánica soluble con materia orgánica coloidal presenta un efecto sinérgico sobre la translocación del metal a la parte aérea de la planta. Este efecto se manifestó para cobre y cadmio en una mayor disminución de su concentración foliar en comparación a la sola aplicación de MOS. Este efecto no fue observado en la raíz. El efecto de cobre cadmio y plomo sobre los sistemas de glutatión reducido/glutatión oxidado y ácido ascórbico/dehidroascórbico en la planta difieren para cada elemento y tipo de tejido. Para los péptidos el efecto se produce principalmente en la raíz. El cobre disminuye los niveles de ambos péptidos, en cambio plomo y cadmio tienen efecto solo sobre glutatión oxidado con disminución e incremento, respectivamente. Para el sistema ácido ascórbico/dehidroascórbico, los tres elementos disminuyen levemente el nivel de ácido ascórbico foliar, en tanto que en la raíz se observó efecto solo para cobre con disminución. Los experimentos de este estudio no evidenciaron la presencia de ácido dehidroascórbico en la planta. La asociación de materia orgánica soluble y metal en comparación al tratamiento solo con metal produce cambios en los niveles de glutatión reducido, glutatión oxidado y ácido ascórbico. Los mayores cambios se observaron para cadmio el cual incrementó los niveles de glutatión oxidado en parte aérea y raíz, en tanto que disminuyó los niveles de glutatión y ácido ascórbico en la raíz. Por su parte, la asociación plomo incrementó los niveles de ambos péptidos en la raíz<br>The purpose of this study was assess the effect of soluble organic matter (SOM) and colloidal organic matter (COM) from two sewage sludge obtained by different processes, on the bioavailability of copper, lead, cadmium and nickel besides of oxidized and reduced forms of glutathione, ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels in tomato plants (Lycopersicon esculentum L.). This study involved the hydroponics cultivation of plants under controlled conditions and their elements analysis through atomic absorption spectrophotometry, atomic emission and molecular spectrophotometry. The analysis of glutathione forms, ascorbic acid and dehydroascorbic acid was carried out by Capillary Zone Electrophoresis (CZE), for which was optimized the analysis and pretreatment conditions of vegetal tissue samples. The conclusions of this study were: The Capillary Electrophoresis is a suitable technique for study the oxidized and reduced forms of ascorbic acid. It was possible to establish a method to quantify ascorbic acid and by subtraction the dehydroascorbic acid, under conditions of electromigration in zones, direct detection by UV absorption, normal polarity set and a high ionic strength of electrolyte. The Tris-(2-carboxyethyl) phosphine (TCEP) was an effective reductor of dehydroascorbic acid in the acid matrix containing MPA 2%. The applications of a concentration of 1mM for 24 hours to 20º C reduced the DHAA, generating quantifying amounts of AA. This reduction effect is independent of the AA into the sample. The soluble organic matter alters the bioavailability of heavy metals in solution, effect that depend of each element and it is expressed for changes in the concentration on the elements in leaves and root of the plants. In leaves the SOM decrease copper and cadmium concentration, raise the lead concentration and does not present an effect on nickel concentration. In the root the behavior is different, copper, lead, and nickel reduce their concentration compared to the treatment with metal only and on the other hand cadmium raises its concentration. The association between soluble organic matter and colloidal organic matter shows synergistic effect on the translocation of metals to leaves of the plant. This effect was observed for copper and cadmium due to a major diminution of its concentration in leaves compared with the application of SOM only. This effect was not observed in the root. The effect of copper, cadmium, and lead over the systems glutathione/oxidized glutathione and ascorbic acid/dehydroascorbic acid in the plant, differs for each element and kind of tissue. For the peptides, the effect is expressed mainly in the root. Copper reduces the levels of both peptides and on the other hand lead and cadmium have an effect only on oxidized glutathione, with a diminution and increment, respectively. For the ascorbic acid/dehydroascorbic acid system, the three elements reduce slightly the ascorbic acid levels in leaves, whereas in root it was observed a diminution for copper only. The experiments in this study didn’t show effects over the dehydroascorbic acid levels. The association between soluble organic matter and metal in comparison with the metal only treatment leads to changes on the glutathione, oxidized glutathione and ascorbic acid levels. The major change was observed for cadmium which raised the glutathione and ascorbic acid levels in root. Respect to the lead, its association with SOM raised the levels of both peptides in root

La premiere partie du memoire est consacree a l'etude des phenomenes de transfert de chaleur et d'eau lors de la cuisson d'un cylindre de pomme de terre. Cinq appareils de cuisson (four a vapeur d'eau surchauffee, four classique a convection naturelle, four classique a convection forcee, four a micro-ondes, autocuiseur) font l'objet de l'etude experimentale et permettent de faire varier les conditions de transfert de chaleur et de matiere entre le milieu de cuisson et la surface de l'aliment. L'evolution des temperatures et de la masse du cylindre est mesuree et l'influence des conditions de transfert est analysee en considerant un critere de fin de cuisson base sur l'obtention d'une temperature minimale a cur. Un modele de transfert de chaleur et de matiere permet de representer les cinetiques experimentales en fonction des variables de fonctionnement du four a vapeur d'eau surchauffee. La prise en compte de la reduction de la fraction de surface humide permet de representer les resultats obtenus lors de la cuisson aux fours classiques. La deuxieme partie du memoire est introduite par des elements bibliographiques consacres a la destruction de la vitamine c lors du traitement thermique de la pomme de terre. L'influence de la teneur en eau de l'aliment et l'existence d'une composante de destruction enzymatique sont mises en evidence. Un modele cinetique prenant en compte trois familles de reactions est propose pour decrire l'evolution de la quantite de vitamine c dans un gratin de pomme de terre modele lors de la cuisson. Les parametres du modele sont identifies en utilisant les resultats des experiences de cuisson. Les resultats montrent qu'il n'est pas possible de differencier les conditions de cuisson au temps de cuisson pour lequel la quantite residuelle de vitamine c se situe a 70%. Par contre, l'utilisation du four a vapeur d'eau surchauffee laisse entrevoir des perspectives interessantes lors de la prolongation du temps de sejour

Determina el efecto de la suplementación de vitamina c oral en cuyes sometidos reducción del espacio vital sobre parámetros productivos en cuyes con alimentación a base de concentrado se diseñó el presente ensayo, se utilizó 50 cuyes recién destetados divididos al azar en 5 grupos diferentes durante los meses de mayo y junio a una temperatura promedio de 20°C. Los grupos fueron: T1: animales alimentados únicamente con concentrado; estos fueron suplementados con vitamina C vía oral a dosis de 25mg/kg/día, diluida en 0.1 ml de agua destilada y mantenidos en un espacio de 0.20m2 por cuy. T2: animales alimentados únicamente con concentrado; estos serán suplementados con vitamina C vía oral a dosis de 25mg/kg/día, diluida en 0.1 ml de agua destilada y mantenidos en un espacio de 0.10m2 por cuy. T3: animales alimentados únicamente con concentrado, sin suplementación de vitamina C y mantenidos en un espacio de 0.20 m2 por cuy. T4: animales alimentados únicamente con forraje (alfalfa fresca ración del 30% de peso vivo) mantenidos en un espacio de 0.20m2 por cuy. T5: animales alimentados únicamente con forraje (alfalfa fresca ración del 30% de peso vivo) y sometidos en un espacio de 0.10m2 por cuy a una temperatura promedio de 20°C. Los parámetros productivos evaluados fueron el peso vivo, consumo de alimento, ganancia de peso, índice de conversión alimenticia y rendimiento de carcasa. Se concluye que los cuyes que recibieron suplementación oral de vitamina C y mantenidos en un espacio vital de 0.20m2 tuvieron un mayor (p<0.05) peso final, ganancia de peso total, rendimiento de la canal y mejor (p<0.05) conversión alimenticia, comparado al resto de los tratamientos.<br>Perú. Universidad Nacional Mayor de San Marcos. Vicerrectorado de Investigación y Posgrado. Programa de Promoción de Tesis de Pregrado

No hay suficientes datos sobre el porcentaje de pérdidas poscosecha durante el manejo de la fresa en la región de Irapuato, ni de los principales factores que reducen la calidad de la fruta. Por lo que el objetivo de este trabajo fue estimar los daños físicos y evaluar la calidad de la fresa durante el manejo poscosecha y el transporte simulado, así como identificar los principales factores que la afectan. Para ello, se procedió a cuantificar las pérdidas en el proceso de producción-expedición de las fresas de la variedad Chandler y Camarosa, así como a evaluar el efecto del manejo sobre la calidad de las fresas durante la recolección, la comercialización y la venta al detalle. Se identificaron los daños y defectos mediante una evaluación visual y se determinó el porcentaje en peso de fresa con daños y defectos. Se estimaron los daños por transporte simulado y la calidad de las fresas sometidas a vibración con tres frecuencias (8 Hz, 12 Hz y 18 Hz) en una plataforma de vibración. Los factores que afectaron la calidad de las fresas fueron: a). El daño mecánico infringido por los propios trabajadores durante la recolección. b). La manipulación excesiva y las altas temperaturas que prevalecen, provocando el suavizamiento de la piel haciéndola más susceptible a los daños, al oscurecimiento del color y a la pérdida de agua que provoca que luzca marchita. c). El transporte que provocó abrasiones y magulladuras. El parámetro de calidad más indicativo del daño mecánico de las fresas fue la firmeza, sin embargo, también se afectó el valor nutricional (contenido de vitamina C), el dulzor (contenido de azúcares), y el peso (contenido de humedad). Por lo que se recomienda implementar un programa de capacitación a los trabajadores para reducir las pérdidas poscosecha de las fresas en la región de estudio.<br>Alcántara González, MDL. (2009). Estimación de los daños físicos y evaluación de la calidad de la fresa durante el manejo poscosecha y el transporte simulado [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/6473<br>Palancia

The major forms of benign hematologic conditions are anemia, neutropenia, transfusion reactions, Gaucher disease, and porphyria. Anemia is a sign of disease rather than a disease itself. Anemia results from 1 or more of 3 pathologic mechanisms: inadequate production of red blood cells (RBCs) by the bone marrow, blood loss, or premature destruction of RBCs. The major causes of neutropenia include hematologic neoplasm, metastatic neoplasm involving the marrow, irradiation, vitamin B12 deficiency and folate deficiency, drugs, infections, congenital or acquired primary disorders of hematopoiesis, autoimmune neutropenia, hypersplenism, hemodilution, and benign idiopathic neutropenia. The porphyrias are enzyme disorders that are autosomal dominant with low disease penetrance, except for congenital erythropoietic porphyria, which is autosomal recessive, and porphyria cutanea tarda, which may be acquired and is associated with hepatitis C and hemochromatosis.

Esta publicación trata sobre los beneficios de la vitamina C o ácido ascórbico, un micronutriente muy ligado al concepto de alimentación saludable, entre cuyos beneficios destacan su efecto antioxidante, su participación en la lucha contra la anemia y su presencia en la síntesis del colágeno, muy valorada por reumatólogos, dermatólogos, cirujanos plásticos y otros profesionales de la salud.

Iron deficiency is the most common nutritional deficiency in the world, affecting around 5 billion people mostly in developing countries. Risk factors in infants include low birthweight, high cow milk consumption, low intake of iron containing complementary foods, low socioeconomic status, and immigrant status. Developmental delay and poor educational achievement are among the long-term complications. Preventative strategies include promotion of breastfeeding, use of iron-fortified formula if breast milk not available, encouraging intake of iron-rich foods, vitamin C-rich drinks with meals to promote iron absorption, and avoiding whole cow’s milk in the first year of life. Poor response to oral iron treatment is most likely due to poor compliance (iron ingestion may cause abdominal pain diarrhoea or constipation) but should also raise the possibility of underlying disease causing inflammation, malabsorption, or blood loss.

Publicación que trata sobre los beneficios de la vitamina C o ácido ascórbico, un micronutriente muy ligado al concepto de alimentación saludable, entre cuyos beneficios destacan su efecto antioxidante, su participación en la lucha contra la anemia y su presencia en la síntesis del colágeno, muy valorada por reumatólogos, dermatólogos, cirujanos plásticos y otros profesionales de la salud.

A Editora Pantanal em seu 3º Volume do E-book “Tópicos nas ciências da saúde”, com seis capítulos traz novos temas no atuar da medicina. A obra, vem a materializar o anseio da Editora Pantanal na divulgação de resultados, que contribuem de modo direto no desenvolvimento e saúde humana. No primeiro capitulo o trabalho nos apresenta uma patologia que, embora muitos pensem que não é comum, tem grande impacto em nossa população mundial. A frequência desta patologia na década de 80 - 90 foi de 2 - 4 x 10.000 habitantes, porém com estudos atuais e levando em consideração não apenas o transtorno autista, mas todos os transtornos generalizados do desenvolvimento ou TEA (sigla em inglês), nesse novo cenário as estimativas aumentam de 21 para 35 x 10.000 habitantes. Com uma intervenção comportamental intensiva precoce, terapia cognitivo-confuctual e treinamento em habilidades sociais, obteve-se que em alguns casos leves os sintomas desaparecem, razão pela qual o diagnóstico precoce e o apoio incondicional da família são necessários; tudo isso refletido em nosso primeiro tópico. Em seguida, nosso pequeno volume faz uma incursão no campo das vitaminas que, como muitos estudiosos sabem, há um total de 13 vitaminas classificadas em dois grupos, solúveis em água (8 do complexo B e vitamina C) e quatro solúveis em gordura; A; D; E e K, que desempenham um papel fundamental no nosso organismo porque participam nos processos e reações que nele ocorrem e é importante não só tomá-los na forma de comprimidos, mas também incorporá-los através de uma alimentação equilibrada, saudável e saudável, para mim sobretudo a fonte da juventude porque atrasa o envelhecimento devido à sua ação antioxidante, aqui mostramos vários deles nas suas diferentes funções. Por fim, encerramos nosso livro com a apresentação de um caso onde mostramos que não é importante apenas tratar o somático, mas fazer um diagnóstico psicossocial do indivíduo se quisermos obter bons resultados em nossa prática profissional. Agradecemos aos autores pela dedicação e os encorajamos a continuar colaborando em nosso projeto. Aos autores dos capítulos, pela dedicação e esforços sem limites, que viabilizaram esta obra que retrata os recentes avanços científicos e tecnológicos na área de Ciências da Saúde, os agradecimentos da Organizadora e da Pantanal Editora. Por fim, esperamos que este e-book possa colaborar e instigar mais estudantes e pesquisadores na constante busca de novas tecnologias e avanços para a medicina. Assim, garantir uma difusão de conhecimento fácil, rápido para a sociedade. Aris Verdecia Peña

The Age-Related Eye Disease Study (AREDS) was a multicenter study of the natural history of age-related cataract and macular degeneration (AMD) in a relatively well-nourished older adult cohort that comprised two clinical trials sharing one pool of participants. The study was designed to determine whether a high-dose antioxidant formulation affected the development and progression of age-related lens opacities and visual acuity loss. The cataract trial showed that use of a high-dose formulation of vitamins having antioxidant characteristics (vitamin C, vitamin E, and beta carotene) had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss.

The Age-Related Eye Disease Study (AREDS) was a randomized, double-masked, clinical trial with two components, an age-related macular degeneration (AMD) trial and a cataract trial. This paper reports the results of the AMD trial, which was designed to determine the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on the progression of AMD and vision loss. Based on the study findings, the authors recommended that individuals fifty-five years of age and older with extensive intermediate size drusen, at least one large druse, noncentral geographic atrophy in one or both eyes, or advanced AMD or vision loss due to AMD in one eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants (consisting of vitamin C and E and beta carotene) plus zinc.

Because of the narrow therapeutic index of warfarin and unfractionated heparin (UFH), monitoring their anticoagulant effects is required. On the other hand, lowmolecular- weight heparin (LMWH) and fibrinolytic agents need to be monitored only under certain circumstances. Although newer anticoagulants will not require routine monitoring for dose titration, a means to determine their systemic effects and individual (patient-specific) response to administration will likely have roles in clinical practice. The prothrombin time is used to monitor vitamin K antagonist therapy. This test is sensitive to the plasma concentrations (activity) of clotting factors II (prothrombin), V, VII, and X. Vitamin K antagonists affect the vitamin K–dependent factors II, VII, IX, and X, as well as proteins C, S, and Z. Thus, the prothrombin time does not reflect the effect of vitamin K antagonists on some factors (IX and proteins C, S, and Z) and is sensitive to others (factor V) (not directly influenced by treatment). The prothrombin time is not an ideal test for monitoring vitamin K antagonists; however, its simplicity and widespread availability have established its place in clinical practice. By convention, prothrombin times are now reported as international normalized ratios (INRs). This is the ratio of the patient’s prothrombin time to a control prothrombin time, raised to a power—the international sensitivity index (ISI). The latter reflects the calibration of the thromboplastin used for the prothrombin time testing to an internationally agreed upon standard. In many laboratories the reagent currently used is a recombinant thromboplastin, which has an ISI of 1.0 There are several cautions related to interpreting the results of prothrombin time tests that are worth monitoring. Since the test is sensitive to the level of factor V in the plasma, improper sample storage or delayed testing may cause loss of factor V (activity) and yield prothrombin time values above the expected range. High concentrations of heparin may also prolong the prothrombin time; this usually occurs when the sample is obtained within a few minutes of administering a bolus dose. Direct thrombin inhibitors, such as hirudin, bivalirudin, argatroban, and ximelagatran, may also prolong the prothrombin time to a variable degree.

Hemostasis, the prompt cessation of bleeding at a site of vascular injury, is among the most fundamental physiologic and teleologically vital defense mechanisms in nature. Without a functionally intact hemostatic mechanism, death could ensue rapidly even after minor traumas associated with everyday life. In mammalian blood coagulation, regulated by a complex network of integrated biochemical events, five protease factors (f ) (fIIa [thrombin], fVIIa, fIXa, fXa, and protein C) interact with five cofactors (tissue factor, f VIIIa, fVa, thrombomodulin, and protein S) to regulate the generation of fibrin (Davidson et al., 2003). Although each component of the mammalian coagulation network has unique functional properties, available data based on gene organizations, protein structure, and sequence analysis suggest that it may have resulted from the reduplication and diversification of two gene structures over 400 million years ago. A vitamin K–dependent serine protease is composed of a γ-carboxylated glutamic acid (GLA) epidermal growth factor-like (EGF) 1–EGF 2-serine protease domain structure common to fVII, fIX, fX, and protein C, and the A1-A2-B-AB-C1-C2 domain structure common to fV and fVIII. Prothrombin is also a vitamin K–dependent serine protease; however, it contains kringle domains rather than EGF domains (suggesting a replacement during gene duplication and shuffling). Analyses of active site function amino acid residues reveal distinguishing characteristics of thrombin from other serine proteases, supporting its position as the ancestral blood enzyme (Krem and Cera, 2002; McLysaght et al., 2002). The rapid transformation of fluid blood to a gel-like substance (clot) has been a topic of great interest to scientists, physicians, and philosophers since the days of Plato and Aristotle ( Jewett, 1892; Lee, 1952). However, it was not until the beginning of the 18th century that blood clotting (coagulation) was appreciated as a means to stem blood loss from wounds (hemostasis) (Petit, 1731). As with other areas of science, the microscope played a pivotal role in the understanding of coagulation. In the mid-17th century, Marcello Malpighi separated the individual components of a blood clot into fibers, cells, and serum (Forester, 1956).

This chapter discusses the neurological basis of scurvy. The physical symptoms of extreme vitamin C deficiency, i.e., scurvy, have been described in numerous ships' logs, diaries, and medical texts, stretching back for hundreds of years. Examples include hemorrhage, and the characteristic broken blood vessels under the skin; and hyperkeratosis, or changes in hair such as thinning, alopecia, and corkscrew hairs on the limbs. However, modern techniques in neuroscience research have revealed the highly complex roles of vitamin C in the brain, which may have changed the behavior of those experiencing long periods of nutritional deficiencies. The most important roles for vitamin C, also known as ascorbate and ascorbic acid, are in the synthesis of neurotransmitters, the chemical messengers of the brain, and for protection of neurons (brain cells) against damage by a constant barrage of free radicals.

Vitamin C is one of the constituents of pequi pulp. It is a natural antioxidant, capable of sequestering free radicals. The present study aimed to freeze dry a pequi pulp encapsulated with maltodextrin and whey protein and analyze vitamin C content. Vitamin C loss was lower in the experimental run that did not use encapsulating agent. Whereas, the run that used 15% of whey protein concentrate as encapsulant agent in relation to pequi solids presented the highest value (220.74 mg vitamin C / g pequi solids). Freeze drying of pequi pulp is a technique for vitamin C conservation independently of the variation in maltodextrin and whey protein proportion.Keywords: drying; encapsulating agent; ascorbic acid.

Protein S is a single chain (Mr 75.000) plasma protein. It is a cofactor to activated protein C (APC) in the regulation of coagulation factors Va and Villa. It has high affinity for negatively charged phospolipids and it forms a 1:1 complex with APC on phospholipid surfaces, platelets and on endothelial cells. Patients with heterozygous protein S deficiency have a high incidence of thrombosis. Protein S is cleaved by thrombin, which leads to a loss of calcium binding sites and of APC cofactor activity. Protein S has two to three high affinity (KD 20uM) calcium binding sites - unrelated to the Gla-region - that are unaffected by the thrombin cleavage. In human plasma protein S (25 mg/liter) circulates in two forms; free (approx. 40%) and in a 1:1 noncovalent complex (KD 1× 10-7M) with the complement protein C4b-binding protein (C4BP). C4BP (Mr 570.000) is composed of seven identical 70 kDa subunits that are linked by disulfide bonds. When visualized by electron microscopy, C4BP has a spiderlike structure with the single protein S binding site located close to the central core and one C4b-binding site on each of the seven tentacles. When bound to C4BP, protein S looses its APC cofactor activity, whereas the function-of C4BP is not directly affected by the protein S binding. Chymotrypsin cleaves each of the seven C4BP subunits close to the central core which results in the liberation of multiple 48 kDa “tentacte” fragments and the formation of a 160 kDa central core fragment. We have successfully isolated a 160 kDa central core fragment with essentially intact protein S binding ability.The primary structure of both bovine and human protein S has been determined and found to contain 635 and 634 amino acids, respectively, with 82 % homology to each other. Four different regions were distinguished; the N-terminal Gla-domain (position 1-45) was followed by a region which has two thrombin-sensitive bonds positioned within a disulfide loop. Position 76 to 244 was occupied by four repeats homologous to the epidermal growth factor (EGF) precursor. In the first EGF-domain a modified aspartic acid was identified at position 95, B-hydroxaspartic acid (Hya), and in corresponding positions in the three following EGF-domains (positions 136,178 and 217) we found B-hydroxyasparagine (Hyn). Hyn has not previously been identified in proteins. The C-terminal half of protein S (from position 245) shows no homology to the serine proteases but instead to human Sexual Hormon Binding Globulin (SHBG)(see separate abstract). To study the structure-function relationship we made eighteen monoclonal antibodies to human protein S. The effects of the monoclonals on the C4BP-protein S interaction and on the APC cofactor activity were analysed. Eight of the antibodies were calciumdependent, four of these were against the Gla-domain, two against the thrombin sensitive portion and two against the region bearing the high affinity calcium binding sites. Three of the monoclonals were dependent on the presence of chelating agents, EDTA or EGTA, and were probably directed against the high affinity calcium binding region. Three other monoclonals inhibited the protein S-C4BP interaction. At present, efforts are made to localize the epitopes to gain information about functionally important regions of protein S.

The vitamin K-dependent microsomal carboxylase converts glutamyl residues in precursor proteins to γ-carboxyglutamyl (Gla) residues in completed proteins. The enzyme activity is present in significant activities in most non-skeletal tissues but has been studied most extensively in rat and bovine liver. Early studies of the enzyme utilized bound precursors of vitamin K-dependent clotting factors as substrates for the enzyme and demonstrated that the enzyme requires the reduced form of vitamin K (vitamin KH2), O2, and CO2. Subsequent investigations have taken advantage of the observation that the enzyme will carboxylate low-molecular-weight peptide substrates with Glu-Glu sequences. Utilizing a substrate such as Phe-Leu-Glu-Glu-Leu, it has been possible to demonstrate that γ-C-H release from the Glu residue of a substrate is independent of CO2 concentration. The formation of vitamin K 2,3-epoxide can also be demonstrated in a crude microsomal system, and it can be shown that the formation of this metabolite can be stimulated by the presence of a peptide substrate of the carboxylase. These observations have led to the general hypothesis that the mechanism of action of the enzyme involves interaction of vitamin KH2 with O2 to form an oxygenated intermediate that can interact with a substrate Glu residue to abstract a γ-hydrogen and in the process he converted to vitamin K epoxide (KO). The current evidence suggests that, either directly or indirectly, removal of the γ-C-H results in the formation of a carbanion at the γ-position of the Glu residue which can interact with CO2 to form Gla. The Glu residue intermediate which is formed can be demonstrated to partition between accepting a proton in the media to reform Glu, or interacting with CO2 to form Gla. Current data do not distinguish between the direct formation of a carbanion coupled to proton removal, or the participation of a reduced intermediate. Recent studies have demonstrated that the enzyme will carry out a partial reaction, the formation of vitamin K epoxide, at a decreased rate in the absence of a Glu site substrate. Epoxide formation under these conditions has the same for O2 as the carboxylation reaction and is inhibited in the same manner as the carboxylation reaction. In the presence of saturating concentrations of a Glu site substrate and C02, the ratio of KO formed, γ-C-H released, and C02 formed is 1:1:1. However, KO formation can be uncoupled from and proceeds at a higher rate than γ-C-H bond cleavage and Gla formation at low Glu site substrate concentrations. At saturating concentrations of CO2, Gla formation is equivalent to γ-C-H bond cleavage, and this unity is not altered by variations in vitamin KH2 or peptide substrate concentrations. Natural compounds with vitamin K activity are 2-Me-l,4-naphthoquinones with a polyprenyl side chain at the 3-position. Studies of vitamin K analogs have demonstrated that a 2-Me group is essential for activity but that the group at the 3-position can vary significantly. Modification of the aromatic ring of the naphthoquinone nucleus by methyl group substitution can result in alterations of either the rate of the carboxylation reaction or the apparent affinity of the enzyme for the vitamin. Studies of a large number of peptide substrates have failed to reveal any unique primary amino acid sequence which is a signal for carboxylation. However, current evidence from a number of sources suggests that a basic amino acid rich "propeptide" region of the intracellular form of the vitamin K-dependent proteins is an essential recognition site for the enzyme. This region of the precursor is lost in subsequent processing, and the manner in which it directs this posttranslational event is not yet clarified. Supported by NIH grant AM-14881.

Protein S, a cofactor for activated protein C, reversibly complexes with a regulatory complement component C4b-binding protein (C4bp) in plasma. In plasma of patients with congenital protein S deficiency, most protein S exists as a complex with C4bp, which has no cofactor activity. C4bp (Mw 550,000) is composed of approximately seven subunits with Mw 75,000 which are linked by disulfide bonds near the carboxy1-terminus. We report here about the complex formation between protein S and C4bp particularly on the binding site of protein S on C4bp molecule. Protein S and C4bp were purified from human plasma. Seventeen mouse monoclonal antibodies against C4bp were prepared. Chymotrypsin-digested C4bp was separated on gel filtration into a fragment with Mw 160,000 derived from the carboxyl-terminal core of the intact C4bp and fragments with Mw 48,000 from the amino-terminus. The carboxy1-terminal fragment with Mw 160,000 was found to be composed of approximately seven polypeptides with Mw 25,000, which were linked by disulfide bonds.The experiments using these fragments and the monoclonal antibodies showed that: (1) Protein S bound not only to the intact C4bp, but also to the fragment with Mw 160,000. (2) The fragment with Mw 160,000 inhibited the binding of protein S to C4bp, but the fragment with Mw 48,000 did not. (3) One of the seventeen monoclonal antibodies blocked the inhibition of C4bp on the cofactor activity of protein S. (4) This antibody inhibited C4bp binding to protein S. (5) The antibody bound to the fragment with Mw 160,000. Based on these results, protein S was suggested to lose its cofactor activity for activated protein C by binding to the carboxyl-terminal core of C4bp where seven subunits are linked by disulfide bonds.