Synthesis Of Vitamin Research Articles

Cardiovascular Effects of Cyclical Dietary Vitamin C Withdrawal in Mice Deficient in Internal Synthesis Vitamin C and producing human lipoprotein (a): Gulo(-/-); Lp(a)+

Background: Scientific knowledge of the impact of periodic dietary vitamin C intake and withdrawal on the development of cardiovascular disease has been limited. Our earlier study using a transgenic Gulo(-/-); Lp(a)+ mouse model mimicking human metabolism in respect to a lack of internal synthesis of vitamin C and expression of human lipoprotein (a) [Lp(a)], a recognized risk factor for cardiovascular disease, showed that vitamin C deficiency triggers vascular deposition of Lp(a) and atherosclerosis. In this study we used this mouse model to investigate the effect of cyclical vitamin C withdrawal and its continuous supplementation on metabolic factors related to cardiovascular health, such as lipid profile and vascular plaque development. Methods: Gulo (-/-); Lp (a)+ mice were subjected to 4 weeks of dietary vitamin C withdrawals followed by 4 weeks of a resupplementation pattern for 20 weeks in total. Mice supplemented with vitamin C continuously for 20 weeks served as reference control. Mice were harvested after 4, 8, 12, 16, and 20 weeks and analyzed. Serum ascorbic acid, lipid profile, lipoproteins, vascular lesion, and Lp(a) deposition were evaluated. Results: We observed that periodic vitamin C withdrawals resulted in a less healthy blood lipid profile and showed indications of metabolic adaptation to vitamin C withdrawals. In addition, mice experiencing recurring dietary vitamin C withdrawals were prone to the development of early atherosclerotic lesions with Lp(a) deposition in the structurally compromised areas of the vascular wall, compared to mice continuously supplemented with vitamin C. Conclusion: This study further supports the importance of consistent and sufficient intake of vitamin C in assuring optimum profile of blood risk factors, and maintaining vascular wall integrity and optimal cardiovascular health.

Vitamin D status of children with moderate to severe chronic Kidney Disease at a Tertiary Pediatric Center in Cape Town.

The prevalence of suboptimal Vitamin D levels is higher in patients with chronic kidney disease (CKD) than in the general population. Recent findings suggest that progression of CKD is linked to a suboptimal Vitamin D level. A high percentage of CKD patients have severe Vitamin D deficiency. These patients also have a low level of 25-hydroxy-vitamin D [25(OH)D] and consequently, a reduced ability to form active 1,25-dihydroxyvitamin D. Various factors underlie the low level of 25(OH)D, including a sedentary lifestyle, decreased intake of Vitamin D due to CKD-related dietary restrictions, and decreased synthesis of Vitamin D in skin due to uremia. All these factors may be particularly influential in patients with progressively worsening CKD, including those receiving chronic dialysis. The objective of our study is to determine the prevalence of Vitamin D deficiency in children with CKD stages three to five and those receiving chronic dialysis, to ascertain whether there is a relationship between Vitamin D deficiency and the stage of CKD, and to identify any clinical correlates associated with the Vitamin D status. A single-center, retrospective review was conducted of 46 children (younger than 18 years) with CKD stages 3-5D who attended the renal clinic of the Red Cross Children's Hospital between October 2013 and November 2014. In total, 73.9% of the study population had suboptimal Vitamin D levels (43.5% and 30.4% had Vitamin D deficiency and insufficiency, respectively). The prevalence of Vitamin D deficiency was significantly higher in older children (≥10 years of age) than in younger children (P = 0.000) but did not significantly differ between males and females (P = 0.693). In total, 12 of 15 black children (80%), 19 of 26 colored children (73.1%), two of four white children (50%), and one Asian child (100%) had suboptimal Vitamin D levels. Neither white nor Asian child had Vitamin D deficiency. In addition, 90% of patients undergoing chronic dialysis, 80% of whom were receiving peritoneal dialysis, had suboptimal Vitamin D levels. Age, weight, height, and the albumin concentration were significantly associated with the Vitamin D level. There was a positive linear relationship between the Vitamin D level and the serum albumin concentration (Spearman's rho correlation coefficient = 0.397, P = 0.007). In total, 87.5% of patients with nephrotic-range proteinuria had suboptimal Vitamin D levels, and 80% were Vitamin D deficient (P = 0.004). A higher percentage of Vitamin D deficiency/insufficiency cases was documented during the winter (24/34, 70.6%) than during the summer (10/34, 29.4%); however, this difference was not statistically significant (P = 0.685). Sub-optimal Vitamin D is high among children with moderate to severe CKD and significantly higher in those undergoing chronic dialysis. The emerging evidence of the role of Vitamin D in slowing progression of CKD highlights the need for monitoring and correction of Vitamin D levels in predialysis children.

Correlative Analysis of Vitamin D Status in People Suffering from Type-2 Diabetes Mellitus in Eastern Region of Nepal

Introduction: Vitamin D deficiency exists as a common problem among population worldwide. The deficient vitamin D level leads to direct impact on various normal functioning of human body systems. It has been observed in few studies that decreased circulating concentration of 25-hydroxyvitamin D is associated with type-2 diabetes mellitus. The possible reason behind such occurrence is due to the direct effect of vitamin D on glucose metabolism. Vitamin D exerts influences on activity of pancreatic β-cell function from where insulin is secreted. In addition, the patients suffering from low vitamin D status show insulin resistance. These affected individuals with low vitamin D status exhibits impaired markers of glucose metabolism such as glycosylated hemoglobin. So, researchers have found vitamin D deficiency to correlate with type-2 diabetes and 80 % of obese adults suffering from vitamin D insufficiency state. In spite of such crucial significance, the correlative studies related to vitamin D status and type-2 diabetes still remains obscure in eastern region of Nepal.
 Objective: We aimed to investigate status of vitamin D among type-2 diabetics and analyze its possible correlation.
 Methodology: In the present study which was hospital-based and cross sectional one, antecubital venous blood samples were collected from patients (n=100) in plain vials with informed written consent. Blood samples were allowed to clot and centrifuged for separation of serum. The separated sera were further processed for determination of glucose (fasting as well as post-prandial) by spectrophotometry and estimation of vitamin D with use of microwell Enzyme-linked immunosorbant assay (ELISA) technique. The data was interpreted by using SPSS software version 16.
 Results: We found that 75 % type-2 diabetics had suffered from “state of vitamin D deficiency”. Among them, females, in contrast, were predominating which was interesting in an analytical point of view.
 Conclusion: Our study reviews evidence on disorders related to type-2 diabetes mellitus and vitamin D status, especially in older people. The biological processes that lead to synthesis of vitamin D in human body tissues become less efficient when an individual's age advances with in additional occurrences of type-2 diabetes mellitus. We should therefore maintain the repletion of vitamin D in healthy older people via supplementary intakes and sensible sun-exposure.

Sun exposure, skin lesions and vitamin D production: evaluation in a population of fishermen

AbstractBackground: Exposure to UVR provides benefits related to vitamin D synthesis, but also causes harms, since UVB is considered a complete carcinogen. There is no definition of the level of sun exposure and the proportion of exposed body required for proper synthesis of vitamin D in the skin without causing it damage.Objectives: This study aims to analyze the sun exposure index, vitamin D levels and clinical changes in the skin caused by constant sun exposure in the fishermen population.Methods: It is a cross-sectional, observational and analytical study The sample consisted of fishermen and was calculated in 174 individuals. The questionnaire was applied, the dermatological examination was carried out and the examinations of calcidiol, parathyroid hormone, calcium and phosphorus were requested. Data were expressed as percentages. The comparative analysis was done through the Chi-square test, and the correlations were established through the Pearson's linear coefficient.Results: We observed that there was vitamin D deficiency in a small part of the cases (11.46%), and the frequency of diagnosis of skin cancer was 2.7% of the cases surveyed.Study limitations: The difficulty in categorizing the sun exposure index.Conclusion: The fact that fishermen expose themselves to the sun chronically and have been exposed to the sun for more than 15 years, between 21 and 28 hours a week, and without photoprotection, were indicative factors for protection against vitamin D deficiency. Chronic exposure to sun and high vitamin levels D may be indicative of protection of this population against skin cancer.

Was the Last Ice Age dusty climate instrumental in spreading of the three “Celtic” diseases (hemochromatosis, cystic fibrosis and palmar fibromatosis)?

Cystic fibrosis, hereditary hemochromatosis and palmar fibromatosis are often described as “Celtic”, based on their contemporary prevalence. The former two are among genetically defined disorders that seem to provide survival advantages to heterozygote individuals, while severe health problems happen in homozygote mutation carriers. Although palmar fibromatosis has no defined mutations, its prevalence has been linked to the prevalence of Y-Chromosome Haplogroup I that expanded after the Last Ice Age, thus making th distribution of all three “Celtic” diseases dependent on the global climate from 40 to 8 Kya. During the Last Ice Age, the global climate was dry and dark due to dust-laden atmosphere (20–25 times more than today). It has been postulated that skin pigmentation was related to insolation, UV protection and skin synthesis of vitamin D, so when our ancestors moved to Eurasia, individuals with pale skin became advantageous.Deficiency of vitamin D has several health consequences and some of them have been proposed by other authors as important for the spreading of cystic fibrosis mutations: rickets/osteomalacia; susceptibility to diarrheal diseases and tuberculosis and salt induced arterial hypertension.The here proposed link is between vitamin D deficiency and the anaemia of chronic disease that might have facilitated spreading of the hemochromatosis mutation. It seems plausible that the risk of health problems in the offspring of close relatives might have resulted in social taboos of consanguinity in Eurasian protosocieties. Ancient steam bath rituals seem linked to lower incidences of cystic fibrosis in several European populations, thus suggesting health protection in an arid, dusty climate of the last glaciation, that made CFTR mutations in heterozygote carriers less advantageous.

Protetores solares, pele negra e mídia em aulas de química

A exposição solar proporciona sensação de bem-estar físico, estimula a produção de melanina e a síntese de vitamina D pelo organismo. As civilizações antigas da África utilizavam base de mamona, extrato de magnólia, jasmim e óleo de amêndoas como protetores solares. Com características de uma pesquisa participante, este estudo teve como objetivo aproximar alunas/os do Ensino Médio de cientistas negras contemporâneas. Os resultados estabeleceram um diálogo sobre as radiações ultravioletas que incidem sobre a Terra pelos raios solares. Pessoas de pele negra representam a maioria da população do Brasil e, ainda assim, a veiculação de comerciais sobre protetores solares apresentam como alvo somente o corpo branco. A/o aluna/o reconhece o fenômeno da estratificação racial da população como construção ideológica realizada por meio de um conjunto de práticas materiais de discriminação racial. Portanto, cabe-nos como professoras/res de Química e sujeitos desta sociedade mediar o discurso que combata o racismo na educação.

Hydrotalcite-Derived Mixed Oxides for the Synthesis of a Key Vitamin A Intermediate Reducing Waste.

The synthesis of hydroxenin monoacetate, a key intermediate in the manufacture of vitamin A, relies on the undesirable use of stoichiometric amounts of organic bases such as pyridine. Although the final product (vitamin A acetate) can be produced from hydroxenin diacetate, using the monoacetylated intermediate improves the overall process yield. Aiming to identify more efficient, environmentally benign alternatives, this work first studies the homogeneous acetylation reaction using pyridine. The addition of the base is found to enhance the rate of hydroxenin monoacetate formation, confirming its catalytic role, but also yields non-negligible amounts of hydroxenin diacetate. On the basis of these insights, Mg- and Al-containing hydrotalcites are explored because of their broad scope as base catalysts and the ability to finely tune their properties. The reaction kinetics are greatly enhanced via controlled thermal activation, forming high surface area mixed metal oxides displaying Lewis basic sites. In contrast, a Brønsted basic material synthesized by the reconstruction of a mixed oxide performs similarly to the as-synthesized hydrotalcite. Variation of the Mg/Al ratio from 1 to 3 has no significant impact, but activity losses are observed at higher values because of a reduced number of basic sites. After optimizing the reaction conditions, hydroxenin monoacetate yields >60% are obtained in five consecutive cycles without the need for any intermediate treatment. The findings confirm the potential of hydrotalcite-derived materials as highly selective catalysts for the production of vitamins with reduced levels of organic waste.

Latitude, Vitamin D, Melatonin, and Gut Microbiota Act in Concert to Initiate Multiple Sclerosis: A New Mechanistic Pathway.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the etiology of MS is still largely unknown, scientists believe that the interaction of several endogenous and exogenous factors may be involved in this disease. Epidemiologists have seen an increased prevalence of MS in countries at high latitudes, where the sunlight is limited and where the populations have vitamin D deficiency and high melatonin levels. Although the functions and synthesis of vitamin D and melatonin are contrary to each other, both are involved in the immune system. While melatonin synthesis is affected by light, vitamin D deficiency may be involved in melatonin secretion. On the other hand, vitamin D deficiency reduces intestinal calcium absorption leading to gut stasis and subsequently increasing gut permeability. The latter allows gut microbiota to transfer more endotoxins such as lipopolysaccharides (LPS) into the blood. LPS stimulates the production of inflammatory cytokines within the CNS, especially the pineal gland. This review summarizes the current findings on the correlation between latitude, sunlight and vitamin D, and details their effects on intestinal calcium absorption, gut microbiota and neuroinflammatory mediators in MS. We also propose a new mechanistic pathway for the initiation of MS.

Modular Enzymatic Cascade Synthesis of Vitamin B5 and Its Derivatives.

Access to vitamin B5 [(R)‐pantothenic acid] and both diastereoisomers of α‐methyl‐substituted vitamin B5 [(R)‐ and (S)‐3‐((R)‐2,4‐dihydroxy‐3,3‐dimethylbutanamido)‐2‐methylpropanoic acid] was achieved using a modular three‐step biocatalytic cascade involving 3‐methylaspartate ammonia lyase (MAL), aspartate‐α‐decarboxylase (ADC), β‐methylaspartate‐α‐decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non‐chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B5 and both diastereoisomers of α‐methyl‐substituted vitamin B5, which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug‐resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B5 derivatives by modifying the pantoyl or β‐alanine moiety.

Species-specific mechanisms of tumor suppression are fundamental drivers of vertebrate speciation: critical implications for the 'war on cancer'.

We recently reported our detection of an anthropoid primate-specific, ‘kill switch’ tumor suppression system that reached its greatest expression in humans, but that is fully functional only during the first twenty-five years of life, corresponding to the primitive human lifespan that has characterized the majority of our species' existence. This tumor suppression system is based upon the kill switch being triggered in cells in which p53 has been inactivated; such kill switch consisting of a rapid, catastrophic increase in ROS caused by the induction of irreversible uncompetitive inhibition of glucose-6- phosphate dehydrogenase (G6PD), which requires high concentrations of both inhibitor (DHEA) and G6P substrate. While high concentrations of intracellular DHEA are readily available in primates from the importation and subsequent de-sulfation of circulating DHEAS into p53-affected cells, both an anthropoid primate-specific sequence motif (GAAT) in the glucose-6-phosphatase (G6PC) promoter, and primate-specific inactivation of de novo synthesis of vitamin C by deletion of gulonolactone oxidase (GLO) were required to enable accumulation of G6P to levels sufficient to enable irreversible uncompetitive inhibition of G6PD. Malignant transformation acts as a counterforce opposing vertebrate speciation, particularly increases in body size and lifespan that enable optimized exploitation of particular niches. Unique mechanisms of tumor suppression that evolved to enable niche exploitation distinguish vertebrate species, and prevent one vertebrate species from serving as a valid model system for another. This here-to-fore unrecognized element of speciation undermines decades of cancer research data, using murine species, which presumed universal mechanisms of tumor suppression, independent of species. Despite this setback, the potential for pharmacological reconstitution of the kill switch tumor suppression system that distinguishes our species suggests that ‘normalization’ of human cancer risk, from its current 40% to the 4% of virtually all other large, long-lived species, represents a realistic near-term goal.

Synthesis of 19-norcalcitriol analogs with pegylated alkylidene chains at C-2

The results presented in this paper constitute an extension of our synthetic efforts focused on 19-norvitamin D compounds possessing elongated 2-alkylidene substituents. Based on our previous results, molecular modeling studies, and docking experiments, we selected a novel 19-norcalcitriol analog with long chain at C-2 containing several ether moieties and terminated by 2-(pyridin-2′-yl)ethylamino fragment. It was expected that such structural modification might allow binding of transition metal by the ligand, increase solubility of the formed complexes as well as improve their affinity to the VDR. For comparison, a 19-norcalcitriol analog was also obtained with the terminal hydroxyl group at its pegylated 2-alkylidene substituent. The synthesis of the target vitamin D compounds described in this work was performed using the Wittig-Horner approach. The respective A-ring phosphine oxide was obtained starting from the D-(-)-quinic acid and then coupled with the known Grundmann ketone.

Synthesis of novel vitamin E containing sulfa drug derivatives and study their antibacterial activity

A new series of ethoxymethyleneimino sulfa drug (2a–d), alpha-tocopheryl acetamide (5), (N-substituted)sulfamoyl)phenylimino)methyl)alpha-tocopheryl acetamide (6a–d), and (N-substituted)sulfamoyl)phenyl)alpha-tocopheryl acetamide (9a–d) derivatives were synthesized. The newly synthesized compounds were confirmed by spectroscopic tools (IR, 1H NMR, and 13C NMR, and mass spectra) and evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria. Gram-negative bacteria, Pseudomonas aeruginosa and Salmonella sp. and Enterococcus italicus showed resistance to all the standard compounds. The compounds 5, 6a, and 9d were the most potent antibacterial compounds on methicillin-resistant Staphylococcus aureus with MIC range from 0.1 to 0.3 mg/mL and MBC range from 0.2 to 0.4 mg /mL, respectively. The combination between sulfa drugs and vitamin E has proved to be effective antimicrobial activity against the Gram-negative for the first time in addition to Gram-positive bacteria.

Milling for better pharmaceuticals: green synthesis, phase transformations and reaction kinetics of vitamin B3:C cocrystal polymorphs studied in situ

Milling for better pharmaceuticals: green synthesis, phase transformations and reaction kinetics of vitamin B₃:C cocrystal polymorphs studied <i>in situ</i>

Evidence of vitamin D synthesis in insects exposed to UVb light

Vertebrates obtain the prohormone vitamin D primarily by endogenous cutaneous synthesis under ultraviolet b (UVb) exposure. To date, endogenous synthesis of vitamin D in insects has never been investigated. In an initial experiment, we exposed four insect species which differ in ecology and morphology (migratory locusts, house crickets, yellow mealworms and black soldier fly larvae (BSFL)) to a low irradiance UVb source. In a second experiment we exposed these species to a higher UV irradiance, and in a third we tested the effect of exposure duration on vitamin D concentrations in yellow mealworms. Low irradiance UVb tended to increase vitamin D3 levels in house crickets, vitamin D2 levels in BSFL and vitamin D2 and D3 in yellow mealworms. Higher UVb irradiance increased vitamin D3 levels in all species but BSFL. Both BSFL and migratory locusts had increased vitamin D2 levels. Longer UVb exposure of yellow mealworms increased vitamin D2 and increased vitamin D3 until a plateau was reached at 6400 IU/kg. This study shows that insects can synthesize vitamin D de novo and that the amounts depend on UVb irradiance and exposure duration.

Optimal Duration of Sun Exposure for Adequate Cutaneous Synthesis of Vitamin D in Indian Cities: An Estimate Using Satellite-Based Ultraviolet Index Data

Optimal Duration of Sun Exposure for Adequate Cutaneous Synthesis of Vitamin D in Indian Cities: An Estimate Using Satellite-Based Ultraviolet Index Data

Synthesis of Side-Chain Locked Analogs of 1α,25-Dihydroxyvitamin D3 Bearing a C17 Methyl Group.

A convergent synthesis of side-chain locked vitamin D analogs 3 and 4, which bind strongly in silico to the vitamin D receptor (VDR), is described. The synthetic approach features an SN2'- syn displacement of carbamates by cuprates to set the challenging quaternary stereogenic center at C17 and a Pd-catalyzed construction of the triene system in the presence of a diyne moiety.

ビタミンD誘導体合成：制がんおよび骨形成活性への効果（日本薬学会第136回シンポジウム「ビタミンのケミカルバイオロジー研究」）

ビタミンD誘導体合成：制がんおよび骨形成活性への効果（日本薬学会第136回シンポジウム「ビタミンのケミカルバイオロジー研究」）

Approaches to cutaneous wound healing: basics and future directions.

The skin provides essential functions, such as thermoregulation, hydration, excretion and synthesis of vitamin D. Major disruptions of the skin cause impairment of critical functions, resulting in high morbidity and death, or leave one with life-changing cosmetic damage. Due to the complexity of the skin, diverse approaches are needed, including both traditional and advanced, to improve cutaneous wound healing. Cutaneous wounds undergo four phases of healing. Traditional management, including skin grafts and wound dressings, is still commonly used in current practice but in combination with newer technology, such as using engineered skin substitutes in skin grafts or combining traditional cotton gauze with anti-bacterial nanoparticles. Various upcoming methods, such as vacuum-assisted wound closure, engineered skin substitutes, stem cell therapy, growth factors and cytokine therapy, have emerged in recent years and are being used to assist wound healing, or even to replace traditional methods. However, many of these methods still lack assessment by large-scale studies and/or extensive application. Conceptual changes, for example, precision medicine and the rapid advancement of science and technology, such as RNA interference and 3D printing, offer tremendous potential. In this review, we focus on the basics of wound treatment and summarize recent developments involving both traditional and hi-tech therapeutic methods that lead to both rapid healing and better cosmetic results. Future studies should explore a more cost-effective, convenient and efficient approach to cutaneous wound healing. Graphical abstract Combination of various materials to create advanced wound dressings.

Mucosal-associated invariant T cells in autoimmune and immune-mediated diseases.

Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I-related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines, suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases. In this review, we described the current knowledge on MAIT cells in these pathologies, based on patients analyses as well as mouse models. While most of the studies support a deleterious role of MAIT cells in tissue inflammation and destruction, a few reports suggest a protective role of MAIT cells. MAIT cells could represent a new biomarker of disease progression, and a better knowledge of their function might open new avenues for therapeutic strategies based on their manipulation.

Surprise: The classic white seedling 3 mutant in maize lacks plastoquinone-9 but can still make carotenoids.

Surprise: The classic white seedling 3 mutant in maize lacks plastoquinone-9 but can still make carotenoids.