The Experts below are selected from a list of 486 Experts worldwide ranked by ideXlab platform
Michael F Holick - One of the best experts on this subject based on the ideXlab platform.
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Sunlight, UV Radiation, Vitamin D, and Skin Cancer: How Much Sunlight Do We Need?
Advances in experimental medicine and biology, 2020Co-Authors: Michael F HolickAbstract:Vitamin D is the sunshine vitamin for good reason. During exposure to sunlight, the ultraviolet B photons enter the skin and photolyze 7-dehydrocholesterol to Previtamin D3 which in turn is isomerized by the body’s temperature to vitamin D3. Most humans have depended on sun for their vitamin D requirement. Skin pigment, sunscreen use, aging, time of day, season and latitude dramatically affect Previtamin D3 synthesis. Vitamin D deficiency was thought to have been conquered, but it is now recognized that more than 50% of the worlds population is at risk for vitamin D deficiency. This deficiency is in part due to the inadequate fortification of foods with vitamin D and the misconception that a healthy diet contains an adequate amount of vitamin D. Vitamin D deficiency causes growth retardation and rickets in children and will precipitate and exacerbate osteopenia, osteoporosis and increase risk of fracture in adults. The vitamin D deficiency has been associated pandemic with other serious consequences including increased risk of common cancers, autoimmune diseases, infectious diseases and cardiovascular disease. There needs to be a renewed appreciation of the beneficial effect of moderate sunlight for providing all humans with their vitamin D requirement for health.
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Environmental determinants of Previtamin D synthesis in the United Arab Emirates
Dermato-endocrinology, 2017Co-Authors: Adam Buckley, Michael F Holick, Zara Hannoun, Nader Lessan, Maha T BarakatAbstract:ABSTRACTDespite abundant sunshine throughout the year, vitamin D deficiency is endemic in the UAE. Solar radiation within the UVB range of the spectrum is required for the photosynthesis of Previtamin D3 in the skin. Atmospheric transmission of UVB is strongly influenced by atmospheric conditions and solar zenith angle. We investigated the effects of diurnal and seasonal variation on the availability of sufficient UVB radiation for adequate Previtamin D3 synthesis using an established in vitro model. Borosilicate ampoules of 7-dehydrocholesterol, the precursor of Previtamin D3, in ethanol (50 µg/mL) were exposed to direct sunlight in an urban area of Abu Dhabi, at one hourly intervals between 0800 and 1700, on one day of each month over a period of one year. Conversion to Previtamin D3, vitamin D3 and metabolically inactive photoisomers was analyzed using high performance liquid chromatography. The efficiency of 7-dehydrocholesterol conversion to Previtamin D3 varied estimated UVB intensity. At the latitu...
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Sunlight, Ultraviolet Radiation, Vitamin D and Skin Cancer
Sunlight Vitamin D and Skin Cancer, 2014Co-Authors: Michael F HolickAbstract:Vitamin D is the sunshine vitamin for good reason. During exposure to sunlight, the UV B photons enter the skin and photolyze 7-dehydrocholesterol to Previtamin D3 which in turn is isomerized by the body’s temperature to vitamin D3 Most humans have depended on sun for their vitamin D requirement. Skin pigment, sunscreen use,aging, time of day,season and latitude dramatically affect Previtamin D3 synthesis. Vitamin D deficiency was thought to have been conquered, but it is now recognized that more than 50% of the world’s population is at risk for vitamin D deficiency. This deficiency is in part due to the inadequate fortification of foods with vitamin D and the misconception that a healthy diet contains an adequate amount of vitamin D. Vitamin D deficiency causes growth retardation and rickets in children and will precipitate and exacerbate osteopenia, osteoporosis and increase risk of fracture in adults. The vitamin D deficiency has been associated pandemic with other serious consequences including increased risk of common cancers, autoimmune diseases, infectious diseases and cardiovascular disease. There needs to be a renewed appreciation of the beneficial effect of moderate sunlight for providing all humans with their vitamin D requirement for health.
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Photobiology of vitamin D in mushrooms and its bioavailability in humans
Dermato-endocrinology, 2013Co-Authors: Raphael-john H. Keegan, Jaimee Bogusz, Jennifer E. Williams, Michael F HolickAbstract:Mushrooms exposed to sunlight or UV radiation are an excellent source of dietary vitamin D2 because they contain high concentrations of the vitamin D precursor, provitamin D2. When mushrooms are exposed to UV radiation, provitamin D2 is converted to Previtamin D2. Once formed, Previtamin D2 rapidly isomerizes to vitamin D2 in a similar manner that Previtamin D3 isomerizes to vitamin D3 in human skin. Continued exposure of mushrooms to UV radiation results in the production of lumisterol2 and tachysterol2. It was observed that the concentration of lumisterol2 remained constant in white button mushrooms for up to 24 h after being produced. However, in the same mushroom tachysterol2 concentrations rapidly declined and were undetectable after 24 h. Shiitake mushrooms not only produce vitamin D2 but also produce vitamin D3 and vitamin D4. A study of the bioavailability of vitamin D2 in mushrooms compared with the bioavailability of vitamin D2 or vitamin D3 in a supplement revealed that ingestion of 2000 IUs of...
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Sunlight and Vitamin D: A global perspective for health
Dermato-endocrinology, 2013Co-Authors: Matthias Wacker, Michael F HolickAbstract:Vitamin D is the sunshine vitamin that has been produced on this earth for more than 500 million years. During exposure to sunlight 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to Previtamin D3 which in turn isomerizes into vitamin D3. Previtamin D3 and vitamin D3 also absorb UV B radiation and are converted into a variety of photoproducts some of which have unique biologic properties. Sun induced vitamin D synthesis is greatly influenced by season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, passing through glass and plastic, and aging. Vitamin D is metabolized sequentially in the liver and kidneys into 25-hydroxyvitamin D which is a major circulating form and 1,25-dihydroxyvitamin D which is the biologically active form respectively. 1,25-dihydroxyvitamin D plays an important role in regulating calcium and phosphate metabolism for maintenance of metabolic functions and for skeletal health. Most cells and organs in the body have a vitamin D receptor and many cells and organs are able to produce 1,25-dihydroxyvitamin D. As a result 1,25-dihydroxyvitamin D influences a large number of biologic pathways which may help explain association studies relating vitamin D deficiency and living at higher latitudes with increased risk for many chronic diseases including autoimmune diseases, some cancers, cardiovascular disease, infectious disease, schizophrenia and type 2 diabetes. A three-part strategy of increasing food fortification programs with vitamin D, sensible sun exposure recommendations and encouraging ingestion of a vitamin D supplement when needed should be implemented to prevent global vitamin D deficiency and its negative health consequences.
Atsushi Kittaka - One of the best experts on this subject based on the ideXlab platform.
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Revisiting the 7,8-cis-vitamin D3 derivatives: synthesis, evaluating the biological activity, and study of the binding configuration
Tetrahedron, 2016Co-Authors: Daisuke Sawada, Shinji Kakuda, Midori Kamimura-takimoto, Akiko Takeuchi, Yotaro Matsumoto, Atsushi KittakaAbstract:Four 7,8-cis-1α,25-dihydroxyvitamin D3 derivatives, 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 as well as 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxyvitamin D3 were synthesized, and their chemical stability was characterized. In our previous work, we disclosed that 14-epi-19-nortachysterol showed the unprecedented binding configuration in human vitamin D receptor (hVDR), that is, 5,6- and 7,8-s-trans configuration. However, this configuration is variable because of the rotation at the single bond between C7 and C8. For the precise discussion of the 7,8-s-trans configuration, we designed and synthesized the 7,8-cis-locked skeleton of vitamin D3 derivatives. Among four analogs, the 19-nor derivatives were stable at ambient temperature, and their hVDR binding affinity and co-crystallographic analysis of their hVDR complexes were studied. The other derivatives with the triene system were isomerized to corresponding Previtamin D3 and vitamin D3.
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synthesis of 2β substituted 14 epi Previtamin D3 and testing of its genomic activity
The Journal of Steroid Biochemistry and Molecular Biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2β-Substituted analogs of 14-epi-Previtamin D 3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D 3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis -hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01–0.18% of VDR binding affinity compared with the natural hormone and EC 50 1.0–9.1 nM for transactivation activity, than 14-epi-Previtamin D 3 with 0.5% (VDR) and EC 50 0.46 nM, respectively.
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Synthesis of 2β-substituted-14-epi-Previtamin D3 and testing of its genomic activity ☆
The Journal of Steroid Biochemistry and Molecular Biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2β-Substituted analogs of 14-epi-Previtamin D 3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D 3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis -hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01–0.18% of VDR binding affinity compared with the natural hormone and EC 50 1.0–9.1 nM for transactivation activity, than 14-epi-Previtamin D 3 with 0.5% (VDR) and EC 50 0.46 nM, respectively.
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Synthesis of 2beta-substituted-14-epi-Previtamin D3 and testing of its genomic activity.
The Journal of steroid biochemistry and molecular biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:2beta-substituted analogs of 14-epi-Previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-Previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.
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Synthesis of 2α- and 2β-substituted-14-epi-Previtamin D3 and their genomic activity
Tetrahedron, 2010Co-Authors: Daisuke Sawada, Tomoyuki Katayama, Yuya Tsukuda, Nozomi Saito, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2α- and 2β-Substituted analogs of 14-epi-Previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-Previtamin D3. We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the Previtamin D form as well as the natural vitamin D form.
Daisuke Sawada - One of the best experts on this subject based on the ideXlab platform.
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Revisiting the 7,8-cis-vitamin D3 derivatives: synthesis, evaluating the biological activity, and study of the binding configuration
Tetrahedron, 2016Co-Authors: Daisuke Sawada, Shinji Kakuda, Midori Kamimura-takimoto, Akiko Takeuchi, Yotaro Matsumoto, Atsushi KittakaAbstract:Four 7,8-cis-1α,25-dihydroxyvitamin D3 derivatives, 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxy-19-norvitamin D3 as well as 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxyvitamin D3 were synthesized, and their chemical stability was characterized. In our previous work, we disclosed that 14-epi-19-nortachysterol showed the unprecedented binding configuration in human vitamin D receptor (hVDR), that is, 5,6- and 7,8-s-trans configuration. However, this configuration is variable because of the rotation at the single bond between C7 and C8. For the precise discussion of the 7,8-s-trans configuration, we designed and synthesized the 7,8-cis-locked skeleton of vitamin D3 derivatives. Among four analogs, the 19-nor derivatives were stable at ambient temperature, and their hVDR binding affinity and co-crystallographic analysis of their hVDR complexes were studied. The other derivatives with the triene system were isomerized to corresponding Previtamin D3 and vitamin D3.
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synthesis of 2β substituted 14 epi Previtamin D3 and testing of its genomic activity
The Journal of Steroid Biochemistry and Molecular Biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2β-Substituted analogs of 14-epi-Previtamin D 3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D 3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis -hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01–0.18% of VDR binding affinity compared with the natural hormone and EC 50 1.0–9.1 nM for transactivation activity, than 14-epi-Previtamin D 3 with 0.5% (VDR) and EC 50 0.46 nM, respectively.
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Synthesis of 2beta-substituted-14-epi-Previtamin D3 and testing of its genomic activity.
The Journal of steroid biochemistry and molecular biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:2beta-substituted analogs of 14-epi-Previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-Previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.
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Synthesis of 2β-substituted-14-epi-Previtamin D3 and testing of its genomic activity ☆
The Journal of Steroid Biochemistry and Molecular Biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2β-Substituted analogs of 14-epi-Previtamin D 3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D 3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis -hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01–0.18% of VDR binding affinity compared with the natural hormone and EC 50 1.0–9.1 nM for transactivation activity, than 14-epi-Previtamin D 3 with 0.5% (VDR) and EC 50 0.46 nM, respectively.
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Synthesis of 2α- and 2β-substituted-14-epi-Previtamin D3 and their genomic activity
Tetrahedron, 2010Co-Authors: Daisuke Sawada, Tomoyuki Katayama, Yuya Tsukuda, Nozomi Saito, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2α- and 2β-Substituted analogs of 14-epi-Previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-Previtamin D3. We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the Previtamin D form as well as the natural vitamin D form.
Kazuya Takenouchi - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 2β substituted 14 epi Previtamin D3 and testing of its genomic activity
The Journal of Steroid Biochemistry and Molecular Biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2β-Substituted analogs of 14-epi-Previtamin D 3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D 3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis -hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01–0.18% of VDR binding affinity compared with the natural hormone and EC 50 1.0–9.1 nM for transactivation activity, than 14-epi-Previtamin D 3 with 0.5% (VDR) and EC 50 0.46 nM, respectively.
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Synthesis of 2beta-substituted-14-epi-Previtamin D3 and testing of its genomic activity.
The Journal of steroid biochemistry and molecular biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:2beta-substituted analogs of 14-epi-Previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-Previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.
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Synthesis of 2β-substituted-14-epi-Previtamin D3 and testing of its genomic activity ☆
The Journal of Steroid Biochemistry and Molecular Biology, 2010Co-Authors: Daisuke Sawada, Yuya Tsukuda, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2β-Substituted analogs of 14-epi-Previtamin D 3 were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D 3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis -hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01–0.18% of VDR binding affinity compared with the natural hormone and EC 50 1.0–9.1 nM for transactivation activity, than 14-epi-Previtamin D 3 with 0.5% (VDR) and EC 50 0.46 nM, respectively.
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Synthesis of 2α- and 2β-substituted-14-epi-Previtamin D3 and their genomic activity
Tetrahedron, 2010Co-Authors: Daisuke Sawada, Tomoyuki Katayama, Yuya Tsukuda, Nozomi Saito, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Kazuya Takenouchi, Atsushi KittakaAbstract:Abstract 2α- and 2β-Substituted analogs of 14-epi-Previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-Previtamin D3. We found that modification at the C2 position of the seco-steroidal skeleton afforded interesting effects for biological genomic activity for the Previtamin D form as well as the natural vitamin D form.
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Synthesis of 2α-substituted-14-epi-Previtamin D3 and its genomic activity
Bioorganic & medicinal chemistry letters, 2009Co-Authors: Daisuke Sawada, Tomoyuki Katayama, Yuya Tsukuda, Nozomi Saito, Hiroshi Saito, Ken Ichiro Takagi, Eiji Ochiai, Seiichi Ishizuka, Masashi Takano, Kazuya TakenouchiAbstract:Abstract We synthesized and isolated 2α-substituted analogs of 14-epi-Previtamin D 3 after thermal isomerization at 80 °C for the first time. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-Previtamin D 3 .
Marc A. Anderson - One of the best experts on this subject based on the ideXlab platform.
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effects of surface adsorption and confinement on the photochemical selectivity of Previtamin D3 adsorbed within porous sol gel derived alumina
Journal of the American Chemical Society, 1999Co-Authors: Forrest S. Schultz, Marc A. AndersonAbstract:It has been demonstrated that porous sol−gel derived (SGD) alumina can function as an effective microorganized medium in which to perform size- or shape-selective organic transformations. For the photolysis of 7-dehydrocholesterol (7D) encapsulated within SGD-alumina, it was found that the adsorption characteristics of 7D and the pore size of the SGD-alumina greatly influenced the photochemical selectivity of the cis−trans isomerization of Previtamin D3 to tachysterol3. An increase in the ratio of Previtamin D3 (P3) to tachysterol3 (T3) was obtained on photolysis of 7D adsorbed within SGD-alumina with a pore size of 10−20 A. This result is attributed to a confinement effect that inhibits the cis−trans isomerization of P3 to T3. In addition to the confinement effect on the photochemical selectivity, it was found that the adsorption characteristics of 7D to the surface of SGD-alumina also play a critical role in the photochemical selectivity. The results indicate that confinement in addition to chemisorptio...
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Effects of Surface Adsorption and Confinement on the Photochemical Selectivity of Previtamin D3 Adsorbed within Porous Sol−Gel Derived Alumina
Journal of the American Chemical Society, 1999Co-Authors: Forrest S. Schultz, Marc A. AndersonAbstract:It has been demonstrated that porous sol−gel derived (SGD) alumina can function as an effective microorganized medium in which to perform size- or shape-selective organic transformations. For the photolysis of 7-dehydrocholesterol (7D) encapsulated within SGD-alumina, it was found that the adsorption characteristics of 7D and the pore size of the SGD-alumina greatly influenced the photochemical selectivity of the cis−trans isomerization of Previtamin D3 to tachysterol3. An increase in the ratio of Previtamin D3 (P3) to tachysterol3 (T3) was obtained on photolysis of 7D adsorbed within SGD-alumina with a pore size of 10−20 A. This result is attributed to a confinement effect that inhibits the cis−trans isomerization of P3 to T3. In addition to the confinement effect on the photochemical selectivity, it was found that the adsorption characteristics of 7D to the surface of SGD-alumina also play a critical role in the photochemical selectivity. The results indicate that confinement in addition to chemisorptio...