The Experts below are selected from a list of 1485 Experts worldwide ranked by ideXlab platform
Norman Camerman - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of the hydrated Strontium Salt of methotrexate two independent molecules with different conformations
Journal of Medicinal Chemistry, 2001Co-Authors: Donald Mastropaolo, Arthur Camerman, Norman CamermanAbstract:The crystal and molecular structure of methotrexate has been determined by X-ray diffraction from a highly hydrated triclinic crystal form in which the asymmetric unit contains two independent methotrexate molecules with their glutamate carboxyl groups coordinated to two Strontium ions. The two methotrexates exhibit differing conformations: They are almost related to one another by a pseudocenter of symmetry. This places the C(9)-N(10) bond vectors on opposite sides of the planes of the pteridine rings. The 2,4-diaminopteridines form 2-fold symmetry-related hydrogen-bonded dimers as well as hydrogen bonds to benzoyl carbonyl oxygens and lattice water molecules. This structure provides experimental proof of the existence of pteridine conformers through rotation about the C(6)-C(9) bond. Comparison of these conformers with other free and enzyme-bound methotrexate conformations shows them all to be different and illustrates the ability of the molecule to adapt to its chemical environment. The results from this crystal structure determination are experimental proof that methotrexate has not one preferred molecular conformation but may freely rotate about several bonds. They also suggest that the dihydrofolate reductase-bound methotrexate conformation is greatly influenced by the specific binding site environment of the enzyme.
Pierre J Marie - One of the best experts on this subject based on the ideXlab platform.
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an uncoupling agent containing Strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen deficient rats
Journal of Bone and Mineral Research, 2005Co-Authors: Pierre J Marie, M Hott, Pascale Deloffre, Dominique Modrowski, Cinderella De Pollak, Joel Guillemain, Y TsouderosAbstract:Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of Strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent Strontium Salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15–25 per group) were sham operated or ovariectomized (OVX) and treated with 17β-estradiol (E2, 10 μg/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone Strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30–36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats. In contrast to this inhibitory effect on bone resorption, the osteoid surface, osteoblast surface, mineral apposition rate, and bone formation rate were as high in OVX rats treated with S12911 as in untreated OVX rats. In addition, plasma osteocalcin (OC) and alkaline phosphatase (ALP) levels remained elevated or were further increased in OVX rats treated with S12911. In contrast, treatment with E2 reduced both bone resorption and formation and plasma ALP and OC to the levels in sham rats. The data indicate that the divalent Strontium Salt S12911 is acting as an uncoupling agent that can prevent the femoral osteopenia and partially prevent the trabecular bone loss in E2-deficient rats by inhibiting bone resorption without reducing bone formation.
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the divalent Strontium Salt s12911 enhances bone cell replication and bone formation in vitro
Bone, 1996Co-Authors: Ernesto Canalis, M Hott, Pascale Deloffre, Y Tsouderos, Pierre J MarieAbstract:Abstract In this study, we have determined the effect of the divalent Strontium Salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3 H-thymidine for the last 6 h of culture or treated with S12911 for 24 h and labeled for 24 h with 3 H-proline 24–48 h after the removal of the agent. Calvariae were then processed for histomorphometry. S12911 at 10 −3 M increased the replication of preosteoblastic cells by 30–50% after 24 h and by 60% after 96 h of treatment. This effect was specific, since the number of labeled osteoblasts and of periosteal cells was not changed. A transient 24 h treatment with S12911 at 10 −3 M increased bone formation 24 and 48 h after the removal of the agent. 3H -proline labeled surfaces and bone formation rates were increased by 20%–35%. In the second series of experiments, sequential collagenase digestions were used to isolate cell populations enriched in fibroblasts or osteoblasts (Ob) from 22 day fetal rat calvariae. Treatment with S12911 at 10 −3 M for 24 h enhanced DNA synthesis by three- to fourfold in cell populations enriched in fibroblasts and preosteoblastic cells. The effect was less pronounced and inconsistent in Ob cells. S12911 at 10 −3 M for 24 h also increased collagen and non-collagen protein synthesis by 35% in Ob cells. These data indicate that the divalent Strontium Salt S12911 enhances bone cell replication and bone formation in vitro, an effect that may contribute to the previously reported effects of S12911 on trabecular bone mass in vivo.
Donald Mastropaolo - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of the hydrated Strontium Salt of methotrexate two independent molecules with different conformations
Journal of Medicinal Chemistry, 2001Co-Authors: Donald Mastropaolo, Arthur Camerman, Norman CamermanAbstract:The crystal and molecular structure of methotrexate has been determined by X-ray diffraction from a highly hydrated triclinic crystal form in which the asymmetric unit contains two independent methotrexate molecules with their glutamate carboxyl groups coordinated to two Strontium ions. The two methotrexates exhibit differing conformations: They are almost related to one another by a pseudocenter of symmetry. This places the C(9)-N(10) bond vectors on opposite sides of the planes of the pteridine rings. The 2,4-diaminopteridines form 2-fold symmetry-related hydrogen-bonded dimers as well as hydrogen bonds to benzoyl carbonyl oxygens and lattice water molecules. This structure provides experimental proof of the existence of pteridine conformers through rotation about the C(6)-C(9) bond. Comparison of these conformers with other free and enzyme-bound methotrexate conformations shows them all to be different and illustrates the ability of the molecule to adapt to its chemical environment. The results from this crystal structure determination are experimental proof that methotrexate has not one preferred molecular conformation but may freely rotate about several bonds. They also suggest that the dihydrofolate reductase-bound methotrexate conformation is greatly influenced by the specific binding site environment of the enzyme.
Y Tsouderos - One of the best experts on this subject based on the ideXlab platform.
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an uncoupling agent containing Strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen deficient rats
Journal of Bone and Mineral Research, 2005Co-Authors: Pierre J Marie, M Hott, Pascale Deloffre, Dominique Modrowski, Cinderella De Pollak, Joel Guillemain, Y TsouderosAbstract:Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of Strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent Strontium Salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15–25 per group) were sham operated or ovariectomized (OVX) and treated with 17β-estradiol (E2, 10 μg/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone Strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30–36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats. In contrast to this inhibitory effect on bone resorption, the osteoid surface, osteoblast surface, mineral apposition rate, and bone formation rate were as high in OVX rats treated with S12911 as in untreated OVX rats. In addition, plasma osteocalcin (OC) and alkaline phosphatase (ALP) levels remained elevated or were further increased in OVX rats treated with S12911. In contrast, treatment with E2 reduced both bone resorption and formation and plasma ALP and OC to the levels in sham rats. The data indicate that the divalent Strontium Salt S12911 is acting as an uncoupling agent that can prevent the femoral osteopenia and partially prevent the trabecular bone loss in E2-deficient rats by inhibiting bone resorption without reducing bone formation.
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the divalent Strontium Salt s12911 enhances bone cell replication and bone formation in vitro
Bone, 1996Co-Authors: Ernesto Canalis, M Hott, Pascale Deloffre, Y Tsouderos, Pierre J MarieAbstract:Abstract In this study, we have determined the effect of the divalent Strontium Salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3 H-thymidine for the last 6 h of culture or treated with S12911 for 24 h and labeled for 24 h with 3 H-proline 24–48 h after the removal of the agent. Calvariae were then processed for histomorphometry. S12911 at 10 −3 M increased the replication of preosteoblastic cells by 30–50% after 24 h and by 60% after 96 h of treatment. This effect was specific, since the number of labeled osteoblasts and of periosteal cells was not changed. A transient 24 h treatment with S12911 at 10 −3 M increased bone formation 24 and 48 h after the removal of the agent. 3H -proline labeled surfaces and bone formation rates were increased by 20%–35%. In the second series of experiments, sequential collagenase digestions were used to isolate cell populations enriched in fibroblasts or osteoblasts (Ob) from 22 day fetal rat calvariae. Treatment with S12911 at 10 −3 M for 24 h enhanced DNA synthesis by three- to fourfold in cell populations enriched in fibroblasts and preosteoblastic cells. The effect was less pronounced and inconsistent in Ob cells. S12911 at 10 −3 M for 24 h also increased collagen and non-collagen protein synthesis by 35% in Ob cells. These data indicate that the divalent Strontium Salt S12911 enhances bone cell replication and bone formation in vitro, an effect that may contribute to the previously reported effects of S12911 on trabecular bone mass in vivo.
Morikazu Hosoe - One of the best experts on this subject based on the ideXlab platform.
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Strontium Isotope Effect in Liquid-Liquid Extraction of Strontium Chloride Using a Crown Ether
Journal of Nuclear Science and Technology, 1995Co-Authors: Kazushige Nishizawa, Tomonori Satoyama, Takahito Miki, Tadashi Yamamoto, Morikazu HosoeAbstract:Isotope effects in a liquid-liquid extraction of Strontium with dicyclohexano-18-crown-6 (DC18C6) were investigated. Unit mass enrichment factors were observed to increase with concentrations of Strontium Salt in an aqueous phase. Isotope distinguishing ability of DC18C6 to Strontium isotopes was calculated as an intrinsic separation factor to be K c =1.00051±0.00004. An odd mass number isotope, 87Sr, was recognized to behave differently from even mass number isotopes, 84Sr, 86Sr and 88Sr. The enrichment factor induced by a nuclear property (odd or even mass number) other than the mass difference was eO/E = −8.0 × 10−4 which was observed with 3.2M Sr aqueous solution. Isotope shift of energy state for 5S-orbital of Strontium produces the isotope shift in vibrational energy between the Strontium ion and the DC18C6.
