bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial protective effects of nicorandil, an opener of potassium channels on senile rat heart
Authors: Liu Jinping , Long Cun , Ji Bingyang , Zhang Hongjia , Wen Fuxing 
Published: April 2006

The purpose of this study was to investigate the cardio-protective effects of nicorandil, an opener of potassium channels, on senile rat hearts from ischemic reperfusion injury. A modified working model of isolated perfused hearts of senile rats was used. After isolation, the hearts underwent 60 min of global hypothermic ischemia treatment, followed by 30 min of reperfusion. These hearts were distributed into three groups, each receiving different cardioplegic solutions: (1) St. Thomas’ solution (Group S), (2) 100 μmol/L nicorandil (Group N), (3) St. Thomas’ solution combined with 100 μmol/L nicorandil (Group S+N). The pre- and post-ischemic myocardial function were assessed by the percentage recovery of the heart rate (HR), ±dp/dtmax (maximal rate of change of left ventricular pressure) and cardiac output (CO). Upon reperfusion, the cardioplegic solution was collected from the coronary sinus and tested for lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. During 30 min of reperfusion, the percentage recovery of HR, +dp/dt and left ventricular stroke work (LVSW) were significantly higher in Group S+N than in Group S and Group N ( p < 0.05). The percentage of recovery in CO was higher in Group N and Group S+N than in Group S. The electrical activities arresting time (EAT) and mechanical activities arresting time (MAT) were longer in Group N than in Group S and Group N+S( p < 0.01). There were no statistical significance between Group S and Group N+ S( p > 0.05). There were no significant differences in the levels of LDH and CK-MB. Electron microscopic examination revealed better preservation of the ultra-structures of the myocardial tissue in Group N+S than the other two groups. These results indicate that nicorandil combined with St. Thomas’ solution can improve the left ventricular function of the post-ischemic senile rat and offer a better myocardial protective effect on the ischemic senile myocardium.
Molecular Design of a Calix[6]arene-Based Super-Uranophile with C3 Symmetry. High UO22+ Selectivity in Solvent Extraction
Authors: Araki Koji , Hashimoto Norifumi , Otsuka Hideyuki , Nagasaki Takeshi , Shinkai Seiji 
Published: April 2006

Abstract
Calix[6]arene bearing three carboxylate groups arranged in C3 symmetry formed a 1 : 1 complex with UO22+ and showed much more excellent selectivity factors for UO22+ in solvent extraction than calix[6]arene bearing six carboxylate groups. This establishes that the essence of “super-uranophiles” is related to the molecular design of C3 symmetry.
Synthesis of the Tetrahydropyran Ring Part of a Marine Toxin Polycavernoside-A
Authors: Fujiwara Kenshu , Amano Seiji , Oka Takahiro , Murai Akio 
Published: April 2006

Abstract
Construction of the tetrahydropyran ring part of polycavernoside A, which has been isolated as one of toxic principles from the red alga Polycavernosa tsudai, is described starting from (S)-(−)- and (R)-(+)-glycidols.
Pd-Catalyzed Cycloaddition of Vinylcyclopentenes with Trimethylenemethane. Substituent Effect on [4+3] vs [3+2] Selectivity
Authors: Trost Barry M , Yamazaki Shoko 
Published: April 2006

Abstract
The Pd-catalyzed reaction of 2-vinylcyclopentenes 2 and 3 with trimethylenemethane gave [4+3] and [3+2] cycloadducts. Derivatization of 2-vinylcyclopentenones with bulky ketal substituents served to enhance seven-membered ring formation.
Effects of Calcitonin on Subchondral Trabecular Bone Changes and on Osteoarthritic Cartilage Lesions After Acute Anterior Cruciate Ligament Deficiency
Authors: Behets Catherine , Williams James M , Chappard Daniel , Devogelaer Jean-Pierre , Manicourt Daniel-Henri 
Published: April 2006

Abstract
Because SBM may contribute to cartilage breakdown in OA, experimental OA was induced in dogs by transecting the anterior cruciate ligament of the knee and treating with either CT or a placebo. CT significantly reduced both SBM and cartilage lesions. This study supports the use of CT in the treatment of canine experimental OA.
Introduction: Because subchondral bone remodeling (SBM) may contribute to cartilage breakdown in osteoarthritis (OA), we evaluated to what extend calcitonin (CT) might affect cartilage and bone changes in the early stages of canine experimental OA.
Materials and Methods: Twelve dogs underwent transection of the anterior cruciate ligament (ACLT) of the right knee. After ACLT, each animal received a daily nasal spray delivering either 400 U of CT (CT-treated group; n = 6) or a placebo (PL-treated group; n = 6). At day 84 after surgery, animals were killed, and cartilage changes were graded. BMD and volume fraction (BVF) were assessed by pQCT in different regions of interest (ROIs) of the subchondral cancellous bone of tibial plateaus (TPs). Statistics included a 2 × 2 factorial analysis with ±CT as one factor and ±ACLT as the other.
Results and Conclusions: Nonoperated (N-OP) knees were normal in both groups. In the PL-treated group, ACLT knees all exhibited OA changes, which predominated in the medial knee compartment. Furthermore, compared with N-OP knees, the BMD and BVF of ACLT joints were both markedly reduced in medial TP but not in lateral TP. In contrast, in the CT-treated group, cartilage OA lesions of ACLT knees were significantly reduced, and there was no difference in BMD and BFV between N-OP and ACLT knees. These findings suggest that the loss of subchondral trabeculae contributes to cartilage breakdown, possibly by enhancing cartilage deformation on joint loading. By counteracting bone loss, CT reduced cartilage OA lesions, and thus, might be useful in the treatment of OA in cruciate-deficient dogs.
Decreased Collagen Organization and Content Are Associated With Reduced Strength of Demineralized and Intact Bone in the SAMP6 Mouse
Authors: Silva Matthew J , Brodt Michael D , Wopenka Brigitte , Thomopoulos Stavros , Williams Derek , Wassen Maurice HM , Ko Mike , Kusano Nozomu , Bank Ruud A 
Published: April 2006

Abstract
To examine the link between bone material properties and skeletal fragility, we analyzed the mechanical, histological, biochemical, and spectroscopic properties of bones from a murine model of skeletal fragility (SAMP6). Intact bones from SAMP6 mice are weak and brittle compared with SAMR1 controls, a defect attributed to reduced strength of the bone matrix. The matrix weakness is attributed primarily to poorer organization of collagen fibers and reduced collagen content.
Introduction: The contribution of age-related changes in tissue material properties to skeletal fragility is poorly understood. We previously reported that bones from SAMP6 mice are weak and brittle versus age-matched controls. Our present objectives were to use the SAMP6 mouse to assess bone material properties in a model of skeletal fragility and to relate defects in the mechanical properties of bone to the properties of demineralized bone and to the structure and organization of collagen and mineral.
Materials and Methods: Femora from 4- and 12-month-old SAMR1 (control) and SAMP6 mice were analyzed using bending and torsional mechanical testing of intact bones, tensile testing of demineralized bone, quantitative histology (including collagen fiber orientation), collagen cross-links biochemistry, and Raman spectroscopic analysis of mineral and collagen.
Results: Intact bones from SAMP6 mice have normal elastic properties but inferior failure properties, with 60% lower fracture energy versus SAMR1 controls. The strength defect in SAMP6 bones was associated with a 23% reduction in demineralized bone strength, which in turn was associated with poorer collagen fiber organization, lower collagen content, and higher hydroxylysine levels. However, SAMP6 have normal levels of collagen cross-links and normal apatite mineral structure.
Conclusions: Bones from SAMP6 osteoporotic mice are weak and brittle because of a defect in the strength of the bone matrix. This defect is attributed primarily to poorer organization of collagen fibers and reduced collagen content. These findings highlight the role of the collagen component of the bone matrix in influencing skeletal fragility.
CCR1 Acts Downstream of NFAT2 in Osteoclastogenesis and Enhances Cell Migration
Authors: Ishida Norihiro , Hayashi Koji , Hattori Asuka , Yogo Keiichiro , Kimura Toru , Takeya Tatsuo 
Published: April 2006

Abstract
We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration.
Introduction: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells.
Materials and Methods: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay.
Results and Conclusions: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Gα inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts.
A Novel Tetracycline Labeling Schedule for Longitudinal Evaluation of the Short-Term Effects of Anabolic Therapy With a Single Iliac Crest Bone Biopsy: Early Actions of Teriparatide
Authors: Lindsay Robert , Cosman Felicia , Zhou Hua , Bostrom Mathias P , Shen Victor W , Cruz JoAnn D , Nieves Jeri W , Dempster David W 
Published: April 2006

Abstract
We describe a quadruple tetracycline labeling method that allows longitudinal assessment of short-term changes in bone formation in a single biopsy. We show that 1 month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation.
Introduction: Iliac crest biopsy, with histomorphometric evaluation, provides important information about cellular activity in bone. However, to obtain longitudinal information, repeat biopsies must be performed. In this study, we show the capability to obtain short-term longitudinal information on bone formation in a single biopsy using a novel, quadruple labeling technique.
Materials and Methods: Two tetracycline labels were administered using a standard 3 days on, 12 days off, 3 days on format. Four weeks later, the tetracycline labeling was repeated using the same schedule but with a different tetracycline that can be distinguished from the first by its color under fluorescent light. Iliac crest biopsies were performed 1 week later and prepared undecalcified for histomorphometry. Indices of bone formation 1 month apart were measured and calculated using the two sets of labels. We used this method to investigate the early effects of teriparatide [hPTH(1-34)] treatment on bone formation. The results were compared with those from a group of control subjects who were quadruple-labeled, but did not receive hPTH(1-34).
Results: Treatment with hPTH(1-34) dramatically stimulated bone formation on cancellous and endocortical surfaces. This was achieved by both an increase in the linear rate of matrix apposition and extension of the bone-forming surface. New bone was deposited on previously quiescent surfaces (i.e., modeling-based formation), but a proportion of this could occur by encroachment from adjacent resorption cavities.
Conclusions: A single transiliac crest bone biopsy, after sequential administration of two sets of tetracycline labels is a useful approach to study the short-term effects of anabolic agents on human bone. One month of hPTH(1-34) treatment extends the bone-forming surface, increases mineral apposition rate, and initiates modeling-based formation.
Short-Term Intravenous Bisphosphonates in Prevention of Postmenopausal Bone Loss
Authors: Heikkinen Jorma E. , Selander Katri S. , Laitinen Kalevi , Arnala Ilkka , Dr. Väänänen H. Kalervo 
Published: April 2006

Abstract
This study was performed to test the efficacy of short-term intravenous clodronate and etidronate in the prevention of postmenopausal bone loss. Healthy postmenopausal women, exhibiting a decreasing trend in bone mineral density, were randomized to five groups (clodronate at doses of 150, 300, and 600 mg; etidronate at a dose of 300 mg; and a placebo group) of 21–22 subjects. The drugs were administered intravenously three times with 1-week intervals, followed by regular evaluation for up to 24 months. During the first year, 300 mg of clodronate retarded bone loss significantly in the lumbar spine and femoral neck, where significant protection still persisted after 24 months. Other doses of clodronate (150 and 600 mg) were not bone protective. Etidronate (300 mg) retarded bone loss significantly in the lumbar spine up to 24 months, relative to placebo. Serum concentrations of procollagen I carboxy-terminal propeptide and urinary Ca2+ and hydroxyproline excretion decreased in all bisphosphonate groups during the first month after treatment, but the values returned later toward baseline. In the etidronate-group, serum osteocalcin concentrations also decreased significantly during the first 3 months of the study. Otherwise, no uniform serum responses to bisphosphonate-treatment were detected in circulating markers of bone formation, alkaline phosphatase, or osteocalcin. No significant differences in the serum concentrations of cross-linked carboxy-terminal telopeptide of type I collagen were detected between the groups. Patient acceptance of both bisphosphonates was excellent, and no drug-related adverse side effects were detected. These results suggest that infrequently repeated intravenous treatment with bisphosphonates may effectively counteract postmenopausal bone loss.
Bone Microdamage and Skeletal Fragility in Osteoporotic and Stress Fractures
Authors: Burr David B. , Forwood Mark R. , Fyhrie David P. , Martin R. Bruce , Schaffler Mitchell B. , Turner Charles H. 
Published: April 2006

Abstract
The accumulation of bone microdamage has been proposed as one factor that contributes to increased skeletal fragility with age and that may increase the risk for fracture in older women. This paper reviews the current status and understanding of microdamage physiology and its importance to skeletal fragility. Several questions are addressed: Does microdamage exist in vivo in bone? If it does, does it impair bone quality? Does microdamage accumulate with age, and is the accumulation of damage with age sufficient to cause a fracture? The nature of the damage repair mechanism is reviewed, and it is proposed that osteoporotic fracture may be a consequence of a positive feedback between damage accumulation and the increased remodeling space associated with repair.
Increased Adipogenesis and Myelopoiesis in the Bone Marrow of SAMP6, a Murine Model of Defective Osteoblastogenesis and Low Turnover Osteopenia
Authors: Kajkenova Oumitana , Lecka-Czernik Beata , Gubrij Igor , Hauser Simon P. , Takahashi Kenshirou , Parfitt A. Michael , Jilka Robert L. , Manolagas Stavros C. , Lipschitz David A. 
Published: April 2006

Abstract
Bone formation and hematopoiesis are anatomically juxtaposed and share common regulatory mechanisms. However, little is known about the interrelationship between these two processes. We have previously shown that the senescence accelerated mouse-P6 (SAMP6) exhibits decreased osteoblastogenesis in the bone marrow that is temporally linked with a low rate of bone formation and decreased bone mineral density. Here we report that in contrast to decreased osteoblastogenesis, ex vivo bone marrow cultures from SAMP6 mice exhibited an increase in the number of colony-forming unit adipocytes, as well as an increase in the number of fully differentiated marrow adipocytes, compared with SAMR1 (nonosteopenic) controls. Further, long-term bone marrow cultures from SAMP6 produced an adherent stromal layer more rapidly, generated significantly more myeloid progenitors and produced more IL-6 and colony-stimulating activity. Consistent with this, the number of myeloid cells in freshly isolated marrow from SAMP6 mice was increased, as was the number of granulocytes in peripheral blood. The evidence that SAMP6 mice exhibit decreased osteoblastogenesis, and increased adipogenesis and myelopoiesis, strongly suggests that a switch in the differentiation program of multipotential mesenchymal progenitors may underlie the abnormal phenotype manifested in the skeleton and other tissues of these animals. Moreover, these observations support the contention for the existence of a reciprocal relationship between osteoblastogenesis and adipogenesis that may explain the association of decreased bone formation and the resulting osteopenia with the increased adiposity of the marrow seen with advancing age in animals and humans.
Cloning and Characterization of a Calcium-Sensing Receptor from the Hypercalcemic New Zealand White Rabbit Reveals Unaltered Responsiveness to Extracellular Calcium
Authors: Butters Robert R. , Chattopadhyay Naibedya , Nielsen Palle , Smith Craig P. , Mithal Ambrish , Kifor Olga , Bai Mei , Quinn Steven , Goldsmith Paul , Hurwitz Shmuel , Krapcho Karen , Busby James , Brown Edward M. 
Published: April 2006

Abstract
The extracellular Ca2+ (Ca   0 2+ )-sensing receptor (CaR) recently cloned from mammalian parathyroid, kidney, brain, and thyroid plays a central role in maintaining near constancy of Ca   0 2+ . We previously showed that the hypercalcemia normally present in New Zealand white rabbits is associated with an elevated set point for Ca   0 2+ -regulated PTH release (the level of Ca   0 2+ half-maximally inhibiting hormonal secretion). This observation suggested an alteration in the Ca   0 2+ -sensing mechanism in the rabbit parathyroid, a possibility we have now pursued by isolating and characterizing the rabbit homolog of the CaR. The cloned rabbit kidney CaR (RabCaR) shares a high degree of overall homology (&gt;90% amino acid identity) with the bovine, human, and rat CaRs, although it differs slightly in several regions of the extracellular domain potentially involved in binding ligands. By Northern analysis and/or immunohistochemistry, a similar or identical receptor is also expressed in parathyroid, thyroid C cells, small and large intestine, and in the thick ascending limb and collecting ducts of the kidney. When expressed transiently in HEK293 cells and assayed functionally through CaR agonist-evoked increases in Ca   i 2+ , the rabbit CaR shows apparent affinities for Ca   0 2+ , Mg   0 2+ , and Gd   0 3+ that are indistinguishable from those observed in studies carried out concomitantly using the human CaR. Therefore, at least as assessed by its ability to increase Ca   i 2+ when expressed in HEK293 cells, the intrinsic functional properties of the rabbit CaR cannot explain the hypercalcemia observed in vivo in the New Zealand white rabbit.
Long-Term Changes in Bone Mineral and Biomechanical Properties of Vertebrae and Femur in Aging, Dietary Calcium Restricted, and/or Estrogen-Deprived/-Replaced Rats
Authors: Jiang Yebin , Zhao Jenny , Genant Harry K. , Dequeker Jan , Geusens Piet 
Published: April 2006

Abstract
To study the long-term effect of aging, low calcium diet (LCD) and/or ovariectomy (OVX), and estrogen replacement therapy (+E) on rat bone quality of both trabecular and cortical bone, 150 female Wistar rats of 4.5 months were divided into baseline, sham-operation (sham), sham + LCD, OVX, OVX + E, OVX + LCD, OVX + LCD + E, and were observed for 3, 6, and 9 months postsurgery. The bone mineral density (BMD) of the lumbar spine L1–L4, the femoral neck, the midshaft, and the distal metaphysis were determined using dual-energy X-ray absorptiometry (DXA) in vitro. Biomechanical tests of the L1 vertebral body and the left femur were performed. The right femoral midshaft and neck were processed undecalcified for determining cross-sectional moments of inertia (CSMIs). BMD in all groups increased rapidly with aging in the femoral midshaft composed only of cortical bone at 3 months post-OVX and stabilized or decreased thereafter, but decreased at all observation periods in the distal femoral metaphysis, consisting mostly of trabecular bone. L1 maximum compressive strength and stiffness increased as a function of aging in sham and sham + LCD but not in OVX and OVX + LCD. The order of loss in BMD at all sites and in L1 strength and stiffness was: OVX + LCD &gt; OVX &gt; LCD. LCD reduced while OVX improved the total femoral area, CSMIs in the femoral midshaft, and the torsional strength. Estrogen treatment preserved BMD and prevented OVX-induced loss in L1 strength. The BMD and biomechanical properties were greater in OVX + E than in OVX + LCD + E. Loss in BMD and CSMIs was greater in the femoral neck than in the midshaft. The data suggest that rat cortical bone might not be matured until 7.5 months of age. It would be more appropriate to consider rats at peak bone mass as a model of mature rat and to perform OVX at that time. LCD and OVX have a great potential for weakening the bone quality of cortical bone and trabecular bone, respectively, and have an additive effect when combined. Estrogen prevents only OVX-induced bone loss.