bluuebunny/crossref_metadata_2025 huggingface dataset:
Doxorubicin conjugated to D‐α‐tocopheryl polyethylene glycol succinate and folic acid as a prodrug for targeted chemotherapy
Authors: Anbharasi Vanangamudi , Cao Na , Feng Si‐Shen
Published: March 2010

This research developed a prodrug strategy to conjugate doxorubicin (DOX) to D‐α‐tocopheryl polyethylene glycol succinate (TPGS) and folic acid (FOL) for targeted chemotherapy to enhance the therapeutic effects and reduce the side effects of the drug. We synthesized two conjugates, TPGS–DOX and TPGS–DOX–FOL, to quantitatively evaluate the advantages of TPGS conjugation and FOL conjugation through passive and active targeting effects. The successful conjugation was confirmed by 1H nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. The in vitro drug release was found pH dependent, which is in favor of cancer treatment. The in vitro cellular uptake and cytotoxicity were evaluated with MCF‐7 breast cancer cells. It was found that the cellular uptake of DOX increased 15.2% by TPGS conjugation and further 6.3% by FOL conjugation after 0.5‐h cell culture. The IC50 after 24‐h cell culture with MCF‐7 cancer cells showed that TPGS–DOX conjugate could be 1.19‐fold effective versus DOX and that TPGS–DOX–FOL could be 38.6‐fold effective than TPGS–DOX and thus 45.0‐fold more effective versus DOX. In vivo experiment showed that the half‐life of TPGS–DOX and TPGS–DOX–FOL were increased 3.79‐ and 3.9‐fold than the free DOX, and the area under the curve were increased 19.2‐ and 14.5‐fold than the DOX, respectively. The biodistribution data showed that TPGS–DOX and TPGS–DOX–FOL significantly lowered drug accumulation in the heart, thereby reducing the cardiotoxicity, which is the main side effect of the DOX. Furthermore, TPGS–DOX can limit, and TPGS–DOX–FOL can further deduce, the gastrointestinal side effect of the drug. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Novel insights into the mechanism of decreased expression of type X collagen in human mesenchymal stem cells from patients with osteoarthritis cultured on nitrogen‐rich plasma polymers: Implication of cyclooxygenase‐1
Authors: Petit Alain , Wang Hong Tian , Girard‐Lauriault Pierre‐Luc , Wertheimer Michael R. , Antoniou John , Mwale Fackson
Published: March 2010

Recent evidence indicates that a major drawback of current cartilage‐ and intervertebral disc (IVD) tissue engineering is that human mesenchymal stem cells (MSCs) from patients with osteoarthritis rapidly express type X collagen (COL10A1), a marker of late stage chondrocyte hypertrophy associated with endochondral ossification. We recently demonstrated that COL10A1 expression was inhibited in MSCs from patients with osteoarthritis cultured on nitrogen‐rich plasma polymerized (PPE:N) coatings. Here, we sought to understand the mechanisms of action of this effect by culturing MSCs on PPE:N surfaces in the presence of different inhibitors of kinases and cyclooxygenases. The effect of PPE:N surfaces on COL10A1 expression was found to be mimicked by the cyclooxygenase inhibitor NPPB, but not by daphnetin (an inhibitor of protein kinases) nor by genistein (an inhibitor of tyrosine kinases). COL10A1 expression was also suppressed by the specific cyclooxygenase‐1 (COX‐1: SC‐560) and 5‐lipoxygenase (5‐LOX: MK‐866) inhibitors, but not by COX‐2 (COX‐2 inhibitor 2) and 12‐LOX (baicalein) inhibitors. Finally, the incubation of MSCs on PPE:N surfaces inhibited the expression of COX‐1 while 5‐LOX was not expressed in these cells. Taken together, these results indicate that PPE:N surfaces inhibit COL10A1 expression via the suppression of COX‐1. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010
Effect of two restorative materials on root dentine erosion
Authors: Domiciano Silvia Jorge , Colucci Vivian , Campos Serra Mônica
Published: March 2010

This study sought to evaluate the microhardness of root dentine adjacent to glass‐ionomer and composite resin restorations after erosive challenge. A crossover study was performed in two phases of 4 consecutive days each. One hundred twelve bovine root dentine slabs were obtained, and standardized box‐shaped cavities were prepared at center of each specimen. The prepared cavities were randomly restored with glass‐ionomer cement or composite resin. The slabs were randomly assigned among 14 volunteers, which wore intraoral palatal device containing four restored root dentin slabs. Starting on the second day, half of the palatal acrylic devices were immersed extraorally in a lemonade‐like carbonated soft drink for 90 s, four times daily for 3 days. After 3‐day wash‐out, dentine slabs restored with the alternative material were placed into palatal appliance and the volunteers started the second phase of this study. After erosive challenges, microhardness measurements were performed. Regardless of the restorative material employed, eroded specimens demonstrated lower microhardness value (p < 0.0001). At eroded condition examined in this study, dentine restored with glass‐ionomer cement showed higher microhardness values (p < 0.0001). It may be concluded that the glass‐ionomer cement decreases the progression of root dentine erosion at restoration margin. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Evaluation of the biocompatibility of novel peptide hydrogel in rabbit eye
Authors: Liang Liang , Xu Xiao‐Ding , Chen Chang‐Sheng , Fang Jia‐Hua , Jiang Fa‐Gang , Zhang Xian‐Zheng , Zhuo Ren‐Xi
Published: March 2010

A peptide containing a RGD (arginine‐glycine‐aspartic acid) sequence as well as a hydrophobic N‐fluorenyl‐9‐methoxycarbonyl (FMOC) tail was prepared via a standard FMOC solid‐phase peptide synthesis technique. The supramolecular self‐assembly of such peptide through π–π stacking from FMOC tail can transfer the peptide aqueous solution into a three‐dimensional hydrogel. The biocompatibility of the peptide hydrogel was evaluated via clinical follow‐up and histological analysis. The data obtained demonstrated that the peptide hydrogel exhibited good biocompatibility when injected to the subconjunctival space and anterior chamber of rabbit, indicating a potential application in ophthalmology as an implantable drug delivery system for the treatment to ocular anterior segment diseases such as glaucoma, iridocyclitis, and keratopathy. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Bone repair by cell‐seeded 3D‐bioplotted composite scaffolds made of collagen treated tricalciumphosphate or tricalciumphosphate‐chitosan‐collagen hydrogel or PLGA in ovine critical‐sized calvarial defects
Authors: Haberstroh Kathrin , Ritter Kathrin , Kuschnierz Jens , Bormann Kai‐Hendrik , Kaps Christian , Carvalho Carlos , Mülhaupt Rolf , Sittinger Michael , Gellrich Nils‐Claudius
Published: March 2010

The aim of this study was to investigate the osteogenic effect of three different cell‐seeded 3D‐bioplotted scaffolds in a ovine calvarial critical‐size defect model. The choice of scaffold‐materials was based on their applicability for 3D‐bioplotting and respective possibility to produce tailor‐made scaffolds for the use in cranio‐facial surgery for the replacement of complex shaped boneparts. Scaffold raw‐materials are known to be osteoinductive when being cell‐seeded [poly(L‐lactide‐co‐glycolide) (PLGA)] or having components with osteoinductive properties as tricalciumphosphate (TCP) or collagen (Col) or chitosan. The scaffold‐materials PLGA, TCP/Col, and HYDR (TCP/Col/chitosan) were cell‐seeded with osteoblast‐like cells whether gained from bone (OLB) or from periost (OLP). In a prospective and randomized design nine sheep underwent osteotomy to create four critical‐sized calvarial defects. Three animals each were assigned to the HYDR‐, the TCP/Col‐, or the PLGA‐group. In each animal, one defect was treated with a cell‐free, an OLB‐ or OLP‐seeded group‐specific scaffold, respectively. The fourth defect remained untreated as control (UD). Fourteen weeks later, animals were euthanized for histo‐morphometrical analysis of the defect healing. OLB‐ and OLP‐seeded HYDR and OLB‐seeded TCP/Col scaffolds significantly increased the amount of newly formed bone (NFB) at the defect bottom and OLP‐seeded HYDR also within the scaffold area, whereas PLGA‐scaffolds showed lower rates. The relative density of NFB was markedly higher in the HYDR/OLB group compared to the corresponding PLGA group. TCP/Col had good stiffness to prepare complex structures by bioplotting but HYDR and PLGA were very soft. HYDR showed appropriate biodegradation, TCP/Col and PLGA seemed to be nearly undegraded after 14 weeks. 3D‐bioplotted, cell‐seeded HYDR and TCP/Col scaffolds increased the amount of NFB within ovine critical‐size calvarial defects, but stiffness, respectively, biodegradation of materials is not appropriate for the application in cranio‐facial surgery and have to be improved further by modifications of the manufacturing process or their material composition. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Bioactive inorganic‐materials/alginate composite microspheres with controllable drug‐delivery ability
Authors: Wu Chengtie , Zhu Yufang , Chang Jiang , Zhang Yufeng , Xiao Yin
Published: March 2010

Alginate microspheres are considered a promising material as a drug carrier in bone repair because of excellent biocompatibility, but their main disadvantage is low drug entrapment efficiency and noncontrollable release. The aim of this study was to investigate the effect of incorporating mesoporous bioglass (MBG), nonmesoporous bioglass (BG), or hydroxyapatite (HAp) into alginate microspheres on their drug‐loading and release properties. X‐ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and atomic emission spectroscopy (AES) were used to analyze the composition, structure, and dissolution of bioactive inorganic materials and their microspheres. Dexamethasone (DEX)‐loading and release ability of four microspheres were tested in phosphate buffered saline with varying pH. Results showed that the drug‐loading capacity was enhanced with the incorporation of bioactive inorganic materials into alginate microspheres. The MBG/alginate microspheres had the highest drug loading ability. DEX release from alginate microspheres correlated to the dissolution of MBG, BG, and HAp in PBS, and that the pH was an efficient factor in controlling the DEX release; a high pH resulted in greater DEX release, whereas a low pH delayed DEX release. In addition, MBG/alginate, BG/alginate, and HAp/alginate microspheres had varying apatite‐formation and dissolution abilities, which indicate that the composites would behave differently with respect to bioactivity. The study suggests that microspheres made of a composite of bioactive inorganic materials and alginate have a bioactivity and degradation profile which greatly improves their drug delivery capacity, thus enhancing their potential applications as bioactive filler materials for bone tissue regeneration. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake
Authors: Koek W Nadia H , van Meurs Joyce B , van der Eerden Bram CJ , Rivadeneira Fernando , Zillikens M Carola , Hofman Albert , Obermayer-Pietsch Barbara , Lips Paul , Pols Huibert A , Uitterlinden André G , van Leeuwen Johannes PTM
Published: March 2010

The C-variant of a T-13910C polymorphism (rs4988235; NT_022135.15:g.25316568G > A) upstream of the lactase phlorizin hydrolase (LPH) gene causes lactose intolerance. Association studies with differences in bone parameters and fracture risk have been inconclusive. The objective of this study was to examine the association of LPH rs4988235 with body height and bone parameters and calcium homeostasis in two elderly populations of Dutch Caucasians and assess interaction with vitamin D receptor (VDR) polymorphisms. Genotyping of LPH and VDR polymorphisms was performed in 6367 individuals from the Rotterdam Study and 844 from the Longitudinal Aging Study Amsterdam (LASA). Associations with age, height, weight, bone mineral density (BMD), skeletal morphometric parameters and serum vitamin D and calcium levels, and dietary calcium intake were assessed using ANOVA or analysis of covariance, and allele dose effect was assessed using linear regression analysis. Fracture risk was analyzed using Cox's proportional hazard regression analysis. Associations with body height (p = 2.7 × 10−8) and vertebral area (p = .048) found in the Rotterdam Study were explained by population stratification, as assessed by principal-component analyses, and disappeared after additional adjustments. No associations with femoral neck or lumbar spine BMD or with fracture risk were detected. Calcium intake and serum ionized serum calcium were significantly lower in C-homozygotes (p = 9.2 × 10−7, p = .02, respectively). For none of the parameters studied was interaction between the T-13910C polymorphism and VDR block 5 haplotype 1 observed. We show that the C allele of the T-13910C polymorphism causing lactose intolerance is associated with lower dietary calcium intake and serum calcium levels but not with BMD or fractures. The associations observed with height and vertebral area were the result of population stratification. This demonstrates the impact of population stratification and urges researchers to carefully take this into account in genetic associations, in particular, in dietary intake–related phenotypes, of which LPH and lactose intolerance are a strong example. © 2010 American Society for Bone and Mineral Research
Src‐like adaptor protein regulates osteoclast generation and survival
Authors: Kim Hyun‐Ju , Zou Wei , Ito Yuji , Kim Shin‐Yoon , Chappel Jean , Ross F. Patrick , Teitelbaum Steven L.
Published: March 2010

Src‐like adaptor protein (SLAP) is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c‐Src, SLAP lacks a tyrosine kinase domain. We investigated the role of SLAP in osteoclast development and resorptive function. Employing SLAP‐deficient mice, we find lack of the adaptor enhances in vitro proliferation of osteoclast precursors in the form of bone marrow macrophages (BMMs), without altering their survival. Furthermore, osteoclastogenic markers appear more rapidly in SLAP−/− BMMs exposed to RANK ligand (RANKL). The accelerated proliferation of M‐CSF‐treated, SLAP‐deficient precursors is associated with enhanced ERK activation. SLAP's role as a mediator of M‐CSF signaling, in osteoclastic cells, is buttressed by complexing of the adaptor protein and c‐Fms in lipid rafts. Unlike c‐Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. Thus, SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. These counterbalancing events yield indistinguishable bones of WT and SLAP−/− mice which contain equal numbers of osteoclasts in basal and stimulated conditions. J. Cell. Biochem. 110: 201–209, 2010. © 2010 Wiley‐Liss, Inc.
Dioscorealide B suppresses LPS‐induced nitric oxide production and inflammatory cytokine expression in RAW 264.7 macrophages: The inhibition of NF‐κB and ERK1/2 activation
Authors: Hiransai Poonsit , Ratanachaiyavong Suvina , Itharat Arunporn , Graidist Potchanapond , Ruengrairatanaroj Prasit , Purintrapiban Juntipa
Published: March 2010

Dioscorealide B (DB), a naphthofuranoxepin has been purified from an ethanolic extract of the rhizome of Dioscorea membranacea Pierre ex Prain & Burkill which has been used to treat inflammation and cancer in Thai Traditional Medicine. Previously, DB has been reported to have anti‐inflammatory activities through reducing nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α) production in lipopolysaccharides (LPS)‐induced RAW 264.7 macrophage cells. In this study, the mechanisms of DB on LPS‐induced NO production and cytokine expression through the activation of nuclear factor‐κB (NF‐κB) and ERK1/2 are demonstrated in RAW 264.7 cells. Through measurement with Griess's reagent, DB reduced NO level with an IC50 value of 2.85 ± 0.62 µM that was due to the significant suppression of LPS‐induced iNOS mRNA expression as well as IL‐1β, IL‐6, and IL‐10 mRNA at a concentration of 6 µM. At the signal transduction level, DB significantly inhibited NF‐κB binding activity, as determined using pNFκB‐Luciferase reporter system, which action resulted from the prevention of IκBα degradation. In addition, DB in the range of 1.5–6 µM significantly suppressed the activation of the ERK1/2 protein. In conclusion, the molecular mechanisms of DB on the inhibition of NO production and mRNA expression of iNOS, IL‐1β, IL‐6, and IL‐10 were due to the inhibition of the upstream kinases activation, which further alleviated the NF‐κB and MAPK/ERK signaling pathway in LPS‐induced RAW264.7 macrophage cells. J. Cell. Biochem. 109: 1057–1063, 2010. © 2010 Wiley‐Liss, Inc.
The role of the cysteine residue in the chaperone and anti‐apoptotic functions of human Hsp27
Authors: Pasupuleti NagaRekha , Gangadhariah Mahesha , Padmanabha Smitha , Santhoshkumar Puttur , Nagaraj Ram H.
Published: March 2010

The small heat shock protein Hsp27 is a molecular chaperone and an anti‐apoptotic protein. Human Hsp27 has one cysteine residue at position 137. We investigated the role of this cysteine residue in the chaperone and anti‐apoptotic functions of Hsp27 by mutating the cysteine residue to an alanine (Hsp27C137A) and comparing it to wild‐type protein (Hsp27WT). Both proteins were multi‐subunit oligomers, but subunits of Hsp27WT were disulfide‐linked unlike those of Hsp27C137A, which were monomeric. Hsp27C137A was indistinguishable from Hsp27WT with regard to its secondary structure, surface hydrophobicity, oligomeric size and chaperone function. S‐thiolation and reductive methylation of the cysteine residue had no apparent effect on the chaperone function of Hsp27WT. The anti‐apoptotic function of Hsp27C137A and Hsp27WT was studied by overexpressing them in CHO cells. No difference in the caspase‐3 or ‐9 activity was observed in staurosporine‐treated cells. The rate of apoptosis between Hsp27C137A and Hsp27WT overexpressing cells was similar whether the cells were treated with staurosporine or etoposide. However, the mutant protein was less protective relative to the wild‐type protein in preventing caspase‐3 and caspase‐9 activation and apoptosis induced by 1 mM H2O2 in CHO and HeLa cells. These data demonstrate that in human Hsp27, disulfide formation by the lone cysteine does not affect its chaperone function and anti‐apoptotic function against chemical toxicants. However, oxidation of the lone cysteine in Hsp27 might at least partially affect the anti‐apoptotic function against oxidative stress. J. Cell. Biochem. 110: 408–419, 2010. © 2010 Wiley‐Liss, Inc.
Rottlerin inhibits migration of follicular thyroid carcinoma cells by PKCδ‐independent destabilization of the focal adhesion complex
Authors: Lin Chien‐Jung , Lin Chieh‐Yu , Chen Ying , Huang Shih‐Horng , Wang Seu‐Mei
Published: March 2010

This study examined the effect of rottlerin on the focal adhesion‐mediated cell migration of CGTH W‐2 human follicular thyroid carcinoma cells. Rottlerin (10 µM) resulted in decreased adhesion of CGTH W‐2 cells to matrix substance, which was correlated with metastatic potential. Rottlerin treatment also resulted in a marked reduction in the migration of CGTH W‐2 cells. Protein levels of integrin β1, FAK, and paxillin were decreased by rottlerin. Consistent with this, immunostaining of FAK, vinculin, and paxillin revealed disassembly of the focal adhesions. Disruption of actin stress fibers was noted, which was compatible with reduced expression levels and activities of Rac‐1 and Rho. The effect of rottlerin on cell migration was not attributable to inhibition of PKCδ activity since siRNA knockdown of PKCδ did not recapitulate the effects of rottlerin on cell adhesion and migration. Furthermore, activation of PKCδ by phorbol esters failed to restore the rottlerin‐inhibited migratory ability. The mitochondrial uncoupler, carbonylcyanide‐4‐(trifluoromethoxy)‐phenylhydrazone, was able to mimic several rottlerin's effects. In summary, we demonstrated that rottlerin inhibits the migration of CGTH W‐2 cells by disassembly of focal adhesion complexes in a PKCδ‐independent manner, and might play as a mitochondrial uncoupler role in these events. J. Cell. Biochem. 110: 428–437, 2010. © 2010 Wiley‐Liss, Inc.
CCAAT/enhancer binding protein beta is up‐regulated in giant cell tumor of bone and regulates RANKL expression
Authors: Ng Patrick Kwok‐Shing , Tsui Stephen Kwok‐Wing , Lau Carol Po‐Ying , Wong Chi‐Hang , Wong Winnie Hiu‐Ting , Huang Lin , Kumta Shekhar‐Madhukar
Published: March 2010

Giant cell tumor (GCT) of bone is an aggressive non‐cancerous tumor, which consists of multi‐nucleated osteoclast‐like giant cells, stromal cells, and monocytes. It is believed that stromal cells are the neoplastic component of this tumor. Expression of the receptor activator of nuclear factor kappa B ligand (RANKL) in the stromal cells stimulates the monocytes to form giant multi‐nucleated osteoclast‐like cells, causing bone over‐resorption at the tumor site. Previously, our group has reported the up‐regulation of RANKL in GCT of bone stromal cells, but the mechanism is unknown. Using stromal cell culture of GCT obtained from patients, we demonstrated the up‐regulation of the transcriptional activator CCAAT/enhancer binding protein beta (C/EBPβ). RANKL promoter studies revealed that C/EBPβ over‐expression induced RANKL promoter activity in a dose‐dependent manner and a CCAAT‐box within the region nt −357/−1 contributed to the basal transcription activity, with a possible C/EBPβ binding element in the region nt −460/−358 leading to further induction. Furthermore, we also showed that C/EBPβ bound to the RANKL promoter in GCT stromal cells in vivo by chromatin immunoprecipitation. To conclude, our study has shown that C/EBPβ is a RANKL promoter activator in stromal cells of GCT of bone and we have proposed a model in which C/EBPβ plays an important role in the osteolytic characteristics and pathological causes of GCT of bone. J. Cell. Biochem. 110: 438–446, 2010. © 2010 Wiley‐Liss, Inc.
The hydro‐meteorological estimation of probable maximum precipitation under varying scenarios in Sri Lanka
Authors: Fernando W. C. D. K. , Wickramasuriya S. S.
Published: March 2010

Probable maximum precipitation (PMP) is widely used as an input in rainfall‐runoff modelling to estimate probable maximum flood (PMF), which is required for the design of spillways of large dams. In relation to dam safety studies at 32 dam sites, an analysis was done of extreme rainfalls in Sri Lanka, which is influenced by the Asian monsoon system and cyclonic effects. Accordingly, the Hershfield's statistical method, which is one of the recommended procedures of the World Meteorological Organization (WMO), was used for estimating PMP. It is also a technique that can be readily used in design office practice. However, it is of significant value and scientific interest to explore what the outcome would have been if the physically based hydro‐meteorological procedure had been adopted. For this purpose, long series of annual maximum daily rainfall data from seven stations were analysed. The research shows that the maximum moisture and corresponding wind run or the use of maximum moisture alone are two scenarios, which yield results compatible with the statistical PMP. Although globally there is a tendency to exclude wind maximization, this does not automatically apply to a country like Sri Lanka, which experiences cyclonic rainfall and special attention should be paid to precipitation efficiency. These results are further confirmed by a frequency analysis based on the generalized extreme value (GEV) distribution. An approximate value of PMP could be in the order of 2.0–3.0 times the maximum observed daily rainfall. However, this aspect needs further investigation when observed maxima are near PMP storms. Copyright © 2010 Royal Meteorological Society
High‐resolution modelling of the potential impact of land surface conditions on regional climate over Indochina associated with the diurnal precipitation cycle
Authors: Takahashi Hiroshi G. , Yoshikane Takao , Hara Masayuki , Takata Kumiko , Yasunari Tetsuzo
Published: March 2010

This study examined the impact of changes in land surface conditions on regional climate over Indochina using a high‐resolution regional climate model. Anthropogenically induced land surface changes are going on in this part of tropical Southeast Asia. Because a previous study suggested that deforestation in this area affected September precipitation, we chose September as the study period. We performed a control simulation (CTL) driven by reanalysis data combined with current land use and predicted soil moisture data. The CTL reproduced the spatial distribution of total precipitation well. In addition, it also simulated a distinct diurnal cycle of precipitation that was previously reported in observational studies. Two sensitivity experiments, assuming wetter and drier land surface conditions over the Khorat Plateau (northeast Thailand) compared with the current land surface condition, were conducted and examined the impact of land surface changes on precipitation. The results indicated that drier land surface conditions increased precipitation over the disturbed region. A pronounced increase in precipitation was found only during nighttime, which coincided with the peak in the climatological diurnal precipitation cycle. Climatologically, the diurnal peak in precipitation occurs from evening to early morning over the Khorat Plateau. Drier conditions intensified the diurnal variation of precipitable water associated with the thermally induced local circulation responsible for a horizontal gradient of near‐surface temperature. The effects of land use and land cover changes in the tropics are shown to be strongly related to the diurnal precipitation cycle. Copyright © 2010 Royal Meteorological Society
Cross‐linking affects cellular condensation and chondrogenesis in type II collagen‐GAG scaffolds seeded with bone marrow‐derived mesenchymal stem cells
Authors: Vickers Scott M. , Gotterbarm Tobias , Spector Myron
Published: March 2010

The formation of cartilaginous tissue by chondroprogenitor cells, whether in vivo or in vitro, appears to require a critical initial stage of “condensation” in which intercellular space is reduced through an aggregation of cells, leading to development of cell‐to‐cell junctions followed by chondrocytic differentiation. The objective of this study was to investigate the association of aggregation (condensation) of mesenchymal stem cell (MSCs) and chondrogenesis in vitro. Previous work with chondrocytes indicated that the cross‐link density and related cell‐mediated contraction of collagen scaffolds significantly affects cartilaginous tissue formation within the cell‐seeded construct. Based on this finding, we hypothesized that the cell‐aggregating effect of the contraction of MSC‐seeded collagen scaffolds of lower cross‐link density favors chondrogenesis; scaffolds of higher cross‐link density, which resist cell‐mediated contraction, would demonstrate a lower cell number density (i.e., subcritical packing density) and less cartilage formation. Type II collagen–GAG scaffolds, chemically cross‐linked to achieve a range of cross‐link densities, were seeded with caprine MSCs and cultured for 4 weeks. Constructs with low cross‐link densities experienced cell‐mediated contraction, increased cell number densities, and a greater degree of chondrogenesis (indicated by the chondrocytic morphology of cells, and synthesis of GAG and type II collagen) compared to more highly cross‐linked scaffolds that resisted cellular contraction. These results provide a foundation for further investigation of the mechanisms by which condensation of mesenchymal cells induces chondrogenesis in this in vitro model, and may inform cross‐linking protocols for collagen scaffolds for use in cartilage tissue engineering. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1184–1192, 2010
Bone deposition, bone resorption, and osteosarcoma
Authors: Toledo Sílvia Regina Caminada , Oliveira Indhira Dias , Okamoto Oswaldo Keith , Zago Marco Antonio , de Seixas Alves Maria Teresa , Filho Reynaldo Jesus Garcia , Macedo Carla Renata Pacheco Donado , Petrilli Antonio Sergio
Published: March 2010

Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real‐time PCR to evaluate the mRNA levels of the tartrate‐resistant acid phosphatase (ACP5), colony stimulating factor‐1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p = 0.041) and event free survival (p = 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p = 0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1142–1148, 2010
Diminished cartilage creep properties and increased trabecular bone density following a single, sub‐fracture impact of the rabbit femoral condyle
Authors: Borrelli Joseph , Zaegel Melissa A. , Martinez Mario D. , Silva Matthew J.
Published: March 2010

Traumatic injury to articular cartilage can lead to post‐traumatic arthritis. We used a custom pendulum device to deliver a single, near‐fracture impact to the medial femoral condyles of rabbits. Impact was localized to a region ∼3 mm in diameter, and impact stress averaged ∼100 MPa. Animals were euthanized at 0, 1, and 6 months after impact. Cartilage mechanical properties from impacted and sham knees were evaluated by creep‐indentation testing, and periarticular trabecular bone was evaluated by microCT and histomorphometry. Impact caused immediate and statistically significant loss of cartilage thickness (−40% vs. sham) and led to a greater than twofold increase in creep strain. From 0 to 6 months after impact, the ability of cartilage to recover from creep deformation became significantly impaired (percent recovery different from control at 1 and 6 months). At 1 month, there was a 33% increase in the trabecular bone volume fraction of the epiphysis beneath the site of impact compared to control, and increased bone formation was observed histologically. Taken together, these findings demonstrate that a single, high‐energy impact below the fracture threshold leads to acute deleterious changes in the viscoelastic properties of articular cartilage that worsen with time, while at the same time stimulating increased bone formation beneath the impact site. Published by Wiley Periodicals, Inc. J Orthop Res 28:1307–1314, 2010
Mouse treadmill running enhances tendons by expanding the pool of tendon stem cells (TSCs) and TSC‐related cellular production of collagen
Authors: Zhang Jianying , Pan Tiffany , Liu Yan , Wang James H‐C.
Published: March 2010

Exercise is known to enhance tendon size and strength, but the stem cell‐based mechanisms for such exercise‐induced effects are largely unknown. This study aims to explore these mechanisms by using a mouse treadmill running model to examine the effects of exercise on newly discovered tendon stem cells (TSCs). After treadmill running, patellar TSCs (PTSCs) and Achilles TSCs (ATSCs) were isolated from the mice, and their proliferation was measured in vitro. We found that treadmill running nearly doubled proliferation rates of both PTSCs and ATSCs compared to cage control mice. Moreover, using a mixed tendon cell culture consisting of TSCs and tenocytes, cellular production of collagen was found to increase by 70% and 200% in PTSCs and ATSCs, respectively, from the treadmill running group over cells from the cage control group. These findings suggest that exercise exerts its anabolic effects on tendons at least in part by increasing proliferation to expand the pool of TSCs and also by increasing TSC‐related cellular production of collagen, the predominant component of tendons. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1178–1183, 2010
Median nerve deformation and displacement in the carpal tunnel during index finger and thumb motion
Authors: van Doesburg Margriet H. M. , Yoshii Yuichi , Villarraga Hector R. , Henderson Jacqueline , Cha Stephen S. , An Kai‐Nan , Amadio Peter C.
Published: March 2010

The purpose of this study was to investigate the deformation and displacement of the normal median nerve in the carpal tunnel during index finger and thumb motion, using ultrasound. Thirty wrists from 15 asymptomatic volunteers were evaluated. Cross‐sectional images during motion from full extension to flexion of the index finger and thumb were recorded. On the initial and final frames, the median nerve, flexor pollicis longus (FPL), and index finger flexor digitorum superficialis (FDS) tendons were outlined. Coordinate data were recorded and median nerve cross‐sectional area, perimeter, aspect ratio of the minimal‐enclosing rectangle, and circularity in extension and flexion positions were calculated. During index finger flexion, the tendon moves volarly while the nerve moves radially. With thumb flexion, the tendon moves volarly, but the median nerve moves toward the ulnar side. In both motions, the area and perimeter of the median nerve in flexion were smaller than in extension. Thus, during index finger or thumb flexion, the median nerve in a healthy human subject shifts away from the index finger FDS and FPL tendons while being compressed between the tendons and the flexor retinaculum in the carpal tunnel. We are planning to compare these data with measurements in patients with carpal tunnel syndrome (CTS) and believe that these parameters may be useful tools for the assessment of CTS and carpal tunnel mechanics with ultrasound in the future. Published by Wiley Periodicals, Inc. J Orthop Res 28:1387–1390, 2010
Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro‐inflammatory stimuli
Authors: Gordon Andrew , Greenfield Edward M. , Eastell Richard , Kiss‐Toth Endre , Wilkinson Jeremy Mark
Published: March 2010

Susceptibility to osteolysis after total hip arthroplasty (THA) varies between individuals. We examined whether patients susceptible to osteolysis (group I, n = 34 subjects) after cemented Charnley THA have quantitatively different innate immune responses to pro‐inflammatory stimuli versus patients without this susceptibility (group II, n = 28 subjects) at a mean of 14 years after primary surgery. Extracted peripheral blood mononuclear cells were stimulated for 3 h using endotoxin (lipopolysaccharide—LPS, 100 ng/mL), endotoxin‐stripped titanium particles (Ti) or endotoxin‐stripped particles with adherent LPS added‐back (TI + LPS). Subjects returned 1 week later and the experimental protocol was repeated. Assays for mRNA induction for interleukin (IL)‐1α, IL‐1β, IL‐1Ra, IL‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF) were made using quantitative real‐time PCR. Although baseline levels of mRNA expression were slightly lower in group I, inducibility of mRNA expression was markedly greater in group I versus group II for all cytokines in response to LPS or Ti + LPS, and for IL‐1α in response to Ti (P < 0.05). LPS or Ti + LPS stimulation also resulted in an increase in the IL‐1/IL‐1Ra mRNA ratio in group I versus group II (P < 0.05). mRNA induction was highly reproducible between subject visits (r > 0.7, P < 0.001). Osteolysis‐susceptible patients show repeatable, quantitatively different patterns of innate cytokine gene expression in response to pro‐inflammatory stimuli versus THA patients who do not display this susceptibility. These innate immune differences may contribute to the variation in osteolysis‐susceptibility observed clinically between individuals. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1127–1135, 2010
New evidence on the sequence of deglacial warming in the tropical Indian Ocean
Authors: Naidu P. Divakar , Govil Pawan
Published: March 2010

The transition from the Last Glacial Maximum to the Holocene was an internal of climate variability that was characterised by large spatial and temporal variations. Here we show that deglaciation warming in the northern Indian Ocean was initiated ca. 19 ka, which is contemporary with deglaciation warming in the Antarctica and Southern Ocean. A gradual warming occurred during the glacial/Holocene transition in the northern Indian Ocean, unlike the two‐step warming seen in Greenland and the North Atlantic. Synchronous deglacial warming ca. 19 ka in Antarctica and the northern Indian Ocean suggests a strong connection in the propagation of climate signals between Antarctica and the Indian Ocean, probably through the Indonesian Throughflow and/or Subantarctic Mode Water. Copyright © 2010 John Wiley & Sons, Ltd.
Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging
Authors: Mouras Rabah , Rischitor G. , Downes A. , Salter D. , Elfick A.
Published: March 2010

A multimodal nonlinear optical microscope that combines coherent anti‐Stokes Raman scattering (CARS), two‐photon excitation fluorescence (TPEF), second‐harmonic generation (SHG) and sum‐frequency generation (SFG) was developed and applied to image breast cancer tissue and MCF‐7 cells as well as monitoring anticancer drug delivery in live cells. TPEF imaging showed that drugs are preferentially localized in the cytoplasm and the nuclear envelope in resistant cells. Moreover, the extracellular matrix was observed by TPEF signals arising from elastin's autofluorescence and SHG signals from collagen fibrils in breast tissue sections. Additionally, CARS signals arising from proteins and (PO2)− allowed identification of tumors. Label‐free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer. Copyright © 2010 John Wiley & Sons, Ltd.
One‐pot synthesis of silver particle aggregation as highly active SERS substrate
Authors: Cai Zhicheng , Tian Chungui , Wang Lei , Zhou Wei , Wang Baoli , Fu Honggang
Published: March 2010

Silver particles with different degrees of aggregation were synthesized through a sodium dodecyl sulfate‐assisted one‐pot reaction in an aqueous medium. The products were characterized by transmission electron microscopy, scanning electron microscopy and UV‐visible spectroscopy. The results showed that the degree of aggregation of the Ag nanoparticles could be tuned by changing the reaction parameters, such as the reaction temperature and time. A possible formation process of the Ag aggregate is proposed on the basis of a series of experimental results. Moreover, the surface‐enhanced Raman scattering (SERS) effect of the Ag aggregates was evaluated by using rhodamine 6G as a Raman probe molecule. It was demonstrated that the SERS enhancement ability is related to the degree of aggregation of Ag particles, and a high SERS signal can be observed by selecting Ag nanoparticles with the proper degree of aggregation as substrates. Moreover, the aggregates showed good reproducibility and stability to SERS from organic molecules. Copyright © 2010 John Wiley & Sons, Ltd.
Kinetics and mechanism of tertiary amine‐catalyzed cleavage of N′‐morpholino‐N‐(2′‐methoxyphenyl)phthalamide: Kinetic evidence for the presence of a reactive intermediate on the reaction path
Authors: Sim Yoke‐Leng , Khan M. Niyaz
Published: March 2010

Pseudo‐first‐order rate constants (kobs) for tertiary amine (DABCO and Me3N) buffer‐catalyzed cyclization of N′‐morpholino‐N‐(2′‐methoxyphenyl)phthalamide (1) to N‐(2′‐methoxyphenyl)phthalimide (2) reveal saturation (nonlinear) plots of kobs versus [Buf]T (total tertiary amine buffer concentration) at a constant pH. Such plots at different pH have been attributed to the presence of a reactive intermediate (T−) formed by tertiary amine buffer‐catalyzed intramolecular nucleophilic addition of the secondary amide nitrogen to the carbonyl carbon of the tertiary amide group of 1. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 263–272, 2010
Computational studies on the reactions of 3‐butenyl and 3‐butenylperoxy radicals
Authors: Miyoshi Akira
Published: March 2010

The reactions of 3‐butenyl (•CH2CH2CHCH2) radicals—unimolecular decomposition, isomerization, as well as reaction with O2—and the subsequent unimolecular rearrangement reactions of the 3‐butenylperoxy radicals have been investigated and are compared to the analogous reactions of butyl (•CH2CH2CH2CH3) and butylperoxy radicals using transition‐state theory based on the quantum chemical calculations at the CBS‐QB3 level. For alkyl‐analogue processes, the reactions of 3‐butenyl and 3‐butenylperoxy radicals can be well characterized by the decreased and increased bond dissociation energies at the allylic and vinylic sites, respectively. The intramolecular addition reactions of the radical center atoms to the double bonds were found to be important non‐alkyl‐analogue reactions of 3‐butenyl and 3‐butenylperoxy radicals. As a consequence, the thermal decomposition of 3‐butenyl radicals was found to be slower than that of butyl radicals by one order of magnitude at temperature near 1000 K. Intramolecular addition reactions are suggested to be the predominant unimolecular rearrangement processes of 3‐butenylperoxy radicals over the entire temperature range investigated (500–1200 K). The intramolecular addition reactions of the alkenyl peroxy radicals, which have not been included in combustion kinetic models, and their implications for the autoignition of alkenes are discussed. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 273–288, 2010
DFT study of nitroxide radicals: explicit modeling of solvent effects on the structural and electronic characteristics of 4‐amino‐2,2,6,6‐tetramethyl‐piperidine‐N‐oxyl
Authors: Ikryannikova Larissa N. , Ustynyuk Leila Yu. , Tikhonov Alexander N.
Published: March 2010

An explicit DFT modeling of water surroundings on the electron paramagnetic resonance properties of 4‐amino‐2,2,6,6‐tetramethyl‐piperidine‐N‐oxyl (TA) has been performed. A stepwise hydration of TA is accompanied with certain changes in geometrical parameters (bond lengths and angles) and redistribution of partial electric charges in TA. An aqueous cluster of 45 water molecules can be considered as an appropriate model for a complete aqueous shell around TA, although most of the structural and electronic characteristics of TA already converge at about 10 water molecules. Water surroundings induce an increase in electron spin density on the nitrogen atom of the nitroxide fragment due to stabilization of the polar resonance structure > N+•O− at the expense of less polar structure > NO•. The water‐induced rise of the isotropic splitting constant aiso, calculated from the contact term of the hyperfine interaction, comprises Δaiso(ρN2) = 2.2–2.5 G, which is typical of experimental value for TA. There are two contributions to the solvent effect on the aiso(ρN2) value: the redistribution of spin density in the nitroxide fragment (polarity effect) and water‐induced distortions of TA geometry. Microscopic variations in a hydrogen‐bonded water network cause noticeable fluctuations of the splitting constant aiso(ρN2). Calculations of the atomic spin density (σN2) allowed us to compute the splitting constant from the relationship aiso(σN2) = QσN2, where Q = 36.2 G. A practical advantage of using this relationship is that it gives ‘smoothed’ values of the splitting constant, which are sensitive to the environment polarity but remain tolerant to microscopic fluctuations of the hydrogen‐bonded water network around a spin‐label molecule. Copyright © 2010 John Wiley & Sons, Ltd.
Numerical modelling of desiccation cracking
Authors: Amarasiri Aruna L. , Kodikara Jayantha K. , Costa Susanga
Published: March 2010

The ability to model and predict the formation of desiccation cracks is potentially beneficial in many applications such as clay liner design, earth dam construction, and crop science, etc. However, most studies have focused on statistical analysis of crack patterns and qualitative study of contributing factors to crack development rather than prediction. Because it is exceedingly difficult to capture the nonlinear processes during desiccation in analytical modelling, most such models handle crack formation without considering variation of material properties with time, and are unattractive to use in realistic modelling. The data obtained from laboratory experiments on clay soil desiccating in moulds were used as a basis to develop a more refined model of desiccation cracking. In this study, the properties, such as matric suction, stiffness and tensile strength of soil, and base adhesion, could be expressed approximately as functions of moisture content. The initial conditions and the development of suction due to desiccation and the varying material properties were inputted to UDEC, a distinct element code, using its internal programming language FISH. The model was able to capture some essential physical aspects of crack evolution in soil contained in moulds with varying lengths, heights, and materials of construction. Extension of this methodology is potentially beneficial not only for modelling desiccation cracking in clay, but also in other systems with evolving material properties such as concrete structures and road pavements. Copyright © 2010 John Wiley & Sons, Ltd.
Rate effects in dense granular materials: Linear stability analysis and the fall of granular columns
Authors: Lemiale V. , Mühlhaus H.‐B. , Mériaux C. , Moresi L. , Hodkinson L.
Published: March 2010

In this paper, the suitability of rate‐dependent constitutive relationships to model the rheology of granular materials is investigated. In particular, the formation of shear bands as predicted by this approach is studied. First, a rate‐dependent model is investigated in terms of a linear stability analysis. It turns out that at low to moderate strain rates, the orientation of shear bands tends to vary from the so‐called Roscoe and Coulomb solutions towards a unique admissible orientation with an increase of the so‐called inertial number I. This effect is confirmed by numerical simulations of a compression test performed with a particle in cell finite element program. To further assess the validity of continuum approaches for the simulation of dense granular flows, a quasi‐static fall of a granular column is studied numerically and the results are confronted to available experimental data. It is shown that a satisfying agreement is obtained at different aspect ratios and for the two materials investigated in this paper, i.e. sand and glass beads. The results reported in the present paper demonstrate the relevance of continuum approaches in the modelling of dense granular flows. Copyright © 2010 John Wiley & Sons, Ltd.