bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytogenetic risk assessment of etoposide from mouse bone marrow
Authors: Choudhury Ramesh C. , Palo Anil K. , Sahu Prajyoti 
Published: March 2004

AbstractIncreased clinical applications of the anticancer drug etoposide (a non‐intercalative epipodophyllotoxin derivative) and the frequent induction of a second malignancy, particularly leukaemia, in post‐etoposide‐treated cancer survivors warrant detailed genotoxicity testing of etoposide. The genotoxicity test results available on etoposide are either primarily in in vitro test systems or in lower organisms after treatment with unusually high doses, or after chronic exposures, having little extrapolative value to humans. Therefore, a cytogenetic risk assessment study on etoposide in mouse in vivo was undertaken after a low dose (in accordance with the human therapeutic dose) single exposure. The cytogenetic toxicity of etoposide was assessed from bone marrow of mouse at three separate endpoints: chromosomal aberration and mitotic index studies at 24 h post‐treatment and the micronucleus test (MNT) at 30 h post‐treatment. The flame drying technique using colchicine, hypotonic sodium citrate, methanol‐glacial acetic acid and Giemsa was followed for the preparation of slides for the metaphase chromosomal aberration and mitotic index studies and a simple technique was followed for the MNT. Although induction of chromosomal aberrations, excluding gaps, per 100 metaphases by 10 and 15 mg kg−1 etoposide was not significant statistically, 20 mg kg−1 of etoposide induced a significantly higher number of chromosomal aberrations in female (P ≤ 0.01) and male (P ≤ 0.05) mice. There was no significant change in the induced percentages of dividing cells by any of the doses of etoposide tested. The micronucleus induction also was not significant statistically with the lowest dose but it was significant in female (P ≤ 0.01) and male (P ≤ 0.05) mice that received 15 mg kg−1 etoposide and was highly significant (P ≤ 0.01) in both female and male mice that received 20 mg kg−1 etoposide. The results indicated the clastogenic action of etoposide in mouse bone marrow after a single treatment with such low doses. However, the drug did not interfere with cell cycle progression. Although it is a DNA‐non‐intercalating agent, etoposide is known for its interference in the activity of DNA topoisomerase IIα enzyme, particularly in the proliferative cells where the concentration and activity of the enzyme are greater. This might be the reason for the induction of leukaemia in post‐etoposide‐treated cancer survivors. Therefore, it has become absolutely necessary to make etoposide target‐specific, i.e. specific to the topoisomerase II enzymes of cancerous cells. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of milk on intestinal fluid accumulation and renal injury following mercuric chloride ingestion in rats
Authors: Kamijo Yoshito , Hayashi Izumi , Yoshimura Kuniko , Soma Kazui 
Published: March 2004

AbstractTo investigate the effect of milk on intestinal fluid accumulation and renal injury following mercuric chloride (HgCl2) ingestion, 10 ml kg−1 of saline or 10 mg kg−1 of HgCl2 dissolved in 10 ml kg−1 of water or raw milk was administered enterally to rats and the mercury content in biological samples was determined by cold vapour atomic absorption spectrometry. Three hours after administration, the intestinal water content in rats that received HgCl2 in water (group S2) was significantly higher than in rats that received saline (group S1) (P < 0.01) or HgCl2 in milk (group S3) (P < 0.01). The amount of mercury detected per gram dry weight of small intestine was higher in group S2 than in group S3 (P < 0.05). Seventy‐two hours after administration, both the serum urea nitrogen and creatinine concentrations in rats that received HgCl2 in milk (group L3) were significantly higher than in rats that received saline (group L1) (P < 0.05) or HgCl2 in water (group L2) (P < 0.05). Mercury levels in many of the biological samples in group L3 were higher than in group L2 (P < 0.05). Milk may reduce the intestinal cytotoxicity of mercury but it promotes its absorption, which may lessen intestinal fluid accumulation but worsen renal injury. Copyright © 2004 John Wiley & Sons, Ltd.
Pulmonary toxicity of wollastonite in vivo and in vitro
Authors: Tátrai E. , Kováčiková Z. , Brózik M. , Six É. 
Published: March 2004

AbstractPulmonary toxicity of wollastonite has been studied in both in vivo long‐term sequential and in vitro methods in Sprague‐Dawley rats. Wollastonite was administered by intratracheal instillation and the lungs were examined after 1, 3 and 6 months by morphological methods. UICC crocidolite was applied as the positive control. In addition, the effects of both ﬁbres were examined in primary cultures of pulmonary alveolar macrophages and type II pneumocytes to determine the effects of the ﬁbres on the membranes of these cells, the activity of Cu,Zn/superoxide dismutase and the redox system and the release of proinﬂammatory peptides: macrophage chemoattractant protein‐1 (MCP‐1) and macrophage inhibitory protein‐1α (MIP‐1α). By the end of six months wollastonite had induced mild pulmonary interstitial ﬁbrosis, whereas crocidolite induced progressive interstitial ﬁbrosis as a function of time. The membranes of macrophages and pneumocytes were disrupted at the lowest concentration of crocidolite. The activity of enzymes of the redox system and cytoplasmic superoxide dismutase signiﬁcantly decreased with crocidolite. Wollastonite decreased only the activity of gamma‐glutamyl transpeptidase and glutathione peroxidase. Crocidolite induced expression of the proinﬂammatory peptides at the lowest concentration (1 µg ml−1) but wollastonite increased production of these peptides only at medium and high concentrations (5 and 10 µg ml−1). These results underline the importance of further human epidemiological studies and the need for the determination of a hygienic standard. Copyright © 2004 John Wiley & Sons, Ltd.
Development of acute inhalation reference exposure levels (RELs) to protect the public from predictable excursions of airborne toxicants
Authors: Collins James F. , Alexeeff George V. , Lewis David C. , Dodge Daryn E. , Marty Melanie A. , Parker Thomas R. , Budroe John D. , Lam Richard H.F. , Lipsett Michael J. , Fowles Jefferson R. , Das Rupali 
Published: March 2004

AbstractUniform guidelines have been developed for the derivation of 1‐h acute inhalation reference exposure levels (RELs) applicable to the general public exposed routinely to hazardous substances released into the environment. Existing acute exposure guidance values developed by other organizations have been examined, and strengths and weaknesses in these existing guidelines have been identiﬁed. The results of that examination have led to the development of a reproducible and resource‐intensive methodology to calculate acute inhalation RELs for 41 prioritized chemicals. Approaches to estimating levels protective against mild and severe acute effects are discussed in this report. The default methodology is the no‐observed‐adverse‐effect level (NOAEL)/uncertainty factor (UF) approach using mainly reports in the peer‐reviewed toxicological and medical literature. For two well‐studied chemicals, ammonia and formaldehyde, the data allowed a benchmark dose (or concentration) methodology, as a departure from the default options, to be used. However, better human dose–response data from, for example, improved workplace monitoring correlated with symptoms, and more extensive epidemiological studies are needed before the departure from default approaches can be expanded to more substances. Copyright © 2004 John Wiley & Sons, Ltd.
Quantitative analysis of three‐dimensional fluid flow in rotating bioreactors for tissue engineering
Authors: Botchwey Edward A. , Pollack Solomon R. , Levine Elliot M. , Johnston Eric D. , Laurencin Cato T. 
Published: March 2004

AbstractTissue engineering has emerged as a viable alternative to the problem of organ and tissue shortage. Our laboratory has developed matrices for bone tissue engineering based on sintered spherical particles and, using bioreactor technology, has demonstrated the ability to produce highly mineralized matrices in vitro. In this study, porous microcapsule scaffolds were developed for bone tissue engineering in the high aspect ratio vessel rotating bioreactor. The motion of individual microcapsules as well as scaffolds in the bioreactor were studied by numerical simulation and in situ imaging analysis. Results show that spherical microcapsules with density less than the surrounding fluid exhibited two motions: (1) a periodic circular orbit with tangential speed equal to the free fall speed of the particle, and (2) an inward radial migration of the circular orbit toward the center of the bioreactor vessel. Lighter‐than‐water scaffolds were fabricated by sintering poly(lactic‐co‐glycolic acid) hollow microcarriers with diameter from 500 to 860 μm into a fixed three‐dimensional geometry with approximately 30% pore volume and 180 to 190 μm median pore size. Scaffolds were fabricated with aggregate densities ranging from 0.65 g/mL and 0.99 g/mL by appropriate combinations of hollow and solid microcarriers within the scaffold. Scaffold velocity in the bioreactor for the above range of densities was accurately predicted by numerical simulation and ranged from 100 mm/s to 3 mm/s. Maximum shear stress estimation due to media flow over the exterior of the scaffold ranged from 0.3 N/m2 to 0.006 N/m2. Internal perfusion velocity through scaffolds also was calculated and ranged from 13 mm/s to 0.2 mm/s. Estimates of maximum interior shear stress ranged from 0.03 to 0.0007 N/m2. These analytical methods provide an excellent vehicle for the study of bone tissue synthesis in three‐dimensional culture with fluid flow. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 205–215, 2004
Preparation and in vitro bioactivity of zinc containing sol‐gel–derived bioglass materials
Authors: Oki Aderemi , Parveen Bushra , Hossain Safiyyah , Adeniji S. , Donahue Henry 
Published: March 2004

AbstractBioactive glass material of the type CaOP2O5SiO2ZnO was obtained by the sol‐gel processing method. This material was produced both in powder and in disks form by compression of the powder. The obtained material was characterized by X‐ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and surface electron micrograph (SEM). The bioactivity was examined in vitro with respect to the ability of hydroxyapatite layer to form on the surface as a result of contact with simulated body fluid (SBF). The XRD and FTIR studies were conducted before and after contact of the material with SBF. The gel‐derived materials were amorphous as shown by XRD, but were able to crystallize calcium phosphates on their surfaces when exposed to SBF. We also examined the alkaline phosphatase (AP) activity of osteoblasts, using human fetal osteoblastic cells (hFOB 1.19) cultured on the zinc bioglass, and compared it with the polystyrene plates. The bone cells consistently expressed higher AP activity in the zinc bioglass materials compared with the polystyrene plates, which indicates the zinc containing composition stimulates bone cells production of AP. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 216–221, 2004
Optimization of bone‐tissue engineering in goats
Authors: Kruyt Moyo C. , Dhert Wouter J. A. , Oner Cumhur , van Blitterswijk Clemens A. , Verbout Abraham J. , de Bruijn Joost D. 
Published: March 2004

AbstractSuccessful bone‐tissue engineering (TE) has been reported for various strategies to combine cells with a porous scaffold. In particular, the period after seeding until implantation of the constructs may vary between hours and several weeks. Differences between these strategies can be reduced to (a) the presence of extracellular matrix, (b) the differentiation status of the cells, and (c) the presence of residual potentially immunogenic serum proteins. These parameters are investigated in two types of calcium phosphate scaffolds in a goat model of ectopic bone formation. Culture‐expanded bone‐marrow stromal cells from eight goats were seeded onto two types of hydroxyapatite granules: HA60/400 (60% porosity, 400‐μm average pore size) and HA70/800. Scaffolds seeded with cells and control scaffolds were cultured for 6 days in medium containing autologous or semisynthetic serum, in the presence or absence of dexamethasone. Other scaffolds were seeded with cells just before implantation in medium with or without serum. All conditions were implanted autologously in the paraspinal muscles. After 12 weeks, bone had formed in 87% of all TE constructs, as demonstrated by histology. Histomorphometry indicated significantly more bone in the HA70/800 scaffolds. Furthermore, a significant advantage in bone formation was found when the constructs had been cultured for 6 days. In conclusion, both scaffold characteristics (porosity) and TE strategy (culturing of the constructs) were demonstrated to be important for bone TE. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 113–120, 2004
Stripe wear rates in alumina THR—Comparison of microseparation simulator study with retrieved implants
Authors: Manaka Masakazu , Clarke Ian C. , Yamamoto Kengo , Shishido Takaaki , Gustafson Allen , Imakiire Atsuhiro 
Published: March 2004

AbstractAlumina‐on‐alumina hip implants with microseparation were run in a hip simulator for comparison of the nonseparation simulator mode and retrievals. The 28‐, 32‐, and 36‐mm Biolox‐forte implants were run to 5 million cycles with the use of 50% newborn calf serum. Howmedica Osteonics Trident cups with titanium backing were used in all sets. In standard (STD) and microseparation (MSX) mode, the typical biphasic wear trend was evident, but the MSX test mode had much higher magnitudes. There was a 5‐fold increase for run‐in wear and up to a 35‐fold increase in steady‐state wear. The stripe wear on the ball formed early, but did not progress in grade beyond 0.6 Mc. The locations of the stripes were similar in retrieved and simulator balls. However, the stripes from the simulator were narrower than short‐term retrievals and much narrower than some long‐term retrievals. The long‐term retrieved balls had a grade of wear greater than the simulators. In vivo a broader range of motion occurs and this may lead to the wider stripe observed on the retrievals. These observations suggested that simulators could produce the loading and kinematics similar to a patient walking but not necessarily the variety of motions possible in the in vivo situation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 149–157, 2004
Alpha‐crystallin‐incorporated collagen matrices as an aid for dermal wound healing
Authors: Ahmed M. Rafiuddin , Gopinath D. , Gomathi K. , Sehgal P. K. , Jayakumar R. 
Published: March 2004

AbstractThis study evaluated the effects of noncovalently incorporated crystallin into the collagen matrix for dermal wound‐healing processes in rats. Crystallin‐incorporated collagen matrix (CIC) showed better healing when compared to wounds treated with collagen matrix (CS) and without collagen (CR). Biochemical parameters and histological analysis revealed that increased wound contraction enhanced cell proliferation and efficient radical scavenging in the CIC group. The higher shrinkage temperature of CIC films when compared to CS groups suggested increased hydrothermal stability for the former material. An in vitro release study of CIC has showed sustained and time‐dependent release of crystallin from the collagen matrix. These results demonstrate the possibility of using crystallin as therapeutic protein in the wound‐healing process. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 69B: 241–248, 2004
Self‐reinforced polylactide/polyglycolide 80/20 screws take more than 1½ years to resorb in rabbit cranial bone
Authors: Tiainen Johanna , Soini Ylermi , Törmälä Pertti , Waris Timo , Ashammakhi Nureddin 
Published: March 2004

AbstractThe aim of this study was to assess tissue reactions to bioabsorbable self‐reinforced polylactide/polyglycolide (SR‐PLGA) 80/20 miniscrews in rabbit cranial bone. One PLGA screw was implanted on one side and one titanium screw on the other side of the sagittal suture (n = 21). Three animals were sacrificed after 2, 4, 8, 16, 24, 54, and 72 weeks. In histological examination the numbers of macrophages, giant cells, active osteoblasts, and fibrous tissue layers were assessed and degradation of the bioabsorbable screws was evaluated. After 2 weeks, macrophages were seen near the heads of both screws. After 4 and 8 weeks, the bioabsorbable screws were surrounded by fibrous tissue. Osteoblastic activity and groups of several giant cells were seen. After 24 weeks, a significant change in the morphology of the PLGA screws had occurred. Osteoblastic activity and the amount of giant cells had decreased. After 1 year, some PLGA biomaterial was still present. PLGA screws had been replaced by adipose tissue, fibrous tissue, and “foamy macrophages” that had PLGA particles inside them. After 1½ years, the amount of biomaterial remaining had decreased remarkably. The particles of biomaterial were inside foamy macrophages. SR‐PLGA 80/20 screws are biocompatible and have no clinically manifested complications when used in the cranial bone of rabbits. No contraindications as regards their clinical use in craniofacial surgery was found when these screws were studied in the cranial bones of rabbits. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 49–55, 2004
Release of anthracyclines adsorbed on copper‐treated hydroxylapatites
Authors: Bacha Rosana Ahamad , Fiallo Marina M. L. , Sharrock Patrick 
Published: March 2004

AbstractAnthracyclines are antibiotics widely used for the treatment of leukemia and solid tumors. Perfusion is the standard clinical administration form. Unfortunately, this does not allow treatment of gastric cancers. A new galenic presentation, consisting of anthracyclines adsorbed onto hydroxylapatite granules, has been developed. It was found to be possible to modulate the release of the drug as a function of the pH by using copper(II) ions. At neutral pH, the drug remains on the mineral support, but at pH 3, the drug is released into solution. Further investigations demonstrate that copper‐containing hydroxylapatite can retain a determined quantity of antibiotic by surface complexation. This result could contribute to new designs for drug carriers targeted for gastric cancers. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 103–105, 2004
Measuring mechanical properties of fine‐wire cross‐sections used in medical devices
Authors: Yu Ning , Polycarpou Andreas A. , Wagoner Johnson Amy J. 
Published: March 2004

AbstractIn this study, it was demonstrated that the nanoindentation technique can be used to measure the elastic modulus and hardness of fine‐wire cross‐sections with diameters ranging from 100–200 μm. Using miniature optics and a specially developed micrometer positioning system, measurements were successfully performed on the wire cross‐sections with an accuracy of 1 μm. Homogeneous wire cross‐sections, such as MP35N (high‐strength nickel–cobalt alloy), composite wires such as MP35N with a silver core (MP35N/Ag‐core), and platinum‐clad tantalum (Pt‐clad Ta) were studied. From the nanoindentation measurements, the elastic modulus and hardness at different positions and depths were calculated. It was found that both elastic modulus and hardness reached a constant value below the hardened surface, which resulted from mechanical polishing. Material properties obtained from the measurements were compared with the literature values of bulk materials as well as available results on fine wires. The data from the wire cross‐sections, especially the uniform material samples, showed that both the elastic modulus and hardness were significantly lower near the outer 10–15 μm of the wire as compared to the rest of the wire, which is due to surface weakening during manufacturing. In addition, both modulus and hardness showed a small but consistent “sawtooth” variation across the diameter of the wires, excluding the outer 10–15 μm, that is postulated to be induced by the distribution of residual stress. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 106–113, 2004
Differential response to keratinocyte growth factor receptor and epidermal growth factor receptor ligands of proliferating and differentiating intestinal epithelial cells
Authors: Visco Vincenzo , Belleudi Francesca , Marchese Cinzia , Leone Laura , Aimati Laura , Cardinali Giorgia , Kovacs Daniela , Frati Luigi , Torrisi Maria Rosaria 
Published: March 2004

AbstractThe expression of the keratinocyte growth factor receptor (KGFR) has been analyzed on intestinal epithelial Caco‐2 cells upon confluence‐induced spontaneous differentiation. Western blot and immunofluorescence analysis showed that the expression of functional KGFRs, differently from that of epidermal growth factor receptor (EGFR), was up‐modulated in post‐confluent differentiated cultures compared with the pre‐confluent cells. Confocal microscopy and immunoelectron microscopy revealed that the up‐regulated KGFRs displayed a basolateral polarized distribution on the cell surfaces in the monolayer. In vivo immunohistochemical analysis on normal human colon tissue sections showed that KGFRs, differently from EGFRs, were mostly distributed on the more differentiated cells located on the upper portion of the intestinal crypt. Bromodeoxyuridine incorporation assay and Ki67 labeling indicated that the differentiated cells were able to proliferate in response to the two ligands of KGFR, KGF and FGF‐10, whereas they were not stimulated by the EGFR ligands TGFα and EGF. Western blot and quantitative immunofluorescence analysis of the expression of carcinoembryonic antigen (CEA) in post‐confluent cells revealed that incubation with KGF induced an increase of cell differentiation. Taken together these results indicate that up‐modulation of KGFR may be required to promote proliferation and differentiation in differentiating cells and that, among the cells componing the intestinal epithelial monolayer, the target cells for KGFR ligands appear to be different during differentiation from those responsive to EGFR ligands. © 2004 Wiley‐Liss, Inc.