bluuebunny/crossref_metadata_2025_split huggingface dataset:
The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study
Authors: Thomopoulos S. , Hattersley G. , Rosen V. , Mertens M. , Galatz L. , Williams G. R. , Soslowsky L. J. 
Published: October 2002

AbstractThe localized expression of a number of extracellular matrix genes was evaluated over time in a novel rat rotator cuff injury model. The supraspinatus tendons of rats were severed at the bony insertion and repaired surgically. The healing response was evaluated at 1, 2, 4, and 8 weeks post‐injury using histologic and in situ hybridization techniques. Expression patterns of collagens (I, II, III, IX, X, XII), proteoglycans (decorin, aggrecan, versican, biglycan, fibromodulin), and other extracellular matrix proteins (elastin, osteocalcin, alkaline phosphatase) were evaluated at the healing tendon to bone insertion site. Histologic results indicate a poor healing response to the injury, with only partial recreation of the insertion site by 8 weeks. In situ hybridization results indicate a specific pattern of genes expressed in each zone of the insertion site (i.e., tendon, fibrocartilage, mineralized cartilage, bone). Overall, expression of collagen types I and XII, aggrecan, and biglycan was increased, while expression of collagen type X and decorin was decreased. Expression of collagen type I, collagen type XII, and biglycan decreased over time, but remained above normal at 8 weeks. Results indicate that the rat supraspinatus tendon is ineffective in recreating the original insertion site, even at 8 weeks post‐injury, in the absence of biological or biomechanical enhancements. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
A novel bisphosphonate inhibits inflammatory bone resorption in a rat osteolysis model with continuous infusion of polyethylene particles
Authors: Iwase Miho , Kim Kang Jung , Kobayashi Yoshiro , Itoh Masatoshi , Itoh Tatsuo 
Published: October 2002

AbstractThis study examined the inhibitory effect of a new bisphosphonate (TRK‐530) on wear debris‐mediated bone resorption in a rat osteolysis model involving continuous infusion of high density polyethylene (HDPE) particles. TRK‐530 (TRK) is a novel synthetic bisphosphonate that has been shown to decrease the level of tumor necrosis factor alpha (TNF‐α) in the bone marrow of rats with adjuvant arthritis. Forty Wistar rats were randomized to two groups (n = 20 each). In each rat, a Kirshner (K) wire was inserted into the femur and HDPE particles were continuously infused into the knee joint. Thereafter, the animals were subcutaneously injected with saline (control group) or 1 mg/kg of TRK (TRK group) every second day, and were sacrificed at 4 or 8 weeks after surgery. Radiographs obtained at the time of sacrifice were evaluated for periprosthetic osteolysis. We also examined the thickness of the reactive membrane as well as the number of osteoclast‐like cells around the K‐wire. In addition, we examined the expression of genes for bone‐resorbing cytokines in the reactive membrane. Radiographic peri‐implant osteolysis was more frequent in the control group compared with the TRK group at each time of assessment (p < 0.01). The interfacial membrane was significantly thinner in the TRK group compared with the control group (p < 0.01) and the average number of osteoclast‐like cells around the K‐wire was significantly fewer in the TRK group (p < 0.01). In addition, the expression of interleukin 1‐alpha messenger ribonucleic acid (IL‐1α mRNA) and TNF‐α mRNA was suppressed in the TRK group at each time of assessment. We conclude that the TRK can inhibit the formation of inflammatory peri‐implant osteolysis induced by HDPE particles. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Collagen‐targeted BMP3 fusion proteins arrayed on collagen matrices or porous ceramics impregnated with Type I collagen enhance osteogenesis in a rat cranial defect model
Authors: Han Bo , Perelman Natalya , Tang Baowei , Hall Fredrick , Shors Edwin C. , Nimni Marcel E. 
Published: October 2002

AbstractBone morphogenetic protein 3 (BMP3) is a potent osteoinductive growth factor belonging to the TGF‐β superfamily. In this study, we engineered a recombinant BMP3 protein to include an auxiliary collagen‐targeting domain derived from von Willebrand coagulation factor (vWF). The collagen‐targeted BMP3 fusion protein (rhBMP3‐C) was expressed in E. coli, purified from bacterial inclusion bodies, renatured under controlled redox conditions, and assayed for biological activity in vitro and in vivo. The renatured rhBMP3‐C fusion protein bound tightly to collagen matrices and inhibited DNA synthesis in normal rat calvaria cells and in two out of three human osteosarcoma cell lines tested. Alkaline phosphatase activity was increased in rat calvarial cells and was decreased in osteosarcoma cells in vitro in a dose‐dependent manner. Collagen sponges impregnated with rhBMP3‐C and implanted subcutaneously in Fischer‐344 rats induced dose‐dependent dystrophic calcification of the collagen matrix, with no evidence of ectopic bone formation. However, local injection of rhBMP3‐C infused in a collagen suspension induced new bone formation on the periosteal surface of rat calvaria. Finally, in a rat cranial defect model, surgical implantation of rhBMP3‐C arrayed on either collagen sponges or on porous ceramics coated with Type I collagen exhibited marked osteoinductive properties. Taken together, these results demonstrate the feasibility of engineering and manufacturing targeted‐BMPs which exhibit an integral gain‐of‐function that may be exploited to therapeutic advantage in (i) the enhancement of effective local concentrations, (ii) the prevention of systemic biodistribution and side effects, and (iii) the design of improved osteoinductive matrices. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The effect of pulsed electromagnetic fields on the osteointegration of hydroxyapatite implants in cancellous bone: a morphologic and microstructural in vivo study
Authors: Fini Milena , Cadossi Ruggero , Canè Valerio , Cavani Francesco , Giavaresi Gianluca , Krajewski Adriano , Martini Lucia , Aldini Nicolò Nicoli , Ravaglioli Antonio , Rimondini Lia , Torricelli Paola , Giardino Roberto 
Published: October 2002

AbstractEffects of pulsed electromagnetic fields (PEMFs, 75 Hz, 1.6 mT) were investigated in 12 rabbits after placing hydroxyapatite (HA) implants in their femoral condyles. Six animals were stimulated with PEMFs for three consecutive weeks, 6 h/day, while the remaining animals were sham‐treated (Control Group). Rabbits were sacrificed at 3 and 6 weeks (after a 3‐week non‐stimulation period) for histomorphometric analysis and microhardness testing (at 200, 500, 1000, 2000 μm from the implant) around the implants around the implants. Histomorphometric analysis did not highlight any significant changes. On the contrary, there were statistically significant differences between the effects produced by PEMFs and Control Groups (F = 149.70, p < 0.0005) on the Affinity Index results, as well as by the experimental time of 6 and 3 weeks (F = 17.12, p = 0.001) on the same results. In PEMF‐stimulated animals the microhardness (HV) values measured in trabecular bone at a distance of 200 and 500 μm from the implants, were significantly higher with respect to controls. At 6 weeks, HV values at the bone‐implant interface in PEMF‐stimulated animals were not significantly different with respect to normal bone, while they remained significantly lower in control animals. Both morphological and structural results demonstrated a positive therapeutic effect of PEMFs in accelerating HA osteointegration in trabecular bone. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Detection and analysis of cartilage degeneration by spatially resolved streaming potentials
Authors: Légaré A. , Garon M. , Guardo R. , Savard P. , Poole A. R. , Buschmann M. D. 
Published: October 2002

AbstractCartilage molecular changes in osteoarthritis are most commonly related to the degradation and loss of proteoglycan and collagen fibrils of the extracellular matrix, which directly influence tissue stiffness and compression‐generated streaming potentials. In this study, we evaluated the potential of a new technique, spatially resolved mapping of streaming potentials, to non‐destructively indicate cartilage health or degeneration. Matched pairs of bovine cartilage/bone explant disks were cultured for 11 days in a serum free medium with and without interleukin‐1α (IL‐1α). The electromechanical properties (static stiffness, dynamic stiffness and streaming potentials) of cartilage disks were measured during unconfined compression using a mechanical tester coupled with a linear array of eight 50 μm diameter platinum‐iridium microelectrodes. After 11 days of culture, the proteoglycan content of IL‐1α treated disks was significantly reduced and the denatured and cleaved collagen content was increased compared to control disks. These biochemical alterations were concomitant with the reductions in the amplitudes of the static stiffness, the dynamic stiffness and the streaming potential profile as well as changes in the shape of the streaming potential profile. We found that spatial mapping of streaming potentials presents several advantages for the development of a clinical instrument to evaluate the degeneration of articular cartilage. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
ATP induces proliferation of retinal cells in culture via activation of PKC and extracellular signal‐regulated kinase cascade
Authors: Sanches Glauco , de Alencar Laura Sá , Ventura Ana Lucia Marques 
Published: October 2002

AbstractBoth ATP and acetylcholine can induce the mobilization of intracellular calcium in the early developing chick embryo retina, a response that decreases during retinal development. In this study, the effects of these transmitters on the turnover of phosphoinositides and proliferation of developing retinal cells in culture were characterized. While ATP, UTP or carbachol were able to induce a >400% accumulation of phosphoinositides in retinal cell cultures, only ATP promoted a dose‐dependent increase in [3H]‐thymidine incorporation in cultured cells (EC50=8.6 μM), a response that was inhibited by the P2 receptor antagonist pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS) (0.1 or 0.25 mM). ADP, but not UTP or adenosine, also stimulated the proliferation of retinal cells (EC50=5.8 μM), indicating that activation of P2Y1 receptors mediates the proliferative response of retinal cells to ATP. The mitogenic effect of ATP was completely prevented by the PKC inhibitor chelerythrine chloride (0.5 μM) and the phospholipase C (PLC) inhibitor U73122 (0.5 μM). PD 98059 (25 or 50 μM), an inhibitor of the activation of extracellular signal‐regulated kinases (ERKs) also blocked the increase in [3H]‐thymidine incorporation induced by ATP. Moreover, the effect of ATP was pronounced in cultures obtained from retinas at embryonic days 6–8, but not at day 9. Since Müller and bipolar cells are the predominant cell types that proliferate at these embryonic stages, our data suggest that ATP, through activation of P2Y1 receptors coupled to phospholipase C, PKC and MAP kinases, affects DNA synthesis in one or both of these cell types in culture.
Influence of progressive renal dysfunction in chronic heart failure
Authors: Maxwell A. Peter , Ong Hean Y. , Nicholls D. Paul 
Published: October 2002

AbstractChronic heart failure (CHF) is often associated with impaired renal function due to hypoperfusion. Such patients are very sensitive to changes in renal perfusion pressure, and may develop acute tubular necrosis if the pressure falls too far. The situation is complicated by the use of diuretics, ACE inhibitors and spironolactone, all of which may affect renal function and potassium balance. Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia and hypertension in CRF contribute to the development of left ventricular hypertrophy (LVH), which carries a poor prognosis, so correction of these factors is important.
Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress
Authors: Ellis Gethin R. , Nightingale Angus K. , Blackman Daniel J. , Anderson Richard A. , Mumford Catherine , Timmins Graham , Lang Derek , Jackson Simon K. , Penney Michael D. , Lewis Malcolm J. , Frenneaux Michael P. , Morris‐Thurgood Jayne 
Published: October 2002

AbstractBackground:Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure.Methods and results:Twenty‐eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid‐derived free radicals, TBARS and neutrophil O2‐generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow‐related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (−0.1±1.2 vs. −0.1±1.0 units, respectively, P ‐ NS), TBARS (−2.2±1.1 vs. −2.6±2.2 μmol/l, respectively, P ‐ NS) or neutrophil O2‐generating capacity (−7.3±5.1 vs. −8.4±7.9 mV/5×105 neutrophils, respectively, P ‐ NS). There was no effect on changes in brachial artery flow‐mediated dilatation (0.5±1.0 vs. 0.8±1.3%, respectively, P ‐ NS) nor peak VO2 (1.6±0.7 ml/kg per min vs. 1.8±0.6 ml/kg per min; P ‐ NS).Conclusion:The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.
Approaches to statistical analysis of repeated echocardiographic measurements after myocardial infarction and its relation to heart failure: Application of a random‐effects model
Authors: de Kam Pieter‐Jan , Voors Adriaan A. , Brouwer Jan , St John Sutton Martin , van Gilst Wiek H. 
Published: October 2002

AbstractBackground:Extensive left ventricular (LV) dilatation after myocardial infarction (MI) is associated with increased heart failure risk.Aims:To investigate whether the power to demonstrate the relation between LV dilatation and heart failure depends on the method applied to predict LV dilatation after MI. Methods: A random‐effects model and ANOVA model for repeated measurements (MANOVA) were applied to predict LV volume index during 1 year for 298 post‐MI patients. Spearman correlation coefficients (r) were calculated and Cox regression analysis was used to calculate risk ratio's (RR).Results:LV volume indices were more accurately predicted by a random‐effects model than by a MANOVA model (systolic/diastolic respectively r‐0.93/0.91 vs. r‐0.67/0.64). Furthermore, patients with high LV volume index as predicted by the random‐effects model, had significantly increased heart failure risk (systolic RR 2.04 (95% CI: 1.31 to 3.17; P‐0.001), diastolic RR 1.80 (95% CI: 1.16 to 2.78; P‐0.007). Using the same data, MANOVA failed to demonstrate this relation significantly (systolic RR 1.77 (95% CI: 0.79 to 3.98; P‐0.16), diastolic RR 1.49 (95% CI: 0.68 to 3.30; P‐0.31).Conclusion:When analyzing repeated measurement data, random‐effect models are more powerful in detecting clinical relations than are MANOVA models, especially in the presence of missing values.
How patients with heart failure are managed in Portugal
Authors: Fonseca Cândida , Ceia Fátima , Brito Dulce , Madeira Hugo 
Published: October 2002

AbstractThe prevalence of heart failure is increasing all over the world. It is a common and growing public health problem in Portugal as in many other European countries. This article provides a review of health service organization and current heart failure management in Portugal, discusses primary care and ward practices in different hospitals and reports on the use of proven standard therapies for the treatment of heart failure in the community. Despite major advances in diagnosis and treatment, heart failure is only satisfactorily managed. Furthermore efforts are necessary before the beneficial effects observed in trials have a real impact in clinical practice. A broader view and priority for the management of this syndrome on a national level are needed to improve the quality of heart failure care in Portugal.
Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure
Authors: Refsgaard Jens , Thomsen Claus , Andreasen Frederik , Gøtzsche Ole 
Published: October 2002

AbstractBackgroundCongestive heart failure (CHF) has previously been shown to be associated with insulin resistance and hyperinsulinemia. A beneficial effect of the non‐selective β‐blocker carvedilol has been demonstrated in patients with CHF. However, whether the drug affects the insulin sensitivity (Si) is unknown.AimsTo investigate whether treatment with carvedilol alters the Si in patients with CHF during a prospective, double‐blinded, placebo‐controlled study. Methods and results: The patients were randomized to receive either carvedilol (n‐29) or matched placebo (n‐17). Insulin and glucose responses were measured during a 0.3 g/kg intravenous glucose tolerance test, and Si was calculated according to Bergman's Minimal Model. Baseline Si values correlated significantly with body mass index (r‐−0.42, P‐0.002), plasma urate (r‐−0.42, P‐0.002), plasma HDL‐cholesterol (r‐0.39, P‐0.003), maximal oxygen uptake (r‐0.35, P‐0.009), plasma triglycerides (r‐−0.34, P‐0.01) and weight (r‐−0.29, P‐0.03). During the study the insulin sensitivity was unchanged in the carvedilol group compared with placebo (2.63±1.45 to 2.38±1.64 vs. 2.81±2.36 to 2.48±1.84×10−4 min−1/mU1−1, P‐0.83).ConclusionAdditional treatment with carvedilol is neutral with regard to influence the insulin sensitivity in patients with mild to moderate CHF.
The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure—a meta‐regression analysis
Authors: Thackray Simon , Easthaugh Joanne , Freemantle Nick , Cleland John G.F. 
Published: October 2002

AbstractAimsTo review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure.MethodsStudies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non‐treatment control, were identified. Drugs of the following classes were included, the β‐agonists; dobutamine, high‐dose (>2.5 μg/kg/min) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context.ResultsWith few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CI‐0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta‐agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data.ConclusionsIntravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials.
Electro‐membrane filtration for the selective isolation of bioactive peptides from an αs2‐casein hydrolysate
Authors: Bargeman Gerrald , Houwing Joukje , Recio Isidra , Koops Geert‐Henk , van der Horst Caroline 
Published: October 2002

AbstractFor the isolation of the ingredients required for functional foods and nutraceuticals generally membrane filtration has too low a selectivity and chromatography is (too) expensive. Electro‐membrane filtration (EMF) seems to be a breakthrough technology for the isolation of charged nutraceutical ingredients from natural sources. EMF combines the separation mechanisms of membrane filtration and electrophoresis. In this study, positively charged peptides with antimicrobial activity were isolated from an αs2‐casein hydrolysate using batch‐wise EMF. αs2‐Casein f(183–207), a peptide with strong antimicrobial activity, predominated in the isolated product and was enriched from 7.5% of the total protein components in the feed to 25% in the permeate product. With conventional membrane diafiltration using the same membrane (GR60PP), isolation of this and other charged bioactive peptides could not be achieved. The economics of EMF are mainly governed by the energy costs and the capital investment, which is affected by the flux of the desired peptide. A maximum average transport rate of αs2‐casein f(183–207) during batch‐wise EMF of 1.2 g/m2 · h was achieved. Results indicate that an increase in the hydrolysate (feed) concentration, the applied potential difference and the conductivity of the permeate and electrode solutions, and a reduction in the conductivity of the feed result in a higher transport rate of αs2‐casein f(183–207). This is in line with the expectation that the transport rate is improved when the concentration, the electrical field strength, or the electrophoretic mobility is increased, provided that the electrophoretic transport predominates. The expected energy consumption of the EMF process per gram of peptide transported was reduced by approximately 50% by applying a low overall potential difference and by processing desalinated hydrolysate. Considerable improvements in transport rate, energy efficiency, and process economics seem to be attainable by additional optimization of the process parameters and the EMF module design. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 599–609, 2002.