bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischaemic preconditioning improves microvascular perfusion and oxygenation following reperfusion injury of the intestine
Authors: Mallick I H , Yang W , Winslet M C , Seifalian A M
Published: July 2005

Background

Ischaemia–reperfusion (IR) injury of the intestine occurs commonly during abdominal surgery. Ischaemic preconditioning (IPC) provides a way of protecting the organ from damage inflicted by IR. This study was designed to evaluate the beneficial effect of IPC, focusing on the intestinal microcirculation and oxygenation in intestinal IR injury.

Methods

Rats were allocated to three groups. Animals in the IR and IPC groups underwent 30 min of intestinal ischaemia followed by 2 h of reperfusion. In the IPC group this was preceded by 10 min of ischaemia and 10 min of reperfusion. Animals in the third group underwent laparotomy but no vascular occlusion. Intestinal microvascular perfusion, oxygenation and portal venous blood flow (PVF) were monitored continuously. At the end of the reperfusion period, blood samples were obtained for measurement of lactate dehydrogenase (LDH) and biopsies of ileum for histological evaluation.

Results

IPC improved intestinal microvascular perfusion and tissue oxygenation significantly at the end of the reperfusion period (P < 0·001). PVF improved significantly in the IPC compared with the IR group (P = 0·005). The serum LDH concentration was significantly lower in the IPC than the IR group (mean(s.e.m.) 667·1(86·8) versus 1973·8(306·5) U/l; P < 0·001) Histological examination showed that ileal mucosa was significantly less injured in the IPC group.

Conclusions

This study demonstrated that IPC improves intestinal microvascular perfusion and oxygenation.
Malignant transformation of high-grade anal intraepithelial neoplasia
Authors: Scholefield J H , Castle M T , Watson N F S
Published: July 2005

Background

The natural history of anal intraepithelial neoplasia (AIN) is uncertain. This makes management problematic as treatment options to eradicate the condition carry morbidity. The authors report their 10-year experience with conservative management of this condition, highlighting the lessons learnt.

Methods

All patients were diagnosed with high-grade AIN (AIN III) between 1994 and 2003. Diagnosis was by full-thickness biopsy and histopathological examination. Excision of localized lesions was undertaken, and all patients underwent follow-up every 6 months. Prospective data were collected regarding recurrence, postoperative complications and progression to invasive carcinoma.

Results

Thirty-five patients were followed for a median of 63 (range 14–120) months. Excision of localized high-grade AIN was carried out in 28 patients with minimal morbidity. Six patients were systemically immunosuppressed at diagnosis, all of whom had multifocal perianal lesions. Three immunosuppressed patients developed invasive anal squamous carcinoma during follow-up. By contrast, no invasive carcinomas were identified among immunocompetent patients with either localized or multifocal perianal disease.

Conclusion

AIN III appears to have a relatively low potential for malignant transformation in the immunocompetent patient. However, immunosuppressed patients are more likely to have extensive AIN III and a greater risk of malignant change.
Evaluation of treatment and long-term follow-up in patients with hepatic alveolar echinococcosis
Authors: Kadry Z , Renner E C , Bachmann L M , Attigah N , Renner E L , Ammann R W , Clavien P-A
Published: July 2005

Background

Alveolar echinococcosis is a rare disorder, which makes a comparison of different treatment modalities within a clinical trial difficult to perform. Data prospectively recorded over a period of 25 years were used to evaluate three therapeutic strategies: benzimidazole therapy alone, complete ‘curative’ resection followed by 2 years of adjuvant benzimidazole treatment, and partial debulking resection followed by continuous administration of a benzimidazole.

Methods

Details of 113 patients with hepatic alveolar echinococcosis treated between 1976 and 2003 were analysed. Kaplan–Meier survival curves were constructed and, using a Cox regression model, patient age, year of initial treatment and PNM stage were entered as co-variates in the analysis.

Results

Kaplan–Meier overall survival curves stratified for treatment strategy indicated an improved long-term survival in patients undergoing the debulking procedure (P = 0·061) or curative resection (P = 0·002) compared with benzimidazole therapy alone. However, when PNM stage, patient age and year of initial treatment were introduced into the analysis, there was a trend for survival advantage only with curative resection (P = 0·07 versus benzimidazole alone). Debulking resulted in a higher rate of progression of hepatic echinococcosis than curative surgery (P = 0·008). The incidence of parasite-related complications was similar for debulking resection and benzimidazole therapy alone (P = 0·706).

Conclusion

Debulking hepatic resections do not appear to offer any advantage in the treatment of patients with alveolar echinococcosis.
Comparison of the effects of nitric oxide donors and calcium channel blockers on the intrinsic myogenic tone of sheep isolated internal anal sphincter
Authors: Jonas-Obichere M , Scholefield J H , Acheson A , Mundey M , Tyler H , Wilson V G
Published: July 2005

Background

Chronic anal fissure is associated with considerable pain and anal hypertonia. Numerous clinical studies attest to the effectiveness of individual nitro-containing drugs and organic calcium channel blockers in this condition but there are few comparative studies.

Methods

Isolated segments of sheep internal anal sphincter were prepared for isometric tension recording. The effect of various drugs on myogenic tone was examined in the absence or presence of sodium orthovanadate (SOV), an agent used to mimic anal hypertonia by increasing myogenic tone.

Results

All the drugs tested produced concentration-dependent inhibition of myogenic tone, with the maximum effect ranging from 66·4 per cent (verapamil) to 100 per cent (sodium nitroprusside). Sodium nitroprusside and diltiazem were the most potent, followed by glyceryl trinitrate (GTN), nifedipine and verapamil, which had similar potency, and finally nicorandil. The potency of GTN and diltiazem was reduced threefold in the presence of 1 mmol/l SOV. The combined effect of GTN and diltiazem was greater than the effect of either agent alone, even in the presence of 3 mmol/l SOV.

Conclusion

Nitro-containing drugs and organic calcium channel blockers are potent inhibitors of anal sphincter myogenic tone that may be used in combination to treat chronic anal fissure.
Percutaneous thermal ablation for recurrent hepatocellular carcinoma after hepatectomy
Authors: Lu M-D , Yin X-Y , Xie X-Y , Xu H-X , Xu Z-F , Liu G-J , Kuang M , Zheng Y-L
Published: July 2005

Background

Tumour ablation using a thermal energy source has shown promising results, and is particularly suitable for recurrent hepatocellular carcinoma (HCC). The present study evaluated long-term outcomes after percutaneous thermal ablation for recurrent HCC following liver resection.

Methods

Radiofrequency ablation or microwave ablation was used to treat a total of 124 tumour nodules (0·9–7·0 cm in diameter) in 72 patients with recurrent HCC.

Results

Complete ablation of 119 (96·0 per cent) of 124 tumour nodules was achieved. There was no treatment-related death and the major complication rate was 4 per cent. During a mean(s.d.) follow-up of 27·9(17·8) months, local recurrence developed in 16 (13·6 per cent) of 118 successfully treated tumour nodules. Distant recurrence developed in 60 (85 per cent) of 71 patients, of whom 26 had repeat metachronous distant recurrence. With repeated ablation for both local and distant recurrence, the 1-, 3- and 5-year overall survival rates after initial ablation were 75, 43 and 18 per cent respectively. Patients with a serum α-fetoprotein level greater than 200 ng/ml before treatment had significantly poorer survival than those with a lower level (P = 0·034) and multivariate analysis identified preablation AFP level as an independent prognostic factor (P = 0·054).

Conclusion

With their advantages of preservation of non-tumorous liver tissue and easy repetition, percutaneous thermal ablative therapies were particularly suitable for recurrent HCC and improved long-term survival.
Meta-analysis of the value of somatostatin and its analogues in reducing complications associated with pancreatic surgery
Authors: Connor S , Alexakis N , Garden O J , Leandros E , Bramis J , Wigmore S J
Published: July 2005

Background

The role of somatostatin and its analogues in reducing complications after pancreatic resection is controversial. This is a meta-analysis of the evidence of benefit.

Methods

A literature search using Medline and ISI Proceedings with exploration of the references identified 22 studies. Of these, ten met the inclusion criteria for data extraction. Estimates of effectiveness were performed using fixed- and random-effects models. The effect was calculated as an odds ratio (OR) with 95 per cent confidence intervals (c.i.) using the Mantel–Haenszel method. Level of significance was set at P < 0·050.

Results

Outcomes for 1918 patients were compared. Somatostatin and its analogues did not reduce the mortality rate after pancreatic surgery (OR 1·17 (0·70 to 1·94); P = 0·545) but did reduce both the total morbidity (OR 0·62 (0·46 to 0·85); P = 0·003) and pancreas-specific complications (OR 0·56 (0·39 to 0·81); P = 0·002). Somatostatin and its analogues reduced the rate of biochemical fistula (OR 0·45 (0·33 to 0·62); P < 0·001) but not the incidence of clinical anastomotic disruption (OR 0·80 (0·44 to 1·45); P = 0·459).

Conclusion

Somatostatin and its analogues reduce the incidence of complications after surgery.
Sacral nerve stimulation reduces corticoanal excitability in patients with faecal incontinence
Authors: Sheldon R , Kiff E S , Clarke A , Harris M L , Hamdy S
Published: July 2005

Background

Sacral nerve stimulation (SNS) can produce symptomatic relief in patients with faecal incontinence. Moreover, peripheral nerve stimulation has been shown to affect brain function. The aim of this study was to determine whether SNS might produce important changes in cortical activity linked to improved continence.

Methods

In an experimental study, ten women with intractable faecal incontinence (mean age 51·3 years) were serially mapped with transcranial magnetic stimulation before and immediately after 14 days of temporary SNS (15 Hz, pulse width 210 µs), and then 2 weeks later. Anal sphincter electromyographic responses were recorded to cortical stimulation of multiple points over a scalp grid covering the bilateral medial cortex. Continence scores, anorectal manometry and rectal sensitivity data were also collected.

Results

SNS improved global symptom scores in the majority of patients; mean(s.e.m.) continence scores fell from 16·9(1·6) to 10·6(1·8) (P = 0·042). Cortical mapping showed a consistent decrease in corticoanal representation and overall excitability immediately after SNS compared with baseline (mean(s.e.m.) 38 083(13 669) versus 42 507(13 297) µV s; P = 0·017), which was reversed 2 weeks after SNS wire removal.

Conclusion

SNS produces symptom benefit in patients with faecal incontinence that is associated with a reversible reduction in corticoanal excitability. SNS therefore drives dynamic brain changes that may play a functional role in influencing anal continence.
Low‐Spin State Structure of [Fe(chloroethyltetrazole)6](BF4)2 Obtained from Synchrotron Powder Diffraction Data
Authors: Dova Eva , Peschar René , Takata Masaki , Nishibori Eiji , Schenk Henk , Stassen Arno F. , Haasnoot Jaap G.
Published: July 2005

The complex [Fe(teec)6](BF4)2 (teec=chloroethyltetrazole) shows a two‐step complete spin‐crossover transition in the temperature range 300–90 K. Time‐resolved synchrotron powder diffraction experiments have been carried out in this temperature range, and crystal structure models have been obtained from the powder patterns by using the parallel tempering technique. Of these models, the low‐spin state structure at 90 K has been refined completely with Rietveld refinement. Its structural characteristics are discussed in relation to the high‐spin state model and other spin‐crossover compounds. The complex shows a remarkable anisotropic unit‐cell parameter contraction that is dependent on the applied cooling rate. In addition, the possible important implications for the interpretation of spin‐crossover behavior in terms of structural changes are discussed.
Homo‐/Heterotrinuclear Mixed‐Valent Oxo‐Centered Iron/Nickel Clusters—Mössbauer Studies on Internal Electron‐Exchange Processes
Authors: Saalfrank Rolf W. , Scheurer Andreas , Reimann Uwe , Hampel Frank , Trieflinger Christian , Büschel Michael , Daub Jörg , Trautwein Alfred X. , Schünemann Volker , Coropceanu Veaceslav
Published: July 2005

In a one‐pot reaction of N‐(5‐methylthiazole‐2‐yl)‐thiazole‐2‐carboxamide HL2 (3) with iron(II) acetate in air, the homotrinuclear heteroleptic mixed‐valent oxo‐centered iron cluster [FeII${{\rm Fe}{{{\rm III}\hfill \atop 2\hfill}}}$O(L2)3(OAc)3] (4) was formed. Exchange of iron(II) in 4 by nickel(II) afforded the heteronuclear cluster [NiII${{\rm Fe}{{{\rm III}\hfill \atop 2\hfill}}}$O(L2)3(OAc)3] (6). To obtain crystals suitable for X‐ray structure analyses, in 4 and 6, the OAc− co‐ligands were exchanged by OBz− ligands to give [FeII${{\rm Fe}{{{\rm III}\hfill \atop 2\hfill}}}$O(L2)3(OBz)3] (5) and [NiII${{\rm Fe}{{{\rm III}\hfill \atop 2\hfill}}}$O(L2)3(OBz)3] (7). The complexes 5 and 7 are isostructural and made up of three ditopic, tridentate ligands (L2)− and three bridging benzoate co‐ligands, which fix the three metal ions in the corners of a triangle with an μ3‐O2− ion in the center. The mixed‐valent character of 4–7, their intramolecular electron‐exchange processes, and their redox properties were studied by variable‐temperature Mössbauer spectroscopy and cyclic voltammetry.
A Small Cavity with Reactive Internal Shell Atoms Spanned by Four {As(W/V)9}‐Type Building Blocks Allows Host–Guest Chemistry under Confined Conditions
Authors: Müller Achim , Pope Michael T. , Merca Alice , Bögge Hartmut , Schmidtmann Marc , van Slageren Joris , Dressel Martin , Kurth Dirk G.
Published: July 2005

The reaction of [H2AsIIIW18O60]7− with VO2+ and SO42− ions in aqueous solution leads to a VIV/VV mixed‐valence cluster anion containing the {As4M40O140}‐type cryptand which has a high formation tendency. An important result is that it exhibits a new type of reactive internal cavity shell. The correspondingly obtained compound Na(NH4)20[{(VIVO(H2O))(VIVO)2(SO4)2}{(AsIIIW9O33)2(AsIIIW7.5VV1.5O31)2(WO2)4}]⋅40 H2O (1), which can also be synthesized from a precursor with the preorganized cryptand, was characterized by elemental and thermogravimetric analyses (determination of crystal water content), redox titrations (determination of the number of VIV centers), electronic absorption as well as vibrational spectra, single‐crystal X‐ray structure analysis (including bond valence sum calculations), and magnetic susceptibility measurements. The relatively small central cavity—formed by the linking of four {AsM9}‐type lacunary units (M=W/V) by four WO6 octahedra—allows positioning of a variety of cationic as well as anionic “guests” under confined conditions according to a new approach: replacement of some of the W by V atoms leads to high reactivity of the internal cavity shell as a result of relatively weak VO bonds compared to the WO bonds. This allows an interesting “encapsulation chemistry” with new options. In the present case the cavity contains besides an arrangement of three VIV centers, two sulfate groups that replace O atoms of the {AsM9} units as well as an interesting hydrogen bond situation.
Cover Picture: Probing Molecular Wires: Synthesis, Structural, and Electronic Study of Donor–Acceptor Assemblies Exhibiting Long‐Range Electron Transfer (Chem. Eur. J. 16/2005)
Authors: Giacalone Francesco , Segura José L. , Martín Nazario , Ramey Jeff , Guldi Dirk M.
Published: July 2005

The rational design of linear donor–acceptor arrays by integrating fully conjugated oligomers with a well‐defined length and constitution is reported by N. Martín, D. M. Guldi et al. on page 4819 ff. Photoinduced electron transfer (shown schematically in the cover picture) over distances of up to 50 Å with formation of the respective radical pairs is demonstrated. The strong electron coupling between the donor and acceptor moieties through the π‐conjugated oligomer is particularly important for the observed wire‐like behavior.
Correlation between annual volume of cystectomy, professional staffing, and outcomes
Authors: Elting Linda S. , Pettaway Curtis , Bekele B. Nebiyou , Grossman H. Barton , Cooksley Catherine , Avritscher Elenir B. C. , Saldin Kamaldeen , Dinney Colin P. N.
Published: July 2005

BACKGROUND

The association between high procedure volume and lower perioperative mortality is well established among cancer patients who undergo cystectomy. However, to the authors' knowledge, the association between volume and perioperative complications has not been studied to date and hospital characteristics contributing to the volume‐outcome correlation are unknown. In the current study, the authors studied these associations, emphasizing hospital factors that contribute to the volume‐outcome correlation.

METHODS

Multiple‐variable models of inpatient mortality and complications were developed among all 1302 bladder carcinoma patients who underwent cystectomy between January 1, 1999 and December 31, 2001 in all Texas hospitals. General estimating equations were used to adjust for clustering within the 133 hospitals. Data were obtained from hospital claims, the 2000 U.S. Census, and databases from the Center for Medicare and Medicaid Services and the American Hospital Association.

RESULTS

Complications were reported to occur in 12% of patients, 2.2% of whom died. Mortality was higher in low‐volume hospitals compared with high‐volume hospitals (3.1% vs. 0.7%; P < 0.001); mortality in moderate‐volume hospitals was reported to be intermediate (2.9%). After adjustment for advanced age and comorbid conditions, treatment in high‐volume hospitals was associated with lower risks of mortality (odds ratio [OR] = 0.35; P = 0.02) and complications (OR = 0.53; P = 0.01). Hospitals with a high registered nurse‐to‐patient ratio also had a lower mortality risk (OR = 0.43; P = 0.04).

CONCLUSIONS

Mortality after cystectomy was found to be significantly lower in high‐volume hospitals, regardless of patient age. Referral to a hospital performing greater than 10 cystectomies annually is indicated for all patients. However, patients with poor access to a high‐volume hospital may derive similar benefit from treatment at a hospital with a high‐registered nurse‐to‐patient ratio. This finding requires further confirmation. Cancer 2005. © 2005 American Cancer Society.
Colon cancer screening practices in New York City, 2003
Authors: Thorpe Lorna E. , Mostashari Farzad , Hajat Anjum , Nash Denis , Karpati Adam , Weber Thomas , Winawer Sidney , Neugut Alfred I. , Awad Amir , Zevallos Mabel , Remy Prospere , Frieden Thomas
Published: July 2005

BACKGROUND

New York City (NYC) has one of the highest concentrations of gastroenterologists in the country, yet only 33% of colorectal cancers in NYC are diagnosed early, and approximately 1500 New Yorkers die from colorectal cancer each year.

METHODS

Using data from a large, local, random‐digit dialed telephone survey (n = 9802), the authors of the current study described types of colorectal cancer screening modalities and characteristics of adults undergoing screening within a recommended timeframe. Multivariate analyses were used to examine demographic, behavioral, socioeconomic, and neighborhood‐level predictors of screening participation, with particular attention to factors associated with colonoscopy, the recommended screening modality in NYC.

RESULTS

Fifty‐five percent of NYC adults aged ≥ 50 years reported a recent colorectal cancer screening test, and 42% reported a colonoscopy within the past 10 years. After multiple statistical adjustments, groups with the lowest likelihood of screening were the poor (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.53–0.83) and uninsured (OR, 0.31; 95% CI, 0.20–0.48), as well as Asians (OR, 0.46; 95% CI, 0.29–0. 72), and current smokers (OR, 0.62; 95% CI, 0.50–0.78). Colonoscopy was less frequently reported by non‐Hispanic Black New Yorkers and by women; both groups reported higher use of fecal occult blood tests. Less than 10% of adult New Yorkers reported a sigmoidoscopy in the past 5 years.

CONCLUSIONS

Low screening uptake in NYC leaves nearly 1 million New Yorkers, particularly poor and uninsured adults, at risk for undetected colorectal cancer. Colonoscopy screening programs in NYC should address health care and socioeconomic barriers and target racial and ethnic minorities and women. Cancer 2005. © 2005 American Cancer Society.
The polygenetically inherited metabolic syndrome of WOKW rats is associated with insulin resistance and altered gene expression in adipose tissue
Authors: Klöting Nora , Blüher Matthias , Klöting Ingrid
Published: July 2005

Background

Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a complete metabolic syndrome closely resembling the human disease. The aim of this study was to characterize the phenotype of adipose tissue in WOKW rats with regard to adipocyte metabolism, insulin resistance, and gene expression and thus to define the phenotype more precisely.

Methods

Glucose metabolism, insulin sensitivity, and gene expression of key adipocyte genes, including adiponectin, interleukin 6 (Il6), 11 beta‐hydroxysteroid dehydrogenase (11β Hsd), peroxisome proliferator‐activated receptor gamma (Pparγ), forkhead box O1 (Foxo1), glucose transporter 4 (Glut4), CCAAT/enhancer binding protein (C/ebpα), and fatty acid synthase (Fasn) were characterized in adipocytes from epididymal and subcutaneous fat depots of 28‐week‐old male WOKW rats and Dark Agouti (DA) controls.

Results

WOKW rats display decreased insulin‐stimulated glucose uptake and decreased insulin sensitivity during lipogenesis and lipolysis in isolated adipocytes. The severe insulin resistance predominantly in epididymal adipose tissue of WOKW rats is associated with a 10‐fold decrease in adipocyte adiponectin gene expression, decreased Pparγ, but increased Foxo1 gene expression compared to DA rats.

Conclusions

Insulin resistance in adipose tissue is associated with altered adipocyte gene expression in WOKW rats, additionally completing the picture of the metabolic syndrome in this animal model. This fact not only qualifies the WOKW rat for further detailed analysis of genetic determinants of metabolic syndrome but also highlights its suitability for pharmacological research. Copyright © 2005 John Wiley & Sons, Ltd.
Alpha-1-Antitrypsin Deficiency: A New Paradigm for Hepatocellular Carcinoma in Genetic Liver Disease *
Authors: Rudnick David A. , Perlmutter David H.
Published: July 2005

Liver disease in alpha-1-antitrypsin (α1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER). The extraordinary degree of variation in phenotypical expression of this liver disease is believed to be determined by genetic modifiers and/or environmental factors that influence the intracellular disposal of the mutant glycoprotein or the signal transduction pathways that are activated. Recent investigations suggest that a specific repertoire of signaling pathways are involved, including the autophagic response, mitochondrial- and ER-caspase activation, and nuclear factor kappaB (NFκB) activation. Whether activation of these signaling pathways, presumably to protect the cell, inadvertently contributes to liver injury or perhaps protects the cell from one injury and, in so doing, predisposes it to another type of injury, such as hepatocarcinogenesis, is not yet known. Recent studies also suggest that hepatocytes with marked accumulation of α1ATZ, globule-containing hepatocytes, engender a cancer-prone state by surviving with intrinsic damage and by chronically stimulating in ‘trans’ adjacent relatively undamaged hepatocytes that have a selective proliferative advantage. Further, this paradigm may apply to other genetic and infectious liver diseases that are predisposed to hepatocellular carcinoma. (Hepatology 2005.)
Simple surface modification of poly(ϵ‐caprolactone) to induce its apatite‐forming ability
Authors: Oyane Ayako , Uchida Masaki , Yokoyama Yoshiro , Choong Cleo , Triffitt James , Ito Atsuo
Published: July 2005

A biodegradable polymer coated with a bone‐like apatite layer on its surface is useful as a scaffold for bone tissue regeneration. In this work, a poly(ϵ‐caprolactone) (PCL) surface was modified by an O2 plasma surface treatment to form oxygen‐containing functional groups. The plasma‐treated samples were subsequently dipped alternately in an alcoholic solution containing calcium ions and one containing phosphate ions to deposit apatite precursors on the surface. The surface‐modified PCL samples formed a dense and uniform surface bone‐like apatite layer after immersion for 24 h in a simulated body fluid with ion concentrations approximately equal to those of human blood plasma. This surface‐modification process is applicable to two‐dimensional PCL plates and three‐dimensional PCL meshes. In the resulting apatite–PCL composite, the apatite layer strongly adhered to the PCL surface and remained intact after a tape‐detachment test. Therefore, this type of composite material will be a useful scaffold for bone tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
In vitro release of clomipramine HCl and buprenorphine HCl from poly adipic anhydride (PAA) and poly trimethylene carbonate (PTMC) blends
Authors: Dinarvand Rassoul , Alimorad Mohammed Massoud , Amanlou Massoud , Akbari Hamid
Published: July 2005

Controlled drug‐delivery technology is concerned with the systematic release of a pharmaceutical agent to maintain a therapeutic level of the drug in the body for modulated and/or prolonged periods of time. This may be achieved by incorporating the therapeutic agent into a degradable polymer vehicle, which releases the agent continuously as the matrix erodes. In this study, poly trimethylene carbonate (PTMC), an aliphatic polycarbonate, and poly adipic anhydride (PAA), an aliphatic polyanhydride, were synthesized via melt condensation and ring‐opening polymerization of trimethylene carbonate and adipic acid, respectively. The release of clomipramine HCl and buprenorphine HCl from discs prepared with the use of PTMC‐PAA blends in phosphate buffer (pH 7.4) are also described. Clomipramine HCl and buprenorphine HCl were both used as hydrophilic drug models. Theoretical treatment of the data with the Peppas model revealed that release of clomipramine HCl (5%) in devices containing 70% PTMC or more followed a Fickian diffusion model. However, the releases of buprenorphine HCl (5%) in the same devices were anomalous. For devices containing 50% and more PAA, surface erosion may play a significant role in the release of both molecules. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Preparation and characterization of nano‐hydroxyapatite/chitosan composite scaffolds
Authors: Kong Lijun , Gao Yuan , Cao Wenling , Gong Yandao , Zhao Nanming , Zhang Xiufang
Published: July 2005

A novel nano‐hydroxyapatite (HA)/chitosan composite scaffold with high porosity was developed. The nano‐HA particles were made in situ through a chemical method and dispersed well on the porous scaffold. They bound to the chitosan scaffolds very well. This method prevents the migration of nano‐HA particles into surrounding tissues to a certain extent. The morphologies, components, and biocompatibility of the composite scaffolds were investigated. Scanning electron microscopy, porosity measurement, thermogravimetric analysis, X‐ray diffraction, X‐ray photoelectron spectroscopy, and Fourier transformed infrared spectroscopy were used to analyze the physical and chemical properties of the composite scaffolds. The biocompatibility was assessed by examining the proliferation and morphology of MC 3T3‐E1 cells seeded on the scaffolds. The composite scaffolds showed better biocompatibility than pure chitosan scaffolds. The results suggest that the newly developed nano‐HA/chitosan composite scaffolds may serve as a good three‐dimensional substrate for cell attachment and migration in bone tissue engineering. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
Improved performance of primary rat hepatocytes on blended natural polymers
Authors: Li Keguo , Qu Xinjian , Wang Yun , Tang Yuefeng , Qin Dajiang , Wang Yanjun , Feng Meifu
Published: July 2005

Alginate (Alg), chitosan (Chi), collagen (Col), gelatin (Gel), and the mixtures of every two of them were screened to determine their suitability for hepatocyte culture. The test materials were fabricated as films and then evaluated on the basis of their abilities to promote the attachment and functions of rat hepatocytes cultured on them. Cellular attachment on Col and Gel was favorable. However, cellular viability, cytoskeleton organization and function, as evaluated by albumin production, ureagenesis, and enzyme activity of cytochrome P450 as well as expression levels of hepatocyte nuclear factor 4α deteriorated. Reverse cellular behavior was observed on Alg and Chi. Two blends, composed of Chi and Col or Gel, were found to be superior to other materials and sustained viability and differentiated functions of hepatocyte. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005
The influence of ultrasound on the release of gentamicin from antibiotic‐loaded acrylic beads and bone cements
Authors: Ensing Geert T. , Hendriks Johannes G.E. , Jongsma Jelmer E. , van Horn Jim R. , van der Mei Henny C. , Busscher Henk J.
Published: July 2005

Gentamicin‐loaded acrylic beads are loosely placed in infected bone cavities, whereas gentamicin‐loaded acrylic bone cement is used as a mechanical filler in bone to anchor prosthetic components. Both drug delivery systems are used to decrease infection rates by gentamicin release. The objective of this study is to investigate the effects of pulsed ultrasound on gentamicin release from both materials. Gentamicin release from gentamicin‐loaded beads (Septopal) and from three commercially‐available brands of gentamicin‐loaded bone cement (CMW 1, Palacos R‐G, and Palamed G) was measured after 18 h of exposure in PBS to an ultrasonic field of 46.5 kHz in a 1:3 duty cycle with an average acoustic intensity of 167 mW/cm2. Samples not exposed to ultrasound were used as controls. Pulsed ultrasound significantly enhanced gentamicin release from gentamicin‐loaded beads, whereas gentamicin release from the gentamicin‐loaded bone cements was not significantly enhanced. Mercury intrusion porosimetry revealed an increased distribution of pores between 0.1 and 0.01 μm in beads after gentamicin release, while in bone cements no increase in the number of pores was found. Increased gentamicin release in beads due to ultrasound may be explained by microstreaming in a porous structure, whereas the absence of changes in pore structure after gentamicin release in bone cement is concurrent with the lack of an enhanced release of the antibiotic by ultrasound. As an effective treatment of infections requires high local concentrations of antibiotic, increased gentamicin release due to ultrasound may be of clinical significance, especially since ultrasound has been demonstrated to increase bacterial killing by antibiotics. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Electron paramagnetic resonance analyses of surface radical chemistries of γ‐sterilized orthopedic materials: Implications pointing to cytotoxicity via wear debris–induced inflammation
Authors: DiCicco Michael , Compton Ryan , Duong Thanh , Jansen‐Varnum Susan A.
Published: July 2005

In this research, electron paramagnetic resonance (EPR) spin‐trapping was utilized to determine if surface radical chemistries occur for gamma (γ)‐sterilized orthopedic materials—ultra‐high molecular weight polyethylene (UHMWPE) and the novel, hybrid, diurethane dimethacrylate (DUDMA)‐based RHAKOSS™. The materials' ability to competitively chelate catalytic ferrous ions (Fe2+) or readily reduce ferric ions (Fe3+), and hydrogen peroxide (H2O2) directly, in facilitating the Fenton reaction (FR), is indicative of cytotoxicity. Validations with a radical scavenger aids to confirm a radical mechanism. In conjunction, materials were thermally annealed and characterized by attenuated total reflectance–Fourier‐transform infrared (ATR‐FTIR) spectroscopy in order to explore accelerated oxidative degradation induced by residual radicals evolving from γ‐sterilization. Particularly, there was a significant decrease in spin‐adduct peak areas obtained from the reduction of H2O2 in the presence of RHAKOSS or UHMWPE, evaluated against their respective controls. Additionally, chelated Fe2+ accelerated the rate of FR. This phenomenon suggests that the materials are not better chelators than the Fe‐activating chelator, edta. Neither material had the propensity to readily reduce Fe3+ to the relevant Fe2+, as certified by a nonradical mechanism. Alternatively, the false spin‐adduct signal acquired when chelated Fe3+ is employed arises via the nucleophilic addition of water onto the DMPO spin trap. Residual radicals in UHMWPE did not recombine/terminate following thermal annealing in an inert atmosphere. The radicals in RHAKOSS, however, did recombine under mild heating in an oxidizing or inert atmosphere. Both materials displayed quenching of ˙OH; however, for UHMWPE, this mechanism was jointly accountable for its accelerated degradation, evidenced by ATR‐FTIR. Quenching of ˙OH by the silica found in RHAKOSS manifested in a competing effect that counterbalanced the observed FR. Implanted RHAKOSS is not likely to promote cytotoxicity and should not degrade, but the damaging effect of γ sterilization on UHMWPE is a serious dilemma confronting its long‐term durability and biocompatibility. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Biomimetic porous scaffolds with high elasticity made from mineralized collagen—An animal study
Authors: Yokoyama Atsuro , Gelinsky Michael , Kawasaki Takao , Kohgo Takao , König Ulla , Pompe Wolfgang , Watari Fumio
Published: July 2005

Histological investigations of a new hydroxyapatite–collagen composite material were carried out to evaluate its possible suitability as a bone substitute. The three‐dimensional scaffolds made from biomimetically mineralized collagen exhibit an interconnecting pore structure and elastic mechanical properties. They were implanted into the subcutaneous tissue and bone defects made in the femur of rats and harvested with the surrounding tissue at 1, 2, 4, 8, and 12 weeks after surgery. The materials implanted in the subcutaneous tissue were covered by fibrous connective tissue with a slight inflammatory response, and many foreign‐body giant cells were observed on the surface of the scaffolds. Most of the material implanted in the subcutaneous tissue was resorbed at 8 weeks by phagocytosis. In the bone defects, new bone formation was observed on the surface of the material at 1 week. New bone increased with time, and osteoclasts were seen on the surface of the scaffolds at 2 weeks. Resorption and replacement by new bone of many parts of the materials implanted in the femur were observed by 12 weeks. These responses occurred faster than those of other hydroxyapatite‐collagen composites. The results suggested that the new biomimetically mineralized collagen scaffolds were suitable as an implant material for bone‐tissue reconstruction. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2005
Collagen‐immobilized poly (vinyl alcohol) as an artificial cornea scaffold that supports a stratified corneal epithelium
Authors: Miyashita Hideyuki , Shimmura Shigeto , Kobayashi Hisatoshi , Taguchi Tetsushi , Asano‐Kato Naoko , Uchino Yuichi , Kato Masabumi , Shimazaki Jun , Tanaka Junzo , Tsubota Kazuo
Published: July 2005

The cornea is a transparent tissue of the eye, which is responsible for the refraction of incoming light. Both biological corneal equivalents and synthetic keratoprostheses have been developed to replace donor tissue as a means to restore vision. However, both designs have drawbacks in terms of stability and biocompatibility. Clinically available synthetic devices do not support an intact epithelium, which poses a risk of microbial infection or protrusion of the prosthesis. In the present study, type I collagen was immobilized onto poly(vinyl alcohol) (PVA‐COL) as a possible artificial cornea scaffold that can sustain a functional corneal epithelium. Human and rabbit corneal epithelial cells were air‐lift cultured with 3T3 feeder fibroblasts to form a stratified epithelial layer on PVA‐COL. The epithelial sheet expressed keratin 3/12 differentiation markers, the tight junction protein occludin, and had characteristic microvilli structures on transmission electron microscopy. Functionally, the stratified epithelium contained normal glycogen levels, and an apical tight‐junction network was observed to exclude the diffusion of horseradish peroxidase. Furthermore, the epithelium‐PVA‐COL composite was suturable in the rabbit cornea, suggesting the possibility of using PVA‐COL as a biocompatible material for keratoprosthesis. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Structural features and mechanical properties of in situ–bonded meshes of segmented polyurethane electrospun from mixed solvents
Authors: Kidoaki Satoru , Kwon Il Keun , Matsuda Takehisa
Published: July 2005

The relationships between the structural features and mechanical properties of electrospun segmented polyurethane (SPU) meshes and electrospinning parameters such as formulation (e.g., polymer concentration and solvent mixing ratio) and operation parameters (e.g., applied voltage, air gap, and flow rate) were studied with the use of a mixed‐solvent system of tetrahydrofuran (THF) and N,N‐dimethylacrylamide (DMF). After the relationships between the structure of electrospun SPU and the operation parameters under a fixed SPU concentration of single THF solution were established, SPU was electrospun from the mixed solvent of THF and DMF with different mixing ratios [DMF content: 5, 10, and 30% (v/v)]. Scanning electron microscopy showed that an increase in DMF ratio significantly enhances the degree of bonding between SPU fibers at contact sites and decreases the diameter of fibers formed. The porosimetric characterization showed the following: (1) The porosity of the electrospun SPU meshes decreased with an increase of DMF ratio. (2) The pore size distribution exhibited three representative peaks of different void sizes (i.e., approximately 5, 20, and 70 μm). (3) The proportion of the 20‐μm void markedly decreased with an increase in DMF ratio. A tensile test on the meshes showed that an increase in DMF ratio induces an increase in elasticity of the mesh. Such a regulation of the structural features and mechanical properties of electrospun SPU meshes using a mixed‐solvent system with low‐ and high‐boiling‐point solvents may be useful in the engineering of SPU‐fiber based matrices or scaffolds. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Biomechanical investigation of the effect of high hydrostatic pressure treatment on the mechanical properties of human bone
Authors: Steinhauser Erwin , Diehl Peter , Hadaller Martin , Schauwecker Johannes , Busch Raymonde , Gradinger Reiner , Mittelmeier Wolfram
Published: July 2005

Several methods are available for reconstruction of bone defects due to malignant tumors. To extracorporally devitalize resected tumor‐bearing bone segments two methods, that is, extracorporal irradiation or autoclaving, are available up to now. However, both methods have substantial disadvantages like decrease of bone's mechanical strength. To develop an alternative method for tumor inactivation in skeletal segments, high hydrostatic pressure (HHP) was applied. Previous investigations have shown that human normal and tumor cell lines as well as tumor‐afflicted human bone specimens were irreversibly damaged at 350 MPa when subjected to HHP. This study was aimed to examine the alterations of biomechanical properties of human bone after exposure to HHP. Trabecular and cortical bone specimens were harvested from six pair of fresh‐frozen human cadaveric femora. The bone specimens from one side were exposed to different pressure values of 300 or 600 MPa over 10 min. Bone samples from the contralateral sites were used as untreated controls. Biomechanical properties were investigated by a quasi‐static compression test for trabecular specimens and by a quasi‐static four‐point bending test for cortical specimens, respectively. Biomechanical properties of the cortical and trabecular bone did not decrease after exposure to 300 MPa regarding the testing parameters Young's modulus and ultimate strength (200.7 ± 38.7 MPa for HHP treated cortical bone versus 186.5 ± 34.3 MPa for the untreated control group). After pressure treatment at 600 MPa Young's modulus and ultimate strength respectively remained almost unchanged in trabecular bone and were reduced about 15% in cortical bone (p < 0.001 and p =0.002, respectively). We anticipate that in orthopedic surgery HHP can serve as a novel, promising methodical approach for tumor cell inactivation, which occurs at pressure levels of about 300 MPa. Thereby immediate reimplantation of treated bone segments by preservation of the essential biomechanical properties of bone could become possible. Even after HHP treatment at 600 MPa the strength of bone only decreases up to 15%. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Joint properties of cast Fe‐Pt magnetic alloy laser welded to gold alloys
Authors: Watanabe Ikuya , Nguyen Khoi , Benson P. Andrew , Tanaka Yasuhiro
Published: July 2005

This study investigated the joint properties of a cast Fe‐Pt magnetic alloy (Fe‐36 at % Pt) laser welded to three gold alloys. The gold alloys used were ADA Type II and Type IV gold alloys, and an Ag‐based (Ag‐Au) gold alloy. Cast plates (0.5 × 3.0 × 10 mm) were prepared for each alloy. After the cast Fe‐Pt plates were heat treated, they were butted against each of the three alloys and then laser welded with Nd:YAG laser at 200 V. Homogeneously welded specimens were also prepared for each alloy. Tensile testing was conducted at a crosshead speed of 1 mm/min. Failure load (N) and elongation (%) were recorded. After tensile testing, the fractured surfaces were examined with the use of SEM. The failure‐load values of the group of alloys welded homogeneously were ranked in the order of: Ag‐Au alloy > Type IV alloy > Type II alloy > Fe‐Pt alloy. The Type IV alloy welded to Fe‐Pt alloy had the highest failure‐load value among the three alloys tested. The elongation results tended to follow a similar pattern. The results of this study indicated that Type IV gold alloy is a suitable alloy for metal frameworks to which cast Fe‐Pt magnetic alloy is laser welded. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Removal of surface by‐products from sintered hydroxyapatite: Effect of a chelation treatment on fibronectin adsorption and cell adhesion
Authors: Pellenc Delphine , Giraudier Sébastien , Champion Eric , Anselme Karine , Larreta‐Garde Véronique , Gallet Olivier
Published: July 2005

It was observed that fibronectin precipitates when deposited on hydroxyapatite (HA) ceramics. Fibronectin's known affinity for calcium and the composition of the ceramic itself suggested that calcium release could be the main cause of this aggregation effect. It was then decided to investigate the effect of a surface chelation treatment on fibronectin adsorption, and MG63 cell adhesion, onto porous ceramics of hydroxyapatite (HA), beta‐tricalcium phosphate (β‐TCP), and HA/TCP biphasic material (BCP). Those ceramics were immersed in an EDTA solution and the effect of this treatment on the material composition was assayed. X‐ray diffraction data showed the presence of α‐ and β‐TCP phases in HA and BCP materials, which were both completely removed by the chelation treatment in the case of HA. On BCP, α‐TCP was removed and β‐TCP partially dissolved. The TCP material, which was pure β‐TCP, underwent a mass loss, but no change in composition was observed. Adhesion of MG63 cells was overall higher on the fibronectin‐coated EDTA‐treated HA material, but was especially enhanced on EDTA‐treated HA. Changes in surface morphologies, as compared with the use of scanning electron microscopy, did not seem to be related to the effects observed. The EDTA treatment proved to be a very efficient way of removing by‐products of HA sintered materials, and thus enhancing the biocompatibility of the material. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Dual‐level direct dynamics studies on the reaction Cl + CHBr2Cl
Authors: Zhang Hui , Wu Jia‐Yan , Li Ze‐Sheng , Liu Jing‐Yao , Sheng Li , Sun Chia‐Chung
Published: July 2005

Theoretical investigations are carried out on the multichannel reaction CHBr2Cl + Cl by means of direct dynamics methods. The minimum energy path (MEP) is obtained at the BH&H‐LYP/6‐311G(d,p) level, and energetic information is further refined at the CCSD(T)/6‐311+G(2df,2p) (single‐point) level. The rate constants for three reaction channels, H‐abstraction, Br‐abstraction, and Cl‐abstraction, are calculated by using the improved canonical variational transition state theory (ICVT) incorporating with the small‐curvature tunneling (SCT) correction. The theoretical overall rate constants are in good agreement with the available experimental data and are found to be k = 2.58 × 10−15 T1.18 exp(−861.17/T) cm3molecule−1s−1 over the temperature range 200–2400 K. For the title reaction, H‐abstraction reaction channel is the major channel at the lower temperatures, while as the temperature increases, the contribution of Br‐abstraction reaction channel should be taken into account. At 2180 K, the rate constants of these two pathways are equal. Cl‐abstraction reaction channel is minor channel over the whole temperature region. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1421–1426, 2005
Radiosyntheses and reactivities of novel [18F]2‐fluoroethyl arylsulfonates
Authors: Musachio John L. , Shah Jay , Pike Victor W.
Published: July 2005

[18F]2‐Fluoroethyl tosylate ([18F]FEOX, X=Ts) is widely used for labeling radiotracers for positron emission tomography (PET). Little work has been reported on syntheses of other [18F]2‐fluoroethyl arylsulfonates ([18F]FEOX) that bear a less electron‐rich aryl group, even though these might offer enhanced reactivities. Thus, a series of novel [18F]FEOX (X=benzenesulfonyl, brosyl, nosyl, 3,4‐dibromobenzenesulfonyl) were synthesized and reactivities compared to [18F]FEOTs. Precursors for radiolabeling (bis‐ethylene glycol arylsulfonates) and reference FEOX were synthesized (alcohol+arylsulfonyl chloride+KOSiMe3 in THF). Regardless of substitution pattern, [18F]FEOX (110°C, 5 min, acetonitrile) were obtained in similar decay‐corrected isolated radiochemical yields (RCY; 47–53%). All [18F]FEOX gave excellent RCYs (64–87%) of the dopamine uptake radioligand, [18F]FECNT (130°C, 10 min, acetonitrile). The 3,4‐dibromobenzensulfonate gave the highest RCY of [18F]FECNT (87%) and this HPLC‐purified labeling agent was used directly for efficient [18F]FECNT production. When the secondary aniline of an amyloid probe (HM‐IMPY) or p‐nitrophenol was reacted with [18F]FEOX, RCYs were appreciably higher for brosylate and nosylate than for tosylate, while 3,4‐dibromobenzenesulfonate again gave the highest RCY. Owing to the high reactivity of the new [18F]FEOX and their ease of syntheses via stable precursors, such agents (particularly 3,4‐dibromobenzenesulfonate) should be considered as alternatives to [18F]FEOTs. Copyright © 2005 John Wiley & Sons, Ltd.