bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential In Vitro Interaction Between Tenecteplase and Unfractionated Heparin
Authors: Tsikouris James P. , Martin Christopher P. , Cox Craig D. , Ziska Martin , Suarez Jose A. , Meyerrose Gary E.
Published: August 2004

Study Objective. To explore the potential of a direct drug interaction between unfractionated heparin (UFH) and tenecteplase that lowers the pharmacologic propensity of UFH to prolong the activated partial thromboplastin time (aPTT).

Design. In vitro experiment.

Setting. Texas Tech University School of Pharmacy, with sample analysis performed at an independent, contract laboratory.

Samples. Blood samples collected from healthy volunteers.

Intervention. Three separate in vitro experiments were conducted to explore the relative influence of various thrombolytic agents with and without UFH on aPTT prolongation. In each experiment, blood from healthy volunteers (12 for each experiment) was treated with different concentrations and combinations of tenecteplase and UFH.

Measurements and Main Results. When the effects of tenecteplase plus UFH versus UFH alone on aPTT prolongation were compared, each experiment demonstrated attenuation of aPTT with the combination versus UFH alone. In contrast, findings for other thrombolytic agents combined with UFH demonstrate elevation of the aPTT compared with UFH alone.

Conclusion. The results indicate a possible drug interaction between tenecteplase and UFH, with tenecteplase attenuating the intensity of anticoagulation of UFH in vitro. Further investigation into this possible interaction is warranted in the clinical setting.
Current and Future Immunosuppressive Strategies in Renal Transplantation
Authors: Hardinger Karen L. , Koch Matthew J. , Brennan Daniel C.
Published: August 2004

The past decade has witnessed the introduction of several new immunosuppressive agents. The availability of these new pharmacologic offerings has not diminished the challenge of achieving a balance of adequate graft protection while minimizing the consequences of excessive immunosuppression. For renal transplant recipients, maintenance immunosuppression generally consists of a calcineurin inhibitor in combination with an antiproliferative agent and a corticosteroid; more recently, mammalian target of rapamycin inhibitors have been used. Excellent results have been achieved at many transplant centers with combinations of these agents in a variety of protocols. Regimens designed to limit or eliminate calcineurin inhibitor and/or corticosteroid therapy are actively being pursued in the transplant community. Allograft tolerance and xenotransplantation are being studied, and the knowledge gained from the effort may help in the development of innovative strategies and new immunosuppressive agents.
Paradoxical Reactions to Benzodiazepines: Literature Review and Treatment Options
Authors: Mancuso Carissa E. , Tanzi Maria G. , Gabay Michael
Published: August 2004

Benzodiazepines frequently are administered to patients to induce sedation. Paradoxical reactions to benzodiazepines, characterized by increased talkativeness, emotional release, excitement, and excessive movement, are relatively uncommon and occur in less than 1% of patients. The exact mechanism of paradoxical reactions remains unclear. Most cases are idiosyncratic; however, some evidence suggests that these reactions may occur secondary to a genetic link, history of alcohol abuse, or psychological disturbances. This review evaluates the numerous cases of paradoxical reactions to benzodiazepines in adult and pediatric patients that have been reported in the biomedical literature. It also explores the advantages and disadvantages of the various available treatment options.
Role of Topiramate for the Treatment of Painful Diabetic Peripheral Neuropathy
Authors: Carroll Dana G. , Kline Kristina M. , Malnar Karen F.
Published: August 2004

Objective. To review the possible role of topiramate for the treatment of neuropathic pain and, specifically, the pain of diabetic peripheral neuropathy.

Data Sources. Clinical studies and abstracts were identified by using PubMed (January 1966–October 2003), Ovid (January 1966–December 2003), and International Pharmaceutical Abstracts (January 1970–December 2003) and by reviewing bibliographies of published studies. Key search terms included pain, peripheral neuropathy, diabetes, and topiramate. English‐language studies were identified, as were pertinent references from these articles.

Data Synthesis. Published data are limited on the successful use of topiramate in the treatment of neuropathic pain syndromes, and only three prospective studies evaluated the effectiveness of topiramate in diabetic peripheral neuropathy. In addition, the use of topiramate to treat diabetic neuropathic pain syndromes successfully may be limited by patients' inability to tolerate the adverse effects associated with the agent.

Conclusions. Topiramate has been used successfully in relieving the pain of various neuropathies, including painful diabetic peripheral neuropathy. Randomized controlled trials that specifically focus on the use of topiramate in patients with painful diabetic peripheral neuropathy are needed to confirm the initial findings in case reports, abstracts, and small clinical trials that have focused on treating numerous neuropathic pain syndromes, including diabetic peripheral neuropathy.
Impact of Oral Direct Thrombin Inhibitors on Anticoagulation Clinics
Authors: Nutescu Edith A. , Pickard A. Simon , Blackburn Juan C. , Wittkowsky Ann K. , Ansell Jack , Schumock Glen T.
Published: August 2004

Objectives. To characterize the services and activities performed by anticoagulation clinics (ACCs) across the United States, examine the anticipated impact that oral direct thrombin inhibitors (DTIs) will have on the clinical services of ACCs, and elicit possible management strategies to realign services provided by ACCs and opportunities for restructuring clinical services.

Methods. A survey was developed in consultation with content experts in the field, pretested by several ACC providers, and subsequently refined. Surveys were mailed to 400 randomly selected ACC‐based providers.

Results. The final usable response rate was 34.5% (115 of 333 surveys). Respondents anticipated that the number of patient visits/month would decrease from a median of 336 (interquartile range [IQR] 151–775) to 150 (IQR 71–350, p<0.001) after the introduction of oral DTIs. In addition, time spent on many direct and indirect patient care activities currently performed by ACCs was expected to decline. Respondents indicated that ACCs may find new roles by providing guidance on individual suitability for therapy, managing the transition to oral DTIs, providing education for patients and health care providers on thrombotic disease state management, monitoring patients for recurrent thrombosis and risk of bleeding complications, monitoring patient compliance, and providing counseling and safety surveillance for patients receiving treatment with oral DTIs.

Conclusion. The advent of oral DTIs is likely to have a significant impact on the structure and delivery of antithrombotic services. Clinics that are proactive and redesign their patient care services to consider emerging anticoagulant agents will be more likely to remain relevant and viable.
Impaired Warfarin Response Secondary to High‐Dose Vitamin K1 for Rapid Anticoagulation Reversal: Case Series and Literature Review
Authors: Fugate Susan E. , Nichols Carrie M. , Cudd Laura A.
Published: August 2004

The literature suggests that unresponsiveness to warfarin can continue for 1 week or longer after administration of high‐dose vitamin K1 10 mg or greater; however, there is a lack of supporting data to define the duration and clinical consequences of impaired warfarin response with high doses of vitamin K1. This case series describes four patients receiving indefinite warfarin therapy who received high and, in most cases, repeated doses of vitamin K1 for urgent reversal of therapeutic anticoagulation for an invasive procedure or surgery. The patients displayed impaired warfarin response for 11 days–3.5 weeks after administration of vitamin K1 10–40 mg. The associated financial burden for the patients was substantial. We reviewed the literature to examine the mechanism of impaired warfarin response, and the clinical efficacy, safety, and appropriateness of vitamin K1 and fresh‐frozen plasma in urgent reversal of anticoagulation.
Acute Pulmonary Edema Caused by Quinine
Authors: Everts Richard J. , Hayhurst Michael D. , Nona Basim P.
Published: August 2004

A 57‐year‐old man who had been intermittently taking one 300‐mg tablet of quinine sulfate orally for leg cramps experienced transient acute pulmonary edema and hypotension 30–40 minutes after ingestion on two consecutive occasions. He was not taking any concomitant drugs, and there was no alternative explanation for either event. Serial troponin T tests and electrocardiograms, obtained on admission to the hospital, followed by an outpatient echocardiogram and a coronary angiogram, were essentially normal. We compared this case with one previously published and nine previously unpublished reports of quinine‐associated pulmonary edema and conclude that some cases of pulmonary edema or adult respiratory distress syndrome in patients with malaria may be caused by an adverse reaction to quinine. Although infrequent, clinicians should be aware of this potentially serious and costly adverse reaction.
Enterococcus faecalis Resistant to Linezolid: Case Series and Review of the Literature
Authors: Burleson Brian S. , Ritchie David J. , Micek Scott T. , Dunne W. Michael
Published: August 2004

Reports of linezolid resistance among Enterococcus faecalis have been relatively rare. We describe three patients with linezolid‐resistant strains of E. faecalis, discovered after the patients had received long courses (> 30 days) of linezolid therapy. All strains contained the G2576U mutation in 23S rRNA. A literature review revealed one other case in the United States and three cases in Europe; all involved patients who had received long courses of therapy. It appears that recent or extended linezolid therapy may be a risk factor for development of resistant E. faecalis. In patients who have recently been treated with linezolid and have an identified new systemic enterococcal isolate, linezolid sensitivity should be verified as soon as possible to guide therapy. This strategy also should be considered for patients with a breakthrough enterococcal isolate during linezolid therapy.
Nesiritide for Treatment of Heart Failure Due to Right Ventricular Dysfunction
Authors: Sharp Randall P. , Gregory Amy , Mowdy Michael H. , Sirajuddin Riaz
Published: August 2004

Little information exists regarding the use of nesiritide for treatment of right‐sided heart failure. Similarly, little information is available regarding routine use of combination nesiritide and diuretics as initial therapy to relieve edema due to heart failure. Nesiritide may be beneficial in combination with diuretics because it reduces activity of the renin‐angiotensin‐aldosterone system. It is unclear how potent nesiritide is as a diuretic. Patients exhibit wide variability in clinical response from the diuretic effects of the drug. Two patients were given a combination of nesiritide and diuretics as initial treatment of right‐sided heart failure; both experienced significant diuresis and weight loss. Further literature is needed to clarify the role of nesiritide in the treatment of right‐sided heart failure.
Effect of Molecular Weight and Annealing of Poly(3‐hexylthiophene)s on the Performance of Organic Field‐Effect Transistors
Authors: Zen A. , Pflaum J. , Hirschmann S. , Zhuang W. , Jaiser F. , Asawapirom U. , Rabe J. P. , Scherf U. , Neher D.
Published: August 2004

The optical, structural, and electrical properties of thin layers made from poly(3‐hexylthiophene) (P3HT) samples of different molecular weights are presented. As reported in a previous paper by Kline et al., Adv. Mater. 2003, 15, 1519, the mobilities of these layers are a strong function of the molecular weight, with the largest mobility found for the largest molecular weight. Atomic force microscopy studies reveal a complex polycrystalline morphology which changes considerably upon annealing. X‐ray studies show the occurrence of a layered phase for all P3HT fractions, especially after annealing at 150 °C. However, there is no clear correlation between the differences in the transport properties and the data from structural investigations. In order to reveal the processes limiting the mobility in these layers, the transistor properties were investigated as a function of temperature. The mobility decreases continuously with increasing temperatures; with the same trend pronounced thermochromic effects of the P3HT films occur. Apparently, the polymer chains adopt a more twisted, disordered conformation at higher temperatures, leading to interchain transport barriers. We conclude that the backbone conformation of the majority of the bulk material rather than the crystallinity of the layer is the most crucial parameter controlling the charge transport in these P3HT layers. This interpretation is supported by the significant blue‐shift of the solid‐state absorption spectra with decreasing molecular weight, which is indicative of a larger distortion of the P3HT backbone in the low‐molecular weight P3HT layers.
Prenatal diagnosis of P450 oxidoreductase deficiency (ORD): A disorder causing low pregnancy estriol, maternal and fetal virilization, and the Antley–Bixler syndrome phenotype
Authors: Shackleton Cedric , Marcos Josep , Arlt Wiebke , Hauffa Berthold P.
Published: August 2004

We report studies on the second pregnancy of a woman who had previously given birth to a virilized female infant. The cause of the virilization had not been established, but common forms of congenital adrenal hyperplasia (CAH) were excluded. Longitudinal monitoring of the second pregnancy revealed that estriol excretion failed to increase normally, reaching a maximum 0.7 mg/24 hr at the end of pregnancy (normal mean 30 mg/24 hr). The mother showed signs of virilization by the 23rd week of gestation and aromatase deficiency was suspected. However, predicted urinary metabolites for diagnosis of aromatase deficiency (for example, 16α‐hydroxyandrosterone) were not increased significantly during the pregnancy. Interestingly, excretion of the androgen metabolite androsterone increased rapidly at the beginning of pregnancy and peaked around the 20th week, suggesting increased production of testosterone and 5αDHT, probably the cause of maternal virilization. Urine steroid analysis by GC/MS showed gradually increasing excretion (9 mg/24 hr) of the normally minor metabolite 5α‐pregnane‐3β,20α‐diol (epiallopregnanediol), an epimer of the dominant progesterone metabolite pregnanediol (5β‐pregnane‐3α,20α‐diol). We believe epiallopregnanediol is largely the maternal urinary excretion product of fetal 5‐pregnene‐3β,20α‐diol, the principal metabolite of pregnenolone, implying a build‐up of the latter steroid in the fetal adrenal. These findings suggested that the ‘block’ in the estriol biosynthetic pathway occurs at an early stage with 17‐hydroxylation of pregnenolone being affected. The male baby born of this pregnancy had normal genitalia but showed a urinary steroid profile indicating partial deficiencies of P450c17 and P450c21. However, no mutations in the corresponding CYP17 and CYP21 genes were identified. Urinary steroid analysis carried out on his virilized older sibling showed the same pattern of metabolites. Recently, we determined that this disorder is caused by mutations in P450 oxidoreductase (OR), the essential redox partner for CYP17 and CYP21 hydroxylases. The novel metabolic profile has now been seen in many patients, most diagnosed with the skeletal dysplasia Antley–Bixler syndrome. We propose that excessive excretion of epiallopregnanediol together with low estriol may be prenatally diagnostic for OR deficiency (ORD). © 2004 Wiley‐Liss, Inc.
Competition, predation, and the evolutionary significance of the cercopithecine cheek pouch: The case of Cercopithecus and Lophocebus
Authors: Lambert Joanna E.
Published: August 2004

Reports of cercopithecine cheek pouch use and functional significance are largely anecdotal, and to date there have been no investigations into its use by species living in closed forest habitats. Here, I report on cheek pouch use in Cercopithecus ascanius and Lophocebus albigena in the Kibale National Park, Uganda, between July–October 1997. Two hypotheses were evaluated: this feature was selected for because of its role in 1) increasing feeding efficiency via a reduction in potential feeding competition, and/or 2) reducing vulnerability to predation. Results indicate that both species were more likely to use their cheek pouches when feeding on contestable foods and, after filling cheek pouches, retreated to more densely vegetated (“safer”) positions for processing food. There was no influence of age and sex on L. albigena cheek pouch use. Subadult C. ascanius cheek‐pouched less frequently than adults, although there were no differences between adult males and females. There was no relationship between feeding‐patch size and number of plant food items cheek‐pouched in either species. However, the diameter of breast height (dbh; a measure of patch size) of trees in which C. ascanius used their cheek pouches was significantly larger than the dbh of trees in which they did not. Both species were more likely to use their cheek pouches in the presence of greater numbers of conspecifics. These data provide insight into the relationship(s) among oral anatomy and feeding efficiency, and facilitate understanding into the selection for this important oral feature in stem cercopithecines. Am J Phys Anthropol 126:183–192, 2005. © 2004 Wiley‐Liss, Inc.
The role of changing childhood diets in the prehistoric evolution of food production: An isotopic assessment
Authors: Schurr Mark R. , Powell Mary Lucas
Published: August 2004

Earlier weaning has often been suggested as a cause for population growth after the evolution of food production. However, evidence for weaning‐time reduction is largely circumstantial. Collagen stable nitrogen‐ and carbon‐isotope ratios from juvenile and adult burials from four sites in eastern North America were measured to estimate weaning onsets and durations before and after the appearance of intensive food production. Two preagricultural Late Archaic sites (Indian Knoll and Carlston Annis) are compared with two highly agricultural Middle Mississippian sites (Angel and Tinsley Hill). Isotopic data and paleodemographic measures of birth rates provide no evidence for changes in weaning behavior or fertility with the development of food production in the prehistoric Lower Ohio Valley. Birth rates and weaning behavior appear to have been roughly the same at all four sites. These results indicate that models attributing population growth after the appearance of food production to earlier weaning are not universally applicable. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
Invisible impacts but long‐term consequences: Hypoplasia and contact in central Australia
Authors: Littleton Judith
Published: August 2004

The dental casts taken of Aboriginal people resident at Yuendumu, Central Australia, between 1950–1970 preserve a unique historical record of defects of the dental enamel (DDEs) among people born from 1890–1960 (n = 377). These data are used, in comparison with precontact data, to trace the chronological changes in childhood development that occurred among Aboriginal people from the point of initial engagement with white settlers to a period of overwhelming government control. The results demonstrate very little change in the frequency of DDE from the precontact period to 1929 but increases after that time, particularly after the forcible settlement of people on a government establishment at Yuendumu in 1946. Apart from the absolute increase in frequency, it is also clear that population variation decreased markedly, with growing numbers of children experiencing multiple defects in early childhood (ca. 0.8–1.5 years of age). The results also indicate that an early onset of DDE constituted a risk for further episodes. These changes in DDE correspond to periods of increasingly intense contact between Aboriginal people and Europeans and with changes to government policy aimed at assimilating the indigenous population. Such policies had marked costs for childhood development. The lack, however, of a visible marker of initial contact demonstrates the importance of the intensity of and motives behind interactions between indigenous and colonial populations in determining the health consequences of colonial encounters. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
Titelbild: Phosphorus Nanorods—Two Allotropic Modifications of a Long‐Known Element (Angew. Chem. 32/2004)
Authors: Pfitzner Arno , Bräu Michael F. , Zweck Josef , Brunklaus Gunther , Eckert Hellmut
Published: August 2004

Alternativen zur Struktur des Hittorfschen Phosphors wurden vor einigen Jahren vorhergesagt und konnten nun in Form von Phosphor‐Nanostäben experimentell nachgewiesen werden. Wie A. Pfitzner, H. Eckert et al. auf S. 4324 ff. berichten, werden diese neuen amorphen Allotrope des Phosphors durch Behandlung der Addukte (CuI)8P12 und (CuI)3P12 mit wässriger Cyanidlösung erhalten. Der nanoskalige Charakter der Stäbe kommt in ihren hochaufgelösten TEM‐Bildern deutlich zum Ausdruck, und aus den 31P‐MAS‐NMR‐Spektren geht hervor, dass sich die Polymere strukturell unverändert isolieren lassen.
DC current voltage characteristics of silicone rubber filled with conductive carbon black
Authors: Zhang Jie , Feng Shengyu , Wang Xinqiang
Published: August 2004

Direct current (DC) current‐voltage (I‐V) characteristics of silicone rubber filled with conductive carbon black (CB) were studied at room temperature in the voltage range of 1–46 V. The current‐voltage relationship can be expressed as I = AVB, where A and B are constants that show capability and property of electrical conduction, respectively. The I‐V curve can be divided into ohmic and nonohmic regions. In nonohmic region, B < 1, and the resistance increases with the rise of voltage. Higher CB loading leads to lower transforming voltage from ohmic to nonohmic region and much deviation from Ohm's law. The reason for this deviation is the unbalance between the heat generated and the heat loss of conductive silicone rubber during the measurement. When the heat effect is eliminated completely, the electrical conduction is ohmic. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 587–592, 2004
Generation of microcellular biodegradable polycaprolactone foams in supercritical carbon dioxide
Authors: Xu Qun , Ren Xianwen , Chang Yuning , Wang Jingwu , Yu Long , Dean Katherine
Published: August 2004

Microcellular foaming of low‐Tg biodegradable and biocompatible polycaprolactone (PCL) in supercritical CO2 has been studied. The purpose is to apply microcellular materials to drug containers and medical materials for artificial skin or bone. Effects of a series of variable factors on the foam structures, such as saturation temperature, saturation pressure, saturation time, and depressurization time were studied. The experimental results indicate that, while keeping other variables unchanged, higher saturation temperature leads to reduced bulk densities and different saturation pressures result in different nucleation processes. In addition, saturation time has a profound effect on the structure of the product. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 593–597, 2004
Thermal properties of hydrophobically modified methacrylic acid–ethyl acrylate copolymer solutions
Authors: Tam K. C. , Ng W. K. , Jenkins R. D.
Published: August 2004

The thermal behavior of a water‐soluble associating polymer system, hydrophobically modified alkali‐soluble emulsion (HASE) polymer, was investigated. This polymer contains a methacrylic acid–ethyl acrylate copolymer backbone with 1 mol % of pendant hydrophobic groups grafted to it. The thermal behavior of the HASE polymer exhibits different trends compared to the hydrophobic ethoxylated urethane (HEUR) system. The lifetime of the hydrophobic junction of the HASE polymer increases with temperature due to the increase in the entropy of the system. However, the structural relaxation time decreases with temperature, caused by the enhanced Brownian dynamics of polymer chains. The relaxation behavior of HASE polymers is either governed by the lifetime of the hydrophobic junction, the structural relaxation time, or a combination of both, depending on the degree of network formation and temperature. Temperature studies indicated that the transient network theory proposed by Tanaka and Edwards is inadequate for describing the activation process of hydrophobic junctions in the HASE associative polymer. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 604–612, 2004
Influence of turbulent mixing on fast polymerization reactions
Authors: Minsker Karl S. , Zakharov Vadim P. , Berlin Alexander Al. , Zaikov Gennadi E.
Published: August 2004

Investigations on development of a macrokinetics approach were generalized to the analysis of fast chemical reactions, mainly using cationic polymerization of isobutylene as an example, which is a new class of liquid‐phase processes. The removal of diffusional constraints on polymer synthesis, by intensification of turbulent mixing in the reaction zone, makes it possible to calculate the kinetic parameters of polymerization and polymer‐analogous reactions, to optimize the molecular characteristics of polymeric products obtained, and to control the character of the process as a whole. The laws pertaining to the progression of fast processes are considered for the synthesis of separate polymers, in particular stereoregular polydienes, ethylene–propylene copolymers, and chlorobutyl rubber. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 613–624, 2004
A gradient structure formed in injection‐molded polycarbonate in situ hybrid composites and its corresponding performances
Authors: Zhang Baoqing , Zhang Jun , He Jiasong
Published: August 2004

Three polycarbonate (PC) composites that were reinforced, respectively, with liquid crystalline polymer (LCP), glass fibers, and both of them were prepared by a single injection‐molding process. The role of LCP in improving the processibility of the composites was characterized by torque measurement test. The transitions of LCP morphology in two‐ and three‐component composites were investigated by using polarizing optical microscopy and scanning electron microscopy. The micrographs showed a skin–core gradient structure in all three systems investigated, and the addition of glass fiber to the PC/LCP blend affected the morphological transition and content distribution of dispersed LCP phase through the thickness of the injection‐molded samples. These results were correlated well with the measurements of tensile mechanical properties and dynamic mechanical analysis. How to fully use the dispersed LCP phase in PC in situ hybrid composites was discussed for the thickness change of core layer and the heterogeneous distribution of more LCP in the core. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 625–634, 2004
Use of a methylolated softwood ammonium lignosulfonate as partial substitute of phenol in resol resins manufacture
Authors: Alonso M. V. , Oliet M. , Rodríguez F. , Astarloa G. , Echeverría J. M.
Published: August 2004

The synthesis of lignin‐phenol‐formaldehyde (LPF) was studied to determine its optimum operating conditions. The lignin proposed as phenol substitute has been the softwood ammonium lignosulfonate. The resin synthesis was optimized by varying the methylolated lignosulfonate content, 18–52%; the sodium hydroxide to phenol‐modified lignosulfonate molar ratio, 0.3–0.94; and the formaldehyde to phenol‐modified lignosulfonate molar ratio, 1.1–3.5. The parameters employed in the characterization of LPF resins were free phenol, free formaldehyde, gel time, alkaline number, viscosity, pH, solid content, and chemical structure changes. The properties of LPF resin comply with the requirements for its utilization in plywood manufacture. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 643–650, 2004
On the modeling of the dynamic‐elastic modulus for polymer materials under isochronal conditions
Authors: Reyes‐Melo E. , Martínez‐Vega J. , Guerrero‐Salazar C. , Ortiz‐Méndez U.
Published: August 2004

A model based on the concept of fractional calculus is proposed for the description of the dynamic elastic modulus, E* = E′ + iE″, of polymer materials. This model takes into account three relaxation phenomena (α, β, and γ) under isochronal conditions. The differential equations obtained for this model have derivatives of fractional order between 0 and 1. Applying the Fourier transform to the fractional differential equations and associating each relaxation mode to cooperative or noncooperative movements, E*(iω,T) was evaluated. The isochronal diagrams of E′ and E″ clearly show three relaxation phenomena, each of them is manifested by a decrease of E′ when temperature increases. This decrease is associated with a maximum in E″(T) diagram for each relaxation mode. The shape of the three peaks (three maxima in E″(T) diagrams) depends of the fractional orders of this new fractional model. The mathematical description obtained of E* corresponds to a nonexponential relaxation behavior often encountered in the dynamics of polymer systems having three relaxation phenomena. This model will enable us to analyze the viscoelastic behavior of polymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 657–670, 2004
Crystallinity and oxygen transport properties of PET bottle walls
Authors: Liu R. Y. F. , Hu Y. S. , Schiraldi D. A. , Hiltner A. , Baer E.
Published: August 2004

Oxygen transport was coupled with other methods to study the relationship of gas barrier to solid state structure in the PET blown bottle wall. Commercial 2‐L carbonated soft drink bottles blown under different process conditions were studied. Crystallinity determinations from heat of melting, density, glycol trans fraction, and oxygen solubility were compared. The reasons for lack of correlation between conventional crystallinity methods based on heat of melting and density were elucidated, and neither was found to be reliable. An alternative approach to determining crystallinity based on oxygen solubility gave reliable results and revealed fundamental characteristics of the amorphous phase, such as amorphous phase density and amorphous phase oxygen solubility. Dedensification of the amorphous phase was responsible for higher oxygen permeability of bottle walls processed under conditions of higher thermal exposure (temperature/time) despite the parallel increase in volume fraction of impermeable crystals. The strong dependence of dedensification on process temperature was explained in terms of the temperature–volume relationship of the amorphous phase. A low process temperature minimized amorphous phase dedensification and delivered a bottle wall with the best oxygen barrier. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 671–677, 2004
Carbon black effect on the acoustic properties of nitrile butadiene rubber
Authors: Jung Kyung‐Il , Yoon Suk Wang , Sung Shi‐Joon , Park Jung‐Ki
Published: August 2004

Acoustic and mechanical properties of nitrile butadiene rubbers (NBR) with the variation of the carbon black contents were investigated. All the composition contents except carbon black were kept constant in the specimens. Acoustic measurements were performed in the frequency range of 300–800 kHz. Increase of the carbon black contents in the rubber resulted in an increase of the mechanical properties such as density, hardness, tensile strength, and glass transition temperature. The sound speed and attenuation in the specimen were mainly affected by the carbon black. The sound speed increased with the carbon black content and depended on the square root of the ratio of hardness to density. However, the sound attenuation was not affected by the carbon black content variation but by the existence of the carbon black. The results with carbon black content variation were also compared with those of the sulfur content variation having a fixed carbon black content (K. I. Jung et al., J Appl Polym Sci 85, 2764–2771, 2002). These results show that the variation of acoustic properties can be used to nondestructively evaluate mechanical properties and to estimate the carbon black content variation in NBR. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 678–683, 2004
Effect of hydrotalcite on the physical properties and drug‐release behavior of nanocomposite hydrogels based on poly[acrylic acid‐co‐poly(ethylene glycol) methyl ether acrylate] gels
Authors: Lee Wen‐Fu , Chen Yung‐Chu
Published: August 2004

A series of nanocomposite hydrogels used for bioadhesive were prepared from acrylic acid, poly(ethylene glycol) methyl ether acrylate, and intercalated hydrotalcite (HT) by photopolymerization. The microstructures of the intercalated HT and sample gels were identified by X‐ray diffraction (XRD). The results showed that the swelling ratio for these nanocomposite hydrogels increased with an increase in HT, but the gel strength and adhesive force for these gels decreased with an increase in HT. The XRD results indicated that the exfoliation of intercalated HT was achieved in the xerogels and swollen gels. Finally, the drug‐release behaviors for these gels were also examined. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 692–699, 2004
Study on pancreatic lymphatics in nonobese diabetic mouse with prevention of insulitis and diabetes by adjuvant immunotherapy
Authors: Qu Peng , Ji Rui‐Cheng , Shimoda Hiroshi , Miura Masahiro , Kato Seiji
Published: August 2004

The present study has investigated the relationship between pancreatic lymphatics, infiltrating cells, and insulitic development after a single injection of complete Freund's adjuvant (CFA) given at an early age in the nonobese diabetic (NOD) mice. No CFA‐treated NOD mice developed hyperglycemia, whereas most CFA‐untreated mice died of diabetes at the age of 20–30 weeks. In untreated NOD mice, the increased infiltration of dendritic cells (DCs) and T‐lymphocytes into the pancreatic islets appeared to be consistent with the increased expression of the secondary lymphoid chemokine (CCL21) and CD31 by the endothelial cell lining of inter‐ and intralobular lymphatics. As the infiltration became severe, the reaction products of CCL21 and CD31 were distributed in the nucleus and cytoplasm of lymphatic endothelial cells (LECs), through which DCs and T‐lymphocytes migrated frequently. Administration of CFA reduced the number of infiltrating DCs and T‐lymphocytes, but did not affect macrophage infiltration. The peri‐insulitis occurred in numerous islets of CFA‐treated NOD mice without the appearance of the intraislet infiltration and islet‐associated lymphoid‐like tissues. Furthermore, significant suppression of CCL21 and CD31 was demonstrated on the infiltrating cells to the islets and islet‐associated lymphatics. The abluminal endothelial cell lining of lymphatic vessels exhibited weaker immunoreactivity of CCL21 and CD31 in comparison with the luminal surfaces. The reaction product of 5′‐nucleotidase (5′‐Nase) was evenly deposited on LECs, which were the absence of open junctions, cytoplasmic protrusions, and vesicles. CFA treatment influenced the migratory processes of the infiltrating cell, which were closely related with structural changes of pancreatic lymphatics and inhibited insulitic development. These findings suggest that in CFA‐treated NOD mice, the suppression of insulitis and prevention of diabetes are secondary to the functional modulation of pancreatic lymphatics and infiltrating cells. © 2004 Wiley‐Liss, Inc.
Immunohistochemical localization of periostin in tooth and its surrounding tissues in mouse mandibles during development
Authors: Suzuki Hironobu , Amizuka Norio , Kii Isao , Kawano Yoshiro , Nozawa‐Inoue Kayoko , Suzuki Akiko , Yoshie Hiromasa , Kudo Akira , Maeda Takeyasu
Published: August 2004

Previous reports have shown expression of immunoreactivity for periostin, originally identified as osteoblast‐specific factor‐2, in the periosteum and periodontal ligament. However, the developmental changes in its expression and the detailed immunolocalization have remained veiled. The present study was undertaken to examine the spatiotemporal expression of this protein in teeth and their associated tissues of mice during development at light and electron microscopic levels. In tooth germs at cap stage, periostin immunoreactivity was recognizable in the interface between inner enamel epithelium and preodontoblasts as well as in the mesenchymal tissues around cervical loop. Dental follicles around tooth germs at bell stage localized periostin immunopositivity in addition to the immunopositive areas observed in cap‐staged tooth germs, although the functional significance of periostin has remained unclear in tooth development. Furthermore, periostin immunoreactivity was also found in the alveolar bone surface. In the incisors of both 7‐ and 21‐day‐old mice, immunoreaction for periostin was discernible in the lingual periodontal ligament and labial fibrous tissue adjacent to the papillary layer. After postnatal day 7, immunoreaction for periostin came to be restricted to the fibrous bundles in the periodontal ligament in accordance with the organization of the periodontal fibers, indicating its localization matched the morphogenesis of the periodontal ligament. Immunoelectron microscopic observation of the mature periodontal ligament verified the localization of periostin between the cytoplasmic processes of periodontal fibroblasts and cementoblasts and the adjacent collagen fibrils. Our findings suggest that periostin is involved at the sites of the cell‐to‐matrix interaction, serving as adhesive equipment for bearing mechanical forces, including occlusal force and tooth eruption. © 2004 Wiley‐Liss, Inc.
Dialysis‐associated systemic fibrosis (nephrogenic fibrosing dermopathy): Study of inflammatory cells and transforming growth factor β1 expression in affected skin
Authors: Jiménez Sergio A. , Artlett Carol M. , Sandorfi Nora , Derk Chris , Latinis Kevin , Sawaya Heloisa , Haddad Richard , Shanahan Joseph C.
Published: August 2004

Objective

Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrotic disorder occurring in individuals with end‐stage renal disease (ESRD). The aim of the present study was to describe the clinical and histopathologic features of 9 new cases and to characterize the inflammatory cells and expression of transforming growth factor β1 (TGFβ1) in affected skin.

Methods

Clinical and laboratory assessments, including serology and pulmonary function studies, were performed in 9 patients undergoing long‐term dialysis (8 hemodialysis; 1 peritoneal dialysis) for ESRD of diverse etiologies. Skin, fascia, striated muscles, lungs, and heart were examined by histopathology. Inflammatory cells were characterized by immunophenotyping using specific monoclonal antibodies. TGFβ1 expression was determined by in situ hybridization.

Results

All patients displayed cutaneous features resembling both systemic sclerosis and diffuse fasciitis, with severe loss of motion and flexion contractures in multiple joints. Six patients displayed woody induration of the muscles of the legs, thighs, and forearms. Five of the 6 patients with lung involvement had a reduced diffusion capacity for carbon monoxide on pulmonary function testing. Marked elevations of the erythrocyte sedimentation rate and/or C‐reactive protein level were found in 6 patients. Antinuclear antibodies were present at low titers in 4 patients. Histopathologic studies indicated that in addition to the dermis, the fibrotic process affected the subcutaneous tissue, fascia, striated muscles, lungs, and myocardium. Large numbers of CD68+/factor XIIIa+ dendritic cells and increased expression of TGFβ1 were found in affected skin and muscle.

Conclusion

Our findings indicate that the fibrotic process of NFD affects not only the dermis, but also the subcutaneous tissues, fascia, and other organs, including striated muscles, heart, and lungs. We therefore believe this is a systemic fibrosing process, and we suggest that dialysis‐associated systemic fibrosis would be a better term for the condition.
Predictors and outcome of renal flares after successful cyclophosphamide treatment for diffuse proliferative lupus glomerulonephritis
Authors: Mok Chi Chiu , Ying King Yee , Tang Sydney , Leung Chung Ying , Lee Ka Wing , Ng Woon Leung , Wong Raymond Woon Sing , Lau Chak Sing
Published: August 2004

Objective

To study the incidence, predictors, and outcome of renal flares after successful cyclophosphamide (CYC) treatment for diffuse proliferative glomerulonephritis (DPGN) in patients with systemic lupus erythematosus (SLE).

Methods

Between 1988 and 2001, patients with biopsy‐proven SLE DPGN who were treated initially with prednisone and CYC were studied. Those who responded to CYC were followed up for the occurrence of renal flares. The cumulative risk, predictors, and outcome of renal flares were evaluated.

Results

We studied 189 patients (167 women; and 22 men) with SLE DPGN. All were initially treated with prednisone and CYC (49% orally; 51% by intravenous pulse). At the last dose of CYC, 103 patients (55%) and 52 patients (28%) had achieved complete and partial renal responses, respectively. Azathioprine (AZA) was given as maintenance therapy in 117 patients (75%). After a mean followup of 96.5 months, 59 patients (38%) experienced renal flares (42% nephritic; 58% proteinuric). The median time to relapse was 32 months. The cumulative risk of renal flare was 28% at 36 months and 44% at 60 months. Independent predictors of nephritic flares were persistently low C3 levels after CYC treatment and absence of AZA maintenance therapy. At the last clinic visit, 16 patients (10.3%) had developed doubling of the serum creatinine level (cumulative risk of creatinine doubling 7.4% at 5 years after renal biopsy and 14.3% at 10 years). Ten patients (6.5%) developed end‐stage renal disease (ESRD). Renal survival rates at 5 and 10 years were 94.9% and 87.5%, respectively. Increasing histologic chronicity scores, failure to achieve complete response, persistent hypertension after CYC treatment, and nephritic renal flares were unfavorable factors for doubling of the serum creatinine level and for ESRD by univariate analysis. The occurrence of nephritic flares was the only predictor of creatinine doubling by Cox regression analysis.

Conclusion

In patients with SLE DPGN, renal flares are common despite initial responses to CYC. Nephritic renal flares are associated with a decline in renal function. Maintenance therapy with AZA reduces, but does not completely prevent, renal flares. More effective maintenance treatment for SLE DPGN after an initial response to CYC should be evaluated.
Identification of two novel female‐specific non–major histocompatibility complex loci regulating collagen‐induced arthritis severity and chronicity, and evidence of epistasis
Authors: Meng Hsiang‐Chi , Griffiths Marie M. , Remmers Elaine F. , Kawahito Yutaka , Li Wentian , Neisa Roberto , Cannon Grant W. , Wilder Ronald L. , Gulko Pércio S.
Published: August 2004

Objective

To identify additional sex‐specific and epistatic quantitative trait loci (QTL) regulating collagen‐induced arthritis (CIA) severity overall, as well as within different stages during the disease course, in an intercross between major histocompatibility complex–identical inbred rat strains DA/Bkl (susceptible) and ACI/Hsd (resistant).

Methods

Arthritic male (DA × ACI)F2 intercross offspring (n = 143) were analyzed separately from the females (n = 184). Phenotypic extremes (maximum arthritis scores [MAS]) were genotyped and used for QTL analysis. All 327 rats were genotyped with the simple sequence‐length polymorphism (SSLP) markers closest to the peak of Cia7 and Cia10, the major loci previously identified in this intercross, and with SSLPs covering chromosomes 12 and 18. Phenotypes studied were disease onset, arthritis severity scores on days 14–39, MAS, mean and cumulative arthritis scores, delayed‐type hypersensitivity, and antibody responses to rat type II collagen.

Results

A new female‐specific arthritis‐severity recessive locus was identified on rat chromosome 12 (Cia25), with a maximum effect observed on day 28 (logarithm of odds [LOD] 4.7). The homozygous DA genotype at Cia25 was associated with a 45% higher median arthritis score in females. Sequencing analyses of the Cia25 candidate gene Ncf1 revealed polymorphisms between DA and ACI. The previously identified locus, Cia10, was found to be male‐specific. A 2‐locus interaction model analysis identified a novel recessive chromosome 18 QTL, Cia26, which was dependent on Cia7, with its maximum effect observed at later stages during the disease course (peak LOD score of 3.6 for arthritis scores on day 39).

Conclusion

This study identified 2 novel female‐specific loci, and 1 male‐specific locus. Cia25 regulates MAS and disease severity during the mid‐to‐late stages of the disease course and may be accounted for by Ncf1 polymorphisms. Cia26 is in epistasis with Cia7 and regulates later stages of disease, suggesting an involvement in disease perpetuation and/or chronicity.
Induction of RANKL expression and osteoclast maturation by the binding of fibroblast growth factor 2 to heparan sulfate proteoglycan on rheumatoid synovial fibroblasts
Authors: Nakano Kazuhisa , Okada Yosuke , Saito Kazuyoshi , Tanaka Yoshiya
Published: August 2004

Objective

Rheumatoid arthritis (RA) is characterized by progressive joint destruction. The aim of this study was to clarify the relevance of RA synovial fibroblasts (RASFs) and fibroblast growth factor 2 (FGF‐2), which is produced abundantly by RASFs, to the osteoclastogenesis and bone resorption in RA.

Methods

Synovial fibroblasts were prepared from the synovial tissues of 10 patients with active RA and 7 patients with osteoarthritis (OA). The expression of RANKL, intercellular adhesion molecule 1 (ICAM‐1), FGF receptor 1 (FGFR‐1), and heparan sulfate proteoglycan (HSPG) on synovial fibroblasts was measured by FACScan. Osteoclast formation in cocultures of RASFs and peripheral blood mononuclear cells (PBMCs) was evaluated by tartrate‐resistant acid phosphatase staining and a pit‐formation assay using dentin slices.

Results

FGF‐2 induced the expression of both RANKL and ICAM‐1 on RASFs more so than on OA synovial fibroblasts (OASFs). FGF‐2–induced up‐regulation of RANKL and ICAM‐1 was inhibited by anti–FGF‐2 antibody. Although FGFR‐1 was equally expressed on RASFs and OASFs, HSPG was highly expressed on RASFs. Up‐regulation of RANKL by FGF‐2 on RASFs was diminished by the removal of heparan sulfate with heparitinase. Osteoclast formation from PBMCs induced by RASFs was inhibited by the addition of either heparitinase, anti–ICAM‐1 antibody, anti–FGF‐2 antibody, or osteoprotegerin. FGF‐2–induced RANKL on RASFs and osteoclast formation were suppressed by an inhibitor of ERK.

Conclusion

FGF‐2 was transferred to FGFR‐1 through binding to HSPG, which is characteristically expressed on RASFs, resulting in RANKL‐ and ICAM‐1–mediated maturation of osteoclasts via ERK activation. Thus, we propose that FGF‐2 not only augments the proliferation of RASFs, but also is involved in osteoclast maturation, which leads to bone destruction in RA.