bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo Pharmacokinetics and Pharmacodynamics of a New Triazole, Voriconazole, in a Murine Candidiasis Model
Authors: Andes D. , Marchillo K. , Stamstad T. , Conklin R. 
Published: September 2003

ABSTRACT

In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated
Candida albicans
infection to similarly characterize the PK-PD of the new triazole voriconazole. PK and PD parameters (percentage of time that the concentration remains above the MIC [
T
> MIC], AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by the organism number in kidney cultures after 24 h of therapy. Voriconazole kinetics and protein binding were studied in infected neutropenic mice. Peak level/dose and AUC/dose values ranged from 0.1 to 0.2 and 0.1 to 0.7, respectively. The serum elimination half-life ranged from 0.7 to 2.9 h. The level of protein binding in mouse serum was 78%. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (
R
2
for AUC/MIC ratio = 82%,
R
2
for peak level/MIC ratio = 63%,
R
2
for
T
> MIC = 75%). Similar studies were conducted with nine additional
C. albicans
isolates with various voriconazole susceptibilities (MICs, 0.007 to 0.25 μg/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The voriconazole free drug AUC/MIC ratios were similar for all of the organisms studied (range, 11 to 58; mean ± standard deviation, 24 ± 17 [
P
= 0.45]). These AUC/MIC ratios observed for free drug are similar to those observed for other triazoles in this model.
Sensitive Assay for Antifungal Activity of Glucan Synthase Inhibitors That Uses Germ Tube Formation in
Candida albicans
as an End Point
Authors: Brayman Timothy G. , Wilks John W. 
Published: September 2003

ABSTRACT

We implemented a simple, sensitive, objective, and rapid cellular assay to reveal the antifungal activity of a novel class of glucan synthase inhibitors. The assay, especially useful for early drug discovery, measures the transformation of
Candida albicans
from the yeast form to the hyphal form. Test compounds were ranked by potency (50% inhibitory concentration) and efficacy (percent inhibition of germ tube formation); the intra-assay coefficients of variation for these parameters were 17 and 5%, respectively. The germ tube formation assay proved useful for the early-stage antifungal characterization of a novel class of glucan synthase inhibitors discovered at Pharmacia. Drug concentrations required in this assay to inhibit germ tube formation were lower for 90% of the novel compounds than the concentrations required to determine MICs. The method may have utility for other mechanistic classes of antifungal compounds during the hit-to-lead transition of drug discovery.
Virucidal Efficacy of Soap and Water against Human Immunodeficiency Virus in Genital Secretions
Authors: Li Jonathan Z. , Mack Elizabeth C. , Levy Jay A. 
Published: September 2003

ABSTRACT
A common bar soap and tap water solution was able to demonstrate a 30-fold human immunodeficiency virus (HIV) inactivation and a 57 to 87% reduction in viable peripheral blood mononuclear cells in a mixture of cervicovaginal lavage fluid and seminal fluid. These observations indicate that soap and water might be used to inactivate HIV and HIV-infected cells in genital secretions.
Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns
Authors: De Wit Dominique , Olislagers Véronique , Goriely Stanislas , Vermeulen Françoise , Wagner Hermann , Goldman Michel , Willems Fabienne 
Published: September 2003

AbstractPlasmacytoid dendritic cells (pDCs) respond to unmethylated cytosine-phosphate-guanosine (CpG) motifs present in bacterial DNA or unmethylated synthetic oligodeoxynucleotides (CpG). In order to assess the function of pDCs in human newborns, interferon-α (IFN-α) production induced by CpG 2216 and phenotypic maturation of pDCs in response to CpG 2006 were compared in cord blood and adult blood. We first observed that neonatal pDCs displayed decreased up-regulation of CD80, CD83, CD86, and CD40, whereas HLA-DR and CD54 up-regulation did not differ significantly between adults and neonates. We then found that the production of IFN-α in response to CpG was dramatically impaired in cord blood. This neonatal defect was detected both at protein and mRNA levels and was still present in blood of 4-day-old babies. Further experiments on enriched pDCs confirmed that these cells are intrinsically deficient in CpG-induced IFN-α production at birth. These findings might be relevant to the increased susceptibility of human newborns to infections as well as to the use of CpG oligodeoxynucleotides as vaccine adjuvants in the neonatal period. (Blood. 2004;103:1030-1032)
Chronic obstructive pulmonary disease as a systemic disease: an epidemiological perspective: Fig. 1.—
Authors: Andreassen H. , Vestbo J. 
Published: September 2003

Chronic obstructive pulmonary disease (COPD) has been increasingly recognised as a systemic disease. The hormonal, metabolic and musculoskeletal implications of the generalised processes involving oxidative stress, inflammatory mediators, cytokines, and endocrine hormones have only begun to be understood.Only a few studies have looked into the epidemiology of inflammatory markers in patients with chronic obstructive pulmonary disease. Common extrapulmonary effects of chronic obstructive pulmonary disease include skeletal muscle dysfunction, wasting and osteoporosis. The resulting effects of a systemic inflammation can be measured at specific extrapulmonary organs such as skeletal muscle or in more general terms using body composition, body weight or derived measures, and only a few studies have set the parameters in an epidemiological context. Nevertheless, these studies indicate an association between inflammatory markers and forced expiratory volume in one second not only in subjects with severe chronic obstructive pulmonary disease. Also, it is increasingly clear that systemic markers in chronic obstructive pulmonary disease have important effects on prognosis.
The Thyroid Hormone Receptor-Associated Protein TRAP220 Is Required at Distinct Embryonic Stages in Placental, Cardiac, and Hepatic Development
Authors: Landles Christian , Chalk Sara , Steel Jennifer H. , Rosewell Ian , Spencer-Dene Bradley , Lalani El-Nasir , Parker Malcolm G. 
Published: September 2003

AbstractRecent work indicates that thyroid hormone receptor-associated protein 220 (TRAP220), a subunit of the multiprotein TRAP coactivator complex, is essential for embryonic survival. We have generated TRAP220 conditional null mice that are hypomorphic and express the gene at reduced levels. In contrast to TRAP220 null mice, which die at embryonic d 11.5 (E11.5), hypomorphic mice survive until E13.5. The reduced expression in hypomorphs results in hepatic necrosis, defects in hematopoiesis, and hypoplasia of the ventricular myocardium, similar to that observed in TRAP220 null embryos at an earlier stage. The embryonic lethality of null embryos at E11.5 is due to placental insufficiency. Tetraploid aggregation assays partially rescues embryonic development until E13.5, when embryonic loss occurs due to hepatic necrosis coupled with poor myocardial development as observed in hypomorphs. These findings demonstrate that, for normal placental function, there is an absolute requirement for TRAP220 in extraembryonic tissues at E11.5, with an additional requirement in embryonic tissues for hepatic and cardiovascular development thereafter.
Phylogeny and cloning of ion transporters in mosquitoes
Authors: Pullikuth Ashok K. , Filippov Valeri , Gill Sarjeet S. 
Published: September 2003

SUMMARYMembrane transport in insect epithelia appears to be energized through proton-motive force generated by the vacuolar type proton ATPase (V-ATPase). However, secondary transport mechanisms that are coupled to V-ATPase activity have not been fully elucidated. Following a blood meal, the female mosquito regulates fluid and ion homeostasis through a series of characteristic behaviors that require brain-derived factors to regulate ion secretion. Despite the knowledge on the behaviors of the mosquito, little is known of the targets of several factors that have been implicated in cellular changes following a blood meal. This review discusses current models of membrane transport in insects and specific data on mosquito ion regulation together with the molecular aspects of membrane transport systems that are potentially linked to V-ATPase activity, which collectively determine the functioning of mosquito midgut and Malpighian tubules. Ion transport mechanisms will be discussed from a comparative physiology perspective to gain appreciation of the exquisite mechanisms of mosquito ion regulation.
Cage versus tricortical graft for cervical interbody fusion
Authors: Siddiqui A. A. , Jackowski A. 
Published: September 2003

We conducted a prospective, randomised study of 42 cervical interbody fusions undertaken with either an autologous tricortical graft or a cage. The factors assessed in the two groups were: (1) time taken to achieve fusion; (2) neck disability index; (3) pain score; (4) interbody height ratio; (5) interbody angle and (6) the influence of smoking on fusion. No statistical difference was seen in the time taken to achieve fusion, neck disability index, interbody height ratio, or interbody angles. Smoking did not have any effect on the fusion process. The pain score was significantly lower in the tricortical graft group at six months. We conclude that both methods of fusion give similar results, although tricortical graft fusion is cheaper than cage fusion, and is more effective in reducing the pain score.
Incidence of clostridial contamination in donors’ musculoskeletal tissue
Authors: Malinin T. I. , Buck B. E. , Temple H. T. , Martinez O. V. , Fox W. P. 
Published: September 2003

Reports of infection by Clostridium sordellii associated with allograft transplantation have generated considerable interest. We report our experience in recognising clostridial contamination in cadaver donors of musculoskeletal tissue. Tissues obtained from 795 consecutive donors were excised using standard surgical techniques. Samples of blood and bone marrow were also obtained. Donors with clostridia recovered from any site were matched with the preceding donor without clostridia as a procedural and environmental control. The histories of the donors were analysed to determine which variables had a relationship to contamination by running a contingency table and chi-squared test on the variables against the event of a donor being contaminated. Sixty-four donors (8.1%) had clostridia, most commonly C. sordellii. Clostridia were grown from the blood, marrow and tissue samples of 52, 37 and 30 donors, respectively. In eight cases, they were cultured from the tissue samples alone. There was no significant difference in age or gender between the contaminated donors and the control group. Open wounds were more common in control than in contaminated subjects, but only death by drowning in the contaminated group was statistically significant (p = 0.02). The time between death and the excision of tissue which was contaminated (16 hrs 10 mins) compared with control (11 hrs 10 mins) donors was also significant (p < 10−6). We conclude that there is clostridial contamination in a significant number of tissue donors, particularly with increasing time between death and tissue excision. Among the most commonly encountered species is C. sordellii. Multiple microbiological cultures, including blood, are necessary in order to identify clostridial contamination.
Mathematical model for the pultrusion of blocked PU–UP matrix composites
Authors: Chen Chin‐Hsing , Yen Chih‐Chao 
Published: September 2003

AbstractThe thermokinetic behavior of blocked polyurethane (PU)–unsaturated polyester (UP)–based composites during the pultrusion of glass‐fiber‐reinforced composites was investigated utilizing a mathematical model that accounted for the heat transfer and heat generation during curing. The equations of continuity and energy balance, coupled with a kinetic expression for the curing system, were solved using a finite difference method to calculate the temperature profiles and conversion profiles in the thickness direction in a rectangular pultrusion die. A kinetic model, dP/dt = A exp(−E/RT)Pm(1 − P)n, was proposed to describe the curing behavior of a blocked PU–UP resin. Kinetic parameters for the model were obtained from dynamic differential scanning calorimetry scans using a multiple regression technique, which was able to predict the effects of processing parameters on the pultrusion. The effects of processing parameters including pulling speed, die wall temperature, and die thickness on the performance of the pultrusion also were evaluated. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1996–2002, 2003
Sulfur‐containing polymers: Effect of composition on melting behavior and crystallization kinetics of poly(butylene terephthalate)
Authors: Siracusa V. , Finelli L. , Lotti N. , Munari A. 
Published: September 2003

AbstractThe melting behavior and crystallization kinetics of poly(butylene terephthalate/thiodipropionate) (PBT) copolymers were investigated using the differential scanning calorimetry technique. Multiple endotherms typical of PBT were observed in the copolymers under investigation and were found to be influenced both by crystallization temperature (Tc) and composition. Wide‐angle X‐ray diffraction measurements permitted the identification of the crystalline structure of PBT in all the copolymers investigated. By applying the Hoffman–Weeks method, the equilibrium melting temperature of the copolymers was derived. Isothermal crystallization kinetics were analyzed according to Avrami's treatment. Values of the exponent n close to 3 were obtained, independent of Tc and composition, results in agreement with it being a crystallization process originating from predetermined nuclei and characterized by three‐dimensional spherulitic growth. The introduction of butylene thiodipropionate units was found to decrease the PBT crystallization rate. The heat of fusion (ΔHm) was correlated to the specific heat increment (Δcp) of samples of different degrees of crystallinity, and the results were interpreted based on there being an interphase, whose amount was found to increase as the sulfur‐containing unit content was increased. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2003–2009, 2003
Impact of H+ ion irradiation on Matrimid®. I. Evolution in chemical structure
Authors: Hu Ling , Xu Xinglong , Ilconich Jeffery B. , Ellis S. , Coleman Maria 
Published: September 2003

AbstractIon beam irradiation can be used to modify the structure and gas transport properties of glassy polymers. This is the first of two studies that focus on the impact of H+ ion irradiation on the structure and permeation properties of the polyimide Matrimid®. Specifically, the evolution in chemical structure after H+ irradiation over a range of fluences was analyzed using FTIR spectroscopy and dissolution studies. Although H+ ion irradiation at very low ion fluences induced little modification in the chemical structure, irradiation at relatively high ion fluences resulted in crosslinking of the irradiated films. The branched structure of the aliphatic methyl (CH3) was the most sensitive to the H+ ion irradiation. The para‐disubstituted aromatic ring showed the strongest resistance toward ion irradiation and required fairly high doses to induce degradation. Two potential crosslinking mechanisms related to the degradation of the aliphatic methyl and the benzophenone carbonyl were presented. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2010–2019, 2003
Crack growth and abrasion resistance of carbon black‐filled purified natural rubber vulcanizates
Authors: Rattanasom N. , Chaikumpollert O. 
Published: September 2003

AbstractThe influence of parameters contributing to rubber stiffness, including, crosslink density, hardness, and modulus, on the crack growth and abrasion resistance of carbon black‐filled purified natural rubber (PNR) vulcanizates as well as a whole natural rubber (WNR) vulcanizate counterpart or a control were elucidated. In addition, the tensile properties of PNR and WNR were also determined. PNR containing the same curative level as that of the control had lower stiffness and exhibited superior crack growth resistance. The results revealed that the improved crack growth resistance of PNR, compared to the control, was due to its lower crosslink density, hardness, and modulus. In addition, the tensile strength and abrasion resistance of PNR vulcanizates were not as sensitive as the crack growth resistance to the changes of their stiffness. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1793–1796, 2003
Arterialization of the portal vein improves hepatic microcirculation and tissue oxygenation in experimental cirrhosis
Authors: Yang W , Koti R , Glantzounis G , Davidson B R , Seifalian A M 
Published: September 2003

Abstract

Background
Arterialization of the portal vein (APV) has shown beneficial effects on liver regeneration and function in selected patients undergoing liver resection and transplantation. Whether APV improves liver perfusion and function in cirrhosis is unclear. This study investigated the effect of APV on hepatic haemodynamics and liver function in a rat model of cirrhosis.

Methods
Male Sprague–Dawley rats (250–300 g) were divided into three groups: normal controls (n = 7), cirrhosis with sham laparotomy (sham; n = 7) and cirrhosis with APV (APV; n = 9). Portal venous blood flow, portal vein pressure and hepatic parenchymal microcirculation (HPM) were measured before and after APV. Hepatic parenchymal oxygenation was assessed by near-infrared spectroscopy and hepatocellular injury by standard liver function tests. Measurements were taken at baseline, after APV and 7 days after surgery.

Results
APV increased portal blood flow and pressure in cirrhotic rats without altering intrahepatic portal resistance. APV increased the HPM in cirrhotic rats by a mean(s.e.m.) of 28·5(0·1) per cent on day 0 and 54·6(0·1) per cent by day 7 (P = 0·001). Liver tissue oxygenation was increased by APV and the plasma γ-glutamyltranspeptidase level was reduced (mean(s.e.m.) 6·0(0·5) versus 3·8(0·3) units/l before and after APV respectively; P = 0·006) at day 7.

Conclusion
APV increases portal blood flow, tissue perfusion and oxygenation in cirrhosis.
Management of accessory breast tissue in the axilla
Authors: Down S , Barr L , Baildam A D , Bundred N 
Published: September 2003

Abstract

Background
Accessory breasts occur in 0·4–6 per cent of women. They may be asymptomatic or cause pain, restriction of arm movement, cosmetic problems or anxiety. It is currently recommended that all accessory breasts be removed surgically but complications following this procedure have been poorly documented.

Methods
All patients who presented with axillary accessory breasts between July 1999 and October 2000 were identified from a computer database. A retrospective review of patients listed for excision of accessory breast tissue was undertaken to determine any postoperative complications.

Results
Women with axillary accessory breasts represented 0·5 per cent of all new referrals. A total of 28 women (80 per cent of those diagnosed) had surgery. Eleven patients experienced postoperative complications; the majority followed operations performed by a trainee.

Conclusion
Excision of accessory axillary breast tissue was associated with significant morbidity.
Glutamate receptors at bipolar synapses in the inner plexiform layer of primate retina: Light microscopic analysis
Authors: Grünert Ulrike , Lin Bin , Martin Paul R. 
Published: September 2003

AbstractAt least 10 different types of bipolar cells have been distinguished in the primate retina. The axon terminals of these cells stratify in distinct strata in the inner plexiform layer and are involved in parallel pathways to distinct types of ganglion cells. Ionotropic glutamate receptor (GluR) subunits also show a stratified distribution in the inner plexiform layer. Here, we investigated whether different types of bipolar cells are associated with different types of ionotropic glutamate receptors in the inner retina of a New World primate, the common marmoset Callithrix jacchus. Vertical cryostat sections through central retina were double labeled with immunohistochemical markers for bipolar cell types and with antibodies to α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor subunits GluR1 to 4, kainate receptor subunits GluR6/7, and the NR1C2′ subunit of the N‐methyl‐D‐aspartate (NMDA) receptor. The axon terminals of bipolar cell types were reconstructed from confocal sections, and the colocalized immunoreactive puncta were quantified. For all bipolar cell types, immunoreactive puncta for the AMPA receptor subunits GluR2, 2/3, and 4 were colocalized at highest densities, whereas GluR1‐immunoreactive puncta were expressed at very low densities. The kainate receptor subunits GluR6/7 were predominantly associated with diffuse bipolar (DB6) and rod bipolar cells. The NMDA receptor subunit NR1C2′ was specifically colocalized with flat midget and DB3 axons. These findings suggest that rod and cone bipolar cell types contribute to multiple but distinct glutamate receptor pathways in primate retina. J. Comp. Neurol. 466:136–147, 2003. © 2003 Wiley‐Liss, Inc.
Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses
Authors: Tsushima Fumihiko , Iwai Hideyuki , Otsuki Noriko , Abe Masaaki , Hirose Sachiko , Yamazaki Tomohide , Akiba Hisaya , Yagita Hideo , Takahashi Yuzo , Omura Ken , Okumura Ko , Azuma Miyuki 
Published: September 2003

AbstractProgrammed death‐1 (PD‐1) and its ligands, B7‐H1/PD‐L1 and B7‐DC/PD‐L2, are new CD28‐B7 family members that may be involved in the regulation of immune responses. We examined the roles of these molecules in mouse hapten‐induced contact hypersensitivity (CH). Administration of anti‐PD‐1 mAb at sensitization significantly enhanced and prolonged ear swelling. Treatment with anti‐B7‐H1 mAb, but not anti‐B7‐DC mAb, also enhanced CH reactions. The anti‐PD‐1 mAb treatment at sensitization significantly increased the T cell number of draining lymph nodes (DLN). B7‐H1 was induced on activated T cells and antigen‐presenting cells (APC) in the skin and the DLN, whereas B7‐DC expression was restricted to dendritic cells (DC) in the dermis and the DLN. A particular subset of DC, B7‐H1+B7‐DC–CD86low, was found in sensitized DLN. The blockade of B7‐H1, but not B7‐DC, dramatically enhanced the initial T cell proliferative responses against hapten‐pulsed DLN APC, suggesting the preferential contribution of B7‐H1 to the T cell‐APC interaction. Our results demonstrate the regulatory role of PD‐1 and the differential roles of B7‐H1 and B7‐DC in hapten‐induced immune responses. The PD‐1‐B7‐H1 pathway may play a unique role in regulating inflammatory responses.