bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study
Authors: Cohen Pinchas , Rogol Alan D. , Howard Campbell P. , Bright George M. , Kappelgaard Anne-Marie , Rosenfeld Ron G. 
Published: March 2007

Abstract
Context: Weight-based dosing of GH is the standard of care for short children, although IGF-I is thought to be the main mediator of GH actions on growth.
Objective: The objective of the study was to test whether IGF-I levels achieved during GH therapy are determinants of the growth responses to GH treatment.
Design: This was a 2-yr, open-label, randomized, IGF-I concentration-controlled trial. Prepubertal short children [n = 172, mean age 7.53 yr, mean height sd score (HT-SDS) −2.64] with low IGF-I levels (mean IGF-I SDS −3.56) were randomized to receive one of two GH dose-titration arms in which GH dosage was titrated to achieve an IGF-I SDS at the mean [IGF(low) group, n = 70] or the upper limit of the normal range [+2 SDS, IGF(high) group, n = 68] or to a comparison group of conventional GH dose of 40 μg/kg/d (n = 34).
Setting: The study was conducted in a multicenter, outpatient setting.
Primary Outcome Measure: Change in HT-SDS over 2 yr was measured.
Results: One hundred forty-seven patients completed the trial. Target IGF-I levels were achieved in the dose-titration arms within 6–9 months. The changes in HT-SDS were +1.0, +1.1, and +1.6 for conventional, IGF(low), and IGF(high), respectively, with IGF(high) showing significantly greater linear growth response (P &lt; 0.001, compared with the other two groups). The IGF(high) arm required higher doses (&gt;2.5 times) than the IGF(low) arm, and these GH doses were highly variable (20–346 μg/kg/d). Multivariate analyses suggested that the rise in the IGF-I SDS significantly impacted height outcome along with the GH dose and the pretreatment peak-stimulated GH level.
Conclusion: IGF-I-based GH dosing is clinically feasible and allows maintaining serum IGF-I concentrations within the desired target range. Titrating the GH dose to achieve higher IGF-I targets results in improved growth responses, although at higher average GH doses.
A Structural and in Vitro Characterization of Asoprisnil: A Selective Progesterone Receptor Modulator
Authors: Madauss Kevin P. , Grygielko Eugene T. , Deng Su-Jun , Sulpizio Anthony C. , Stanley Thomas B. , Wu Charlene , Short Steve A. , Thompson Scott K. , Stewart Eugene L. , Laping Nicholas J. , Williams Shawn P. , Bray Jeffrey D. 
Published: March 2007

AbstractSelective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone receptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT. This is the first report of steroid nuclear receptor crystal structures with ligand and corepressors. These structures show PR in a different conformation than PR complexed with progesterone (P4). We profiled asoprisnil in PR-dependent assays to understand further the PR-mediated mechanism of action. We confirmed previous findings that asoprisnil demonstrated antagonism, but not agonism, in a PR-B transfection assay and the T47D breast cancer cell alkaline phosphatase activity assay. Asoprisnil, but not RU486, weakly recruited the coactivators SRC-1 and AIB1. However, asoprisnil strongly recruited the corepressor NCoR in a manner similar to RU486. Unlike RU486, NCoR binding to asoprisnil-bound PR could be displaced with equal affinity by NCoR or TIF2 peptides. We further showed that it weakly activated T47D cell gene expression of Sgk-1 and PPL and antagonized P4-induced expression of both genes. In rat leiomyoma ELT3 cells, asoprisnil demonstrated partial P4-like inhibition of cyclooxygenase (COX) enzymatic activity and COX-2 gene expression. In the rat uterotrophic assay, asoprisnil demonstrated no P4-like ability to oppose estrogen. Our data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus.
Systemic Anticoagulant Prophylaxis for Central Catheter–Associated Venous Thrombosis in Cancer Patients
Authors: Chan Alexandre , Iannucci Andrea , Dager William E 
Published: March 2007

Objective: To review the literature regarding the incidence of thrombosis in cancer patients with central venous catheters (CVCs) and weigh the evidence supporting thromboprophylaxis in this patient population. Data Sources: Clinical literature was identified by searching MEDLINE (1966–February 2007) using the key search terms malignancy, cancer, catheters, prophylaxis, thrombosis, and central venous catheters. Study Selection and Data Extraction: An evaluation of retrospective and prospective clinical trials that studied the use of systemic anticoagulants (eg, warfarin, heparin, and low-molecular-weight heparin [LMWH]) to prevent thrombosis with CVCs was performed. Different patient populations, including those manifesting with solid tumor or hematologic malignancy and those undergoing hematopoietic stem cell transplant, were evaluated for this review. Data Synthesis: Thrombosis associated with CVCs is a common complication in cancer patients. Most CVC thrombosis will occur within 30 days after placement, with a majority within 8 days. The incidence may depend on the type of CVC and location of the catheter tip. Despite recommendations against the use of systemic anticoagulation for prophylaxis against CVC thrombosis, a potential role continues to be explored in selected settings. Several variables are noted between published clinical trials, making any comparisons difficult to determine whether any benefit exists. Generally, the use of mini-dose warfarin, LMWH, or low-dose unfractionated heparin did not consistently reach significance in reporting a reduction in CVC thrombosis. Conclusions: Available data do not support the routine use of anticoagulants for thromboprophylaxis to prevent CVC-related thrombosis. However, several inconsistencies can be found in the studies done to date. More studies are needed to identify subsets of cancer patients who are at higher risk of developing CVC thrombosis and may benefit from prophylactic systemic anticoagulation.
Bevacizumab for Neovascular Ocular Diseases
Authors: Lynch Shalini S , Cheng Christine M 
Published: March 2007

Objective: To review the efficacy and safety of off-label use of bevacizumab for neovascular ocular diseases. Data Sources: A PubMed (1966–January 2007) search was conducted using the terms human, intravitreal, bevacizumab, macular, and retinopathy. Meeting abstracts from the American Academy of Ophthalmology, Retina Society, Macula Society, and Association for Research in Vision and Ophthalmology were reviewed. Study Selection and Data Extraction: Controlled studies, unpublished reports involving 100 or more subjects, and published reports describing 5 or more subjects were reviewed. Only English-language articles were considered. Data Synthesis: Intravitreal bevacizumab has been evaluated in 133 patients in unpublished controlled studies. Over 3500 patients have been evaluated in open-label studies with duration of follow-up ranging from 3 months to 1 year. The most common use was neovascular age-related macular degeneration (AMD). Other conditions studied included diabetic retinopathy, pathological myopia, neovascular glaucoma, and macular edema due to diabetes, retinal vein occlusion, or uveitis. Statistically significant improvements in visual acuity, as well as decreases in retinal thickness and the extent of choroidal neovascularization, were noted. Intravitreal bevacizumab was well tolerated over the short term. In a registry compiling adverse experiences of 7113 intravitreal injections, rates of adverse events were less than or equal to 0.21%. Conclusions: Uncontrolled studies support a benefit of intravitreal bevacizumab in neovascular AMD for 3 months to 1 year. Low cost is a significant advantage of bevacizumab. Patients should discuss the potential risks and benefits of intravitreal bevacizumab and other available therapies with their physicians before receiving treatment. Controlled trials are needed to characterize the safely and efficacy of intravitreal bevacizumab and determine the optimal treatment regimen.
The CFTR-derived peptides as a model of sequence-specific protein aggregation
Authors: Bąk Daniel , Cutting Garry , Milewski Michał 
Published: March 2007

AbstractProtein aggregation is a hallmark of a growing group of pathologies known as conformational diseases. Although many native or mutated proteins are able to form aggregates, the exact amino acid sequences involved in the process of aggregation are known only in a few cases. Hence, there is a need for different model systems to expand our knowledge in this area. The so-called ag region was previously found to cause the aggregation of the C-terminal fragment of the cystic fibrosis transmembrane conductance regulator (CFTR). To investigate whether this specific amino acid sequence is able to induce protein aggregation irrespective of the amino acid context, we altered its position within the CFTR-derived C-terminal peptide and analyzed the localization of such modified peptides in transfected mammalian cells. Insertion of the ag region into a different amino acid background affected not only the overall level of intracellular protein aggregation, but also the morphology and subcellular localization of aggregates, suggesting that sequences other than the ag region can substantially influence the peptide’s behavior. Also, the introduction of a short dipeptide (His-Arg) motif, a crucial component of the ag region, into different locations within the C-terminus of CFTR lead to changes in the aggregation pattern that were less striking, although still statistically significant. Thus, our results indicate that even subtle alterations within the aggregating peptide can affect many different aspects of the aggregation process.
Second Generation Nanostructured Metal Oxide Matrices to Increase the Thermal Stability of CO and NO2 Sensing Layers Based on Iron(II) Phthalocyanine
Authors: Fernández‐Sánchez J. F. , Fernández I. , Steiger R. , Beer R. , Cannas R. , Spichiger‐Keller U. E. 
Published: March 2007

AbstractAn iron(II) phthalocyanine (FePc) complex solubilized by decylamine (DA) and benzylamine (BA) is incorporated into a nanoparticulate metal oxide matrix to develop optical sensor films sensitive to NO2 and CO. Eleven amine solvents have been tested as N‐donor ligands that permit ligand exchange with the gas molecules. We have systematically investigated the suitability of different N‐donor ligands, studied the thermal stability of the NO2‐ and CO‐sensing films at 4, 25, 60, and 80 °C by photometry, and corroborated our findings by using NMR experiments. A satisfactory thermal stability of the films has not been obtained for chemically unmodified nanoparticulate metal oxide matrices. We have therefore developed a second generation of nanostructured metal oxide supports that show increased thermal stability and adequate sensitivity to NO2 and CO. These novel nanostructured matrices have been chemically modified using amines, alumina oligomers, and/or anti‐gas‐fading agents. These components have been integrated into the metal oxide matrices to avoid degradation of the optical films and to preserve their sensitivity.
3D π‐Conjugated Oligothiophenes Based on Sterically Twisted Bithiophene Nodes
Authors: Karpe S. , Cravino A. , Frère P. , Allain M. , Mabon G. , Roncali J. 
Published: March 2007

Abstract3D conjugated architectures consisting of short oligothiophene chains attached to a connecting node formed by a sterically twisted bithiophenic system have been synthesized by various combinations of bromination and organometallic couplings. The analysis of the electronic properties of these systems by UV‐vis absorption spectroscopy and cyclic voltammetry shows that the effective conjugation length depends on the twist angle in the central bithiophene node and on the number, length, and composition of the conjugated branches. A first evaluation of the potential of this new class of compounds for the realization of organic solar cells has been carried out. To this end two prototype bulk heterojunctions based on two representative compounds as donors and [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM) as acceptor have been realized. A short‐circuit current density of 1.33 mA cm–2 and a power conversion efficiency of 0.20 % have been measured under AM 1.5 (air‐mass 1.5) simulated solar irradiation.
Effects of Annealing on the Nanomorphology and Performance of Poly(alkylthiophene):Fullerene Bulk‐Heterojunction Solar Cells
Authors: Nguyen L. H. , Hoppe H. , Erb T. , Günes S. , Gobsch G. , Sariciftci N. S. 
Published: March 2007

AbstractThe evolution of nanomorphology within thin solid‐state films of poly(3‐alkylthiophene):[6,6]‐phenyl‐C61 butyric acid methyl ester (P3AT:PCBM) blends during the film formation and subsequent thermal annealing is reported. In detail, the influence of the P3AT's alkyl side chain length on the polymer/fullerene phase separation is discussed. Butyl, hexyl, octyl, decyl, and dodecyl side groups are investigated. All of the P3ATs used were regioregular. To elucidate the nanomorphology, atomic force microscopy (AFM), X‐ray diffraction, and optical spectroscopy are applied. Furthermore, photovoltaic devices of each of the different P3ATs have been constructed, characterized, and correlated with the nanostructure of the blends. It is proposed that the thermal‐annealing step, commonly applied to these P3AT:PCBM blend films, controls two main issues at the same time: a) the crystallization of P3AT and b) the phase separation and diffusion of PCBM. The results show that PCBM diffusion is the main limiting process for reaching high device performances.
Glucocorticoid levels in free ranging resident mantled howlers: a study of coping strategies
Authors: Cristóbal‐azkarate Jurgi , Chavira Roberto , Boeck Lourdes , Rodríguez‐luna Ernesto , VEÀ Joaquím J. 
Published: March 2007

AbstractA growing amount of data shows that
a preference for passive‐nonaggressive over
active‐aggressive problem solving is associated
with higher levels of glucocorticoids (GC). For
mantled howlers, the arrival of an adult male in a new
group is a potential source of psychological stress for
both resident males and females. Resident mantled howler
males take an active stand and aggressively repel the
entrance of solitary males, while females take a
passive‐nonaggressive stand. In order to study
whether the relationship between coping strategies and the
activation of the
hypothalamic‐pituitary‐adrenal
(HPA) axis observed in other species applies to
the response of resident mantled howlers to the presence
of solitary males, we examine the relationship between
different group and subpopulation variables and the GC
levels measured in feces collected from 10 groups living
in six forest fragments, in Los Tuxtlas, Mexico. The
results of our study suggest that the resident mantled
howler females' passive response to the presence of
solitary males is accompanied by the activation of the HPA
axis, whereas resident males' aggressive response is
not accompanied by any changes in the HPA axis. In
contrast, a previous study suggests that resident male
howlers respond by increasing their testosterone levels to
the presence of solitary males
(Cristobal‐Azkarate et al., Hormones and
Behavior 2006;49 261–267).These different
behavioral and hormonal responses coincide with the active
and passive coping styles described for other species. The
conditions in which howlers live in our study area may be
favoring the interaction between solitary and resident
howlers, and inducing chronically high GC levels, which in
turn could negatively affect the fitness of these
subpopulations. Am. J. Primatol. 69:866–876, 2007.
© 2007 Wiley‐Liss, Inc.
The function of teeth chattering in male Barbary macaques (Macaca sylvanus)
Authors: Wiper Susan M. , Semple Stuart 
Published: March 2007

AbstractTeeth chattering is seen in many primate species and has been proposed to have a range of social functions. This observational study tested specific hypotheses relating to the function of teeth chattering in a semi‐free‐ranging group of Barbary macaques, Macaca sylvanus. During focal watches of males, the outcome of male–male dyadic social interactions in which teeth chattering was present or absent was compared. Using these data, we tested the predictions of four hypotheses: teeth chattering functions as a signal of submission, appeasement, affiliation or reassurance. Support was found for all four hypotheses. In addition, in some contexts, an exchange of teeth chattering appeared to have a greater impact on the outcome of interactions than one male alone giving this signal. These findings suggest that teeth chattering serves an important role in coordinating the social interactions of male Barbary macaques. Am. J. Primatol. 69:1179–1188, 2007. © 2007 Wiley‐Liss, Inc.
Sympathetic neural activity, sex dimorphism, and postural tachycardia syndrome
Authors: Bonyhay Istvan , Freeman Roy 
Published: March 2007

AbstractObjectiveTo elucidate the mechanisms whereby postural tachycardia syndrome (POTS) patients maintain orthostatic blood pressure and explain the greater prevalence of female cases in POTS cohorts.MethodsWe investigated muscle sympathetic nerve (MSN) discharge characteristics in 12 female POTS patients and in 9 male and 12 female control subjects using the burst amplitude distribution and the relative contribution of burst frequency and burst amplitude.ResultsAt rest, burst distribution was shifted toward larger amplitudes in POTS patients (p < 0.005), consistent with increased sympathetic activity. During hypotension, the distribution shifted toward larger amplitude bursts in control subjects (p < 0.001), whereas it did not change in POTS patients. Total MSN activity increase to hypotension did not differ between subject groups, but the relative contribution of burst frequency change to the total activity increase was greater in POTS patients than in female (p < 0.05) and male (p < 0.001) control subjects. In contrast, the relative contribution of burst amplitude change to total MSN activity increase was greater in male compared with female control subjects (p < 0.05) and POTS patients (p < 0.001).InterpretationAt rest, the burst amplitude distribution was consistent with increased sympathetic activity in POTS and did not change in response to hypotension. In response to hypotension, burst frequency makes a proportionally greater contribution to the increase in total MSN activity in POTS patients compared with female control subjects, and female compared with male control subjects. These physiological differences in MSN discharge characteristics, in the setting of sympathetic fiber loss associated with POTS, may contribute to the predisposition to and greater prevalence of POTS in female individuals. Ann Neurol 2007
Synthesis of 4′‐Hydroxy‐3′‐piperidinomethylchalcone Derivatives and Their Cytotoxicity Against PC‐3 Cell Lines
Authors: Gul Halise I. , Yerdelen Kadir O. , Gul Mustafa , Das Umashankar , Pandit Bulbul , Li Pui‐Kai , Secen Hasan , Sahin Fikrettin 
Published: March 2007

AbstractA new series of mono Mannich bases of 4′‐hydroxychalcones 2a–e carrying a variety of aryl groups was synthesized and the in vitro cytotoxic activities of the new compounds were screened against PC‐3 cell lines. Bioactivities of 2a–e, which are reported for the first time in this study, were compared against their precursor 4′‐hydroxychalcones 1a–e. Compound 2b was found to be the most potent (IC50 = 3.7 μM) among the compounds synthesized. In addition, the compounds 1a–c and 2d showed moderate cytotoxicity. Incorporation of the 3′‐piperidinomethyl group in 1b and 1d raised the potency by 1.68 and 2.19 times respectively and, therefore, seemed to be a noteworthy molecular modification. Correlations were noted between cytotoxicity and one or more physiochemical constants of the aryl ring as well as log P values for the compounds 2a–e. The significant improvement of cytotoxicity of 2b, 2d, and 2e against PC‐3 cell lines compared with their chalcone precursors suggests that the incorporation of a piperidinomethyl group is a useful molecular modification and further development of these compounds as candidate cytotoxic agents may be warranted.
Synthesis of Some Novel Substituted Purine Derivatives As Potential Anticancer, Anti‐HIV‐1 and Antimicrobial Agents
Authors: Rida Samia M. , Ashour Fawzia A. , El‐Hawash Soad A.M. , El‐Semary Mona M. , Badr Mona H. 
Published: March 2007

AbstractIn search of novel purine antimetabolites, a series of 8‐substituted methylxanthine derivatives was prepared in order to explore their in vitro anticancer, anti‐HIV‐1 and antimicrobial activities. The target compounds include: 8‐[(3‐substituted‐4‐oxo‐thiazolidin‐2‐ylidene)hydrazino]‐1,3‐dimethyl (or 1,3,7‐trimethyl)‐3,7‐dihydropurine‐2,6‐diones 5a–e, 8‐[(3,4‐disubstituted 2,3‐dihydrothiazol‐2‐ylidene)hydrazino]‐1,3,7‐trimethyl‐3,7‐dihydropurine‐2,6‐diones 6a–d and 8‐(5‐amino‐3‐arylpyrazol‐1‐yl)‐1,3‐dimethyl‐ (or 1,3,7‐trimethyl)‐3,7‐dihydropurine‐2,6‐diones 7a–g. The in vitro anticancer results revealed that compound 5d exhibited a super sensitivity profile towards leukemia K‐562 with a GI50 value of <0.01 μM. Compound 7c showed significant activity against colon cancer HCT‐15 and renal cancer CAKI‐1 (GI50 values of 0.47 and 0.78 μM, respectively). Compound 7a displayed high activity against colon cancer HCT‐15 (GI50 = 0.8 μM). The anti‐HIV‐1 results indicated that compound 6b displayed a good reduction of viral cytopathic effect (56.69%). The antimicrobial results showed that compound 5a was four times more active than ampicillin against P. aerugenosa (MIC = < 25 μg/mL), compound 5b had twice the activity of ampicillin, while compounds 5d, 7c and 7f were equipotent to ampicillin. On the other hand, compound 7a was equipotent to ampicillin against P. vulgaris (MIC = 50 μg/mL).
Introduction to Chemical Proteomics for Drug Discovery and Development
Authors: Han Sung‐Young , Hwan Kim Seong 
Published: March 2007

AbstractA fundamental goal of chemical proteomics is to identify target proteins for bioactive small molecules and then apply them to drug discovery and development as valid and drugable targets. Here, we introduce integrated technologies for the rapid identification of target proteins, methodologies for validating them as drugable targets, and applications of chemical proteomics in drug discovery and development.
Novel Aldose Reductase Inhibitors Derived from 6‐[[(Diphenylmethylene)amino]oxy]hexanoic Acid
Authors: Rakowitz Dietmar , Piccolruaz Grete , Pirker Cornelia , Matuszczak Barbara 
Published: March 2007

AbstractStarting from the recently identified aldose reductase inhibitor 6‐[[(diphenylmethylene)amino]oxy]hexanoic acid 1, the following systematic structural modifications were performed: (a) formal substitution of the phenyl rings, (b) isosteric replacement of the benzene core by the heteroarenes pyridine and thiophene, (c) formal reduction of the aromatic substructure and subsequent diminution of the cyclohexyl ring, (d) introduction of methylene spacer between C=N and the phenyl rings, and finally (e) formal ring closure in order to get derivatives of the tricycles fluorenone, xanthone, and thioxanthone, respectively. Out of these series, compounds 22–24 bearing disubstituted phenyl rings exhibit the highest inhibitory activity (IC50 value approx. 3 μM) which lie almost in the range of the reference sorbinil.