bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey
Authors: FAGÖ‐OLSEN CARSTEN L. , HØGDALL CLAUS , KEHLET HENRIK , CHRISTENSEN IB J. , OTTESEN BENT 
Published: November 2010

Abstract Objective. This retrospective, nationwide, observational study was designed to compare treatment in tertiary referral centers vs. regional hospitals on overall survival for patients with stage IIIC and IV ovarian cancer. Material and methods. The study took place in all gynecological departments in Denmark, involving a total of 1,160 patients with stage IIIC or IV ovarian cancer. Data were extracted for 2,024 patients with all stages of ovarian cancer recorded in the Danish Gynecological Cancer Database between 1 January 2005 and 31 December 2008. The main outcome measure was overall survival. Results. No difference was found between tertiary centers and regional hospitals with regard to age, body mass index, American Society of Anesthesiologists score or comorbidity. Patients in regional hospitals had poorer Eastern Cooperative Oncology Group performance status, i.e.1.0 vs. 2.0 (p= 0.005). Patients in referral centers presented more often with stage IIIC and IV disease, i.e. 59.7 vs. 51.7% (p < 0.001). Patients with stage IIIC and IV disease in regional vs. tertiary hospitals had a higher rate of primary cytoreductive surgery, i.e. 89.5 vs. 82.5% (p= 0.004), a poorer rate of complete cytoreductive surgery following primary cytoreductive surgery, i.e. 13.9 vs. 25.2% (p < 0.001), a lower rate of neoadjuvant chemotherapy, i.e. 5.5 vs. 13.4% (p < 0.001), and more often underwent acute surgery, i.e. 17.0 vs. 9.2% (p < 0.001). Patients treated in referral centers had better overall survival (p= 0.021). Treatment in a referral center was an independent prognostic factor for overall survival hazard ratio, 0.83 (confidence interval 0.70–0.98). Conclusion. Patients with stage IIIC and IV ovarian cancer benefit from treatment in a tertiary referral center.
Traumatic dental injuries during anaesthesia: part I: clinical evaluation
Authors: Rosa Maria Gaudio , Paolo Feltracco , Stefania Barbieri , Letizia Tiano , Martina Alberti , Massimiliano Delantone , Carlo Ori , Maria Avato Francesco 
Published: November 2010

Abstract –  Dental injuries represent the most common claims against the anaesthesiologist. Dental lesions are frequent complications of oro‐tracheal intubation and major causal factors are (i) poor dentition, (ii) aggressive laryngoscopy, (iii) insufficient anaesthesia and curarization, (iv) emergency interventions and (v) lack of experience by the anaesthesiologist. Materials and methods: We conducted a retrospective analysis of 83 cases of dental lesions occurring during elective, emergent and urgent surgery requiring general anaesthesia with tracheal tube placement in the years between 2000 and 2008. Preoperative evaluation of dental status was obtained from the anaesthesiology chart, filled by an experienced anaesthesiologist during the preoperative visit. Anaesthesiological records were inspected by physicians of Legal Medicine Department with the aim to attribute responsibility for the damage and manage potential reimbursements. Costs related to the required dental repair were also noted. Results: Eighty‐three patients of a total of 60.000 surgical procedures (no day surgery) under general anaesthesia were affected by dental lesions (0.13%). Seventy‐five per cent of lesions occurred during intubation manoeuvres for elective major surgery, 15% occurred at tracheal intubation for minor surgery and 10% were related to emergency surgery. Teeth avulsions accounted for 50% of lesions, followed by damage to crowns and bridges (14%), luxations and fractures (>15%). Discussion: The overall incidence of dental injury in our retrospective study was 1.38 per 1000 anaesthetics, which is slightly higher than those reported by some and lower with respect to others. Avulsion of a permanent tooth occurred in patients who were affected by severe mobility of native teeth while undergoing surgery. Even though the majority of anaesthesiologists were trained enough in the use of airway devices and aware of the potential damage while using excessive forces, some unexpected difficulties may have led to lesions. It is known that damage to teeth can occur even in the absence of negligence.
Hot Money and Business Cycle Volatility: Evidence from China
Authors: Guo Feng , Huang Ying 
Published: November 2010

AbstractThis paper investigates the link between hot money and business cycle volatility in China from January 1997 to December 2009. Using the structural vector error correction model, we find a considerable degree of long‐run cointegration and bidirectional causality effects between hot money and business cycle volatility. The speculative shocks are found to temporarily promote China's economic growth, but also to exacerbate business cycle volatility. The liquidity shock stemming from hot money is shown to be the primary factor responsible for the significantly enhanced fluctuation in business cycles during the most recent global financial crisis period. This could be detrimental to the smooth operation of financial markets. Therefore, in forming future policies, it is critical for policy‐makers to take precautions against the speculative factors.
Empirical Evaluation of a Simple Analytical Formula for the Ultraviolet Index
Authors: Antón Manuel , Serrano Antonio , Cancillo María Luísa , García José Agustín , Madronich Sasha 
Published: November 2010

AbstractThis paper focuses on the estimation of the UV Index (UVI) for all sky conditions using a simple analytical parameterization involving three independent variables: the solar zenith angle, the total ozone column and the clearness index. Measurements of the UVI made at Badajoz and Cáceres (Southwestern Spain) from January 2006 to December 2007 are used to estimate optimal fitting parameters for the model formula, while measurements from January to December 2008 are used to show that the formula‐based estimations have mean absolute errors lower than 6% and R2ca 0.99.
Advancement in carbon nanotubes: basics, biomedical applications and toxicity
Authors: Beg Sarwar , Rizwan Mohammad , Sheikh Asif M , Hasnain M Saquib , Anwer Khalid , Kohli Kanchan 
Published: November 2010

Abstract

Objectives
Carbon nanotubes (CNTs) have attracted much attention by researchers worldwide in recent years for their small dimensions and unique architecture, and for having immense potential in nanomedicine as biocompatible and supportive substrates, as a novel tool for the delivery of therapeutic molecules including peptides, RNA and DNA, and also as sensors, actuators and composites.

Key findings
CNTs have been employed in the development of molecular electronic, composite materials and others due to their unique atomic structure, high surface area-to-volume ratio and excellent electronic, mechanical and thermal properties. Recently they have been exploited as novel nanocarriers in drug delivery systems and biomedical applications. Their larger inner volume as compared with the dimensions of the tube and easy immobilization of their outer surface with biocompatible materials make CNTs a superior nanomaterial for drug delivery. Literature reveals that CNTs are versatile carriers for controlled and targeted drug delivery, especially for cancer cells, because of their cell membrane penetrability.

Summary
This review enlightens the biomedical application of CNTs with special emphasis on utilization in controlled and targeted drug delivery, as a diagnostics tool and other possible uses in therapeutic systems. The review also focuses on the toxicity aspects of CNTs, and revealed that genotoxic potential, mutagenic and carcinogenic effects of different types of CNTs must be explored and overcome by formulating safe biomaterial for drug delivery. The review also describes the regulatory aspects and clinical and market status of CNTs.
Relative similarity within purine nucleotide and ligand structures operating on nitric oxide synthetase, guanylyl cyclase and potassium (KATP, BKCa) channels
Authors: Williams W Robert 
Published: November 2010

AbstractObjectivesPurine nucleotides play a central role in signal transduction events initiated at the cell membrane. The NO–cGMP–cGK pathway, in particular, mediates events involving NOS and some classes of K+ ion channel. The aim of this study is to investigate relative molecular similarity within the ligands binding to NOS, KATP, BKCa channels and regulatory nucleotides.MethodsMinimum energy conformers of the ligand structures were superimposed and fitted to l-arginine and the nucleotides of adenine and guanine using a computational program.Key findingsDistinctive patterns were evident in the fitting of NOS isoform antagonists to l-arginine. KATP channel openers and antagonists superimposed on the glycosidic linkage and imidazole ring of the purine nucleotides, and guanidinium and ribose groups of GTP in the case of glibenclamide. The fits of BKCa channel openers and antagonists to cGMP were characterized by the linear dimensions of their structures; distances between terminal oxy groups in respect of dexamethasone and aldosterone.ConclusionsThe findings provide structural evidence for the functional interaction between K+ channel openers/antagonists and the regulatory nucleotides. Use of the purine nucleotide template systematizes the considerable heterogeneity evident within the structures of ligands operating on K+ ion channels.
Fast-dissolving sublingual solid dispersion and cyclodextrin complex increase the absorption of perphenazine in rabbits
Authors: Turunen Elina , Mannila Janne , Laitinen Riikka , Riikonen Joakim , Lehto Vesa-Pekka , Järvinen Tomi , Ketolainen Jarkko , Järvinen Kristiina , Jarho Pekka 
Published: November 2010

Abstract

Objectives
The sublingual administration route as well as solid dispersion formation with macrogol 8000 and complexation with β-cyclodextrin (β-CyD) were investigated as ways for improving the absorption of perphenazine, a poorly water-soluble drug subjected to substantial first-pass metabolism.

Methods
The absorption of perphenazine was studied in rabbits after sublingual administration of perphenazine/macrogol solid dispersion, solid perphenazine/β-CyD complex and plain micronized perphenazine, as well as after peroral administration of an aqueous perphenazine solution. Solid formulations were prepared by freeze-drying (perphenazine/macrogol solid dispersion) or spray-drying (perphenazine/β-CyD complex).

Key findings
The value for area under the curve from 0 to 360 min (AUC0–360 min) of perphenazine after peroral administration was only 8% of the AUC0–360 min value obtained after intravenous administration, while the corresponding values for the sublingually administered formulations were 53% (perphenazine/macrogol solid dispersion), 41% (perphenazine/β-CyD complex) and 64% (micronized perphenazine). There are three possible mechanisms to explain these results: avoidance of the first-pass metabolism; good sublingual absorption of perphenazine; and rapid dissolution rate of perphenazine from the studied formulations.

Conclusions
With sublingual administration, the drug has to dissolve rapidly in a small volume of saliva. Based on the present absorption studies in rabbits, the solid dispersion preparation and cyclodextrin complexation were postulated to be useful ways to attain successful sublingual administration of perphenazine. Good sublingual absorption was also achieved by micronization of perphenazine. As far as we are aware, this paper is one of the first to evaluate the sublingual administration of a solid dispersion in vivo.
Investigation of the interaction of biodegradable micro- and nanoparticulate drug delivery systems with platelets
Authors: Ramtoola Zebunnissa , Lyons Pierce , Keohane Kieran , Kerrigan Steve W , Kirby Brian P , Kelly John G 
Published: November 2010

AbstractObjectivesBiodegradable micro- and nanoparticles are being increasingly investigated for drug delivery and targeting of therapeutics. The size and surface properties of these particles are important factors influencing their interaction and uptake by various cells, tissues and organs. Optimising these properties, to enhance cellular uptake, may increase their potential for interaction with other physiological components such as platelets resulting in platelet activation and inappropriate thrombus formation. The aim of this study was to investigate the potential interaction of particulates with platelets.MethodsBiodegradable micro- and nanoparticles based on poly-lactide-co-glycolide (PLGA), poly-lactide-co-glycolide–macrogol (PLGA-macrogol) and chitosan were prepared using solvent evaporation, spray drying or solvent dispersion techniques.Key findingsMicroparticles formulated had a median diameter (D50%) of 2–9 µm, while nanoparticles had an average diameter of 100–500 nm. The surface morphology ranged from smooth and spherical to irregular depending on polymer and preparation method used. Particles, reconstituted in the concentration range of 0.1–500 µg/ml, were tested for their ability to induce or inhibit platelet aggregation. No effects on either induction of platelet activity or inhibition of aggregation were detected.ConclusionsNone of the particles examined were found to alter platelet activity. These results suggested that the biodegradable micro- and nanoparticles tested were safe for use as potential drug carriers of therapeutic agents.
Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of liquiritigenin and its two glucuronides, M1 and M2, in rats
Authors: Kang Hee E , Sohn Se I , Baek Seung R , Lee Jee W , Lee Myung G 
Published: November 2010

AbstractObjectivesLiver disease and acute renal failure (ARF) are closely associated. The pharmacokinetics of liquiritigenin (LQ), a candidate therapy for inflammatory liver disease, and its metabolites M1 and M2 were evaluated in rats with ARF induced by uranyl nitrate (U-ARF rats).MethodsLQ was administered intravenously (20 mg/kg) or orally (50 mg/kg) in U-ARF and control rats, and uridine diphosphate-glucuronosyltransferases (UGT) activity and uridine 5′-diphosphoglucuronic acid (UDPGA) concentrations were determined in the liver and intestine.Key findingsAfter intravenous LQ administration, U-ARF rats displayed significantly slower LQ renal clearance but no significant changes in the LQ area under the plasma concentration–time curve (AUC) compared with controls. This was because of similar hepatic UGT activity and UDPGA levels between two groups, which resulted in comparable non-renal clearance, as well as the limited contribution of LQ renal clearance to total LQ clearance. However, the AUC and AUCM/AUCLQ ratios of M1 and M2 were significantly increased in U-ARF rats because of decreased urinary excretion of M1 and M2. Similar results were observed following oral administration because of the comparable LQ intestinal metabolism in both groups and decreased urinary excretion of M1 and M2 in U-ARF rats.ConclusionsU-ARF rats displayed decreased urinary excretion of LQ glucuronides, resulting in significantly greater AUC and metabolite ratios of M1 and M2 following LQ administration.
Effect of P2 receptor blockade with pyridoxine on sympathetic response to exercise pressor reflex in humans
Authors: Cui Jian , Leuenberger Urs A. , Blaha Cheryl , King Nicholas C. , Sinoway Lawrence I. 
Published: November 2010

Non‐technical summaryDuring exercise, sympathetic nervous system activity increases and this contributes to an increase in blood pressure (i.e. exercise pressor reflex). Although animal studies suggest that purinergic P2 receptors on thin fibre sensory nerves are stimulated and evoke this reflex, human data are lacking. In this study, young healthy volunteers performed fatiguing isometric handgrip before and after a local infusion of pyridoxine (i.e. vitamin B6) into the ‘isolated’ circulation of the human forearm. Pyridoxine is converted into a P2‐purinoceptor antagonist. Muscle sympathetic nerve activity and blood pressure responses to fatiguing handgrip and post‐exercise circulatory occlusion were significantly less after pyridoxine than they were before. These effects were not observed after infusion of saline. These data suggest that P2 receptors contribute to the exercise pressor reflex in humans.
Testosterone restores respiratory long term facilitation in old male rats by an aromatase‐dependent mechanism
Authors: Nelson N. R. , Bird I. M. , Behan M. 
Published: November 2010

Non‐technical summarySteroidal sex hormones (testosterone, oestradiol and progesterone) play an important role in the neural control of breathing. Hormone levels typically change throughout life. Testosterone levels increase during puberty in boys, but from ∼30 years of age levels decline gradually. The typical age of onset for obstructive sleep apnoea, a prominent breathing disorder of older humans, is ∼50 years of age in men. In a study in old male rats, we show that testosterone supplementation can reverse the age‐associated decrease in one measurement of the neural control of breathing. We conclude that testosterone supplementation can potentially be used to enhance upper airway function in the elderly.
Renal mechanisms contributing to the antihypertensive action of soluble epoxide hydrolase inhibition in Ren‐2 transgenic rats with inducible hypertension
Authors: Honetschlägerová Zuzana , Husková Zuzana , Vaňourková Zdeňka , Sporková Alexandra , Kramer Herbert J. , Hwang Sung Hee , Tsai Hsing‐Ju , Hammock Bruce D. , Imig John D. , Červenka Luděk , Kopkan Libor 
Published: November 2010

Non‐technical summaryArachidonic acid metabolites called epoxyeicosatrienoic acids (EETs) influence vascular tone and renal tubular sodium and water transport and thus have been implicated in the control of blood pressure. Inhibition of the enzyme soluble epoxide hydrolase (sEH), which reduces EET degradation to the corresponding diols, leads to substantial attenuation of malignant hypertension in a transgenic rat strain harbouring the mouse renin gene particularly via an improvement of renal function. The observed antihypertensive and renoprotective effects of this novel pharmacological approach provide a potentially new direction in antihypertensive therapy.
Unperturbed islet α‐cell function examined in mouse pancreas tissue slices
Authors: Huang Ya‐Chi , Rupnik Marjan , Gaisano Herbert Y. 
Published: November 2010

Non‐technical summaryCritical investigation into pancreatic islet α‐cell biology in health and diabetes has been sparse and inconsistent because of technical difficulties in islet isolation and dispersion into single cells. We have circumvented these difficulties by employing the pancreas slice preparation. We functionally characterized (electrophysiologically) the α‐cells in their in situ native state, then loaded the tested cells with biocytin dye to subsequently confirm the cell identities by immunocytochemistry. We characterized a very large number of α‐cells, which showed a wide‐range distribution in the electrophysiological parameters of several ion channels (ATP‐sensitive K+, Na+ and Ca2+ currents) and capacitance changes as measure of exocytosis of glucagon granules. This could explain the apparent inconsistency of previous reports on α‐cells that inadvertently showed skewed data due to insufficient sampling of α‐cells. Our innovative approaches will enable future studies into elucidating α‐cell dysregulation in diabetes.
Role of blood flow in carotid body chemoreflex function in heart failure
Authors: Ding Yanfeng , Li Yu‐Long , Schultz Harold D. 
Published: November 2010

Non‐technical summaryActivation of the sympathetic nervous system hastens the rate of progression and severity of chronic heart failure (CHF). Chemically sensitive nerves in the carotid body (CB) that stimulate sympathetic nerve activity become overly active in CHF and contribute to this phenomenon. The stimulus for activation of these CB chemoreceptors is not known. Blood supply to tissues is impaired due to the failing heart. In this study we tested whether a chronic reduction in blood flow to the CB may contribute to altered CB chemoreceptor function. The results show that changes that occur in CB chemoreceptor function during CHF are identical to those that occur if blood flow is simply reduced to the CB for several weeks. The results suggest that chronic impairment of blood flow may be the key step in the pathophysiological events that cause sympathetic nervous system activation in heart failure.
Peptide Antibiotic Sensing and Detoxification Modules of
Bacillus subtilis
Authors: Staroń Anna , Finkeisen Dora Elisabeth , Mascher Thorsten 
Published: November 2010

ABSTRACT

Peptide antibiotics are produced by a wide range of microorganisms. Most of them target the cell envelope, often by inhibiting cell wall synthesis. One of the resistance mechanisms against antimicrobial peptides is a detoxification module consisting of a two-component system and an ABC transporter. Upon the detection of such a compound, the two-component system induces the expression of the ABC transporter, which in turn removes the antibiotic from its site of action, mediating the resistance of the cell. Three such peptide antibiotic-sensing and detoxification modules are present in
Bacillus subtilis
. Here we show that each of these modules responds to a number of peptides and confers resistance against them. BceRS-BceAB (BceRS-AB) responds to bacitracin, plectasin, mersacidin, and actagardine. YxdJK-LM is induced by a cationic antimicrobial peptide, LL-37. The PsdRS-AB (formerly YvcPQ-RS) system responds primarily to lipid II-binding lantibiotics such as nisin and gallidermin. We characterized the
psdRS-AB
operon and defined the regulatory sequences within the P

psdA

promoter. Mutation analysis demonstrated that P

psdA

expression is fully PsdR dependent. The features of both the P

bceA

and P

psdA

promoters make them promising candidates as novel whole-cell biosensors that can easily be adjusted for high-throughput screening.
Resistance of Herpes Simplex Viruses to Nucleoside Analogues: Mechanisms, Prevalence, and Management
Authors: Piret Jocelyne , Boivin Guy 
Published: November 2010

ABSTRACTHerpes simplex viruses (HSV) type 1 and type 2 are responsible for recurrent orolabial and genital infections. The standard therapy for the management of HSV infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valacyclovir and famciclovir. These compounds are phosphorylated by the viral thymidine kinase (TK) and then by cellular kinases. The triphosphate forms selectively inhibit the viral DNA polymerase (DNA pol) activity. Drug-resistant HSV isolates are frequently recovered from immunocompromised patients but rarely found in immunocompetent subjects. The gold standard phenotypic method for evaluating the susceptibility of HSV isolates to antiviral drugs is the plaque reduction assay. Plaque autoradiography allows the associated phenotype to be distinguished (TK-wild-type, TK-negative, TK-low-producer, or TK-altered viruses or mixtures of wild-type and mutant viruses). Genotypic characterization of drug-resistant isolates can reveal mutations located in the viral TK and/or in the DNA pol genes. Recombinant HSV mutants can be generated to analyze the contribution of each specific mutation with regard to the drug resistance phenotype. Most ACV-resistant mutants exhibit some reduction in their capacity to establish latency and to reactivate, as well as in their degree of neurovirulence in animal models of HSV infection. For instance, TK-negative HSV mutants establish latency with a lower efficiency than wild-type strains and reactivate poorly. DNA pol HSV mutants exhibit different degrees of attenuation of neurovirulence. The management of ACV- or PCV-resistant HSV infections includes the use of the pyrophosphate analogue foscarnet and the nucleotide analogue cidofovir. There is a need to develop new antiherpetic compounds with different mechanisms of action.