bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of (19E)-17β-hydroxy-3-oxo-5α-androstan-19-al 19-(O-carboxymethyl)oxime
Authors: Fajkoš Jan , Pouzar Vladimír
Published: August 2009

The title compound IX was synthesized from triol diester I. Catalytic hydrogenation over Adams’ catalyst afforded the 5α and 5β isomers II and III which were oxidized under mild conditions to the aldehydes IV and XII. Reaction with (O-carboxymethyl)hydroxylamine hemihydrochloride followed by methylation with diazomethane gave the oximes VIII and XIV. Partial hydrolysis to the alcohols VI and XIII and Jones’ oxidation yielded the 3-oxo derivatives XI and XVI. Complete hydrolysis of the diester XI afforded the desired hapten IX.
An unusual reaction of a bridged triterpenoid α-diketone with acetic anhydride
Authors: Klinotová Eva , Křeček Václav , Klinot Jiří , Buděšínský Miloš , Podlaha Jaroslav , Podlahová Jana , Ječný Jiří
Published: August 2009

3β-Acetoxy-21,22-dioxo-18α,19βH-ursan-28,20β-olide (IIIa) reacts with acetic anhydride in pyridine under very mild conditions affording β-lactone IVa and γ-lactones Va and VIIa as condensation products. On reaction with pyridine, lactones Va and VIIa undergo elimination of acetic acid to give unsaturated lactones VIIIa and IXa, respectively. Similarly, the condensation of 20β,28-epoxy-21,22-dioxo-18α,19βH-ursan-3β-yl acetate (IIIb) with acetic anhydride leads to β-lactone IVb and γ-lactone Vb; the latter on heating with pyridine affords unsaturated lactone VIIIb and 21-methylene-22-ketone Xb. The structure of the obtained compounds was derived using spectral methods, particularly 1H and 13C NMR spectroscopy; structure of lactone IVa was confirmed by X-ray diffraction.
The synthesis of 4-O-oligoethylene glycol derivatives of 1,6-anhydro-β-D-glucopyranose and crown-ethers formed by their intramolecular cyclization
Authors: Jindřich Jindřich , Černý Miloslav , Trnka Tomáš , Buděšínský Miloš
Published: August 2009

Using acid catalysed reaction of 1,6 : 3,4-dianhydro-2-O-p-toluenesulfonyl-β-D-galactopyranose (I) with mono-, di-, tri- and tetraethylene glycol, 4-O-oligoethylene glycol derivatives of 1,6-anhydro-2-O-p-toluenesulfonyl-β-D-glucopyranose II - V were obtained which were converted to 4-O-substituted 1,6 : 2,3-dianhydro-β-D-mannopyranones VI - IX under the effect of sodium hydroxide. Of them 4-O-(2-hydroxyethyl)- and 4-O-(11-hydroxy-3,6,9-trioxaundecyl) derivatives VI and IX were intramolecularly cyclized in basic medium under formation of 1,6-anhydro-3,4-O-ethlene-β-D-altropyranose (X) or 1,6-anhydro-2,4-O-(3,6,9-trioxaundecane-1,11-diyl)-β-D-glucopyranose (XV), respectively. Oxidation of the hydroxyl group in compound XV led to corresponding 3-ulose XIX, the reduction of which with sodium borohydride gave an isomer of compound XV, i.e. compound XX of D-allo-configuration. The structures of the compounds described in this paper were proved using 1H and 13C NMR spectra. Compounds XV, XIX and XX represent a new structural type of sugar crown-ethers.
Determination of the substituent constant σp- for the thioamide group -CSNH2 from the ionization of anilines and phenols
Authors: Polášek Miroslav , Waisser Karel , Bouček Tomáš
Published: August 2009

Thermodynamic ionization constants pKa 2.62 ± 0.01 for the primary aromatic amino group of 4-aminothiobenzamide and pKa 8.28 ± 0.01 for the phenolic hydroxy group of 4-hydroxythiobenzamide have been determined by ultra-violet spectrophotometry at 25°C. By using these pKa values and the Hammett equations (log Ka vs σ) for the ionization of fourteen 3- or 4-substituted phenols and thirteen 3- or 4-substituted anilines the substituent constant σp- = 0.68 (from the ionization of anilines) or σp- = 0.73 (from the ionization of phenols) of the thioamide group -CSNH2 was calculated.
Would you sell a kidney in a regulated kidney market? Results of an exploratory study
Authors: Rid A , Bachmann L M , Wettstein V , Biller-Andorno N
Published: August 2009

Background:

It is often claimed that a regulated kidney market would significantly reduce the kidney shortage, thus saving or improving many lives. Data are lacking, however, on how many people would consider selling a kidney in such a market.

Methods:

A survey instrument, developed to assess behavioural dispositions to and attitudes about a hypothetical regulated kidney market, was given to Swiss third-year medical students.

Results:

Respondents’ (n = 178) median age was 23 years. Their socioeconomic status was high or middle (94.6%). 48 (27%) considered selling a kidney in a regulated kidney market, of whom 31 (66%) would sell only to overcome a particularly difficult financial situation. High social status and male gender was the strongest predictor of a disposition to sell. 32 of all respondents (18%) supported legalising a regulated kidney market. This attitude was not associated with a disposition to sell a kidney. 5 respondents (2.8%) endorsed a marketandconsidered providing a kidney to a stranger if and only if paid. 4 of those 5 would sell only under financial duress.

Conclusions:

Current understanding of a regulated kidney market is insufficient. It is unclear whether a regulated market would result in a net gain of kidneys. Most possible kidney vendors would only sell in a particularly difficult financial situation, raising concerns about the validity of consent and inequities in the provision of organs. Further empirical and normative analysis of these issues is required. Any calls to implement and evaluate a regulated kidney market in pilot studies are therefore premature.
Ethical analysis of the justifiability of labelling with COPD for smoking cessation
Authors: Kotz D , Vos R , Huibers M J H
Published: August 2009

Background:

Spirometry for early detection of chronic obstructive pulmonary disease (COPD) and smoking cessation is criticised because of the potential negative effects of labelling with disease.

Aim:

To assess the effects of opinions of smokers with mild to moderate COPD on the effectiveness of spirometry for smoking cessation, the justification of early detection of airflow limitation in smokers and the impact of confrontation with COPD.

Design:

Qualitative study with data from a randomised controlled trial.

Setting:

General population of Dutch and Belgian Limburg.

Methods:

Semistructured ethical exit interviews were conducted with 205 smokers who were motivated to quit smoking and had no prior diagnosis of COPD but were detected with airflows limitation by means of spirometry. They received either (1) counselling, including labelling with COPD, plus with nortriptyline for smoking cessation, (2) counselling excluding labelling with COPD, plus nortriptyline for smoking cessation or (3) care as usual for smoking cessation by the general practitioner, without labelling with COPD.

Results:

Of the participants, 177 (86%) agreed or completely agreed that it is justified to measure lung function in heavy smokers. These participants argued that measuring lung function raises consciousness of the negative effects of smoking, helps to prevent disease or increases motivation to stop smoking. Most of the 18 participants who disagreed argued that routinely measuring lung function in smokers would interfere with freedom of choice.

Conclusions:

Labelling with disease is probably a less important issue in the discussion about the pros and cons of early detection of COPD.
Functional Maturity and Terminal Molt of Male Snow Crab, Chionoecetes opilio
Authors: Conan Gérard Y. , Comeau Michel
Published: August 2009

Bivariate and multivariate analyses of allometric relationships between chela size and carapace size of snow crab, Chionoecetes opilio, show that mature males are recognizable by morphometry. The most simple procedure is to plot logarithms of chela height (Ch) against logarithms of carapace width (Lc). Data from mature and immature males fit into two distinct ellipses with parallel major axes. The discriminant function Y = −0.78893 loge. Lc + 0.614488 logeCh + 1.76051 will assign individuals to the correct groups in 99% of cases (for mature males: Y > 0). Spermatophores are present in the vasa deferentia of all males larger than 60 mm Lc. The molt to morphometric maturity occurs later at Lc sizes ranging from 60 to 120 mm; it is identified as final. Only morphometrically mature males larger than 96 mm Lc have been observed to mate efficiently with multiparous females in intermolt and be functionally mature. In the catch, as many as 40% of males larger than the minimal legal size of 95 mm can be immature.
Food Limitation of Larval Dragonflies: A Field Test of Spacing Behaviour
Authors: Baker Robert L.
Published: August 2009

Density-dependent growth and survival of larval odonates may result from some larvae excluding others from profitable hunting sites. This hypothesis predicts that both degree and variation in food limitation should increase with population density; it also suggests that large larvae should show less food limitation than small larvae. I tested these predictions by analyzing food limitation, determined by mass of fecal pellets, and population density of larval Ischnura verticalis and Enallagma ebrium from a pond in southern Ontario. When data from all sampling days were combined, population densities of both species were negatively correlated with gut fullness but there was no correspondence between population density and gut fullness measured at different sites on any given day. Also, there was no correlation between population density and variation in food limitation and there was no evidence that small larvae suffered a greater degree of food limitation than larger larvae. A lack of discrete and persistent prey patches and/or low larval population densities may account for the lack of evidence that larvae are excluded from patches of prey.
Dynamics of Unexploited and Lightly Exploited Populations of Rainbow Trout (Salmo gairdneri) from Coastal, Montane, and Subalpine Lakes in Western Canada
Authors: Donald D. B. , Alger D. J.
Published: August 2009

Populations of rainbow trout (Salmo gairdneri) in one coastal and two montane lakes were characterized by a relatively stable age structure, approximately 50% annual mortality, maximum longevity of 7 yr, and close to linear growth beginning at age 1 or age 2. In contrast, populations in subalpine lakes were characterized by an unstable age structure, large annual variation in recruitment, maximum longevity of 13 yr or more, and growth patterns that were either asymptotic, complex, or linear. Age structure and thus year-class strength was directly related to cumulative summer temperature in one subalpine lake (r = 0.71, N = 11), and in others, strong year-classes were often associated with warm summers. These analyses indicate that the magnitude of recruitment in subalpine lakes was either primarily or at least partly due to annual differences in summer temperature. Longevity was inversely related to midsummer water temperature.
EVOLVING DECISION TREES IN HARDWARE
Authors: STRUHARIK RASTISLAV J. R. , NOVAK LADISLAV A.
Published: August 2009

This paper, according to the best of our knowledge, provides the very first solution to the hardware implementation of the complete decision tree inference algorithm. Evolving decision trees in hardware is motivated by a significant improvement in the evolution time compared to the time needed for software evolution and efficient use of decision trees in various embedded applications (robotic navigation systems, image processing systems, etc.), where run-time adaptive learning is of particular interest. Several architectures for the hardware evolution of single oblique or nonlinear decision trees and ensembles comprised from oblique or nonlinear decision trees are presented. Proposed architectures are suitable for the implementation using both Field Programmable Gate Arrays (FPGA) and Application Specific Integrated Circuits (ASIC). Results of experiments obtained using 29 datasets from the standard UCI Machine Learning Repository database suggest that the FPGA implementations offer significant improvement in inference time when compared with the traditional software implementations. In the case of single decision tree evolution, FPGA implementation of H_DTS2 architecture has on average 26 times shorter inference time when compared to the software implementation, whereas FPGA implementation of H_DTE2 architecture has on average 693 times shorter inference time than the software implementation.
ANALYSIS OF GENERIC CYCLOCONVERTER OPERATION WITH INSTANTANEOUS COMMUTATION UNDER TRANSIENT AND STEADY-STATE CONDITIONS
Authors: KATZ INNA , ABRAMOVITZ ALEXANDER , HOREN YORAM , KUPERMAN ALON , BRONSHTEIN SVETLANA
Published: August 2009

This paper offers a new approach to analyses of cycloconverter operation. The difference equations describing the cycloconverters' transient and steady-state operating regimes are derived. Theoretical predictions were validated by a computer program which calculated the load current of different cycloconverter topologies using the proposed methodology. The calculated and experimental results are compared and found to be in good agreement.
Stewardship of Human Biospecimens, DNA, Genotype, and Clinical Data in the GWAS Era
Authors: O'Brien Stephen J.
Published: August 2009

An ethical quandary is emerging over custodianship of and access to DNA specimens and attached data, clinical and genetic, held in large disease cohort collections. The balance of patients’ rights and science/society's quest for broad open access must be resolved in order to realize the promise of gene association studies of complex human disease. A way forward may be to convene a colloquium of international medical and science organizations charged with developing global consensus guidance and ethical principles for access to and use of genomic biobanks.
Chromosomes in Leukemia and Beyond: From Irrelevant to Central Players
Authors: Rowley Janet D.
Published: August 2009

Although it was definitely not obvious at first, consistent chromosomal translocations are major contributors to cellular transformation in some leukemias, lymphomas, sarcomas, prostate cancer, and other benign and malignant neoplasms. In the 50 years since the discovery of the Ph chromosome, the elucidation of recurring abnormalities has been an ongoing challenge that has evolved as new technologies allowed an ever more accurate definition of the precise changes in DNA resulting from these abnormalities. As we enter a new era of understanding enriched by gene expression studies, we still know little about the changes in the level of critical proteins, which may be the ultimate effectors of the genetic/epigenetic abnormalities in cancer.

Despite remarkable progress in identifying both obvious chromosome abnormalities and subtle changes in DNA such as mutations and small copy-number variations, the impact of this knowledge has been variable. The challenge for the future is to enhance our ability to translate these genetic changes into effective therapies for other malignant diseases.
Genotype Imputation
Authors: Li Yun , Willer Cristen , Sanna Serena , Abecasis Gonçalo
Published: August 2009

Genotype imputation is now an essential tool in the analysis of genome-wide association scans. This technique allows geneticists to accurately evaluate the evidence for association at genetic markers that are not directly genotyped. Genotype imputation is particularly useful for combining results across studies that rely on different genotyping platforms but also increases the power of individual scans. Here, we review the history and theoretical underpinnings of the technique. To illustrate performance of the approach, we summarize results from several gene mapping studies. Finally, we preview the role of genotype imputation in an era when whole genome resequencing is becoming increasingly common.
Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice
Authors: Haub Synia , Kanuri Giridhar , Volynets Valentina , Brune Thomas , Bischoff Stephan C. , Bergheim Ina
Published: August 2009

Elevated dietary fructose intake, altered intestinal motility, and barrier function may be involved in the development of nonalcoholic fatty liver disease (NAFLD). Because intestinal motility and permeability are also regulated through the bioavailability of serotonin (5-HT), we assessed markers of hepatic injury in serotonin reuptake transporter knockout (SERT−/−) and wild-type mice chronically exposed to different monosaccharide solutions (30% glucose or fructose solution) or water for 8 wk. The significant increase in hepatic triglyceride, TNF-α, and 4-hydroxynonenal adduct as well as portal endotoxin levels found in fructose-fed mice was associated with a significant decrease of SERT and the tight-junction occludin in the duodenum. Similar effects were not found in mice fed glucose. In contrast, in SERT−/−mice fed glucose, portal endotoxin levels, concentration of occludin, and indices of hepatic damage were similar to those found in wild-type and SERT−/−mice fed fructose. In fructose-fed mice treated with a 5-HT3 receptor antagonist, hepatic steatosis was significantly attenuated. Our data suggest that a loss of intestinal SERT is a critical factor in fructose-induced impairment of intestinal barrier function and subsequently the development of steatosis.
Sulforaphane treatment protects skeletal muscle against damage induced by exhaustive exercise in rats
Authors: Malaguti Marco , Angeloni Cristina , Garatachea Nuria , Baldini Marta , Leoncini Emanuela , Collado Pilar S. , Teti Gabriella , Falconi Mirella , Gonzalez-Gallego Javier , Hrelia Silvana
Published: August 2009

Sulforaphane (SF), one of the most important isothiocyanates in the human diet, present in cruciferous vegetables, is known to have chemopreventive activities in different tissues. No data are available on its effects in the prevention of skeletal muscle damage. In this study, we investigated the potential protective effects of SF treatment on muscle damage and oxidative stress induced by an acute bout of exhaustive exercise in rats. Male Wistar rats were treated with SF (25 mg/kg body wt ip) for 3 days before undergoing an acute exhaustive exercise protocol in a treadmill (+7% slope and 24 m/min). Acute exercise resulted in a significant increase in plasma lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities. It also resulted in a significant increase in thiobarbituric acid-reactive substances, in a significant decrease in tissue total antioxidant capacity, and in a significant decrease in NAD(P)H:quinone oxidoreductase 1 (NQO1) expression and activity in vastus lateralis muscle. SF treatment significantly increased muscle NQO1, glutathione- S-transferase, and glutathione reductase expression and activity, with no effect on glutathione peroxidase and thioredoxin reductase. The observed SF-induced upregulation of phase II enzymes was accompanied by a significant increase in nuclear erythroid 2 p45-related factor 2 expression and correlated with a significant increase in total antioxidant capacity and a decrease in plasma LDH and CPK activities. Our data demonstrate that SF acts as an indirect antioxidant in skeletal muscle and could play a critical role in the modulation of the muscle redox environment, leading to the prevention of exhaustive exercise-induced muscle damage.
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Peptide Receptor Radionuclide Therapy with Radiolabeled Somatostatin Analogs
Authors: Kwekkeboom Dik J. , Krenning Eric P. , Lebtahi Rachida , Komminoth Paul , Kos-Kudła Beata , de Herder Wouter W. , Plöckinger Ursula
Published: August 2009

The purpose of this guideline is to assist physicians caring for patients with neuroendocrine tumors in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT), and in defining the minimum requirements for PRRT. This guideline also makes recommendations on what minimal patient, tumor, and treatment outcome characteristics should be reported for PRRT in order to make comparisons between studies possible. It is not this guideline’s aim to give specific recommendations on the use of specific radiolabeled somatostatin analogs for PRRT because different analogs are being used, and their availability depends on national law and local permissions.
Patient with Postcentral Gyrectomy Demonstrates Reliable Localization of Hand Motor Area Using Magnetoencephalography
Authors: Pang Elizabeth W. , Gaetz William , Drake James M. , Strantzas Samuel , MacDonald Matthew J. , Otsubo Hiroshi , Snead O. Carter
Published: August 2009

Magnetoencephalography (MEG) data analyzed with novel spatial filtering methods, namely event-related beamforming (ERB), have shown success in localizing hand motor areas in healthy adults and in a group of pediatric patients with peri-Rolandic tumors. The validity of this method to localize the primary motor field in a pediatric tumor case was confirmed by intraoperative direct cortical stimulation. Currently, the reliability of this method has not been demonstrated. We report on a 16-year-old boy with localization-related epilepsy originating from his right hemisphere sensory cortex. Hand motor and sensory areas were identified preoperatively by ERB analysis of MEG data. The patient underwent invasive monitoring which localized the epileptic focus to right postcentral gyrus, immediately posterior to the MEG motor area and adjacent to the MEG sensory area. The patient received a gyrectomy of sensory cortex guided by intraoperative direct cortical stimulation to ensure sparing of hand motor cortex. Replication of the MEG motor mapping protocol postoperatively demonstrated reliable localization of the motor and sensory areas. We also discuss caveats for future applications of this protocol.
Wild-Type JAK2 Secondary Acute Erythroleukemia Developing after JAK2-V617F-Mutated Primary Myelofibrosis
Authors: Kreft Andreas , Springer Erik , Lipka Daniel B. , Kirkpatrick Charles J.
Published: August 2009

A 54-year-old female patient developed acute erythroleukemia after an 8-year course of primary myelofibrosis. The latter harbors the JAK2-V617F mutation and was treated with hydroxyurea and anagrelide. A bone marrow trephine biopsy disclosed 2 morphologically distinct areas of chronic primary myelofibrosis and acute erythroleukemia. Microdissection and a separate molecular pathological analysis was performed. Although the activating JAK2-V617F mutation was not maintained in blasts of acute erythroleukemia, it was detectable in the chronic phase of primary myelofibrosis, indicating that this mutation did not play a role in the leukemic transformation of erythroid cells.
Intraoperative X-Ray Detection and MRI-Based Quantification of Brain Shift Effects Subsequent to Implantation of the First Electrode in Bilateral Implantation of Deep Brain Stimulation Electrodes
Authors: Hunsche Stefan , Sauner Dieter , Maarouf Mohammad , Poggenborg Jörg , Lackner Klaus , Sturm Volker , Treuer Harald
Published: August 2009

Objective: After implantation of the first electrode in bilateral deep brain stimulation (DBS) lead implantation, brain shift effects in the target region and along the implantation trajectory of the second electrode are quantified with intraoperative magnetic resonance imaging (MRI). We investigated intraoperative X-ray imaging for its feasibility in indirect detection of brain shift. Methods: In 25 patients who underwent bilateral DBS lead implantation, X-ray and MRI were performed before and after implantation of the first electrode. Two parameters of brain shift were assessed with nonrigid free-form deformation field analysis of the MRI data: global brain shift along the anterior and posterior commissure (AC-PC) line and specific brain shift along the implantation trajectory of the second electrode. Pre- and intraoperative X-ray images were geometrically and intensity corrected for detection of significant signal changes through intracranial air accumulation during implantation of the first electrode. Results: After implantation of the first electrode, brain shift greater than 1 mm (maximum 1.3 mm) was observed at the AC and brain shift greater than 2 mm (maximum 2.5 mm) was observed along the planned implantation trajectory of the second electrode. In 1 patient, the implantation trajectory of the second electrode went through a sulcus after cortical brain shift. In 9 patients, intracranial air volume between 0.1 and 38.5 ml was observed with MRI after implantation of the first electrode. Significant X-ray absorption changes were induced by an intracranial air volume of greater than 8 ml. Conclusion: In bilateral DBS implantation, brain shift effects can cause misallocation of the second electrode with the risk of adverse or no stimulation effects as well as unnecessary cortical damage. A lack of X-ray signal changes caused by intracranial air invasion during DBS lead implantation indicates a lack of clinically relevant brain shift.
Dyna-CT as an Imaging Adjunct to Routine Percutaneous Balloon Compression for Trigeminal Neuralgia
Authors: Van Gompel Jamie J. , Kallmes David F. , Morris Jonathan M. , Fode-Thomas Nicolee C. , Atkinson John L.D.
Published: August 2009

Objective and Importance: Intraprocedural three-dimensional (3D) axial tomography reconstructions have improved aneurysm detection, pedicle screw placement and more, resulting in less morbidity and improved outcomes. Currently, relative to balloon compression for trigeminal neuralgia, we are dependent upon lateral 2-dimensional imaging for the classic ‘pear shape’ imaging to determine correct positioning. ClinicalPresentation: Our patient was a 97-year-old woman with a 4-year history of V2 and V3 intermittent severe pain with typical features of trigeminal neuralgia. Intervention: After induction of anesthesia on the Dyna-CT (Siemens) angiogram table, Meckl’s cave was accessed as guided by fluoroscopy, a 4-French Fogarty catheter was introduced, and its balloon was inflated tightly for 90 s with soluble contrast agent to compress the gasserian ganglion. As would be done for 3D angiogram, the Dyna-CT was used to perform image acquisition for image reconstruction. Two additional cases are supplied to show the variability of volume filling of the balloon compression. Conclusion: We speculate that 3D reconstructions of percutaneous balloon compression of the trigeminal ganglion may aid in the identification of an ideal balloon configuration of a volume which could impact the outcome, or perhaps reduce complications such as masseter weakness or dysesthesias. Here we show the first clinical images available demonstrating volumetric reconstruction of a balloon compression for trigeminal neuralgia utilizing Dyna-CT.
Transcriptional Control of Cytokine Release from Monocytes of the Newborn: Effects of Endogenous and Exogenous Interleukin-10 versus Dexamethasone
Authors: Chusid Lina A. , Pereira-Argenziano Lucy , Miskolci Veronika , Vancurova Ivana , Davidson Dennis
Published: August 2009

Background: Monocytes play an important role in the fetal and neonatal inflammatory response syndrome. They are also the precursors of alveolar macrophages, microglial and Kupffer cells. Monocytes have pro-inflammatory (PI) and anti-inflammatory (AI) functions. Interleukin (IL)-10 is a potent AI cytokine released by monocytes. Objective: We determined the effects of endogenous and exogenous IL-10 versus equimolar levels of dexamethasone (DEX) on PI and AI cytokine release, as well as transcription factor DNA-binding activity, in endotoxin (lipopolysaccharide, LPS)-stimulated monocytes of the newborn. Methods: Monocytes were isolated into culture media from cord blood. ELISAs, electrophoretic mobility shift assays and Western blots were employed. Results: LPS-stimulated monocyte release of PI cytokines, tumor necrosis factor-α (TNF-α), IL-1β and IL-8, over 18 h was significantly augmented by addition of an IL-10 monoclonal antibody. Exogenous IL-10 at 10–8M inhibited PI cytokine release by 89–97%, while DEX at an equimolar level had no effect. DNA-binding activities of the PI transcription factors nuclear factor-ĸB (NF-ĸB) and activator protein-1 (AP-1), and the AI transcription factor signal transducer and activator of transcription 3 (STAT3) were induced over 18 h. DEX at 10–8M had no effect on any transcription factor DNA binding, but exogenous IL-10 at 10–8M produced a 60% inhibition of AP-1 DNA binding and enhanced phosphorylation of nuclear STAT3 for 18 h. Conclusion: At therapeutic levels of DEX, monocyte release of PI cytokine was insensitive to DEX in comparison to IL-10. IL-10 or its mechanism of action could lead to new therapy for inflammatory disorders in the perinatal period.
Symmetry of Retinal Vessel Arborisation in Normal and Amblyopic Eyes
Authors: Liberek Iwona , Chaberek Sławomir , Anielska Ewa , Kowalska Katarzyna , Ostrowski Kazimierz
Published: August 2009

Purpose: Arborisation of retinal vessels might be influenced by the physiological activity of the retina. It seems that the pattern of retinal vessels is an obvious object for fractal analysis. The fractal dimension of normal retinas was therefore used by us as a control value for comparison with the values collected from patients with amblyopia in one eye connected with strabismus and normal vision in the other. Methods: The ‘box-counting method’ was used for calculation of self-similarity dimension in 54 control patients, i.e. comparing 54 left retinas with 54 right ones. Statistical analysis was performed for these groups. This value was therefore used as a control for comparison with the values of fractal dimensions measured in patients with amblyopia connected with strabismus in one eye and normal vision in the other. The retinas of 30 patients with strabismus in one eye and of 1 patient with strabismus in both eyes were analysed. Results: The measurements performed on digitised photos of the retinas of these patients proved statistically significant differences between the control group and the fractal dimensions for the arborisation of retinal vessels in the eyes of patients with normal vision as well as differences in comparison with the retinas of functionally disabled eyes with defective vision connected with strabismus. Conclusion: The final conclusion is not obvious. It seems that normal vision has a statistically confirmed influence on the development of retinal vessels. Defective vision connected with strabismus is disturbing the process of arborisation of the retinal vessels. The retinal vessels of the patient eyes with normal vision differ from the normal pattern as defined by fractal dimensions of control eyes.
Experimental Models in Predicting Topical Antifungal Efficacy: Practical Aspects and Challenges
Authors: Lai J. , Maibach H.I.
Published: August 2009

What are efficient screening models for improved topical antifungals? The use of minimum inhibitory concentrations (MICs) as one such parameter is discussed; we focus on the use of animal membranes for in vitro testing while highlighting the pros and cons of each model, exploring alternatives and discussing the importance of data transferability to humans and the influence of penetration kinetics in topical antifungal efficacy. Ultimately, the gold standard of testing is in vivo in humans; however, initiating with human testing, especially for novel topical antifungal agents, may be impractical, which is why we seek the ideal experimental model that most closely mimics human skin. We conclude that the pig may be an appropriate model membrane for topical antifungal testing based on its similarities in anatomical structure, physiology and permeation to human skin. Most importantly, pig and human skins appear equally permeable to several antifungals in prior in vitro and in vivo work. We do not discuss all prior work but highlight important issues in designing the protocol and parameters of the ideal experimental model for topical antifungals.
Different Distribution Patterns of Cerebral Microbleeds in Acute Ischemic Stroke Patients with and without Hypertension
Authors: Sun Jian , Soo Yannie Oi Yan , Lam Wynnie Wai Man , Wong Ka Sing , Zeng Jin Sheng , Fan Yu Hua
Published: August 2009

Background: Cerebral microbleeds (CMBs) were found in patients with and without hypertension. We aimed to investigate different distribution patterns of CMBs in patients with and without hypertension. Methods: We examined acute ischemic stroke patients using a standardized MRI protocol that included T1, T2 and gradient-echo T2*. Clinical and imaging characteristics were collected from all patients. Results: Among 998 patients, CMBs were detected in 273 patients (27.3%). Of these, 62 did not have hypertension (22.7%). The incidence of CMBs among patients without hypertension (62/335, 18.5%) was lower than among those with hypertension (211/663, 31.8%; p < 0.01). The location of CMBs in patients without hypertension was limited to the cortical-subcortical (CSC) region in 40.3% (25/62) compared to 20.4% of those with hypertension (43/211; p = 0.01). No significant difference was found between CMB locations within the intra-CSC region in both groups. The severity of white matter changes and systolic blood pressure on admission were found to be independent predictors for CMBs in patients without hypertension. Conclusions: CMBs in patients with and without hypertension have different distribution patterns and may have a different pathogenesis. Blood pressure controlling is important in both groups because systolic blood pressure is an independent predictor of CMBs in patients without hypertension.
Porous Acellular Porcine Dermal Collagen Implants to Repair Fascial Defects in a Rat Model: Biomechanical Evaluation up to 180 Days
Authors: Ozog Yves , Konstantinovic Maja , Zheng Fang , Spelzini Federico , Verbist Godelieve , Luyten Catherina , De Ridder Dirk , Deprest Jan
Published: August 2009

Aim: To investigate the biomechanical properties of porous collagen matrices in a rat abdominal wall defect model. Study Design: 112 rats were implanted with non-cross-linked InteXèn LP, cross-linked Pelvicol, and two investigational acellular collagen matrices (ACMs) sterilized either with ethylene oxide (ACM ETO) or γ-irradiation (ACM GI). After 14, 30, 90 and 180 days, 7 animals per group were sacrificed to document adhesions, herniation, infection, stress resistance and histology. Results: The 2 sterilization methods did not cause measurable differences between ACMs. Pelvicol was more resistant than ACMs but showed degradation at 90 days without loss of strength. InteXèn LP became remodeled as a thin fibrous scar and was more resistant at all time points; however, some animals developed bulging. Conclusions: Non-cross-linked InteXèn LP became remodeled by 180 days with remarkable stress resistance. Despite cross-linking Pelvicol showed degradation. Comparable but investigational ACM explants were less resistant without morphologic differences to explain this.
Stretching Exercise Program Improves Gait in the Elderly
Authors: Cristopoliski Fabiano , Barela José Angelo , Leite Neiva , Fowler Neil E. , Rodacki André L. Felix
Published: August 2009

Background: Ageing is characterized by a number of physical changes that contribute to a decline in the ability to perform daily tasks. Stretching has been proposed to reduce hip flexion contracture and increase hip and pelvis range of motion, thus improving gait performance. Objective: The purpose of this study was to determine whether a supervised stretching program designed to improve the range of motion of the lower limbs alters gait kinematics in older adults. Methods: Twenty healthy older adult women (65.9 ± 4.2 years old and BMI 24.9 ± 3.5) were divided into 2 groups. The experimental group undertook 12 sessions of stretching exercises, whereas the control group did not engage in any physical activity. Gait performance was assessed at the beginning of the experiment and after the 4-week intervention period. Results: Those in the experimental group showed increased step length, higher velocity and reduced double support time after training. In addition, participants involved in the stretching program showed greater anterior and lateral pelvis tilt and also greater rotation (p < 0.05). Conclusions: Based on our results, we can suggest that a supervised stretching program is effective to alter a number of gait variables. Moreover, after the stretching protocol, aged participants displayed gait parameters which were similar to those reported in young healthy adults. Therefore, stretching can be used as an effective means to improve range of motion and reverse some age-related changes that influence gait performance.
Cortisol Metabolism in Depressed Patients and Healthy Controls
Authors: Römer Benedikt , Lewicka Sabina , Kopf Daniel , Lederbogen Florian , Hamann Bettina , Gilles Maria , Schilling Claudia , Onken Vera , Frankhauser Pascal , Deuschle Michael
Published: August 2009

Background: Chronic stress as well as major depressive disorders are associated with hypercortisolemia and impaired hypothalamic-pituitary-adrenocortical axis functioning. The aim of this study was to determine whether in major depression changes in the activity patterns of local modulators of glucocorticoid action might contribute to an increase in cortisol bioavailability and if they change during antidepressant treatment and clinical response. Methods: Concentrations of urinary total cortisol (UFF), urinary total cortisone (UFE), tetrahydrocortisone (THE), tetrahydrocortisol (THF) and allo-THF (5α-THF) were measured in 10-hour nocturnal urine samples of 19 depressed patients and 15 healthy controls. The activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) as well as 5α- and 5β-reductases was assessed by calculating the ratios of glucocorticoid metabolites. Patients were treated for 28 days with either mirtazapine or venlafaxine. Enzyme activity was observed during the course of treatment and compared to healthy controls. Responders to treatment were selected for this analysis. Results: Depressed patients showed reduced 5α-reductase activity manifested as a significantly lower amount of 5α-THF (102.8 ± 167.2 vs. 194.6 ± 165.8 μg, p = 0.019). The increase in the UFF/UFE ratio (0.73 ± 0.32 vs. 0.29 ± 0.13, p < 0.0001) indicates reduced activity of renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). During pharmacological treatment, 5α-reductase activity in patients returned to the level of the control group, while the decrease in 11β-HSD2 activity persisted until day 28. Conclusions: Our results show changes in activity of intracellular modulators of steroid action in major depressive disorders, particularly a reduced activity of the intracellular cortisol-deactivating enzymes 5α-reductase and 11β-HSD2. These changes suggest an increase in cortisol bioavailability within tissues.
Dietary Habits in Middle Age and Future Changes in Activities of Daily Living – NIPPON DATA80
Authors: Nakamura Yasuyuki , Hozawa Atsushi , Turin Tanvir Chowdhury , Takashima Naoyuki , Okamura Tomonori , Hayakawa Takehito , Kita Yoshikuni , Okayama Akira , Miura Katsuyuki , Ueshima Hirotsugu
Published: August 2009

Background: Almost no studies have investigated the relationship between food intake measured at middle age and future disability. Objective: To examine the association of meat, fish and egg intake with risk of subsequent mortality and/or future decline in activities of daily living (ADL) among the elderly. Methods: The cohort consisted of 2,316 Japanese individuals aged 47–60 at the baseline who were randomly selected throughout Japan and followed up for 19 years from 1980. Results: Those who ate meat at least once every 2 days were younger, there were more men, daily drinkers, professional workers and urban residents compared to those who ate meat less than once every 2 days. Over 19 years of follow-up, 75 participants became dependent due to impaired ADL. A higher intake of meat was associated with a statistically significant decrease in impaired ADL occurrence (odds ratio = 0.61, 95% confidence intervals 0.38–0.99, p = 0.04). Fish and egg intake were not associated with any difference in impaired ADL occurrence. None of the 3 foods were associated with any changes in mortality. Conclusion: A higher intake of meat may prevent impaired ADL occurrence, although this was not associated with a lower mortality.
Recombinant Murine Interleukin 4 Protein Therapy for Psoriasis in a Transgenic VEGF Mouse Model
Authors: Ren Xiaoxiao , Li Jiong , Zhou Xikun , Luo Xiaolei , Huang Nongyu , Wang Yongsheng , Chen Xiancheng , Wei Yuquan
Published: August 2009

Background: Psoriasis is a typical autoimmune disease caused by a deregulation of the Th1/Th2 balance, and immunotherapy for psoriasis has been shown to be clinically efficacious. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis. Evidence suggests that the chronic delivery of VEGF to the skin can result in a profound inflammatory condition with many of the cellular and molecular hallmarks of human psoriasis. In this study, we investigated whether the transgenic VEGF mouse is a suitable model for antipsoriatic studies. Aim: To determine the effect of a recombinant murine interleukin 4 (rmIL-4) in the transgenic VEGF mouse model. Methods: Fifteen homozygous K14-VEGF transgenic mice were injected subcutaneously with rmIL-4 protein for 30 consecutive days with a prospective dose escalation of 0.5, 2 or 5 μg/kg. Hematoxylin-eosin staining, immunohistochemistry and real-time polymerase chain reaction analyses were performed with ear samples. Results: The rmIL-4 protein therapy was well tolerated. Tissue sections from treated skin showed improvements upon morphological and histological examinations: diminution of erythematous appearance and regression of epidermal thickness were observed, and T lymphocyte infiltration decreased significantly. The expressions of adhesion molecules, such as vascular cell adhesion molecule 1 and intracellular adhesion molecule 1, were found reduced. The level of IL-4 mRNA also increased while the level of γ-interferon mRNA decreased, resulting in a 10-fold increase in the ratio of Th1/Th2. Conclusions: Our results reveal that rmIL-4 has clinical efficacy for the treatment of K14-VEGF transgenic mice. Angiogenesis and inflammation were ameliorated by therapy with rmIL-4.
Vascular-Directed Tissue Factor Pathway Inhibitor Overexpression Regulates Plasma Cholesterol and Reduces Atherosclerotic Plaque Development
Authors: Pan Shuchong , White Thomas A. , Witt Tyra A. , Chiriac Anca , Mueske Cheri S. , Simari Robert D.
Published: August 2009

Rationale:

Tissue factor pathway inhibitor (TFPI) is a potent regulator of the tissue factor pathway and is found in plasma in association with lipoproteins.

Objective:

To determine the role of TFPI in the development of atherosclerosis, we bred mice which overexpress TFPI into the apolipoprotein E–deficient (apoE
−/−
) background.

Methods and Results:

On a high-fat diet, smooth muscle 22α (SM22α)-TFPI/apoE
−/−
mice were shown to have less aortic plaque burden compared to apoE
−/−
mice. Unexpectedly, SM22α-TFPI/apoE
−/−
had lower plasma cholesterol levels compared to apoE
−/−
mice. Furthermore, SM22α-TFPI mice fed a high-fat diet had lower cholesterol levels than did wild-type mice. Because TFPI is associated with lipoproteins and its carboxyl terminus (TFPIct) has been shown to be a ligand for the very-low-density lipoprotein (VLDL) receptor, we hypothesized that TFPI overexpression may regulate lipoprotein distribution. We quantified VLDL binding and uptake in vitro in mouse aortic smooth muscle cells from SM22α-TFPI and wild-type mice. Mouse aortic smooth muscle cells from SM22α-TFPI mice demonstrated higher VLDL binding and internalization compared to those from wild-type mice. Because SM22α-TFPI mice have increased circulating levels of TFPI antigen, we examined whether TFPIct may act to alter lipoprotein distribution. In vitro, TFPIct increased VLDL binding, uptake, and degradation in murine embryonic fibroblasts. Furthermore, this effect was blocked by heparinase treatment. In vivo, systemic administration of TFPIct reduced plasma cholesterol levels in apoE
−/−
mice.

Conclusions:

These studies suggest that overexpression of TFPI lowers plasma cholesterol through the interaction of its carboxyl terminus with lipoproteins and heparan sulfate proteoglycans.
Association of Asymptomatic Peripheral Arterial Disease With Vascular Events in Patients With Stroke or Transient Ischemic Attack
Authors: Sen Souvik , Lynch Donald R. , Kaltsas Effie , Simmons Jennifer , Tan Walter A. , Kim Jongyeol , Beck James , Rosamond Wayne
Published: August 2009

Background and Purpose—

Patients with stroke and patients with transient ischemic attack (TIA) are at high risk for vascular events and may not exhibit the signs and symptoms of peripheral arterial disease (PAD). We investigated if asymptomatic PAD detected by ankle brachial index <0.9 is independently associated with recurrent vascular events in patients with stroke or TIA.

Methods—

In this prospective longitudinal hospital-based cohort study, asymptomatic PAD was detected by ankle brachial index measurement in consecutive patients with stroke and patients with TIA. They were assessed for stroke risk factors, ankle brachial index measurement, and laboratory parameters known to be associated with stroke risk. These patients were followed for composite vascular events, including stroke, TIA, myocardial infarction, and vascular death.

Results—

In a 1-year period, 102 patients were evaluated, of whom 26% had asymptomatic PAD. All patients were followed for a median period of 2.1 years from the index stroke/TIA (range, 1.0 to 2.7 years) for vascular events. Kaplan–Meier curve showed fewer patients with asymptomatic PAD remained free of composite vascular events (48% compared with 84% in the no-PAD group; log rank,
P
=0.0001). Asymptomatic PAD was significantly associated with composite vascular events before (hazard ratio, 4.2; 95% CI, 1.9 to 9.3;
P
=0.0003) and after adjustment for confounders (hazard ratio, from Model 1, 2.8; 95% CI, 1.1 to 7.2;
P
=0.03 and Model 2, 3.4; 95% CI, 1.4 to 8.2,
P
=0.006). Asymptomatic PAD was also significantly associated with stroke before (hazard ratio, 6.5; 95% CI, 2.1 to 19.9;
P
=0.001) and after adjustment for confounders (hazard ratio from Model 1, 4.8; 95% CI, 1.5 to 15.3;
P
=0.009 and Model 2, 5.2; 95% CI, 1.5 to 17.6;
P
=0.008).

Conclusions—

In patients with stroke or TIA, asymptomatic PAD is independently associated with recurrent vascular events and stroke.
Hospital Rates of Thrombolysis for Acute Ischemic Stroke
Authors: van Wijngaarden Jeroen D.H. , Dirks Maaike , Huijsman Robbert , Niessen Louis W. , Fabbricotti Isabelle N. , Dippel Diederik W.J. ,   the Promoting Acute Thrombolysis for Ischaemic Stroke (PRACTISE) Investigators
Published: August 2009

Background and Purpose—

The purpose of this study was to determine if organizational culture explains differences in rates of intravenous thrombolysis for acute ischemic stroke between different hospitals.

Methods—

A cohort study was done in 12 centers admitting 5515 consecutive patients with acute stroke in The Netherlands. A multilevel logistic regression model was used to relate the likelihood of treatment with thrombolysis to characteristics of the organizational culture of the centers. Organizational culture was defined by 10 characteristics and scored by a panel. A sum score was created by adding all scores and dividing by 10.

Results—

Thrombolysis rates varied from 5.7% to 21.7%. We observed an association between thrombolysis and the availability of informal and formal feedback (OR, 1.18; 95% CI, 1.09 to 1.28); a learning culture (OR, 1.12; 95% CI, 1.02 to 1.23); uncompromising, individual clinical leadership (OR, 1.12; 95% CI, 1.03 to 1.23); explicit goals (OR, 1.08; 95% CI, 1.01 to 1.17); and with the sum score (OR, 1.12; 95% CI, 1.02 to 1.23).

Conclusions—

Several cultural characteristics of the hospital organization are related to thrombolysis rate. Organizational culture may be an important target for interventions aimed at increasing rates of thrombolysis for acute ischemic stroke in hospitals.