bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycerophosphate Is Interchangeable with Inorganic Phosphate in Terms of Safety and Serum Pharmacokinetics
Authors: Topp Heinrich , Hochfeld Olena , Bark Staffan , Grossmann Matthias , Joukhadar Christian , Westphal Martin , Straatsma Harald , Rothenburger Markus
Published: October 2011

Objective: The primary aim of the present investigation was to determine and compare the pharmacokinetic (PK) profiles of inorganic phosphate in serum and urine after intravenous administration of sodium glycerophosphate and inorganic sodium phosphate. Additionally, study product safety profiles were evaluated. Subjects and Methods: In total, 27 healthy, white volunteers (17 male/10 female) were enrolled in this double-blinded, randomized, 2-sequence, crossover study and were assigned to receive an organic test drug (sodium glycerophosphate) and an inorganic reference preparation (sodium phosphate) on 2 occasions. Validated analytical methods were used, and concentrations of total inorganic phosphate in serum and urine were determined over 24 h following a single 4-hour continuous intravenous infusion of test and reference drugs at a dose of 80 mmol. Study days were separated by washout periods of 7 days. An analysis of variance, based on population means and 90% confidence intervals (CIs), was used for testing bioequivalence (BE; range 0.8–1.25) between investigational products. Results: The geometric means of the ratio of the point estimates and corresponding 90% CIs for the area under the concentration-versus-time curve of inorganic serum phosphate from 0 to 24 h (AUC0–24), the phosphate’s maximum concentration in serum (Cmax) and the total amount of inorganic phosphate excreted in urine over 24 h corrected for individual baseline values (Ae0–24 bc) were estimated. The test/reference ratios for inorganic phosphate were 1.04 (CI 1.00–1.07), 0.85 (CI 0.84–0.87) and 0.84 (CI 0.77–0.92) for AUC0–24, Cmax in serum and Ae0–24 bc in urine, respectively. Hence, standard BE criteria were met for AUC0–24 and Cmax in serum, while Ae0–24 bc marginally failed to demonstrate BE. After drug administration, a total of 15 subjects reported the occurrence of at least 1 treatment emergent adverse event (AE). All AEs were classified as mild to moderate in severity, and the two treatment groups were equally affected. No serious AEs occurred. Conclusion: The serum PK profiles of inorganic phosphate were almost superimposable following intravenous administration of equimolar doses of test and reference drugs. Thus, we conclude that the two study drugs are essentially similar in terms of serum PK profiles, safety and tolerability.
Use of Adjuvant Therapy in Patients with FIGO Stage III Endometrial Carcinoma: A Multicenter Retrospective Study
Authors: Marchetti Claudia , Pisano Carmela , Mangili Giorgia , Lorusso Domenica , Panici Pierluigi Benedetti , Silvestro Giustino , Candiani Massimo , Greggi Stefano , Perniola Giorgia , Di Maio Massimo , Pignata Sandro
Published: October 2011

Objectives: Adjuvant treatment for stage III endometrial cancer is not yet defined. Previous experiences support the usefulness of combined chemotherapy and radiotherapy. The aim of this retrospective study was to describe the outcome in a cohort of patients with stage III endometrial cancer treated with chemotherapy and/or radiotherapy. Methods: A multicenter retrospective analysis of patients with stage III endometrial cancer from 1998 to 2009 was conducted. The impact on relapse-free survival of clinical and pathological variables and adjuvant treatment received was analyzed by univariate and multivariate analysis. Results: Eighty-two patients were considered. Median age was 62 years (range 38–82). Seventy-eight (95%) patients received an adjuvant treatment: chemotherapy (41; 50%), radiotherapy (18; 22%), or combined chemo-radiotherapy (19; 23%). Four patients were excluded from analysis because they were not treated with any adjuvant therapy. At univariate analysis, tumor grade (G3 vs. G1–G2; p = 0.003) was associated with risk of recurrence; similarly, patients treated with radiotherapy alone (p = 0.031, hazard ratio 0.19, 95% CI 0.04–0.86) or chemotherapy alone (p = 0.053, hazard ratio 0.54, 95% CI 0.29–1.01) had a significantly higher risk for relapse, compared to those treated with the multimodality approach. Relapse-free survival at 3 years was 86.5, 65.8 and 44.1%, with the multimodality approach, chemotherapy and radiotherapy, respectively. At multivariable analysis, age and grading were independently associated with recurrence-free survival. Hazard ratio for relapse-free survival was 0.14 (95% CI 0.02–1.04) and 0.20 (95% CI 0.04–1.11) for multimodality treatment compared to chemotherapy alone and radiotherapy alone, respectively. Conclusions: Age and grading are independent prognostic factors. A combined approach with radiotherapy and chemotherapy may induce an advantage in relapse-free survival compared to radiotherapy or chemotherapy alone. Prospective clinical trials are needed to verify this clinical hypothesis.
Expiratory Flow-Volume Loop Profile and Patient Outcome in Chronic Obstructive Pulmonary Disease in Acute Respiratory Failure: A Prospective Observational Study in a Single Intensive Care Unit
Authors: Porot Véronique , Ernesto Sylvie , Leray Véronique , Delannoy Bertrand , Bourdin Gael , Bayle Frédérique , Richard Jean-Christophe , Guérin Claude
Published: October 2011

Background: Expiratory flow-volume (EFV) loops are continuously displayed on the screen of intensive care unit (ICU) ventilators. Objectives: It was the aim of this study to investigate the relationships of EFV to chronic obstructive pulmonary disease (COPD) patient outcome. Methods: This is a prospective study on COPD patients who received invasive mechanical ventilation for acute respiratory failure in the ICU. Within the 24-hour post-intubation period, the angle of the EFV slope during the last 50% of expiration was computed and patients were stratified into 4 quartiles. Resistance, compliance of the respiratory system and change in end-expiratory lung volume above relaxation volume were assessed. Patients were followed up to hospital discharge. The main outcome was hospital mortality. Secondary outcomes were ICU mortality, length of ICU stay, duration of invasive ventilation, number of intubations, oxygen and non-invasive ventilation. Results: Thirty-eight patients were analysed. The first quartile comprised 9 patients (median angle 11°, interquartile range 8–12), the second 10 patients (median angle 26°, range 19–30), the third 10 patients (median angle 42°, range 39–46), and the fourth 9 patients (median angle 53°, range 49–64). Hospital and ICU mortality were not different between groups. Lengths of ICU and hospital stay and length of invasive ventilation were significantly different between groups, with the highest values observed in the first quartile. The rate of oxygen use and non-invasive ventilation in the ICU and at hospital discharge was significantly different between groups, with the highest rate observed in the first quartile. There was a significant negative correlation between angle and resistance, compliance of the respiratory system and change in end-expiratory lung volume above the relaxation volume. Conclusion: The slope of the angle during the last 50% of expired volume in the COPD patients was associated with worsened respiratory mechanics and higher morbidity.
Induction of Vascular GTP-Cyclohydrolase I and Endogenous Tetrahydrobiopterin Synthesis Protect Against Inflammation-Induced Endothelial Dysfunction in Human Atherosclerosis
Authors: Antoniades Charalambos , Cunnington Colin , Antonopoulos Alexis , Neville Matt , Margaritis Marios , Demosthenous Michael , Bendall Jennifer , Hale Ashley , Cerrato Ruha , Tousoulis Dimitris , Bakogiannis Constantinos , Marinou Kyriakoula , Toutouza Marina , Vlachopoulos Charalambos , Leeson Paul , Stefanadis Christodoulos , Karpe Fredrik , Channon Keith M.
Published: October 2011

Background—

The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) is essential for maintenance of enzymatic function. We hypothesized that induction of BH4 synthesis might be an endothelial defense mechanism against inflammation in vascular disease states.

Methods and Results—

In Study 1, 20 healthy individuals were randomized to receive
Salmonella typhi
vaccine (a model of acute inflammation) or placebo in a double-blind study. Vaccination increased circulating BH4 and interleukin 6 and induced endothelial dysfunction (as evaluated by brachial artery flow-mediated dilation) after 8 hours. In Study 2, a functional haplotype (X haplotype) in the
GCH1
gene, encoding GTP-cyclohydrolase I, the rate-limiting enzyme in biopterin biosynthesis, was associated with endothelial dysfunction in the presence of high-sensitivity C-reactive protein in 440 coronary artery disease patients. In Study 3, 10 patients with coronary artery disease homozygotes for the
GCH1
X haplotype (XX) and 40 without the haplotype (OO) underwent
S Typhi
vaccination. XX patients were unable to increase plasma BH4 and had a greater reduction of flow-mediated dilation than OO patients. In Study 4, vessel segments from 19 patients undergoing coronary bypass surgery were incubated with or without cytokines (interleukin-6/tumor necrosis factor-α/lipopolysaccharide) for 24 hours. Cytokine stimulation upregulated
GCH1
expression, increased vascular BH4, and improved vasorelaxation in response to acetylcholine, which was inhibited by the GTP-cyclohydrolase inhibitor 2,4-diamino-6-hydroxypyrimidine.

Conclusions—

The ability to increase vascular
GCH1
expression and BH4 synthesis in response to inflammation preserves endothelial function in inflammatory states. These novel findings identify BH4 as a vascular defense mechanism against inflammation-induced endothelial dysfunction.
Angiotensin-Converting Enzyme 2 Deficiency Is Associated With Impaired Gestational Weight Gain and Fetal Growth Restriction
Authors: Bharadwaj Manish S. , Strawn William B. , Groban Leanne , Yamaleyeva Liliya M. , Chappell Mark C. , Horta Carina , Atkins Katie , Firmes Luciana , Gurley Susan B. , Brosnihan K. Bridget
Published: October 2011

Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system that influences the relative expression of angiotensin II (Ang II) and Ang-(1-7). Although ACE2 expression increases in normal pregnancy, the impact of ACE2 deficiency in pregnancy has not been elucidated. We determined the influence of ACE2 deficiency on circulating and tissue renin-angiotensin system components, fetal and maternal growth characteristics, and maternal hemodynamics (mean blood pressure and cardiac output) at day 18 of gestation. Gestational body weight gain was lower in the ACE2 knockout (KO) versus C57BL/6 (wild-type) mice (30.3±4.7 versus 38.2±1.0 g;
P
<0.001). Fetal weight (0.94±0.1 versus 1.24±0.01 g;
P
<0.01) and length (19.6±0.2 versus 22.2±0.2 mm;
P
<0.001) were less in KO. Mean blood pressure was significantly reduced in C57BL/6 with pregnancy; it was elevated (
P
<0.05) in the KO virgin and pregnant mice, and this was associated with an increased cardiac output in both C57BL/6 and KO pregnant mice (
P
<0.05). Plasma Ang-(1-7) was reduced in pregnant KO mice (
P
<0.05). Placenta Ang II levels were higher in KO mice (52.9±6.0 versus 22.0±3.3 fmol/mg of protein;
P
<0.001). Renal Ang II levels were greater in KO virgin mice (30.0±1.7 versus 23.7±1.1 fmol/mg of protein;
P
<0.001). There was no change in the Ang-(1-7) levels in the KO placenta and virgin kidney. These results suggest that ACE2 deficiency and associated elevated placenta Ang II levels impact pregnancy by impairing gestational weight gain and restricting fetal growth.
Social Memory and Identity: Luke 19:12b—24 and 27
Authors: van Eck Ernest
Published: October 2011

Based on a specific understanding of social memory, this article develops a social-scientific model of social memory. The model is then applied to three social memories of the events surrounding Archelaus’ journey to Rome to get his kingship over Judaea confirmed in 4 BCE: Josephus’ War (2.80—100), his Antiquities (17.208—323), and the social memory of the event in Luke’s Gospel, as part of the parable of the minas (Lk 19:12b—24 and 27).
Beach ridge systems – archives for Holocene coastal events?
Authors: Scheffers Anja , Engel Max , Scheffers Sander , Squire Peter , Kelletat Dieter
Published: October 2011

Holocene coastal evolution has been extensively studied by workers from various earth science disciplines, particularly sedimentologists and geomorphologists. Some of these studies have focused on the history of regional sea-level changes in various ocean basins and the mechanisms – such as eustasy, glacio-isostasy, sediment compaction, neotectonics and climatic forces – involved in such changes. Although beach ridges have been used to identify steps in coastal evolution, only in a few cases have beach ridge systems been investigated with respect to event histories (for example, cyclones and tsunamis). Beach ridge systems, however, belong to the most promising geo-archives for the study of climate change and sea-level variations over the Holocene, as well as for deciphering event histories. This paper presents examples of some studies in this field, in relation to a global overview of beach ridge systems and their morphological characteristics.
Ecosystem services
Authors: Potschin Marion B. , Haines-Young Roy H.
Published: October 2011

The ‘ecosystem service’ debate has taken on many features of a classic Kuhnian paradigm. It challenges conventional wisdoms about conservation and the value of nature, and is driven as much by political agendas as scientific ones. In this paper we review some current and emerging issues arising in relation to the analysis and assessment of ecosystem services, and in particular emphasize the need for physical geographers to find new ways of characterizing the structure and dynamics of service providing units. If robust and relevant valuations are to be made of the contribution that natural capital makes to human well-being, then we need a deeper understanding of the way in which the drivers of change impact on the marginal outputs of ecosystem services. A better understanding of the trade-offs that need to be considered when dealing with multifunctional ecosystems is also required. Future developments must include methods for describing and tracking the stocks and flows that characterize natural capital. This will support valuation of the benefits estimation of the level of reinvestment that society must make in this natural capital base if it is to be sustained. We argue that if the ecosystem service concept is to be used seriously as a framework for policy and management then the biophysical sciences generally, and physical geography in particular, must go beyond the uncritical ‘puzzle solving’ that characterizes recent work. A geographical perspective can provide important new, critical insights into the place-based approaches to ecosystem assessment that are now emerging.
“I Dream of Them Almost Every Night”
Authors: Ramey Jessie B.
Published: October 2011

This article reconceptualizes orphanages as child care, exploring the ways in which working-class fathers used institutions in times of family crisis to meet their child care needs. By examining the white, largely widowed men who placed their children in the United Presbyterian Orphan’s Home in Pittsburgh from the 1880s through the 1920s, the study sheds light on working-class fatherhood, a little understood aspect of family history. Using rich new sources not previously available to scholars, the article incorporates rigorous quantitative analysis of the records of 590 children at the institution, providing new insight into the lives of working-class fathers struggling to balance their labor and parenting responsibilities as they used the orphanage as a strategy for family survival.
Construction and demolition waste as a source of PVC for recycling
Authors: Prestes Sabrina Moretto Darbello , Mancini Sandro Donnini , Rodolfo Antonio , Keiroglo Raquel Carramillo
Published: October 2011

Construction and demolition waste can contain considerable amounts of polyvinyl chloride (PVC). This paper describes a study of the recycling of PVC pipes collected from such waste materials. In a sorting facility for the specific disposal of construction and demolition waste, PVC was found to represent one-third of the plastics separated by workers. Pipes were sorted carefully to preclude any possible contamination by poly(ethylene terephthalate) (PET) found in the waste. The material was ground into two distinct particle sizes (final mesh of 12.7 and 8 mm), washed, dried and recycled. The average formulation of the pipes was determined based on ash content tests and used in the fabrication of a similar compound made mainly of virgin PVC. Samples of recycled pipes and of compound based on virgin material were subjected to tensile and impact tests and provided very similar results. These results are a good indication of the application potential of the recycled material and of the fact that longer grinding to obtain finer particles is not necessarily beneficial.
Developmental and Behavior Problems Predict Parenting Stress in Young Children With Global Delay
Authors: Tervo Raymond C.
Published: October 2011

To identify parent-reported symptoms that predict parenting stress in preschoolers with global developmental delay, 201 parents/guardians of 142 boys and 59 girls with global delay, mean age 39.1 months (range, 18 to 63 months) were studied retrospectively. Parents completed the following: (a) a semistructured interview; (b) the Child Development Inventory, (c) Child Behavior Checklist 1½-5, and the (d) Parenting Stress Index-Short Form. Forty-two percent of parents described clinically significant parenting stress (≥ 85th percentile). The Parenting Stress Index-Short Form subscales Difficult Child and Parent–Child Dysfunctional Interactions were elevated. Parental stress increased with higher gross motor development and decreased as social and fine-motor ratios increased. Furthermore, stress increased when parents reported higher levels on the Emotionally Reactive and Withdrawn scale scores and when parents reported Pervasive Developmental and Oppositional Defiant Problems. In mobile children with global delay, behavior problems predict parenting stress.
Source localization of multiple impacts in a plate
Authors: Park J H , Moon Y S , Lee S K
Published: October 2011

Source localization technology (SLT) for impact loads in a plate structure has been used for health monitoring, damage identication, fatigue analysis, human-interaction technology, etc. Much research on source localization has been focused only on the localization of single impacts. This article presents novel research into the source localization of multiple impacts. It is difficult to localize the sources of multiple impacts using current SLT because of the overlapping of dispersive waves induced by multiple impacts and the reflection of those waves from the edge of the plate. The new method functions by solving the overlapping problem and the reflection problem. These two problems are solved by adopting pre-signal processing based on band pass filtering and linear-prediction filtering. The method is applied to the localization of multiple impacts on an isotropic plate. Results from numerical simulation and from experimentation are presented and these verify the capability of the proposed method.
Cooperative regenerative braking control algorithm for an automatic-transmission-based hybrid electric vehicle during a downshift
Authors: Jo C , Ko J , Yeo H , Yeo T , Hwang S , Kim H
Published: October 2011

A cooperative regenerative braking control algorithm is proposed for a six-speed automatic-transmission-based parallel hybrid electric vehicle (HEV) during a downshift that satisfies the requirements for braking force and driving comfort. First, a downshift strategy during braking is suggested by considering the re-acceleration performance. To maintain driving comfort, a cooperative regenerative braking control algorithm is developed that considers the response characteristics of the electrohydraulic brake. Using the electrohydraulic brake’s hardware and an HEV simulator, a hardware-in-the-loop simulation (HILS) is performed. From the HILS results, it is found that the proposed cooperative regenerative braking control algorithm satisfies the demanded braking force and driving comfort during the downshift with regenerative braking.
An investigation of icing in a liquid petroleum gas liquid phase fuel injector with a shut-off valve
Authors: Wi H-S , Yi J-P , Lee J-H , Park J-I
Published: October 2011

Liquefied petroleum gas (LPG) engines are considered to be a clean energy source. The fuel supply strategy for this type of engine is moving away from a mixer-type fuel supply and towards an LPLI (liquid phase LPG injection) system, which injects liquid phase LPG directly into the manifold, enhancing volumetric efficiency, giving a faster response, and providing more precise fuel control. The LPLI system requires a new development to meet more stringent emissions regulations than previous regulations. This new development is motivated by the tendency of LPG in an LPLI system to leak out of the injector after the engine is shut off. Installing a shut-off valve directly after the injector is one possible strategy for preventing this leakage. To install the shut-off valve in the injector, it is necessary to change its structure. In a prototype of the shut-off valve type injector, the fuel path inside the adapter becomes longer and more complicated than in a conventional LPLI injector, which may cause icing at the injector tip. Because LPG absorbs heat for evaporation when it is injected into the manifold, the temperature of the injector tips is decreased to a temperature even below freezing. Water vapour in the intake air passing the cold injector can form ice that sticks on the surface of the injector. This phenomenon is called icing and can become disruptive to precise air/fuel control as ice particles fall off and enter the cylinder. Using injection visualization, emissions analysis, and data on engine running conditions, these icing phenomena are classified into two types: one at the cold adapter surface and the other at the LPG transfer tube (a Teflon tube) tip, which is placed in the centre of the injector adapters. The icing phenomena in shut-off valve type LPLI injectors are significantly reduced by enhancing heat transfer between the cold injector tip and the hot intake manifold, and by surrounding the injecting tip with a shroud.
High-speed maglev train-guideway–tunnel–soil modelling of ground vibration
Authors: Wang J , Jin X , Cao Y
Published: October 2011

A fully coupled three-dimensional multi-body finite element model coupled with a perfect matching layer approach is presented to study the ground vibrations created by a high-speed maglev train running in a tunnel. The maglev train is assumed to consist of multiple rigid bodies and the magnetic force between the maglev train and its guideway is simulated using linear springs and dampers. The guideway, tunnel and soil are modeled by three dimensional finite elements with PML as the artificial boundary condition. The results obtained for a maglev train running on a viaduct line show a reasonable agreement with available experimental data, which demonstrates the validity of the proposed model. This model is subsequently utilized to simulate the vibration levels created by the train running in a tunnel in terms of parameters related to the maglev train, tunnel, and soil.
Short-Term Music Training Enhances Verbal Intelligence and Executive Function
Authors: Moreno Sylvain , Bialystok Ellen , Barac Raluca , Schellenberg E. Glenn , Cepeda Nicholas J. , Chau Tom
Published: October 2011

Researchers have designed training methods that can be used to improve mental health and to test the efficacy of education programs. However, few studies have demonstrated broad transfer from such training to performance on untrained cognitive activities. Here we report the effects of two interactive computerized training programs developed for preschool children: one for music and one for visual art. After only 20 days of training, only children in the music group exhibited enhanced performance on a measure of verbal intelligence, with 90% of the sample showing this improvement. These improvements in verbal intelligence were positively correlated with changes in functional brain plasticity during an executive-function task. Our findings demonstrate that transfer of a high-level cognitive skill is possible in early childhood.
Electrorheology Improves Transportation of Crude Oil
Authors: Tang Hong , Huang Ke , Tao R.
Published: October 2011

A system to simulate crude oil flow in pipeline is established in the authors’ lab. The system measures the crude oil flow rate with and without the electric field treatment. With this system, it is demonstrated that the crude oil flow rate is increased by about 20% after an electric field of 12,000 V/cm is applied in the direction parallel to the flow direction. The electric energy for this electric field treatment is very small and oil temperature is almost unchanged. The electrorheology-induced thinning effect will have significant application in crude oil pipeline transportation.
The Effect of Low-Dose Pravastatin in Metabolic Syndrome for Primary Prevention of Cardiovascular Disease in Japan
Authors: Matsushima Teruhiko , Nakaya Noriaki , Mizuno Kyoichi , Ohashi Yasuo , Teramoto Tamio , Yokoyama Shinji , Ichikawa Shuichi , Ishikura Norio , Kamiyama Kimihide , Nakamura Haruo ,   for the MEGA Study Group
Published: October 2011

The Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study demonstrated the beneficial effect of low-dose pravastatin treatment (10-20 mg/d) on cardiovascular disease (CVD) in Japanese patients with mild-to-moderate hypercholesterolemia. However, it is not known whether mild lipid modification is effective even for patients at high risk. In this study, we evaluated low-dose pravastatin treatment in patients with metabolic syndrome in the MEGA Study. Metabolic syndrome (MetSyn) was defined according to the modified US National Cholesterol Education Program criteria. There were 72 coronary heart disease (CHD) events and 130 CVD events in 2636 patients with MetSyn, and 70 CHD events and 125 CVD events in 5196 patients without MetSyn (hazard ratios 1.85 and 1.90, respectively). No significant risk reduction in CHD was found in the diet plus pravastatin group compared with the diet group patients with MetSyn (hazard ratio .78, P = .29). On the other hand, there was a significant 36% CVD risk reduction ( P = .01) in the diet plus pravastatin group compared with the diet group patients with MetSyn, with a small number needed to treat (45). These results indicate that low-dose pravastatin provides a substantial beneficial effect for the prevention of CVD in Japanese patients with MetSyn without known CVD, a population at proportionally high risk in primary prevention.
Effectiveness of adsorbed film and gel layer in hydration lubrication as adaptive multimode lubrication mechanism for articular cartilage
Authors: Murakami T , Nakashima K , Yarimitsu S , Sawae Y , Sakai N
Published: October 2011

With various daily activities, the effectiveness of adsorbed film formed on a gel-like layer at the uppermost superficial articular cartilage in natural synovial joints becomes important to control the friction and wear of articular cartilage in mixed or boundary lubrication regime as an adaptive multimode lubrication mechanism. Furthermore, in the case where the adsorbed film has been removed, the proteoglycan gel layer is expected to preserve low friction and protect against the wear of bulk cartilage tissue with an effective hydration lubrication mechanism. Besides, it is indicated that the biphasic lubrication plays an important role in lowering of friction in articular cartilage containing a large amount of water. At the present stage, however, the detailed relationship between adsorbed films and hydrated gel layers has not yet been elucidated. In this article, the frictional behaviours of articular cartilage on a glass plate were observed in the reciprocating tests with the restarting process after interruption and unloading. The lubricating effectiveness of adsorbed films in hyaluronate (HA) solutions was examined using intact and partially damaged cartilage specimens. The role of albumin and γ-globulin in relation to the surface conditions of gel layer is discussed. The restarting friction immediately after reloading became lower as a result of recovery of the effective interstitial fluid pressurization and hydration and adsorbed films have a significant effect on the frictional behaviour at local contacts. To clarify the molecular phenomena taking place under rubbing condition, in situ observations of the forming adsorbed film were conducted. The measurements were performed using the fluorescent staining method for protein and HA molecules at low contact pressures.
Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell transplantation
Authors: Horch Matthew , Nguyen Vu H.
Published: October 2011

From mouse studies to recently published clinical trials, evidence has accumulated on the potential use of regulatory T cells (Treg) in preventing and treating graft- versus-host disease following hematopoietic-cell transplantation (HCT). However, controversies remain as to the phenotype and stability of various Treg subsets and their respective roles in vivo, the requirement of antigen-specificity of Treg to reduce promiscuous suppression, and the molecular mechanisms by which Treg suppress, particularly in humans. In this review, we discuss recent findings that support a heterogeneous population of human Treg, address advances in understanding how Treg function in the context of HCT, and present data on recent clinical trials that highlight the feasibility and limitations on Treg immunotherapy for graft- versus-host disease.
Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by outside-in signaling
Authors: Buitrago Lorena , Langdon Wallace Y. , Sanjay Archana , Kunapuli Satya P.
Published: October 2011

c-Cbl protein functions as an E3 ligase and scaffolding protein, where 3 residues, Y700, Y731, and Y774, upon phosphorylation, have been shown to initiate several signaling cascades. In this study, we investigated the role of these phospho-tyrosine residues in the platelet functional responses after integrin engagement. We observed that c-Cbl Y700, Y731 and Y774 undergo phosphorylation upon platelet adhesion to immobilized fibrinogen, which was inhibited in the presence of PP2, a pan-src family kinase (SFK) inhibitor, suggesting that c-Cbl is phosphorylated downstream of SFKs. However, OXSI-2, a Syk inhibitor, significantly reduced c-Cbl phosphorylation at residues Y774 and Y700, without affecting Y731 phosphorylation. Interestingly, PP2 inhibited both platelet-spreading on fibrinogen as well as clot retraction, whereas OXSI-2 blocked only platelet-spreading, suggesting a differential role of these tyrosine residues. The physiologic role of c-Cbl and Y731 was studied using platelets from c-Cbl KO and c-CblYF/YF knock-in mice. c-Cbl KO and c-CblYF/YF platelets had a significantly reduced spreading over immobilized fibrinogen. Furthermore, clot retraction with c-Cbl KO and c-CblYF/YF platelets was drastically delayed. These results indicate that c-Cbl and particularly its phosphorylated residue Y731 plays an important role in platelet outside-in signaling contributing to platelet-spreading and clot retraction.
Stereotactic Brachytherapy With Iodine-125 Seeds for the Treatment of Inoperable Low-Grade Gliomas in Children: Long-Term Outcome
Authors: Ruge Maximilian I. , Simon Thorsten , Suchorska Bogdana , Lehrke Ralph , Hamisch Christina , Koerber Friederike , Maarouf Mohammad , Treuer Harald , Berthold Frank , Sturm Volker , Voges Jürgen
Published: October 2011

Purpose

Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 (125I) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series.

Patients and Methods

All pediatric patients treated with SBT (125I seeds; cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with follow-up of more than 6 months were included. Clinical and radiologic outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky performance score, tumor volume, and histology) for survival and disease progression were investigated.

Results

In all, 147 of 160 pediatric patients treated with SBT (from 1982 through 2009) were analyzed in detail. Procedure-related mortality was zero, and the 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively, with no significant difference between WHO grades I and II tumors (median follow-up, 67.1 ± 57.7 months). Twenty-one (14.8%) of 147 patients presented with tumor relapse. The remaining 126 patients revealed complete response in 24.6%, partial response in 31.0%, and stable disease in 29.6%. Neurologic status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had significant impact on the study's end points except tumor volume more than 15 mL, which caused significantly higher rates of tumor recurrence (P < .05).

Conclusion

We demonstrate that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO grades I and II.
Plasma Platelet-Activating Factor–Acetyl Hydrolase Activity and the Levels of Free Forms of Biomarker of Lipid Peroxidation in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Hirashima Yutaka , Doshi Masaru , Hayashi Nakamasa , Endo Shunro , Akazawa Yoko , Shichiri Mototada , Yoshida Yasukazu
Published: October 2011

Background:

Free radicals and lipid peroxidation are thought to be related to the vasospasm generation after subarachnoid hemorrhage (SAH). Plasma platelet-activating factor-acetyl hydrolase (PAF-AH) degrades phospholipids with an oxidatively modified fatty acyl chain.

Objective:

To compare plasma PAF-AH activity and free forms of biomarker of lipid peroxidation in cerebrospinal fluid (CSF) between patients with and without symptomatic vasospasm (SVS) after SAH.

Methods:

The identification of PAF-AH in CSF was performed by Western blotting. The genotype at position 279 of the plasma PAF-AH gene was determined. The activities of PAF-AH and the levels of free 8-iso-prostaglandin F2α (free isoPs), free hydroxyoctadecadienoic acid (free HODE), and free hydroxyeicosatetraenoic acid (free HETE) in CSF were measured.

Results:

The PAF-AH in CSF was confirmed to be only the plasma type. The genotype of the plasma PAF-AH was not different between patients with and without SVS. Free isoPs, free HODE, and free HETE showed higher values in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The PAF-AH activity also was higher in patients without SVS in 0 to 4 days and 5 to 9 days after SAH. The associations between PAF-AH activity and free isoPs, and between PAF-AH activity and free HODE were significant.

Conclusion:

Oxidized lipids of lipoproteins and blood cell membranes produced by reactive oxygen species in CSF when SAH occurs may be the main source of lipid peroxidation. Plasma PAF-AH can hydrolyze oxidized phospholipids, and may attenuate the spreading of lipid peroxidation and participate in defense mechanisms against vasospasm after SAH.
Anatomical Study on the “Perforator-free Zone”: Reconsidering the Proximal Superior Cerebellar Artery and Basilar Artery Perforators
Authors: Garcia-Gonzalez Ulises , Cavalcanti Daniel D. , Agrawal Abhishek , Spetzler Robert F. , Preul Mark C.
Published: October 2011

Background:

The proximal superior cerebellar artery (pSCA) is often considered a perforator-free area. Precise anatomical knowledge of this region clarifies the pathophysiology underlying posterior fossa ischemic syndromes and helps avoid treatment-related complications.

Objective:

To anatomically evaluate perforating branches arising from the pSCA and the upper basilar artery (BA).

Methods:

Forty-four SCAs from 20 cadaveric heads were examined to determine patterns of the pSCA; its morphometry for medial and lateral branches; and frequency, number, diameter, distribution, and vascular territory of perforators arising from the pSCA and rostral BA.

Results:

SCA arose as a single trunk in 36 sides (90%): mean diameter at origin was 1.38 mm; mean length was 14.± 6 7.9 mm. Ninety-nine pSCA perforator branches were present in 82% of specimens (mean, 2.3 ± 1.6; range, 0-7 perforators/side). Of these, 59% were direct, belonging to the interpeduncular group in 85% of cases; 28% were short circumflex, belonging to lateral and medial pontine group; and 13% were long circumflex, reaching the medullary perforation zone (basal cerebellar group). Median distance to the first perforator was 2.0 mm (range, 0.1–15 mm). There were 132 perforator branches in the last centimeter of the BA.

Conclusion:

The pSCA should not be regarded as a perforator-free area. Although the pSCA territories likely overlap with the posterior cerebral artery, BA, and anterior inferior cerebellar artery, the pSCA segment cannot be surgically manipulated with impunity.
Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases in breast cancer
Authors: Hahn Steffen , Heusner Till , Kümmel Sherko , Köninger Angelika , Nagarajah James , Müller Stefan , Boy Christian , Forsting Michael , Bockisch Andreas , Antoch Gerald , Stahl Alexander
Published: October 2011

Background

Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy.

Purpose

To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients.

Material and Methods

Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients.

Results

A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases.

Conclusion

On a lesion-basis whole-body FDG-PET/CT is more sensitive and equally specific for the detection of bone metastases compared with bone scintigraphy.
Classification of persistent primitive trigeminal artery (PPTA): a reconsideration based on MRA
Authors: Weon Young Cheol , Choi Seong Hoon , Hwang Jae Cheol , Shin Shang Hun , Kwon Woon-Jung , Kang Byeong Seong
Published: October 2011

Background

Persistent primitive trigeminal artery (PPTA) is the most common permanent carotid-basilar anastomosis. Magnetic resonance angiography (MRA) has become the primary non-invasive imaging technique for evaluation of cerebral vascular anatomy and can provide detailed 3D imaging of intracranial vessels.

Purpose

To evaluate the usefulness of MRA for the detection of PPTA and to re-classify its variations based on the embryologic types of PcomA and its relationship with the basilar artery and its branches.

Material and Methods

Of the total 7329 patients who underwent MRA at our institution from March 2008 through November 2010, we retrospectively analyzed the MRAs of 24 patients with a PPTA. Special attention was given to defining the relationship of the PPTA and the basilar artery with PcomA and to determine the site of origin, size, and course of the PPTA. The PPTA classification included five types based on their anatomic relationship to the neighboring arteries. Clinical features and associated vascular anomalies are also described.

Results

Twenty-four (17 women and seven men, 34 ~ 81 years of age, mean age 59.67 years) of the 7329 patients had a PPTA (0.33 %). Eleven cases (45.8%) were classified as type 1, three (12.5%) as type 2, five (20.8%) as type 3, one (4.2%) as type 4, and four (16.7%) as type 5b. Fifteen PPTAs (62.5%) were located on the left side and nine were located (37.5%) on the right side. The basilar artery proximal to the insertion of the PPTA showed severe to moderate hypoplasia in 13 cases (54%). Nine intracranial artery aneurysms were detected in seven (29%) of the 24 study patients.

Conclusion

This study revealed five types of PPTA and necessitates an adjustment of the previous classification of PPTA on the basis of our MRA examinations. A PPTA should be considered by both the clinician and the radiologist who interpret MR angiography.
Melittin attenuates liver injury in thioacetamide-treated mice through modulating inflammation and fibrogenesis
Authors: Park Ji-Hyun , Kum Yoon-Seup , Lee Tae-Im , Kim Soo-Jung , Lee Woo-Ram , Kim Bong-Il , Kim Hyun-Soo , Kim Kyung-Hyun , Park Kwan-Kyu
Published: October 2011

Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Following injury, an acute inflammation response takes place resulting in moderate cell necrosis and extracellular matrix damage. Melittin, the major bioactive component in the venom of honey bee Apis mellifera, is a 26-residue amphipathic peptide with well-known cytolytic, antimicrobial and proinflammatory properties. However, the molecular mechanisms responsible for the anti-inflammatory activity of melittin have not been elucidated in liver fibrosis. We investigated whether melittin ameliorates liver inflammation and fibrosis in thioacetamide (TAA)-induced liver fibrosis. Two groups of mice were treated with TAA (200 mg/L, in drinking water), one of the groups of mice was co-treated with melittin (0.1 mg/kg) for 12 weeks while the other was not. Hepatic stellate cells (HSCs) were cultured with tumor necrosis factor α in the absence or presence of melittin. Melittin suppresses the expression of proinflammatory cytokines through the nuclear factor (NF)- κB signaling pathway. Moreover, melittin reduces the activity of HSCs in vitro, and decreases the expression of fibrotic gene responses in TAA-induced liver fibrosis. Taken together, melittin prevents TAA-induced liver fibrosis by inhibiting liver inflammation and fibrosis, the mechanism of which is the interruption of the NF- κB signaling pathway. These results suggest that melittin could be an effective agent for preventing liver fibrosis.
My Patient Has No Blood Pressure: Have They Got an Abdominal Aortic Aneurysm? Point-Of-Care Ultrasound of the Abdominal Aorta in Hypotensive Patients
Authors: Gedmintas Audra , Grabove Matthew , Atkinson Paul
Published: October 2011

Among patients presenting to the emergency department (ED) with undifferentiated hypotension, how can point-of-care ultrasound (PoCUS) help identify abdominal aortic aneurysm (AAA) as the cause of the hypotension? Many hypotensive patients in the ED are critically ill, with only minutes available to find the cause of the hypotension and treat it before the patient decompensates. While the classic description of the presentation of a ruptured AAA is of collapse with sudden onset abdominal pain and a palpable, pulsatile abdominal mass, detection of AAA by palpation is notoriously unreliable, and many patients are unaware of their underlying condition. This life-threatening situation is made even more difficult by virtue of the fact that the patient is often too unstable to travel for traditional diagnostics such as computed tomography. This article will address the use of PoCUS for the detection of AAA in the evaluation of the hypotensive patient.
Effect of growth hormone and melatonin on the brain: from molecular mechanisms to structural changes
Authors: Kireev Roman A. , Cuesta Sara , Vara Elena , Tresguerres Jesus A.F.
Published: October 2011

Aging of the brain causes important reductions in quality of life and has wide socio-economic consequences. An increase in oxidative stress, and the associated inflammation and apoptosis, could be responsible for the pathogenesis of aging associated brain lesions. Melatonin has neuroprotective effects, by limiting the negative effects of oxygen and nitrogen free radicals. Growth hormone (GH) might exert additional neuro-protective and or neurogenic effects on the brain. The molecular mechanisms of the protective effects of GH and melatonin on the aging brain have been investigated in young and old Wistar rats. A reduction in the total number of neurons in the hilus of the dentate gyrus was evident at 24 months of age and was associated with a significant increase in inflammation markers as well as in pro-apoptotic parameters, confirming the role of apoptosis in its reduction. Melatonin treatment was able to enhance neurogenesis in old rats without modification of the total number of neurons, whereas GH treatment increased the total number of neurons without enhancing neurogenesis. Both GH and melatonin were able to reduce inflammation and apoptosis in the hippocampus. In conclusion, neuroprotective effects demonstrated by GH and melatonin in the hippocampus were exerted by decreasing inflammation and apoptosis.