bluuebunny/crossref_metadata_2025_split huggingface dataset:
Could hyperoxic ventilation impair oxygen delivery in septic patients?
Authors: Rossi Pascal , Tauzin Laurent , Weiss Michel , Rostain Jean‐Claude , Sainty Jean‐Marie , Boussuges Alain 
Published: March 2007

SummaryObjective:  In critically ill patients, a decrease in whole body oxygen consumption under hyperoxia has been reported and this could be related to hyperoxia‐induced arterial changes. We investigated changes in brachial artery circulation and tone during short‐term hyperoxic ventilation in septic patients.Design and setting:  Prospective clinical study in the intensive care unit of a university hospital.Patients:  Fourteen patients (severe sepsis n = 3 and septic shock n = 11) requiring mechanically controlled ventilation due to sepsis syndrome were investigated under stable clinical conditions.Interventions:  After a 20‐min period of hyperoxic ventilation (inspired oxygen fraction = 100%), two‐dimensional images of brachial artery cross‐sectional area and brachial blood flow velocities were recorded using conventional ultrasonography and pulsed Doppler simultaneously with invasive arterial pressure measurements.Measurements and main results:  Hyperoxia did not affect heart rate, but increased mean arterial pressure and decreased cross‐sectional areas both at the end of diastole and at the end of systole. Haemodynamic study showed an increase in resistance index, and a decrease in distensibility and compliance coefficients. Furthermore, a decrease in brachial artery blood flow and arterial oxygen delivery was observed during hyperoxic exposure.Conclusions:  Hyperoxia was paradoxically demonstrated to decrease oxygen delivery in upper limbs during septic shock.
Pulse wave velocity reference values in healthy adults aged 26–75 years
Authors: Koivistoinen T. , Kööbi T. , Jula A. , Hutri‐Kähönen N. , Raitakari O. T. , Majahalme S. , Kukkonen‐Harjula K. , Lehtimäki T. , Reunanen A. , Viikari J. , Turjanmaa V. , Nieminen T. , Kähönen M. 
Published: March 2007

SummaryThe stiffening of arteries is associated with various cardiovascular diseases. Arterial stiffening can be studied utilizing arterial pulse wave velocity (PWV), but the absence of reliable reference values for PWV has limited its use in clinical practice. The aim of this study was to establish a range of reference values for PWV. PWV was examined by measuring the time difference of systolic pulse waves in arteries from the aortic arch to the popliteal artery using whole‐body impedance cardiography (ICG). The study population consisted of 799 individuals (age range 25–76 years), 283 of whom had no evidence of cardiovascular disease, and a low burden of risk factors was selected to represent an apparently healthy population. In healthy study population, PWV was higher in males (8·9 ± 1·8 m s−1) than females (8·1 ± 2·0 m s−1, P<0·001). Young males had lower PWV values than old males. Correspondingly, young females also had lower PWV values than old females. PWV was clearly associated with age, and PWV was higher in young and middle‐aged males than in females. There was no statistically significant difference between old males and females in PWV. In conclusion, whole‐body ICG provides a practical method for PWV measurement. Reference values can be useful in the clinical management of patients, especially in detecting early vascular disease or an increased risk of cardiovascular complications.
Drug‐induced liver injury at an Asian center: a prospective study
Authors: Wai Chun‐Tao , Tan Bee‐Him , Chan Cheng‐Leng , Sutedja Dede S. , Lee Yin‐Mei , Khor Christopher , Lim Seng‐Gee 
Published: March 2007

AbstractBackground/Aims: The aetiology of drug‐induced liver injuries (DILI) in Asia is different from that in the West, as anecdotal studies have shown that traditional complementary and alternative medicines (CAM) accounted for a major proportion of offending drugs in DILI in Asia. We aimed to study DILI in Asia prospectively, and to test whether DILI caused by traditional CAM was related to adulterants.Methods: A collaborative group consisting of a tertiary‐hospital hepatology department, a pharmaceutical laboratory, and a pharmacovigilance unit was formed to study patients with DILI at a tertiary hospital over a 26‐month period prospectively. Traditional medicines that were implicated were tested for the presence of adulterants.Results: Thirty‐one patients with DILI were enrolled: age 51±3 (18–79) years, 17 (55%) male. Twenty‐three (74%) had hepatocellular, six (19%) had cholestatic, and two (7%) had a mixed pattern of injury. Chinese traditional CAM was the most common medication type implicated, accounting for 17 (55%) patients, followed by Malay CAM in five (16%). Thirty‐one traditional medicines from 17 patients were available for chemical analysis. Adulterants were found in nine (29%) of them.Conclusions: DILI in Asia has a different aetiology as compared with the West, and could be related to presence of adulterants in traditional CAM.
Long‐term production of major coagulation factors and inhibitors by primary human hepatocytes in vitro: perspectives for clinical application
Authors: Boost Kim A. , Auth Marcus K. H. , Woitaschek Dirk , Kim Hyun‐Soo , Hilgard Philip , Nadalin Silvio , Blaheta Roman A. 
Published: March 2007

AbstractBackground/Aims: Patients with coagulation factor disorders require lifelong symptomatic treatment. This is associated with limited efficacy and transmission risks. From a clinical point of view, hepatocyte transplantation offers a rational alternative but is currently being hampered by lack of functional stability of engrafted cells. It was the aim of our study to devise culture conditions providing stable cell polarity, attachment and growth factor stimulation to improve longevity and coagulation factor production.Methods: Human hepatocytes (HC) were plated on different extracellular matrices, inside collagen gel or Matrigel. HC were grown inside growth factor‐enriched serum‐free medium (SFM) or exposed to media switching from differentiation (DM) to dedifferentiation (DeDM).Results: Over more than 30 days in vitro human HC synthesized coagulation factors (factors VII, VIII, IX, fibrinogen) and coagulation inhibitors (antithrombin III, protein C). Protein synthesis was augmented when HC were grown inside a 3D collagen type I matrix, while Matrigel showed no additional benefit. Soluble growth factors improved coagulation factor production when applied in SFM or in sequential DM/DeDM. Coagulation factor levels ranged from 3% to 12% in the first week to 2.5–5% after 4 weeks, reaching biologically relevant levels.Conclusion:
Preserved synthesis and secretion of coagulation factors in balanced proportion by human HC in this model may offer new perspectives for HC transplantation in coagulation defects of patients.
Local and systemic responses induced by aphids in Solanum tuberosum plants
Authors: Dugravot Sébastien , Brunissen Laurence , Létocart Emilie , Tjallingii W. Freddy , Vincent Charles , Giordanengo Philippe , Cherqui Anas 
Published: March 2007

AbstractThe aphids Macrosiphum euphorbiae (Thomas) and Myzus persicae (Sulzer) (Homoptera: Aphididae) are serious pests of potato (Solanum tuberosum L.) (Solanaceae), notably in transmitting several plant viruses. Heterospecific interactions may occur between these two species as they are often seen at the same time on the same potato plant in the field. As aphid infestation is known to induce both local and systemic changes, we conducted experiments to determine the effect of previous infestation on probing behaviour and feeding‐related parameters. We used the DC electrical penetration graph technique to characterize the influence of previous infestation by conspecific M. persicae or by heterospecific Ma. euphorbiae on M. persicae feeding behaviour at both local and systemic levels, i.e., on previously infested leaves and on non‐previously infested leaves of infested plants, respectively. Conspecific and heterospecific infestation led to similar modification of M. persicae feeding activities. However, the effects of previous infestation occurring at the local level were opposite to those observed at the systemic level. Myzus persicae food acceptance was slightly enhanced on previously infested leaves, whereas it was inhibited on non‐infested leaves of infested plants, which indicated an induced resistance mechanism. Our results advance the understanding of the mechanisms involved in aphid–host plant acceptance and colonization processes on potato plants in conspecific and heterospecific situations.
Tissue engineering of bone: the reconstructive surgeon's point of view
Authors: Kneser U. , Schaefer D. J. , Polykandriotis E. , Horch R. E. 
Published: March 2007

AbstractBone defects represent a medical and socioeconomic challenge. Different types of biomaterials are applied for reconstructive indications and receive rising interest. However, autologous bone grafts are still considered as the gold standard for reconstruction of extended bone defects. The generation of bioartificial bone tissues may help to overcome the problems related to donor site morbidity and size limitations. Tissue engineering is, according to its historic definition, an “interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function”. It is based on the understanding of tissue formation and regeneration and aims to rather grow new functional tissues than to build new spare parts. While reconstruction of small to moderate sized bone defects using engineered bone tissues is technically feasible, and some of the currently developed concepts may represent alternatives to autologous bone grafts for certain clinical conditions, the reconstruction of largevolume defects remains challenging. Therefore vascularization concepts gain on interest and the combination of tissue engineering approaches with flap prefabrication techniques may eventually allow application of bone‐tissue substitutes grown in vivo with the advantage of minimal donor site morbidity as compared to conventional vascularized bone grafts. The scope of this review is the introduction of basic principles and different components of engineered bioartificial bone tissues with a strong focus on clinical applications in reconstructive surgery. Concepts for the induction of axial vascularization in engineered bone tissues as well as potential clinical applications are discussed in detail.
Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions
Authors: Butt Arthur M. , Kalsi Amanpreet 
Published: March 2007

AbstractGlia in the central nervous system (CNS) express diverse inward rectifying potassium channels (Kir). The major function of Kir is in establishing the high potassium (K+) selectivity of the glial cell membrane and strongly negative resting membrane potential (RMP), which are characteristic physiological properties of glia. The classical property of Kir is that K+ flows inwards when the RMP is negative to the equilibrium potential for K+ (Ek), but at more positive potentials outward currents are inhibited. This provides the driving force for glial uptake of K+ released during neuronal activity, by the processes of “K+ spatial buffering” and “K+ siphoning”, considered a key function of astrocytes, the main glial cell type in the CNS. Glia express multiple Kir channel subtypes, which are likely to have distinct functional roles related to their differences in conductance, and sensitivity to intracellular and extracellular factors, including pH, ATP, G‐proteins, neurotransmitters and hormones. A feature of CNS glia is their specific expression of the Kir4.1 subtype, which is a major K+ conductance in glial cell membranes and has a key role in setting the glial RMP. It is proposed that Kir4.1 have a primary function in K+ regulation, both as homomeric channels and as heteromeric channels by co‐assembley with Kir5.1 and probably Kir2.0 subtypes. Significantly, Kir4.1 are also expressed by oligodendrocytes, the myelin‐forming cells of the CNS, and the genetic ablation of Kir4.1 are also expressed by Oligodendrocytes, the myelin‐forming cells of the CNS, and the genetic ablation of Kir4.1 results in severe hypomyelination. Hence, Kir, and in particular Kir4.1, are key regulators of glial functions, which in turn determine neuronal excitability and axonal conduction.
Arteriogenesis versus angiogenesis: similarities and differences
Authors: Heil M. , Eitenmüller Inka , Schmitz‐Rixen T. , Schaper W. 
Published: March 2007

AbstractCardiovascular diseases account for more than half of total mortality before the age of 75 in industrialized countries. To develop therapies promoting the compensatory growth of blood vessels could be superior to palliative surgical surgical interventions. Therefore, much effort has been put into investigating underlying mechanisms. Depending on the initial trigger, growth of blood vessels in adult organisms proceeds via two major processes, angiogenesis and arteriogenesis. While angiogenesis is induced by hypoxia and results in new capillaries, arteriogenesis is induced by physical forces, most importantly fluid shear stress. Consequently, chronically elevated fluid shear stress was found to be the strongest trigger under experimental conditions. Arteriogenesis describes the remodelling of pre‐existing arterio‐arteriolar anastomoses to completely developed and functional arteries. In both growth processes, enlargement of vascular wall structures was proposed to be covered by proliferation of existing wall cells. Recently, increasing evidence emerges, implicating a pivotal role for circulating cells, above all blood monocytes, in vascular growth processes. Since it has been shown that monocytes/macrophage release a cocktail of chemokines, growth factors and proteases involved in vascular growth, their contribution seems to be of a paracrine fashion. A similar role is currently discussed for various populations of bone‐marrow derived stem cells and endothelial progenitors. In contrast, the initial hypothesis that these cells ‐after undergoing a (trans‐)differentiation‐ contribute by a structural integration into the growing vessel wall, is increasingly challenged.
Morphological aspects of apoptosis in heart diseases
Authors: Takemura Genzou , Fujiwara Hisayoshi 
Published: March 2007

AbstractIt has been suggested that apoptosis may be responsible for a significant amount of cardiomyocyte death during acute myocardial infraction as well as for a progressive loss of surviving cells in failing hearts. Typical apoptosis can indeed be induced in cardiomyocytes at the experimental conditions. In actual heart diseases, in contrast, there is very little direct morphological evidence of apoptosis in cardiomyocytes occuring at any stage of myocardial infarction and heart failure, despite the availability of much indirect evidence that includes detection of DNA fragmentation and apoptosis‐related factors. For that reason, the potential efficacy of therapeutic intervention to prevent apoptosis remains controversial. This review will survey available data from both animals and humans to critically assess the role of cardiomyocyte apoptosis during myocardial infarction and its relevance to myocardial remodeling and during progression to heart failure. Also considered will be nonmyocyte interstitial cells, which have received less attention than myocytes despite definitive evidence of their apoptosis in the infarcted heart and recent studies suggesting that blockade of apoptosis among these cells mitigates postinfarction cardiac remodeling and heart failure. We conclude from our survey that there are many hurdles to surmount before regulation of apoptosis can be clinically applied in the treatment of myocardial infarction and heart failure.
Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF‐β as major players and therapeutic targets
Authors: Gressner A. M. , Weiskirchen R. 
Published: March 2007

AbstractHepatic fibrosis is a scarring process that is associated with an increased and altered deposition of extracellular matrix in liver. At the cellular and molecular level, this progressive process is mainly characterized by cellular activation of hepatic stellate cells and aberrant activity of transforming growth factor‐β1 and its downstream cellular mediators. Although the cellular responses to this cytokine are complex, the signalling pathways of this pivotal cytokine during the fibrogenic response and its connection to other signal cascades are now understood in some detail. Based on the current advances in understanding the pleiotropic reactions during fibrogenesis, various inhibitors of transforming growth factor‐β were developed and are now being investigated as potential drug candidates in experimental models of hepatic injury. Although it is too early to favour one of these antagonists for the treatment of hepatic fibrogenesis in human, the experimental results obtained yet provide stimulatory impulses for the development of an effective treatment of choice in the not too distant future. The present review summarises the actual knowledge on the pathogenesis of hepatic fibrogenesis, the role of transforming growth factor‐β and its signalling pathways in promoting the fibrogenic response, and the therapeutic modalities that are presently in the spotlight of many investigations and are already on the way to take the plunge into clinical studies.
Epigenetics of prostate cancer: beyond DNA methylation
Authors: Schulz W. A. , Hatina J. 
Published: March 2007

AbstractEpigenetic mechanisms permit the stable inheritance of cellular properties without changes in DNA sequence or amount. In prostate carcinoma, epigenetic mechanisms are essential for development and progression, complementing, amplifying and diversifying genetic alterations. DNA hypermethylation affects at least 30 individual genes, while repetitive sequences including retrotransposons and selected genes become hypomethylated. Hypermethylation of several genes occurs in a coordinate manner early in carcinogenesis and can be exploited for cancer detection, whereas hypomethylation and further hypermethylation events are associated with progression. DNA methylation alterations interact with changes in chromatin proteins. Prominent alterations at this level include altered patterns of histone modification, increased expression of the EZH2 polycomb histone methyltransferase, and changes in transcriptional corepressors and coactivators. These changes may make prostate carcinoma particularly susceptible to drugs targeting chromatin and DNA modifications. They relate to crucial alterations in a network of transcription factors comprising ETS family proteins, the androgen receptor, NKX3.1, KLF, and HOXB13 homeobox proteins. This network controls differentiation and proliferation of prostate epithelial cells integrating signals from hormones, growth factors and cell adhesion proteins that are likewise distorted in prostate cancer. As a consequence, prostate carcinoma cells appear to be locked into an aberrant state, characterized by continued proliferation of largely differentiated cells. Accordingly, stem cell characteristics of prostate cancer cells appear to be secondarily acquired. The aberrant differentiation state of prostate carcinoma cells also results in distorted mutual interactions between epithelial and stromal cells in the tumor that promote tumor growth, invasion, and metastasis.
Discovery of the ‘porosome’ the universal secretory machinery in cells
Authors: Anderson L. L. 
Published: March 2007

AbstractThe release of neurotransmitters at the nerve terminal for neurotransmission, release of insulin from β‐cells of the endocrine pancreas for regulating blood glucose levels, the release of growth hormone from GH cells of the pituitary gland to regulate body growth, or the expulsion of zymogen from exocrine pancreas to digest food, are only a few examples of key physiological processes made possible by cell secretion. It comes as no surprise that defects in cell secretion are the cause for numerous diseases, and have been under intense investigation for over half century. Only in the last decade, the molecular machinery and mechanism of cell secretion has become clear. Cell secretion involves the docking and transient fusion of membrane‐bound secretory vesicles at the base of plasma membrane structures called porosomes, and the regulated expulsion of intravesicular contents to the outside, by vesicle swelling. The discovery of the porosome in live cells, its morphology and dynamics at nanometer resolution and in real time, its isolation, its composition, and its structural and functional reconstitution in lipid membrane, are complete. The molecular mechanism of secretory vesicle fusion at the base of porosomes, and the regulated expulsion of intravesicular contents during cell secretion, are also resolved. In this minireview, the monumental discovery of the porosome, a new cellular structure at the cell plasma membrane, is briefly discussed.
N‐Acetyl‐L‐Cysteine abrogates fibrogenic properties of fibroblasts isolated from Dupuytren's disease by blunting TGF‐β signalling
Authors: Kopp Jürgen , Seyhan Harun , Müller Bastian , Lanczak Johanna , Pausch Elke , Gressner Axel M. , Dooley Steven , Horch Raymund E. 
Published: March 2007

AbstractDupuytren's disease, a benign fibroproliferative disorder of the palmar fascia, represents an ideal model to study tissue fibrosis. Transforming growth factor‐β1 (TGF‐β1) and its downstream Smad signalling system is well established as a key player during fibrogenesis. Thus, targeting this basic pathomechanism seems suitable to establish new treatment strategies. One such promising treatment involves the substance N‐acetyl‐L‐cysteine (NAC), shown to have antifibrotic properties in hepatic stellate cells and rat fibroblasts. In order to investigate antifibrotic effects of N‐acetyl‐L‐cysteine (NAC), fibroblasts were isolated from surgically resected fibrotic palmar tissues (Dupuytren fibroblasts, DF) and exposed to different concentrations of NAC and recombinant TGF‐β1. Fibroblasts isolated from tendon pulleys served as controls (control fibroblasts, CF). Smad signalling was investigated by a Smad binding element driven reporter gene analysis. Both cell types express TGF‐β1, indicating autocrine signalling in DF and CF. This was confirmed by comparing reporter gene activity from LacZ and Smad7 adenovirus infected cells. NAC treatment resulted in abrogation of Smad mediated signalling comparable to ectopically overexpressed Smad7, even when the cells were stimulated with recombinant TGF‐β1 or ectopically expressed a constitutively active TGF‐β receptor type I. Additionally, NAC dose‐dependently decreased expression of three major indicators of impaired fibrotic matrix turnover, namely alpha‐smooth muscle actin (α‐SMA), α 1 type I procollagen (CollA1), and plasminogen activator inhibitor‐type I (PAI‐1). Our results suggest that TGF‐β signalling and subsequent expression of fibrogenesis related proteins in Dupuytren's disease is abrogated by NAC thus providing a basis for a therapeutic strategy in Dupuytren's disease and other fibroproliferative disorders.