bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of recombinant human brain tandem P domain K+channels by hypoxia: a role for O2in the control of neuronal excitability?
Authors: Kemp P. J. , Peers C. , Lewis A. , Miller Paula 
Published: May 2007

AbstractThe tandem P domain potassium channels, TREK1 and TASK1, are expressed throughout the brain but expression patterns do not significantly overlap. Since normal pO2in central nervous tissue is as low as 20 mmHg and can decrease even further in ischemic disease, it is important that the behaviour of human brain ion channels is studied under conditions of acute and chronic hypoxia. This is especially true for brain‐expressed tandem P‐domain channels principally because they are important contributors to neuronal resting membrane potential and excitability. Here, we discuss some recent data derived from two recombinant tandem P‐domain potassium channels, hTREK1 and hTASK1. Hypoxia represents a potent inhibitory influence on both channel types and occludes the activation by arachidonic acid, intracellular acidosis and membrane deformation of TREK1. This casts doubt on the idea that TREK1 activation during brain ischemia might facilitate neuroprotection via hyperpolarising neurons in which it is expressed. Interestingly, hypoxia is unable to regulate alkalotic inhibition of TREK1 suggesting that this channel may be more intimately involved in control of excitability during physiological or pathological alkalosis.
Molecular mechanisms of neuroprotective action of immunosuppressants ‐ facts and hypotheses
Authors: Kaminska Bozena , Gaweda‐Walerych Katarzyna , Zawadzka Malgorzata 
Published: May 2007

AbstractCyclosporin A (CsA) and FK506 (Tacrolimus) are short polypeptides which block the activation of lymphocytes and other immune system cells. Immunosuppressants exert neuroprotective and neurotrophic action in traumatic brain injury, sciatic nerve injury, focal and global ischemia in animals. Their neuroprotective actions are not understood and many hypotheses have been formed to explain such effects. We discuss a role of drug target ‐ calcineurin in neuroprotective action of immunosuppressants. Protein dephosphorylation by calcineurin plays an important role in neuronal signal transduction due to its ability to regulate the activity of ion channels, glutamate release, and synaptic plasticity.In vitroFK506 protects cortex neurons from NMDA‐induced death, augments NOS phosphorylation inhibiting its activity and NO synthesis. However,in vivoexperiments demonstrated that FK506 in neuroprotective doses did not block excitotoxic cell death nor did it alter NO production during ischemia/reperfusion. Tissue damage in ischemia is the result of a complex pathophysiological cascade, which comprises a variety of distinct pathological events. Resident non‐neuronal brain cells respond rapidly to neuronal cell death and may have both deleterious and useful role in neuronal damage. There is increasing evidence that reactive gliosis and post‐ischemic inflammation involving microglia contribute to ischemic damage. We have demonstrated that FK506 modulates hypertrophic/proliferative responses and proinflammatory cytokine expression in astrocytes and microglia in vitro and in focal transient brain ischemia. Our findings suggest that astrocytes and microglia are direct targets of FK506 and modulation of glial response and inflammation is a possible mechanism of FK506‐mediated neuroprotection in ischemia.
Anti‐atherosclerotic effects of vitamin E – myth or reality?
Authors: Munteanu Adelina , Zingg J.‐M. , Azzi A. 
Published: May 2007

AbstractAtherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non‐antioxidant effects. Vitamin E influences the activity of several enzymes (e.g.PKC, PP2A, COX‐2, 5‐lipooxygenase, nitric oxide synthase, NADPH oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g.scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
Role of human prostasomes in the activation of spermatozoa
Authors: Arienti G. , Carlini E. , Saccardi C. , Palmerini C. A. 
Published: May 2007

AbstractProstasomes are small vesicles of prostatic origin contained in human semen. Their composition is peculiar under many aspects. Cholesterol is abundant and many proteins are endowed with enzymatic or other activities. The function of prostasomes has been amply debated and several hypotheses have been put forward. The liquefaction of semen, spermatozoa motility, antibacterial activity and immunological functions have been related to prostasomes. Under certain aspects, prostasomes resemble synaptosomes. The fusion of prostasomes to spermatozoa enriches spermatozoa with cholesterol and causes bursts of cytoplasmic sperm calcium. The interaction of spermatozoa and prostasomes should be limited to vagina since prostasomes are immobile and do not follow spermatozoa in the superior female genital tract. Calcium bursts would increase spermatozoa motility, where cholesterol would decapacitate spermatozoa, so preventing untimely activation. Since spermatozoa receive many different molecules from prostasomes, additional effects are also possible. Prostasomes makes spermatozoa more apt to be activated by progesterone in the proximity of the ovum. Therefore, the fusion between spermatozoa and prostasomes would influence spermatozoa behaviour under many aspects and might be relevant for fecundation. The richness of molecular species in prostasomes is amazing and these small vesicles are expected to lead to many more discoveries in the field of human reproduction.
The development of larger cells that spontaneously escape senescence ‐ a step during the immortalization of a human cancer cell line
Authors: Diaconu Carmen C. , Bleotu Coralia , Chivu Mihaela , Alexiu Irina , Petrusca Daniela , Anton Gabriela , Achim Ruxandra , Ruta Simona M. , Cernescu C. 
Published: May 2007

AbstractThere are few information concerning the changes associated with the transition interval when slow growing, primary explanted human cancer cells are displaced by new selected faster growing cells and became an immortal cell line. In a previous paper (J. Cell. Mol. Med., 5: 49–59, 2001) we described the TV cell line derived from a laryngeal tumor which harbors human papillomavirus (HPV) gene sequences throughout more than sixty in vitro passages. In this paper we analyze the modifications observed during the crisis interval when significant amount of cells senesce but occasional cells acquire some mutations that make them immortal. Confocal microscopy analysis revealed the heterogeneity of the cells in terms of their size and nucleus/cell ratio. Proliferation capacity was assessed by flow cytometry analyzing DNA content and expression of transferrin receptor (CD71). We discussed the possibility that HPV genome sequences alleviate a proliferation block during the crisis growth arrest of human larynx carcinoma cell line and the possibility that the cells monitor their size and growth by measuring the levels of some protein whose synthesis is coupled to cell development.
Changes in oxidative balance in rat pericytes exposed to diabetic conditions
Authors: Manea A. , Constantinescu Elena , Popov Doina , Raicu Monica 
Published: May 2007

AbstractRecent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE‐Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2′‐7′ dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE‐Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. Athree times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro‐diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy.
S‐Glutathionylation: from redox regulation of protein functions to human diseases
Authors: Giustarini Daniela , Rossi R. , Milzani A. , Colombo R. , Dalle‐Donne Isabella 
Published: May 2007

AbstractReactive oxygen species (ROS) and reactive nitrogen species (RNS) play an integral role in the modulation of several physiological functions but can also be potentially destructive if produced in excessive amounts. Protein cysteinyl thiols appear especially sensitive to ROS/RNS attack. Experimental evidence started to accumulate recently, documenting that S‐glutathionylation occurs in a number of physiologically relevant situations, where it can produce discrete modulatory effects on protein function. The increasing evidence of functional changes resulting from this modification, and the growing number of proteins shown to be S‐glutathionylated both in vitro and in vivo support this contention, and confirm this as an attractive area of research. S‐glutathionylated proteins are now actively investigated with reference to problems of biological interest and as possible biomarkers of human diseases associated with oxidative/nitrosative stress.
Coenzyme Q10inhibits mitochondrial complex‐1 down‐regulation and nuclear factor‐kappa B activation
Authors: Ebadi M. , Sharma S. K. , Wanpen S. , Amornpan A. 
Published: May 2007

AbstractWe have used control‐homozygous weaver mutant, and ‐heterozygous weaver mutant mice in order to explore the basic molecular mechanism of neurodegeneration and the neuroprotective potential of coenzyme Q10. Homozygous weaver mutant mice exhibited progressive neurodegeneration in the hippocampus, striatum, and cerebellum, and a reduction in the striatal levels of dopamine and coenzyme Qs (Q9and Q10) without any significant changes in norepinephrine and serotonin. Mitochondrial complex‐1 was down regulated; whereas nuclear factor‐kappa B was up regulated in homozygous weaver mutant mice. Rotenone inhibited complex‐1, enhanced nuclear factor‐kappa B, and caused apoptosis in human dopaminergic (SK‐N‐SH) neurons; whereas nuclear factor‐kappa B antibody suppressed rotenone‐induced apoptosis, suggesting that enhancing coenzyme Q10synthesis and suppressing the induction of NF‐kappa B, may provide neuroprotection.
Expression of Dishevelled‐1 in wound healing after acute myocardial infarction: possible involvement in myofibroblast proliferation and migration
Authors: Chen Lijun , Wu Qingfeng , Guo Feng , Xia Beili , Zuo Ji 
Published: May 2007

AbstractOne of our previous studies indicated that the expression of β‐catenin, which is the key factor of wnt‐frizzled pathway, increased significantly in the ischemic area of the rat heart 7 days after myocardial infarction (MI). Together with the results of other recent studies, we made an assumption that wnt‐frizzled pathway may be involved in the controlled cell proliferation and migration during repair processes after MI. To verify this assumption we tried to investigate the expression of another signal transduction molecule called Dishevelled in wnt‐frizzled pathway during the wound healing process after MI. The left descending coronary arteries of rats were ligated to induce MI. Immunohistochemistry SABC method and in situ hybridization were performed to detect the expression of Dishevelled‐1. The results showed, that one day after MI, Dishevelled‐1 mRNA but not protein expression was detected in the cells at the border zone of the infarction area; 4 days after MI the expression of Dishevelled‐1 increased exclusively and cytoplasmic Dishevelled‐1 was observed not only at the border zone but also in the infarct area; 7 days after MI, it seems that the expression reached its peak, the positive staining even spread into the endothelial and smooth muscle cells of the newly formed and pre‐existing blood vessels in the infarction area; after that the Dishevelled‐1 expression decreased abruptly and could hardly be detected 28 days after MI. Thus cytoplasmic Dishevelled‐1 may be involved in the controlled proliferation and migration of myofibroblasts and vascular endothelial cells, hence play a role during the wound healing process after MI.
Somatic stem cell research for neural repair: current evidence and emerging perspectives
Authors: Corti Stefania , Locatelli Federica , Papadimitriou Dimitra , Strazzer Sandra , Comi G. P. 
Published: May 2007

AbstractRecent evidence supports the existence of adult mammalian stem cell subpopulations, particularly within the bone marrow, that may be able to “transdifferentiate” across tissue lineage boundaries, thus offering an accessible source for therapeutic applications even for neural tissue repair. However, the difficulties in reproducing some experimental data, the rarity of the transdifferentiation events and observations that cell fusion may be an alternative explanation argue against the idea of stem cell plasticity. Investigations going beyond descriptive experiments and more mechanicistic approaches may provide a more solid foundation to adult stem cell therapeutic potential.
Etoposide differentially affects bone marrow and dermal derived endothelial cells
Authors: Adams S. W. , Wang Lin , Fortney J. , Gibson Laura F. 
Published: May 2007

AbstractChemotherapy alteration of the bone marrow microenvironment has the potential to influence hematopoietic recovery following transplantation. To discern the effect of specific drugs on components of the complex marrow microenvironment,in vitromodels have significant utility. In the current study we sought to determine whether dermal (HEMEC‐1) and marrow derived endothelial cells (BMEC‐1) respond differently to identical chemotherapy exposure. BMEC‐1 cells were consistently more sensitive to etoposide exposure than HMEC‐1 cells, measured as reduced viability. BMEC‐1 also had reduced focal adhesion kinase (FAK) and VCAM‐1 protein expression following chemotherapy, in contrast to dermal derived endothelial cells in which neither protein was influenced dramatically by etoposide. The two endothelial cell lines had markedly different levels of baseline VE‐Cadherin protein, which was modestly altered by treatment. These data indicate that marrow derived endothelial cells have disruption of specific proteins following chemotherapy that may influence their ability to facilitate hematopoietic cell entry or egress from the marrow. In addition, these observations suggest that while BMEC‐1 and HMEC‐1 share a variety of characteristics, they differ significantly in their response to stress and should be incorporated into specific models with this consideration.
Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of patients with multiple sclerosis
Authors: Polosukhina Darya I. , Kanyshkova Tatyana G. , Doronin Boris M. , Tyshkevich Olga B. , Buneva Valentina N. , Boiko Alexey N. , Gusev Evgenii I. , Favorova Olga O. , Nevinsky Georgy A. 
Published: May 2007

AbstractVarious catalytic antibodies or abzymes have been detected recently in the sera of patients with several autoimmune pathologies, where their presence is most probably associated with autoimmunization. Recently we have shown that DNase, RNase, and polysaccharide‐hydrolyzing activities are associated with IgGs from the sera of patients with multiple sclerosis (MS). Here we present evidence demonstrating that highly purified MS IgGs (but not Igs from the sera of healthy individuals) catalyze specifically hydrolysis of human myelin basic protein (hMBP). In contrast to many known proteases, IgGs do not hydrolyze many other different proteins. Specific inhibitors of acidic and thiol proteases have no remarkable effect on proteolytic activity of IgGs. However, specific inhibitor of serine (PMSF, AEBSF, and benzamidin) and metal‐dependent (EDTA) proteases significantly inhibit activity of proteolytic abzymes. Interestingly, the ratio of serine‐like and metal‐dependent activities of MS IgGs varied very much from patient to patient. The findings speak in favor of the generation by the immune systems of individual MS patients of a variety of polyclonal anti‐MBP IgGs with different catalytic properties.
The ultrastructural aspects of neoplastic myoepithelial cell in pleomorphic adenomas of salivary glands
Authors: Margaritescu C. , Raica M. , Florescu Maria , Simionescu Cristiana , Surpateanu M. , Jaubert F. , Bogdan FI. 
Published: May 2007

AbstractThe purpose of this study has been to establish the major ultrastructural aspects of the myoepithelial cell and the myoepithelial‐like cells proliferated in the pleomorphic adenomas of salivary glands. Thus, twelve benign pleomorphic adenomas of salivary glands have been studied by electron‐microscopy transmission techniques. Our analysis has proved the proliferation of two major cellular populations, one of ductal type and one of myoepithelial type, which tried to reproduce the tubulo‐acinar cytoarchitecture from the normal salivary glands. We have also noticed the key role of the so‐called ‘modified’ myoepithelial cells from the periphery of the proliferating epithelial units in the genesis of the myxoid and chondromyxoid tumoral stromal areas. All these ultrastructural aspects have explained the great histological diversity of these salivary gland neoplasms as well as the key role of the myoepithelial cell in its histogenesis.
Use of an improved zirconyl hematoxylin stain in the diagnosis of Barrett's esophagus
Authors: McNulty Jeannette M. , Kambour Michael J. , Smith Allen A. 
Published: May 2007

AbstractBarrett's esophagus is a precancerous condition characterized by replacement of the normal stratified squamous epithelium by a simple columnar epithelium with goblet cells that secrete an acidic mucin. As originally formulated, fresh solutions of zirconyl hematoxylin stain goblet cells poorly. An improved formula, quintupling the amount of oxidant, yields zirconyl hematoxylin solutions that stain goblet cells darkly even when fresh. The improved zirconyl hematoxylin can be used in place of alcian blue in the diagnosis of Barrett's esophagus. The ingredients of zirconyl hematoxylin are always readily available and are generally recognized as safe.
Langerhans cell histiocytosis: report of a single organ involvement in a child
Authors: Buza Natalia , Lagarde D. C. , Dash Srikanta , Haque Salima 
Published: May 2007

AbstractLangerhans cell histiocytosis is a rare disorder characterized by abnormal proliferation of Langerhans cells that can affect various organ systems. The disease usually presents as a unifocal lytic bone lesion and can affect any age group. Less frequently it presents as a disseminated disease with multisystem involvement. Hepatic manifestation in Langerhans cell histiocytosis is relatively rare and usually presents as a part of a disseminated process. We report a case of Langerhans cell histiocytosis involving only the liver in a 9‐years‐old child.
Skeletal muscle tissue engineering
Authors: Bach A. D. , Beier J. P. , Stern‐Staeter J. , Horch R. E. 
Published: May 2007

AbstractThe reconstruction of skeletal muscle tissue either lost by traumatic injury or tumor ablation or functional damage due to myopathies is hampered by the lack of availability of functional substitution of this native tissue. Until now, only few alternatives exist to provide functional restoration of damaged muscle tissues. Loss of muscle mass and their function can surgically managed in part using a variety of muscle transplantation or transposition techniques. These techniques represent a limited degree of success in attempts to restore the normal functioning, however they are not perfect solutions. A new alternative approach to addresssing difficult tissue reconstruction is to engineer new tissues. Although those tissue engineering techniques attempting regeneration of human tissues and organs have recently entered into clinical practice, the engineering of skletal muscle tissue ist still a scientific challenge. This article reviews some of the recent findings resulting from tissue engineering science related to the attempt of creation and regeneration of functional skeletal muscle tissue.
HIF‐1 and p53: communication of transcription factors under hypoxia
Authors: Schmid Tobias , Zhou Jie , Brüne Bernhard 
Published: May 2007

AbstractOxygen sensing and reactivity to changes in the concentration of oxygen is a fundamental property of cell physiology. The lack of O2 (hypoxia) is transmitted into many adaptive responses, a process that is largely controlled by a transcription factor known as hypoxia inducible factor‐1 (HIF‐1). More recent reports suggest that besides its traditional regulation via proteasomal degradation other signaling pathways contribute to stability regulation of the HIF‐1α subunit and/or HIF‐1 transactivation. These regulatory circuits allow for the integration of HIF‐1 into scenarios of cell‐survival vs. cell‐death with the rule of the thumb that short‐term mild hypoxia maintains cell viability while prolonged and severe hypoxia provokes cell demise. Cell death pathways are associated with stabilization of the tumor suppressor p53, a response also seen under hypoxic conditions. Here we summarize recent information on accumulation of HIF‐1α and p53 under hypoxia and provide a model to explain the communication between HIF‐1 and p53 under (patho)physiological conditions.