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Selected AbstractsChanges in the expression of P-cadherin in the normal, cryptorchid and busulphan-treated rat testisINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2007K. Pospechova Summary Adhesion between Sertoli cells and germ cells is important for spermatogenesis. Cadherins are Ca2+ -dependent transmembrane proteins that mediate cell,cell adhesion. The aim of this study was to compare the expression of P-cadherin in unilaterally cryptorchid and busulphan-treated rat testes using immunohistochemistry. The pattern of expression of P-cadherin in the seminiferous epithelium changed with the stage of the seminiferous epithelium. The membranes of round spermatids and membranes and cytoplasm of spermatocytes were strongly positive. Our experiments revealed that busulphan treatment (2 doses , 10 mg/kg of body weight , 21 days apart) and cryptorchism led to destructive changes in the structure of seminiferous tubules, together with the decrease in P-cadherin expression. The expression of P-cadherin disappeared in the spermatids segregated from the epithelium while segregated spermatocytes remained still positive for P-cadherin during the 3- to 11-day cryptorchid period. In busulphan-treated animals, the expression of P-cadherin was dependent on the presence or absence of the spermatocytes and spermatids in the tubules. Strong positivity for P-cadherin was observed in the spermatocytes that re-appeared in the regenerating seminiferous epithelium. We suggest that P-cadherin participates in the architecture of adherens junctions in testis, plays an important role in maintaining normal spermatogenesis and that cryptorchism and busulphan treatment lead to adherens junction disintegration. [source] Void formation in the Cu layer during thermal treatment of SiNx/Cu/Ta73Si27/SiO2/Si systemsCRYSTAL RESEARCH AND TECHNOLOGY, Issue 1-2 2005R. Hübner Abstract The thermal stability of a SiNx passivation layer and its influence on the annealing behavior of an amorphous Ta73Si27 diffusion barrier deposited between copper and SiO2 were analyzed by X-ray diffraction, glow discharge optical emission spectroscopy, Auger electron spectroscopy, scanning electron microscopy, and transmission electron microscopy. During heat treatment at a temperature Tan = 500 °C, diffusion of Cu atoms out of the Cu metallization into the SiNx passivation occurs. The Cu diffusion intensifies with increasing annealing temperature and annealing time and seems to be a necessary precondition for a defect formation process observed within the Cu metallization. Depending on the chemical composition of the SiNx/Cu interface, voids in the ,m-range can be formed within the Cu film. Compared to an unpassivated sample, heat treatment leads to a reduced diffusion of Ta atoms from the barrier through the copper into the SiNx/Cu interface. The barrier crystallization process into Ta5Si3 occurring during annealing at Tan = 600 °C is principally not affected by the presence of a SiNx passivation. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] The value of early treatment in patients with haemophilia and inhibitorsHAEMOPHILIA, Issue 3 2010K. KAVAKLI Summary., Development of inhibitors to infused factor concentrates represents a major clinical and economic challenge in the treatment of haemophilic patients. It has been shown that a delay in initiation of treatment leads to requirement of a larger number of injections to stop the bleeding but this has never been formally linked to costs associated with the bleeding. The objectives of this study were to assess the relationship between time to initiation of NovoSeven® and total costs, number of doses administered and time to bleeding resolution in mild to moderate bleeding episodes. Data on time to treatment initiation, time to bleeding resolution and on all resource use related to the bleeding were extracted from medical records in Turkey for 129 bleeding episodes. Regression analysis was used to assess the impact of time to treatment on outcomes. Longer time to treatment initiation increased both total costs associated with the bleeding, the number of doses needed and the time to bleeding resolution. Treatment in hospital was associated with significantly longer time to treatment, higher costs and longer time to bleeding resolution as compared with home treatment or outpatient treatment. When controlling for other bleeding characteristics, the cost of bleedings treated in hospital was more than 150% higher. This study shows that treatment with NovoSeven® should be initiated as soon as possible after the onset of bleeding in order to minimize costs and optimize outcomes. Home treatment reduces time to treatment initiation and also reduces costs related to the bleeding. [source] Hierarchical model of the population dynamics of hippocampal dentate granule cellsHIPPOCAMPUS, Issue 5 2002G.A. Chauvet Abstract A hierarchical modeling approach is used as the basis for a mathematical representation of the population activity of hippocampal dentate granule cells. Using neural field equations, the variation in time and space of dentate granule cell activity is derived from the summed synaptic potential and summed action potential responses of a population of granule cells evoked by monosynaptic excitatory input from entorhinal cortical afferents. In this formulation of the problem, we have considered a two-level hierarchy: the synapses of entorhinal cortical axons define the first level of organization, and dentate granule cells, which include these synapses, define the second, higher level of organization. The model is specified by two state field variables, for membrane potential and for synaptic efficacy, respectively, with both evolving according to different time scales. The two state field variables introduce new parameters, physiological and anatomical, which characterize the dentate from the point of view of neuronal and synaptic populations: (1) a set of geometrical constraints corresponding to the morphological properties of granule cells and anatomical characteristics of entorhinal-dentate connections; and (2) a set of neuronal parameters corresponding to physiological mechanisms. Assuming no interaction between granule cells, i.e., neither ephaptic nor synaptic coupling, the model is shown to be mathematically tractable and allows solution of the field equations leading to the determination of activity. This treatment leads to the definition of two state variables, volume of stimulated synapses and firing time, which describe observed activity. Numerical simulations are used to investigate the populational characterization of the dentate by individual parameters: (1) the relationship between the conditions of stimulation of active perforant path fibers, e.g., stimulating intensity, and activity in the granule cell layer; and (2) the influence of geometry on the generation of activity, i.e., the influence of neuron density and synaptic density-connectivity. As an example application of the model, the granule cell population spike is reconstructed and compared with experimental data. Hippocampus 2002;12:698,712. © 2002 Wiley-Liss, Inc. [source] Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomasHISTOPATHOLOGY, Issue 7 2010Maximino Redondo Redondo M, Rodrigo I, Alcaide J, Tellez T, Roldan M J, Funez R, Diaz-Martin A, Rueda A & Jiménez E (2010) Histopathology,56, 932,936 Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomas Aims:, It has been demonstrated that increased clusterin expression is involved in malignant progression and that anticlusterin treatment leads to selective apoptosis. The aim of this study was to determine the clinicopathological significance of clusterin expression in human colorectal carcinomas. Methods and results:, The expression of clusterin was examined in 31 adenomas and 103 colorectal carcinomas. Normal epithelial cells were always negative for clusterin expression, but clusterin expression was present in 16% (5/31) of adenomas and this percentage increased in colorectal carcinomas (30%, 31/103). Immunopositivity always presented an apical cytoplasmic pattern. The expression level of clusterin did not correlate with age, gender, grade or stage. However, its expression was significantly associated with a decrease in disease-free survival (P < 0.05). In a multivariate Cox proportional hazards model, clusterin expression remained a significant independent predictor. Conclusions:, Clusterin expression may have a role in colonic carcinogenesis and may help identify patients with more aggressive tumours who may benefit from targeted therapy. [source] Caldesmon is a cytoskeletal target for PKC in endotheliumJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2006Natalia V. Bogatcheva Abstract We have previously shown that treatment of bovine endothelial cell (EC) monolayers with phorbol myristate acetate (PMA) leads to the thinning of cortical actin ring and rearrangement of the cytoskeleton into a grid-like structure, concomitant with the loss of endothelial barrier function. In the current work, we focused on caldesmon, a cytoskeletal protein, regulating actomyosin interaction. We hypothesized that protein kinase C (PKC) activation by PMA leads to the changes in caldesmon properties such as phosphorylation and cellular localization. We demonstrate here that PMA induces both myosin and caldesmon redistribution from cortical ring into the grid-like network. However, the initial step of PMA-induced actin and myosin redistribution is not followed by caldesmon redistribution. Co-immunoprecipitation experiments revealed that short-term PMA (5 min) treatment leads to the weakening of caldesmon ability to bind actin and, to the lesser extent, myosin. Prolonged incubation (15,60 min) with PMA, however, strengthens caldesmon complexes with actin and myosin, which correlates with the grid-like actin network formation. PMA stimulation leads to an immediate increase in caldesmon Ser/Thr phosphorylation. This process occurs at sites distinct from the sites specific for ERK1/2 phosphorylation and correlates with caldesmon dissociation from the actomyosin complex. Inhibition of ERK-kinase MEK fails to abolish grid-like structure formation, although reducing PMA-induced weakening of the cortical actin ring, whereas inhibition of PKC reverses PMA-induced cytoskeletal rearrangement. Our results suggest that PKC-dependent phosphorylation of caldesmon is involved in PMA-mediated complex cytoskeletal changes leading to the EC barrier compromise. J. Cell. Biochem. 99: 1593,1605, 2006. © 2006 Wiley-Liss, Inc. [source] PIKE/nuclear PI 3-kinase signaling in preventing programmed cell deathJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2005Keqiang Ye Abstract PI 3-kinase enhancer (PIKE) is a nuclear GTPase that enhances PI 3-kinase (PI3K) activity. Nerve growth factor (NGF) treatment leads to PIKE activation by triggering the nuclear translocation of PLC-,1, which acts as a physiological guanine nucleotide exchange factor (GEF) for PIKE. PI3K occurs in the nuclei of a broad range of cell types, and various stimuli elicit PI3K nuclear translocation. While cytoplasmic PI3K has been well characterized, little is known about the biological function of nuclear PI3K. Surprisingly, nuclei from 30 min NGF-treated PC12 cells are resistant to DNA fragmentation initiated by the activated cell-free apoptosome, and both PIKE and nuclear PI3K are sufficient and necessary for this effect. Moreover, pretreatment of the control nucleus with PI(3,4,5)P3 alone mimics the anti-apoptotic activity of NGF by selectively preventing apoptosis, for which nuclear Akt is required but not sufficient. Recently, a nuclear PI(3,4,5)P3 receptor, nucleophosmin/B23, has been identified from NGF-treated PC12 nuclear extract. PI(3,4,5)P3/B23 complex mediates the anti-apoptotic effects of NGF by inhibiting DNA fragmentation activity of caspase-activated DNase (CAD). Thus, PI(3,4,5)P3/B23 complex and nuclear Akt effectors might coordinately mediate PIKE/nuclear PI3K signaling in promoting cell survival by NGF. © 2005 Wiley-Liss, Inc. [source] Astroglia growth retardation and increased microglia proliferation by lithium and ornithine decarboxylase inhibitor in rat cerebellar cultures: Cytotoxicity by combined lithium and polyamine inhibition,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2007Gad M. Gilad Abstract Lithium, the most prevalent treatment for manic-depressive illness, might have a neuroprotective effect after brain injury. In culture, lithium can exert neurotoxic effects associated with reduction in polyamine synthesis but neuroprotective effects as cultured neurons mature. Cumulative evidence suggests that lithium may exert some of its effects on neurons indirectly, by initially acting on glial cells. We used rat cerebellar cultures to ascertain the effects of lithium on ornithine decarboxylase (ODC) activity, the enzyme catalyzing the first step in polyamine synthesis, and to compare effects of lithium with those of the ODC inhibitor ,-difluoromethylornithine (DFMO) on neuron survival and glial growth. Switching cultures from high (25 mM) to low (5 mM) KCl concentrations served as the traumatic neuronal insult. The results indicate the following. 1) Whereas high depolarizing KCl concentration enhances neuron survival, it inhibits astroglial growth. 2) Lithium (LiCl; 1,5 mM) enhances neuronal survival but inhibits astroglial growth. 3) Lithium treatment leads to reduced ODC activity. 4) DFMO enhances neuron survival but inhibits astroglial growth. 5) Lithium and DFMO lead to transformation of astroglia from epithelioid (flat) to process-bearing morphology and to increased numbers of microglia. 6) Combined lithium plus DFMO treatment is cytolethal to both neurons and glia in culture. In conclusion, lithium treatment results in growth retardation and altered cell morphology of cultured astroglia and increased microglia proliferation, and these effects may be associated with inhibition of polyamine synthesis. This implies that direct effects on astrocytes and microglia may contribute to the effects of lithium on neurons. © 2006 Wiley-Liss, Inc. [source] Complaints related to respiratory events in anaesthesia and intensive care medicine from 1994 to 1998 in DenmarkACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2001C. Rosenstock Background: In Denmark, a National Board of Patients' Complaints (NBPC) was founded in 1988. This study analyses anaesthetic complaints related to adverse respiratory events filed at the NBPC from 1994 to 1998 to point out directions for possible preventive measures. Methods: All decisions made by the NBPC from 1994 to 1998 concerning personnel employed in the Danish health care system were scrutinized. Cases related to anaesthesia and intensive care medicine were reviewed. Adverse respiratory events were identified and classified by mechanism of the incident that had caused the complaint. Detailed information on anaesthetic technique, personnel involved, sequence of events, clinical manifestation of injury, and outcome was recorded. Results: A total of 284 cases was identified. One-fifth (n=60) of the complaints were related to an adverse respiratory event. The overall mortality in these cases was 50% (n=30). In 19 complaints (32%), the treatment was considered substandard. Conclusion: Complaints related to respiratory events reveal that inadequate anaesthetic and intensive care medicine treatment leads to patient damage and death. Preventive strategies should be directed at the development of guidelines for handling the difficult airway, education in the management of the difficult airway, instruction in the correct use of anaesthetic equipment, improvement of interpersonnel communication routines, as well as implementation of simulator training. [source] Reaction Chemistry of 1,4-Benzopyrone Derivates in Non-Equilibrium Low-Temperature PlasmasPLASMA PROCESSES AND POLYMERS, Issue 6 2010Franziska Grzegorzewski Abstract 1,4-Benzopyrone derivates are exposed to different cold gas discharges. Reactions are carried out using different feed gases (argon, oxygen) and excitation sources (radio frequency, microwave) at both atmospheric and low pressure. A structure-dependent degradation upon plasma-chemical reactions can be observed. From contact-angle measurements a strong surface oxidation is suggested. Independent of the source used plasma treatment leads to a significant increase in oxygen content of the samples through newly introduced carbonyl- and carboxyl-functions. This is in agreement to results showing that during thermal food processes oxidative species lead to the formation of characteristic low-molecular weight degradation products. [source] Gene therapy for cartilage defectsTHE JOURNAL OF GENE MEDICINE, Issue 12 2005Magali Cucchiarini Abstract Focal defects of articular cartilage are an unsolved problem in clinical orthopaedics. These lesions do not heal spontaneously and no treatment leads to complete and durable cartilage regeneration. Although the concept of gene therapy for cartilage damage appears elegant and straightforward, current research indicates that an adaptation of gene transfer techniques to the problem of a circumscribed cartilage defect is required in order to successfully implement this approach. In particular, the localised delivery into the defect of therapeutic gene constructs is desirable. Current strategies aim at inducing chondrogenic pathways in the repair tissue that fills such defects. These include the stimulation of chondrocyte proliferation, maturation, and matrix synthesis via direct or cell transplantation-mediated approaches. Among the most studied candidates, polypeptide growth factors have shown promise to enhance the structural quality of the repair tissue. A better understanding of the basic scientific aspects of cartilage defect repair, together with the identification of additional molecular targets and the development of improved gene-delivery techniques, may allow a clinical translation of gene therapy for cartilage defects. The first experimental steps provide reason for cautious optimism. Copyright © 2005 John Wiley & Sons, Ltd. [source] Emergency Use of Extracorporeal Membrane Oxygenation in Cardiopulmonary FailureARTIFICIAL ORGANS, Issue 9 2009Matthias Arlt Abstract Severe pulmonary and cardiopulmonary failure resistant to critical care treatment leads to hypoxemia and hypoxia-dependent organ failure. New treatment options for cardiopulmonary failure are necessary even for patients in outlying medical facilities. If these patients are in need of specialized center treatment, additional emergency medical service has to be carried out quick and safely. We describe our experiences with a pumpless extracorporeal lung assist (PECLA/iLA) for out-of-center emergency treatment of hypercapnic respiratory failure and the use of a newly developed hand-held extracorporeal membrane oxygenation (ECMO) system in cardiac, pulmonary, and cardiopulmonary failure (EMERGENCY-LIFE Support System, ELS System, MAQUET Cardiopulmonary AG, Hechingen, Germany). Between March 2000 and April 2009, we used the PECLA System (n = 20) and the ELS System (n = 33) in adult patients. Cannulation was employed using percutaneous vessel access. The new hand-held ELS System consists of a centrifugal pump and a membrane oxygenator, both mounted on a special holder system for storing on a standard patient gurney for air or ground ambulance transfer. Bedside cannulation processes were uneventful. The PECLA System resulted in sufficient CO2 removal. In all ECMO patients, oxygen delivery and systemic blood flow could be restored and vasopressor support was markedly down. Hospital survival rate in the PECLA group was 50%, and 61% in the ECMO group. Out-of-center emergency treatment of hypercapnic pulmonary failure with pumpless extracorporeal gas exchange and treatment of cardiac, pulmonary, and cardiopulmonary failure with this new hand-held ECMO device is safe and highlyeffective. Patient outcome in cardiopulmonary organ failure could be improved. [source] Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2002K. Breuer SummaryBackground,,The skin of up to 100% of patients with atopic dermatitis (AD) is colonized with Staphylococcus aureus. Of all S. aureus strains isolated from lesional skin, up to 65% have been shown to produce exotoxins with superantigenic properties. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. These studies did not consider the anterior nares as a reservoir of S. aureus, or the possibility of transmission between patients and their contacts. Moreover, adult patients have not so far been investigated. Objectives,,To investigate the colonizing features of S. aureus in adults with AD and in their contacts, and the effect of an antimicrobial treatment of the patients and their partners. Methods,Swabs were taken from the skin and anterior nares of 66 adults with AD. S. aureus strains were screened for the production of exotoxins in 32 patients. Ten patients (two with toxigenic strains, eight with non-toxigenic strains) were treated orally with cefalexin, chlorhexidine ointment was applied to the skin, and the anterior nares were treated with mupirocin ointment. A bath containing potassium permanganate was taken daily. In addition, their partners were treated topically. Results,,Sixty-two of 66 patients (94%) were carriers of S. aureus, and mostly harboured the bacteria on both skin and anterior nares. Ten of 32 (31%) patients were colonized with toxigenic strains. The Severity Scoring in AD (SCORAD) score decreased in nine of 10 patients who received antimicrobial treatment (P < 0·001), and this effect was more pronounced in patients with a baseline SCORAD >,50. Conclusions,,S. aureus may play an important role as an aggravating factor in adults with AD, as antimicrobial treatment leads to a significant improvement of AD in patients who are colonized with the bacterium. [source] | |||||||||||||