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Significant Alterations (significant + alteration)
Selected AbstractsMouse toxicity of Anabaena flos-aquae from Lake Dianchi, ChinaENVIRONMENTAL TOXICOLOGY, Issue 1 2009Xiaojie Pan Abstract Some species of the genera Anabaena can produce various kinds of cyanotoxins, which may pose risks to environment and human health. Anabaena has frequently been observed in eutrophic freshwater of China in recent years, but its toxicity has been reported only in a few studies. In the present study, the toxicity of an Anabaena flos-aquae strain isolated from Lake Dianchi was investigated. Acute toxicity testing was performed by mouse bioassay using crude extracts from the lyophilized cultures. The mice exposed to crude extracts showed visible symptoms of toxicity and died within 10,24 h of the injection. Serum biochemical parameters were evaluated by the use of commercial diagnostic kits. Significant alterations were found in the serum biochemical parameters: alkaline phosphatase (AKP), ,-glutamyl transpeptidase (,-GT), aspartate amino transferase (AST), alanine amino transferase (ALT), AST/ALT ratio, total protein content, albumin content, albumin/globulin (A/G) ratio, blood urea nitrogen (BUN), serum creatinine (Ssr), and total antioxidative capacity (T-AOC). Histopathological observations were carried out with hematoxylin and eosin (HE) stain under light microscope. Severe lesions were seen in the livers, kidneys, and lungs of the mice injected with crude extracts. The alterations of biochemical parameters were in a dose-dependent manner, and the severities of histological lesions were in the same manner. Based on biochemical and histological studies, this research firstly shows the presence of toxin-producing Anabaena species in Lake Dianchi and the toxic effects of its crude extracts on mammals. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Activation of hepatic stellate cells after phagocytosis of lymphocytes: A novel pathway of fibrogenesis,HEPATOLOGY, Issue 3 2008Nidal Muhanna Increased CD8-T lymphocytes and reduced natural killer (NK) cells contribute to hepatic fibrosis. We have characterized pathways regulating the interactions of human hepatic stellate cells (HSCs) with specific lymphocyte subsets in vivo and in vitro. Fluorescence-activated cell sorting (FACS) was used to characterize human peripheral blood lymphocytes (PBLs) and intrahepatic lymphocytes (IHLs) obtained from healthy controls and from patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) with advanced fibrosis. Liver sections were analyzed by immunohistochemistry and confocal microscopy. To investigate in vitro interactions, PBLs from healthy controls or patients with HCV cirrhosis were co-cultured with an immortalized human HSC line (LX2 cells) or with primary HSCs. Significant alterations in lymphocyte distribution were identified in IHLs but not PBLs. The hepatic CD4/CD8 ratio and NK cells were significantly reduced in HBV/HCV patients. Expression of alpha-smooth muscle actin and infiltration of CD4, CD8, and NK cells were readily apparent in liver sections from patients with cirrhosis but not in healthy controls. Lymphocytes from each subset were in proximity to HSCs primarily within the periportal regions, and some were directly attached or engulfed. In culture, HSC activation was stimulated by HCV-derived CD8-subsets but attenuated by NK cells. Confocal microscopy identified lymphocyte phagocytosis within HSCs that was completely prevented by blocking intracellular adhesion molecule 1 (ICAM-1) and integrin molecules, or by irradiation of HSCs. LX2 knockdown of either Cdc42 or Rac1 [members of the Rho-guanosine triphosphatase (GTPase) family] prevented both phagocytosis and the activation of HSC by HCV-derived lymphocytes. Conclusion: The CD4/CD8 ratio and NK cells are significantly decreased in livers with advanced human fibrosis. Moreover, disease-associated but not healthy lymphocytes are engulfed by cultured HSCs, which is mediated by the Rac1 and Cdc42 pathways. Ingestion of lymphocytes by HSCs in hepatic fibrosis is a novel and potentially important pathway regulating the impact of lymphocytes on the course of hepatic fibrosis. (HEPATOLOGY 2008.) [source] Mucosal remodeling in long-standing ulcerative colitis with colorectal neoplasia: Significant alterations of NCAM+ or ,-SMA+ subepithelial myofibroblasts and interstitial cellsPATHOLOGY INTERNATIONAL, Issue 10 2009Isao Okayasu Evidence has been provided in ulcerative colitis (UC) that early genomic instability of both epithelial and stromal cells is important for colorectal tumorigenesis, as well as remodeling and morphological alterations of mucosal crypts. To clarify roles of stromal cells in tumor development in UC, the present study focused on heterogeneous phenotypes of subepithelial myofibroblasts and interstitial cells, in association with mucosal remodeling. To clarify the relationship of alterations to tumorigenesis, mucosa of resected rectae from patients with UC (n= 49) and sporadic cancer (n= 10) were analyzed on immunohistochemistry and also on immunoelectron microscopy. Heterogeneous phenotypes of neural cell adhesion molecule (NCAM)+ and/or ,-smooth muscle actin (,-SMA)+ subepithelial myofibroblasts and interstitial cells were demonstrated, corresponding to colonic stellate cells. Decrease of NCAM+ subepithelial myofibroblasts and interstitial cells, and increase of ,-SMA+ interstitial cells were significant in UC with neoplasia as compared to without neoplasia. ,-SMA+ muscularis mucosae was significantly more thickened in tumor cases. Deposits of Masson's trichrome+ and type III and I collagen in the muscularis mucosae and lamina propria appeared to increase in relation to the numbers of ,-SMA+ interstitial cells. Mucosal remodeling with alterations of NCAM+ or ,-SMA+ subepithelial and interstitial cells may play a critical role in UC-associated tumorigenesis. [source] A gel-free quantitative proteomics approach to investigate temperature adaptation of the food-borne pathogen Cronobacter turicensis 3032PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 18 2010Paula Carranza Abstract The opportunistic food-borne pathogen Cronobacter sp. causes rare but significant illness in neonates and is capable to grow at a remarkably wide range of temperatures from 5.5 to 47°C. A gel-free quantitative proteomics approach was employed to investigate the molecular basis of the Cronobacter sp. adaptation to heat and cold-stress. To this end the model strain Cronobacter turicensis 3032 was grown at 25, 37, 44, and 47°C, and whole-cell and secreted proteins were iTRAQ-labelled and identified/quantified by 2-D-LC-MALDI-TOF/TOF-MS. While 44°C caused only minor changes in C. turicensis growth rate and protein profile, 47°C affected the expression of about 20% of all 891 identified proteins and resulted in a reduced growth rate and rendered the strain non-motile and filamentous. Among the heat-induced proteins were heat shock factors, transcriptional and translational proteins, whereas proteins affecting cellular morphology, proteins involved in motility, central metabolism and energy production were down-regulated. Notably, numerous potential virulence factors were found to be up-regulated at higher temperatures, suggesting an elevated pathogenic potential of Cronobacter sp. under these growth conditions. Significant alterations in the protein expression profile and growth rate of C. turicensis exposed to 25°C indicate that at this temperature the organism is cold-stressed. Up-regulated gene products comprised cold-shock, DNA-binding and ribosomal proteins, factors that support protein folding and proteins opposing cold-induced decrease in membrane fluidity, whereas down-regulated proteins were mainly involved in central metabolism. [source] Protein expression changes induced in murine peritoneal macrophages by Group B StreptococcusPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2010Federica Susta Abstract Protein expression changes induced in thioglycolate-elicited peritoneal murine macrophages (M,) by infection with type III Group B Streptococcus (GBS) are described. Proteins from control M, and M, incubated 2,h with live or heat-inactivated GBS were separated by 2-DE. Proteins whose expression was significantly different in infected M,, as compared with control cells, were identified by MS/MS analysis. Changes in the expression level of proteins involved in both positive and negative modulation of phagocytic functions, stress response and cell death were induced in M, by GBS infection. In particular, expression of enzymes playing a key role in production of reactive oxygen species was lowered in GBS-infected M,. Significant alterations in the expression of some metabolic enzymes were also observed, most of the glycolytic and of the pentose-cycle enzymes being down-regulated in M, infected with live GBS. Finally, evidence was obtained that GBS infection affects the expression of enzymes or enzyme subunits involved in ATP synthesis and in adenine nucleotides interconversion processes. [source] Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque depositionPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2007Frank Gillardon Dr. Abstract Synaptic dysfunction is an early event in Alzheimer's disease patients and has also been detected in transgenic mouse models. In the present study, we analyzed proteomic changes in synaptosomal fractions from Tg2576 mice that overexpress mutant human amyloid precursor protein (K670N, M671L) and from their nontransgenic littermates. Cortical and hippocampal tissue was microdissected at the onset of cognitive impairment, but before deposition of amyloid plaques. Crude synaptosomal fractions were prepared by differential centrifugation, proteins were separated by 2-D DIGE and identified by MS/MS. Significant alterations were detected in mitochondrial heat shock protein 70 pointing to a mitochondrial stress response. Subsequently, synaptosomal versus nonsynaptic mitochondria were purified from Tg2576 mice brains by density gradient centrifugation. Mitochondrial proteins were separated by IEF or Blue-native gel electrophoresis in the first dimension and SDS-PAGE in the second dimension. Numerous changes in the protein subunit composition of the respiratory chain complexes I and III were identified. Levels of corresponding mRNAs remain unchanged as shown by Affymetrix oligonucleotide array analysis. Functional examination revealed impaired state 3 respiration and uncoupled respiration in brain mitochondria from young Tg2576 mice. By immunoblotting, amyloid-beta oligomers were detected in synaptosomal fractions from Tg2576 mice and reduced glucose metabolism was observed in Tg2576 mice brains by [14C]-2-deoxyglucose infusion. Taken together, we demonstrate alterations in the mitochondrial proteome and function that occur in Tg2576 mice brains before amyloid plaque deposition suggesting that mitochondria are early targets of amyloid-beta aggregates. [source] Accommodation in ABO-Incompatible Kidney Allografts, a Novel Mechanism of Self-Protection Against Antibody-Mediated InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2003Walter D. Park To elucidate the mechanism of self-protection against anti-donor blood-group antibody known as accommodation, we studied 16 human ABO-incompatible living-donor kidney transplant recipients at 3 and 12 months post transplantation. Both circulating anti-blood-group antibody and the target blood-group antigen in the graft were demonstrable in all patients after transplantation. Thirteen of 16 grafts had normal renal function and histology, while three grafts with prior humoral rejection demonstrated significant glomerulopathy and thus did not meet the criterion for accommodation. Using microarrays, we compared five 1-year protocol ABO-compatible renal graft biopsies to four accommodated ABO-incompatible graft biopsies. Significant alterations in gene expression in 440 probe sets, including SMADs, protein tyrosine kinases, TNF-, and Mucin 1 were identified. We verified these changes in gene expression using RT-PCR and immunohistochemistry. Heme oxygenase-1, Bcl-2 and Bcl-xl were not increased in ABO-incompatible grafts at any time-point. We conclude that accommodation is always present in well-functioning, long-surviving ABO-incompatible kidney transplants. This self-protection against antibody-mediated damage may involve several novel mechanisms including the disruption of normal signal transduction, attenuation of cellular adhesion and the prevention of apoptosis. [source] Histological and Histomorphometrical Alterations of the Periodontal Ligament in Gerbils Submitted to Teeth ExtractionANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 4 2008M. M. Iyomasa Summary This study verified the effect of unilateral teeth extraction on the periodontal ligament in gerbils (Meriones unguiculatus). Ten adult male gerbils weighing about 50 g had induced occlusal alterations by upper left molar extractions while the other ten animals, only submitted to surgical stress, were considered as controls. The periodontal ligament was characterized by qualitative and quantitative analysis, histological description and histomorphometric quantification. Significant alterations were observed on the left side of the experimental group (P < 0.05), the hypofunctional region, when it was compared with the contralateral side and the corresponding region of the control group. Two months after occlusal alterations induced by unilateral teeth extraction, atrophic histological alterations and a decrease in the periodontal space on the ipsilateral side characterized the periodontal ligament. In this study it was possible to conclude that the gerbil can be used in experimental models attempting to correlate the periodontium's biological response to various mechanical stresses, as the periodontal ligament was shown to be highly sensitive to occlusal alterations. [source] RPP25 is developmentally regulated in prefrontal cortex and expressed at decreased levels in autism spectrum disorderAUTISM RESEARCH, Issue 4 2010Hsien-Sung Huang Abstract Dysfunction of cerebral cortex in autism is thought to involve alterations in inhibitory neurotransmission. Here, we screened, in prefrontal cortex (PFC) of 15 subjects diagnosed with autism and 15 matched controls the expression of 44 transcripts that are either preferentially expressed in gamma-aminobutyric acidergic interneurons of the mature cortex or important for the development of inhibitory circuitry. Significant alterations in the autism cohort included decreased expression (,45%) of RPP25 (15q24.1), which is located within the autism susceptibility locus, 15q22-26. RPP25, which encodes the 25,kDa subunit of ribonuclease P involved in tRNA and pre-ribosomal RNA processing, was developmentally regulated in cerebral cortex with peak levels of expression during late fetal development (human) or around birth (mouse). In the PFC, RPP25 chromatin showed high levels of histone H3-lysine 4 trimethylation, an epigenetic mark associated with transcriptional regulation. Unexpectedly, and in contrast to peripheral tissues, levels of RPP25 protein remained undetectable in fetal and adult cerebral cortex. Taken together, these findings suggest a potential role for the RPP25 gene transcript in the neurobiology of developmental brain disorders. [source] Effects of dietary N -acetylcysteine on the oxidative stress induced in tilapia (Oreochromis Niloticus) exposed to a microcystin-producing cyanobacterial water bloom,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2009María Puerto Abstract Fish can be exposed to toxic cyanobacterial cells in natural waters and fish farms and suffer from oxidative damage. The present study investigates the effects of N-acetylcysteine (NAC), a glutathione (GSH) precursor, on the oxidative stress induced by Microcystis cyanobacterial cells containing microcystins (MCs) in tilapia fish (Oreochromis niloticus). Variation in lipid peroxidation (LPO) levels, carbonyl group content, reduced glutathione to oxidized glutathione ratio (GSH: GSSG), and catalase (Enzyme Commission [EC] 1.11.1.6), superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC 1.8.1.7), glutathione peroxidase (GPx; EC 1.11.1.9), and glutathione S-transferase (EC 2.5.1.18) activities in liver and kidney of tilapia exposed to a single oral dose of 120 ,g MC-LR (with leucine [L] and arginine [R])/fish and killed in 24 h were investigated in the absence and presence of 20.0, 44.0, and 96.8 mg NAC/fish/d. Results showed a protective role of NAC, depending on the dose and the biomarker considered. The increase in LPO (1.9-and 1.4-fold in liver and kidney, respectively) and the decreased protein content and GSH:GSSG in the liver induced by MCs were recovered mainly by the lower doses of NAC employed. Antioxidant enzyme activities increased (range, 1.4-to 1.7-fold) by MCs also were ameliorated by NAC, although the highest level used induced significant alteration of some enzymatic activities, such as SOD, GPx, and GR. Thus, NAC can be considered to be a useful chemoprotectant that reduces hepatic and renal oxidative stress in the prophylaxis and treatment of MC-related intoxications in fish when careful attention is given to its application dose because of its own pro-oxidant activity, as shown in the present study at 96.8 mg NAC/ fish/d. [source] Spatio-temporal distribution of cellular retinoid binding protein gene transcripts in the developing and the adult cochlea.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000CRBPI-null mutant mice, Morphological, functional consequences in CRABP- Abstract The expression patterns of the mouse cellular retinoid binding protein genes were investigated by in situ hybridization analysis in the inner ear from 10.5 days post coïtum (dpc) up to the adult stage. The cellular retinoic acid binding protein II (CRABPII) and cellular retinol binding protein I (CRBPI) were present in a widespread and abundant pattern in cochlear structures during embryogenesis. Expression of the cellular retinoic acid binding protein I (CRABPI) is restricted during development in Kölliker's organ whilst cellular retinol binding protein II (CRBPII) is only visible after birth with a ubiquitous distribution in most regions of the cochlea including nervous components. No CRABP or CRBP transcripts were observed in the auditory receptors. Morphological observations of CRBPI- and CRABPI/CRABPII-null mutant fetus at 18.5 dpc do not show any structural modification at the level of the organ of Corti. Furthermore, electrophysiological tests performed by measuring distorsion-product otoacoustic emissions and auditory brainstem evoked responses did not present significant alteration of the auditory function for the different types of mutants. The expression of retinoid binding proteins in cochlear structures during embryogenesis could suggest important roles for these proteins during ontogenesis and morphogenesis of the inner ear. Despite these observations, morphological and functional data from mutant mice did not present obvious modifications of the cochlear structures and auditory thresholds. It is therefore unlikely that CRABPs and CRBPI are directly involved in development of the cochlea and hair cell differentiation. [source] Contact Angle Analysis During the Electro-oxidation of Self-Assembled Monolayers Formed by n -OctadecyltrichlorosilaneADVANCED FUNCTIONAL MATERIALS, Issue 19 2010Nicole Herzer Abstract The electrochemical oxidation process of self-assembled monolayers formed by n -octadecyltrichlorosilane (OTS) molecules on silicon wafers has been studied in a droplet of water by means of in situ water contact angle measurements. The application of different bias voltages between the substrate and a counter electrode placed into the droplet resulted in changes of the chemical nature of the monolayer, which yielded a significant alteration of the surfaces properties. Due to the changes of the wetting properties of the monolayer during the electro-oxidation process a change in the contact angles of the water droplet is concomitantly observed. This allows the in situ monitoring of the electro-oxidation process for large modified areas of several millimeters in diameter. The chosen approach represents an easy way to screen the major parameters that influence the oxidation process. Afterwards, the oxidized regions are characterized by Fourier-transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) measurements, and atomic force microscopy (AFM) investigations to obtain more information about the electro-oxidation process. The observations are correlated to experimental results obtained for oxidations performed on a smaller dimension range in the water meniscus of a conductive, biased AFM tip. A good correlation of the results in the different dimension ranges could be found. [source] Allosteric activation of pyruvate kinase via NAD+ in rat liver cellsFEBS JOURNAL, Issue 14 2001Anne Devin In isolated rat hepatocytes, it has previously been reported that a rise in the ATP content induces a proportional increase in cytosolic NAD+ concentration [Devin, A., Guérin, B. & Rigoulet, M. (1997) FEBS Lett.410, 329,332]. This occurs under physiological conditions such as various substrates or different energetic states. To investigate the effect of a physiological rise in cytosolic [NAD+] per se on glycolysis and gluconeogenesis, an increase in [NAD+] induced by exogenous nicotinamide addition was obtained without a change in redox potential, ATP/ADP ratio and ATP concentration. Using dihydroxyacetone as substrate, we found that an increase in cytosolic [NAD+] decreases gluconeogenesis and enhances glycolysis without significant alteration of dihydroxyacetone consumption rate. These modifications are the consequence of an allosteric activation of pyruvate kinase via cytosolic NAD+ content. Thus, in addition to the well-known thermodynamic control of glycolysis by pyridine-nucleotide redox status, our study points to a new mechanism of glycolytic flux regulation by NAD+ concentration at the level of pyruvate kinase activity. [source] Post-excavation deterioration of the Copney Bronze Age Stone Circle Complex: A geomorphological perspectiveGEOARCHAEOLOGY: AN INTERNATIONAL JOURNAL, Issue 5 2010Patricia A. Warke Post-excavation deterioration of stones from under blanket peat at the Copney Bronze Age Stone Circle Complex in County Tyrone, Northern Ireland, proceeded through widespread scaling, flaking, and splitting of stones. Investigation showed that prior to burial the porphyritic stones already possessed a complex legacy of geological weaknesses derived from hydrothermal alteration and tectonic deformation. Analysis indicated that significant alteration occurred during approximately 2000 years of burial under acidic peat cover, with development of a secondary porosity, alteration of primary minerals, and the opening of preexisting lines of weakness within the stones. Burial under peat also resulted in "bleaching" the stones so that they appeared white in color following excavation. These alterations during burial left the stones in a significantly weakened state and particularly susceptible to the effects of subaerial weathering processes. Data underline the potential fragility of excavated stonework and highlight the need to plan for its aftercare before complete excavation is undertaken. © 2010 Wiley Periodicals, Inc. [source] Effect of improvement in anemia on electroneurophysiological markers (P300) of cognitive dysfunction in chronic kidney diseaseHEMODIALYSIS INTERNATIONAL, Issue 3 2006Narinder P. SINGH Abstract Our aim is to study the effect of improvement in anemia on event-related potentials (ERPs; P300) as markers of cognitive dysfunction in predialysis and dialysis patients of chronic kidney disease (CKD). Thirty anemic patients of CKD (hemoglobin [Hb]<9 g%), 15 in the predialysis group (Group A), and 15 patients on biweekly hemodialysis (Group B) were recruited for the study. Patients of uremic encephalopathy, dyselectrolytemia, and those with hearing problems were excluded. Both groups were given recombinant human erythropoietin (rhuEPO) 100 IU/kg biweekly for 6 weeks by the subcutaneous route. No intervention was performed in the third control group (Group C), which consisted of 30 normal healthy volunteers. The improvement in Hb was assessed every 2 weeks, and the amplitude and latency of the P300 component of the ERPs were studied before initiating treatment and after 6 weeks of rhuEPO administration. There was a significant increase in Hb in both the study groups without any significant alteration in kidney functions. A significant reduction in P300 latency was noted in both the study groups after intervention. Similarly, the amplitude of P300 also increased in both study groups, but attained statistical significance for the dialysis group only. No significant changes were observed in the control group. Administration of EPO in patients of anemia with CKD resulted in a significant improvement in the electrophysiological markers of cognitive function in the form of increased amplitudes and decreased latencies of P300 in both predialysis and dialysis patients. [source] Rethinking what constitutes suspended sedimentHYDROLOGICAL PROCESSES, Issue 9 2001Ian G. Droppo Abstract Although cohesive suspended sediment is now known to be transported primarily as flocculated material, there is still a misconception of what constitutes suspended sediment. Flocs represent a complex matrix of microbial communities, organic particles (e.g. detritus, extracellular polymers and cellular debris), inorganic particles (e.g. clays and silts) and substantial interfloc spaces (pores), which allow for the retention or flow through of water. Flocculation results in significant alteration of the hydrodynamics of the constituent particles (by modifying their effective size, shape, density and porosity), thereby affecting the transport of sediment and associated contaminants. The composition and structure of a floc is in a continuous state of change as the medium in which it is transported provides the floc with further building materials, energy, nutrients and chemicals for biological growth, chemical reactions and morphological development. As such, a floc's physical (e.g. transport), chemical (e.g. contaminant adsorption) and biological (community development and contaminant biotransformation) behaviour are also in a continuous state of change, with concomitant effects on their aquatic environment as a whole. Although it is recognized that floc form will influence floc behaviour, there is still a basic lack of knowledge of the complex links between the structural components of a floc and how their individual properties and behaviours in combination with others will influence a floc's physical, chemical and biological behaviour. This paper provides a comprehensive conceptual model that links the many interrelated structural components of typical flocs and their interrelated behavioural aspects, in order to enhance our understanding of what constitutes suspended sediment. Copyright © 2001 John Wiley & Sons, Ltd. [source] An obesity drug sibutramine reduces brain natriuretic peptide (BNP) levels in severely obese patientsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2010D. Taner Ertugrul Summary Objectives:, Sibutramine is a selective inhibitor of the reuptake of monoamines. Plasma levels of brain natriuretic peptide (BNP) appear to be inversely associated with body mass index (BMI) in subjects with and without heart failure for reasons that remain unexplained. The aim of this study was to investigate the possible influence of sibutramine treatment on BNP levels in severely obese patients. Methods:, Fifty-two severely obese female patients with BMI > 40 kg/m2 were included to this study. The women were recommended to follow a weight-reducing daily diet of 25 kcal/kg of ideal body weight. During the treatment period, all patients were to receive 15 mg of sibutramine once a day. Blood chemistry tests were performed before the onset of the medication and after 12 weeks of treatment. Results:, None of the subjects was withdrawn from the study because of the adverse effects of sibutramine. Body weight (108.8 ± 13.3 kg vs. 101.7 ± 15.6 kg, p < 0.001), BMI (44.6 ± 4.6 kg/m2 vs. 41.8 ± 5.7 kg/m2, p < 0.001) and BNP [8.6 (0.5,49.5) ng/l vs. 3.1 (0.2,28.6) ng/l, p = 0.018] levels were significantly decreased after 12 weeks of sibutramine treatment. Total cholesterol (5.19 ± 0.90 mmol/l vs. 4.82 ± 1.05 mmol/l respectively; p < 0.001), low-density lipoprotein-cholesterol (3.26 ± 0.86 mmol/l vs. 2.99 ± 0.40 mmol/l respectively; p = 0.008), levels were significantly decreased; however, there was no significant alteration in high-density lipoprotein-cholesterol and triglyceride levels. Conclusion:, This study has shown a decrease in BNP levels which may lead to improvement in cardiac outcome after sibutramine treatment. Further randomised studies are needed to be conducted to clarify the relationship between sibutramine and BNP. [source] Fetal Ethanol Exposure Disrupts the Daily Rhythms of Splenic Granzyme B, IFN- ,, and NK Cell Cytotoxicity in AdulthoodALCOHOLISM, Issue 6 2006Alvaro Arjona Background: Circadian (and daily) rhythms are physiological events that oscillate with a 24-hour period. Circadian disruptions may hamper the immune response against infection and cancer. Several immune mechanisms, such as natural killer (NK) cell function, follow a daily rhythm. Although ethanol is known to be a potent toxin for many systems in the developing fetus, including the immune system, the long-term effects of fetal ethanol exposure on circadian immune function have not been explored. Methods: Daily rhythms of cytotoxic factors (granzyme B and perforin), interferon- , (IFN- ,), and NK cell cytotoxic activity were determined in the spleens of adult male rats obtained from mothers who were fed during pregnancy with chow food or an ethanol-containing liquid diet or pair-fed an isocaloric liquid diet. Results: We found that adult rats exposed to ethanol during their fetal life showed a significant alteration in the physiological rhythms of granzyme B and IFN- , that was associated with decreased NK cell cytotoxic activity. Conclusion: These data suggest that fetal ethanol exposure causes a permanent alteration of specific immune rhythms that may in part underlie the immune impairment observed in children prenatally exposed to alcohol. [source] Temporal Discrimination Learning in Abstinent Chronic AlcoholicsALCOHOLISM, Issue 6 2002Regina McGlinchey-Berroth Background: Converging evidence from varied experimental paradigms has demonstrated that the cerebellum is involved in the timing of learned behavior. Given the documented neurological changes secondary to chronic alcoholism, particularly cerebellar degeneration, the ability of recovered chronic alcoholics to learn a temporal discrimination was assessed by using delayed eyeblink classical conditioning. Methods: Twelve abstinent alcoholic participants and 12 matched control participants were randomly presented 2 clearly discriminable tone conditioned stimuli that were individually paired with 2 different interstimulus intervals. Results: The data revealed a significant alteration in the abstinent alcoholics' peak latency measure at the long interstimulus intervals and an overall impairment in their level of acquisition of conditioned responses. No group differences in extinction were observed. Conclusions: It was speculated that cerebellar cortical atrophy caused by years of alcohol abuse resulted in the peak latency alteration and that atrophy extending into deep cerebellar nuclei caused the overall impairment in conditioned response acquisition. [source] Pilocarpine for the treatment of salivary glands' impairment caused by radioiodine therapy for thyroid cancerORAL DISEASES, Issue 3 2006DJ Aframian Objectives:, To study the effect of single-dose pilocarpine hydrochloride 5 mg on the whole unstimulated and stimulated salivary flow in patients suffering from thyroid cancer treated with radioiodine therapy, and to investigate the changes in vital signs during the treatment. Subjects and methods:, Five such patients were referred with complaints of dry mouth, rampant caries, and pain in the parotid gland region or history of chronic recurrent suppurative sialodenitis. A single dose of 5 mg pilocarpine hydrochloride was administered to each patient and blood pressure, heart rate, body temperature and salivary secretion rate were monitored at 1, 2 and 3 h. Results:, A significant elevation of unstimulated and stimulated saliva flow rate was observed in four patients without significant alteration of the monitored vital signs. Conclusions:, Treatment with pilocarpine hydrochloride may be beneficial in the case of impaired salivary function in patients treated with radioiodine. [source] Activation of the prefrontal cortex to trauma-related stimuli measured by near-infrared spectroscopy in posttraumatic stress disorder due to terrorismPSYCHOPHYSIOLOGY, Issue 4 2003Koji Matsuo Abstract To develop a noninvasive method for psychophysiological assessment of posttraumatic stress disorder (PTSD), 34 victims of the Tokyo Subway Sarin Attack in 1995 including 8 diagnosed as PTSD and 12 controls were examined by a multichannel near-infrared spectroscopy (NIRS) system. Hemodynamic response in the prefrontal cortex was monitored during the presentation of trauma-related and control stimuli by video images. Skin conductance response (SCR) was also examined. Oxygenated hemoglobin significantly increased during the trauma-related image in the victims with or without PTSD. Deoxygenated hemoglobin significantly decreased only in victims with PTSD. No significant alteration was found in controls. Significantly enhanced SCR was also observed in the victims with PTSD during trauma-related stimuli. The findings suggest that measurement of cerebral hemodynamic response by NIRS is useful for psychophysiological assessment of PTSD. [source] The Effect of Ovariectomy on Rat Vaginal Tissue Contractility and HistomorphologyTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006F. Fatih Önol MD ABSTRACT Introduction., Ovarian hormones have an important role in age-related genital arousal disorders; however, our knowledge regarding possible vaginal wall morphology and contractility changes in low-hormonal states is limited. Aims., To investigate morphological and functional alterations in the vaginal tissue in a rat ovariectomy model and to show the differences between proximal and distal vagina. Methods., Six weeks following ovariectomy, vaginal tissues were examined under light and electron microscopy. Circularly cut distal and proximal tissues were studied in the organ bath under isometric tension and compared with age-matched controls. Contractile responses to electrical field stimulation (EFS), phenylephrine, carbachol, and the effects of alpha-1 and alpha-2 blockade on EFS-induced contractility were investigated. Relaxation responses to EFS and vardenafil were investigated in precontracted strips. Main Outcome Measures., Differences between control and ovariectomy groups in terms of vaginal tissue contractility and histomorphological properties. Results., Distal vagina showed different epithelial characteristics and a better-developed muscularis compared with proximal vagina. Ovariectomy caused thinning of the epithelium, severe degeneration in epithelial architecture, and smooth muscle atrophy. Contraction and relaxation responses of distal strips were significantly lower in ovariectomized rats. Contractile responses to neuropharmacological stimulation were insignificant in proximal strips of both groups. EFS-induced contractions in distal strips diminished significantly after alpha-1 and alpha-2 adrenergic blockade. EFS caused frequency-dependent relaxation responses in precontracted distal strips, which were significantly decreased after nitric oxide synthase inhibition. Conclusions., Ovariectomy causes significant alteration in rat vaginal tissue morphology and contractility. Contraction and relaxation responses of distal vagina are significantly greater compared with morphologically distinct proximal vagina. Alpha-1 and alpha-2 receptors are the main mediators of contraction in distal rat vaginal tissue whereas nitric oxide pathway may have at least a partial role in relaxation. Main mediators of the rat vaginal tissue relaxation and the effect of ovariectomy on this regulation are yet to be defined. Önol FF, Ercan F, and Tarcan T. The effect of ovariectomy on rat vaginal tissue contractility and histomorphology. J Sex Med 2006;3:233,241. [source] Strong decrease in lignin content without significant alteration of plant development is induced by simultaneous down-regulation of cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) in tobacco plantsTHE PLANT JOURNAL, Issue 3 2001Matthieu Chabannes Summary Different transgenic tobacco lines down-regulated for either one or two enzymes of the monolignol pathway were compared for their lignin content and composition, and developmental patterns. The comparison concerned CCR and CAD down-regulated lines (homozygous or heterozygous for the transgene) and the hybrids resulting from the crossing of transgenic lines individually altered for CCR or CAD activities. Surprisingly, the crosses containing only one allele of each antisense transgene, exhibit a dramatic reduction of lignin content similar to the CCR down-regulated parent but, in contrast to this transgenic line, display a normal phenotype and only slight alterations of the shape of the vessels. Qualitatively the lignin of the double transformant displays characteristics more like the wild type control than either of the other transgenics. In the transgenics with a low lignin content, the transformations induced other biochemical changes involving polysaccharides, phenolic components of the cell wall and also soluble phenolics. These results show that the ectopic expression of a specific transgene may have a different impact depending on the genetic background and suggest that the two transgenes present in the crosses may operate synergistically to reduce the lignin content. In addition, these data confirm that plants with a severe reduction in lignin content may undergo normal development at least in controlled conditions. [source] Localization of binding sites of naturally occurring antisperm antibodies on human spermatozoa by immunofluorescenceANDROLOGIA, Issue 5 2004C. Bohring Summary. Antisperm antibodies (ASA) may affect sperm motility, acrosome reaction, sperm penetration of cervical mucus, binding to the zona pellucida, and sperm,egg fusion. We investigated the localization of ASA of infertile men or men after vasectomy bound on the sperm surface using an immunofluorescence method. Binding occurred in the acrosomal region, midpiece, and tail. Most of the ASA in both groups of patients bound to the midpiece alone or in combination with other regions of spermatozoa. Only few ASA samples showed binding to all the three sperm regions. A combination of binding to the acrosomal region and to the midpiece was never observed. In infertile patients with ASA, the binding site was compared with sperm parameters. ASA binding to the sperm head influenced the acrosome reaction. Binding of ASA on tail and/or midpiece was not associated with a significant alteration of viability and motility. Immunofluorescence appears to be a valuable tool in the diagnosis of immune infertility, in particular when impairment of the acrosome activity is suggested. [source] Haematological and biochemical alterations in Korean catfish, Silurus asotus, experimentally infected with Edwardsiella tardaAQUACULTURE RESEARCH, Issue 2 2010Jin Ha Yu Abstract This study determined the haematological changes in Korean catfish, Silurus asotus, experimentally infected with Edwardsiella tarda. Twenty-four or 48 h after infection with 1 × 104 colony-forming units (CFU) mL,1 of E. tarda, the fish were anaesthetized and the blood was collected. The haematological and biochemical tests included haematocrit (Ht), haemoglobin (Hb), leucocyte counts (Lc), total calcium (Ca), total protein (TP) concentration, alkaline phosphatase (ALP), glucose (GLU), aspartate aminotransferase, lysozyme and differential leucocyte populations. After 24- and 48-h infection, the values of Ht, Hb, Lc, TP, ALP and GLU were significantly decreased with respect to the control. Aspartate aminotransferase and lysozyme activity in both the 24- and 48-h groups exhibited higher levels compared with those in the control. However, the bacterial infection did not induce any significant alteration in the Ca concentration. After the 48-h infection, neutrophils and macrophage populations were reduced whereas lymphocytes were increased with respect to those in the control and the 24-h infection groups. The present study demonstrates that E. tarda infection causes haemato-biochemical responses that are related to the general physiological condition and defence system in catfish. [source] scFv-based fluorogen activating proteins and variable domain inhibitors as fluorescent biosensor platformsBIOTECHNOLOGY JOURNAL, Issue 9 2009Crystal N. Falco Abstract Single chain antibodies (scFvs) are engineered proteins composed of IgG variable heavy (VH) and variable light (VL) domains tethered together by a flexible peptide linker. We have characterized the individual VH or VL domain activities of several scFvs isolated from a yeast surface-display library for their ability to bind environmentally sensitive fluorogenic dyes causing them to fluoresce. For many of the scFvs, both VH and VL domains are required for dye binding and fluorescence. The analysis of other scFvs, however, revealed that either the VH or the VL domain alone is sufficient to cause the fluorogenic dye activation. Furthermore, the inactive complementary domains in the original scFvs either contribute nothing to, or actually inhibit the activity of these active single domains. We have explored the interactions between active variable domains and inactive complementary domains by extensive variable domain swapping through in vitro gene manipulations to create hybrid scFvs. In this study, we demonstrate that significant alteration of the fluorogenic dye activation by the active VH or VL domains can occur by partnering with different VH or VL complementary domains in the scFv format. Hybrid scFvs can be generated that have fluorogen-activating domains that are completely inhibited by interactions with other domains. Such hybrid scFvs are excellent platforms for the development of several types of genetically encoded, fluorescence-generating biosensors. [source] Regulatory T cells in atopic dermatitis: epidermal dendritic cell clusters may contribute to their local expansionBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2009A. Szegedi Summary Background, Regulatory T cells (Tregs) have an essential role in tolerance and immune regulation. However, few and controversial data have been published to date on the role and number of these cells in atopic dermatitis (AD). Objectives, To investigate the number of CD4+CD25+FOXP3+ Tregs and interleukin 10-producing T regulatory type 1 (Tr1) cells in patients with AD. Methods, Peripheral blood and skin biopsy samples from atopy patch test (APT)-positive patients with acute- and chronic-phase AD were investigated. Immunohistochemistry was applied to identify CD4+CD25+FOXP3+ Tregs in the skin, while flow cytometry was used to detect CD4+CD25highFOXP3+ Tregs and Tr1 cells in the peripheral blood. Results, In the peripheral blood samples of patients with AD significantly elevated numbers of Tr1 cells were found. Although neither the absolute number nor the percentage of CD4+CD25highFOXP3+ Tregs showed significant alteration in the peripheral blood of patients, increased numbers of FOXP3+ Tregs were detected in skin biopsy specimens. All of the APT-positive skin samples showed epidermal dendritic cell aggregates, morphologically consistent with so-called Langerhans cell microgranulomas, which also contained intermingled FOXP3+ Tregs. Conclusions, Tr1 cell numbers were elevated in the peripheral blood and increased numbers of CD4+CD25highFOXP3+ Tregs were detected in the skin of patients with AD. The epidermal dendritic cell clusters in APT-positive lesional skin showed a close connection to the FOXP3+ Tregs. [source] Augurin stimulates the hypothalamo-pituitary-adrenal axis via the release of corticotrophin-releasing factor in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2010JA Tadross Background and purpose:, The functional characterization of secreted peptides can provide the basis for the development of novel therapeutic agents. Augurin is a recently identified secreted peptide of unknown function expressed in multiple endocrine tissues, and in regions of the brain including the hypothalamus. We therefore investigated the effect of hypothalamic injection of augurin on the hypothalamo-pituitary-adrenal (HPA) axis in male Wistar rats. Experimental approach:, Augurin was given as a single injection into the third cerebral ventricle (i.c.v.) or into the paraventricular nucleus (iPVN) of the hypothalamus. Circulating hormone levels were then measured by radioimmunoassay. The effect of augurin on the release of hypothalamic neuropeptides was investigated ex vivo using hypothalamic explants. The acute effects of iPVN augurin on behaviour were also assessed. Key results:, i.c.v. injection of augurin significantly increased plasma ACTH and corticosterone, compared with vehicle-injected controls, but had no effect on other hypothalamo-pituitary axes hormones. Microinjection of lower doses of augurin into the PVN caused a similar increase in plasma ACTH and corticosterone, without significant alteration in behavioural patterns. Incubation of hypothalamic explants with increasing doses of augurin significantly elevated corticotrophin-releasing factor (CRF) and arginine vasopressin release. In vivo, peripheral injection of a CRF1/2 receptor antagonist prevented the rise in ACTH and corticosterone caused by i.c.v. augurin injection. Conclusions and implications:, These data suggest that augurin stimulates the release of ACTH via the release of hypothalamic CRF. Pharmacological manipulation of the augurin system may therefore be a novel target for regulation of the HPA axis. [source] Prospective assessment of emotional distress, cognitive function, and quality of life in patients with cancer treated with chemotherapyCANCER, Issue 2 2004Gregoris Iconomou Ph.D. Abstract BACKGROUND The current study sought to delineate prospectively the rates and clinical course of emotional distress, cognitive impairment, and quality of life (QOL) in chemotherapy-naive patients with cancer and to consider the determinants of global QOL. METHODS Patients who consented to participate were administered the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale before and at the end of treatment (EOT). RESULTS Of the 102 patients initially assessed, 80 (78.4%) completed the study. Most aspects of QOL did not change considerably over time. At EOT, patients reported only significant increases in fatigue and significant decreases in sleep disturbance. Although no significant changes emerged in the rates of anxiety or depression throughout chemotherapy, nearly one-third of the patients experienced severe emotional distress at both points in time. In addition, the authors observed neither significant alteration in the cognitive performance over time nor reliable associations between scores on the MMSE and subjective cognitive function, emotional distress, or QOL. Finally, depression proved to be the leading predictor of global QOL at baseline and at EOT. CONCLUSIONS The results indicated that a significant proportion of Greek patients with cancer experienced intense anxiety and depression throughout chemotherapy and confirmed the importance of depression as a strong predictor of global QOL. Routine screening of emotional distress across all phases of cancer is mandatory because it will contribute to the identification of patients who are in need of pharmaceutical and/or psychologic intervention. Cancer 2004. © 2004 American Cancer Society. [source] Screening the Structural and Functional Properties of Bicyclo-DNA: bcox -DNACHEMBIOCHEM, Issue 14 2008Samuel Luisier Abstract The synthesis of two novel pyrimidine bicyclonucleosides (bcox -nucleosides) has been accomplished. These bicyclonucleosides each carry a lipophilic benzyloxime substituent on the carbocyclic ring and show improved conformational similarity to 2,-deoxyribonucleosides as shown by their X-ray structures. The thymine-containing bcox -nucleoside was converted into the corresponding phosphoramidite building block and incorporated into oligodeoxyribonucleotides by standard phosphoramidite chemistry. Tm data with complementary RNA and DNA were measured and compared to corresponding cases of natural and unfunctionalized bc-DNA. It was found that single incorporations of bcox residues destabilize duplexes by roughly 5,°C per modification. The destabilization was found to be due to the oxime substituent and not to the bicyclic scaffold itself. No significant alteration of the base-pairing selectivity as a function of the modification was observed. With RNA (but not with DNA) as a complement the relative thermal destabilization of bcox -oligothymidylates was gradually reduced and converted into a stabilizing interaction with increasing numbers of consecutive modifications. While no cellular uptake of bcox -oligonucleotides into HeLa cells occurred without transfecting agents, a significant increase in the transfection rate relative to unmodified DNA was observed in complexation with lipofectamine. [source] | |||||||||||||||||||||||||||||||||||||||||||