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Potential Role (potential + role)
Selected AbstractsPotential Role of Type 5 Phosphodiesterase Inhibition in the Treatment of Congestive Heart FailureCONGESTIVE HEART FAILURE, Issue 1 2003Stuart D. Katz MD Endothelial dysfunction is associated with impairment of aerobic capacity in patients with heart failure and may play a role in the progression of disease. Impaired endothelium-dependent vasodilation in patients with heart failure can be attributed to decreased bioavailability of nitric oxide and attenuated responses to nitric oxide in vascular smooth muscle. Impaired vasodilation in response to nitric oxide derived from vascular endothelium or organic nitrates in vascular smooth muscle may be related in part to increased degradation of the second messenger cyclic guanosine monophosphate by type 5 phosphodiesterase. Sildenafil, a specific type 5 phosphodiesterase inhibitor currently approved for the treatment of erectile dysfunction, has been shown to acutely enhance endothelium-dependent vasodilation in patients with heart failure. Further studies are warranted to characterize the safety and efficacy of type 5 phosphodiesterase inhibition in the treatment of chronic heart failure. [source] Bog Iron Ores and their Potential Role in Arsenic Dynamics: An Overview and a "Paleo Example"ENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 6 2008A. Banning Abstract Bog iron ores (BIOs), i.e. terrestrial accumulations of iron (Fe) minerals forming within the zone of groundwater oscillation, have been described in several regions in Germany and other countries. Since BIOs are composed of a variety of Fe minerals, primarily amorphous Fe hydroxides, they are likely to have an influence on the arsenic (As) dynamics of an area, as these minerals represent important natural As sources and sinks. In this study, mineralogical research results (XRD, microscopy) of altered BIOs of Tertiary age ("paleo" BIOs or PBIOs), occurring within Cretaceous sands in an area of North Rhine-Westphalia, are briefly presented. Genesis and mineralogical evolution of the categorized five different types of PBIOs, along with hydrogeochemical data from the literature, are discussed and compared to studies describing Holocene BIOs from other areas. In doing so, striking similarities (depositional environment, substratum, Fe source and its transport, geochemical evolution, and mineralogy) became evident. Differences in mineralogical and chemical composition can be attributed to the longer period of oxidation that the PBIOs have undergone (Fe hydroxide "aging"). This process is still ongoing (most of the groundwaters in the area plot in the goethite stability field) and leads to a higher stability of the Fe phases and thus, a stronger As retention. The known impact of the PBIOs on the As budget of the study area (they represent the source for elevated As concentrations in soils) can be transferred to more recent environments fostering BIO formation. These are likely to be even more important As sinks , and sources , as they contain higher Fe concentrations, higher shares of potentially mobile As and highly variable redox conditions which might lead to an As output from the BIOs into groundwater, soils and plants. Therefore, BIOs and their potential role in As behaviour are not only of scientific, but also of public interest. [source] The Midline Thalamus: Alterations and a Potential Role in Limbic EpilepsyEPILEPSIA, Issue 8 2001Edward H. Bertram Summary: ,Purpose: In limbic or mesial temporal lobe epilepsy, much attention has been given to specific regions or cell populations (e.g., the hippocampus or dentate granule cells). Epileptic seizures may involve broader changes in neural circuits, and evidence suggests that subcortical regions may play a role. In this study we examined the midline thalamic regions for involvement in limbic seizures, changes in anatomy and physiology, and the potential role for this region in limbic seizures and epilepsy Methods: Using two rat models for limbic epilepsy (hippocampal kindled and chronic spontaneous limbic epilepsy) we examined the midline thalamus for evidence of involvement in seizure activity, alterations in structure, changes in the basic in vitro physiology of the thalamic neurons. We also explored how this region may influence limbic seizures. Results: The midline thalamus was consistently involved with seizure activity from the onset, and there was significant neuronal loss in the medial dorsal and reuniens/rhomboid nuclei. In addition, thalamic neurons had changes in synaptically mediated and voltage-gated responses. Infusion of lidocaine into the midline thalamus significantly shortened afterdischarge duration. Conclusions: These observations suggest that this thalamic region is part of the neural circuitry of limbic epilepsy and may play a significant role in seizure modulation. Local neuronal changes can enhance the excitability of the thalamolimbic circuits. [source] Potential Role of Pancreatic and Enteric Hormones in Regulating Bone Turnover,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Jackie A Clowes MB First page of article [source] Focal Adhesion Kinase pp125FAK Interacts With the Large Conductance Calcium-Activated hSlo Potassium Channel in Human Osteoblasts: Potential Role in Mechanotransduction,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2003Roger Rezzonico Abstract Molecular events of mechanotransduction in osteoblasts are poorly defined. We show that the mechanosensitive BK channels open and recruit the focal adhesion kinase FAK in osteoblasts on hypotonic shock. This could convert mechanical signals in biochemical events, leading to osteoblast activation. Introduction: Mechanical strains applied to the skeleton influence bone remodeling and architecture mainly through the osteoblast lineage. The molecular mechanisms involved in osteoblastic mechanotransduction include opening of mechanosensitive cation channels and the activation of protein tyrosine kinases, notably FAK, but their interplay remains poorly characterized. The large conductance K+ channel (BK) seems likely as a bone mechanoreceptor candidate because of its high expression in osteoblasts and its ability to open in response to membrane stretch or hypotonic shock. Propagation of the signals issued from the mechanosensitivity of BK channels inside the cell likely implies complex interactions with molecular partners involved in mechanotransduction, notably FAK. Methods: Interaction of FAK with the C terminus of the hSlo ,-subunit of BK was investigated using the yeast two-hybrid system as well as immunofluorescence microscopy and coimmunoprecipitation experiments with a rabbit anti-hslo antibody on MG63 and CAL72 human osteosarcoma cell lines and on normal human osteoblasts. Mapping of the FAK region interacting with hSlo was approached by testing the ability of hSlo to recruit mutated ot truncated FAK proteins. Results: To the best of our knowledge, we provide the first evidence of the physical association of FAK with the intracellular part of hslo. We show that FAK/hSlo interaction likely takes place through the Pro-1-rich domain situated in the C-terminal region of the kinase. FAK/hSlo association occurs constitutively at a low, but appreciable, level in human osteosarcoma cells and normal human osteoblasts that express endogenous FAK and hSlo. In addition, we found that application of an hypo-osmotic shock to these cells induced a sustained activation of BK channels associated to a marked increase in the recruitment of FAK on hSlo. Conclusions: Based on these data, we propose that BK channels might play a triggering role in the signaling cascade induced by mechanical strains in osteoblasts. [source] Osteoblastic Tartrate-Resistant Acid Phosphatase: Its Potential Role in the Molecular Mechanism of Osteogenic Action of Fluoride,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2003K-H William Lau Abstract Although type 5 TRACP is recognized as a histochemical and biochemical marker of osteoclasts, there is evidence that bone forming cells, osteoblasts, and osteocytes also express a type 5 TRACP. Accordingly, an osteoblastic type 5 TRACP has been purified from human osteoblasts and from bovine cortical bone matrices. Comparison of biochemical properties of osteoblastic type 5 TRACP with those of osteoclastic type 5 TRACP suggests that osteoblastic type 5 TRACP is a different isoenzyme from osteoclastic type 5 TRACP. Two properties of osteoblastic type 5 TRACP may be relevant to its physiological functions: (1) it acts as a protein-tyrosine phosphatase (protein tyrosine phosphorylation) under physiologically relevant conditions, and (2) it is sensitive to inhibition by clinically relevant concentrations of fluoride. Because fluoride is a stimulator of osteoblastic proliferation and differentiation and a potent osteogenic agent and because protein tyrosine phosphorylation plays an important regulatory role in cell proliferation and differentiation, these unique properties and other evidence summarized in this review led to the proposal that the osteogenic action of fluoride is mediated, at least in part, by the fluoride-mediated inhibition of osteoblastic type 5 TRACP/protein tyrosine phosphorylation, which leads to a stimulation of osteoblast proliferation and differentiation, and subsequently, an increase in bone formation. [source] Potential Role of Enhanced Cytokinemia and Plasma Inhibitor on the Decreased Activity of Plasma ADAMTS13 in Patients With Alcoholic Hepatitis: Relationship to EndotoxemiaALCOHOLISM, Issue 2010Masatoshi Ishikawa Background:, Deficiency of ADAMTS13 (adisintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) results in an increase in unusually large von Willebrand factor multimer (UL-VWFM) of the plasma and finally causes microcirculatory disturbance. Our previous study demonstrated that the imbalance of increased UL-VWFM over decreased ADAMTS13 activity may contribute to the development of multiorgan failure in patients with alcoholic hepatitis (AH). The aim of this study was to explore the potential mechanism to reduce the activity of plasma ADAMTS13. Methods:, Plasma cytokine levels including interleukin (IL)-6, IL-8, and tumor necrosis factor-, (TNF-,), plasma endotoxin concentration, and the plasma inhibitor against ADAMTS13 were determined together with ADAMTS13 activity, VWF antigen (VWF:Ag), and UL-VWFM in 24 patients with AH and 5 patients with severe alcoholic hepatitis (SAH). Results:, The concentrations of IL-6, IL-8, and TNF-, on admission were significantly higher in patients with SAH than in those with AH and controls. The ADAMTS13 activity concomitantly decreased, and the VWF:Ag progressively elevated with increasing concentrations of these cytokines from normal range to over 100 pg/ml. Plasma endotoxin concentration was markedly higher in patients with SAH (mean 52.3 pg/ml) and AH (21.7 pg/ml) than in controls (7.9 pg/ml). The endotoxin concentration inversely correlated with ADAMTS13 activity and was higher in patients with UL-VWFM than those without. The inhibitor was detected in 4 patients with SAH (0.9 to 2.1 BU/ml) and 6 patients with AH (0.5 to 1.6 BU/ml). Patients with the inhibitor showed lower functional liver capacity, higher endotoxin concentration, and marked inflammatory signs than those without. At the recovery stage, the ADAMTS13 activity increased to normal range, the VWF:Ag decreased, and the UL-VWFM disappeared with the decrease in the concentrations of cytokines and endotoxin, and the disappearance of the inhibitor. Conclusion:, Decreased ADAMTS13 activity and increased VWF:Ag could be induced not only by pro-inflammatory cytokinemia, but also by its inhibitor, both of which may be closely related to enhanced endotoxemia in patients with AH and SAH. [source] Probiotics: A Critical Review of Their Potential Role as Antihypertensives, Immune Modulators, Hypocholesterolemics, and Perimenopausal TreatmentsNUTRITION REVIEWS, Issue 7 2007Min-Tze Liong PhD The conventional use of probiotics to modulate gastrointestinal health, such as in improving lactose intolerance, increasing natural resistance to infectious diseases in the gastrointestinal tract, suppressing traveler's diarrhea, and reducing bloating, has been well investigated and documented. Most of the mechanisms reported to date are mainly caused by the suppression of pathogenic bacteria. Currently, the potential applications of probiotics are being expanded beyond alleviating gastrointestinal disorders to include benefits involving antihypertension, immu-nomodulation, improving serum lipid profiles, and the alleviation of postmenopausal disorders. Although they seem promising, most of these postulated benefits are based on in vitro evaluations, and the lack of in vivo evidence and/or incompatible outcomes between in vitro experiments and in vivo trials has led to inconclusive claims. This present review highlights some of the previous roles of probiotics on gut health and addresses several potential roles currently being investigated. [source] A Potential Role for Vitamin D on HIV Infection?NUTRITION REVIEWS, Issue 5 2006Eduardo Villamor MD Despite advances in the knowledge of vitamin D's potent immunomodulatory activity, its role on HIV disease progression is unknown. Decreased concentrations of 1,,25-hydroxyvitamin D3, or 1,25(OH)2D, the active form of vitamin D, have been reported among HIV-infected people and attributed to defects in renal hydroxylation and increased utilization. A few studies also described low levels of 25-hydroxyvitamin D3, 25(OH)D, the vitamin obtained from solar synthesis and diet. An inverse association between 1,25(OH)2D concentrations and mortality has been reported from a small cohort of HIV-infected adults, and some cross-sectional studies have indicated positive correlations between 1,25(OH)2D and CD4+ cell counts. Additional observational studies are needed to confirm the associations between vitamin D status and HIV disease progression. These investigations would provide useful insights on the potential role of vitamin D supplementation to HIV-infected persons and the planning of intervention trials. [source] Potential Role of NKG2D and Its Ligands in Organ Transplantation: New Target for ImmunointerventionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009B. Suárez-Álvarez NKG2D is one of the best characterized activating receptors on Natural Killer (NK) and CD8+ T cells. This receptor recognizes several different ligands (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to the role described in cancer surveillance, recent data highlight the importance of NKG2D and its ligands in organ transplantation. Allografts show evidence of MICA and MICB expression in both acute and chronic rejection. The presence of anti-MICA antibodies has been correlated with incidence of graft rejection. Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated NK cells may function as a bridge between innate and adaptive immunity associated with transplantation. Activated NK cells in response to IL-15 can also trigger organ rejection through NKG2D and affect the maturation of both donor and recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic response. Regulatory T cells, which modulate T-cell responses in organ transplantation and infections, were reduced in numbers by NK cells exposed to intracellular pathogens, possibly via interaction with one NK2GD receptor. Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development of inhibitors. These studies have important clinical and therapeutic implications in solid organ transplantation. [source] 5-Aminoimidazole-4-carboxamide-1-,- d -ribofuranoside Increases Myocardial Glucose Uptake during Reperfusion and Induces Late Pre-conditioning: Potential Role of AMP-Activated Protein KinaseBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2009Steen B. Kristiansen AMP-activated protein kinase (AMPK) is activated by exercise and 5-aminoimidazole-4-carboxamide-1-,- d -ribofuranoside (AICAR). Early pre-conditioning involves AMPK activation and increased myocardial glucose uptake. The aim of the present study was to determine whether AICAR activates myocardial AMPK and induces late pre-conditioning and whether myocardial glucose uptake during reperfusion was modulated. Twenty-four hours after AICAR treatment or exercise, Wistar rats were subjected to ischaemia and reperfusion in a Langendorff model and compared to control rats. AMPK activity increased immediately 2.5-fold in AICAR-treated animals (P < 0.01) and twofold in exercised animals (P < 0.05). AICAR and exercise reduced infarct size by 60% and 50% (both P < 0.01), respectively, and increased myocardial glucose uptake during reperfusion (AICAR; 45%, P < 0.05, exercise; 40%, P < 0.05). In conclusion, AICAR induces late pre-conditioning and increases myocardial glucose uptake during reperfusion in rat hearts. AICAR and exercise activate AMPK, suggesting a role of AMPK in the signalling mechanisms behind late pre-conditioning. [source] Kaempferol Glycosides from Lobularia maritima and Their Potential Role in Plant InteractionsCHEMISTRY & BIODIVERSITY, Issue 2 2009Antonio Fiorentino Abstract Six kaempferol glycosides, four of them characterized for the first time, were isolated from the leaf extract of Lobularia maritima. The structural elucidation was performed by a combined approach using Electrospray-Ionization Triple-Quadrupole Mass-Spectrometric (ESI/TQ/MS) techniques, and 1D- and 2D-NMR experiments (1H, 13C, DEPT, DQ-COSY, TOCSY, ROESY, NOESY, HSQC, HMBC, and HSQC-TOCSY). The isolated kaempferol derivatives have different disaccharide substituents at C(3) and four of them have a rhamnose unit at C(7). To evaluate their potential allelopathic role within the herbaceous plant community, the compounds, as well as the aglycone obtained from enzymatic hydrolysis, have been tested in vitro on three coexisting plant species, Dactylis hispanica, Petrorhagia velutina, and Phleum subulatum. The results obtained allow us to hypothesize that the type of the sugar modulates the biological response. The bioassay data, analyzed by a multivariate approach, and grouping the compounds on the basis of the number of sugar units and the nature of carbohydrates present in the disaccharide moiety, indicate a structure,activity relationship. [source] Alcohol-Induced Disruption of Endocrine SignalingALCOHOLISM, Issue 8 2007Martin J. J. Ronis This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of Long-Term Ethanol Consumption on Liver Injury and Repair, by Jack R. Wands; (2) Alcohol-Induced Insulin Resistance in Liver: Potential Roles in Regulation of ADH Expression, Ethanol Clearance, and Alcoholic Liver Disease, by Thomas M. Badger; (3) Chronic Gestational Exposure to Ethanol Causes Brain Insulin and Insulin-Like Growth Factor Resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 Signaling in Muscle: A Mechanism Underlying Alcoholic Myopathy, by Charles H. Lang; (5) The Role of Reduced Plasma Estradiol and Impaired Estrogen Signaling in Alcohol-Induced Bone Loss, by Martin J. Ronis; and (6) Short-Term Influence of Alcohol on Appetite-Regulating Hormones in Man, by Jan Calissendorff. [source] Potential role of colour-Doppler cystosonography with echocontrast in the screening and follow-up of vesicoureteral refluxACTA PAEDIATRICA, Issue 11 2000G Ascenti Primary vesicoureteral reflux is a predisposing factor for urinary tract infections in children. The first-choice technique for the diagnosis of vesicoureteral reflux is voiding cystourethrography, followed by cystoscintigraphy; cystoscintigraphy, however, has the advantage of only minor irradiation of the patient, but it does not allow the morphological evaluation of bladder and vesicoureteral reflux grading. Colour-Doppler cystosonography with echocontrast is a recently introduced method for imaging vesicoureteral reflux. The aim of our study is to evaluate the role of colour-Doppler cystosonography with echocontrast in the diagnosis of vesicoureteral reflux. Twenty children (11M, 9F) aged between 0.4 and 4.9 y underwent colour-Doppler cystosonography using a diluted solution of Levovist® (Schering, Germany), after filling up the bladder with saline. In all patients, vesicoureteral reflux diagnosis and grading had been performed previously by voiding cystourethrography within 5 d from ultrasonography. Our data showed high accuracy in the detection of medium to severe vesicoureteral reflux (grades III-V), confirmed by radiological features in 9/9 patients. Conversely, in the 11 patients with mild vesicoureteral reflux (grades I-II), this technique showed extremely low sensitivity, allowing diagnosis in only four cases. Conclusions: Colour-Doppler cystosonography, because of the absence of ionizing radiations, has great advantages, particularly in patients needing prolonged monitoring. Despite experiences reported in the literature, this technique has a role in the diagnosis of vesicoureteral reflux. Our group chooses colour-Doppler cystosonography for the follow-up of medium-severe grade vesicoureteral reflux already diagnosed by radiology and/or scintigraphy. Cystoscintigraphy is employed only to confirm cases resulting negative at ultrasonography. [source] Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2006I. E. Koutroubakis Abstract Background, Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Materials and methods, Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. Results, Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0·05 and P < 0·001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0·04) median serum Ang-2 levels but significantly lower (P = 0·02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0·02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. Conclusions, Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD. [source] Potential role of thioredoxin in immune responses in intestinal lamina propria T,lymphocytesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2005Bernd Sido Abstract Thioredoxin (TRX) is a ubiquitous oxidoreductase with strong co-cytokine, chemoattractant and anti-apoptotic activities. TRX expression was found to be particularly elevated in the intestinal mucosa, where its physiologic function is entirely unknown. Here, we demonstrate a high level of TRX expression in lamina propria T,cells (LP-T) as opposed to autologous peripheral blood T,lymphocytes (PB-T). Addition of recombinant human TRX (rhTRX) to PB-T enhances TRX gene expression. This autoregulation involves the calcineurin signaling pathway, as rhTRX antagonizes the cyclosporine,A (CsA)- and tacrolimus-mediated suppression of TRX gene expression. Similarly, rhTRX reverses the suppression of IL-2 mRNA production by CsA and enhances cytokine production preferentially in prestimulated cells. The differential TRX expression in LP-T versus PB-T may thus contribute to the high-level, CsA-resistant IL-2 production characteristic for CD2-stimulated LP-T. Inversely, inactivation of TRX in LP-T through inhibition of TRX reductase abolishes cytokine gene expression. TRX may play a key role in the specialized intestinal microenvironment in amplifying immediate immune responses of LP-T whenever appropriate costimulation of LP-T is provided. [source] Potential role of radial glia in adult neurogenesis of teleost fishGLIA, Issue 1 2003Günther K.H. Zupanc Abstract Persistence of radial glia within the adult central nervous system is a widespread phenomenon among fish. Based on a series of studies in the teleost species Apteronotus leptorhynchus, we propose that one function of this persistence is the involvement of radial glia in adult neurogenesis, i.e., the generation and further development of new neurons in the adult central nervous system. In particular, evidence has been obtained for the involvement of radial glia in the guidance of migrating young neurons in both the intact and the regenerating brain; for a possible role as precursor cells from which new neurons arise; and for its role as a source of trophic substances promoting the generation, differentiation, and/or survival of new neurons. These functions contribute not only to the potential of the intact brain to generate new neurons continuously, and of the injured brain to replace damaged cells by newly generated ones, but they also provide an essential part of the cellular substrate of behavioral plasticity. GLIA 43:77,86, 2003. © 2003 Wiley-Liss, Inc. [source] Potential role for Interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection,HEPATOLOGY, Issue 4 2010Jason Grebely Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ,26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). Conclusion: During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;) [source] Potential role of CB2 receptors in Cannabis smokers with chronic hepatitis C,HEPATOLOGY, Issue 4 2005Robert F. Schwabe M.D. No abstract is available for this article. [source] Hippocampus modulates the behaviorally-sensitizing effects of nicotine in a rat model of novelty-seeking: Potential role for mossy fibersHIPPOCAMPUS, Issue 10 2007Amrinder S. Bhatti Abstract Present experiments investigate interactions between a rat model of the novelty-seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally-sensitizing effects of NIC. Outbred rats were phenotype-screened as high-responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low-responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3-d intervals on postnatal days 33,44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra-pyramidal mossy fiber (SP-MF) terminal field. The increase in the SP-MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC-induced locomotion and the SP-MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC. © 2007 Wiley-Liss, Inc. [source] Potential role of CXCL10 in the induction of cell injury and mitochondrial dysfunctionINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2010Lipi Singh Summary Chemokines have been known to play a critical role in pathogenesis of chronic pancreatitis and acinar cell death. However, the role played by one of the CXC chemokines: CXCL10 in regulation of acinar cell death has remained unexplored. Hence, this study was designed to assess the role of CXCL10 promoting apoptosis in ex vivo cultured acinar cells. Primary human pancreatic acinar cell cultures were established and exposed to varying doses of CXCL10 for different time intervals. Apoptotic induction was evaluated by both qualitative as well as quantitative analyses. Various mediators of apoptosis were also studied by Western blotting, membrane potential (,m) and ATP depletion in acinar cells. Analysis of apoptosis via DNA ladder and cell death detection , ELISA demonstrated that CXCL10 induced 3.9-fold apoptosis when administrated at an optimal dose of 0.1 ,g of recombinant CXCL10 for 8 h. Quantitative analysis using FACS and dual staining by PI-annexin showed increased apoptosis (48.98 and 53.78% respectively). The involvement of upstream apoptotic regulators like pJNK, p38 and Bax was established on the basis of their increased expression of CXCL10. The change of ,m by 50% was observed in the presence of CXCL10 in treated acinar cells along with enhanced expression of Cytochrome C, apaf-1 and caspase 9/3 activation. In addition, ATP depletion was also noticed in CXCL10 stimulated acinar cells. CXCL10 induces cell death in human cultured pancreatic cells leading to apoptosis and DNA fragmentation via CXCR3 signalling. These signalling mechanisms may play an important role in parenchymal cell loss and injury in pancreatitis. [source] Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine HeartJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2009KAPIL KUMAR M.D. Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI-36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals. Methods and Results: In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (,9 ,M plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29,50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24,34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71,109) ms to 98 (86,121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811,1220) seconds to 621 (549,761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7,20.5) Hz to 7.6 (2.9,8.8) Hz (P = 0.02, n = 6). Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency-dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation. [source] Potential role of phosphate buffering capacity of soils in fertilizer management strategies fitted to environmental goals,JOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 4 2003Phillip Ehlert Abstract Sorption behavior and buffering of phosphorus (P) are important, both from an agricultural and an environmental point of view. The objectives of this study were to investigate: (1) the kinetics of the transfer of P from soil to soil solution and assessing P buffering capacity of soils (PBC), as a function of soil solution P; (2) the effect of PBC on soil P status fitted to environmental targets for water quality; (3) the effect of PBC on crop response. PBC was derived from the non-linear Q-I curve describing the time-dependent relationship between plant-available reserve of soil P (Q) versus soil solution P (I). The Q-I curve was determined in soil suspension using sorption and isotopic dilution methods for soil samples from French, Swedish, and Dutch field trials. Soils with low PBC values were more sensitive to the loss of P to the environment, required higher critical value in soil solution P to comply with P demand of maize, and had higher change in soil solution P per unit of P budget. In different soils, both the critical soil solution P for maize and the change in soil solution P per unit of P balance varied inversely with PBC. It is concluded that (1) PBC plays a key role in determining the agronomic and environmental threshold levels of available P content in the soils, and (2) PBC is a prerequisite for the development of more environmentally oriented fertilization recommendation systems. Potenzielle Bedeutung der Phosphat-Pufferkapazität des Bodens für umweltgerechte Düngungsstategien Bindungsverhalten und Pufferkapazität des Phosphors (P) im Boden ist wichtig, sowohl aus Sicht der Landwirtschaft als auch des Umweltschutzes. In dieser Untersuchung sollten folgende Probleme untersucht werden: (1) Kinetik des P-Transfers von der Festphase in die Bodenlösung und Abschätzung der P-Pufferkapazität (PBC) als Funktion der P-Konzentration in der Bodenlösung; (2) die Wirkung der PBC auf den Boden-P-Status im Hinblick auf Qualitätsziele für Wasser; (3) Wirkung der PBC auf die P-Aufnahme der Pflanze. Die PBC wurde abgeleitet aus der nichtlinearen Q-I-Kurve, die die zeitabhängige Beziehung zwischen dem Gehalt an pflanzenverfügbarem Boden-P (Q) und der P-Konzentration in der Bodenlösung (I) beschreibt. Die Q-I-Kurve wurde in Bodensupensionen mit Sorptions- und Isotopen-Verdünnungsmethoden an Bodenproben aus Feldversuchen in Frankreich, Schweden und den Niederlanden bestimmt. Böden mit niedriger PBC waren sensitiver für P-Austräge in die Umwelt, erforderten höhere Grenzkonzentrationen in der Bodenlösung zur Bedarfsdeckung bei Mais und zeigten größere Konzentrationsveränderungen in der Bodenlösung je Einheit der P-Bilanz. Die Grenzkonzentrationen in der Bodenlösung zur Bedarfsdeckung bei Mais und Konzentrationsveränderungen in der Bodenlösung je Einheit der P-Bilanz variierten in unterschiedlichen Böden invers mit Variation der PBC. Aus den Untersuchungen folgte, dass (1) die PBC ein Schlüssel-Parameter zur Bestimmung agronomischer und umweltrelevanter Grenzwerte der Gehalte an verfügbarem P im Boden ist und (2) somit eine Voraussetzung für die Entwicklung mehr umweltorientierter Systeme der Düngungsempfehlungen. [source] Alcohol Metabolism: Role in Toxicity and CarcinogenesisALCOHOLISM, Issue 2 2003Thomas M. Badger This article contains the proceedings of a symposium at the 2002 RSA Meeting in San Francisco, organized and co-chaired by Thomas M. Badger, Paul Shih-Jiun Yin, and Helmut Seitz. The presentations were (1) First-pass metabolism of ethanol: Basic and clinical aspects, by Charles Lieber; (2) Intracellular CYP2E1 transport, oxidative stress, cytokine release, and ALD, by Magnus Ingelman-Sundberg; (3) Pulsatile ethanol metabolism in intragastric infusion models: Potential role in toxic outcomes, by Thomas M. Badger and Martin J.J. Ronis; (4) Free radicals, adducts, and autoantibodies resulting from ethanol metabolism: Role in ethanol-associated toxicity, by Emanuele Albano; and (5) Gastrointestinal metabolism of ethanol and its possible role in carcinogenesis, by Helmut Seitz. [source] Potential role of the cannabinoid receptor CB1 in the pathogenesis of erosive and non-erosive gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010C. Calabrese Aliment Pharmacol Ther 2010; 32: 603,611 Summary Background, Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB1 receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. Aim, To evaluate the CB1 expression in oesophageal mucosa. Methods, A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin,eosin, MIB1/CB1 evaluation and three for the RNA and proteins extraction. Results, The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB1mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB1/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB1 expression, performed with WB, shows in NERD patients a higher CB1 receptor expression than ERD patients. Conclusions, With this study, we showed for the first time the presence of CB1 receptors in the human oesophageal epithelium. [source] Potential role of the cellular allergen stimulation test (CAST) in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue 4 2007Stephanie Ringer MD Abstract Allergic bronchopulmonary aspergillosis (ABPA) is a severe complication in cystic fibrosis (CF), which is difficult to identify because of overlapping unspecific diagnostic features with common CF-manifestations. The cellular allergen stimulation test (CAST) is used in diagnosis of allergic and pseudoallergic reactions. This assay is based on the determination of sulfidoleukotrienes, which are produced by allergen-stimulated basophils in vitro. The potential role of CAST in diagnosis of ABPA was evaluated in this study. The CAST assay was applied in 27 CF-patients including eight subjects with positive clinical and serological signs of ABPA. Additional to the Nelson-criteria for diagnosis of ABPA specific IgE against recombinant Aspergillus antigens (rAsp f 1, 2, 3, 4, and 6) were assessed. The CAST results were positive in all ABPA-patients and in five controls without any sign of ABPA except positive specific IgE against Aspergillus fumigatus (sensitivity of 100%, specificity of 74%). Specific IgE against rAsp f 4 and/or f 6 were positive in six of the eight ABPA-patients, but not in the controls. Positive CAST results, total serum IgE,>,500 U/ml and positive IgE antibodies against rAsp f 4 and/or f 6 were only found in ABPA-patients (specificity of 100%). The CAST assay on its own includes high sensitivity with lower specificity. For the discrimination of ABPA from sensitization to Aspergillus, the CAST, the highly elevated total serum IgE and rAsp in combination are potential auxiliary diagnostic parameters. Pediatr Pulmonol. 2007; 42:314,318. © 2007 Wiley-Liss, Inc. [source] Potential role of formaldehyde in the mechanism of action of ascorbigens on the basis of BioArena studiesBIOMEDICAL CHROMATOGRAPHY, Issue 4 2009György Kátay Abstract The effect of ascorbigen and 1,-methylascorbigen as a model compound pair was studied on the phytopathogenic bacterium Pseudomonas savastanoi pv. phaseolicola in the BioArena experimental system after overpressured layer chromatography. Results showed a characteristic, strong antibacterial effect of 1,-methylascorbigen and weak effect of ascorbigen present on the adsorbent layer as chromatographic spot. Addition of formaldehyde capture compounds (l -arginine, glutathione, dimedone) partially or totally reduced the antibacterial effect of 1,-methylascorbigen and ascorbigen. On adding Cu(II) ions,which mobilize and coordinate formaldehyde,to the culture medium, the antibacterial effect of both compounds became stronger. It is supposed that the weak antibacterial effect of ascorbigen may have originated from the 1,-methylascorbigen formed in situ on the adsorbent layer by partial enzymatic methylation of ascorbigen. Copyright © 2008 John Wiley & Sons, Ltd. [source] Potential role of human papillomavirus in the development of subsequent primary in situ and invasive cancers among cervical cancer survivors,,CANCER, Issue S10 2008Appathurai Balamurugan MD Abstract BACKGROUND. The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development of primary in situ and invasive cervical cancers and possibly other HPV-associated cancers such as vaginal, vulvar, and anal cancers. Because the HPV vaccine has the ability to impact the development of >1 HPV-associated cancer in the same individual, the risk of developing subsequent primary cancers among cervical cancer survivors was examined. METHODS. Using the 1992 through 2004 data from the Surveillance, Epidemiology, and End Results (SEER) program, 23,509 cervical cancer survivors were followed (mean of 4.8 person-years) for the development of subsequent primary cancers. The observed number (O) of subsequent cancers of all sites were compared with those expected (E) based on age-/race-/year-/site-specific rates in the SEER population. Standardized incidence ratios (SIRs = O/E) were considered statistically significant if they differed from 1, with an , level of 0.05. RESULTS. Among cervical cancer index cases, there was a significant elevated risk for subsequent in situ cancers of the vagina and vulva (SIRs of 53.8 and 6.6, respectively); and invasive vaginal, vulvar, and rectal cancers (SIRs of 29.9, 5.7, and 2.2, respectively). Significantly elevated risks were observed across race and ethnic populations for subsequent vaginal in situ (SIR for whites of 49.4; blacks, 52.8; Asian/Pacific Islander [API], 91.4; and Hispanics, 55.7) and invasive cancers (SIR for whites of 25.7; blacks, 34.5; API, 48.5; and Hispanics, 25.2). CONCLUSIONS. The results of the current study demonstrate a substantially increased risk of the development of subsequent primary in situ and invasive cancers among cervical cancer survivors and have implications for the development of prevention and early detection strategies as the role of HPV infection becomes evident. Cancer 2008;113(10 suppl):2919,25. Published 2008 by the American Cancer Society. [source] Thrombolysis in ST-segment elevation myocardial infarction: Potential role of thin-slice computed tomography in the assessment of reperfusion and plaque characterizationCLINICAL CARDIOLOGY, Issue 7 2006E. Martuscelli M.D. No abstract is available for this article. [source] AMP-activated protein kinase control of fat metabolism in skeletal muscleACTA PHYSIOLOGICA, Issue 1 2009D. M. Thomson Abstract AMP-activated protein kinase (AMPK) has emerged as a key regulator of skeletal muscle fat metabolism. Because abnormalities in skeletal muscle metabolism contribute to a variety of clinical diseases and disorders, understanding AMPK's role in the muscle is important. It was originally shown to stimulate fatty acid (FA) oxidation decades ago, and since then much research has been accomplished describing this role. In this brief review, we summarize much of these data, particularly in relation to changes in FA oxidation that occur during skeletal muscle exercise. Potential roles for AMPK exist in regulating FA transport into the mitochondria via interactions with acetyl-CoA carboxylase, malonyl-CoA decarboxylase, and perhaps FA transporter/CD36 (FAT/CD36). Likewise, AMPK may regulate transport of FAs into the cell through FAT/CD36. AMPK may also regulate capacity for FA oxidation by phosphorylation of transcription factors such as CREB or coactivators such as PGC-1,. [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||