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Terms modified by Recent Data Selected AbstractsOvercoming surfactant inhibition with polymersACTA PAEDIATRICA, Issue 12 2000PA Dargaville Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextrano and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration. [source] Treatment-resistant bipolar depression: towards a new definitionACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009I. Pacchiarotti Objective:, To summarize the conceptual and operational definitions of treatment-resistant bipolar depression and to review the evidence-based therapeutic options. Method:, Structured searches of PubMed, Index Medicus, Excerpta Medica and Psyclit conducted in December 2008. Results:, Criteria for treatment resistance in bipolar depression are commonly based on concepts stemming from treatment resistance as defined for unipolar depression, an approach that proved to be inadequate. In fact, the addition of an ad hoc criterion based on lithium and other mood stabilizer unresponsiveness after reaching adequate plasma levels appears to be a patch that attempts to take into account the uniqueness of bipolar depression but fails to become operational. Recent data from randomized clinical trials of new anticonvulsants and second-generation antipsychotics should lead to the development of a modern definition of treatment-resistant bipolar depression, and specific therapeutic algorithms. Conclusion:, We suggest a redefinition of resistant bipolar I and II depression. We propose different degrees of severity within bipolar depression in a stepwise manner. [source] Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic plasticityDEVELOPMENTAL NEUROBIOLOGY, Issue 10 2008J.E. Lochner Abstract Recent data suggest that tissue plasminogen activator (tPA) influences long-term plasticity at hippocampal synapses by converting plasminogen into plasmin, which then generates mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF. Motivated by this hypothesis, we used fluorescent chimeras, expressed in hippocampal neurons, to elucidate (1) mechanisms underlying plasminogen secretion from hippocampal neurons, (2) if tPA, plasminogen, and proBDNF are copackaged and cotransported in hippocampal neurons, especially within dendritic spines, and (3) mechanisms mediating the transport of these neuromodulators to sites of release. We find that plasminogen chimeras traffic through the regulated secretory pathway of hippocampal neurons in dense-core granules (DCGs) and that tPA, plasminogen, and proBDNF chimeras are extensively copackaged in DCGs throughout hippocampal neurons. We also find that 80% of spines that contain DCGs contain chimeras of these neuromodulators in the same DCG. Finally, we demonstrate, for the first time, that neuromodulators undergo cotransport along dendrites in rapidly mobile DCGs, indicating that neuromodulators can be efficiently recruited into active spines. These results support the hypothesis that tPA mediates synaptic activation of BDNF by demonstrating that tPA, plasminogen, and proBDNF colocalize in DCGs in spines, where these neuromodulators can undergo activity-dependent release and then interact and/or mediate changes that influence synaptic efficacy. The results also raise the possibility that frequency-dependent changes in extents of neuromodulator release from DCGs influence the direction of plasticity at hippocampal synapses by altering the relative proportions of two proteins, mBDNF and proBDNF, that exert opposing effects on synaptic efficacy. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Plasma IL-6 concentration is inversely related to insulin sensitivity, and acute-phase proteins associate with glucose and lipid metabolism in healthy subjectsDIABETES OBESITY & METABOLISM, Issue 6 2005M. K. Heliövaara Aim:, It has been shown that atherosclerosis is an inflammatory disease. Recent data suggest that inflammation precedes type 2 diabetes. Hence, we wanted to study the interrelationship between IL-6, insulin sensitivity, lipids and numerous acute-phase proteins. Methods:, Twenty-one healthy individuals [16 males/5 females, age 27.9 ± 1.8 years, body mass index (BMI) 24.1 ± 0.8 kg/m2] participated in the study. Each patient went through a 4-h hyperinsulinaemic (40 mU/m2/min) euglycaemic clamp and 4-h saline infusion. Blood samples were taken before and at the end of the infusions. Results:, Plasma interleukin (IL)-6 concentration correlated inversely with insulin sensitivity (M -value) (r = ,0.49, p < 0.05). Moreover, the plasma levels of IL-6 associated with c-peptide (r = 0.49, p < 0.05), fat% (r = 0.43, p < 0.05) and diastolic blood pressure (r = 0.46, p < 0.05). ,-1-acid glycoprotein was related to HbA1c (r = 0.47, p < 0.05), insulin (r = 0.55, p < 0.01), diastolic blood pressure (r = 0.58, p < 0.01), systolic blood pressure (r = 0.58, p < 0.01) and triglycerides (r = 0.58, p < 0.01). Haptoglobin was correlated with insulin (r = 0.46, p < 0.05), total cholesterol (r = 0.61, p < 0.01), BMI (r = 0.58, p < 0.01), fat% (r = 0.63, p < 0.01) and lipid oxidation during clamp (r = 0.43, p < 0.05). Diastolic blood pressure decreased during the clamp (from 78.3 ± 1.9 to 72.1 ± 2.0 mmHg, p = 0.001). Insulin infusion did not affect the serum levels of most acute-phase proteins. Conclusions:, Our study suggests that low grade inflammation, as reflected by IL-6, A1GP and haptoglobin contributes to the regulation of insulin sensitivity, lipid metabolism and blood pressure in normal human physiology. [source] Neuronal plasticity: implications in epilepsy progression and managementDRUG DEVELOPMENT RESEARCH, Issue 8 2007Sherifa A. HamedArticle first published online: 12 FEB 200 Abstract Epilepsy is a common neurological disease. A growing number of research studies provide evidence regarding the progressive neuronal damage induced by prolonged seizures or status epilepticus (SE), as well as recurrent brief seizures. Importantly, seizure is only one aspect of epilepsy. However, cognitive and behavioral deficits induced by progressive seizures or antiepileptic treatment can be detrimental to individual function. The neurobiology of epilepsy is poorly understood involving complex cellular and molecular mechanisms. The brain undergoes changes in its basic structure and function, e.g., neural plasticity with an increased susceptibility in neuronal synchronization and network circuit alterations. Some of these changes are transient, while others are permanent with an involvement of both glutamatergic and ,-aminobutyric acid (GABA)ergic systems. Recent data suggest that impaired neuronal plasticity may underlie the cognitive impairment and behavioral changes associated with epilepsy. Many neurologists recognize that the prevention or suppression of seizures by the use of antiepileptic drugs (AEDs) alone is insufficient without clear predictions of disease outcome. Hence, it is important to understand the molecular mechanisms underlying epileptogenesis because this may allow the development of innovative strategies to prevent or cure this condition. In addition, this realization would have significant impact in reducing the long-term adverse consequences of the disease, including neurocognitive and behavioral adverse effects. Drug Dev Res 68:498,511, 2007. © 2008 Wiley-Liss, Inc. [source] Letter: Antiepileptogenic and neuroprotective effects of erythropoietin: Recent dataEPILEPSIA, Issue 6 2009Mohamad A. Mikati No abstract is available for this article. [source] Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematologyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2009W. R. Sperr Abstract Background, Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable. Materials and methods, We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders (n = 156), myelodysplastic syndromes (MDS, n = 241), acute myeloid leukaemia (AML, n = 317), systemic mastocytosis (SM, n = 81), non-Hodgkin,s lymphoma (n = 59) and acute lymphoblastic leukaemia (n = 26). Moreover, tryptase was measured in 136 patients with non-neoplastic haematological disorders, 102 with non-haematological disorders and 164 healthy subjects. Results, In healthy subjects, the median serum tryptase was 5·2 ng mL,1. Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL,1) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL,1, were found in advanced SM and core-binding-factor leukaemias. In most patients with non-neoplastic haematological disorders and non-haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end-stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found. Conclusions, In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology. [source] Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2008L. Puccetti ABSTRACT Background, Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized-low-density lipoprotein cholesterol (ox-LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox-LDL lectin-like receptor-1 (LOX-1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment. Materials and methods, A prospective 4-year study involving 1039 event-free subjects (643 males, 396 females) treated with atorvastatin (10,40 mg day,1) to reach the appropriate Adult Treatment Panel-III LDL target of 3·36 mmol L,1. Enrolled subjects were evaluated every 6 months or at a clinical event. LOX-1 3,UTR/T-C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic-colorimetric method, ox-LDL by enzyme linked immunosorbent assay, platelet activation by P-selectin (P-sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C-reactive protein (CRP) by sensitive nephelometric technique. Results, LOX-1 3,UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4·90, 95% CI 3·19,6·98, P < 0·00001). Smoking influenced events in LDL-targeted subjects (P < 0·0001). Ox-LDL and P-sel were better indicators than LDL or other variables according to 3,UTR/C genotype regardless of the magnitude of LDL reduction (OR 4·21, 95% CI 2·29,6·70 P < 0·0001). Conclusions, LOX-1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity. [source] Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2005M. D. Säemann Abstract Urinary tract infection (UTI) is the most common nonepidemic bacterial infection in humans, representing a constant danger for the host. Both innate and adaptive components of the immune system as well as stromal cells including bladder epithelium are involved in the prevention and clearance of UTI. However, the particular properties of the urogenital tract, which does not comprise typical physical barriers like a mucus or ciliated epithelium, necessitate soluble mediators with potent immunomodulatory capabilities. One candidate molecule capable of both mediating direct antimicrobial activity and alerting immune cells is the evolutionary conserved Tamm-Horsfall protein (THP). Tamm-Horsfall protein is exclusively produced by the kidney in the distal loop of Henle; however, its definite physiological function remains elusive. Mounting evidence indicates that beyond a mere direct antimicrobial activity, THP exerts potent immunoregulatory activity. Furthermore, the genetic ablation of the THP gene leads to severe infection and lethal pyelonephritis in an experimental model of UTI. Recent data are provided demonstrating that THP links the innate immune response with specific THP-directed cell-mediated immunity. In light of these novel findings we discuss the particular role of THP as a specialized defence molecule. We propose an integrated model of protective mechanisms against UTI where THP acts by two principle nonmutually exclusive mechanisms involving the capture of potentially dangerous microbes and the ability of this peculiar glycoprotein to induce robust protective immune responses against uropathogenic bacteria. [source] Expression of angiogenic factors in chronic myeloid leukaemia: role of the bcr/abl oncogene, biochemical mechanisms, and potential clinical implicationsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2004C. Sillaber Abstract Chronic myeloid leukaemia (CML) is a stem cell disease characterized by an increased production and accumulation of clonal BCR/ABL,positive cells in haematopoietic tissues. The chronic phase of CML is inevitably followed by an accelerated phase of the disease, with consecutive blast crisis. However, depending on genetic stability, epigenetic events, and several other factors, the clinical course and survival appear to vary among patients. Recent data suggest that angiogenic cytokines such as vascular endothelial growth factor (VEGF), are up-regulated in CML, and play a role in the pathogenesis of the disease. These factors appear to be produced and released in leukaemic cells in patients with CML. In line with this notion, increased serum-levels of angiogenic growth factors are measurable in CML patients. In this study we provide an overview of angiogenic growth factors expressed in CML cells, discuss the possible pathogenetic role of these cytokines, the biochemical basis of their production in leukaemic cells, and their potential clinical implications. [source] Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and ,-cell dysfunctionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2002G. Boden Abstract Plasma free fatty acids (FFA) play important physiological roles in skeletal muscle, heart, liver and pancreas. However, chronically elevated plasma FFA appear to have pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral and hepatic insulin resistance and, while the precise action in the liver remains unclear, a model to explain the role of raised FFA in the development of skeletal muscle insulin resistance has recently been put forward. Over 30 years ago, Randle proposed that FFA compete with glucose as the major energy substrate in cardiac muscle, leading to decreased glucose oxidation when FFA are elevated. Recent data indicate that high plasma FFA also have a significant role in contributing to insulin resistance. Elevated FFA and intracellular lipid appear to inhibit insulin signalling, leading to a reduction in insulin-stimulated muscle glucose transport that may be mediated by a decrease in GLUT-4 translocation. The resulting suppression of muscle glucose transport leads to reduced muscle glycogen synthesis and glycolysis. In the liver, elevated FFA may contribute to hyperglycaemia by antagonizing the effects of insulin on endogenous glucose production. FFA also affect insulin secretion, although the nature of this relationship remains a subject for debate. Finally, evidence is discussed that FFA represent a crucial link between insulin resistance and ,-cell dysfunction and, as such, a reduction in elevated plasma FFA should be an important therapeutic target in obesity and type 2 diabetes. [source] Pressor and vascular effects of cardiac glycosidesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue S2 2001W. Kirch Background: For the past two decades, it has generally been accepted ('Blaustein hypothesis') that cardiac glycosides such as ouabain and digoxin increase the sodium and calcium content of smooth muscle cells, so inducing arterial vasoconstriction and a rise in blood pressure. Recent data from an experimental study we carried out led us to question this assumption. Design: A retrospective literature survey covering 20 years and including animal and human studies was performed. Representative results are presented. Results: Contradictory effects of cardiac glycosides on blood pressure and vasculature have been described. Increased, decreased or unaltered blood-pressure values have been observed following administration of the glycosides ouabain, digoxin and digitoxin. Moreover, vasoconstricting as well as vasodilating effects of cardiac glycosides have been demonstrated. Several recent studies show that cardiac glycosides such as digoxin and digitoxin can lead to a reduction of at least diastolic blood pressure. Conclusion: A slight vasodilation of resistance vessels followed by a fall in diastolic blood pressure could be a contributing factor for the beneficial effects of cardiac glycosides in patients with congestive heart failure. This vasodilation may be caused by central (neurohumoral) effects of digitalis glycosides. [source] Activation drives PD-1 expression during vaccine-specific proliferation and following lentiviral infection in macaquesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008David Abstract Recent data supports that increased expression of PD-1, a negative regulator of immune function, is associated with T cell exhaustion during chronic viral infection. However, PD-1 expression during acute infection and vaccination has not been studied in great detail in primates. Here, we examine PD-1 expression on CD3+ T cells following DNA vaccination or lentiviral infection of macaques. Ex vivo peptide stimulation of PBMC from DNA-vaccinated uninfected macaques revealed a temporal increase in PD-1 expression in proliferating antigen-specific CD8+ T cells. Following the initial increase, PD-1 expression steadily declined as proliferation continued, with a concomitant increase in IFN-, secretion. Subsequent examination of PD-1 expression on T cells from uninfected and lentivirus-infected non-vaccinated macaques revealed a significant increase in PD-1 expression with lentiviral infection, consistent with previous reports. PD-1 expression was highest on cells with activated memory and effector phenotypes. Despite their decreased telomere length, PD-1hi T cell populations do not appear to have statistically significant uncapped telomeres, typically indicative of proliferative exhaustion, suggesting a different mechanistic regulation of proliferation by PD-1. Our data indicate that PD-1 expression is increased as a result of T cell activation during a primary immune response as well as during persistent immune activation in macaques. Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/37857_s.pdf [source] IL-15 and IL-16 overexpression in cutaneous T-cell lymphomas: stage-dependent increase in mycosis fungoides progressionEXPERIMENTAL DERMATOLOGY, Issue 4 2000K. Asadullah Abstract: Cytokines are of major importance for the pathogenesis of cutaneous T-cell lymphomas (CTCL). Recent data suggested that IL-15 and IL-16 are survival/growth factors for the malignant T cells in these entities. To investigate the expression of IL-15 and IL-16 in mycosis fungoides (MF) and CD30+ pleomorphic T-cell lymphoma in vivo, we established a competitive RT-PCR technique. Analyzing skin biopsies from CTCL patients at different stages in comparison to psoriatic and healthy skin, we found IL-15 and IL-16 mRNA overexpression in both CTCL entities. Remarkably, there was some evidence for a stage-dependent increase during MF progression. We found only slight overexpression in early stage MF, when only few tumor cells are detectable within the infiltrates, whereas marked overexpression was found in more advanced lesions, which are characterized by a higher density of malignant cells. These results suggested that CTCL cells themselves might produce the cytokines. To further elucidate this hypothesis, two CTCL cell lines were analyzed but gave conflicting results. Therefore, the cellular origin of the IL-15 and IL-16 overexpression in CTCL remains unclear. Considering the significant overexpression of IL-15 and IL-16 and their biological capacities it is likely that these cytokines contribute to the tumor development. So, they might be involved in growth and skin homing of CTCL cells. [source] Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumptionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2009Sabine Gaubert Abstract Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (,8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene. [source] Calcineurin phosphatase in signal transduction: lessons from fission yeastGENES TO CELLS, Issue 7 2002Reiko Sugiura Calcineurin (protein phosphatase 2B), the only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an important mediator in signal transmission, connecting the Ca2+ -dependent signalling to a wide variety of cellular responses. Furthermore, calcineurin is specifically inhibited by the immunosuppressant drugs cyclosporin A and tacrolimus (FK506), and these drugs have been a powerful tool for identifying many of the roles of calcineurin. Calcineurin is enriched in the neural tissues, and also distributes broadly in other tissues. The structure of the protein is highly conserved from yeast to man. The combined use of powerful genetics and of specific calcineurin inhibitors in fission yeast Schizosaccharomyces pombe (S. pombe) identified new components of the calcineurin pathway, and defined new roles of calcineurin in the regulation of the many cellular processes. Recent data has revealed functional interactions in which calcineurin phosphatase is involved, such as the cross-talk between the Pmk1 MAP kinase signalling, or the PI signalling. Calcineurin also participates in membrane traffic and cytokinesis of fission yeast through its functional connection with members of the small GTPase Rab/Ypt family, and Type II myosin, respectively. These findings highlight the potential of fission yeast genetic studies to elucidate conserved elements of signal transduction cascades. [source] GROWTH OF CRUSTOSE LICHENS: A REVIEWGEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 1 2010RICHARD ARMSTRONG ABSTRACT. Crustose species are the slowest growing of all lichens. Their slow growth and longevity, especially of the yellow-green Rhizocarpon group, has made them important for surface-exposure dating (lichenometry). This review considers various aspects of the growth of crustose lichens revealed by direct measurement including: 1) early growth and development; 2) radial growth rates (RGR, mm yr,1); 3) the growth rate,size curve; and 4) the influence of environmental factors. Many crustose species comprise discrete areolae that contain the algal partner growing on the surface of a non-lichenized fungal hypothallus. Recent data suggest that ,primary' areolae may develop from free-living algal cells on the substratum while ,secondary' areolae develop from zoospores produced within the thallus. In more extreme environments, the RGR of crustose species may be exceptionally slow but considerably faster rates of growth have been recorded under more favourable conditions. The growth curves of crustose lichens with a marginal hypothallus may differ from the ,asymptotic' type of curve recorded in foliose and placodioid species; the latter are characterized by a phase of increasing RGR to a maximum and may be followed by a phase of decreasing growth. The decline in RGR in larger thalli may be attributable to a reduction in the efficiency of translocation of carbohydrate to the thallus margin or to an increased allocation of carbon to support mature ,reproductive' areolae. Crustose species have a low RGR accompanied by a low demand for nutrients and an increased allocation of carbon for stress resistance; therefore enabling colonization of more extreme environments. [source] Modeling of a Deep-Seated Geothermal System Near Tianjin, ChinaGROUND WATER, Issue 3 2001Zhou Xun A geothermal field is located in deep-seated basement aquifers in the northeastern part of the North China Plain near Tianjin, China. Carbonate rocks of Ordovician and Middle and Upper Proterozoic age on the Cangxian Uplift are capable of yielding 960 to 4200 m3/d of 57°C to 96°C water to wells from a depth of more than 1000 m. A three-dimensional nonisothermal numerical model was used to simulate and predict the spatial and temporal evolution of pressure and temperature in the geothermal system. The density of the geothermal water, which appears in the governing equations, can be expressed as a linear function of pressure, temperature, and total dissolved solids. A term describing the exchange of heat between water and rock is incorporated in the governing heat transport equation. Conductive heat flow from surrounding formations can be considered among the boundary conditions. Recent data of geothermal water production from the system were used for a first calibration of the numerical model. The calibrated model was used to predict the future changes in pressure and temperature of the geothermal water caused by two pumping schemes. The modeling results indicate that both pressure and temperature have a tendency to decrease with time and pumping. The current withdrawal rates and a pumping period of five months followed by a shut-off period of seven months are helpful in minimizing the degradation of the geothermal resource potential in the area. [source] Acute cognitive effects of standardised Ginkgo biloba extract complexed with phosphatidylserineHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2007D. O. Kennedy Abstract Recent data suggest that the complexation of standardised Ginkgo biloba extract (GBE) with soy-derived phospholipids enhances the bio-availablity of GBE's active components. The current study therefore aimed to assess the comparative cognitive and mood effects of a low dose of GBE and products complexing the same extract with either phosphatidylserine or phosphatidylcholine. The study utilised a placebo-controlled, multi-dose, double-blind, balanced-crossover design. Twenty-eight healthy young participants received 120,mg GBE, 120,mg GBE complexed with phosphatidylserine (VirtivaÔ), 120,mg GBE complexed with phosphatidylcholine and a matching placebo, on separate days 7 days apart. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and Serial Subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6,h thereafter. The primary outcome measures were the four aspects of cognitive performance, which have previously been derived by factor analysis of CDR subtests. Levels of terpenoids (bilobalide, ginkgolide A and ginkgolide B) were concomitantly assessed in plasma samples taken pre-dose and at 3 and 6.5,h post-dose. In keeping with previous research utilising the same methodology, 120,mg of GBE was not associated with markedly improved performance on the primary outcomes. However, administration of GBE complexed with phosphatidylserine resulted both in improved secondary memory performance and significantly increased speed of memory task performance across all of the post-dose testing sessions. Enhancement following GBE complexed with phosphatidylcholine was restricted to a modest improvement in secondary memory performance which was restricted to one post-dose time point. All three treatments were associated with improved calmness. There were no significant differences in post-dose levels of terpenoids between the Ginkgo containing treatments, although this latter finding may be attributable to methodological factors. Complexation with phosphatidylserine appears to potentiate the cognitive effects associated with a low dose of GBE. Further research is required to identify whether this effect is due to the complexation of the extracts, their mere combination, or the separate psychopharmacological actions of the two extracts. Copyright © 2007 John Wiley & Sons, Ltd. [source] The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanismsIMMUNOLOGICAL REVIEWS, Issue 1 2004John P. Cannon Summary:, The adaptive immune system arose in ancestors of the jawed vertebrates approximately 500 million years ago. Homologs of immunoglobulins (Igs), T-cell antigen receptors (TCRs), major histocompatibility complex I (MHC I) and MHC II, and the recombination-activating genes (RAGs) have been identified in all extant classes of jawed vertebrates; however, no definitive homolog of any of these genes has been identified in jawless vertebrates or invertebrates. RAG-mediated recombination and associated junctional diversification of both Ig and TCR genes occurs in all jawed vertebrates. In the case of Igs, somatic variation is expanded further through class switching, gene conversion, and somatic hypermutation. Although the identity of the ,primordial' receptor that was interrupted by the recombination mechanism in jawed vertebrates may never be established, many different families of genes that exhibit predicted characteristics of such a receptor have been described both within and outside the jawed vertebrates. Recent data from various model systems point toward a continuum of immune receptor diversity, encompassing many different families of recognition molecules whose functions are integrated in an organism's response to pathogenic invasion. Various approaches, including both genomic and protein-functional analyses, currently are being applied in jawless vertebrates, protochordates, and other invertebrate deuterostome systems and may yield definitive evidence regarding the presence or absence of adaptive immune homologs in species lacking adaptive immune systems. Such studies have the potential for uncovering previously unknown mechanisms of generating receptor diversity. [source] The aryl hydrocarbon receptor: a perspective on potential roles in the immune systemIMMUNOLOGY, Issue 3 2009Emily A. Stevens Summary The aryl hydrocarbon receptor (AHR) is a protein best known for its role in mediating toxicity. Over 30 years of research has uncovered additional roles for the AHR in xenobiotic metabolism and normal vascular development. Activation of the AHR has long been known to cause immunotoxicity, including thymic involution. Recent data suggesting a role for the AHR in regulatory T-cell (Treg) and T-helper 17 (Th17) cell development have only added to the excitement about this biology. In this review, we will attempt to illustrate what is currently known about AHR biology in the hope that data from fields as diverse as evolutionary biology and pharmacology will help elucidate the mechanism by which AHR modifies immune responses. We also will discuss the complexities of AHR pharmacology and genetics that may influence future studies of AHR in the immune system. [source] CD56bright natural killer (NK) cells: an important NK cell subsetIMMUNOLOGY, Issue 4 2009Aurélie Poli Summary Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56bright CD16dim/, and CD56dim CD16+, respectively. In this review, we will focus on the CD56bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56dim NK cells. CD56bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear. [source] Developmental path between language and autistic-like impairments: a twin studyINFANT AND CHILD DEVELOPMENT, Issue 2 2008Katharina Dworzynski Abstract Autism spectrum disorders (ASDs) are diagnosed when individuals show impairments in three behavioural domains: communication, social interactions, and repetitive, restrictive behaviours and interests (RRBIs). Recent data suggest that these three sets of behaviours are genetically heterogeneous. Early language delay is strongly associated with ASD, but the basis for this association and the relationship with individual sub-domains of ASD has not been systematically investigated. In the present study, data came from a population-based twin sample with language development data at 2,4 years, measured by the MacArthur Communicative Development Inventory (MCDI), and data at 8 years using the Childhood Asperger Syndrome Test (CAST). For the total CAST and the three subscales at 8 years, approximately 300 same-sex twin pairs were selected as showing extreme autistic-like traits (ALTs), defined here as pairs in which at least one member of the twin pair scored in the highest 5% of the distribution. Phenotypic analyses indicated that children showing extreme social and communication ALTs (but not the RRBI subscale) at 8 years were below average in language development at 2,4 years. A regression model for selected twin data suggested that genetic influences account for this overlap, but that these effects are only in part mediated by genes that are shared between language and extreme autistic traits. Copyright © 2008 John Wiley & Sons, Ltd. [source] The emerging role of adipocytokines as inflammatory mediators in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2005Konstantinos Karmiris MD Abstract Anorexia, malnutrition, altered body composition and development of mesenteric obesity are well known features of inflammatory bowel disease (IBD). Recent data suggest that dysregulation of protein secretion by white adipose tissue is involved in these manifestations of patients with IBD. Adipocytes are recently recognized as endocrine cells that secrete a variety of bioactive substances known as adipocytokines. There is evidence that adipocytokines are involved in inflammatory and metabolic pathways in human beings. Overexpression of adipocytokines such as leptin, adiponectin and resistin in mesenteric adipose tissue of operated patients with Crohn's disease has recently been reported, suggesting that mesenteric adipocytes in IBD may act as immunoregulating cells. Therefore, it could be suggested that adipocytokines play an important role in the disease pathogenesis. Moreover, modulators of mesenteric adipose function have been suggested as potential therapeutic drugs in IBD. In this review, the importance of white adipose tissue function and adipocytokines, is discussed with respect to IBD. [source] Neuropeptide Y and alpha-melanocyte-stimulating hormone: interaction in obesity and possible role in the development of hypertensionINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008M. Baltatzi Summary Aim:, Obesity and hypertension frequently coexist and both represent important risk factors for cardiovascular disease. The mechanisms implicated in the regulation of food intake have not been completely elucidated. Recent data suggests that peripheral and central neuropeptides play an important role in the maintenance of energy balance. More specifically, leptin, neuropeptide Y (NPY) and alpha-melanocyte-stimulating hormone (a-MSH) appear to be implicated in the pathogenesis of obesity and also contribute to the development of hypertension in obesity. Methods:, Analysis of the pertinent bibliography published in PubMed database. Results:, Leptin is produced in the adipose tissue directly correlated with fat tissue mass. Leptin acts on two distinct neural populations in the hypothalamus: the first expresses the orexigenic peptides NPY and agouti-related protein (AgRP), the second pro-opiomelanocortin (POMC). The activation of POMC neurons increases the production of the anorexigenic hormone a-MSH and inhibits the release of NPY and AgRP. In addition, the hypothalamus integrates the neuroendocrine systems with the autonomic nervous system and controls the activity of the latter. Stimulation of hypothalamic nuclei elicits sympathetic responses including blood pressure elevation. Both NPY and a-MSH appears to be implicated in the hypothalamic regulation of sympathetic nervous system (SNS) activity. Conclusion:, Alterations in leptin, NPY and a-MSH are frequently observed in obesity and might stimulate SNS activity, contributing to the development of hypertension in obese patients. These neuropeptides might provide a pathophysiologic link between excess weight and hypertension. However, more research is needed before the pharmacologic manipulation of these complex neuroendocrine systems can be applied in the treatment of obesity and hypertension. [source] A practical guide to the evaluation and treatment of male lower urinary tract symptoms in the primary care settingINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007M. T. Rosenberg Summary Aims:, Lower urinary tract symptoms (LUTS) are common in both men and women, and are among the most prevalent patient complaints heard by primary care physicians (PCPs). This article aims to provide PCPs with a logical algorithm for the assessment and initiation of treatment for LUTS in the male patient. Results:, Management of LUTS involves a focused history and physical, as well as the assessment of bother. In patients for whom treatment is warranted, a series of decisions regarding therapy should be considered. Male patients commonly suffer from storage and/or voiding symptoms. Treatment of male LUTS is commonly begun with agents that are aimed at remedying the outlet symptoms of benign prostatic hyperplasia (BPH). When this intervention is ineffective or when refractory symptoms persist, consideration should be given to treating the storage symptoms characteristic of overactive bladder (OAB). Discussion:, This article is intended to provide the PCP with a logical guide to the treatment of male LUTS. Benign prostatic hyperplasia and OAB predominate among the causes of these symptoms, and the PCP should be comfortable treating each. Recent data detailing the safety of the use of these treatments in the male patient are reviewed and incorporated into the algorithm. Conclusion:, Primary care physicians are in a unique position to successfully identify and treat male patients with LUTS. With this paper, they now have a tool to approach treatment logically and practically. [source] Gene,environment interactions and the response to exerciseINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2000Hugh Montgomery Many of the symptoms of heart failure (breathlessness and fatigue) are not primarily due to reduced cardiac output, but relate to an impairment of peripheral muscle performance and metabolic efficiency. With regular training it is possible to increase skeletal muscle performance through improvements in muscle efficiency. Recent data suggest that such improvements may be modulated by local tissue renin-angiotensin systems and, in particular, by the local activity of angiotensin-converting enzyme (ACE). These findings might explain the remarkable benefits of ACE inhibition in the treatment of heart failure. [source] Cytochrome c oxidase biogenesis: New levels of regulationIUBMB LIFE, Issue 9 2008Flavia Fontanesi Abstract Eukaryotic cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is a multimeric enzyme of dual genetic origin, whose assembly is a complicated and highly regulated process. COX displays a concerted accumulation of its constitutive subunits. Data obtained from studies performed with yeast mutants indicate that most catalytic core unassembled subunits are posttranslationally degraded. Recent data obtained in the yeast Saccharomycescerevisiae have revealed another contribution to the stoichiometric accumulation of subunits during COX biogenesis targeting subunit 1 or Cox1p. Cox1p is a mitochondrially encoded catalytic subunit of COX which acts as a seed around which the full complex is assembled. A regulatory mechanism exists by which Cox1p synthesis is controlled by the availability of its assembly partners. The unique properties of this regulatory mechanism offer a means to catalyze multiple-subunit assembly. New levels of COX biogenesis regulation have been recently proposed. For example, COX assembly and stability of the fully assembled enzyme depend on the presence in the mitochondrial compartments of two partners of the oxidative phosphorylation system, the mobile electron carrier cytochrome c and the mitochondrial ATPase. The different mechanisms of regulation of COX assembly are reviewed and discussed. © 2008 IUBMB IUBMB Life, 60(9): 557,568, 2008 [source] T-armless tRNAs and elongated elongation factor TuIUBMB LIFE, Issue 2 2007Takashi Ohtsuki Abstract Most tRNAs share a common secondary structure containing a T arm, a D arm, an anticodon arm and an acceptor stem. However, there are some exceptions. Most nematode mitochondrial tRNAs and some animal mitochondrial tRNAs lack the T arm, which is necessary for binding to canonical elongation factor Tu (EF-Tu). The mitochondria of the nematode Caenorhabditis elegans have a unique EF-Tu, named EF-Tu1, whose structure has supplied clues as to how truncated tRNAs can work in translation. EF-Tu1 has a C-terminal extension of about 60 aa that is absent in canonical EF-Tu. Recent data from our laboratory strongly suggests that EF-Tu1 recognizes the D-arm instead of the T arm by a mechanism involving this C-terminal region. Further biochemical analysis of mitochondrial tRNAs and EF-Tu from the distantly related nematode Trichinella spp. and sequence information on nuclear and mitochondrial DNA in arthropods suggest that T-armless tRNAs may have arisen as a result of duplication of the EF-Tu gene. These studies provide valuable insights into the co-evolution of RNA and RNA-binding proteins. IUBMB Life, 59: 68-75, 2007 [source] Torpor in an African caprimulgid, the freckled nightjar Caprimulgus tristigmaJOURNAL OF AVIAN BIOLOGY, Issue 3 2007Andrew E. McKechnie Recent data suggest that facultative hypothermic responses such as torpor are more important in the energy balance of birds from tropical and sub-tropical regions than previously thought. We used telemetric measurements of skin temperature (Tskin) for five individuals on 151 bird-nights to investigate the occurrence of torpor during winter in an 81 g African caprimulgid, the freckled nightjar Caprimulgus tristigma. We found that freckled nightjars have the capacity to enter torpor, with a minimum observed Tskin of 12.8°C. During the torpor bouts we observed, complete rewarming typically occurred after sunrise, and coincided with the availability of solar radiation. There was considerable inter-individual variability in the frequency and depth of torpor bouts, with one female nightjar exhibiting particularly frequent and deep torpor. Our results confirm the ability to use torpor by a nocturnal aerial insectivore from the Afrotropics, and reiterate the variability in patterns of torpor that can exist within a population. [source] | ||||||||||||||||||||||||||||||||||||||||||||||