Home About us Contact
|
Home About us Contact | ||
|
|
||
Several Pathways (several + pathway)
Selected AbstractsCellulose and Glass Fiber Affinity Membranes for the Chromatographic Separation of BiomoleculesBIOTECHNOLOGY PROGRESS, Issue 1 2004Eli Ruckenstein Macroporous cellulose and glass membranes were prepared from filter paper and glass fiber filter, respectively. To enhance their stability, the cellulose membranes were crosslinked with epichlorohydrin, and the glass membranes were crosslinked with glutaraldehyde or organic bifunctional silanes. Several pathways for the modification, activation, and ligand immobilization were used and compared. For cellulose membranes, the diazotization method provided the best results, whereas the glutaraldehyde method provided the best performance for glass membranes, regarding both their stability and ligand immobilization capacity. The characterization of the membranes was made by using a triazine dye, bovine serum albumin, and trypsin as test ligands. The membrane morphologies and the uniformities of ligand distribution across the membrane cartridges were investigated. Numerous affinity ligands were immobilized onto the membranes, and the prepared affinity membranes have been used to separate or purify concanavalin A, peroxidase, protease inhibitors, globulin, fibronectin, and other biomolecules. [source] Psychiatric services for people with severe mental illness across western Europe: what can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care?ACTA PSYCHIATRICA SCANDINAVICA, Issue 2006T. Becker Objective:, To report recent findings regarding differences in the provision, cost and outcomes of mental health care in Europe, and to examine to what extent these studies can provide a basis for improvement of mental health services and use of findings across countries. Method:, Findings from a number of studies describing mental health care in different European countries and comparing provision of care across countries are reported. Results:, The development of systems of mental health care in western Europe is characterized by a common trend towards deinstitutionalization, less in-patient treatment and improvement of community services. Variability between national mental healthcare systems is still substantial. At the individual patient level the variability of psychiatric service systems results in different patterns of service use and service costs. However, these differences are not reflected in outcome differences in a coherent way. Conclusion:, It is conceivable that the principal targets of mental healthcare reform can be achieved along several pathways taking into account economic, political and sociocultural variation between countries. Differences between mental healthcare systems appear to affect service provision and costs. However, the impact of such differences on patient outcomes may be less marked. The empirical evidence is limited and further studies are required. [source] Mechanistic studies of blood pressure in rats treated with a series of cholesteryl ester transfer protein inhibitors,DRUG DEVELOPMENT RESEARCH, Issue 1 2009Michael DePasquale Abstract ILLUMINATE, the Phase 3 clinical trial of morbidity and mortality (M&M) with the cholesteryl ester transfer protein inhibitor (CETPi), torcetrapib (CP-529,414), was terminated in December 2006 due to an imbalance in all cause mortality. The underlying cause of the M&M remains undetermined. While torcetrapib produced dose-related increases in blood pressure in clinical trials, the mechanism of the increase in blood pressure is also undetermined. The pressor effects of torcetrapib and structurally related compounds were studied in several pathways involved in blood pressure control. Studies were conducted in rats treated with a series of structurally related molecules (CP-529,414, CP-532,623, PF-868,348, CP-746,281, CP-792,485, PF-868,343, and CE-308,958). CP-529,414, CP-532,623, CP-868,343, and CP-792,485 are potent CETP inhibitors; PF-868,348 is weakly potent and CP-746,281 and CE-308,958 are CETP-inactive. Changes in blood pressure were determined in conscious animals in conjunction with pharmacologic blockade of numerous pressor agents/pathways. Torcetrapib and CP-532,623 increased blood pressure following both chronic PO and acute IV administration. The CETP-inactive enantiomer of CP-532,623, CP-746,281 failed to raise blood pressure. PF-868,348, a structural analogue with ,50-fold lower CETPi activity also displayed pressor activity. Blockade of adrenergic, cholinergic, angiotensin, endothelin, NOS, Rho kinase, and thromboxane pathways failed to attenuate the pressor response. These data demonstrate that the blood pressure activity seen with torcetrapib can be dissociated from CETP inhibitor pharmacology and numerous pharmacology pathways can be discounted in the attempt to understand the molecular basis of the pressor pharmacology. Drug Dev Res 70:2009 © 2009 Wiley-Liss, Inc. [source] Role of the pro-inflammatory cytokines TNF-, and IL-1, in HIV-associated dementiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2006N. A. C. H. Brabers Abstract Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin-1, (IL-1,), which are thought to play a major role in inducing neuronal death. Both TNF-, and IL-1, increase the permeability of the blood,brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca2+ levels. Additionally, TNF-, co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-, and IL-1, in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-, and IL-1, on neuronal life and death in HAD is discussed. [source] Self-esteem: a behavioural genetic perspectiveEUROPEAN JOURNAL OF PERSONALITY, Issue 5 2002Michelle B. Neiss Self-esteem, the affective or evaluative appraisal of one's self, is linked with adaptive personality functioning: high self-esteem is associated with psychological health benefits (e.g. subjective well-being, absence of depression and anxiety), effective coping with illness, and satisfactory social relationships. Although several pathways have been hypothesized to effect within-family transmission of self-esteem (e.g. parenting style, family relationship patterns), we focus in this article on genetic influences. Genetic studies on both global and domain-specific self-esteem and on both level and stability of self-esteem converge in showing that (i) genetic influences on self-esteem are substantial, (ii) shared environmental influences are minimal, and (iii) non-shared environmental influences explain the largest amount of variance in self-esteem. We advocate that understanding of current issues in self-esteem research will be enriched by including behavioural genetic approaches. Copyright © 2002 John Wiley & Sons, Ltd. [source] Absence of Gup1p in Saccharomyces cerevisiae results in defective cell wall composition, assembly, stability and morphologyFEMS YEAST RESEARCH, Issue 7 2006Célia Ferreira Abstract Saccharomyces cerevisiae Gup1p and its homologue Gup2p, members of the superfamily of membrane-bound O -acyl transferases, were previously associated with glycerol-mediated salt-stress recovery and glycerol symporter activity. Several other phenotypes suggested Gup1p involvement in processes connected with cell structure organization and biogenesis. The gup1, mutant is also thermosensitive and exhibits an altered plasma membrane lipid composition. The present work shows that the thermosensitivity is independent of glycerol production and retention. Furthermore, the mutant grows poorly on salt, ethanol and weak carboxylic acids, suggestive of a malfunctioning membrane potential. Additionally, gup1, is sensitive to cell wall-perturbing agents, such as Calcofluor white, Zymolyase, lyticase and sodium dodecyl sulphate and exhibits a sedimentation/aggregation phenotype. Quantitative analysis of cell wall components yielded increased contents of chitin and ,-1,3-glucans and lower amounts of mannoproteins. Consistently, scanning electron microscopy showed a strikingly rough surface morphology of the mutant cells. These results suggest that the gup1, is affected in cell wall assembly and stability, although the Slt2p/MAP kinase from the PKC pathway was phosphorylated during hypo-osmotic shock to a normal extent. Results emphasize the pleiotropic nature of gup1,, and are consistent with a role of Gulp1p in connection with several pathways for cell maintenance and construction/remodelling. [source] Helicobacter pylori Infection and Iron Stores: A Systematic Review and Meta-analysisHELICOBACTER, Issue 5 2008Khitam Muhsen Abstract Background and Aims:, We carried out a systematic literature review and meta-analysis to evaluate the existing evidence on the association between Helicobacter pylori infection and iron stores. Methods:, Twelve case reports and case series, 19 observational epidemiologic studies and six intervention trials were included in the review. Results:, Although only few studies controlled for multiple potential confounders, most studies reported a positive association, linking between H. pylori and decreased body iron stores in symptomatic and asymptomatic H. pylori -infected subjects. H. pylori infection may be regarded as a risk factor for reduction in body iron stores and also for iron deficiency or iron deficiency anemia, especially in high-risk groups. The results of the meta-analysis of thoroughly designed and analyzed studies revealed an increased risk for iron deficiency anemia; pooled odds ratio (OR) 2.8 (95% confidence interval (CI) 1.9, 4.2) and also for iron deficiency; pooled OR 1.38 (95%CI 1.16,1.65) among H. pylori -infected subjects. The biologic mechanism by which H. pylori induces the alteration in the iron stores is not fully understood, but it seems to involve several pathways, including gastrointestinal blood loss, decrease in the absorption of dietary iron, and enhanced uptake of the iron by the bacterium. Conclusions:,H. pylori is associated with reduced iron stores. Future research is needed to determine whether this relationship is a causal association and to better understand its biologic mechanism. The impact of anti- H. pylori therapy on improvement of iron stores needs to be further evaluated in large and well-controlled trials. [source] Patterns of reproductive effort and success in birds: path analyses of long-term data from European ducksJOURNAL OF ANIMAL ECOLOGY, Issue 2 2002Peter Blums Summary 1We tested ecological hypotheses about timing of breeding and reproductive effort in birds, by analysing > 15-year data sets for individually marked females in three species of Latvian ducks (northern shoveler, tufted duck, common pochard). 2Duckling survival and recruitment declined with advancing hatch date in pochard and tufted duck, after controlling for effects of female age and other factors with path analysis, a novel finding which indicates that fitness advantages associated with early hatching extended beyond the prefledging period. Logistic regression analysis suggested further that individual duckling prefledging survival was moderate in the earliest phase of the breeding season, greatest in mid-season and lowest later on. 3However, selection acting against early hatched ducklings was surpassed by strong directional selection favouring recruitment of the earliest hatching females. The absolute and relative numbers of female recruits produced by a breeding female declined sharply with advancing hatch date in all species. 4Unlike previous studies, an hypothesized intraspecific trade-off between duckling mass and brood size was detected, being very robust in two of three species. 5Unexpectedly, female age effects on recruitment were manifested only indirectly by several pathways, the most important being the earlier hatching dates of older females. Size-adjusted body mass (i.e. condition index) was positively related to reproductive success, and was 2,8-fold more influential than female size (indexed by wing length). 6Overall, fecundity-independent variables (e.g. hatching date, weather, indices of duckling production and habitat quality) generally had 2,10 times greater influence on recruitment rates than did fecundity-dependent variables such as female size or condition, duckling mass and brood size, suggesting a critical role for external environmental factors vs. individual female-specific traits in the recruitment process. [source] Biomarkers, regerons, and pathways to lethal cancer,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2007Meng Qiao Abstract Cancer is a disease of "outlaw" cells that become mutated in regulatory mechanisms. They have lost normal self controls and relationships to the whole organism. Cancers can progress by several pathways from a normal cell to malignant cancer, from bad to worse. Questions about advisability of treatment for some cancers arise from the possibility that they are arrested during progression and so never become lethal. Techniques could be developed to determine the degree of progression and possibility for successful treatment. This article is intended to suggest a way of looking at cancer. It is not a review so references to research articles are infrequent. J. Cell. Biochem. 102: 1076,1086, 2007. © 2007 Wiley-Liss, Inc. [source] Cellular lifespan and senescence signaling in embryonic stem cellsAGING CELL, Issue 6 2004Takumi Miura Summary Most mammalian cells when placed in culture will undergo a limited number of cell divisions before entering an unresponsive non-proliferating state termed senescence. However, several pathways that are activated singly or in concert can allow cells to bypass senescence at least for limited periods. These include the telomerase pathway required to maintain telomere ends, the p53 and Rb pathways required to direct senescence in response to DNA damage, telomere shortening and mitogenic signals, and the insulin-like growth factor , Akt pathway that may regulate lifespan and cell proliferation. In this review, we summarize recent findings related to these pathways in embryonic stem (ES) cells and suggest that ES cells are immortal because these pathways are tightly regulated. [source] The Effect of Dietary Carotenoids on Gonad Production and Carotenoid Profiles in the Sea Urchin Lytechinus variegatusJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 2 2002Larry R. Plank Although dietary carotenoids are generally considered important in sea urchin aquaculture only for their effect on gonad color, they also have important biological roles. The effects of dietary carotenoids on gonad production and organ carotenoid profiles of Lytechinus variegatus were examined. Individuals were collected in January 1999 and fed a replete diet with a level of 0.60 mg carotenoids/kg for 4 wk, followed by one of four prepared diets for 8 wk: one without supplemental carotenoids, one with ,-carotene (16.92 mg carotenoids/kg feed), and two carotenoid mixtures, one high in zeaxanthin (5.28 mg carotenoids/kg feed) and another high in capsanthin (9.63 mg carotenoids/kg feed). The carotenoid profiles of the body compartments differed. The primary carotenoid in gonads of males and females was echi-nenone. The carotenoid profile of the test was similar to that of the gonad. The carotenoid profile of the gut varied with diet, but was not identical to composition of the diet. The gut profiles included echinenone but at lower concentrations than in the gonad and test. The carotenoid profile in the gut probably results from the presence of the carotenoids absorbed and those metabolized. The results suggest that several pathways exist to metabolize dietary carotenoids and that some of them are in the gut. The concentration of carotenoids in the gut (g wet weight) was higher than that of the gonad, which was higher than that of the test. The gonads increased significantly in size regardless of diet, indicating carotenoids are not required for gonad production under the conditions of this experiment. Although the concentration of carotenoids in the gonad decreased over time, the absolute amount of carotenoids increased with the increase in gonad size. Either gonad growth was more rapid than carotenoid deposition or differential deposition in nutritive cells and gametogenic cells occurred, or the amount of carotenoids used in the diets was too low to have an effect. [source] The treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2001O. H. Nielsen The thioguanine derivative, azathioprine, is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6-mercaptopurine have been used in the treatment of inflammatory bowel disease, i.e. ulcerative colitis and Crohn's disease, for more than 30 years. However, widespread use of azathioprine or 6-mercaptopurine in inflammatory bowel disease is of more recent origin, the primary reason being a long-standing debate on the efficacy of these agents in inflammatory bowel disease. Both drugs are slow acting, which is why clinical efficacy cannot be expected until several weeks or even months of treatment have elapsed. Consequently, azathioprine and 6-mercaptopurine have no place as monotherapy in the treatment of acute relapsing inflammatory bowel disease. Today, azathioprine and 6-mercaptopurine are the most commonly used immunomodulatory drugs in the treatment of inflammatory bowel disease. Their clinical effects are probably identical, although their exact mode of action is still unknown. The mode of action of azathioprine is thought to be multifactorial, including conversion to 6-mercaptopurine (which acts as a purine antimetabolite), possible blockade of thiol groups by alkylation, inhibition of several pathways in nucleic acid biosynthesis (preventing proliferation of cells involved in the determination and amplification of the immune response) and damage to DNA through the incorporation of thiopurine analogues. However, 6-thioguanine nucleotides may accumulate in toxic doses in myeloid precursor cells, resulting in life-threatening myelosuppression. Azathioprine and 6-mercaptopurine are further known to alter lymphocyte function, reduce the number of lamina propria plasma cells and affect natural killer cell function. The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease. [source] Potential of resveratrol in anticancer and anti-inflammatory therapyNUTRITION REVIEWS, Issue 8 2008Chibuike C Udenigwe Phytochemicals present in food have shown significant prospects in the treatment and management of a vast array of human diseases. Resveratrol is a stilbene-type aromatic phytoalexin predominantly found in grapes, peanuts, berries, turmeric, and other food products. Resveratrol has been reported to exhibit several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans. Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations. Hence, resveratrol possesses good potential to be used as an adjunctive or alternative therapy for cancer and inflammatory diseases. [source] During Pregnancy, in the Context of a Th2-Type Cytokine Profile, Serum IL-6 Levels Might Condition the Quality of the Synthesized AntibodiesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2001RICARDO A. MARGNI PROBLEM: In recent years, the central role of cytokines in the immune response has been widely studied. It is considered that a T helper (Th)1-type cytokine profile is associated with the rejection phenomenon, whereas a Th2-type cytokine profile is associated with immunological tolerance. In pregnancy, the enhanced Th2/Th1 ratio seems to be necessary to fetal protection. Taking into account that a Th2-type response means antibody production by B cells, and that these antibodies could induce degradation of the paternal antigens, we investigated the quality of the antibodies produced during pregnancy and their regulation. METHOD OF STUDY: Review of previous data. RESULTS: The regulation of protective antibodies by IL-6 in a dose-dependent fashion is proposed as a hypothesis. CONCLUSION: Cytokines play a central role in the success (or failure) of pregnancy. However, the quality of the synthesized antibodies is also a regulatory key. The preferential synthesis of asymmetric immunoglobulin G antibodies during pregnancy could be one of the several pathways that lead to a successful pregnancy [source] Sustained effects of nonallele-specific Huntingtin silencing,ANNALS OF NEUROLOGY, Issue 3 2009Valérie Drouet MS Objective Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin (htt) protein. No cure is available to date to alleviate neurodegeneration. Recent studies have demonstrated that RNA interference represents a promising approach for the treatment of autosomal dominant disorders. But whether an allele-specific silencing of mutant htt or a nonallele-specific silencing should be considered has not been addressed. Methods We developed small hairpin RNA targeting mutant or wild-type htt transcripts, or both. Results We confirmed the therapeutic potential of sihtt administered with lentiviral vectors in rodent models of HD and showed that initiation of small interfering RNA treatment after the onset of HD symptoms is still efficacious and reduces the HD-like pathology. We then addressed the question of the impact of nonallele-specific silencing and demonstrated that silencing of endogenous htt to 25 to 35% in vivo is altering several pathways associated with known htt functions but is not inducing overt toxicity or increasing striatal vulnerability up to 9 months after treatment. Interpretation These data indicate that the coincident silencing of the wild-type and mutant htt may be considered as a therapeutic tool for HD. Ann Neurol 2009;65:276,285 [source] | |||||||||||||