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Potential Mechanisms (potential + mechanism)
Terms modified by Potential Mechanisms Selected AbstractsSoybean Foods and Their Benefits: Potential Mechanisms of ActionNUTRITION REVIEWS, Issue 8 2005Adetayo O. Omoni MSc Isoflavones have been proposed to be the active component responsible for the beneficial effects of soybean foods, and appear to work in conjunction with the proteins to protect against cancer, cardiovascular disease, and osteoporosis. Most of the research activities on the benefits of soybean foods have focused on the role these isoflavones play in disease prevention or treatment; however, there is also some evidence that the benefits are attributable to certain peptides or protein fractions from soybeans. This review will focus on some of the potential mechanisms whereby soybeans exert their protective effects against heart disease, cancer, and osteoporosis. [source] The effects of Tween 20 and sucrose on the stability of anti-L-selectin during lyophilization and reconstitutionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2001Latoya S. Jones Abstract We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1466,1477, 2001 [source] Potential mechanism for detection by Apis mellifera of the parasitic mite Varroa destructor inside sealed brood cellsPHYSIOLOGICAL ENTOMOLOGY, Issue 3 2002Caroline Martin Abstract The parasitic mite Varroa destructor Anderson & Trueman is a major pest of the honeybee Apis mellifera L. throughout the world. Chemical agents currently used for mite control leave contaminating residues and promote pesticide resistance. As an alternative means of control, it would be useful to identify natural substances enabling bees to detect Varroa inside brood cells. These substances could then be used to trigger mite hygienic behaviour by bees. In this study several techniques were used to screen substances that might allow detection of infested brood cells by bees. Gas chromatography-mass spectrometry analysis was performed on substances extracted in dichloromethane from the contents of brood cells. Solid phase microextraction and solid injection were performed on substances obtained from living and dead Varroa, respectively. Electroantennography was performed to assess the sensitivity of olfactory receptors in bee antennae to some of these substances. Principal component analysis based on proportions of cuticular substances allowed discrimination between bees and other cell contents. Foundress Varroa exhibited the greatest dissimilarity to healthy pupae that were used as controls. Immature Varroa and faecal material were intermediate. High molecular weight compounds, mainly dimethylalkanes, were proportionally the most characteristic components of foundress Varroa. This finding suggests that these compounds would be the most apt to induce uncapping of cells infested by Varroa. Solid-phase microextraction and solid injection demonstrated the presence of aliphatic acids, esters, and one alcohol, eicosenol, in Varroa. Electroantennographic recordings showed that mite-resistant bees were more responsive to some acids and one ester. We speculate that these compounds may be involved in recognition of living Varroa by honeybees. [source] Expression of estrogen receptor alpha increases leptin-induced STAT3 activity in breast cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Nadine A. Binai Abstract Adipositas correlates with an enhanced risk of developing malignant diseases such as breast cancer, endometrial tumor or prostate carcinoma, but the molecular basis for this is not well understood. Potential mechanisms include increased bioavailability of adipocytokines (e.g. leptin) and steroid hormones. Here, we investigated cross-talk between ER, (estrogen receptor alpha) and leptin-induced activation of signal transducer and activator of transcription 3 (STAT3), a transactivator of important oncogenes. Upon leptin binding to its receptor Ob-RL (obesity receptor), STAT3 tyrosine phosphorylation and transactivation activity were enhanced by simultaneously expressing ER,. Downregulation of ER, using small interfering RNA abolished leptin-induced STAT3 phosphorylation. Interestingly, leptin-mediated STAT3 activation was unaffected by co-stimulation with the ER, ligands estradiol (E2) or estrogen antagonists ICI182,780 and tamoxifen, implying that enhancement of leptin-mediated STAT3 activity is independent of ER, ligands. We also detected ER, binding to STAT3 and JAK2 (Janus kinase 2), resulting in enhanced JAK2 activity upstream of STAT3 in response to leptin that might lead to an increased ER,-dependent cell viability. Altogether, our results indicate that leptin-induced STAT3 activation acts as a key event in ER,-dependent development of malignant diseases. [source] The effect of IFN, on the hepatocyte: cell cycle and apoptosisINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2001Benjamin J. Tura The inflammatory cytokine interferon gamma (IFN,) can cause cell cycle arrest and apoptosis in the hepatocyte. Primarily these processes are protective but in chronic liver disease oncogenic mutations may prosper. IFN, signalling is discussed showing how p53 is induced to cause cell cycle arrest. While caspases are are known to be responsible for IFN, induced apoptosis, how they are activated is unclear. Potential mechanisms are reviewed. [source] Comparison of genomic and cDNA sequences of guinea pig CYP2B18 and rat CYP2B2: Absence of a phenobarbital-responsive enhancer module in the upstream region of the CYP2B18 geneJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2004Midori Yamamoto Abstract Potential mechanisms were investigated whereby CYP2B18, a cytochrome P450 gene exhibiting high constitutive expression but only low levels of phenobarbital-inducibility in the guinea pig liver, may be differentially regulated versus the highly inducible rat CYP2B2 gene. To comparatively assess potential regulatory sequences associated with CYP2B18, a guinea pig genomic library was screened enabling isolation of the CYP2B18 gene. The genomic screening process resulted in the identification of at least four closely-related CYP2B18 genes, designated here as CYP2B18A-D. Of these isolates, CYP2B18A exhibited sequence identical to that of the CYP2B18 cDNA. Further, the deduced amino acid sequence of the CYP2B18 cDNA was identical to that of N-terminal and internally-derived peptide sequences obtained in this investigation from CYP2B18 protein isolated from guinea pig liver. Genomic structural sequences were derived for CYP2B18A, together with the respective 5,-upstream and intronic regions of the gene. Comparison of the CYP2B18A and CYP2B2 gene sequences revealed the lack of repetitive LINE gene sequences in CYP2B18A, putative silencing elements that effect neighboring genes, although these sequences were present in both 5,-upstream and 3,-downstream regions of CYP2B2. We determined that the phenobarbital-responsive enhancer module was absent from the 5,-upstream region as well as the intronic regions of CYP2B18A gene. We hypothesize that the compromised phenobarbital inducibility of CYP2B18A stems from its lack of a functional phenobarbital responsive enhancer module. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:124,130, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20016 [source] Affective reactivity in response to criticism in remitted bipolar disorder: a laboratory analog of expressed emotion,JOURNAL OF CLINICAL PSYCHOLOGY, Issue 9 2009Amy K. Cuellar Abstract Potential mechanisms to explain the relationship between Expressed Emotion (EE) and poor outcome within bipolar disorder are poorly understood. One possibility is that people with bipolar disorder have difficulty regulating their affect in response to criticism. The present study examined whether participants with bipolar disorder were more affectively dysregulated than control participants when presented with a criticism by a confederate. There was a trend for people with bipolar disorder to react more negatively to the criticism, but there was also evidence that they recovered as quickly as controls. Exploratory analyses found that female gender, the perception of the criticism as more negative, being disabled, and having fewer positive relationships predicted greater reactivity to criticism among people with bipolar disorder. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1,17, 2009. [source] Mycorrhizal fungi as mediators of defence against insect pests in agricultural systemsAGRICULTURAL AND FOREST ENTOMOLOGY, Issue 4 2009Rachel L. Vannette Abstract 1Below-ground organisms influence above-ground interactions in both natural and agricultural ecosystems. Among the most important below-ground organisms are mycorrhizal fungi, comprising ubiquitous and ancient plant mutualists that have significant effects on plant growth and fitness mediated by resource exchange with plants. In the present study, we focus on the effects of arbuscular mycorrhizal fungi (AMF) on crop defence against insect pests. 2AMF alter the availability of resources used by crop plants to manufacture defences against pests and to compensate for pest damage. However, AMF also provide plants with nutrients that are known to increase insect performance. Through potentially opposing effects on plant nutritional quality and defence, mycorrhizal fungi can positively or negatively affect pest performance. 3Additionally, AMF may directly affect gene expression and plant defence signalling pathways involved in the construction and induction of plant defences, and these effects are apparently independent of those caused by nutrient availability. In this way, AMF may still influence plant defences in the fertilized and highly managed systems typical of agribusiness. 4Because AMF can affect plant tolerance to pest damage, they may have a significant impact on the shape of damage,yield relationships in crops. Potential mechanisms for this effect are suggested. 5We highlight the need for continuing research on the effects of AMF identity and the abundance on crop defences and tolerance to pest attack. Much work is needed on the potential effects of mycorrhizal colonization on plant signalling and the induction of direct and indirect defences that may protect against pest damage. [source] SYSTEMIC TRAUMATIC STRESS: THE COUPLE ADAPTATION TO TRAUMATIC STRESS MODELJOURNAL OF MARITAL AND FAMILY THERAPY, Issue 2 2005Briana S. Nelson Goff Research traditionally has focused on the development of symptoms in those who experienced trauma directly but overlooked the impact of trauma on the families of victims. In recent years, researchers and clinicians have begun to examine how individual exposure to traumatic stress affects the spouses/partners, children, and professional helpers of trauma survivors. However, empirically supported, theory-based literature that identifies the mechanisms by which interpersonal or "secondary trauma" occurs in response to traumatic events is limited. Here, we present the Couple Adaptation to Traumatic Stress Model, a systemic model of the development of interpersonal symptoms in the couple dyad based on empirical literature. Potential mechanisms and clinical vignettes are included to describe the systemic processes that occur with trauma couples. Areas for future research and clinical implications also are identified. [source] Potential mechanisms for astrocyte-TIMP-1 downregulation in chronic inflammatory diseasesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Jessica Gardner Abstract The pathogenesis of many neurodegenerative disorders, including human immunodeficiency virus (HIV)-1 associated dementia, is exacerbated by an imbalance between matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). In the context of disease, TIMP-1 has emerged as an important multifunctional protein capable of regulating inflammation. We previously reported differential TIMP-1 expression in acute versus chronic activation of astrocytes. This study investigates possible mechanisms underlying TIMP-1 downregulation in chronic neuroinflammation. We used interleukin (IL)-1, as a model pro-inflammatory stimulus and measured TIMP-1 binding to extracellular matrix, cell death, receptor downregulation, TIMP-1 mRNA stability and transcriptional regulation in activated astrocytes. TIMP-1 remained localized to the cell body or was secreted into the cell supernatant. DNA fragmentation ELISA and MTT assay showed that prolonged IL-1, activation of astrocytes induced significant astrocyte death. In acute and chronic IL-1,-activated astrocytes, IL-1 receptor levels were not significantly different. TIMP-1 mRNA stability was measured in astrocytes and U87 astroglioma cells by real-time PCR, and TIMP-1 promoter activation was studied using TIMP-1-luciferase reporter constructs in transfected astrocytes. Our results indicated that TIMP-1 expression is regulated through multiple mechanisms. Transcriptional control and loss of mRNA stabilization are, however, the most likely primary contributors to chronic downregulation of TIMP-1. These data are important for unraveling the mechanisms underlying astrocyte responses during chronic neuroinflammation and have broader implications in other inflammatory diseases that involve MMP/TIMP imbalance. © 2006 Wiley-Liss, Inc. [source] Hypocalcemia in a critically ill patientJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2005Tamara B. Wills DVM Abstract Objective: To present a case of clinical hypocalcemia in a critically ill septic dog. Case summary: A 12-year old, female spayed English sheepdog presented in septic shock 5 days following hemilaminectomy surgery. Streptococcus canis was cultured from the incision site. Seven days after surgery, muscle tremors were noted and a subsequent low serum ionized calcium level was measured and treated. Intensive monitoring, fluid therapy, and antibiotic treatment were continued because of the sepsis and hypocalcemia, but the dog was euthanized 2 weeks after surgery. New or unique information provided: Low serum ionized calcium levels are a common finding in critically ill human patients, especially in cases of sepsis, pancreatitis, and rhabdomyolysis. In veterinary patients, sepsis or streptococcal infections are not commonly thought of as a contributing factor for hypocalcemia. Potential mechanisms of low serum ionized calcium levels in critically ill patients include intracellular accumulation of calcium ions, altered sensitivity and function of the parathyroid gland, alterations in Vitamin D levels or activity, renal loss of calcium, and severe hypomagnesemia. Pro-inflammatory cytokines and calcitonin have also been proposed to contribute to low ionized calcium in the critically ill. Many veterinarians rely on total calcium levels instead of serum ionized calcium levels to assess critical patients and may be missing the development of hypocalcemia. Serum ionized calcium levels are recommended over total calcium levels to evaluate critically ill veterinary patients. [source] Linaclotide , a secretagogue and antihyperalgesic agent , what next?NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2010A. E. Bharucha Abstract Ongoing clinical trials suggest that linaclotide, a first-in-class, 14-amino acid peptide guanylate cyclase-C (GC-C) receptor agonist and intestinal secretagogue is an effective treatment for chronic constipation. A study in this issue of the Journal suggests that linaclotide also has antihyperalgesic effects in three common rat models of inflammation- and stress-induced hypersensitivity (i.e., acute trinitrobenzene sulfonic acid colitis, water avoidance stress [WAS], and restraint-induced stress) but not in naïve animals. In mice, linaclotide at least partly reduces hyperalgesia via GC-C receptors. Dose,effect relationships of linaclotide were complicated and non-linear. This viewpoint discusses human clinical trials with linaclotide and the results of this study. Potential mechanisms and clinical significance of these findings are explored. Collectively, these data suggest that GC-C receptors exert other, as yet poorly understood, effects on gastrointestinal sensitivity in conditions associated with inflammation and/or stress-induced increased intestinal permeability. However, the data need to be confirmed in humans and in long-term animal models. Further studies are also necessary to elucidate the mechanisms as these effects cannot be explained by linaclotide's known effects on epithelial GC-C receptors. [source] The Link Between Childhood Undernutrition and Risk of Chronic Diseases in Adulthood: A Case Study of BrazilNUTRITION REVIEWS, Issue 5 2003Ana L. Sawaya PhD Obesity, cardiovascular disease, and type 2 diabetes mellitus are now prevalent among adults living in developing countries; these chronic diseases affect socioeconomically disadvantaged adults living in impoverished families with under-nourished children. This review summarizes data from Brazil - a developing country undergoing the nutrition transition - suggesting an association between childhood undernutrition and obesity and chronic degenerative disease. Potential mechanisms for the association include longterm effects of childhood undernutrition on energy expenditure, fat oxidation, regulation of food intake, susceptibility to the effects of high-fat diets, and altered insulin sensitivity. The combination of childhood undernutrition and adult chronic degenerative disease results in enormous social and economic burdens for developing countries. Further research is urgently needed to examine the effect of childhood undernutrition on risk of obesity and chronic degenerative diseases; one goal of such research would be to determine and provide low-cost methods for prevention and treatment. [source] Exclusive Breast-feeding: Does It Have the Potential to Reduce Breast-feeding Transmission of HIV-1?NUTRITION REVIEWS, Issue 11 2000Melanie M. Smith M.N.S. Exclusive breast-feeding is unambiguously the optimal infant feeding practice and is universally promoted in the absence of human immunodeficiency virus (HIV-1). It is associated with reduced morbidity and mortality from diarrheal and respiratory diseases. Recent findings suggest that exclusive breast-feeding may pose less risk of HIV-1 transmission than the more common practice of mixed feeding (i.e., breast-feeding concurreptwith the feeding of water, other fluids, and foods), which has important infant feeding policy implications for low-resource settings. This paper reviews the biologic mechanisms associated with exclusive breast-feeding that provide protection against gastrointestinal, respiratory, and atopic diseases, and evaluates the relevance of these mechanisms for HIV-1 transmission. Potential mechanisms include reduction in dietary antigens and enteric pathogens that may maintain integrity of the intestinal mucosal barrier and limit inflammatory responses of the gut mucosa; promotion of beneficial intestinal microflora that may increase resistance to infection and modulate the infant's immune response; alteration in specific antiviral or anti-inflammatory factors in human milk that may modulate maternal hormonal or immunologic status; and maintenance of mammary epithelial integrity that may reduce viral load in breast milk. [source] Non-cardiogenic pulmonary edema during basiliximab induction in three adolescent renal transplant patientsPEDIATRIC TRANSPLANTATION, Issue 4 2003Fatai O. Bamgbola Abstract:, Background:, Introduction of the anti-CD-25 mAb basiliximab into renal transplant protocols has reduced the incidence of acute rejection. However, its side-effect profile is still unfolding. We report three adolescents who developed severe non-cardiogenic PE within 2 days of renal transplantation. Methods:, Pretransplant cardiorespiratory evaluation was normal in all cases. Transplant immunosuppression consisted of basiliximab induction, corticosteroids, and tacrolimus. Patients received standard fluid management during and after the transplant surgery. Case reports:, Patients 1 and 2 were 17- and 21-yr-old females. Pretransplant Hct values were 35 and 25% respectively. Each received 5-L normal saline during surgery. EBL was 200 and 500 mL in patients 1 and 2, respectively. There was immediate post-operative diuresis. Both developed non-cardiogenic PE by POD no. 2. BIPAP and PRVC were administered respectively. In both cases PE resolved within 1 wk. Patient 3 was a 19-yr-old male with pretransplant Hct of 43% who received a cadaveric renal transplant after 23.5-h cold-ischemia; 3.5 L normal saline was given during surgery. EBL was 100 mL. Non-cardiogenic PE ensued on POD no. 2 warranting assisted ventilation. The patient died following a sudden cardiopulmonary arrest on POD no. 3. Conclusions:, Potential mechanisms for the development of PE include cytokine release from basiliximab with increased capillary permeability, volume overload and ischemic-reperfusion injury. Improved awareness of this potential complication, prudent fluid management, and efforts to minimize graft-ischemia are recommended to prevent further cases. [source] Potential mechanisms of avian sex manipulationBIOLOGICAL REVIEWS, Issue 4 2003THOMAS W. PIKE ABSTRACT The aim of this review is to consider the potential mechanisms birds may use to manipulate the sex of their progeny, and the possible role played by maternal hormones. Over the past few years there has been a surge of reports documenting the ability of birds to overcome the rigid process of chromosomal sex determination. However, while many of these studies leave us in little doubt that mechanisms allowing birds to achieve this feat do exist, we are only left with tantalizing suggestions as to what the precise mechanism or mechanisms may be. The quest to elucidate them is made no easier by the fact that a variety of environmental conditions have been invoked in relation to sex manipulation, and there is no reason to assume that any particular mechanism is conserved among the vast diversity of species that can achieve it. In fact, a number of intriguing proposals have been put forward. We begin by briefly reviewing some of the most recent examples of this phenomenon before highlighting some of the more plausible mechanisms, drawing on recent work from a variety of taxa. In birds, females are the heterogametic sex and so non-Mendelian segregation of the sex chromosomes could conceivably be under maternal control. Another suggestion is that follicles that ultimately give rise to males and females grow at different rates. Alternatively, the female might selectively abort embryos or,dump lay'eggs of a particular sex, deny certain ova a chance of ovulation, fertilization or zygote formation, or selectively provision eggs so that there is sex-specific embryonic mortality. The ideas outlined in this review provide good starting points for testing the hypotheses both experimentally (behaviourally and physiologically) and theoretically. [source] Co-inheritance of ,+ -thalassaemia and sickle trait results in specific effects on haematological parametersBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2006Sammy Wambua Abstract Both the sickle cell trait (HbAS) and ,+ -thalassaemia are common in many tropical areas. While their individual haematological effects are well described, few studies describe their effects when inherited together. We present data from the Kenyan coast, which suggest that HbAS and ,+ -thalassaemia may interact to produce specific effects on haematological parameters. Overall, the difference in Hb concentrations between non-thalassaemics (,,/,,) and ,+ -thalassaemia homozygotes (,,/,,) was greater in non-HbAS (HbAA) (0·63 g/dl) than in HbAS children (0·25 g/dl). HbAS also ameliorated both the reduced mean cell volume and mean cell haemoglobin normally associated with the ,,/,, genotype. Potential mechanisms and implications are discussed. [source] Alcohol , the neglected risk factor in head and neck cancerCLINICAL OTOLARYNGOLOGY, Issue 4 2004H. Viswanathan Alcohol remains second only to cigarette smoking as a risk factor for head and neck cancer worldwide. The increase in incidence in head and neck cancer in a number of countries appears linked at least in part to contemporaneous rises in alcohol consumption. The relative increase in risk in women may also relate to increasing alcohol consumption. Women may be particularly sensitive to alcohol-induced tumours in the oral/oropharyngeal sites. The risk is dose related, but with a non-linear increase for heavy drinkers (>100 g i.e. 12 units/day). The type of alcoholic beverage consumed seems less important. Potential mechanisms include local toxic cellular proliferation; carcinogenic action of metabolites e.g. acetaldehyde or impurities; induction of enzymes which activate procarcinogens; reduction of the protective retinoic acid; genetic polymorphism may play a part in certain geographic locations. Alcohol is also linked to stage at presentation, risk of second primary and the occurrence of comorbidity. Public awareness of the risks of alcohol remains disappointingly low. Those in identifiable high-risk groups should perhaps be targeted specifically for counselling. [source] Anoxia,ischemia: A mechanism of seizure termination in ictal asystoleEPILEPSIA, Issue 1 2010Stephan U. Schuele Summary Cerebral anoxia,ischemia (CAI) is a potent inhibitor of cerebral hyperactivity and a potential mechanism of seizure self-termination. Prolonged ictal asystole (IA) invariably leads to CAI and has been implicated as a potential cause of sudden unexplained death in epilepsy (SUDEP). IA was seen in eight consecutive patients (0.12% of all patients monitored). Ten of their seizures with IA had evidence of CAI on electroencephalography (EEG), manifested by bilateral hypersynchronous slowing (BHS), and were compared to 18 seizures without signs of CAI. The ictal EEG pattern resolved in all 10 CAI events with onset of the BHS. The period from IA onset to seizure end was reduced in events with BHS compared to events without BHS (10.5 s vs. 28.3 s, respectively; p = 0.005), and the total seizure duration tended to be shorter. Anoxia,ischemia as a result of IA may represent an effective endogenous mechanism for seizure termination and may explain why the hearts of patients with ictal asystole reported to date in the literature resumed beating spontaneously. [source] Expression of the Multidrug Transporter P-glycoprotein in Brain Capillary Endothelial Cells and Brain Parenchyma of Amygdala-kindled RatsEPILEPSIA, Issue 7 2002Ulrike Seegers Summary: ,Purpose: Based on data from brain biopsy samples of patients with pharmacoresistant partial epilepsy, overexpression of the multidrug transporter P-glycoprotein (PGP) in brain capillary endothelium has recently been proposed as a potential mechanism of resistance to antiepileptic drugs (AEDs). We examined whether PGP is overexpressed in brain regions of amygdala-kindled rats, a widely used model of temporal lobe epilepsy (TLE), which is often resistant to AEDs. Methods: Rats were kindled by stimulation of the basolateral amygdala (BLA); electrode-implanted but nonkindled rats and naive (not implanted) rats served as controls. PGP was determined by immunohistochemistry either 1 or 2 weeks after the last kindled seizure, by using a monoclonal anti-PGP antibody. Six brain regions were examined ipsi- and contralateral to the BLA electrode: the BLA, the hippocampal formation, the piriform cortex, the substantia nigra, the frontal and parietal cortex, and the cerebellum. Results: In both kindled rats and controls, PGP staining was observed mainly in microvessel endothelial cells and, to a much lesser extent, in parenchymal cells. The distribution of PGP expression across brain regions was not homogeneous, but significant differences were found in both the endothelial and parenchymal expression of this protein. In kindled rats, ipsilateral PGP expression tended to be higher than contralateral expression in several brain regions, which was statistically significant in the piriform cortex and parietal cortex. However, compared with controls, no significant overexpression of PGP in capillary endothelial cells or brain parenchyma of kindled rats was seen in any ipsilateral brain region, including the BLA. For comparison with kindled rats, kainate-treated rats were used as positive controls. As reported previously, kainate-induced seizures significantly increased PGP expression in the hippocampus and other limbic brain regions. Conclusions: Amygdala-kindling does not induce any lasting overexpression of PGP in several brain regions previously involved in the kindling process. In view of the many pathophysiologic and pharmacologic similarities between the kindling model and TLE, these data may indicate that PGP overexpression in pharmacoresistant patients with TLE is a result of uncontrolled seizures but not of the processes underlying epilepsy. It remains to be determined whether transient PGP overexpression is present in kindled rats shortly after a seizure, and whether pharmacoresistant subgroups of kindled rats exhibit an increased expression of PGP. Furthermore, other multidrug transporters, such as multidrug resistance,associated protein, might be involved in the resistance of kindled rats to AEDs. [source] The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002H.-G. Yu Summary Background Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. Materials and Methods After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. Results ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. Conclusion Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells. [source] Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppressionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007Mariela Segura Abstract To determine whether helminth-derived products modulate dendritic cell (DC) function, we investigated the effects of excretory-secretory products (ES) and adult worm homogenate (AWH) derived from the gastrointestinal nematode Heligmosomoides polygyrus (Hp) on murine bone marrow-derived DC (BMDC). Compared to the TLR9 ligand CpG, Hp-derived products alone failed to induce DC activation. ES, but not AWH, inhibited BMDC cytokine and chemokine production and co-stimulatory molecule expression (CD40, CD86 and MHC class,II) induced by TLR ligation. TLR ligand-independent, PMA-induced DC activation was unaffected by ES. Recipients of ES-treated BMDC pulsed with OVA had suppressed Ab responses in vivo, irrespective of the Th1 or Th2 isotype affiliation, compared to recipients of control OVA-pulsed BMDC. Importantly, suppression occurred even in the presence of the potent type,1 adjuvant CpG. In contrast to untreated OVA-pulsed BMDC, ES-treated BMDC pulsed with OVA had reduced co-stimulatory molecule and cytokine expression. CD4+CD25+Foxp3, T cells, which secreted high IL-10 levels, were generated in co-cultures of OT-II OVA-specific TCR-transgenic CD4+ T cells and ES-treated BMDC. These IL-10-secreting T cells suppressed effector CD4+ T cell proliferation and IFN-, production, the latter effect mediated by an IL-10-dependent mechanism. Together, these results demonstrate that nematode ES impaired DC function and suppressed both Th1 and Th2 adaptive immune responses possibly by inducing regulatory T cells. [source] Muscarinic control of graded persistent activity in lateral amygdala neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Alexei V. Egorov Abstract The cholinergic system is crucially involved in several cognitive processes including attention, learning and memory. Muscarinic actions have profound effects on the intrinsic firing pattern of neurons. In principal neurons of the entorhinal cortex (EC), muscarinic receptors activate an intrinsic cation current that causes multiple self-sustained spiking activity, which represents a potential mechanism for transiently sustaining information about novel items. The amygdala appears to be important for experience-dependent learning by emotional arousal, and cholinergic muscarinic influences are essential for the amygdala-mediated modulation of memory. Here we show that principal neurons from the lateral nucleus of the amygdala (LA) can generate intrinsic graded persistent activity that is similar to EC layer V cells. This firing behavior is linked to muscarinic activation of a calcium-sensitive non-specific cation current and can be mimicked by stimulation of cholinergic afferents that originate from the nucleus basalis of Meynert (n. M). Moreover, we demonstrate that the projections from the n. M. are essential and sufficient for the control and modulation of graded firing activity in LA neurons. We found that activation of these cholinergic afferents (i) is required to maintain and to increase firing rates in a graded manner, and (ii) is sufficient for the graded increases of stable discharge rates even without an associated up-regulation of Ca2+. The induction of persistent activity was blocked by flufenamic acid or 2-APB and remained intact after Ca2+ -store depletion with thapsigargin. The internal ability of LA neurons to generate graded persistent activity could be essential for amygdala-mediated memory operations. [source] Acute signalling responses to intense endurance training commenced with low or normal muscle glycogenEXPERIMENTAL PHYSIOLOGY, Issue 2 2010Wee Kian Yeo We have previously demonstrated that well-trained subjects who completed a 3 week training programme in which selected high-intensity interval training (HIT) sessions were commenced with low muscle glycogen content increased the maximal activities of several oxidative enzymes that promote endurance adaptations to a greater extent than subjects who began all training sessions with normal glycogen levels. The aim of the present study was to investigate acute skeletal muscle signalling responses to a single bout of HIT commenced with low or normal muscle glycogen stores in an attempt to elucidate potential mechanism(s) that might underlie our previous observations. Six endurance-trained cyclists/triathletes performed a 100 min ride at ,70% peak O2 uptake (AT) on day 1 and HIT (8 × 5 min work bouts at maximal self-selected effort with 1 min rest) 24 h later (HIGH). Another six subjects, matched for fitness and training history, performed AT on day 1 then 1,2 h later, HIT (LOW). Muscle biopsies were taken before and after HIT. Muscle glycogen concentration was higher in HIGH versus LOW before the HIT (390 ± 28 versus 256 ± 67 ,mol (g dry wt),1). After HIT, glycogen levels were reduced in both groups (P < 0.05) but HIGH was elevated compared with LOW (229 ± 29 versus 124 ± 41 ,mol (g dry wt),1; P < 0.05). Phosphorylation of 5,AMP-activated protein kinase (AMPK) increased after HIT, but the magnitude of increase was greater in LOW (P < 0.05). Despite the augmented AMPK response in LOW after HIT, selected downstream AMPK substrates were similar between groups. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was unchanged for both groups before and after the HIT training sessions. We conclude that despite a greater activation AMPK phosphorylation when HIT was commenced with low compared with normal muscle glycogen availability, the localization and phosphorylation state of selected downstream targets of AMPK were similar in response to the two interventions. [source] Leptin receptor 170 kDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistanceEXPERIMENTAL PHYSIOLOGY, Issue 1 2010T. Fuentes To examine whether obesity-associated leptin resistance could be due to down-regulation of leptin receptors (OB-Rs) and/or up-regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2-dependent leptin signalling and signal transducer and activator of transcription 3 (STAT3) phosphorylation and reduce AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) phosphorylation. Deltoid and vastus lateralis muscle biopsies were obtained from 20 men: 10 non-obese control subjects (mean ±s.d. age, 31 ± 5 years; height, 184 ± 9 cm; weight, 91 ± 13 kg; and percentage body fat, 24.8 ± 5.8%) and 10 obese (age, 30 ± 7 years; height, 184 ± 8 cm; weight, 115 ± 8 kg; and percentage body fat, 34.9 ± 5.1%). Skeletal muscle OB-R170 (OB-R long isoform) protein expression was 28 and 25% lower (both P < 0.05) in arm and leg muscles, respectively, of obese men compared with control subjects. In normal-weight subjects, SOCS3 protein expression, and STAT3, AMPK, and ACC, phosphorylation, were similar in the deltoid and vastus lateralis muscles. In obese subjects, the deltoid muscle had a greater amount of leptin receptors than the vastus lateralis, whilst SOCS3 protein expression was increased and basal STAT3, AMPK, and ACC, phosphorylation levels were reduced in the vastus lateralis compared with the deltoid muscle (all P < 0.05). In summary, skeletal muscle leptin receptors and leptin signalling are reduced in obesity, particularly in the leg muscles. [source] Offspring performance and the adaptive benefits of prolonged pregnancy: experimental tests in a viviparous lizardFUNCTIONAL ECOLOGY, Issue 4 2009Geoffrey M While Summary 1Offspring locomotor performance has been shown to influence fitness related traits in a wide range of taxa. One potential mechanism by which viviparous animals can increase the performance (e.g. sprint speed) of their offspring is by prolonging pregnancy (beyond that required for complete development). However, to date studies examining this potentially important maternal effect have been largely descriptive. 2The skink Egernia whitii is an ideal candidate species to examine the consequences of delayed parturition on the performance of offspring as it routinely gives birth asynchronously despite synchronous offspring development. 3Using correlative data from a natural population and experimental manipulations of birthing asynchrony, we tested the prediction that, within litters, last born offspring have a better locomotor performance than first born offspring. 4We show that prolonged pregnancy does significantly influence average offspring locomotor performance; however, contrary to predictions, the direction of this effect is dependent on gestation length and thus offspring date of birth. Last born offspring had significantly poorer performance than first born offspring in litters early in the season with this pattern reversed late in the season. 5These results do not support the hypothesis that prolonged retention of fully formed offspring consistently increases offspring performance; however, they may help us understand the asymmetries in offspring competitive ability generated by birthing asynchrony. [source] Territorial behaviour and immunity are mediated by juvenile hormone: the physiological basis of honest signalling?FUNCTIONAL ECOLOGY, Issue 1 2009Jorge Contreras-Garduño Summary 1The role of the juvenile hormone (JH) as a potential mediator in the trade-off between male,male competition and immune response has not been tested, but its study could reveal a potential mechanism that mediates resource allocation between these two traits. 2Controlling for body size, we tested whether males of the territorial damselfly Calopteryx virgo administrated with methoprene acid, an analog of the JH (JHa), compared to control males, increased their aggression and occupation time on territories but decreased their phenoloxidase (PO) activity (a key enzyme used during immune response after a bacterial challenge). We found an increase in aggression in JHa treated males compared to control males, but the opposite was found for PO activity. 3As fat load and muscle mass are also important traits during a contest, we tested whether JHa males compared to control males showed more fat and muscle content 2 h after JHa administration. Our results did not show a significant difference between both male groups, suggesting that JHa only increased aggression. 4These results and a review of other published articles, which have documented an effect of JH on a variety of functions in insects, suggest that JH may be a target of sexual selection: this hormone not only promotes the expression of secondary sexual characters but also seems condition-dependent and so its titers may indicate male condition. [source] Accelerating seismicity of moderate-size earthquakes before the 1999 Chi-Chi, Taiwan, earthquake: Testing time-prediction of the self-organizing spinodal model of earthquakesGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 1 2003Chien-chih Chen SUMMARY Seismic activation of moderate-size earthquakes for the 1999 Chi-Chi, Taiwan, earthquake has been found. A self-organizing spinodal (SOS) model can explain some observations concerning seismic activation, but the equal time durations of the mid and precursory periods during an earthquake cycle conjectured in the original, published, SOS model have not been supported in this case. The Chi-Chi test presented here shows unequal time durations of the mid and precursory periods of an earthquake cycle. This, in turn, makes the possibility of time prediction of a characteristic earthquake impossible in the context of the SOS model. In addition, comparisons with numerical simulations of the sliding-block model suggest the change in the system's stiffness is a potential mechanism of seismic activation. [source] Surfactant-Assisted Synthesis of Alumina with Hierarchical NanoporesADVANCED FUNCTIONAL MATERIALS, Issue 1 2003W. Deng Abstract Using surfactant-assisted synthesis, aluminas with hierarchical nanopores are produced. The hierarchical structures are composed of mesopores of 4 nm diameter, and macropores with diameters of about 300 nm. The structures were found to be stable to the thermal removal of the surfactant. Synthesis factors affecting the appearance of the hierarchically structured alumina material are presented. A potential mechanism for the formation of the uniquely structured aluminas is proposed. [source] Enhanced expression of vascular endothelial growth factor-A in ground glass hepatocytes and its implication in hepatitis B virus hepatocarcinogenesis,HEPATOLOGY, Issue 6 2009Jui-Chu Yang Ground glass hepatocytes (GGH) in chronic hepatitis B virus (HBV) infection harbor HBV pre-S deletion mutants in endoplasmic reticulum (ER) and exhibit complex biologic features such as ER stress, DNA damage, and growth advantage. The presence of pre-S mutants in serum has been shown to predict the development of hepatocellular carcinoma (HCC) in HBV carriers. GGHs hence represent a potentially preneoplastic lesion. Whether a specific growth factor is overexpressed and activated in GGHs remains to be clarified. In this study, growth factor(s) up-regulated by pre-S mutants was identified using a growth factor array in HuH-7 cells. Immunohistochemistry, reverse-transcriptase polymerase chain reaction, and Western blot analysis were performed to study the participation of these genes and their signal pathways in HuH-7 cells and liver tissues. We demonstrate that vascular endothelial growth factor-A (VEGF-A) was up-regulated by pre-S mutants in HuH-7 cells and further confirmed in GGHs by immunostaining. The VEGF-A up-regulation by pre-S mutants could be suppressed by vomitoxin, an ER stress inhibitor. Furthermore, pre-S mutants-expressed HuH-7 cells exhibited activation of Akt/mTOR (mammalian target of rapamycin) signaling and increased growth advantage, which could be inhibited by VEGF-A neutralization. Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling, comparable to the levels of paired HCC tissues, were also detected in HBV-related nontumorous livers. Conclusion: The enhanced expression of VEGF-A in GGHs provides potential mechanism to explain the progression from preneoplastic GGHs to HCC in chronic HBV infection. (HEPATOLOGY 2009;49:1962,1971.) [source] | ||||||||||||||||||||||||||||||||||||||||