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Marked Decrease (marked + decrease)
Selected AbstractsImpact of the heroin ,drought' on patterns of drug use and drug-related harmsDRUG AND ALCOHOL REVIEW, Issue 2 2004Dr MARIE C. LONGO Senior Research Officer Abstract Since late 2000, anecdotal reports from drug users and health professionals have suggested that there was a reduction in the supply of heroin in Adelaide in the first half of 2001, referred to as a heroin ,drought'. The aim of this paper was to critically review evidence for this, using data obtained from 100 injecting drug users surveyed for the 2001 Illicit Drug Reporting System (IDRS). This project is carried out annually in all Australian jurisdictions, and collects up-to-date information on the markets for heroin, methamphetamine, cocaine and cannabis. This paper also investigates the possible implications of this ,drought' on patterns of drug use and drug-related harms. The 2001 IDRS found consistent reports by users of an increase in the price of heroin, together with decreases in purity and availability. These factors resulted in a decrease in the frequency of self-reported heroin use among those surveyed in 2001, and a concomitant increase in the use of other drugs, in particular methamphetamine and morphine. The heroin ,drought' appears to have had a substantial impact on several indices of drug-related harm. There was a marked decrease in the number of opioid-related fatalities, and hospital data also showed reductions in heroin-related presentations. Treatment service data showed an increase in the number of admissions related to amphetamines. There is a need for health promotion and education on the adverse effects of methamphetamine use, and the development of improved treatment protocols for methamphetamine abuse and dependence. [source] The Effect of Beta-Blocker (Carvedilol) Therapy on N-Terminal Pro-Brain Natriuretic Peptide Levels and Echocardiographic Findings in Patients with Congestive Heart FailureECHOCARDIOGRAPHY, Issue 2 2007Fuat Gundogdu M.D. Background: The favorable effects of beta-blockers on decreasing mortality in contemporary heart failure management have been demonstrated in recent years. N-terminal pro-brain natriuretic (NT-proBNP) peptide levels increase in patients with heart failure. The purpose of this study was to investigate the correlation between the NT-proBNP levels and echocardiographic findings for the patients who received carvedilol therapy in addition to standard therapy for congestive heart failure. Methods and Results: A total of 25 patients with symptomatic congestive heart failure and 25 healthy individuals were enrolled in the study. Before introducing beta-blocker into their therapy regimens, baseline transthoracic echocardiography recordings were made and venous blood samples were drawn for establishing NT-proBNP levels. The patients were administered with a minimum dose of carvedilol. Three months after reaching the maximum tolerable dose, blood samples were drawn from the patients once again for NT-proBNP measurements, and transthoracic echocardiography was performed. There was a significant drop in plasma NT-proBNP levels at the end of the study in comparison to the baseline values (baseline: 381.20±35.06 pg/mL, at the end of the third month: 254.44±28.64 pg/mL; P < 0.001). While left ventricular end-diastolic and end-systolic diameters were observed to have significantly decreased as a result of the therapy (P < 0.001), left ventricular ejection fraction (P<0.001) was established to have increased significantly. Conclusions: Carvedilol therapy resulted in a marked decrease in plasma NT-proBNP levels and increase left ventricular ejection fraction in patients with congestive heart failure. [source] Mothers reduce egg provisioning with ageECOLOGY LETTERS, Issue 4 2003David Giron Abstract Precise and comprehensive data on resource allocation into individual eggs are rare and this empirical void in the literature of life history strategies contrasts with the large number of theoretical studies. We show a marked decrease in reproductive investment in eggs with mother's age for egg size, sugar, protein, lipid and energy contents of eggs for a parasitic wasp. Egg size is a good predictor of offspring fitness, measured as survival of starving neonate larvae, but does not reveal possible biochemical changes. Lipids stabilize quickly at a minimal threshold while proteins and sugars decrease smoothly down to about 30% of the amount invested in the first egg. Because proteins have the highest correlation with egg size, we predict that they should be better predictors of larval fitness than lipids and sugars. Assessing the adaptive value of the observed patterns will require a multidimensional approach to egg provisioning. [source] Multiple Subpial Transections: The Yale ExperienceEPILEPSIA, Issue 2 2001Lisa P. Mulligan Summary: ,Purpose: Although resection of an epileptogenic region is the mainstay of epilepsy surgery, epileptogenic areas in functionally critical cortex cannot be approached in that manner. Multiple subpial transection (MST) was developed to treat those refractory seizures without causing unacceptable neurologic deficit. We review our experience with this technique. Methods: Twelve patients who underwent MST with or without resection between 1990 and 1998 were retrospectively reviewed with regard to seizure and neurologic outcome, and predictive factors. Results: Five (42%) of 12 patients obtained a significant improvement in seizure frequency, and two other patients had a marked decrease in the severity of their seizures. Resection with MST reduced seizure frequency more, but this was not a significant difference. No predictive factors for outcome were identified. Only one patient sustained any persistent neurologic deficit. Conclusions: In selected patients, MST may be a viable alternative when the epileptogenic focus lies in unresectable cortex. A multicenter study with appreciable patient numbers will be necessary to define predictive factors for success. [source] SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARSEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2009G. Y. Oudit Abstract Background, Angiotensin converting enzyme 2 (ACE2), a monocarboxylase that degrades angiotensin II to angiotensin 1,7, is also the functional receptor for severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and is highly expressed in the lungs and heart. Patients with SARS also suffered from cardiac disease including arrhythmias, sudden cardiac death, and systolic and diastolic dysfunction. Materials and methods, We studied mice infected with the human strain of the SARS-CoV and encephalomyocarditis virus and examined ACE2 mRNA and protein expression. Autopsy heart samples from patients who succumbed to the SARS crisis in Toronto (Canada) were used to investigate the impact of SARS on myocardial structure, inflammation and ACE2 protein expression. Results, Pulmonary infection with the human SARS-CoV in mice led to an ACE2-dependent myocardial infection with a marked decrease in ACE2 expression confirming a critical role of ACE2 in mediating SARS-CoV infection in the heart. The SARS-CoV viral RNA was detected in 35% (7/20) of autopsied human heart samples obtained from patients who succumbed to the SARS crisis during the Toronto SARS outbreak. Macrophage-specific staining showed a marked increase in macrophage infiltration with evidence of myocardial damage in patients who had SARS-CoV in their hearts. The presence of SARS-CoV in the heart was also associated with marked reductions in ACE2 protein expression. Conclusions, Our data show that SARS-CoV can mediate myocardial inflammation and damage associated with down-regulation of myocardial ACE2 system, which may be responsible for the myocardial dysfunction and adverse cardiac outcomes in patients with SARS. [source] IP3 receptor in the hair cells of frog semicircular canal and its possible functional roleEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Maria Lisa Rossi Abstract The presence and functional role of inositol trisphosphate receptors (IP3R) was investigated by electrophysiology and immunohistochemistry in hair cells from the frog semicircular canal. Intracellular recordings were performed from single fibres of the posterior canal in the isolated, intact frog labyrinth, at rest and during rotation, in the presence of IP3 receptor inhibitors and drugs known to produce Ca2+ release from the internal stores or to increase IP3 production. Hair cell immunolabelling for IP3 receptor was performed by standard procedures. The drug 2-aminoethoxydiphenyl borate (2APB), an IP3 receptor inhibitor, produced a marked decrease of mEPSP and spike frequency at low concentration (0.1 mm), without affecting mEPSP size or time course. At high concentration (1 mm), 2APB is reported to block the sarcoplasmic-endoplasmic reticulum Ca2+ -ATPase (SERCA pump) and increase [Ca2+]i; at the labyrinthine cytoneural junction, it greatly enhanced the resting and mechanically evoked sensory discharge frequency. The selective agonist of group I metabotropic glutamate receptors (RS)-3,5-dihydroxyphenylglycine (DHPG, 0.6 mm), produced a transient increase in resting mEPSP and spike frequency at the cytoneural junction, with no effects on mEPSP shape or amplitude. Pretreatment with cyclopiazonic acid (CPA, 0.1 mm), a SERCA pump inhibitor, prevented the facilitatory effect of both 2APB and DHPG, suggesting a link between Ca2+ release from intracellular stores and quantal emission. Consistently, diffuse immunoreactivity for IP3 receptors was observed in posterior canal hair cells. Our results indicate the presence and a possibly relevant functional role of IP3-sensitive stores in controlling [Ca2+]i and modulating the vestibular discharge. [source] Changes in signaling pathways regulating neuroplasticity induced by neurokinin 1 receptor knockoutEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005Laura Musazzi Abstract Neurokinin 1 (NK-1) receptor knockout mice showed behavioral responses similar to animals chronically treated with antidepressants. The aim of this study was to analyse, in NK-1 receptor knockout, the molecular modifications of signaling pathways involved in the pathophysiology of depression and antidepressant mechanism. We found, in total cell cytosol from the prefrontal/frontal cortex, hippocampus and striatum, a marked up-regulation of Ca2+ -independent enzymatic activity and Thr286 autophosphorylation of Ca2+/calmodulin-dependent protein kinase (CaMK) II. Similar changes in CaMKII regulation were previously observed in rats chronically treated with antidepressants. In striatum, up-regulation of the activity and phosphorylation of CaMKII was also found in the homogenate and synaptosomes. No major changes were observed in the Ca2+ -dependent kinase activity, with the exception of homogenate from the prefrontal/frontal cortex. We also analysed the expression and phosphorylation of presynaptic proteins, which modulate synaptic vesicle trafficking and exocytosis, and found a marked decrease in synapsin I total expression and basal phosphorylation of Ser603 (the phosphorylation site for CaMKII) in the prefrontal/frontal cortex. Accordingly, the Ca2+/calmodulin-dependent posthoc endogenous phosphorylation of synapsin I in the same area was increased. The knockout of NK-1 receptor had no consequences on the expression or phosphorylation levels of the transcription factor cAMP-responsive element-binding protein and its regulating kinase CaMKIV. However, phosphorylation of ERK1/2-mitogen-activated protein kinases was reduced in the hippocampus and striatum, again resembling an effect previously observed in antidepressant-treated rats. These results show similarities between NK-1 knockouts and animals chronically treated with antidepressants and support the putative antidepressant activity of NK-1 receptor antagonists. [source] Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighboursEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Janet R. Keast Abstract In rats, following lesion of lumbar or sacral preganglionic axons, many pelvic ganglion cells undergo axogenesis to form baskets of terminals around select populations of nearby ganglion cells. The aim of the current study was to address mechanisms underlying initiation of this sprouting, focusing on a possible role for nerve growth factor (NGF). Immunohistochemical localization of NGF receptors (trkA and p75) showed that virtually all noradrenergic and a minority of cholinergic pelvic neurons expressed both receptors. Terminals immunoreactive for each substance were found in pelvic viscera. In pelvic ganglia, many glial cells expressed p75 but not trkA, and very few lumbar or sacral preganglionic neurons expressed either receptor. Lumbar and/or sacral preganglionic inputs were removed from ganglion cells by cutting the hypogastric, pelvic or both nerves, and tissues analysed 8 days later. Levels of receptor expression in noradrenergic pelvic ganglion cells were estimated by calculating the proportion that were receptor-immunopositive, and quantifying the intensity of trkA or p75 immunofluorescence. No lesion had a significant effect on trkA expression, however, a marked decrease in p75 occurred after cutting pelvic nerves, i.e. after deafferentation of neighbouring cholinergic neurons. These injuries appeared to cause little overall change in glial p75 expression. This study shows that manipulations that trigger sprouting from noradrenergic pelvic neurons cause downregulation of p75 but not trkA. Interestingly, this is occurring while some of their target organs are synthesizing high levels of NGF. This contrasts with other NGF-sensitive cells, in which one or both receptor types are upregulated by increased exposure to the ligand. The current study is also the first to show a change in p75 expression in neurons that are neither deafferented nor axotomized. [source] Inhibition of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression reduces dopaminergic sprouting in the injured striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2000P. E. Batchelor Abstract After striatal injury, sprouting dopaminergic fibres grow towards and intimately surround wound macrophages which, together with microglia, express the dopaminergic neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). To evaluate the importance of these endogenously secreted neurotrophic factors in generating striatal peri-wound dopaminergic sprouting, the peri-wound expression of BDNF or GDNF was inhibited by intrastriatal infusion of antisense oligonucleotides for 2 weeks in mice. Knock-down of both BDNF and GDNF mRNA and protein levels in the wounded striatum were confirmed by in situ hybridization and enzyme-linked immunosorbent assay, respectively. Dopamine transporter immunohisto-chemistry revealed that inhibition of either BDNF or GDNF expression resulted in a marked decrease in the intensity of peri-wound sprouting. Quantification of this effect using [H3]-mazindol autoradiography confirmed that peri-wound sprouting was significantly reduced in mice receiving BDNF or GDNF antisense infusions whilst control infusions of buffered saline or sense oligonucleotides resulted in the pronounced peri-wound sprouting response normally associated with striatal injury. BDNF and GDNF thus appear to be important neurotrophic factors inducing dopaminergic sprouting after striatal injury. [source] Fate of airborne metal pollution in soils as related to agricultural management.EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 3 2007Summary The fate of airborne metal pollutants in soils is still relatively unknown. We studied the incorporation of such airborne metal pollution in two soils under long-term permanent pasture (PP) and conventional arable land (CA). Both soils were located at an almost equal distance from a former zinc smelter complex and developed under comparable pedogenetic conditions. Profiles of total concentrations of Zn, chosen as a mobile, and Pb as a little- or non-mobile element, were examined and compared with macro- and micromorphological soil characteristics (soil colour, biological activity). The two soils showed different profiles of total Zn and Pb concentrations, with a marked decrease of concentrations of both elements under the plough layer in CA, whereas the decrease was more progressive in PP. However, the stocks of Zn and Pb for the 1-m soil profiles of CA and PP were comparable. Correlation of Zn and Pb concentration at different depths with total Fe contents and comparison with estimated data for the local geochemical background (LGCB), suggests transport of Zn from the surface to depth in CA and PP, and Pb movement in PP. In CA, 53% of Zn and 92.5% of Pb stocks derived from airborne metal pollution were located at depths < 26 cm. In PP, only 40% of Zn and 82% of Pb, derived from airborne pollution, were found in the A11 and A12 horizons (< 26 cm), the remaining 18% of the Pb stock being incorporated until 50 cm depth; one-third of total Zn stock ascribed to airborne pollution was found at depths > 50 cm. Studies of the composition of gravitational water collected in soils from the same study area suggest two mechanisms for metal movement. First, mobile metal ions (Zn2+) move in the soil solution and are intercepted by iron-clay complexes in deeper soil horizons. Second, observed only in PP, simultaneous movement of Zn and Pb is ascribed to bioturbation by earthworms. [source] Interferon-, and lipopolysaccharide regulate the expression of Nramp2 and increase the uptake of iron from low relative molecular mass complexes by macrophagesFEBS JOURNAL, Issue 22 2000S. L. Wardrop The natural resistance associated macrophage protein 2 (Nramp2) is a transporter that is involved in iron (Fe) uptake from transferrin (Tf) and low molecular mass Fe complexes. Here we describe the effect of the inflammatory mediators interferon-, (IFN-,) and lipopolysaccharide (LPS) on the expression of Nramp2 mRNA and Fe uptake by cells of the macrophage lineage. After incubation of the RAW264.7 macrophage cell line with LPS there was a sevenfold increase in the expression of the 2.3 kb Nramp2 mRNA transcript when compared with the control, but little effect on the Nramp2 3.1 kb transcript. These results indicate differential regulation of the two transcripts. Treatment with LPS resulted in an increase in 59Fe uptake from 59Fe,nitrilotriacetic acid, while transferrin receptor (TfR) mRNA levels and 59Fe uptake from 59Fe,Tf were decreased. Paradoxically, at the same time, an increase in iron regulatory protein (IRP)1 RNA-binding activity was observed. Incubation with IFN-, (50 U·mL,1) resulted in a marked decrease in TfR mRNA levels but had no effect on Nramp2 mRNA expression. Exposure of RAW264.7 cells to both IFN-, and LPS resulted in a fourfold increase in the Nramp2 2.3-kb transcript and a four to fivefold decrease in the 3.1-kb transcript when compared with the control. Furthermore, there was a decrease in TfR mRNA levels despite an increase in IRP1 RNA-binding activity and a marked increase in inducible nitric oxide synthase mRNA expression. Hence, TfR and Nramp2 mRNA expression did not appear to be regulated in a concerted manner. Similar responses to those found above for RAW264.7 cells were also observed in the J774 macrophage cell line and also for primary cultures of mouse peritoneal macrophages. These results are of interest as the TfR and Nramp2 are thought to act together during Fe uptake from Tf. This is the first report to demonstrate regulation of the Nramp2 mRNA transcripts by inflammatory mediators. [source] K+ influx by Kup in Escherichia coli is accompanied by a decrease in H+ effluxFEMS MICROBIOLOGY LETTERS, Issue 1 2001Ella Zakharyan Abstract Escherichia coli accumulates K+ by means of multiple uptake systems of which Kup is the major transport system at acidic pH. In cells grown under fermentative conditions at pH 5.5, K+ influx by a wild-type strain upon hyper-osmotic stress at pH 5.5 was accompanied by a marked decrease in H+ efflux, with a 1:1 ratio of K+ to H+ fluxes. This was observed with cells treated with N,N,-dicyclohexylcarbodiimide. Similar results with a mutant defective in Kdp and TrkA but with a functional Kup system but not in a mutant defective in Kdp and Kup but having an active TrkA system suggest that Kup operates as a H+,K+ -symporter. [source] A flammability performance comparison between synthetic and natural clays in polystyrene nanocompositesFIRE AND MATERIALS, Issue 4 2005Alexander B. Morgan Abstract Polymer-clay nanocomposites are a newer class of flame retardant materials of interest due to their balance of mechanical, thermal and flammability properties. Much more work has been done with natural clays than with synthetic clays for nanocomposite flammability applications. There are advantages and disadvantages to both natural and synthetic clay use in a nanocomposite, and some of these, both fundamental and practical, will be discussed in this paper. To compare natural and synthetic clays in regards to polymer flammability, two clays were used. The natural clay was a US mined and refined montmorillonite, while the synthetic clay was a fluorinated synthetic mica. These two clays were used as inorganic clays for control experiments in polystyrene, and then converted into an organoclay by ion exchange with an alkyl ammonium salt. The organoclays were used to synthesize polystyrene nanocomposites by melt compounding. Each of the formulations was analysed by X-ray diffraction (XRD), thermogravimetric analysis (TGA) and transmission electron microscopy (TEM). Flammability performance was measured by cone calorimeter. The data from the experiments show that the synthetic clay does slightly better at reducing the heat release rate (HRR) than the natural clay. However, all the samples, including the inorganic clay polystyrene microcomposites, showed a decreased time to ignition, with the actual nanocomposites showing the most marked decrease. The reason for this is postulated to be related to the thermal instability of the organoclay (via the quaternary alkyl ammonium). An additional experiment using a more thermally stable organoclay showed a time to ignition identical to that of the base polymer. Finally, it was shown that while polymer-clay nanocomposites (either synthetic or natural clay based) greatly reduce the HRR of a material, making it more fire safe, they do not provide ignition resistance by themselves, at least, at practical loadings. Specifically, the cone calorimeter HRR curve data appear to support that these nanocomposites continue to burn once ignited, rather than self-extinguish. Copyright © 2004 John Wiley & Sons, Ltd. [source] Effects of Distraction Versus Spatial Discrimination on Laser-Evoked Potentials in MigraineHEADACHE, Issue 3 2008Marina De Tommaso MD Objectives., To evaluate whether migraine patients exhibit less inhibition to painful stimuli when distracted from pain as compared to healthy subjects, testing the spatial discrimination of painful stimuli, the performance during the mental arithmetic task used to contrast the discrimination performance and the behavior of N1 and N2-P2 laser-evoked potentials (LEPs) amplitudes during spatial discrimination and during distraction. Methods., Eight migraine patients and 8 healthy controls were examined. During repetitive series of painful laser stimulation of the hand, they had to (1) perform a spatial discrimination task, contrasted by (2) a mental arithmetic task that served as distraction. Results., Patients made 50% to 100% more mistakes than controls in the spatial discrimination task (P < .001) as well as during mental arithmetic (P < .05). Whereas healthy subjects showed a marked decrease of the LEP vertex potential amplitudes during distraction compared to the discrimination task, no such attenuation of LEPs was seen in migraine patients (group × task interaction, P < .05). N1 amplitude exhibited a left-hemisphere dominance in both groups, significantly smaller amplitude in migraine patients, but no significant task modulation. Conclusion., Migraine patients exhibited reduced inhibition by attentional modulation of pain processing, accompanied by impaired spatial discrimination of painful stimuli. [source] Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterpartsINTERNATIONAL JOURNAL OF CANCER, Issue 7 2008Jean-Philippe Theurillat Abstract NY-BR-1 is a differentiation antigen and a potential target for cancer immunotherapy. Its mRNA expression is restricted to breast, testis, prostate and breast cancer by RT-PCR. In this study, we correlated NY-BR-1 protein and mRNA expression on tissue microarrays of mammary, prostatic and testicular malignancies using immunohistochemisty and in situ hybridization with probes for exon 4,7 and 30,33. NY-BR-1 mRNA was confined to primary spermatocytes, suggesting a role in spermatogenesis. Exon 4,7 and 30,33 were equally expressed this cell type. However, NY-BR-1 was absent in all germ cell tumours analyzed (n = 475) and present in one of 56 (2%) prostate carcinomas. In breast, NY-BR-1 mRNA expression was detected in 307 of 442 (70%) primary carcinomas, with strong correlation to its protein expression (p < 0.0001). mRNA expression was significantly stronger and more frequently detected by the exon 30,33 probe than by the exon 4,7 probe (70% vs. 35%, p < 0.0001), indicating the presence of alternative splice variants that lack 5-prime sequences. A similar restricted mRNA pattern was also observed in the normal breast epithelium. NY-BR-1 protein and mRNA correlated significantly with estrogen receptor , (ER,) protein expression (p < 0.0001), with stronger association to NY-BR-1 mRNA than protein (odds ratio 7.7 compared to 4.6). We identified 4 estrogen response elements (ERE)-like sequences nearby the promoter region, suggesting that NY-BR-1 transcription might be controlled by ER,. Accordingly, analysis of matching pairs of primary tumors with their recurrences showed a marked decrease of NY-BR-1 expression in recurrences after tamoxifen treatment (p < 0.0001). © 2007 Wiley-Liss, Inc. [source] Induction of cytotoxicity in human lung adenocarcinoma cells by 6- O -carboxypropyl-,-tocotrienol, a redox-silent derivative of ,-tocotrienolINTERNATIONAL JOURNAL OF CANCER, Issue 5 2005Yoshihisa Yano Abstract Tocotrienols are one of the most potent anticancer agents of all natural compounds and the anticancer property may be related to the inactivation of Ras family molecules. The anticancer potential of tocotrienols, however, is weakened due to its short elimination half life in vivo. To overcome the disadvantage and reinforce the anticancer activity in tocotrienols, we synthesized a redox-silent analogue of ,-tocotrienol (T3), 6- O -carboxypropyl-,-tocotrienol (T3E). We estimated the possibility of T3E as a new anticancer agent against lung adenocarcinoma showing poor prognosis based on the mutation of ras gene. T3E showed cytotoxicity against A549 cells, a human lung adenocarcinoma cell line with a ras gene mutation, in a dose-dependent manner (0,40 ,M), whereas T3 and a redox-silent analogue of ,-tocopherol (T), 6- O -carboxypropyl-,-tocopherol (TE), showed much less cytotoxicity in cells within 40 ,M. T3E cytotoxicity was based on the accumulation of cells in the G1-phase of the cell-cycle and the subsequent induction of apoptosis. Similar to this event, 24-hr treatment of A549 cells with 40 ,M T3E caused the inhibition of Ras farnesylation, and a marked decrease in the levels of cyclin D required for G1/S progression in the cell-cycle and Bcl-xL, a key anti-apoptotic molecule. Moreover, the T3E-dependent inhibition of RhoA geranyl-geranylation is an inducing factor for the occurrence of apoptosis in A549 cells. Our results suggest that T3E suppresses Ras and RhoA prenylation, leading to negative growth control against A549 cells. In conclusion, a redox-silent analogue of T3, T3E may be a new candidate as an anticancer agent against lung adenocarcinoma showing poor prognosis based on the mutation of ras genes. © 2005 Wiley-Liss, Inc. [source] Aberrant p53 alters DNA damage checkpoints in response to cisplatin: Downregulation of CDK expression and activityINTERNATIONAL JOURNAL OF CANCER, Issue 5 2004Katharine H. Wrighton Abstract The p53 tumor suppressor protein is a critical mediator of cell cycle arrest and apoptosis in response to genotoxic stress. Abrogation of p53 function is a major feature of tumor development and may result in a compromised DNA-damage response. In our study, we examined the effect of expressing a human p53 cDNA, encoding a histidine to leucine amino acid substitution at codon 179 (H179L), on the ability of wild-type p53-containing NIH3T3 cells to respond to treatment with the chemotherapeutic cisplatin. After 72 hr of cisplatin treatment control cells underwent apoptosis preceded by a combination of S- and G2 arrest, as judged by flow cytometry of propidium iodide-stained cells, and TUNEL and caspase-3 assays. This correlated with increased expression of the pro-apoptotic protein Bax. In contrast, cells stably expressing H179L-p53 arrested in S-phase following cisplatin treatment, which correlated with a marked decrease in the expression of cdc2, cyclin B1 and cyclin A, and a decrease in CDK2 and cyclin A-associated kinase activity. Interestingly, H179L p53 expressing cells underwent apoptosis earlier than control cells, indicating that this aberrant p53 may enhance cisplatin chemosensitivity. These data suggest that dominant-negative p53 can influence the expression and activity of CDK complexes, thereby modifying cell behavior following cisplatin-induced genotoxicity. © 2004 Wiley-Liss, Inc. [source] ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastasesINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Laurent Candeil Abstract Overcoming drug resistance has become an important issue in cancer chemotherapy. Among all known mechanisms that confer resistance, active efflux of chemotherapeutic agents by proteins from the ATP-binding cassette family has been extensively reported. The aim of the present study was to determine the involvement of ABCG2 in resistance to SN38 (the active metabolite of irinotecan) in colorectal cancer. By progressive exposure to increasing concentrations of SN38, we isolated 2 resistant clones from the human colon carcinoma cell line HCT116. These clones were 6- and 53-fold more resistant to SN38 than the HCT116-derived sensitive clone. Topoisomerase I expression was unchanged in our resistant variants. The highest resistance level correlated with an ABCG2 amplification. This overexpression was associated with a marked decrease in the intracellular accumulation of SN38. The inhibition of ABCG2 function by Ko143 demonstrated that enhanced drug efflux from resistant cells was mediated by the activity of ABCG2 protein and confirmed that ABCG2 is directly involved in acquired resistance to SN38. Furthermore, we show, for the first time in clinical samples, that the ABCG2 mRNA content in hepatic metastases is higher after an irinotecan-based chemotherapy than in irinotecan-naive metastases. In conclusion, this study supports the potential involvement of ABCG2 in the development of irinotecan resistance in vivo. © 2004 Wiley-Liss, Inc. [source] Analysis of hair lipids and tensile properties as a function of distance from scalpINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 4 2005L. Duvel Synopsis Cuticle cells form the outer covering surrounding and protecting the cortex. The cuticle cells are thin, flat and overlap, and intercellular lipid lamellae are found in the gaps between the cell boundaries. The lipid lamellae are also found within the cortex in the cell boundaries between the long fribrous corticle cells. In addition, the outer surfaces of the cuticle cells are covered by a monolayer of covalently bound fatty acids, a major component of which is 18-methyleicosanoic acid. The fatty acids are thought to be attached through thio-ester linkages. Together these lipids are thought to be major determinants of the physical properties of the hair. The present study tested the hypothesis that both free and covalently bound lipids are progressively lost during normal environmental exposures. This progressive loss within the cuticle layers may, in part, lead to an increased susceptibility of the protein and lipid lamellae in the cortex to degradation. This degradation, in turn, would contribute to a progressive decrease in the tensile properties of the hair. Research grade hair was cut into five segments from the root to the distal end. Lipids from each segment were extracted and analyzed by thin-layer chromatography in conjunction with photodensitometry. The major free polar lipid classes in the hair included ceramides, glucosylceramides and cholesterol sulfate. The concentrations of all of the free polar lipids as well as the covalently bound fatty acids decreased in going from the root to the distal end of the hair. In addition, there was a significant reduction in tensile properties of the hair from the root to distal end. In conclusion, the progressive loss of endogenous free and covalently bound lipids from hair, which are probably related to normal weathering of the hair and grooming practices, may help contribute to a marked decrease in tensile properties to the hair. Résumé Les cellules de la cuticule forment le revêtement externe qui protège le cortex des cheveux. Les cellules de la cuticule sont minces, plates et se chevauchent. De fines couches de lipides sont présentes dans le matériau assurant la jonction entre les cellules cuticulaires. D'autres fines couches de lipides sont également présentes dans les espaces intercellulaires du cortex, entre les longues cellules corticales fibreuses. De plus, les surfaces externes des cellules de la cuticule sont recouvertes d'une couche monomoléculaire d'acides gras liés par covalence, un des composants majoritaires étant l'acide 18-méthyleicosanoique. On pense que ces acides gras sont fixés par liaisons thioesters. On pense également que l'ensemble de ces lipides joue un rôle important sur les propriétés physiques du cheveu. L'hypothèse testée dans cette étude est que les lipides libres et ceux liés par covalence sont progressivement éliminés lors de l'exposition normale des cheveux à l'environnement extérieur. Cette délipidation progressive de la cuticule pourrait, en partie, entraîner une plus grande sensibilité des constituants lipidiques et protéiniques du cortex aux agressions externes et accroître leur dégradation. Cette dégradation, à son tour, contribuerait à une diminution progressive des propriétés mécaniques en extension des cheveux. Des cheveux de provenance commerciale ont été coupés en cinq segments de leur racine à leur extrémité distale. Les lipides de chaque segment ont été extraits, séparés par chromatographie couche mince et dosés par densitométrie photographique. Les classes majoritaires de lipides polaires libres sont constituées de céramides, de glucosylcéramides et de sulfate de cholestérol. Les teneurs de tous les lipides polaires libres ainsi que des acides gras liés par covalence diminuent de la racine à l'extrémité distale du cheveu. De plus, on constate une réduction considérable des propriétés mécaniques en extension des cheveux de la racine à l'extrémité distale.-.En conclusion, la perte progressive des lipides endogènes libres et liés par covalence, probablement attribuables aux expositions à l'environnement et au stress des traitements capillaires peut aider à contribuer à une baisse marquée des propriétés mécaniques en extension des cheveux. [source] Desorption of zinc by extracellularly produced metabolites of Trichoderma harzianum, Trichoderma reesei and Coriolus versicolorJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007P. Adams Abstract Aims:, To determine the role of fungal metabolites in the desorption of metals. Methods and Results:, Desorption of Zn from charcoal by three different fungi was compared against metal desorption with reverse osmosis water, a 0·1% Tween 80 solution and a 0·1 mol l,1 CaCl2 solution. All three fungal filtrates desorbed three times more Zn than either 0·1% Tween 80 or 0·1 mol l,1 CaCl2. Metal chelator production in Trichoderma harzianum and Coriolus versicolor was constitutively expressed while chelator production in Trichoderma reesei was induced by Zn. The presence of Zn inhibited the production of metal chelators by C. versicolor. Only C. versicolor was found to produce oxalic acid (a strong metal chelator). All fungi caused a marked decrease in pH, although this was not enough to explain the increased desorption of the metals by the different fungal filtrates. Conclusions:, Metal chelation via organic acids and proteins are the main mechanisms by which the fungal filtrates increase zinc desorption. Significance and Impact of the Study:, The results of this study explain why plants inoculated with T. harzianum T22 take up more metal from soil, than noninoculated plants while metabolites produced by fungi could be used for metal leaching from contaminated soils. [source] Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient miceJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2008Christian Brenneis Abstract Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E2 synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2 synthase-1 (mPGES-1) isomerizes COX-2-derived PGH2 to PGE2. Here, we evaluated the effect of mPGES-1-deficiency on the noci-ceptive behavior in various models of nociception that depend on PGE2 synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES-1-deficient mice despite a marked decrease of the spinal PGE2 synthesis. Similarly, the nociceptive behavior was unaltered in mPGES-1-deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES-1-deficient mice showed a redirection of the PGE2 synthesis to PGD2, PGF2, and 6-keto-PGF1, (stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci-ception they may compensate the loss of PGE2 synthesis in mPGES-1-deficient mice. [source] Age-dependent telomere-shortening is repressed by phosphorylated ,-tocopherol together with cellular longevity and intracellular oxidative-stress reduction in human brain microvascular endotheliocytesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007Yasufumi Tanaka Abstract Cellular life-span of neonatal human brain microvascular endotheliocytes (HBME) was estimated by population doubling levels (PDLs) for serial subcultivations until spontaneous proliferation stoppage, and was 2.4-fold longer for continuous administration with the 6- O -phosphorylated derivative (TocP) of ,-tocopherol (Toc), being bio-available owing to its water-solubility, or TocP plus 2- O -phosphorylated ascorbate (Asc2P), and 1.3-fold longer with Asc2P, at a dose of 150 µM, than for the non-administered control. Enlarged cell diameters indicative of cellular aging were repressed for TocP-administered cells as analyzed with a channelizer. Age-dependent shortening of telomeric DNA length (291 bp/PDL) was slowed markedly for TocP (165 bp/PDL) or TocP plus Asc2P, but slightly for Asc2P. Telomerase activity as assessed by the PCR-based TRAP method was detectable slightly at younger ages but no longer at middle ages for the non-administered cells, but, for TocP-administered cells, was intensely detected at younger ages and appreciably until middle ages. Intracellular TocP amounts were not changed age-dependently in contrast to a marked decrease in Toc which accrued from TocP esterolysis. This may be partly attributed to age-dependent changes in the lipid peroxidation product acrolein (ACR), which was abundant at older ages in non-administered cells, but scarcely in TocP-administered cells. Furthermore, intracellular reactive oxygen species (ROS) such as H2O2 and hydroperoxides as detected using the redox indicator CDCFH-DA was less abundant in TocP-administered cells than in non-administered cells. Thus the telomeric-DNA retention, concurrently with retained telomerase activity, was shown to be correlated with cellular longevity, and may be supported by diminished oxidative stress, in hydrophobic microenvironment, which can be achieved by TocP rather than AscP. J. Cell. Biochem. 102: 689,703, 2007. © 2007 Wiley-Liss, Inc. [source] Insulin receptor substrate 1 (IRS-1) plays a unique role in normal epidermal physiology,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2007Marianna Sadagurski Insulin receptor substrate (IRS) proteins play a central role in insulin signaling. Previously we have demonstrated that insulin is essential for normal skin development and function. In the present study we investigated the involvement of the IRS-1 and IRS-2 proteins in skin physiology and in mediating insulin action in skin. For this purpose we have investigated the effects of inactivation of each of the IRSs on skin, studying skin sections and primary skin cells derived from IRS-1 or IRS-2 null mice. We have demonstrated that while the skin of the IRS-2 null mice appeared normal, the skin of the IRS-1 null mice was thinner and translucent. Histological analysis revealed that the thinning of the IRS-1 null skin was a consequence of the thinning of the spinous compartment, consisting of fewer layers. Proliferation of the IRS-1 and IRS-2 null skin epidermal cells was normal. However, the differentiation process of the IRS-1 skin and skin cells was impaired. There was a marked decrease in the induction of the expression of K1, the marker of advanced stages of skin differentiation. In contrary, IRS-2 inactivation had no effects on skin differentiation. In conclusion, we have shown for the first time that IRS-1 but not IRS-2 has an effect on skin formation and development, being one of the main activators of the differentiation process in skin keratinocytes. Furthermore, we suggest that IRS-1 and IRS-2 have distinct roles in skin physiology. J. Cell. Physiol. 213: 519,527, 2007. © 2007 Wiley-Liss, Inc. [source] Expression of phospholipase C beta family isoenzymes in C2C12 myoblasts during terminal differentiation,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Irene Faenza In the present work, we have analyzed the expression and subcellular localization of all the members of inositide-specific phospholipase C (PLC,) family in muscle differentiation, given that nuclear PLC,1 has been shown to be related to the differentiative process. Cell cultures of C2C12 myoblasts were induced to differentiate towards the phenotype of myotubes, which are also indicated as differentiated C2C12 cells. By means of immunochemical and immunocytochemical analysis, the expression and subcellular localization of PLC,1, ,2, ,3, ,4 have been assessed. As further characterization, we investigated the localization of PLC, isoenzymes in C2C12 cells by fusing their cDNA to enhanced green fluorescent protein (GFP). In myoblast culture, PLC,4 was the most expressed isoform in the cytoplasm, whereas PLC,1 and ,3 exhibited a lesser expression in this cell compartment. In nuclei of differentiated myotube culture, PLC,1 isoform was expressed at the highest extent. A marked decrease of PLC,4 expression in the cytoplasm of differentiated C2C12 cells was detected as compared to myoblasts. No relevant differences were evidenced as regards the expression of PLC,3 at both cytoplasmatic and nuclear level, whilst PLC,2 expression was almost undetactable. Therefore, we propose that the different subcellular expression of these PLC isoforms, namely the increase of nuclear PLC,1 and the decrease of cytoplasmatic PLC,4, during the establishment of myotube differentiation, is related to a spatial-temporal signaling event, involved in myogenic differentiation. Once again the subcellular localization appears to be a key step for the diverse signaling activity of PLC,s. © 2004 Wiley-Liss, Inc. [source] Preoperative therapeutic plasma exchange in patients with thyrotoxicosisJOURNAL OF CLINICAL APHERESIS, Issue 3 2009Ali Ezer Abstract The purpose of this report was to determine the effectiveness of therapeutic plasma exchange (TPE) in preoperative preparation of patients with thyrotoxicosis scheduled for either thyroid or nonthyroid surgery. We retrospectively reviewed 11 patients with thyrotoxicosis and those who prepared surgery with plasmapheresis between 1999 and 2008 at our institution. Ten patients underwent thyroid surgery and one patient was operated for femur fracture during antithyroid drug treatment. The indications for plasmapheresis in all patients with severe thyrotoxicosis were poor response to medical treatment (seven patients), agronulocytosis due to antithyroid drugs (three patients), iodine-induced thyrotoxicosis (Jodd Basedow effect in one patient), and rapid preparation for urgent orthopedic operation (one patient). After TPE, we observed a marked decrease in free thyroxin (FT3) and free triiodothyronin (FT4) levels; however, the decline in the biochemical values were not statically significant (P > 0.62, P > 0.15). Although both FT3 and FT4 levels remained above the normal limits in two of 11 patients, the signs and symptoms of thyrotoxicosis improved in all patients and no thyroid storm observed during the perioperative period. TPE can be considered a safe and effective alternative to prepare patients with thyrotoxicosis for surgery when drug treatment fails or is contraindicated and when emergency surgery is required. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Effects of anthropogenic disturbances on the diversity and composition of the butterfly fauna of sites in the Sango Bay and Iriiri areas, Uganda: implications for conservationAFRICAN JOURNAL OF ECOLOGY, Issue 2008Perpetra Akite Abstract In assessing environmental change, butterflies have been proven as replicable indicators of biodiversity and functional integrity that can be monitored at a range of scales. Butterflies have been identified as important bio-indicators for assessing biodiversity and monitoring ecosystem responses to environmental perturbations. The objectives of this study were to determine changes in the butterfly fauna of differing sites in the Sango Bay Area (SBA) and Iriiri (Karamoja) in comparison with data collected 10 years ago, and to investigate the impact of different degrees of habitat disturbance on butterflies. The general butterfly diversity was determined by trapping and sweep netting along transect lines and by random sweeping. The impact of human-induced disturbance was assessed by comparing species richness and composition between the sites and regressing the weighted disturbances against species diversity per site. There was a marked decrease in species diversity and varied species composition between the two studies and between the habitat types. Charcoal burning and grazing had significant negative correlations with diversity within forest sites (r2 = 0.825, P < 0.05), whereas cultivation and tree cutting/logging had significant negative correlations with diversity of open savannas (r2 = 0.718, P < 0.05 and r2 = 0.999, P < 0.05, respectively). [source] Venous air embolism induces both platelet dysfunction and thrombocytopeniaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009S. T. SCHÄFER Background: In vitro, air bubbles can induce platelet activation and platelet to air bubble binding. We therefore tested in vivo the hypothesis that venous air embolism (VAE) induces (1) platelet dysfunction and (2) thrombocytopenia. Methods: Adult swine (60.8±3.9 kg; n=8) were anaesthetized, mechanically ventilated, and placed in a semi-upright position. Air boli (0.5,80 ml) were injected randomly via an ear vein, and arterial blood was sampled after cumulative air dosages of 0, 80, 160, and 240 ml. Coagulation was assessed by impedance aggregometry, rotational thrombelastometry, whole blood count, plasmatic coagulation variables, and fibrinogen, d -dimer, protein C, and antithrombin plasma concentrations, respectively. Results: VAE induced a 47% decrease in platelet count (303 vs. 160 nl,1; P<0.001) over the dose range assessed, with haematocrit being unaltered. Furthermore, VAE-impaired platelet aggregation induced by adenosine diphosphate, arachidonic acid, collagen, and the thromboxan analogue U46619 over the dose range assessed independent of thrombocytopenia. (P<0.05 vs. baseline). In contrast, rotational thrombelastometry alone was quite insensitive in detecting VAE-induced coagulation changes, showing only at near lethal air dosages a prolonged clot formation time following activation with tissue factor, contact activator, and during spontaneous coagulation (P<0.05 vs. baseline). Conclusions: VAE induces both a dose-dependent decrease in platelet count and a marked decrease in platelet aggregation, independent of thrombocytopenia (P<0.05 vs. baseline). [source] Effect of Heat-Moisture Treatment and Acid Modification on Rheological, Textural, and Differential Scanning Calorimetry Characteristics of Sweetpotato StarchJOURNAL OF FOOD SCIENCE, Issue 6 2005Sukhcharn Singh ABSTRACT Sweetpotato starches were characterized to understand the changes upon modification by acid and heat-moisture treatment (HMT) in the rheological, differential scanning calorimetry (DSC), and textural characteristics of starch isolated from the sweetpotato variety PSP-21 and to compare these findings with those of commercially available arrowroot starch. The native sweetpotato starch had a Type A pasting profile characterized by a high peak viscosity (PV) (741.5 rapid viscoanalyzer unit [rvu]), with a high breakdown (378.8 rvu) and low cold paste viscosity (CPV) (417.6 rvu). After HMT, there was a marked decrease in the PV (639.1), a very slight breakdown (113.5 rvu) and an increase in CPV (759.5 rvu), more like a Type C pasting profile. However, acid modification did not notably change the pasting profile of native sweetpotato starch. The DSC characteristics were also affected significantly after modifications. The gelatinization temperature parameter to onset (To) decreased significantly after HMT and acid modification. The gelatinization enthalpy decreased during HMT from 15.98 to 14.42 J/g. The gel strength of acid-modified starch was the highest compared with that of HMT and native sweetpotato and arrowroot starches. [source] Tenderization of Heated Sliced Beef by Succinylated Glycerol Monostearate, a Novel Meat TenderizerJOURNAL OF FOOD SCIENCE, Issue 4 2001K. Mori ABSTRACT Succinylated glycerol monostearate (SGMS) was most effective in reducing shear-force value when used as a surfactant to tenderize meat using sheep casings as a model of intramuscular connective tissue. Roasted beef slices that had been treated with 2% granular SGMS showed a marked decrease in toughness due to the penetration of SGMS along the perimysium during heating. Collagen fibrils in the perimysium were transformed into a sheet-like structure that seemed very likely to be a complex of SGMS and thermally denatured collagen. These structural changes could account for the tenderness of the roasted beef slices. [source] Reconstitution of Photosystem II Reaction Center with Cu-Chlorophyll aJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 11 2006Shuang Liu Abstract An isolated photosystem (PS) II reaction center (RC) with altered pigment content was obtained by chemical exchange of native chlorophyll a (Chl) with externally added Cu-Chl a (Cu-Chl). Pigment composition and spectroscopic properties of the RC exchanged with Cu-Chl were compared with native RC and RC treated with Chl in the same way. High-performance liquid chromatography analysis showed approximately 0.5 Cu-Chl per two pheophytin in the Cu-Chl-reconstituted RC preparation. Insertion of Cu-Chl resulted in a decrease in absorption at 670 nm and an increase at 660 nm, suggesting that the peripheral Chl may have been displaced. Fluorescence emission spectra of the Cu-Chl-reconstituted RC displayed a marked decrease in fluorescence yield and a blue shift of the band maximum, accompanied by the appearance of a broad peak at a shorter wavelength, indicating that energy transfer in the modified RC was disturbed by Cu-Chl, a quencher of the excited state. However, there were few differences in the circular dichroism (CD) spectra, suggesting that the arrangement of pigments and proteins responsible for the CD signal was not significantly affected. In addition, no obvious change in peptide components was found after the exchange procedure. (Managing editor: Ping He) [source] | |||||||||||||||||||||||||||||||||||||||||||||||||