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Concomitant Decrease (concomitant + decrease)
Selected AbstractsCurcumin reduces indomethacin-induced damage in the rat small intestineJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2007Nageswaran Sivalingam Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical medicine. Their utility is, however, often limited by the adverse effects they produce in the gastrointestinal tract. Oxidative stress has been shown to occur in the small intestine in response to the oral administration of indomethacin, an NSAID commonly used in toxicity studies. In view of this, the effect of curcumin, an agent with anti-oxidant properties, was evaluated on indomethacin-induced small intestinal damage in a rat model. Rats were pretreated with various doses of curcumin (20 mg kg,1, 40 mg kg,1 and 80 mg kg,1) before administering indomethacin at 20 mg kg,1. Various parameters of oxidative stress and the extent of small intestinal damage produced by indomethacin, with and without pretreatment with curcumin, were measured. Macroscopic ulceration was found to occur in the small intestine in response to indomethacin. The viability of enterocytes from indomethacin-treated animals was significantly lower than those from control animals. Drug-induced oxidative stress was also evident as seen by increases in the levels of malondialdehyde and protein carbonyl and in activities of pro-oxidant enzymes such as myeloperoxidase and xanthine oxidase in indomethacin-treated rats. Concomitant decreases were seen in the activities of the antioxidant enzymes catalase and glutathione peroxidase in these animals. Pretreatment with curcumin was found to ameliorate these drug-induced changes. Thus, curcumin appears to hold promise as an agent that can potentially reduce NSAID-induced small intestinal damage. Copyright © 2007 John Wiley & Sons, Ltd. [source] Opposing Effects of Chronic Alcohol Consumption on Hepatic Gluconeogenesis for Female Versus Male RatsALCOHOLISM, Issue 10 2005Ken D. Sumida Abstract: Background: The impact of chronic alcohol consumption on hepatic gluconeogenesis (HGN) between males and females is unknown. To determine the effects of chronic alcohol consumption (8 weeks) on HGN, the isolated liver perfusion technique was used on 24-hr-fasted male and female Wistar rats. Methods: After surgical isolation, livers were perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes with no added substrate (washout period). After the washout period, livers were perfused with lactate (10 mM) and [U- 14C]lactate (15,000 dpm/ml) using the recirculation method. Results: There was no significant difference in HGN between males and females fed the control diet. In contrast, the females chronically fed the ethanol diet (FE) had significantly lower HGN rates (2.73 ± 0.37 ,mol/min × g liver protein,1), whereas males fed the ethanol diet (ME) had significantly higher HGN rates (4.99 ± 0.45 ,mol/min × g liver protein,1) than controls (3.83 ± 0.34 ,mol/min × g liver protein,1). Concomitant decreases were also observed for both 14C-lactate incorporation into 14C-glucose and rates of lactate uptake for FE, while corresponding increases were observed for 14C-lactate incorporation into 14C-glucose for ME. The livers from ME were able to convert a greater percentage of the lactate into glucose, resulting in the elevation in gluconeogenic capacity. Conclusion: Chronic alcohol consumption lowers the hepatic gluconeogenic capacity from lactate in females and elevates HGN in males. [source] How adhesion, migration, and cytoplasmic calcium transients influence interleukin-1, mRNA stabilization in human monocytesCYTOSKELETON, Issue 3 2004P. Pomorski Abstract We investigated the mechanisms by which primary human monocyte migration and the production of important cytokines are co-regulated. Motile monocytes underwent cyclic morphologic and adhesive changes that were associated with intracellular free calcium changes; in such cells, cytokine transcripts were unstable and translationally repressed. Agents that activate monocytes, including lipopolysacharrides (LPS), cytomegalovirus (CMV), and tumor necrosis factor (TNF,), have been shown to de-repress translation and these agents stabilize adhesion-induced transcripts for IL-l, and IL-8 and markedly diminish cell migration in the presence of autologous serum. LPS suppressed Rho A activity and either this agent or C3 transferase elevated intracellular free calcium, stabilized transcripts, and, in tandem, inhibited cell migration by preventing tail retraction, a prerequisite for cell translocation. These results, therefore, suggest that monocyte activating agents inhibit the RhoA pathway and continuously elevate intracellular calcium leading to a concomitant decrease in monocyte migration and stabilization of cytokine transcripts prior to translation. Cell Motil. Cytoskeleton 57:143,157, 2004. © 2004 Wiley-Liss, Inc. [source] Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patientsDIABETES OBESITY & METABOLISM, Issue 6 2008A. Brunani Aim:, In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. Methods:, From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18,65 years and body mass index 35,50 kg/m2 and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. Results:, A significant weight loss and reduction of fat mass was demonstrated with metformin (,9.7 ± 1.8 kg and ,6.6 ± 1.1 kg) and also with rosiglitazone (,11.0 ± 1.9 kg and ,7.2 ± 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 ± 0.1 vs. 4.4 ± 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 ± 1.5 vs. 8.0 ± 0.,7 ,U/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 ± 8.8 vs. 109.9 ± 10.3, p < 0.005) with a concomitant decrease in ,-cell function as measured by HOMA of ,-cell function (163.2 ± 16.1 vs. 127.4 ± 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. Conclusion:, Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction. [source] Smaller and more numerous harvesting gaps emulate natural forest disturbances: a biodiversity test case using rove beetles (Coleoptera, Staphylinidae)DIVERSITY AND DISTRIBUTIONS, Issue 6 2008Jan Klimaszewski ABSTRACT Aim To evaluate changes in the abundance, species richness and community composition of rove beetles (Coleoptera, Staphylinidae) in response to three configurations of experimental gap cuts and to the effects of ground scarification in early succession yellow birch-dominated boreal forest. In each experimental treatment, total forest removed was held constant (35% removal by partial cutting with a concomitant decrease in gap size) but the total number of gaps was increased (two, four and eight gaps, respectively), resulting in an experimental increase in the total amount of ,edge' within each stand. Location Early succession yellow birch-dominated forests, Quebec, Canada. Methods Pitfall traps, ANOVA, MIXED procedure in sas®, post hoc Tukey's adjustment, rarefaction estimates, sum-of-squares and distance-based multivariate regression trees (ssMRT, dbMRT). Results Estimates of species richness using rarefaction were highest in clearcut and two-gap treatments, decreased in smaller and more numerous gaps and were significantly higher in scarified areas than in unscarified areas. ANOVA indicated a significant impact of harvesting on the overall standardized catch. Post hoc Tukey's tests indicated that the total catch of all rove beetles was significantly higher in uncut forests than in the treated areas. Both sum-of-squares and distance-based multivariate regression trees indicated that community structure of rove beetles differed among treatments. Assemblages were grouped into (a) control plots, (b) four- and eight-gap treatments and (c) two-gap and clearcut treatments. Main conclusions Rove beetle composition responded significantly to increasing gap size. Composition among intermediate and small-sized gap treatments (four- and eight-gap treatments) was more similar to uncut control forests than were larger gap treatments (two-gap) and clearcuts. Effects of scarification were nested within the harvested treatments. When the total area of forest removed is held constant, smaller, more numerous gaps are more similar to uncut control stands than to larger gaps and falls more closely within the natural forest heterogeneity. [source] On the kinetics of voltage formation in purple membranes of Halobacterium salinariumFEBS JOURNAL, Issue 19 2000Richard W. Hendler The kinetics of the bacteriorhodopsin photocycle, measured by voltage changes in a closed membrane system using the direct electrometrical method (DEM) of Drachev, L.A., Jasaitus, A.A., Kaulen, A.D., Kondrashin, A.A., Liberman, E.A., Nemecek, I.B., Ostroumov, S.A., Semenov, Yu, A. & Skulachev, V.P. (1974) Nature249, 321,324 are sixfold slower than the kinetics obtained in optical studies with suspensions of purple membrane patches. In this study, we have investigated the reasons for this discrepancy. In the presence of the uncouplers carbonyl cyanide m -chlorophenylhydrazone or valinomycin, the rates in the DEM system are similar to the rates in suspensions of purple membrane. Two alternative explanations for the effects of uncouplers were evaluated: (a) the ,back-pressure' of the ,µ,H+ slows the kinetic steps leading to its formation, and (b) the apparent difference between the two systems is due to slow major electrogenic events that produce little or no change in optical absorbance. In the latter case, the uncouplers would decrease the RC time constant for membrane capacitance leading to a quicker discharge of voltage and concomitant decrease in photocycle turnover time. The experimental results show that the primary cause for the slower kinetics of voltage changes in the DEM system is thermodynamic back-pressure as described by Westerhoff, H.V. & Dancshazy, Z. (1984) Trends Biochem. Sci.9, 112,117. [source] Assessment of salmon stocks and the use of management targets; a case study of the River Tamar, EnglandFISHERIES MANAGEMENT & ECOLOGY, Issue 1 2007K. HENDRY Abstract, Over recent years the rod and net catch of Atlantic salmon, Salmo salar L., on the River Tamar in south-west England has decreased markedly, resulting in a consistent failure to meet the minimum egg deposition target (conservation limit). Compliance with the target is by annual assessment using rod catch as the major input variable. Further analysis suggested a disproportionate deterioration in the rod fishery performance of the Tamar compared with rivers locally, regionally and nationally. A concomitant decrease in rod licence sales and fishing effort, above both national and regional trends was also evident. However, examination of juvenile electric fishing and adult fish counter data revealed a different trend for the past 10 years, indicating a stable fish population, albeit at a lower level of abundance than previously. The analyses suggested that without consideration of changes in effort and rod exploitation rate, rod catch alone is not a reliable indicator of stock abundance and hence should not be used as such in stock assessment. [source] Determining thymic output quantitatively: using models to interpret experimental T-cell receptor excision circle (TREC) dataIMMUNOLOGICAL REVIEWS, Issue 1 2007Ruy M. Ribeiro Summary:, T cells develop in the thymus and then are exported to the periphery. As one ages, the lymphoid mass of the thymus decreases, and a concomitant decrease in the ability to produce new T cells results. Human immunodeficiency virus (HIV) infects CD4+ T cells and, hence, can also affect thymic function. Here we discuss experimental techniques and mathematical models that aim to quantify the rate of thymic export. We focus on a recent technique involving the quantification of T-cell receptor excision circles (TRECs). We discuss how proper interpretation of TREC data necessitates the critical development of appropriate mathematical models. We review the theory for interpretation of TREC data during aging, HIV infection, and anti-retroviral treatment. Also, we show how TRECs can be used to accurately quantify thymic output in the context of thymectomy experiments. We show that mathematical models are not only useful but absolutely necessary for these analyses. As such, they should be taken as just another tool in the immunologist's arsenal. [source] Expression of Fas and Fas ligand in human testicular germ cell tumoursINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2009E. Baldini Summary In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant (p < 0.01) increase of the FasL mRNA expression of 21.1 ± 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly (p < 0.01) reduced to 0.27 ± 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno-reactivity in six out of eight TGCT samples analysed, while Fas immuno-positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient's age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non-seminomatous TGCT and six age-matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT. [source] Are ectoparasite communities structured?JOURNAL OF ANIMAL ECOLOGY, Issue 6 2006Species co-occurrence, null models, temporal variation Summary 1We studied temporal variation in the structure of flea communities on small mammalian hosts from eastern Slovakia using null models. We asked (a) whether flea co-occurrences in infracommunities (in the individual hosts) in different hosts as well as in the component communities (in the host species) demonstrate a non-random pattern; (b) whether this pattern is indicative of either positive or negative flea species interactions; (c) whether this pattern varies temporally; and (d) whether the expression of this pattern is related to population size of either fleas or hosts or both. 2We constructed a presence/absence matrix of flea species for each temporal sample of a host species and calculated four metrics of co-occurrence, namely the C -score, the number of checkerboard species pairs, the number of species combinations and the variance ratio (V -ratio). Then we compared these metrics with the respective indices calculated for 5000 null matrices that were assembled randomly using two algorithms, namely fixed-fixed (FF) and fixed-equiprobable (FE). 3Most co-occurrence metrics calculated for real data did not differ significantly from the metrics calculated for simulated matrices using the FF algorithm. However, the indices observed for 42 of 75 presence/absence matrices differed significantly from the null expectations for the FE models. Non-randomness was detected mainly by the C -score and V -ratio metrics. In all cases, the direction of non-randomness was the same, namely the aggregation, not competition, of flea species in host individuals and host species. 4The inclusion or exclusion of the uninfested hosts in the FE models did not affect the results for individual host species. However, exclusion of the uninfested host species led to the acceptance of the null hypothesis for only six of 13 temporal samples of the component flea communities for which non-randomness was detected when the uninfested hosts were included in the analysis. 5In most host species, the absolute values of the standardized size effect of both the C -score and V -ratio increased with an increase in host density and a concomitant decrease in flea abundance and prevalence. 6Results of this study demonstrated that (a) flea assemblages on small mammalian hosts were structured at some times, whereas they appeared to be randomly assembled at other times; (b) whenever non-randomness of flea co-occurrences was detected, it suggested aggregation but never segregation of flea species in host individuals or populations; and (c) the expression of structure in flea assemblages depended on the level of density of both fleas and hosts. [source] A Communication Training Programme for Residential Staff Working with Adults with Challenging Behaviour: Pilot Data on Intervention EffectsJOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 1 2007Andy Smidt Background, Challenging behaviour often serves a communicative function. It therefore stands to reason that the residential staff working in developmental disability services require training to foster appropriate communicative interactions with adults with challenging behaviour. Method, Eighteen members of staff working in three residential services participated in a 4 week communication training programme. The programme focused on staff attitudes to and beliefs about challenging behaviour, communicative interactions between staff and residents and working as a team. Objective measurements were made of the effects of the training programme on staff use of augmentative and alternative communication, praise and use of inappropriate language in a multiple-baseline design across three organizations. Changes in the rate of challenging behaviours among the residents were also evaluated. Results, As staff's use of AAC and praise increased, and inappropriate language decreased, there was some concomitant decrease in residents' levels of challenging behaviour; however, these results were not sustained in the long-term. Conclusion, This pilot data suggest that an approach to staff training based on modifying attitudes and beliefs is potentially beneficial to both staff and residents. [source] Studies on the mechanism of rapid activation of protein tyrosine phosphorylation activities, particularly c-Src kinase, by TCDD in MCF10AJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2005Olga Mazina Abstract While the process of the Ah receptor activation leading to cytochrome P450 induction has been well studied, the mechanism and the process through which the Ah receptor activates tyrosine kinases, within a few minutes of its ligand binding, is not known. Previously, it was reported by Tannheimer et al. (Carcinogenesis 1998; 19:1291,1297) that TCDD causes rapid induction of tyrosine phosphorylation activities in the MCF10A human mammary epithelial cell line. To study the mechanistic aspect of this phenomenon, particularly that occurs within a few minutes after administration, we first studied the effect of insulin on MCF10A under serum free conditions with added EGF. The addition of insulin induced a rapid (5 min) tyrosine phosphorylation on several 160,190 kDa proteins which was followed by significant dephosphorylation activities on these proteins by 15 min. TCDD increased the rate of tyrosine phosphorylation on those proteins but at 15 min, the level of phosphorylation was still high. When insulin and TCDD were added together, the ability of insulin to induce de-phosphorylation by 15 min disappeared. Such an action of TCDD was accompanied by an increase in the titer of the activated form of Src kinase (i.e. c-Src protein with 418 tyrosine phosphorylation), and a concomitant decrease in the level of 529 tyrosine phosphorylated form (an inactivated form). The TCDD-induced activation of c-Src could be blocked by pretreated MCF10A cells with antisense oligonucleotides against c-src or with a specific inhibitor of Src kinase, PP-2. These results support the conclusion that c-Src kinase is at least one of the earliest and the most upstream components of toxic signaling of the Ah-receptor activated by TCDD through the post-transcriptional process. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:313,321, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20041 [source] Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetismJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2009Noritaka Nakamichi Abstract We have previously shown significant potentiation of Ca2+ influx mediated by N-methyl- D -aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain. © 2009 Wiley-Liss, Inc. [source] Role of Wake-Promoting Basal Forebrain and Adenosinergic Mechanisms in Sleep-Promoting Effects of EthanolALCOHOLISM, Issue 6 2010Mahesh M. Thakkar Background:, Ethanol intake has significant impact on sleep. However, the cellular substrates responsible for sleep promotion following ethanol intake are unknown. The purine nucleoside, adenosine, is responsible for mediating many neuronal and behavioral responses to ethanol. Studies performed in cell cultures suggest that ethanol inhibits equilibrative nucleoside transporter 1 to block the reuptake of adenosine resulting in increased extracellular adenosine. Adenosine also has a pivotal role in sleep regulation. Adenosine acts via A1 receptor to inhibit the wake-promoting neurons of the basal forebrain (BF) resulting in the promotion of sleep. Is ethanol-induced sleep associated with the inhibition of the BF wake-promoting neurons? Do adenosinergic mechanisms in the BF have a role in sleep-promoting effects of ethanol? Methods:, To address these questions, we performed 3 experiments in Sprague,Dawley rats. First, we verified the effect of ethanol on sleep promotion. Second, we evaluated the effect of ethanol on c-Fos expression (a marker of neuronal activation) in the BF wake-promoting neurons and third we monitored the effects of A1 receptor blockade in the BF on ethanol-induced sleep. Results:, Significant increase in non-rapid eye movement (NREM) sleep with a concomitant decrease in wakefulness was observed during the first 12 hours postethanol. REM sleep remained unaffected. Ethanol administration caused a significant decrease in the number of BF wake-promoting neurons with c-Fos immunoreactivity. Bilateral microinjections of a selective A1R receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine into the BF significantly attenuated sleep-promoting effects of ethanol. Conclusion:, These results suggest that the inhibition of BF wake-promoting neurons by adenosinergic mechanism may be responsible for the sleep promoting effects of ethanol. We believe our study is the first to investigate the cellular mechanisms responsible for the somnogenic effects of ethanol. [source] Melatonin ameliorates chronic renal failure-induced oxidative organ damage in ratsJOURNAL OF PINEAL RESEARCH, Issue 4 2004Göksel, ener Abstract:, Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05,0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05,0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH-Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH-Px activities of plasma demonstrate the role of oxidative mechanisms in CRF-induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF-induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit. [source] Electrophoretic patterns of microwaved and ,-irradiated beef liver proteinsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 10 2001S Farag Abstract The effects of ,-irradiation treatments (2.5, 5 and 10,kGy) and microwaves generated from an oven at low and defrost power settings for 0.5, 1 and 2,min on the total proteins and protein patterns of beef liver immediately after treatment and during frozen storage (,18,°C) for different periods were studied. Chemical analyses indicated that the protein content of beef liver was reduced after exposure to ,-radiation or microwaves and also during frozen storage. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used to illustrate the changes in protein bands of different molecular weights and their percentages before and after exposure to gamma and microwave radiation. The main effect of ,-radiation on the protein patterns of beef liver was the disappearance of some high-molecular-weight protein bands and the development of other bands characterised by moderate and low molecular weights. This finding indicates the degradation of beef liver proteins by ,-irradiation. In contrast, microwave treatment caused an increase in the levels of high-molecular-weight protein bands with a concomitant decrease in low-molecular-weight protein bands. This phenomenon demonstrates the polymerisation of low-molecular-weight proteins under the influence of microwaves. © 2001 Society of Chemical Industry [source] Penile morphology of African mole rats (Bathyergidae): structural modification in relation to mode of ovulation and degree of socialityJOURNAL OF ZOOLOGY, Issue 2 2006A. Parag Abstract The penile morphology and bacular structure of five species of African mole rat are described in relation to the method of ovulation, degree of sociality and polygynandry. We predicted that, with an increase in sociality, and a concomitant decrease in polygynandry and sperm competition, there would be a decrease in penis ornamentation (spinosity) and baculum size. In solitary species of African mole rat with marked seasonal reproduction and induced ovulation (Bathyergus suillus and Georychus capensis), males have numerous epidermal spines on the penis. Social, seasonally breeding, induced ovulating mole rats Cryptomys hottentotus natalensis possess less elaborate ornamentation in the form of small protrusions that are rounded at the apex. Two aseasonally breeding eusocial species with spontaneous ovulation Cryptomys damarensis and Heterocephalus glaber have ridges on the penis but lack any elaborate ornamentation. Baculae, however, showed a trend to become proportionally smaller in the solitary species. Our prediction that, with an increase in sociality and a move from induced to spontaneous ovulation, the amount and degree of penile ornamentation declines was, therefore, generally supported. [source] Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic miceLIVER TRANSPLANTATION, Issue 3 2005Ryan N. Fiorini Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant. (Liver Transpl 2005;11:298,308.) [source] Protective effect of vitamin E on ultraviolet B light,induced damage in keratinocytesMOLECULAR CARCINOGENESIS, Issue 3 2002Samar Maalouf Abstract Ultraviolet (UV) B radiation is the most common environmental factor in the pathogenesis of skin cancer. Exposure of human skin to UVB radiation leads to the depletion of cutaneous antioxidants, the activation of nuclear factor kappa B (NF-,B), and programmed cell death (apoptosis). Although antioxidant supplementation has been shown to prevent UVB-induced photooxidative damage, its effect on components of cell signaling pathways leading to gene expression has not been clearly established. In the present study, the effect of the antioxidant vitamin, ,-tocopherol (,-T), and its acetate analog, ,-tocopherol acetate (,-TAc), on UVB-induced damage in primary and neoplastic mouse keratinocytes was investigated. The ability of both vitamins to modulate UVB-induced apoptosis and activation of the transcription factor NF-,B were studied. Treatment of normal and neoplastic mouse epidermal keratinocytes (308 cells) with 30,60 mJ/cm2 UVB markedly decreased viable cell number and was accompanied by DNA fragmentation. When both vitamins were applied to cells at times before and after UVB radiation, a significant increase in the percentage of viable cells and concomitant decrease in the number of apoptotic cells was noted, with vitamin pretreatment providing a better protection than posttreatment. Simultaneous posttreatment of irradiated cells with ,-TAc abolished the cytotoxic effects of UVB and restored cell viability to control levels. In addition, simultaneous posttreatment of irradiated cells with ,-T reduced the number of apoptotic cells by half, indicating a synergistic effect of two such treatments compared with any single one. Flow cytometry analysis indicated that vitamin treatment suppressed both an increase in pre-G0 cells and a decrease in cycling cells by UVB exposure. In addition, NF-,B activation was detected 2 h after UV exposure and was maintained for up to 8 h. Pretreatment with vitamins significantly inhibited NF-,B activation at 4 and 8 h. These results indicate that vitamin E and its acetate analog can modulate the cellular response to UVB partly through their action on NF-,B activation. Thus, these antioxidant vitamins are potential drugs for the protection from or the reduction of UVB-associated epidermal damage. © 2002 Wiley-Liss, Inc. [source] Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriaeMOLECULAR MICROBIOLOGY, Issue 4 2007Anu Swaminathan Summary Many surface proteins in Gram-positive bacteria are covalently linked to the cell wall through a transpeptidation reaction catalysed by the enzyme sortase. Corynebacterium diphtheriae encodes six sortases, five of which are devoted to the assembly of three distinct types of pilus fibres , SrtA for the SpaA-type pilus, SrtB/SrtC for the SpaD-type pilus, and SrtD/SrtE for the SpaH-type pilus. We demonstrate here the function of SrtF, the so-called housekeeping sortase, in the cell wall anchoring of pili. We show that a multiple deletion mutant strain expressing only SrtA secretes a large portion of SpaA polymers into the culture medium, with concomitant decrease in the cell wall-linked pili. The same phenotype is observed with the mutant that is missing SrtF alone. By contrast, a strain that expresses only SrtF displays surface-linked pilins but no polymers. Therefore, SrtF can catalyse the cell wall anchoring of pilin monomers as well as pili, but it does not polymerize pilins. We show that SrtA and SrtF together generate wild-type levels of the SpaA-type pilus on the bacterial surface. Furthermore, by regulating the expression of SpaA in the cell, we demonstrate that the SrtF function becomes critical when the SpaA level is sufficiently high. Together, these findings provide key evidence for a two-stage model of pilus assembly: pilins are first polymerized by a pilus-specific sortase, and the resulting fibre is then attached to the cell wall by either the cognate sortase or the housekeeping sortase. [source] Oocyte-selective expression of MT transposon-like element, clone MTi7 and its role in oocyte maturation and embryo developmentMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2004Chang-Eun Park Abstract Previously, we found MT transposon-like element, clone MTi7 (MTi7) is highly expressed in the mouse ovary. Here, we show that the MTi7 is expressed in the oocyte from the primordial to the preovulatory follicles. For RNA interference (RNAi), double stranded RNAs (dsRNAs) were prepared for MTi7 and c-mos, a control gene with known functions. Each dsRNA was microinjected into germinal vesicle (GV) stage oocytes or zygotes with pronuclei (PN), after which developmental changes, mRNA expression, and nuclear and microtubular organization were analyzed. We found a 43.4,53% GV arrest in the microinjected oocytes with a concomitant decrease in targeted mRNA expression. In MTi7 dsRNA-injected early and late PN zygotes, a 92.9% 1-cell arrest and 76.9% 2-cell arrest were observed, respectively. This is the first report of an oocyte-selective expression of MTi7 mRNA, and our results strongly suggest that MTi7 involved in the nuclear membrane breakdown during oocyte maturation and embryo development. Mol. Reprod. Dev. 69: 365,374, 2004. © 2004 Wiley-Liss, Inc. [source] Gated dynamic 31P MRS shows reduced contractile phosphocreatine breakdown in mice deficient in cytosolic creatine kinase and adenylate kinaseNMR IN BIOMEDICINE, Issue 5 2009Hermien E. Kan Abstract We developed a new dedicated measurement protocol for dynamic 31P MRS analysis in contracting calf muscles of the mouse, using minimally invasive assessment of the contractile force combined with the acquisition of spectroscopic data gated to muscle contraction and determination of phosphocreatine (PCr) recovery rate and ATP contractile cost. This protocol was applied in a comparative study of six wild type (WT) mice and six mice deficient in cytosolic creatine kinase and adenylate kinase isoform 1 (MAK,/, mice) using 70 repeated tetanic contractions at two contractions per minute. Force levels during single contractions, and metabolite levels and tissue pH during resting conditions were similar in muscles of MAK,/, and WT mice. Strikingly, muscle relaxation after contraction was significantly delayed in MAK,/, mice, but during repeated contractions, the decrease in the force was similar in both mouse types. Gated data acquisition showed a negligible PCr breakdown in MAK,/, immediately after contraction, without a concomitant decrease in ATP or tissue pH. This protocol enabled the determination of rapid PCr changes that would otherwise go unnoticed due to intrinsic low signal-to-noise ratio (SNR) in mouse skeletal muscles combined with an assessment of the PCr recovery rate. Our results suggest that MAK,/, mice use alternative energy sources to maintain force during repeated contractions when PCr breakdown is reduced. Furthermore, the absence of large increases in adenosine diphosphate (ADP) or differences in force compared to WT mice in our low-intensity protocol indicate that creatine kinase (CK) and adenylate kinase (AK) are especially important in facilitating energy metabolism during very high energy demands. Copyright © 2009 John Wiley & Sons, Ltd. [source] Panax ginseng reduces adriamycin-induced heart failure in ratsPHYTOTHERAPY RESEARCH, Issue 12 2005Jyh-Sheng You Abstract The purpose of this study was to investigate the protective effects of Panax ginseng on adriamycin-induced heart failure. Wistar rats were divided into four groups: control, adriamycin, ginseng and adriamycin with ginseng. Adriamycin (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks. Ginseng was administered via an oral feeding tube once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5 week post-treatment period, the hearts of the rats were used to study the synthesis rates of DNA, RNA and protein, myocardial antioxidants and lipid peroxidation. At the end of 3 weeks treatment, heart failure was characterized by ascites, congested liver and depressed cardiac function. Nucleic acid as well as protein synthesis was inhibited, lipid peroxidation was increased and myocardial glutathione peroxidase activity was decreased indicating adriamycin-induced heart failure. In contrast, the administration of ginseng, before and concurrent with adriamycin, significantly attenuated the myocardial effects, lowered the mortality as well as the amount of ascites, increased in myocardial glutathione peroxidase, macromolecular biosynthesis and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. These findings indicated that ginseng may be partially protective against adriamycin-induced heart failure. Copyright © 2005 John Wiley & Sons, Ltd. [source] Yield assessment of integument-led seed growth following targeted repair of auxin response factor 2PLANT BIOTECHNOLOGY JOURNAL, Issue 8 2008Rhiannon Hughes Summary It is becoming increasingly vital to improve the yield of seed crops to feed an expanding population and, more recently, for biofuel production. One strategy to increase the yield is to increase the seed size, provided that there is not a concomitant decrease in seed number. In a previous study, we described a mutant in the AUXIN RESPONSE FACTOR 2 (ARF2) gene which produced extra cells in the seed coat and, subsequently, enlarged seeds. However, arf2 mutant plants also show severely reduced self-fertility caused, in part, by over-elongated sepals that prevent flower opening. As a low seed set increases individual seed size, a meaningful comparison of the yield in arf2 and wild-type plants could not be conducted. In this study, we show that targeted expression of wild-type ARF2 in the sepals and petals of arf2-9 mutant flowers restores flower opening and dramatically increases seed set. The restored plants retain both enlarged integuments and increased seed size, reinforcing previous evidence that arf2 mutations increase seed weight through their effect on integuments and not only via reduced fertility. We also show that the measurement of the harvest index in Arabidopsis is useful in assessing the impact of introduced traits on the yield. [source] Nitrogen purity influences the occurrence of As+ ions in high-performance liquid chromatography/electrospray ionization mass spectrometric analysis of four common arsenosugarsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2003Doris Kuehnelt High-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC/ESI-MS) can provide both elemental and molecular information and, therefore, is a very useful tool for the identification of arsenic compounds. When a method for the identification of four arsenosugars was employed in our laboratory with an HPLC/ESI-MS system equipped with a Whatman model 75-72 nitrogen generator, a signal at m/z 75 (As+) could not be observed. When the HPLC/ESI-MS system was operated with nitrogen 5.0 (nitrogen of a purity of at least 99.999%) all four arsenosugars gave a signal at m/z 75. Because of this observation the influence of the quality of the nitrogen drying gas on the fragmentation of the four arsenosugars was systematically investigated. Standard solutions containing the four arsenosugars (0.5 ng As each) were separated on an anion-exchange column and detected with ESI-MS in the positive ion mode by monitoring the signals for [M+H]+, m/z 237, 91, and 75. Nitrogen with defined oxygen concentrations was used as drying gas. The purity of the nitrogen ranged from 99 to 99.999% (10,400 to 10 ppm oxygen impurity). The nitrogen with 99% purity gave no signal at m/z 75, but signals were obtained at m/z 91, 237, and for [M+H]+. When higher purity nitrogen (99.9%) was used, a signal was obtained at m/z 75, which accounted for 0.8,1.1% (depending on the kind of arsenosugar) of the sum of the signals for m/z 75, 91, 237 and [M+H]+. As the level of oxygen in the nitrogen decreased, the m/z 75 signal increased to 2.0,3.1%. This was accompanied by a concomitant decrease in the m/z 91 signal from 5.2,6.6% to 0.7,1.5%, whereas the signals for [M+H]+ and m/z 237 were essentially unchanged. Signals at m/z 75 with intensities comparable with those observed for the 99.9% pure nitrogen were also obtained for all the arsenosugars when the HPLC/ESI-MS system was operated with a Domnick Hunter Nitrox UHPLCMS18 nitrogen generator. Dimethylarsinic acid, arsenobetaine, trimethylarsine oxide, arsenocholine and the tetramethylarsonium cation also gave no signal at m/z 75 when they were analyzed with the Whatman model 75-72 nitrogen generator, but clear signals at m/z 75 were observed with the Domnick Hunter Nitrox UHPLCMS18 nitrogen generator. A nitrogen quality of at least 99.9% is required to obtain elemental information (m/z 75) when arsenic compounds are investigated by HPLC/ESI-MS. Molecular and elemental information from one chromatographic run is a valuable tool for the characterization of unknown arsenic compounds. Copyright © 2003 John Wiley & Sons, Ltd. [source] Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermiaANDROLOGIA, Issue 1 2010T. K. Biswas Summary The safety and spermatogenic activity of processed Shilajit (PS) were evaluated in oligospermic patients. Initially, 60 infertile male patients were assessed and those having total sperm counts below 20 million ml,1 semen were considered oligospermic and enrolled in the study (n = 35). PS capsule (100 mg) was administered twice daily after major meals for 90 days. Total semenogram and serum testosterone, luteinising hormone and follicle-stimulating hormone were estimated before and at the end of the treatment. Malondialdehyde (MDA), a marker for oxidative stress, content of semen and biochemical parameters for safety were also evaluated. Twenty-eight patients who completed the treatment showed significant (P < 0.001) improvement in spermia (+37.6%), total sperm count (+61.4%), motility (12.4,17.4% after different time intervals), normal sperm count (+18.9%) with concomitant decrease in pus and epithelial cell count compared with baseline value. Significant decrease of semen MDA content (,18.7%) was observed. Moreover, serum testosterone (+23.5%; P < 0.001) and FSH (+9.4%; P < 0.05) levels significantly increased. HPLC chromatogram revealed inclusion of PS constituents in semen. Unaltered hepatic and renal profiles of patients indicated that PS was safe at the given dose. The present findings provide further evidence of the spermatogenic nature of Shilajit, as attributed in Ayurvedic medicine, particularly when administered as PS. [source] Effects of dietary protein and lipid level, and water temperature, on the post-feeding oxygen consumption of Atlantic cod and haddockAQUACULTURE RESEARCH, Issue 2 2010Juan C Pérez-Casanova Abstract Tank respirometry was used to study the interactive effects of protein:lipid level (55%:11% vs. 42%:16%; both diets isoenergetic) and temperature (11, 6 and 2 °C) on the magnitude and duration of specific dynamic action (SDA) in juvenile Atlantic cod and haddock. The protein:lipid level did not affect any measured variable. However, numerous temperature and species effects were observed. For example, although the maximum post-feeding oxygen consumption (30,50% above routine metabolic rate; RMR) and SDA duration (,55,85 h; SDADUR) were not affected by temperature, SDADUR g,1 of food increased from 11 to 2 °C (from ,3 to 12 h g food,1). While absolute SDA (mg O2) decreased by ,60,65% in cod and ,75% in haddock from 11 to 2 °C, due to a concomitant decrease in food consumption from ,2.0% to 0.6% body mass, SDA comprised between 3.3% and 5.2% of the dietary energy content at all temperatures. Finally, RMR at 11 and 2 °C and SDADUR at 2 °C were 25,35% and 25% greater in cod, respectively, as compared with haddock. These results suggest that feeding reduced protein diets at low water temperatures is unlikely to improve the growth of these species. [source] Hypoxia and glucocorticoid signaling converge to regulate macrophage migration inhibitory factor gene expressionARTHRITIS & RHEUMATISM, Issue 8 2009Laura M. Elsby Objective Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator involved in the pathogenesis of rheumatoid arthritis. This study was undertaken to identify the MIF promoter elements responsible for regulating gene expression. Methods Luciferase reporter gene assays were used to identify the MIF promoter sequence responsible for basal activity. Bioinformatic analysis was used to predict transcription factor binding sites, and electrophoretic mobility shift assay (EMSA) was used to demonstrate transcription factor binding. Chromatin immunoprecipitation (ChIP) was used to demonstrate transcription factor loading on the MIF promoter. Results We identified the minimal promoter sequence required for basal MIF promoter activity that was also capable of conferring glucocorticoid-dependent inhibition in a T lymphocyte model cell line. Deletion studies and EMSA revealed 2 elements in the MIF promoter that were responsible for basal promoter activity. The 5, element binds CREB/activating transcription factor 1, and the 3, element is a functional hypoxia-responsive element binding hypoxia-inducible factor 1,. Further studies demonstrated that the cis elements are both required for glucocorticoid-dependent inhibition. ChIP demonstrated glucocorticoid-dependent recruitment of glucocorticoid receptor , to the MIF promoter in lymphocytes within 1 hour of treatment and a concomitant decrease in acetylated histone H3. Conclusion Our findings indicate that hypoxia and glucocorticoid signaling converge on a single element regulating MIF; this regulatory unit is a potential interacting node for microenvironment sensing of oxygen tension and glucocorticoid action in foci of inflammation. [source] Regulation of autophagy in human and murine cartilage: Hypoxia-inducible factor 2 suppresses chondrocyte autophagyARTHRITIS & RHEUMATISM, Issue 5 2009Jolene Bohensky Objective We have previously demonstrated that the transcription factor hypoxia-inducible factor 1 (HIF-1) promotes the onset of autophagy in chondrocytes. The overall goal of this study was to test the hypothesis that another HIF family transcription factor, HIF-2, modulates the induction of autophagy by chondrocytes. Methods Expression of HIF-1, HIF-2, and light chain 3 (LC3) in human and murine articular cartilage was visualized by immunohistochemistry. Suppression of HIF-2 was achieved using small interfering RNA technology. Assessments of autophagic flux and lysosomal activity, as well as ultrastructural analysis, were performed in chondrocytes in cell culture. Results HIF-2 was expressed abundantly by cells in human and murine articular cartilage and in the cartilage of mineralizing vertebrae from neonatal mice. Protein levels were reduced in articular cartilage from older mice, in end-plate cartilage from mice, and in chondrocytes from human osteoarthritic (OA) cartilage. HIF-2 was robustly expressed in the prehypertrophic cells of mouse growth cartilage. When HIF-2, was silenced, the generation of reactive oxygen species was found to be elevated, with a concomitant decrease in catalase and superoxide dismutase activity. Suppression of HIF-2 was associated with decreased Akt-1 and mammalian target of rapamycin activities, reduced Bcl-xL expression, and a robust autophagic response, even under nutrient-replete conditions. In these silenced chondrocytes, HIF-1 expression was elevated. Decreased HIF-2 expression was associated with autophagy in OA tissues and aging cartilage samples. The autophagic response of chondrocytes in HIF-2,,knockout mouse growth plate showed an elevated autophagic response throughout the plate. Conclusion Based on these observations, we conclude that HIF-2 is a potent regulator of autophagy in maturing chondrocytes. Our data suggest that this protein acts as a brake on the autophagy-accelerator function of HIF-1. [source] Effects of Embelin on Lipid Peroxidation and Free Radical Scavenging Activity against Liver Damage in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2009Dharmendra Singh Carbon tetrachloride (CCl4) treatment to rats has been more susceptible to peroxidative damage through production of reactive metabolites, namely trichloromethyl-free radicals (CCl?3 and/or CCl3OO?) as measured by thiobarbituric acid reactive species. After the induction of liver damage by CCl4 intoxication to rats, the concentration of lipid peroxidation was significantly (P , 0.001) higher in liver and serum, along with concomitant decrease in the levels of antioxidants and cytochrome P450 enzyme in liver as compared to vehicle controls. The activities of marker enzymes , transaminases (AST, ALT), alkaline phosphatase (ALP), ,-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) , along with the total bilirubin and total protein levels were altered significantly (P , 0.001) in the serum of CCl4 -treated rats. When these rats received embelin orally (25 mg/kg) from day 1 to day 15, peroxidative damage was minimal in both liver and serum along with effectively inducing the antioxidant potential in CCl4 -treated rats. The biochemical results were compared with the standard drug silymarin , a combination of flavonolignans of Silybum marianum and histology of liver sections. In conclusion, this study suggests that embelin acts as a natural antioxidant against hepatotoxicity induced in rats. [source] | |||||||||||||||||||||||||||||||