999 resultados para Whittle, Andrea
Resumo:
Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.
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The high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a cytokine-specific alpha-subunit (hGMR alpha) and a common signal-transducing beta-subunit (hpc) that is shared with the interleukin-3 and -5 receptors, We have previously identified a constitutively active extracellular point mutant of hpc, I374N, that can confer factor independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells (Jenkins, B. J., D'Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276-4287), This restricted activity suggested the involvement of cell type-specific signaling molecules in the activation of this mutant. We report here that one such molecule is the mouse GMR alpha (mGMR alpha) subunit, since introduction of mGMR alpha, but not hGMR alpha, into BAF-B03 or CTLL-2 cells expressing the I374N mutant conferred factor independence, Experiments utilizing mouse/human chimeric GMR alpha subunits indicated that the species specificity lies in the extracellular domain of GMRa. Importantly, the requirement for mGMR alpha correlated with the ability of I374N (but not wild-type hpc) to constitutively associate with mGMRa. Expression of I374N in human factor-dependent UT7 cells also led to factor-independent proliferation, with concomitant up-regulation of hGMR alpha surface expression. Taken together, these findings suggest a critical role for association with GMR alpha in the constitutive activity of I374N.
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Myriogenospora atramentosa has been found on lemongrass (Cymbopogon citratus) and sugarcane (Saccharum interspecific hybrids) in Queensland. These are the first records of this fungus outside of the Americas.
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Human acetyl coenzyme A-dependent N-acetyltransferase (EC 2.3.1.5) (NAT) catalyzes the biotransformation of a number of arylamine and hydrazine compounds. NAT isozymes are encoded at 2 loci; one encodes NAT1, formerly known as the monomorphic form of the enzyme, while the other encodes the polymorphic NAT2, which is responsible for individual differences in the ability to acetylate certain compounds. Human epidemiological studies have suggested an association between the acetylator phenotype and particular cancers such as those of the bladder and colon. In the present study, NAT1- and NAT2-specific riboprobes were used in hybridization histochemistry studies to localize NAT1 and NAT2 mRNA sequences in formalin-fixed, paraffin-embedded human tissue sections. Expression of both NAT1 and NAT2 mRNA was observed in liver, gastrointestinal tract tissues (esophagus, stomach, small intestine, and colon), ureter, bladder, and lung. In extrahepatic tissues, NAT1 and NAT2 mRNA expression was localized to intestinal epithelial cells, urothelial cells, and the epithelial cells of the respiratory bronchioles. The observed heterogeneity of NAT1 and NAT2 mRNA expression between human tissue types may be of significance in assessing their contribution to known organ-specific toxicities of various arylamine drugs and carcinogens.
Resumo:
Activation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) family of receptors promotes the survival, proliferation, and differentiation of cells of the myeloid compartment. Several signaling pathways are activated downstream of the receptor, however it is not clear how these induce specific biologic outcomes. We have previously identified 2 classes of constitutively active mutants of the shared signaling subunit, human (h) betac, of the human GM-CSF/interieukin-3 (IL-3)/IL-5 receptors that exhibit different modes of signaling. In a factor-dependent bipotential myeloid cell line, FDB1, an activated mutant containing a substitution in the transmembrane domain (V449E) induces factor-independent proliferation and survival, while mutants in the extracellular domain induce factor-independent granulocyte-macrophage differentiation. Here we have used further mutational analysis to demonstrate that there are nonredundant functions for several regions of the cytoplasmic domain with regard to mediating proliferation, viability, and differentiation, which have not been revealed by previous studies with the wild-type GM-CSF receptor. This unique lack of redundancy has revealed an association of a conserved membrane-proximal region with viability signaling and a critical but distinct role for tyrosine 577 in the activities of each class of mutant.
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The purpose of this article is to examine the causality between government size and corruption, and to verify if there is a different pattern of causality between developed Organization for Economic Co-operation and Development (OECD) countries (excluding Mexico) and developing countries (Latin American countries) during the period 1996 to 2003. Applying Granger and Huang`s (1997) methodology we find evidence that size of government Granger causes corruption in both samples. Since a larger government involvement in private markets today will be followed in future by a higher level of corruption a policy advice would be to enhance governance. The promotion of good governance helps to combat corruption given that it complements efforts to reduce corruption more directly, and it is strongly recommended by the International Monetary Fund, other multilateral institutions, and all worried with the negative impacts of corruption on economic activity.
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The symbiotic lifestyle is widespread among porcellanid crabs, which maintain ecological and co-evolutionary associations with annelid polychaetes, poriferans, cnidarians, echinoderms, gastropod. mollusks, and other crustaceans such as shrimps and hermit crabs, among others. We investigated the ecological association between the hermit crab Dardanus insignis and the porcellanid Porcellana sayana, in southeastern Brazil. Porcellanid crabs, hermit crabs, and available shells were collected monthly from July 2001 to June 2003, with a shrimp boat equipped with two double-rig trawl nets. The majority of P. sayana specimens were collected in shells occupied by D. insignis (96.6%); a few were found in empty shells (3.4%). The catch of both symbionts and hosts increased with increasing depth, with the highest occurrence at 35 m. The F. sayana crabs of various sizes could be found solitary or forming aggregations of up to 14 individuals per host, showing no sex or size segregation. In spite of the high diversity of shell species occupied by the hermit crabs and also available in the field, only a few of them were also utilized by P. sayana. The majority (93%) of shells utilized by P. sayana also hosted other symbiont species, constituting the basis of extensive symbiotic complexes. Thus, the ecological relationship between D. insignis and P. sayana may be classified as a non-obligate and non-specific symbiosis that may also involve other facultative organisms such as sea anemones. (C) 2008 Elsevier B.V. All rights reserved.
Resumo:
Poly(pyrrole) (PPY) coating was prepared on a stainless-steel (SS) wire for solid-phase microextraction (SPME) by electrochemical deposition (cyclic voltammetric). The PPY was evaluated by analyzing new-generation antidepressants (mirtazapine, citalopram, paroxetine, duloxetine, fluoxetine, and sertraline) in plasma sample by SPME and liquid chromatography with UV detection (LC-UV). The effect of electrolyte Solution (lithium perchlorate or tetrabutylammonium perchlorate) and the number of cycles (50, 100 or 200) applied during the polymerization process on the SPME performance was evaluated. Important factors in the optimization of SPME efficiency such as extraction time, temperature, pH, influence of plasma proteins on sorption mechanisms, and desorption conditions are discussed. The SPME-PPY/LC method showed to be linear in concentrations ranging from the limit of quantification (LOQ) to 1200 ng mL(-1). The LOQ values range from 16 to 25 ng mL-1. The inter-day precision of the SPME-PPY/LC method presented coefficient of variation (CV) lower than 15%. Based on analytical validation results, the SPME-PPY/LC methodology showed to be adequate for antidepressant analysis, from therapeutic to toxic levels. In order to evaluate the proposed method for clinical use, the SPME-PPY/LC method was applied to the analysis of plasma samples from elderly depressed patients. (c) 2009 Elsevier B.V. All rights reserved,
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A sensitive and reproducible stir bar-sorptive extraction and high-performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. Important factors in the optimization of SBSE efficiency such as pH, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) assured recoveries ranging from 72 to 86%, except for phenytoin (62%). Separation was obtained using a reverse phase C-18 column with UV detection (210 nm). The mobile phase consisted of water: acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08-40.0 mu g mL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125-40.0 mu g mL(-1) for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0 mu g mL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8% and all inter-CVs were less than 10%. Limits of quantification were 0.08 mu g mL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125 mu g mL(-1) for phenytoin. No interference of the drugs normally associated with antiepileptic drugs was observed. Based on figures of merit results, the SBSE/HPLC-UV proved adequate for antiepileptic drugs analyses from therapeutic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method. (c) 2008 Elsevier B.V. All rights reserved.
Resumo:
Reactions of the model acylium ion (CH3)(2)N-C+=O with acyclic, exocyclic, and Spiro acetals of the general formula (RO)-O-1-(CRR4)-R-3-OR2-upole mass spectrometry. Characteristic intrinsic reactivities were observed for each of these classes of acetals. The two most Characteristic intrinsic reactivities were observed for each of these classes of acetals. The two most common reactions observed were hydride and alkoxy anion [(RO-)-O-1 and (RO-)-O-2] abstraction. Other specific reactions were also observed: (a) a secondary polar [4(+) + 2] cycloaddition for acetals bearing alpha,beta-unsaturated R-3 or R-4 substituents and (b) OH- abstraction for exocyclic and spiro acetals. These structurally diagnostic reactions, in conjunction with others observed previously for cyclic acetals, are shown to reveal the class of the acetal molecule and its ring type and substituents and to permit their recognition and distinction from other classes of isomeric molecules.
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A sensitive and reproducible method by microextraction packed sorbent and liquid chromatography with UV detection (MEPS/LC-UV) is described for the determination of new generation antidepressants (sertraline, mirtazapine, fluoxetine, citalopram and paroxetine) in human plasma samples. The MEPS variables, such as sample volume, pH, number of extraction cycles (draw-eject), and desorption conditions (solvent and solvent volume of elution) influenced the MEPS/LC efficiency significantly. Important factors in the optimization of MEPS efficiency, as well as washing steps and carryover effect are discussed. The analyses were carried out using small sample volumes (400 mu L.), and in a short time period (3 min for the entire sample preparation step). The MEPS/LC-UV method was shown to be linear at concentrations ranging from the limit of quantification (LOQ) to 1000 ng mL(-1). The LOQ values ranged from 10 to 25 ng mL(-1). The inter-day precision of the method presented coefficient of the variation ranging from 1.3% to 8.7%. On the basis of analytical validation, it is shown that the MEPS/LC-UV methodology is adequate for antidepressant analysis, from therapeutic to toxic levels. In order to evaluate the proposed method for clinical use, the MEPS/LC-UV method was applied to analysis of plasma samples from elderly depressed patients. (C) 2010 Elsevier B.V. All rights reserved.
Resumo:
The effect of intraseptal injections of lidocaine before a first or a second session in the elevated plus-maze, in a test-retest paradigm, was investigated. In addition to gross session analyses, a minute-by-minute analysis of the sessions was used to evaluate both anxiety and memory. Lidocaine injections before the test session produced increases in the frequency of entries, time spent and distance run in the open arms without affecting activity occurring in the closed arms. During the retest session, saline- and lidocaine-treated rats exhibited increased indices of anxiety and lidocaine-treated rats exhibited decreased closed-arm entries. The minute-by-minute analysis showed a faster decrease in anxiety-related behaviors during the test session by saline- than by lidocaine-treated rats and a significant decrease in closed-arm exploration by saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection before the retest session produced increases in the frequency of entries, time spent and distance run in the open arms in the second session when compared with saline-treated rats. Minute-by-minute analysis showed an increase in the time spent in the open arms by lidocaine animals at the beginning of the retest session in comparison to saline animals and a significant decrease in closed-arm exploration by both groups. These results suggest that inactivation of the medial septum by lidocaine affects the expression of unconditioned and conditioned forms of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and retention of spatial information. (C) 2010 Elsevier B.V. All rights reserved.
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By using the theory of semigroups of growth a, we discuss the existence of mild solutions for a class of abstract neutral functional differential equations. A concrete application to partial neutral functional differential equations is considered. (C) 2011 Elsevier Ltd. All rights reserved.
Resumo:
Objective: The objective is to evaluate the prevalence and associated clinical characteristics of eating disorders (ED) in patients with obsessive compulsive disorder (OCD). Method: This is a cross-sectional study comparing 815 patients with OCD. Participants were assessed with structured interviews and scales: SCID-I, Y-BOCS, Dimensional Y-BOCS, BABS, Beck Depression and Anxiety Inventories. Results: Ninety-two patients (11.3%) presented the following EDs: binge-eating disorders [= 59 (7.2%)], bulimia nervosa [= 16 (2.0%)], or anorexia nervosa [= 17 (2.1%)]. Compared to OCD patients without ED (OCD-Non-ED), OCD-ED patients were more likely to be women with previous psychiatric treatment. Mean total scores in Y-BOCS, Dimensional Y-BOCS, and BABS were similar within groups. However, OCD-ED patients showed higher lifetime prevalence of comorbid conditions, higher anxiety and depression scores, and higher frequency of suicide attempts than did the OCD-Non-ED group. Primarily diagnosed OCD patients with comorbid ED may be associated with higher clinical severity. Discussion: Future longitudinal studies should investigate dimensional correlations between OCD and ED. (C) 2009 by Wiley Periodicals, Inc.