Underexpression of MMP-2 and its Regulators, TIMP2, MT1-MMP and IL-8, is Associated with Prostate Cancer

Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (>= 7) over-expressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

OBJECTIVE: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). MATERIALS AND METHODS: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. RESULTS: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (> 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). CONCLUSION: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.

Structural and vibrational study of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone: a potential metal-protein attenuating compound (MPAC) for the treatment of Alzheimer's disease

A comprehensive structural and vibrational study of the potential metal-protein attenuating compound 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone is reported. X-ray diffraction data, as well as FT-IR and Raman frequencies, were compared with the respective theoretical values obtained from DFT calculations. Theory agrees well with experiment. In this context, an attempt of total assignment concerning the FT-IR and Raman spectra of the title compound was performed, shedding new light on previous partial assignments published elsewhere.

Chromatin Structure of Ribosomal RNA Genes in Dipterans and Its Relationship to the Location of Nucleolar Organizers

Nucleoli, nuclear organelles in which ribosomal RNA is synthesized and processed, emerge from nucleolar organizers (NORs) located in distinct chromosomal regions. In polytene nuclei of dipterans, nucleoli of some species can be observed under light microscopy exhibiting distinctive morphology: Drosophila and chironomid species display well-formed nucleoli in contrast to the fragmented and dispersed nucleoli seen in sciarid flies. The available data show no apparent relationship between nucleolar morphology and location of NORs in Diptera. The regulation of rRNA transcription involves controlling both the transcription rate per gene as well as the proportion of rRNA genes adopting a proper chromatin structure for transcription, since active and inactive rRNA gene copies coexist in NORs. Transcription units organized in nucleosomes and those lacking canonical nucleosomes can be analyzed by the method termed psoralen gel retarding assay (PGRA), allowing inferences on the ratio of active to inactive rRNA gene copies. In this work, possible connections between chromosomal location of NORs and proportion of active rRNA genes were studied in Drosophila melanogaster, and in chironomid and sciarid species. The data suggested a link between location of NORs and proportion of active rRNA genes since the copy number showing nucleosomal organization predominates when NORs are located in the pericentric heterochromatin. The results presented in this work are in agreement with previous data on the chromatin structure of rRNA genes from distantly related eukaryotes, as assessed by the PGRA.

Capillary electrophoretic enantioselective determination of zopiclone and its impurities

A capillary electrophoretic enantioselective method with UV detection was developed and validated for the simultaneous quantification of zopiclone enantiomers and its impurities, zopiclone-N-oxide enantiomers, and 2-amino-5-chloropyridine, in tablets. The analytes were extracted from the tablets using ACN and were separated in an uncoated fused-silica capillary (50 mu m, 42 cm effective length, 50 cm total length) using 80 mM sodium phosphate buffer pH 2.5 and 5 mM carboxymethyl-beta-cyclodextrin as running buffer. The analytes and the internal standard (trimethoprim) were detected at 305 and 200 nm, respectively. A voltage of 27 kV was applied and the capillary temperature was maintained at 25 degrees C. All enantiomers were analyzed within 8 min and linear calibration curves over the concentration range of 0.40.8 mg mL-1 for each zopiclone enantiomer, 0.81.6 mu g mL-1 for 2-amino-5-chloropyridine and 0.40.8 mu g mL-1 for each zopiclone-N-oxide enantiomer were obtained. The coefficients of correlation obtained for the linear curves were greater than 0.99. The intra-day and inter-day accuracy and precision were lower than 2% for all analytes. This validated method was employed to study the degradation and racemization of zopiclone under stress conditions. This application demonstrated the importance of a stability-indicating assay method for this drug.

Analysis of anti-Mullerian hormone (AMH) and its receptor (AMHR2) genes in patients with persistent Mullerian duct syndrome

Objective: To screen for mutations in AMH and AMHR2 genes in patients with persistent Mullerian duct syndrome (PMDS). Patients and method: Genomic DNA of eight patients with PMDS was obtained from peripheral blood leukocytes. Directed sequencing of the coding regions and the exon-intron boundaries of AMH and AMHR2 were performed. Results: The AMH mutations p.Arg95*, p.Arg123Trp, c.556-2A>G, and p. Arg502Leu were identified in five patients; and p.Gly323Ser and p.Arg407* in AMHR2 of two individuals. In silico analyses of the novel c.556-2A>G, p.Arg502Leu and p.Arg407* mutations predicted that they were harmful and were possible causes of the disease. Conclusion: A likely molecular etiology was found in the eight evaluated patients with PMDS. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p. Arg502Leu in AMH; and p.Gly323Ser in AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8

Prescribed use of methylphenidate hydrochloride and its correlates among Brazilian college students

Background: The prevalence of prescribed use of methylphenidate (MPH) and its correlates are not well-known in Brazil. Objective: To estimate the prevalence of prescribed use of MPH and its correlates in a sample of Brazilian college students. Methods: Twelve-thousand seven hundred and eleven college students filled out a drug use questionnaire. They were divided into two groups based on the lifetime use of MPH: MPH users (MPHU) and MPH non-users (MPHNU). Quasi-binomial regression models were carried out in order to evaluate the correlation among MPHU and other variables. Results: A lifetime use of MPH was reported from 0.9% of college students (MPHU). Being from the Midwest (PR = 4.8, p < 0.01) and South (PR = 5.2, p < 0.05), living in students housing (PR = 5.8, p < 0.001), prescribed use of amphetamines (PR = 8.9, p < 0.001) and benzodiazepines (< 3 weeks: PR = 4.4, p < 0.001; >= 3 weeks: PR = 6.7, p < 0.001), and harmful use of alcohol (PR = 4.0, p < 0.05) were correlated with MPHU. Discussion: The association of alcohol and drug use with prescribed use of MPH among college students suggests the importance of screening drinking patterns and use of other drugs among students with ADHD symptoms. Cesar ELR, et al. / Rev Psiq Clin. 2012; 39(6):183-8

Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase

This work describes the synthesis of a series of sialylmimetic neoglycoconjugates represented by 1,4-disubstituted 1,2,3-triazole-sialic acid derivatives containing galactose modified at either C-1 or C-6 positions, glucose or gulose at C-3 position, and by the amino acid derivative 1,2,3-triazole fused threonine-3-O-galactose as potential TcTS inhibitors and anti-trypanosomal agents. This series was obtained by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between the azido-functionalized sugars 1-N(3)-Gal (commercial), 6-N(3)-Gal, 3-N(3)-Glc and 3-N(3)-Gul with the corresponding alkyne-based 2-propynyl-sialic acid, as well as by click chemistry reaction between the amino acid N(3)-ThrOBn with 3-O-propynyl-GalOMe. The 1,2,3-triazole linked sialic acid-6-O-galactose and the sialic acid-galactopyranoside showed high Trypanosoma cruzi trans-sialidase (TcTS) inhibitory activity at 1.0 mM (approx. 90%), whilst only the former displayed relevant trypanocidal activity (IC(50) 260 mu M). These results highlight the 1,2,3-triazole linked sialic acid-6-O-galactose as a prototype for further design of new neoglycoconjugates against Chagas' disease. (C) 2011 Elsevier Ltd. All rights reserved.

DEPTOR Cell-Autonomously Promotes Adipogenesis, and Its Expression Is Associated with Obesity

DEP domain-containing mTOR-interacting protein (DEPTOR) inhibits the mechanistic target of rapamycin (mTOR), but its in vivo functions are unknown. Previous work indicates that Deptor is part of the Fob3a quantitative trait locus (QTL) linked to obesity/leanness in mice, with Deptor expression being elevated in white adipose tissue (WAT) of obese animals. This relation is unexpected, considering the positive role of mTOR in adipogenesis. Here, we dissected the Fob3a QTL and show that Deptor is the highest-priority candidate promoting WAT expansion in this model. Consistently, transgenic mice overexpressing DEPTOR accumulate more WAT. Furthermore, in humans, DEPTOR expression in WAT correlates with the degree of obesity. We show that DEPTOR is induced by glucocorticoids during adipogenesis and that its overexpression promotes, while its suppression blocks, adipogenesis. DEPTOR activates the proadipogenic Akt/PKB-PPAR-gamma axis by dampening mTORC1-mediated feedback inhibition of insulin signaling. These results establish DEPTOR as a new regulator of adipogenesis.

Automated analysis of lidocaine and its metabolite in plasma by in-tube solid-phase microextraction coupled with LC-UV for pharmacokinetic study

A sensitive, selective, and reproducible in-tube solid-phase microextraction and liquid chromatographic (in-tube SPME/LC-UV) method for determination of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in human plasma has been developed, validated, and further applied to pharmacokinetic study in pregnant women with gestational diabetes mellitus (GDM) subjected to epidural anesthesia. Important factors in the optimization of in-tube SPME performance are discussed, including the draw/eject sample volume, draw/eject cycle number, draw/eject flow rate, sample pH, and influence of plasma proteins. The limits of quantification of the in-tube SPME/LC method were 50 ng/mL for both metabolite and lidocaine. The interday and intraday precision had coefficients of variation lower than 8%, and accuracy ranged from 95 to 117%. The response of the in-tube SPME/LC method for analytes was linear over a dynamic range from 50 to 5000 ng/mL, with correlation coefficients higher than 0.9976. The developed in-tube SPME/LC method was successfully used to analyze lidocaine and its metabolite in plasma samples from pregnant women with GDM subjected to epidural anesthesia for pharmacokinetic study.

Pyostomatitis vegetans and its relation to inflammatory bowel disease, pyoderma gangrenosum, pyodermatitis vegetans, and pemphigus

J Oral Pathol Med (2012) 41: 584588 Pyostomatitis vegetans (PSV) is an intraoral pustular eruption considered by most authors to represent the mucous analogous of cutaneous pyoderma gangrenosum and its vegetating presentations (pyodermatitis vegetans). A strong correlation of PSV with inflammatory bowel disease (IBD) is well documented. The histopathology of PSV lesions usually reveals acanthosis, and neutrophils and/or eosinophils infiltration with intraepithelial or subepithelial abscesses; acantholysis is present in some cases. We studied four patients with IBD that presented oral lesions suggestive of PSV. Two male and two female patients were included. The histopathology of oral lesions of two patients revealed findings typical for PSV. The other two patients showed findings typical for pemphigus vulgaris (PV), although the course of their symptoms paralleled that of the bowel disease. Our findings may suggest that pustular lesions in patients with IBD can be a presentation of both PSV and PV; adequate diagnosis is required because clinical presentation is very similar.

The Southern Ocean and Its Climate in CCSM4

The new Community Climate System Model, version 4 (CCSM4), provides a powerful tool to understand and predict the earth's climate system. Several aspects of the Southern Ocean in the CCSM4 are explored, including the surface climatology and interannual variability, simulation of key climate water masses (Antarctic Bottom Water, Subantarctic Mode Water, and Antarctic Intermediate Water), the transport and structure of the Antarctic Circumpolar Current, and interbasin exchange via the Agulhas and Tasman leakages and at the Brazil-Malvinas Confluence. It is found that the CCSM4 has varying degrees of accuracy in the simulation of the climate of the Southern Ocean when compared with observations. This study has identified aspects of the model that warrant further analysis that will result in a more comprehensive understanding of ocean-atmosphere-ice dynamics and interactions that control the earth's climate and its variability.

Integral form of Yang-Mills equations and its gauge invariant conserved charges

Despite the fact that the integral form of the equations of classical electrodynamics is well known, the same is not true for non-Abelian gauge theories. The aim of the present paper is threefold. First, we present the integral form of the classical Yang-Mills equations in the presence of sources and then use it to solve the long-standing problem of constructing conserved charges, for any field configuration, which are invariant under general gauge transformations and not only under transformations that go to a constant at spatial infinity. The construction is based on concepts in loop spaces and on a generalization of the non-Abelian Stokes theorem for two-form connections. The third goal of the paper is to present the integral form of the self-dual Yang-Mills equations and calculate the conserved charges associated with them. The charges are explicitly evaluated for the cases of monopoles, dyons, instantons and merons, and we show that in many cases those charges must be quantized. Our results are important in the understanding of global properties of non-Abelian gauge theories.

AN EFFICIENT HPLC-UV METHOD FOR THE QUANTITATIVE DETERMINATION OF CEFADROXIL IN HUMAN PLASMA AND ITS APPLICATION IN PHARMACOKINETIC STUDIES

Cefadroxil is a semi-synthetic first-generation oral cephalosporin used in the treatment of mild to moderate infections of the respiratory and urinary tracts, skin and soft tissue infections. In this work a simple, rapid, economic and sensitive HPLC-UV method is described for the quantitative determination of cefadroxil in human plasma samples using lamivudine as internal standard. Sample pre-treatment was accomplished through protein precipitation with acetonitrile and chromatographic separation was performed with a mobile phase consisting of a mixture of sodium dihydrogen phosphate monohydrate solution, methanol and acetonitrile in the ratio of 90:8:2 (v/v/v) at a flow rate of 1.0mL/min. The proposed method is linear between 0.4 to 40.0 mu g/mL and its average recovery is 102.21% for cefadroxil and 97.94% for lamivudine. The method is simple, sensitive, reproducible, less time consuming for determination of cefadroxil in human plasma. The method can therefore be recommended for pharmacokinetics studies, including bioavailability and bioequivalence studies.

Morbidity among nursing personnel and its association with working conditions and work organization

Introduction: Work organization patterns and working conditions experienced by nursing personnel in the hospital settings may be associated to increased morbidity among these health workers. Aim: To estimate the prevalence and factors associated with self-reported diseases among nursing personnel at the emergency hospital in Rio Branco/ State of Acre, Brazil. Methods: A cross-sectional study was conducted involving 272 participants who answered a questionnaire including sociodemographic characteristics, working conditions, lifestyles, work ability, and a fatigue perception scale. The self-reported diseases in the 12 months prior to data collection were considered the dependent variable. Results: A total of 85.7% of the participants reported one or more diseases in the past 12 months. Most prevalent diseases were: musculoskeletal diseases (37.1%), digestive diseases (28.7%), mental disorders (28.3%), work injuries (27.9%), and respiratory diseases (26.8%). The following significant variables remained in the final model: high work demands (OR 2.69), reported fatigue (OR 3.59), night work (OR 6.55) and being a technician or nursing assistant (OR 4.23). Conclusions: Variables related to working conditions and work organization were associated with the occurrence of reported diseases among nursing professionals. Health promotion measures at work require a comprehensive approach including the working conditions and the work organization.