Synthesis And Antiproliferative Activity Of 8-hydroxyquinoline Derivatives Containing A 1,2,3-triazole Moiety.

Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 < 0.25 μg mL(-1)); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 μg mL(-1)). In structure-activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the α-glucosidase active site to predict the possible mechanism of action of this series of compounds.

DNA sequences generated by BCH codes over GF(4)

The question raised by researchers in the field of mathematical biology regarding the existence of error-correcting codes in the structure of the DNA sequences is answered positively. It is shown, for the first time, that DNA sequences such as proteins, targeting sequences and internal sequences are identified as codewords of BCH codes over Galois fields.

Host-guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), Hydroxypropyl-beta-cyclodextrin (HP-beta-CD), Dimethyl-beta-cyclodextrin (DM-beta-CD) and gamma-cyclodextrin (gamma-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand-Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-beta-CD > beta-CD > alpha-CD > HP-beta-CD > gamma-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.

Staphylococcus hominis subsp novobiosepticus strains causing nosocomial bloodstream infection in Brazil

To report the isolation of six Staphylococcus hominis subsp. novobiosepticus (SHN) strains from hospitalized patients with bloodstream infections in two Brazilian hospitals and to characterize their susceptibility profile to several antimicrobials. Species identification was performed by biochemical methods and sodA gene sequencing. The MICs of antimicrobials were determined by broth and agar dilution methods and by Etest. Isolates were typed by PFGE and PCR amplification was used to detect the ccr gene complex and the mec class. Morphometric evaluation of cell wall was performed by transmission electron microscopy (TEM). Susceptibility profiles indicated that the majority of isolates (five) were multidrug-resistant. Overlapping and multiplex PCR showed that five out of the six strains harboured SCCmec type III with class A mec and type 3 ccr. The initial vancomycin MIC value of 4 mg/L for these strains increased to 16-32 mg/L after growth for 10 days in BHI broth supplemented with this antimicrobial. TEM indicated that vancomycin resistance was associated with cell wall thickening and to another mechanism not fully elucidated. Only one SHN strain was oxacillin- and vancomycin-susceptible. The nosocomial infections in at least five of the patients from both hospitals were caused by a single clone of SHN. It is very important to consider SHN strains as the cause of nosocomial infections. The clinical implications resulting from the pattern of multidrug resistance in these strains may be complicated by the emergence of vancomycin resistance.

Prevalence and characterization of Enterococcus spp. isolated from Brazilian foods

Enterococci can be used in the food industry as starter or probiotic cultures. However, enterococci are also implicated in severe multi-resistant nosocomial infections. In this study, the prevalence of enterococci in selected Brazilian foodstuffs (raw and pasteurized milk, meat products, cheeses and vegetables) was evaluated. Phenotypic and PCR protocols were used for species identification. Tests for production of gelatinase, haemolysin, bacteriocin and bile salt hydrolysis were done with all enterococci isolates, whereas molecular determination of virulence markers (genes esp, gel, ace, as, efaA, hyl and cylA) and antibiotic resistance was checked only for Enterococcus faecium and Enterococcus faecalis isolates. The antibiotic-resistant isolates were assayed for biofilm formation and adhesion to mammalian cells. From the 120 food samples analyzed, 52.5% were positive for enterococci, meat and cheese being the most contaminated. E. faecium was the predominant species, followed by E. faecalis, E. casseliflavus and Enterococcus gallinarum. Phenotypic tests indicated that 67.7% of isolates hydrolyzed bile salts, 15.2% produced bacteriocin, 12.0% were beta-hemolytic and 18.2% produced gelatinase. Antibiotic resistance (gentamicin, tetracycline and erythromycin) and genes encoding for virulence traits were more frequent in E. faecalis than in E. faecium. Three E. faecium isolates were resistant to vancomycin. Among antibiotic-resistant isolates, 72.4% of E. faecalis were able to form biofilm and 13.8% to adhere to Caco-2 cells. Antibiotic-resistant E. faecalis and E. faecium isolates were grouped by RAPD-PCR and a scattered distribution was noted, indicating that resistance was not related to a particular clone. The spread of virulence/resistance traits in isolates of the two species and different RAPD-types suggest the pathogenic potential of both species. By contrast, the recovery of bacteriocinogenic E. faecium isolates with no virulence traits suggests their potential for biotechnological applications. In conclusion, our results showed that enterococci from Brazilian foods present important dualist aspects for food safety. (C) 2008 Elsevier Ltd. All rights reserved.

Clonal transmission of ESBL-producing Klebsiella spp. at a university hospital in Brazil

The present study was designed to determine the prevalence and extended-spectrum beta-lactamase (ESBL) types in clinical isolates of Klebsiella spp. at a university hospital located in the Brazilian southern region (Ribeirao Preto, Sao Paulo) as well as their antibiotic susceptibility and genetic profiles. This study included 147 non-repeat Klebsiella spp. isolates collected from January to June 2000, of which 23 K. pneumoniae and 8 K. oxytoca were selected as ESBL producers by using the Oxoid combination disk method and Etest ESBL strip. beta-lactamases were characterized by IEF, PCR and sequencing assays using primers for ESBL genes. Antibiotic susceptibility was evaluated by MicroScan system. Dissemination of two major clones of ESBL-producing Klebsiella spp. occurred in the hospital. According to the results obtained in this study there was a clonal spread of CTX-M-producing K. oxytoca in five clinics and dissemination of ESBL-producing K. pneumoniae in the nursery and pediatrics wards.

Determinants of beta-lactam resistance in meningitis-causing Enterobacteriaceae in Brazil

This study analyzed resistance determinants in extended-spectrum beta-lactamase (ESBL)-producing enterobacteria and the epidemiology of 11 Escherichia coli isolates obtained from meningitis patients in a region of Brazil from 2000 to 2005. ESBL-encoding genes and their genetic environment were investigated by PCR and sequencing. The gene bla(CTX-M-2) was identified in 3 different enterobacteria (E. coli. Serratia marcescens, and Proteus mirabilis) downstream of the insertion sequence ISCR1 (localized in class 1 integrons), hut not as part of the resistance cassettes region. Multi locus sequence typing (MLST) was used to investigate genetic relationships between the 11 E. coil isolates in this study and strains associated with meningitis in the E. coil MLST database. MLST analysis indicated high genetic diversity among isolates, and no significant genetic relationship was identified with meningitis-causing E. coil in the database. The results in this report reinforce the need to be attentive to meningitis suspected to be due to ESBL-producing enterobacterial isolates, especially where ESBL epidemiology is well known.

Changes in vancomycin-resistant Enterococcus faecium causing outbreaks in Brazil

Enterococci have been implicated in severe human infections as a consequence of associated determinants of virulence and antimicrobial resistance. The majority of vancomycin-resistant Enterococcus faecium (VRE(fm)) connected to outbreaks worldwide pertains to the clonal complex 17 (CC17). In Brazil, the majority of VRE(fm) involved in outbreaks reported so far are not related to CC17. VRE(fm) strains responsible for an outbreak and sporadic cases in hospitals located in the city of Campinas, Brazil, were compared to other VRE(fm) strains in the country. Twenty-two out of 23 E. faecium were vancomycin-resistant and harboured the vanA gene. One vancomycin-susceptible E. faecium (VSE(fm)) strain was included in this study because it was isolated from a patient who one week later harboured a VRE(fm). All strains, except VSE, showed the same alteration in the VanA element characterised by deletion of the left extremity of the transposon and insertion of IS1251 between the vanS and vanH genes. Genes codifying virulence factors such as collageneadhesin protein, enterococcal surface protein and hyaluronidase were detected in the VRE(fm) and VSE(fm) studied. Both pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed that VRE(fm) and VSE(fm) strains have a clonal relationship. New sequence types (STs) were identified by MLST as ST447, ST448, ST478 and ST412 but all belonged to the CC17. The present study revealed that VRE(fm) outbreaks in Brazil were caused by strains that did not share a common evolutionary history, and that VRE(fm) strains belonging to CC17 could be predominant in Brazil as in other countries. (C) 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Evaluation of IFA, MAT, ELISAs and immunoblotting for the detection of anti-Toxoplasma gondii antibodies in paired serum and aqueous humour samples from experimentally infected pigs

The study evaluated the efficiency of diagnostic laboratory methods to detect anti-Toxoplasma gondii antibodies in paired serum and aqueous humour samples from experimentally infected pigs. 18-mixed breed pigs were used during the experiment; these were divided into two groups, G I (infected group, n = 10) and G2 (uninfected group, n = 8). Infection was performed with 4 x 10(4) VEG strain oocysts at day 0 by the oral route in G1 animals. All pigs were euthanized at day 60, when retina, aqueous humour, and blood samples were collected. Anti-T gondii antibody levels were assessed in serum (s) and aqueous humour (ah) by indirect immunofluorescence assay (IFA), modified agglutination test (MAT), m-ELISA (using crude membranes from T gondii tachyzoites as antigen) and r-ELISA (using rhoptries from T gondii tachyzoites as antigen). Polymerase chain reactions (PCR) of samples from the retina were performed by using Tox4 and Tox5 primers. Antibody titers of G1 animals ranged from 128 to 1024 and from 16 to 256 in serum and aqueous humour, respectively. There were differences in the correlation coefficients between IFA(s) x IFA (ah) (r = 0.62, P = 0.05), MAT(s) x MAT (ah) (r = 0.97, P < 0.0001); however, there was no significant difference between r-ELISA(s) x r-ELISA (ah) (r = 0. 14, P = 0.7). Antibodies present in serum and aqueous humour recognized similar antigens. Samples of retina were positive by PCR in 30% (3/10) of infected pigs. G2 animals remained without antibody levels and were PCR negative throughout the experiment. These results suggest that the use of a combination of tests and immunoblotting for paired aqueous humour and serum samples could improve the sensitivity and specificity for the diagnosis of ocular toxoplasmosis. (c) 2007 Elsevier Ltd. All rights reserved.

Violência física e fatores associados: estudo de base populacional no sul do Brasil

OBJETIVO: Estimar a prevalência de violência física e sua associação com aspectos sociodemográficos, eventos estressantes e utilização de serviços de saúde por problemas emocionais. MÉTODOS: Estudo transversal de base populacional realizado em amostra de 1.954 sujeitos com 14 anos ou mais, residentes em Canoas, RS, 2002-2003. A amostragem por conglomerados seguiu sistemática pré-estabelecida. Os dados foram coletados em visitas domiciliares com questionário semi-estruturado e confidencial. Foram realizadas as análises: bivariada, por meio de regressão logística multinomial e multivariada, por regressão politômica, categorizando o desfecho por faixa etária. RESULTADOS: Foi encontrada prevalência de 9,7% (IC 95%: 8,37;11,03) e associação com: sexo feminino a partir dos 20 anos de idade (OR=2,74; IC 95%: 1,52;4,94), maior escolaridade (p<0,03), maior vivência de eventos estressantes com 20 anos ou mais (OR=6,61; IC 95%: 2,71;16,1) e consulta por problemas emocionais a partir dos 10 anos de idade (p>0,001). CONCLUSÕES: A prevalência da violência física na população foi significativa, com conseqüências emocionais e impacto nos serviços de saúde, requerendo capacitação dos profissionais da área.

Sentimento de discriminação em estudantes: prevalência e fatores associados

OBJETIVO: Estimar a prevalência e fatores associados ao sentimento de discriminação entre estudantes. MÉTODOS: Estudo transversal com amostra representativa de 1.170 escolares de um total de 2.282 matriculados na sétima série do ensino fundamental em escolas municipais de Gravataí (RS), em 2005. Os participantes foram selecionados por amostragem aleatória por conglomerado. Os dados foram obtidos com instrumentos auto-aplicados (Global School-based Student Health Survey, body shape questionnaire, classificação socioeconômica) preenchidos em sala de aula. Foi utilizada a regressão de Cox modificada para estudos transversais, segundo modelo hierarquizado em quatro etapas. RESULTADOS: A prevalência de sentimento de discriminação foi de 21,0%, mais prevalente entre: as meninas (RP=1,93, IC 95% 1,51;2,46); os que apresentaram absenteísmo escolar (RP=1,54, IC 95% 1,21;1,97); os que fizeram uso na vida de tabaco (RP=1,53, IC 95% 1,18;1,98); os preocupados com sua imagem corporal (RP=1,42, IC 95% 1,07;1,88); os com sentimento de solidão (RP=2,50, IC 95% 1,80;3,46) e tristeza (RP=1,29, IC 95% 1,02;1,62); os com dificuldade para dormir (RP:1,41, IC 95% 1,08;1,83); os com ideação suicida (RP=1,45, IC 95% 1,13;1,85) e os que sofreram algum tipo de injúria acidental (RP=1,56, IC 95% 1,23;1,97) ou intencional (RP=2,04, IC 95% 1,51;2,76). CONCLUSÕES: O sentimento de discriminação esteve associado ao sexo e à experiência com tabaco. Sua associação com fatores psicossociais indica a coexistência de situações adversas, como a insatisfação com a imagem corporal, sintomas depressivos e presença de injúrias. Esses resultados mostram a importância da atuação conjunta de professores e profissionais de saúde na identificação precoce desse sentimento, orientação e acompanhamento de jovens enfrentando essas situações.

Síndrome de Burnout: estudo de base populacional com servidores do setor público

OBJETIVO: Identificar preditores da síndrome de Burnout em trabalhadores do setor público. MÉTODOS: Estudo transversal com amostra representativa de 879 servidores públicos municipais de uma cidade da região metropolitana de Porto Alegre, RS. Utilizou-se um questionário elaborado para a coleta de variáveis demográficas e relacionadas às características do trabalho. A percepção sobre o ambiente laboral foi analisada a partir da Work Atmosphere Scale; para avaliar a síndrome de Burnout, utilizou-se o Maslach Burnout Inventory. Foram realizadas três análises de regressão linear múltipla pelo método stepwise em que cada dimensão da síndrome foi considerada como desfecho, enquanto as demais variáveis foram estimadas como preditoras e controladas por sexo e idade. RESULTADOS: As variáveis relacionadas à percepção do ambiente de trabalho foram as que mais contribuíram para a ocorrência de burnout. A percepção do trabalho como estressante e a presença de pessoas que atrapalham o ambiente laboral participaram do modelo explicativo das três dimensões. Nove variáveis compuseram o modelo preditor, que explicou 43% da ocorrência da Exaustão Emocional. "Perceber o trabalho como estressante" apresentou maior poder explicativo. Na Despersonalização, oito variáveis compuseram o modelo em 25%; "perceber o trabalho como estressante" foi, mais uma vez, a variável de maior poder explicativo. A Baixa Realização Profissional mostrou um conjunto de variáveis com poder explicativo de 20%; ambiente de trabalho considerado bom apresentou maior peso, associando-se inversamente. CONCLUSÕES: A percepção dos servidores públicos sobre seu ambiente de trabalho tem importante papel como preditor da síndrome de Burnout. Avaliar o trabalho como estressante e presença de pessoas que atrapalham o ambiente mostraram-se como elementos de maior relevância.