Slow Spread of SARS-CoV-2 in Southern Brazil Over a 6-Month Period: Report on 8 Sequential Statewide Serological Surveys Including 35 611 Participants.

Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 serological surveys. Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies. Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval [CI] = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%). Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.

Cross Talk between Apical Periodontitis and Metabolic Disorders: Experimental Evidence on the Role of Intestinal Adipokines and Akkermansia muciniphila.

INTRODUCTION: Infection and dysbiosis present a close relationship with metabolic diseases although the influence of apical periodontitis (AP) in this context needs further investigation. This study evaluated the influence of AP in a rat model of metabolic syndrome induced by 10% fructose supplementation. METHODS: Male Wistar rats were used. Animals that received a high-fructose diet (HFD, n = 30) or filtered water (control, n = 30) were subdivided into the following groups: (1) without induction of AP (no AP, n = 10 each), (2) with AP induction 2 weeks before euthanasia (AP 14 days, n = 10 each), and (3) with AP induction 4 weeks before euthanasia (AP 28 days, n = 10 each). RESULTS: HFD triggered metabolic syndrome, as indicated by the induction of overweight and hyperglycemia, besides polydipsia, regardless of the AP induction. Serum or intestinal tumor necrosis factor, interleukin 1 beta, and interleukin 6 levels were undetectable, regardless of the experimental group. Serum leptin and adiponectin levels were significantly elevated in the HFD group without AP induction. The intestinal levels of leptin were significantly increased in the groups with 28 days of AP induction despite HFD. A significant elevation of liver glutathione levels was observed in animals submitted to HFD and AP for 14 days. AP induction (14 or 28 days) led to pulp and periapical tissue inflammation without any influence of HFD. Either HFD or AP induction led to dysbiosis, as indicated by a significant reduction of fecal A. muciniphila expression. CONCLUSIONS: We provide novel evidence that AP can have systemic impacts on metabolic disorders, likely by modulating intestinal metabolism and microbiota.

Toxicological evaluation of a standardized hydroethanolic extract from leaves of Plantago australis and its major compound, verbascoside.

ETHNOPHARMACOLOGICAL RELEVANCE: Plantago australis is a perennial plant widely distributed in Latin America, and its seeds and leaves are used in folk medicine to treat many diseases and conditions. Among its various chemical compounds, verbascoside is one of the most present, and has several pharmacological activities described, but there is not much information about its toxicity. AIMS OF THE STUDY: The aims of this study were to optimize the extraction of verbascoside from P. australis leaves with ultrasound methods, to develop a validated HPLC method to quantify verbascoside, and to evaluate the toxicological safety of the extract and verbascoside using in vitro and in vivo assays. MATERIALS AND METHODS: Dried leaves of P. australis were submitted to different extraction methods (percolation and ultrasound). The optimization of the ultrasound extraction was carried out by complete factorial design (22) and response surface methodology (RSM), followed by HPLC analysis for marker compounds. HPLC analysis was performed to verify the presence of the marker compounds aucubin, baicalein, oleanolic acid, ursolic acid and verbascoside. Mutagenicity was assessed by Salmonella/microsome mutagenicity assay. Cytotoxicity and genotoxicity were evaluated in V79 cells by reduction of tetrazolium salt (MTT) and neutral red uptake (NRU) assays, and alkaline comet assay, respectively. Verbascoside phototoxicity was assessed in 3T3 cells by the NRU phototoxicity assay. Wistar rats were used to perform the acute and sub-chronic toxicity tests. RESULTS: Among the marker compounds, only verbascoside was found in the hydroethanolic extract of P. australis leaves (PAHE); its highest concentration was obtained with the ultrasound-assisted extraction (UAE) method, optimized in 40 min and 25 °C, and the method validation was successfully applied. Neither PAHE nor verbascoside showed mutagenic or genotoxic activities. Cytotoxicity assays demonstrated that both PAHE and verbascoside reduced cell viability only at the highest concentrations, and verbascoside had no phototoxic properties. The in vivo toxicity evaluation of PAHE suggested that the LD50 is higher than 5000 mg/Kg, indicating that this extract is safe for use. In addition, no signs of toxicity were found in subchronic exposure. CONCLUSION: The HPLC method to quantify verbascoside was validated, and the extraction of verbascoside from P. australis leaves through ultrasound method was optimized, yielding an extract with 6% verbascoside. Our results suggest the toxicological safety of PAHE and verbascoside, corroborating the use of P. australis in folk medicine, and also indicate verbascoside as a potential ingredient in topical formulations.

Study of correlation between imatinib mesylate plasma levels and hematological profile of patients undergoing treatment for chronic myeloid leukemia / Estudo da correlação entre os níveis plasmáticos de mesilato de imatinibe e o perfil hematológico de pacientes com leucemia mieloide crônica em tratamento

ABSTRACT Introdution: Chronic myeloid leukemia (CML) is a genetic disorder of hematopoietic stem cells, resulting in a myeloproliferative expansion of blood cells. CML is associated with the presence of the Philadelphia chromosome (Ph), generating an oncogene (BCR-ABL). The current treatment of choice is imatinib mesylate (IM). Objective: To correlate serum levels of MI with hematological parameters in patients with CML. Method: A retrospective cross-sectional study in patients treated for CML. Serum level of IM was determined by a high-performance liquid chromatography with diode array detector (HPLC-DAD), and statistical analysis was performed using SPSS version 20.0 software. Results: We studied 55 CML patients - 24 men (43.6%) and 31 women (56.4 %) - with a mean age of 54 years, who used IM. Among these, 45 patients were in the chronic phase (81.6 %); seven, in the accelerated phase (13.1%); and three, in the blast crisis (5.2%). Patients received a mean IM dose of 434 mg/day. Serum levels of the patients presented an average of 1,092 ± 617 ng/ml, and, in all, 47 patients (85.4%) had hematologic response (HR). Conclusion: There was no correlation between the number of leukocytes, platelets and hemoglobin and the serum level of IM, although there is a trend with respect to hemoglobin (p = 0.062).

RESUMO Introdução: Leucemia mieloide crônica (LMC) é uma desordem genética de células-tronco hematopoiéticas, resultando em uma expansão mieloproliferativa das células sanguíneas. A LMC está associada à presença do cromossomo Philadelphia (Ph), o que gera um oncogene (BCR-ABL). Atualmente, o tratamento de primeira escolha é o mesilato de imatinibe (MI). Objetivo: Correlacionar os níveis séricos de MI com parâmetros hematológicos em pacientes com LMC. Método: Estudo transversal retrospectivo em pacientes com LMC em tratamento. O nível sérico de MI foi determinado por um sistema de cromatografia líquida de alta eficiência com detector de arranjo de diodos (CLAE-DAD), e a análise estatística foi realizada no programa SPSS versão 20.0. Resultados: Foram estudados 55 pacientes - 24 homens (43,6%) e 31 mulheres (56,4%) - com média de idade de 54 anos, portadores de LMC que utilizavam MI. Destes, 45 encontravam-se em fase crônica (81,6%); sete, em fase acelerada (13,1%) e três, em crise blástica (5,2%). Os pacientes em questão receberam uma média de dose do MI de 434 mg/dia. O nível sérico dos pacientes apresentou média de 1.092 ± 617 ng/ml e, ao todo, 47 pacientes (85,4%) apresentaram resposta hematológica (RH). Conclusão: Não houve correlação do número de leucócitos, plaquetas e hemoglobina com o nível sérico de MI, embora exista uma tendência observada com relação à hemoglobina (p = 0,062).

Prevalência de rubéola nos pacientes atendidos na unidade básica de saúde áurora, Campo Bom, RS / Prevalence of rubella in patients attended at the aurora basic unit health, Campo Bom, RS

Introdução: A rubéola é uma doença exantemática aguda, de origem viral. Sua transmissão ocorre por meio de contato de secreções de vias aéreas de pessoas infectadas ou por transmissão vertical. A síndrome da rubéola congênita (SRC) ocorreem função de infecção materna, durante os três primeiros meses de gestação, quando pode haver a invasão da placenta pelo vírus, com disseminação pelos tecidos embrionários, acarretando aborto espontâneo, natimortos e efeitos congênitos. A determinação dos anticorpos IgG e IgM específicos são muito importantes para o diagnóstico sorológico das infecções pela rubéola congênita pós-natal ou primária. O tratamento é relativo aos sintomas apresentados e o período de gestação da mãe. A vacinação é o procedimentomais eficaz, onde se adquire a munidade, que é duradoura. Objetivos: Verificar a prevalência de rubéola nos pacientes atendidos na Unidade Básica de Saúde (UBS), em Campo Bom, no Rio Grande do Sul (RS), e examinar os fatores de risco da doença e susceptibilidade na população estudada. Metodologia: Estudo transversal, utilizando dados de 94 pacientes atendidos na UBS, em Campo Bom (RS), entre maio de 2005 e maio de 2009. Para a realização dos testes, foram coletadas 5 mL de sangue periféricocom o paciente em jejum. Utilizou-se soro para dosar IgG e IgM antirrubéola, através do teste de ELISA. As amostras foram processadas no Laboratório de Biomedicina do Centro Universitário Feevale, em Novo Hamburgo (RS). Resultados: Dos 94 pacientes com faixa etária dos 2 aos 51 anos, 87 (92,5%) eram do sexo feminino, sendo que, 15destes (17,2%) estavam em período gestacional e 7 (7,4%) eram do sexo masculino. Dos pacientes analisados, 89 (94%) apresentaram IgG positivo. Conclusão: O presente estudo demonstrou que a população avaliada pode ter adquirido imunidade através deinfecção primária ou por vacinação, diminuindo, dessa maneira, o contágio nos grupos de risco

Introduction: Rubella is an acute exanthematous disease of viralorigin. It is transmission occurs through contact of airway secretionsof infected people or by vertical transmission. The congenital rubellasyndrome (CRS) occurs due to maternal infection during the first 3months of pregnancy, can occur when the invasion of the placentaby the virus to spread by the embryonic tissues, leading tomiscarriage, stillbirth and birth defects. The determination of IgGand IgM specific are very important for the serological diagnosis ofcongenital rubella infection by postnatal or primary. The treatmentis on the symptoms and the gestation period of the mother. Sincethe vaccination the most effective procedure, which is acquiredimmunity, which is long lasting. Objectives: To assess theprevalence of rubella in patients enrolled in the Basic Health Unitin Campo Bom, Rio Grande do Sul (RS). To examine the riskfactors and disease susceptibility in the population. Methodology:Cross-sectional study using data from 94 patients treated in theBasic Health Unit in Campo Bom (RS) between May 2005 and May2009. For the tests, were collected 5 mL of peripheral blood withthe patient fasting, serum was used for measuring rubella IgG andIgM by ELISA. The samples were processed at the Laboratory ofBiomedicine in the Feevale University Center in Novo Hamburgo(RS). Results: Of 94 patients, aged from 2 to 51, 87 (92.5%) werefemale, and 15 of these (17.2%) are in the gestational period and 7(7.4%) is male. Of the patients studied, 89 (94%) had positive IgGwhich could mean the effectiveness of public awareness of theneed for prevention of rubella. Conclusion: This studydemonstrates that the study population may have acquired immunitythrough primary infection or through vaccination, decreasing thespread of disease in risk groups.

Concordância dos resultados do sistema BD Phoenix com provas bioquímicas manuais na identificação de enterobactérias em amostras clínicas / Agreement of results of the BD Phoenix system and manual biochemical tests in the identification of Enterobacteriaceae from clinical samples

Enterobactérias pertencem a um grupo grande e heterogêneo de bacilos Gram-negativos cujo habitat natural é o cólon de humanos e animais, sendo microrganismos amplamente distribuídos na natureza. Devido a essas características são frequentemente responsáveis por infecções hospitalares. O principal objetivo desse estudo foi avaliar a concordância entre as provas bioquímicas manuais e o sistema automatizado BD Phoenix 100 na identificação de enterobactérias, a partir da análise de registros de pacientes hospitalizados. Métodos: No período de agosto de 2011 a abril de 2012, foram realizados 303 exames no Laboratório Exame de Análises Clinicas pelos métodos manual e automatizado, os quais foram submetidos a análise dos dados. Resultados: Do total, 27,7% foram positivos para enterobactérias. Os microrganismos mais frequentes isolados foram a Klebsiella pneumoniae (36,9%) e Escherichia coli (29,8%). O estudo apresentou uma alta concordância entre os métodos, principalmente na identificação dos gêneros, caso em que a concordância chegou a 97% dos registros. Na identificação das espécies, as bactérias dos gêneros Klebsiella spp. e Serratia spp. não tiveram suas espécies identificadas pelo método manual em sete dos registros observados, sendo identificadas somente pela automação. Da mesma forma, algumas amostras de Escherichia coli não foram detectadas pelo método manual, que as identificou como indeterminadas em quatro dos registros analisados. Conclusão: Verificou-se uma boa concordância entre os métodos na identificação das principais enterobactérias isoladas de amostras clínicas...

Enterobacteriaceae are microorganisms that are widely distributed in nature and belong to a large and heterogeneous group of Gram-negative bacilli whose natural habitat is the colon of human beings and animals and are. Because of these characteristics they are often responsible for hospital infections. The main objective of this study was to assess the agreement between manual biochemical tests and the BD Phoenix 100 automated system in the identification of the Enterobacteriaceae, based on an analysis of hospitalized patients’ records. Methods: In the period between August 2011 and April 2012, 303 tests were made at Laboratório Exame de Análises Clinicas by the manual and automated methods, which were subjected to analysis. Results: Results revealed that 27.7% of the tests were positive for Enterobacteriaceae. The most commonly isolated microorganisms were Klebsiella pneumoniae (36.9%) and Escherichia coli (29.8%). The study showed a high agreement between the methods, especially in the identification of genders, in which case agreement reached 97% of records. When it comes to identifying the species, seven samples of Klebsiella spp. and Serratia spp. bacteria had their species identified only by the automated method and not by the manual method. Similarly, some samples of Escherichia coli, were not detected by the manual, which identified them as indeterminate in four of the records analyzed. Conclusions: There was a good agreement between both methods in identifying the major Enterobacteriaceae isolated from clinical samples...

Modulatory effect of resveratrol on SIRT1, SIRT3, SIRT4, PGC1α and NAMPT gene expression profiles in wild-type adult zebrafish liver.

Sirtuins (SIRTs) are NAD(+)-dependent deacetylases that catalyze the hydrolysis of acetyl-lysine residues. They play an important role in many physiological and pathophysiological processes, such as the regulation of lifespan and the prevention of metabolic diseases. In this study, we analyzed the effect of resveratrol on the gene expression levels of SIRT1, SIRT3, SIRT4, PGC1α, and NAMPT, as well as its effect on NAD(+) and NADH levels, in the liver of non stressed or non impaired wild-type zebrafish. Semiquantative RT-PCR assays showed that resveratrol did not change the mRNA levels of SIRT1 and PGC1α but decreased the expression levels of the SIRT3, SIRT4, and NAMPT genes. The decrease in NAMPT mRNA levels was accompanied by an increase in NADH levels, thereby decreasing the NAD(+)/H ratio. Taken together, our results suggest that resveratrol plays a modulatory role in the transcription of the NAMPT, SIRT3, and SIRT4 genes. Zebrafish is an interesting tool that can be used to understand the mechanisms of SIRTs and NAMPT metabolism and to help develop therapeutic compounds. However, further investigations using healthy experimental animals are required to study the modulation of the SIRT and NAMPT genes by resveratrol before it is used as a nutraceutical compound in healthy humans.

The role of calcium channel blockers and resveratrol in the prevention of paraquat-induced parkinsonism in Drosophila melanogaster: a locomotor analysis.

Studies have suggested that neuronal loss in Parkinson's disease (PD) could be related to the pacemaker activity of the substantia nigra pars compacta generated by L-type Ca(v) 1.3 calcium channels, which progressively substitute voltage-dependent sodium channels in this region during aging. Besides this mechanism, which leads to increases in intracellular calcium, other factors are also known to play a role in dopaminergic cell death due to overproduction of reactive oxygen species. Thus, dihydropyridines, a class of calcium channel blockers, and resveratrol, a polyphenol that presents antioxidant properties, may represent therapeutic alternatives for the prevention of PD. In the present study, we tested the effects of the dihydropyridines, isradipine, nifedipine, and nimodipine and of resveratrol upon locomotor behavior in Drosophila melanogaster. As previously described, paraquat induced parkinsonian-like motor deficits. Moreover, none of the drugs tested were able to prevent the motor deficits produced by paraquat. Additionally, isradipine, nifedipine, resveratrol, and ethanol (vehicle), when used in isolation, induced motor deficits in flies. This study is the first demonstration that dyhidropyridines and resveratrol are unable to reverse the locomotor impairments induced by paraquat in Drosophila melanogaster.

Zebrafish as a model organism to evaluate drugs potentially able to modulate sirtuin expression.

Sirtuins comprise a unique class of NAD(+)-dependent deacetylases that are key regulators of many physiological processes. They appear to be a potential target set of enzymes for treatment of age-associated diseases and have attracted interest in many research areas involving chemical and cellular investigations to understand them and discover potential ligands. For molecular screening, a cost-effective, easily manipulated, and consolidated model organism is needed, and the zebrafish fits these requirements perfectly. Here, we report the identification of sirtuin-related genes and their expression patterns in nine tissues of adult zebrafish. The investigation identified eight sirtuin-related genes, and their phylogenetic analysis resulted in seven well-resolved terminal clades, corresponding to each sirtuin (SIRT1, 2, 4-7) and two SIRT3 paralogs. Each gene showed a unique expression profile, illustrating a wide tissue distribution of sirtuins in zebrafish. SIRT1, SIRT3, SIRT5, and SIRT6 genes were expressed in all tissues, and SIRT1 exhibited the highest level of expression in all organs. A modulation experiment was performed using resveratrol, and results confirmed to the predicted scenario: altered sirtuin expression levels. Drugs based on sirtuin modulators may be tested using this system and could lead us to more selective and powerful therapies for age-related disorders.