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Plasmodium vivax Infection Alters Mitochondrial Metabolism in Human Monocytes
No full textMonocytes play an important role in the host defense against Plasmodium vivax as the main source of inflammatory cytokines and mitochondrial reactive oxygen species (mROS). Here, we show that monocyte metabolism is altered during human P. vivax malaria, with mitochondria playing a major function in this switch. The process involves a reprograming in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation. P. vivax infection results in dysregulated mitochondrial gene expression and in altered membrane potential leading to mROS increase rather than ATP production. When monocytes were incubated with P. vivax-infected reticulocytes, mitochondria colocalized with phagolysosomes containing parasites representing an important source mROS. Importantly, the mitochondrial enzyme superoxide dismutase 2 (SOD2) is simultaneously induced in monocytes from malaria patients. Taken together, the monocyte metabolic reprograming with an increased mROS production may contribute to protective responses against P. vivax while triggering immunomodulatory mechanisms to circumvent tissue damage. IMPORTANCE Plasmodium vivax is the most widely distributed causative agent of human malaria. To achieve parasite control, the human immune system develops a substantial inflammatory response that is also responsible for the symptoms of the disease. Among the cells involved in this response, monocytes play an important role. Here, we show that monocyte metabolism is altered during malaria, with its mitochondria playing a major function in this switch. This change involves a reprograming process in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation. The resulting altered mitochondrial membrane potential leads to an increase in mitochondrial reactive oxygen species rather than ATP. These data suggest that agents that change metabolism should be investigated and used with caution during malaria
Phytochemical characterization and inhibition of Candida sp. by the essential oil of Baccharis trimera (Less.) DC
No full textFundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico, FUNCAP for financial supportThis study aimed to investigate the chemical composition and antifungal potential of the essential oil of Baccharis trimera (Less.) DC. against Candida strains. The half maximal inhibitory concentration (IC50) was assessed by the microdilution method using the essential oil at a concentration range of 8192 to 8 μg/mL. The minimum fungicide concentration (MFC) was determined by subculture in solid medium. The ability of the essential oil to modulate the activity of antifungals was determined in wells treated simultaneously with the oil at a subinhibitory concentration (MFC/16) and fluconazole (FCZ). The fungal morphology was analyzed by microscopy. Gas chromatography coupled with mass spectrometry (GC/MS) was used to identify the chemical composition. The essential oil presented an CI50 of 11.24 and 1.45 μg/mL, which was found to potentiate the effect of FCZ against Candida albicans. On the other hand, this combined treatment resulted in antagonism against Candida tropicalis and no evident modulation against Candida krusei was observed. The essential oil significantly inhibited hyphae growth. However, with a MFC ≥ 16,384 μg/mL, it is assumed that it has a fungistatic action. The antifungal properties demonstrated in this study might be related to the presence of sesquiterpenes and monoterpenes, and the interaction between them. In conclusion, Baccharis trimera showed promising anti-Candida effects, in addition to potentiating the activity of FCZ against Candida albicans, affecting its morphological transition. Therefore, this species constitutes a source of chemical compounds with the potential to be used in the combat of fungal infections
Genomic and temporal analyses of Mycobacterium bovis in southern Brazil
No full textMycobacterium bovis is a causal agent of bovine tuberculosis (bTB), one of the most important diseases currently facing the
cattle industry worldwide. Tracing the source of M. bovis infections of livestock is an important tool for understanding the
epidemiology of bTB and defining control/eradication strategies. In this study, whole genome sequencing (WGS) of 74 M. bovis
isolates sourced from naturally infected cattle in the State of Rio Grande do Sul (RS), southern Brazil, was used to evaluate the
population structure of M. bovis in the region, identify potential transmission events and date the introduction of clonal complex
(CC) European 2 (Eu2). In silico spoligotyping identified 11 distinct patterns including four new profiles and two CCs, European 1
(Eu1) and Eu2. The analyses revealed a high level of genetic diversity in the majority of herds and identified putative transmis sion clusters that suggested that within- and between-herd transmission is occurring in RS. In addition, a comparison with
other published M. bovis isolates from Argentina, Brazil, Paraguay and Uruguay demonstrated some evidence for a possible
cross-border transmission of CC Eu1 into RS from Uruguay or Argentina. An estimated date for the introduction of CC Eu2 into
RS in the middle of the 19th century correlated with the historical introduction of cattle into RS to improve existing local breeds.
These findings contribute to the understanding of the population structure of M. bovis in southern Brazil and highlight the poten tial of WGS in surveillance and helping to identify bTB transmission
Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis
No full textNoroviruses are a leading cause of acute gastroenteritis
(AGE) among adults and children worldwide. Noro-
Surv is a global network for norovirus strain surveillance
among children <5 years of age with AGE. Participants in
16 countries across 6 continents used standardized protocols
for dual typing (genotype and polymerase type)
and uploaded 1,325 dual-typed sequences to the Noro-
Surv web portal during 2016–2020. More than 50% of
submitted sequences were GII.4 Sydney[P16] or GII.4
Sydney[P31] strains. Other common strains included
GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses.
In total, 22 genotypes and 36 dual types, including GII.3
and GII.20 viruses with rarely reported polymerase
types, were detected, refl ecting high strain diversity. Surveillance
data captured in NoroSurv enables the monitoring
of trends in norovirus strains associated childhood
AGE throughout the world on a near real-time basis
Individual responses to a single oral dose of albendazole indicate reduced efficacy against soil-transmitted helminths in an area with high drug pressure
No full textBackground: Albendazole (ALB) is administered annually to millions of children through global deworming programs targeting soil-transmitted helminths (STHs: Ascaris lumbricoides, Trichuris trichiura and hookworms, Necator americanus and Ancylostoma duodenale). However, due to the lack of large individual patient datasets collected using standardized protocols and the application of population-based statistical methods, little is known about factors that may affect individual responses to treatment.
Methodology/principal findings: We re-analyzed 645 individual patient data from three standardized clinical trials designed to assess the efficacy of a single 400 mg oral dose of ALB against STHs in schoolchildren from different study sites, each with varying history of drug pressure based on duration of mass drug administration programs: Ethiopia, low; Lao People's Democratic Republic (PDR), moderate; Pemba Island (Tanzania), high. Using a Bayesian statistical modelling approach to estimate individual responses (individual egg reduction rates, ERRi), we found that efficacy was lower in Pemba Island, particularly for T. trichiura. For this STH, the proportion of participants with a satisfactory response (ERRi ≥50%), was 65% in Ethiopia, 61% in Lao PDR but only 29% in Pemba Island. There was a significant correlation between ERRi and infection intensity prior to drug administration (ERRi decreasing as a function of increasing infection intensity). Individual age and sex also affected the drug response, but these were of negligible clinical significance and not consistent across STHs and study sites.
Conclusions/significance: We found decreased efficacy of ALB against all the STHs analyzed in Pemba Island (Tanzania), an area with high drug pressure. This does not indicate causality, as this association may also be partially explained by differences in infection intensity prior to drug administration. Notwithstanding, our results indicate that without alternative treatment regimens, program targets will not be achievable on Pemba Island because of inadequate efficacy of ALB
The influence of the U.S. response to COVID-19 in Global Health
No full textA resposta americana à pandemia envolve um proeminente volume de recursos federais, em especial destinados ao desenvolvimento e aquisição de produtos no uso interno, como diagnósticos ou vacinas. As justificativas para esse desembolso se baseiam em mecanismos de investimentos e aspectos históricos. Assim, a construção social do nacionalismo na formação na sociedade americana prejudica o acesso a tecnologias em saúde. A revisão desses aspectos demonstra como os Estados Unidos (EUA) garantiram compra de grande quantitativo de produtos em potencial, inclusive assegurando excessiva produção local. Essa política externa unilateral tem influenciado outros países ou blocos regionais e prejudicado a cooperação e a solidariedade global com impacto na saúde coletiva de diversas nações.The American response to the pandemic involves a prominent volume of federal resources, especially for developing and acquiring products for internal use, such as diagnostics or vaccines. Investment mechanisms and historical aspects justify this expenditure. Thus, the social construction of nationalism in American society hinders access to health technologies. The review of such aspects shows how the United States (U.S.) secured a large number of potential products, ensuring excessive local production. This unilateral foreign policy has influenced other countries or regional blocs and undermined global cooperation and solidarity, affecting the collective health of several nations
Hospitalizações por doença de Chagas em hospital terciário em Teresina, Piauí: uma série de casos
No full textINTRODUÇÃO: Atualmente estima-se uma prevalência de 4,6 milhões de pessoas portadoras de T. cruzi no Brasil, predominando casos crônicos, que podem apresentar-se nas formas indeterminada, cardíaca, digestiva ou mista. As complicações crônicas levam a hospitalizações em seu curso, sendo nestas, a forma cardíaca a mais prevalente. OBJETIVOS: Avaliar o perfil clínico e epidemiológico de pacientes com doença de Chagas crônica hospitalizados no Hospital Universitário da Universidade Federal do Piauí(HU-UFPI) entre março de 2014 e março de 2019. METODOLOGIA. Série de casos utilizando dados de prontuários. RESULTADOS: Foram analisados dados de 76 pacientes, com idade igual ou superior a 60 anos (68,4%), sexo masculino (56,6%), nasceram no Piauí, principalmente no semiárido piauiense, predominantemente no polígono formado pelos municípios de Oeiras, Picos e São João do Piauí. Dos 76 pacientes, 42 (55,3%) forma cardíaca isolada, 23 (30,3%) tinham a forma digestiva, e 11 (14,4%) tinham a forma mista. Entre os 34 pacientes com a forma digestiva, (76,5%) tinham megaesôfago, (23,5%) tinham megacólon, sendo que (17,7%) tinham comprometimento simultâneo do esôfago e do cólon. Alguns destes 34 apresentam também cardiopatia. Entre os pacientes com forma digestiva, os sintomas mais prevalentes foram: disfagia (69,6%), perda de peso (39,1%) e constipação (34,8%). E dispnéia(50%), taquicardia/arritmia (47,6%) e síncope (40,5%) nos pacientes com forma cardíaca isolada. A IC foi o achado clínico mais prevalente nos pacientes com forma cardíaca. Os achados eletrocardiográficos foram: BAV em 66,7%, HBAE em 40,7%, BRD em 33,3% e extrassístoles em 14,8% Ao ecocardiograma as alterações segmentares observadas foram disfunção sistólica (40,7%) e disfunção diastólica do VE(29,6%). E 68% destes pacientes apresentaram FEVE <45%. As drogas mais utilizadas foram: os IECA(57,9%), diuréticos (66,7%), bloqueadores adrenégicos (31,6%) e antiarrítmicos (21,1%). O uso de aminas vasoativas ocorreu em 18,4% dos casos, com média de 2,8 dias de uso, sendo a noradrenalina a mais utilizada. Entre os procedimentos cirúrgicos, o mais utilizado foi o implante de marca-passo em 27 pacientes (35,5%). Seis (14,3%) receberam implante de CDI. Entre os pacientes da forma digestiva, os exames mais realizados foram EDA, em 23,7%, esofagograma (9,2%) e colonoscopia (3,9%). Foram realizados os seguintes procedimentos cirúrgicos: esofagectomia, esofagogastrostomia e esofagomiotomia. Em relação às 76 internações, a maioria 33 (43,4%), ocorreram por pacientes que foram transferidos para o HU-UFPI de outro serviço para tratamento especializado. A média de tempo de internação foi de 11,5 dias. Quanto aos desfechos intra-hospitalares de pacientes com DC, a alta ocorreu em 90,8% e óbito ocorreu em 9,2%. CONCLUSÕES: A doença de Chagas é causa frequente de hospitalizações no HU-UFPI, observando-se maior incidência da forma cardíaca. A maioria dos pacientes é natural de municípios nas regiões sudeste e sudoeste do estado, regiões de maior endemicidade. As hospitalizações de pacientes com a forma cardíaca da doença de Chagas são menos prolongadas e associadas frequentemente à implantação de marca-passo e cardioversor-desfibrilador implantável e com letalidade nula. Na forma digestiva, a maioria das internações está associada ao comprometimento esofágico, requerendo intervenções cirúrgicas, cursando com taxa de letalidade considerávelINTRODUCTION: Currently, there is an estimated prevalence of 4.6 million people with T. cruzi in Brazil, predominantly chronic cases, which may present as indeterminate, cardiac, digestive or mixed forms. Chronic complications lead to hospitalizations during its course, and in these, the cardiac form is the most prevalent. OBJECTIVES: To evaluate the clinical and epidemiological profile of patients with chronic Chagas disease hospitalized at the University Hospital of the Federal University of Piauí (HUUFPI) between March 2014 and March 2019. METHODOLOGY: Case series using data from medical records. RESULTS: 76 patients had their data analyzed, age 60 years or older (68.4%), male (56.6%), born in Piauí, mainly in the semi-arid region of Piauí, predominantly in the polygon formed by the cities of Oeiras, Picos, and São João do Piauí. Of these 76 patients, 42 (55.3%) had the isolated cardiac form, 23 (30.3%) had the digestive form, and 11 (14.4%) had the mixed form. Among the 34 patients with the digestive form, (76.5%) had megaesophagus, (23.5%) had megacolon, and (17.7%) had simultaneous involvement of the esophagus and colon. Some of these 34 also had heart disease. Among patients with the digestive form, the prevalent symptoms were dysphagia (69.6%), weight loss (39.1%), and constipation (34.8%). In addition, there was dyspnea (50%), tachycardia or arrhythmia (47.6%), and syncope (40.5%) in patients with the isolated cardiac form. CI was the most prevalent clinical finding in patients with cardiac forms. The electrocardiographic findings were AV block in 66.7%, LAHB in 40.7%, RBBB in 33.3% and extrasystoles in 14.8% of the patients On echocardiography, the segmental changes observed were systolic dysfunction (40.7%) and LV diastolic dysfunction (29.6%), and 68% of these patients had LVEF <45%. The most used drugs were ACE inhibitors (57.9%), diuretics (66.7%), adrenergic blockers (31.6%) and antiarrhythmics (21.1%). Vasoactive amines it were used in 18.4% of the cases, with a mean of 2.8 days of use, noradrenaline being the most used. Regarding surgical procedures, the most used was pacemaker implantation in 27 patients (35.5%). Six (14.3%) received implantable ICD. Considering other patients with the digestive form, the most performed tests were EGD, in 23.7%, esophagogram (9.2%) and colonoscopy (3.9%). As to the others patients with the digestive form, the most performed tests were EGD, in 23.7%, esophagogram (9.2%) and colonoscopy (3.9%). The following surgical procedures were performed esophagectomy, esophagogastrostomy, and esophagomyotomy. As for the 76 hospitalizations, the majority 33 (43.4%), occurred by patients who were transferred to HU-UFPI from another service for specialized treatment. The average length of hospitalization was 11.5 days. As for the in-hospital outcomes of CD patients, discharge occurred in 90.8% and death occurred in 9.2%. CONCLUSIONS: Chagas disease is a frequent cause of hospitalizations in HU-UFPI, with a higher incidence of the cardiac form. Most patients are from cities in the southeastern and southwestern regions of the state, regions of higher endemicity. Hospitalizations for patients with the cardiac form of Chagas Disease are less prolonged and are often associated with pacemaker and implantable cardioverter-defibrillator implantation and with no lethality. In the digestive form, most hospitalizations are associated with esophageal impairment, requiring surgical interventions, with a considerable mortality rat
Inclusion Complexes of Non-Steroidal Anti-Inflammatory Drugs with Cyclodextrins: A Systematic Review
No full textNon-steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used classes
of medicines in the treatment of inflammation, fever, and pain. However, evidence has demonstrated
that these drugs can induce significant toxicity. In the search for innovative strategies to overcome
NSAID-related problems, the incorporation of drugs into cyclodextrins (CDs) has demonstrated
promising results. This study aims to review the impact of cyclodextrin incorporation on the
biopharmaceutical and pharmacological properties of non-steroidal anti-inflammatory drugs. A
systematic search for papers published between 2010 and 2020 was carried out using the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and the following
search terms: “Complexation”; AND “Cyclodextrin”; AND “non-steroidal anti-inflammatory drug”.
A total of 24 different NSAIDs, 12 types of CDs, and 60 distinct inclusion complexes were identified,
with meloxicam and -CD appearing in most studies. The results of the present review suggest that
CDs are drug delivery systems capable of improving the pharmacological and biopharmaceutical
properties of non-steroidal anti-inflammatory drugs
Metodologia para identificação de tipos de dados de pesquisa: a experiência da Fundação Oswaldo Cruz (Fiocruz)
No full textO artigo discorre sobre o desenvolvimento e a aplicação de metodologia para identificação de tipos de dados de pesquisa produzidos e coletados nas pesquisas da Fundação Oswaldo Cruz (Fiocruz). Trata-se de um relato de experiência do grupo de trabalho interdisciplinar que aplicou a metodologia no âmbito do projeto-piloto de gestão de dados de pesquisa coordenado pela Vice-Presidência de Ensino, Informação e Comunicação da Fiocruz.The article discusses the development and application of a methodology to identify types of research data produced and collected in research by the Oswaldo Cruz Foundation (Fiocruz). This is an experience report of the interdisciplinary working group that applied the methodology within the scope of the research data management pilot project coordinated by Fiocruz's Vice-Presidency of Teaching, Information and Communication