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OBJECTIVE: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research. DESIGN: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM. RESULTS: From 426 manuscripts identified, 15 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence. CONCLUSION: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.
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BACKGROUND: Parasacral Transcutaneous Electrical Nerve Stimulation (PTENS) is a treatment used in enuresis refractory to first-line treatment. This review aimed to evaluate the effectiveness of PTENS in treating monosymptomatic enuresis (MNE) in children and adolescents. METHODS: The study followed the Preferred Reporting Items for Systematic (PRISMA) guidelines. The search was carried out in the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Central Cochrane Library and Physiotherapy Evidence Database (PEDro). The selected studies were randomized clinical trials (RCTs). The "Risk of Bias tool for randomized trials" and the "Risk of Bias VISualization" were used to analyze the risk of bias. RESULTS: Of the 624 studies selected, four RCTs were eligible. Three included 146 children and adolescents aged between six and 16.3 years and used similar PTENS protocols with a frequency of 10 Hz, pulse duration of 700 µs and 20 minutes three times/week. One study enrolled 52 patients aged seven to 14 years used PTENS at home, with a pulse duration of 200 µs and 20 to 60 minutes twice/day. Risk of bias was observed in three studies due to results' randomization and measurement. Two studies showed a partial response with a reduction in wet nights, one a complete response in 27% of patients, and one showed no improvement. CONCLUSION: PTENS reduces wet nights' frequency but does not cure them, except in 27% of patients in one study. Limited RCTs and data heterogeneity are limitations.
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Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Elétrica Nervosa Transcutânea , Humanos , Criança , Estimulação Elétrica Nervosa Transcutânea/métodos , Adolescente , Resultado do Tratamento , Feminino , Masculino , Enurese Noturna/terapia , Reprodutibilidade dos TestesRESUMO
Dengue is an acute viral disease whose clinical condition is related to the interaction of factors related to the Dengue virus (DENV), environment and the host, with the immunity of the human host contributing a substantial role in the pathogenesis of DENV infection. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes such as tumor necrosis factor (TNF-α) affect transcription and/or expression; and therefore, may influence the pathogenesis of infectious diseases, such as dengue. Consequently, the objective of this study was to assess through a case-control study whether there was an association between the presence of SNPs -308G/A and -238G/A in the TNF-α gene and 158 patients with dengue and 123 controls. No association was found between the SNPs and the dengue cases in the study population. We then performed a meta-analysis, retrieving data from case-control studies in the literature for the same polymorphisms. For SNP-308G/A, the GG genotype was associated with dengue fever (DF) risk (OR = 1.24, 1.00-1.53; p = 0.05; I2 = 0%), while the GA genotype (OR = 0.75, 0.60-0.93; p = 0.01; I2 = 0%) and allele A (OR = 0.75, 0.60-0.93; p = 0.01; I2 = 0%) were associated with protection. The genotype GG population in the Asian continent (OR = 1.81 [1.06, 3.09], p = 0.03, I2 = 0%) and American (OR = 1.29 [1.00, 1.65], p = 0.05, I2 = 0%) was also associated with protection in the comparison between the cases versus the control group. In each comparison, the dominant model AA + GA (p < 0.00001) conferred protection. For SNP-238G/A the GA genotype was associated with risk for dengue hemorrhagic fever (DHF; OR = 2.17, 1.28-3.67; p = 0.004; I2 = 0%)), and the dominant AA + GA model (p < 0.00001) was associated with protection in each comparison. In summary, our results did not associate SNPs in the TNF-α gene to dengue in the Brazilian northeast population. However, combined literature data suggested the effect of the GG and GA genotypes of the SNP-308G/A on risk and protection, respectively, in Asian and American populations.
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Dengue/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Viruses are the most numerous entities on Earth and have also been central to many episodes in the history of humankind. As the study of viruses progresses further and further, there are several limitations in transferring this knowledge to undergraduate and high school students. This deficiency is due to the difficulty in designing hands-on lessons that allow students to better absorb content, given limited financial resources and facilities, as well as the difficulty of exploiting viral particles, due to their small dimensions. The development of tools for teaching virology is important to encourage educators to expand on the covered topics and connect them to recent findings. Discoveries, such as giant DNA viruses, have provided an opportunity to explore aspects of viral particles in ways never seen before. Coupling these novel findings with techniques already explored by classical virology, including visualization of cytopathic effects on permissive cells, may represent a new way for teaching virology. This work aimed to develop a slide microscope kit that explores giant virus particles and some aspects of animal virus interaction with cell lines, with the goal of providing an innovative approach to virology teaching. METHODS: Slides were produced by staining, with crystal violet, purified giant viruses and BSC-40 and Vero cells infected with viruses of the genera Orthopoxvirus, Flavivirus, and Alphavirus. Slides with amoebae infected with different species of giant viruses and stained with hemacolor reagents were also produced. RESULTS: Staining of the giant viruses allowed better visualization of the viral particles, and this technique highlights the diversity in morphology and sizes among them. Hemacolor staining enabled visualization of viral factories in amoebae, and the staining of infected BSC-40 and Vero cell monolayers with crystal violet highlights plaque-forming units. CONCLUSIONS: This kit was used in practical virology classes for the Biological Sciences course (UFMG, Brazil), and it will soon be made available at a low-cost for elementary school teachers in institutions that have microscopes. We hope this tool will foster an inspiring learning environment.
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Materiais de Ensino , Ensino , Virologia/educação , Vírus , Animais , Linhagem Celular , Chlorocebus aethiops , Vírus Gigantes/fisiologia , Humanos , Microscopia/instrumentação , Estudantes , Células VeroRESUMO
This review summarizes the recent knowledge on the epidemiology of Helicobacter pylori and the potential modes of transmission. In addition to English language publications, the authors have included original full-text publications from Russia and Latin America published in the original languages. High H pylori prevalence has been reported in Russia, Jordan, Iran, China, and Latin American countries as well as in Arctic populations in Canada. Indigenous inhabitants in the Arctic were found to be infected substantially more frequently than non-indigenous inhabitants. In Amsterdam, the Netherlands, the ethnic minority groups were at a significantly higher risk of being H pylori seropositive compared to the Dutch population. For the first time, data on the prevalence from Armenia have been published indicating 41.5% H pylori prevalence. Convincing evidence on the decline of H pylori prevalence in Southeast Hungary and Taiwan was published. A study from Chile suggested high infection rates in newborns during the first month after birth. Two meta-analyses covered the potential correlation between H pylori and periodontal diseases, therefore addressing the potential oro-oral transmission rates. Periodontal disease was found to be more prevalent in H pylori-infected subjects. Other studies addressed the potential role of drinking water and food products as well as socioeconomic factors in transmitting the infection. Several studies in Asia addressed annual reinfection rates of H pylori, ranging from 1.5% in China to 3.1% in Korea. Finally, a review was published on the current evidence and future perspective of analysing H pylori in ancient human remains by a metagenomic approach.
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Infecções por Helicobacter , Adolescente , Idoso , América/epidemiologia , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/transmissão , Humanos , Recém-Nascido , Masculino , Metanálise como Assunto , Prevalência , Reinfecção , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Intestinal and diffuse gastric adenocarcinomas differ in clinical, epidemiological and molecular features. However, most of the concepts related to the intestinal-type are translated to gastric adenocarcinoma in general; thus, the peculiarities of the diffuse-type are underappreciated. RESULTS: Besides its growing importance, there are many gaps about the diffuse-type carcinogenesis and, as a result, its epidemiologic and pathogenetic features remain poorly understood. CONCLUSIONS: Alternative hypotheses to explain these features are discussed, including the role of the gastric microbiota, medical therapies, and modifications in the stomach's microenvironment.
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Adenocarcinoma , Microbiota , Neoplasias Gástricas , Adenocarcinoma/epidemiologia , Carcinogênese , Humanos , Neoplasias Gástricas/epidemiologia , Microambiente TumoralRESUMO
Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53-a highly mutated and informative gene in GAC-to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash-GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon-capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post-treatment (196 samples), with high vertical coverage >8,000×. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW- (15.2%) and 6/46 PL-samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW-exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene-panel designed for this malignancy.
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Adenocarcinoma/genética , Adenocarcinoma/patologia , Mutação/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Análise Mutacional de DNA/métodos , Feminino , Seguimentos , Humanos , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.
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Carcinogênese , Disbiose , Gastrite/microbiologia , Microbioma Gastrointestinal , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Neoplasias Gástricas/microbiologia , Gastrite Atrófica/microbiologia , Humanos , Estômago/microbiologia , Microambiente TumoralRESUMO
Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF-α, JAK1, VDR, DC-SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obtained from healthy individuals. The individuals were genotyped for SNPs in DC-SIGN (rs4804803), FcγRIIa (rs1801274), JAK1 (rs11208534), TNF-α (rs1800629) and VDR (rs7975232) by real-time PCR and allele discrimination method. Granulomas were classified as loose or dense according to the histological pattern. In the VDR (rs7975232), the CC genotype (P < 0.001, OR = 5.94, 95% CI = 2.07-17.05), and the C allele (P = 0.027, OR = 2.71, 95% CI = 1.07-6.86), as well as the GG genotype in DC-SIGN (rs4804803) (P = 0.032, OR: 3.76, 95%, I = 1.06-13.38) are associated with an increased risk of oral PCM. Our data indicate that VDR and DC-SIGN genetics variations are related to the susceptibility of oral PCM in the group of patients analysed.
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Moléculas de Adesão Celular/genética , Predisposição Genética para Doença , Lectinas Tipo C/genética , Doenças da Boca/genética , Doenças da Boca/patologia , Paracoccidioidomicose/genética , Paracoccidioidomicose/patologia , Receptores de Calcitriol/genética , Receptores de Superfície Celular/genética , Adulto , Alelos , Doença Crônica , Estudos de Coortes , Feminino , Granuloma/patologia , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Paracoccidioidomycosis (PCM) is a neglected fungal infection with a high impact on the quality of life of the affected patients. The disease presents primary pulmonary involvement and systemic dissemination may occur. About 50% of the cases show oral involvement, and the factors that lead to this manifestation are not clear. OBJECTIVES: The aim of this study was to evaluate the DNA methylation profile in PCM patients with oral lesions. MATERIAL AND METHODS: Genomic DNA was extracted from whole blood of eighteen PCM patients, being ten with oral lesions and eight with no oral lesion. Analysis of methylation profile was performed using the technique of methylation-sensitive arbitrarily primed PCR (MS-AP-PCR). The sequences of recombinant plasmids obtained were evaluated according to parameters that define a CpG island, as well as their relative position in the known human genome genes and/or CpG islands. RESULTS: After DNA amplification, three different expressed bands were observed between the two groups, being found in the samples of patients with no oral manifestations. The cloned fragment in the plasmid showed similarity with a DNA sequence present in chromosome 20, next to the YTHDF1 gene. Other bands showed homology with intronic region in the genes RBPMS2 and DPH6 and no CpG island was identified. CONCLUSIONS: DNA methylation was found in PCM patients with no oral lesion affecting the YTHDF1 gene. Further studies are necessary to elucidate to role of YTHDF1 gene in the oral PCM manifestations.
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Metilação de DNA , Boca/microbiologia , Boca/patologia , Paracoccidioidomicose/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paracoccidioides , Análise de Sequência de DNARESUMO
What controls the formation of patchy substrates of white sand vegetation in the Amazonian lowlands is still unclear. This research integrated the geological history and plant inventories of a white sand vegetation patch confined to one large fan-shaped sandy substrate of northern Amazonia, which is related to a megafan environment. We examined floristic patterns to determine whether abundant species are more often generalists than the rarer one, by comparing the megafan environments and older basement rocks. We also investigated the pattern of species accumulation as a function of increasing sampling effort. All plant groups recorded a high proportion of generalist species on the megafan sediments compared to older basement rocks. The vegetation structure is controlled by topographic gradients resulting from the smooth slope of the megafan morphology and microreliefs imposed by various megafan subenvironments. Late Pleistocene-Holocene environmental disturbances caused by megafan sedimentary processes controlled the distribution of white sand vegetation over a large area of the Amazonian lowlands, and may have also been an important factor in species diversification during this period. The integration of geological and biological data may shed new light on the existence of many patches of white sand vegetation from the plains of northern Amazonia.
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Sedimentos Geológicos , Fenômenos Geológicos , Melastomataceae , Traqueófitas , Brasil , Geografia , AreiaRESUMO
Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.
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Dengue/genética , Dengue/imunologia , Receptores de IgG/genética , Adulto , Arginina/genética , Brasil , Moléculas de Adesão Celular/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lectinas Tipo C/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Receptores de Calcitriol/genética , Receptores de Superfície Celular/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Important progress is being made in endoscopic methods which allow clinicians to predict the presence of Helicobacter pylori based on characteristics of gastric mucosa and to obtain targeted biopsies. There are also important developments in molecular methods with various techniques derived from standard PCR, applied both on gastric biopsies and stool specimens. Progress is being made in microfluidic systems to get a reliable diagnosis in a very short time. The interest of the 13 C urea breath test has been confirmed as well as stool antigen tests. Attempts are being made to find biological markers of premalignant conditions by serology, other than pepsinogens.
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Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Antígenos de Bactérias/análise , Biópsia , Testes Respiratórios/métodos , Endoscopia Gastrointestinal/métodos , Fezes/microbiologia , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/patologia , Técnicas de Diagnóstico Molecular/métodos , Ureia/análiseRESUMO
Dengue is the most prevalent arthropod-borne viral illness in humans. The overexpression of cytokines by Dengue virus (DENV) infected cells is associated with the most severe forms of the disease. Unmethylated CpG islands are related to a transcriptionally active structure, whereas methylated DNA recruits methyl-binding proteins that inhibit gene expression. Several studies have described the importance of epigenetic events in the regulation and expression of many cytokines. The purpose of the present study was to evaluate the methylation status of the IFN-γ and TNF-α promoters in DNA extracted from dengue infected patients using methylation-specific polymerase chain reaction. A high frequency of demethylation was observed in the TNF-α promoter of DENV infected patients when compared to non-infected controls. The patients with an unmethylated profile showed higher expression of TNF-α mRNA than patients with the methylated status. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-γ promoter or in the expression of IFN-γ transcripts. The present study provides the first association of TNF-α promoter demethylation in DENV infected individuals and demonstrates a correlation between the methylation status of the region analyzed and the expression of TNF-α transcripts in DENV infected patients. J. Med. Virol. 88:1297-1302, 2016. © 2016 Wiley Periodicals, Inc.
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Metilação de DNA , Vírus da Dengue/imunologia , Dengue/genética , Dengue/imunologia , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , Adulto , Ilhas de CpG , Feminino , Humanos , Interferon gama/genética , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Viral/sangue , RNA Viral/isolamento & purificação , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
In this work, we present the in vitro schistosomicidal activity evaluation of the most active dichloromethane fraction (FDm) (ED50=83.5µg/mL) and of a mixture of the major alkaloids ((-)-cassine/(-)-spectaline, C/E) (ED50=37.4µg/mL) from the flowers of Senna spectabilis against adult worms and cercariae. We also demonstrate other toxic effects including paralysis of the adult worms, inhibition of the secretory activity, tegument lesions and cercaricidal activity. In the association test of Praziquantel (PZQ)-C/E, we observed up to 80% mortality of Schistosoma mansoni in comparison to PZQ monotherapy. Due to the diversity of the toxic effects, the schistosomicidal activity of C/E is likely a result of a multitarget mechanism involving the tegument, secretory system and neuromotor action.
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Alcaloides/química , Fabaceae/química , Piperidinas/química , Extratos Vegetais/química , Esquistossomicidas/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Fabaceae/metabolismo , Feminino , Flores/química , Flores/metabolismo , Cetonas/isolamento & purificação , Cetonas/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Piperidinas/isolamento & purificação , Piperidinas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/isolamento & purificação , Esquistossomicidas/farmacologia , EstereoisomerismoRESUMO
A novel series of ester and carbamate derivatives was synthesized and evaluated its activities against Leishmania amazonensis. All compounds exhibited weaker leishmanicidal activity than amphotericin B. However, results indicated that substituents on the aryl-acyl subunit are important for modulation of the leishmanicidal effect. The nitro derivative showed the highest activity of the series with an IC50 = 17.24 µM, and comparable potency to the 3,4-benzodioxole ester and n-hexyl carbamate derivatives. All compounds showed low toxicity against human cells. These results revealed interesting novel piperine-like molecular pattern for exploitation in search and development of effective and low toxic antileishmanial drug candidates.
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Benzodioxóis/síntese química , Benzodioxóis/farmacologia , Leishmania/efeitos dos fármacos , Piperidinas/síntese química , Piperidinas/farmacologia , Antiprotozoários/síntese química , Antiprotozoários/química , Antiprotozoários/farmacologia , Benzodioxóis/química , Descoberta de Drogas , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Piperidinas/químicaRESUMO
In most South American countries, Helicobacter pylori infection prevalence is high, affecting over 70% in populations with precarious living conditions. It is worth pointing out that there is initial evidence of a decline in prevalence of H. pylori infection at least in some more privileged fragments of the population. It is estimated that gastric cancer, the main clinical sequela of H. pylori infection, has an average incidence rate of 12.4 cases per 100,000 inhabitants (8.4 cases per 100,000 inhabitants for women and 17.3 cases per 100,000 for men) in the region. Classical triple therapy [proton pump inhibitor (PPI), amoxicillin and clarithromycin] is still the most used regimen with eradication rates around 80%. The rates of resistance to clarithromycin range from 2 to 24%. Recurrence rates of the infection are described as 2.9% in Argentina, 4.2% in Chile, 2-7% in Brazil, and 11.5% in a trial involving 7 Latin American countries. After failure of clarithromycin-containing regimens, second- and third-line therapies using PPI, amoxicillin and levofloxacin and quadruple therapy with PPI, colloidal bismuth subcitrate, tetracycline hydrochloride and metronidazole are recommended. Due to the high rates of primary resistance to metronidazole in the Latin American countries, use of the quadruple therapy, replacing metronidazole for furazolidone, is a frequent option. Rescue triple therapy regimens using furazolidone in association with levofloxacin and PPI have also been used. Most recommended rescue therapies reach eradication rates close to 80%.
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Infecções por Helicobacter/terapia , Helicobacter pylori/fisiologia , Países Bálticos , Farmacorresistência Bacteriana , Infecções por Helicobacter/prevenção & controle , Humanos , América Latina , Resultado do TratamentoRESUMO
An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.
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Comportamento Animal/fisiologia , Citocromos b/genética , Psychodidae/fisiologia , Animais , Comportamento Animal/classificação , Gatos , Bovinos , Cães , Comportamento Alimentar/fisiologia , Cavalos , Humanos , Refeições , Mitocôndrias/enzimologia , Gambás , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Psychodidae/classificação , Ratos , SuínosRESUMO
Introduction One of the paths in the investigation of congenital sensorineural hearing loss (CSNHL) is to try to characterize its etiology through the inner ear evaluation using high resolution computer tomography (CT) scans. With minor malformation, it is not always possible for a simple visual inspection to recognize if the structure in the inner ear is normal or not. Objective To verify if measurements of the inner ear are predictive of sensorineural hearing loss (SNHL) and suggest cutoff points of size limits. Methods Retrospective cross-sectional study of inner ear CT scan measurements of 214 patients, 50 with congenital SNHL (CSNHL) and 164 acquired SNHL (ASNHL) (control group). Results In the CSNHL group, central bony island (CBI) were 0.48 mm smaller ( p < 0.001), cochlear nerve aperture was (CNA) 0.10 mm smaller ( p < 0.001), and cochlea height was (CH) 0.15 mm smaller ( p < 0.001). Vestibular aqueduct (VA) and cochlea width (CW) were similar between groups (0.70 vs 0.72, p = 0.19, and 7.20 vs 7.15 p = 0.23). The predictive cutoff points for CSNHL were CBI = 3.6 mm, CAN = 1.4 mm, CH = 3.4 mm, CW = 7.0 mm, and VA = 0.9 mm. Conclusion Congenital sensorineural hearing loss determined a decrease in CBI, opening of the cochlear nerve (OCN), and CW. Thus, these measures, at the cutoff points indicated, should make us aware of the diagnosis of congenital hearing loss.
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Clostridioides difficile infection (CDI) poses a significant global health threat owing to its substantial morbidity and associated healthcare costs. A key challenge in controlling CDI is the risk of multiple recurrences, which can affect up to 30% of patients. In such instances, fecal microbiota transplantation (FMT) is increasingly recognized as the optimal treatment. However, few related studies have been conducted in developing countries, and the microbiota composition of Brazilian patients and its dynamic modification post-FMT remain largely unexplored. This study aimed to evaluate the changes in the bacterial gut microbiome in Brazilian patients with recurrent CDI post-FMT. Ten patients underwent FMT, and the primary and overall CDI resolution rates were 80% and 90% after the first and second FMT, respectively. FMT was associated with an early increase in Shannon's diversity, evident as soon as 1 week post-FMT and persisting for at least 25 days post-treatment. Post-treatment, the abundance of Firmicutes increased and that of Proteobacteria decreased. Specifically, the abundance of the genera Ruminococcus, Faecalibacterium, Lachnospira, and Roseburia of the Firmicutes phylum was significantly higher 1 week post-transplantation, with Ruminococcus and Faecalibacterium remaining enriched 25 days post-transplantation. This study is the first of its kind in Brazil to evaluate the microbiota of a donor and patients undergoing FMT. Our findings suggest that FMT can induce remarkable changes in the gut microbiota, characterized by an early and sustained increase in diversity lasting at least 25 days. FMT also promotes enrichment of genera such as Ruminococcus spp., Faecalibacterium spp., and Roseburia spp., essential for therapeutic success.