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1.
Cureus ; 16(2): e54933, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38544612

RESUMO

Airway complications account for a significant amount of post-thyroidectomy complications. Forgotten goiter is a residual thyroid mass left after total thyroidectomy, an event already depicted in the literature. Clinical presentation is diverse, ranging from asymptomatic tracheal deviation to symptoms caused by hormonally active thyroid tissue or airway obstruction due to mass effect. However, it has never been documented as the cause of acute respiratory distress following thyroid surgery. We report the case of a 65-year-old female undergoing left hemithyroidectomy due to long-standing substernal goiter. Anesthesia induction and surgery were uneventful. On extubation, the patient presented with acute respiratory distress requiring prompt airway management. A computed tomography scan revealed residual intrathoracic goiter resulting in significant airway compression. Therefore, although a rare event, a forgotten goiter should be considered by a multidisciplinary team when patients undergoing surgery for substernal goiter develop acute postoperative airway obstruction after common post-thyroidectomy complications have been excluded.

2.
PLoS Negl Trop Dis ; 18(3): e0012013, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484018

RESUMO

BACKGROUND: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent. METHODOLOGY/PRINCIPAL FINDINGS: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR. CONCLUSIONS/SIGNIFICANCE: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention.


Assuntos
Aedes , Febre de Chikungunya , Vírus Chikungunya , Dengue , Animais , Humanos , Vírus Chikungunya/genética , Estudos Prospectivos , Brasil/epidemiologia , Filogenia , Estudos Soroepidemiológicos , Febre de Chikungunya/epidemiologia , Anticorpos Antivirais , Dengue/diagnóstico , Dengue/epidemiologia , Anticorpos Neutralizantes/genética , Imunoglobulina G , Imunoglobulina M
3.
Res Sq ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38343798

RESUMO

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

4.
Diabetes Technol Ther ; 26(4): 252-262, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38090767

RESUMO

Introduction: Continuous glucose monitoring (CGM) has shown favorable outcomes in patients with type 2 diabetes (T2D) who are on insulin therapy. However, the efficacy of CGM in managing glucose levels in noninsulin-treated people with T2D remains controversial. Methods: PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing CGM to self-monitoring of blood glucose (SMBG) in people with T2D not using insulin. We computed weighted mean differences (WMDs) and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Statistical analyses were performed using R version 4.2.3. Results: We included six RCTs comprising 407 noninsulin-treated people with T2D of whom 228 were randomized to CGM. Diabetes duration ranged from 5.4 to 13.9 years. The mean age was 57.9 years and the mean body mass index was 30.8 kg/m2. Four trials used real-time CGM (rt-CGM) and two intermittent scanning CGM (is-CGM). Compared with SMBG, CGM significantly reduced the glycated hemoglobin level (WMD -0.31%; 95% CI -0.42 to -0.21; I2 = 0%), glucose level (WMD -11.16 mg/dL; 95% CI -19.94 to -2.39; I2 = 0%), time in hypoglycemia level 2 (WMD -0.28%; 95% CI -0.52 to -0.03; I2 = 91%), glucose time >180 mg/dL (WMD -7.75%; 95% CI -12.04 to -3.45; I2 = 0%), and the standard deviation of glucose variation (WMD -4.00 mg/dL; 95% CI -6.86 to -1.14; I2 = 0%). CGM also increased time in range (WMD 8.63%; 95% CI 4.54-12.71; I2 = 0%) and treatment satisfaction (SMD 0.79; 95% CI 0.54-1.05; I2 = 0%). Conclusion: In this meta-analysis, rt-CGM and is-CGM were associated with improvement in glycemic control in people with T2D not using insulin when compared to SMBG.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Pessoa de Meia-Idade , Glicemia/análise , Monitoramento Contínuo da Glicose , Ensaios Clínicos Controlados Aleatórios como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Automonitorização da Glicemia , Insulina Regular Humana
5.
FASEB J ; 37(10): e23187, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37718489

RESUMO

Despite decades of effort, the preservation of complex organs for transplantation remains a significant barrier that exacerbates the organ shortage crisis. Progress in organ preservation research is significantly hindered by suboptimal research tools that force investigators to sacrifice translatability over throughput. For instance, simple model systems, such as single cell monolayers or co-cultures, lack native tissue structure and functional assessment, while mammalian whole organs are complex systems with confounding variables not compatible with high-throughput experimentation. In response, diverse fields and industries have bridged this experimental gap through the development of rich and robust resources for the use of zebrafish as a model organism. Through this study, we aim to demonstrate the value zebrafish pose for the fields of solid organ preservation and transplantation, especially with respect to experimental transplantation efforts. A wide array of methods were customized and validated for preservation-specific experimentation utilizing zebrafish, including the development of assays at multiple developmental stages (larvae and adult), methods for loading and unloading preservation agents, and the development of viability scores to quantify functional outcomes. Using this platform, the largest and most comprehensive screen of cryoprotectant agents (CPAs) was performed to determine their toxicity and efficiency at preserving complex organ systems using a high subzero approach called partial freezing (i.e., storage in the frozen state at -10°C). As a result, adult zebrafish cardiac function was successfully preserved after 5 days of partial freezing storage. In combination, the methods and techniques developed have the potential to drive and accelerate research in the fields of solid organ preservation and transplantation.


Assuntos
Preservação de Órgãos , Peixe-Zebra , Animais , Bioensaio , Técnicas de Cocultura , Larva , Mamíferos
6.
Viruses ; 15(9)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37766255

RESUMO

Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years of age, and adults over 75. The main causative agents are viruses, such as influenza and respiratory syncytial virus (RSV). Viral LRIs in adults have historically received less attention. This study investigated the incidence of RSV and influenza in adult patients admitted to a referral hospital, as well as the clinical profile of these infections. Molecular testing was conducted on nasopharyngeal samples taken from a respiratory surveillance cohort comprising adult (15-59 years) and elderly (60+ years) hospitalized patients who tested negative for SARS-CoV-2, to determine the prevalence for influenza and RSV. Influenza was found to be less frequent among the elderly. The main symptoms of RSV infections were cough, fever, dyspnea, malaise, and respiratory distress, while headache, nasal congestion, a sore throat, and myalgia were most frequent in influenza. Elderly patients with RSV were not found to have more severe illness than adults under age 60, underscoring the importance of providing the same care to adults with this viral infection.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Idoso , Adulto , Humanos , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Doenças Negligenciadas , Influenza Humana/epidemiologia , SARS-CoV-2
7.
Cureus ; 15(6): e41195, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37525785

RESUMO

Anesthesia for major head and neck surgery is historically heavily reliant on opioids with deleterious consequences. We reported a case of a patient with a history of heroin abuse submitted to a tongue carcinoma excision, followed by free-flap reconstruction under opioid-free anesthesia. We used a propofol total intravenous anesthesia and perfusions of ketamine, dexmedetomidine, lidocaine, and magnesium sulfate for analgesia, complemented by boluses of dexamethasone, acetaminophen, parecoxib, and metamizole. Hemodynamic needs of the procedure were addressed by titrating perfusions of sodium nitroprusside or dobutamine. The patient was weaned from the ventilator at the end of the surgery. Surgical outcomes were achieved and opioid-free analgesia allowed early reestablishment of bodily functions without compromise of adequate pain control. Anesthesia protocols for free-flap surgery still lack scientific evidence, especially in the context of substance abuse: opioid-sparing approaches seem a viable option, which requires further studies and familiarity by health care professionals.

8.
Braz J Microbiol ; 54(3): 1827-1834, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37589928

RESUMO

Acute respiratory infections are a constant public health problem causing childhood morbidity and mortality worldwide. Reported cases of major respiratory infections decreased in 2020 after restrictive measures were adopted to contain the COVID-19 pandemic, but there is little data on the impact after these measures were relaxed in the subsequent years. This study conducted molecular analysis to identify rhinovirus, respiratory syncytial virus, influenza A virus, and adenovirus in SARS-CoV-2-negative samples taken from symptomatic pediatric patients during 2021 and 2022 to ascertain the impact of pandemic response measures within the broader epidemiological scenario. The positivity rates found were 28.3% and 50.8%, in 2021 and 2022, respectively, representing a significant increase (1.8 times) in the circulation of non-SARS-CoV-2 viruses after the reduction of non-pharmacological measures to contain the COVID-19 pandemic. Within the positive samples, rhinovirus and respiratory syncytial virus were most frequent (44.4 and 18% in 2021; 44.5 and 22.5% in 2022), whereas influenza A and adenovirus were found in lower frequency (12.5 and 5.5% in 2021; 13.4 and 4.9% in 2022, respectively). Because these different respiratory virus diseases produce similar symptoms, diagnosis based on clinical condition alone can be inaccurate, and more reliable testing is required to select the best therapeutic approach for each case. The loosening of restrictive measures to contain the COVID-19 pandemic led to higher numbers of other respiratory infections in pediatric patients. Ongoing surveillance and differential diagnosis of respiratory viruses are required to better understand their seasonal patterns after the COVID-19 pandemic to guide prevention and control strategies.


Assuntos
COVID-19 , Infecções por Enterovirus , Infecções Respiratórias , Humanos , Criança , Pandemias , Brasil/epidemiologia , COVID-19/epidemiologia , Estações do Ano , SARS-CoV-2 , Vírus Sinciciais Respiratórios , Rhinovirus , Infecções Respiratórias/epidemiologia
9.
Braz J Microbiol ; 54(3): 1411-1419, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37178262

RESUMO

The genetic diversity of the dengue virus is characterized by four circulating serotypes, several genotypes, and an increasing number of existing lineages that may have differences in the potential to cause epidemics and disease severity. Accurate identification of the genetic variability of the virus is essential to identify lineages responsible for an epidemic and understanding the processes of virus spread and virulence. Here, we characterize, using portable nanopore genomic sequencing, different lineages of dengue virus 2 (DENV-2) detected in 22 serum samples from patients with and without dengue warning signs attended at Hospital de Base of São José do Rio Preto (SJRP) in 2019, during a DENV-2 outbreak. Demographic, epidemiological, and clinical data were also analyzed. The phylogenetic reconstruction and the clinical data showed that two lineages belonging to the American/Asian genotype of DENV-2-BR3 and BR4 (BR4L1 and BR4L2)-were co-circulating in SJRP. Although preliminary, these results indicate no specific association between clinical form and phylogenetic clustering at the virus consensus sequence level. Studies with larger sample sizes and which explore single nucleotide variants are needed. Therefore, we showed that portable nanopore genome sequencing could generate quick and reliable sequences for genomic surveillance to monitor viral diversity and its association with disease severity as an epidemic unfolds.


Assuntos
Vírus da Dengue , Dengue , Humanos , Vírus da Dengue/genética , Dengue/epidemiologia , Filogenia , Sequência de Bases , Surtos de Doenças , Sorogrupo , Genótipo , Variação Genética
10.
Viruses ; 14(7)2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35891460

RESUMO

Our effort in SARS-CoV-2 genomic surveillance in Brazil has detected the Alpha Variant of Concern with a predominance higher than 75% in the population of Ilhabela island (São Paulo State) at a time when the Gamma VOC was already predominating the mainland raised concerns for closer surveillance on this island. Therefore, we intensified the surveillance for 24 weeks by generating data from 34% of local positive cases. Our data show that the patterns of VOC predominance dynamics and infection rates were in general distinct from the mainland. We report here the first known case of Alpha predominance in a Brazilian population, a delay greater than 3 months for the Gamma to dominate the previous variants compared to the mainland, and a faster dispersion rate of Gamma and Delta VOCs compared to the mainland. Phylogenetic analysis revealed the SARS-CoV-2 transmission dynamics in Ilhabela were characterized by multiple independent introduction events of Gamma and Delta, with a few events of Alpha introduction, two of them followed by community transmission. This study evidenced the peculiar behavior of SARS-CoV-2 variants in an isolated population and brought to light the importance of specific programs for SARS-CoV-2 genomic surveillance in isolated populations.


Assuntos
COVID-19 , SARS-CoV-2 , Brasil/epidemiologia , COVID-19/epidemiologia , Humanos , Filogenia , SARS-CoV-2/genética
11.
Commun Med (Lond) ; 2: 41, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603276

RESUMO

Background: The emergence of the Brazilian variant of concern, Gamma lineage (P.1), impacted the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Methods: We sequenced 305 SARS-CoV-2 whole-genomes and performed phylogenetic analyses to identify introduction events and the circulating lineages. Additionally, we use epidemiological data of COVID-19 cases, severe cases, and deaths to measure the impact of vaccination coverage and mortality risk. Results: Here we show that Gamma introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of seven circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection in January 2021. Moreover, Gamma variant is associated with increased mortality risk and severity of COVID-19 cases in younger age groups, which corresponds to the unvaccinated population at the time. Conclusions: Our findings highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.

12.
Int J Offender Ther Comp Criminol ; : 306624X221086574, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35450471

RESUMO

The current study builds on prior work examining the association between futurelessness and commitment institutional rules among correctional populations. Using cross-sectional data from a sample of 413 people incarcerated in United States jails from 2018 to 2019, this study employs Ordinary Least Squares regression to examine the association between futurelessness and commitment to institutional rules controlling for various importation and deprivation factors previously linked with institutional misconduct. Results provide support for the importance of futurelessness for commitment to institutional rules, suggesting that this finding is consistent across correctional environments. In addition, findings suggest that an index measure of futurelessness is a stronger construct for testing futurelessness than single-item measures used in prior studies. Consistent with prior literature on futurelessness, our findings suggest that among people incarcerated in jail futurelessness is linked to a weaker commitment to institutional rules.

13.
Viruses ; 13(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206727

RESUMO

The rapid development of efficacious and safe vaccines against coronavirus disease 2019 (COVID-19) has been instrumental in mitigating the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, the emergence of SARS-CoV-2 variants raised concerns on the efficacy of these vaccines. Herein, we report two cases of breakthrough infections with the P1 variant in patients vaccinated with CoronaVac, which is one of the two vaccines authorized for emergency use in the Brazilian immunization program. Our observations suggest that the vaccine reduced the severity of the disease and highlight the potential risk of illness following vaccination and subsequent infection with the P1 variant as well as for continued efforts to prevent and diagnose infection in vaccinated persons.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/diagnóstico por imagem , COVID-19/imunologia , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Brasil , COVID-19/prevenção & controle , Teste de Ácido Nucleico para COVID-19 , Vacinas contra COVID-19/administração & dosagem , Ensaios Clínicos como Assunto , Dexametasona/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vacinação/estatística & dados numéricos , Tratamento Farmacológico da COVID-19
14.
PLoS One ; 16(5): e0251290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33983964

RESUMO

Extracellular vesicles (EVs) have emerged as promising candidates in biomarker discovery and diagnostics. Protected by the lipid bilayer, the molecular content of EVs in diverse biofluids are protected from RNases and proteases in the surrounding environment that may rapidly degrade targets of interests. Nonetheless, cryopreservation of EV-containing samples to -80°C may expose the lipid bilayer to physical and biological stressors which may result in cryoinjury and contribute to changes in EV yield, function, or molecular cargo. In the present work, we systematically evaluate the effect of cryopreservation at -80°C for a relatively short duration of storage (up to 12 days) on plasma- and media-derived EV particle count and/or RNA yield/quality, as compared to paired fresh controls. On average, we found that the plasma-derived EV concentration of stored samples decreased to 23% of fresh samples. Further, this significant decrease in EV particle count was matched with a corresponding significant decrease in RNA yield whereby plasma-derived stored samples contained only 47-52% of the total RNA from fresh samples, depending on the extraction method used. Similarly, media-derived EVs showed a statistically significant decrease in RNA yield whereby stored samples were 58% of the total RNA from fresh samples. In contrast, we did not obtain clear evidence of decreased RNA quality through analysis of RNA traces. These results suggest that samples stored for up to 12 days can indeed produce high-quality RNA; however, we note that when directly comparing fresh versus cryopreserved samples without cryoprotective agents there are significant losses in total RNA. Finally, we demonstrate that the addition of the commonly used cryoprotectant agent, DMSO, alongside greater control of the rate of cooling/warming, can rescue EVs from damaging ice formation and improve RNA yield.


Assuntos
Vesículas Extracelulares/metabolismo , RNA/isolamento & purificação , Manejo de Espécimes/métodos , Criopreservação/métodos , Meios de Cultura/química , Voluntários Saudáveis , Humanos , Plasma/química , RNA/metabolismo , Estabilidade de RNA/efeitos dos fármacos , Estabilidade de RNA/fisiologia
15.
Rev Bras Med Trab ; 19(1): 68-72, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33986782

RESUMO

INTRODUCTION: Occupational accidents occur as a result of work, and can lead to bodily harm or functional impairments that lead to death, or to the reduction or loss of working capacity. Occupational accidents are associated with two possible outcomes: morbidity or mortality. Morbidity refers to the subset of a population that develops an illness over a given period of time, while mortality refers to the number of individuals who die over a specified time period. OBJECTIVES: To assess occupational morbidity and mortality in Brazil in the period of 2009 to 2016. METHODS: An ecological study was conducted based on secondary data collected from incident records in the Social Security database. RESULTS: The outcomes of all occupational accidents reported in Brazil from 2009 to 2016 were extracted from the database. These data were then classified by geographical region and category in the National Classification of Economic Activities (Classificação Nacional de Atividades Econômicas), so as to calculate the prevalence of each outcome and the accident mortality rates, and compare these values across regions and occupational categories. CONCLUSIONS: The data show that the outcomes of occupational accidents are directly associated with socioeconomic sectors and the sociocultural characteristics of different regions in the country. These results make an important contribution to the characterization of occupational morbidity and mortality in Brazil.

16.
Bioorg Chem ; 110: 104773, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33744807

RESUMO

In the present study, a series of chalcones and their B-aryl analogues were prepared and evaluate as inhibitors of myeloperoxidase (MPO) chlorinating activity, using in vitro and ex vivo assays. Among these, B-thiophenyl chalcone (analogue 9) demonstrated inhibition of in vitro and ex vivo MPO chlorinating activity, exhibiting IC50 value of 0.53 and 19.2 µM, respectively. Potent ex vivo MPO inhibitors 5, 8 and 9 were not toxic to human neutrophils at 50 µM, as well as displayed weak 2,2-diphenyl-1-pycrylhydrazyl radical (DPPH•) and hypochlorous acid (HOCl) scavenger abilities. Docking simulations indicated binding mode of MPO inhibitors, evidencing hydrogen bonds between the amino group at 4'position (ring A) of chalcones with Gln91, Asp94, and Hys95 MPO residues. In this regard, the efficacy and low toxicity promoted aminochalcones and arylic analogues to the rank of hit compounds in the search for new non-steroidal anti-inflammatory compounds.


Assuntos
Chalconas/síntese química , Chalconas/farmacologia , Peroxidase/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Sequestradores de Radicais Livres , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Conformação Proteica
17.
Bioorg Chem ; 109: 104668, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33601139

RESUMO

Curcumin (CUR) is a symmetrical dicarbonyl compound with antibacterial activity. On the other hand, pharmacokinetic and chemical stability limitations hinder its therapeutic application. Monocarbonyl analogs of curcumin (MACs) have been shown to overcome these barriers. We synthesized and investigated the antibacterial activity of a series of unsymmetrical MACs derived from acetone against Mycobacterium tuberculosis and Gram-negative and Gram-positive species. Phenolic MACs 4, 6 and 8 showed a broad spectrum and potent activity, mainly against M. tuberculosis, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA), with MIC (minimum inhibitory concentration) values ranging from 0.9 to 15.6 µg/mL. The investigation regarding toxicity on human lung cells (MRC-5 and A549 lines) revealed MAC 4 was more selective than MACs 6 and 8, with SI (selectivity index) values ranging from 5.4 to 15.6. In addition, MAC 4 did not demonstrate genotoxic effects on A549 cells and it was more stable than CUR in phosphate buffer (pH 7.4) for 24 h at 37 °C. Fluorescence and phase contrast microscopies indicated that MAC 4 has the ability to disrupt the divisome of Bacillus subtilis without damaging its cytoplasmic membrane. However, biochemical investigations demonstrated that MAC 4 did not affect the GTPase activity of B. subtilis FtsZ, which is the main constituent of the bacterial divisome. These results corroborated that MAC 4 is a promising antitubercular and antibacterial agent.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular , Curcumina/química , Desenho de Fármacos , Desenvolvimento de Medicamentos , Humanos , Pulmão/citologia , Estrutura Molecular
18.
J Periodontol ; 92(2): 225-233, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32716571

RESUMO

BACKGROUND: Dentofacial features are related to increased bullying episodes in young people. The aim of this study was to assess the association between gingival bleeding and reports of verbal bullying among adolescents. METHODS: This is a cross-sectional study conducted with a representative sample of 608 12-year-old adolescents from southern Brazil. The occurrence of verbal bullying was verified through adolescents' self-report. Oral health measurements included the presence of gingival bleeding, dental fracture, dental fluorosis, and dental caries experience. Gingival bleeding was assessed through adolescent self-perception by the following question: "Did you notice any bleeding in your gums?" Demographic, socioeconomic, and psychosocial variables were also evaluated. Poisson regression models with robust variance were used to evaluate the influence of gingival bleeding on the occurrence of verbal bullying. Results are presented as prevalence ratio (PR) and 95% confidence interval (95% CI). RESULTS: Out of 608 adolescents evaluated, 577 answered bullying questions. The prevalence of self-reported verbal bullying was 12.8%. Adolescents who presented gingival bleeding had an 80% higher prevalence of verbal bullying than their counterparts (PR 1.80; 95% CI 1.01 -3.19). Dental shame, speech difficulties and influence of dental condition on studies also impacted the higher prevalence of bullying. CONCLUSION: Our results suggest that the presence of gingival bleeding negatively impacts the social life of adolescents, causing more episodes of verbal bullying. These findings encourage public health policies aimed at reducing oral health inequities, thus reflecting on the well-being and quality of life of this target population.


Assuntos
Bullying , Cárie Dentária , Adolescente , Brasil/epidemiologia , Estudos Transversais , Humanos , Saúde Bucal , Prevalência , Qualidade de Vida , Fatores Socioeconômicos
19.
Biotechnol Rep (Amst) ; 28: e00539, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33145190

RESUMO

This study aims to evaluate the efficacy of slow release phenobarbital in the control of convulsions triggered by pentylenetetrazole (PTZ), verifying the time of permanence in the anticonvulsant effect through behavior and electroencephalographic records. A total of 162 male Wistar rats weighing between 100 and 120 g were divided into two groups, one for behavior analysis (n = 90) and biochemistry, and another for the acquisition of electrocorticographic record (n = 72). Hepatic enzymes were measured by obtaining a blood sample from the animals studied by means of a biochemical analysis. The procedures for electrode implant and electrocorticographic recordings were performed. The intercalation of phenobarbital in layered double hydroxide (LDH) nanocarrier allowed us to evaluate a new slow release pharmaceutical formulation based on methodologies that have proven longer residence time and lower side effects. This study demonstrates that phenobarbital can be a new perspective pharmaceutical formulation.

20.
Molecules ; 25(20)2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33050236

RESUMO

Xanthomonas citri subsp. citri (X. citri) is an important phytopathogen and causes Asiatic Citrus Canker (ACC). To control ACC, copper sprays are commonly used. As copper is an environmentally damaging heavy metal, new antimicrobials are needed to combat citrus canker. Here, we explored the antimicrobial activity of chalcones, specifically the methoxychalcone BC1 and the hydroxychalcone T9A, against X. citri and the model organism Bacillus subtilis. BC1 and T9A prevented growth of X. citri and B. subtilis in concentrations varying from 20 µg/mL to 40 µg/mL. BC1 and T9A decreased incorporation of radiolabeled precursors of DNA, RNA, protein, and peptidoglycan in X. citri and B. subtilis. Both compounds mildly affected respiratory activity in X. citri, but T9A strongly decreased respiratory activity in B. subtilis. In line with that finding, intracellular ATP decreased strongly in B. subtilis upon T9A treatment, whereas BC1 increased intracellular ATP. In X. citri, both compounds resulted in a decrease in intracellular ATP. Cell division seems not to be affected in X. citri, and, although in B. subtilis the formation of FtsZ-rings is affected, a FtsZ GTPase activity assay suggests that this is an indirect effect. The chalcones studied here represent a sustainable alternative to copper for the control of ACC, and further studies are ongoing to elucidate their precise modes of action.


Assuntos
Antibacterianos/farmacologia , Chalconas/farmacologia , Doenças das Plantas/microbiologia , Xanthomonas/patogenicidade , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/patogenicidade , Chalconas/química
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