RESUMO
Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.
Assuntos
Antivirais/uso terapêutico , Dengue/tratamento farmacológico , Transcriptoma , Adenosina Trifosfatases/antagonistas & inibidores , Antagonistas Adrenérgicos/farmacologia , Antagonistas Adrenérgicos/uso terapêutico , Antivirais/farmacologia , Encéfalo/metabolismo , Simulação por Computador , Dengue/sangue , Dengue/genética , Dengue/metabolismo , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Fígado/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , NF-kappa B/metabolismo , Antagonistas da Serotonina/farmacologia , Antagonistas da Serotonina/uso terapêutico , Dengue Grave/sangue , Dengue Grave/tratamento farmacológico , Dengue Grave/genética , Dengue Grave/metabolismo , Baço/metabolismoRESUMO
Carbapenem-resistance mechanisms are a challenge in the treatment of Pseudomonas aeruginosa infections. We investigated changes in P. aeruginosa carbapenem-resistance determinants over a time period of eight years after the emergence of São Paulo metallo-ß-lactamase in a university hospital in Rio de Janeiro, Brazil. Patients admitted to the intensive care unit (ICU) were screened for P. aeruginosa colonisation and followed for the occurrence of infections from April 2007 to April 2008. The ICU environment was also sampled. Isolates were typed using random amplified polymorphic DNA, pulsed-field gel electrophoresis and multilocus sequence typing. Antimicrobial susceptibility was determined by disk diffusion and E-test, production of carbapenemases by a modified-CarbaNP test and presence of carbapenemase-encoding genes by polymerase chain reaction. Non-carbapenemase resistance mechanisms studied included efflux and AmpC overexpression by PAßN and cloxacillin susceptibility enhancement, respectively, as well as oprD mutations. From 472 P. aeruginosa clinical isolates (93 patients) and 17 isolates from the ICU environment, high genotypic diversity and several international clones were observed; one environment isolate belonged to the blaSPM-1 P. aeruginosa epidemic genotype. Among isolates from infections, 10 (29%) were carbapenem resistant: none produced carbapenemases, three exhibited all non-carbapenemase mechanisms studied, six presented a combination of two mechanisms, and one exclusively displayed oprD mutations. Carbapenem-resistant P. aeruginosa displayed a polyclonal profile after the SPM-1 epidemic genotype declined. This phenomenon is connected with blaSPM-1 P. aeruginosa replaced by other carbapenem-resistant pathogens.
Assuntos
Carbapenêmicos/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/enzimologia , Resistência beta-Lactâmica/genética , beta-Lactamases/biossíntese , Antibacterianos/farmacologia , DNA Bacteriano/genética , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Eletroforese em Gel de Campo Pulsado , Genótipo , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Estudos Prospectivos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Resistência beta-Lactâmica/efeitos dos fármacosRESUMO
Carbapenem-resistance mechanisms are a challenge in the treatment of Pseudomonas aeruginosa infections. We investigated changes in P. aeruginosa carbapenem-resistance determinants over a time period of eight years after the emergence of São Paulo metallo-β-lactamase in a university hospital in Rio de Janeiro, Brazil. Patients admitted to the intensive care unit (ICU) were screened for P. aeruginosa colonisation and followed for the occurrence of infections from April 2007 to April 2008. The ICU environment was also sampled. Isolates were typed using random amplified polymorphic DNA, pulsed-field gel electrophoresis and multilocus sequence typing. Antimicrobial susceptibility was determined by disk diffusion and E-test, production of carbapenemases by a modified-CarbaNP test and presence of carbapenemase-encoding genes by polymerase chain reaction. Non-carbapenemase resistance mechanisms studied included efflux and AmpC overexpression by PAβN and cloxacillin susceptibility enhancement, respectively, as well as oprD mutations. From 472 P. aeruginosa clinical isolates (93 patients) and 17 isolates from the ICU environment, high genotypic diversity and several international clones were observed; one environment isolate belonged to the blaSPM-1 P. aeruginosa epidemic genotype. Among isolates from infections, 10 (29%) were carbapenem resistant: none produced carbapenemases, three exhibited all non-carbapenemase mechanisms studied, six presented a combination of two mechanisms, and one exclusively displayed oprD mutations. Carbapenem-resistant P. aeruginosa displayed a polyclonal profile after the SPM-1 epidemic genotype declined. This phenomenon is connected with blaSPM-1 P. aeruginosa replaced by other carbapenem-resistant pathogens.
Assuntos
Humanos , Resistência beta-Lactâmica/genética , beta-Lactamases/biossíntese , Carbapenêmicos/farmacologia , Pseudomonas aeruginosa/enzimologia , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Resistência beta-Lactâmica/efeitos dos fármacos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Hospitais Universitários , Unidades de Terapia Intensiva , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Estudos Prospectivos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genéticaRESUMO
Building renovations increase the concentration of Aspergillus conidia in the air. In 2010, one wing of the hospital building was imploded due to structural problems. To evaluate the impact of building implosion on the concentration of fungi in the air, the demolition was performed in two phases: mechanical demolition of 30 m of the building, followed by implosion of the wing. Patients at high risk for aspergillosis were placed in protected wards. Air sampling was performed during mechanical demolition, on the day of implosion and after implosion. Total and specific fungal concentrations were compared in the different areas and periods of sampling, using the anova test. The incidence of IA in the year before and after implosion was calculated. The mean concentration of Aspergillus increased during mechanical demolition and on the day of implosion. However, in the most protected areas, there was no significant difference in the concentration of fungi. The incidence of invasive aspergillosis (cases per 1000 admissions) was 0.9 in the 12 months before, 0.4 during, and 0.5 in the 12 months after mechanical demolition (P > 0.05). Continuous monitoring of the quality of air and effective infection control measures are important to minimize the impact of building demolition.
Assuntos
Microbiologia do Ar , Aspergilose/prevenção & controle , Aspergillus/isolamento & purificação , Infecção Hospitalar/prevenção & controle , Esporos Fúngicos/isolamento & purificação , Colapso Estrutural , Análise de Variância , Aspergilose/epidemiologia , Contagem de Colônia Microbiana , Monitoramento Ambiental , Arquitetura Hospitalar , Humanos , Controle de InfecçõesRESUMO
A utilização dos implantes dentários para reabilitações do aparelho estomatognático deve ser racional e respeitar os desafios mecânicos da prótese submetida aos esforços, relacionando com o número e localização das fixações. O objetivo do trabalho foi relatar a utilização da guia multifuncional para determinação do sistema reabilitador, analisar a relação de posicionamento dos implantes com o tecido ósseo remanescente, orientar no posicionamento e quantidade do enxerto com finalidade de otimizar o local dos implantes a serem instalados, obedecendo o planejamento do alinhamento dental da prótese previamente confeccionada. A técnica cirúrgica consistiu de reconstrução alveolar de maxila com enxerto de crista ilíaca e em seis meses foram instalados cinco implantes, ambos procedimentos foram orientados pela guia multifuncional. Após seis meses foi instalada uma prótese fixa implantoretida provisória e posteriormente a definitiva, ressaltando que a mesma guia foi utilizada para moldeira de transferência dos implantes e padrão para confecção da barra metálica. Com três anos de acompanhamento o paciente relata que a reabilitação com prótese fixa sobre implantes após recebimento de enxerto de crista ilíaca, atendeu seus anseios estéticos e funcional
Assuntos
Humanos , Feminino , Adulto , Transplante Ósseo , Implantação Dentária , Reabilitação Bucal , Sistema EstomatognáticoRESUMO
BACKGROUND: Listeriosis occurs mainly in persons at extremes of age and with immunocompromising conditions. It is believed that most cases of listeriosis are acquired in the community. A cluster of listeriosis in hospitalized patients prompted the present investigation. METHODS: We conducted a case series study of listeriosis from August 21, 2006, to June 1, 2007, in a hospital in the city of Rio de Janeiro, Brazil. RESULTS: Six patients with Listeria monocytogenes infection were identified: 5 during hospitalization and 1 at a day clinic. By the time the infection was diagnosed, 5 patients had been in the hospital for a mean of 9 days. All patients were elderly (median age, 80 years) and had immunocompromising conditions. Five (83%) patients died. Four patients developed bloodstream infections, 3 caused by serotype 1/2b. Two patients had peritonitis: one caused by serotype 3b and another by serotype 1/2b. Four L monocytogenes isolates belonged to a single pulse-field gel electrophoresis genotype, suggesting a common source. An epidemiologic investigation pointed to the hospital kitchen as the possible contamination. CONCLUSION: Data suggest a health care-associated outbreak of listeriosis and highlight the importance of developing guidelines for prevention and treatment of health care-associated foodborne diseases, especially in hospitals with immunocompromised adult patients.
Assuntos
Infecção Hospitalar/epidemiologia , Surtos de Doenças , Listeria monocytogenes/classificação , Listeria monocytogenes/isolamento & purificação , Listeriose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Técnicas de Tipagem Bacteriana , Brasil , Infecção Hospitalar/mortalidade , Impressões Digitais de DNA , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Hospitalização , Humanos , Hospedeiro Imunocomprometido , Listeriose/mortalidade , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Peritonite/epidemiologia , Peritonite/microbiologia , SorotipagemRESUMO
OBJECTIVE: To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI). DESIGN AND SETTING: Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006. PATIENTS: Twenty-five patients with BCC-BSI. DESIGN: After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar chi(2) adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using SpeI. RESULTS: The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals. CONCLUSION: Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.
Assuntos
Bacteriemia , Complexo Burkholderia cepacia , Surtos de Doenças , Contaminação de Equipamentos , Injeções Intravenosas/efeitos adversos , Metoclopramida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Brasil/epidemiologia , Infecções por Burkholderia/epidemiologia , Infecções por Burkholderia/microbiologia , Complexo Burkholderia cepacia/classificação , Complexo Burkholderia cepacia/genética , Complexo Burkholderia cepacia/isolamento & purificação , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Estudos Cross-Over , Eletroforese em Gel de Campo Pulsado , Feminino , Hospitais Privados/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Masculino , Metoclopramida/administração & dosagem , Pessoa de Meia-IdadeRESUMO
In only a few instances has the clonal composition of Staphylococcus aureus collections that include methicillin-susceptible S. aureus (MSSA) been extensively characterized. In order to investigate the clonal composition of MSSA and methicillin-resistant S. aureus (MRSA) and examine whether the infections diagnosed at our hospital were related to internationally distributed S. aureus lineages, we collected 89 clinical S. aureus isolates from patients at a public university hospital in Rio de Janeiro, Brazil, from September 1999 to June 2000. All S. aureus isolates were genotyped by pulsed-field gel electrophoresis and multilocus restriction fragment typing (MLRFT), and a subset (n = 17) was further characterized by multilocus sequence typing (MLST). The 34 MRSA isolates were additionally characterized by SCCmec typing. The MSSA population (n = 55) was grouped into 18 restriction fragment types (RFTs); of these, five RFTs accounted for 67% (37) of the MSSA isolates. MRSA isolates were clustered into only three RFTs (P = 0.02). The majority of MSSA RFTs were related to sequence type 30 (ST30) (12 isolates, 22%), ST1, ST188, and ST432 (6 isolates, 11% each). The predominant MRSA RFT comprised 31 (91%) of 34 isolates; four randomly selected isolates of this RFT were ST239, the previously described widely disseminated Brazilian clone. However, a fifth isolate belonging to this RFT was the ST644, a new single locus variant of ST239. By applying MLRFT and MLST, we found evidence for a clonal structure in MSSA isolates and detected the dissemination of MSSA clonal complexes 1, 5, 8, 30, and 45.
Assuntos
Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Tipagem Bacteriana , Brasil , Farmacorresistência Bacteriana/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Hospitais Universitários , Humanos , Masculino , Resistência a Meticilina/genética , Pessoa de Meia-Idade , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genéticaRESUMO
Buscou-se, por meio de questionários respondidos por professores e alunos da Disciplina de Clínica Integrada, verificar a ocorrência da prática interdisciplinar e identificar o grau de integração existente entre os docentes de uma mesma especialidade e de especialidades diferentes, durante a execução das atividades clínicas na Faculdade de Odontologia da Universidade Federal de Uberlândia - FOUFU. As respostas foram analisadas e interpretadas de forma quantitativa qualitativa e os resultados permitiram concluir que não foi possível detectar uma efetividade prática interdisciplinar, em tampouco a integração dos professores envolvidos no ensino odontológico