RESUMO
Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti-Mycobacterium tuberculosis effects) was proved by 9. Compounds 7, 8, and 9 determined blocking of G1 phase. Compound 7 proved to be toxic, inducing apoptosis in 54% of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound 9 had the best antibacterial activity, being used as a disinfectant agent. Compounds 7, 8, and 9, seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.
Assuntos
Anti-Infecciosos/química , Antineoplásicos/síntese química , Antituberculosos/química , Hidrazinas/síntese química , Oxidiazóis/síntese química , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Arilamina N-Acetiltransferase/metabolismo , Benzoatos/química , Ácidos Carboxílicos/química , Avaliação Pré-Clínica de Medicamentos , Fase G1/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrazinas/farmacologia , Isoniazida/química , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Oxidiazóis/química , Oxidiazóis/farmacologia , RNA Mensageiro/efeitos dos fármacosRESUMO
This paper presents a unique case of double meningitis with enterovirus and reactivated varicella-zoster virus without shingles in an immunocompetent male teenager, a case that offers many important medical lessons, all "gravitating" around physiopathological reasoning of any clinical case in general.
Assuntos
Infecções por Enterovirus , Herpesvirus Humano 3 , Humanos , Masculino , Adolescente , Herpesvirus Humano 3/isolamento & purificação , Infecções por Enterovirus/virologia , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/complicações , Enterovirus/isolamento & purificação , Enterovirus/genética , Meningite Viral/diagnóstico , Meningite Viral/virologia , Infecção pelo Vírus da Varicela-Zoster/complicações , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/virologiaRESUMO
BACKGROUND: Knowledge-based systems (KBS) are software applications based on a knowledge base and an inference engine. Various experimental KBS for computer-assisted medical diagnosis (CAMD) and treatment were started to be used since 70 s (VisualDx, GIDEON, DXPlain, CADUCEUS, Internist-I, Mycin etc). OBJECTIVES: This article briefly presents and tests the "Electronic Pediatrician (EPed)", a prototype medical user-interface-based stand-alone KBS software created by the author (in Romanian language) that offers both a computer-assisted pathophysiologic diagnosis and treatment of ill children. EPed currently covers the most frequent (and mainly infectious) respiratory, digestive, renal and central nervous system pediatric diseases treated in the Department of Pediatric Infectious Diseases (DPID) of the County Emergency Hospital of TârgoviÈte town (DâmboviÈa County, Romania). METHODS: EPed uses a new type of pathophysiologically-based diagnosis algorithm, which combines the relative incidences of diseases and the degree of covering any clinical picture of any patient. EPed was tested by a retrospective study in which the author has chosen 34 clinical child cases diagnosed and treated in DPID in the period of pandemics. The diagnoses predicted by EPed for each tested patient in part was compared to the diagnoses established by the clinician for each patient, so that to test the diagnostic accuracy of EPed. RESULTS: The real diagnoses of the 34 children tested were found to occupy an average list-index of 12 (varying from 1 to 57) in the lists of EPed-predicted diagnoses for each case in part (based on the clinical and paraclinical signs inputs), which is considered an acceptable result for a demo version. CONCLUSIONS: The diagnostic accuracy of EPed was acceptable and is perfectible in the future by using other formulas of scoring which combine the relative incidences of diseases and the degree of covering the clinical picture of a patient. EPed is the first pathophysiologically-based KBS focused on general pediatrics (mainly on pediatric infectious diseases) written in Romanian.
Assuntos
Diagnóstico por Computador , Software , Criança , Humanos , Estudos Retrospectivos , Computadores , PediatrasRESUMO
BACKGROUND: The correlation of the inflammatory profile with the severity of the disease in neoplastic patients with SARS-CoV-2 infection was addressed. METHODS: A database of 1537 patients hospitalized in the pneumology department was analyzed. After applying the inclusion and exclusion criteria, 83 patients (67% males, 33% females) were included. RESULTS: Most of the analyzed patients were hospitalized with a moderate form of disease, explaining the significant percentage of 25% mortality. The frequency of the type of neoplasm was higher for lung cancer, followed by malignant colon tumor. We identified a significant association between the increased value of ferritin (p < 0.0001, OR = 22.31), fibrinogen (p = 0.009, OR = 13.41), and C-reactive protein (p = 0.01, OR = 7.65), respectively, and the level of severity of COVID-19. The results of the univariate logistic regression analysis for predicting the severity of the disease revealed that the increased values of ferritin (p = 0.001, OR = 22.31) and fibrinogen (p = 0.02, OR = 13.41) represent a risk for a serious negative prognosis of COVID-19. CONCLUSIONS: Our study demonstrated that the value of the analyzed inflammatory parameters increased in direct proportion to the severity of the disease and that higher values were associated with increased mortality in the study group.