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1.
Br J Radiol ; 95(1137): 20211151, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35762317

RESUMO

Diagnostic imaging allows for accurate and early recognition of acute renal pathologies, thus allowing for appropriate clinical triage, life-saving treatments, and preservation of renal function. In this review, we discuss the clinical presentation and imaging findings of renal emergencies with infectious, hemorrhagic, vascular, and traumatic etiologies.


Assuntos
Emergências , Rim , Diagnóstico por Imagem , Humanos , Rim/diagnóstico por imagem , Rim/fisiologia , Triagem
2.
Cell Chem Biol ; 26(9): 1274-1282.e4, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31279606

RESUMO

Common approaches to antibiotic discovery include small-molecule screens for growth inhibition in target pathogens and screens for inhibitors of purified enzymes. These approaches have a shared intent of seeking to directly target a vital Achilles heel in a pathogen of interest. Here, we report the first screen against a sporulation pathway in a non-pathogenic bacterium as a means of discovering novel antibiotics-this effort has resulted in two important discoveries. First, we show that the sporulation program of Streptomyces venezuelae is exquisitely sensitive to numerous forms of DNA damage. Second, we have identified a DNA gyrase inhibitor. This molecule, EN-7, is active against pathogenic species that are resistant to ciprofloxacin and other clinically important antibiotics. We suggest that this strategy could be applied to other morphogenetic pathways in prokaryotes or eukaryotes as a means of identifying novel chemical matter having scientific and clinical utility.


Assuntos
DNA Girase/efeitos dos fármacos , Descoberta de Drogas/métodos , Inibidores da Topoisomerase II/isolamento & purificação , Antibacterianos/farmacologia , DNA Girase/metabolismo , Testes de Sensibilidade Microbiana , Esporos Bacterianos/efeitos dos fármacos , Streptomyces/efeitos dos fármacos , Streptomyces/metabolismo , Inibidores da Topoisomerase II/metabolismo , Inibidores da Topoisomerase II/farmacologia
3.
ACS Chem Biol ; 14(4): 688-695, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30848888

RESUMO

Bacteria exhibit complex responses to biologically active small molecules. These responses include reductions in transcriptional and translational efficiency, alterations in metabolic flux, and in some cases, dramatic changes in growth and morphology. Here, we describe Min-1, a novel small molecule that inhibits growth of Gram-positive bacteria by targeting the cell envelope. Subinhibitory levels of Min-1 inhibits sporulation in Streptomyces venezuelae and reduces growth rate and cell length in Bacillus subtilis. The effect of Min-1 on B. subtilis cell length is significant at high growth rates sustained by nutrient-rich media but drops off when growth rate is reduced during growth on less energy-rich carbon sources. In each medium, Min-1 has no impact on the proportion of cells containing FtsZ-rings, suggesting that Min-1 reduces the mass at which FtsZ assembly is initiated. The effect of Min-1 on size is independent of UDP-glucose, which couples cell division to carbon availability, and the alarmone ppGpp, which reduces cell size via its impact on fatty acid synthesis. Min-1 activates the LiaRS stress response, which is sensitive to disruptions in the lipid II cycle and the cell membrane, and also compromises cell membrane integrity. Therefore, this novel synthetic molecule inhibits growth at high concentrations and induces a short-cell phenotype at subinhibitory concentrations that is independent of known systems that influence cell length, highlighting the complex interactions between small molecules and cell morphology.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Pirazóis/farmacologia , Bacillus subtilis/citologia , Bacillus subtilis/metabolismo , Crescimento Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ácidos Graxos/metabolismo , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Streptomyces/efeitos dos fármacos , Uridina Difosfato Glucose/metabolismo , Uridina Difosfato Ácido N-Acetilmurâmico/análogos & derivados , Uridina Difosfato Ácido N-Acetilmurâmico/metabolismo
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