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1.
Temperature (Austin) ; 10(2): 159-165, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37332302

RESUMEN

Among the vital signs collected during hospital triage, respiratory rate is an important parameter associated with physiological, pathophysiological, and emotional changes. In recent years, the importance of its verification in emergency centers due to the severe acute respiratory syndrome 2 (SARS2) pandemic has become very clear, although it is still one of the least evaluated and collected vital signs. In this context, infrared imaging has been shown to be a reliable estimator of respiratory rate, with the advantage of not requiring physical contact with patients. The objective of this study was to evaluate the potential of analyzing a sequence of thermal images as an estimator of respiratory rate in the clinical routine of an emergency room. We used an infrared thermal camera (T540, Flir Systems) to obtain the respiratory rate data of 136 patients, based on nostrils' temperature fluctuation, during the peak of the COVID-19 pandemic in Brazil and compared it with the chest incursion count method, commonly employed in the emergency screening procedures. We found a good agreement between both methods, with Bland-Altman limits of agreement ranging from -4 to 4 min-1, no proportional bias (R2 = 0.021, p = 0.095), and a strong correlation between them (r = 0.95, p < 0.001). Our results suggest that infrared thermography has potential to be a good estimator of respiratory rate in the routine of an emergency room.

2.
ACS Infect Dis ; 6(8): 2192-2201, 2020 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-32603583

RESUMEN

Dihydrofolate reductase (DHFR), a key enzyme involved in folate metabolism, is a widely explored target in the treatment of cancer, immune diseases, bacteria, and protozoa infections. Although several antifolates have proved successful in the treatment of infectious diseases, they have been underexplored to combat tuberculosis, despite the essentiality of M. tuberculosis DHFR (MtDHFR). Herein, we describe an integrated fragment-based drug discovery approach to target MtDHFR that has identified hits with scaffolds not yet explored in any previous drug design campaign for this enzyme. The application of a SAR by catalog strategy of an in house library for one of the identified fragments has led to a series of molecules that bind to MtDHFR with low micromolar affinities. Crystal structures of MtDHFR in complex with compounds of this series demonstrated a novel binding mode that considerably differs from other DHFR antifolates, thus opening perspectives for the development of relevant MtDHFR inhibitors.


Asunto(s)
Antagonistas del Ácido Fólico , Mycobacterium tuberculosis , Tuberculosis , Diseño de Fármacos , Antagonistas del Ácido Fólico/farmacología , Humanos , Tetrahidrofolato Deshidrogenasa/genética , Tuberculosis/tratamiento farmacológico
3.
Future Med Chem ; 10(8): 935-959, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29629843

RESUMEN

Folate pathway is a key target for the development of new drugs against infectious diseases since the discovery of sulfa drugs and trimethoprim. The knowledge about this pathway has increased in the last years and the catalytic mechanism and structures of all enzymes of the pathway are fairly understood. In addition, differences among enzymes from prokaryotes and eukaryotes could be used for the design of specific inhibitors. In this review, we show a panorama of progress that has been achieved within the folate pathway obtained in the last years. We explored the structure and mechanism of enzymes, several genetic features, strategies, and approaches used in the design of new inhibitors that have been used as targets in pathogen chemotherapy.


Asunto(s)
Antiinfecciosos/química , Antiinfecciosos/farmacología , Vías Biosintéticas/efectos de los fármacos , Diseño de Fármacos , Antagonistas del Ácido Fólico/química , Antagonistas del Ácido Fólico/farmacología , Ácido Fólico/metabolismo , Animales , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Infecciones Bacterianas/tratamiento farmacológico , Enfermedades Transmisibles/tratamiento farmacológico , Hongos/efectos de los fármacos , Guanosina Trifosfato/metabolismo , Humanos , Modelos Moleculares , Micosis/tratamiento farmacológico , Tetrahidrofolatos/metabolismo
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