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Métodos Terapéuticos y Terapias MTCI
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1.
BMC Complement Altern Med ; 17(1): 372, 2017 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-28720134

RESUMEN

BACKGROUND: The emergence of drug resistant malaria is threatening our ability to treat and control malaria in the Southeast Asian region. There is an urgent need to develop novel and chemically diverse antimalarial drugs. This study aimed at evaluating the antimalarial and antioxidant potentials of Acacia nilotica plant extracts. METHODS: The antioxidant activities of leaves, pods and bark extracts were determined by standard antioxidant assays; reducing power capacity, % lipid peroxidation inhibition and ferric reducing antioxidant power assay. The antimalarial activities of plant extracts against Plasmodium falciparum parasites were determined by the 48 h schizont maturation inhibition assay. Further confirmation of schizonticide activity of extracts was made by extending the incubation period up to 96 h after removing the plant extract residues from parasites culture. Inhibition assays were analyzed by dose-response modelling. RESULTS: In all antioxidant assays, leaves of A. nilotica showed higher antioxidant activity than pods and bark. Antimalarial IC50 values of leaves, pods and bark extracts were 1.29, 4.16 and 4.28 µg/ml respectively, in the 48 h maturation assay. The IC50 values determined for leaves, pods and bark extracts were 3.72, 5.41 and 5.32 µg/ml respectively, after 96 h of incubation. All extracts inhibited the development of mature schizont, indicating schizonticide activity against P. falciparum. CONCLUSION: A. nilotica extracts showed promising antimalarial and antioxidant effects. However, further investigation is needed to isolate and identify the active components responsible for the antimalarial and antioxidant effects.


Asunto(s)
Acacia , Antimaláricos/farmacología , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Plasmodium falciparum/efectos de los fármacos , Resistencia a Medicamentos , Frutas , Concentración 50 Inhibidora , Malaria/tratamiento farmacológico , Fitoterapia , Corteza de la Planta , Hojas de la Planta
2.
Molecules ; 22(1)2017 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-28098806

RESUMEN

Medicinal plants are frequently used for the treatment of various infectious diseases. The objective of this study was to evaluate the antibacterial activity and mode of action of Acacia nilotica and the antibiogram patterns of foodborne and clinical strains of Escherichia coli and Salmonella. The mechanism of action of acacia extracts against E. coli and Salmonella was elucidated by observing morphological damages including cell integrity and cell membrane permeability, as well as changes in cell structures and growth patterns in kill-time experiments. The clinical isolates of E. coli and Salmonella were found resistant to more of the tested antibiotics, compared to food isolates. Minimum inhibitory concentration and minimum bactericidal concentration of acacia leaf extracts were in the ranges of 1.56-3.12 mg/mL and 3.12-6.25 mg/mL, respectively, whereas pods and bark extracts showed somewhat higher values of 3.12-6.25 mg/mL and 6.25-12.5 mg/mL, respectively, against all tested pathogens. The release of electrolytes and essential cellular constituents (proteins and nucleic acids) indicated that acacia extracts damaged the cellular membrane of the pathogens. These changes corresponded to simultaneous reduction in the growth of viable bacteria. This study indicates that A. nilotica can be a potential source of new antimicrobials, effective against antibiotic-resistant strains of pathogens.


Asunto(s)
Acacia/química , Antibacterianos/farmacología , Proteínas Bacterianas/agonistas , ADN Bacteriano/agonistas , Escherichia coli/efectos de los fármacos , Salmonella/efectos de los fármacos , Antibacterianos/aislamiento & purificación , Proteínas Bacterianas/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , ADN Bacteriano/metabolismo , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Escherichia coli/ultraestructura , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Hojas de la Planta/química , Salmonella/crecimiento & desarrollo , Salmonella/metabolismo , Salmonella/ultraestructura
3.
Artículo en Inglés | MEDLINE | ID: mdl-27872070

RESUMEN

The MIC of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle. To ensure the cure of malaria, the MIC must be exceeded until all parasites have been eliminated. The development of highly sensitive and accurate PCR quantitation of low-density malaria parasitemia enables the prospective pharmacokinetic-pharmacodynamic (PK-PD) characterization of antimalarial drug effects and now allows identification of the in vivo MIC. An adaptive design and a PK-PD modeling approach were used to determine prospectively the MIC of the new antimalarial cipargamin (KAE609) in adults with uncomplicated Plasmodium falciparum malaria in an open-label, dose-ranging phase 2a study. Vietnamese adults with acute P. falciparum malaria were allocated sequentially to treatment with a single 30-mg (n = 6), 20-mg (n = 5), 10-mg (n = 7), or 15-mg (n = 7) dose of cipargamin. Artemisinin-based combination therapy was given after parasite densities had fallen and then risen as cipargamin levels declined below the MIC but before a return of signs or symptoms. The rates of parasite clearance were dose dependent, with near saturation of the effect being seen at an adult dose of 30 mg. The developed PK-PD model accurately predicted the therapeutic responses in 23/25 patients. The predicted median in vivo MIC was 0.126 ng/ml (range, 0.038 to 0.803 ng/ml). Pharmacometric characterization of the relationship between antimalarial drug concentrations and parasite clearance rates following graded subtherapeutic antimalarial drug dosing is safe and provides a rational framework for dose finding in antimalarial drug development. (This study has been registered at ClinicalTrials.gov under identifier NCT01836458.).


Asunto(s)
Antimaláricos/farmacocinética , Antimaláricos/uso terapéutico , Indoles/farmacocinética , Indoles/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/metabolismo , Compuestos de Espiro/farmacocinética , Compuestos de Espiro/uso terapéutico , Adulto , Antimaláricos/efectos adversos , Pueblo Asiatico , Humanos , Indoles/efectos adversos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Compuestos de Espiro/efectos adversos , Adulto Joven
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