RESUMEN
Increase in antimicrobial resistance to antibiotics is the product of the evolution and natural adaptation of microorganisms through mutations and genetic recombination caused by the indiscriminate use of antibiotics and the ineffective control and prevention of infection. The current study analyzes the profile of multiresistant hospital bacteria in two hospitals in Pelotas, state of Rio Grande do Sul, Brazil. Over the course of 4 months, patient's gender and age, hospital accommodation type, and sample site were evaluated. Two hundred and eighty-six microbiological culture antibiogram reports of hospitalized patients and outpatients of both sexes, between zero and 96 years of age, were analyzed. Bacterium Klebsiella pneumoniae was the most prevalent. The most resistant Gram-negative bacilli (GNB) were K. pneumoniae (27.5%); Acinetobacter baumannii (24.1%); Escherichia coli (14.7%); and Pseudomonas aeruginosa (14.5%). The most resistant Gram-positive cocci (GPC) were Enterococcus faecium (27.5%) and Staphylococcus aureus (25.5%). The classes of antibiotics with the greatest number of resistant GNB included penicillins (84.8%), quinolones (77.5%), and cephalosporins (75.7%). In the case of GPC, the most resistant were macrolides (95.4%); lincosamides (90.3%), and penicillins (77%). Among GNBs, polypeptides had the highest sensitivity rate (81.3%), whereas, among GPC, fusidanes, glycylcyclines, and lipopeptides had 100% sensitivity.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Femenino , Hospitales , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Adulto JovenRESUMEN
(S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate, a new telluroamino acid derivative, showed remarkable glutathione peroxidase (GPx)-like activity, attesting to its antioxidant potential. However, the stability and toxicity of this compound has not yet been investigated. The present study was designed to investigate the pharmacological/toxicological properties of this compound in vitro and in vivo. In vitro, this telluroamino acid derivative significantly blocked spontaneous and Fe(II)-induced TBARS formation in rat brain homogenates, demonstrating high antioxidant activity. In addition, it exhibited GPx-like and thiol oxidase activities. However, when subcutaneously administered to mice, (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate indicated genotoxic and mutagenic effect in adult male mice. Considering the differential effects of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate in vitro and in vivo, additional experiments are needed to elucidate the mechanism(s) by which this compound displays its antioxidant/toxicological effects.
Asunto(s)
Antioxidantes/farmacología , Ácido Aspártico/análogos & derivados , Succinatos/farmacología , Administración Oral , Análisis de Varianza , Animales , Ácido Aspártico/toxicidad , Ensayo Cometa , Daño del ADN , Compuestos Ferrosos/metabolismo , Glutatión Peroxidasa/metabolismo , Dosificación Letal Mediana , Masculino , Ratones , Compuestos Organometálicos/metabolismo , Compuestos Organometálicos/farmacología , Compuestos Organometálicos/toxicidad , Ratas , Ratas Wistar , Succinatos/toxicidad , Telurio/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
BACKGROUND: Bone marrow transplantation (BMT) is often used in the treatment of various diseases. Before BMT, patients are submitted to a conditioning regimen (CR), which consists of the administration of high doses of chemotherapy. The action of many cytostatic drugs involves the overproduction of reactive oxygen species, which together with inadequate antioxidant protection can lead to oxidative stress and this has been implicated in the etiology of various diseases. The objectives of this study were to look for evidence of oxidative stress and also to analyze delta-Aminolevulinato dehydratase (delta-ALA-D) activity as a possible marker of oxidative stress in autologous and allogeneic BMT patients. METHODS: Lipid peroxidation, vitamin C and thiol group levels as well as catalase, superoxide dismutase and delta-ALA-D activity were determined in 37 healthy controls, 13 patients undergoing autologous peripheral blood stem cell transplantation and 24 patients undergoing allogeneic BMT. RESULTS: We found that patients presented signs of oxidative stress before they were submitted to BMT, during CR and up to 20 days after BMT. There was a decrease in enzymatic and non enzymatic antioxidant defenses, in delta-ALA-D activity, and an increase in lipoperoxidation in the blood of both patient groups. CONCLUSION: This study has indicated that autologous and allogeneic BMT are associated with oxidative stress. Moreover, blood delta-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.
Asunto(s)
Trasplante de Médula Ósea , Estrés Oxidativo , Porfobilinógeno Sintasa/sangre , Adulto , Ácido Ascórbico/sangre , Biomarcadores/metabolismo , Catalasa/sangre , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/sangre , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante HomólogoRESUMEN
Severe toxicity is associated with cytotoxic drugs used during the conditioning regimen (CR) preceding bone marrow transplantation (BMT). The aim of this study was to evaluate the involvement of oxidative stress and possible use of delta-aminolevulinate dehydratase (delta-ALA-D) activity as a marker of oxidative stress in autologous BMT patients. We have also compared common drugs that are used during CR, namely, melphalan (M-200) and cyclophosphamide-BCNU-etoposide (CBV), in order to determine whether either of them could be less toxic to patients in terms of oxidative stress. The sample consisted of 10 patients admitted for autologous BMT, 5 with M-200 CR and 5 with CBV CR and 10 healthy controls. Lipid peroxidation (estimated as thiobarbituric acid-reactive substances, TBARS), vitamin C, thiol levels, catalase, superoxide dismutase and delta-ALA-D activity were determined before CR, during CR and on days 10 and 20 after BMT. Signs of exacerbated oxidative stress were minimal before CR, except for the CVB group (patients with lymphoma) where an increase in TBARS and a decrease in P-SH were detected. Indices of oxidative stress changed in both groups (CBV and M-200) during CR and up to 20 days after BMT. There was a decrease in enzymatic and non-enzymatic antioxidant defenses and in delta-ALA-D activity and an increase in lipoperoxidation in the blood of both patient groups. In conclusion, CBV and, principally, M-200 caused oxidative stress in patients undergoing autologous BMT and blood delta-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Melfalán/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Porfobilinógeno Sintasa/sangre , Acondicionamiento Pretrasplante/efectos adversos , Ácido Ascórbico/sangre , Biomarcadores/análisis , Carmustina/efectos adversos , Estudios de Casos y Controles , Ciclofosfamida/efectos adversos , Etopósido/efectos adversos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Persona de Mediana Edad , Especies Reactivas de Oxígeno/sangre , Compuestos de Sulfhidrilo/sangre , Trasplante AutólogoRESUMEN
OBJECTIVES: To compare different conditioning regimens (CR), in order to determine whether either of them could be less toxic to allogeneic bone marrow transplantation (BMT) patients in terms of oxidative stress and also analyze delta-ALA-D activity as a possible marker of oxidative stress. DESIGN AND METHODS: Lipid peroxidation, vitamin C, thiol groups levels and catalase, superoxide dismutase and delta-ALA-D activity were determined in 21 healthy controls, 5 patients with fludarabine+cyclophosphamide (FluCy) CR, 12 with busulfan+cyclophosphamide (BuCy) and 4 with cyclophosphamide+total body irradiation (CyTBI). RESULTS: There were a decrease in enzymatic and non enzymatic antioxidants, in delta-ALA-D activity, and in all CRs and an increase in lipid peroxidation more pronounced in CyTBI CR. CONCLUSIONS: All CRs promoted oxidative stress in allogeneic BMT patients, but this was more pronounced with CyTBI and delta-ALA-D activity seemed to be an additional biomarker of oxidative stress in these patients.