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1.
Lett Appl Microbiol ; 72(6): 767-773, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33629416

RESUMO

Therapeutic options for infections caused by Carbapenem-resistant Enterobacterales (CRE) are restricted and include polymyxins-centred schemes. Evaluation of in vitro susceptibility is difficult and time consuming. Agar-based methodologies are an alternative to broth microdilution (BMD) and we aimed to evaluate the accuracy of those methods among Enterobacterales. A total of 137 non-duplicated CRE were subjected to polymyxin B BMD, agar screening test (Mueller Hinton plates containing 3 µg ml-1 of polymyxin B) and agar dilution (antibiotic serially diluted 0·25-64 µg ml-1 ). CRE of 42·3% were resistant to polymyxin B (MICs range: 0·25->64 µg ml-1 ) and 16·8% presented borderline MICs. Sensitivity, specificity, PPV and NPV were 86·2, 98·7, 98 and 90·7% for screening test and 86·2, 97·5, 96·1 and 90·6% for agar dilution. ME was 0·73 and 1·5% for screening and agar dilution respectively; VME was 5·8% for both techniques. In general, agar-based methods had a good performance. As far as we know, this is the first study to propose an agar screening test using polymyxin B instead of colistin.


Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/crescimento & desenvolvimento , Polimixina B/farmacologia , Ágar/química , Carbapenêmicos , Colistina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Polimixinas
2.
Sci Adv ; 6(22): eaba6712, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32524002

RESUMO

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate.


Assuntos
Microfluídica , Saccharomyces cerevisiae , Eletrodos , Microfluídica/métodos
3.
Int Nurs Rev ; 65(4): 542-549, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29436708

RESUMO

AIM: To describe the facilitators and barriers for nurses to perform quality wound care in three surgical wards of a hospital in Port-au-Prince, Haiti. BACKGROUND: Up to a quarter of patients in low- and middle-income countries may acquire at least one infection while hospitalized. There is a paucity of research investigating nursing wound care practices in low- and middle-income countries regarding the prevention of hospital-acquired infections. METHODS: The design was qualitative descriptive. We observed nursing staff on the general surgery, orthopaedics and maternity units while they performed routine dressing changes (n = 15). We interviewed nursing (n = 13) and medical residents (n = 3) and inquired about their perceptions of facilitators and barriers for nurses to perform quality wound care. FINDINGS: A number of wound care practices appeared well integrated including using gloves to remove dressings, applying sterile dressings, properly disposing of soiled materials, inspecting wounds for signs of infection and employing comfort and privacy measures. Areas that may need improvement included aseptic technique, hand hygiene, pain assessments, patient education and documentation. We identified four themes related to barriers and facilitators to perform quality wound care: (i) materials and resources; (ii) nurse-to-patient ratios, workload and support; (iii) roles and responsibilities of nurses; and (iv) knowledge and training of nurses. CONCLUSION: Nursing wound care practices may be optimized by improving nurses' professional status and working conditions. IMPLICATIONS FOR NURSING PRACTICE AND HEALTH POLICY: Greater financial investment in health care and (continuing) education, self-regulation and development of the nursing role, including more autonomy, are needed to elevate the professional status of nurses in Haiti. Institutional policies should promote best practices, clarify nursing roles and responsibilities and foster interdisciplinary collaboration in patient care.


Assuntos
Infecção Hospitalar/prevenção & controle , Acessibilidade aos Serviços de Saúde , Papel do Profissional de Enfermagem , Qualidade da Assistência à Saúde , Infecção da Ferida Cirúrgica/prevenção & controle , Ferida Cirúrgica/enfermagem , Haiti , Humanos
4.
Ann Oncol ; 28(7): 1612-1617, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28472235

RESUMO

BACKGROUND: In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. PATIENTS AND METHODS: PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. RESULTS: Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37-88], and women accounted for 59%. ECOG PS 0-1 (46%), PS 2 (37%) and PS 3-4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118-4314]; median serum albumin was 35 g/l [13-54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209-348] for the 130 patients in population C, 66% and 79 days [71-114] for the 111 patients in population B, and 24% and 35 days for [14-56] the 21 patients in population A. These three populations survival were statistically different (P <0.0001). CONCLUSION: PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.


Assuntos
Assistência Ambulatorial , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Técnicas de Apoio para a Decisão , Neoplasias/tratamento farmacológico , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Progressão da Doença , Feminino , França , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/sangue , Neoplasias/mortalidade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Albumina Sérica Humana/análise , Fatores de Tempo , Resultado do Tratamento
8.
J Nat Prod ; 64(5): 634-7, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11374961

RESUMO

Three new limonoids, named haperforins C2 (1), F (2), and G (3), were isolated from a sample of Harrisonia perforata leaves collected in Central Vietnam. Their structures were determined by single-crystal X-ray diffraction analyses, and their NMR and mass spectral data are reported.


Assuntos
Limoninas , Plantas Medicinais/química , Triterpenos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Extratos Vegetais/química , Folhas de Planta/química , Triterpenos/isolamento & purificação , Vietnã , Difração de Raios X
9.
J Nat Prod ; 63(7): 1015-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10924191

RESUMO

Two new rearranged limonoids, named haperforine A (1) and haperforine E (2), were isolated from a sample of Harrisonia perforata leaves collected in Center Vietnam and their structures determined by X-ray diffraction analysis. The structure of a minor compound was established as 12-desacetylhaperforine A (3) by chemical correlation. Their NMR and mass spectroscopic properties are reported.


Assuntos
Flavonoides/química , Flavonoides/isolamento & purificação , Plantas Medicinais/química , Cristalografia por Raios X , Estrutura Molecular , Análise Espectral
11.
Acta Crystallogr C ; 56 (Pt 4): 473-4, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10815215
12.
Org Lett ; 2(8): 1053-6, 2000 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-10804552

RESUMO

[formula: see text] Cycloaddition between gamma,delta-unsaturated beta-enamino ester 9 and camphor-derived oxazoline N-oxide 8 afforded a single adduct, 14. Dipolarophile 9 proved to be very reactive despite the substitution on the double bond. Stereoselective sodium cyanoborohydride reduction of the imminium intermediate 14a gave rise stereoselectively to beta-amino ester derivative 15a. Oxidative acidic hydrolysis, oxidation of the resulting aldehyde 18, deprotection, and cyclization afforded the beta-lactam 23, a direct precursor of (+)-carpetimycin A.


Assuntos
Óxidos N-Cíclicos/química , Oxazóis/química , Tienamicinas/síntese química , Cristalografia por Raios X , Hidrólise , Estrutura Molecular , Oxirredução
13.
J Nat Prod ; 63(4): 441-6, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10785410

RESUMO

Bioassay-guided fractionation of a leaf extract of G. bracteata has yielded six new prenylxanthones, bractatin (1), isobractatin (2), 1-O-methylbractatin (3), 1-O-methylisobractatin (4), 1-O-methyl-8-methoxy-8,8a-dihydrobractatin (5), and 1-O-methylneobractatin (6). The structures of these compounds have been elucidated by spectroscopic means (NMR, MS), literature data, and X-ray crystallographic analysis of 2. These compounds possess significant cytotoxicity against the KB cell line.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Plantas Medicinais/química , Xantenos/isolamento & purificação , Alquil e Aril Transferases/antagonistas & inibidores , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Inibidores Enzimáticos/farmacologia , Humanos , Células KB , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Folhas de Planta/química , Espectrofotometria Ultravioleta , Xantenos/farmacologia
15.
Retina ; 18(6): 526-30, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9869461

RESUMO

PURPOSE: Penetration of piperacillin into the vitreous cavity after intravenous administration was investigated in humans. METHODS: Forty-five eyes undergoing vitrectomy between November 1993 and December 1994 were included. Each patient received a single intravenous dose of piperacillin 4 g 2 hours before ocular incision. A 0.2-mL vitreous sample was aspired at the beginning of vitrectomy, a blood sample was obtained, and piperacillin level was assessed. RESULTS: There were no detectable drug concentrations in 25 eyes. Mean vitreous drug concentration in the remaining evaluable eyes (n = 14) was 2.33 microg/mL (+/-0.76). We divided samples into two groups: 23 uninflamed (Group 1) and 16 inflamed (Group 2) eyes. Mean vitreous drug concentration was 0.42 microg/mL in Group 1 and 4.95 microg/mL in Group 2 (P < 0.2). Piperacillin concentration was higher than the minimum inhibitory concentration for gram-positive bacteria in 13% of uninflamed and 69% of inflamed eyes (P < 0.001). CONCLUSION: Studies show that intravenously administered piperacillin can penetrate the vitreous cavity in rabbits. Our study suggests that a single dose of piperacillin can produce intravitreal concentrations sufficient to kill gram-positive bacteria in inflamed eyes. The poor intraocular penetration of systemically administered piperacillin in uninflamed eyes raises questions about its usefulness as a prophylactic agent in ophthalmic surgery.


Assuntos
Penicilinas/farmacocinética , Piperacilina/farmacocinética , Corpo Vítreo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Corpos Estranhos no Olho/metabolismo , Corpos Estranhos no Olho/cirurgia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/prevenção & controle , Feminino , Humanos , Injeções Intravenosas , Subluxação do Cristalino/metabolismo , Subluxação do Cristalino/cirurgia , Masculino , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Piperacilina/administração & dosagem , Doenças Retinianas/metabolismo , Doenças Retinianas/cirurgia , Estudos Retrospectivos , Vitrectomia , Corpo Vítreo/cirurgia , Hemorragia Vítrea/metabolismo , Hemorragia Vítrea/cirurgia
16.
Drug Metab Dispos ; 26(8): 769-74, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9698291

RESUMO

Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecine++ +] is a water-soluble analogue of camptothecine used in the second-line treatment of advanced colon cancer. Recently, we identified, in the plasma of patients and in human liver microsomal incubations, the presence of a new metabolite of irinotecan, 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecine (NPC), which is produced by cleavage of the distal piperidine ring of irinotecan. The kinetics of biotransformation of the lactone and carboxylate forms of irinotecan into NPC were studied using human liver microsomes. The formation of NPC was characterized by the following parameters: KM = 48.2 +/- 6.8 and 273 +/- 122 microM and Vmax = 74.1 +/- 4.9 and 78.6 +/- 27.7 pmol/min/mg of protein for the lactone and carboxylate forms of irinotecan, respectively. Interestingly, there was no formation of NPC from 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecine, a major metabolite of irinotecan that has an open distal piperidine ring and could be considered a possible metabolic precursor of NPC. The transformation of irinotecan into NPC was found to be catalyzed principally by cytochrome P450 (CYP) 3A, based on three key results, as follows: 1) the CYP3A-selective inhibitors ketoconazole (1 microM) and troleandomycin (100 microM) inhibited NPC formation by 99 and 100%, respectively; 2) of a series of microsomal preparations from transfected lymphoblastoid cells expressing specific CYPs, only those from CYP3A4 cDNA-transfected cells transformed irinotecan into NPC; and 3) incubations with 15 individual preparations of human liver microsomes yielded highly significant correlations between the formation of NPC and both immunoreactivity with anti-CYP3A antibodies and testosterone 6beta-hydroxylation (an activity specifically mediated by CYP3A). The effects of 11 drugs (used at 100 microM) on this metabolism were studied with irinotecan lactone (25 microM). Although ondansetron, loperamide, and racecadotril inhibited this pathway by 75, 95, and 95%, respectively, the concentrations used may not be clinically achievable. However, significant inhibition by ketoconazole and troleandomycin indicates that NPC formation in patients may be influenced by coadministration of drugs with known anti-CYP3A activities.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos/metabolismo , Camptotecina/análogos & derivados , Microssomos Hepáticos/metabolismo , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos Fitogênicos/farmacocinética , Biotransformação , Camptotecina/metabolismo , Camptotecina/farmacocinética , Cimetidina/farmacologia , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Humanos , Irinotecano , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Cetoconazol/farmacologia , Cinética , Troleandomicina/farmacologia
17.
Drug Metab Dispos ; 26(3): 257-60, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9492389

RESUMO

Ritonavir, indinavir, and saquinavir, all human immunodeficiency virus-1 protease inhibitors with a potent antiviral effect during triple therapy, are extensively metabolized by liver cytochrome P450 3A4. As this P450 isoform is involved in the metabolism of about 50% of drugs, coadministration of protease inhibitors with other drugs may lead to serious effects due to enzyme inhibition. Among these drugs, methadone and buprenorphine, both metabolized by P450 3A4, are potential candidates to drug interactions. In this study, metabolic interactions between these protease inhibitors and methadone or buprenorphine were studied in vitro in a panel of 13 human liver microsomes. Ritonavir was the most potent competitive inhibitor with Ki about 50 and 20 nM for methadone and buprenorphine metabolisms, respectively. Indinavir and saquinavir also inhibited methadone N-demethylation (Ki about 3 and 15 microM, respectively) and buprenorphine N-dealkylation (Ki about 0.8 and 7 microM, respectively). The rank order of inhibition potency against metabolism of methadone and buprenorphine was ritonavir > indinavir > saquinavir. There is obvious potential for clinically significant drug interactions, particularly with ritonavir. In brief, caution should be advised if human immunodeficiency virus-1 protease inhibitors are coadministered with methadone and buprenorphine.


Assuntos
Buprenorfina/metabolismo , Inibidores da Protease de HIV/farmacologia , Metadona/metabolismo , Alquilação/efeitos dos fármacos , Citocromo P-450 CYP3A , Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/farmacologia , Humanos , Indinavir/farmacologia , Cinética , Microssomos Hepáticos/enzimologia , Oxigenases de Função Mista/antagonistas & inibidores , Oxirredutases N-Desmetilantes/antagonistas & inibidores , Ritonavir/farmacologia , Saquinavir/farmacologia
18.
Cancer Res ; 58(3): 468-72, 1998 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-9458091

RESUMO

Irinotecan (CPT-11) is a water-soluble analogue of camptothecin showing activity in colon cancer. Recently, we identified a major metabolite of CPT-11 in patients' plasma, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin (APC), which is produced by the oxidation of the distal piperidine ring (P. Rivory et al, Cancer Res., 56: 3689-3694, 1996). As with all active camptothecin derivatives, CPT-11 is subject to spontaneous interconversion between a lactone and a carboxylate form in aqueous media. The kinetics of biotransformation of the two forms of CPT-11 into APC was studied using pooled human liver microsomes. The formation of APC was characterized by the following parameters: Km = 18.4 +/- 1.4 and 39.7 +/- 11.6 microM; and Vmax = 26.0 +/- 0.6 and 13.4 +/- 1.7 pmol/min/mg protein for the lactone and carboxylate forms of CPT-11, respectively. This reaction was found to be catalyzed principally by cytochrome P-450 (CYP) 3A because of three key results: (a) the CYP 3A-selective inhibitors ketoconazole (1 microM) and troleandomycin (100 microM) inhibited APC formation by 98 and 100%, respectively, mostly in a competitive way; (b) using microsomes from transfected lymphoblastoid cells expressing specific CYPs, we found that only those from CYP 3A4 cDNA-transfected cells transformed CPT-11 into APC; and (c) using 15 individual preparations of human liver microsomes, we observed highly significant correlations between the activity of CPT-11 metabolism into APC and both immunoreactivity with anti-CYP 3A antibodies and testosterone 6beta hydroxylation, an activity specifically mediated by CYP 3A. The effect on this metabolism of 11 drugs used at 100 microM was studied with CPT-11 lactone at 25 microM. Amikacin, Bactrim, ciprofloxacin, rocephine, 5-fluorouracil, metoclopramide, morphine, and paracetamol had no effect, but ondansetron, loperamide, and racecadotril inhibited this pathway by 25, 50, and 50%, respectively. These concentrations exceed those expected in vivo. APC formation in patients may thus be influenced by coadministered ketoconazole therapy and may decline after administration of CPT-11 because of the lactonolysis of the latter.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Hidrocarboneto de Aril Hidroxilases , Camptotecina/análogos & derivados , Sistema Enzimático do Citocromo P-450/metabolismo , Microssomos Hepáticos/metabolismo , Oxirredutases N-Desmetilantes/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Biotransformação/efeitos dos fármacos , Camptotecina/metabolismo , Camptotecina/farmacologia , Citocromo P-450 CYP3A , Inibidores das Enzimas do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/genética , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Humanos , Irinotecano , Cetoconazol/farmacologia , Estrutura Molecular , Oxirredutases N-Desmetilantes/antagonistas & inibidores , Oxirredutases N-Desmetilantes/genética , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Transfecção , Troleandomicina/farmacologia
19.
Pharmacogenetics ; 8(2): 101-8, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10022747

RESUMO

The aim of the present study was to evaluate the use of recombinant human cytochrome P-450 1A2 (rH-CYP1A2) in studies performed in vitro in order to predict metabolic drug-drug interactions occurring in man. In vitro metabolism of tacrine (a CYP1A2 probe) in the presence and absence of fluvoxamine, a CYP1A2 inhibitor, was investigated in human liver mircrosomes and with different rH-CYP. Vmax, Km and Ki determined with human liver microsomes were compared with those observed using rH-CYP1A2, assuming that 1 mg of liver microsomes contains, on average, 69 pmol of CYP1A2. The extent of tacrine metabolism inhibition procured by fluvoxamine with rH-CYP1A2, was compared with previous results observed in man. The Vax and Km for 1-hydroxytacrine formation rates obtained with rH-CYP1A2 were in good agreement with those observed in human liver microsomes (175+/-9 versus 140+/-60 pmol/min/mg for Vmax and 14+/-2 versus 16+/-2 microM for Km, respectively. The Ki of fluvoxamine on 1-hydroxytacrine formation rate observed with rH-CYP1A2 was similar to that observed with human liver microsome (0.35+/-0.05 versus 0.20+/-0.20 microM, respectively). Using the Km, Vmax and Ki determined with rH-CYP1A2, we calculated that fluvoxamine produced an inhibition of 1-, 2- and 4-hydroxytacrine formation rate of 91, 87 and 88%, respectively, in the range of tacrine and fluvoxamine concentrations observed in man. These percentages of inhibition calculated in vitro were in agreement with the percentage of fluvoxamine-dependent decrease in tacrine apparent oral clearance previously observed in man (83+/-13%). We conclude that human CYP1A2 expressed in yeast is a powerful tool to predict and to quantify drug-drug interactions in man.


Assuntos
Citocromo P-450 CYP1A2/genética , Fluvoxamina/farmacologia , Tacrina/farmacologia , Antidepressivos de Segunda Geração/metabolismo , Antidepressivos de Segunda Geração/farmacologia , Citocromo P-450 CYP1A2/metabolismo , Inibidores do Citocromo P-450 CYP1A2 , Interações Medicamentosas , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Fluvoxamina/metabolismo , Humanos , Hidroxilação , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Nootrópicos/metabolismo , Nootrópicos/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tacrina/metabolismo
20.
Toxicol In Vitro ; 12(2): 183-90, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20654399

RESUMO

The effects of chronic exposure to phytosanitary products are difficult to determine because of their use in combination with other products and their variety of formulations containing additives or contaminants. In order to evaluate, at the cellular level, the risk of myelosuppressive effects caused by two widely used herbicides, atrazine and dinoterb, we performed in vitro assays on human granulo-monocytic progenitor-cells (CFU-GM) and also granulomonocytic expansion in liquid media. Both of these techniques were carried out in the presence of each molecule. Seven stable environmental metabolites of atrazine were studied using the above techniques in addition to supernatants of rat hepatocytes preincubated with atrazine and dinoterb for 24 hr. Parent atrazine and dinoterb showed similar moderate-direct toxicity on CFU-GM. In cells grown in liquid media for a period longer than 14 days, dinoterb toxicity appeared delayed but increased when compared with atrazine. 2-chloro-diamino-atrazine was found to be as toxic as atrazine on CFU-GM. Supernatants of rat hepatocyte preincubated for 24 hr with dinoterb exhibited a 150-fold increase in toxicity compared with the parent molecule, while toxicity remained unchanged for atrazine. This phenomenon was directly correlated to toxicity on rat hepatocytes. The present study will be useful in defining tissue-specific toxicities of phytosanitary products, including environmental or biotransformed metabolites.

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