We have studied the protonation equilibria of a dicopper(II) complex [Cu 2 (μ-OH)(C 21 H 33 ON 6 )](ClO 4 ) 2 ·H 2 O, (1), in aqueous solution, its interactions with DNA, its cytotoxic activity, and its uptake in tumoral cells. C 21 H 33 ON 6 corresponds to the ligand ...

O presente trabalho foi realizado objetivando validar um método analítico para a determinação do ácido trans,trans-mucônico (ATTM) urinário empregando-se cromatografia líquida de alta eficiência com detecção UV. O ATTM foi previamente extraído das amostras biológicas, utilizando-se colunas de troca iônica e identificado por cromatografia líquida de alta eficiência (CLAE). O cromatógrafo foi equipado com coluna de fase reversa Lichrosorb RP 18, 5 µm (250 x 4,2 mm). A temperatura da coluna foi mantida a 40 o C. A fase móvel utilizada foi ácido acético 1% -metanol (90-10 v/v), pH = 2,72 a um fluxo de 1 mL/min e detecção UV em comprimento de onda de 264 nm. O método apresentou linearidade instrumental (0,006 a 10,0 µg/mL), limites de detecção (0,006 µg/ mL) e quantificação (0,03 µg/mL), precisão (CV intra-ensaio: 9,57%, CV interensaio: 11,15%) e recuperação (86,45%) adequados à determinação da concentração urinária de ATTM em trabalhadores expostos ao benzeno. Unitermos: • Ácido trans,trans-mucônico • Benzeno • Validação • Cromatografia líquida de • alta eficiência

Comparative studies using the univariate and multivariate optimizations (factorial design) were undertaken to determine manganese in antihypertensive drugs by electrothermal atomic absorption spectrometry (ET AAS). For the univariate method, the optimum pyrolysis and atomization temperatures were 500 and 2200°C, and for multivariate analysis, the temperatures were 500 and 2400°C, respectively. No differences were observed between the methods with respect to the slopes of the calibration curves, recoveries, results for certified urine samples for the two levels, and the averages of the intra-and inter-assay coefficients of variation (CV) using Student t and F tests as a statistical tool (P < 0.05). Calibration was performed by matrix matching. All other studies were made using the optimized multivariate conditions. The characteristic mass was of 0.68 ± 0.17 pg (the recommended mass is 0.60 pg). The limits of detection and quantification were 0.23 and 0.77 µg L -1 , respectively. Intra-and inter-assay studies on the drug spiked with 0.5, 1.0, and 1.5 µg L -1 of Mn yielded mean results of 3.6 ± 1.9% and 9.6 ± 2.2%, respectively. For the intra-assay evaluation, seven samples of each concentration were evaluated for Mn on the same day, whereas, for the inter-assay study, these solutions were analyzed in three replicates during three consecutive days. Recovery studies on the drug spiked with three levels of Mn (n = 7 for each level) furnished results between 101.4 ± 17.2% and 106.6 ± 7.5%. The results of a certified urine sample analysis (two levels of Mn) agreed at a 95% level of confidence. Forty eight antihypertensive drug samples were analyzed, and the drug contents varied between 2.9 ng and 1.9 µg capsule -1 . antihypertension, spectrométrie d'absorption atomique électrothermique, optimisation à plusieurs variables.

Este artigo descreve a síntese e a caracterização de três novos complexos de platina(II) com a oxitetraciclina, doxiciclina e clortetraciclina por análise elementar, espectroscopias IV e RMN de 195 Pt. As interações da doxiciclina com íons Pt II em função do pH foram estudadas por RMN de 1 H. Todas as tetraciclinas investigadas formam complexos 1:1 com a Pt II via oxigênio do grupo hidroxila e oxigênio do grupo amida do anel A. As concentrações mínimas inibitórias (MIC) dos ligantes e de seus complexos de Pt II foram determinadas em duas cepas sensíveis (E. coli HB 101 and E. coli ATCC 25922) e em uma resistente (E. coli HB101/pBR322). O complexo de platina da doxiciclina é duas vezes mais potente do que o antibiótico livre na cepa resistente. Os coeficientes de partição dos complexos em octanol e água foram determinados. O aumento da lipofilia causa um aumento da atividade antimicrobiana na cepa resistente.

Background: Naturalistic studies evaluate individuals in their usual way of living, presenting more &quot;real-life&quot; data regarding patients and their diseases. Objective: To investigate demographic, clinical, and genetic factors that could be predictive of good response to cholinesterase inhibitors (ChEI) treatment in Alzheimer&#39;s disease (AD) and AD + cerebrovascular disease (CVD). Patients and Methods: A total of 129 patients were diagnosed with AD or AD + CVD and with mild-to-moderate dementia. After a 12-month treatment, 97 patients completed the study. They were evaluated at baseline and after three, six, and 12 months of ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6 polymorphisms were determined for all of the participants. In each visit, we used cognitive, functional, mood, and behavior scales. We classified patients according to their scores in the Mini-Mental State Examination (MMSE). Good responders were defined as those scoring ≥2 ...

We encapsulated cisplatin into stealth pH-sensitive liposomes and studied their stability, cytotoxicity and accumulation in a human small-cell lung carcinoma cell line (GLC4) and its resistant subline (GLC4/CDDP). Since reduced cellular drug accumulation has been shown to be the main mechanism responsible for resistance in the GLC4/CDDP subline, we evaluated the ability of this new delivery system to improve cellular uptake. The liposomes were composed of dioleoylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG 2000 ) and were characterized by determining the encapsulation percentage as a function of lipid concentration. Among the different formulations, DOPE/CHEMS/DSPE-PEG liposomes (lipid concentration equal to 40 mM) encapsulated cisplatin more efficiently than other concentrations of liposomes (about 20.0%, mean diameter of 174 nm). These liposomes presented good stability in mouse plasma which was obtained using a 0.24-M EDTA solution (70% cisplatin was retained inside the liposomes after 30 min of incubation). Concerning cytotoxic effects, they are more effective (1.34-fold) than free cisplatin for growth inhibition of the human lung cancer cell line A549. The study of cytotoxicity to GLC4 and GLC4/ CDDP cell lines showed similar IC 50 values (approximately 1.4 µM), i.e., cisplatin-resistant cells were sensitive to this cisplatin formulation. Platinum accumulation in both sensitive and resistant cell lines followed the same pattern, i.e., approximately the same intracellular platinum concentration (4.0 x 10 -17 mol/cell) yielded the same cytotoxic effect. These results indicate that long-circulating pH-sensitive liposomes, also termed as stealth pH-sensitive liposomes, may present a promising delivery system for cisplatin-based cancer treatment. This liposome system proved to be able to circumvent the cisplatin resistance, whereas it was not observed when using non-long-circulating liposomes composed of phosphatidylcholine, phosphatidylserine, and cholesterol.

Recebido em 1/2/02; aceito em 14/2/03 2,5-HEXANODIONE DETERMINATION IN URINE SAMPLES SUBJECTED TO ACID HYDROLYSIS: RELEVANCE OF THE CHROMATOGRAPHIC COLUMN AND THE pH. Acidic hydrolysis of samples is frequent in urinary 2,5-hexanodione determination. This hydrolysis should be performed under proper conditions, in order to avoid interference, such as the presence of 2,5-dimethylfurane and 2-acetylfurane. The results of the present work, as well as data from the literature, show that the use of non-polar or slightly polar chromatographic columns of 30 m length is an essential condition for 2,5-HD determination in an acid hydrolysed urine sample. In the same way the pH should be kept between 0.3 and 0.5. The mean concentrations of 2,5-HD in samples submitted to hydrolysis (0.50 ± 0.28 mg/g of creatinine) was about 3 times higher than those found in the samples without acid hydrolysis (0.19 ± 0.3 mg/g of creatinine).