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911.
José Lamartine Soares-Sobrinho Mônica Felts de La Roca Soares Pablo Queiroz Lopes Lidiane Pinto Correia Fábio Santos de Souza Rui Oliveira Macêdo Pedro José Rolim-Neto 《AAPS PharmSciTech》2010,11(3):1391-1396
This work aimed the studies of physicochemical characterization, thermal stability, and compatibility of benznidazole (BNZ)
drug by spectroscopy (NMR, IR), thermoanalytical (differential thermal analysis, differential scanning calorimetry, and thermogravimetry),
and chromatographic (HPLC) techniques, beyond the analytical tools of Van’t Hoff equation and Ozawa model. The compatibility
study was conducted by binary mixtures (1:1, w/w) of the drug with microcrystalline cellulose 102 and 250, anhydrous lactose, and sodium starch glycolate. The physicochemical
characterization confirmed data reported in scientific literature, guaranteeing authenticity of the analyzed raw material.
The drug melts at 191.68°C (∆H, 119.71 J g−1), characteristic of a non-polymorphic raw material, and a main stage decomposition at 233.76–319.35°C (∆m, 43.32%) occurred, ending the study with almost all mass volatilized. The quantification of drug purity demonstrated a correlation
of 99.63% between the data obtained by chromatographic (99.20%) and thermoanalytical technique (99.56%). The Arrhenius equation
and Ozawa model showed a zero-order kinetic behavior for the drug decomposition, and a calculated provisional validity time
was 2.37 years at 25°C. The compatibility study evidenced two possible chemical incompatibilities between BNZ and the tested
excipients, both associated by the authors to the reaction of the BNZ’s amine and a polymer carbohydrate’s carbonile, being
maillard reactions. The BNZ reaction with anhydrous lactose is more pronounced than with the sodium starch glycolate because
the lactose has more free hydroxyl groups to undergo reduction by the drug. In this sense, this work guides the development
of a new solid pharmaceutical product for Chagas disease treatment, with defined quality control parameters and physicochemical
stability. 相似文献
912.
The probability of the most sensitive genotypes being eliminated from a population due to a contaminant pulse–genetic erosion–is negatively associated to the within-genotype variation. A sensitive genotype with a small phenotypic variation would be more prone to be lost–a critically sensitive genotype. Furthermore, natural populations inhabiting contaminated sites are usually exposed to several pollutants. Such co- or sequential exposure can have severe effects if at least some tolerant clonal lineages surviving one contaminant are sensitive to the others. Such an inverse relationship coupled with a low within-genotype variation potentially enhances genetic erosion. Accordingly, this study evaluated co-tolerance and the occurrence of clonal lineages critically sensitive to 48-hours lethal exposures of copper, zinc, cobalt, and chromium among eight clonal lineages of the cladocerans Daphnia longispina. Median lethal concentrations (LC50) of each metal were found to have the potential to provoke genetic erosion. Pairwise comparisons of LC50, from the eight clonal lineages, revealed neither negative nor positive correlations (r ≤ |0.56|; p ≥ 0.18), but inversely sensitive clonal lineages were found for all pairs of metals. Therefore, besides having the potential to eliminate critically sensitive clonal lineages in a first intermediately lethal pulse, all tested metals may provoke further losses of clonal lineages in an already genetically eroded population. 相似文献
913.
Richard Gill Alvaro A.T. Lopes Anthony C. Moffat 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1981,226(1):117-123
A high-performance liquid chromatographic (HPLC) assay for the identification and quantification of barbiturates in blood at therapeutic levels has been developed. An ODS-silica column is used with an eluent of 40% methanol at pH 8.5. The barbiturates are detected at 240 nm. The sample preparation procedure involves extraction of unfractionated blood (100 μl) with hexane—diethyl ether (50:50, v/v) and is very rapid. Talbutal is used as an internal standard.The method has been applied to the determination of five barbiturates (amylobarbitone, butobarbitone, cyclobarbitone, pentobarbitone and quinalbarbitone) in blood after therapeutic doses of the drugs. An application of the HPLC assay to forensic casework is demonstrated. 相似文献
914.
915.
This work demonstrates, for the first time, the potential of using multi-parameter flow cytometry to monitor changes in the microbial cytoplasmic membrane integrity and polarization during microbial fuel cells (MFC) operation. Such information is crucial to follow the dynamics of bacteria colonization of the electrodes and their viability maintenance during electrical current production. Interestingly, the results show that during voltage production, the electrostatic gradients of the bacteria cytoplasmic membrane are disturbed, leading to depolarization of a subpopulation (where less than 40% of the cells were polarized). Once the voltage dropped, due to substrate limitation, several cells in the anode supernatant restored their polarized state. This process was reversible and observed over more than 4 cycles of fresh substrate addition. Similar power outputs induced similar membrane polarization results, regardless of the substrate used. The percentage of non-viable cells was maintained constant during current production. This study opens new opportunities to monitor cell behavior, and thus increase the knowledge of dynamic mechanisms responsible for current production at the individual cell level. This technique could be of great interest for the development of new MFC configurations and optimization of MFC operation conditions toward increased performance. 相似文献
916.
P. V. Lopes‐Costa A. R. Dos Santos L. G. Dos Santos B. B. Da Silva 《Cell proliferation》2010,43(2):124-129
Objectives: To evaluate the effect of raloxifene on Ki‐67 and Bcl‐2 antigen expression in operable, stage II, oestrogen‐receptor‐positive invasive ductal breast carcinomas. Materials and methods: Twenty post‐menopausal women who had taken 60 mg of raloxifene daily for 28 days prior to definitive surgery were enrolled in the investigation. Two tumour samples were obtained by incisional biopsy during the study, one at the time of confirmation of diagnosis of invasive ductal carcinoma and evaluation of oestrogen receptor status, and the other 29 days later, at the time of definitive surgery. Immunohistochemistry was performed on tumour samples, prior to and after raloxifene treatment, to evaluate Ki‐67 and Bcl‐2 expression. Friedman and McNemar tests were used for statistical analysis of the data, significance being established at 5%. Results: Mean percentage of Ki‐67‐stained nuclei was 24.86 ± 2.95 prior to raloxifene treatment and 13.33 ± 1.52 after treatment (P < 0.001). Prior to raloxifene treatment, only 9/20 cases (45%) were classified as Bcl‐2‐positive, whereas after treatment, 17/20 (85%) were classified as Bcl‐2‐positive (P < 0.013). Conclusions: Raloxifene treatment significantly reduced Ki‐67 antigen expression and increased Bcl‐2 expression in breast carcinomas of post‐menopausal women. 相似文献
917.
Species diversity of Brazilian cave fauna has been seriously underestimated. A karst area located in Felipe Guerra, northeastern Brazil, which is a hotspot of subterranean diversity in Brazil, has revealed more than 20 troglobitic species, most of them still undescribed. Based on recent samplings in this karst area, we document the occurrence of the suborder Cavernicola (Platyhelminthes) in South American hypogean environments for the first time and describe a new genus and species for this suborder. Hausera Leal-Zanchet & Souza, gen. n. has features concordant with those defined for the family Dimarcusidae. The new genus is characterized by two unique features, viz. an intestine extending dorsally to the brain and ovovitelline ducts located dorsally to the nerve cords, which is complemented by a combination of other characters. The type-specimens of Hausera
hauseri Leal-Zanchet & Souza, sp. n. are typical stygobionts, unpigmented and eyeless, and they may constitute an oceanic relict as is the case of other stygobiotic invertebrates found in this karst area in northeastern Brazil. 相似文献
918.
Aur��le Piazza Alexandre Serero Jean-Baptiste Boul�� Patricia Legoix-N�� Judith Lopes Alain Nicolas 《PLoS genetics》2012,8(11)
Genomes contain tandem repeats that are at risk of internal rearrangements and a threat to genome integrity. Here, we investigated the behavior of the human subtelomeric minisatellites HRAS1, CEB1, and CEB25 in Saccharomyces cerevisiae. In mitotically growing wild-type cells, these GC–rich tandem arrays stimulate the rate of gross chromosomal rearrangements (GCR) by 20, 1,620, and 276,000-fold, respectively. In the absence of the Pif1 helicase, known to inhibit GCR by telomere addition and to unwind G-quadruplexes, the GCR rate is further increased in the presence of CEB1, by 385-fold compared to the pif1Δ control strain. The behavior of CEB1 is strongly dependent on its capacity to form G-quadruplexes, since the treatment of WT cells with the Phen-DC3 G-quadruplex ligand has a 52-fold stimulating effect while the mutation of the G-quadruplex-forming motif reduced the GCR rate 30-fold in WT and 100-fold in pif1Δ cells. The GCR events are telomere additions within CEB1. Differently, the extreme stimulation of CEB25 GCR depends on its affinity for Cdc13, which binds the TG-rich ssDNA telomere overhang. This property confers a biased orientation-dependent behavior to CEB25, while CEB1 and HRAS1 increase GCR similarly in either orientation. Furthermore, we analyzed the minisatellites‚ distribution in the human genome and discuss their potential role to trigger subtelomeric rearrangements. 相似文献
919.