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81.
Carlos M.G. Azevedo Carlos M.M. Afonso Diana Sousa Raquel T. Lima M. Helena Vasconcelos Madalena Pedro João Barbosa Arlene G. Corrêa Salette Reis Madalena M.M. Pinto 《Bioorganic & medicinal chemistry》2013,21(11):2941-2959
A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (Kp) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log Kp between 3 and 5 and the two membrane models showed a good correlation (r2 = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues. 相似文献
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83.
This work reports the biochemical and functional analysis of the Burkholderia cenocepacia J2315 bceN gene, encoding a protein with GDP-D-mannose 4,6-dehydratase enzyme activity (E.C.4.2.1.47). Data presented indicate that the protein is active when in the tetrameric form, catalyzing the conversion of GDP-D-mannose into GDP-4-keto-6-deoxy-D-mannose. This sugar nucleotide is the intermediary necessary for the biosynthesis of GDP-D-rhamnose, one of the sugar residues of cepacian, the major exopolysaccharide produced by environmental and human, animal and plant pathogenic isolates of the Burkholderia cepacia complex species. Vmax and Km values of 1.5±0.2 µmol.min−1.mg−1 and 1024±123 µM, respectively, were obtained from the kinetic characterization of the B. cenocepacia J2315 BceN protein by NMR spectroscopy, at 25°C and in the presence of 1 mol MgCl2 per mol of protein. The enzyme activity was strongly inhibited by the substrate, with an estimated Ki of 2913±350 µM. The lack of a functional bceN gene in a mutant derived from B. cepacia IST408 slightly reduced cepacian production. However, in the B. multivorans ATCC17616 with bceN as the single gene in its genome with predicted GMD activity, a bceN mutant did not produce cepacian, indicating that this gene product is required for cepacian biosynthesis. 相似文献
84.
Kim P. C. Kuypers Eef L. Theunissen Janelle H. P. van Wel Elizabeth B. de Sousa Fernandes Perna Anke Linssen Anke Sambeth Benjamin G. Schultz Johannes G. Ramaekers 《PloS one》2016,11(2)
Background
Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group.Methods
WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions.Results
Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired.Conclusion
The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse ‘user categories’ using a combination of genetics, imaging techniques and neuropsychological assessments. 相似文献85.
Beatriz Helena B. Vasconcelos Givago S. Souza Tatiana G. C. P. Barroso Luiz Carlos L. Silveira Rita Catarina M. Sousa Bianca Callegari Marília B. Xavier 《PloS one》2016,11(3)
Background
The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals.Methodology
We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient’s clinical history and examinations of the patient’s reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed.Main Findings
The prevalence of neurological disturbances—altered reflexes and skin tactile sensitivity and increased risk of falling—was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects.Conclusions
The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection. 相似文献86.
André Escobar Rozana Wendler da Rocha Bruno Henri Pypendop Darcio Zangirolami Filho Samuel Santos Sousa Carlos Augusto Araújo Valad?o 《PloS one》2016,11(3)
The aim of this study was to measure the temporal effects of intramuscular methadone administration on the minimum anesthetic concentration (MAC) of isoflurane in hens, and to evaluate the effects of the isoflurane-methadone combination on heart rate and rhythm, blood pressure and ventilation. Thirteen healthy adult hens weighing 1.7 ± 0.2 kg were used. The MAC of isoflurane was determined in each individual using the bracketing method. Subsequently, the reduction in isoflurane MAC produced by methadone (3 or 6 mg kg-1, IM) was determined by the up-and-down method. Stimulation was applied at 15 and 30 minutes, and at 45 minutes if the bird had not moved at 30 minutes. Isoflurane MAC reduction was calculated at each time point using logistic regression. After a washout period, birds were anesthetized with isoflurane and methadone, 6 mg kg-1 IM was administered. Heart rate and rhythm, respiratory rate, blood gas values and invasive blood pressure were measured at 1.0 and 0.7 isoflurane MAC, and during 45 minutes after administration of methadone once birds were anesthetized with 0.7 isoflurane MAC. Fifteen minutes after administration of 3 mg kg-1 of methadone, isoflurane MAC was reduced by 2 (-9 to 13)% [logistic regression estimate (95% Wald confidence interval)]. Administration of 6 mg kg-1 of methadone decreased isoflurane MAC by 29 (11 to 46)%, 27 (-3 to 56)% and 10 (-8 to 28)% after 15, 30 and 45 minutes, respectively. Methadone (6 mg kg-1) induced atrioventricular block in three animals and ventricular premature contractions in two. Methadone caused an increase in arterial blood pressure and arterial partial pressure of carbon dioxide, while heart rate and pH decreased. Methadone, 6 mg kg-1 IM significantly reduced isoflurane MAC by 30% in hens 15 minutes after administration. At this dose, methadone caused mild respiratory acidosis and increase in systemic blood pressure. 相似文献
87.
Fabianne?CarlesseEmail author Adriana?Maria?Paix?o?de?Sousa?da?Silva Maria?Elena?Santolaya 《Current fungal infection reports》2016,10(1):10-23
Invasive fungal disease (IFD) is an important infection with high rates of morbidity and mortality in hospitalized patients. Data on incidence, risk factors, and mortality of IFD in the pediatric population, mainly in South America, are scarce. The aim of this paper was to review the literature about the most important IFD in pediatrics in South America. We searched three electronic databases (Medline, Lilacs, and Cochrane databases) for studies published between 2012 and 2015; case reports and editorial were excluded. Twenty-two articles were found on Candida spp. infections; eight on Paracoccidiodes spp.; two on Cryptococcus spp.; and one on Aspergillus spp. Candida albicans was the main agent, followed by Candida parapsilosis in pediatric population. Paracoccidioides spp. had a prevalence ranging from 2.3 to 35.3 % with ages between 11 and 29 years, malnutrition, and hepatic involvement related to the worst prognosis. Cryptococcus spp. showed a prevalence of 2.6 % in under 16 years old, with cryptococcal meningitis most observed, mainly by Cryptococcus neoformans (94.1 %). Aspergillosis and other mold infections, as zygomycosis and fusariosis occurring mostly in immunocompromised children, related with relevant morbidity and mortality in this population. 相似文献
88.
Ocellatin‐PT antimicrobial peptides: High‐resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems
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Mayara Oliveira Ana Georgina Gomes‐Alves Carla Sousa Mariela Mirta Marani Alexandra Plácido Nuno Vale Cristina Delerue‐Matos Paula Gameiro Selma A. S. Kückelhaus Ana M. Tomas José Roberto S. A. Leite Peter Eaton 《Biopolymers》2016,105(12):873-886
Although the mechanism of action of antimicrobial peptides (AMPs) is not clear, they can interact electrostatically with the cell membranes of microorganisms. New ocellatin‐PT peptides were recently isolated from the skin secretion of Leptodactylus pustulatus. The secondary structure of these AMPs and their effect on Leishmania infantum cells, and on different lipid surface models was characterized in this work. The results showed that all ocellatin‐PT peptides have an α‐helix structure and five of them (PT3, PT4, PT6 to PT8) have leishmanicidal activity; PT1 and PT2 affected the cellular morphology of the parasites and showed greater affinity for leishmania and bacteria‐mimicking lipid membranes than for those of mammals. The results show selectivity of ocellatin‐PTs to the membranes of microorganisms and the applicability of biophysical methods to clarify the interaction of AMPs with cell membranes. 相似文献
89.
90.
Sunita M. C. De Sousa Liam C. McIntyre Chan-Eng Chong Hamish S. Scott 《BMC endocrine disorders》2016,16(1):58