Self-organizing maps and VolSurf approach to predict aldose reductase inhibition by flavonoid compounds

Aldose Reductase (AR) is the polyol pathway key enzyme which converts glucose to sorbitol. High glucose availability in insulin resistant tissues in diabetes leads into an accumulation of sorbitol, which has been associated with typical chronic complications of this disease, such as neuropathy, nephropathy and retinopathy. In this study, 71 flavonoids AR inhibitors were subjected to two methods of SAR to verify crucial substituents. The first method used the PCA (Principal Component Analysis) to elucidate physical and chemical characteristics in the molecules that would be essential for the activity, employing VolSurf descriptors. The rate obtained explained 53% of the system total variance and revealed that a hydrophobic-hydrophilic balance in the molecules is required, since very polar or nonpolar substituents decrease the activity. Artificial Neural Networks (ANNs) was also employed to determine key substituents by evaluating substitution patterns, using NMR data. This study had a high success rate (85% accuracy in the training set and 88% accuracy in the test set) and showed polihydroxilations are essential for high activity and methoxylations and glicosilations primarily at positions C7, C3' and C4' decrease the activity.CNPqFAPES

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 mu g/mL. In vitro cytotoxicity assays were performed according to the MTT (methyl tetrazolium) assay protocol described in ISO 10993-5. The viability of treated Caco-2 cells was greater than 83% for all tested nitrofurantoin concentrations, while those treated with nifuroxazide at 2, 4 and 6 mu g/mL had viabilities greater than 70%. Treatment with the nifuroxazide analogues resulted in viability values greater than 70% at 2 and 4 mu g/mL with the exception of the thiophenic methyl-substituted derivative, which resulted in cell viabilities below 70% at all tested concentrations. Caco-2 cells demonstrated reasonable viability for all nifuroxazide derivatives, except the thiophenic methyl-substituted compound. The former were selected for further permeability studies using Caco-2 cells. (C) 2012 Elsevier Ltd. All rights reserved.CNPqCNPqFAPESP [2010/07188-7]FAPES

Desempenho e rendimento de carcaça de frangos de corte alimentados com mistura de aditivos fitogênicos na dieta

O objetivo deste trabalho foi avaliar o efeito de misturas de aditivos fitogênicos na dieta de frangos de corte, sobre seu desempenho zootécnico e rendimento de carcaça. Foram avaliados 660 pintos de sexo misto, entre 1 e 42 dias de idade, em delineamento inteiramente casualizado, com cinco tratamentos e seis repetições de 22 aves (11 machos e 11 fêmeas). Além do controle, foram avaliados tratamentos com antibiótico (10 ppm de virginiamicina) ou com misturas de aditivos fitogênicos: mistura A, 150 ppm de óleos essenciais de alecrim, cravo, gengibre e orégano; mistura B, 150 ppm de óleos essenciais de canela, sálvia, tomilho branco e óleo-resina de copaíba; e mistura A+B, 50% da mistura A e 50% da B. A mistura B proporcionou maior ganho de peso e melhor conversão alimentar das aves, no período de 36 a 42 dias de idade. No período total do experimento, o antibiótico e a mistura B proporcionaram maior ganho de peso das aves. O consumo de ração foi maior com o antibiótico do que com o controle. A mistura A+B e o tratamento controle proporcionaram maior rendimento de coxa+sobrecoxa e maior peso relativo do baço. As mistura B e A+B apresentam potencial como melhoradores de desempenho para frangos de corte

Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones

Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). Chemical studies showed that the cytotoxic activity is due to the reaction of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as cysteine. These studies support the view that SLs inhibit tumour growth by selective alkylation of growth-regulatory biological macromolecules, such as key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which directs the cells into apoptosis. In this study we investigated a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22 germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor-derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties. The experimental results and 3D molecular descriptors were submitted to Kohonen self-organizing map (SOM) to classify (training set) and predict (test set) the cytotoxic activity. From the obtained results, it was concluded that only the geometrical descriptors showed satisfactory values. The Kohonen map obtained after training set using 25 geometrical descriptors shows a very significant match, mainly among the inactive compounds (similar to 84%). Analyzing both groups, the percentage seen is high (83%). The test set shows the highest match, where 89% of the substances had their cytotoxic activity correctly predicted. From these results, important properties for the inhibition potency are discussed for the whole dataset and for subsets of the different structural skeletons. (C) 2008 Elsevier Masson SAS. All rights reserved

Ocorrência de Mazama gouazoupira (Fischer, 1814) na região sudoeste do Rio Grande do Sul, pampa brasileiro

Este estudo fornece registros de Mazama gouazoupira, conhecido popularmente por veado-catingueiro, para a região Sudoeste do Rio Grande do Sul. A espécie foi registrada em vários estudos de levantamentos realizados na região, inclusive em maio de 2008, registrada através da coleta de vestígios na área do Parque Estadual do Espinilho, no município de Barra do Quaraí. Pertencente à família Cervidae, esta espécie é geralmente encontrada em bordas de mata, vassourinhas, banhados, savanas e outros tipos de vegetação aberta. Considerada vulnerável segundo o Livro Vermelho da fauna ameaçada de extinção no Rio Grande do Sul, Mazama gouazoupira é registrada somente para a Estação Ecológica de Aracuri - Esmeralda localizada no planalto, em região de matas com araucária, vassourais e campos, há cerca de 270 Km da capital do Estado do Rio Grande do Sul, Porto Alegre. A importância destes registros sugere a existência de populações associadas à Bacia do Rio Quaraí e outros locais isolados onde possa ser um dos poucos ambientes com um número significativo de indivíduos. O registro desta espécie demonstra a necessidade de maiores investigações sobre as populações de Mazama gouazoupira, para esta e demais regiões do Estado, contribuindo assim, para a ampliação do conhecimento sobre este tipo de fauna da região

Safety and Performance of Narhinel 0.9% Sodium Chloride Monodose and Otrisal 0.74% Sodium Chloride Monodose Nasal Saline Solutions and Nasal Aspirators in Real-World Settings: Postmarket Clinical Follow-up Study Results

ABSTRACT: Background: Blocked or stuffy nose is a common and bothersome symptom of colds, particularly for young children who are unable to clear their noses on their own. Nasal saline solutions and nasal aspirators are designed to gently cleanse and remove blocking nasal secretions. Objective: To assess the safety and performance of 2 monodose isotonic saline solutions (Narhinel 0.9% and Otrisal 0.74% sodium chloride; GSK Consumer Healthcare SARL, a Haleon company, Nyon, Switzerland) and 2 nasal aspirators with disposable hard- and soft-nozzle refills used as a standalone or combination treatment. Methods: We conducted 2 observational, online questionnaire-based, postmarket clinical follow-up studies in Europeans who had used any of the devices ≥1 time in the past 6 months. Coprimary objectives were to confirm the safety and performance of the saline solutions (Narhinel and Otrisal, Study 1) and nasal aspirators (with hard- and soft-nozzle refills, Study 2). Safety was assessed via the proportion of patients reporting adverse events and/or device malfunctions while using the devices within the previous 6 months, and performance was assessed by satisfaction rated on a 5-point scale, with “satisfied” and “very satisfied” being the highest performance ratings. Results: A total of 1136 (Study 1) and 1237 (Study 2) questionnaires were initiated by volunteer participants. Less than 2% of participants reported adverse events for any evaluated product in the previous 6 months. Most participants were “satisfied” or “very satisfied” with the devices for their intended use, with 78% to 91% of participants in the Narhinel arm, 73%–94% in the Otrisal arm, 71% to 95% in the soft-nozzle arm, and 71% to 80% in the hard-nozzle arm giving these ratings. Conclusions: These data support the safety and performance of 2 monodose saline solutions (Narhinel and Otrisal) for nasal cleansing, nasal moisturization, and/or loosening nasal secretions, and of nasal aspirators (with hard- and soft-nozzle refills) for clearing a blocked nose and removing nasal secretions