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

A list of land plants of Parque Nacional do Caparaó, Brazil, highlights the presence of sampling gaps within this protected area

Brazilian protected areas are essential for plant conservation in the Atlantic Forest domain, one of the 36 global biodiversity hotspots. A major challenge for improving conservation actions is to know the plant richness, protected by these areas. Online databases offer an accessible way to build plant species lists and to provide relevant information about biodiversity. A list of land plants of “Parque Nacional do Caparaó” (PNC) was previously built using online databases and published on the website "Catálogo de Plantas das Unidades de Conservação do Brasil." Here, we provide and discuss additional information about plant species richness, endemism and conservation in the PNC that could not be included in the List. We documented 1,791 species of land plants as occurring in PNC, of which 63 are cited as threatened (CR, EN or VU) by the Brazilian National Red List, seven as data deficient (DD) and five as priorities for conservation. Fifity-one species were possible new ocurrences for ES and MG states

Integrated Process of Biosurfactant Production by <i>Bacillus atrophaeus</i> ATCC-9372 Using an Air-Lift Bioreactor Coupled to a Foam Fraction Column

Biosurfactants are surface-active molecules, produced by several microorganisms, that possess unique properties such as low toxicity and biodegradability. Their application in various industries depends on their purity and their specific properties, such as emulsification and stability. Therefore, this study focuses on the production of biosurfactant from Bacillus atrophaeus in an air-lift bioreactor. It analyzes the effects of agitation rate and temperature on biosurfactant production, as well as the concurrent separation process using a foam fractionation column. Moreover, the ability of the produced biosurfactant to form emulsions in water with several substrates (vegetables oils, hydrocarbons, and fossil fuels) was determined, and the stability of the soybean oil–water emulsion (used as an example) at different temperatures and pH values was verified. The biosurfactant produced, tentatively identified as iturin, was only detected in the coalescent liquid after passing through the foam fractionation column, demonstrating the complete separation of the biosurfactant. The best operational conditions for production and separation were an air flow of 1.00 vvm and a temperature of 34 °C (emulsifier index (EI24) = 66.9%, and productivity (Pp) = 967.5% mL h−1). Vegetable oils, hydrocarbons, and fossil fuels were emulsified in water, highlighting the soybean oil, whose emulsion oil–water had the highest ES (3333.3 min) at a temperature of 50 °C and a pH value of 9.0

Comparative Study of Two Oxidizing Agents, Chloramine T and Iodo-Gen®, for the Radiolabeling of β-CIT with Iodine-131: Relevance for Parkinson’s Disease

Parkinson&rsquo;s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to alteration of the integrity of dopaminergic transporters (DATs). In recent years, some radiopharmaceuticals have been used in the clinic to evaluate the integrity of DATs. These include tropane derivatives such as radiolabeled &beta;-CIT and FP-CIT with iodine-123 (123I), and TRODAT-1 with metastable technetium-99 (99mTc). Radiolabeling of &beta;-CIT with radioactive iodine is based on electrophilic radioiodination using oxidizing agents, such as Chloramine T or Iodo-Gen&reg;. For the first time, the present work performed a comparative study of the radiolabeling of &beta;-CIT with iodine-131 (131I), using either Chloramine T or Iodo-Gen&reg; as oxidizing agents, in order to improve the radiolabeling process of &beta;-CIT and to choose the most advantageous oxidizing agent to be used in nuclear medicine. Both radiolabeling methods were similar and resulted in high radiochemical yield (&gt; 95%), with suitable 131I-&beta;-CIT stability up to 72 h. Although Chloramine T is a strong oxidizing agent, it was as effective as Iodo-Gen&reg; for &beta;-CIT radiolabeling with 131I, with the advantage of briefer reaction time and solubility in aqueous medium

Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies. [68Ga]Ga-PSMA-11 was evaluated to determine the radiochemical purity (RCP), stability in saline solution and serum, lipophilicity, affinity to serum proteins, binding and internalization to lymph node carcinoma of the prostate (LNCaP) cells, and ex vivo biodistribution in mice. The radiopharmaceutical was produced with an RCP of 99.06 ± 0.10%, which was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). The product was stable in saline solution for up to 4 h (RCP &gt; 98%) and in serum for up to 1 h (RCP &gt; 95%). The lipophilicity was determined as −3.80 ± 0.15, while the serum protein binding (SPB) was &lt;17%. The percentages of binding to LNCaP cells were 4.07 ± 0.51% (30 min) and 4.56 ± 0.46% (60 min), while 19.22 ± 2.73% (30 min) and 16.85 ± 1.34% (60 min) of bound material was internalized. High accumulation of [68Ga]Ga-PSMA-11 was observed in the kidneys, spleen, and tumor, with a tumor-to-contralateral-muscle ratio of &gt;8.5 and a tumor-to-blood ratio of &gt;3.5. In conclusion, an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment

Comparative Evaluation of Radiochemical and Biological Properties of 131I- and [99mTc]Tc(CO)3-Labeled RGD Analogues Planned to Interact with the &alpha;v&beta;3 Integrin Expressed in Glioblastoma

Radiolabeled peptides with high specificity for overexpressed receptors in tumor cells hold great promise for diagnostic and therapeutic applications. In this work, we aimed at comparing the radiolabeling efficiency and biological properties of two different RGD analogs: GRGDYV and GRGDHV, labeled with iodine-131 (131I) and technetium-99m-tricarbonyl complex [99mTc][Tc(CO)3]+. Additionally, we evaluated their interaction with the &alpha;v&beta;3 integrin molecule, overexpressed in a wide variety of tumors, including glioblastoma. Both peptides were chemically synthesized, purified and radiolabeled with 131I and [99mTc][Tc(CO)3]+ using the chloramine-T and tricarbonyl methodologies, respectively. The stability, binding to serum proteins and partition coefficient were evaluated for both radioconjugates. In addition, the binding and internalization of radiopeptides to rat C6 glioblastoma cells and rat brain homogenates from normal animals and a glioblastoma-induced model were assessed. Finally, ex vivo biodistribution studies were carried out. Radiochemical yields between 95&ndash;98% were reached for both peptides under optimized radiolabeling conditions. Both peptides were stable for up to 24 h in saline solution and in human serum. In addition, the radiopeptides have hydrophilic characteristics and a percentage of binding to serum proteins around 35% and 50% for the [131I]I-GRGDYV and [99mTc]Tc(CO)3-GRGDHV fragments, respectively. Radiopeptides showed the capacity of binding and internalization both in cell culture (C6) and rat brain homogenates. Biodistribution studies corroborated the results obtained with brain homogenates and confirmed the different binding characteristics due to the exchange of radionuclides and the presence of the tricarbonyl complex. Thereby, the results showed that both radiopeptides might be considered for future clinical applications

Genotyping did not evidence any contribution of Mycobacterium bovis to human tuberculosis in Brazil

Submitted by Sandra Infurna ([email protected]) on 2016-10-11T15:30:42Z No. of bitstreams: 1 alexandre_santos_etal_IOC_2011.pdf: 239001 bytes, checksum: 50d5454a5f61743435cbeee1d8103caf (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2016-10-11T15:46:25Z (GMT) No. of bitstreams: 1 alexandre_santos_etal_IOC_2011.pdf: 239001 bytes, checksum: 50d5454a5f61743435cbeee1d8103caf (MD5)Made available in DSpace on 2016-10-11T15:46:25Z (GMT). No. of bitstreams: 1 alexandre_santos_etal_IOC_2011.pdf: 239001 bytes, checksum: 50d5454a5f61743435cbeee1d8103caf (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Laboratório de Micobacteriologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Laboratório de Micobacteriologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Ministério da Saúde. Fundação Oswaldo Cruz. Centro de Referência Nacional em Tuberculose Prof. Hélio Fraga. Rio de Janeiro, RJ, Brasil.Clínica de Tuberculose Augusto Guimarães, Centro de Referencia Regional em Tuberculose. Program de Controle de Tuberculose. Campos, RJ, Brasil;.EMBRAPA. Divisão de Saúde Animal. Juiz de Fora, MG, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Laboratório de Micobacteriologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Laboratório de Pesquisa Multidisciplinar. Rio de Janeiro, RJ, Brasil.The contribution of Mycobacterium bovis to the global burden of tuberculosis (TB) in man is likely to be underestimated due to its dysgonic growth characteristics and because of the absence of pyruvate in most used media is disadvantageous for its primary isolation. In Brazil Mycobacterium culture, identification and susceptibility tests are performed only in TB reference centers, usually for selected cases. Moreover, solid, egg-based, glycerol-containing (without pyruvate supplementation) Löwenstein-Jensen (L-J) or Ogawa media are routinely used, unfavouring M. bovis isolation. To determine the importance of M. bovis as a public health threat in Brazil we investigated 3046 suspected TB patients inoculating their clinical samples onto routine L-J and L-J pyruvate enriched media. A total of 1796 specimens were culture positive for Mycobacterium spp. and 702 TB cases were confirmed. Surprisingly we did not detect one single case of M. bovis in the resulting collection of 1674 isolates recovered from M. bovis favourable medium analyzed by conventional and molecular speciation methods. Also, bacillary DNA present on 454 sputum smears from 223 TB patients were OxyR genotyped and none was recognized as M. bovis. Our data indicate that M. bovis importance on the burden of human TB in Brazil is marginal

Active Video Game Exercise Training Improves the Clinical Control of Asthma in Children: Randomized Controlled Trial

<div><p>Objective</p><p>The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with moderate to severe asthma.</p><p>Design</p><p>A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing (Bruce protocol) and lung function.</p><p>Results</p><p>No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p < 0.05). Although the mean energy expenditure at rest and during exercise training was similar for both groups, the maximum energy expenditure was higher in the VGG.</p><p>Conclusion</p><p>The present findings strongly suggest that aerobic training promoted by an active video game had a positive impact on children with asthma in terms of clinical control, improvementin their exercise capacity and a reductionin pulmonary inflammation.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01438294?term=NCT01438294&rank=1" target="_blank">NCT01438294</a></p></div