Orofacial antinociceptive effects of perillyl alcohol associated with codeine and its possible modes of action

Abstract This study evaluated the orofacial antinociceptive effect of (S)-(-)-perillyl alcohol (PA) associated with codeine (C) and investigated the possible molecular anchorage mechanisms of PA. Mice (n = 5 per group) were treated with PA alone and associated with codeine and assigned to the following groups: 75.0 mg/kg PA; 75.0 mg/kg PA + C 30 mg/kg; PA 37.5 mg/kg + C 15.0 mg/kg; C 30.0 mg/kg; and control. Nociception was induced by formalin, capsaicin, and glutamate, and was quantified based on the duration (in seconds) of face grooming. The possible mechanisms of action were evaluated by molecular docking study. In the formalin test, PA75/C30 presented an effect in the neurogenic (p < 0.0001) and inflammatory (p < 0.005) phases. Mice treated with PA75 (p < 0.0001) and PA75/C30 (p < 0.0005) showed a reduced nociceptive behavior in the capsaicin test. Glutamate-induced nociception also was blocked by PA75 (p < 0.0005) and C30 (p < 0.0005). The molecular anchorage analysis indicated high negative binding energy values for the evaluated receptors, especially glutamate receptors (AMPA -79.57 Kcal/mol, mGLUR6 -71.25, and NMDA -66.33 Kcal/mol). PA associated with codeine showed orofacial antinociceptive activity, with theoretical evidence of interaction with glutamate receptors.

Comparação das metodologias óptica e de impedância para a determinação de parâmetros hematológicos no analisador Sysmex-XN

Objetivo: Comparar as metodologias de impedância e óptica para contagem de eritrócitos (RBC) e dosagem de hemoglobina (HGB) como forma de corrigir a contagem de eritrócitos em casos de pacientes que apresentam índice de concentração de hemoglobina corpus- cular média (CHCM) acima do ponto de corte. Métodos: Para comparar as metodologias, foram utilizadas amostras com CHCM normal e aumentado. Os parâmetros avaliados foram RBC, HGB e CHCM. Resultados: As amostras com valores de CHCM aumentado demonstraram uma correlação significativa entre RBC e HGB, porém o CHCM apresen- tou uma correlação fraca. Observamos que a metodologia por impedância obteve maior sucesso na correção do CHCM quando as amostras apresentavam aglutinação. Conclusão: A metodologia óptica é uma boa alternativa para correção de valores aumentados de CHCM em situações específicas, mas para casos de aglutinação não se mostrou efetiva.

Objetctive: Compare the impedance and optical methodologies for red blood cells (RBC) count and hemoglobin (HGB) measurement as a way to correct the RBC count in cases of patients who have a MCHC index above the cutoff. Methods: To compare the methodologies, samples with normal and augmented MCHC were used. The parameters evaluated were RBC, HGB and MCHC. Results: Samples with increased MCHC values demonstrated a significant correlation between RBC and HGB, but the MCHC showed a weak correlation. We observed that the impedance methodology was more successful in correcting the MCHC when the samples presented agglutination. Conclusion: Optical methodology is a good alternative for correction of increased CHCM values in specific situations, but for cases of agglutination it has not been shown to be effective.

Orofacial antinociceptive activity and anchorage molecular mechanism in silico of geraniol

Abstract We aimed to evaluate the orofacial antinociceptive effect of geraniol in mice and its molecular anchorage mechanism. Seven mice per group (probabilistic sample) were treated with geraniol (12.5, 25 and 50 mg/kg, i.p.), morphine (6 mg/kg, i.p.) and vehicle (saline + Tween 80 at 0.2%, i.p.) 30 minutes prior to the beginning of the experiment. Injecting glutamate (25 μM), capsaicin (2.5 μg) and formalin (2%) into the right upper lip (perinasal) of the mouse induced nociception. Behavioral analysis of the animals considered the friction time (in seconds) of the mentioned region using hind or front paws by a researcher blinded to the treatment groups. The statistical analysis was performed blindly, considering α = 5%. The results showed that in the glutamate and capsaicin tests, concentrations of 25 mg/kg and 50 mg/kg presented antinociceptive activity (p < 0.005, power> 80%). In the formalin test, geraniol was able to reduce nociception at a concentration of 50 mg/kg (p < 0.005, power> 80%). In the molecular anchorage study, high values of binding between the evaluated substance and receptors of glutamate were observed (metabotropic glutamate receptor, -87.8501 Kcal/mol; N-methyl-D-aspartate, -86.4451 Kcal/mol; α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, -85.6755 Kcal/mol). Geraniol presented orofacial antinociceptive activity, probably by interacting with glutamate-related receptors.

Diagnóstico de enfermagem risco de sangramento como indicador de qualidade assistencial à segurança de pacientes / Diagnóstico de enfermería riesgo de sangrado como indicador de calidad asistencial de la seguridad de pacientes / Nursing diagnosis risk for bleeding as an indicator of quality of care for patient safety

Resumo OBJETIVO Descrever a implantação de um indicador de qualidade assistencial associado ao diagnóstico de enfermagem de pacientes com alto risco de sangramento, com base nos resultados alarmantes de tempo de protombina (TP), tempo de tromboplastina parcialmente ativada (TTPa) e plaquetas. MÉTODOS Relato de experiência retrospectivo de ações multidisciplinares desenvolvidas em um hospital universitário. As etapas do estudo envolveram reuniões de equipes, busca de estratégias de comunicação efetiva e criação de um novo indicador de qualidade assistencial. RESULTADOS O indicador foi denominado "Conformidade do Diagnóstico de Enfermagem Risco de Sangramento", monitorado mensalmente desde junho de 2016. A ficha técnica contempla as características e atributos do indicador. Com base nas suas análises são estabelecidos planos de ações para sua qualificação. CONCLUSÃO A implantação do indicador de qualidade assistencial associado ao diagnóstico de enfermagem aprimorou o processo de comunicação, monitoramento e cuidado de enfermagem a pacientes com risco de sangramento.

Resumen OBJETIVO Describir la implementación de un indicador de calidad asistencial asociado al diagnóstico de enfermería de pacientes con alto riesgo de sangrado, con base en los resultados alarmantes de tiempo de protombina (Tp), tiempo de tromboplastina parcialmente activada (TTPa) y plaquetas. MÉTODO Relato de experiencia retrospectiva de acciones multidisciplinares desarrolladas en un hospital universitario. Las etapas del estudio involucraron reuniones de equipos, búsqueda de estrategias de comunicación efectiva y creación de un nuevo indicador de calidad asistencial. RESULTADOS El indicador se denominó "Conformidad del Diagnóstico de Enfermería Riesgo de Sangrado", y se monitoreó mensualmente desde junio de 2016. La ficha técnica contempla las características y atributos del indicador. Con base en los análisis del indicador se establecen planes de acción para su cualificación. CONCLUSIÓN La implementación del indicador de calidad asistencial asociado al diagnóstico de enfermería mejoró el proceso de comunicación, el monitoreo y el cuidado de enfermería a pacientes con riesgo de sangrado.

Abstract OBJECTIVE To describe the implantation of a care quality indicator associated to the nursing diagnosis of patients at high risk of bleeding, based on the alarming results of prothrombin time (PT), partially activated thromboplastin time (aPTT) and platelets. METHODS Retrospective experience report of multidisciplinary actions developed in a university hospital. The stages of the study involved team meetings, search for effective communication strategies and creation of a new indicator of quality of care. RESULTS The indicator was called "Compliance of Nursing Diagnosis Risk for bleeding", monitored monthly since June 2016. The technical file includes the characteristics and attributes of the indicator. Based on the analyzes of the indicator, action plans are established for its qualification. CONCLUSION The implementation of the quality of care indicator associated to the nursing diagnosis improved the communication process, the monitoring and the nursing care to patients at risk of bleeding.

Virtual screening of secondary metabolites of the genus Solanum with potential antimicrobial activity

ABSTRACT Infectious diseases are a health problem today and have high mortality rates with a wide diversity of potentially pathogenic microorganisms. Research that is based either on the search for new drugs from plants or on the improvement of phytotherapeutics is prominent and continues to play an important role nowadays. From this perspective, use of in silico studies to carry out investigations of new molecules potentially active for methicillin-resistant Staphylococcus aureus and Escherichia coli using an in-house database with 421 different secondary metabolites selected from the literature from Solanum genus was performed. We also realized an in vitro study with strains of S. aureus and E. coli and compared the results. Two databases from ChEMBL were selected, the first one with activity against methicillin-resistant S. aureus and another against E. coli. The compounds were classified according to the pIC50 values to generate and validate the model using a "Random Forest". The "Random Forest" prediction model for methicillin-resistant S. aureus obtained an accuracy of 81%, area under the Receiver Operating Characteristic curve of 0.885, selecting eight molecules with an active potential above 60%. The prediction model for E. coli obtained an accuracy rate of 88%, area under the Receiver Operating Characteristic curve of 0.932, selecting four molecules with potential probability above 84%. Rutin proved to be potentially active in the in silico study for S. aureus and E. coli. Microbiological tests have shown that rutin has activity only for E. coli. An interaction study with strains of S. aureus ATCC 25923, a standard strain sensitive to all antibiotics, and SAM-01, a multidrug-resistant strain, was designed. There was interaction only between rutin and oxacillin, one of the three antibiotics studied in the interaction, for the strain SAM-01, reducing the resistance of this strain.

Quantification of peripheral blood CD34+ cells prior to stem cell harvesting by leukapheresis: a single center experience

ABSTRACT Background: Due to laboratory logistic issues, our center has traditionally scheduled peripheral blood stem cell harvests based on timing from the start of mobilization. This has proved to be useful in some cases, but also resulted in many fruitless harvests due to poor mobilization. In order to improve the efficiency of collections and compare the effectiveness of peripheral blood CD34+ cells as a predictor with data from other reports, this study analyzed the implementation of this routine. Methods: Peripheral blood and leukapheresis samples were quantified by flow cytometry and the association between these parameters was assessed. Results: Sixty-six consecutive leukapheresis samples were collected from 34 patients after the collection of peripheral blood samples for CD34+ quantification. A moderate positive correlation was observed between peripheral blood CD34+ cell count and total CD34+ cell count/kg (r = 0.596; p-value < 0.001). A multivariable regression model also confirmed this association and allowed the estimation that for every increase in five CD34+ cells/µL in the peripheral blood, a mean increase of 0.38 × 106 CD34+ cells/kg could be predicted. Demographic characteristics, baseline comorbidities and mobilization regimen did not influence final CD34+ cell count in this sample. Conclusions: As observed in other centers, quantification of peripheral blood CD34+ progenitor cells is a strong predictor of effectiveness to guide stem cell harvesting. Due to the results of this study, a modification in the peripheral blood stem cell harvesting logistics was implemented at our center in order to incorporate this routine.

Drug discovery and computational strategies in the multitarget drugs era

The pharmaceutical industry is increasingly joining chemoinformatics in the search for the development of new drugs to be used in the treatment of diseases. These computational studies have the advantage of being less expensive and optimize the study time, and thus the interest in this area is increasing. Among the techniques used is the development of multitarget directed ligands (MTDLs), which has become an ascending technique, mainly due to the improvement in the quality of treatment involving several drugs. Multitarget therapy is more effective than traditional drug therapy that emphasizes maximum selectivity for a single target. In this review a multitarget drug survey was carried out as a promising strategy in several important diseases: neglected diseases, neurodegenerative diseases, AIDS, and cancer. In addition, we discuss Computer-Aided Drug Design (CADD) techniques as a tool in the projection of multitarget compounds against these diseases.

Determination of reference ranges for immature platelet and reticulocyte fractions and reticulocyte hemoglobin equivalent

ABSTRACT Introduction: The immature platelet and immature reticulocyte fractions represent the ratios of platelets and reticulocytes recently released into the circulation and thus with higher RNA content. They are considered early indicators of bone marrow recovery. Objective: The aim of this study was to determine the reference ranges for the immature platelet and reticulocyte fractions of hematologically normal individuals in a university hospital. Methods: Venous blood samples collected in ethylenediaminetetraacetic acid K3 were analyzed using a Sysmex XE-5000™ analyzer. Individuals with platelet and reticulocyte counts within the reference ranges, and a blood count within the laboratory's screening criteria were included. Individuals with clinical conditions that could affect hematological results were excluded. The immature platelet fraction, high, medium and low fluorescence reticulocyte fractions and reticulocyte hemoglobin equivalent were evaluated. The reference ranges were determined according to the recommendations of the International Federation of Clinical Chemistry. Results: One hundred and thirty-two outpatients were evaluated. The mean age was 44 years (range: 13-80 years), 72 (54.5%) were women treated in a university hospital. The mean platelet count was 250.8 × 109/L and the mean reticulocyte count was 0.052 × 109/L. The following reference ranges were obtained: immature reticulocyte fraction 1.6-12.1%, the high, medium and low fluorescence reticulocyte fractions were 0.0-1.7%, 1.6-11.0% and 87.9-98.4%, respectively, the reticulocyte hemoglobin equivalent was 30.0-37.6% and immature platelet fraction was 0.8-5.6%. There was a statistically significant difference (p-value = 0.006) between genders in respect to the immature platelet fraction with 0.8-4.7% for females and 0.7-6.1% for males. The immature reticulocyte fraction was directly correlated with the reticulocyte count. Conclusion: Determining the reference range is critical to the introduction of a new parameter. The reference ranges obtained herein corroborate those reported in previous publications and will contribute to the clinical and laboratory application of the indices.

Combined structure- and ligand-based virtual screening to evaluate caulerpin analogs with potential inhibitory activity against monoamine oxidase B

Abstract Natural marine products can help increase the quality of life in patients with neurological diseases. A large number of marine products act against Alzheimer's disease through varying pathways. According to structure- and ligand-based analyses, caulerpin, an alkaloid primarily isolated from the genus Caulerpa, possesses activity against monoamine oxidase B. To predict the activity of caulerpin, we employed Volsurf descriptors and the machine learning Random Forest algorithm in parallel with a structure-based methodology that included molecular docking. Using caulerpin as a lead compound, a database containing 108 analogs was evaluated, and nine were selected as active. The structures selected as active exhibited polar and non-polar substitutions on the caulerpin skeleton, which were relevant for their activity. Dragon consensus drug-like scoring was applied to identify the active analogs that might serve as good drug candidates, and the entire group presented satisfactory performance. These results indicate the possibility of using these analogs as potential leads against Alzheimer's disease.

13C NMR spectral data and molecular descriptors to predict the antioxidant activity of flavonoids / Dados espectrais de RMN 13C e descritores moleculares para prever a atividade antioxidante dos flavonóides

Tissue damage due to oxidative stress is directly linked to development of many, if not all, human morbidity factors and chronic diseases. In this context, the search for dietary natural occurring molecules with antioxidant activity, such as flavonoids, has become essential. In this study, we investigated a set of 41 flavonoids (23 flavones and 18 flavonols) analyzing their structures and biological antioxidant activity. The experimental data were submitted to a QSAR (quantitative structure-activity relationships) study. NMR 13C data were used to perform a Kohonen self-organizing map study, analyzing the weight that each carbon has in the activity. Additionally, we performed MLR (multilinear regression) using GA (genetic algorithms) and molecular descriptors to analyze the role that specific carbons and substitutions play in the activity.

Danos aos tecidos devido ao estresse oxidativo estão diretamente ligados ao desenvolvimento de muitos, senão todos, os fatores de sedentarismo e de doenças crônicas. Neste contexto, a busca de moléculas naturais, que participam da nossa dieta e que possuam atividade antioxidante, flavonóides, torna-se de grande interesse. Neste estudo, nós investigamos um conjunto de 41 flavonóides (23 flavonas e 18 flavonóis), relacionando suas estruturas e atividade antioxidante. Os dados experimentais foram submetidos à análise de QSAR (relações quantitativas estrutura-atividade). Dados de RMN 13C foram utilizados para realizar um estudo do mapa auto-organizável de Kohonen, analisando o peso que cada carbono tem na atividade. Além disso, realizamos uma MLR (regressão múltipla) usando GA (algoritmos genéticos) e descritores moleculares para avaliar a influência de carbonos e substituições na atividade.

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 percent 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 percent accuracy in the training set and 88 percent 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.

Molecular physicochemical parameters predicting antioxidant activity of Brazilian natural products / Parâmetros físico-químicos na predição da atividade antioxidante de produtos naturais brasileiros

Reactive oxygen species (ROS) are capable of oxidizing cellular proteins, nucleic acids and lipids, contributing to cellular aging, mutagenesis, carcinogenesis, coronary heart and neurodegenerative diseases. Free radicals-scavenging by phenolic compounds occurs by the transfer of one electron followed by the H-abstraction. In order to evaluate the antioxidant activity of a series of seventeen phenolic compounds extracted from Brazilian flora (Chimarrhis turbinata and Arrabidea samydoides), some physicochemical parameters (heat formation of the neutral, radical, and cationic compounds; orbitals' energies; ClogP; ΔH OX; and ΔHf) were calculated. Considering the results from the calculated descriptors, the molecules 10a-f can be classified as having a higher antioxidant activity.

Espécies reativas de oxigênio (ROS) são capazes de oxidar proteínas celulares, ácidos nucléicos e lipídios; contribuindo para os processos de envelhecimento celular, mutações genéticas, doenças coronarianas, neoplásicas, degenerativas, dentre outras. Compostos fenólicos neutralizam a reatividade radicalar através da transferência de um elétron da sua estrutura molecular, seguida da abstração de um próton. Este trabalho avaliou a atividade antioxidante de dezessete compostos fenólicos, extraídos de duas plantas da flora nacional (Chimarrhis turbinata e Arrabidea samydoides). Através da modelagem molecular foram obtidos diversos parâmetros, como energias orbitalares, calor de formação das espécies neutras, radicalares e catiônicas, ΔH OX, ΔHf e ClogP; que permitem predizer a atividade e indicar maior poder antioxidante nas moléculas 10 (a a f) para avaliação experimental.

Modelagem molecular aplicada ao desenvolvimento de moléculas com atividade antioxidante visando ao uso cosmético / Molecular modeling applied to the development of molecules with antioxidant activity for cosmetic use

Várias hipóteses e constantes estudos são realizados com o intuito de elucidar o envelhecimento cutâneo. Para prevenir e contornar este processo torna-se necessário reforçar nossas defesas naturais antioxidantes endógenas. Diversas substâncias antioxidantes exógenas, como vitaminas, extratos vegetais, dentre outras, são utilizadas pela Cosmetologia nos produtos antienvelhecimento. O objetivo deste artigo é apresentar de que forma a Modelagem Molecular pode ser uma ferramenta útil na pesquisa por novas substâncias cosméticas antioxidantes para combater o envelhecimento cutâneo.

Some hypotheses and constants studies are made with intention to elucidate the aging process. To prevent and to attenuate the cutaneous aging it becomes necessary to strengthen our endogenous antioxidant natural defenses. Diverse exogenous antioxidant substances, as vitamins, vegetal extracts and others, have been used by the Cosmetology in antiaging products. The objective of this paper is to show how the Molecular Modeling can be an useful tool in the research for new antioxidant cosmetic substances to face the cutaneous aging.

Modelagem molecular aplicada à cosmetologia: planejamento de compostos antienvelhecimento / Molecular modeling used by the Cosmetology: a research for new cosmetic substances to fight the cutaneous aging

Nesta pesquisa, calculou-se, por meio da modelagem molecular, parâmetros físico-químicos importantes à capacidade anti-radicalar de compostos fenólicos extraídos de plantas da flora nacional, Chimarrhis turbinata e Arrabidaea samydoides. As propriedades eletrônicas também podem ser analisadas por meio de superfícies representadas por legendas de cores no campo 3D. Mapa de potencial eletrostático, distribuição orbitalar de HOMO e de LUMO e densidade de spin foram superfícies avaliadas neste trabalho. Em adição, estudos de QSAR (Quantitative Structure-Activity Relationships), cálculos de descritores moleculares holísticos por meio dos programas DRAGON e VOLSURF, cálculos estatísticos incluindo algoritmo genético e PLS (Partial Least Squares), demonstraram a influência de determinadas características moleculares como fundamentais à atividade biológica. A pesquisa concluiu que o grupo farmacofórico favorável à atividade antioxidante é estrutura que apresenta predominantemente características hidrofílicas, grupos hidroxila como substituintes, características eletrônicas favoráveis à doação de elétron e à estabilização do radical fenóxi formado, além de reduzido comprometimento estérico. Consideramos que os métodos empregados no trabalho podem ser considerados com abordagem inovadora para a Ciência Cosmética, indicando potencial ação antioxidante, que poderá ser utilizada em formulações antienvelhecimento

In this research, the calculated physico-chemical parameters, by molecular modelling, have been reported in the literature for supplying important information about the antiradicalar behavior of phenolic compounds, as the studied herein from Chimarrhis turbinata sp. and Arrabidaea samydoides sp. The electronic properties also can be analyzed by means of surfaces represented by legends of colors in the 3D field. Map of electrostatic potential, HOMO and LUMO distribution orbitalar and spin density have been used in this work. In addition, QSAR studies (Quantitative Structure-Activity Relationships), calculations of holistic molecular descriptors by softwares DRAGON and VOLSURF, statistical analysis including genetic algorithm and PLS (Partial Least Squares), demonstrate the influence of the molecular structure in the biological activity. Therefore, pharmacofor favorable to the antioxidant activity structure that presents predominantly characteristic hydrophilic, groups hydroxyl as substituintes, electronic characteristics favorable to the donation of electron and the stabilization of the radical formed, besides reduced inibition esteric. These recent methods can be considered as an innovative approach for Cosmetic Science toward antioxidant action that could be used in antiaging products.