Chemometric methods in antimalarial drug design from 1,2,4,5-tetraoxanes analogues.

A set of 23 steroidal 1,2,4,5-tetraoxane analogues were studied using quantum-chemical method (B3LYP/6-31 G*) and multivariate analyses (PCA, HCA, KNN and SIMCA) in order to calculate the properties and correlate them with antimalarial activity (log RA) against Plasmodium falciparum clone D-6 from Sierra Leone. PCA results indicated 99.94% of the total variance and it was possible to divide the compounds into two classes: less and more active. Descriptors responsible for separating were: highest occupied molecular orbital energy (HOMO), bond length (O1-O2), Mulliken electronegativity (χ) and Bond information content (BIC0). We use HCA, KNN and SIMCA to explain relationships between molecular properties and biological activity of a training set and to predict antimalarial activity (log RA) of 13 compounds (#24-36) with unknown biological activity. We apply molecular docking simulations to identify intermolecular interactions with a selected biological target. The results obtained in multivariate analysis aided in the understanding of the activity of the new compound's design (#24-36). Thus, through chemometric analyses and docking molecular study, we propose theoretical synthetic routes for the most promising compounds 28, 30, 32 and 36 that can proceed to synthesis steps and in vitro and in vivo assays.

Efficacy of 1-day vs. 2-day intestinal preparation using peg 3350 + Bisacodyl: A randomized clinical trial. / Eficacia de la preparación intestinal con un día de PEG 3350 + bisacodilo en comparación con dos días: ensayo clínico aleatorizado.

OBJECTIVE: The objective was to compare the efficacy of 1-day intestinal preparation for colonoscopy using PEG 3350 (polyethylene glycol) (4 g/kg/day) + bisacodyl vs. 2-day intestinal preparation using PEG 3350 (2 g/kg/day) + bisacodyl in pediatric patients. MATERIALS AND METHODS: A blind, randomized clinical trial was carried out with endoscopists who assessed colon cleansing. Patients aged 2-18 years old undergoing scheduled colonoscopy were included. They were randomized into 2 groups: 1-day preparation using PEG 3350 (4 g/kg/day) + bisacodyl, and 2-day preparation using PEG 3350 (2 g/kg/day) + bisacodyl. Endoscopic evaluation (Boston Scale) allowed the efficacy of both preparations to be assessed. Statistical analysis: T of Student for quantitative variables, and Chi square for qualitative variables. RESULTS: 72 patients with a mean age of 94 ± 49 months were included. No significant difference was found between groups regarding preparation difficulty and safety. Efficacy, assessed using the Boston Scale score and the proportion of excellent and good grades achieved, was higher in the 1-day group. Left colon score and total score were higher than in the 2-day group (left colon: 2.20 vs. 1.89, p=0.03; total score: 7.28 vs. 6.76, p=0.01) (left colon: 94.4% vs. 83.4%, p=0.034). CONCLUSIONS: Efficacy in the quality of intestinal preparation for colonoscopy was higher in the 1-day group using PEG 3350 + oral bisacodyl than in the 2-day group.

OBEJTIVO: Comparar la eficacia de la preparación intestinal para colonoscopia con 1 día de preparación con PEG 3350 (polietilenglicol) (4 g/kg/día) + bisacodilo en comparación con 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo en pacientes pediátricos. MATERIAL Y METODOS: Se realizó un ensayo clínico, aleatorizado y cegado para los médicos endoscopistas que evaluaron la limpieza del colon. Se incluyeron pacientes de 2 a 18 años, que ameritaban colonoscopia en forma programada. Se aleatorizaron a los pacientes en dos grupos: 1 día de preparación con PEG 3350 (4 g/kg/día) + bisacodilo y 2 días de preparación con PEG 3350 (2 g/kg/día) + bisacodilo. Por medio de valoración endoscópica (escala de Boston) se determinó la eficacia de las dos preparaciones a evaluar. Análisis estadístico: T de student para cuantitativas y Chi2 para cualitativas. RESULTADOS: Se incluyeron 72 pacientes con edad promedio de 94 ± 49 meses. No hubo diferencia significativa entre los grupos con respecto a la dificultad y seguridad de la preparación. La eficacia, evaluada por el puntaje de la escala de Boston y la proporción de calificación excelente o buena, fue mejor en el grupo de un 1 día, el colon izquierdo y el puntaje total fue mejor en comparación al grupo de 2 días (colon izquierdo 2,20 vs. 1,89 p= 0,03 y total 7,28 vs. 6,76 p= 0,01) (colon izquierdo 94,4 vs. 83,4% p= 0,034). CONCLUSIONES: La eficacia de la calidad en la preparación intestinal para colonoscopia fue mejor entre el grupo de 1 día con PEG 3350 + bisacodilo vía oral en comparación a la preparación de 2 días.

Recuperação anestésica e analgesia residual da infusão continua intravenosa de fantanil, lidocaína, cetamina e fentanyl-lidocaína-cetamina associados à anesthesia total intravenosa com Propofol em cadelas submetidas à ovariossalpingo-histerectomia eletiva / Anesthetic recovery and residual analgesia of constant rate infusion intraoperative of fentanyl, lidocaine, ketamine or fentanyl-lidocaine-ketamine associated with total intravenous anesthesia with propofol in bitches submitted to elective ovariohysterectomy

Avaliou-se a recuperação anestésica e a analgesia residual da infusão contínua (IC) de fentanil (F), lidocaína (L), cetamina (K) e fentanil-lidocaína-cetamina (FLK), associados à anestesia total intravenosa com o propofol, em cadelas submetidas à ovariossalpingo-histerectomia. Foram utilizados 32 animais pré-medicados com acepromazina, distribuídos em quatro grupos de acordo com o tratamento analgésico: F: bolus de 0,0036mg/kg de fentanil e IC de 0,0036mg mg/kg/h; L: bolus de 3mg/kg de lidocaína e IC de 3mg/kg/h; K: bolus de 0,6mg/kg de cetamina e IC de 0,6mg/kg/h; e FLK: bolus e IC dos três fármacos nas doses supracitadas. Após o bolus do tratamento analgésico, foi realizada a indução e o início da IC do tratamento analgésico e do propofol. Para avaliação da recuperação anestésica, foram considerados os tempos de extubação, decúbito esternal, posição quadrupedal e os efeitos adversos. A avaliação da analgesia foi realizada por meio da escala visual analógica e modificada de Glasgow, durante seis horas. Os efeitos adversos observados foram vômito, sialorreia e tremor muscular. Receberam analgesia de resgate 100% dos animais do grupo F, 87,5% do K, 50% do L e 12,5% do FLK. O FLK demonstrou maior analgesia, e a recuperação anestésica foi semelhante em todos os grupos.(AU)

The anesthetic recovery and residual analgesia of continuous rate infusion (CRI) of fentanyl (F), lidocaine (L), ketamine (K) and fentanyl-lidocaine-ketamine (FLK) associated with total intravenous anesthesia with propofol in bitches submitted to ovariohysterectomy were evaluated. 32 animals were used, pre-medicated with acepromazine and distributed into four groups according to analgesic treatment: F loading dose (LD) of 0.0036mg/kg fentanyl, and CRI of 0.0036mg/kg/h, L: LD of 3mg/kg lidocaine, and CRI of 3mg/kg/h; K: LD of 0.6mg/kg ketamine, and CRI of 0.6mg/kg/h and FLK: LD and CRI of the three drugs in the above mentioned doses. After the LD of analgesic treatment, the induction was performed and the CRI of the analgesic treatment and propofol started. To evaluate the anesthetic recovery, the time of extubation, sternal decubitus, quadrupedal position and adverse effects were considered. The analgesia evaluation was performed using the visual scale and modified Glasgow for six hours. The adverse effects observed were vomiting, sialorrhea and muscle tremor. 100% of the animals in group F, 87.5% of K, 50% of L and 12.5% of FLK received rescue analgesia. FLK demonstrated greater analgesia, and anesthesia recovery was similar in all groups.(AU)

[Functional endoscopic evaluation of swallowing in infants with deglutition disorders]. / Evaluación funcional endoscópica de la deglución en lactantes con alteración en la mecánica de la deglución.

BACKGROUND: Functional endoscopic evaluation of swallowing (FEES) is a recognized method for Deglutition Disorders (DD) in adults, with anecdotal experience in children, obtaining not conclusive results. OBJECTIVE: To compare the accuracy of test FEES in infants with high suspicion of altered DD seen in a third level hospital with the gold standard Videofluoroscopic (VF). PATIENTS, MATERIAL AND METHODS: The results and findings by FEES and VF of 66 children with clinical diagnosis of DD were compared. STATISTICAL ANALYSIS: An estimate of the sensitivity and specificity of FEES was performed. As well as calculating positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios. RESULTS: 60 patients enrolled, 4 and FEES showed high sensitivity to identify the presence of aspiration and penetration (9 98%) and high specificity for the arrest of spillage and waste (94% and 95%). Gastroesophageal reflux to make the diagnosis of DD with FEES had a sensitivity of 80% and specificity of 84%. Spill and penetration had the highest agreement with respect to the gold standard of 0.81. CONCLUSIONS: FEES in infants diagnosed with DD had a sensitivity of 80.8% and specificity 85.3%. 0696 concordance regarding to the VFD in the diagnosis of DD, and to identify suction stroke had a kappa of 0815.

ANTECEDENTES: La Evaluación Funcional Endoscópica de la deglución (EFED) es un método reconocido para evaluar alteración en la mecánica de la deglución (AMD), con experiencia anecdótica en niños, y con resultados no concluyentes. OBJETIVO: Comparar la exactitud de la EFED en lactantes con alta sospecha de alteración en la mecánica de la deglución atendidos en un hospital de tercer nivel, con el estándar de oro, la Vídeo Fluoroscopia de Deglución (VFD). Tipo de estudio: transversal, analítico, observacional, ambilectivo. Diseño: Prueba diagnóstica. PACIENTES, MATERIAL Y METODOS: Se compararon los resultados y hallazgos por EFED y VFD de 66 niños con diagnóstico clínico de AMD. ANALISIS ESTADISTICO: Se realizó la estimación de sensibilidad y especificidad de la EFED, así como cálculo de valor predictivo positivo (VPP), valor predictivo negativo (VPN) y razones de verosimilitud. RESULTADOS: De los 60 pacientes incluidos, el EFED presentó una alta sensibilidad para la presencia de aspiración y penetración (94 y 98%), y una alta especificidad para la detención de derrame y residuo (94% y 95%). El reflujo gastroesofágico para hacer el diagnóstico de AMD con el EFED tuvo una sensibilidad del 80% y especificidad del 84%. Derrame y penetración tuvieron la más alta concordancia con respecto al estándar de oro de 0.81. CONCLUSIONES: La EFED tuvo una sensibilidad del 80,8% y especificidad 85,3% en lactantes con diagnóstico de AMD. Una concordancia del 0,696 con respecto a la VFD en el diagnóstico de la AMD, y para identificar derrame y aspiración tuvo una kappa de 0,815.

Sucrose substitutes affect the cariogenic potential of Streptococcus mutans biofilms.

Streptococcus mutans is considered the primary etiologic agent of dental caries and contributes significantly to the virulence of dental plaque, especially in the presence of sucrose. To avoid the role of sucrose on the virulence factors of S. mutans, sugar substitutes are commonly consumed because they lead to lower or no production of acids and interfere with biofilm formation. This study aimed to investigate the contribution of sugar substitutes in the cariogenic potential of S. mutans biofilms. Thus, in the presence of sucrose, glucose, sucralose and sorbitol, the biofilm mass was quantified up to 96 h, the pH of the spent culture media was measured, the expression of biofilm-related genes was determined, and demineralization challenge experiments were conduct in enamel fragments. The presence of sugars or sugar substitutes profoundly affected the expression of spaP, gtfB, gtfC, gbpB, ftf, vicR and vicX in either biofilm or planktonic cells. The substitution of sucrose induced a down-regulation of most genes involved in sucrose-dependent colonization in biofilm cells. When the ratio between the expression of biofilm and planktonic cells was considered, most of those genes were down-regulated in biofilm cells in the presence of sugars and up-regulated in the presence of sugar substitutes. However, sucralose but not sorbitol fulfilled the purpose of reducing the cariogenic potential of the diet since it induced the biofilm formation with the lowest biomass, did not change the pH of the medium and led to the lowest lesion depth in the cariogenic challenge.

Efeitos do extrato de Ginkgo biloba (EGb 761) e da natação repetida sobre a memória, ansiedade e atividade motora de ratos / Effects of Ginkgo biloba extract (EGb 761) and repeated swimming on memory, anxiety and motor activity of rat

O extrato de Ginkgo biloba (EGb 761) e exercícios físicos isoladamente são capazes de modificar as funções cognitivas e aliviar os sintomas de ansiedade. Contudo, estes tratamentos em conjunto devem ser caracterizados. Em nossa pesquisa, verificamos que a administração oral repetida do extrato (40 ou 80 mg/kg/dia) e o exercício de natação ao qual os ratos eram submetidos causaram aumento de entradas destes animais nos braços fechados do labirinto em cruz elevado e diminuição da imobilidade dos mesmos no campo aberto, sugerindo um aumento de suas atividades motoras. Além disso, o exercício de natação aumentou a exploração no campo aberto e o tratamento com EGb 761 cancelou este efeito, sugerindo a interação entre EGb 761 e exercício de natação, provavelmente com um mesmo substrato neurobiológico capaz de minimizar a atividade exploratória em ratos nadadores. Análises comportamentais sobre o teste de reconhecimento de objetos mostraram que, quando submetidos a exercício de natação e/ou tratamento com EGb 761 durante testes de 24 horas, os ratos nadadores levaram mais tempo explorando os novos objetos do que os familiares. Estes resultados mostram que o EGb 761 e os exercícios, ambos isolados ou em conjunto, têm um poderoso efeito sobre a memória de longo-prazo. Entretanto, o proposto efeito ansiolítico do EGb 761 e de exercícios de natação pode ser questionado.

Either ingestion of a Ginkgo biloba proprietary extract (EGb 761) or physical exercise can enhance cognitive functioning and alleviate symptoms of anxiety; however, their combined effects have yet to be characterized. Rats subjected to repeated oral administration of the extract (40 or 80 mg/kg/day) and swimming exercise exhibited an increased number of closed-arm entries in the elevated plus-maze and decreased immobility in the open , suggesting an increase in motor activity. In addition, the exercise of swimming increased the exploration of the open and chronic treatment with EGb 761 could cancel this effect; this indicates interaction between EGb 761 and swimming exercise, which may show a common neurobiological substrate, capable of reducing exploratory activity in swimming rats. Analysis of behavior in the object-recognition test showed that rats subjected to swimming exercise and/or treatment with EGb 761, during tests of 24 hours, spent more time exploring novel objects than familiar ones. These results show that EGb 761 and/or physical exercise have powerful effects on long-term memory. However, the proposed anxiolytic characteristics of EGb 76 and swimming exercise may be questioned.

[Inflammatory chronic processes of the central nervous system. Neurosurgical aspects]. / Processos inflamatorios cronicos do sistema nervoso central. Aspectos neurocirurgicos

A study into the neurosurgical approach to thirty-five patients with increased intracranial pressure due to inflamatory diseases affecting the central nervous system and meninges is reported. The entitites under consideration were found to have similar surgical aspects despite the heterogeneity of etiologic agents. As regards the surgical treatment, two groups of cases were recognized. Group 1 comprises 7 patientes with symptoms of a space-occupying lesion; in these patients craniotomies were performed with good results. Group 2 included the remainder 28 cases with acquired hydrocephalus. In this group differents methods for ventricular drainage were used, but ventriculo-auriculostomy and specially ventriculo-peritoneal shunts proved to give more gratifying results. Chemotherapy was administred when the etiologic agent was disclosed. Corticosteroids were institued to reduce inflammatory reations and cerebral edema. A review of the literature supported the practical classification and surgical techniques employed.