Synthesis and Biological Activity of Trolox Amide Derivatives

Abstract A series of Trolox amide derivatives were synthesized by modifying the carboxyl groups of Trolox. Thirty target compounds were obtained and characterized through nuclear magnetic resonance and mass spectrometry. Trolox derivatives were employed to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and hydroxyl radical assays. DPPH scavenging activity test results illustrated that compounds exhibited scavenging activities similar to L-ascorbic acid and Trolox, with compounds 14a, 18a, 24a and 26a in particular exhibiting higher scavenging activities than L-ascorbic acid. The results demonstrated that compounds displayed ABTS scavenging activities similar to L-ascorbic acid and Trolox, with compounds 26a and 29a in particular having potency twofold higher. FRAP assay results indicated that compounds 11a, 19a, 25a, 29a and 30a had activity similar to Trolox. The results revealed that compounds 6a and 19a had similarly high hydroxyl radical-scavenging activities as Trolox. The results of α-glucosidase experiments uncovered that compounds 10a, 25a, 28a and 29a had excellent inhibitory activity, which was similar to that of acarbose and different from Trolox. The results of acetylcholinesterase and butyrylcholinesterase experiments demonstrated that some compounds had weak anticholinesterase activities. 26a and 29a are important Trolox derivatives with better biological activity profiles and deserve further study

Relation of breast cancer and malathion aerial spraying in Arica, Chile / Relación entre cáncer mamario y aspersiones aéreas con malatión en Arica, Chile

Breast cancer mortality has been increasing in Arica Chile where it has surpassed the national rates 11 times between 1990 and 2010. The city of Arica was sprayed with the organophosphrous pesticide malathion in order to control the Mediterranean fly 33 years ago. Moreover we have demonstrated that a malathion treatment induces the formation of breast carcinomas in Sprague Dowley female rats. The objective of this work was to find a relationship between malathion aerial spraying and the increased mortality rate due to breast cancer that has been observed in Arica in recent years. We extracted city data bases with all breast cancer cases diagnosed from 1995 to 2005 from the Dr. Juan Noe Crevani Hospital of Arica city and Ernesto Torres Hospital of Iquique. The number of patients was 100 in Arica and 58 in Iquique, nearby city that has never been sprayed with malathion which had a similar population than Arica in those years. The statistical analysis of the characteristics of the sample related to breast cancer risk showed that there is no significant difference between women from Arica and from Iquique. Nevertheless the patients with more times of exposure to malathion were 5.7-times more likely to be diagnosed with breast cancer (OR= 5.7; p<0.02). In addition, metastases were found in 30.5 percent of the malathion-exposed group and only in 16 percent in the group never exposed (p<0.05). This study suggests that the increase in the mortality rate due to breast cancer occurring in Arica has a significant correlation with the exposure to malathion sprayed over the city more than 30 years ago.

La mortalidad por cáncer de mama ha ido aumentando en Arica Chile, donde ha sobrepasado las tasas nacionales 11 veces entre los años 1990 y 2010. La ciudad de Arica recibió aspersiones del pesticida organofosforado malatión, con el fin de controlar la mosca mediterránea, por primera vez hace 33 años. Por otra parte hemos demostrado que un tratamiento con malatión induce la formación de carcinomas mamarios en ratas hembras Sprague Dowley. El objetivo de este trabajo es encontrar una relación entre las aspersiones con malatión y el aumento en la tasa de mortalidad por cáncer de mama que se ha observado en Arica en los últimos años. Se extrajeron de bases de datos, los casos de cáncer mamario diagnosticados entre 1995 y 2005, en los Hospitales Dr. Juan Noé Crevani de Arica y Ernesto Torres de Iquique. El número de pacientes diagnosticados con cáncer de mama fue 100 en Arica y 58 en Iquique, ciudad que nunca fue fumigada con malatión y con una población similar a la de Arica durante esos años. El análisis estadístico de las características de la muestra, en relación a los factores de riesgo de cáncer mamario, mostró que no hay diferencia significativa entre las mujeres de Arica y de Iquique. Sin embargo, las mujeres con mayor tiempo de exposición al malatión fueron 5,7 veces más propensas a ser diagnosticadas con cáncer de mama (OR = 5,7, p <0.02). Además el 30,5 por ciento del grupo expuesto a malatión presentó metástasis y en el grupo no expuesto sólo el 16 por ciento (p <0.05). Este estudio sugiere que el aumento de la tasa de mortalidad por cáncer de mama que se ha producido en Arica tiene una correlación significativa con la exposición al malatión esparcido sobre la ciudad hace más de 30 años.

The use of rocuronium in giant Amazon turtle Podocnemis expansa (Schweigger, 1812) (Testudines, Podocnemididae) / Uso do rocurônio em tartaruga da Amazônia Podocnemis expansa (Schweigger, 1812) (Testudines, Podocnemididae)

PURPOSE: To determine whether rocuronium would provide safe, short-term immobilization in Podocnemis expansa. METHODS: Twenty P. expansa, weighing on average 1.59 ± 0.28 kg, were subjected to two protocols: G1 0.25 mg/kg IM of rocuronium and 0.07 mg/kg IM of neostigmine, while G2 received 0.50 mg/kg IM of rocuronium and 0.07 mg/kg IM of neostigmine. The drugs were applied, respectively, in the left and right thoracic members. Assessments were made of the anesthetic parameters of respiratory frequency, heartbeat, righting reflex, cloacal relaxation, palpebral and pupilar reflexes, easy handling, muscle relaxation, locomotion, response to pain stimuli in the right thoracic members, pelvic members and tail, ambient humidity and temperature. RESULTS: They were not found statistical differences between the dosages for the majority of the assessments. G1 was as efficient as G2. A consistent neuromuscular blockade effect was recorded 12 ± 4.21 minutes in G1 and G2. All the animals were recovered in 150 minutes. CONCLUSIONS: Administration of rocuronium at dose of 0.25 to 0.5 mg/kg IM is a safe and effective adjunct to clinical proceedings or pre-anesthetics in P. expansa. Because rocuronium does not provide any analgesic or sedative effects, the duration of neuromuscular blockade without anesthesia should be minimized to avoid undue stress.

OBJETIVO: Determinar se o rocurônio promove imobilização segura e de curta duração em Podocnemis expansa. MÉTODOS: Vinte P. expansa com média de peso 1,59 ± 0,28 kg, foram submetidas a dois protocolos: G1 recebeu rocurônio 0,25 mg/kg IM e neostigmina 0,07 mg/kg IM enquanto G2 rocurônio 0,50 mg/kg IM e neostigmina 0,07 mg/kg IM, aplicados no membro torácico esquerdo e direito, respectivamente. Observaram-se os parâmetros anestésicos: freqüência respiratória e cardíaca, reflexo de endireitamento, relaxamento do esfíncter da cloaca, reflexo palpebral e pupilar, facilidade de manipulação, relaxamento muscular, locomoção, resposta aos estímulos dolorosos no membro torácico direito, nos membros pelvinos e na cauda, temperatura e umidade ambiental. RESULTADOS: Não foram encontradas diferenças estatísticas entre as doses para a maioria dos parâmetros e o G1 foi tão eficiente quanto o G2. Um bloqueio neuromuscular consistente foi observado aos 12 ± 4,21 minutos tanto no G1 como no G2. A recuperação de todos os animais ocorreu em até 150 minutos. CONCLUSÕES: Administração de rocurônio nas doses 0,25 e 0,50 mg/kg IM é segura e efetiva para os procedimentos clínicos ou pré-anestésicos em P. expansa. Como o rocurônio não produz efeitos sedativos ou analgésicos, a duração do bloqueio neuromuscular sem anestesia deverá ser minimizado para evitar estresse.

The effect of Galantamine on sleep quality in Thai Alzheimer's disease patients.

OBJECTIVE: To study the effect of Galantamine on sleep quality in Thai Alzheimer's disease (AD) patients with or without cerebrovascular disease. MATERIAL AND METHOD: A 6 month, multicenter open-label, uncontrolled trial was undertaken in 75 mild to moderate Alzheimer's disease patients with or without cerebrovascular disease. Eligible patients received a flexible-dose of Galantamine 16 or 24 mg/day for 24 weeks. The Pittsburgh Sleep Quality Index (PSQI) with self-analysis questionnaires were used to evaluate sleep quality. Analyses were based on the intent-to-treat population. RESULTS: Seventy-five eligible patients with mild to moderate Alzheimer's disease with or without cerebrovascular disease (male:female = 32:43, age range 74.5 +/- 0.9) were included and 58 patients (79%) completed the present study. The global PSQI scores showed some improvement over baseline (week 0 = 5.10 +/- 3.08, week 4 = 4.37 +/- 2.48, week 8 = 4.65 +/- 2.71, week 24 = 3.70 +/- 2.12) but were not yet statistical significant. In contrast, most of each component scores such as sleep quality, sleep latency, sleep duration, sleep disturbances, sleep medication, and daytime dysfunction except sleep efficiency, showed significant differences from baseline after week 8. Moreover, there were no significant differences in global PSQI and component scores between mild and moderate stages of Thai AD patients or between men and women patients. CONCLUSION: The result of the present study may be consistent with Galantamine being safe and can maintain good sleep quality for mild to moderate Thai AD patients with or without VaD. Galantamine doses of 16-24 mg/day were well tolerated.

Recent advances in the management of Alzheimer's disease.

Alzheimer's disease is a chronic degenerative disorder of the central nervous system. As the disease progresses there is gradual increase of mental and physical incapacitation, ultimately leading to death. Recent advances in the management of the disease focused the most extensive drug development activity towards the anticholinesterase agents.

Farmacologia dos inibidores da acetilcolinesterase e interaçöes medicamentosas com drogas psiquiátricas / Pharmacology of cholinesterase inhibitors and their interactions with psychiatric drugs

O tratamento farmacológico da doença de Alzheimer inclui drogas para os sintomas cognitivos, particularmente os inibidores da acetilcolinesterase, e näo-cognitivos, como antipsicóticos, antidepressivos e benzodiazepínicos. Frequentemente estes pacientes necessitam de drogas de ambos os tipos, o que pode acarretar interaçöes farmacológicas indesejáveis. O presente artigo apresenta uma revisäo sobre a farmacologia dos inibidores da acetilcolinesterase, com ênfase nas suas interaçöes farmacocinéticas e farmacodinâmicas com as drogas psiquiátricas comumente empregadas no manejo dos transtornos de comportaento destes pacientes

Tratamento da doença de Alzheimer: avaliaçäo crítica sobre o uso de anticolonesterásicos / Treatment of Alzheimer'diseases: critical evaluation about the use of anticholinesterase

A demência do tipo Alzheimer (DA) é uma doença degenerativa que há até pouco tempo nao tinha nenhum tratamento eficaz. Pesquisas realizadas a partir da década de 70 revelaram que os sistemas cerebrais que utilizam acetilcolina encontram-se gravemente comprometidos nesses pacientes, o que serviu de base para a introduçao da terapêutica de base colinérgica da doença. Os inibidores da acetilcolinesterase foram os primeiros medicamentos que demonstraram ser úteis para o tratamento da DA em ensaios clínicos controlados contra placebo. Este artigo revê os principais estudos desenhados para investigar eficácia e efeitos adversos da tacrina, donepezil, rivastigmina, e metrifonato em pacientes com DA. Discutem-se, ainda, os fatores que podem interferir na resposta do paciente ao tratamento com anticolinesterásicos, bem como as limitaçoes inerentes a esse tipo de abordagem terapêutica.

Seminarios de capacitación de laboratorios trabajando con la técnica de magnotti / Seminary trainning of laboratory

Se presentan los temas de los seminarios de capacitación ha desarrollarse trabajando con la técnica de Magnotti. Entre ellos se destaca tres seminarios: Seminario I: Acción de los plaguicidas organofosforados en el sistema nervioso central; Seminario II: Importancia, implicaciones y objetivos de la calidad de la medición utilizando el método de magnotti y el Seminario III Método de maggnotti para la determinación de colinesterasa

Validación de la calidad de las mediciones de la colinesterasa / Quality of medition colinesterasa

Estudio realizado mediante un taller con técnicos que realizan las mediciones de colinesterasa y que habían participado en investigaciones de salud ocupacional. Asimismo, se utilizaron 6 equipos, 4 de los cuales habían sido enviados a Cincinati a calibrar y dos permanecieron trabajando en monitoreos de colinesterasa por tres años sin ser calibrados. Se observó que habían variaciones en el procedimiento de medición de la colinesterasa, lo que provocaba variaciones en los resultados de medición

Perfil de la colinesterasa sanguínea en la población de Panamá / Cholinesterase blood profile in the panamenian population

Presenta información sobre la actividad de en sangre total, la finalidad de conocer los niveles de esta enzima y su variación en la población panameña tomando en consideración los siguientes parámetros: exposición a plaguicidas, sexo, edad y área de trabajo. Se empleó el método de Hidroxamato, de Trunaut-Vernin para las determinaciones analíticas de la actividad de la Colinesterasa en muestras de sangre en un total de 103 varones y 52 mujeres, en algunos casos expuestos y en otros no expuestos a plaguicidas inhibidores de la colinesterasa en diferentes provincias del país (Chiriquí, Coclé, Herrera, Panamá y Veraguas)

"Effect of organophosphorus insecticides on pregnant rabbits"

The effect of chronic maternal exposure to the organophosphorus insecticide [Tamaron, Bayer], throughout gestation, was studied in 20 pregnant Buscat rabbits and was compared with 10 pregnant controls. A significant reduction in the litter size and in the foetal birth weight was observed in Tamaron-exposed animals. In pregnant rabbits exposed to the insecticide, 10% of the mothers and 9% of their foetuses showed pathologic changes in the liver in the form of zonal necrosis, associated fatty changes and lymphocytic infiltration