Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer / Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease

Introducción: En el mundo, alrededor de 50 millones de personas padecen demencia; la forma más común es la enfermedad de Alzheimer (EA), que representa el 60-70% de los casos. Dada su alta incidencia, se hace imperativo diseñar estudios que permitan ampliar el conocimiento sobre su aparición y desarrollo, para proponer diagnósticos tempranos y/o posibles tratamientos. Una de las estrategias metodológicas que se han desarrollado son los modelos transgénicos murinos para el estudio de los factores involucrados en su etiología, y entre ellos, el estrés oxidativo y la respuesta inmune.DesarrolloSe realizó una búsqueda de artículos originales y revisiones en PubMed, Scopus y Google Scholar (2013-2019). En esta revisión abordamos dos factores que han sido estudiados de forma independiente: el estrés oxidativo y la respuesta inmune en modelos transgénicos para la EA, y se discute la relación que existe entre ellos y que impacta en la pérdida de la plasticidad sináptica y estructural, produciendo como efecto final el deterioro cognitivo.ConclusiónEsta revisión describe posibles mecanismos en donde participan el estrés oxidativo y la respuesta inmune sobre los efectos moleculares, celulares y conductuales en la EA, observando una estrecha relación entre estos elementos que conducen hacia el deterioro cognitivo. (AU)

Introduction: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response.DevelopmentWe searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment.ConclusionThis review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment. (AU)

Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease.

INTRODUCTION: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response. DEVELOPMENT: We searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address 2 factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment. CONCLUSION: This review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment.

Oxidative stress, the immune response, synaptic plasticity, and cognition in transgenic models of Alzheimer disease. / Estrés oxidativo, respuesta inmune, plasticidad sináptica y cognición en modelos transgénicos de la enfermedad de Alzheimer.

INTRODUCTION: Worldwide, approximately 50 million people have dementia, with Alzheimer disease (AD) being the most common type, accounting for 60%-70% of cases. Given its high incidence, it is imperative to design studies to expand our knowledge about its onset and development, and to develop early diagnosis strategies and/or possible treatments. One methodological strategy is the use of transgenic mouse models for the study of the factors involved in AD aetiology, which include oxidative stress and the immune response. DEVELOPMENT: We searched the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2013 and 2019. In this review, we address two factors that have been studied independently, oxidative stress and the immune response, in transgenic models of AD, and discuss the relationship between these factors and their impact on the loss of synaptic and structural plasticity, resulting in cognitive impairment. CONCLUSION: This review describes possible mechanisms by which oxidative stress and the immune response participate in the molecular, cellular, and behavioural effects of AD, observing a close relationship between these factors, which lead to cognitive impairment.

Anticancer and antimicrobial activity of mangrove derived fungi Hypocrea lixii VB1.

AIM: Mangrove is one of the oldest living tree species and its leaves are among the most extensively studied botanicals in use today. Scientific research throughout the world has found evidence to support the fact that its foliar extracts have great potential against human microbial pathogens. This study highlights the isolation of foliar fungi from Rhizophora mucronata, Avicenna officialis and Avicenna marina. METHOD: It was isolated in Sabouroud's Dextrose Agar and mass cultivation was done in Sabouroud's Dextrose broth. RESULTS: The ethyl acetate extract showed maximum antibacterial activity which inturn checked for different concentration against bacterial pathogens and anticancer activity for Hep2 and MCF7 cell line in vitro. The DNA was isolated from the fungi and the ITS region of 5.8 s RNA was sequenced and assigned to new species as they are separated from the type strains phylogenetic neighbors by sequence similarities. CONCLUSION: This preliminary screening of fungal endophytes revealed their potential to yield potent bioactive compounds for drug discovery programmes.

Characterization of cytotoxic compound from mangrove derived fungi Irpex hydnoides VB4.

OBJECTIVE: To investigate the cytotoxic activity of endophytic fungi isolated from mangrove fungi. METHODS: In the present study the DNA was isolated and the ITS region of 5.8s rRNA was amplified using specific primers ITS 1 and ITS4 and sequence was determined using automated sequencers. Blast search sequence similarity was found against the existing non redundant nucleotide sequence database thus, identified as Aspergilus flavus, Hyporcaea lixii, Aspergillus niger, Eutorium amstelodami, Irpex hydnoides and Neurospora crassa. Among the seven isolates, one fungi Irpex hydnoides was selected for further studies. The fungi were grown in sabouraud broth for five days and filtrate were separated and subjected to ethyl acetate for further studies. RESULTS: Nearly half (49.25%) of the extracts showed activity (IC50 of 125µg/mL). These values were within the cutoff point of the National Cancer Institute criteria for cytotoxicity (IC50<20 µg/mL) in the screening of crude plant extracts. The GC MS analysis revealed that the active principals might be Tetradecane (6.26%) with the RT 8.606. CONCLUSIONS: It is clear from the present study that mangrove fungi with bioactive metabolites can be expected to provide high quality biological material for high throughout biochemical, anti cancer screening programmes. The results help us conclude that the potential of using metabolic engineering and post genomic approaches to isolate more novel bioactive compounds and to make their possible commercial application is not far off.

Monitoramento do ácido chiquímico no manejo de plantas daninhas com glifosato em pomar comercial de citros / Shikimic acid monitoring in weed control with glyphosate in a commercial citrus orchard

Com o objetivo de verificar o acúmulo de ácido chiquímico em plantas de laranja pêra (Citrus sinensis) num pomar comercial manejado com glifosato, um herbicida sistêmico de amplo espectro, foram coletadas amostras na Fazenda Jequitibá, tradicional no cultivo de citros, situada no Município de Santo Antônio de Posse, SP. O produtor aplicou de forma convencional Roundup® Original a 1.440 g.ha-1 de equivalente ácido (e.a.) do sal de isopropilamino de glifosato em 19/12/ 2006 na entrelinha de 15 plantas, deixando outras cinco como testemunha. A reaplicação de glifosato a 1.260 g.ha-1 de e.a. foi realizada em 2/4/2007. Em ambos os casos, imediatamente antes da aplicação e aos 3, 7, 10, 15, 20 e 35 dias após, foram coletadas 20 folhas de cada planta tanto da área tratada como da não tratada, analisando-se o teor de ácido chiquímico por cromatografia líquida de alta eficiência (CLAE) de forma isocrática após extração por micro-ondas. Os resultados mostraram não ocorrer acúmulo do ácido chiquímico nas plantas de laranja pêra, não havendo diferenças significativas nos teores deste composto entre o material proveniente da área tratada com glifosato e o daquela capinada manualmente.

In order to check the accumulation of shikimic acid in a traditional commercial grove of citrus "Pêra" cultivar (Citrus sinensis) managed for weed control with glyphosate, a systemic herbicide with wide spectrum, samples were collected at Fazenda Jequitibá, in Santo Antonio de Posse County, São Paulo State, Brazil. The producer applied the following treatments of Roundup Original® glyphosate at 1,440 g.ha-1 a.e. of the isopropylamine salt on 19 December 2006 between rows of 15 plants, leaving five others as control. The reapplication of glyphosate at 1,260 g ha-1 was done on 2 April 2007. In both cases, immediately before application and at 3, 7, 10, 15, 20 and 35 days thereafter, 20 leaves from each treated and untreated plants were collected for analysis of the content of shikimic acid by isocratic high performance liquid chromatography (HPLC) assisted with microwave. The results showed no significant differences in levels of shikimic acid between the material from the area treated with glyphosate and that weeded manually.

5-FU multifocal inflammatory leukoencephalopathy and dihydropyrimidine dehydrogenase deficiency.

Multifocal inflammatory leukoencephalopathy (MIL) is a cerebral demyelinating syndrome that develops after chemotherapy with 5-fluorouracil (5-FU) and levamisole. The authors report a patient who developed MIL after 5-FU administration not in association with levamisole. She was subsequently diagnosed with partial deficiency of dihydropyrimidine dehydrogenase, an enzyme necessary for 5-FU catabolism. The authors suggest that MIL is a direct result of 5-FU chemotherapy and that patients with dihydropyrimidine dehydrogenase deficiency are at increased risk for this and other toxic effects of 5-FU.

Lidocaine-sensitive atrial tachycardia: lidocaine-sensitive, rate-related, repetitive atrial tachycardia: a new arrhythmogenic syndrome.

OBJECTIVES: The goal of this study was to report a variety of atrial tachycardia that might be caused by an unusual electrophysiologic substrate. BACKGROUND: The mechanism of atrial tachycardias is attributed to re-entry, abnormal automaticity or triggered activity, based on their electropharmacological responses. A rate-related and lidocaine-sensitive atrial tachycardia has not been reported. METHODS: Eight patients (3 women and 5 men, aged 14 to 60 years) with repetitive, uniform atrial tachycardias were studied. In six patients the arrhythmia had been refractory to at least three antiarrhythmic agents (class 1A and C sodium channel blockers, amiodarone, beta-adrenergic blocking agents, verapamil, digoxin). Conventional electrocardiograms, Holter recordings and B mode echocardiograms were performed in each patient. Intravenous lidocaine and verapamil were tested in the eight patients. Six patients underwent an electrophysiologic study. RESULTS: The baseline electrocardiogram showed nearly incessant runs of atrial tachycardia in all patients. The mean atrial ectopic cycle length ranged from 376 to 502 ms. In seven patients a progressive prolongation of the cycle length from the beginning to the end of the salvos was documented. The arrhythmia was suppressed by increments of sinus node rate and by atrial pacing at cycle lengths longer than that of the atrial tachycardia. In all patients the arrhythmia was abolished by intravenous lidocaine, whereas intravenous verapamil was ineffective. Four symptomatic patients were successfully treated with radiofrequency ablation of the ectopic focus, and two patients were treated with oral mexiletine. CONCLUSIONS: The peculiar electropharmacological responses of this arrhythmia suggest an uncommon underlying mechanism that remains to be elucidated.

Overdrive prolongation of refractoriness and fatigue in the early stages of human bundle branch disease.

OBJECTIVES: The aim of this study was to assess the response of refractoriness in normal and diseased human bundle branches to changes in cycle length, as well as during a long period of continuous overdrive pacing. BACKGROUND: The anterograde refractory period of the bundle branches in patients with functional bundle branch block shortens as the rate is increased. The rate-dependent response of refractoriness in diseased bundle branches is quite different. However, this difference has not been precisely delineated, and its physiologic meaning is uncertain. METHODS: Refractoriness of the bundle branches was measured by the extrastimulus technique in 16 patients with tachycardia-dependent bundle branch block and 10 patients with functional bundle branch block, both after basic trains of 8 atrial-paced impulses at different cycle lengths and during a 10-min period of continuous overdrive pacing. RESULTS: The baseline refractory period in the bundle branches of patients with functional bundle branch block measured 430 +/- 32 ms (mean +/- SD) and shortened to 368 +/- 30 ms at the shortest cycle length. The maximal effect was reached within the 1st min of overdrive pacing. The baseline refractory period of the bundle branches was significantly longer in patients with tachycardia-dependent bundle branch block (611 +/- 184 ms) and demonstrated a cumulative overdrive prolongation in 15 (83%) of 18 studies with typical manifestations of fatigue. In two other studies, this occurred only after ajmaline administration. CONCLUSIONS: A rate- and time-dependent prolongation of refractoriness frequently occurs in diseased human bundle branches. When absent, this response may be induced under the effects of sodium channel blockers. This would suggest that an abnormality in the recovery from inactivation of the sodium channel might underlie the early stages of bundle branch disease.