Epigenetics, oxidative stress, and Alzheimer disease

Alzheimer disease (AD) is a progressive neurodegenerative disorder whose clinical manifestations appear in old age. The sporadic nature of 90% of AD cases, the differential susceptibility to and course of the illness, as well as the late age onset of the disease suggest that epigenetic and environmental components play a role in the etiology of late-onset AD. Animal exposure studies demonstrated that AD may begin early in life and may involve an interplay between the environment, epigenetics, and oxidative stress. Early life exposure of rodents and primates to the xenobiotic metal lead (Pb) enhanced the expression of genes associated with AD, repressed the expression of others, and increased the burden of oxidative DNA damage in the aged brain. Epigenetic mechanisms that control gene expression and promote the accumulation of oxidative DNA damage are mediated through alterations in the methylation or oxidation of CpG dinucleotides. We found that environmental influences occurring during brain development inhibit DNA-methyltransferases, thus hypomethylating promoters of genes associated with AD such as the β-amyloid precursor protein (APP). This early life imprint was sustained and triggered later in life to increase the levels of APP and amyloid-β (Aβ). Increased Aβ levels promoted the production of reactive oxygen species, which damage DNA and accelerate neurodegenerative events. Whereas AD-associated genes were overexpressed late in life, others were repressed, suggesting that these early life perturbations result in hypomethylation as well as hypermethylation of genes. The hypermethylated genes are rendered susceptible to Aβ-enhanced oxidative DNA damage because methylcytosines restrict repair of adjacent hydroxyguanosines. Although the conditions leading to early life hypo- or hypermethylation of specific genes are not known, these changes can have an impact on gene expression and imprint susceptibility to oxidative DNA damage in the aged brain

Operational characterisation of a Micro-SME producing farmhouse cheese in the south of Venezuela

A piece of research is presented that was conducted on the Guayanes Farmhouse Telita Cheese Producers Network located in the Piar and Padre Chien rural municipalities of Bolivar state in Venezuela. Guayanes telita cheese is a regional dairy product. The producers are to be found in a rural area with a high potential for marketing the label in the Southern Common Market (MERCOSUR). This market is the focal point of the strategic importance of this study for the Region and the Country. The research is of a descriptive scope conducted in the field. A questionnaire based on good food production practice was used as a data gathering technique. The final sample comprised 30 production units. Statistical processing was performed with version 15.2 of the STATGRAPHICS Centurion computational tool. The results would appear to confirm previous studies that point to the existence of factors that prevent these Micro-SMEs from guaranteeing the food safety of the product. The results indicate that new lines of research need to be opened up. These are oriented towards formulating strategies for the continuous improvement of these micro-SMEs, including quality control indicators

Alzheimer\u27s Disease (AD)-Like Pathology in Aged Monkeys after Infantile Exposure to Environmental Metal Lead (Pb): Evidence for a Developmental Origin and Environmental Link for AD

The sporadic nature of Alzheimer\u27s disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic β-amyloid (Aβ) product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 (β-site APP cleaving enzyme 1)] as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Aβ staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD

Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase

Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung-/-) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung-/- embryonic fibroblasts, and conferred death of cultured Ung-/- hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung-/- but not Ung+/+ mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung-/- mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency

Abstract Number ‐ 83: First WEB case. Direct vertebral artery access for basilar tip artery aneurysm

Introduction being able to think of different accesses does not change the possibilities with each patient Methods case report Results Patient with subarachnoid hemorrhage in the posterior fossa. A tomography is performed that confirms the hemorrhage and a vascular lesion that is visualized at the top of the basilar artery. For the procedure, radial and femoral access was performed without achieving stable access to the basilar artery. Therefore, after multiple attempts, we consider that the best option is direct V2 left vertebral puncture. Access was achieved by vertebral puncture to the aneurysm and occlusion was performed on the top of the basilar artery. Tomographic controls were performed without complications. Patient then presented severe pulmonary compromise that required intubation and prolonged stay in the ICU. Control is performed after a month with adequate occlusion of the aneurysmal lesion. Conclusions it’s nothing new just follow what nelson hopkins says: If You Want to Learn New Things, Read Old Books: Cutdown Techniques Are Well Described in the Old Literatur

Abstract Number ‐ 174: Direct carotid puncture for mechanical thrombectomy in acute ischaemic stroke

Introduction While the benefit of mechanical thrombectomy (MT) for patients with acute ischemic stroke with large‐vessel occlusion (AIS‐LVO) has been clearly established, difficult vascular access may make the intervention impossible or unduly prolonge. In the following cases, functional and safety outcomes of mechanical thrombectomy via direct carotid puncture were evaluated in patients with acute ischemic stroke with limited vascular access. Methods We evaluated seven patients with AIS‐LVO who underwent attempted MT in last year with limmited vascular access for aborted MT after failed transfemoral access or attempted MT via DCP. Results Of 11 patients with AIS‐LVO who underwent attempted MT, Direct carotid access was successfully obtained in all patients, mean age [± SD] 63 ±15 years. Successful reperfusion (thrombolysis in cerebral infarction score 2b or 3) was achieved in 11 patients (100%). Carotid access complications included disection vascular in 1 pacient, with second vascular Access (carotid puncture) required. In 3 patients (42.8%) thrombolysis therapy with IV r‐TPA were administered during thrombectomy by direct carotid puncture. 3 patients presented neck hematomas but they did not require any subsequent interventions. All patients required angio‐seal vascular closure device for direct carotid Access 6F. We found that the final functional outcome was based on modified Rankin Scale score between 1 and 3 achieve in 8 of 11 patients (71.4%). Conclusions DCP for emergency MT in patients with AIS‐LVO and prohibitive vascular access is safe and effective and is associated with higher recanalization rates