Irma E. Velázquez-Brizuela

Cellular and biochemical actions of melatonin which protect against free radicals: role in neurodegenerative disorders.

Molecular oxygen is toxic for anaerobic organisms but it is also obvious that oxygen is poisonous to aerobic organisms as well, since oxygen plays an essential role for inducing molecular damage. Molecular oxygen is a triplet radical in its ground-stage (.O-O.) and has two unpaired electrons that can undergoes consecutive reductions of one electron and generates other more reactive forms of oxygen known as free radicals and reactive oxygen species. These reactants (including superoxide radicals, hydroxyl radicals) possess variable degrees of toxicity. Nitric oxide (NO•) contains one unpaired electron and is, therefore, a radical. NO• is generated in biological tissues by specific nitric oxide synthases and acts as an important biological signal. Excessive nitric oxide production, under pathological conditions, leads to detrimental effects of this molecule on tissues, which can be attributed to its diffusion-limited reaction with superoxide to form the powerful and toxic oxidant, peroxynitrite. Reactive oxygen and nitrogen species are molecular “renegades”; these highly unstable products tend to react rapidly with adjacent molecules, donating, abstracting, or even sharing their outer orbital electron(s). This reaction not only changes the target molecule, but often passes the unpaired electron along to the target, generating a second free radical, which can then go on to react with a new target amplifying their effects. This review describes the mechanisms of oxidative damage and its relationship with the most highly studied neurodegenerative diseases and the roles of melatonin as free radical scavenger and neurocytoskeletal protector.

Physical function and associated factors in community-dwelling elderly people in Jalisco, Mexico

PURPOSE To determine the prevalence of disability in Basic Activities of Daily Living and Instrumental Activities of Daily Living (ADL and IADL, respectively), as well as associated factors in the Mexican community-dwelling elderly population. MATERIALS AND METHODS This is a cross-sectional study of a population 60 years and older who live in the State of Jalisco (Mexico). A total of 2553 persons were assessed regarding their functional and health conditions. The ADL and IADL were classified as dependent and non-dependent, and crude and adjusted Odds Ratio (OR) were calculated. RESULTS Mean age of participants was 71.6±8.7, 61.2% were women. A disability prevalence of 9.6% was found to perform ADL and of 31.5% for the IADL, 14.3% had cognitive impairment and 30.9% depression. Risk factors were found for dependence: being a woman, being ≥75 years old, low education level, having at least one chronic disease, cognitive impairment, depression, previous history of disability, and having been a lifelong housewife. CONCLUSIONS Functional difficulties are common in Mexican elderly population. These data show key variables for functional disability risk. A better understanding of functional capabilities, as well as of risk factors older adults face every day provide us with a guide to devise a prevention plan, to implement adequate interventions, or to provide appropriate care.

Detection of membrane fluidity in submitochondrial particles of platelets and erythrocyte membranes from Mexican patients with Alzheimer disease by intramolecular excimer formation of 1,3 dipyrenylpropane

It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes. The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 ± 0.008) than aged-matched control subjects (0.363 ± 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged-matched controls: the fluorescent intensity ratios were 0.312 ± 0.03 and 0.305 ± 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged-matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.

Prevalence of Cognitive Impairment and Depression among a Population Aged over 60 Years in the Metropolitan Area of Guadalajara, Mexico

Background. Cognitive impairment is an important clinical issue among elderly patients with depression and has a more complex etiology because of the variable rate of neurodegenerative changes associated with depression. The aim of the present work was to examine the prevalence of cognitive impairment and depression in a representative sample of adults aged ≥60 years. Methods. The presented work was a cross-sectional study on the prevalence of cognitive impairment and depression. Door-to-door interview technique was assigned in condition with multistage probability random sampling to obtain subjects that represent a population of the Guadalajara metropolitan area (GMA), Mexico. Cognitive function and depression were assessed by applying standardized Mini-Mental State Examination of Folstein (MMSE) and the Geriatric Depression Scale (GDS), respectively. Results. Prevalence of cognitive impairment was 13.8% (14.5% women, 12.6% men); no significant differences by gender and retired or pensioner were found. Prevalence of depression was 29.1% (33.6% women, 21.1% men); no significant differences by retired or pensioner were found. Cognitive impairment was associated with depression (OR  =  3.26, CI 95%, 2.31–4.60). Prevalence of cognitive impairment and depression is associated with: being woman, only in depression being older than 75 years being married, and a low level of education. Conclusion. Cognitive impairment and depression are highly correlated in adults aged ≥60.

Prevalence of Dementia, Emotional State and Physical Performance among Older Adults in the Metropolitan Area of Guadalajara, Jalisco, Mexico

Background. Dementia affects memory, thinking, language, judgment, and behavior. Depression, is common in older adults with dementia. The concomitance of dementia and depression increases disability with impaired activities of daily living (ADL), increasing the chances of institutionalization and mortality. Methods. Cross-sectional study of a population 60 years and older who live in the State of Jalisco, Mexico. A total of 1142 persons were assessed regarding their cognitive function, emotional state, and physical performance. Door-to-door interview technique was assigned in condition with multistage probability random sampling. Cognitive function, depression and functional disability were assessed by applying standardized Minimental State Examination (Folstein), Geriatric Depression Scale, and the Katz index, respectively. Diagnosis of dementia was performed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, the Fourth Edition. Data were analyzed using SPSS software. Results. Prevalence of demency was 9.5% (63.35% women, and 36.7% men). Demency was associated with being woman, being older than 70 years, low level of education, not having the economic benefit of retirement, being single or living without a partner, low level of education, suffering from depression and have functional disability in ADL. Conclusion. Dementia is more common in women and is related to depression and disability.

Altered β-amyloid precursor protein isoforms in Mexican Alzheimer's Disease patients

Objective: To determine the β-amyloid precursor protein (βAPP) isoforms ratio as a risk factor for Alzheimer’s Disease and to assess its relationship with demographic and genetic variables of the disease. Methods: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for βAPP. A ratio of βAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106–110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component. Results: βAPP ratio on AD subjects was lower than that of control subjects: 0.3662 ± 0.1891 vs. 0.6769 ± 0.1021 (mean ± SD, p<0.05). A low βAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45 ± 15.33). When onset of disease was taken into account, a βAPP ratio on EOAD subjects of 0.3965 ± 0.1916 was found vs. 0.3445 ± 0.1965 on LOAD subjects (p>0.05). Conclusions: Altered βAPP isoforms is a high risk factor for Alzheimer’s disease, although it has no influence on the time of onset of the disease.

NutriSim© Protects-Against Apoptosis in Hippocampus Induced by Transient Ischemia in Mongolian Gerbils (Meriones Unguiculatus)

Mongolian gerbil model has been extensively used for the study of neuroprotective drugs since transient bilateral common carotid artery occlusion induces neuronal cell death to selectively vulnerable regions, including the CA1 sector of the hippocampus. Previously we have shown that NutriSim©, a nutritive supplement used empirically in the treatment of several degenerative disorders protects against brain damage induced by ischemia-reperfusion in Mongolian gerbils. These effects are partly attributed to its antioxidant action. The purpose of this study was to further investigate the potential neuroprotective effects of NutriSim© with histological measures of global ischemia in gerbils. We found that a single dose of NutriSim© was able to prevent significantly the ischemia-induced pyramidal cell loss as well as the number of hyperchromatic cells and glial cells after a week of treatment. In consonance with these data, increased TUNEL positive cells after ischemia is reduced in NutriSim© treated animal after a week.

Alzheimer Disease and Metabolism: Role of Cholesterol and Membrane Fluidity

Alzheimers disease (AD) is an age-related disorder characterized by deposition of amyloid β-peptide (Aβ) and degeneration of neurons in brain regions such as the hippocampus, re‐ sulting in progressive cognitive dysfunction. The causes of Alzheimers disease (AD) have not been fully discovered, there are three main hypotheses to explain the phenomenon: a) The deficit of acetylcholine; b) The accumulation of beta-amyloid (Aβ and / or tau protein; and c) Metabolic disorders.

Multiple Sclerosis and Its Relationship with Oxidative Stress, Glutathione Redox System, ATPase System, and Membrane Fluidity

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a focus on inflammation, demyelination, and damage to axons leading to neurological deficits. MS pathology is associated with excessive reactive oxygen species (ROS) and generation of reactive nitrogen species (RNS), causing oxidative/nitrosa‐ tive stress. Deregulation of glutathione homeostasis and alterations in glutathione‐ dependent enzymes are implicated in MS. Reactive oxygen species enhance both monocyte adhesion and migration across brain endothelial cells. In addition, ROS can activate the expression of the nuclear transcription factor‐kappa, which upregulates the expression of many genes involved in MS, such as tumor necrosis factor‐α and nitric oxide synthase, among others, leading to mitochondrial dysfunction and energy deficits that result in mitochondrial and cellular calcium overload. Loss of mitochondrial membrane potential can increase the release of cytochrome c, one pathway that leads to neuronal apoptosis. Clinical studies suggest that omega‐3 long‐chain polyunsaturat‐ ed fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti‐inflammatory, antioxidant, and neuroprotective effects in MS and animal models of MS. Here, we review the relationship of oxidative stress, the

Oxidative Stress and Parkinson’s Disease: Effects on Environmental Toxicology

Epidemiological studies have found an increased risk of Parkinson’s disease (PD) with environmental factors such as exposure to substances derived from industrial processes, use of agrochemicals, or living in a rural environment. The hypothesis that certain environmental toxins could be the source of the EP is supported by the discovery that chemicals such as herbicides paraquat, diquat, and the fungicide maneb are selectively toxic in nigrostriatal dopaminergic neurons. Also, one of the insecticides produced by plants, such as rotenone, and by-product of the synthesis of synthetic heroin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can be reproduced in animal models where neurochemicals, histopathological, and clinical characteristic of PD can be found. Interestingly, there are similarities in the chemical structure of paraquat and MPTP. Recent evidence exhibited that inflammation and oxidative stress play an essential role in the development of PD. So, in our laboratory we found that in an animal model melatonin decreases the products of lipid oxidation, nitric oxide metabolites, and the activity of cyclooxygenase 2, which are induced by an intraperitoneal injection of MPTP. This suggests that the neuroprotective effects of melatonin are partially attributed to its antioxidant scavenging and anti-inflammatory action.