Frontotemporal-TDP and LATE Neurocognitive Disorders: A Pathophysiological and Genetic Approach.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system, which is crucial for memory, emotions, and learning. However, distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

Genetic Basis of Inflammatory Demyelinating Diseases of the Central Nervous System: Multiple Sclerosis and Neuromyelitis Optica Spectrum.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

Neurocognitive Psychiatric and Neuropsychological Alterations in Parkinson's Disease: A Basic and Clinical Approach.

The main histopathological hallmarks of Parkinson's disease (PD) are the degeneration of the dopaminergic neurons of the substantia nigra pars compacta and the loss of neuromelanin as a consequence of decreased dopamine synthesis. The destruction of the striatal dopaminergic pathway and blocking of striatal dopamine receptors cause motor deficits in humans and experimental animal models induced by some environmental agents. In addition, neuropsychiatric symptoms such as mood and anxiety disorders, hallucinations, psychosis, cognitive impairment, and dementia are common in PD. These alterations may precede the appearance of motor symptoms and are correlated with neurochemical and structural changes in the brain. This paper reviews the most crucial pathophysiology of neuropsychiatric alterations in PD. It is worth noting that PD patients have global task learning deficits, and cognitive functions are compromised in a way is associated with hypoactivation within the striatum, anterior cingulate cortex, and inferior frontal sulcus regions. An appropriate and extensive neuropsychological screening battery in PD must accurately assess at least five cognitive domains with some tests for each cognitive domain. This neuropsychological screening should consider the pathophysiological and clinical heterogeneity of cognitive dysfunction in PD.

Neuromyelitis optica spectrum disorder: pathophysiological approach.

Aim: To review the main pathological findings of Neuromyelitis Optica Spectrum Disorder (NMOSD) associated with the presence of autoantibodies to aquaporin-4 (AQP4) as well as the mechanisms of astrocyte dysfunction and demyelination. Methods: An comprehensive search of the literature in the field was carried out using the database of The National Center for Biotechnology Information from . Systematic searches were performed until July 2022. Results: NMOSD is an inflammatory and demyelinating disease of the central nervous system mainly in the areas of the optic nerves and spinal cord, thus explaining mostly the clinical findings. Other areas affected in NMOSD are the brainstem, hypothalamus, and periventricular regions. Relapses in NMOSD are generally severe and patients only partially recover. NMOSD includes clinical conditions where autoantibodies to aquaporin-4 (AQP4-IgG) of astrocytes are detected as well as similar clinical conditions where such antibodies are not detected. AQP4 are channel-forming integral membrane proteins of which AQ4 isoforms are able to aggregate in supramolecular assemblies termed orthogonal arrays of particles (OAP) and are essential in the regulation of water homeostasis and the adequate modulation of neuronal activity and circuitry. AQP4 assembly in orthogonal arrays of particles is essential for AQP4-IgG pathogenicity since AQP4 autoantibodies bind to OAPs with higher affinity than for AQP4 tetramers. NMOSD has a complex background with prominent roles for genes encoding cytokines and cytokine receptors. AQP4 autoantibodies activate the complement-mediated inflammatory demyelination and the ensuing damage to AQP4 water channels, leading to water influx, necrosis and axonal loss. Conclusions: NMOSD as an astrocytopathy is a nosological entity different from multiple sclerosis with its own serological marker: immunoglobulin G-type autoantibodies against the AQP4 protein which elicits a complement-dependent cytotoxicity and neuroinflammation. Some patients with typical manifestations of NMSOD are AQP4 seronegative and myelin oligodendrocyte glycoprotein positive. Thus, the detection of autoantibodies against AQP4 or other autoantibodies is crucial for the correct treatment of the disease and immunosuppressant therapy is the first choice.

Melatonin: A Neurotrophic Factor?

Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina's exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin's role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.

Dietary fish oil increases catalase activity in patients with probable Alzheimer's disease.

Introduction: Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of neuritic plaques and neurofibrillary tangles that finally result in synaptic and neuronal loss. Oxidative stress accompanies pathological changes in AD. Objective: to assess the efficacy of dietary omega 3 polyunsaturated fatty acids supplementation on the levels of proteins oxidation, hydroperoxides and enzymatic activities of catalase and superoxide dismutase in AD patients. Methods: clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or placebo for one year. Oxidative stress markers were assessed in plasma using spectrophotometric methods. Results: carbonyl groups in proteins and hydroperoxides in plasma have similar values in both treatment groups at the beginning of the study. At six and 12 months of treatment, these values decreased significantly in the fish oil group, while in the placebo group no changes were observed in both oxidative stress markers. Catalase activity increased significantly at six and twelve months after treatment in patients treated with fish oil. While the superoxide dismutase activity was not modified in both study groups. Conclusions: patients who consume omega 3 polyunsaturated fatty acids at a stable dose of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) show decreased oxidation of proteins and lipids in plasma. In addition, an increase in catalase activity was detected. Thus, the presented data warrants further studies evaluating the antioxidant effect of omega 3 polyunsaturated fatty acids.

Introducción: Antecedentes: la enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo caracterizado por la presencia de placas neuríticas y ovillos neurofibrilares que finalmente resultan en pérdida sináptica y neuronal. El estrés oxidativo acompaña los cambios patológicos en la EA. Objetivo: evaluar la eficacia de la suplementación dietética con ácidos grasos poliinsaturados omega 3 sobre los niveles de oxidación de proteínas, hidroperóxidos y actividades enzimáticas de catalasa y superóxido dismutasa en pacientes con EA. Métodos: ensayo clínico, controlado, aleatorizado, doble ciego. Los pacientes consumieron aceite de pescado o placebo durante un año. Los marcadores de estrés oxidativo se evaluaron en plasma mediante métodos espectrofotométricos. Resultados: los grupos carbonilo en proteínas e hidroperóxidos en plasma tuvieron valores similares en ambos grupos de tratamiento al inicio del estudio. A los seis y 12 meses de tratamiento estos valores disminuyeron significativamente en el grupo de aceite de pescado, mientras que en el grupo placebo no se observaron cambios en ambos marcadores. La actividad de catalasa aumentó significativamente a los seis y doce meses después del tratamiento en pacientes tratados con aceite de pescado; sin embargo, la actividad superóxido dismutasa no se modificó en ambos grupos de estudio. Conclusiones: los pacientes que consumieron los ácidos grasos poliinsaturados omega 3 a una dosis estable de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) muestran una oxidación reducida de proteínas y lípidos en plasma. Además, se detectó un aumento en la actividad de la catalasa. Por tanto, los datos presentados justifican más estudios que evalúen el efecto antioxidante de dichos ácidos grasos.

Alzheimer's Disease and SARS-CoV-2: Pathophysiological Analysis and Social Context.

The COVID-19 pandemic has proven to be a challenge for healthcare systems, especially in terms of the care of patients with Alzheimer's disease (AD). Age is one of the major risk factors for severe forms of COVID-19, most probably due to the presence of comorbidities and inflammations. It is known that SARS-CoV-2 invades nerve endings and olfactory nerves through the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor. This interaction triggers an inflammatory cascade that results in cognitive impairment. In turn, the isoform of apolipoprotein-E4 (APOE-4ε) in AD is a risk factor for increased neuroinflammation through microglia activation, increased oxidative stress, and neurodegeneration. AD and SARS-CoV-2 are associated with increases in levels of inflammatory markers, as well as increases in levels of APOE-4ε, ACE2 and oxidative stress. Thus, there is a synergistic relationship between AD and SARS-CoV-2. In addition, the social isolation and other health measures resulting from the pandemic have led to a higher level of anxiety and depression among AD patients, a situation which may lead to a decline in cognitive function. Therefore, there is a need to develop strategies for keeping the patient calm but active.

Beneficial Effect of Melatonin Alone or in Combination with Glatiramer Acetate and Interferon ß-1b on Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon ß-1b (IFNß-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNß-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNß-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.

Alterations in blink and masseter reflex latencies in older adults with neurocognitive disorder and/or diabetes mellitus.

BACKGROUND: Blink and masseter reflexes provide reliable, quantifiable data on the function of the central nervous system: Delayed latencies have been found in patients with neurocognitive disorder (ND) and type 2 diabetes mellitus (T2DM), but this has not been studied in patients with both pathologies. AIM: To investigate if older adults with ND plus T2DM have prolonged latencies of blink and masseter-reflex and if they were associated with disease progression. METHODS: This cross-sectional study included 227 older adults (> 60 years) from Colima, Mexico. Neurocognitive disorder was identified by a neuropsychological battery test, and T2DM identified by medical history, fasting glucose, and glycosylated hemoglobin. Latencies in the early reflex (R1), ipsilateral late (R2), and contralateral late (R2c) components of the blink reflex were analyzed for all subjects, and 183 subjects were analyzed for latency of the masseter reflex. RESULTS: In 20.7% of participants, ND was detected. In 37%, T2DM was detected. Latencies in R1, R2, and R2c were significantly prolonged for groups with ND plus T2DM, ND, and T2DM, compared with the control group (P < 0.0001). The masseter reflex was only prolonged in older adults (regardless of T2DM status) with ND vs controls (P = 0.030). In older adults with ND and without T2DM, the more the cognitive impairment progressed, the more prolonged latencies in R2 and R2c presented (P < 0.01). CONCLUSION: These findings suggest that blink and masseter reflexes could be used to evaluate possible changes in brainstem circuits in older adults with ND and T2DM.

Effect of Melatonin Administration on Mitochondrial Activity and Oxidative Stress Markers in Patients with Parkinson's Disease.

Mitochondrial dysfunction and oxidative stress are extensively linked to Parkinson's disease (PD) pathogenesis. Melatonin is a pleiotropic molecule with antioxidant and neuroprotective effects. The aim of this study was to evaluate the effect of melatonin on oxidative stress markers, mitochondrial complex 1 activity, and mitochondrial respiratory control ratio in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial study was conducted in 26 patients who received either 25 mg of melatonin or placebo at noon and 30 min before bedtime for three months. At the end of the trial, in patients who received melatonin, we detected a significant diminution of lipoperoxides, nitric oxide metabolites, and carbonyl groups in plasma samples from PD patients compared with the placebo group. Conversely, catalase activity was increased significantly in comparison with the placebo group. Compared with the placebo group, the melatonin group showed significant increases of mitochondrial complex 1 activity and respiratory control ratio. The fluidity of the membranes was similar in the melatonin group and the placebo group at baseline and after three months of treatment. In conclusion, melatonin administration was effective in reducing the levels of oxidative stress markers and restoring the rate of complex I activity and respiratory control ratio without modifying membrane fluidity. This suggests that melatonin could play a role in the treatment of PD.

Are electrophysiological and oligodendrocyte alterations an element in the development of multiple sclerosis at the same time as or before the immune response?

Efficient communication between the glial cells and neurons is a bi-directional process that is essential for conserving normal functioning in the central nervous system (CNS). Neurons dynamically regulate other brain cells in the healthy brain, yet little is known about the first pathways involving oligodendrocytes and neurons. Oligodendrocytes are the myelin-forming cells in the CNS that are needed for the propagation of action potentials along axons and additionally serve to support neurons by neurotrophic factors (NFTs). In demyelinating diseases, like multiple sclerosis (MS), oligodendrocytes are thought to be the victims. Axonal damage begins early and remains silent for years, and neurological disability develops when a threshold of axonal loss is reached, and the compensatory mechanisms are depleted. Three hypotheses have been proposed to explain axonal damage: 1) the damage is caused by an inflammatory process; 2) there is an excessive accumulation of intra-axonal calcium levels; and, 3) demyelinated axons evolve to a degenerative process resulting from the lack of trophic support provided by myelin or myelin-forming cells. Although MS was traditionally considered to be a white matter disease, the demyelination process also occurs in the cerebral cortex. Recent data supports the notion that initial response is triggered by CNS injury. Thus, the understanding of the role of neuron-glial neurophysiology would help provide us with further explanations. We should take in account the suggestion that MS is in part an autoimmune disease that involves genetic and environmental factors, and the pathological response leads to demyelination, axonal loss and inflammatory infiltrates.

Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)

El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)

Marcadores de estrés oxidativo en pacientes con esclerosis múltiple durante un brote y su remisión / Oxidative stress markers in patients with multiple sclerosis during an outbreak and its remission / Marcadores de estresse oxidativo em pacientes com esclerose múltipla durante um surto e sua remissão

La esclerosis múltiple remitente-recurrente (EM-RR) es una enfermedad desmielinizante del sistema nervioso central. A fin de entender la asociación del estrés oxidativo a nivel periférico con la recaída de la enfermedad se determinaron los niveles de marcadores de estrés oxidativo en plasma de pacientes en la recaída o brote y una semana después de la misma. Se analizaron muestras de 60 personas (20 pacientes con recaída, 20 pacientes sin recaída y 20 controles sanos). Se cuantificaron mediante métodos espectrofotométricos las actividades enzimáticas de óxido nítrico sintasa (ONS), glutatión peroxidasa (GPx), los niveles de lipoperóxidos y nitritos-nitratos y la fluidez de membrana. En el brote de la enfermedad aumentan significativamente los niveles de las actividades enzimáticas de ONS y GPx y los niveles de nitritos-nitratos y lipoperóxidos (p<0,01 en todos los casos), al ser comparados con los de individuos sanos. Dichos parámetros disminuyeron significativamente una semana después de iniciado el brote. Además, los parámetros evaluados se mantuvieron elevados en pacientes que no experimentaron un brote de la enfermedad cuando se los comparó con individuos sanos. La fluidez de membrana en los pacientes con y sin brote fue similar a la de los controles. En conclusión, el estrés oxidativo es un componente importante en los pacientes con esclerosis múltiple.

Recurrent-remitting multiple sclerosis (RR-MS) is a demyelinating disease of the central nervous system. In order to understand the association of oxidative stress at the peripheral level with the relapse of the disease, the levels of oxidative stress markers in plasma of patients in the relapse or outbreak and one week after relapse were determined. Samples of 60 subjects were analyzed (20 patients in relapse, 20 patients without relapse, and 20 healthy controls). The enzymatic activities of nitric oxide synthase (NOS), glutathione peroxidase (GPx), lipoperoxides and nitrite-nitrate levels and membrane fluidity were quantified by spectrophotometric methods. In relapse, the levels of enzymatic activities of NOS and GPx, and the levels of lipoperoxides and nitrites-nitrates were significantly increased (p<0.01, in all cases), compared with healthy individuals. These parameters decreased significantly 1 week after the start of the outbreak. In addition, the parameters evaluated remained high in patients who did not experience an outbreak of the disease compared to healthy subjects. The membrane fluidity in the patients with and without outbreak was similar to that of the controls. In conclusion, oxidative stress is an important component in patients with multiple sclerosis.

A esclerose múltipla recorrente-remitente (EM-RR) é uma doença desmielinizante do sistema nervoso central. Para compreender a associação do estresse oxidativo a nível periférico com a recaída da doença foram determinados os níveis de marcadores de estresse oxidativo em plasma de doentes na recaída ou surto e uma semana após a recaída. Foram analisadas a amostras de 60 pessoas (20 pacientes com recaída, 20 pacientes sem recaída e 20 controles saudáveis). As atividades enzimáticas de óxido nítrico sintase (ONS), glutationa peroxidase (GPX), os níveis de lipoperóxidos e nitritos-nitratos e a fluidez de membrana foram quantificadas por métodos espectrofotométricos. No surto da doença aumentam em forma significativa os níveis da atividade enzimática de ONS e GPX, e os níveis de nitritos-nitratos e lipoperóxidos (p<0,01 em todos os casos), em comparação com os indivíduos saudáveis. Esses parâmetros diminuíram significativamente uma semana após o início do surto. Além disso, os parâmetros avaliados permaneceram elevados em pacientes que não experimentaram um surto da doença quando comparados com indivíduos saudáveis. A fluência de membrana nos pacientes com e sem surto foi semelhante à dos controles. Em conclusão, o estresse oxidativo é um componente importante nos pacientes com esclerose múltipla.

Effect of symbiotic supplementation on fecal calprotectin levels and lactic acid bacteria, Bifidobacteria, Escherichia coli and Salmonella DNA in patients with cervical cancer.

BACKGROUND: patients with cervical cancer (CC) receiving chemotherapy and radiotherapy have several gastrointestinal adverse effects. OBJECTIVE: to evaluate the effect of dietary symbiotic supplementation on fecal calprotectin (FCP), bacterial DNA levels, and gastrointestinal adverse effects in patients with CC. METHODS: clinical, controlled, randomized, double-blind trial. Patients consumed symbiotics or placebo three times a day for seven weeks. FCP was assessed by Elisa method. DNA from probiotic and pathogenic bacteria were determined by quantitative real-time polymerase chain reaction. Diarrheal evacuations were evaluated with the Bristol stool form scale and nausea and vomiting were measured using the scale of the National Institute of Cancerology of the United States. RESULTS: after a seven-week treatment, FCP concentration was lower in the symbiotic group compared to the control group (p < 0.001). Stool consistency in the placebo and symbiotic groups was similar at baseline. A significant improvement in stool consistency was obtained in both groups at the end of the intervention (p < 0.001). The concentrations and total proportions of the probiotic and pathogenic bacteria were similar in both groups. Nausea significantly diminished in both groups (p < 0.001) at the end of the trial. Furthermore, the symbiotic group had a statistically significant decrease in the frequency and intensity of vomiting when compared to the control group (p < 0.001). CONCLUSIONS: the symbiotic treatment decreases significantly the FCP levels and the frequency and intensity of vomiting in patients with CC.

Effect of symbiotic supplementation on fecal calprotectin levels and lactic acid bacteria, Bifidobacteria, Escherichia coli and Salmonella DNA in patients with cervical cancer / Efecto de la suplementación con simbióticos sobre los niveles de calprotectina fecal y ADN de bacterias ácido lácticas, Bifidobacteria, Escherichia coli y Salmonella en pacientes con cáncer cervical

Background: patients with cervical cancer (CC) receiving chemotherapy and radiotherapy have several gastrointestinal adverse effects. Objective: to evaluate the effect of dietary symbiotic supplementation on fecal calprotectin (FCP), bacterial DNA levels, and gastrointestinal adverse effects in patients with CC. Methods: clinical, controlled, randomized, double-blind trial. Patients consumed symbiotics or placebo three times a day for seven weeks. FCP was assessed by Elisa method. DNA from probiotic and pathogenic bacteria were determined by quantitative real-time polymerase chain reaction. Diarrheal evacuations were evaluated with the Bristol stool form scale and nausea and vomiting were measured using the scale of the National Institute of Cancerology of the United States. Results: after a seven-week treatment, FCP concentration was lower in the symbiotic group compared to the control group (p < 0.001). Stool consistency in the placebo and symbiotic groups was similar at baseline. A significant improvement in stool consistency was obtained in both groups at the end of the intervention (p < 0.001). The concentrations and total proportions of the probiotic and pathogenic bacteria were similar in both groups. Nausea significantly diminished in both groups (p < 0.001) at the end of the trial. Furthermore, the symbiotic group had a statistically significant decrease in the frequency and intensity of vomiting when compared to the control group (p < 0.001). Conclusions: the symbiotic treatment decreases significantly the FCP levels and the frequency and intensity of vomiting in patients with CC

Introducción: los pacientes con cáncer cervical (CC) tratados con quimioterapia y radioterapia tienen frecuentemente efectos gastrointestinales adversos (EGA). Objetivo: evaluar el efecto de la suplementación dietética con simbióticos en la calprotectina fecal (FCP), el DNA bacteriano y sobre los EGA en pacientes con CC. Métodos: se realizó un ensayo clínico, aleatorizado y doble ciego. Los pacientes ingirieron simbióticos o placebo tres veces al día durante siete semanas. La FCP se evaluó mediante el método de ELISA. El ADN bacteriano se cuantificó mediante PCR en tiempo real. Las evacuaciones se evaluaron con la escala de Bristol y las náuseas y los vómitos se cuantificaron utilizando la escala del Instituto Nacional de Cancerología (USA). Resultados: después de siete semanas de tratamiento, la concentración de FCP fue menor en el grupo tratado con simbióticos en comparación al grupo control (p < 0,001). La consistencia de las heces en los grupos tratados con placebo y simbióticos fue similar al inicio del estudio. Se obtuvo una mejora significativa en la consistencia de las heces en ambos grupos al final de la intervención (p < 0,001). Los niveles de las bacterias probióticas y patogénicas fueron similares en ambos grupos. Los casos de náuseas disminuyeron en ambos grupos (p < 0,001) y el grupo tratado con simbióticos tuvo una disminución significativa en la frecuencia e intensidad de los vómitos en comparación al grupo control (p < 0,001). Conclusiones: el tratamiento simbiótico disminuye significativamente los niveles de FCP y la frecuencia e intensidad del vómito en pacientes con CC

Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system (CNS). Neuroinflammation and oxidative stress are involved in the pathogenesis of MS, promoting tissue damage and demielinization. Current research findings suggest that melatonin has antioxidant and neuroprotective effects. The aim of this study was to evaluate the efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing-remitting multiple sclerosis (RRMS). 36 patients diagnose with RRMS treated with Interferon ß-1b (IFNß-1b) were enrolled in a double bind, randomized, placebo controlled trial. The experimental group received orally 25 mg/d of melatonin for 6 months. After melatonin administration, we observed a significant decrease in serum concentration of pro-inflammatory cytokines and oxidative stress markers; 18% for TNF-α (p <0.05), 34.8% for IL-1ß (p <0.05), 34.7% for IL-6 (p <0.05), 39.9% for lipoperoxides (LPO) (p <0.05) and 24% for nitric oxide catabolites (NOC) levels (p <0.05), compared with placebo group. No significant difference in clinical efficacy outcomes were found between groups. Melatonin treatment was well tolerated and we did not observe significant differences in rates of side effects between the two groups. We concluded that melatonin administration during 6 months period is effective in reducing levels of serum pro-inflammatory cytokines and oxidative stress markers in patients with RRMS. These data support future studies evaluating the safety and effectiveness of melatonin supplementation in RRMS patients.

Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson's disease / Efecto de la administración de melatonina sobre la actividad de la ciclooxigenasa-2, la concentración sérica de metabolitos del óxido nítrico, los lipoperóxidos y la actividad de la glutatión peroxidasa en pacientes con enfermedad de Parkinson.

Objective: To determine the effect of melatonin (MEL) administration on ciclooxigenase 2 (COX-2) activity and serum concentration of nitric oxide metabolites, lipoperoxides and glutathione peroxidase (GPx) activity in patients with Parkinson's disease. Methods: Prospective double-blind randomized clinical pilot trial. 13 patients were included and two groups were formed: MEL at doses of 25 mg orally every 12 hours for 12 months and placebo with corn starch. Patients were assessed using the Unified Parkinson's Disease Scale. A blood sample was taken at baseline and every 3 months until 12 months. Results: COX-2 activity decreased as did nitrates/nitrites (3, 6 and 9 months) and lipoperoxides (9 and 12 months); GPx exhibited no significant differences.

Oxidative Stress: Love and Hate History in Central Nervous System.

Molecular oxygen is essential for aerobic organisms in order to synthesize large amounts of energy during the process of oxidative phosphorylation and it is harnessed in the form of adenosine triphosphate, the chemical energy of the cell. Oxygen is toxic for anaerobic organisms but it is also less obvious that oxygen is poisonous to aerobic organisms at higher concentrations of oxygen. For instance, oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at increased partial pressures. Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen that are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis. However, in pathological conditions ROS levels can increase dramatically. This may result in significant damage to cell structures. Living organisms have been adapted to the ROS in two ways: they can mitigate the unwanted effects through removal by the antioxidant systems and can advantageously use them as messengers in cell signaling and regulation of body functions. Some other physiological functions of ROS include the regulation of vascular tone, detection, and adaptation to hypoxia. In this review, we describe the mechanisms of oxidative damage and its relationship with the most highly studied neurodegenerative diseases.

[NUTRITIONAL AND SOCIODEMOGRAPHIC FACTORS IN PARKINSON'S DISEASE: RURAL VIEW]. / HÁBITOS ALIMENTARIOS Y FACTORES SOCIODEMOGRÁFICOS DE PACIENTES CON ENFERMEDAD DE PARKINSON EN ZONAS RURALES.

Parkinson's disease (PD), its prevalent in population to 65 years of age, nevertheless can occur earlier. Patients with PD exhibit motor and no motor symptoms these may relate with changes in nutritional habits during disease progression. The prevalence of PD and nutritional factor could be different in rural areas compared to urban regions and can be associated with sociocultural and demographic features. It has been suggested a possible association between excessive intake of saturated fats and low consumption of vitamins such as B6 with EP, however, the results are still not conclusive. Some of significant factors could affect nutritional habits and status in PD in rural areas, are: health status, economic availability, environmental and geographical factors, among others. This review presents some eating habits and sociodemographic factors in PD principally in rural areas.

La enfermedad de Parkinson (EP) predomina en la población de 65 años de edad o más y se caracteriza tanto por síntomas motores como no motores, los cuales pueden asociarse con cambios en la conducta alimentaria. Los factores nutricionales pueden depender de las características socioculturales y sociodemográficas, y esto a su vez podrían ser diferente en el medio rural en comparación con el medio urbano. Se ha propuesto una posible asociación entre el exceso en la ingesta de grasas saturadas y la baja ingesta de vitaminas como la B6 y los antioxidantes con la EP; sin embargo, los resultados aún no son concluyentes. Entre los factores significativos que podrían afectar a los hábitos nutricionales y condicionar el estado nutricional en la EP en zonas rurales se encuentran: el estado de salud, la disponibilidad económica, los factores ambientales y geográficos, entre otros. La presente revisión analiza algunos de los hábitos alimentarios y los factores sociodemográficos en la EP, principalmente en zonas rurales.

Beneficial effects of quercetin on oxidative stress in liver and kidney induced by titanium dioxide (TiO2) nanoparticles in rats.

TiO2 nanoparticles used as vectors for the delivery of drugs have shown greater effectiveness. However, TiO2 nanoparticles can cause oxidative stress in liver and kidney, so we analyzed if a previous or simultaneous quercetin treatment could counteract this in rats. Five groups of male Wistar rats (200-250 g) were included: (1) healthy controls, (2) TiO2 group, (3) quercetin group, (4) preventive group: quercetin for 5 days prior to exposure of TiO2, and (5) therapeutic group: TiO2 (5 mg/kg, i.v.) plus quercetin single dose for 5 days (5 mg/kg/day, i.p.). Hepatic and renal function tests were made. Five animals from each group were sacrificed (0, 14 and 28 days), and liver and kidney tissue were obtained. Malondialdehyde (MDA), reduced/oxidized glutathione, and activity of glutathione peroxidase/reductase were measured, as well as the level of gene expression by q-PCR. There were no significant changes in serum ALT and AST activities. More damage was observed at 14 versus 28 days, because TiO2 was excreted in urine. Quercetin indeed showed a renal protective effect by increasing glutathione reductase and peroxidase levels and reducing MDA levels. On the other hand, TiO2 liver damage was less pronounced with quercetin as therapeutic treatment. TiO2 induces significantly the glutathione reductase expression and it can be down-regulated by quercetin. Biochemical tests in serum and urine showed a better effect of quercetin administered in the therapeutic group. Care should be taken with the dose and time of administration of quercetin, because this antioxidant could also have a pro-oxidant effect.