Nutritional, Clinical and Sociodemographic Profiles of Spanish Patients with Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a chronic and progressive neurodegenerative disease that leads to the loss of motor neurons. The dietary intake of ALS patients is thought to influence the prognosis and progression of the disease. The aim of this study was to examine the nutritional, clinical and sociodemographic characteristics of ALS patients in Spain. A cross-sectional descriptive study with demographics, clinical anamnesis and anthropometric assessment was carried out. Nutritional intake was recorded and compared with dietary reference intakes (DRI). Forty subjects (25 males; 15 females) aged 54.7 ± 10.17 were included in the study. The mean weight and height were 67.99 ± 8.85 kg and 167.83 ± 8.79 cm, respectively. Clinical phenotype, time to diagnosis, year of onset and family history were not associated with the place of origin. Clinical phenotype had no influence on time of diagnosis. Caloric and protein intakes were adequate, while carbohydrate, vitamin B8 and iodine intakes were significantly lower than the DRI. Lipids; vitamins B1, B2, B3, B5, B6, B12, C and E; sodium; phosphorus; and selenium intakes were significantly higher than the recommended nutritional standards. ALS patients, who are homogeneously distributed throughout our national territory, should modify their dietary habits to minimize ultra-processed products and prioritize foods rich in healthy fats and fiber.

Usnea aurantiaco-atra (Jacq) Bory: Metabolites and Biological Activities.

BACKGROUND: Lichens are complex symbiotic associations between a fungus and an alga or cyanobacterium. Due to their great adaptability to the environment, they have managed to colonize many terrestrial habitats, presenting a worldwide distribution from the poles to the tropical regions and from the plains to the highest mountains. In the flora of the Antarctic region, lichens stand out due to their variety and development and are a potential source of new bioactive compounds. METHODS: A phytochemical study of the Antarctic lichen Usnea aurantiaco-atra (Jacq) Bory was conducted with the intention of determining the most important metabolites. In addition, the cytotoxic and antioxidant activities of its extracts were determined. RESULTS: Cytotoxicity studies revealed that the hexane extract contains usnic acid as a majority metabolite, in addition to linoleic acid, ergosterols and terpenes, and demonstrates cytotoxic activity against an A375 melanoma cell line. On the other hand, the presence of total phenols in the extracts did not influence their antioxidant activity. CONCLUSIONS: U. aurantiaco-atra contains mainly usnic acid, although there are terpenes and ergosta compounds that could be responsible for its cytotoxic activity. The presence of phenols did not confer antioxidant properties.

Effect of the Mediterranean diet supplemented with nicotinamide riboside and pterostilbene and/or coconut oil on anthropometric variables in amyotrophic lateral sclerosis. A pilot study.

Amyotrophic Lateral Sclerosis (ALS) is a chronic and progressive neurodegenerative disease that causes the death of motor neurons and alters patients' body composition. Supplementation with the antioxidants nicotinamide riboside (NR) and pterostilbene (PTER) can combat associated oxidative stress. Additionally, coconut oil is an alternative energy substrate that can address mitochondrial dysfunction. The aim of the present study is to assess the impact of a Mediterranean Diet supplemented with NR and PTER and/or with coconut oil on the anthropometric variables of patients with ALS. A prospective, mixed, randomized, analytical and experimental pilot study in humans was performed through a clinical trial (registered with ClinicalTrials.gov under number NCT03489200) with pre- and post-intervention assessments. The sample was made up of 40 subjects categorized into four study groups (Control, Antioxidants, Coconut oil, and Antioxidants + Coconut oil). Pre- and post-intervention anthropometric assessments were carried out to determine the following data: weight, percentage of fat and muscle mass, skinfolds, body perimeters, Body Mass Index (BMI), Waste-to-Hip Index (WHI) and Waist-Height Ratio (WHR). Compared to the Control group, GAx significantly increased muscle mass percentage and decreased fat mass percentage, triceps, iliac crest, and abdominal skinfolds. GCoco significantly increased muscle mass percentage and decreased fat mass percentage, subscapular skinfolds, and abdominal skinfolds. GAx + coco significantly increased muscle mass percentage and decreased abdominal skinfolds. Therefore, our results suggest that the Mediterranean Diet supplemented with NR and PTER and the Mediterranean Diet supplemented with coconut oil (ketogenic diet) are the two nutritional interventions that have reported the greatest benefits, at anthropometric level.

A comparative study between olive oil and corn oil on oxidative metabolism.

Fats are an important part of diet, but not all lipids have the same structure and chemical properties. Unsaturated fatty acids have one or more double bonds in their structure and can be monounsaturated or polyunsaturated, respectively. Most vegetable oils, such as olive oil and corn oil, contain significant amounts of these fatty acids. The presence of double bonds in the molecule of a fatty acid constitutes vulnerable sites for oxidation reactions generating lipid peroxides, potentially toxic compounds that can cause cellular damage. In response to this oxidative damage, aerobic organisms have intracellular enzymatic antioxidant defense mechanisms. The aim of the present investigation was to study comparatively the effects of control liquid diets, of a defined composition, containing olive oil or corn oil as a lipid source respectively of monounsaturated and polyunsaturated fatty acids, on the oxidative metabolism of rats. Rats were divided into three groups which received a control animal feed diet (A.F.), olive oil liquid diet (O.O) and corn oil liquid diet (C.O) for 30 days. It was observed that the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), increased in the liver and white fat tissue of rats fed with olive oil when compared to the corn oil group. However, in brown fat tissue and blood cells, the enzyme activities showed a tendency to decrease in the olive oil group. In addition, the effect of olive oil and corn oil on several glucose metabolism parameters (pyruvate, lactate, LDH, acetoacetate and beta-hydroxybutyrate) showed that corn oil impairs to a greater extent the cellular metabolism. All these results helped in concluding that some body tissues are more adversely affected than others by the administration of corn oil or olive oil, and their antioxidant defenses and cellular metabolism respond differently too.

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study.

Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time-condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.

Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that produces a selective loss of the motor neurons of the spinal cord, brain stem and motor cortex. Oxidative stress (OS) associated with mitochondrial dysfunction and the deterioration of the electron transport chain has been shown to be a factor that contributes to neurodegeneration and plays a potential role in the pathogenesis of ALS. The regions of the central nervous system affected have high levels of reactive oxygen species (ROS) and reduced antioxidant defenses. Scientific studies propose treatment with antioxidants to combat the characteristic OS and the regeneration of nicotinamide adenine dinucleotide (NAD+) levels by the use of precursors. This review examines the possible roles of nicotinamide riboside and pterostilbene as therapeutic strategies in ALS.

The Relation between Eating Habits and Abdominal Fat, Anthropometry, PON1 and IL-6 Levels in Patients with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative disease of an inflammatory, demyelinating and autoimmune nature. Diets with a high caloric density could be especially relevant in terms of the pathogenesis related to an increase in adipose tissue that is metabolically active and releases mediators, which can induce systemic inflammation and an increased oxidation state. The aim of this study was to analyse the eating habits related to calorie intake and their impact on abdominal obesity associated with anthropometric variables, the activity of the oxidation marker paraoxonase 1 (PON1), and interleukin 6 (IL-6) levelsin MS patients. METHODS: An analytical and quantitative observational study was conducted with a population of 57 MS patients. The dietary-nutritional anamnesis was gained through the Food Frequency Questionnaire and a food diary. Diet and eating habits have been analysed through the Easy Diet-Programa de gestión de la consulta® software. Anthropometric measurements were taken in order to determine the presence of abdominal obesity. In addition, PON1 was quantified in serum by means of automated spectrophotometric assays and IL-6 was quantified using the ELISA technique. RESULTS: A normal calorie intake was determined for women, yet a slightly lower intake was observed in men. Carbohydrate consumption was below what was established, and protein and lipids were over, in both cases. Furthermore, most patients had abdominal obesity, with significantly higher body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and IL-6 levels. IL-6 is greatly correlated with waist circumference and WHtR. CONCLUSION: MS patients' nutrient intake shows an imbalance between macronutrients. This seems to favour the abdominal obesity associated with high values of proinflammatory IL-6 that is not correlated with a lower activity of PON1.

Oxygenic metabolism in nutritional obesity induced by olive oil. The influence of vitamin C.

Obesity is a medical and sociological problem of great importance due to the high percentage of people affected and the important health consequences that it involves. Most cases of obesity are related to an inadequate diet, rich in fats, which could lead to changes in the patient's oxygenic metabolism. That is why this study has been proposed to evaluate how some aspects of oxygenic metabolism are affected in a nutritional experimental model, with a controlled hyperlipidic liquid diet based on olive oil, and the effect of the antioxidant vitamin C on these conditions. Wistar rats were divided into four groups which received a control and hyperlipidic liquid diet for 30 days, with or without a vitamin C supplement (CO, COC, HO and HOC). First of all the body and fat tissue development was measured in the four groups. Our results showed that the excessive intake of nutritional and healthy fat such as olive oil did not prevent the appearance of obesity and the supplementation with vitamin C did not have a protective effect on body and fat development. The study of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in total liver, liver cytosol, abdominal white fat, brown fat and blood cells showed that vitamin C could have different selectivities and affinities for different enzymes and compartments/tissues of the body. Finally, the effect of vitamin C on various metabolic parameters (glucose, pyruvate, lactate, LDH, ATP, acetoacetate and beta-hydroxybutyrate) provided positive protection against oxidative stress especially under hyperlipidic conditions. All things considered, the present study concludes that vitamin C treatment could protect Wistar rats from the oxidative stress impairment induced by obesity generated by an excessive intake of fats.

Autophagy Dysfunction and Oxidative Stress, Two Related Mechanisms Implicated in Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is one of the most common clinical subtypes of retinal degeneration (RD), and it is a neurodegenerative disease that could cause complete blindness in humans because it ultimately affects the photoreceptors viability. RP afflicts an estimated 1.5 million patients worldwide. The retina is highly susceptible to oxidative stress which can impair mitochondrial function. Many retina pathologies, such as diabetic retinopathy and secondary cone photoreceptor death in RP, have been related directly or indirectly with mitochondrial dysfunction. The possible role of autophagy in retina and cell differentiation is described and also the implications of autophagy dysregulation in RP. The present review shows the crucial role of autophagy in maintaining the retina homeostasis and possible therapeutic approaches for the treatment of RP.

Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model.

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Material and Methods: Blood-aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. Results: The aqueous humor's cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.

Disulfide stress and its targets in acute pancreatitis.

Under physiological conditions, the balance between ROS production and removal properly maintains the intracellular redox-sensitive signaling as well as the appropriate status of protein thiols and disulfides. However, inflammation among other factors can modify this balance causing a rapid increase in intracellular ROS levels and hence thiol oxidation, eventually leading to oxidative stress. In the case of acute pancreatitis, both redox signaling and oxidative stress seem to contribute to the progression of the severe form of the disease. In this review we will focus on the reversible oxidation of protein cysteines during the course of acute pancreatitis. We describe disulfide stress in an acute inflammatory process, which is characterized by thiol oxidation in proteins, particularly protein cysteinylation, without significant changes in the glutathione redox status.

Disulfide stress: a novel type of oxidative stress in acute pancreatitis.

Glutathione oxidation and protein glutathionylation are considered hallmarks of oxidative stress in cells because they reflect thiol redox status in proteins. Our aims were to analyze the redox status of thiols and to identify mixed disulfides and targets of redox signaling in pancreas in experimental acute pancreatitis as a model of acute inflammation associated with glutathione depletion. Glutathione depletion in pancreas in acute pancreatitis is not associated with any increase in oxidized glutathione levels or protein glutathionylation. Cystine and homocystine levels as well as protein cysteinylation and γ-glutamyl cysteinylation markedly rose in pancreas after induction of pancreatitis. Protein cysteinylation was undetectable in pancreas under basal conditions. Targets of disulfide stress were identified by Western blotting, diagonal electrophoresis, and proteomic methods. Cysteinylated albumin was detected. Redox-sensitive PP2A and tyrosine protein phosphatase activities diminished in pancreatitis and this loss was abrogated by N-acetylcysteine. According to our findings, disulfide stress may be considered a specific type of oxidative stress in acute inflammation associated with protein cysteinylation and γ-glutamylcysteinylation and oxidation of the pair cysteine/cystine, but without glutathione oxidation or changes in protein glutathionylation. Two types of targets of disulfide stress were identified: redox buffers, such as ribonuclease inhibitor or albumin, and redox-signaling thiols, which include thioredoxin 1, APE1/Ref1, Keap1, tyrosine and serine/threonine phosphatases, and protein disulfide isomerase. These targets exhibit great relevance in DNA repair, cell proliferation, apoptosis, endoplasmic reticulum stress, and inflammatory response. Disulfide stress would be a specific mechanism of redox signaling independent of glutathione redox status involved in inflammation.

Oxidative and nitrosative stress in acute pancreatitis. Modulation by pentoxifylline and oxypurinol.

Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol - as inhibitor of xanthine oxidase- and pentoxifylline - as inhibitor of TNF-α production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-α is responsible for glutathione depletion in acute pancreatitis; and (3) to elucidate the role of oxidative stress in the inflammatory cascade in pancreatic AR42J acinar cells. We report here that oxidative stress and nitrosative stress occur in pancreas and lung in acute pancreatitis and the co-treatment with oxypurinol and pentoxifylline prevents oxidative stress in both tissues. Oxypurinol was effective in preventing glutathione oxidation, whereas pentoxifylline abrogated glutathione depletion. This latter effect was independent of TNF-α since glutathione depletion occurred in mice deficient in TNF-α or its receptors after induction of pancreatitis. The beneficial effects of oxypurinol in the inflammatory response may also be ascribed to a partial inhibition of MEK1/2 activity. Pentoxifylline markedly reduced the expression of Icam1 and iNos induced by TNF-α in vitro in AR42J cells. Oxidative stress significantly contributes to the TNF-α-induced up-regulation of Icam and iNos in AR42J cells. These results provide new insights into the mechanism of action of oxypurinol and pentoxifylline as anti-inflammatory agents in acute pancreatitis.