2. Universidad Cardenal Herrera-CEU

Oxidative stress is associated with multiple pathologies such as cancer and can exacerbate the development of them. In this work, we have studied the antioxidant capacity of 5-Fluorouracile (5-FU) which is an antineoplastic drug that is used in the treatment of colorectal cancer. 5-FU is a compound that has a chemical structure similar to uracil and is also fluorinated. New fluorinated derivates previously obtained in our laboratory were tested to study its antioxidant activity. All the compounds analyzed were able to inhibit lipid peroxidation when used in concentrations of 10 μM.

Alcohol is a legal drug present in several drinks commonly used worldwide (chemically known as ethyl alcohol or ethanol). Alcohol consumption is associated with several disease conditions, ranging from mental disorders to organic alterations. One of the most deleterious effects of ethanol metabolism is related to oxidative stress. This promotes cellular alterations associated with inflammatory processes that eventually lead to cell death or cell cycle arrest, among others. Alcohol intake leads to bone destruction and modifies the expression of interleukins, metalloproteinases and other pro-inflammatory signals involving GSKβ, Rho, and ERK pathways. Orthodontic treatment implicates mechanical forces on teeth. Interestingly, the extra- and intra-cellular responses of periodontal cells to mechanical movement show a suggestive similarity with the effects induced by ethanol metabolism on bone and other cell types. Several clinical traits such as age, presence of systemic diseases or pharmacological treatments, are taken into account when planning orthodontic treatments. However, little is known about the potential role of the oxidative conditions induced by ethanol intake as a possible setback for orthodontic treatment in adults.

En este trabajo, inspirados por la mentalidad agustiniana, trataremos el libre albedrío como medio necesario para lograr la felicidad. Tras unas reflexiones generales sobre la mente, el libre albedrío y la felicidad, hablaremos acerca del libre albedrío como requisito para la felicidad y nos centraremos en el libertarismo. Los partidarios de esta corriente sostienen que el libre albedrío existe pero es incompatible con el determinismo, de modo que requiere alguna clase de indeterminismo. Esto trae consigo un problema de inteligibilidad: ¿acaso el indeterminismo no conlleva aleatoriedad y, como consecuencia, carencia de control sobre lo que decidimos y hacemos? Sin embargo, describiremos dos propuestas libertaristas que tratan de dar una explicación inteligible al papel que desempeña el indeterminismo en el ejercicio de nuestro libre albedrío. La primera propuesta, que es ampliamente conocida internacionalmente, es la de Robert Kane. La segunda ha sido defendida por Carlos Moya, el más importante pensador libertarista dentro del ámbito hispano. / In this work we will deal with free will as a necessary means to achieve happiness, inspired by the Augustinian mentality. After some general reflections on mind, free will and happiness, we will address free will as a requirement for happiness and will focus on libertarianism. The advocates for this trend argue that free will exists but is incompatible with determinism, so it requires some kind of indeterminism. This poses a problem of intelligibility: does not indeterminism entail randomness and, consequently, lack of control over what we decide and do? However, we will describe two libertarian proposals that try to give an intelligible explanation to the role played by indeterminism in the exercise of our free will. The first proposal, which is widely known internationally, is that of Robert Kane. The second has been defended by Carlos Moya, the most important libertarian thinker within the Hispanic sphere.

Myopia is one of the commonest eye pathologies that could affect 2.56 billion people by 2020. Today high myopia is a leading cause of blindness worldwide due to associated ocular illness. Nevertheless, the cellular bases for these diseases to develop are unclear in many areas. We conducted a prospective study of oxidative stress and growth factors in human myopic and non myopic eyes in an attempt to increase our understanding of the underlying physiopathological conditions to adequately early diagnose, prevent and treat the retina problem that derives from myopia. Aqueous humor samples were obtained from 41 patients being operated for cataracts in our hospital. Axial length, refractive status and complete ophthalmologic examination were recorded. The VEGF and HGF levels were determined by an ELISA kit. Total antioxidant capacity and total nitrites/nitrate levels were established with a lab kit. We show for the first time an increase in the total nitrite levels in high myopia. We also propose for the first time the concurrence of three factors: myopia, oxidative stress, and oxidative stress together with growth factors in the same group of patients. In this way, it would not be accurate to envision high myopia as a type of normal myopia, but one with more diopters or longer axial length.

The retina is subjected to oxidative stress due to its high vascularization, long time light exposition and a high density of mitochondria. Oxidative stress can lead to pathological processes, like cell apoptosis, angiogenesis and inflammation ending in retinal pathologies. Curcumin, a major bioactive component obtained from the spice turmeric (Curcuma longa) rhizome has been used for centuries in Asian countries for cooking and for curing all kinds of diseases like dysentery, chest congestion and pain in general, due to its antioxidant e ects. Curcumin prevents the formation of reactive oxygen species and so it is a good protective agent. Curcumin has shown also anti-inflammatory, and antitumor properties. Curcumin is a natural product, which can be a therapeutic option in a variety of retinal diseases due to its pleiotropic properties. Some drawbacks are its poor solubility, bioavailability and lack of stability at physiological conditions; which have been shown in curcumin skeptical publications. In this review, we provide some lights and shadows on curcumin administration on the major retinal pathologies.

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.

Aims. The main goal of this study was to evaluate the presence of oxidative damage and to quantify its level in gestational diabetes. Methods. Thirty-six healthy women and thirty-six women with gestational diabetes were studied in the three trimesters of pregnancy regarding their levels of oxidative stress markers. These women were diagnosed with diabetes in the second trimester of pregnancy. Blood glucose levels after 100g glucose tolerance test were higher than 190, 165 or 145 mg/dl, 1, 2 or 3 hours after glucose intake. Results. The group of women with gestational diabetes had higher serum malondialdehyde levels, with significant differences between groups in the first and second trimester. The mean values of serum glutathione peroxidase activity in the diabetic women were significantly lower in the first trimester. In the group of women with gestational diabetes there was a negative linear correlation between serum malondialdehyde concentration and glutathione peroxidase activity in the second and third trimester. Conclusions. In this observational and longitudinal study in pregnant women, the alterations attributable to oxidative stress were present before the biochemical detection of the HbA1c increase. Usual recommendations once GD is detected (adequate metabolic control, as well as any other normally proposed to these patients) lowered the concentration of malondialdehyde at the end of pregnancy to the same levels of the healthy controls. Serum glutathione peroxidase activity in women with gestational diabetes increased during the gestational period.

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.

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.