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When breast milk extraction and storage is required before ingestion, it is important to establish the conditions that ensure the least losses in milk quality, like the antioxidant capacity. The present study evaluates glutathione peroxidase activity and malondialdehyde concentration of breast milk when stored frozen, comparing the effects of 2 temperatures (-20 degrees C and -80 degrees C) and different storage times (15, 30, and 60 days). The results indicate that freezing induces losses in the antioxidant properties of breast milk and that such losses increase with the duration of storage and differ in intensity according to the temperature. It is concluded that to maximally preserve the antioxidant properties of breast milk, it is advisable to store the latter at -80 degrees C for a period of less than 30 days, rather than for shorter time periods at the usual temperature of -20 degrees C. J Hum Lact. 26(1):35-41. [ABSTRACT FROM AUTHOR]

Background: A strong seal of soft-tissue around dental implants is essential to block pathogens from entering the peri-implant interface and prevent infections. Therefore, the integration of soft-tissue poses a challenge in implant-prosthetic procedures, prompting a focus on the interface between peri-implant soft-tissues and the transmucosal component. The aim of this study was to analyse the effects of sandblasted roughness levels on in vitro soft-tissue healing around dental implant abutments. In parallel, proteomic techniques were applied to study the interaction of these surfaces with human serum proteins to evaluate their potential to promote soft-tissue regeneration., Results: Grade-5 machined titanium discs (MC) underwent sandblasting with alumina particles of two sizes (4 and 8 μm), resulting in two different surface types: MC04 and MC08. Surface morphology and roughness were characterised employing scanning electron microscopy and optical profilometry. Cell adhesion and collagen synthesis, as well as immune responses, were assessed using human gingival fibroblasts (hGF) and macrophages (THP-1), respectively. The profiles of protein adsorption to the surfaces were characterised using proteomics; samples were incubated with human serum, and the adsorbed proteins analysed employing nLC-MS/MS. hGFs exposed to MC04 showed decreased cell area compared to MC, while no differences were found for MC08. hGF collagen synthesis increased after 7 days for MC08. THP-1 macrophages cultured on MC04 and MC08 showed a reduced TNF-α and increased IL-4 secretion. Thus, the sandblasted topography led a reduction in the immune/inflammatory response. One hundred seventy-six distinct proteins adsorbed on the surfaces were identified. Differentially adsorbed proteins were associated with immune response, blood coagulation, angiogenesis, fibrinolysis and tissue regeneration., Conclusions: Increased roughness through MC08 treatment resulted in increased collagen synthesis in hGF and resulted in a reduction in the surface immune response in human macrophages. These results correlate with the changes in protein adsorption on the surfaces observed through proteomics., (© 2024. The Author(s).)

Background: Introduction: Prehabilitation in the field of oncology has been defined as "the process in the continuum of care that occurs between diagnosis and the start of treatment involving physical and psychological measures that determine the patient's baseline functional status.", Aim: To determine the effectiveness of a Prehabilitation consultation on self-care and targeted physical exercise for patients diagnosed with abdominopelvic cancer., Design: An observational study that will evaluate the pre-post efficacy of an ad-hoc designed Prehabilitation intervention. The study population consists of patients diagnosed with colon or gynecological cancer with a surgical indication as part of their therapeutic plan from the General Surgery Services. It is configured around four key interventions: (a) health education and self-care, (b) specific nutritional counseling, (c) initial psychological assessment, and (d) directed physical exercise intervention. Health education, self-care interventions, and physical exercise will be carried out weekly from diagnosis to the scheduled surgery day., Results: Aspects such as self-care capacity or agency, perioperative anxiety, aerobic capacity, strength and flexibility, postoperative complications, and recovery time to adjuvant treatment will be measured using tools such as Appraisal of self-care agency scale (ASA), State Trait Anxiety Inventory (STAI), walking test, sit and Reach, Hand Grip or Squad Jump., Conclusion: Utilizing validated tools for analyzing selected variables will contribute to refining and expanding care guidelines, ultimately enhancing support for both patients and their caregivers.

Background: Exercise is an accepted intervention to improve the quality of life (QoL) of breast cancer patients. Exercise programs have been developed, and all have shown satisfactory results in improving the QoL. There is a lack of research comparing different prescription modalities. The aim of this study is to evaluate the effectiveness of physical exercise (in-person and home-based, compared to the exercise recommendation) on the QoL in breast cancer patients actively undergoing treatment., Methods: This is a randomized clinical trial with three groups (in-person: guided and supervised in-person exercise program; home-based exercise: guided and supervised exercise program with streaming monitoring both as a intervention groups; and recommendation: exercise recommendation as a control group). The QoL was measured using the EORTIC QLQ-C30 questionnaire. A baseline and 24-week analysis were investigated., Results: The total sample analyzed was n = 80. The QoL improved significantly at 24 weeks in the face-to-face and home-based exercise groups, but not in the control group. Exercise in all modalities improved fatigue, nausea, vomiting, appetite, and constipation. The QoL at 24 weeks depended on active chemotherapy, tumor type, and assigned exercise group (r 2 = 0.503; p < 0.001)., Conclusions: The QoL in breast cancer patients undergoing active treatment improved after a 24-week exercise program, especially in face-to-face and home-based exercise. Home-based exercise and streaming-based recommendation is a viable option for exercise recommendation.

(1) Background: Ultra-endurance exercise involves a high physical impact, resulting in muscle damage, inflammatory response and production of free radicals that alter the body's oxidative state. Supplementation with antioxidants, such as beetroot, may improve recovery in ultra-endurance runners. The aim of this study was to determine whether there is a correlation between beetroot intake and recovery of serum oxidative status, inflammatory response and muscle damage parameters after an ultra-endurance race. (2) Methods: An observational and longitudinal study was conducted by means of surveys and blood samples collected from 32 runners during the IX Penyagolosa Trails CSP ®® race and the two following days. The variables C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase (CK), the activity of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) as well as the oxidative damage markers malondialdehyde (MDA), carbonyl groups (CG) and loss of muscle strength using the squat jump (SJ) test were analyzed to discriminate whether beetroot consumption can modulate the recovery of ultra-trail runners. (3) Results: Significant differences were observed between runners who ingested beetroot and those who did not, in terms of oxidative status, specifically in serum GPx activity at 24 and 48 h, muscle damage variables CK and LDH and regarding the SJ test results at the finish line. Therefore, the intake of supplements containing beetroot positively influences the recovery of serum oxidative status and muscle damage after ultra-endurance running.

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.

Exosomes or small extracellular vesicles (sEVs) represent a pivotal component in intercellular communication, carrying a diverse array of biomolecules. Several factors can affect sEVs release dynamics, as occurs in hyperglycemia or inflammation. In fact, sEVs release has been associated with the promotion of physio-pathological processes. Among the sEVs cargo, microRNAs play an essential role in cell-to-cell regulation. More concretely, miR-205-5p is related to angiogenesis and cell proliferation. The aim of this study is to understand the specific role of sEVs containing miR-205-5p under high glucose conditions. ARPE-19 cells were cultured with high glucose (HG) for 5 days. sEVs were isolated and characterized. sEVs from ARPE-19 were used for angiogenesis and cell proliferation. HG increased sEVs release but downregulated miR-205-5p cargo expression compared to the control. sEVs from HG-treated ARPE-19 cells promoted tube formation and migration processes. In contrast, miR-205-5p overexpression (by mimic transfection) decreased angiogenesis and cell migration. Our results demonstrate how ARPE-19 cells respond to HG challenge by increasing sEVs with weak miR-205-5p cargo. The absence of this miRNA in sEVs is enough to promote angiogenesis. In contrast, restoring sEVs-miR-205-5p levels decreased it. These findings open new possibilities in sEVs-based therapies containing miR-205-5p against angiogenesis.

Calcium and magnesium are two elements essential for bone structure and metabolism. However, their synergistic or competitive effects on bone regeneration are often overlooked during biomaterial development. We examined the interactions between Ca and Mg in sol-gel coatings doped with mixtures of CaCl 2 (0.5%) and MgCl 2 (0.5, 1, and 1.5%). After physicochemical characterisation, the materials were incubated in vitro with MC3T3-E1 osteoblastic cells and RAW264.7 macrophages, and the protein adsorption was analysed using nLC-MS/MS. The incorporation of the ions did not lead to the formation of crystalline structures and did not affect the sol-gel network cross-linking. The release of the ions did not cause cytotoxic effects at any tested concentration. The proteomic analysis showed that adding the Ca and Mg ions elevated the adsorption of proteins associated with inflammatory response regulation ( e.g. , ALBU, CLUS, HPT, HPTR, A1AG1 and A1AG2) but decreased the adsorption of immunoglobulins. The CaMg coatings had reduced affinity to proteins associated with coagulation ( e.g. , FA9, FA10, FA11, FA12) but increased the adsorption of proteins involved in cell adhesion (DSG1, DESP, FBLN1, ZA2G). In vitro assays revealed that the cellular response was affected by changing the concentration of Mg. Moreover, our results show that these differences reflect the changes in the concentrations of both ions in the mix but are not a simple additive effect.

Extracellular vesicles are released from cells under diverse conditions. Widely studied in cancer, they are associated with different diseases playing major roles. Recent reports indicate that oxidative damage promotes the release of small extracellular vesicle (sEVs) from the retinal pigment epithelium (RPE), with an angiogenic outcome and changes in micro-RNA (miRNA) levels. The aim of this study was to determine the role of the miRNA miR-302a-3p, included within RPE-released sEVs, as an angiogenic regulator in cultures of endothelial cells (HUVEC). ARPE-19 cell cultures, treated with H 2 O 2 to cause an oxidative insult, were transfected with a miR-302a-3p mimic . Later, sEVs from the medium were isolated and added into HUVEC or ARPE-19 cultures. sEVs from ARPE-19 cells under oxidative damage presented a decrease of miR-302a-3p levels and exhibited proangiogenic properties. In contrast, sEVs from miR-302a-3p- mimic transfected cells resulted in control angiogenic levels. The results herein indicate that miR-302a-3p contained in sEVs can modify VEGFA mRNA expression levels as part of its antiangiogenic features.

Mastitis is the inflammation of one or several mammal lobes which can be accompanied by a mammary gland infection, and is the leading cause of undesired early weaning in humans. However, little information exists regarding the changes that this disease may induce in the biochemical composition of human milk, especially in terms of oxidative status. Given that newborns are subject to a significant increase in total ROS burden in their transition to neonatal life and that their antioxidant defense system is not completely developed, the aim of this study was to evaluate antioxidant defense (glutathione peroxidase (GPx), reduced glutathione (GSH), total polyphenol content (TPP), and total antioxidant capacity (TAC)) in milk samples from mothers suffering from mastitis and controls. We also measured the oxidative damage to lipids (malondyaldehyde (MDA)) and proteins (carbonyl group content (CGC)) in these samples. Finally, we tested whether dietary supplementation with cranberries (a product rich in antioxidants) in these breastfeeding mothers during 21 days could improve the oxidative status of milk. GPx activity, TPP, and TAC were increased in milk samples from mastitis-affected women, providing a protective mechanism to the newborn drinking mastitis milk. MDA concentrations were diminished in the mastitis group, confirming this proposal. Some oxidative damage might occur in the mammary gland since the CGC was increased in mastitis milk. Cranberries supplementation seems to strengthen the antioxidant system, further improving the antioxidative state of milk.

Cocaine can induce severe neurobehavioral changes, among others, the ones involved in learning and memory processes. It is known that during drug consumption, cocaine-associated memory and learning processes take place. However, much less is known about the effects of this drug upon the mechanisms involved in forgetting.The present report focuses on the mechanisms by which cocaine affects memory consolidation of experiences acquired prior to drug administration. We also study the involvement of hippocampus in these processes, with special interest on the role of Nuclear factor kappa B (NF-κB), N-methyl-D-aspartate glutamate receptor 2B (GluN2B), and their relationship with other proteins, such as cyclic AMP response element binding protein (CREB). For this purpose, we developed a rat experimental model of chronic cocaine administration in which spatial memory and the expression or activity of several proteins in the hippocampus were assessed after 36 days of drug administration. We report an impairment in memory acquisition of experiences gathered prior to cocaine administration, associated to an increase in GluN2B expression in the hippocampus. We also demonstrate a decrease in NF-κB activity, as well as in the expression of the active form of CREB, confirming the role of these transcription factors in the cocaine-induced memory impairment., (© 2021. The Author(s).)

In recent years, increasing numbers of women have participated in extremely long races. In adult males, there is a clear association between physiological levels of endogenous sex hormones and physical performance. However, the influence of plasmatic sex hormones and the effects of different types of hormonal contraception (HC) on the modulation of physical performance in adult females remain to be fully clarified. Eighteen female ultra-endurance athletes were recruited to participate in the study. Different variables were studied, including hematological parameters, body mass index, and body composition. Strength measurements were obtained using the squat-jump and hand-grip test. A repeated-measures analysis demonstrated significant differences in hematological values of CK and LDH pre-race as compared to immediately post-race and after 24/48 h. Furthermore, statistical differences were found in squat-jump and hand-grip test results after the ultramarathon. Testosterone, estradiol, and the testosterone/estrogen ratio were significantly correlated with muscle fatigue and were found to be indirect markers of muscle damage. A multivariate analysis demonstrated the protective role of testosterone against muscle damage and severe fatigue. Fluctuations in endogenous testosterone levels were correlated with greater fatigability and muscle damage after the competition. Adjusting the menstrual cycle with HC would not provide any further benefit to the athlete's competitive capacity.

The immune system plays a crucial role in determining the implantation outcome, and macrophages are in the frontline of the inflammatory processes. Further, cellular oxidative stress resulting from the material recognition can influence how cell responses develop. Considering this, the aim of this study was to study oxidative stress and macrophages phenotypes in response to sol-gel materials with distinct in vivo outcomes. Four materials were selected (70M30T and 35M35G30T, with high biocompatibility, and 50M50G and 50V50G, with low biocompatibility). Gene expression, immunocytochemistry and cytokine secretion profiles for M1 and M2 markers were determined. Moreover, oxidative stress markers were studied. Immunocytochemistry and ELISA showed that 50M50G and 50V50G lead to a higher differentiation to M1 phenotype, while 70M30T and 35M35G30T promoted M2 differentiation. In oxidative stress, no differences were found. These results show that the balance between M1 and M2, more than individual quantification of each phenotype, determines a biomaterial outcome., (© 2021 Wiley Periodicals LLC.)

Oxidative stress has been widely studied in association to ultra-endurance sports. Although it is clearly demonstrated the increase in reactive oxygen species and free radicals after these extreme endurance exercises, the effects on the antioxidant defenses and the oxidative damage to macromolecules, remain to be fully clarified. Therefore, the aim of this study was to elucidate the impact of an ultramarathon race on the plasma markers of oxidative stress of 32 runners and their post-race recovery, with especial focused on sex and age effect. For this purpose, the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) activity, as well as the lipid peroxidation product malondialdehyde (MDA) and the carbonyl groups (CG) content were measured before the race, in the finish line and 24 and 48 h after the race. We have reported an increase of the oxidative damage to lipids and proteins (MDA and CG) after the race and 48 h later. Moreover, there was an increase of the GR activity after the race. No changes were observed in runners' plasma GPx activity throughout the study. Finally, we have observed sex and age differences regarding damage to macromolecules, but no differences were found regarding the antioxidant enzymes measured. Our results suggest that several basal plasma markers of oxidative stress might be related to the extent of muscle damage after an ultraendurance race and also might affect the muscle strength evolution.

Ethanol abuse is a common issue in individuals with sedentary lifestyles, unbalanced diets, and metabolic syndrome. Both ethanol abuse and metabolic syndrome have negative impacts on the central nervous system, with effects including cognitive impairment and brain oxidative status deterioration. The combined effects of ethanol abuse and metabolic syndrome at a central level have not yet been elucidated in detail. Thus, this work aims to determine the effects of ethanol intake on a mouse model of metabolic syndrome at the behavioral and biochemical levels. Seven-week-old male control (B6.V-Lep ob/+JRj) and leptin-deficient (metabolic syndrome) (B6.V-Lep ob/obJRj) mice were used in the study. Animals were divided into four groups: control, ethanol, obese, and obese-ethanol. Ethanol consumption was monitored for 6 weeks. Basal glycemia, insulin, and glucose overload tests were performed. To assess short- and long-term memory, an object recognition test was used. In order to assess oxidative status in mouse brain samples, antioxidant enzyme activity was analyzed with regard to glutathione peroxidase, glutathione reductase, glutathione, glutathione disulfide, lipid peroxidation products, and malondialdehyde. Ethanol intake modulated the insulin response and impaired the oxidative status in the ob mouse brain.

The COVID-19 pandemic has caused an unprecedented health crisis worldwide, with the numbers of infections and deaths worldwide multiplying alarmingly in a matter of weeks. Accordingly, governments have been forced to take drastic actions such as the confinement of the population and the suspension of face-to-face teaching. In Spain, due to the collapse of the health system the government has been forced to take a series of important measures such as requesting the voluntary incorporation of final-year nursing and medical students into the health system. The objective of the present work is to study, using a phenomenological qualitative approach, the perceptions of students in this exceptional actual situation. A total of 62 interviews were carried out with final-year nursing and medicine students from Jaime I University (Spain), with 85% reporting having voluntarily joined the health system for ethical and moral reasons. Results from the inductive analysis of the descriptions highlighted two main categories and a total of five sub-categories. The main feelings collected regarding mood were negative, represented by uncertainty, nervousness, and fear. This study provides a description of the perceptions of final-year nursing and medical students with respect to their immediate incorporation into a health system aggravated by a global crisis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Ethanol (EtOH), one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. EtOH is centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of EtOH. Although some of the consequences of chronic EtOH administration on cell oxidative status have been described, the mechanisms by which acute EtOH administration affects the brain's cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail., Methods: Swiss CD-I mice were pretreated with the acetaldehyde-sequestering agent d-penicillamine (DP; 75 mg/kg, i.p.) or the antioxidant lipoic acid (LA; 50 mg/kg, i.p.) 30 minutes before EtOH (2.5 g/kg, i.p.) administration. Animals were sacrificed 30 minutes after EtOH injection. Glutathione peroxidase (GPx) mRNA levels; GPx and glutathione reductase (GR) enzymatic activities; reduced glutathione (GSH), glutathione disulfide (GSSG), glutamate, g-L-glutamyl-L-cysteine (Glut-Cys), and malondialdehyde (MDA) concentrations; and protein carbonyl group (CG) content were determined in whole-brain samples., Results: Acute EtOH administration enhanced GPx activity and the GSH/GSSG ratio, while it decreased GR activity and GSSG concentration. Pretreatment with DP or LA only prevented GPx activity changes induced by EtOH., Conclusions: Altogether, these results show the capacity of a single dose of EtOH to unbalance cellular oxidative homeostasis., (© 2019 by the Research Society on Alcoholism.)

Ischemic retinopathies (IRs) are the main cause of severe visual impairment and sight loss, and are characterized by loss of blood vessels, accompanied by hypoxia, and neovascularization. Actual therapies, based on anti-vascular endothelial growth factor (VEGF) strategies, antioxidants or anti-inflammatory therapies are only partially effective or show some adverse side effects. Abscisic acid (ABA) is a phytohormone present in vegetables and fruits that can be naturally supplied by the dietary intake and has been previously studied for its benefits to human health. It has been demonstrated that ABA plays a key role in glucose metabolism, inflammation, memory and tumor growth. This review focuses on a novel and promising role of ABA as a potential modulator of angiogenesis, oxidative status and inflammatory processes in the retina, which are the most predominant characteristics of the IRs. Thus, this nutraceutical compound might shed some light in new therapeutic strategies focused in the prevention or amelioration of IRs-derived pathologies.

Autophagy and exosome secretion play important roles in a variety of physiological and disease states, including the development of age-related macular degeneration. Previous studies have demonstrated that these cellular mechanisms share common pathways of activation. Low oxidative damage in ARPE-19 cells, alters both autophagy and exosome biogenesis. Moreover, oxidative stress modifies the protein and genetic cargo of exosomes, possibly affecting the fate of surrounding cells. In order to understand the connection between these two mechanisms and their impact on angiogenesis, stressed ARPE-19 cells were treated with a siRNA-targeting Atg7, a key protein for the formation of autophagosomes. Subsequently, we observed the formation of multivesicular bodies and the release of exosomes. Released exosomes contained VEGFR2 as part of their cargo. This receptor for VEGF-which is critical for the development of new blood vessels-was higher in exosome populations released from stressed ARPE-19. While stressed exosomes enhanced tube formation, exosomes became ineffective after silencing VEGFR2 in ARPE-19 cells and were, consequently, unable to influence angiogenesis. Moreover, vessel sprouting in the presence of stressed exosomes seems to follow a VEGF-independent pathway. We propose that abnormal vessel growth correlates with VEGFR2-expressing exosomes release from stressed ARPE-19 cells, and is directly linked to autophagy., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Usually several environmental stresses occur in nature simultaneously causing a unique plant response. However, most of the studies until now have focused in individually-applied abiotic stress conditions. Carrizo citrange (Poncirus trifoliata L. Raf. X Citrus sinensis L. Osb.) and Cleopatra mandarin (Citrus reshni Hort. ex Tan.) are two citrus rootstocks with contrasting tolerance to drought and heat stress and have been used in this work as a model for the study of plant tolerance to the combination of drought and high temperatures. According to our results, leaf integrity and photosynthetic machinery are less affected in Carrizo than in Cleopatra under combined conditions of drought and heat stress. The pattern of accumulation of three proteins (APX, HSP101 and HSP17.6) involved in abiotic stress tolerance shows that they do not accumulate under water stress conditions individually applied. However, contents of APX and HSP101 are higher in Carrizo than in Cleopatra under stress combination whereas HSP17.6 has a similar behavior in both types of plants. This, together with a better stomatal control and a higher APX activity of Carrizo, contributes to the higher tolerance of Carrizo plants to the combination of stresses and point to it as a better rootstock than Cleopatra (traditionally used in areas with scare water supplies) under the predictable future climatic conditions with frequent periods of drought combined with high temperatures. This work also provides the basis for testing the tolerance of different citrus varieties grafted on these rootstocks and growing under different field conditions., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

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.

Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction.

Diabetes and alcohol misuse are two of the major challenges in health systems worldwide. These two diseases finally affect several organs and systems including the central nervous system. Hippocampus is one of the most relevant structures due to neurogenesis and memory-related processing among other functions. The present review focuses on the common profile of diabetes and ethanol exposure in terms of oxidative stress and proinflammatory and prosurvival recruiting transcription factors affecting hippocampal neurogenesis. Some aspects around antioxidant strategies are also included. As a global conclusion, the present review points out some common hits on both diseases giving support to the relations between alcohol intake and diabetes.

Purpose: Cocaine abuse is a major public health problem with multiple-related complications. Indeed, cocaine can affect almost every organ of the human body, but little is known about its effects on the visual system. The main purpose of this work was to study if topiramate was able to reverse changes in retinal metabolism and retinal function induced by chronic cocaine exposure in adult rats., Materials and Methods: Sixteen Wistar rats were treated with a daily oral dose of cocaine during 36 days. Sixteen rats receiving NaCl 0.9% served as controls. Eight control and eight cocaine animals were administered topiramate from day 18 to day 36 of the experiment. Malondialdehyde (MDA), glutathione (GSH) and glutamate content, as well as glutathione peroxidase (GPx) activity in retina tissue homogenates were determined. Retinal function was assessed by electroretinogram (ERG)., Results: Glutamate concentration was increased in the retinas of cocaine-treated rats. No changes in oxidative stress parameters were observed in the retinas of cocaine-treated rats when compared with the control ones. Cocaine induced a decrease in the a-wave and b-wave ERG amplitude. The administration of topiramate reversed cocaine-induced increase in glutamate concentration and had little effect on a-wave and b-wave ERG amplitude. Topiramate, a drug used during the last decade for the treatment of epileptic seizures, is able to reverse the cocaine-induced alterations observed in retinal glutamate concentration., Conclusions: We can conclude that retinal glutamate metabolism and function may be affected by exposure to cocaine. We confirm that topiramate, a treatment recently proposed for cocaine dependence, is also able to recover partially cocaine-induced changes in the retina.

The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60-70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration.

Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB), a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation.

Naltrexone, an antagonist of μ-opioid receptors, is clinically used as adjuvant therapy of alcohol dishabituation. The aim of the present work was to test the effect of 1 mg/kg body weight of naltrexone to revert oxidative stress-related biochemical alterations, in the hippocampus and serum of chronic alcoholic adult rats. Malondialdehyde concentration was increased and glutathione peroxidase activity was decreased in hippocampus and serum of alcohol-treated rats. Naltrexone treatment restored these alterations. The in vitro antioxidant ability of Ntx could not justify these effects considering the doses used. Thus this apparent protective effect of Ntx can only be attributed to its pharmacological effects, as herein discussed.

Aims: Early ethanol consumption could be a risk factor for young brain integrity and its maturation, and also for the development of addictive behaviors in adulthood. Neuronal nitric oxide synthase (nNOS) expressing neurons are specifically located in the subgranular layer (SGL) of dentate gyrus and may be relevant for hippocampal neurogenesis. The focus of this work is aimed to determine local changes in the nNOS-like immunoreactive (nNOS-LIR) cell populations of the SGL after chronic ethanol exposure in young adult and mature adult rats., Methods: We used the nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPH-d) reaction as a qualitative marker of nNOS enzyme activity. We also analyzed the nNOS-LIR cell density by the nNOS immunocytochemistry in order to compare these two methods of labeling. Dorsal striatum (CPu) was also analyzed in order to compare two neural areas with high nNOS-LIR cell density., Results: The young adult group showed less hippocampal NADPH-d(+) cell density than the mature adult group. Interestingly, the NADPH-d(+) cell density was increased in the SGL of the young adult ethanol-treated group, whereas it decreased in the mature adult ethanol-treated group, when compared with their respective controls. No change was observed in any of the groups for the hippocampal nNOS-LIR cell density and no differences could be established in CPu for nNOS-LIR and NADPH-d(+) cell densities in any of the groups studied., Conclusion: The NADPH-d expression is affected by chronic ethanol exposure in opposite ways between both age groups studied. Further studies are needed to evaluate the relative importance of these findings, especially when considering human subjects.

Purpose: Bevacizumab is currently used as an intravitreal agent in the treatment of inflammatory-associated eye diseases. The aim of the current study is to explore the effects of the intravitreal injection of bevacizumab on aqueous humour cytokines and chemokines in an experimental uveitis model., Methods: Endotoxin-induced uveitis was induced in rats by footpad injections. Bevacizumab was administered by intravitreal injection (75 µg in 3-µL samples) and different chemokine and cytokine proteins were quantified in aqueous humor., Results: Intravitreal administration of bevacizumab led to a several-fold increase of RANTES, MCP-1, and IFN-γ concentrations in aqueous humor of endotoxin-treated rats., Conclusions: Given the exacerbating effect of bevacizumab on inflammation agents and considering the increasing use of bevacizumab as an off-label intravitreal agent, care should be taken if an underlying inflammatory disease is present.

Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.

When breast milk extraction and storage is required before ingestion, it is important to establish the conditions that ensure the least losses in milk quality, like the antioxidant capacity. The present study evaluates glutathione peroxidase activity and malondialdehyde concentration of breast milk when stored frozen, comparing the effects of 2 temperatures (-20 degrees C and -80 degrees C) and different storage times (15, 30, and 60 days). The results indicate that freezing induces losses in the antioxidant properties of breast milk and that such losses increase with the duration of storage and differ in intensity according to the temperature. It is concluded that to maximally preserve the antioxidant properties of breast milk, it is advisable to store the latter at -80 degrees C for a period of less than 30 days, rather than for shorter time periods at the usual temperature of -20 degrees C.

Background: Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. It is often associated with complications, such as cataracts. Cataract, characterized by cloudiness or opacity of the eye lens, is the leading cause of blindness worldwide., Methods: The present study investigated the effect of lutein, alone or combined with insulin on the progression of eye lens opacities in streptozotocin-diabetic rats for a period of 12 weeks. Tissue markers of oxidative stress were also determined at the end of the experiment., Results: Herein we demonstrate that lutein treatment prevents the development and progression of cataracts (0 eyes with mature cataract, and ten out of 16 eyes with clear lenses in the lutein-treated diabetic animals group, vs. seven and three eyes in the non-treated diabetic group, respectively). Lipid peroxidation is significantly increased in diabetic lens (up to three-fold); lutein and insulin, alone or in combination, are able to prevent this alteration. Only insulin and lutein together could prevent the diabetes-induced decrease of glutathione content., Conclusions: The combined treatment with lutein and insulin is useful in preventing the development of cataracts in streptozotocin-induced diabetic rats, supporting its utility in diabetes management, especially when a tight metabolic control is difficult to achieve.

Aims: To study the histopathological, biochemical and functional effects of intravitreal bevacizumab on the rat eye, with special emphasis on its immediate pro-inflammatory features eventually associated with cellular oxidative burden., Methods: Histopathological evaluation was performed 24 h, 1 and 4 weeks after bevacizumab (75 microg/rat eye) or saline intravitreal injection, as well as biochemical analysis of oxidative stress-related markers and electroretinograms., Results: Bevacizumab induces a transient inflammatory reaction together with a modification of the b-wave amplitude and latency of the electroretinogram. No changes were observed in any of the oxidative stress markers studied at any time after injection., Conclusion: Intravitreal bevacizumab injection per se generates an immediate, transient and mild inflammation of the rat eye, which is not associated with oxidative stress in ocular tissues., (Copyright 2008 S. Karger AG, Basel.)