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Objective: Protein-energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols (PP), in combination with muscle anabolic effect of adequate dietary protein intake and physical exercise to prevent the age-dependent decline of muscle mass and its key underpinning mechanisms including mitochondrial function, and nutrient metabolism in muscle in the elderly., Methods and Analysis: In 2020, a 6-month double-blind randomised controlled trial in 75 predementia older people was launched to prevent muscle mass loss, in respond to the 'Joint Programming Initiative A healthy diet for a healthy life'. In the run-in phase, participants will be stabilised on a protein-rich diet (0.9-1.0 g protein/kg ideal body weight/day) and physical exercise programme (high-intensity interval training specifically developed for these subjects). Subsequently, they will be randomised into three groups (1:1:1). The study arms will have a similar isocaloric diet and follow a similar physical exercise programme. Control group (n=25) will maintain the baseline diet; intervention groups will consume either 30 g/day of dark chocolate containing 500 mg total PP (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (n=25); or the high polyphenol chocolate without additional vitamin E (n=25). Muscle mass will be the primary endpoint. Other outcomes are neurocognitive status and previously identified biomolecular indices of frailty in predementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Blood and plasma samples will be analysed for laboratory endpoints including nutrition metabolism and omics., Ethics and Dissemination: All the ethical and regulatory approvals have been obtained by the ethical committees of the Azienda Ospedaliera Universitaria Integrata of Verona with respect to scientific content and compliance with applicable research and human subjects' regulation. Given the broader interest of the society toward undernutrition in the elderly, we identify four main target audiences for our research activity: national and local health systems, both internal and external to the project; targeted population (the elderly); general public; and academia. These activities include scientific workshops, public health awareness campaigns, project dedicated website and publication is scientific peer-review journals., Trial Registration Number: NCT05343611., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Centenarians exhibit extreme longevity and compression of morbidity and display a unique genetic signature. Centenarians' offspring seem to inherit centenarians' compression of morbidity, as measured by lower rates of age-related pathologies. We aimed to ascertain whether centenarians' offspring are less frail and whether they are endowed with a "centenarian genetic footprint" in a case-control study, matched 1:1 for gender, age ±5 years, and place of birth and residence. Cases must have a living parent aged 97 years or older, aged 65-80 years, community dwelling, not suffering from a terminal illness, or less than 6 months of life expectancy. Controls had to meet the same criteria as cases except for the age of death of their parents (not older than 89 years). Centenarians were individuals 97 years or older. Frailty phenotype was determined by Fried's criteria. We collected plasma and peripheral blood mononuclear cells from 63 centenarians, 88 centenarians' offspring, and 88 noncentenarians' offspring. miRNA expression and mRNA profiles were performed by the GeneChip miRNA 4.0 Array and GeneChip Clariom S Human Array, respectively. We found a lower incidence of frailty among centenarians' offspring when compared with their contemporaries' noncentenarians' offspring (p < .01). Both miRNA and mRNA expression patterns in centenarians' offspring were more like those of centenarians than those of noncentenarians' offspring (p < .01). In conclusion, centenarians' offspring are less frail than age-matched noncentenarians' offspring, and this may be explained by their unique genetic endowment., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

RCAN1 is an inhibitor of the phosphatase calcineurin, which is involved in the regulation of oxidative stress and apoptosis, among other important cell processes. Here we have used RCAN1 deficient mice (RCAN1 -/- ) to elucidate its role after an acute oxidative insult such as paraquat injection. We have observed that RCAN1 -/- mice show less oxidative damage than wildtype (WT) mice after treatment. Under basal conditions, RCAN1 -/- animals express more calcineurin, heme oxygenase-1, Nrf2, and catalase compared to WT mice (controls). This may explain the less severe effect of paraquat treatment on RCAN1 -/- mice compared to WT. We showed that oxidative stress is involved in the early stages of apoptosis, thus we determined the apoptotic effector BAD and found that decreases in RCAN1 -/- mice after treatment with paraquat compared with WT in similar experimental conditions. Our results suggest that RCAN1 may be involved in the balance between oxidant and antioxidant species production in vivo .

Physical exercise performed regularly is known to improve health and to reduce the risk of age-related diseases. Furthermore, there is some evidence of cognitive improvement in physically active middle-aged and older adults. We hypothesized that long-term physically active middle-aged men may have developed brain resilience that can be detected with the analysis of peripheral blood markers. We aimed to analyze the activation of pathways potentially modulated by physical activity in a cohort of healthy amateur rugby players ( n = 24) and control subjects with low physical activity ( n = 25) aged 45-65 years. We had previously reported neuropsychological improvement in immediate memory responses in the player group compared to the controls. Here, we tested the expression of selected genes of longevity, inflammation, redox homeostasis, and trophic signaling in whole blood mRNA. Analyses were also performed on blood samples of young (aged 15-25 years) control subjects with low physical activity ( n = 21). Physical activity and other lifestyle factors were thoroughly recorded with standardized questionnaires. Interestingly, middle-aged control subjects showed lower levels of expression of SIRT1, SIRT3, CAT, and SOD1 than the young controls, although rugby players maintained the expression levels of these genes at a young-like level. Middle-aged players showed lower levels of IL1B than the non-physically active groups. However, there was a tendency towards a decrease in trophic and transduction factors in middle-aged groups as compared to the young controls. A statistical study of Spearman's correlations supported a positive effect of sporting activity on memory and executive functions, and on peripheral gene expression of SIRT1, SIRT3 and downstream genes, in the middle-aged rugby players. Our results indicate that the SIRT1-SIRT3 axis, and associated neuroprotective signaling, may contribute to the anti-aging resilience of the brain mediated by physical exercise., (Copyright © 2019 Corpas, Solana, De la Rosa, Sarroca, Griñán-Ferré, Oriol, Corbella, Rodríguez-Farré, Vina, Pallàs, Bartrés-Faz, Gomez-Cabrera and Sanfeliu.)

The data presented in this article are related to the research paper entitled "Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1alpha overexpression in vivo" (Yeo et al., 2019). The data explained the surgical procedure of in vivo local transfection by electroporation method in aged mouse tibialis anterior muscle, and plasmid DNA preparation and verification protocol. The data also showed the transfection efficiency levels of GFP or GFP-tagged PGC-1alpha through immunohistochemistry method for frozen muscle cross-sections.

Purpose: To analyze, in vitro, the influence of O₂ pressure on the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells (DPSC) on β-tricalcium phosphate (β-TCP) scaffold., Materials and Methods: DPSC, positive for the molecular markers CD133, Oct4, Nestin, Stro-1, and CD34, and negative for CD45, were isolated from extracted third molars. Experiments were started by seeding 200,000 cells on β-TCP cultured under 3% or 21% O₂ pressure. No osteogenic medium was used. Eight different cultures were performed at each time point under each O₂ pressure condition. Cell adhesion, proliferation, and differentiation over the biomaterial were evaluated at 7, 13, 18, and 23 days of culture. Cell adhesion was determined by light microscopy, proliferation by DNA quantification, and osteogenic differentiation by alkaline phosphatase (ALP) activity analysis., Results: DPSC adhered to β-TCP with both O₂ conditions. Cell proliferation was found from day 7 of culture. Higher values were recorded at 3% O₂ in each time point. Statistically significant differences were recorded at 23 days of culture (P = .033). ALP activity was not detectable at 7 days. There was, however, an increase in ALP activity over time in both groups. At 13, 18, and 23 days of culture, higher ALP activity was recorded under 3% O₂ pressure. Statistical differences were found at day 23 (P = .014)., Conclusion: DPSC display capacity of adhering to β-TCP under 3% or 21% O₂ pressure conditions. Cell proliferation on β-TCP phosphate is significantly higher at 3% than at 21% O₂ pressure, the most frequently used O₂ tension. β-TCP can itself promote osteogenic differentiation of DPSC and is enhanced under 3% O₂ compared with 21%.

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Free radicals and oxidants are now implicated in physiological responses and in several diseases. Given the wide range of expertise of free radical researchers, application of the greater understanding of chemistry has not been uniformly applied to biological studies. We suggest that some widely used methodologies and terminologies hamper progress and need to be addressed. We make the case for abandonment and judicious use of several methods and terms and suggest practical and viable alternatives. These changes are suggested in four areas: use of fluorescent dyes to identify and quantify reactive species, methods for measurement of lipid peroxidation in complex biological systems, claims of antioxidants as radical scavengers, and use of the terms for reactive species., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Muscle atrophy is linked to reactive oxygen species (ROS) production during hindlimb-unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of our study was to determine the mechanism by which ROS cause muscle atrophy and its possible prevention by allopurinol, a well-known inhibitor of XO widely used in clinical practice, and indomethacin, a nonsteroidal anti-inflammatory drug. We studied the activation of p38 MAP Kinase and NF-?B pathways, and the expression of two E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFb) and Muscle RING Finger-1 (MuRF-1). Male Wistar rats (3 mold) conditioned by 14 days of hindlimb unloading (n=18), with or without the treatment, were compared with freely ambulating controls (n=18). After the experimental intervention, soleus muscles were removed, weighted and analyzed to determine oxidative stress and inflammatory parameters. We found that hindlimb unloading induced a significant increase in XO activity in plasma (39%, p=0.001) and in the protein expression of CuZnSOD and Catalase in skeletal muscle. Inhibitionof XO partially prevented protein carbonylation, both in plasma and in soleus muscle, in the unloaded animals. The most relevant new fact reported is that allopurinol prevents soleus muscle atrophy by ~20% after hindlimb unloading. Combining allopurinol and indomethacin we found a further prevention in the atrophy process. This is mediated by the inhibition of the p38 MAPK-MAFbx and NF-?B -MuRF-1 pathways. Our data point out the potential benefit of allopurinol and indomethacin administration for bedridden, astronauts, sarcopenic and cachexic patients., (Copyright © 2014. Published by Elsevier Inc.)

The anaphase-promoting complex APC/C is a E3 ligase. It is regulates important functions in neural cells. Its inactivation and accumulation of its substrates has been related with neurodegenerative diseases. Glutaminase is an important target of APC/C-Cdh1 in primary neurons. It catalyzes the conversion of glutamine into glutamate. When cdh1 decreases due to incubation with Aβ, glutaminase concentration increases as does cyclin B1, a known target of the ubiquitin ligase that is involved in the pathophysiology of Alzheimer's disease (AD). The same treatment causes a high increase of glutamate levels in the supernatant of neurons in culture, which subsequently leads to an increase of Ca(2) inside the cells. The increase of glutamate due to the Aβ treatment can be partially reversed by a glutaminase inhibitor. This result suggests that the APC/C-Cdh1 signaling way is involved in the glutamate increase after the treatment with Aβ. Moreover, high levels of glutamate have been observed to further decrease cdh1 levels what also leads to an accumulation of gls. These results lead us to propose that neurons might enter into a positive feedback loop of glutamate production due to a lack of APC/C-Cdh1 signaling. This signaling pathway reveals a new mechanism to cause excitotoxicity in neurons, which could be relevant in AD., (Copyright © 2014. Published by Elsevier Inc.)

One of the most significant achievements of the twentieth century is the increase in human lifespan. In any period studied, females live longer than males. We showed that mitochondrial oxidative stress is higher in males than females and that the higher levels of estrogens in females protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. The chemical structure of estradiol confers antioxidant properties to the molecule. However, the low concentration of estrogens in females makes it unlikely that they exhibit significant antioxidant capacity in the organism. Therefore we studied the mechanisms enabling estradiol to be antioxidant at physiological levels. Our results show that physiological concentrations of estrogens activate estrogen receptors and the MAPK and NFKB pathway. Activation of NFkB by estrogens subsequently activates the expression of Mn-SOD and GPx. Moreover, we have demonstrated that genistein, the most abundant phytoestrogen in soya, reproduces the antioxidant effect of estradiol at nutritionally relevant concentrations by the same mechanism, both in healthy ageing and in Alzheimer's disease. We conclude that estrogens and phytoestrogens up-regulate expression of antioxidant enzymes via the estrogen receptor and MAPK activation, which in turn activate the NFkB signalling pathway, resulting in the up-regulation of the expression of longevity-related genes.

Lipid peroxidation products like malondialdehyde, 4-hydroxynonenal and F(2)-isoprostanes are widely used as markers of oxidative stress in vitro and in vivo. This study reports the results of a multi-laboratory validation study by COST Action B35 to assess inter-laboratory and intra-laboratory variation in the measurement of lipid peroxidation. Human plasma samples were exposed to UVA irradiation at different doses (0, 15 J, 20 J), encoded and shipped to 15 laboratories, where analyses of malondialdehyde, 4-hydroxynonenal and isoprostanes were conducted. The results demonstrate a low within-day-variation and a good correlation of results observed on two different days. However, high coefficients of variation were observed between the laboratories. Malondialdehyde determined by HPLC was found to be the most sensitive and reproducible lipid peroxidation product in plasma upon UVA treatment. It is concluded that measurement of malondialdehyde by HPLC has good analytical validity for inter-laboratory studies on lipid peroxidation in human EDTA-plasma samples, although it is acknowledged that this may not translate to biological validity.

Skeletal muscle contraction, growth, differentiation and adaptation are governed by complicated biological mechanisms still being studied intensively. Generation of reactive oxygen and nitrogen species (RS) is one of the most prominent events during contractile activity that could influence muscle function and health. While RS generation is known to cause oxidative stress, activate certain pathogenic pathways and aging, they also serve as useful signaling molecules to regulate gene expression of proteins and enzymes that play a vital role in the normal muscle function and defense against detrimental effects of RS. The purpose of the present review is two-fold: first, to provide an overview of cell signaling controlled by a redox sensitive mechanism and its impact on skeletal muscle health and function; and second, to review the various muscular diseases and disorders that have an etiological origin of RS overproduction and/or inadequate antioxidant defense. Given the physiological role of skeletal muscle we will emphasize the importance of physical exercise in promoting cellular antioxidant defense and its benefits in the maintenance of muscle health.

Activation of nuclear factor (NF) kappaB and mitogen-activated protein kinase (MAPK) pathways in skeletal muscle has been shown to enhance the gene expression of several enzymes that play an important role in maintaining oxidant-antioxidant homeostasis, such as mitochondrial superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS). While an acute bout of exercise activates NF kappaB and MAPK signaling and upregulates MnSOD and iNOS, administration of chemical agents that suppress reactive oxygen species (ROS) production can cause attenuation of exercise-induced MnSOD and iNOS expression. Thus, ROS generation during exercise may have duel effects: the infliction of oxidative stress and damage, and the stimulation of adaptive responses favoring long-term protection. This scenario explains why animals and humans involved in exercise training have demonstrated increased resistance to oxidative damage under a wide range of physiological and pathological stresses.

Females live longer than males in many mammalian species, including humans. This natural phenomenon can be explained on the basis of the mitochondrial theory of aging. Mitochondria are a major source of free radicals in cells. Mitochondria from female rats generate half the amount of hydrogen peroxide than those of males and have higher levels of mitochondrial reduced glutathione. The latter is due to females behaving as double transgenic in over-expressing antioxidant enzymes. Estrogens bind to the estrogen receptors and subsequently activate the mitogen activated protein (MAP) kinase and nuclear factor kappa B (NFkappaB) signalling pathways, resulting in an upregulation of antioxidant enzymes. Moreover, the 16S rRNA expression, which decreases significantly with aging, is four times higher in mitochondria from females than in those from males of the same chronological age. On the contrary, the oxidative damage of mitochondrial DNA is fourfold higher in males than in females. Ovariectomy abolishes the gender differences between males and females and estrogen replacement rescues the effect of ovariectomy. The challenge for the future is to find molecules that have the beneficial effects of estradiol, but without its feminizing effects. Phytoestrogens or phytoestrogen-related molecules may be good candidates to meet this challenge.

Oxidative stress is involved in the pathogenesis and progression of different liver diseases, such as alcoholic liver disease and biliary cirrhosis. The increased mitochondrial production of O2(-) at complexes I and III, and consequently of H2O2 and other reactive oxygen species (ROS), triggered by NADH overproduction seems the major cause of mitochondrial and cellular oxidative stress and damage in chronic alcoholism. The mitochondrial oxidative stress renders hepatocytes susceptible to ethanol- or acetaldehyde-induced mitochondrial membrane permeability transition (MMPT) and apoptosis. Nitrosative stress contributes to cell death by peroxynitrite formation. The expression of the death receptor ligand CD95 is also up-regulated by acetaldehyde metabolism. Consequently, a dual mechanism, NADH-driven MMPT and CD95-mediated apoptosis, involving in both cases acetaldehyde metabolism and ROS production, operates in ethanol-induced apoptosis. In the biliary cirrhosis induced by chronic cholestasis, liver mitochondria show increased H2O2 production and GSH depletion and oxidation. Dysfunctional hepatocytes, with a loss in mitochondrial cardiolipin and decreased mitochondrial membrane potential evolve during cholestasis to apoptosis. Ursodeoxycholic acid prevents enlargement of this population as well as mitochondrial oxidative stress. Mitochondrial oxidative stress precedes the initiation and execution of hepatocyte apoptosis in chronic alcoholism and biliary cirrhosis. We suggest that overproduction of mitochondrial NADH is the primary cause for the development of alcoholic and non-alcoholic liver disease by a situation of chronic mitochondrial oxidative stress, which should be considered the second hit that renders hepatocytes susceptible to cell injury and apoptosis.

Contraction-induced production of reactive oxygen species (ROS) has been shown to cause oxidative stress to skeletal muscle. As an adaptive response, muscle antioxidant defense systems are upregulated after heavy exercise. Nuclear factor (NF) kappaB and mitogen-activated protein kinases (MAPKs) are the major oxidative stress-sensitive signal transduction pathways in mammalian tissues. Activation of NF-kappaB signaling cascade has been shown to enhance the gene expression of important enzymes, such as mitochondrial superoxide dismutase (MnSOD) and inducible nitric oxide synthase (iNOS). MAPK activations are involved in a variety of cellular functions including growth, proliferation, and adaptation. We investigated the effect of an acute bout of exercise on NF-kappaB and MAPK signaling, as well as on the time course of activation, in rat skeletal muscle. In addition, we studied the role of ROS in the exercise-induced upregulation of MnSOD and iNOS, and the potential interactions of NF-kappaB and MAPK in the signaling of these enzymes. Our data suggest that ROS may serve as messenger molecules to activate adaptive responses through these redox-sensitive signaling pathways to maintain cellular oxidant-antioxidant homeostasis during exercise.

There is increasing evidence that reactive oxygen species (ROS) are not only toxic but play an important role in cellular signalling and in the regulation of gene expression. We, here, discuss two examples of improved adaptive response to an altered cellular redox state. First, differences in longevity between males and females may be explained by a higher expression of antioxidant enzymes in females resulting in a lower yield of mitochondrial ROS. Oestrogens are made responsible for these phenomena. Oestradiol induces glutathione peroxidase-1 and MnSOD by processes requiring the cell surface oestrogen receptor (ER) and the activation of pathways usually involved in oxidative stress response. Second, oxygen radicals produced during moderate exercise as performed during training up-regulate the expression of antioxidant enzymes in muscle cells. An increased level of these enzymes might prevent oxidative damage during exhaustive exercise and should, therefore, not be prevented by antioxidants. The relevance of these findings is discussed in the context with observations made in transgenic animals overexpressing MnSOD or catalase.

Oxidants may play a role in hypoxia-induced respiratory muscle dysfunction. In the present study we hypothesized that hypoxia-induced impairment in diaphragm contractility is associated with elevated peroxynitrite generation. In addition, we hypothesized that strenuous contractility of the diaphragm increases peroxynitrite formation. In vitro force-frequency relationship, isotonic fatigability, and nitrotyrosine levels were assessed under hypoxic (Po(2) approximately 6.5 kPa) and hyperoxic (Po(2) approximately 88.2 kPa) control conditions and also in the presence of authentic peroxynitrite (60 min), ebselen (60 min), and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine acetate (L-NMMA) (90 min). A hypoxia-induced downward shift of the force-frequency relationship was associated with elevated nitrotyrosine level in the diaphragm. During hypoxia, both ebselen and L-NMMA decreased nitrotyrosine levels but did not affect force generation. Strenuous contractions impaired force generation but did not affect nitrotyrosine levels in the diaphragm during hypoxia. But under hyperoxic conditions, fatiguing contractions were associated with elevated diaphragm nitrotyrosine levels. Under hyperoxic conditions exogenous peroxynitrite impaired force generation and increased nitrotyrosine level. These studies show that hypoxia-induced impairment in diaphragm contractility is associated with increased diaphragm protein nitration, but no causal relationship was found between diaphragm nitrotyrosine formation and in vitro force generation.

Free radicals may be involved in apoptosis although this is the subject of some controversy. Furthermore, the source of free radicals in apoptotic cells is not certain. The aim of this study was to elucidate the role of oxidative stress in the induction of apoptosis in serum-deprived fibroblast cultures and in weaned lactating mammary glands as in vitro and in vivo experimental models, respectively. Oxidative damage to mtDNA is higher in apoptotic cells than in controls. Oxidized glutathione (GSSG) levels in mitochondria from lactating mammary gland are also higher in apoptosis. There is a direct relationship between mtDNA damage and the GSSG/reduced glutathione (GSH) ratio. Furthermore, whole cell GSH is decreased and GSSG is increased in both models of apoptosis. Glutathione oxidation precedes nuclear DNA fragmentation. These signs of oxidative stress are caused, at least in part, by an increase in peroxide production by mitochondria from apoptotic cells. We report a direct relationship between glutathione oxidation and mtDNA damage in apoptosis. Our results support the role of mitochondrial oxidative stress in the induction of apoptosis.

The ability of nonprotein thiols to modulate rates of protein synthesis was investigated in isolated rat hepatocytes. Addition of cysteine stimulates protein labelling by [14C]Leucine. Glutathione depletion, induced by in vivo administration of L-buthionine sulfoximine and diethylmaleate, did not alter the effect of cysteine, although it decreased the rate of protein synthesis by 32%. The effect of cysteine on protein synthesis does not seem to be related to a perturbation of the redox state of the NAD+/NADH system or to changes in the rate of gluconeogenic pathway. The following observations indicate that cysteine may stimulate protein synthesis by increasing intracellular levels of aspartate: 1. Amino-oxyacetate, an inhibitor of pyridoxal-dependent enzymes, inhibits protein labelling and decreases aspartate cellular content, whereas most amino acids accumulate or remain unchanged; 2. Cysteine, in the absence or in the presence of amino-oxyacetate, stimulates protein labelling and induces aspartate accumulation, although most amino acids diminish or remain unchanged.

Ureteropelvic junction (UPJ) obstruction constitutes the most common form of upper urinary tract obstruction in children. We study the role of diuretic renography and its correlation with other diagnostic methods for postoperative evaluation of this malformation. We reviewed 13 patients, 10 males and 3 females aged 1 months to 15 years, and with right UPJ obstruction in six and left obstruction in seven. In all of them pre and postoperative IVP, abdominal ultrasound, diuretic renography, and pressure flow studies. Were performed our results demonstrated a non-correlation between the findings of excretory urogram, abdominal ultrasound and diuretic renography and a close relation between pressure flow studies and diuretic nephrography. This two last methods are good tools for assessment of UPJ obstruction.

The influence of several anti-inflammatory drugs, steroidal and nonsteroidal, on infarct size (quantification by epicardial electrocardiograms and expressed as percentage of left ventricular weight), coronary retrograde flow (measured by collection), frequency of infarction-arrhythmias (expressed as number of premature ventricular beats per min in the after-occlusion period) and hemodynamics, was examined on a model of acute transmural infarction in anesthetized open-chest dogs. Propranolol, used as a reference drug, produced a significant decrease of the infarct size. Indomethacin, (10 mg/kg i.v.) increased infarct size and ectopic rate and decreased retrograde flow while developing greater tachycardia and less hypotension than in controls. Acetylsalicylic acid (30 mg/kg i.v.) and meclofenamic acid (1 mg/kg i.v.) decreased infarct size without altering other parameters except for an increase in retrograde flow produced by acetylsalicylic acid. Ibuprofen (15 mg/kg i.v.) did not significantly affect any of the parameters considered in this study. Hydrocortisone (25 mg/kg i.v.) did not modify infarct size, collateral flow or hemodynamics but increased ectopic rate. These results emphasize the differential effects of anti-inflammatory drugs on acute myocardial infarction and suggest that mechanisms other than stabilization of myocardial lysosomes of inhibition of platelet aggregation may be involved, probably of direct, metabolic or cellular, nature.

Glutathione (GSH) decreases in dog myocardium upon acute coronary occlusion when compared with sham-operated dogs. Total glutathione content (GSHeq = GSH + 2GSSG) remains unchanged throughout the experiment (6 h after surgery) in both sham- and acute coronary occlusion-operated dogs. GSSG and GSH/GSSG ratio increases and decreases respectively in all animals but tends to reach the normal value after 6 h in sham-operated dogs. Both parameters (GSSG and GSH/GSSG ratio) remain altered in acute coronary occlusion-operated ones. This alteration of glutathione status in ischemic myocardium is discussed.