The challenges of formal volunteering in hospitals.

The role and tasks performed by hospital volunteers (HV), their relationship with other stakeholders and the management of volunteers, are controversial topics, not widely explored in literature. Through an exploratory study, which incorporated the collection and analysis of qualitative data, involving 46 interviews with volunteers, staff and hospital administration from three hospitals in Portugal, we analyze hospital volunteers, as well as the tasks they perform, how these tasks are assigned, and how they relate to other stakeholders. As a result, we conclude that the job definition of HV is generic, open to different interpretations and that the assigned functions of HV are not known from all stakeholders. This problem can have negative repercussions in the relationship between volunteers and health professionals, potentially fostering conflict. Nevertheless, most respondents are satisfied with the current format of volunteer management.

Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease.

Alzheimer disease (AD) is a neurodegenerative disease which is characterized by the presence of extracellular senile plaques mainly composed of amyloid-beta peptide (Abeta), intracellular neurofibrillary tangles, and selective synaptic and neuronal loss. AD brains revealed elevated levels of oxidative stress markers which have been implicated in Abeta-induced toxicity. In the present work we addressed the hypothesis that oxidative stress occurs early in the development of AD and evaluated the extension of the oxidative stress and the levels of antioxidants in an in vivo model of AD, the triple-transgenic mouse, which develops plaques, tangles, and cognitive impairments and thus mimics AD progression in humans. We have shown that in this model, levels of antioxidants, namely, reduced glutathione and vitamin E, are decreased and the extent of lipid peroxidation is increased. We have also observed increased activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. These alterations are evident during the Abeta oligomerization period, before the appearance of Abeta plaques and neurofibrillary tangles, supporting the view that oxidative stress occurs early in the development of the disease.

Doxorubicin increases the susceptibility of brain mitochondria to Ca(2+)-induced permeability transition and oxidative damage.

This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg(-1)), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca2+. No statistical differences were observed in the other parameters analyzed. Altogether our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca(2+)-induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death.

The effect of soybean oil on glycaemic control in Goto-kakizaki rats, an animal model of type 2 diabetes.

UNLABELLED: Several studies in humans and laboratory animals with type 2 diabetes indicate that antioxidant supplements lessen the impact of oxidative damage caused by dysregulation of glucose metabolism. The present study was undertaken to examine the effect of soybean oil on glycaemic control and lipid metabolism in Goto-kakizaki (GK) rats, a model of type 2 diabetes. Rats were divided into three groups, a control group of non-diabetic (Wistar) rats, a group of diabetic GK rats and a group of GK rats treated with soybean oil. Plasma samples from the different groups were analysed for total alpha-tocopherol, coenzyme Q and glucose levels. Glycated haemoglobin was also compared between the different groups. Fasting and non-fasting blood glucose levels were significantly decreased in soybean oil group compared with GK group. There was also a 14 % reduction in the levels of HbA(1c) in SO-treated GK when compared with the diabetic control group. Diabetes induced a decrease in coenzyme Q plasma levels that prevailed after treatment with soybean oil. Moreover, the plasma alpha-tocopherol levels were higher after treatment with soybean oil. CONCLUSIONS: Our observations suggest that soybean oil treatment may be beneficial in type 2 diabetes. Since soybean oil has very high amounts of coenzyme Q and other antioxidants one possible mechanism of action could be as an antioxidant.

Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes.

We aimed to investigate whether metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H(2)O(2)) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK rats, while TBARS levels, carbonyl groups, glutathione content and vitamin E levels remain statistically unchanged when compared with control rats. In contrast, MnSOD activity and the levels of H(2)O(2) are significantly decreased in untreated GK rats when compared with control animals. However, metformin treatment normalized the majority of the parameters altered by diabetes. We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity. These results indicate that metformin protects against diabetes-associated oxidative stress suggesting that metformin could be an effective neuroprotective agent.

Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress.

We previously demonstrated that insulin has a neuroprotective role against oxidative stress, a deleterious condition associated with diabetes, ischemia, and age-related neurodegenerative diseases. In this study, we investigated the effect of insulin on neuronal glucose uptake and metabolism after oxidative stress in rat primary cortical neurons. On oxidative stress, insulin stimulates neuronal glucose uptake and subsequent metabolism into pyruvate, restoring intracellular ATP and phosphocreatine. Insulin also increases intracellular and decreases extracellular adenosine, counteracting the effect of oxidative stress. Insulin effects are apparently mediated by phosphatidylinositol 3-K and extracellular signal-regulated kinase signaling pathways. Extracellular adenosine under oxidative stress is largely inhibited after blockade of ecto-5'-nucleotidase, suggesting that extracellular adenosine results preferentially from ATP release and catabolism. Moreover, insulin appears to interfere with the ATP release induced by oxidative stress, regulating extracellular adenosine levels. In conclusion, insulin neuroprotection against oxidative stress-mediated damage involves 1) stimulation of glucose uptake and metabolism, increasing energy levels and intracellular adenosine and, ultimately, uric acid formation and 2) a decrease in extracellular adenosine, which may reduce the facilitatory activity of adenosine receptors.

Endothelial dysfunction in type 2 diabetes: effect of antioxidants.

Individuals with insulin resistance and diabetes mellitus have increased cardiovascular morbidity and mortality, caused in part by vascular complications. Endothelial dysfunction has been implicated in the pathogenesis of vascular diabetic disease. This abnormal function of the vasculature precedes cardiovascular disease and is associated with impaired endothelium-dependent vasorelaxation. The main etiology of the increased mortality and morbidity of type 2 diabetic patients is atherosclerosis. Increased production of free radicals is associated with the pathophysiology of diabetes, resulting in oxidative damage to lipids and proteins. Reduction of oxidative stress in diabetic patients may delay the onset of atherogenesis and the appearance of micro- and macrovascular complications. Alpha-lipoic acid (LA) is a multifunctional antioxidant that has been shown to have beneficial effects on polyneuropathy and on markers of oxidative stress in various tissues. This study was conducted to investigate the effects of LA on endothelial function in diabetic and hyperlipidemic animal models. Carbohydrate and lipid metabolism, endothelial function, plasma malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated diabetic Goto-Kakizaki (GK) rats and, atherogenic diet (AD)-fed GK rats (fed with atherogenic diet only, treated with alpha-lipoic acid and treated with vehicle, for 3 months). AD resulted in a 3-fold increase in both total and non-HDL serum cholesterol levels and in a 2-fold increase triglyceride levels while endothelial function was significantly reduce MDA and 8-OHdG levels were higher in the GK and GK hyperlipidemic groups and were completely reversed by the antioxidant. Hyperlipidemic GK diabetic rats showed significantly reduced endothelial function that was partially improved with LA. Furthermore, lipoic acid significantly reduced serum cholesterol levels, without lowering HDL cholesterol. Alpha-lipoic acid supplementation represents an achievable adjunct therapy to improve endothelial function and reduce oxidative stress, factors that are implicated in the pathogenesis of atherosclerosis in diabetes.

Oxidative stress adaptation in aggressive prostate cancer may be counteracted by the reduction of glutathione reductase.

Oxidative stress has been associated with prostate cancer development and progression due to an increase of reactive oxygen species (ROS). However, the mechanisms whereby ROS and the antioxidant system participate in cancer progression remain unclear. In order to clarify the influence of oxidative stress in prostate cancer progression, we performed this study in two human prostate cancer cell lines, PC3 and HPV10 (from metastasis and from localized cancer, respectively) and RWPE1 cells derived from normal prostate epithelium. Cells were treated with hydrogen peroxide (H2O2) and PC3 cells were also treated with diethyl maleate (DEM). The effect on cell growth, viability, mitochondria membrane potential and oxidative stress was analysed. Oxidative stress was evaluated based on ROS production, oxidative lesion of lipids (MDA) and on determination of antioxidants, including enzyme activity of glutathione peroxidase (Gl-Px), glutathione reductase (Gl-Red) and on the quantification of glutathione (GSH), glutathione-s-transferase (GST) and total antioxidant status (TAS). PC3 shows higher ROS production but also the highest GSH levels and Gl-Red activity, possibly contributing to oxidative stress resistance. This is also associated with higher mitochondrial membrane potential, TAS and lower lipid peroxidation. On the other hand, we identified Gl-Red activity reduction as a new strategy in overcoming oxidative stress resistance, by inducing H2O2 cytotoxicity. Therefore these results suggest Gl-Red activity reduction as a new potential therapeutic approach, in prostate cancer.

Neuroprotective effects of statins in an in vitro model of Alzheimer's disease.

Statins, used as cholesterol-lowering drugs, were reported to reduce the progression of Alzheimer's disease (AD). However, the molecular mechanisms underlying these findings remain to be clarified and it is not well understood whether this beneficial effect is due to simply lowering cholesterol levels. This study was aimed to investigate the neuroprotective effect of simvastatin and lovastatin, lipophilic statins that can transverse the blood brain barrier, against the toxicity triggered by the AD-associated amyloid-beta (Abeta) peptides and to analyze if such protection is cholesterol-independent. Using primary cultures of cortical neurons treated with Abeta1-40 peptide, we have demonstrated that pre-incubation with statins prevents the rise in cytosolic Ca2+ concentration and the accumulation of reactive oxygen species induced by Abeta through mechanisms independent of cholesterol reduction. The neuroprotective actions of statins were rather attributable to their ability to reduce isoprenyl intermediates levels in the cholesterol biosynthetic pathway since their effect was reversed by geranyl pyrophosphate while cholesterol addition was ineffective. Consequently, statins were shown to rescue cortical neurons from Abeta-40-induced caspase-3-dependent apoptosis. Moreover, our results revealed that simvastatin, at neuroprotective concentrations against Abeta-induced toxicity, is not able to activate Akt or ERK2, two signaling kinases with neuroprotective roles against apoptosis.

Supplementation of coenzyme Q10 and alpha-tocopherol lowers glycated hemoglobin level and lipid peroxidation in pancreas of diabetic rats.

The importance of nutritional supplementation in diabetes remains an unresolved issue. The present study was undertaken to examine the effects of alpha-tocopherol and CoQ(10), powerful antioxidants, on metabolic control and on the pancreatic mitochondria of GK rats, a model of type 2 diabetes. We also evaluated the efficacy of these nutrients in preventing the diabetic pancreatic lesions observed in GK rats. Rats were divided into 4 groups, a control group of diabetic GK rats and 3 groups of GK rats administered with alpha-tocopherol and CoQ(10) alone or both in association, during 8 weeks. Fasting blood glucose levels were not significantly different between the groups, nor were blood glucose levels at 2 hours after a glucose load. HbA1c level was significantly reduced in the group supplemented with both antioxidants. Diabetes induced a decrease in coenzyme Q plasma levels that prevailed after treatment with antioxidants. In addition, the plasma alpha-tocopherol levels were higher after treatment with the antioxidants. An increment in some components of the antioxidant defense system was observed in pancreatic mitochondria of treated GK rats. Moreover, the antioxidants tested either alone or in association failed to prevent the pancreatic lesions in this animal model of type 2 diabetes. In conclusion, our results indicate that CoQ(10) and alpha-tocopherol decrease glycated HbA1c and pancreatic lipid peroxidation. These antioxidants increase some components of the antioxidant defense system but do not prevent pancreatic lesions. Thus, we cannot rule out the potential benefit of antioxidant treatments in type 2 diabetes in the prevention of their complications.

Blood oxidative stress markers in non-alcoholic steatohepatitis and how it correlates with diet.

OBJECTIVE: Non-alcoholic fatty liver disease is a common condition that can progress to endstage liver disease. The steatotic liver seems to be particularly susceptible to oxidative stress damage. The aim of this study was to evaluate the redox state in patients with non-alcoholic steatohepatitis (NASH) and its correlation with dietary intake. MATERIAL AND METHODS: Plasma concentrations of 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHdG), reduced and oxidized glutathione (GSH and GSSG), vitamins A and E, total antioxidant status (TAS), glutathione peroxidase (GSH-Px) and reductase (GSH-Red) erythrocyte activities were compared between 43 NASH patients and 33 healthy controls. 4-HNE, GSH-Px, GSH-Red and TAS were evaluated by spectrophotometry, 8-OHdG by ELISA assay, GSH and GSSG by fluorimetric assay and vitamins A and E by high performance liquid chromatography. Dietary habits were also evaluated in these patients. RESULTS: GSH levels (21.1 +/- 18.3 versus 33.1 +/- 22.2 microM, p = 0.01) and GSH/GSSG ratio (0.9 +/- 0.7 versus 1.5 +/- 0.8, p = 0.01) were lower and TAS (832 +/- 146 versus 630 +/-140 microM, p < 0.001) and vitamin E (47.1 +/- 14.9 versus 34.5 +/- 7.3 microM, p < 0.001) were higher in NASH patients, although there was no difference in GSH-Px and GSH-Red activities, 8-OHdG and 4-HNE levels between groups. After adjusting for total energy consumption, a negative correlation was found with total and saturated fat intake and GSH/GSSG ratio, and a positive correlation with carbohydrates, fiber, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), specifically N-3 PUFA, and vitamins E, C, selenium and folate. CONCLUSIONS: Our data suggest an impaired glutathione metabolism towards an oxidant status in NASH patients, correlating with a higher intake of saturated fat and a lower intake of carbohydrates. Plasmatic concentrations of oxidative stress cellular markers did not translate to hepatic oxidative damage.

[Inherited disorders of purine and pyrimidine metabolism. State of art. Contribution for diagnosis]. / Doenças hereditárias das purinas e pirimidinas. Estado da arte. Contribuição para o diagnóstico.

Inherited errors of purine and pyrimidine metabolism are a group of disorders with a broad spectrum of clinical manifestations. They may involve nervous, renal, haematological and immunological systems, presenting at any age. The incidence and prevalence of these disorders are unknown. Most clinicians are not aware of their existence and hospital laboratories do not offer conditions for the screening. We have been associated contractor in an european project for the study of these disorders. It enabled us to set up urinary screening methods and establish normal values for urinary purine and pyrimidine in our paediatric population.