COVID-19 impact on nurses in Spain: a considered opinion survey.

AIM: To survey nurses' opinions about their work conditions at the onset of the COVID-19 pandemic in Spain. BACKGROUND: For the Spanish General Council of Nursing (the Consejo General de Enfermería de España), it was essential to have information on nursing workforce conditions and nurses' preparedness to wear protective measures at the pandemic's onset. The coronavirus outbreak was believed to have started in China and rapidly spread as a global pandemic requiring policies and actions for planning emergency healthcare delivery. METHODS: A cross-sectional survey was conducted online. Data were collected during April 2020 and covered social demography, working conditions, training, availability of personal protective equipment, and nurses' health conditions, including the impact of COVID-19. FINDINGS: From all national territories in Spain, 11 560 registered nurses from different services completed the questionnaire. Findings indicated that the lack of personal protective equipment was a crucial issue, as well as service planning and organization, and 80.2% reported high or very high psychological impact of COVID-19. Alarmingly, 29.5% of the nurses reported COVID-19 symptoms. Of these 23.3% had been tested, and 30.2% were confirmed as being positive to the virus. The nurses deemed proper preparedness for emergencies and disasters as a significant concern. CONCLUSION: Nurses' responses showed evidence of health services deficiencies as a source of damage to their capacity to provide safe patient care and protect themselves and their families' health. The working conditions of the nurses are at critical levels and are unacceptable. The study results provide evidence regarding the necessity of suitable planning and actions being taken to enable safe patient care and safety for nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Our survey gathered nurses' views at the pandemic's onset. The evidence gathered is being used to advise policymakers and nursing organizations to take actions to control public health risks to populations. It is necessary that more investment in growing nursing workforce expertise and health infrastructure for pandemic and epidemic emergencies is provided.

Decreased messenger RNA expression of key markers of the nigrostriatal dopaminergic system following vitamin E deficiency in the rat.

We have evaluated the effect of a vitamin E-deficient diet on the rat nigrostriatal dopaminergic system. After 15 days of deficient diet, the amount and activity of striatal and nigral tyrosine hydroxylase increased, which contrasted with a decreased messenger RNA expression for tyrosine hydroxylase and the dopamine transporter in the ventral mesencephalon. When we prolonged the deficiency of vitamin E for 30 days, dopamine levels did not differ in both areas. In contrast, messenger RNA levels for tyrosine hydroxylase and the dopamine transporter were markedly reduced in 30-day deficient rats. In addition, the number of oxidatively modified proteins significantly increased in the striatal and nigral areas studied. Overall, we propose that these changes suggest an important role of vitamin E in maintaining the normal equilibrium of the dopaminergic nigrostriatal system.

Increased activity and expression of tyrosine hydroxylase in the rat substantia nigra after chronic treatment with nomifensine.

We have studied the effect of chronic treatment with nomifensine on dopaminergic functioning in the nigrostriatal system. The striatal dopaminergic system was not altered by chronic nomifensine treatment. In contrast, there were overall decreases of different dopamine (DA) metabolites in the cell body region in the substantia nigra after nomifensine treatment, which clearly indicates a diminished DA turnover. These results suggest that long-lasting inhibition of the high affinity DA uptake system triggers long term regulatory, compensatory mechanisms in the cell body region to preserve normal dopaminergic function in the terminal field in striatum. We also tested whether transcriptional regulatory mechanisms were altered. We studied the cellular expression of tyrosine hydroxylase (TH) mRNA in substantia nigra by in situ hybridization, and the amount and activity of TH enzyme in the cell body and terminal field regions. Our results indicate that nomifensine treatment increased TH mRNA levels within individual nigral cells, which paralleled the changes in TH enzyme amount and activity in this brain area. Our data confirm the important role of the high affinity DA uptake system in regulating dopaminergic transmission in the nigrostriatal system.

Low selenium diet increases the dopamine turnover in prefrontal cortex of the rat.

It has been proposed that interaction of catecholamines and indoleamines with free radicals may result in the formation of endogenous neurotoxins. In order to better understand the mechanisms involved in neurodegenerative disorders showing evidence of oxidative stress, we have studied the basal concentrations and the turnover rates of dopamine, noradrenaline, serotonin and their metabolites in the prefrontal cortex of rats that were fed on control or low selenium diets. Nutritional deficit of selenium decreases the brain antioxidant protection in experimental conditions by the decrease in glutathione peroxidase activity. The dopamine and serotonin turnover increased and noradrenaline and 5-hydroxy-3-indoleacetic acid turnover decreased compared to experimental control animals. The increase of dopamine turnover in experimental rats was accompanied by an increase in tyrosine hydroxylase activity. These results suggest that the decrease of brain protection against oxidative damage could induce brain damage by disturbing the turnover rate of some monoamines.

Deprenyl induces the tyrosine hydroxylase enzyme in the rat dopaminergic nigrostriatal system.

Chronic treatment of aged rats with deprenyl prevents age-induced protein oxidation in substantia nigra and protects tyrosine hydroxylase (TH) enzyme against inactivation [11]. With these precedents, we treated adult rats with deprenyl for 3 weeks in order to get further insight in the mechanism by which deprenyl exerts such actions. After completing the treatment, dopamine (DA) levels markedly increased in both striatum and substantia nigra while levels of the acid DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), decreased in the two brain areas, thus proving MAO-inhibiting properties of the treatment. We then studied the cellular expression of TH mRNA by in situ hybridization. Following treatment with deprenyl, levels of TH mRNA were significantly higher in individual dopaminergic nigral cell bodies than in those of control rats (+74%). Western blotting analysis of TH enzyme amount revealed a positive effect of the treatment in both the terminal field (+44%) and the cell body region (+31%). This correlation between TH mRNA and amount was also extended to TH enzyme activity in the two brain areas studied, which significantly increased in striatum (+57%) and substantia nigra (+35%) following deprenyl treatment. Taken together, our results clearly suggest a TH-inducing effect of deprenyl in the dopaminergic nigrostriatal system, which seems to be independent of its protective action against oxidative stress described previously. These results expand our knowledge about the beneficial effect of deprenyl in the therapy of Parkinson's disease.

(-)-Deprenyl treatment restores serum insulin-like growth factor-I (IGF-I) levels in aged rats to young rat level.

We studied the effects of treatment with (-)-deprenyl, a monoamine oxidase B inhibitor, on plasma levels of insulin-like growth factor-I (IGF-I) (as indicator of growth hormone (GH) secretion), levels of monoamines and their metabolites, and the activity and content of tyrosine hydroxylase - the rate-limiting enzyme in the biosynthesis of catecholamines - in the hypothalamus and hypophysis of old male rats. Male Wistar rats (22 months old) were treated with 2 mg deprenyl/kg body weight s.c. three times a week for 2 months. At the end of the treatment period, blood was collected for measurement of plasma IGF-I levels by radioimmunoassay (RIA). The concentrations of dopamine, serotonin (5-HT) and their main metabolites were determined by high performance liquid chromatography (HPLC) with electrochemical detection, and the tyrosine hydroxylase content in hypothalamus and hypophysis was determined by enzyme-linked immunoabsorbent assay (ELISA). (-)-Deprenyl treatment produced a pronounced increase in dopamine and 5-HT in both the hypothalamus and hypophysis (P < 0.01). The main dopaminergic metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), decreased in hypothalamus but not in hypophysis, and treatment had no effect on the concentration of 5-hydroxyindole-3-acetic acid (5-HIAA). The tyrosine hydroxylase activity and tyrosine hydroxylase content increased in hypothalamus and hypophysis (P < 0.05). In the hypophysis the increase in tyrosine hydroxylase activity was consistent with the increase in tyrosine hydroxylase amount. Moreover, (-)-deprenyl treatment restored the IGF-I plasma levels in old rats to a concentration similar to those found in young animals. Postulated anti-aging effects of (-)-deprenyl could hence be due to restoration of hypothalamic hormones such as GH.

Chronic inhibition of the high-affinity dopamine uptake system increases oxidative damage to proteins in the aged rat substantia nigra.

The effect of chronic treatment of aged rats with nomifensine has been studied in the rat nigrostriatal dopaminergic system. The rat substantia nigra suffers an oxidative damage during aging that results in both an increase in carbonyl groups of its total proteins and the oxidative inactivation of tyrosine hydroxylase (TH) enzyme, which are partially reversed by chronic treatment with deprenyl. Different mechanisms may account for this effect, including inhibition of the high-affinity dopamine uptake system. We treated aged rats chronically with nomifensine for 2 months and found some significant effects. Nomifensine treatment significantly increased TH enzyme amount in substantia nigra (39.2%), which was accompanied by a significant increase in TH enzyme activity (47.8%). However, these effects were not observed in the terminal field (striatum). As a further step we quantified the oxidative level of proteins by measuring the number of carbonyl groups coupled either to total proteins or specifically to TH enzyme. The proteins of aged rat substantia nigra showed a significant increase of carbonyl groups following nomifensine treatment. The number of carbonyl groups coupled to nigral TH enzyme also increased in the nomifensine-treated animals. However, this increase was lower than that found in the total homogenate proteins. All these results show that the oxidative damage produced during aging in tyrosine hydroxylase enzyme and total proteins is not reduced by nomifensine treatment. On the contrary, the nomifensine treatment increased the oxidative damage to proteins. These results suggest the capability of deprenyl to induce TH enzyme could be due to inhibition of the high-affinity dopamine uptake system, but its ability to protect against oxidative damage is not produced by this mechanism.

Protection of the aged substantia nigra of the rat against oxidative damage by (-)-deprenyl.

1. We have studied the effect of (-)-deprenyl on the oxidative damage that the rat substantia nigra suffers during aging. 2. (-)-Deprenyl (2 mg kg-1, three times a week) administered for two months, beginning at 22 months of age, produced a significant increase in tyrosine hydroxylase (TH) activity (2.67 +/- 0.40 and 3.64 +/- 0.38 nmol mg-1 protein h-1 in untreated aged rats and treated aged rats respectively, P < 0.05) and in TH amount (0.072 +/- 0.012 and 0.128 +/- 0.38 absorbance 405 nm in untreated aged and treated aged rats respectively, P < 0.05). 3. The proteins of aged rat substantia nigra showed a significant decrease of carbonyl groups in treated animals compared with saline-injected control rats (136.2 +/- 21.8 and 71.5 +/- 13.2 c.p.m. microgram-1 protein in untreated aged and treated aged rats respectively, P < 0.05). 4. The carbonyl groups measured in TH enzyme showed a statistically significant decrease (42.3%) after (-)-deprenyl treatment (471.4 +/- 73.0 and 271.9 +/- 50.00 c.p.m. in untreated aged and treated aged rats respectively, P < 0.001). 5. All these results suggest that oxidative damage produced during aging is prevented by (-)-deprenyl treatment and could explain the effect of this drug in Parkinson's disease (PD) and other degenerative diseases such as Alzheimer's disease.

Increase in dopamine turnover and tyrosine hydroxylase enzyme in hippocampus of rats fed on low selenium diet.

We have studied the turnover of dopamine, noradrenaline, and serotonin and their metabolites in hippocampus of adult female rats that were fed control or selenium-deficient diets during 15 days. Under these circumstances, there was an increase of dopamine turnover (4-fold) in rats fed with selenium-deficient diet with respect to controls and also an increase in the tyrosine hydroxylase activity (75.8%), which was the result of the increase of the amount of the enzyme (2-fold), without significant change in the phosphorylation of the tyrosine hydroxylase. In addition the glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase activities have been studied. After selenium-deficient diet, the enzymatic activities of superoxide dismutase and catalase did not show change with respect to the controls; however glutathione reductase and glutathione peroxidase significantly decreased 15% and 29%, respectively. It is concluded that the increase in dopamine turnover seems to be associated with the induction of tyrosine hydroxylase enzyme. In these conditions the decrease in antioxidant capacity may produce a cascade of events, which accelerates the degenerative process, since the increase in dopamine turnover produces an increase in oxygen radical by monoamine oxidase activity.

The effect of age on the monoamines of the hypothalamus.

Measurement of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) homovanillic acid (HVA), 3-methoxytyramine (3-MT), noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG) and serotonin (5-HT) and its main metabolite, 5-hydroxyindol-3-acetic acid (5-HIAA) was assessed in hypothalamus and median eminence of aged rats. Age-related changes were not observed in the concentration of NA and its metabolites in median eminence. In contrast, there was a significant NA decrease in aged hypothalamus compared with 12 months (no differences were found compared with 3 months). No significant differences were found in DA concentration and its metabolites in hypothalamus but DA decreased significantly in aged median eminence compared with 12 months. The ratio 5-HIAA/5-HT, indicative of 5-HT turnover, appeared to increase in the hypothalamus and median eminence of the aged rat. Morphological dissimilarities between hypothalamus of young and aged rats were demonstrated using serotonin-immunocytochemistry. A degeneration of the serotoninergic system, denoted by the appearance of enlarged or swollen varicosities, was observed in the hypothalamus of the aged rat. These aberrant serotoninergic fibers may reflect the local degeneration of serotoninergic hypothalamic afferents during ageing. Such differential age-dependent alterations of the serotoninergic system might be responsible for at least some of the functional deficits in aged animals.