[Burnout and executive functions in Palliative Care health professionals: influence of burnout on decision making]. / Burnout y funciones ejecutivas en personal sanitario de Cuidados Paliativos: influencia del desgaste profesional sobre la toma de decisiones.

BACKGROUND: Health professionals show a high prevalence of burnout syndrome. This syndrome could be involved in the alteration of higher cognitive functions in the clinical setting. The aim of this study is to evaluate whether burnout is related to the executive functions of inhibition, working memory, decision-making, and cognitive flexibility in palliative care health professionals. METHOD: Degree of burnout was evaluated in seventy-seven health professionals from palliative care units by the Maslach Burnout Inventory (MBI-HSS), while executive functions were evaluated by Stroop test (inhibition), Letter-Number Sequencing (working memory), Iowa Gambling Task (decision-making) and Trail Making Test (cognitive flexibility). The total sample was classified in relation to both degree of burnout (low, medium, high) in each subscale of MBI-HSS (emotional exhaustion, depersonalization, and reduced personal accomplishment), and the number of dimensions altered (high levels in none, one or more than one). RESULTS: Burnout syndrome was present in 54.5% of palliative care health professionals, 15.6% of them with more than one dimension altered; these professionals showed significantly lower scores than professionals without burnout in the Stroop test, the Letter-Number Sequencing and the Iowa Gambling Task. Higher levels of emotional exhaustion and depersonalization were associated with significantly lower scores in the Iowa Gambling Task for assessing decision-making. CONCLUSIONS: The results showed that palliative care health professionals with a higher level of burnout have an alteration of inhibition, working memory and decision-making. These executive functions can be relevant in the clinical setting since they could be related to the cognitive thinking required for correct clinical reasoning by health professionals.

The effects of corticosteroids on cognitive flexibility and decision-making in women with lupus.

The aim of this study was to investigate the possible effects of corticosteroids in women with systemic lupus erythematosus (SLE) in two processes of executive function: cognitive flexibility and decision-making. To that end, we evaluated 121 women divided into three groups: 50 healthy women, 38 women with SLE not receiving corticosteroid treatment and 33 women with SLE receiving corticosteroid treatment. Cognitive flexibility was measured with the Trail Making Tests A and B; decision-making was measured with the Iowa Gambling Task. Additionally, demographic (age and education level), clinical (SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and disease duration) and psychological characteristics (stress vulnerability, perceived stress and psychopathic symptomatology) were evaluated. The results showed that both SLE groups displayed poorer decision-making than the healthy women ( p = 0.006) and also that the SLE group receiving corticosteroid treatment showed lower cognitive flexibility than the other two groups ( p = 0.030). Moreover, SLE patients showed poorer scores than healthy women on the following SCL-90-R subscales: somatisation ( p = 0.005), obsessions and compulsions ( p = 0.045), depression ( p = 0.004), hostility ( p = 0.013), phobic anxiety ( p = 0.005), psychoticism ( p = 0.016) and positive symptom total ( p = 0.001). In addition, both SLE groups were more vulnerable to stress ( p = 0.000). These findings help to understand the effects of corticosteroid treatment on cognitive flexibility and decision-making, in addition to the disease-specific effects suffered by women with SLE.

Quality-of-life predictor factors in patients with SLE and their modification after cognitive behavioural therapy.

OBJECTIVE: The aim of the study was to determine the clinical and psychological factors linked to health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE) and test the effectiveness of cognitive behavioural therapy in changing these factors. METHODS: We evaluated 34 patients with SLE over a period of 15 months. In order to study the variables related to items of QOL and the physical (PCS) and mental (MCS) component summaries of the SF-36, several multiple linear regression models were constructed. Patients were randomized and distributed into two similar groups; one of them received cognitive behavioural therapy and the other received the usual controlled care. The psychological aspects as well as the related-disease factors were evaluated four times during the study. RESULTS: Self-perceived stress (R² corrected: 0.314, t: -2.476, p < 0.021), vulnerability to stress (R² corrected: 0.448, T: -2.166, p < 0.04) and anxiety (R² corrected: 0.689, T: -7.294, p < 0.00) were predictor variables of MCS. The group of patients who received the therapy improved their level of physical role functioning, vitality, general health perceptions and mental health, compared with the group of patients who only received conventional care. CONCLUSION: QOL usually depends on multiple factors, some of which are stress and anxiety, which can be modified by a cognitive behavioural therapy, in order to obtain a significant improvement in the HRQOL, irrespective of the activity level of the disease. Frequent evaluations of the quality of life in patients with SLE and psychological treatment should also be considered.

[Physiopathologic implications of telomerase]. / Implicaciones fisiopatológicas de la telomerasa.

Telomerase is a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes. Telomerase gene expression is active in germinal, stem and tumoral cells and repressed in normal human somatic cells. Activation of telomerase involves immortalization, while repression of this enzyme involves the shortening of telomeres in each round of chromosomal replication. Telomere shortening constitutes a mechanism for cells to control cell division and the entrance in the replicative senescence state. If the expression of this enzyme is forced, senescent human cells will extend their life span reaching the immortalization and malignization of the cells. Activation or depression of telomerase activity has important implications in aging and cancer therapy. Telomerase regulation is a multifactorial process in which telomerase expression, post-translational protein-protein interactions and protein phosphorylation are involved.

Effect of chronic ethanol or acetaldehyde on hepatic alcohol and aldehyde dehydrogenases, aminotransferases and glutamate dehydrogenase.

Ethanol or acetaldehyde orally administered (15% and 2% respectively in drinking water) to male Wistar rats for three months induced alterations in the main liver enzymes responsible for ethanol metabolism, aspartate and alanine aminotransferases and NAD glutamate dehydrogenase. Ethanol produced a significant decrease in the activity of soluble alcohol dehydrogenase, while acetaldehyde induced alterations both in soluble and mitochondrial aldehyde dehydrogenases: soluble activity was significantly higher than in the control and ethanol-treated groups, and mitochondrial activity was significantly diminished. Both soluble aspartate and alanine aminotransferases showed pronounced increases by the chronic effect of acetaldehyde, while mitochondrial activities were practically unchanged by the effect of ethanol or acetaldehyde. Mitochondrial NAD glutamate dehydrogenase showed a rise in its activity both by the effect of chronic ethanol and acetaldehyde consumption. The level of metabolites assayed in liver extracts showed marked differences between ethanol and acetaldehyde treatment which indicates that ethanol produced a remarkable increase in glutamate, aspartate and free ammonia together with marked decrease in pyruvate and 2-oxoglutarate concentrations. Acetaldehyde consumption induced a significant decrease in 2-oxoglutarate and pyruvate concentrations. These observations suggest that ethanol has an important effect on the urea cycle enzymes, while the effect of acetaldehyde contributes to the impairment of the citric acid cycle.

The effect of chronic ethanol administration on lipogenesis in liver and adipose tissue in the rat.

Rates of lipogenesis de novo have been studied in liver and epididymal fat pads of male rats chronically treated with ethanol. A solution of ethanol (150 ml/l) was administered as the only drinking fluid for 3 months with a standard solid diet; both food and drink were available ad lib. Lipogenesis in vivo was measured by the incorporation of tritiated water into lipid fractions: non-saponifiable lipid and fatty acids. Non-saponifiable lipid, both in liver and in adipose tissue, was unaffected by ethanol treatment. However, fatty acid synthesis de novo was significantly enhanced in both liver and adipose tissue, by 150 and 300% respectively. Plasma triacylglycerol and non-esterified fatty acid levels were unchanged and plasma glucose concentration slightly increased by ethanol administration. The rate of lipogenesis increased when insulin: glucagon increased twofold due to the effect of ethanol.

[Changes caused by thioacetamide in GOT and GPT aminotransferases and glutamate dehydrogenase in rat liver. Ultrastructural study]. / Alteraciones producidas por la tioacetamida sobre las aminotransferasas GOT y GPT y la glutamato deshidrogenasa en hígado de rata. Estudio ultraestructural.

Measurements have been made of the hepatic soluble and mitochondrial GOT and GPT and mitochondrial NAD+ glutamate dehydrogenase activities in thioacetamide-treated rats for 30 days. There is a significant fall in the GOT and GPT soluble activities from the effect of chronic thioacetamide administration while the mitochondrial activities become markedly increased in both cases. Glutamate dehydrogenase also increased from the effect of this hepatotoxic substance. Protein determined in the soluble and mitochondrial fractions, showed decreased levels in the cytosolic extracts and increased levels in the mitochondrial ones. Morphological aspects of liver cells showed hypertrophic mitochondria located around the likewise hypertrophic nucleus. The existence of functionally very active mitochondria in the generating liver, induced by thioacetamide, as well as metabolic mechanisms for the regulating control under pathological circumstances, can be a consequence of the increased ammonia concentration.

[Profile of the capacity for lipid synthesis in vivo in various rat tissues: effect of age]. / Perfil de la capacidad de síntesis lipídica in vivo en diversos tejidos de rata: efecto de la edad.

Changes in 3H2O incorporation in vivo to lipid fractions have been studied in rats 1, 3 and 13 months old. The incorporation of tritiated water into non-saponifiable fraction showed and age-dependent decrease in liver. The values were 4.32, 2.91 and 2.56 mumol 3H2O incorporated/g wet weight of liver/hour, at 1, 3 and 13 months respectively. Similar variations could be observed in adipose tissue and in blood. The rates of lower lipogenesis increase markedly from 1 to 3 months (7.02 to 13.36 mumol 3H2O/g/h) and decrease sharply from the 3rd to 13th months (13.36 to 3.75 mumol 3H2O/g/h). The incorporation of radioactivity into blood and adipose tissue fatty acids, also decrease by age.

[Effect of pH and activation on the arginase activity of rat liver treated with thioacetamide]. / Efecto del pH y activation sobre la actividad arginásica de hígado de rata tratada con tioacetamida.

Arginase (E.C. 3.5.3.1) activity of liver from thioacetamide treated rats has been investigated in relation to 6.5 pH in the reaction medium, as well as stability against activation process. The results suggest that thioacetamide damage affects enzyme protein at the level of ionizing groups of active center and/or binding to Mn2+.

[Effect of thioacetamide on the incorporation of tritiated water into rat liver phospholipids]. / Efecto de la tioacetamida sobre la incorporación de agua tritiada a fosfolípidos hepáticos de rata.

Male Wistar rats received an intraperitoneally daily dose of thioacetamide of 100 mg/kg body weight during 3, 8 and 30 days. Phospholipid levels and radioactive incorporation of 3H2O into total lipids, polar lipids and phospholipids 1 h after intraperitoneal administration of 5 mCi of tritiated water, were determined in livers of untreated control rats and of animal treated during the above mentioned periods. Earlier doses of thioacetamide provoked an increase in the 3H2O incorporation into total lipid fraction. Prolonged treatment resulted in an inhibition of tritiated water incorporation. After three days of thioacetamide administration the incorporated radioactivity in phospholipid fraction decreased. There was also observed a decrease in the radioactivity incorporated into the major phospholipids: phosphatidylcholine and phosphatidyl ethanolamine. However, the levels of these phospholipids showed no significant changes. These observations support the suggestion that de novo biosynthesized fatty acids are being utilized for 1-palmitoyl-2-oleoyl and 1-palmitoyl-2-linoleoyl phospholipids biosinthesis in lesser proportion in rats treated with thioacetamide than in control rats.

[Effect of thioacetamide on the incorporation of 32P into phospholipids of rat liver]. / Efecto de la tioacetamida sobre la incorporación de 32P a fosfolípidos de hígado de rata.

The effect of thioacetamide on rat liver phospholipids biosynthesis was investigated using 32P as precursor. The incorporation of 32P-ortophosphate in the polar lipid fraction and the specific radioactivities of individual phospholipids in the liver fraction and the specific radioactivities of individual phospholipids in the liver of control rats and rats treated with thioacetamide were determined 75 min after intraperitoneal administration of 32P-ortophosphate. Intraperitoneal injection of thioacetamide (daily dose of 100 mg/kg body weight) in male Wistar rats resulted in an increase of 32P incorporation in the over-all phospholipids, after 8 doses administration and a significant decrease during the chronic intoxication. Specific activity of phosphatidylcholine decreased and a parellel increase in specific radioactivity of lisophosphatidylcholine was found after three days of thioacetamide treatment. There was also observed a marked increase in specific radioactivity of sphingomyelin, which could be due to a stimulation of CDP-choline: ceramide cholinephosphotransferase reaction with subsequent diminution of the rate of phosphatidylcholine synthesis via the CDP-amine pathway (involving cytidine diphosphocholine).

Metabolic repercussion of coenzyme-A (CoA) in experimental ethanol hepatopathy.

The administration of ethanol plus fat diet has been investigated in our laboratory in relation to the experimental fatty liver in rats. Considering that lipid metabolism are markedly altered in these experimental conditions, the present work studies the effect of simultaneous administration of Coenzyme A (CoA) on the alterations produced by ethanol and lipid diet on glycolytic and lipogenic routes. Ethanol was administered in a 15% solution as the only drinking fluid and a high fat diet (45% vegetable fat as total calories) for three months. CoA was intraperitoneally administered at a dose level of 1.0 mg/Kg body weight/day. Enzymatic activities were determined in the soluble fraction of liver homogenates. The methods used for the estimation of the enzymatic activities are described by Bergmeyer. The most significant changes found by the effect of CoA administration correspond to malic enzyme, citrate lyase and 6-phosphogluconate dehydrogenase. Fatty acid synthetase and glycolytic kinases, especially diminished by the effect of fat diet, did not show any significant restoration of their activities when ethanol and CoA were simultaneously administered.

[Changes in lipid metabolism which accompany thioacetamide-induced cirrhosis]. / Alteraciones en el metabolismo lipídico que acompañan a la cirrosis inducida por tioacetamida.

Intraperitoneally-administered thioacetamide to rats produces the incorporation of 3H2O into the liver lipids during eight days, diminishing thereafter together with a decrease in 32P incorporation to phosphatidyl choline. Contrarily, the sphingomyelin incorporated 32P increases by the effect of the toxic action of the drug, while the 3H binding decreases. The cirrhosis-inducing agent possibly produces a shunt of the common CDP-choline precursor to the biosynthesis of sphingomyelin with detriment to the synthesis of phosphatidyl choline. The role of the unsaturation of fatty acids by thioacetamide is considered.

[Effect of the administration of nucleotide coenzymes on the lipogenic enzyme changes caused by chronic alcohol intoxication]. / Efecto de la administración de coenzimas nucleotídicos sobre las variaciones de enzimas lipogénicos orginadas por intoxicación etílica crónica.

Lipogenic enzymes glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase NADP+ soluble and malic enzyme have been determined in the hepatic soluble fraction of rats chronically treated with ethanol and a lipid rich diet. The treatment based on protectives and lipotropic substances administered as nucleotides: UDP-glucose, CDP-choline, S-adenosyl methionine and Coenzyme A, elicits a significant restoration on the activities of G6PDH, 6PGDH and ICDH. These results show that the treatment, on promoting lipid mobilization, could increase the rate of hepatic lipogenesis. The malic enzyme enhanced activities, when ethanol and lipid diet were simultaneously administered, may be interpreted as a requirement for NADPH by the microsomic drug oxidation system.

[Topography of the metabolic cycle of 4-aminobutyrate]. / Topografía del ciclo metabólico del 4-aminobutirato.

This work describes, with some detail the intervention of 4-aminobutyrate as protagonist of a derivation of tricarboxylic cycle. Its vicarial mission is emphasized in connection with its existence in microorganisms (Escherichia coli and Pseudomonas fluorescens), plants (Helianthus tuberosus. Lupinus albus and Agave americana), neoplasic cells (ascitic tumor of Ehrlich and HeLa cells) and animal tissues (adrenal medulla and brain.

The effect of thioacetamide on urea cycle enzymes of rat liver.

The urea cycle enzymes, carbamoyl-P-synthetase, ornithine transcarbamylase, arginase and other enzymes related to ammonia metabolism, such as glutamate dehydrogenase, glutamine synthetase and alanine and aspartate aminotransferases,have been studied in thioacetamide-induced liver disease in rats. Urea and ammonia were determined both in serum and in liver extracts. Glutamate and aspartate were determined in liver extracts. There was a marked decrease (in brackets: fraction of control) in carbamoyl-P-synthetase (0.23), ornithine transcarbamylase (0.36) and arginase (0.62). The accumulation of ammonia (3.22) and the decreased urea level (0.80) are well known indications of liver failure. Glutamate dehydrogenase and glutamine synthetase increased respectively to 1.50 and 1.33, and the changes in glutamate and aspartate levels were respectively 1.68 and 0.92; this indicates that the metabolic route: 2-oxoglutarate leads to glutamate leads to glutamine is increased, and thereby compensates for the low rate of urea formation. Aminotransferase activities were respectively 0.43 and 0.25. No significant differences were found in serum aminotransferases, or in the concentrations of ammonia and urea.