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Biomedical subjects

A Castaño

Publications and source records attributed to A Castaño.

At least 37 records · Page 2Linked to original sources

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.

3,4-Dihydroxyphenylacetic Acid↗

Adhesion molecules involved in macrophage responses to Wallerian degeneration in the murine peripheral nervous system.

When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the beta1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including alpha4beta1- and alpha5beta1-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of alphaLbeta2/alphaMbeta2-ICAM-1 or alpha4beta1/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a beta1-integrin other than alpha4beta1 or alpha5beta1.

Animals↗

Biological and chemical tools in the toxicological risk assessment of Jarama River, Madrid, Spain.

Four river water samples (R) and three sewage samples (S) were collected at different points in the Jarama River, Spain. Organic concentrates were tested on the RTG-2 in vitro cytotoxicity test and analyzed by HPLC and GC/MS. The cytotoxicity assessment demonstrated a progressive increase in the toxicity of the river water when moving downstream. A wide range, from slightly harmful to highly toxic, was observed for sewage samples. The most toxic samples produced decreases of 95% to 100% in the ATP content, cell viability and cell detachment (a parameter to estimate mortality). The most toxic organic concentrates (the sewage from an urban + industrial effluent collected in Paracuellos, Madrid, Spain, and the river 100 m downstream from the discharge of this effluent) were fractioned by an HPLC system. Each chromatographic peak was collected as a fraction of the whole concentrate. The cytotoxicity of each fraction was also assessed on RTG-2 cells. A toxic peak with a retention time of 38.3 min was detected in both samples; this time belongs to the PAHs retention time interval under our chromatographic conditions. Analytical procedures identified fluorene (0.62 microg/l) and benz(a)anthracene (0.44 microg/l) in the sewage and anthracene (0.40 microg/l) and benz(a)anthracene (0.14 microg/l) in the river water. However, the observed cytotoxicity could not be explained by the PAH concentrations. Five additional toxic peaks were observed in each sample. Results suggest that the combination of HPLC with cost-effective toxicity tests produces a useful tool to define environmental management decisions when the chemical analysis cannot identify the substances responsible for the environmental risk.

Journal Article↗

Activation and proliferation of murine microglia are insensitive to glucocorticoids in Wallerian degeneration.

Activation and proliferation of microglia are commonly described in the central nervous system after a wide range of insults, but the mechanisms that regulate their phenotype in vivo are still poorly understood. We have studied the effect that adrenalectomy and dexamethasone treatment have on the proliferation and activation of microglia during Wallerian degeneration of the optic nerve in BALB/c mice. We found that the onset and rate of microglia proliferation is independent of glucocorticoids. There was an increase in F4/80-positive cells 3 days after optic nerve crush, with a peak at 7 days, both in the optic nerve and its target, the superior colliculus. The numbers of F4/80-positive cells remained high up to 3 weeks after crush, the longest time point examined. We also found that up-regulation of F4/80 and the complement receptor type 3 and expression of major histocompatibility complex class II antigens were not affected by adrenalectomy or dexamethasone treatment. These observations show that, unlike microglia in vitro or peripheral macrophages, microglia do not readily respond to glucocorticoids, which could indicate a lack of or reduced expression of glucocorticoid receptor in these cells.

Animals↗

[Incidence of insulin-dependent diabetes mellitus in Santiago, Chile (1990-1993)].

The aim of this study was to determine IDDM incidence in the Metropolitan Region of Chile, during the period 1990-1993 as part of the Multinational Project for Childhood Diabetes (WHO DIAMOND Project Group). The studied population was 1499.784 inhabitants. All children in whom the diagnosis was made between January 1, 1990 and December 31, 1993 were included. We used a retrospective and prospective search and confirmation method, using as data sources public and private hospitals and medical records of Pediatricians. The Juvenile Diabetes Foundation was used as a secondary data source. All cases had at least two confirmation sources. A total of 176 new cases (90 male) were diagnosed in the study period, with an annual incidence of 2.92/100,000 for females and 2.95 for males. The group of children from 10 to 14 years old had the highest incidence rate (4.9/100,000), specially in women (5.25/100,000). The yearly incidence was 1.31 in 1990, 2.71 in 1991, 2.93 in 1992 and 3.7/1000,000 in 1993. It is concluded that the Metropolitan Region has one of the lowest incidences of IDDM in Latin America, although it increased along the study years.

Adolescent↗

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.

3,4-Dihydroxyphenylacetic Acid↗

Toxicity identification evaluations for the investigation of fish kills: a case study.

A large fish-kill was observed in the river Tajo during the Spring-Summer of 1991. The mortality was first detected between Aranjuez and Toledo, affecting several fish species. Then it was slowly going downstream, affecting only carp (Cyprinus carpio), reaching the Spanish-Portuguese border several months later. Short-term toxicity tests on Daphnia magna and in vitro cytotoxicity tests on RTG-2 cells were used as toxicity monitoring systems in water samples and different water fractions. The fish kill was associated to the outbreak of infectious diseases, spring viremia of carp and saprolegniosis, related to an increase in the fish's susceptibility due to the presence of a toxic chemical. Bioassay-directed sample fractionations allowed to detect a toxic chemical. HPLC-MS identified the compound as dehydroabietic acid, a resin acid previously described immunotoxic.

Abietanes↗

Turnover of monoamines in hippocampus of rats fed on vitamin E-deficient diet.

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult hippocampus. Moreover, we have measured in vitro receptor binding of [3H]5-HT in hippocampal membranes from control and vitamin E-deficient rats. Turnover rates of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy-3-indolacetic acid (5-HIAA) have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase (MAO). DA, NA, 5-HT, normetanephrine (NMN) and 3-methoxytyramine (3-MT) turnover rates have been measured as accumulation rates of DA, NA, 5-HT, NMN and 3-MT after pargyline inhibition of MAO. An increase was found in the turnover rate of DA between control and experimental animals. In contrast, no changes were found in the turnover rate of 3-MT and DOPAC. No change was found in the turnover rate of NA although there was an increase of the turnover rate of NMN in vitamin E-deficient diets. No changes was found in the turnover rate of 5-HT although there was a decrease of 5-HIAA turnover rate in the animals fed on a low vitamin-E diet. With respect to the 5-HT1 receptors, no changes were found in the affinity (kd) but the receptor number (Bmax) was increased in vitamin E-deficient rats.

3,4-Dihydroxyphenylacetic Acid↗

Effects of a short period of vitamin E-deficient diet in the turnover of different neurotransmitters in substantia nigra and striatum of the rat.

Measurement of turnover of dopamine, noradrenaline and serotonin and their metabolites was assessed in striatum and substantia nigra of adult female rats that were fed control or vitamin E-deficient diets over 15 days. The levels and turnover of dopamine increased and the levels of serotonin decreased in both structures whereas serotonin turnover decreased only in striatum. No change was found in the turnover rate of noradrenaline between control and experimental animals. However, the most striking result was the increase of dopamine turnover found in substantia nigra. This dopamine increase was accompanied by an increase in 3-methoxytyramine turnover which seems to indicate an increase in dopamine release after vitamin E deficiency. The present study indicates that the nigrostriatal dopamine neurons are susceptible to the deficiency of vitamin E. Moreover, these data suggest that substantia nigra may be more susceptible to damage from vitamin E deficiency than striatum.

3,4-Dihydroxyphenylacetic Acid↗

Low selenium diet affects monoamine turnover differentially in substantia nigra and striatum.

Turnover of dopamine, noradrenaline, serotonin, and their metabolites has been measured in striatum and substantia nigra of adult female rats that were fed control or selenium-deficient diets for 15 days. In addition, the glutathione peroxidase activity has been studied. The most striking result was the increase of dopamine turnover (63%) and 3-methoxytyramine turnover (55%) in substantia nigra between control and experimental animals. On the other hand, no changes were found in the turnover rate of dopamine and its metabolites in the striatum. Likewise, no changes were found in noradrenaline turnover in substantia nigra. In the striatum, there was a significant increase of serotonin turnover versus no change for 5-hydroxy-3-indoleacetic acid. However, in the substantia nigra, serotonin turnover did not show significant changes, whereas 5-hydroxy-3-indoleacetic acid turnover decreased. At the same time, glutathione peroxidase activity significantly decreased in both structures after selenium-deficient diets. These results suggest that a selenium-deficient diet for a short period of time decreases brain protection, principally in the substantia nigra, against oxidative damage.

Animals↗

[Epidermoid carcinoma of the pancreas associated with malignant humoral hypercalcemia].

Pure squamous carcinoma is a rare pancreas cancer histological variety. Moreover the association of malign humoral hypercalcemia and neoplasia of the pancreas exocrine portion is extremely rare. The case of a patient with pure squamous pancreas carcinoma and hypercalcemia is discussed. The absence of bone metastasis allowed to classify it within the malign humoral hypercalcemia syndrome. It is the first case described in the spanish scientific literature and the third in the international literature of an epidermoid pancreas carcinoma associated to malign humoral hypercalcemia.

Aged↗

Changes in the turnover of monoamines in prefrontal cortex of rats fed on vitamin E-deficient diet.

Turnover of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites has been measured after a 15-day vitamin E-deficient diet in adult rat prefrontal cortex. Turnover rates of 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxy-3-indoleacetic acid have been assayed from the disappearance rates after blocking by pargyline inhibition of monoamine oxidase. NA, DA, and 5-HT turnover rates have been measured as accumulation rates of NA, DA, and 5-HT after pargyline inhibition of monoamine oxidase. No change was found in the turnover rate of NA between control and experimental animals. In contrast, turnover rates of DA and homovanillic acid significantly increased in the animals fed on a low-vitamin E diet. However, the most striking results were found on the serotoninergic system. Levels of 5-HT and its main metabolite, 5-hydroxy-3-indoleacetic acid, and their respective turnover rates were lower in the vitamin E-deficient diet. These results could indicate that vitamin E is necessary for the normal functioning of the serotoninergic neurons in the rat prefrontal cortex. The involvement of vitamin E in preventing the formation of free radicals is well known. Therefore, this lack of protective effect after a 15-day vitamin E-deficient diet could be responsible for the neuronal damage to the serotoninergic system. The opposing results found in DA (increase) and 5-HT (decrease) turnover could provide further evidence for an inhibitory control of the serotoninergic ascending pathways to the dopaminergic system in the prefrontal cortex.

Animals↗

[Carcinoma of the penis. Our experience with 22 cases].

The penis carcinoma is a neoplasia representing 0.7% of all male neoplasias, with an annual incidence between 1 and 2 cases per 100,000 inhabitants/year. The present study compiles the authors' experience in treating 22 patients presenting this neoplasia in the period between 1977-90. The procedures carried out included local resection, partial amputation, radical penectomy with lymphadenectomy plus radiotherapy, and palliative surgery plus radiotherapy all based on staging made following TNM grading. Therapy complications, follow-up, and survival results are explained. There were 5 occasions of spinocellular carcinoma co-existing with other neoplasias: 1 colon adenocarcinoma, 1 prostate carcinoma, 1 cleaved small cell centrocytic diffuse lymphoma, and 2 skin epithelioma in other sites, and relevant literature was reviewed. A background of psoriasis treated with psoralens plus UV was present in 4 cases, and caution was advised towards genital protection in patients undergoing UV radiations whether for therapeutic, recreational or cosmetic reasons.

Adult↗

Involvement of diminution of glutathione, produced by deficiency of methionine in the diet, in the elevation of malic enzyme level in rat liver.

Rats fed on a low protein diet show an increase in the specific activity of malic enzyme and a concomitant decrease of glutathione concentration. We have studied the effect on malic enzyme activity of supplementing of low protein diet with essential amino acids. Only when methionine was excluded from the diet did the specific activity of malic enzyme increase to the same extent as found in rats fed with low protein diet. Immunoprecipitation of malic enzyme indicated that specific activity changes are the result of changes in the amounts of enzyme. Under all dietary conditions studied, the increase in malic enzyme activity is associated with a decrease in the concentration of GSH. To evaluate the possible causative role of GSH in malic enzyme induction, the specific activity of malic enzyme was measured in rats treated with BSO, an inhibitor of GSH biosynthesis. The results show that in BSO-treated rats the decrease of GSH levels is also accompanied by an increase in the activity of malic enzyme.

Amino Acids, Essential↗

Age-dependent changes in the activity and isoenzymatic pattern of the phosphofructokinase in different areas of the central nervous systems.

Regional activity of phosphofructokinase enzyme and the amount of the isoenzyme C in 7 areas of young, adult and aged rats brain have been studied. The phosphofructokinase activity in substantia nigra decreased in adult and aged rats, but the maximum decrease was found in the septum of aged rats. There is a regional distribution of the isoenzyme C in the different areas studied. There was a general decrease in the amount of this isoenzyme in the areas studied with the exception of the hippocampus and the amygdala. The highest decrease was found in the septal area and in the diagonal band of Broca. These results are discussed in relation to the aging in different regions.

Aging↗

[Spinal cord compression by epidural metastases of urologic tumors].

We report our experience of 5 consecutive cases of acute spinal cord compression from epidural metastasis of genitourinary tumors seen over a period of 14 months. Three patients developed paraplegia and the remaining two patients developed paraparesis of the lower extremities. Four patients underwent emergency decompression laminectomy and the remaining patient received spot radiotherapy to the metastatic vertebral lesion. The degree of neurologic deterioration and its rapid progression to the more severe forms have significantly influenced patient quality of life and survival. The literature is reviewed highlighting the epidemiological, physiopathological, clinical, diagnostic and therapeutic aspects of this condition.

Adenocarcinoma↗