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Biomedical subjects

P Morata

Publications and source records attributed to P Morata.

At least 19 recordsLinked to original sources

Antiproliferative effect of dehydrodidemnin B (DDB), a depsipeptide isolated from Mediterranean tunicates.

The biological effects of dehydrodidemnin B(DDB), a novel depsipeptide isolated from Aplidium albicans, were studied on Ehrlich carcinoma growing in vivo and in primary cultures, and compared with those reported for Didemnin B (DB). Daily administration of DB or DDB (2.5 micrograms/mouse) almost duplicated the animal life-span and total number of tumour cells decreased by 70-90%. Results suggest a major effect of DDB when administered in the lag phase of growth. DDB behaved as a very potent inhibitor of protein synthesis; consequently, ornithine decarboxylase activity (ODC, EC 4.1.1.17) is drastically reduced by DDB-treatment.

Animals

Chlorpheniramine inhibits the synthesis of ornithine decarboxylase and the proliferation of human breast cancer cell lines.

Proliferation of both mouse and human breast cancer cells was inhibited by chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential phase of growth (two days after seeding), 250 microM CPA was able to reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). The antiproliferative effect of CPA was also tested on a poorly-differentiated and hormone-insensitive human breast cancer cell line (MDA-MB231) and on a highly proliferative human colon cancer cell line (clone 3). CPA was cytotoxic for MDA-MB231 cells at concentrations higher than 50 microM, and it was also cytotoxic for the colon cancer cell clone 3 at 250 microM CPA. Nevertheless, colon cancer cells were slightly stimulated at CPA concentrations less than 100 microM. CPA reduced (by 50-70%) the ornithine decarboxylase induction occurring early after culture seeding of experimental mammary tumors (Ehrlich carcinoma cells) and human breast cancer cells (MCF-7). The presented data suggest that in addition to ODC inhibition, CPA presents other still unknown cytotoxic effects.

Animals

Vinca alkaloids enhance the half-life of tumour ornithine decarboxylase.

Naturally occurring vinca alkaloids, vincristine and vinblastine, at micromolar concentrations enhanced the ornithine decarboxylase activity in a dose-response manner in primary cultures of Ehrlich ascites carcinoma cells. After 8 h of culture in the presence or absence of vinblastine, cycloheximide was added to the medium, a 4.5-fold increase in the half-life of the ornithine decarboxylase activity was observed in vinblastine-treated cells. This effect is probably due to the inhibition of the intracellular enzyme degradation by the vinca alkaloids.

Animals

Phagocytic cell function in active brucellosis.

In this study, we analyzed phagocytic cell function in 51 patients with active brucellosis and its relationship with different clinical, serological, and evolutionary variables. A control group was made up of 30 blood donors of similar geographic extraction, age, and sex, with no previous history of brucellosis or known exposure ot the infection or specific antibodies. The investigations were carried out at the time of diagnosis, at the conclusion of treatment, and after 6 months of follow-up. Polymorphonuclear leukocyte adherence and nitroblue tetrazolium reduction in response to Brucella antigen were significantly increased in the patients at the time of diagnosis with respect to the control group. In contrast, chemotaxis in response to Brucella antigen and phagocytosis were significantly reduced in the patients with respect to the control group. The alterations in phagocytic cell function were greater in patients with bacteremia, with focal forms of the disease, or with a longer diagnostic delay. Most of these initial alterations tended to normalize with treatment, indicating their transient character.

Adolescent

5' Deiodinase activity in brain regions of adult rats: modifications in different situations of experimental hypothyroidism.

In the central nervous system, type II 5' deiodinase (5'D-II) is highly regulated, as judged by the dramatic changes in enzyme levels observed after abrupt alterations in thyroid status. In this work, the 5'-DII activity has been studied in different situations of experimental hypothyroidism (propylthiouracil, methimazole, thyroidectomy, and low iodine diet), in various brain regions (pituitary, cerebellum, brain stem, hypothalamus, cortex, and whole brain) in adult rats. Propylthiouracil and methimazole significantly increase the activity in all brain regions. These increases are higher in rats treated with methimazole. Thyroidectomy significantly increases the activity in cortex and pituitary. A low iodine diet significantly increases in all brain regions except in the hypothalamus. The concentration of triiodothyronine (T3) studied in the major brain regions remained unchanged. The results obtained show a compensatory mechanism in pituitary and other brain regions in order to maintain the T3 levels in brain tissue.

Animals

Rat serum fructose 1,6 bisphosphatase: modifications in different experimental conditions.

Fructose 1,6 bisphosphatase activity was measured in rat serum. The activity of the enzyme presented the following characteristics: pH optimum alkaline, between 8-8.5 and inhibited by AMP. The activity was measured in different experimental situations, such as streptozotocin diabetes, hepatocellular injury produced by carbon tetrachloride (CCl4), and bile-duct ligation. In diabetic rat, serum activity increased 2-fold with respect to the control values. In animals treated with CCl4 the activity increased 10-14 fold. On the contrary bile duct ligation decreased activity according to the cholestasis time. The results obtained in this study show that fructose 1,6 bisphosphatase is an enzyme measurable in serum, which changes according to different situations of liver cell injury.

Animals

[L-thyroxine and L-triiodothyronine in the cerebral tissues of the adult rat. Effect of hypothyroidism].

The L-thyroxine and L-triiodothyronine concentrations in several brain areas (cerebral cortex, brain stem, hypothalamus, total brain and hypophysis) in normal and hypothyroid rats have been studied. Results show that L-thyroxine values at tissue level are inferior in the hypothyroid group, although non-significant with respect to the control group, whereas L-triiodothyronine presents values similar to the hypothyroid group and its control in all the brain regions studied with the exception of hypophysis. These results show that in hypothyroid situations exist a compensatory mechanism for maintaining the adequate L-triiodothyronine levels in several brain areas, although the serum levels are strongly decreased in hypothyroid animals.

Animals

Serum activity of the key gluconeogenic enzymes in carbon-tetrachloride-induced experimental hepatotoxicity.

Serum activity has been measured in three of the key enzymes in the gluconeogenic pathway in rats subjected to experimental hepatotoxicity after intraperitoneal administration of carbon tetrachloride. The levels of phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-biphosphatase (FBPase) showed a similar behavior to the transaminase (AST and ALT), increasing markedly with respect to the controls at 12 h after administration of the poison, reaching their maximum peak of activity at between 24 and 36 h, and returning to normal values at 96 h. The activity of glucose-6-phosphatase was not significantly modified throughout the treatment. These results seem to demonstrate that the determination of the serum activity of PEPCK and FBPase could be a sensitive and specific marker of hepatic cytolysis.

Alanine Transaminase

Evaluation of key gluconeogenic enzymes in experimental biliary obstruction.

In order to evaluate the usefulness of key gluconeogenic enzymes, in relation to the markers commonly used (alkaline phosphatase and gamma-glutamyl transpeptidase) for the diagnose of cholestasis the serum activity of phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose-6-phosphatase has been measured in rats with bile-duct ligation. Among the gluconeogenic enzymes studied only phosphoenolpyruvate carboxykinase activity increased significantly in the first 48 hours after cholestasis, decreasing thereafter to normal values. Both alkaline phosphatase and gamma-glutamyl transpeptidase activities showed a very significant increase which persisted throughout the experiment. These results seem to indicate that in spite of the high organ specificity of these enzymes they do not appear to be useful for the diagnosis of cholestasis.

Alanine Transaminase

Effect of low-iodine diet and propylthiouracil on glycolytic enzymes in brain areas of adult rats.

Glycolytic activity of five brain areas in the rat was studied under two hypothyroid states: (1) induced by low-iodine diet from weaning, and (2) induced by propylthiouracil. The areas studied were the anterior cortex, amygdala, hypothalamus, septum and hippocampus. A low-iodine diet induced a decrease of pyruvate kinase activity in three region and of phosphofructokinase in the hippocampus, while hexokinase increased in both the amygdala and septum. Propylthiouracil treatment produced an increase in hexokinase activity in the hypothalamus and septum, and a decrease in the anterior cortex, while phosphofructokinase decreased significantly in the hippocampus. No significant changes of lactate dehydrogenase activity were observed. The correlation between the results and type of hypothyroidism is discussed.

Animals

Fructose bisphosphatase activity in the serum of rats treated with carbon tetrachloride.

In this work, fructose bisphosphatase activity in the serum of rats treated by different carbon tetrachloride doses was measured. Fructose bisphosphatase activity increased very significantly with respect to the control animals in all groups assayed. The severe reduction of the activity measured in the presence of adenosine-5'-monophosphate and its stability when measured in the presence of 1-p-bromotetramisole oxalate support its specific origin. These data suggest that serum FBPase activity measurement could be used as a biochemical marker in the diagnosis of hepatocellular injury.

Animals

Activities of glycolytic enzymes in some brain areas of thyroidectomized rats and their response to replacement therapy.

Glycolytic metabolism has been assessed by studying a set of key enzymes, in anterior cortex, amygdala, hypothalamus septum and hippocampus, in thyroidectomized rats. The reversibility of the changes induced by the thyroidectomy has been assessed by replacement therapy. In thyroidectomized rats the hexokinase activity was significantly decreased in anterior cortex and hypothalamus. The increase in phosphofructokinase and pyruvate kinase activity was probably due to an increase in cellular energy requirements. Hexokinase activity was best restored by treatment with L-thyroxine (T4) or T4+ propylthiouracil (PTU). The low response of pyruvate kinase activity in all treated animals could suggest that this metabolic step is the least reversible.

Animals

Influence of thyroid hormone deficiency on the citrate synthase activity in rat brain regions during early postnatal development.

The developmental pattern of citrate synthase activity has been studied in the liver and several brain areas of hypothyroid rats during the 4 first weeks of life. While citrate synthase activity in the liver showed a rise during the 2 first weeks of life, different patterns of enzyme activity were found in the brain regions of euthyroid animals. Citrate synthase activity increased in the cerebellum, decreased in the cerebral cortex and did not change significantly in the brain stem during the period studied. In the liver and brain areas, too, a decrease in citrate synthase activity was observed during hypothyroidism. From the 2nd week of birth, the citrate synthase activity in the brain but not in the liver was found to have recovered. The newly elevated citrate synthase activity coincided with a slight increase in thyroid hormone serum levels.

Animals

[Changes in dehydrogenase glutamate in the rat brain caused by thyroid hormone deficiency].

The dependent GDH-NADPH activity in adenohypophysis and other cerebral areas, has been studied in hypothyroid rats, in which hypothyroidism has been induced surgically. After thyroidectomy a decrease of GDH activity in limbic system (amygdala, septum and hippocampus), and an increase of this enzyme in cortex and hypothalamus have been found, with no changes in adenohypophysis. The alterations of GDH activity, induced by thyroidectomy, have been corrected, although not uniformly in the different brain areas after L-T3 treatment.

Animals

Effect of thyroid hormones on the glycolytic enzyme activity in brain areas of the rat.

The glycolytic metabolism through the key enzymes, hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, have been studied in the brain areas: anterior cortex, amygdala, hypothalamus, septum and hippocampus in adult rats with pharmacologically induced hyperthyroidism. The oxidative metabolism of glucose is accelerated in most brain areas by treatment with high doses of T3, as is shown by the increase in HK activity, approaching normality on reducing the dose. This decrease can also by observed in the PFK activity through the effect of assayed doses of thyroxine. The anterior cortex is the only brain area that does not show significant variations of PK activity through the effects of treatment with thyroid hormones. On the other hand, a general inhibition of the glycolytic anaerobic pathway by treatment with T3 was observed.

Amygdala

[Effect of thyroid hormones on the activity of pyruvate kinase and lactate dehydrogenase in mature rat brain].

The enzymatic activities of two "key" enzymes of the glycolytic pathway, pyruvate kinase and lactic dehydrogenase, were studied in seven areas of the brain in male adult rats in states of pharmacologically induced hyper and hypothyroidism. The brain areas were: anterior cortex, adenohypophysis, hypothalamus, amygdaline nucleus, septum, hippocampus and cerebellum. In T3 treated animals, pyruvate kinase activity showed significant increase in all the areas studied while lactic dehydrogenase activity decreased. In propyl-thiouracil treated animals these enzyme activities showed no significant variations from those in animals of the control group.

Animals

Evolution of gluconeogenic enzyme activities during starvation in liver and kidney of the rainbow trout (Salmo gairdneri).

1. There was a general increase in the activities of enzymes involved in gluconeogenesis in liver and kidney of rainbow trout, Salmo gairdneri, during the second month of starvation. 2. The need of gluconeogenesis during the first month of the starvation period was probably minimal because of the utilization of liver glycogen as a source of blood glucose. 3. The decline of fat was more pronounced than that of protein total content in absolute values, suggesting that lipid reserved were the main sources of energy during starvation.

Animals

Hormonal effects on the liver glucose metabolism in rainbow trout (Salmo gairdneri).

1. Glucagon, adrenaline and dibutyril cyclic AMP increased the release of glucose to the medium during incubation of liver slices from rainbow trout (Salmo gairdneri) while insulin had no effect. 2. Glycogen content decreased only slightly after cyclic AMP addition and even increased in the presence of glucagon and adrenaline. Consequently, the release of glucose was due mainly to gluconeogenesis. 3. This is corroborated by the reduction of glucose liberation in presence of alpha-cyanocinnamate, an inhibitor of gluconeogenesis.

Animals