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Biomedical subjects

A Ortega

Publications and source records attributed to A Ortega.

At least 181 records · Page 10Linked to original sources
PubMed1991

Developmental toxicity evaluation of orthovanadate in the mouse.

Sodium orthovanadate in deionized water was administered once daily by gavage on gestational days 6-15 to mice at doses of 0, 7.5, 15, 30, and 60 mg/kg. Dams were killed on day 18 of pregnancy, and fetuses were examined for external, visceral, and skeletal defects. Maternal toxicity was observed at the highest doses of sodium orthovanadate, as evidenced by a significant number of deaths (60 and 30 mg/kg/d) and reduced weight gain and food consumption (30 and 15 mg/kg/d). Embryolethality and teratogenicity were not observed at maternally toxic doses and below, but fetal toxicity was evidenced by a significant delay in the ossification process of some skeletal districts at 30 mg/kg/d. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 7.5 mg/kg/d, and 15 mg/kg/d represented a NOAEL for developmental toxicity in mice under the conditions of this study.

Animals↗
PubMed1991

Influence of chronic exposure to uranium on male reproduction in mice.

Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day.

Animals↗
PubMed1991

Properties of kainate receptor/channels on cultured Bergmann glia.

Following the localization, at the electron microscope level, of the immunoreactivity towards a putative kainate receptor on Bergmann glial cells in the chick cerebellar cortex, cultures of Bergmann glia were used to establish the presence of functional kainate receptor/channels and study their properties. Bergmann glia were identified by their fusiform morphology and their ability to bind an anti-kainate binding protein monoclonal antibody, a kainate receptor high affinity ligand--kainyl-bovine serum albumin--and a glial marker--anti-vimentin monoclonal antibody. Membranes prepared from the culture cells displayed, using 25 nM [3H]kainate, the binding of 4.1 pmol of [3H]kainate/mg protein and showed the presence in Western blots of the two polypeptides of 49 and 93 kDa attributed to the kainate binding protein. Kainate, at concentrations above 0.1 mM, was found to increase the influx into cultured Bergmann glia of 22Na+, 86Rb+, 45Ca2+ and 36Cl- ions. The traffic of 22Na+, induced by kainate and glutamate, observed only in the presence of 1 mM ouabain, was blocked by kainate receptor antagonists and by 0.01 mM quisqualate. Analysis of the kinetics of incorporation of 22Na+ and 45Ca2+ ions showed an initial accumulation of 22Na+ and 45Ca2+ ions followed by their total dissipation. The results indicate that the kainate-induced influx of Na+ ions through the kainate receptor/channel causes the reverse transport of Na+ ions, by activation of the Na+/Ca2+ and Na+/H+ exchangers which remove intracellular Na+ ions. Pre-exposure of the cells to 0.5 mM dibutyryl cAMP was found to greatly enhance the kainate-induced 22Na+ ion influx. We propose that the Bergmann glia kainate receptors modulate the efficacy of the glutamatergic synapses between the parallel fibers and Purkinje cell spines and form part of a glial machinery responsible for plastic changes in synaptic transmission.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Effects of administration route on valproate pharmacokinetics in the rabbit.

The absorption of sodium valproate was studied in 5 rabbits. Each animal received the drug (70 mg/kg) via 3 routes: intravenous, gastric and duodenal. For the 2 extravascular routes, the absolute bioavailability F, maximal plasma concentrations Cmax, times to peak Tmax and absorption coefficients Kabs were the same. Absolute bioavailability was always close to unity. This indicated that valproic acid was absorbed from the intestine as well as from the whole gastrointestinal tract. The other pharmacokinetic parameters such as terminal plasma half-life, total clearance and volume of distribution remained unchanged whatever the route of administration.

Animals↗
PubMed1991

Developmental toxicity evaluation of tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) in mice.

Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating agent used in the treatment of experimental metal poisoning, was evaluated for developmental toxicity in pregnant Swiss mice. Tiron was administered intraperitoneally on gestational days 6 through 15 at doses of 0, 750, 1500, or 3000 mg/kg/day. Cesarean sections were performed on gestation day 18. All fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with Tiron resulted in maternal toxicity at 3000 mg/kg/day as evidenced by a high number of deaths, reduced body weight during gestation and increased relative liver and kidney weights. There were no significant differences between treated and control animals on the number of total implants, dead fetuses, or sex ratio. However, embryo fetotoxicity was evidenced at 3000 mg/kg/day by a significant increase in the number of resorptions per litter, and a significant decrease in the average fetal body weight. There were no significant changes in the incidence of abnormalities (expressed as total, individual, external, visceral, or skeletal). The no observable adverse effect level (NOAEL) for maternal and developmental toxicity was 1500 mg Tiron/kg/day.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1990

Phosphorylation of the 49-kDa putative subunit of the chick cerebellar kainate receptor and its regulation by kainatergic ligands.

The traffic of ions through the kainic acid (KA) receptor/channels present on chick cerebellar glia is modulated by intracellular events likely to involve phosphorylation reactions. The protein carrying the KA binding sites has been isolated from chick cerebellum and shown to be composed of a 49-kDa polypeptide. Its primary structure, established via cDNA cloning, shows the presence of two putative phosphorylation sites. We report here that this 49-kDa polypeptide is a substrate of the cAMP-dependent protein kinase which catalyzes the incorporation of up to 2 mol of phosphate/mol of KA binding site. KA prevents this phosphorylation reaction in a concentration range similar to that needed to activate the KA receptor/channels but higher by 3 orders of magnitude than that needed to saturate the KA binding sites. Kainatergic ligands produce similar effects to those of KA, but 1 mM N-methyl-D-aspartic acid and 1 mM quisqualic acid have no effect. However, 0.01 mM quisqualic acid prevents the inhibitory action of KA. These results raise the possibility that the phosphorylation of KA receptor/channels in their cellular environment is negatively regulated by KA.

Animals↗
PubMed1990

[Cerebral infarct in a young adult, as the presenting form of myeloencephalopathic syndrome with lactic acidosis and cerebral ischemia].

We report a 26-year-old male who developed aphasia due to an ischemic cerebral infarction caused by MELAS (myoencephalophatic syndrome with lactic acidosis and cerebral ischemia). The most common causes of cerebral infarction in young patients were ruled out by laboratory investigations. The diagnosis of MELAS was suspected on the basis of past history of epilepsy, migraine and progressive sensory deafness, and increased resting blood lactic acid. Cerebral computed tomography showed bilateral caudate-putamen-pallidal calcification and nuclear magnetic resonance scan disclosed a left ischemic parietal-temporal-occipital infarction. The diagnosis was confirmed by muscular biopsy, which was characteristic of mitochondrial myopathy showing "red disarrayed" fibers in the histologic modified trichromic Gomori stain. Our patient showed that MELAS should be considered in young adults with cerebral infarction. The diagnosis should initially be suspected on a clinical basis, and confirmed by the presence of "red disarrayed" fibers with modified trichromic Gomori stain histologic muscle study.

Acidosis, Lactic↗
PubMed1990

Effects of protein deprivation on pyramidal cells of the visual cortex in rats of three age groups.

The effect of protein deprivation on rapid Golgi impregnated pyramidal neurons in layers II/III and V of the rat visual cortex was studied at 30, 90, and 220 days of age using morphometric methods. In order to mimic human under-nutrition female rats were adapted to either an 8% or control 25% casein diet 5 weeks prior to conception and maintained on these diets during gestation and lactation. The pups were then weaned and maintained on their respective diets. The undernourished rats showed a significant decrease in brain weight only at 90 days, indicating that the protein deprivation had a mild effect on brain development. Correspondingly, the number of significant histological differences between the two diet groups were least at 30 and 220 days of age. The effect of the diet was greater on layer V than on layer II/III pyramids. At 30 days of age the effect of the diet was different on the pyramids of these two cell layers, at 90 days there was a mixture of similar and dissimilar effects, and at 220 days the pyramids of these two cell layers showed only minor differences between the two diet groups. Analysis of age-related changes indicated that the effect of the diet was different on layer II/III pyramids compared to layer V pyramidal cells. These different effects apparently accounted for the progression from a dissimilar effect of the diet at 30 days on the pyramids of the two cell layers to only minor differences between them at 220 days. Further analysis of these age-related changes shows that two prominent effects of protein deprivation are for age-related changes to occur in undernourished rats but not in controls and for age-related changes to be out-of-phase with each other in the two diet groups. From these findings, and a review of similar studies in the literature, we propose that these mechanisms are a prominent effect of undernutrition in the post-weaning period and help account for the unexpected increases in morphometric measurements noted in undernourished rats in this and other studies.

Aging↗
PubMed1990

Skin biopsy findings in glycogenosis III: clinical, biochemical, and electrophysiological correlations.

Electron microscopy of skin specimens was performed in 4 patients (age range, 7 months-40 years) with glycogenosis III and revealed consistent abnormalities. Massive glycogen storage was observed in epithelial secretory cells of eccrine sweat glands and, less markedly, in smooth muscle fibers from the erector pili. Other cells, including Schwann cells of myelinated and unmyelinated fibers, were not affected. The extent of glycogen storage was similar in all patients and unrelated to age or duration of disease. The extralysosomal nature and selectivity of glycogen deposits, sparing fibroblasts and other cells, differ clearly from the findings in skin from patients with glycogenosis II. The purpose of this study was to show that glycogen deposits in glycogenosis III are not restricted to skeletal muscle and liver, and to assess the usefulness of skin biopsy in this disorder.

Adolescent↗
PubMed1990

Developmental toxicity of vanadium in mice after oral administration.

Vanadium, as vanadyl sulphate pentahydrate, was evaluated for its embryotoxic, fetotoxic and teratogenic potential in Swiss mice. The compound was administered by gavage to pregnant mice at doses of 0, 37.5, 75 or 150 mg kg-1 day-1 on days 6-15 of pregnancy. On gestation day 18, all live fetuses were examined for external, visceral and skeletal malformations and variations. Maternal toxicity was observed in the vanadium-treated animals, as evidenced by reduced weight gain, reduced body weight on gestation day 18 (corrected for gravid uterine weight) and decreased absolute liver and kidney weights at 75 and 150 mg kg-1 day-1. The number of total implants, live and dead fetuses, late resorptions, the sex ratio and the post-implantation losses were not significantly different between the vanadium-treated mice and the controls. However, there was a significant increase in the number of early resorptions per litter at all dose levels. Fetotoxicity was evidenced by lower fetal weights and fetal lengths, and the presence of developmental variations. Malformation incidence also was increased by the administration of vanadium. Thus, the 'no observable effect level' (NOEL) for maternal toxicity, embryofetotoxicity and teratogenicity for vanadyl sulphate pentahydrate under these test conditions was below 37.5 mg kg-1 day-1 for Swiss mice.

Abnormalities, Drug-Induced↗
PubMed1990

Evaluation of the developmental effects on mice after prenatal, or pre- and postnatal exposure to 2,3-dimercaptopropane-1-sulfonic acid (DMPS).

The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a water soluble metal complexing agent, was administered to four groups of pregnant Swiss mice at 0, 70, 210, and 630 mg/kg/day by two dosing schedules: gestation day 14 until birth (prenatal exposure), and gestation day 14 until postnatal day 21 (pre- and postnatal section). Dams were allowed to deliver and the number of live and dead pups recorded. Each pup was sexed and weighed on days 0, 4, 14, and 21. Also, pinna detachment, incisor eruption and eye opening were monitored. No adverse effects on offspring survival or development were evident in either exposures at doses employed in this study. The "no observable effect level" (NOEL) for health hazard to the developing fetus or pup was 630 mg DMPS/kg/day. This dose is much higher than the amounts of DMPS usually administered in human heavy metal poisoning.

Animals↗
PubMed1990

Effectiveness of chelation therapy with time after acute uranium intoxication.

The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1990

Oral meso-2,3-dimercaptosuccinic acid in pregnant Sprague-Dawley rats: teratogenicity and alterations in mineral metabolism. I. Teratological evaluation.

meso-2,3-Dimercaptosuccinic acid (DMSA), an effective antagonist for the treatment of lead, arsenic, mercury, and cadmium poisoning, was evaluated for developmental toxicity in pregnant Sprague-Dawley rats. DMSA was administered by gavage on d 6-15 of gestation at doses of 0, 100, 300, or 1000 mg DMSA/kg/d. At termination on d 20 of gestation, fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal toxicity was observed at all doses, as evidenced by a significant decrease in body weight gain. There were no effects with respect to hematology or clinical chemistry. Increased early resorptions, increased percentage postimplantation loss, and reduced fetal body weight per litter were observed at 100, 300, and 1000 mg/kg/d. Examination of fetuses for gross external abnormalities, visceral and skeletal malformations, or ossification variations revealed that DMSA did not produce teratogenicity at any dosage level. However, significant fetotoxicity was observed at 100, 300, and 1000 mg/kg/d. The no-observable-effect level (NOEL) for maternal and developmental toxicity was less than 100 mg DMSA/kg/d.

Administration, Oral↗
PubMed1990

Oral meso-2,3-dimercaptosuccinic acid in pregnant Sprague-Dawley rats: teratogenicity and alterations in mineral metabolism. II. Effect on mineral metabolism.

The effect of meso-2,3-dimercaptosuccinic acid (DMSA) on mineral metabolism was investigated in pregnant Sprague-Dawley rats. Animals were given by gavage doses of 0, 100, 300, or 1000 mg DMSA/kg/d on gestational d 6-15. On d 20 of gestation dams were killed and fetuses were removed from the uterus. The levels of calcium, magnesium, zinc, copper, and iron were measured in maternal liver, kidney, and intestine, as well as in whole fetus and in fetal liver. Mineral analysis of maternal and fetal tissues revealed pronounced effects of DMSA on mineral metabolism. The results of this investigation indicate a strong possibility that the negative effects of the drug on pregnancy are due in part to the changes in mineral metabolism.

Administration, Oral↗
PubMed1989

[Neurologic manifestations of dissecting aneurysms of the aorta].

Dissecting aneurysm of the aorta keeps on being nowadays a diagnostic problem, although it is a well known entity. Dissecting aneurysms may be classified into type A, dissection involving the ascending aorta, and type B, dissection involving descending aorta. The frequency of neurologic manifestations oscillates from 18 to 30%. From the 133 cases of dissecting aneurysm attended at our hospital, 30 (22.5%) presented neurologic manifestations. Nine patients (30%) had symptoms of ischemic neuropathy; 13 (43.3%) presented symptoms compatible with spinal ischemia and 14 (46.7%) presented manifestations of brain ischemia, with involvement of supraaortic trunks proven at autopsy in eight cases. The neurologic complications of type A and B dissecting aneurysms were similar (28 and 26%); in up to 30% of patients, it was the initial symptom. In type A dissecting aneurysm, the most frequent neurologic manifestation was brain ischemia (57.1%) whereas ischemic neuropathy and spinal ischemia predominated in type B dissecting aneurysm. The overall mortality rate reached 76.7% (85.7% for type A and 55.5% for type B). The modality of treatment had no clear influence on the survival. In the presence of brain complications, the mortality was 100%.

Aged↗
PubMed1989

Kainyl-bovine serum albumin: a novel ligand of the kainate sub-type of glutamate receptor with a very high binding affinity.

Bovine serum albumin has been conjugated with kainylaminooxyacetylglycine to afford a multivalent kainylated protein called kainyl-bovine serum albumin (KA-BSA). This derivative, radiolabelled with 125I to more than 5000 Ci/mmol, was found to interact in the chick, goldfish and rat brain to specific membranous sites displaying the pharmacological properties attributed to the kainate sub-type of glutamate receptor. Measurements of the kinetics of association and dissociation of KA-BSA showed a quasi-irreversible binding with dissociation constants in the subpicomolar and nanomolar range. The chemical properties and the binding characteristics of KA-BSA suggest that it interacts mainly with kainate binding sites present in clusters in the membrane. Localization of the KA-BSA binding sites, by autoradiography in the chick cerebellum and by immunoperoxidase staining in the goldfish cerebellum, revealed an exclusive association with the molecular layer.

Animals↗