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Biomedical subjects

D Acosta

Publications and source records attributed to D Acosta.

At least 163 records · Page 9Linked to original sources
PubMed1990

[Treatment of macroprolactinomas with delayed bromocriptine. Effectiveness of a single intramuscular injection].

The aim of the present study was to evaluate the effectiveness and tolerance of a new pharmaceutical preparation of long acting bromocryptine (bromocryptine depot of L.A.), characterized by the slow release of bromocryptine during 4 or 6 weeks after a deep intramuscular injection. It was administered to 9 patients with macroprolactinoma, 7 of which had visual abnormalities. The tolerance of the drug was excellent, and only one patient had nausea within the first 24 hours. In all cases, PRL values fell between 40% and 97%. All patients with visual abnormalities, including 2 patients with cranial nerve palsy (IIIth and VIIth pairs) returned to normal or improved. In the CT controls carried out after 4 weeks of therapy a reduction in tumor size was observed in 7 of 9 patients. Two patients were operated through the transesphenoidal route, PRL being demonstrated in the immunohistochemical study of the resected specimen. Subsequently, all patients received oral bromocryptine therapy with perfect tolerance. The results show that parenteral long acting bromocryptine is an effective, well tolerated and convenient way to start the therapy of macroprolactinoma, even when severe visual abnormalities are present.

Adolescent↗
PubMed1990

Toxicity assessment of papaverine hydrochloride and papaverine-derived metabolites in primary cultures of rat hepatocytes.

The present study was undertaken to assess and compare the toxic effects of papaverine hydrochloride and its metabolites. Primary cell cultures of rat hepatocytes were treated with papaverine (papaver), 3'-O-desmethyl (3'-OH), 4'-O-desmethyl (4'-OH), and 6-O-desmethyl (6-OH) papaverine at 1 x 10(-5), 1 x 10(-4), and 1 x 10(-3) M for 4, 8, 12, and 24-h periods. Cell injury was determined by: a) cell viability using the trypan blue exclusion test; b) cytosolic enzyme leakage of lactate dehydrogenase and aspartate aminotransferase; c) morphologic alterations; and d) lactate:pyruvate (L:P) ratios. Cell cultures showed concentration- and time-dependent toxic responses. For example, a decrease in cell viability and an increase in enzyme leakage were observed after cell treatment with 1 x 10(-4) and 1 x 10(-3) M papaver for 8 h; 1 x 10(-3) M 6-OH papaverine for 8 h and 1 x 10(-4) M for 24 h; and 1 x 10(-3) M 4'-OH papaverine for 24 h (P less than 0.05). Furthermore, changes in morphology correlated to cell viability and enzyme release in those cultures treated with papaver, 4'-OH and 6-OH papaverine. Some of these changes included size deformation, cell detachment from the dishes, and cell necrosis. On the other hand, an increase in L:P ratios (P less than 0.05) was detected with papaver as early as 8 h with 1 x 10(-4) and 1 x 10(-3) M and 12 h with 1 x 10(-5) M; 6-OH showed an increase in L:P ratios at 8 h with 1 x 10(-3) M and 12 h with 1 x 10(-4) M; these changes were evident with with 4'-OH at 12 h with 1 x 10(-3) M. In contrast, cells treated with 3'-OH papaverine did not show significant damage with any time period and concentration used in this study. The results of this study indicate that papaverine-derived metabolites are less cytotoxic than its parent compound, papaver. The toxicity was ranked as follows: papaver greater than 6-OH greater than 4'-OH greater than -3'-OH.

Animals↗
PubMed1990

Lack of changes in cytosolic ionized calcium in primary cultures of rat kidney cortical cells exposed to cytotoxic concentrations of gentamicin.

Gentamicin nephrotoxicity in vivo has a delayed onset. Our assessment of gentamicin-induced cell death in vitro, by measuring the release of cytosolic lactate dehydrogenase (LDH), indicated a prolonged onset as well. A recent study, which showed that gentamicin caused an abrupt increase in the concentration of cytosolic free calcium ([Ca2+]i) in a trypsin-harvested kidney cell line, suggested that immediate changes in calcium homeostasis may initiate the pathogenesis of gentamicin nephrotoxicity. To study the immediate effect of gentamicin on [Ca2+]i, gentamicin was perfused for 1 hr over primary monolayer cultures of renal cortical epithelial cells, and suspensions of trypsin-harvested renal cells (from primary cultures and a cell line) were treated with gentamicin for 30 min. [Ca2+]i was determined using the fluorescent probe fura-2. Positive controls (ionomycin and mercury) reliably increased [Ca2+]i in each experimental model, but no increase in [Ca2+]i was observed with gentamicin. Because enzyme release data indicated that significant cytotoxicity did not occur until 48 hr of exposure to 2 mM gentamicin, primary cultures were exposed to gentamicin (1-2 mM) for 24-48 hr and [Ca2+]i was measured. No gentamicin-induced increase in [Ca2+]i was observed in these longer exposures, whether or not significant LDH release occurred. These results do not support a role for elevated [Ca2+]i in the cytotoxicity of gentamicin in cultured kidney cells, either immediately after exposure or following prolonged exposures.

Animals↗
PubMed1990

Cytotoxicity induced by papaverine hydrochloride in fungal cell systems.

Cunninghamella echinulata was used to assess the cytotoxicity of papaverine (papaver), at concentrations ranging from 1 x 10(-5) to 1 x 10(-3) M for 1-6 days. Leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and changes in alkaline phosphatase (AP) activity and lactate/pyruvate (L/P) ratios were used as indices of cytotoxicity. Leakage of LDH occurred at the 6th day with 1 x 10(-3) M; AP activity and L/P ratios decreased after 6 days treatment with 1 x 10(-4) M, after 1 day with 1 x 10(-3) M, and after 3 days with 1 x 10(-4) M, respectively. This study provides support for the use of fungal cell systems to evaluate the toxicity of drugs and chemicals.

Alanine Transaminase↗
PubMed1990

Microbial models of mammalian metabolism: biotransformations of phenacetin and its O-alkyl homologues with Cunninghamella species.

1. The analgesic compound phenacetin and its O-alkyl homologues were metabolized by Cunninghamella elegans to yield the O-dealkylation product paracetamol (acetaminophen), and metabolites resulting from omega-1 hydroxylation and further oxidations. 2. Structural identification was based upon physical, spectral and chromatographic comparisons of isolated metabolites with synthetic standards generated by alkylation of paracetamol with the appropriate alkyl halide, epoxide, or alpha,beta-unsaturated ketone. 3. The rank order of O-dealkylation within the homologous series based upon either substrate disappearance or phenol formation was found to be ethyl greater than isopropyl greater than n-propyl greater than n-butyl greater than methyl.

Acetaminophen↗
PubMed1990

Toxic mechanisms of the heart: a review.

Toxic injury is one of the many ways by which the functional integrity of the heart may become compromised. Any of the subcellular elements may be the target of toxic injury, including all of the various membranes and organelles. Understanding the mechanisms underlying cardiotoxicity may lead to treatment of the toxicity or to its prevention. Doxorubicin and its analogs are very important cancer chemotherapeutic agents that can cause cardiotoxicity. Other agents which are cardiotoxic and which have profound public health implications include the alkaloid emetine in ipecac syrup, cocaine, and ethyl alcohol. The most important cardiotoxic mechanisms proposed for doxorubicin include oxidative stress with its resultant damage to myocardial elements, changes in calcium homeostasis, decreased ability to produce ATP, and systemic release of cardiotoxic humoral mediators from tissue mast cells. Each of the first 3 mechanisms can lead to each of the other 2, and the causal relationships between all of these mechanisms are not clear. New evidence suggests that doxorubicinol, one of the metabolites of doxorubicin may be the moiety responsible for cardiotoxicity. Several other potential mechanisms also have been proposed for doxorubicin. Emetine in ipecac syrup is the first aid treatment of choice for many acute toxic oral ingestions and the alkaloid, itself, is used to treat amebiasis. Cardiotoxicity occurs following chronic exposure, such as occurs therapeutically in amebiasis and with ipecac abuse by bulemics. A number of mechanisms are proposed for emetine cardiotoxicity, but the current mechanistic literature is quite scarce. Cocaine abuse recently has caught the public interest, in particular because of the drug-related sudden deaths of certain athletes. Cocaine can cause hypertension, arrhythmias, and reduced coronary blood flow, each of which can contribute to its lethality. However, it may be possible that cocaine sudden death episodes are more related to hyperthermia and convulsive seizures, rather than to cardiovascular toxicity. Chronic alcohol use leads to dilated cardiomyopathy and failure as part of the general physical degeneration that occurs with alcoholism. Several mechanisms are proposed for the cardiomyopathy, but only 2 things seem clear. The cardiotoxicity is due to an intrinsic effect of alcohol, rather than to malnutrition or co-toxicity, and abstinence is the only effective treatment for the cardiomyopathy. Recent articles indicate that very moderate use of alcohol may be beneficial and protect against cardiovascular-related morbidity. One explanation for these findings seems to be that the non-drinking groups, against whom the moderate drinking comparisons were made, were enriched in former drinkers with significant alcohol-related cardiovascular pathology.

Animals↗
PubMed1990

[Atrioventricular block in Kearns-Sayre syndrome].

We report a case of a 17-year-old woman with Kearns-Sayre Syndrome who developed a high degree atrioventricular block. She had intraventricular conduction disturbances with normal atrioventricular conduction in previous electrocardiograms. The diagnosis criteria of this rare syndrome are commented on, and we describe the electrophysiological features, prognostic and treatment that atrioventricular conduction disturbances produce in these patients. We emphasize the necessary collaboration between neurologists and cardiologists in the early recognition of the conduction disturbances for implanting a prophylactic pacemaker.

Adolescent↗
PubMed1989

Protective effect of flavonoids on drug-induced hepatotoxicity in vitro.

Primary cell cultures of neonatal hepatocytes were used to examine the protective effect of flavonoids in the presence of hepatotoxins. Catechin (CAT) and silybin (SIL) protected the hepatocytes against cell injury produced by erythromycin estolate (EE), amitriptyline (AT), nortriptyline (NT), and tert-butylhydroperoxide (TBOOH). Leakage of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as morphological parameters, were used as indices of hepatotoxicity. Hepatocytes were exposed to EE (1 X 10(-4) M and 2 X 10(-4) M), AT, NT, and TBOOH (1 X 10(-4) M and 1 X 10(-3) M) for a 2-h period. These hepatotoxins caused significant LDH, AST, and ALT leakage (P less than 0.05) when compared to untreated control groups. NT was less toxic than its parent compound, AT. Changes in morphology were evident after 1 h of treatment with the toxicants, including: vacuole formation, size deformation and cell necrosis. As the concentration of hepatotoxins was increased, the changes were more pronounced. Pretreatment of the cultures with either CAT or SIL resulted in less enzyme leakage and morphological alterations by the hepatotoxins. The results of this study suggest that CAT and SIL may act by stabilizing the plasma membrane against toxic insult.

Alanine Transaminase↗
PubMed1989

Rapid improvement of visual defects with parenteral depot-bromocriptine in a patient with a non-functioning pituitary adenoma.

The management of non-functioning pituitary adenomas with bromocriptine is controversial, and surgical treatment is usually prescribed when the visual field is affected. Here we report, what we believe to be the first case of a patient with a non-functioning pituitary adenoma who experienced normalization of visual field defects and a substantial improvement in visual acuity after the parenteral administration of depot-bromocriptine. The patient's tolerance to the drug was excellent. The results of the immunohistochemical study of the surgically removed tumor were negative for PRL, GH, LH, FSH, TSH and ACTH. In our opinion, the use of depot-bromocriptine may represent an alternative to surgery in patients with non-functioning pituitary adenomas associated with visual lesions.

Adenoma↗
PubMed1988

Cardiotoxicity of Kenyan green mamba (Dendroaspis angusticeps) venom and its fractionated components in primary cultures of rat myocardial cells.

The cardiotoxic actions of Kenyan green mamba (Dendroaspis angusticeps) venom have been investigated using primary myocardial cell cultures isolated from neonatal rat hearts. The cardiotoxic actions of the whole venom and its fractionated components were evaluated on the basis of leakage of lactate dehydrogenase (LDH), changes in morphology, cell membrane lysis, decreases in viability and inhibition of spontaneous beating activity. The whole venom caused time- and concentration-dependent arrest of myocardial contraction, leakage of LDH, extensive disruption of cell monolayer, and decreases in viability. The venom was separated into 6 (DaI to DaVI) fractions by gel permeation chromatography on Sephadex G-50. Spontaneous beating activity was abolished by DaI to DaVI at high concentrations, while at lower doses they induced progressive depression of beating frequency after a 3-h treatment period. DaI to DaIV caused significant leakage of LDH, morphological damage, and decreases in viability after a 6-h incubation period. The most cardiotoxic fraction (DaIV), which also contains about 54% of the total protein of the whole venom, was fractionated into 18 polypeptides (Da1 to Da18) by ion exchange chromatography on Bio-Rex 70. On the basis of their ability to abolish myocardial contractility, release LDH, alter cellular structure, lyse cell membranes and reduce viability, the 18 fractions have been divided into 4 arbitrary subgroups of cytotoxins: cardiotoxins, Da1 to Da3; cardiotoxin-like polypeptides, Da4 to Da12, Da14; less active membrane lytic polypeptides, Da13, Da15 to Da17; and membrane lytic polypeptide, Da18. Marked synergistic cell membrane lysis occurred in myocardial cell cultures treated simultaneously with 2 cardiotoxin-like polypeptides, Da7 and Da11. It is suggested that the additive and synergistic cardiotoxic effects of high molecular weight cytotoxic proteins (DaI to DaIII), very low molecular weight cholinomimetic substances (DaV to DaVI) and the 4 subgroups of cardiotoxins may directly contribute to the pronounced cardiovascular problems observed in victims of green mamba bites.

Animals↗
PubMed1988

Cardiotoxicity of Jamesoni's mamba (Dendroaspis jamesoni) venom and its fractionated components in primary cultures of rat myocardial cells.

Primary cultures of spontaneously beating myocardial cells isolated from neonatal rat hearts were used to screen the cardiotoxic effects of Jamesoni's mamba (Dendroaspis jamesoni) venom and components isolated from the venom by gel filtration and ion exchange chromatography. Cardiotoxicity was evaluated on the basis of leakage of lactate dehydrogenase (LDH), changes in morphology, cell membrane lysis, cellular viability, and alterations in spontaneous beating activity. The whole venom caused dose- and time-dependent leakage of LDH, disruption of the cell monolayer, decreases in viability, and inhibition of beating activity. Gel filtration of the venom yielded eight fractions (DjI to DjVIII). DjI (30 micrograms/ml), DjII (20 micrograms/ml), and DjV (20 micrograms/ml) caused significant (P less than 0.001) leakage of LDH, extensive morphologic damage, and decreases in viability. At lower concentrations DjI to DjVIII caused progressive inhibition of spontaneous beating activity. The main fraction (DjV), which was the most toxic, was further separated into 14 polypeptides (Dj1 to Dj14) by ion-exchange chromatography using Bio-Rex 70. Based on the ability to induce LDH leakage, produce morphologic damage, lyse cell membranes, and arrest beating activity, four categories of polypeptides were identified: cardiotoxins, Dj1 and Dj2; cardiotoxinlike polypeptides, Dj3 to Dj8; less active membrane lytic polypeptides, Dj9 to Dj13; and membrane lytic polypeptide, Dj14.

Animals↗
PubMed1988

Beta-adrenergic receptor characteristics of postnatal rat myocardial cell preparations.

Primary myocardial cell cultures and freshly isolated cardiac cells in suspension represent two isolated, whole cell models for investigating cellular transsarcolemmal 45Ca++ exchange in response to a receptor-coupled stimulus. Studies were performed to characterize beta-adrenergic receptor binding, beta-adrenergic receptor mediated cellular calcium (45Ca++) exchange, and viability in purified primary myocardial cell cultures and freshly isolated cardiac cells in suspension obtained from 3- to 5-d-old Sprague-Dawley rats. In addition, beta-adrenergic receptor binding was characterized in whole-heart crude membrane preparations. All three preparations had saturable beta-adrenergic binding sites with the antagonist [125I]iodopindolol [( 125I]IPIN). The suspensions had a significantly lower Bmax (42 +/- 6 fmol/mg protein) than the membranes and cultures (77 +/- 8 and 95 +/- 10 fmol/mg protein, respectively). The KD of the cultures (218 +/- 2.0 pM) was significantly higher than that for the suspensions (107 +/- 1.3 pM) and membranes (93 +/- 1.3 pM). Viability was significantly lower in the suspensions (57%) when compared to 94% viability in myocardial cell cultures after 3 h of incubation in Kreb's Henseleit buffer. Incubation of the cultures with 5.0 X 10(-7) M isoproterenol resulted in a significant increase in 45Ca++ exchange as early as 15 s. In contrast, 45Ca++ exchange into the suspensions was not increased. Although both primary cell cultures and cardiac cells in suspension possess saturable beta-adrenergic receptors, only the monolayer cultures exhibited functional beta-adrenergic receptor-mediated 45Ca++ exchange. Of the two intact cell models investigated, these data suggest that primary myocardial cell cultures are more suitable than cell suspensions for investigating beta-adrenergic receptor binding and functions in the postnatal rat heart.

Animals↗
PubMed1988

Size changes of a growth hormone- and prolactin-producing adenoma during and after sandostatin treatment.

A 46-year-old woman with acromegaly and marked hyperprolactinemia was treated chronically with sandostatin (50 micrograms b.i.d. up to 100 micrograms t.i.d.). Plasma growth hormone (GH) was reduced by 90% of basal values and prolactin (PRL) dropped from initially 204 to 74 ng/ml. Serial CAT scans detected a volume reduction of the pituitary adenoma of 46.7%, but discontinuation of therapy was followed by re-expansion of the tumor. Tissue collected at transsphenoidal adenomectomy was examined by immunohistology and found positive for both GH and PRL. This characteristic would explain the dual hormonal response to the specific GH inhibitor sandostatin.

Adenoma↗
PubMed1987

The effects of ethanol on cellular calcium content in primary myocardial cell cultures from offspring of sedentary and swim-trained pregnant rats.

Primary myocardial cell cultures obtained from offspring of swim-trained (T) and sedentary (S) Sprague-Dawley rat mothers (dams) were used to evaluate the influence of exercise training and ethanol on cellular calcium (45Ca) content. The pregnant rats swam in water maintained at 37 degrees C 6 days/week during gestation. The dams swam continuously for 30 min on the first day of gestation. The swimming time was increased by 5 min until the rats swam continuously for 1.5 hr. After the cultures had been in incubation for 4 days, the cells were treated with 600, 800, and 1000 mg% ethanol for 30 min and 1 hr. 45Ca content (nmol/mg protein) of the untreated controls and all but one of the ethanol treated groups from the T cultures (1000 mg%) were significantly elevated over the comparable groups from the S cultures for both 30 min and 1 hr of incubation (p less than or equal to 0.05). The data suggest that exercise during pregnancy induces adaptations in myocardial cell cultures from the offspring such that 45Ca content levels are elevated which may provide protection against ethanol toxicity.

Adaptation, Physiological↗
PubMed1987

Effect of alpha-tocopherol and free radicals on anoxic damage in the rat hippocampal slice.

The effect of alpha-tocopherol on irreversible transmission loss subsequent to anoxia was examined using the hippocampal slice preparation. A population spike was recorded from the dentate granule cell layer after stimulation of the perforant path. The amplitude of the population spike was compared before and after anoxia. Control slices recovered to 22 +/- 7% of their preanoxic amplitude after 7 min of anoxia. Slices treated with alpha-tocopherol showed significantly greater recovery after anoxia (P less than 0.001). The population spike recovered to 64 +/- 15% of its preanoxic amplitude. As alpha-tocopherol is a free radical scavenger, our results provide evidence that free radicals are partly responsible for irreversible anoxic damage. alpha-Tocopherol is not toxic and may prove efficacious in protecting the brain against anoxic damage.

Animals↗
PubMed1986

Oral toxicity of carbon tetrachloride: acute, subacute, and subchronic studies in rats.

This investigation was conducted to characterize the acute, subacute, and subchronic toxic potency of ingested carbon tetrachloride (CCl4). In the first acute and subacute toxicity study, male Sprague-Dawley rats of 300-350 g were gavaged with 0, 20, 40, or 80 mg CCl4/kg once daily for 5 consecutive days, rested for 2 days, and dosed once daily for 4 additional days. Rats of 200-250 g were gavaged with 0, 20, 80, or 160 mg CCl4/kg according to the same dosage regimen in the second acute and subacute study. In the first and second studies one group of rats at each dosage level was sacrificed for clinical chemistry and histopathological evaluation at 24 hr, 4 days, and 11 days after initiation of dosing. Single 20- and 40-mg/kg doses had no apparent toxic effect at 24 hr, although 80 mg/kg caused mild hepatic centrilobular vacuolization and significant increases in some serum enzyme levels. In general, there was progressively severe hepatic injury at each dosage level over the 11-day period. CCl4 was more hepatotoxic to the 200-250-g rats than to the 300-350-g rats. In the subchronic study, rats initially 200-250 g were gavaged 5 times weekly for 12 weeks with 0, 1, 10, or 33 mg CCl4/kg. Body weight and clinical chemistry indices were monitored during the 12 weeks of dosing and 2 weeks after cessation of dosing. A dose of 1 mg/kg had no apparent adverse effect; 10 mg/kg produced slight, but statistically significant increases in sorbitol dehydrogenase activity and mild hepatic centrilobular vacuolization; 33 mg/kg caused marked hepatotoxicity. Serum enzyme levels remained elevated during the 12-week dosing period, but returned toward normal within 13 days of cessation of CCl4 exposure. Microscopic examination of livers of the 33-mg/kg rats revealed cirrhosis, characterized by bile duct proliferation, fibrosis, lobular distortion, parenchymal regeneration, hyperplastic nodules, and single-cell necrosis. The fibrosis was not reversed within the 13-day recovery period.

Alanine Transaminase↗