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J C Davila

Publications and source records attributed to J C Davila.

At least 19 recordsLinked to original sources
PubMed1996

Analysis of rat cytochrome P450 isoenzyme expression using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

A method was developed using reverse transcriptase-polymerase chain reaction (RT-PCR) to selectively detect and qualitatively determine the levels of mRNA expression of the major isoenzymes of cytochrome P450 (P450 1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1) and fatty acyl-CoA oxidase (FACO) in the rat. Total liver RNA was isolated from male Sprague-Dawley rats treated with various inducers of cytochrome P450 (P450) and analyzed for the presence and relative quantities of each P450 isoenzyme mRNA using this technique. The specificity of the oligonucleotide primers used in the detection of each P450 mRNA was tested and confirmed through the simultaneous analysis of liver microsomal protein preparations for the presence of constitutive or inducible P450 apoprotein and enzyme activities using western immunoblotting and specific enzyme activity measures, respectively. This method of P450 expression analysis is proven to be highly specific and readily applicable for the assessment of P450 enzyme induction and down-regulation in the rat during routine toxicology studies when expression of the gene product is regulated by transcriptional activation and/or mRNA stabilization.

Animals↗
PubMed1993

Phencyclidine, a psychotomimetic agent and drug of abuse, is a suicide inhibitor of brain nitric oxide synthase.

Phencyclidine, 1-(1-phenylcyclohexyl)piperidine, was shown in this study to be an effective irreversible inhibitor of brain nitric oxide synthase, the enzyme responsible for the conversion of L-arginine to nitric oxide. The inactivation of nitric oxide synthase was time- and concentration-dependent and required reduced nicotinamide adenine dinucleotide phosphate, a necessary cofactor for nitric oxide synthesis. These results indicate that phencyclidine is metabolized by nitric oxide synthase to reactive intermediates that irreversibly inactivate the enzyme. The inactivation of nitric oxide synthase by xenobiotics, such as phencyclidine, may be pharmacologically and toxicologically important due to the role of nitric oxide in a variety of physiological processes.

Amino Acid Oxidoreductases↗
PubMed1991

Changes in glutathione and cellular energy as potential mechanisms of papaverine-induced hepatotoxicity in vitro.

The purpose of this study was to elucidate the mechanism of hepatotoxicity of papaverine hydrochloride (papaver) in vitro. To evaluate the role of metabolism in the toxicity of papaver, cells were pretreated with SKF-525A or benzyl imidazole (cytochrome P450 system inhibitors) for 24 hr at 1 x 10(-5) or 1 x 10(-4) M, respectively, or with phenobarbital sodium (cytochrome P450 system inducer) for 3 days at 2 x 10(-3) M. Cells then were exposed to concentrations of papaver ranging from 1 x 10(-5) to 1 x 10(-3) M for 4 to 24 hr. Cytotoxicity was evaluated by enzyme leakage (lactate dehydrogenase) and by energy status of the cells (ATP/ADP). The role of biological reactive intermediates in the toxicity of papaver was investigated by measuring changes in cellular reduced glutathione levels (GSH), by inhibiting GSH synthesis, and by determining the production of lipid peroxidation (LPX). Papaverine produced concentration- and time-dependent increases in enzyme leakage, with significant effects occurring by the 8-hr exposure period. Pretreatment with SKF-525A or benzyl imidazole increased enzyme leakage induced by papaver especially at a later time frame (24 hr), but pretreatment with phenobarbital delayed the onset of cytotoxicity from 8 to 12 hr. Decreases in GSH levels paralleled the time course of enzyme leakage. However, the administration of buthionine sulfoximine to cell cultures dramatically decreased the time by which papaver induced cellular injury (2 hr vs 8 hr). Changes in cellular energy status (ATP/ADP) were also detected earlier than enzyme leakage (4 hr vs 8 hr). In contrast, no significant production of lipid peroxidation was noted in papaver-treated cultures. We suggest that the mechanism of papaver-induced hepatotoxicity may be related to alterations in glutathione balance of the cells and to disruption of energy homeostasis.

Adenosine Diphosphate↗
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

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↗
PubMed1989

Where is the ideal heart valve substitute? What has frustrated its realization?

Laboratory and clinical experience in cardiac valve operations and use of imperfect but serviceable valve substitutes over the past four decades have framed the general specifications for an ideal heart valve substitute. This report covers four major aspects of prosthesis characteristics. (1) Implantability: Essentially stable, viable tissue-to-prosthesis linkage is achievable with a porous fixation element. (2) Hemodynamics: Minimal resistance and efficient opening and closing are best attained with bioprostheses and homografts. (3) Thromboembolism: Thromboembolism is a persistent problem with mechanical valves. It is minimized by biological valves and abolished, experimentally, by appropriately encapsulated implants. (4) Durability: Mechanical valves are best. Tanned bioprostheses undergo "spontaneous degeneration"; untanned homografts are a little better. Knowledge and technology are needed to develop a synthetic leaflet membrane that possesses inherent physical, visco-elastic-rheologic properties of natural valve leaflets and is compatible with natural healing processes.

Bioprosthesis↗
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↗
PubMed1986

Retinal projections in the lizard Podarcis hispanica.

The retinofugal of the lizard Podarcis hispanica has been examined by means of enzymatic method with horseradish peroxidase (HRP). The retinal ganglion cells project contralaterally to thalamus (nucleus geniculatus lateralis pars dorsalis, nucleus geniculatus lateralis pars ventralis and nucleus ventrolateralis pars ventralis and nucleus ventrolateralis pars ventralis), pretectum (nucleus lentiformis mesencephali, nucleus geniculatus pretectalis and nucleus posterodorsalis) and optic tectum (layers 14 and 12, mainly, and layers 13 and 11). A small ipsilateral tract has been observed. Some of these fibers project to the lateral geniculate complex and the nucleus ventrolateralis pars ventralis. Most of the ipsilateral fibers have been observed in the neuropil of nucleus geniculatus pretectalis and the layer 14 of the optic tectum. The ipsilateral component, an inconstant structure in reptiles, presents an important development in Podarcis hispanica, although the number of its fibers is relatively small.

Animals↗
PubMed1986

Ultrastructure of the dorsal cortex of the lizard Psammodromus algirus.

The dorsal cortex of Psammodromus algirus shows three layers, superficial plexiform layer (SPL), cellular layer (CL), and deep plexiform layer (DPL), from the pia mater to the ependyma. The marginal glial sheet constitutes the outer limit of the SPL. This glial sheet consists of flattened tanycytic processes running parallel to the cortical surface. A few globous neurons are scattered within the neuropil of the SPL which is formed by axons, axon terminals, dendrites and dendritic spines. Three types of axon terminals, type S, type F, and axon terminals with large dense core vesicles, can be observed in the SPL. The CL presents numerous neuronal somata tightly packed. Large neurons with spherical to oval nucleus and dispersed chromatin, and smaller neurons with chromatin clumps are found in this layer. The DPL consists of neuropil with many solitary or clustered neurons. Three neuronal types are found: neurons with indented nucleus, small neurons with spherical nucleus and large juxtaependymal neurons. Glial cells are present throughout the dorsal cortex. Astrocytes are most abundant and do not show a defined pattern of distribution. Oligodendrocytes are frequently related to the alveus fibers. The ependyma forms the ventral limit of the dorsal cortex. It is formed by clear and electron-dense cells.

Animals↗
PubMed1983

Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium.

Selenium may be related to the hepatic metabolism of the coumarin compounds aflatoxin B1 and warfarin. Selenium evidently increased the pharmacologic activity of warfarin, probably due to a displacement of warfarin from albumin by selenium, the close relationship among selenium, vitamin E, and sulphur-containing groups (eg, glutathione), or the antioxidant effect of selenium. A diet containing selenium in a concentration of 2.5 mg/kg of feed was protective against the toxic effects of both coumarins in pigs given 4 daily oral doses of 0.2 mg/kg of body weight. Selenium, as glutathione peroxidase, at least in part, protects the hepatic cells against the toxic effects of aflatoxin B1 and warfarin. The protection was demonstrated by alteration of clinical responses and hematologic (prothrombin times), electrophoretic, and clinical chemistry values. It also was demonstrated that selenium at 2.5 mg/kg of feed does not produce toxic effects; however, dietary selenium at a concentration of 5 mg/kg (and in the presence of both toxic agents) was toxic for young pigs within the 3-week experimental period. Warfarin was more active as an anticoagulant than aflatoxin B1.

Aflatoxin B1↗
PubMed1979

Innominate artery disruption due to blunt trauma.

Two patients had innominate artery disruption due to blunt trauma. Compression forces between the sternum and vertebral column and rotational forces were the mechanisms of injury. Mediastinal widening led to the diagnosis in one patient who underwent successful repair with preservation of cerebral flow by an aortic to subclavian bypass graft prior to oversewing the innominate artery. A normal mediastinal shadow led to a delay in diagnosis in the second patient who underwent surgery after the appearance of focal neurologic signs. The use of a temporary indwelling aortic-carotid shunt during repair did not prevent residual hemiparesis.

Accidents, Traffic↗
PubMed1978

Late results of atrial septal defect repair in adults.

Repair of secundum atrial septal defects in 75 patients older than age 40 years was associated with a good long-term result, from five to 21 years postoperatively, in 89% of patients who were class I and II preoperatively and in 86% of those in normal sinus rhythm preoperatively. Functional class III or IV, atrial fibrillation, a higher pulmonary artery mean pressure and higher pulmonary vascular resistance affected the prognosis adversely. Repair of atrial septal defect in adults did not reverse existing atrial fibrillation and did not protect against the onset of new atrial fibrillation.

Adult↗
PubMed1978

Is the Hancock porcine valve the best cardiac valve substitute today?

Valve replacement with the Hancock stabilized glutaraldehyde porcine aortic valve has been accomplished in 454 patients. Hospital mortality (influenced by a high proportion of patients in New York Heart Association Functional Class IV) was 17.6% (80/454). The first 221 patients discharged from hospital were followed for 36 to 75 months after valve replacement. There have been 26 late deaths among these patients; 88% (195/221) are alive. Of these 221 patients, 185 had single-valve replacement, (125 mitral and 60 aortic), and 36 underwent multiple-valve replacement. There have been 260 valves at risk up to 6 1/4 years, which is equivalent to 12,984.5 valve-months or 1,082 valve-years. Average follow-up is 4.16 years. There have been 13 valve failures in 10 patients. In 4 patients endocarditis was proved to be the cause of failure, and in 5 it was suspected; in 1 patient the failure the failure is unexplained. The pathological similarity between those in whom infection was documented and the other 5 is remarkable and raises the question of whether low-grade infections may be the cause of certain types of valve failure.

Adolescent↗