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Biomedical subjects

J L Valentine

Publications and source records attributed to J L Valentine.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cardiovascular effects of tropacocaine in conscious and anesthetized rabbits: lack of evidence for neuro-cardiac interactions and acute neurotoxicity.

The cardiovascular effects of tropacocaine, a structural analog of cocaine, were investigated in both conscious and anesthetized New Zealand white rabbits to determine if such effects were mediated through the CNS as had been demonstrated with cocaine, i.e., did a neuro-cardiac pathway exist? To facilitate the requisite cardiovascular measurements in both urethane- and pentobarbital-anesthetized animals, the right femoral artery and vein were cannulated for the measurement of arterial blood pressure and subsequent delivery of drugs, respectively. In addition, urethane-anesthetized animals had a branch of the left renal nerve isolated and multiunit renal nerve activity was monitored to obtain measures of sympathetic nerve activity originating from the CNS. Animals utilized in conscious experiments were surgically prepared 3 days prior to drug administration by placing canulae in the femoral artery and vein that were tunneled subcutaneously to the back between the scapulae. ECG and respiratory activity were also monitored in each animal. Doses of 0.3, 1, 3, and 10 mg/kg of tropacocaine were administered in both an ascending and descending fashion at 15 min intervals to 5 animals in each group, i.e., conscious, urethane-, and pentobarbital-anesthetized. In urethane-anesthetized animals a comparison was made between sympathetic renal nerve activity, systolic and diastolic blood pressure, respiratory rate, and heart rate. No pressor effects were observed and the changes in renal nerve activity could not be assigned as the cause of the observed depressor effects at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1994

Daily selenium intake estimates for residents of arsenic-endemic areas.

The selenium in the diet of persons in arsenic-endemic areas, high levels of arsenic in the drinking water, was evaluated. The methodology used was that of 24-hr dietary recall. Daily selenium intakes of two rural towns in northern Mexico were found to be similar, approximating 72.9 and 60.6 micrograms. These values were similar to those of a previously arsenic-exposed area from California, Edison community. The Edison participants had a daily selenium intake of 61.8 micrograms. The possible negative effect of selenium to produce differences in reported geographical variation in disease could not be substantiated in this study. Other nutrient intakes, protein and energy were also found similar for communities. Differences were noted in vitamin A intake where one-third the daily requirement was experienced by Mexican participants compared to two-thirds the requirement being satisfied by those participants from Edison.

Adult↗
PubMed1994

Anti-phencyclidine monoclonal Fab fragments markedly alter phencyclidine pharmacokinetics in rats.

The purpose of these studies was to explore the use of phencyclidine (PCP)-specific high affinity antibodies as a possible treatment for phencyclidine toxicity. High affinity (Kd = 1.8 nM) anti-PCP monoclonal Fab fragments were purified from papain digested anti-PCP immunoglobulin produced in mouse ascites. Control animals (n = 5) received an i.v. bolus dose of 1 mg/kg of PCP, along with a tracer dose of 250 microCi of [3H]PCP. Fab-treated rats (n = 5) also received this PCP dose, but at 2 hr after dosing (when PCP distribution was complete) they received an equimolar dose of anti-PCP Fab (50 mg). Within 5 min after the anti-PCP Fab administration, serum [3H]PCP concentrations increased approximately 60- to 100-fold. Fab treatment caused the [3H]PCP volume of distribution at steady state to decrease from 12.6 +/- 3.0 liters/kg (mean +/- S.D.) in control animals to 0.6 +/- 0.2 liters/kg in the Fab-treated animals (about 5% of control values). Systemic clearance changed from 66.3 +/- 16.9 to 6.8 +/- 2.8 ml/min/kg (about 10% of control values). Because both volume of distribution and systemic clearance decreased to a similar degree, the terminal elimination half-life did not change significantly (3.9 hr in controls vs. 4.9 hr in treated animals, harmonic means). Renal clearance decreased from 1.8 +/- 0.6 to 0.62 +/- 0.17 ml/min/kg after Fab treatment. The anti-PCP Fab caused the percentage of PCP recovered in urine to increase from 2.5 +/- 0.5 to 10.3 +/- 4.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Disposition of a monoclonal anti-phencyclidine Fab fragment of immunoglobulin G in rats.

Treatment of drug toxicity is problematic for compounds like phencyclidine (PCP) which have no known antagonists. With the advent of technology for production of large amounts of monoclonal antibody, it is now possible to explore the use of these antibodies as high affinity in vivo antagonists for treatment of PCP overdose. In the current study, the pharmacokinetics of an anti-PCP monoclonal antibody Fab (antigen binding fragment of immunoglobulin G) were determined in adult male Sprague-Dawley rats (n = 5). Each animal was cannulated and dosed with approximately 0.12 g/kg of unlabeled anti-PCP Fab fragments (Kd for PCP = 1.8 +/- 0.27 nM) along with a tracer dose of anti-PCP [3H]Fab. Blood was drawn at predetermined intervals and serum was analyzed for total radioactivity by liquid scintillation spectrometry. Serum and urine were analyzed for intact anti-PCP [3H]Fab after fractionation on a high-performance liquid chromatography molecular weight sizing column followed by quantitation by liquid scintillation spectrometry. The pharmacokinetic parameters for the [3H]Fab in rat serum were a terminal elimination T1/2 of 7.5 hr (harmonic mean), a volume of the central compartment of 0.17 +/- 0.026 liters/kg and a steady-state volume of distribution of 0.55 +/- 0.15 liters/kg (mean +/- S.D.). Systemic and renal clearances were 2.7 +/- 0.9 and 0.47 +/- 0.24 ml/min/kg, respectively. The total amount of the radioactive dose ([3H] Fab plus radioactive catabolic products) appearing in the urine was 51 +/- 11%, whereas urinary excretion of intact [3H]Fab accounted for 21 +/- 15% of the total dose. All animals tolerated the Fab infusion without adverse effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Dose- and time-dependent changes in phencyclidine metabolite covalent binding in rats and the possible role of CYP2D1.

We determined whether chronic dosing with phencyclidine (PCP) could affect the in vitro function of liver microsomal enzymes in male Sprague-Dawley rats. PCP chronic dosing of rats (n = 3 per group) for 3 days with 2.5, 10 and 18 mg/kg/day caused a dose-dependent decrease (23, 36 and 53%, respectively) in the ability of the microsomal enzymes to bind covalently PCP metabolites. The 10- and 18-mg/kg/day dosing groups were significantly different from the 3-day saline-infused control group (P < .05). The results from time-dependent dosing studies indicated PCP covalent binding was significantly reduced (P < .05) in rats (n = 3 per group) infused with 18 mg/kg/day of PCP for 1, 2, 3, 4 and 10 days. Subsequently, it returned to near control values in rats infused for 20 days. In parallel with the time-dependent decreases in covalent binding, the concentrations of at least three phase I PCP mono- and dihydroxylated metabolites were also significantly reduced (P < .05) at the earlier time periods of dosing (3 and 10 days), but the rate of their formation returned to near normal values by 20 days of dosing. Total cytochrome P450 content did not differ from the control groups at any of the doses or time points. As dose- and time-dependent decreases in covalent binding suggested a specific metabolic pathway or isoenzyme was affected, we studied the affect on specific isoenzyme pathways. For these studies a series of cytochrome P450 inhibitors were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Health response by questionnaire in arsenic-exposed populations.

The health status of populations exposed to arsenic through drinking water was determined by a mailed questionnaire. Participants were selected from three communities located in Nevada with 1977 tap water arsenic levels of approximately 0.1 mg/l and one California community with 1977 levels around 0.39 mg/l. The questionnaire responses were obtained in 1979 from the four exposed communities and compared to those of a Wyoming community whose tap water levels of arsenic were less than 0.001 mg/l in 1979. No difference in health status for gastrointestinal, neurological, musculoskeletal, circulatory and skin disorders was found. The average number of years of consumption given by length of residence was 6-16 years. We conclude that the health status of these arsenic-exposed populations has not been adversely affected.

Adolescent↗
PubMed1991

Detection of Helicobacter pylori by using the polymerase chain reaction.

A 1.9-kb cloned fragment of chromosomal DNA randomly selected from a Helicobacter pylori cloned library was evaluated as a potential probe. The probe detected 19 of 19 H. pylori strains and yielded a specificity of 98.7% when tested against 306 other bacterial strains representing 32 different species. False-positive results with non-H. pylori strains were due to the presence of contaminating vector sequences. A polymerase chain reaction (PCR) assay was developed by using 20-base oligonucleotide primers homologous to a portion of the 1.9-kb fragment. The PCR assay amplified a 203-nucleotide-pair product which was analyzed by agarose gel electrophoresis and Southern hybridization by using a third 20-base 32P-labeled oligonucleotide complementary to a region of DNA between the primers. The PCR assay was 100% sensitive, detecting all 35 H. pylori strains tested, and did not amplify sequences in several closely related species. The assay was sensitive for as little as one copy of the cloned plasmid DNA or 100 H. pylori bacterial cells. To evaluate the PCR assay for clinical samples, gastric biopsy and aspirate specimens were tested by PCR, and the results were compared with those of microbiologic culture and histologic examination. In fresh biopsy specimens, H. pylori sequences were detected by PCR in 13 of 14 (93%) positive tissues and 0 of 19 negative tissues. In gastric aspirate specimens, 11 of 13 (85%) positive tissues were positive by PCR. H. pylori DNA was detected in 1 of 14 aspirate specimens negative by culture, histology, and PCR of the accompanying biopsy tissue. PCR is a rapid, accurate, and sensitive method for the detection of H. pylori.

Base Sequence↗
PubMed1991

Intervascular occlusion of canine renal, splenic, and vertebral arteries using electromagnetic field focusing (EFF) probe.

Electromagnetic field-focusing (EFF) probe is a precision surgical and interventional tool. Use of the device produces maximum temperature in excess of 1800 degrees C by convergence of radio-frequency (RF) induced eddy currents in biological tissues. Applications of the EFF probe in angioplasty, aneurysm thrombosis, and neurosurgery have been previously reported. In the present work, the EFF probe was guided under fluoroscopic control and used to occlude renal, splenic, and vertebral arteries in dogs. The occlusion was typically accomplished with about one minute of RF power application. Histology of the treated vessel three to six weeks posttreatment showed total occlusion consisting of intimal and subintimal changes and organized thrombus in the lumen. This suggests that the EFF probe in comparison with other procedures is an inexpensive, relatively safe precision interventional tool for performing an occlusion for experimental and therapeutic purposes.

Animals↗
PubMed1991

Effects of cocaine on canines' coronary arteries.

Nine canines were anesthetized with pentobarbital and studied by both selective and semiselective coronary artery angiography following intravenous bolus doses of 1,3,5,8, or 10 mg/kg of cocaine. Catheterization was accomplished with a 5 Fr catheter over a 0.035 inch guidewire under fluoroscopic control, and angiograms were obtained by injection of a diatrizoate solution. Digital subtraction angiography (DSA) was performed prior to cocaine administration and at minutes 0.5, 1, 1.5, 3, 5, and, in some cases, minutes 10 and 15 after cocaine administration. The 1 and 3 mg/kg doses of cocaine had no effect on the coronary arteries. The 5 mg/kg dose significantly dilated the coronary arteries. The 8 mg/kg dose produced significant dilation at 30 seconds after cocaine but nonsignificant dilation of the coronary arteries at all other times. The 10 mg/kg dose produced significant dilation at 30 seconds, nonsignificant dilation at 60 seconds followed by significant constriction at 90 seconds after cocaine, which led to immediate death in most animals. The coronary dilation and constriction produced by 10 mg/kg of cocaine could be prevented by either preadministration or postadministration of naloxone, but this did not prevent subsequent death.

Angiography, Digital Subtraction↗
PubMed1990

Toxic effects of cocaine to the cardiovascular system in conscious and anesthetized rats and rabbits: evidence for a direct effect on the myocardium.

The cardiovascular toxicity of cocaine is complex because it has local anesthetic properties, central nervous system stimulatory effects, as well as cardiac effects. Recreational use of this drug has increased recently, but the precise mechanism of sudden cardiac death induced by cocaine is not known. The primary objective of this work was to test for a direct cardiovascular toxicity of cocaine. Rats and rabbits were anesthetized, and the femoral vein and artery were cannulated for drug infusion and blood pressure monitoring. Different doses of cocaine (0.3, 1, 3, 10 mg/kg) were infused. For conscious animal experiments, the animals were allowed to recover from the anesthesia and then were subjected to cocaine. Low doses of cocaine (0.3 and 1 mg/kg) increased systolic as well as diastolic pressure in conscious rats and rabbits. In anesthetized rats and rabbits, the same dose of cocaine increased blood pressure with a decrease in heart rate. With the high doses of cocaine (3 and 10 mg/kg), all cardiac parameters were reduced in both rats and rabbits. In isolated rabbit hearts, cocaine decreased all cardiac parameters. Based on the fact that high doses of cocaine severely depressed all cardiac parameters and its effect on the isolated heart, cocaine-induced sudden cardiac death appears to be due to a primary effect on the myocardium.

Animals↗
PubMed1989

Precocious retinal adhesion is affected by furosemide and ouabain.

A "precocious" adhesive force develops between the neurosensory retina (NSR) and the retinal pigment epithelium (RPE) 15-30 minutes after eyes are removed from day 15 embryonic chickens and incubated at 37 degrees C. Precocious adhesion has been reported to be blocked by exposure to cold but to be unaffected by exposure to furosemide and ouabain. Since RPE transport is thought to play a major role in the adhesion between the RPE and NSR of adult mammals, and since ouabain and furosemide block RPE transport in embryonic chickens, it has been thought that precocious adhesion in embryonic chickens is not a good model for studying adhesion between the RPE and the NSR of adult mammals. We have found, however, that when steps are taken to ensure that ouabain and furosemide reach the transport sites on RPE apical membrane before precocious adhesion develops, that ouabain and furosemide do affect precocious adhesion.

Animals↗
PubMed1989

The plasma endorphin, prostaglandin and catecholamine profile of patients with fibrositis treated with cyclobenzaprine and placebo: a 5-month study.

During a 5 month, double blind crossover study of the clinical effect of cyclobenzaprine on 7 patients with fibrositis, weekly measurements were done of plasma beta-endorphin (endorphin, prostaglandin E (PGE) and catecholamines). Endorphin levels were normal but varied with tender point tenderness. Mean plasma dopamine and PGE were elevated. Norepinephrine was normal to very high while epinephrine levels were continuously low to normal. We conclude that patients with fibrositis have a neurotransmitter plasma profile like other chronic pain states having stress and increased vasomotor activity with the possible exception of having low circulating epinephrine. This disparity may mark a failure of central nervous system pain modulation in fibrositis.

Adult↗
PubMed1989

Furosemide-sensitive Cl transport in bovine retinal pigment epithelium.

Bovine retinal pigment epithelium (RPE)-choroid explants were sealed in an Ussing chamber. Typical preparations produced a transepithelial voltage (Ve) of 12 mV (retina side positive) and had an electrical resistance (R) of 300 ohm-cm2. These values can be attributed to the RPE. Furosemide and ouabain reduced the Ve without affecting R when applied to the apical side of the RPE, but had no effect upon Ve and R when applied to the choroidal side. Acetazolamide had no effect upon Ve and R when applied to either side of the tissue. In Cl-free medium, ouabain reduced Ve without affecting R, while furosemide had no effect upon Ve and R. In Na-free medium, ouabain and furosemide had no effect upon Ve and R. Unidirectional isotope flux studies performed under open circuit conditions showed a net retina-to-choroid Cl flux that was abolished by furosemide. These results indicate that bovine RPE possesses a furosemide-sensitive Cl transport system.

Animals↗
PubMed1989

Topical phenylephrine for mydriasis affects rabbit retinal pigment epithelial transport.

Rabbit retinal pigment epithelium (RPE) has an alpha-1 adrenoreceptor that substantially reduces RPE short circuit current (Isc) when stimulated. Since phenylephrine is a potent alpha adrenergic agonist frequently used to obtain pupil dilation, we examined the effect of topically applied phenylephrine for pupil dilation on RPE transport. Naive black dutch-belted rabbits received either one drop of 10% phenylephrine applied at t = 0 and t = 30 min or one drop of 1% cyclopentolate applied at t = 30 min. At t = 50 min, RPE-choroid-sclera explants from these animals were sealed in an Ussing chamber. At t = 60-70 min, 1.4 X 10(-4) M epinephrine was introduced into both sides of the Ussing chamber. The change in Isc produced by epinephrine was measured. The Isc reduction in rabbits receiving phenylephrine was 26% (+/- 5% SD, n = 6). The Isc reduction in rabbits receiving cyclopentolate was 39% (+/- 6% SD, n = 5). These values are significantly different (P less than 0.02, student two-tail t-test). These results indicate that topical phenylephrine reached the RPE in vivo and prestimulated the alpha-1 adrenoreceptors.

Administration, Topical↗
PubMed1988

Human glutathione peroxidase activity in cases of high selenium exposures.

Four communities with water supplies having selenium concentrations of less than 3.1, 1.7, 189, and 496 micrograms/liter were selected for study. Samples of blood, urine, and tap water were obtained from participants in each community and analyzed for selenium content. Blood samples were also analyzed for glutathione peroxidase activity. Results showed an increase in selenium concentration in the urine as the water selenium increased. Selenium concentrations in blood did not reflect the increased selenium exposure. Glutathione peroxidase activity in whole blood decreased in highly exposed participants compared to those with low exposure. We conclude that glutathione peroxidase activity in cases of possible environmental toxic exposures will not show the increased activity seen in supplementation of selenium to deficient subjects.

Adolescent↗
PubMed1988

Effects of extended feeding of decocainized erythroxylon coca leaves on growth and selected organs in rats and rabbits.

Erythroxylon coca leaves from the Trujillo area of Peru were extracted with methylene chloride to remove most cocaine-like alkaloids. The decocainized leaves were formulated in a honey-water vehicle and fed on a chronic basis to female rats for 32 weeks and female rabbits for 13 weeks. Rabbits fed decocainized leaves at doses of 21 or 210 mg demonstrated no significant change in growth (weight gain) when compared with those receiving vehicle. Histological findings were unremarkable except for fatty islands in the myocardium. Rats fed the decocainized leaves at doses of 1.5 and 15 mg demonstrated no significant changes in weight, whereas those receiving 150 mg had a significant decrease in weight gain when compared with control animals receiving vehicle. Necropsy findings in rats demonstrated pyometra in all groups receiving decocainized leaves as well as in some of the controls. Those rats with pyometra often exhibited endometrial metaplasia. Renal tubular calcification and proteinaceous material were consistently noted at all dose levels. Portal triaditis was also found in the livers of most rats.

Alkaloids↗
PubMed1988

Electromagnetic field focusing system in the treatment of brain tumors.

The electromagnetic field focusing (EFF) probe, which is based on the principle of eddy current convergence, produces intense pinpoint heat at its point of contact with tissue. This allows cutting and vaporization of tissue and coagulation of vessels. The present experiments were conducted to study heat distribution to the surrounding tissue in brain and phantom and the effect on the brain of vaporization of intracerebral tumors in 19 rabbits. The follow-up period was as long as 47 days. The heating pattern showed a rise of temperature up to 250 degrees C at the probe tip, with minimal or no temperature increase at 2 mm and beyond. Minimal or no change was noted in the surrounding brain after tumor vaporization, indicating that this system would be safe in the vaporization of brain tumors in clinical neurosurgery.

Animals↗