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A A Li

Publications and source records attributed to A A Li.

At least 19 recordsLinked to original sources
PubMed2001

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.

Animals↗
PubMed2001

[Organ-conserving operations in treatment of breast cancer].

The report deals with the results of conservative surgery carried out in 261 patients with breast tumors T1-2N0-1M0. Special procedure was employed to assess edges of removed segments of tumor tissue in 46. A classification of edge condition is offered. It was found that degree of intervention should depend on whether tumor segments are left in the edge. The end results were evaluated on the basis of tumor dissemination to the regional lymph nodes, survival duration and frequency of locally-advanced relapse. Five-year survival was 91.4%; localized recurrence incidence--3.8%.

Breast Neoplasms↗
PubMed1999

Neurotoxicity evaluation of rats after subchronic inhalation exposure to isobutanol.

The subchronic neurotoxic effects of isobutanol were studied by exposing Sprague-Dawley rats to isobutanol vapor concentrations of 0, 250, 1000, and 2500 ppm for 6 hrs/day, 5 days/wk, for 3 months. A comprehensive set of neurotoxicity tests (functional observational battery, motor activity, perfusion fixation neuropathology, and schedule-controlled operant behavior) including an assessment of complex behavior dependent on learning and memory was conducted. In addition, full histopathology and blood chemistry evaluations were conducted in order to assess any potential functional/behavioral effects in the context of other possible systemic toxicities. There were no morphological or behavioral effects indicative of a specific, persistent or progressive effect of isobutanol on the nervous system at exposure concentrations up to 2500 ppm. A slight decrease in response to external stimuli was observed during exposures at all concentrations. These effects are likely transient effects of acute exposure to isobutanol.

Administration, Inhalation↗
PubMed1997

EPA's neurotoxicity risk assessment guidelines.

The proposed Neurotoxicity Risk Assessment Guidelines (U.S. EPA, 1995c Fed. Reg. 60(192), 52032-52056) of the U.S. Environmental Protection Agency (EPA) were the subject of a workshop at the 1997 Meeting of the Society of Toxicology. The workshop considered the role of guidelines in the risk assessment process, the primary features, scientific basis, and implications of the guidelines for EPA program offices, as well as for industrial neurotoxicologists from the perspectives of both pesticides and toxic substances regulation. The U.S. National Academy of Sciences (NAS, 1983, Risk Assessment in the Federal Government: Managing the Process) established a framework for distinguishing risk management from risk assessment, the latter being the result of integrating hazard identification, hazard characterization, and exposure assessment data. The guidelines are intended to establish operating principles that will be used when examining data in a risk assessment context. The proposed neurotoxicity risk assessment guidelines provide a conceptual framework for deciding whether or not a chemically induced effect can be considered to be evidence of neurotoxicity. Topics in the proposed guidelines include structural and functional effects, dose-response and -duration considerations, and relationships between effects. Among the issues that must be considered are the multiplicity of chemical effects, the levels of biological organization in the nervous system, and the tests, measurements, and protocols used. Judgment of the adversity of an effect depends heavily on the amount and types of data available. The attribution of a chemically induced effect to an action on the nervous system depends on several factors such as the quality of the study, the nature of the outcome, dose-response and time-response relationships, and the possible involvement of nonneural factors. The guidelines will also serve as a reference for those conducting neurotoxicity testing, as well as establish a consistent approach to neurotoxicity risk assessment by regulators. Extending this approach through international harmonization would be advantageous to the development of products for a worldwide market. Thus, both risk assessors and regulated industries have a large stake in the guidelines to provide a framework that will lead to accurate risk assessment decisions.

Data Collection↗
PubMed1993

Effects of caffeine and PD 116,600 on the differential-reinforcement-of-low rate 72-S (DRL 72-S) schedule of reinforcement.

Caffeine and PD 116,600 were found to decrease the reinforcement rate and increase the response rate in rats performing under a differential-reinforcement-of-low rate 72-s (DRL 72-s) schedule of reinforcement. In contrast, antidepressant drugs previously have been found to increase the reinforcement and decrease the response rate. Caffeine has been found to test similar to antidepressant drugs on at least one other behavioral screen, but caffeine does not possess clinical antidepressant properties. These results provide further support for the DRL 72-s schedule as a behavioral screen for antidepressant drugs.

Animals↗
PubMed1990

Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine.

Trazodone is an atypical antidepressant drug (i.e. blocks neither monoamine uptake nor monoamine oxidase) which tests as an antidepressant drug on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement by increasing the reinforcement rate and decreasing the response rate. m-Chlorophenylpiperazine (m-CPP) is a 5-HT1B and 5-HT1C agonist, weak 5-HT2 antagonist, and trazodone metabolite. It has been suggested that formation of m-CPP is responsible for the antidepressant action of trazodone. Administration of m-CPP (1-10 mg/kg i.p.) 60, 30 or 10 min before the behavioral session did not mimic the reinforcement rate-increasing effects of trazodone (10-20 mg/kg i.p.) on rats performing under the DRL 72-s schedule of water reinforcement. Pretreatment with proadifen (50 mg/kg i.p.), an inhibitor of trazodone metabolism, caused a greater than 30-fold leftward shift in the dose-response curve for both the reinforcement rate and the response rate. These results suggest that the parent compound and not the trazodone metabolite m-CPP, mediates the antidepressant-like effects of trazodone on DRL 72-s behavior.

Animals↗
PubMed1989

Experiments with extracorporeal shock wave nephrolithotripsy.

Two sets of experiments were carried out on 14 live rabbits having renal calculi from nephrolithiasis patients implanted in their kidneys. Shock waves were used to disintegrate the implanted concrements. It took 100 to 150 sound pulses to crush struvite stones to fragments less than 2 mm in size, with 400 to 800 pulses needed to destroy calcium oxalate stones. After multiple exposures to shock waves there were no indications of any gross damage to the soft tissues of the experimental animals. Mechanisms for destruction of kidney stones by shock waves were considered.

Animals↗
PubMed1989

Long-term central 5-HT depletions resulting from repeated administration of MDMA enhances the effects of single administration of MDMA on schedule-controlled behavior of rats.

The behavioral effect of single administration of +/- 3,4-methylene-dioxymethamphetamine (MDMA) on rats performing on the differential-reinforcement-of-low-rate 72-second schedule (DRL 72-sec) was compared before and after a period of repeated administration of MDMA known to deplete 5-hydroxytryptamine (5-HT) levels in the brain. Single administration of MDMA decreased reinforcement rate (1, 2, 4, 6 mg/kg) and increased response rate (4,6 mg/kg) of rats performing on the DRL 72-sec schedule. This effect is typical of amphetamines and other psychomotor stimulants. Four weeks after repeated administration of MDMA (6 mg/kg twice daily for 4 days) there was an increase in sensitivity to the effect of single administration of MDMA. Doses of 2, 4 and 6 mg/kg of MDMA resulted in increases in response rate that were significantly greater after repeated MDMA administration than before. Doses of 0.5, 2, and 6 mg/kg of MDMA resulted in decreases of reinforcement rate that were significantly greater after repeated MDMA administration than before. Repeated administration of MDMA resulted in long-term depletion of serotonin levels by 30-50% in the amygdala, neostriatum, hippocampus and the frontal cortex. Norepinephrine and dopamine (DA) levels were not significantly different from control in any of the brain regions analyzed. The behavioral and neurochemical results suggest that serotonergic neurons normally exert an inhibitory action upon the psychomotor stimulant effects of MDMA. Since the psychomotor stimulant effects of amphetamines appear to be mediated primarily by the dopamine system, these results provide evidence that 5-HT and DA may represent opposing systems in the DRL schedule-controlled behavior.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Selective 5-hydroxytryptamine2 antagonists have antidepressant-like effects on differential-reinforcement-of-low-rate 72-second schedule.

The effects of eleven 5-hydroxytryptamine antagonists with varying selectivity for the 5-hydroxytryptamine2 (5-HT2) relative to the 5-HT1 binding site were assessed in rats responding under a differential-reinforcement-of-low rate 72-sec (DRL 72-s) schedule of reinforcement. Three drugs with a 1000-fold selectivity for the 5-HT2 binding site (ketanserin, ritanserin, pipamperone) increased the reinforcement rate and decreased the response rate similar to antidepressant drugs. The two drugs with roughly the same affinity for both 5-HT1 and 5-HT2 binding sites (methysergide and metergoline) did not increase the reinforcement rate. The maximal increase in the reinforcement rate after 5-HT antagonist administration was positively correlated with the selectivity of the 5-HT antagonists for the 5-HT2 versus the 5-HT1 binding site. The increase in the reinforcement rate after administration of 5-HT antagonists was not correlated with the affinity of the 5-HT antagonists for the alpha-1 adrenergic, alpha-2 adrenergic, histamine-1 or dopamine-2 receptors. The 1000-fold selective 5-HT2 antagonist xylamidine, which does not pass the blood-brain barrier, did not increase the reinforcement rate or decrease the response rate. Thus, selective antagonism of central 5-HT2 relative to 5-HT1 receptors results in antidepressant-like effects on the DRL 72-s schedule. Furthermore, the specificity of the DRL 72-s schedule as a screen for antidepressant drugs was strengthened by the observation that the alpha-1 adrenergic antagonist, prazosin, did not increase the reinforcement rate despite significant decreases in the response rate.

Animals↗
PubMed1989

Evidence for involvement of 5-hydroxytryptamine1 receptors in antidepressant-like drug effects on differential-reinforcement-of-low-rate 72-second behavior.

Previous work in this laboratory has suggested that antagonist action of 5-hydroxytryptamine2 (5-HT2) receptors and agonist action of 5-HT1 receptors results in antidepressant-like effects (increased reinforcement rate and decreased response rate) in rats performing under the differential-reinforcement-of-low-rate 72-sec schedule (DRL 72-s) of reinforcement. Serotonergic mediation of antidepressant drug effects on DRL 72-s behavior was assessed with a series of 5-HT agonists, and blockade of the effects of the antidepressant drugs clorgyline and fluoxetine (which presumably indirectly stimulate 5-HT1 receptors) was attempted in separate experiments with the 5-HT1 and 5-HT2 antagonist methysergide and the 5-HT neurotoxin 5,7-dihydroxytryptamine. Direct 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methoxy-N,N-dimethyltryptamine and the 5-HT precursor 5-hydroxytryptophan all increased the reinforcement rate. The 5-HT1B and 5-HT1C agonists m-chlorophenylpiperazine and 1-(m-trifluoromethylphenyl)piperazine did not increase the reinforcement rate. The 5-HT2 agonist and 5-HT3 antagonist quipazine also did not increase the reinforcement rate. The monoamine oxidase inhibitor clorgyline and the 5-HT uptake inhibitor fluoxetine increased the reinforcement rate and decreased the response rate as seen with other antidepressant drugs on the DRL 72-s schedule. Methysergide antagonized the reinforcement rate increasing effects of both clorgyline and fluoxetine. Depletion of brain 5-HT with i.v.t. 5,7-dihydroxytryptamine blocked the antidepressant-like effects of clorgyline. These results suggest that central 5-HT1A receptors are involved in mediating the antidepressant-like effects of some drugs on DRL 72-s behavior. These results provide evidence that stimulation of 5-HT1A receptors and antagonism of 5-HT2 receptors lead to an antidepressant-like effect on the DRL 72-s schedule and implies that these two receptors may be important in mediating clinical drug effects in depression.

Animals↗
PubMed1988

Physical methods used in the complex therapy of chronic non-specific urinary tract diseases.

A total of 237 patients with non-specific diseases of the urinary tract have been examined and treated. The observations conducted indicate that correctly chosen therapeutic techniques in this category of patients palliate the inflammatory process, normalize the function of the kidneys, and thus provoke a positive effect on the course of chronic pyelonephritis and cystitis by enhancing the urodynamics of the lower urinary tract.

Balneology↗
PubMedDate not supplied

[The staged medical rehabilitation of patients with secondary chronic pyelonephritis in infravesical obstructions].

The authors believe that chronic pyelonephritis patients operated for infravesical obstructions need staged postoperative rehabilitation. In antibacterial postoperative treatment, a significant response was seen in 7.9%, a partial response in 18.4% and no response in 73.7% of patients. After combined physiotherapy--in 38%, 41.7% and 20.3% of patients, respectively.

Chronic Disease↗
PubMedDate not supplied

[The use of laser radiation and sinusoidal modulated currents in the therapy of patients with chronic calculous pyelonephritis].

The authors present a technique of treating chronic calculous pyelonephritis with laser radiation and sinusoidal modulated currents which promotes a complete elimination of the calculus fragments in 100, 70 and 50% of the patients in the stone size 0.2-0.5 cm, 0.5-0.7 cm and > 7 cm, respectively. This combined therapy had also antiinflammatory, and immunity-stimulating effects.

Antibody Formation↗
PubMedDate not supplied

[The use of physical factors in the rehabilitative treatment of patients with stone fragments in the upper urinary tract after extracorporeal shockwave lithotripsy].

155 patients with fragments of the crushed stones in the upper urinary tract after lithotripsy were divided into 3 groups. 60 patients of group 1 received dynamic amplipulse therapy, oral mineral water, iodobromine baths. Elimination of the fragments was observed in 91.7% of the patients. Group 2 patients (n = 60) were exposed to local vibration, ultrasound and iodobromine baths. The effect occurred in 96.7% of the cases. 35 patients of group 3 were exposed to impulse low-frequency magnetic field and took iodobromine baths. The elimination of the fragments occurred in 62.9% of the cases after a single treatment course.

Baths↗