Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management.

This review is intended to provide risk assessors and risk managers with a better understanding of issues associated with total exposures of human populations to ethylene oxide from endogenous and exogenous pathways. Biomonitoring of human populations and lab animals exposed to ethylene oxide has relied upon the detection of hemoglobin adducts such as 2-hydroxyethylvaline (HEV), which provides a useful measure of total exposure to ethylene oxide from all pathways. Recent biomonitoring data from CDC provide an excellent characterization of total exposure to ethylene oxide to the general U.S. population by demographic factors such as age, gender, and race as well as smoking habit, which might be comparable to previous measurements reported for humans and lab animals. The biochemical pathways including gastrointestinal (production by bacteria) and systemic (enzymatic production) pathways by which endogenous ethylene is generated and converted to ethylene oxide are described. The relative importance of endogenous pathways and exogenous pathways via ambient air or tobacco smoke was quantified based upon available data to characterize their relative importance to total exposure. Considerable variation was noted for HEV measurements in human populations, and important sources of variation for all pathways are discussed. Issues related to risk assessment and risk management of human populations exposed to ethylene oxide are provided within the context of characterizing total exposure, and data needs for supporting future risk assessment identified.

[Physical factors for the treatment of patients with chronic bacterial prostatitis].

This lecture is based on the review of the literature data concerning the application of physical factors (including sinusoidal modulated currents, laser radiation, ultrasound, medicamental ultrafonophoresis, ozonotherapy, etc) for the rehabilitative treatment of patients presenting with chronic bacterial prostatitis.

[Application of physiobalneotherapeutic factors in the combined rehabilitative treatment of patients with chronic bacterial prostatitis complicated by erectile dysfunction].

Patients with chronic bacterial prostatitis complicated by erectile dysfunction received combined rehabilitative treatment based on the use of various combinations of physiobalneotherapeutic factors, such as ultrasound, local negative pressure, white and yellow turpentine or sodium chloride baths, supplemented by basal medicamentous therapy in the form of rectal suppositories. Efficiency of therapy involving sodium chloride, white and yellow turpentine baths was estimated at 85, 60, and 75% respectively.

[Application of the pulsed low-frequency electrostatic field in the early rehabilitative treatment of patients following surgery for the correction of valgus deformation of the first toe].

This paper describes the method and results of application of the pulsed low-frequency electrostatic field (PLFESF) to the lower extremities of the patients who underwent surgical treatment for the correction of valgus deformation of the first toe. The efficiency of the method used in the early period of rehabilitative treatment was estimated at 93.3% compared with 96.7% in the patients who were managed by the same therapy in combination with polyoxdonium.

[Use of white turpentine bath emulsion and yellow turpentine solution for the treatment of chronic prostatitis complicated by excretory pathospermia].

The paper reports a review of up-to-date methods for the use of white turpentine bath emulsion and yellow turpentine solution in the treatment of chronic prostatitis complicated by excretory pathospermia. The results of bath therapy are presented. It is shown that the efficiency of white turpentine bath emulsion amounted to 69.7% compared with 88.3% in patients treated with the use of yellow turpentine solution.

[Therapeutic effect of impulse low-frequency electrostatic field on the local hemodynamics in the lower extremity after surgery for the correction of valgus deformity of the first toe].

This paper reports the results of the measurement of the linear blood flow velocity in the dorsal artery of the foot following surgical treatment. Rheovasographic characteristics of the lower extremity were obtained after the application of a pulsed low frequency electrostatic field (PLFESF) to correct valgus deformity of the first toe. It was shown that treatment with PLFESF significantly improved arterial and venous circulation in the operated leg.

[Rehabilitative treatment of patients with ureterolithiasis using pulsed vacuum depression, pulsed low-frequency electric current, and radon therapy].

The authors report results of the treatment of 60 patients with ureterolithiasis using a combination of pulsed vacuum depression (local vibrotherapy), low-frequency pulsed (alternating sinusoidal) current, radon water and radon baths. Clinical efficiency of combined therapy is estimated at 93.3%.

[Ultrasound in the treatment of patients with varicocele complicated by secretory form of pathospermia].

This paper presents a method for the ultrasound treatment of the skin of the male genital sphere and reports the results of therapy. The efficiency of this method for the management of varicocele was verified by its application in 64 patients with this pathology. Clinical efficacy of therapy was estimated at 56.4%.

[Classification of male infertility].

The article presents a new classification of male infertility which takes into consideration new data on aspermia, aspermatism and pathospermia. This brief classification is convenient for every day practice of physicians engaged in rehabilitation of patients with urological and andrological diseases.

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.

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.

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.

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.

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.

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.

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.

[Organ-conserving operations in treatment of breast cancer]. / Organosokhraniaiushchie operatsii v lechenii raka molochnoi zhelezy.

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%.

[Penetration of ultrasound and electromagnetic energy: a mathematical model]. / Matematicheskaia otsenka glubiny proniknoveniia énergii izlucheniia ul'trazvukovykh i élektromagnitnykh polei.

The authors present calculations on penetration of ultrasonic and electromagnetic fields in model space of the patient's body depending on the wave length and frequency of compressional waves emission.

[Mechanisms of action of some physical factors in therapy of patients with urolithiasis]. / Mekhanizmy deistviia nekotorykh fizicheskikh faktorov, primeniaemykh v terapii bol'nykh urolitiazom.

The authors consider four principal physiotherapeutic complexes applied in stone-eliminating therapy of patients with urolithiasis and mechanisms of action of these physical factors. In all cases of stones detection in the upper urinary tracts lithokinetic therapy begins with therapeutic impacts on the area of the affected kidney and upper ureter followed by the action on the affected part of the ureter.