Absorption, disposition kinetics, and metabolic pathways of cyclohexene oxide in the male Fischer 344 rat and female B6C3F1 mouse

Cyclohexene oxide (CHO) is a monomer intermediate used in the synthesis of pesticides, pharmaceuticals, and perfumes. Although CHO has a variety of industrial uses where direct human exposure is possible, very little is known about its fate in the body. Therefore, the objectives of this study were to determine the absorption, distribution, metabolism, and excretion of cyclohexene oxide after oral, intravenous, and dermal exposure in male Fischer 344 rats and female B6C3F, mice. After intravenous administration of [14C]CHO (50 mg/kg), CHO was rapidly distributed, metabolized, and excreted into the urine. Plasma concentrations of CHO rapidly declined and were below the limit of detection within 60 min. Average (+/- SD) values for terminal disposition half-life, apparent volume of distribution at steady-state, and systemic body clearance were: 19.3 +/- 1.6 min; 0.44 +/- 0.08 liter/kg; and 31.3 +/- 0.5 ml/kg * min, respectively. After oral administration of [14C]CHO (10 and 100 mg/kg), it was found that 14C-equivalents were rapidly excreted in the urine of both species. At 48 hr, the majority of the dose (73-93%) was recovered in urine, whereas fecal elimination accounted for only 2-5% of the dose. At no time after oral administration was parent CHO detected in the blood. However, its primary metabolite cyclohexane-1,2-diol was present for different lengths of time depending on the dose. Four metabolites were detected and identified in mouse urine by MS: cyclohexane-1,2-diol; cyclohexane-1,2-diol-O-glucuronide; N-acetyl-S-(2-hydroxycyclohexyl)-L-cysteine; and cyclohexane-1,2-diol-O-sulfate. The sulfate conjugate was not present in rat urine. Topical application of [14C]CHO (60 mg/kg) provided poor absorption in both species. The majority of 14C-equivalents applied dermally were recovered from the charcoal skin trap (approximately 90% of the dose). Only 4% of the dose was absorbed, and the major route of elimination was via the urine. To evaluate the toxicity of CHO, animals were given daily doses of CHO orally and topically for 28 days. No statistically significant changes in final body weights or relative organ weights were noted in rats or mice treated orally with CHO up to 100 mg/kg or up to 60 mg/kg when given topically. Very few lesions were found at necropsy, and none were considered compound related. In conclusion, regardless of route, CHO is rapidly eliminated and excreted into the urine. Furthermore, after either oral or dermal administration, it is unlikely that CHO reaches the systemic circulation intact due to its rapid metabolism, and is therefore unable to cause toxicity in the whole animal under the test conditions used in this study.     

Excitatory interactions in neuronal networks which include cells of the auditory cortex and the medial geniculate body

The use of the method of cross-correlation analysis to elucidate the interactions between simultaneously recorded neurons from various loci of the auditory cortex (AC) and the medial geniculate body (MGB) has made it possible to identify the following characteristics of the functional organization of the excitatory interactions in the thalamocortical neuronal networks: the interdependant impulse action of neurons located at various loci of the AC and MGB was determined by reciprocal excitatory connections; the efficiency of the connections between neurons of the AC, 400-500 microns apart, and between tonotopically associated neurons of the AC and MGB was approximately identical (associations were identified in 12% of the cases); the "divergent" properties of the MGB (AC) neurons were manifested in the fact that one and same neuron could simultaneously excite both neighboring cells and neurons from one or several loci of the AC (MGB); the "convergent" properties of the AC and MGB neurons were manifested in the fact that cells located at various loci of the AC and MGB simultaneously excited one neuron. The results make it possible to explain the deviations observed in the investigation of RF of neurons of the AC and MGB from the principle of tonotopical organization. It is hypothesized that the character of the organization of the excitatory connections in the thalamocortical networks may promote the creation of the necessary conditions for the modification of the efficiency of synapses between all of the elements of the network during the stimulation of individual elements.     

Initial experience in vascular plastic surgery in the surgical treatment of metastases of laryngopharyngeal cancer

The paper concerns conduction of the internal carotid artery and internal jugular vein reconstruction in 3 and 2 patients, respectively, operated for metastases of laryngopharyngeal carcinoma. 4 patients are still alive, 1 died on postoperative day 6. Bilateral one-stage Crile operation with application of autograft venous reconstruction of the internal jugular vein is detailed. Further research in this field is necessary.     

High-performance liquid chromatography of amino acids, peptides and proteins. CXXXIX. Impact of operating parameters in large-scale chromatography of proteins

Large-scale chromatography has been playing an important role in downstream treatment processing in biotechnology. In order to improve the productivity, the throughput of the chromatographic equipment was often increased by increasing the flow-rate and/or by increasing the column sample loading. This paper reports the results of a study on the impact of these and other operating parameters in affinity and ion-exchange chromatographic columns when used for protein purification. A sectional model was developed to predict protein adsorption processes in a packed column. The formulations of this mathematical model are presented in the Appendix. The present study was carried out with computer simulation based on this model and using data obtained from laboratory-scale columns. This model can simulate both the adsorption and washing stages of the protein purification process for both porous and non-porous particles. The effects of changing operating parameters were simulated and contour plots were generated for the easy identification of these effects. It was shown that both flow-rate and column loading can have a considerable impact on the processing rate and the yield of the column. As for the column capacity utilization, the impact of changing flow-rate is not significant at column loading of less than 80% in the test case. It was suggest that the present investigation provides a systematic predictive strategy which will greatly reduce the need for expensive, labour-intensive and time-consuming experimental work during process scale-up.     

Aspirative lipectomy in patients with alimentary-constitutional obesity

The results of aspirative lipectomy in patients with 2nd and 3rd stage of alimentary-constitutional obesity are analysed. The effectiveness of lipectomy with surgical creation of a small ventricle and without previous surgery, has been demonstrated. The criteria of patients selection, based on their somatic and psychic features, are formulated. Aspirative lipectomy has certain advantages over other types of plastic surgery as it has the minimal rate of postoperative complications.     

Characteristics and mechanisms of the interhemisphere synchronization in the rat motor cortex

Synchronised activity of the callosal cells was studied in the rat motor cortex. Cross-correlation analysis revealed narrow symmetrical peaks (less than 20 ms) and intermediate ones (30-80 ms). Common neuron(s) located in one hemisphere reciprocally connected callosal cells can play the role of a "common input" that synchronises discharges of the cells in both hemispheres. The narrow and intermediate peaks seem to be mediated by mono- and polysynaptic connections, resp.     

Psychosocial elements in the work environment of a large call center operation

The author investigates psychosocial factors that prevent early detection of injuries and the effect of late reporting on the long-term health of workers.