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C L Mitchell

Publications and source records attributed to C L Mitchell.

106 records · Page 6Linked to original sources

Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path.

The ability of diethyldithiocarbamate (DEDTC) to prolong electrical afterdischarge (AD) and lower the threshold for behavioral seizures elicited by stimulation of the perforant path (PPS) was examined. DEDTC was given in doses of 25, 50, and 100 mg/kg, IP. The effects of DEDTC on the threshold for wet dog shakes (WDS) and the number of WDS elicited by PPS were inconsistent. It had no effect on the duration of AD accompanied with WDS. However, DEDTC, at both 50 and 100 mg/kg, significantly lowered the threshold for rearing accompanied with forelimb clonus. At 100 mg/kg, it also prolonged the duration of AD occurring with these seizures. The effects of DEDTC were transitory and coincided with the time course for its ability to chelate the mossy fiber intravesicular pool of zinc (i.e., that which is released by activation of dentate granule cells). It is suggested that release of zinc from the mossy fibers may serve to protect the hippocampus from paroxysmal seizure activity.

Animals↗

Temporary occlusion of the common iliac artery during hemipelvectomy.

The surgical technique for temporarily occluding the common iliac artery during hemipelvectomy has been described. Not only can this technique significantly reduce the blood loss and operative time, but it may also minimize postoperative complications and increase the chances of a complete eradication of the primary malignant disease.

Amputation, Surgical↗

Assessment of chemicals using a battery of neurobehavioral tests: a comparative study.

Single-dose LD10S and LD50S were determined in male, Fischer-344 rats for acrylamide monomer, arsenic trioxide, chlordecone, lead acetate, methylmercury hydroxide, monosodium salicylate, tetraethyl tin, and triethyl lead chloride. Proportions of the single-dose LD10S were used in a subacute study to estimate the 28-day LD20S for each chemical. Proportions of the 28-day LD20S were used in a subchronic (105 days of dosing) study to determine the effectiveness of a battery of neurobehavioral tests for detecting and characterizing the neurotoxic effects of each chemical. The battery consisted of undifferentiated motor activity, forelimb and hindlimb grip strengths, rotation orientation, thermal sensitivity, startle responsiveness to acoustic and air-puff stimuli, and performance of a multisensory conditioned pole-climb avoidance response task; body weight and rectal temperature were also monitored. The battery of tests was administered on eight occasions, that is, before, at three-week intervals during dosing (PO or IP, five days each week for 15 weeks), and at three and six weeks after dosing. Normative data (controls from each experiment) indicated fair overall stability of the measures over the eight test sessions, but experiment-to-experiment variability in this regard was clearly evident. The inherent statistical sensitivity of the tests varied greatly as estimated by their coefficients of variation, which ranged from 1% (rectal temperature) to over 100% (rotation orientation). Intercorrelations among the various measures were low to moderate indicating relatively little redundancy. The various measures were differentially affected by the eight chemicals: body weight by all eight; rectal temperature by one; undifferentiated motor activity by three; forelimb grip strength by two; hindlimb grip strength by four; rotation orientation by one; thermal sensitivity by one; startle responsiveness by three; and CAR performance by five. A profile analysis using the slopes of the dose-response functions after 15 weeks of dosing indicated clearly different patterns of effect among the eight chemicals. A composite score derived from a multidimensional analysis of the data suggested that the eight chemicals could be ranked from most to least neurotoxic as defined by these tests as acrylamide greater than methylmercury greater than chlordecone greater than tetraethyl tin greater than triethyl lead greater than lead acetate greater than arsenic greater than monosodium salicylate. This ranking and the results in general are in good agreement with what is known about these chemicals from other experiments with animals and from human experience. This battery of tests, or subsets thereof, may therefore have utility in the assessment of the potential neurobehavioral toxicity of various chemicals.

Acrylamides↗

Conditioned taste aversion following acutely administered acrylamide.

Fischer-344 rats were acclimated to a daily 15 min period of water availability. After water consumption had stabilized, the rats were permitted a 15 min access to 0.15% (w/v) solution of saccharin. One to two min following saccharin presentation, they were given various doses of acrylamide (10-50 mg/kg) or lithium chloride (LiCl; 3 mEq/kg) by gavage. Three days later, aversion to the saccharin solution was determined. Acrylamide, like LiCl, produced an aversion to saccharin. The effect of acrylamide appeared to be dose-related with the threshold dose being 10 mg/kg.

Acrylamides↗

Neurobehavioral assessment of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats.

2,4-Dichlorophenoxyacetic acid (2,4-D), an organic acid commonly used as a herbicide, was assessed for behavioral and neurological toxicity in male Fischer-344 rats. When given by gavage twice weekly for 5 weeks, 2,4-D produced a significant increase in fore- and hindlimb grip strength. Other neurological measurements such as negative geotaxis, hindlimb splay, motor activity, and startle responsiveness, were not affected. A second experiment, in which rats were dosed 5 days per week for 4 weeks, replicated the finding that 2,4-D increases grip strength of rats. In addition, the neurological effect was found to dissipate with time following cessation of dosing. That 2,4-D increases grip strength may be related to the observation that it induces myotonia, a condition characterized by difficulty in relaxation of skeletal musculature following forceful contraction.

2,4-Dichlorophenoxyacetic Acid↗