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One of the critical issues confronting the evolving discipline of behavioral and neurological toxicology is the general lack of test validation in animal models. This paper seeks to provide a strategy aimed at resolving this important problem. It is proposed that test validation be accomplished by evaluating known neurotoxins in a battery of tests chosen to assess in animal models a wide range of effects on the basis of reported human toxicosis symptomatology. We propose to measure ongoing home cage motor activity, food consumption, water consumption, clay consumption (and the diurnal cycling of these), neurological/physiological indices (reflexes, autonomic signs, equilibrium/gait, balance, tremor, reactivity, and muscular strength), and aspects of cognitive and associative behavior involving both endogenous and exogenous (sensory) control of responding. An integrated, time-efficient scheme, covering 90 days of chemical treatment and 30 days of post-dosing recovery will be used. Chemical substances to be evaluated were chosen with the view of representing classes of neurotoxic effects. For initial study, triethyltin was chosen as an agent producing demyelination of nerves, acrylamide as an agent producing "dying-back" neuropathy, and methylmercury as an agent producing mixed central and peripheral neuropathies. Agents which attack specific loci in the nervous system and those producing anoxia will not be assessed in the first stages of this research due to lack of species generality of known effects, present lack of appropriate exposure facilities, or other problems. In addition, two drugs (amphetamine and sodium salicylate) will be investigated to support the generality of the testing procedures. By comparing the observed results of the neurotoxins in the animal models with the predicted effects based on reported human symptomatology, some decision concerning the validity of each procedure will be made. It is expected that the validation of tests to be used in behavioral and neurological toxicology will permit the meaningful assessment of more complex issues, such as the mechanisms by which neurotoxins act.
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PMID:Strategy for the assessment of neurobehavioral consequences of environmental factors. 72 Mar 19

The patient, a manic depressive who was treated with lithium for three years, suddenly developed severe neurotoxicity and a glomerulonephritis-like syndrome. The author believes that the lithium toxicity was facilitated by hot weather with excessive sweating, gall bladder pathology with fever, and decreased water and salt intake. The patient improved except for a persistent hypertension. Propranolol not only improved the hypertension but alleviated a lithium-induced tremor as well.
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PMID:Severe neurotoxicity and lithium therapy. 74 6

Propagules of Rhizoctonia solani grown in modified Czapek's medium containing sodium polypectate or carboxymethyl cellulose as a sole carbon source produced both extracellular and cell-bound polygalacturonase (PG), and cellulase (Cx), respectively. The cell-bound enzymes can be released to various extents by shaking the germinating propagules in solutions of NaCl, KCl, phosphate buffer, Na2EDTA (ethylenediaminetetraacetate), detergents such as Triton X-100 (octyl phenoxypolyethoxyethanol), Tween 80 (polyoxyethylene sorbitan monooleate), Celmusol, and distilled water. Sodium dodecyl sulfate (SDS) inactivated both PG and Cx but did no affect Cx activity in phosphate buffer solution. PG was more easily released by salts from the mycelium of R. solani than Cx. The release of both enzymes was a passive process and was not due to an osmotic effect. The amount of the cell-bound fraction was correlated with the total amount of the extracellular fraction rather than with the mycelial growth. At least one-third of the cell-bound fractions of both enzymes was found to be associated with the cell wall fraction of the mycelium.
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PMID:Release of cell-bound polygalacturonase and cellulase from mycelium of Rhizoctonia solani. 80 41

Two hoggets and 56 albino mice were used to study the effect of a water-extracted antigen of Listeria monocytogenes, strains 1,4b and St. r., through freezing, thawing, shaking, and filtrating (Seitz filter). A histologic examination was made of sections of the brain, lungs, heart, liver, spleen, and kidneys, stained with hematoxylin-eosin. Most characteristic of the toxic effect were the necrobiotic changes in the brain and viscera as well as the histiocytic infiltrations with the formation of granulomas. The extracted antigen could be inactivated at 60 degrees C. The mortality rate of mice infected with both the antigen and Listeria organisms was highest, and this showed that the toxic substance participates in the Listeria infection.
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PMID:[Toxic action of Listeria monocytogenes]. 81 54

In hydrocarbon fermentation, the efficiency of hydrocarbon uptake by cells is one of the keys to the economical production of single-cell protein. This work is concerned with characterization of cultures with two liquid phases for understanding the hydrocarbon uptake process by cells. Batch cultivation of Candida lipolytica was carried out in shaking flasks and in a tower fermentor with motionless mixers. Microscopic observation and cell and hydrocarbon concentration distribution in batch cultivation showed that some cells are attached to the large oil drops and others are free from them. Interfacila tension between oil and water and Sauter mean drop size decreased as cultivation proceeded. On the basis of the experimental results, the process of hydrocarbon uptake by cells is discussed.
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PMID:Characteristics of hydrocarbon uptake in cultures with two liquid phases. 84 16

Different quantities of sorbite-electrolyte solution were intravenously administered to eight heads of cattle and four heads of sheep (application values being 50 g sorbite, 0.3049 g MgCl2-6H2O, 0.3728 g KCl, 0.5477 g CaCl2-6H2O, 5.265 g NaCl, 6.804 g sodium acetate-3H2O with 1,000 ml distilled water). Different rises of sorbite, fructose, and glucose were recorded from the blood plasma. Certain manifestations of incompatibility and intolerance phenomena were observed, among them increase of cardiorespiratory activity and muscular tremor. Those findings were obtained primarily from animals which exhibited also strong rise in glucose concentration. One of the sheep died. Larger quantities of solution (2,000 ml or 4,000 ml) were intraperitoneally applied to ten heads of cattle and tolerated by them with no reaction. Sorbite in blood plasma usually reached its maximum two or three hours from application, however, without any rise of fructose or glucose. Slow drip infusion or intraperitoneal infusion are the techniques recommended for application of the above sorbite-electrolyte solution to ruminants.
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PMID:[Variations of glucose, fructose, sorbite and electrolyte concentration following intravenous or intraperitoneal administration of sorbite-electrolyte solution to cattle and sheep]. 96 80

Central activity, antihypertensive action and antiulcerogenic actions of Neurotropin (NSP), an extract isolated from vaccinia virus-innoculated skin or tissues of rabbits were investigated herein. When actions of NSP were examined in isolated muscle preparations by the Magnus-method, peristalsis and ACh-induced contraction in the small intestine isolated from crayfish were not influenced, peristalsis and ACh-induced contraction in the small intestine from mice were slightly accelerated, but adrenaline-induced relaxation in the small intestine from mice was not affected. Histamine-induced contraction in the small intestine and tracheal muscles isolated from guinea pigs was antagonized slightly, or not at all by NSP in a high concentration. NSP had no direct action nor anti-ACh action on abdominal muscles from frogs. NSP had no influence on E1-mice-convulsions. Both spontaneous motor activities and exploratory movements in mice were depressed. Sleeping time induced by hexobarbital-Na was prolonged in mice. Tremorine-induced tremor in mice was inhibited by NSP, while perphenazine-induced catalepsy in rats was not. Normal blood pressure in Wistar rats was not influenced, but high blood pressure in SHR (spontaneously hypertensive rats) decreased close to normal levels after NSP. NSP had antiulcerogenic effects on Takagi's restraint-plus-water-immersing ulcers in rats and histamine-induced duodenal ulcers in guinea pigs, but no influence on Shay ulcers in Wistar rats. From the data obtained herein, it may be concluded that NSP has many central depressant-like activities.
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PMID:[Central activity, antihypertensive action and antiulcerogenic effects of neurotropin]. 103 90

The bone inducing factor derived from BF osteosarcoma was purified in the following manner. Step 1. The sarcoma, grown in CBA mice, was excised and lyophilized. Step 2. The powder was washed with chilled acetone. Step 3. The acetone-treated powder was then homogenized with chilled distilled water. Step 4. Washing with 0.15M KCl. Step 5. The precipitate was incubated in in 0.2 N NH2OH, pH7.0, for 48 H at 25 degrees. After Step 5, the bone-forming activity showed a slight increase; however, the factor remained insoluble. The properties of the factor were as follows. The factor is relatively relatively heat stable; the osteogenic activity survived the treatment at 75 degrees for 15 min or at 55 degrees for 19 h. The activity was easily lost by mechanical shaking. Incubation with DNase, RNase, neuraminidase, chondroitinase ABC and beta-galactosidase left the osteogenic activity intact, but treatment with either pronase or collagnease destroyed this activity. The results suggest that the factor may be a protein. The activity was seen with the lyophilized BF osteosarcoma cells (without matrix), and it is probable that the factor was exclusively synthesized in the cells. The bone formation, observed across a millipore filter when living BF osteosarcoma enclosed in a millipore chamber was implanted in mice, suggests the synthesis and secretion of the factor from the cells.
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PMID:Studies on a factor responsible for new bone formation from osteosarcoma in mice. 105 58

With its chronic administration in a dose of 100 mg/kg lithium carbonate inhibited shaking of the head induced in mice with 5-hydroxytryptophan (5-HTP). This effect did not differ from the action following a single injection of lithium, when the interval between injection of lithium and of 5-HTP was one hour. With the interval lengthened to 24 hours the frequency of shaking diminished only under the effect of chronic administration. At the 5th, 10th and 21st day of a daily administration lithium failed to produce any effect on the hypothermal action of a reserpine-like agent Po 4-1284, but would reduce the protective action of imipramine in a ptosis test. A single injection of lithium made against the background of a chronic injection of water produced an opposite effect, viz. it significantly reduced the protective action of imipramine in hypothermia, but did not affect it with reference to ptosis. Hence, chronic administration of lithium leads to potentiation in its action of the serotonin-negative and central adreno-negative componets and to extenuating the peripheral adreno-negative component.
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PMID:[Effect of lithium on the central serotonin- and adrenergic processes after its chronic administration]. 108 64

The aim of this investigation was to determine the brain regions which were most sensitive to the inhibitory effects of morphine on the shaking response of pentobarbital-anesthetized rats to ice water. The median inhibitory dose (ID50) of morphine sulfate administered intraventricularly was found to be 0.35 mug/rat. When morphine was bilaterally injected into different regions of the brain, the ID50 values ranged from 0.04 to 17.9 mug/rat. The lowest ID50 values (0.04-0.20 mug) were found in the periaqueductal gray, the medial preoptic area and the locus ceruleus. The ID50 values ranged from 0.65 to 1.6 mug for areas around the nucleus accumbens, the fasciculus retroflexus, the medical thalamus and the septal area; from 5.6 to 7.3 mug for various hypothalamic nuclei; and from 11.0 to 17.9 mug for the basal ganglia, reticular formation substantia nigra and the reticular nucleus of the thalamus. The brain areas with the lowest ID50 values are known to have thermoregulatory functions. The similarity of the shaking response to shivering is discussed. It is concluded that the central inhibitory effects of morphine on shaking are subserved by discrete neuroanatomical substrates located in medial subcortical structures.
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PMID:Regional sensitivity of the rat brain to the inhibitory effects of morphine on wet shake behavior. 109 8


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