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Biomedical subjects

M Berlin

Publications and source records attributed to M Berlin.

At least 73 records · Page 4Linked to original sources

Methyl mercury binding substances from the brain of experimentally exposed squirrel monkeys (Saimiri sciureus).

Squirrel monkeys were given a single subtoxic dose of 203Hg-labelled methyl mercuric hydroxide. After three weeks the brains were dissected out, homogenized and separated into particulate and soluble fractions by ultracentrifugation. The soluble fractions were further separated into high molecular weight and low molecular weight components by ultrafiltration. The major part (75%) of the radioactivity was associated with the particulate fraction while high molecular weight compounds in the soluble fraction accounted for 16%. The remainder (9%) was bound to glutathione.

Animals↗

Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene.

Human subjects were exposed to known concentrations of benzene in air for single and repeated daily periods. The breath concentrations measured repeated exposures approached a maximum after 3 d, and this phenomenon indicated that the tissues were approaching saturation under the experimental conditions. The breath concentrations measured after exposure indicated an initial rapid clearance of benzene with a half-time of 2.6 h, followed by a slower phase with a half-time of 24 h. The decay in breath concentration after prolonged occupational exposure appeared to be slower; the difference between the laboratory and industrial studies was, however, not significant. The hygienic significance of these results was discussed, and it was recommended that control measures be employed when a morning breath concentration exceeds 10 ppb.

Atmosphere Exposure Chambers↗

Biological threshold limits for benzene based on pharmacokinetics of inhaled benzene in man.

Volunteers were exposed to benzene, 2--10 ppm, under controlled conditions up to 6 h a day during five consecutive days. The accumulation and elimination of benzene was measured by determination of benzene concentration -- down to 0.001 ppm -- in exhaled breath. From these observations, a multicompartment model, which approximately describes the kinetics of benzene elimination and accumulation has been designed. On the basis of this model, benzene concentrations in breath, corresponding to exposure levels of benzene, have been estimated. Thus, at a daily exposure to 10 ppm the exhaled benzene concentration in the morning after a day of exposure will not exceed 0.1 ppm.

Aerosols↗

Interaction between selenium and inorganic mercury.

Data on mercury and selenium interaction in the mammalian body are reviewed. Experimental data from studies on rats show that selenium interacts with mercury metabolism and toxicity after exposure to mercuric mercury. Autopsy data from workers exposed to mercury vapor indicate an association between mercury and selenium retention in the central nervous system, suggesting the formation of a mercury-selenium complex. In animal experiments, mercuric mercury interferes with selenium metabolism and toxicity. Available data do not, at present, permit deduction as to whether additional selenium intake in man, exposed to mercury vapor or mercuric mercury, will have any effect, beneficial or adverse.

Animals↗

Aging and the central nervous system.

This review of the literature on aging and the central nervous system attempts to cover the basic perameters investigated at both human and infrahuman levels for the better part of the last century. The results have indicated that there is a rather considerable lack of consistency in the data both within the frame of reference of a single species, and with regard to intraspecies comparisons. We have suggested that possible reasons for the contradictory findings would rest upon variability in techniques employed but, perhaps more importantly, on the failure of investigators in this area to standardize terminology. It is suggested that such a standardization might well be one of the more useful things to be accomplished in order to facilitate the interpretation of future work. The literature review first dealt with gross, i.e., macroscopic changes in brain morphology that could correlate with age, and then covered changes at the microscopic level. Finally, a brief review of the literature with regard to the biochemistry of aging was carried out. Implications of the data were noted where appropriate.

Aging↗

Distribution and metabolism of 2,4,5,2', 5'-pentachlorobiphenyl.

Single doses of 2,4,5,2',5-pentachlorobiphenyl uniformly labeled with 14-C have been administered intravenously and orally to mice. Whole-body autoradiograms and scintillation counting of tissue samples have shown that most radioactivity leaves the circulation for the tissues within one hour. Peak concentrations varied, being highest in brown fat, which after 24 hours comprised the major reservoir of the unchanged compound in the body. Radioactivity disappeared rather rapidly drom most other tissues, although the longest retention occurred in bronchial epithelium and some parts of the renal tubules. The excretion of radioactivity was mainly through the bile, into feces, with a half-time of six days. There was little unchanged compound in the feces, the major metabolite was a hydroxylated derivative, both free and conjugated.

Adipose Tissue, Brown↗

Dose-dependence of methylmercury metabolism. A study of distribution: biotransformation and excretion in the squirrel monkey.

The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of 203-MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1 mug/gm. Above this level, the ratio of concentration in the brain and blood was increased. The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in the blood. The total Hg concentration in feces was always more than ten times that in urine. Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain less than 5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of 203-MeHg, the halftime for total Hg in blood was 49 plus or minus 2.8 days, and in the whole body 134 plus or minus 2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.

Animals↗

Neurotoxicity of methylmercury in squirrel monkeys. Cerebral cortical pathology, interference with scotopic vision, and changes in operant behavior.

Blood mercury was raised to levels exceeding 1,000 ng/gm by weekly oral doses of methylmercury hydroxide to squirrel monkeys. Operant behavior tests were employed and neurological signs were recorded on film. Sudden visual disturbance occured with subacute exposure. Prolonged exposure resulted in impaired coordination with impairment of scotopic vision and possibly also sensory disturbances. Scotopic vision was tested by determining the critical fusion intensity (cfi) at 10 cps. An increase in cfi was the earliest neurological sign appearing in some monkeys months before other signs could be detected. Poisoned monkeys exhibited typical cerebral cortical lesions. The visual cortex was invariably involved. Extension to adjacent cortical areas increased with increasing duration of exposure and increasing brain mercury. The microgram per gram brain tissue was the lowest concentration of methylmercury seen wiht morphological lesions.

Animals↗

Tritiated methylmercury in the brain of squirrel monkeys.

Tritiated methylmercuty hydroxide (MeHgOH) with a specific activity of 306 curies/mol was synthesized by a Grignard reagent from tritiated methyl iodide with a yield of 70%. Tritiated MeHg was given to squirrel monkeys by stomach tube in weekly doses of 0.8 mg/kg. The animals were killed after one dose or six doses. The distribution of the substance in the brain was then studied by microautoradiography and by fractionation of brain tissue into cellular and subcellular fractions. Part of the MeHg in the brain is in a water-soluble form. Methylmercuty was found autoradiographically mainly in the neuropile of the cortex. At subtoxic doses (one dose), more protein-bound radioactivity was found in the glial fraction than in the neuronal fraction. At toxic dose (six doses), the protein-bound fraction of MeHg increased significantly (P less than .02) in the neurons relative to nontoxic dose (one dose). Methylmercury was demonstrated autoradiographically in damaged neurons but not in undamaged neurons.

Animals↗