Plasma Depression Research Articles

Exposure to the organophosphate diazinon: data from a human volunteer study with oral and dermal doses

Biological monitoring of occupational exposure to diazinon is possible by the determination of blood cholinesterase activity and by the measurement of metabolites in urine. However, there is little data to aid in the interpretation of results. This study gave oral (11 μg kg −1 (36 nmol kg −1) body weight) and occluded dermal (100 mg (329 μmol)) doses of diazinon to five volunteers and analysed blood and urine samples for plasma and erythrocyte cholinesterase and urinary dialkyl phosphate (DAP) metabolites of diazinon: diethyl phosphate (DEP) and diethyl thiophosphate (DETP). Following oral and dermal exposure, peak urinary DAP levels occurred at 2 and 12 h, respectively. The apparent urinary elimination half-lives of DAP metabolites following oral and dermal exposure were approximately 2 and 9 h, respectively. Approximately 60% of the oral dose and 1% of the dermal dose was excreted as urinary DAP metabolites, with 90% of the dermal dose being recovered from the skin surface. On a group basis, there was no statistically significant mean depression in plasma or erythrocyte cholinesterase when compared with pre-exposure levels for either dosing experiment. The observed elimination kinetics of diazinon metabolites suggest a biological monitoring strategy for occupational exposure to diazinon based on urine samples collected at the end of shift.

Stress inhibition of reproductive endocrine processes in a natural population of the spiny damselfish Acanthochromis polyacanthus

Stress–reproduction interactions were assessed by in situ sampling and laboratory manipulation of fish from a natural population of A. polyacanthus. Mean plasma cortisol concentrations for fish sampled under water immediately after capture were <11 ng mL–1 (range <1 to 42 ng mL–1 ); the variation was not a function of disturbance before capture,with no differences in mean cortisol concentrations between 5 min time blocks for chase times of up to 30 min. Fish confined for 2 or 6 h after capture showed significant increases in plasma cortisol concentrations, and depression of plasma T and E 2 in females and T and 11KT in males in summer but not in winter. There was no correlation between plasma concentrations of cortisol and sex steroids at capture. Underwater treatment of fish with cortisol had no effect on brood-guarding behaviour.Injection of fish either at capture or 24 h afterwards with human chorionic gonadotropin or luteinizing hormone-releasing hormone analogue had no effect on plasma concentrations of gonadal steroids, which remained low. Incubation in vitro of ovarian follicles from these fish showed that gonadal tissue was still steroidogenically active. This study suggests that inhibition of reproduction by stress in spiny damelfish is above the level of steroid biosynthesis.

Effects of cortisol on aspects of 3,5,3′-triiodo- l-thyronine metabolism in rainbow trout ( Oncorhynchus mykiss)

Aspects of 3,5,3′-triiodo- l-thyronine (T 3) metabolism were studied in fed rainbow trout ( Oncorhynchus mykiss) held at 11.5–14° and intraperitoneally implanted with hydrogenated corn oil (controls) or oil containing cortisol. Cortisol implants caused dose-related plasma cortisol elevations within the physiological range for 2–3 weeks, loss in body weight, and depression in plasma T 3 and free T 3 index with no consistent change in plasma thyroxine (T 4) or free T 4 index. Plasma T 3 clearance rate and plasma T 3 appearance rate were both increased by cortisol, with no change in hepatic microsomal T 4 5′-monodeiodinase activity ( K m or V max), but with a significant decrease in muscle T 3 concentration. It is concluded that chronic physiologic cortisol treatment enhances plasma T 3 clearance without change in hepatic T 4 to T 3 conversion, resulting in a decline in T 3 concentration in both plasma and tissue (muscle) compartments.

Effects of chronic and acute ethanol treatment during prenatal and early postnatal ages on testosterone levels and sexual behaviors in rats

This study was prompted by previous findings that prenatal ethanol exposure may interfere with the differentiation of the sexual behavior in rats. Ethanol (6 g/kg) administered daily from day 15 postconception, resulted in elevated testosterone (T) levels on Day 18 in male and female fetuses. No alterations of sexual behavior in the ethanol-treated male offspring were seen under these conditions. However, in ethanol-treated female offspring the onset of regular estrous cycling was significantly delayed. Acute treatment with doses of ethanol, 2, 4 or 6 g/kg, was ineffective in influencing plasma T levels of the fetuses. Acute treatment with 3 g/kg ethanol did not prevent the rise of T levels normally occurring immediately after birth. In adulthood, but not at prepubertal age (Day 30), treatment of male rats with 2 g/kg ethanol caused a depression of plasma T levels. Possible mechanisms affected by ethanol exposure and influencing on the fetal development were discussed.

Effects of catecholamines on plasma thyroid hormone levels in arctic charr, Salvelinus alpinus

Plasma levels of l-thyroxine (T 4) and 3,5,3′-triiodo- l-thyronine (T 3) were measured in arctic charr at 2, 6, or 24 hr after single intraperitoneal injection of epinephrine (E) or norepinephrine (NE). At a dose of approximately 1 μg/g body wt (sufficient to cause a submaximal dermal melanophore pallor response) plasma T 4 was usually elevated at 2 hr, consistently depressed at 6 hr, and unaffected at 24 hr. There was no effect of E on plasma [ 125I]T 4 kinetics or [ 125I]T 4 5′-monodeiodination to [ 125I]T 3. Plasma T 3 showed no consistent response to E or NE at any sampling time. At an E dose of 4 ng/g body wt (probably sufficient to cause a physiological elevation in plasma E level), neither plasma T 4 nor T 3 levels were altered at 6 hr. Acute depression in plasma T 4 by the high doses of E and NE may reflect a local neurotransmitter role of catecholamines in inhibiting thyroidal T 4 release through action at thyroidal, hypophysial, or hypothalamic levels.

The effects of dietary cholecalciferol steroids and gonadal hormone implantation on plasma 1,25-dihydroxycholecalciferol and bone calcification in preovulatory and senescent female Japanese quail

Using preovulatory Japanese quail hens (28d), one of two forms of vitamin D 3, cholecalciferol (CC) or the analog 1α-hydroxycholecalciferol (1α-OH-CC), was fed in combination with silastic implant treatments of 17β-estradiol benzoate, and/or testosterone propionate, and/or sham implants in a 2×2×2 factorial arrangement. The 5 μg/kg dietary level of 1α-OH-CC maintained plasma levels of 1,25-dihydroxycholecalciferol (1,25-(OH) 2CC) on an equal basis with a 20 μg/kg level of CC (800 I.U., 2×requirement level). Testosterone treatment caused a significant depression in plasma 1,25-(OH) 2CC, while 17β-estradiol (E 2) had no significant effect. Treatment with E 2 resulted in a marked increase in plasma calcium and the total calcium, % calcium, and medullary bone contents of the femur. In a second experiment, a population of 130 wk old Japanese quail hens were used in a 3×2 factorial design to test for the main effects of dietary vitamin D source (CC, 1α-OH-CC or 1,25-(OH) 2CC) and E 2 implantation on similar plasma and bone parameters. Again, significant stimulatory effects of E 2 treatment were observed upon most bone calcification measurements, and total bone calcium (P<0.04). In addition, plasma levels of 1,25 (OH) 2CC were elevated with E 2 implantation. These results indicate the ability of 1α-OH-CC (5 μg/kg diet) to maintain plasma levels of 1,25-(OH) 2CC on an equivalent basis with an above requirement level of CC. The lack of a significant effect of 17β-estradiol on 1,25-(OH) 2CC plasma levels in preovulatory quail hens suggests that estrogens do not have a direct effect upon the renal 25-OH-CC-1α-hydroxylase in vivo.

Effect of protein source on the bioavailability of zinc in human subjects

The purpose of this study was to compare the availability of zinc from a soyprotein versus animal protein based diet in human subjects. Five healthy male volunteers were given an animal protein diet (standard hospital diet) (APD), containing 12.26±0.7 mg zinc/day, for a period of 3 months followed by a soyprotein based diet (SPD), which contained 14.3±1.0 mg zinc/day for the following 3 months. Recommended dietary allowances for all other nutrients were met by supplementation. One week collection of urine and feces was done once at the third month on each dietary treatment and venous blood was drawn twice a month throughout the study period. Zinc was analyzed in urine, feces, red blood cells, plasma, and neutrophils. Results showed a significant difference in apparent zinc balance (p<.05) when subjects were fed SPD (−2.39±0.8 mg zinc/day) compared to APD (±3.25±1.6 mg zinc/day). There was no significant change in the zinc concentration of red blood cells and body weight of subjects throught the study. A significant depression in plasma (p<.05) and neutrophil (p<.01) zinc concentrations was observed at the end of 3 months when subjects consumed SPD compared to APD (plasma zinc 95.79±11.4 vs. 127.56±1.9 μg/100 ml and neutrophil zinc 93.56±11.6 vs. 135.33±3.5 μg/10 10 cells). At the end of 4 weeks on the soyprotein diet, the neutrophil zinc concentrations dropped significantly, whereas plasma zinc level showed no significant change from the base level. Our data indicate that if soyprotein is the major source of protein, then up to 15 mg of dietary zinc may not be sufficient to meet the daily zinc requirement for adult human subjects. Furthermore, we conclude that neutrophil zinc could be used as a sensitive criterion for diagnosing marginal zinc deficiency in humans.

Effects of cortisol administration on development of the thyroid and adrenal axes in rats

Intraperitoneal (IP) injections of cortisol were administered to neonatal male rats on postnatal days 1 to 4. Plasma triiodothyronine (T 3), thyroxine (T 4) and corticosteroids were determined on days 5, 10, 13, 16, 20, 30 and 60 of age, and all animals were weighed weekly. Neonatal cortisol treatment resulted in depressed body weight gain and transient depression in plasma T 4. These results indicate that while body weight is significantly affected by cortisol treatment ontogenic patterns of plasma T 3, T 4 and corticosteroids develop normally.

Application of a dermal self-exposure model to worker reentry.

The dermal toxicity of five commonly used organophosphate insecticides was investigated with a mouse intermittent self-exposure model. Blood cholinesterases were monitored on d -3 and -1 before exposure and for 4--6 d during exposure to foliar residues. Responses were much greater in unmuzzled than in muzzled animals due to oral contamination. After two 10-h exposures, muzzled mice showed log-linear cholinesterase responses across a wide range of foliar pesticide concentrations. Foliar pesticide levels that caused 50% depression in plasma or red blood cell cholinesterase were determined with log-probit dose-response analysis. The greatest cholinesterase responses for both emulsifiable concentrate and encapsulated formulations were found with diazinon, followed by parathion and methyl parathion. Azinphos-methyl and mevinphos produced no significant responses in muzzled mice at maximal foliar concentrations. Symptomatology, food consumption, and body weight provided less sensitive indicators of response than cholinesterases. No consistent relation existed between the mouse intermittent self-exposure toxicities and mouse dermal LD50 values. Use of data from acutely exposed animals to predict the hazard of intermittent foliar exposure appears inadvisable.

Health risks in ultra-low-volume (ULV) aerial spray of malathion for mosquito control.

A field study was undertaken to evaluate health risks in persons engaged in ultra-low-volume (ULV) aerial application of technical malathion for mosquito control. No specific toxicity signs and symptoms were observed except nausea and irritation of eyes in a few cases. Observations on the ChE activity has revealed a significant depression in plasma at the end of spray operation in labourers employed in loading and unloading of insecticide and in field workers. Red blood cells ChE activity was not affected in any group of subjects. At the end of spray operation the insecticide residue on the grass used as cattle feed were about 315 ppm, which are much above the permissible level. However, 4 days after the application normal levels of the insecticide residues were detected.

Suppression of testosterone production by ethyl alcohol. Possible mode of action

Intragastric administration of ethyl alcohol (1.24 g/kg body weight) to adult male mice caused a drastic decrease in the concentration of testosterone (T) in peripheral plasma. The depression of plasma T levels was significant at 30, 60 and 90 minutes after alcohol administration, but by 120 min, the normal T levels were re-established. This transient decrease in peripheral T levels was probably due to a reduction in testicular T production, because at 1 hr after alcohol administration, the concentration of T in the testis was also significantly depressed. The ability of the testes of alcohol-treated mice to produce T in response to gonadotropic stimulation in vitro was not affected. Addition of 5, 10, 20 or 50 μl of alcohol per ml of the medium used for the incubation of decapsulated testes had no significant effect on the accumulation of T, but similar doses of acetaldehyde caused a pronounced inhibition of T production. The decrease in plasma T levels observed after administration of ethyl alcohol in vivo may be related to a direct inhibition of testicular T production by acetaldehyde derived from the metabolism of alcohol.

Teratological studies with dichlorvos vapour in rabbits and rats.

The teratogenic potential of inhaled dichlorvos vapour for rabbits and rats was investigated on the offspring of primiparous female Dutch rabbits weighing 2 to 3 kg and primiparous female Carworth E strain rats weighing 200 to 300 g. The animals were exposed throughout pregnancy at concentrations of 0.25, 1.25 and 6.25 μg dichlorvos per litre of air. In an additional experiment pregnant rabbits were exposed to concentrations of 2 and 4 μg dichlorvos per litre of air. The results gave no indication that dichlorvos vapour is teratogenic in rabbits or rats even at exposure concentrations resulting in maternal deaths in rabbits, and causing depression of plasma, erythrocyte and brain cholinesterase activities in pregnant animals of both species.