Aldicarb Immunotoxicity: Functional Analysis of Cell-Mediated Immunity and Quantitation of Lymphocyte Subpopulations

Aldicarb Immunotoxicity: Functional Analysis of Cell-MediatedImmunity and Quantitation of Lymphocyte Subpopulations. THOMAS,P., RATAJCZAK, H., DEMETRAL, D., HAGEN, K., AND BARON, R. (1990).Fundam. Appl. Toxicol. 15, 221–230. Adult female B6C3F1mice received distilled water only or water containing 1.0,10, or 100 ppb of aldicarb daily for 34 days. The target concentrationof aldicarb present in the 100 ppb dosing solution was analyticallyverified. To further develop an immune profile of this compound,following aldicarb exposure, the ability of splenic naturalkiller cells and specifically sensitized cytotoxic T-lymphocytesto lyse YAC-1 lymphoma and P815 tumor cells, respectively, wasevaluated. To supplement the functional assays, the impact ofaldicarb exposure on the percentages and absolute numbers oftotal T-cells, T-suppressor, T-helper, and B-cells was evaluated.The absence of statistically significant effects on any of theseparameters supports earlier reports that aldicarb does not resultin adverse effects on the immune system of mice.     

EFFECT OF DOPAMINE AND A DOPAMINE D-1 RECEPTOR AGONIST ON PULSATILE THYROTROPHIN SECRETION IN NORMAL WOMEN

The inhibitory effect of a pharmacological dose of dopamine and the specific dopamine D-1 receptor agonist fenoldopam on basal and pulsatile TSH secretion was investigated in normal women. The TSH response to fenoldopam and subsequent releasing hormone administration was also studied. Six women received placebo or dopamine infusion (4.0 micrograms/kg min) for 17 h. After 9 h, blood samples were collected every 10 min between 0800 and 1600 h for measurement of TSH. Eight women received 8-h (0900-1700 h) infusions of either fenoldopam (0.5 micrograms/kg min) or placebo. After 7 h of infusion 10 micrograms TRH, 5 micrograms GnRH and 25 micrograms CRF was given i.v. Blood samples were collected every 10 min. Dopamine infusion as well as fenoldopam infusion significantly reduced both mean basal TSH secretion and TSH pulse frequency compared with corresponding control infusions (P less than 0.05). However, while the effect on TSH pulsatility was comparable (P greater than 0.05), the percentage decrease in basal TSH levels after 16 h of dopamine infusion was 51 +/- 16% (mean +/- SD) and after 7 h of fenoldopam infusion 19 +/- 12% (P less than 0.05). Neither of the drugs affected TSH pulse amplitude and fenoldopam did not influence TRH-stimulated TSH release (P greater than 0.05). The results suggest that dopamine D-1 receptors are involved in modulation of TSH pulsatility probably at the hypothalamic level. It is argued that dopaminergic inhibition of basal TSH secretion and TSH pulsatility is predominantly regulated through dopamine D-2 receptors at the pituitary level, and through D-1 receptors at the hypothalamic level, respectively.     

The ESPAD Study: implications for prevention

The European Schools Project on Alcohol and other Drugs (ESPAD) was concerned with the substance use, beliefs, attitudes and risk factors among over 50,000 16-year-olds in 26 European countries. Based on this data, the present paper focuses on critical issues in prevention and uses a country-level analysis with focus on the extent that contextual and cultural factors interact with factors influencing the use of alcohol and other drugs. The results indicate that: (i) an emphasis on risks and dangers may be a poor prevention strategy since many young people do not believe the widely accepted dangers of certain forms of substance use (e.g. cigarette smoking); (ii) misperception of norms in relation to substance use, that is, the belief that use of alcohol and other drugs is more common than it actually is, emerged in most countries with the exception of Nordic countries; (iii) the correlation between perceived access to substances and actual use depended on the substance involved; correlations were strongest for cannabis but low for alcohol; (iv) the measure of problem behaviour was used in the ESPAD study (truancy from school), is correlated with substance use in a way that is opposite to that predicted in problem behaviour theory; and (v) there were no indications that the potential restraining factors that were examined in this study (involvement in athletics and leisure) acted in a way that prevented people from experimenting with drugs. The results of this analysis suggests that far from our having identified a core set of universal influences that act to determine substance use, the importance of cultural and contextual factors have been underestimated as has the importance of the specific substance involved.     

Pituitary-Thyroid Function and Thyrotropin,Prolactin and Growth Hormone Responses to TRH in Patients with Chronic Alcoholism

ABSTRACT Basal plasma concentrations of thyroxine (T₄), 3,3′,5-triiodothyronine (T₃), free T₄ index (TF₄I), free T₃ index (FT₃I) reverse T₃, 3,3′,5-triiodothyronine (rT₃), resin T₃ uptake (TR₃U), thyroxine-binding globulin (TBG), thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) as well as thyrotropin releasing hormone (TRH) stimulated TSH, PRL and GH were investigated in 31 consecutive male patients (mean age 41 years) with chronic alcoholism. According to the histology of their liver biopsies the patients were divided into three groups: patients with normal livers, steatosis and cirrhosis. The control group consisted of 30 healthy males. The patients had abstained from alcohol for at least one week when studied, and they were on a nutritionally adequate diet. All had consumed a daily minimum of 52 g ethanol for at least 5 years. None of the patients had severe or decompensated liver disease. The patients had significantly reduced T₃ and rT₃ plasma levels compared to normals. Patients with cirrhosis of the liver had increased TBG and normal RT₃U levels, while those without cirrhosis had increased RT₃U and normal TBG levels. Plasma concentrations of basal as well as TRH-stimulated TSH and PRL were unchanged in alcoholic patients, whereas basal as well as stimulated GH levels were increased in cirrhotic alcoholics. It is concluded that alcohol per se influences T₃ levels, but not the part of the hypothalamic-pituitary axis studied, and that the binding proteins are mostly determined by the degree of liver disease.