Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin

The dose of nicotine and the frequency of its administration appear to be essential determinants of its action on multiple systems including the neuroendocrine regulation of the adrenocorticotropin (ACTH)-corticosterone and prolactin (PRL) axes in the rat. Because desensitization to the acute depressive effects of nicotine has been observed after both acute and chronic administration, these investigations assessed whether desensitization to the stimulative effects of nicotine on ACTH and PRL secretion occurs with repetitive dosing. Extensive dose and time course experiments showed that nicotine rapidly elevates rat plasma ACTH and PRL levels with a threshold dose between 0.1 to 0.25 mg/kg b.wt. i.p. After the stimulation of PRL, levels became significantly depressed. Desensitization to the acute stimulatory effects of nicotine on both hormones was induced by a single dose of nicotine (0.5 mg/kg). One hour later nicotine (1.0 mg/kg) failed to significantly stimulate PRL levels and resulted in a modest increase of ACTH. Desensitization was maximal by 1 hr after the first dose and persisted for at least 6 hr. Adrenalectomy, performed to eliminate corticosterone-induced negative feedback, did not enhance PRL responsiveness to a second dose of nicotine but it partially restored the ACTH response. Pretreatment with corticosterone also failed to modify the PRL response to a single dose of nicotine whereas it partially suppressed the ACTH response. Rapid desensitization to the acute stimulatory effects of nicotine on plasma PRL is independent of glucocorticoid negative-feedback whereas desensitization of the ACTH response is modestly dependent.     

The cytochromes P-450 concentrations in microsomes of liver, kidney and duodenal mucosa of the camel, sheep and goat

The concentration of microsomal cytochromes P-450, and of protein in the homogenate, cytosol and microsomes were measured in the liver, kidney and duodenal mucosa of healthy well-fed male and female camels, sheep and goats. For comparison, data from the liver of male and female rats were also obtained. The protein concentrations in the tissues of adult animals were broadly similar in the four species. The concentration of cytochromes P-450 was highest in the liver, followed by the kidney, then the duodenal mucosa in all the species. No cytochromes P-450 were detected in the tissues of immature (less than 1 mo) male goats, whereas the female goat had the highest concentrations of these enzymes in the liver and kidney when compared with the respective tissues in the other species studied. Males had higher activity of cytochromes P-450 than females in the three tissues, except in the duodenal mucosa of sheep, where males had lower activity than females. In camel liver and sheep kidney, the amount of cytochromes P-450 were similar in the two sexes. The present results suggest that the mature female goat is the species best equipped to handle xenobiotics which are detoxified by the cytochromes P-450 and other drug metabolizing enzymes in diseased or malnourished animals is suggested as these two conditions are known to modify drug metabolizing enzymes.     

Trans fatty acids– Metabolic and nutritional significance

'Trans' fatty acids are unsaturated acids with special structural features that occur naturally in dietary fats from animal and plant sources and in fats processed by catalytic hydrogenation. They are readily metabolized by the human body. Thus, although when consumed in the diet they are incorporated into body fat (including depot and milk fats), they are subject to rapid 'turnover'. In physical properties, trans monounsaturatedfatty acids are intermediate between cis-monounsaturated and saturated acids, and they tend to be treated either as saturated or cis-monounsaturated acids in metabolic pathways. The author argues in this article that any adverse effects on health or metabolism that may have been observed can be ascribed to an imbalance between the intake of trans and essential fatty acids. Such imbalances, could also occur with non-essential fatty acids other than trans fats. Normally, the amounts eaten in average diets would not pose serious problems and only when products have excessively high trans contents and make a significant contribution to the diet need trans acids be highlighted on labels.     

The in vitro permeability of human skin to benzene, ethylene glycol, formaldehyde, and n-hexane

The permeability of human skin to benzene, ethylene glycol, formaldehyde, and n-hexane was studied using excised skin in a flow-through diffusion cell. The rate of resorption was determined by measuring the amount of substance found in the receptor fluid beneath the skin at steady-state. The rates of resorption (microgram X cm-2 X hr-1) were: benzene 99. ethylene glycol 118, formaldehyde from a concentrated solution of formalin 319, formaldehyde from a solution of 10% formalin in phosphate buffer 16.7, and n-hexane 0.83. The amount of substance in the skin at steady-state and after 0.5 hr of exposure was also determined. For all substances, the sum of the amount in the receptor medium and in the skin at steady-state, were larger than the amount obtained by multiplying the resorption rate by the time of exposure. For benzene, ethylene glycol and n-hexane the amount absorbed during the first half-hour of exposure was considerable larger than the amount resorbed during a same unit of time at steady-state. These data call attention to the fact that the absorption rate is higher before steady state is attained.     

Effects of neurotransmitters or drugs on the in vivo release of dopamine and its metabolites

The effects of neurotransmitters or drugs on the release of endogenous dopamine (DA) and extracellular levels of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were examined in vivo by intracerebral dialysis. A dialysis tube was implanted stereotaxically through bilateral caudate nuclei of rats and perfused with the Ringer solution. Amounts of DA, DOPAC and HVA in the perfusates were measured by high performance liquid chromatography (HPLC) with electrochemical detection. The basal level of DA was 2.76 +/- 0.64 pg/min, whereas the levels of DOPAC and HVA were 218.7 +/- 20.7 and 142.4 +/- 10.6 pg/min, respectively. Apomorphine (4 mg/kg, i.v.) reduced the efflux of DA and its metabolites. Haloperidol (0.4 mg/kg, i.v.) did not change DA release and produced only a minor increase of its metabolites. This increase of metabolites was inhibited by pargyline. Met-enkephalin (10(-4) M), substance P (10(-4) M) and acetylcholine chloride (10(-4) M) added to the perfusing medium increased the release of DA. Met-enkephalin also increased the release of DOPAC. gamma-Amino-n-butyric acid (GABA, 10(-4) M) reduced the release of DOPAC and HVA when added to the perfusing medium. Thyrotropin releasing hormone (TRH, 5 mg/kg, i.v.) increased the release of HVA. These findings indicated that different mechanisms mediated effects of neurotransmitters or drugs on the release and metabolism of DA in the rat striatum.     

Affinity purification of a high molecular weight human breast cancer-associated antigen identified by the BCD-B4 monoclonal antibody

This study reports the purification and characterization of a high molecular weight human breast cancer-associated antigen identified by a previously described (1,2) murine monoclonal antibody, BCD-B4. Immunohistochemical analysis indicated that BCD-B4 recognizes an antigen expressed in an altered form on the human breast carcinoma cell line, BT-20, compared to the non-malignant human mammary epithelial cell line, HBL-100. Chemical treatments and enzymatic digestions suggested that the recognized moiety was a protein. The antigenic determinant was resistant to neuraminidase and periodate treatments but was sensitive to trypsin and proteinase K. The antigen was purified by affinity chromatography and its molecular weight, determined by SDS-PAGE analysis under non-reducing conditions, was proven to be 250 Kd. Under reducing conditions, the molecule dissociated into two polypeptides of 125 and 45 Kd, respectively. Both subunits could be isolated from normal HBL-100 and neoplastic BT-20 cellular protein extracts by affinity chromatography. The higher molecular weight subunit showed; however, qualitative and quantitative differences between the two cell lines: it was expressed in greater quantity on BT-20 cells and its molecular weight was 15 Kd higher. Both subunits could also be identified by immunoblots of BT-20 cells.