Expression and complement d activity of porcine adipsin.

To learn how signals from adipocytes might be involved in regulation of energy intake and storage, we have begun to characterize the porcine complement protein, adipsin. Adipsin was originally identified as a protein that is produced rather specifically by adipocytes, is secreted, and is nearly absent in several obese rodent models. We now report that porcine adipsin mRNA sequence is 74% identical to rat and predicts a protein that has 82 and 68% identity to human and rat forms, respectively. Porcine adipsin has none of the asparagine glycosylation consensus sites which make recombinant expression of mouse adipsin in Escherichia coli impractical. We present a method for engineering the porcine cDNA to facilitate expression by E. coli and provide a protocol for refolding and purifying porcine adipsin protein and for immunoassay. We have found that in addition to adipose tissue, adipsin mRNA is present in gut tissues. Coupled with the fact that adipsin is required for processing of complement C3a-desArg, and that C3a-desArg is a potent stimulant of fatty acid acylation in adipocytes, the production of adipsin in the gut may be related to a mechanism for adipocyte removal of lipid from chylomicrons.

Characterization of the endothelin receptor subtypes in human prostate.

Endothelin (ET) receptor subtypes in human prostate with benign prostatic hyperplasia were investigated by binding and functional studies. In the displacement experiment, LU224332 [endothelin-A/-B (ET(A)/ET(B)) nonselective antagonist] competed for [125I]ET-1 binding with a monophasic curve. On the other hand, LU135252 (ET(A)-selective antagonist) and sarafotoxin S6c (S6c, ET(B)-selective agonist) competed for [125I]ET-1 binding with shallow and biphasic curves. The analysis of the displacement curves for LU135252 and S6c showed that both ET(A) and ET(B) subtypes coexist but that ET(A) is the dominantly expressed receptor. In human prostate strips, 10 microM of both LU135252 and LU224332 strongly inhibited the contractile response to ET-1 with equal potency. However, 10 microM of BQ788 (ET(B)-selective antagonist) did not show a clear inhibition. S6c also produced a contractile response, which was potently inhibited by LU224332 or BQ788, and slightly suppressed by LU135252. These results suggest that in human prostate both ET(A) and ET(B) subtypes are functional receptors mediating contraction, but that ET-1-mediated contractions are predominantly mediated by activation of dominant receptor subtype, ET(A).

Regulation of adipsin and body composition in the monosodium glutamate (MSG)-treated mouse.

Changes in food intake, serum adipsin, and obesity were evaluated in the MSG-treated mouse. In Experiment 1, mice treated with MSG had 50% lower serum adipsin and over 2-fold higher percentage of body fat than the lean controls. Both feeding caffeine and restricting intake normalized serum adipsin and caused weight loss, but did not normalize the percentage of body fat. No additional effect was gained by feeding isoproterenol or ephedrine in combination with caffeine. In Experiment 2, we separated the direct effect of caffeine from the associated depression in intake using a paired feeding design, and also determined the effects of selected adrenergic agents and somatotropin (S). Somatotropin increased weight gain and reduced the percentage of body fat in healthy and obese mice, and tended to lower serum adipsin. Caffeine clearly depressed intake, caused weight loss, and increased serum adipsin, but similar results were achieved by restricting intake. None of the adrenergic drugs tested changed serum adipsin. Ephedrine depressed food intake and caused weight loss, but reduced the percentage of body fat only at the highest dietary concentration (2000 mg per kg of diet). Phenylephrine reduced weight gain without a concomitant effect on the percentage of body fat, and isoproterenol did not influence weight gain or body fat.

Antihypertensive efficacy of anipamil in mild to moderate hypertension.

The antihypertensive efficacy of anipamil, a novel calcium antagonist of the verapamil type, was tested in an open group comparison. One hundred twenty-one hypertensive patients (World Health Organization stage I-II) entered the study in 17 centers in Germany and Austria. After a placebo washout period patients were randomly allocated to either 40, 80, or 120 mg of anipamil for a period of 7 days. This treatment period was followed by another 7-day placebo period. Anipamil lowered systolic and diastolic blood pressure in all three dosages tested. The 80-mg dose was more effective than 40 mg. The 120-mg dose did not show an increased effect over 80 mg. Heart rate was slightly lowered, reaching statistical significance in the groups receiving 80 and 120 mg. In the dosages tested, anipamil had no effect on PQ-interval or other electrocardiogram parameters. Major or clinically relevant changes in the laboratory parameters could not be detected. Side effects were rare, mild, and transient. No patient had to be discharged from the trial due to severe side effects.

Monitoring personal exposure to ethylenediamine in the occupational environment.

A method for monitoring exposure to ethylenediamine (EDA) in the occupational environment is described. The EDA is adsorbed on activated silica gel, desorbed with 0.5 percent aqueous cupric chloride, and analyzed by gas chromatography using a 2 percent KOH on a Chromosorb 103 column. The method is sensitive to 200 micrograms/mL EDA and can detect 1.0 ppmv EDA in samples collected for 4.5 hours at a 300 cc per minute flow. The method has been evaluated in the laboratory and under plant conditions. Other amines do not interfere with the determination of EDA.

[Dose finding for clinical trials of antiarrhythmic substances (author's transl)]. / Dosisfindung in der klinischen Prüfung von Antiarrhythmika

Specific difficulties connected with clinical evaluation and especially dose finding for antiarrhythmic substances are discussed. They are mainly due to the differences in pathogenesis, clinical significance and to the inconsistency of the symptom arrhythmia. Therefore special cardiologic skills are required for performance and interpretation of respective studies. The importance of selection of patients and determination of plasma levels of the substance is demonstrated. Possible procedures for determination of the therapeutic dosage are described and the necessity of detailed documentation of side effects is stressed.

Experimental toxicology of pyrolysis and combustion hazards.

Data are presented on the acute toxicity (mortality only) of the thermal degradation products of polymers obtained by two methods of degradation. One system utilized a slowly increasing temperature (5 degrees C/min) and gradual degradation of the polymer with the rats being exposed to degradation products as they were evolved. In this system the more toxic polymers included wool, polypropylene, poly(vinyl chloride), and urethane foam. The second system utilized conditions of rapid combustion and exposure of rats to the total products of combustion for a period of 4 hr. In this system the more toxic materials included red oak, cotton, acrylonitrile-butadiene-styrene (ABS), and styrene-acrylonitrile. It is of interest to note that the natural product wool is among the least toxic under these rapid combustion conditions and among the most toxic under slow pyrolysis conditions. Other materials also vary in the comparative toxicity of their thermal degradation products, depending upon the conditions of degradation and animal exposure. The two experimental techniques presented here may well represent the two extreme conditions of rapid combustion versus slow pyrolysis. Intermediate types of fire situations might be expected to result in relative acute toxicities somewhere between these two extremes. This report deals with acute toxicity on the basis of mortality data only and does not include other parameters of toxicity such as organ weights and histopathology.

Morphology of gastrointestinal effects of aspirin.

The effect of acetylsalicylic acid (aspirin) on the ultrastructure of gastric and jejunal mucosa was investigated in patients undergoing gastric surgery and in guinea pigs. The drug caused various degrees of damage to the surface mucous cells in both species perceptible as general signs of cytolysis in situ or as desquanmation. In patients pretreated with aspirin, an increase of secondary lysosomes was noted in the gastric parietal cells but not in the animals. In the intestinal epithelial cells of both species there was a marked increase of multivesicular bodies and the occurrence of transitional stages between the two organoids suggest a functional interrelationship. Since no specific alteration of any cellular organoid was detected, the drug-induced injury is assumed to occur on a molecular level in the cytoplasm. It is concluded that the intracellular concentrations of aspirin in gastrointestinal mucosal cells mechanims but that high drug concentrations may lead to irreversible cell damage.