Objectives: To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis (RA). Methods: Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass index. Concentrations of glucose, adrenocorticotropic hormone (ACTH), cortisol, D4-androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17a-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor a (TNFa) were analysed in plasma.Results: Patients had comparable responses of glucose, cortisol, ACTH, ASD, and 17OHP to hypoglycaemia, without any signs of hypothalamic insufficiency. Patients had lower basal DHEAS than controls (3.03 (0.37) mmol/l v 5.1 (0.9) mmol/l, respectively; p,0.05); borderline lower basal DHEA levels (p = 0.067); while the response of DHEA to hypoglycaemia was comparable to that of controls. Patients with RA had lower EPI (p = 0.005) and NE (p,0.001) responses to hypoglycaemia. TNFa and IL6 were higher (p,0.05) in patients with RA (TNFa 8 (2.8) pg/ml in RA v 1.1 (0.5) pg/ml in controls and IL6 15.1 (6.7) pg/ml v 1.4 (0.7) pg/ml). Conclusions: Lower basal DHEAS levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA.

Fourteen 3-carboxypropionyl-tripeptide-p-nitroanilides of the general formula 3-carboxypropionyl-alanyl-alanyl-Y-p-nitroanilide (Y = glycine, norvaline, S-methylcysteine, valine, norleucine, S-ethylcysteine, methionine, leucine, isoleucine, phenylalanine, tyrosine, S-benzylcysteine, C"-phenylglycine, and proline) were synthesized and their cleavage by elastase, trypsin, and chymotrypsin (Km, kcat and k,at/Km) was determined.The significance of amino acid residues in the position of Y was evaluated firstly with respect to their structure (topographically), and secondly with respect to their free energy (thermodynamically). The alanine residue substrate was cleaved best by elastase, the phenylalanine substrate by chymotrypsin. Trypsin cleaved two substrates only, that is those containing a phenylalanine and a tyrosine residue.The optimum length of the elastolytic substrates was studied in a series of N-3-carboxypropionyl-(Ala),-p-nitroanilides (n = 1, 2, 3, 4, 5), N-3-carboxypropionyl-(Gly),-p-nitroanilides (n = 1, 2, 3), and in p-nitroanilides of fatty acids with two to seven carbon atoms. Elastase cleaved tri, tetra, and pentapeptides of alanine.p-Nitroanilides of the glycine series, as well as p-nitroanilides of fatty acids were not cleaved. 3-Carboxypropionyl-tetra-alanine-p-nitroanilide was the most suitable substrate so far found for elastase cleavage; it is not cleaved by trypsin nor chymotrypsin. The optimum distance between Y and the terminal anionic carboxyl residue was found to be 1.8 nm in elastolytic substrates.Pancreatic elastase has lately been the subject of interest concerning the mechanism of its effect, and also concerning its presumed participation in the pathogenesis of some diseases, such as pancreatitis [l -31, lung emphysema [4,5], and atherosclerosis [6].A series of various peptides has already been prepared to elucidate and determine the optimum amino acid sequences in synthetic substrates [7 -101. The bond between C-terminal alanine and the corresponding amide or ester bond is the most easily split. Succinyl-alanyl-alanyl-alanine-p-nitroanilide, described in the preceding communication, has been shown to be the most specific substrate [ll]. (The positions of amine acid residues, discussed below, are defined in this peptide as P4-P3-PI-P1-Pi .) The principal reason for the synthesis of the anionic substrates has been perceived as the proof of electrostatic interactions between the substrate and elastase (in the sense of Gertler's conception of the natural substrate bonding) [12]. Electrostatic induction brings about a change in the elastase conformation according to Koshland's theory of 'induced fit' [13]. Since this change is caused also by natural ionogenic substances (salts of cholic acids) [14] and thus probably occurs under physiological conditions, it has been considered adequate to modify our type of ionogenic peptide and to prove 'optimalization' of the amino acid residue in the position PI [15]. The use of p-nitroaniline as chromogenic residue permits the cleavage between the pos...

Activities of disaccharidases were studied in 115 jejunal biopsies af adults and children with celiac sprue (both florid and in remission), of patients with mucoviscidosis (with normal histological findings in the jejunal mucosa) and of control persons. Results of both biochemical and histochemical methods were compared with the histological picture. Patients with florid celiac sprue have a lowered activity of all disaccharidases (particularly of lactase and trehalase). In the remission of celiac sprue these activities improved. The improvement of lactase and trehalase proceeds more slowly than that of other disaccharidases. Patients with mucoviscidosis have significantly lower activities of trehalase than control persons. It is not possible to pass a correct judgement on the level of disaccharidase activities on the basis of the histological picture alone. Histochemical methods are sufficient for the assessment of disaccharidase activities in routine practice. For a correct quantitative determination biochemical methods are indispensable, however. The necessity of the determination of disaccharidase activities in whole non-centrifuged homogenates of biopsies was pointed out.

SUMMARY Cycloheximide, 5-azacytidine, and 4-methoxybenzoyl-/3-bromoacrylate (Cytembena) block the development of experimental acute pancreatitis in rats when mediated by the administration of 5 % bile solution into the pancreas in vivo. Six hours after drug treatment the pathological changes, evaluated macroscopically or using histological sections of the pancreas, were significantly decreased. The drugs affected the amount of abdominal fluid and lowered its lipase and amylase activity. The known inhibitory mechanism of the active drugs and the possible advantage of cycloheximide for clinical use are briefly mentioned.

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