5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

Interim results on the clinical effects of i.v. administered thymopentin in active rheumatoid arthritis

Forty-one patients with active rheumatoid arthritis entered a controlled, double-blind, randomized study; 21 received prolonged i.v. injections (10 min) of thymopentin 50 mg 3 times a week for 3 consecutive weeks; the other 20 received placebo under the same conditions. The groups were comparable at the start of the study. Statistical tests of changes within the treatment groups after 3 weeks showed that the improvement achieved in the thymopentin group was significant (p less than 0.05 or p less than 0.01) for each clinical parameter, except for left-hand grip strength. On the other hand, no significant improvement was observed for any parameter except morning stiffness in the patients on placebo. The intergroup comparison showed significant differences, favouring thymopentin over placebo treatment, in the Ritchie index, scores for swollen joints, assessment of severity of pain and scores for changes in the activity of the disease. Only minor side-effects were experienced in the two treatment groups. The present placebo-controlled double-blind study confirms the previous positive results achieved in open studies, i.e., the beneficial therapeutic effect of prolonged i.v. injections of thymopentin in patients with severe rheumatoid arthritis observed after 3 weeks of therapy. The drug appears to be safe at the dose regimen used.     

Some observations on various dose regimens of thymopentin treatment in rheumatoid arthritis

Immunologic Research - Eight patients suffering from active rheumatoid arthritis were treated with thymopentin, 50 mg, administered as fractionated intravenous infusion over 10 min 3 times weekly...     

Age-related changes in immune function of rats and the effect of long-term hypophysectomy.

The effect of age on the ability of rats to raise antibodies to sheep erythrocytes and on the number of IgM plaque-forming cells in the spleen was investigated. An age-related decline in both parameters was observed. Additionally, the possibility that long-term hypophysectomy coupled with minimal replacement therapy might result in a delay and/or reversal of the age-related decline in immune function was studied. It was observed that long-term hypophysectomized rats responded better to immunization with sheep erythrocytes than did their age-matched unoperated littermates. The possible relationship of this to aging is discussed.     

Patients at high risk of progression after radical prostatectomy: Do they all benefit from immediate post-operative irradiation? (EORTC trial 22911)

EORTC trial 22911 demonstrated that immediate postoperative irradiation significantly improved biochemical failure free survival (BPFS) compared to wait-and-see (W and S) until relapse in patients with pT2-3 tumours and pathological risk factors after radical prostatectomy. In this study, we have investigated the heterogeneity of the treatment benefit across defined subgroups of patients. Data from 972 patients were used. A risk model was developed in the W and S group and the Log-rank test for heterogeneity was applied (alpha=0.05). Positive surgical margin (SM+), seminal vesicle invasion (SV+), WHO differentiation grade, pre- and post-operative PSA were independent predictors for BPFS in the W and S group. Men with SV+ were at higher risk of relapse whereas those with SM+ but no capsule infiltration (ECE-) did not seem to differ from those with SM-ECE+ or with SM+ECE+. Postoperative irradiation improved biochemical progression-free survival in all patient groups. Longer follow-up is needed to assess the endpoint of clinical progression-free survival.