Release of 3H-5-Hydroxytryptamine from Isolated Rabbit Aorta

Abstract: The main aim of the present investigation was to study systematically the passive and stimulation-evoked release of ³H-5-hydroxytryptamine (³H-5-HT) from rabbit isolated aorta. This was accomplished by preloading rings of aorta with ³H-5-HT (10^–6M) and then monitoring by fractional collection the basal ³H-outflow and stimulation-evoked ³H-overflow. The basal ³H-outflow from aorta preloaded with 10^–6M of either ³H-5-HT or (-)-³H-noradrenaline (³H-NA) leveled off about 100 min. after the onset of wash-out and remained almost constant thereafter (100–240 min.). The basal ³H-outflow from tissue preloaded with ³H-5-HT was almost 3-fold higher (70–240 min.) than that seen after preloading with ³H-NA. Cocaine (3x10^–5M) did not alter the basal ³H-outflow (15–240 min.) from tissue preloaded with ³H-5-HT, while pargyline (5X10^–4M) decreased it by about 66% (100–240 min.). Electrical-field stimulation (S₁S₇, 200 mA, 600 pulses, 0.5 msec, 3 Hz) were applied to the tissue. The initial stimulation-evoked ₃H-overflow from aorta preloaded with ³H-5-HT was higher than the subsequent ones (S₁-S₇: 100, 35, 35, 35, 35, 37, and 40%). Similar results to these were obtained with tissues preloaded with ³H-NA. The stimulation (S₁-S₇; 200 mA; 600 pulses, 0.5 msec, 3 Hz)-evoked ³H-overflow increased in an apparent linear manner with the amount of current used (50–200 mA). This was also the case for number of pulses (100–900) in the stimulus. The stimulation-evoked ³H-overflow depended in part on the stimulation frequency: unchanged at 2–4 Hz; small increase at 8 Hz; and a 15-fold increase at 16 Hz relative to 2 Hz. Tetrodotoxin (10^–6M) decreased the stimulation-evoked ³H-overflow from aorta preloaded with ³H-5-HT (S₂-S₆) by about 60%, while S₁ was not affected. The inhibitory effect of tetrodotoxin was fully reversed by washing the aorta with drug-free salt solution. Omission of Ca²⁺ from the salt solution reduced the stimulation ³H-overflow by 47–57% (S₂-S₆) while S₁ was unaffected. 6-Hydroxydopamine markedly increased the stimulation-evoked ³H-overflow from ³H-5-HT preloaded rings (180–323% of control). Pargyline (5x10^–4M), cocaine (3x10^–5M) and removal of endothelium did not alter the stimulation-evoked ³H-overflow evoked by stimulation (S₁-S₆) of aorta preloaded with ³H-5-HT. It is concluded that ³H-5-HT can be released by electrical-field stimulation as a “false transmitter'’from rabbit isolated aorta. Most of the release is probably of neuronal origin. However, some of the stimulation-evoked ³H-overflow is derived from extraneuronal sites.     

Ambroxol inhibits IgE-dependent mediator secretion from human skin mast cells

Inflammation Research -     

Synergistic actions of the vitamin D analogue MC 1288 and 15-deoxyspergualin in xenotransplantation

Abstract: The vitamin D analogue MC 1288 (20-epi-1α,25-dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25-dihydroxycholecalciferol, the active form of vitamin D. 1α,25-Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin-2, interferon-γ, granulocyte macrophage colony-stimulating factor, and interleukin-12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse-to-rat cardiac xenografts, alone and in combination with 15-deoxyspergualin (DSG). Combined treatment with MC 1288 (given days -1 to 9) and DSG (given day -1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production.     

Thoracotomy in the acute phase of staphylococcal lung disease

Two cases of staphylococcal lung disease in young infants are described. In each instance a life-threatening bronchopleural fistula in the acute phase was successfully managed by thoracotomy and suture repair. Offprint requests to: A. W. Auldist     

Nodus migrans: the case of the migrating knot.

Flow-directed pulmonary artery catheters provide important information regarding intravascular volume status, cardiac function and vascular resistance. We describe an unusual complication of pulmonary artery catheterization in which a knot formed at the distal end was torn away from the catheter body and migrated from its original position in the right subclavian vein to a distal branch of the right pulmonary artery. Careful attention to insertion and withdrawal techniques could prevent this potentially serious complication.     

Epidural Epinephrine and Clonidine: Segmental Analgesia and Effects on Different Pain Modalities

Background: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues.

Methods: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 micro gram, in saline; clonidine, 8 micro gram/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined.

Results: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve.