Biomedical subjects
O Thulesius
Publications and source records attributed to O Thulesius.
Aqueous extracts of garlic (Allium sativum) inhibit prostaglandin synthesis in the ovine ureter.
The prostaglandins (PGs) synthesized from C14-arachidonic acid by the homogenized sheep ureter were identified as being prostacyclin (PGI2), PGF2 alpha and thromboxane B2 (TXB2). The radioimmunoassay (RIA) estimation of 6-keto-PGF1 alpha, a stable metabolite of PGI2, confirms that it was the major metabolite of arachidonic acid. Aqueous extracts of fresh garlic (5, 12.5, 25 and 50 mg/ml) were shown to inhibit the synthesis of the prostanoids in a dose dependent manner. Fresh garlic extracts (1, 2.5, 5 and 10 mg/ml) also dose dependently inhibited spontaneous rhythmic contractions of the isolated ureter. Boiled garlic (5, 12.5, 25 and 50 mg/ml) had no effect on either ureteral motility or the PG synthesizing capacity of the sheep ureter.
Effect of temperature on finger artery pressure evaluated by volume clamp technique.
We examined the effect of temperature on digital arterial blood pressure obtained by continuous beat-to-beat non-invasive monitoring with a volume-clamp technique (Finapres). In 10 normal volunteers and 13 patients with symptoms of vasospasm, digital pressure and brachial artery pressure (cuff method) was simultaneously recorded in control conditions at room temperature, during body cooling, finger heating, and truncal heating. In the control condition digital systolic blood pressure was significantly higher (16.1 +/- 14.2 mmHg) than brachial systolic pressure. The augmentation of digital systolic pressure correlated inversely with finger tip temperature. Diastolic and mean arterial pressure did not differ significantly between the two methods. Body cooling augmented the systolic finger-arm gradient while truncal heating and finger heating had the opposite effect. Finger heating reduced systolic augmentation without changing the mean and diastolic blood pressure. Similar changes were also observed in the patients with vasospasm except in one case with a pronounced Raynaud syndrome where digital blood pressure was lower than brachial artery pressure. We conclude that augmentation of finger systolic pressure seems to be dependent on local vasoconstriction of A/V shunts and that finger heating may be a useful procedure to improve the reliability of Finapres readings.
[Forskolin impregnation of small caliber polytetrafluoroethylene arterial prostheses].
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Capillaroscopy with fibreoptic video microscope.
A new method of skin capillaroscopy for the evaluation of cutaneous capillaries is presented. The technique is based on a fibreoptic video microscope, using an optical surface sensor attached by a flexible fibreoptic system connected with a TV monitor. Colour or black and white hard copies as well as videotapes can be obtained for documentation. The system enables rapid investigation of skin areas of all parts of the body including mucous membranes.
[The man behind the drug. Peter Forsskål: the father of the forskolin. Linne's disciple who died hunting for unknown plants on an expedition in "Prosperous Arabia"].
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Effect of the molsidomine metabolite SIN-1 on coronary arteries and peripheral vessels of sheep with special reference to tolerance and endothelium.
In vitro experiments on rings from coronary arteries, femoral arteries, and femoral veins of sheep were performed, and cumulative concentration-relaxation responses were established for glyceryl trinitrate (GTN) and the molsidomine metabolite SIN-1. Paired preparations of control and deendothelialized coronary artery rings were used, and the vessels were precontracted with different agonists at a concentration that elicited 30% of maximal contractions (EC-30). In coronary arteries, the responses for GTN and SIN-1 on normal and deendothelialized preparations were not significantly different. In coronary arteries preincubated with 0.44 mM GTN or SIN-1 to study tolerance development, there was a significant loss of efficacy to the relaxant effect of GTN, whereas the effect SIN-1 was essentially maintained. Femoral arteries and veins were readily relaxed with GTN. and SIN-1. In veins relaxation in relation to resting tone was much more pronounced than in coronary or femoral arteries. In conclusion, the molsidomine metabolite SIN-1 is a potent coronary and venous vasodilator that does not induce tolerance.
Forskolin impregnation of small calibre PTFE grafts lowers early platelet graft sequestration and improves patency in a sheep model.
Synthetic vascular grafts have a thrombogenic surface which plays a role in graft failure. Systemic pharmacologic interventions have been used to lower platelet sequestration onto the graft surface but are associated with side effects. In this communication we describe the results of a new therapeutic principle of applying forskolin, a powerful cyclic adenosine monophosphate stimulator (cAMP) to the inner surface of PTFE vascular grafts. The grafts were evaluated with Indium-III-oxine labelled platelets and by graft patency on 3 consecutive days after implantation at 1 month and 3 months. Forskolin significantly lowered early platelet sequestration onto the treated graft surface when compared with controls. Graft potency at 1 and 3 months was also significantly higher in the forskolin treated grafts.
Coronary artery constriction is enhanced with nicotine and propranolol, particularly after endothelial damage.
Coronary artery ring preparations from sheep were used for in vitro assessment of isometric tension after stimulation with adrenaline (NA), serotonin (5-HT) and nicotine (NC). From concentration-response curves the following observations were made on potency of agonist: 5-HT greater than NC greater than NA and efficacy: 5-HT = NC greater than NA. Removal of the intima increased sensitivity to stimulation with NA and 5-HT (lower EC50 values) and augmented the maximal response. Preincubation of the vessels with NC and propranolol (PR) resulted in a leftward shift of the concentration-response curves to NA and 5-HT. Sensitivity and maximal response to NA and 5-HT were further enhanced by endothelial removal and pretreatment with NC and PR. It can be concluded that vasoconstriction to NA and 5-HT is enhanced by nicotine (smoking) and administration of beta-blockers (propranolol), particularly in coronary arteries with endothelial damage.
Endothelial mediated enhancement of noradrenaline induced vasoconstriction in normal and varicose veins.
The role of the endothelium to influence smooth muscle contraction in normal and varicose veins was investigated in vitro using saphenous vein preparations obtained at vascular surgery. Paired control and endothelium-denuded rings were tested simultaneously and contracted with noradrenaline (10(-9)-10(-4) M). Identical experiments were also performed on sheep femoral veins and arteries. Noradrenaline induced maximal tension was 30% lower in varicose compared to normal veins. In normal veins removal of endothelium significantly reduced the maximal response to noradrenaline by 40% whereas in varicose veins no significant reduction could be seen. In the sheep femoral vein removal of the endothelium also resulted in decrease of noradrenaline-induced contraction. It can be concluded that in the human saphenous vein the endothelium has a contraction facilitating effect in response to stimulation with noradrenaline. In varicose veins the endothelial-mediated enhancement of noradrenaline-induced vasoconstriction is reduced probably because of endothelial damage. This observation may be of importance in the pathogenesis of varicose veins.
Na+,K(+)-ATPase inhibition, a new mechanism for cold-induced vasoconstriction in cutaneous veins.
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Effect of Ridogrel, a thromboxane receptor blocker and synthesis inhibitor on plasma and red blood cell flow in an arterial skin flap in sheep.
This study evaluates the effect of the new combined thromboxane synthesis inhibitor and receptor blocker, ridogrel, on the circulation of arterial skin flaps in sheep. Sixteen flaps, 8 controls and 8 treated with 5 mg/kg ridogrel, were investigated using 111Indium chloride labelled plasma and 99mTc labelled red blood cells (RBCs). Dynamic imaging was performed after a bolus injection using a GE 400 AT gamma camera. For each flap quantitative analysis of plasma and RBC flow was based on time activity curves obtained from 12 regions of interest. Analysis of flow data was made immediately after flap elevation and three hours later. Both plasma and RBC flows declined after 3 hours. Treatment with ridogrel significantly prevented deterioration of perfusion by increasing plasma and RBC flow mostly in the distal, ischaemic regions of the flap where stasis was evident in the control flaps.
[The man behind the syndrome. Theodor Bilharz. He tried to explain the mystery of the worm--it is still a big global health problem].
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Increased skin flap viability after treatment with forskolin or with ridogrel, a thromboxane synthesis inhibitor and receptor blocker.
Two ventral skin flaps were raised in each of 60 rats and viability was assessed 48 h after operation. Twenty animals served as controls and immediately preoperatively 20 received an intraperitoneal injection of either 5 mg/kg body weight ridogrel, a combined thromboxane synthesis inhibitor and receptor blocker, or 4 mg/kg forskolin, a cAMP stimulator. The mean total and surviving flap areas measured 14.3 +/- 1.4 and 10.1 +/- 3.2 cm2 respectively for the control group. In the treated groups it was 16.4 +/- 1.3 cm2 and 15.6 +/- 2.6 cm2 for ridogrel and 17.8 +/- 1.1 cm2 and 15.8 +/- 4.3 cm2 for forskolin respectively. The differences between the areas of each treated group and the control group were statistically significant (p less than 0.0001). It can be concluded that both ridogrel and forskolin afford protection against skin necrosis probably because of improved conditions in the microcirculation due to reduced platelet aggregation in the vasculature of the distal part of the flap.
The effect of indomethacin and metamizole on ureteral motility and urine flow in sheep.
The objective of this study was to evaluate the effect of two non-steroid anti-inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1-2 mg/kg) and metamizole (60-120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction.
Toxicological screening: a three year experience in poisonings in Kuwait.
The results of toxicological screening of body fluids (urine, blood and gastric lavage) from pediatric patients were analyzed for the period January 1985 - December 1988. Of the 119 cases, approximately one half were positive for at least one foreign substance. In about one fifth of the cases, multiple substances were detected. The most commonly implicated drugs were those acting on the central nervous system including the barbiturates, tricyclic antidepressants, phenothiazines, benzodiazepines and carbamazepine.
Impregnation of polytetrafluoethylene (PTFE) vascular grafts with C-14-forskolin, a new concept in surface treatment of grafts.
Ten prosthetic polytetrafluoroethylene grafts (50 mm length, i.d. 4 mm) were surface treated with a 0.01% C-14-forskolin solution prior to interposition in the femoral arteries of 5 Australian sheep. The following parameters were monitored: femoral artery blood flow, platelet aggregation, C-14 blood and graft activity measured at intervals up to 120 minutes after declamping (DC). There was only a slightly decreased platelet aggregation in arterial blood samples 30 min. after DC and no changes in blood flow. After an initial peak C-14-forskolin graft activity declined rapidly during the first 30 minutes, thereafter only very slowly. C-14-forskolin blood activity also showed an initial peak and thereafter a fairly steady level 20-120 minutes after DC. These results are discussed in relation to previously very encouraging results in improving graft patency using an identical protocol of graft treatment with forskolin.
The effect of ureteral distension on peristalsis. Studies on human and sheep ureters.
Isolated sheep and human ureteral preparations (from patients with bilharzia) were subjected in-vitro to graded elongation and the effect on tension and spontaneous peristaltic frequency was assessed. Sheep specimens were obtained from three locations: the intra- and extrarenal portion of the pelvis and distal ureter. Elongation (stretch) induced an increase in spontaneous frequency only in pelvic ureteric specimens, but not in the distal ureter. Basal tension increased exponentially with stretch and most markedly in the distal sheep ureter and also in human preparations. Active tension (amplitude of phasic contractions) increased with stretch in specimens from all locations and reached a maximum at 110-115% elongation. These data suggest that acute distension of the ureter increases frequency of peristaltic waves only in the intrarenal parts of the ureter. Acute obstruction in renal colic can induce hypermotility in terms of increased frequency and force of contraction.