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Biomedical subjects

O Thulesius

Publications and source records attributed to O Thulesius.

At least 73 records · Page 4Linked to original sources
PubMed1989

The effect of glucocorticosteroids on in vitro motility of the ureter of the sheep.

1. The effects of three glucocorticosteroids, hydrocortisone, methylprednisolone and dexamethasone, as well as two non-steroidal anti-inflammatory agents (NSAIDs) indomethacin and diclofenac sodium were tested in vitro on the spontaneously rhythmic contracting ureteral preparation of the sheep. 2. The NSAIDs and the steroids methylprednisolone (10(-7)-10(-4) M) and dexamethasone (10(-8) - 10(-4) M), dose-dependently inhibited ureteral motility. Hydrocortisone caused a cessation of spontaneous contractions only at the high concentration of 10(-4) M. 3. Pretreatment of ureteral strips with the protein synthesis inhibitor cycloheximide (10(-6) M) abolished the inhibitory action of the corticosteroids on peristalsis, consistent with the suggestion that the action of steroids on the ureter is mediated via the synthesis of the anti-phospholipase protein, lipocortin. 4. The potency of the steroids in descending order was found to be dexamethasone greater than methylprednisolone greater than hydrocortisone.

Animals↗
PubMed1988

Mast cells and histamine responses of the ureter, ultrastructural features of cell-to-cell associations and functional implications.

In this study of normal adult human and ovine ureters, a characteristic distribution of a large population of typical mast cells was described by light and electron microscopy. Pharmacological studies were used to ascribe a functional role for these cells in normal and pathological states. In the structural investigations typical mast cells with their cytoplasm packed with characteristic electron dense granules were found in close vicinity to smooth muscle cells. A close association between mast cells and a fibroblast like La-cell and non myelinated nerve fibers was noted. The prevalence of mast cells was higher in human ureters. Human and sheep ureteral ring preparations exhibited spontaneous rhythmical contractions in vitro. Addition of histamine (10(-6)-10(-5) M) induced an increase in the frequency of contractions and enhanced the basal tone particularly in human samples. It is likely that histamine under pathological conditions such as renal colic and inflammatory reactions is released from mast cells within the ureter and induces a state of forceful contractions and pain fibre stimulation.

Animals↗
PubMed1988

The effects of urine on mast cells and smooth muscle of the human ureter.

Electron microscopy was performed on normal human ureteral rings before and after incubation in human urine for 30 minutes. A large number of mast cells was detected subepithelially and in close proximity to smooth muscle fibres. Treatment with urine (346 mOsm/l) induced various degrees of degranulation in the majority of mast cells. Some membrane bound granules were found free in the surrounding connective tissue and near smooth muscle cells indicating rupture of the cell membrane. In the functional study frequency and amplitude of peristaltic contractions were studied in-vitro. Addition of urine increased frequency and amplitude of peristaltic contractions and addition of the histamine-1-blocker mepyramine (10(-6) M) partially reversed these changes. It can be concluded that in a situation with urothelial damage such as ureteral calculus, urine can penetrate subepithelially and induce degranulation of mast cells with release of mediators. This is followed by forceful peristaltic contractions which are induced by histamine and other newly formed mediators such as prostaglandins. The process is likely to occur in renal colic with impacted kidney stones.

Histamine Release↗
PubMed1988

The effect of urothelial damage on ureteric motility. An ultrastructural and functional study.

Evidence of a leaky urothelial barrier in bilharzial uropathy is presented. The ultrastructural basis of this concept is demonstrated together with its functional consequences. The study was conducted on 4 ureters obtained at surgery from patients with non-functioning kidneys due to chronic bilharzial infections. Six normal ureters from kidney donors served as controls. Light and electron microscopic studies showed a reduced thickness of the transitional epithelium together with localised disruption of intercellular junctions and infiltration of red blood cells. The functional studies involved in vitro demonstration of stable phasic peristaltic contractions which were fundamentally altered by the addition of urine. The changes in motility included increase in contractile frequency and elevation of basal tone, inducing a state of hypermotility which could be equated with ureteric spasm. These changes were partly reversible upon administration of the histamine l-blocker, mepyramine. Evidence is presented to show that these changes might be induced in vivo by histamine released from mast cells triggered by urine leaking through a damaged urothelial barrier. The functional consequences (pain, spasm) are discussed.

Epithelium↗
PubMed1988

The role of the endothelium in the control of venous tone: studies on isolated human veins.

The role of the endothelium in the vasomotor control of veins was investigated in 14 isolated ring preparations of presumably normal saphenous veins obtained from vein grafts in connection with vascular surgery. The investigations were performed with the specimens mounted for recording isometric tension in organ baths. Paired rings were used, one normal and the other de-endothelialized by gentle rubbing. The responses to noradrenaline (10(-8)-2 X 10(-5) M), acetylcholine (10(-6) M) and 120 mM KCl solution were tested. After precontraction with 10(-7) M noradrenaline, acetylcholine at 10(-6) M did not induce cholinergic relaxation, but in the majority of experiments induced a further increase in tone. Maximal contraction with noradrenaline was significantly higher in normal compared to de-endothelialized vessels. Therefore, endothelium-derived relaxation as in arteries did not occur in human saphenous veins and the existence of an endothelial-derived contracting factor in response to acetylcholine and noradrenaline is a possibility.

Biological Products↗
PubMed1988

A comparison of antibiotics consumption and bacterial resistance patterns in Kuwait and Sweden.

The total utilization of antimicrobial drugs, expressed as DDD/1000 inhibitants/day, was 19 in Kuwait and 15 in Sweden. Aminoglycosides, tetracyclines and trimethoprim/sulphonamide were used more in Kuwait than in Sweden. The utilization of cephalosporins, however, was more prevalent in Sweden than in Kuwait. Hospital use of aminoglycosides was more pronounced in Kuwait than in Sweden, whereas trimethoprim/sulphonamide was less utilized in Kuwait. The overall consumption of antimicrobial drugs expressed as DDD/500 hospital beds, was highest in one of the Swedish hospitals where, for example, the consumption of tetracyclines was 15-fold higher than that in the comparable Kuwaiti hospital. Regarding bacterial resistance patterns, the large use of aminoglycosides and ampicillin was reflected in a higher resistance frequency among the Kuwaiti isolates. Resistance frequencies for trimethoprim/sulphonamide was also relatively much higher in Kuwait than in Sweden. In this case there was, however, no simple correlation to utilization figures, which are lower for the Kuwaiti hospital than for the Swedish. Resistance to chloramphenicol was prevalent in both countries, in spite of the very limited use of this drug.

Anti-Bacterial Agents↗
PubMed1987

The effect of urine on ureteral motility.

Ureteral rings were used to study in vitro spontaneous phasic contractions, similar to the peristaltic waves in vivo. Addition of small amounts of sheep or human urine inhibited or totally blocked rhythmic contractions, and induced tonic contracture. Changes in osmolality induced by the addition of urine were analysed and electrolyte and protein catabolites determined. Similar changes in osmolality which were induced by the addition of urine were elected by adding sucrose to the organ bath. This had the opposite effect, it increased both the frequency and the amplitude of rhythmic contractions. Therefore, an increase in osmolality per se cannot be responsible for the observed changes of motility. A reduction of pH, resulted in similar changes of motility. In an in-vivo situation with a damaged urothelial barrier there is reason to believe that entrance of urine to the lamina propria and smooth muscle cells will induce profound changes of motility.

Animals↗
PubMed1987

The effect of uropathogenic bacteria on ureteral motility.

The effect of bacterial products of various strains obtained from patients with urinary tract infections was tested on peristalsis of sheep ureteral rings. In 55-70% spontaneous rhythmic contractions were inhibited by addition of small amounts of growth supernatants from Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The isolates were also tested on mesenteric artery ring preparations. In these vessels the isolates induced tonic contractions, particularly when the vessel had been depolarised and precontracted with a 40 mM KCl solution. This response is characteristic of a calcium ionophore, known to occur in some bacterial toxins. The active principle of the bacterial ureteroplegic factor (BUF) is heat sensitive and distinct from endotoxins which speed up peristalsis. It is suggested that the ureteroplegic action depends on an exotoxin with ionophoric properties.

Animals↗
PubMed1987

Ovine ureteral motility as a new assay for the cyclo-oxygenase blocking potency of non steroidal anti-inflammatory drugs.

Isolated sheep ureteral ring suspended in an organ bath exhibits rhythmic contractions which are dose-dependently inhibited by indomethacin and revived by prostaglandin E2 or F2 alpha. Seven non-steroidal anti-inflammatory drugs (NSAID) belonging to different chemical groups were tested on the isolated ureteral ring model in molar concentrations of 10(-8)-10(-4) to determine the time elapsing from application of test drug to complete inhibition of ureteral contraction ("stop-time"). The descending order of potency of the NSAID was: flurbiprofen greater than indomethacin greater than flufenamic acid greater than tolmetin greater than aspirin greater than phenylbutazone greater than isoxicam. A parallelism was observed in the plot of log concentration of NSAID and "stop-time" amongst all compounds except aspirin and isoxicam. The sheep isolated ring preparation is a simple reproducible biological model for assessment of anti-inflammatory cyclo-oxygenase inhibitory activity of compounds.

Animals↗
PubMed1987

Umbilical artery reactivity and ultrastructural changes in pregnancy-induced hypertension and other complicated pregnancies.

Abnormal pressor responses are known to occur in the maternal circulation in pregnancy-induced hypertension (PIH), but little is know of the response of the foetal circulation. The responsiveness of umbilical arteries in PIH can be studied after delivery, and this is a useful model to explore the pathophysiological mechanisms involved. In the present experiments, the in vitro response of umbilical artery rings to bradykinin and 5-hydroxytryptamine (5-HT) was tested and ultrastructural changes investigated. Umbilical arteries from 48 cords were studied. Fifteen of the mothers had PIH, five had essential hypertension pre-dating the pregnancy and five had diabetes. Twenty-three women had pregnancies uncomplicated by hypertension or serious medical or obstetric problems and these served as controls. Umbilical arteries from the severe proteinuric PIH group were significantly more responsive to 5-HT as assessed by affinity constants (P less than 0.05). The responsiveness of arteries from all other groups did not differ from the normal cases. A probable mechanism for the findings is endothelial damage as a result of pre-eclamptic disease. This was substantiated by ultrastructural evidence.

Adult↗
PubMed1987

The effect of prostaglandin synthesis inhibition on motility of the sheep ureter.

To determine the effect of prostaglandin-synthesis inhibition on ureteral motility, isolated rings of sheep ureters were suspended for recording isometric tension in organ baths filled with Krebs-Henseleit solution. The non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac sodium (10(-5) M) inhibited rhythmic ureteral motility by reducing frequency, amplitude and finally stopping contractions. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and thromboxane B2 were determined by radioimmunoassay in the bathing solution before and after addition of NSAIDs. Peak contractile activity at 100 min of suspension was associated with increased concentration of all three prostanoids and 50 min after addition of indomethacin and diclofenac sodium when rhythmic contractions stopped, concentration dropped to low levels. The concentration of prostaglandins released into the organ bath were not quantitatively related to the frequency of contractions and therefore do not seem to affect pacemaker activity within ureteral smooth muscle but rather intercellular recruitment of myo-genically active fibres. These findings indicate that prostaglandins play a role in the motor control of the ureter, and that non-steroidal anti-inflammatory drugs exert an inhibitory action.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

The effect of labetalol on contractility of human myometrial preparations.

Because of results in animal experiments which demonstrated a partial beta 2-adrenoceptor activity of labetalol on rat uterine smooth muscle the present study was conducted in human preparations. The following results were obtained: 1. Rhythmic uterine contractions with a defined steady-state amplitude and frequency were elicited spontaneously and after methylergometrine. 2. Labetalol reduced amplitude of contractions dose-dependently after 3 h of incubation. Frequency was unaffected. 3. The tocolytic effect of labetalol is apparent only at high concentrations, above those used in the treatment of hypertension. 4. Neither beta 2-specific adrenoceptor blockade with ICI 118,551 nor alpha-blockade with phentolamine changed amplitude of contraction, either alone or in combination with labetalol. 5. Labetalol has little tocolytic effect on human myometrium in vitro. This effect is unrelated to alpha- or beta-antagonism, but seems to depend on a direct smooth muscle depressant effect. In conclusion, from the present in vitro experiments using human myometrial preparations, it seems unlikely that labetalol would interfere with the normal process of labor when used for the treatment of pregnancy hypertension.

Adrenergic beta-Antagonists↗
PubMed1987

Ketanserin in intermittent claudication: effect on walking distance, blood pressure, and cardiovascular complications.

In a 7-center Scandinavian double-blind placebo-controlled study of 179 patients with intermittent claudication, the effect of the serotonin antagonist ketanserin was evaluated on walking distance, brachial and ankle blood pressure, and symptoms. For all centers together, pain-free walking distance was significantly increased after 6 months with both ketanserin (+65%; 71 patients) and placebo (+42%; 78 patients), with no significant difference. However, there was large variability among centers. Classification of "responders" (doubling of walking distance) and patients who deteriorated (decrease of walking distance or dropout for inefficacy) showed significantly more patients responding and significantly fewer patients deteriorating with ketanserin than with placebo. Systemic blood pressure was significantly decreased by ketanserin in hypertensive, but not normotensive, patients, while ankle pressure was unaffected. The incidence and nature of side effects were equal with ketanserin and placebo, but there were more side effects causing dropout in the ketanserin group. An unexpected and possibly important observation was the occurrence of six serious cardiovascular events (myocardial infarction, cerebrovascular complications, and development of rest pain) in the placebo group but none in ketanserin-treated patients. Moreover, there were four additional similar complications in the placebo run-in period. Ketanserin appears to be beneficial in a subgroup of patients with intermittent claudication. A fortuitous finding of this study is that ketanserin might possess a protective effect against thrombovascular complications in patients with intermittent claudication.

Adult↗
PubMed1986

Vasoconstrictor components in the Arabian Gulf catfish (Arius thalassinus, Ruppell) proteinaceous skin secretion.

The Arabian Gulf catfish (Arius thalassinus, Ruppell) produces toxic substances from its skin and from venom glands located near the base of the pectoral fins. Investigation of the pharmacological properties of the skin toxin have previously shown cholinergic vasoconstrictor activity in umbilical arteries. Cholinergic vasoconstriction was confirmed in sheep renal arteries. This activity was partially blocked by atropine, while most of the residual contraction was eliminated by simultaneous addition of indomethacin. Skin toxin treatment of arterial specimens caused a release of prostaglandin (PGE2, TXB2 and 6-keto-PGF1 alpha) into the organ bath. Prostaglandin release was blocked by pretreatment with indomethacin. Heat denaturation of skin toxin caused a loss of only the indomethacin-sensitive muscle contraction activity; most of the residual activity was blocked by atropine.

Animals↗
PubMed1986

The effect of calcium-blockers nicardipine, darodipine, PN-200-110 and nifedipine on insulin release from isolated rat pancreatic islets.

The effect of the calcium-blockers nicardipine, darodipine, PN-200-110 on insulin release from pancreatic islets was studied using nifedipine as a reference compound. All drugs at a concentration of 10(-6)M significantly inhibited insulin release in response to both low (5.5 mM) and high (22 mM) glucose. The present observations support previous reports that calcium blockers of the dihydropyridine series are effective inhibitors of glucose-induced insulin release.

Animals↗