Urothelial synthesis of prostanoids in the ovine ureter.

The purpose of this study was to investigate the site of production (urothelium/smooth muscle) and quantitative release of prostanoids in the ureter. Quantitative analysis of prostacyclin (PGI2) was by its metabolite, 6-keto PGFalpha, thromboxane (TXB2) and prostaglandin F2alpha. Synthesis by radiometry and radioimmunoassay was performed in vitro in sheep ureter specimens before and after removal of the inner epithelial layer and after addition of indomethacin. The major prostanoids present in the ureter were PGI2 and TXB2; PGI2 was quantitatively the largest component. Removal of the thin inner epithelial layer (urothelium) reduced mostly PGI2; addition of arachidonic acid significantly augmented PGI2 only in ureters with intact urothelium but did not alter TXB2 levels. The main source of prostanoid synthesis (PGI2) of the ureter is to be found in the urothelium. The functional role of the prostanoids may be related to coordination of peristalsis.

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.

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.

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.

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.

Correlates of alcohol-related casualty in Kuwait.

This paper reports the extent to which alcohol consumption is associated with casualties in a country in which alcohol is prohibited religiously and culturally. Selective screening of particular casualty groups by blood test established qualitative evidence of alcohol use in 107 out of 1058 patients (10%) examined at a general hospital and a traumatology hospital in Kuwait. The rate of alcohol-associated casualty was significantly higher in traumatology hospital patients (15%) than in general hospital (7%), stressing the association between alcohol and trauma. Absence of differences by place of casualty disproves lay beliefs that motor vehicle casualty is the major alcohol-associated risk in Kuwait. Other casualties, particularly work and domestic injuries, should be regarded as being affected by alcohol consumption. Statistically significant high alcohol-associated casualty rates characterized Kuwaitis (14%), the unemployed/retired (20%) and coma cases (22%) suggesting that these categories may suffer from serious alcohol problems.

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.

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.

Generation and transmission of ovine ureteral contractions, with special reference to prostaglandins.

The pattern of spontaneous rhythmic contractions was studied in isolated preparations from calyx, pelvic, middle and distal parts of the sheep ureter. The frequency of contractions was highest in intrarenal specimens (13.3 +/- 0.8 contractions min-I). The regional difference in contractions is consistent with proximal dominant pacemaker cells. In isolated rings, indomethacin (10(-5) M) inhibited and finally stopped rhythmic motility. After stoppage prostaglandin PGF2 alpha (10(-6)-10(-5) M) promptly re-established contractions in a manner characteristic of each specimen, apparently according to the pre-existent dominant pacemaker (frequency and pattern). This was demonstrated in a frequency analysis which showed a highly significant correlation of pacemaker frequencies before and after indomethacin. Experiments using dual recordings from both ends of a longitudinal preparation (tandem mode) showed that co-ordinated contractile waves travelling from one end to the other could be initiated with PGF2 alpha. These results have been interpreted to indicate that prostaglandins in ureteral smooth muscle play a predominant role in co-ordinating intercellular impulse transmission for which gap junctions could be responsible. The presence of such structures, as clearly demonstrated by an ultrastructural study, lends support to this hypothesis.

New evidence for prostaglandin induced motility of the ureter.

In the search for particular ultrastructural features which could be responsible for the persistent rhythmic contractility in sheep ureteral preparations we detected a large number of extracellular electron dense granules in the lamina propria of the ureter. These structures are very similar to lipid granules previously described in the renal papilla of the rat and man. Ureteral motility is blocked by indomethacin and prostaglandins are powerful stimulators of rhythmic contractions. Tissue extracts from the ureter contain substances which exhibit smooth muscle stimulating properties as shown in bioassays. Evidence is presented which shows that the ureteral granules contain lipid material which could be the source (precursor) of smooth muscle stimulating factors, probably prostaglandins.

The effect of indomethacin on the motility of isolated sheep ureters.

The possible spasmolytic effect of indomethacin was studied on isolated sheep ureteral preparations. Ureteral ring preparations suspended in an organ bath exhibited long lasting rhythmic contractions quite similar to the in vivo situation. This spontaneous motility was unaffected by hyoscine, phenoxybenzamine, propranolol, mepyramine and methysergide. Addition of indomethacin resulted in a dose dependent reduction in amplitude and frequency of the contractions, the threshold value being 10(-8) M. Washing reestablished motility and both PGE2 and PGF2 alpha were powerful stimulators of rhythmic contractions. Our conclusion is that in vitro rhythmic activity of the ureter is dependent on endogenous PG-synthesis and the cyclooxygenase inhibitor indomethacin dose-dependently blocks this.

Motility of the human ureter, with special reference to the effect of indomethacin.

Ureteral motility was studied in isolated preparations obtained from 19 patients at surgery. Contraction was monitored in an organ bath and contraction recorded isometrically. In all but one patient rhythmic activity with a frequency of 2.0 +/- 0.3 contractions/min was recorded. In 6 patients contractions had to be elicited by stimulation with prostaglandin E2 or F2 alpha. In the remaining cases motility started spontaneously within 30 min. In patients with bilharzia nephropathy various pathological types of contraction were recorded. Motility was dose-dependently inhibited with indomethacin.

Vascular effects of glucocorticosteroids, with special reference to budesonide.

The effect of glucocorticosteroids was tested on in vitro responses of tension developed by strips of umbilical blood vessels. 1. Hydrocortisone, methylprednisolone and dexametasone in concentrations of 10(-4)-10(-3) mainly inhibited spontaneous tone. Hydrocortisone and methylprednisolone induced a biphasic response with an initial small contraction followed by a more long lasting relaxation. 2. Budesonide, a novel powerful, non-halogenated steroid only induced a long lasting contraction. 3. The relaxation with hydrocortisone was of the same magnitude as after indomethacine, therefore, this response may be due to inhibition of prostaglandin-synthesis. 4. There was no leftward shift of the dose response curve to catecholamine stimulation but rather a slightly higher maximal response. There is no clear evidence of a uptake-2 blockade in our preparation.