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Biomedical subjects

A Mattiasson

Publications and source records attributed to A Mattiasson.

At least 73 records · Page 4Linked to original sources

Effects of morphine metabolites on micturition in normal, unanaesthetized rats.

1. By means of continuous cystometry in normal, unanaesthetized rats, the effects on micturition of intrathecally (i.t.) administered morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), the two main metabolites of morphine, were studied and compared with those of i.t. morphine. 2. Both M6G (0.01, 0.1, and 0.5 microgram) and M3G (5 micrograms) were found to have significant effects on micturition. Like morphine (0.1, 0.5, and 10 micrograms), M6G was able to inhibit the micturition reflex, and produce urinary retention and dribbling incontinence in a dose-dependent manner. The potency of M6G for inhibiting micturition was approximately 10 times higher than that of morphine, and the duration of its effect was longer. All effects of M6G could be reversed by naloxone. 3. M3G (5 micrograms) facilitated the micturition reflex, resulting in decreases in bladder capacity and micturition volume, and an increase in spontaneous contractile activity. Pretreatment with naloxone (10 micrograms), which by itself had no effect on micturition, enhanced the facilitatory effects of M3G. In addition, M3G tended to counteract the inhibitory effects of both morphine and M6G on micturition. M3G (5 micrograms) also produced an excitatory behavioural syndrome. 4. It is concluded that in rats, i.t. M3G has excitatory effects on micturition and behaviour, probably not mediated via opioid receptors. I.t M6G has a potent inhibitory effect on micturition mediated by stimulation of opioid receptors. It may have effects on somatosensory afferent input in lower doses than those required for effects on micturition.

Animals↗

Urodynamic effects of intravesical instillation of terodiline in healthy volunteers and in patients with detrusor hyperactivity.

The effects of intravesical instillation of terodiline on urodynamic parameters were investigated in 8 healthy volunteers (10(-4) M.) and in 34 patients with detrusor hyperactivity (10(-5) M.) of neurogenic (22) or nonneurogenic (12) origin. The volunteers were investigated with conventional medium-fill cystometry, while in the patients a modified cystometric technique with slow intermittent filling was used. The reproducibility of the procedure was verified in 17 patients. Instillation of terodiline had no effect on the normal bladders nor were any improvements found in the nonneurogenic patients. In 12 patients in the neurogenic group treated with terodiline instillation the bladder capacity increased significantly (p < 0.05) from 289 +/- 32 to 413 +/- 55 ml. Within this group 5 patients were responders. It is suggested that pathophysiological changes may explain the difference between the neurogenic and nonneurogenic groups, and that the number of responders within the neurogenic group may be increased by an optimal drug preparation and increased dosage. Intravesical administration of terodiline may offer an alternative treatment in selected patients with detrusor hyperreflexia.

Administration, Intravesical↗

Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro.

1. The present study was performed to investigate how blockade of the L-arginine/nitric oxide (NO) pathway influences the function of the lower urinary tract in vivo, as studied by cystometry in conscious rats and in vitro, in isolated muscle preparations from the rat detrusor and urethra. 2. L-NG-nitro arginine methyl ester (L-NAME), 10 and 20 mg kg-1, administered intra-arterially, decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions. D-NAME (20 mg kg-1) had no effect. No changes in the urodynamic parameters were recorded if L-NAME (20 mg kg-1) was administered in combination with L-arginine (200 mg kg-1). 3. Cystometries performed after intra-arterial administration of sodium nitroprusside (SNP) (3 mg kg-1) and 3-morpholino-sydnonimin hydrochloride (SIN-1, 2 mg kg-1) showed a decrease in bladder capacity, micturition volume and threshold pressure. SIN-1, but not SNP, induced spontaneous bladder contractions. 4. Isolated precontracted urethral preparations responded to electrical stimulation with a frequency-dependent tetrodotoxin-sensitive relaxation. L-NAME (10(-4) M), but not D-NAME, reduced the maximal relaxation to 31 +/- 8% (n = 8) of the response prior to drug administration. The inhibition induced by L-NAME was completely reversed by L-arginine (10(-3) M). SNP (10(-8)-10(-4) M), SIN-1 (10(-6)-3 x 10(-4) M) and NO (10(-5)-10(-3) M; present in acidified solution of NaNO2), caused relaxation (93-100%) of urethral preparations. L-NAME did not affect these relaxations.5. Detrusor strips contracted by carbachol or K' showed contractions in response to electrical stimulation, even when pretreated with a,p-methylene ATP and/or atropine. Small relaxations (14-41%) of detrusor strips were evoked by SNP (10-6-10-4M), SIN-1 (10-5-3 x 10-4M) and NO (10-5-10-3M). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition of L-NAME (10-6_10-4 M) or L-arginine (10-3 M).6. The present results suggest that the L-arginine/NO pathway is of functional importance for the bladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site of action of L-NAME for inducing bladder hyperactivity in the rat is the outlet region rather than the detrusor muscle.

Animals↗

General joint hypermobility and temporomandibular joint derangement in adolescents.

Joint mobility was assessed in each member of an epidemiological sample of 96 girls and 97 boys, 17 years old, and graded by means of the hypermobility score of Beighton et al. Twenty two per cent of the girls and 3% of the boys could perform five or more of the nine manoeuvres. The prevalence of symptoms and signs of internal derangement in the temporomandibular joint was higher in adolescents with hypermobility of joints (score greater than or equal to 5/9). In subjects with a high mobility score oral parafunctions (overuse) correlated more strongly with several signs and symptoms of craniomandibular disorder than in those with a low score.

Adolescent↗

Observer variation in functional examination of the temporomandibular joint.

Agreement between observers classifying TMJ sounds from data given in records of nonpatient adolescents was almost perfect in this interobserver study. Intraobserver and interobserver agreement in classifying all specific TMJ sounds at palpation and auscultation was acceptable to moderate (kappa value = 0.49 to 0.74). The agreement was considerably more reliable when classifying only one specific TMJ sound. Measurements of linear jaw opening showed small interobserver differences (coefficient of variation = 2.4 to 3.8). The significant difference found in calculating the angular mandibular opening may be the result of difficulties in maintaining maximum passive opening.

Adolescent↗

Effects of pinacidil on detrusor instability in men with bladder outlet obstruction.

In a double-blind, crossover study the effect of the potassium channel opener pinacidil (N''-cyano-N'4-pyridyl-N-1,2,2-trimethylpropylguanidine monohydrate) at 25 mg. per day was evaluated in 10 patients with detrusor instability and bladder outlet obstruction. Nine patients completed the study: in 7 pinacidil was without significant effect on urodynamic variables and in 2 detrusor instability was not found at the end of the pinacidil period. Maximum urinary flow, frequency and nocturia were unchanged during pinacidil treatment, compared to the initial test and the placebo period. There was a significant decrease in standing blood pressure but heart rate was stable throughout the study. No patient experienced distinct symptomatic improvement or side effects during pinacidil treatment. The results suggest that pinacidil at the dosage given is not effective for treatment of unstable detrusor contractions associated with bladder outflow obstruction.

Administration, Oral↗

Background factors in craniomandibular disorders: reported symptoms in adolescents with special reference to joint hypermobility and oral parafunctions.

Correlations between craniomandibular disorders (CMD) symptoms and an inherited factor (general joint hypermobility) were studied in 193 adolescents (96 girls and 97 boys). They answered a questionnaire concerning CMD symptoms, oral parafunctions, head and jaw trauma and symptoms from other joints. Joint mobility was assessed by determining the Beighton score (0-9). Twenty-eight percent of the girls and 21% of the boys could perform four or more of the manoeuvres. Twenty-two percent of the girls and 3% of the boys were extremely hypermobile (score greater than or equal to 5). Eighty-nine percent were aware of some oral parafunction and the prevalences of oral habits were about the same in the two groups. Girls reported significantly more dysfunction symptoms than boys. No indication was found that oral parafunctions generally produced CMD but a systemic factor (joint hypermobility) seemed to play an important role when the masticatory system was exposed to local forces as in oral parafunction. This may be one explanation for the predominance of females among CMD patients.

Adolescent↗

Effects of parasympathetic decentralization on some nerve-mediated functions in the feline urinary bladder.

Isolated detrusor muscle from control cats and cats parasympathetically decentralized for 3 and 10 weeks responded to electrical field stimulation by tetrodotoxin-sensitive, frequency-dependent contractions. There were no significant differences in the frequencies producing 50% response. However, the amplitude of the scopolamine-resistant contraction was distinctly lower in decentralized bladder preparations than in controls. Decentralized detrusor muscle (10 weeks) showed no increased response to alpha-adrenoceptor stimulation (phenylephrine, clonidine, noradrenaline), but the sensitivity to carbachol (at 3 and 10 weeks) was significantly decreased compared with controls. The release of [3H]noradrenaline was decreased by carbachol 10(-7) to 10(-5) M both in controls and in decentralized (10 weeks) detrusor muscle, the decrease being significantly more pronounced in the decentralized group at carbachol concentrations of 10(-7) and 10(-6) M. There were no differences between controls and decentralized bladders of muscarinic receptor concentration, but decentralization significantly reduced the affinity for the radioligand used to label the receptors. Thus, the main changes caused by parasympathetic decentralization of the feline bladder seem to be a reduced post-junctional, but an increased prejunctional response to muscarinic receptor stimulation.

Animals↗

Collagen content in the rat urinary bladder following removal of an experimental infravesical outlet obstruction.

A partial urethral obstruction was induced in female rats. After 6 weeks, detrusor weight had increased eightfold and collagen concentration had decreased to about 40% compared to controls. Due to the weight gain, the total amount of detrusor collagen had increased more than threefold. Removal of the obstruction led to a rapid decrease in detrusor weight to 70, 34 and 30%, 2, 4 and 6 weeks postobstruction, although control levels were not reached. Collagen content decreased more slowly than detrusor weight, and for the same groups was 97, 69 and 67% of the value in the obstructed detrusor. This led to a rapid increase in detrusor collagen concentration which already 4 weeks after removal of the obstruction had increased to a level that did not significantly differ from the control value. The discrepancy between decrease in detrusor weight and in collagen content after removal of the obstruction suggests that a large proportion of the collagen synthesized during the period of outlet obstruction remained. Changes in the ratio between muscle and nonmuscle tissue were limited between control, obstructed and nonobstructed bladders. This suggests that the collagen concentration following obstruction and removal of obstruction is to a large extent due to changes in collagen concentration in the interstitial connective tissue rich in collagen.

Animals↗

Nerve-mediated functions in the circular and longitudinal muscle layers of the proximal female rabbit urethra.

In the present study, nerve mediated functions in the circular and longitudinal muscle layers of the female rabbit urethra were characterized. Based on light microscopic findings, the interest was focused on the proximal third of the organ. A microsurgical dissection technique was developed, allowing separation of the two muscle layers. The following studies were carried out: functional in vitro investigations including exogenous application of drugs and electrical field stimulation, investigations of the release of 3H-noradrenaline (NA), and autoradiography for visualization of muscarinic receptors. The results can be summarized as follows: the adrenergic nervous influence, which was mediated mainly via alpha 1-adrenoceptors, dominated the contractile response of the circular layer and contributed significantly to the contraction of the longitudinal layer. A previously described fast, non-adrenergic, non-cholinergic response was found in the circular muscle layer. This response should probably be ascribed to striated muscle with a different innervation and/or structure than skeletal muscle in general. Muscarinic cholinoceptors were abundant in the outer parts of the urethral wall and decreased in density in luminal direction. A significant cholinergic contractile component was demonstrated in the longitudinal muscle. A non-adrenergic, non-cholinergic nerve-mediated relaxant response was found in both layers, although more pronounced in the circular one. Vasoactive intestinal polypeptide completely relaxed both circular and longitudinal preparations contracted by noradrenaline. A possible basis for an interaction between adrenergic and cholinergic nerve endings was demonstrated in the circular muscle layer. Stimulation of muscarinic receptors on the adrenergic nerve endings markedly reduced the release of 3H-NA. The present results support the findings in previous studies on circularly and longitudinally oriented full-thickness preparations of the female urethra and further underline the differences in structure, innervation and receptor functions between the different muscle layers of the urethral wall.

Adrenergic Fibers↗

Mutans streptococci in saliva and dental caries in children living in a high and a low fluoride area.

The aim of this study was to obtain information about the quantitative distribution of salivary mutans streptococci and the relation to dental caries in children with contrasting levels of natural water fluoride. A total of 698 schoolchildren aged 12 yr were selected from areas with high (1.2 ppm) or low (0.1 ppm) fluoride concentration in the drinking water. They were all examined for the presence and number of mutans streptococci in saliva by a specially prepared plastic strip, the "Strip mutans" method, cultivated in a selective broth. Data on the caries experience were obtained from the dental records and from bite-wing radiographs. Mutans streptococci were identified in 82% of all children with no difference between the two areas. The number of mutans streptococci was however significantly (p less than 0.05) lower among the children from the high fluoride area than those from the low fluoride area. Children with no detectable or low levels (0-10 CFU) of mutans streptococci had less caries experience than children with moderate or high levels (11- greater than 500 CFU) in both areas investigated.

Child↗

Effects of intravesical instillation of verapamil in patients with detrusor hyperactivity.

The effects of verapamil instilled intravesically were investigated in patients with detrusor hyperactivity of neurogenic and non-neurogenic origin. An intermittent, well reproducible cystometric technique with stepwise infusion of fluid was used. Verapamil produced a significant increase of the bladder capacity in patients with detrusor hyperreflexia, but not in patients with detrusor instability. The drug had no significant influence on any other cystometric parameter. It is suggested that pathophysiological differences between hyperactivity of neurogenic and non-neurogenic origin may be responsible for the difference observed. The possible diagnostic and/or therapeutic importance of the present findings remains to be established.

Administration, Intravesical↗

Contents and effects of substance P and vasoactive intestinal polypeptide in the bladder of rats with and without infravesical outflow obstruction.

The concentrations of substance P and vasoactive intestinal polypeptide (VIP) were determined in the upper, middle, and lower part of the bladder of rats with and without infravesical outflow obstruction. In the obstructed animals there was a significant increase in bladder weight and the total amounts of substance P and VIP were increased. However, the concentrations of substance P were significantly lower than in the control bladders. The concentrations of VIP, on the other hand, were significantly higher in the middle and lower parts of obstructed bladders than in the controls. In isolated strips of the normal and obstructed bladders VIP had neither contractile nor relaxant effects. The peptide had no effect on electrically induced contractions. Substance P produced concentration-dependent contractions in both normal and obstructed bladders. However, obstructed bladders were significantly less sensitive than controls. It is concluded that the bladder instability seen in rats with infravesical outflow obstruction cannot be explained only in terms of changes in the bladder content of substance P or VIP.

Animals↗

Reversibility of detrusor hypertrophy and hyperplasia after removal of infravesical outflow obstruction in the rat.

The present investigation was performed in order to study the degree of reversibility of changes of the rat detrusor secondary to infravesical outflow obstruction for various periods of time. In a previous study it was shown that outflow obstruction induced both hypertrophy and hyperplasia of the smooth muscle cells. This was determined by means of morphometry and analyses of DNA and RNA. The results of the present investigation confirm the findings of previous studies that these changes to a considerable extent are reversible after removal of the outflow obstruction. This seems to be true both in animals obstructed for a short period of time (10 days) and in animals where the hypertrophy and hyperplasia processes have diminished (six weeks).

Animals↗

Actions of terodiline, its isomers and main metabolite on isolated detrusor muscle from rabbit and man.

The effects of racemic terodiline on isolated detrusor preparations from rabbit and man were compared with those of its (+)- and (-)-isomers, and with those of its main metabolite, parahydroxy-terodiline. Concentration-response (c-r) relations for carbachol and frequency-response relations for electrical stimulation were determined before and after addition of drugs. In preparations from both rabbit and man, all the drugs tested concentration-dependently shifted the c-r curve for carbachol to the right. (+)-Terodiline was more potent than (+/-)-terodiline, whereas (-)-terodiline and parahydroxy-terodiline were less potent. All drugs in concentrations greater than 10(-6) M had a non-competitive effect, depressing the maximum of the carbachol contraction. All drugs had a depressant effect on electrically evoked contractions. (+)-Terodiline was as effective (rabbit) or more effective (man) than (+/-)-terodiline, whereas (-)-terodiline and parahydroxy-terodiline were less effective. It is concluded that (+)-terodiline contributes to a main part of the detrusor effects of the racemate, and that part of this action is anticholinergic. Parahydroxy-terodiline had a profile of action similar to that of (+/-) terodiline, but its potency was low. Since it is present in plasma in low concentrations, its contribution to the clinical effects of terodiline is probably small. (+)-Terodiline may have a therapeutic potential.

Animals↗

Different effects of neuropeptide Y on electrically induced contractions in the longitudinal and circular smooth muscle layers of the female rabbit urethra.

The effects of neuropeptide Y (NPY) on preparations of isolated longitudinal and circular smooth muscle from rabbit urethra were studied. In both types of muscle, electrically induced contractions and relaxations could be abolished by tetrodotoxin, (TTX). In the longitudinal muscle preparations the contraction was slightly reduced by prazosin, but markedly reduced by scopolamine and NPY. The NPY effect was not influenced by pretreatment with rauwolscine. Pretreatment with NPY had no effect on contractions induced by noradrenaline (NA) or carbachol and the peptide did not relax preparations contracted by these agents. In circular muscle an initial, fast response, not sensitive to prazosin or scopolamine was occasionally observed following electrical stimulation. A slow contraction component was regularly seen; this response was abolished by prazosin. Neuropeptide Y did not influence any of these responses. The preparations were concentration-dependently contracted by NA, whereas carbachol had no effect. Pretreatment with NPY did not affect contractions induced by NA, nor did the peptide relax NA-contracted preparations. In neither longitudinal nor circular muscle strips did NPY affect the electrically induced TTX sensitive relaxation of NA-contracted preparations. The results suggest that in the rabbit urethra NPY reduces contractions in the longitudinal muscle layer by selectively inhibiting the release of acetylcholine from cholinergic nerves. Neuropeptide Y did not appear to have any significant postjunctional effects nor to interfere with the release, or effects of NA or other transmitter agents. The physiological importance of the urethral effects of NPY remains to be established.

Animals↗