Inhibitory innervation of cat sphincter of Oddi.
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1 Electrical stimulation with trains of 0.1-0.2 ms pulses of the cat isolated sphincter of Oddi inhibited the spontaneous contractile activity and lowered base-line tension considerably. A contraction usually followed the period of stimulation. 2 These inhibitory effects were prevented by tetrodotoxin 0.1-0.5 mug/ml but were not reduced by hexamethonilm, morphine, or blockade of alpha- or beta-adrenoreceptors of cholinoceptors with phenoxy-benzamine propranolol or atropine, respectively. 3 Adenosine-5'-triphosphate (ATP) and adenosine-5'-diphosphate (ADP) inhibited the spontaneous sphincter activity and caused relaxation thus mimicking the effects of the C-terminal octapeptide of cholecystokinin (C8-CCK), isoprenaline and prostaglandin E1 and E2. 4 ATP alone (greater than 100 mug/ml) or ATP (greater than 10 mug/ml) plus dipyridamole (1 mug/ml), relaxed the sphincter to the same degrees as did the field stimulation. 5 In sphincter maximally contracted by acetylcholine, the effect of stimulation was more marked than that recorded in uncontracted preparations. 6 The present findings suggest that the sphincter of Oddi receives inhibitory nerves that are neither cholinergic nor adrenergic. (+info)
Single blind, randomised controlled trial of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine stress incontinence in women.
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OBJECTIVE: To compare the effect of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment for genuine stress incontinence. DESIGN: Stratified, single blind, randomised controlled trial. SETTING: Multicentre. PARTICIPANTS: 107 women with clinically and urodynamically proved genuine stress incontinence. Mean (range) age was 49.5 (24-70) years, and mean (range) duration of symptoms 10.8 (1-45) years. INTERVENTIONS: Pelvic floor exercise (n=25) comprised 8-12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week. The electrical stimulation group (n=25) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day. The vaginal cones group (n=27) used cones for 20 minutes a day. The untreated control group (n=30) was offered the use of a continence guard. Muscle strength was measured by vaginal squeeze pressure once a month. MAIN OUTCOME MEASURES: Pad test with standardised bladder volume, and self report of severity. RESULTS: Improvement in muscle strength was significantly greater (P=0.03) after pelvic floor exercises (11.0 cm H2O (95% confidence interval 7.7 to 14.3) before v 19.2 cm H2O (15.3 to 23.1) after) than either electrical stimulation (14.8 cm H2O (10. 9 to 18.7) v 18.6 cm H2O (13.3 to 23.9)) or vaginal cones (11.8 cm H2O (8.5 to 15.1) v 15.4 cm H2O (11.1 to 19.7)). Reduction in leakage on pad test was greater in the exercise group (-30.2 g; -43. 3 to 16.9) than in the electrical stimulation group (-7.4 g; -20.9 to 6.1) and the vaginal cones group (-14.7 g; -27.6 to -1.8). On completion of the trial one participant in the control group, 14 in the pelvic floor exercise group, three in the electrical stimulation group, and two in the vaginal cones group no longer considered themselves as having a problem. CONCLUSION: Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence. (+info)
Cerebellar Purkinje cell simple spike discharge encodes movement velocity in primates during visuomotor arm tracking.
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Pathophysiological, lesion, and electrophysiological studies suggest that the cerebellar cortex is important for controlling the direction and speed of movement. The relationship of cerebellar Purkinje cell discharge to the control of arm movement parameters, however, remains unclear. The goal of this study was to examine how movement direction and speed and their interaction-velocity-modulate Purkinje cell simple spike discharge in an arm movement task in which direction and speed were independently controlled. The simple spike discharge of 154 Purkinje cells was recorded in two monkeys during the performance of two visuomotor tasks that required the animals to track targets that moved in one of eight directions and at one of four speeds. Single-parameter regression analyses revealed that a large proportion of cells had discharge modulation related to movement direction and speed. Most cells with significant directional tuning, however, were modulated at one speed, and most cells with speed-related discharge were modulated along one direction; this suggested that the patterns of simple spike discharge were not adequately described by single-parameter models. Therefore, a regression surface was fitted to the data, which showed that the discharge could be tuned to specific direction-speed combinations (preferred velocities). The overall variability in simple spike discharge was well described by the surface model, and the velocities corresponding to maximal and minimal discharge rates were distributed uniformly throughout the workspace. Simple spike discharge therefore appears to integrate information about both the direction and speed of arm movements, thereby encoding movement velocity. (+info)
Spinal cord-evoked potentials and muscle responses evoked by transcranial magnetic stimulation in 10 awake human subjects.
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Transcranial magnetic stimulation (TCMS) causes leg muscle contractions, but the neural structures in the brain that are activated by TCMS and their relationship to these leg muscle responses are not clearly understood. To elucidate this, we concomitantly recorded leg muscle responses and thoracic spinal cord-evoked potentials (SCEPs) after TCMS for the first time in 10 awake, neurologically intact human subjects. In this report we provide evidence of direct and indirect activation of corticospinal neurons after TCMS. In three subjects, SCEP threshold (T) stimulus intensities recruited both the D wave (direct activation of corticospinal neurons) and the first I wave (I1, indirect activation of corticospinal neurons). In one subject, the D, I1, and I2 waves were recruited simultaneously, and in another subject, the I1 and I2 waves were recruited simultaneously. In the remaining five subjects, only the I1 wave was recruited first. More waves were recruited as the stimulus intensity increased. The presence of D and I waves in all subjects at low stimulus intensities verified that TCMS directly and indirectly activated corticospinal neurons supplying the lower extremities. Leg muscle responses were usually contingent on the SCEP containing at least four waves (D, I1, I2, and I3). (+info)
Vasoactive intestinal peptide (VIP) is a naturally occurring 28-amino acid peptide with a wide range of biological activities. Recent reports suggest that VIP receptors are expressed on a variety of malignant tumor cells and that the receptor density is higher than for somatostatin. Our aims were to label VIP with 99mTc--a generator-produced, inexpensive radionuclide that possesses ideal characteristics for scintigraphic imaging--and to evaluate 99mTc-VIP for bioactivity and its ability to detect experimental tumors. METHODS: VIP28 was modified at the carboxy terminus by the addition of four amino acids that provided an N4 configuration for a strong chelation of 99mTc. To eliminate steric hindrance, 4-aminobutyric acid (Aba) was used as a spacer. VIP28 was labeled with 1251, which served as a control. Biological activity of the modified VIP28 agonist (TP3654) was examined in vitro using a cell-binding assay and an opossum internal anal sphincter (IAS) smooth muscle relaxivity assay. Tissue distribution studies were performed at 4 and 24 h after injection, and receptor-blocking assays were also performed in nude mice bearing human colorectal cancer LS174T. Blood clearance was examined in normal Sprague-Dawley rats. RESULTS: The yield of 99mTc-TP3654 was quantitative, and the yields of 125I-VIP and 1251-TP3654 were >90%. All in vitro data strongly suggested that the biological activity of 99mTc-TP3654 agonist was equivalent to that of VIP28. As the time after injection increased, radioactivity in all tissues decreased, except in the receptor-enriched tumor (P = 0.84) and in the lungs (P = 0.78). The tumor uptake (0.23 percentage injected dose per gram of tissue [%ID/g]) was several-fold higher than 125I-VIP (0.06 %ID/g) at 24 h after injection in the similar system. In mice treated with unlabeled VIP or TP3654, the uptake of 99mTc-TP3654 decreased in all VIP receptor-rich tissues except the kidneys. The blood clearance was biphasic; the alpha half-time was 5 min and the beta half-time was approximately 120 min. CONCLUSION: VIP28 was modified and successfully labeled with 99mTc. The results of all in vitro examinations indicated that the biological activity of TP3654 was equivalent to that of native VIP28 and tumor binding was receptor specific. (+info)
Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin.
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Uterine peristalsis, directing sustained and rapid sperm transport from the external cervical os or the cervical crypts to the isthmic part of the tube ipsilateral to the dominant follicle, changes in direction and frequency during the menstrual cycle, with lowest activity during menstruation and highest activity at mid cycle. It was therefore suggested that uterine peristalsis is under the control of the dominant follicle with the additional involvement of oxytocin. To test this hypothesis, vaginal sonography of uterine peristalsis was performed in the early, mid and late proliferative phases, respectively, of cycles of women treated with oestradiol valerate and with human menopausal gonadotrophin following pituitary downregulation, with clomiphene citrate and with intravenous oxytocin, respectively. Administration of oestradiol valerate resulted in oestradiol serum concentrations comparable with the normal cycle with a simulation of the normal frequency of peristaltic contractions. Elevated oestradiol concentrations and bolus injections of oxytocin resulted in a significant increase in the frequency of peristaltic contractions in the early and mid follicular phases, respectively. Chlomiphene tended, though insignificantly so, to suppress the frequency of peristaltic waves in the presence of elevated oestradiol concentrations. In the late follicular phase of the cycle extremely elevated oestradiol concentrations as well as the injection of oxytocin resulted only in an insignificant further increase of peristaltic frequency. In the normal cycles, as well as during extremely elevated oestradiol concentrations and following oxytocin administration, the peristaltic contractions were always confined to the subendometrial layer of the muscular wall. The results and the review of literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion. Since unphysiological stimulation with oestradiol and oxytocin did not significantly increase the frequency of uterine peristalsis in the late follicular phase of the cycle it is assumed that normal preovulatory frequency of uterine peristalsis is at a level which cannot be significantly surpassed due to phenomena of refractoriness of the system. (+info)
Adrenoreceptors of the guinea-pig urinary bladder.
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1 Adrenaline, noradrenaline and isoprenaline (5 mug/ml) did not affect the resting tone of the isolated urinary bladder of the guinea-pig. 2 The catecholamines (1-2 mug/ml) inhibited neuronally evoked contractions at various stimulation frequencies; the inhibition was maximum at 2 Hz and minimum at 50 Hz. Isoprenaline produced maximum inhibition. 3 Propranolol (0.5 mug/ml) completely blocked the catecholamine-induced inhibition at all the frequencies employed. The concentration-response curves of isoprenaline at 2, 10 and 50 Hz were characteristically shifted by propranolol (50 ng/ml). Phenoxybenzamine (0.2 mug/ml) was totally ineffective. 4 In some experiments adrenaline significantly raised the tone of the bladder exposed to propranolol; this effect could be blocked by phenoxybenzamine. 5 Acetylcholine-induced bladder contractions were inhibited by adrenaline (2 mug/ml); the inhibition was completely blocked by propranolol (0.5 mug/ml). 6 The results indicate the presence of an inhibitory beta-adrenoceptor and suggest the possibility of an excitatory alpha-adrenoceptor in guinea-pig urinary bladder. (+info)
The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea.
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1 A new in vitro preparation, the isolated lung strip of the cat, is described for investigating the direct effect of drugs on the smooth muscle of the peripheral airways of the lung. The preparation comprises a thin strip of lung parenchyma which can be mounted in a conventional organ bath for isometric tension recording. Its pharmacological responses have been characterized and compared with the isolated tracheal preparation of the cat. 2 The lung strip exhibited an intrinsic tone which was relaxed by catecholamines, aminophylline and flufenamate. It was contracted strongly by histamine, prostaglandin F2alpha, acetylcholine, compound 48/80, potassium depolarizing solution and alternating current field stimulation. In contrast, the cat trachea was unresponsive to histamine and prostaglandin F2alpha and did not exhibit an intrinsic tone. 3 (-)-Isoprenaline and (-)-adrenaline were much more potent in relaxing the lung strip than the trachea. The potency order of relaxation responses to isoprenaline, adrenaline and (+/-)-noradrenaline in the lung strip was isoprenaline greater than adrenaline greater than noradrenaline but in the trachea was isoprenaline greater than noradrenaline greater than or equal to adrenaline. 4 beta2-Adrenoceptor selective agonists salbutamol and terbutaline were more potent in the lung strip than the trachea, suggesting beta2-adrenoceptors predominated in the lung strip. Propranolol was equipotent in inhibiting isoprenaline relexations of the lung strip and trachea, whereas practolol was much less effective in inhibiting lung strip than trachea, further supporting a predominance of beta2-adrenoceptors in lung strip and beta1-adrenoceptors in trachea. 5 Strong Schultz-Dale type contractions were elicited in both lung strips and trachea by Ascaris lumbricoides antigen in actively sensitized cats. The initial phase of the contractile response of the lung strip following challenge was shown to be due to histamine release and was absent in the trachea. The delayed phase of the contraction which took several minutes to develop in both the mepyramine-treated lung strip and trachea was not due to prostaglandins E1, F2alpha or bradykinin, the probable mediator being slow reacting substance of anaphylaxis (SRS-A). 6 It is concluded that the isolated lung strip of the cat is useful as an in vitro model for investigating the effect of drugs on the smooth muscle of the peripheral airways of the lungs. (+info)