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At least 199 records · Page 11Linked to original sources

PubMed1977

Postganglionic cholinergic dysautonomia.

A 9-year-old boy presented with symptoms and signs of marked postganglionic cholinergic autonomic dysfunction manifested by bilateral internal ophthalmoplegia, impaired secretion of tears and saliva, lack of gastrointestinal motility, atony of the bladder, generalized absence of sweating, and hypertension. Clinical and pharmacological studies confirmed that the abnormalities were restricted mainly to the postganglionic cholinergic autonomic system and showed evidence of postdenervation supersensitivity to parasympathomimetic drugs. The patient was treated in the early phase of his illness by the administration of carbachol, and eventually he made a slow and partial spontaneous recovery. Histoimmunofluorescent studies on a skin biopsy specimen suggested an autoimmune origin for his disease, with IgG antibodies being produced against postganglionic cholinergic autonomic fibers.

Autoimmune Diseases↗

PubMed1982

Methacholine provocation of Prinzmetal's variant angina pectoris: a revised perspective.

We report 13 patient with unequivocal Prinzmetal's variant angina pectoris as the entire experience with this syndrome during a 7-year period in a single institution. The clinical diagnosis of this relatively uncommon disorder is emphasized. Five patients were given 10 mg of methacholine subcutaneously. Three demonstrated subsequent delayed appearance of chest pain, ECG change, and coronary vasospasm following early appearance of muscarinic effects. Two Prinzmetal patients had no provocation of variant angina following methacholine, though they did experience significantly less blood pressure fall in response to muscarinic provocation. Another 23 subjects with incompletely explained chest pain given methacholine had neither ECG change nor spasm. Methacholine provocation of variant angina need not necessarily implicated a parasympathomimetic mechanism for otherwise spontaneous episodes. Rather, provocation would appear to occur via the customary reflex adrenergic response to drug-induced hypotension. Methacholine is probably safe though unreliable as an agent to be used for spasm provocation.

Adult↗

PubMed1994

A review of electron probe X-ray microanalysis studies of salivary gland cells.

Electron probe X-ray microanalysis (EPXMA) has now been successfully applied to several salivary gland preparations. This paper briefly reviews the principles underlying this technique and the specific sample preparation procedures which permit accurate measurement of elemental concentrations in the various intracellular spaces. Findings from salivary gland studies indicate that cytoplasmic and nuclear spaces of nonstimulated acinar cells have high concentrations of K and P, and low concentrations of Mg, Ca, and S; and that mature secretory granules have high concentrations of Ca and S, and relatively low concentrations of K and P. No consistent differences have been found between the elemental concentrations of mucous and serous secretory granules. In vivo and in vitro EPXMA studies of the elemental changes associated with secretory granule maturation indicate there are at least two stages in this process: an early stage during which granule S concentration increases in parallel with mass density as condensing vacuoles mature into secretory granules, and a late stage during which granule mass density and protein content increase with no further elemental concentration changes. Findings from other in vivo and in vitro studies indicate that secretory granule membranes are permeable to Na, K, and Cl ions because the granular concentrations of these elements are altered by electrochemical gradients. Recent EPXMA results indicate that cells stimulated with parasympathomimetic agonists have decreased K and Cl concentrations, and increased Na concentrations. Furthermore, the magnitude of these changes are quantitatively consistent with changes measured using radio-isotope equilibration and other techniques. In contrast, cells stimulated with the beta-adrenergic agonist, isoproterenol, have increased concentrations of Na and Cl, but unchanged K concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Prostaglandin effects on the contractility of bovine trabecular meshwork and ciliary muscle.

The ocular hypotensive activity of prostaglandins (PGs) has previously been demonstrated in various species including man. The underlying mechanism of action of prostanoids other than PGF2 alpha remains contentious. Because the trabecular meshwork and ciliary muscle are believed to have a role in the regulation of aqueous humor outflow, the aim of this study was to identify the PG-receptor subtypes present in these tissues using receptor-selective agonists. Contractions of isolated strips of bovine trabecular meshwork and ciliary muscle were recorded isometrically in continuously perfused tissue chambers. Contractile activity of PGs was determined relative to a maximally effective concentration of carbachol (1 microM) as a standard agonist. The following prostanoids were employed: PGF2 alpha, 17-phenyl PGF2 alpha (FP-receptor agonists), sulprostone (EP3 > EP1-agonist), AH13205 (EP2-agonist), 11-deoxy PGE1 (non-selective EP-agonist), and U-46619 (TP-agonist). The thromboxane-mimetic U-46619 elicited a strong contraction of the trabecular meshwork with the highest concentration (1 microM) being almost twice as efficacious (186.6%) as the maximal carbachol concentration, whereas the effect on the ciliary muscle was small. The U-46619 induced trabecular meshwork contraction could be blocked with a potent and selective TP-receptor antagonist, 1 microM SQ29548, indicating the involvement of TP-receptors. The other PG-analogs studied had either no or a small but statistically significant effect. Thus, 17-phenyl PGF2 alpha (1 microM) weakly contracted the ciliary muscle (4.8%), sulprostone (1 microM) the trabecular meshwork (10.1%), 11-deoxy PGE1 (1 microM) and AH13205 (10 microM) elicited relaxations in both tissue precontracted with carbachol (1 microM). The relaxant effects were more pronounced in trabecular meshwork (15.6% for 11-deoxy PG1 and 21.4% for AH13205) than ciliary muscle (6.8 and 7.4% respectively). PGF2 alpha did not elicit a significant response in either tissue. Our studies suggest the existence of TP- and EP2-receptors in the bovine trabecular meshwork and potentially FP- and EP2-receptors in the ciliary muscle. In conclusion, thromboxane-mimetics and EP2-agonists have opposing activities on contractile elements in the meshwork and may modulate trabecular outflow in a functionally antagonistic manner. Prostanoid effects on ciliary muscle appear rather modest compared to parasympathomimetic drugs. It is conceivable that TP-agonists may substantially affect trabecular outflow.

Animals↗

PubMed1977

Regulation of the secretory cycles of mucous and serous cells in the human bronchial gland.

Studies of the human bronchial gland in organ culture have allowed us to elucidate some of the factors controlling the synthesis and secretion of bronchial mucus. The secretory cycles of mucous and serous cells appear to differ, the former alternately accumulating and discharging secretory material, while in the latter synthesis and discharge occur simultaneously. Parasympathomimetic agents increase the secretory rate of mucous and serous cells by stimulating discharge, but have no effect on the rate of precursor incorporation into intracellular glycoproteins. Glycoprotein synthesis inhibitors reduce the incorporation of precursors into intracellular macromolecules but do not reduce the rate of discharge of preformed glycoproteins. The rate of glycoprotein synthesis appears to be greater in mucus-secreting cells of hypertrophied glands than of normals. Ouabain reduces the incorporation of glucose and threonine, but not glucosamine, into mucous and serous cells but has no effect on the rate of discharge. In hypertrophied glands, ouabain--sensitive threonine, but not glucose, transport appears to be increased. Exposure of rats to tobacco smoke causes an increase in the size of tracheal and laryngeal glands and in the secretory rate of mucous cells. The anti-inflammatory agent, phenylmethyloxadiazole, prevents both tobacco smoke-induced effects, presumably by reducing the secretory activity of mucous cells.

Animals↗

PubMed1996

The human bronchus model in vitro. Pharmacological approach of various components involved in the functional response.

Studying the human bronchi in vitro, and therefore sheltered from the toxicity problems inherent in human experiments, makes it possible to conduct a monofactorial analysis, disregarding the perturbations engendered by reflex phenomena, hemodynamic changes, etc. Analysing the effects of mediators on tissues may be less simple that it looks, due to the multiplicity of the cell types that are present. For example, in studying the effects of bradykinin we have shown that bradykinin is a potent contractile agent of small-diameter isolated bronchi, whereas it has no significant contractile effect on larger bronchi. The bradykinin-induced contraction results from a contractile component due to stimulation of the TP receptor, and of a relaxant component due to relaxant prostanoids. The two components of the bradykinin effects are produced by stimulation of B2 receptors. In vitro stimulation of bronchi by LPS or interleukin-1 beta permits us to obtain hyperreactivity to bradykinin due to induction of thromboxane synthetase or isomerase rather than to induction of B2 receptors or cyclooxygenase. Involvement of the nervous system may persist in the in vitro bronchial model, and indeed we have shown, for example, that pentamidine, well known for its tussigenic effect, is an indirect parasympathomimetic compound. Thus, study of the isolated bronchus permits an approach to the mechanisms of action of medicinal drugs. Despite the simplification provided compared to the in vivo study, analysis of bronchoreactivity on the isolated bronchus must take into account numerous parameters which interfere with the proper effects of the substances.

Bronchi↗

PubMed1977

The production of an alternative laboratory model of the Parkinson syndrome using a new benzylimidoylurea derivative LON 954.

N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON 954) causes a reproducible rest tremor in mice, of rapid onset and short duration with no associated rigidity or akinesia and in the absence of any marked changes in body temperature or accompanying peripheral parasympathomimetic effects. This tremor can be antagonised by the dopamine receptor agonists L-Dopa, bromocriptine, nomifensine and piribedil, as well as by anticholinergic anti-Parkinson drugs having an inhibitory effect on dopamine uptake such as benapryzine and benztropine. In contrast, benzhexol, orphenadrine and amantadine had no effect. LON 954 appears to be more specific than oxotremorine for the detection of drugs having therapeutic potential in the treatment of Parkinson's disease, particularly those exerting their effect through dopaminergic systems. An antagonist (BS 100-141), which is a structural isomer of LON 954, is also described.

Animals↗

PubMed1981

Effect of bethanechol on gastric functions in primary anorexia nervosa.

We have shown previously that patients with primary anorexia nervosa (PAN) have decreased gastric emptying and acid output. The present studies were designed to explore the possibility that bethanechol, a parasympathomimetic agent, would acutely restore normal gastric function in those patients. We used a dye dilution technique to determine acid output and fractional emptying rate in 5 patients with PAN and 11 healthy controls during a basal period and following bethanechol (0.06 mg/kg, subcutaneously). Although bethanechol caused fractional emptying and acid output to increase threefold in PAN (P less than 0.05), it failed to produce stimulation of gastric emptying and acid output to levels similar to those achieved in controls. Therefore, gastric emptying and acid output were less in PAN than in controls, both basally and after bethanechol. Since bethanechol failed to completely restore acute gastric function, the defect of emptying and acid output in PAN does not appear to be caused by a deficiency of parasympathetic neurotransmitter but, instead, could reflect undetermined inhibitory influences or impaired function of the muscular and glandular cells. Following weight gain, fractional emptying rate and acid output were still slightly less in PAN patients than in controls, but the difference was statistically significant only for basal acid output.

Adolescent↗

PubMedDate not supplied

Effects of Betel chewing on the central and autonomic nervous systems.

Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work. Betel chewing also leads to habituation, addiction and withdrawal. However, the mechanisms underlying these effects remain poorly understood. Arecoline, the major alkaloid of Areca nut, has been extensively studied, and several effects of betel chewing are thought to be related to the actions of this parasympathomimetic constituent. However, betel chewing may produce complex reactions and interactions. In the presence of lime, arecoline and guvacoline in Areca nut are hydrolyzed into arecaidine and guvacine, respectively, which are strong inhibitors of GABA uptake. Piper betle flower or leaf contains aromatic phenolic compounds which have been found to stimulate the release of catecholamines in vitro. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Betel chewing produces an increase in heart rate, blood pressure, sweating and body temperature. In addition, EEG shows widespread cortical desynchronization indicating a state of arousal. In autonomic function tests, both the sympathetic skin response and RR interval variation are affected. Betel chewing also increases plasma concentrations of norepinephrine and epinephrine. These results suggest that betel chewing mainly affects the central and autonomic nervous systems. Future studies should investigate both the acute and chronic effects of betel chewing. Such studies may further elucidate the psychoactive mechanisms responsible for the undiminished popularity of betel chewing since antiquity.

Animals↗

PubMed1997

Prophylaxis and treatment of bladder dysfunction after Wertheim-Meigs operation: the positive effect of early postoperative detrusor stimulation using the cholinergic drug betanecholchloride.

The efficacy of betanecholchloride in the postoperative treatment of bladder dysfunction is controversial. We therefore performed a comparative study on the effect of this therapy for the prophylaxis of detrusor hypotonia after Wertheim-Meigs operation. Forty patients with cervical cancer FIGO stage Ib/IIa were divided into two study groups. The control group (24 patients) only received betanecholchloride if the residual urine persisted above 50 ml after the 10th postoperative day. The study group (16 patients) received 50 mg betanecholchloride three times a day from the 3rd postoperative day onward. In this group postoperative catheter treatment, and consequently hospital stay, were significantly shorter (9.6 versus 13.3 days and 15.5 versus 18.6 days). The residual urinary volume normalized faster (8.0 versus 13.0 days) and the rate of cystitis was lower (18.8 versus 25%). According to our study, a prophylactic application of the parasympathomimetic drug betanecholchloride diminishes postoperative complications associated with bladder dysfunction after Wertheim-Meigs operation.

Adult↗

PubMed1998

ATP-induced ventricular asystole and hypotension during endovascular stenting surgery.

PURPOSE: To describe four cases of endoluminal stenting surgery in which adenosine 5'-triphosphate (ATP) was used to arrest the heart for accurate placement of the stent-graft. CLINICAL FEATURES: Four patients with descending thoracic aortic aneurysm were anaesthetized for deployment of a self-expanding stent-graft. Maintenance of general anaesthesia was performed with isoflurane and nitrous oxide in three patients, and with fentanyl and propofol in another. An initial trial of 20 mg ATP was administered via a central venous catheter as rapidly as possible, and produced third degree AV block of 8 +/- 1.7 sec and 59.7 +/- 17.5 sec hypotension, mean blood pressure < 60 mmHg, in three patients. The time to onset of AV block was 15.7 +/- 6.7 sec. In these patients, deployment of the stent-graft was performed during ventricular asystole produced by 30 mg ATP, which produced 16.3 +/- 2.1 sec third and second degree AV block. In one patient anaesthetized with fentanyl and propofol, 20 mg ATP did not change AV conduction. However, after 10 mg edrophonium, 20 mg ATP produced 9 sec third degree AV block. In all cases, heart rate and PQ interval were restored to the pre-drug control level within 50 sec after the commencement of AV block. There were no clinical complications related to this procedure in any patient. CONCLUSION: ATP is a convenient and suitable agent to produce transient ventricular asystole for the precise deployment of a self-expanding stent-graft. Co-administration of a parasympathomimetic agent might potentiate the inhibitory effect of ATP on AV conduction.

Adenosine Triphosphate↗

PubMed2005

[Drug therapy of female urinary incontinence].

Drug treatment for female urinary incontinence requires a thorough knowledge of the differential diagnosis and pathophysiology of incontinence as well as of the pharmacological agents employed. Pharmacotherapy has to be tailored to suit the incontinence subtype and should be carefully balanced according to efficacy and side effects of the drug. Women with urge incontinence require treatment that relaxes or desensitizes the bladder (antimuscarinics, estrogens, alpha-blockers, beta-mimetics, botulinum toxin A, resiniferatoxin, vinpocetine), whereas patients with stress incontinence need stimulation and strengthening of the pelvic floor and external sphincter (alpha-mimetics, estrogens, duloxetine). Females with overflow incontinence need reduction of outflow resistance (baclofen, alpha-blockers, intrasphincteric botulinum toxin A) and/or improvement of bladder contractility (parasympathomimetics). If nocturia or nocturnal incontinence are the major complaints, control of diuresis is obtained by administration of the ADH analogue desmopressin. Future developments will help to further optimize the pharmacological therapy for female urinary incontinence.

Adrenergic alpha-Antagonists↗

PubMed1998

Analysis of parotid and mixed saliva in Roe deer (Capreolus capreolus L.).

In ruminants, different functions have been ascribed to the different salivary glands according to the feeding type. In this context, possible adaptations of salivary functions were investigated regarding the secretion of various proteins by different types of salivary glands. To yield uncontaminated parotid saliva in large quantities, a non-surgical method has been developed. Parotid gland secretions were collected via endoscopic placement of guide wires into each parotid duct, which were subsequently used for placement of collection catheters. Salivary flow was stimulated by intra-glandular administration of the parasympathomimetic compound pilocarpine-hydrochloride into the parotid gland. Mixed saliva (excluding parotid saliva) was collected into sterile tubes by normal outflow during the sampling of parotid saliva. The total flow volume, flow rate and the content of proteins as well as of several ions (Na+, K+, Ca2+, inorganic phosphate) of both types of saliva were measured in sheep, fallow deer and roe deer. Roe deer secreted the highest amount of total salivary proteins relative to body mass [mg/kg body mass] and the highest relative volume [ml/10 min/kg body mass], both in parotid and mixed saliva, of all ruminant species examined. Additionally, the protein profile and the tannin-binding properties of parotid and mixed saliva in roe deer were investigated. Parotid saliva bound almost twice as much tannin as mixed saliva, underlining the importance of yielding uncontaminated parotid saliva for tannin-binding studies.

Adaptation, Physiological↗

PubMed2006

Chronic paroxysmal hemicrania: from the index patient to the disease.

The first patient with chronic paroxysmal hemicrania (CPH), a 41-year-old woman, first seen in 1961, was followed until an adequate treatment was found, 12 years later. Clinically, attack frequency and duration differed widely from the general pattern of cluster headache. Ocular variables, such as intraocular pressure and corneal indentation pulse amplitudes, also differed in our case (clear symptomatic side increment during attacks) and cluster headache. Pupil reactions to directly and indirectly acting sympathicomimetic drugs were also vastly different in our case and cluster headache: no signs of Horner s syndrome in our patient, while cluster headache exhibits a "Horner-like pattern." In cluster headache, there is a relative hypohidrosis in the forehead on the symptomatic side if body temperature is increased, and a clear hyperhidrosis on direct parasympathomimetic stimulation. This was not so in our case. Indomethacin was highly effective in our case, while "cluster headache drugs," such as ergotamine/sumatriptan, were ineffective. Indomethacin was inactive in cluster headache. Accordingly, our case seemed to differ decisively from cluster headache: CPH had been discovered.

Humans↗

PubMed1989

Sympathetic nervous system during converting enzyme inhibition.

Angiotensin II can stimulate the sympathetic system and inhibit vagal (parasympathetic) outflow under experimental circumstances in animals. Blockade of angiotensin II formation by angiotensin-converting enzyme (ACE) inhibitors might therefore be expected to result in a reduction of sympathetic activity and enhanced parasympathetic activity. Whether this is so in normotensive or hypertensive humans and in human cardiac failure is unclear, since available techniques for recording activity of the sympathetic and parasympathetic systems are imperfect. Nevertheless, most evidence that comes from measurements of venous norepinephrine suggests that the ACE inhibitors have little or no effect on sympathetic activity in normotension and hypertension, although the activated sympathetic system in severe cardiac failure is probably suppressed. It appears that the ACE inhibitors have a parasympathomimetic action that may contribute to the hemodynamic effects of these drugs. Additional information using direct recordings of sympathetic traffic or measurements of norepinephrine "spillover" is needed to clarify the effects of ACE inhibitors on the sympathetic system.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1976

Electromyographic and pressure studies in the canine bladder.

The dog is unable to void until funnelling of the bladder neck occurs, even when the bladder is stressed with a large volume and with parasympathomimetic drugs. Nil or very little pressure rise occurs just prior to micturition. Well-coordinated voiding is associated with simultaneous electrical activity in either the upper urethra and bladder neck or these two areas plus the fundus, with predominance of electrical activity (frequency and amplitude) in the bladder neck in both circumstances. In cooordinate electrical activity is seen in bladder fundus, bladder neck, and upper urethra with incoordinate voiding.

Animals↗

PubMed1986

Assay of trypsin-like protease in rat submandibular saliva and gland.

Trypsin-like protease activity was high in the submandibular gland, low in the pancreas, and absent in the liver, kidney and brain of adult rats. The alpha-sympathomimetic agent, norepinephrine, induced a marked secretion of the enzyme into submandibular saliva and the remaining protease activity within the gland decreased to about 64 per cent of control levels. Six peaks of protease activity, found by isoelectric focusing in intact submandibular glands, were also detected in the saliva of norepinephrine-stimulated rats. Isoprenaline also increased the protease activity in saliva, but far less so than norepinephrine. The parasympathomimetic agent, pilocarpine, had little effect on the secretion of the enzyme into saliva.

Animals↗

PubMed1990

The effects of a liquid diet on initial and sustained, stimulated parotid salivary secretion and on parotid structure in the rat.

Adult male rats were maintained on a nutritionally adequate liquid diet, or laboratory chow and water (controls), for 7 days. They were then anaesthetized and parotid flow was recorded after isoprenaline or pilocarpine stimulation, each collected over two, timed sampling periods--an initial 5 min and a subsequent 15 min. The isoprenaline-induced flow rates in liquid diet rats were reduced to 45 and 30% of those in control rats for the first and subsequent samples respectively (p less than 0.02). After pilocarpine stimulation there were no significant differences in the first samples, but in the subsequent samples the flow rate in liquid diet rats was reduced to 54% of that in controls (p less than 0.001). The parotid gland weights were reduced by 35% in liquid diet rats compared to controls (p less than 0.05). On computerized planimetric analysis, parotids (from rats that had not been given secretagogues) had significantly smaller mean acinar areas, mean acinar profile perimeters and mean acinar transection diameters after liquid feeding (p less than 0.001). The findings support the notion that there is a functional reserve capacity available in atrophied glands to support the relatively fast flow that occurs on initial stimulation but which becomes exhausted during sustained stimulation. This exhaustion occurs more severely and more rapidly in the low-volume, protein-rich saliva elicited by sympathomimetic stimulation than in the high-volume, low-protein saliva formed in response to parasympathomimetic stimulation.

Animals↗