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Biomedical subjects

L Malmberg

Publications and source records attributed to L Malmberg.

At least 19 recordsLinked to original sources

Effects of drugs and electrical field stimulation on isolated muscle strips from rabbit pharyngoesophageal segment.

Muscle activity of isolated muscle strips from the middle pharyngeal constrictor, the inferior pharyngeal constrictor, the cricopharyngeal muscle, and the cervical esophagus of the rabbit was studied in organ baths in response to drugs and electrical field stimulation. These muscles of the pharyngoesophageal segment seem to lack an autonomic adrenergic and cholinergic innervation, as determined by responses to specific drugs. The nerve-evoked contractile responses of the two lower muscles of the segment were almost completely abolished by the curarelike drug gallamine, suggesting a somatic cholinergic nerve supply. However, in the two upper muscles, the major part of the response was resistant to gallamine, which suggests involvement of non-adrenergic, nonmuscarinic, nonnicotinic receptors in the transmission of nerve impulses in these muscles. These results suggest a differential innervation of the upper and lower pharyngeal muscles.

Animals

Winter weather conditions and myocardial infarctions.

The daily number of cases of myocardial infarctions admitted to a hospital in middle Sweden over three winter seasons 1984-87 was correlated to the weather conditions on a day-to-day basis. The study encompassed 634 days and all cases younger than 70 years, living within the catchment area, in all 382 subjects. Information on temperature, wind force, precipitation and atmospheric pressure was obtained from the Swedish Institute of Meteorology and Hydrology. A low number of myocardial infarctions was seen on Saturdays and Sundays with a mild wind chill factor and on days with moderate snowfall and high atmospheric pressure. A high number was observed for workdays, especially Mondays, as day of diagnosis. Heterogeneity of the study population and a misclassification of the time relationships between dates of diagnosis and weather changes may have caused an underestimation of the impact of weather conditions. However, weather conditions do not seem to be a major triggering factor of myocardial infarctions in Sweden.

Catchment Area, Health

Neuropeptide-containing nerve fibers in the pharynx of the rabbit.

The distribution of peptide-containing nerve fibers in the pharyngeal region of rabbits was studied by immunocytochemistry. Neuropeptide Y (NPY)-containing fibers were numerous around blood vessels and moderate in number among bundles of striated muscle fibers. A few NPY-containing fibers were seen around seromucous glands and beneath the epithelium. Nerve fibers containing vasoactive intestinal peptide (VIP) were numerous around seromucous glands and moderate in number around blood vessels, bundles of muscle, and in the subepithelial layer. A few nerve fibers containing substance P (SP) were seen around blood vessels, seromucous glands, among bundles of muscle, and in the subepithelial layer. Nerve fibers containing calcitonin gene-related peptide (CGRP) were numerous. They were distributed close to blood vessels, among bundles of muscle, in the subepithelial layer, and within the epithelium. A conspicuous finding was the occurrence of CGRP within motor end plates of striated muscle.

Animals

A prospective controlled five-year follow-up study of primiparas with gestational hypertension.

Primiparas with hypertension first recognized in pregnancy and an age- and parity-matched control group, normotensive throughout pregnancy, were monitored during 5-6 years with blood pressure recordings performed in a standardized way. At the end of the study period, 21 out of 49 women with hypertension in pregnancy had developed hypertension requiring therapy or borderline hypertension, compared with 2 women in the control group who had developed borderline hypertension. Therapy was required in 7 of the women. Factors associated with increased risk of developing hypertension were gestational week at diagnosis of gestational hypertension, 1st diastolic blood pressure during follow-up, family history, smoking, and age.

Adult

Biochemical and functional evidence for nerve sprouting in the decentralized, hypertrophied rat urinary bladder.

The preganglionic nerves of the rat urinary bladder were cut. The decentralized bladders gained markedly in weight. Both one and four weeks post-operatively, transmural nerve stimulation evoked contractile responses of the muscle strips of the decentralized bladders, that were of the same magnitude as those of the control bladders. However, four weeks post-operatively, the atropine resistant fraction of the response was decreased; consequently, the atropine sensitive (cholinergic) fraction was increased. The activity of the acetylcholine synthesizing enzyme, choline acetyltransferase, was increased at the late time of observation. The present biochemical and functional findings may suggest outgrowth of branches from the decentralized post-ganglionic cholinergic nerves.

Animals

Muscarinic receptor density in the rat urinary bladder after denervation, hypertrophy and urinary diversion.

Parasympathetic denervation of the urinary bladder results in supersensitivity to muscarinic agonists and in bladder hypertrophy. In the present study, the effects of denervation on the muscarinic receptors in the rat bladder were investigated, using a receptor binding technique with (-)3H-QNB as radioligand. The density of muscarinic receptors was increased in denervated, hypertrophied bladders but it was decreased, below that in control bladders, when the development of hypertrophy was prevented by urinary diversion. A decreased receptor density was also found in innervated bladders after urinary diversion, whereas the receptor density was unaffected by hypertrophy alone. Competition experiments with methacholine revealed no changes in the agonist binding properties of the receptors. When the present data are combined with those in previous functional studies, it seems unlikely that the muscarinic receptors in the bladder are involved in the development of supersensitivity. It is suggested that the density of muscarinic receptors in the bladder may be related to the bladder function.

Animals

Transient supersensitivity in the hypertrophied rat urinary bladder.

The presence of a paraffin bolus intravesically for 1 or 4 weeks was accompanied by an approximate three-fold increase in bladder weight. A supersensitivity to methacholine was demonstrated in these hypertrophied bladders at 1 week but not at 4 weeks. At the earlier time of observation, the contractile responses in vitro to nerve stimulation were reduced, while at the later time of observation the responses were the same as those of controls; the atropine-sensitive fraction of the response was entirely responsible for the recovery. The concentration of choline acetyltransferase, indicating cholinergic nerve density and initially reduced by about 50%, rose in course of time. It is suggested that in the beginning of the experimental period, the muscle cells of the hypertrophied bladders in situ are exposed to 'subnormal' transmitter concentration. An extension of the field of innervation of the cholinergic nerves may explain the disappearance of the supersensitivity.

Animals

Disuse as cause of supersensitivity in the rat urinary bladder.

Ureterostomia in situ was performed to reduce the nervous reflex activation of the bladders without concomitant hypertrophy. In muscle strips of these disused and non-hypertrophied bladders, supersensitivity to methacholine was demonstrated, which did not increase between 1 and 3 weeks. The supersensitivity did not increase further by combining urinary diversion with section of the preganglionic bladder nerves (decentralization). From the present results it may be concluded that in decentralized and hypertrophied bladders not only hypertrophy per se, previously studied (Ekström et al. 1985), but also loss of nerve impulse traffic (cf. urinary diversion) contribute to the development of supersensitivity.

Animals

Unilateral denervation of the rat urinary bladder and reinnervation: a predominance for ipsilateral changes.

Unilateral removal of the pelvic ganglion affected the bladder-half on the denervated side more profoundly than that on the non-denervated side. At an early stage (3-7 days) the former was heavier, had a lower choline acetyltransferase activity, developed less tension to nerve stimulation and, in course of time, became more sensitized to methacholine in vitro than the latter. At a late stage (30-60 days) the nerve-evoked contractile responses on the denervated side had increased, which was almost wholly attributed to the atropine-sensitive part of the contraction, but the recovery was not complete. On the non-denervated side the nerve-evoked responses were not significantly changed. It was calculated that in the normally innervated bladders 25-30% of the cholinergic nerves of each half were of contralateral origin. The figure was lower (18%) for the nerves mediating the atropine-resistant response.

Animals

Supersensitivity to methacholine in rat urethra following hypertrophy or disuse.

It has been possible to sensitize the rat urethra without cutting its nerves. This was achieved by hypertrophy or disuse. Hypertrophy of the urethra (2-4-fold weight increase) was caused by the presence of an intraluminal paraffin bolus. Disuse was caused by diverting the flow of urine from the lower urinary tract. When examined in vitro after an experimental period of 1 to 4 weeks the EC50 value of the parasympathomimetic drug methacholine was in both cases half of that of controls. The common cause of the development of supersensitivity in the two types of experiments is thought to be decreases in the local concentration of transmitter at the muscle cells. The present findings favour the idea of a parasympathetic motor control of the rat urethra.

Animals

On a cholinergic motor innervation of the rat urethra.

Choline acetyltransferase activity was demonstrated in the proximal part of the male rat urethra, indicating a cholinergic innervation of this tissue. The cholinergic nerve fibres emanated evidently from the pelvic nerves, since bilateral removal of the pelvic ganglion caused a major fall in the activity of this enzyme. The muscle activity of the circular layer of the proximal urethra was recorded in vitro. The basal activity of this segment was low. The parasympathomimetics acetylcholine and methacholine, evoked rapid and marked contractile responses; the maximal responses to these drugs were 36 and 44%, respectively, of that to potassium. The corresponding figures for phenylephrine and noradrenaline were found to be 79 and 88%, respectively. The responses evoked by the parasympathomimetics were unaffected by the ganglion blocker hexamethonium, the alpha-adrenoceptor blocker dihydroergotamine and the beta-adrenoceptor blocker propranolol. Atropine, however, abolished the responses completely. Following degeneration of adrenergic or cholinergic nerves of the urethra the parasympathomimetics still evoked contractions. Taken together these findings indicate that the parasympathomimetics exert their contractile effect through a direct action on muscarinic receptors. Parasympathectomy but not sympathectomy (caused by 6-hydroxydopamine treatment) gave rise to a supersensitivity to methacholine, as judged by a leftward shift of the dose-response curve for this drug, the ED50-value being ten times less than that of the controls. The observations seem to suggest that the proximal urethra normally is under the influence of cholinergic activity beside that of adrenergic activity previously demonstrated.

Animals

Force development in muscle strips of the disused and nondistended rat urinary bladder.

In rats the flow of urine was diverted from the bladder over a period of 7-10 days. Active length-tension curves of muscle strips of such disused bladders did not differ from those of controls, provided lengths were related to optimum length for force development. When, however, lengths were related to length in situ the active length-tension curves were shifted to the left. The muscle strips of the disused bladders showed a higher degree of stiffness than those of controls. The present findings are related to previous ones made on disused but distended bladders showing changes in the opposite direction. Taken together they demonstrate the importance of filling and periodic emptying for the preservation of normal length-tension relations in the bladder.

Animals

Functional evidence for sprouting or decentralized parasympathetic neurons in rat urinary bladder.

The pelvic nerve, carrying parasympathetic nerve fibres, distributes bilaterally in the rat urinary bladder. Preganglionic parasympathetic denervation (decentralization) on one side and postganglionic parasympathetic denervation on the other are followed by an initial decrease in acetylcholine forming capacity and in number of acetylcholinesterase positive nerves in the bladder. However, within a few weeks a marked recovery in acetylcholine synthesis and in number of nerves, based on collateral sprouting, occurs. In this study muscle strips of the rat urinary bladder exposed to the combined surgical procedure was studied. The strips were taken from "denervated" and "decentralized" halves of the bladder. Their contractile responses to methacholine and transmural electrical field stimulation were isometrically recorded in vitro. A supersensitivity to methacholine was found to have developed, of about the same degree, in the two halves 1 week postoperatively. In the denervated halves 4 weeks postoperatively, the supersensitivity was even more marked, whereas in the decentralized halves it tended to be less than after 1 week. The responses of denervated halves to electrical stimulation were reduced 1 week postoperatively. This was also the case for decentralized halves, although the reduction was not large enough to be significant. When examined 4 weeks postoperatively the responses, in particular in denervated halves, were enlarged compared to those 1 week postoperatively. The atropine-sensitive portion of the responses increased with time. Increases in contractile responses to electrical stimulation accompanied by a tendency to desensitization to methacholine are taken as functional evidence for outgrowth of decentralized parasympathetic neurones in the decentralized halves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hyperplasia and hypertrophia in the denervated and distended rat urinary bladder.

The parasympathetically denervated and distended rat urinary bladder was found to have increased fourfold in weight when examined 3 weeks postoperatively. Both in muscularis and mucosa of such a bladder the synthesis of proteins, RNA and DNA was increased severalfold. An increase in the polyamines putrescine, spermidine and spermine was also found; these polyamines are usually linked to protein synthesis. The results suggest that the cells of the two layers increase both in size and number. Hyperplasia was, in a previous study, suggested as a possible explanation for a right-ward shift of the active length-tension curve of muscle strips in the denervated rat urinary bladder.

Animals

Development of supersensitivity to methacholine in the rat detrusor following either parasympathetic denervation or decentralization.

The male rat urinary bladder belongs to those few structures where both the post- and preganglionic parasympathetic nerves are accessible for severance. In the present study the sensitivity to the parasympathomimetic drug methacholine of muscle strips of either denervated or decentralized bladders was examined in vitro. One week postoperatively denervated and decentralized bladders were sensitized to the same degree, the ED50 values being 4 times less than ED50 of unoperated control bladders. In contrast to the decentralized bladders the supersensitivity in the denervated ones was found to have increased further when tested four weeks postoperatively, the ED50 value being about 20 times less than that of controls. The present findings are in agreement with Cannon's "law of denervation". The results are discussed in relation to possible mechanisms behind the phenomenon of supersensitivity.

Animals

Peripheral vasodilatation in the treatment of hypertension. Prazosin compared with hydralazine in patients not responding to beta-receptor blockade.

Prazosin was compared with hydralazine in 39 patients (mean age 49 years), who were already on beta-blockade for arterial hypertension. They all had a resting DBP greater than 100 mm Hg on propranolol 80 mg b i d. They were randomly allocated to prazosin or hydralazine treatment. Blood pressure was measured after 4, 8 and 12 weeks. We noted a significant fall in blood pressure in both groups, in most cases to normotensive levels. Side-effects and other variables of interest are discussed. Together with beta blockade, i e propranolol, both prazosin and hydralazine give good blood-pressure control and no important differences could be found.

Adult