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Biomedical subjects

E Theodorsson

Publications and source records attributed to E Theodorsson.

At least 235 records · Page 13Linked to original sources
PubMed1989

Combined retrograde tracing and enzyme/immunohistochemistry of trigeminal ganglion cell bodies innervating tooth pulps in the rat.

Rat trigeminal neurons innervating tooth pulps were retrogradely labelled with fluorogold and analysed enzyme- and immunohistochemically for their content of substance P, calcitonin gene-related peptide, fluoride-resistant acid phosphatase, GM 1 ganglioside, carbonic anhydrase and neurofilament protein. The data showed that both small, medium-sized and large trigeminal neurons were labelled after fluorogold deposition in maxillary molar pulps, with a majority of the cells being medium-sized and large. Less than 2% of the pulpal neurons showed substance P-like immunoreactivity. Fifty-six per cent of the pulpal nerve cells were calcitonin gene-related peptide-positive. These cells were small, medium-sized and large. Only 1% of the fluorogold-labelled cells contained fluoride-resistant acid phosphatase enzyme activity. This paralleled the finding that the pulpal neurons were unstained by Griffonia simplicifolia isolectin I-B4, a plant lectin which preferentially binds to fluoride-resistant acid phosphatase-positive cells. Choleragenoid-like immunoreactivity, which identifies cells with the GM 1 ganglioside receptor, was found in 70% of the fluorogold-labelled pulpal neurons. Approximately 80% of the fluorogold-labelled cells showed RT 97-immunoreactivity. RT 97 labels neurofilament protein and is present in large light primary sensory neurons. No pulpal neurons appeared to contain carbonic anhydrase, as judged from both enzyme- and immunocytochemical observations. The findings suggest that, in the rat, trigeminal tooth pulp neurons, which according to the classical view are nociceptive, form a heterogeneous group of neurons with a minority of small cells which may contain calcitonin gene-related peptide but rarely either substance P or fluoride-resistant acid phosphatase. However, the vast majority of pulpal nerve cells appear to have sizes and cytochemical characteristics which are not generally associated with nociceptive primary sensory neurons.

Acid Phosphatase↗
PubMed1989

Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin.

The temporal course of changes in peptide expression in the dorsal root ganglia L4 and L5 and in the dorsal horn of the spinal cord has been studied in rats subjected to a sciatic nerve transection at a mid-thigh level following different survival times. Galanin-, substance P-, vasoactive intestinal polypeptide-, peptide histidine-isoleucine- and calcitonin gene-related peptide-like immunoreactivities have been studied both by immunohistochemistry and radioimmunoassay. Galanin messenger ribonucleic acid has also been studied by in situ hybridization in the dorsal root ganglia of normal and lesioned animals. In addition, a group of animals with a sciatic nerve crush was studied to compare possible differences in peptide expression after both types of lesions. The results show that the transection induces an increase in the number of cell bodies expressing galanin-like immunoreactivity in the ganglia, and that the galanin levels rise about 120-fold after three and 14 days of survival. This increase reflected increased synthesis of the peptide, since there was a rise in the galanin messenger ribonucleic acid already at 24 h post-lesion, which was maintained for at least 60 days. In the spinal cord there was an increase of staining in the midportion of the outer layers of the dorsal horn that corresponded to fibers thought to arise from cells of the dorsal root ganglia affected by the transection. Also a depletion of substance P-like and an increase in vasoactive intestinal polypeptide- and peptide histidine-isoleucine-like immunoreactivities in the dorsal root ganglia were confirmed. These changes were shown to be rapidly detectable and were paralleled by similar changes in the dorsal horn of the spinal cord. For calcitonin gene-related peptide the immunohistochemistry was inconclusive, and the radioimmunoassay showed no detectable changes. After nerve crush a transient increase in the number of galanin immunoreactive neurons was observed, as well as a decrease in the number of neurons showing substance P-like immunoreactivity. These changes were most noticeable between six and 14 days of survival. After this, peptide expression seemed to return slowly to normal, that is by day 45 post-crush only a few cells showed galanin-like, and many sensory neurons expressed substance P-like immunoreactivity. The results demonstrate that when primary sensory neurons are peripherally lesioned they respond in a complex manner, altering their normal production of peptides by increasing or decreasing their synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Plasma concentrations of calcitonin gene-related peptide increase during haemodialysis: relation to blood pressure.

The authors measured the plasma levels of calcitonin gene-related peptide (CGRP), the most potent vasodilatator known, during sequential ultrafiltration and haemodialysis in 12 patients using a radio-immunoassay method. Mean plasma levels of CGRP were 70.3 +/- 16.5 (mean +/- SE) pmol l-1 at the start of treatment, it increased to 85.3 +/- 17.6 pmol l-1 during ultrafiltration and to 114.5 +/- 25.3 pmol l-1 during dialysis. Systolic blood pressure decreased during haemodialysis. Plasma levels of CGRP were negatively correlated to systolic blood pressure before and at the end of dialysis, and changes in plasma levels of CGRP were strongly correlated to changes in systolic blood pressure. The increase in CGRP levels was not correlated to the fluid removal, toxin removal or changes in osmolality. The increase in plasma levels of CGRP observed during dialysis may be an important cause of dialysis induced vasodilatation and fall in blood pressure.

Adult↗
PubMed1989

VIP antisera inhibit the relaxatory motor responses of the feline sphincter of Oddi and gall-bladder induced by VIP or vagal nerve stimulation.

Regional administration of VIP elicited a dose-dependent relaxation of the feline sphincter of Oddi and gall-bladder. Relaxatory motor responses of these regions at efferent electrical stimulation of the vagal nerves were unmasked after atropine (resistant to propranolol but sensitive to hexamethonium). These findings in combination with the presence of a rich VIP-ergic innervation, including intrinsic VIP neurons, have made VIP a tentative post-ganglionic non-adrenergic, non-cholinergic neurotransmitter to these regions. The relaxatory motor responses elicited by VIP or vagal activation were selectively antagonized using regional administration of specific VIP antisera in support of this hypothesis.

Ampulla of Vater↗
PubMed1989

The effects of octreotide on basal and stimulated hormone levels in patients with carcinoid syndrome.

The carcinoid syndrome, a common feature of small intestinal carcinoid tumors with liver metastases, includes flushing, diarrhea, bronchoconstriction, and right heart failure. The etiology of the carcinoid syndrome is not well understood, but serotonin seems to be involved in the diarrhea, whereas tachykinins may play a role in the flush reaction. In a double blind placebo-controlled study, we studied the effect of octreotide in 20 patients with midgut carcinoid tumors and liver metastases. A sc injection of 50 micrograms octreotide caused a significant (P less than 0.001) decrease in median plasma tachykinins and serum pancreatic polypeptide, GH, and insulin for up to 4 h. Administration of octreotide (50 micrograms, twice daily, sc) caused a 26% decrease in urinary 5-hydroxyindoleacetia acid excretion, but the number of flushing attacks or bowel movements did not change significantly. A typical flush was provoked by pentagastrin, and plasma tachykinin and serotonin levels were measured. The flush reaction was graded on a 10-point visual analog scale. Octreotide (50 micrograms, sc) given 45 min before flush stimulation prevented tachykinin release completely and significantly reduced the median flushing score from 8.5 to 2. Placebo administered in the same way did not prevent tachykinin release after pentagastrin administration. Thus, octreotide prevents pentagastrin-induced flushing and the related hormonal changes in patients with the carcinoid syndrome.

Aged↗
PubMed1989

Expression of gastrointestinal endocrine tumours in culture systems.

Human endocrine tumours were studied in in vitro systems (cell suspensions and tissue cultures) and in in vivo systems (tumour transplants to the anterior eye-chamber of immunosuppressed rats). In the experimental systems the tumour cells were demonstrated to synthesize and secrete the same hormonal products as in the patient. Intraocular transplants of a gastrinoma secreted gastrin-17 into the chamber fluid. This molecule, normally not secreted in the rat, was also detected in the peripheral plasma of tumour-bearing rats. Intraocular transplants of midgut carcinoid tumours released serotonin (5-HT) at adrenoceptor stimulation, of a similar type as demonstrated in acute tumour cell suspensions. However, in tissue cultures genuine beta-adrenoceptors seemed to be modified, since pretreatment with beta-adrenoceptor antagonists or calcium deprivation did not prevent stimulated 5-HT release. Tachykinins were not liberated by adrenoceptor stimulation. In certain cultures of midgut carcinoid tumour cells, two different phenotypes developed: small rounded endocrine tumour cells with positive immunoreactions against 5-HT and tachykinins (TK), and large elongated neuron-like cells, which gradually lost 5-HT immunoreactivity, while TK immunoreactivity remained unchanged. These cultured tumour cells may produce an endogenous factor inducing transformation into a neuron-like phenotype. One candidate factor is nerve growth factor (NGF), since NGF-like immunoreactivity was demonstrated in cells of the endocrine phenotype.

Gastrointestinal Neoplasms↗
PubMed1989

Regulatory peptides as tumour markers.

Assay of regulatory peptides has an established role in the diagnosis and management of several peptide-producing tumours, including endocrine pancreatic tumours, carcinoid tumours, medullary thyroidea carcinomas, pheochromocytomas, and neuroblastomas. Proper sample handling (rapid cooling and freezing) is important since most regulatory peptides (except gastrin and pancreatic polypeptide) are labile in plasma. The immunoassay should preferably have broad specificity for the peptide family to be analysed since endocrine tumours may result in elevated concentrations of different spectra of the peptides in individual patients. From the analytical point of view, this is in contrast with the preferences of the physiologist who is usually interested in measuring the concentration of a single member of the peptide family with as high specificity as possible.

Biomarkers, Tumor↗
PubMed1989

Serotonin-producing carcinoid tumour cells in long-term culture. Studies on serotonin release and morphological features.

Tumour cells from a hepatic metastasis of a midgut carcinoid tumour were studied during 240 days of culture. A cell line could not be established, but the cells regularly formed large clusters and islets. The spontaneous release of serotonin (5-HT) and neuropeptide K-like immunoreactivity from cultures were followed. The amine and the peptide levels were unstable without evident covariation. The response to stimulation with noradrenaline and isoprenaline was studied during the culture period. The tumour cells released 5-HT selectively at stimulation with isoprenaline. This responsiveness also showed considerable variation with long periods of quiescence. Ultrastructurally the tumour cells showed a certain degree of polarization with apical microvilli and a supranuclear Golgi apparatus. When studied by confocal laser scanning the tumour cells were demonstrated to be cylindrical in shape with a cytoplasmic attachment to the matrix.

Carcinoid Tumor↗
PubMed1988

Carcinoid tumour cells in long-term culture: release of serotonin but not of tachykinins on stimulation with adrenoceptor agonists.

Tumour cells from a lymph-node metastasis of a midgut carcinoid tumour, immunoreactive for serotonin and substance P, were isolated and kept in culture for 2 months. The formation of large clusters or islets of tumour cells was paralleled by an increase in immunoreactive tachykinins (neuropeptide K and substance P) in the culture medium. The concentration of tachykinins declined subsequently despite good viability of the cells. Spontaneous release of serotonin into the culture medium was much greater than that of tachykinins, and remained stable throughout the study. These findings indicate different turnover rates and/or different storage sites for the peptides and the amine. In stimulation experiments, a dose-dependent release of serotonin, but not of tachykinins, was induced by a beta-adrenoceptor agonist (isoprenaline), while stimulation of alpha-adrenoceptors (noradrenaline) was not effective in releasing any of the substances. Pretreatment of the cultures with a beta-adrenoceptor antagonist (propranolol) or stimulations after calcium deprivation did not influence the isoprenaline-induced release of serotonin. These findings may indicate a modification of genuine beta-adrenoceptors during culture.

Adrenergic alpha-Agonists↗
PubMed1988

Release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from organs of the genitourinary tract in rats.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was detected in the rat urinary bladder, ureter and vas deferens and was depleted by systemic capsaicin desensitization. Exposure to capsaicin in vitro produced a prompt increase in CGRP-LI outflow in superfusates of these tissues, while a second application of the drug was ineffective indicating desensitization. These findings provide further evidence for a transmitter role of CGRP from peripheral endings of sensory nerves and the involvement of CGRP-LI in the specific motor response to capsaicin in the rat genitourinary tract.

Animals↗
PubMed1988

Several neuropeptides determine the visceromotor response to capsaicin in the guinea-pig isolated ileal longitudinal muscle.

Capsaicin (1 microM) produced, after an initial contraction, a depression of the field stimulation-induced contraction of the guinea-pig isolated ileal longitudinal muscle. Both effects exhibited prompt desensitization, indicating the involvement of a specific action on sensory nerves. The initial contraction was inhibited by [D-Pro4,D-Trp7,9,Phe11]SP-(4-11), a substance P (SP) antagonist, which did not affect the inhibitory component of the response. Incubation of the strips with antiCGRP (CGRP = calcitonin gene-related peptide) serum did not modify the amplitude of the capsaicin-induced contraction but inhibited the twitch depression induced by capsaicin. AntiCGRP serum blocked the effects of exogenous CGRP but not the inhibitory response induced by baclofen. These findings provide evidence that the release of several neuropeptides from sensory nerves determines the visceromotor response to capsaicin in this preparation. In particular, a CGRP-like peptide could be responsible for the inhibitory phase which follows the initial contraction which is due to release of SP and/or related peptides.

Animals↗
PubMed1988

The contribution of capsaicin-sensitive sensory nerves to xylene-induced visceral pain in conscious, freely moving rats.

1. Intravesical instillation of xylene (10-100%, dissolved in silicone oil) through a catheter implanted into the bladder of conscious, freely-moving rats produced behavioural effects (licking of lower abdomen or perineal region) suggestive of intense visceral pain, not mimicked by topical application of the irritant on the urethral outlet. 2. The xylene-induced visceral pain was prevented, to the same extent, by systemic desensitization to capsaicin (50 mg/kg s.c.) performed in either adult or newborn rats, as well as by extrinsic bladder denervation (pelvic ganglionectomy), thus indicating the involvement of primary afferents in the bladder wall. 3. Other behavioural responses induced by xylene instillation into the bladder (hind limb hyperextension, grooming) were not affected by systemic capsaicin desensitization in either adult or newborn rats, but were abolished by bladder denervation. 4. Systemic capsaicin desensitization produced an almost complete depletion of substance P-, neurokinin A-like and calcitonin gene-related peptide-like immunoreactivity in the rat urinary bladder. 5. These findings indicate that, in addition to their role in activating reflex micturition, the neuropeptides-containing capsaicin-sensitive sensory nerves of the rat bladder are involved in chemogenic visceral pain.

Aging↗
PubMed1988

Distribution of calcitonin gene-related peptide-like immunoreactivity in various rat tissues: correlation with substance P and other tachykinins and sensitivity to capsaicin.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) has been measured in various tissues of control rats and rats pretreated with systemic capsaicin, s.c. (50 mg/kg as newborns or as adults, 125 mg/kg as adults) and compared with the tissue level of substance P- and tachykinin-like immunoreactivities (SP-LI and TK-LI). The rank order of CGRP-LI concentration in various tissues was as follows: trigeminal ganglion greater than urinary bladder greater than ureter much greater than distal duodenum much greater than proximal duodenum much greater than skin (snout) greater than thymus = right atrium = vas deferens. A complete depletion of CGRP-LI following capsaicin treatment of both adult and newborn animals was observed in urinary bladder, ureter, atrium, vas deferens and skin. Capsaicin pretreatment of both adult and newborn rats reduced CGRP-LI in the duodenum by about 50%. CGRP-LI in trigeminal ganglion was reduced only in newborn animals, while it was not affected in the thymus. The CGRP-LI/SO-LI ratio varied in these tissues between 33.2 (urinary bladder) and 0.9 (proximal duodenum). A significant correlation was found between CGRP-LI and SP-LI or TK-LI in tissues where immunoreactivities were depleted by capsaicin, as well as in the urinary bladder of individual animals. The correlation between CGRP-LI with SP-LI and TK-LI upon treatment with capsaicin indicates that neurons containing SP and TK as well as CGRP, and neurons containing CGRP only, are affected in a similar manner by capsaicin.

Animals↗
PubMed1988

Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves.

The tachykinin-like immunoreactivity of the urinary bladder has been measured in various species by means of an antiserum (K12) having negligible cross-reactivity with substance P. The rank order for bladder content of tachykinin-like immunoreactivity was guinea-pig greater than mice greater than rat, similar to that found for substance P-like immunoreactivity. In all three species, both substance P- and tachykinin-like immunoreactivities were depleted by systemic capsaicin desensitization. The time course for depletion of substance P- and tachykinin-like immunoreactivities of the rat bladder following extrinsic denervation was almost superimposable. At reverse phase high pressure liquid chromatography, the major constituent of tachykinin-like immunoreactivity of the rat bladder co-eluted with neurokinin A. In vitro, the contractile response of the rat bladder to capsaicin (1 microM) was directly proportional to bladder tachykinin-like immunoreactivity while the response to field stimulation was not. In vivo, the volume threshold for reflex micturition was inversely proportional to bladder tachykinin-like immunoreactivity while amplitude of micturition contraction was not. Similar correlations were found in a previous study for substance P-like immunoreactivity. The contractile response to capsaicin or neurokinin A of the rat isolated bladder were significantly reduced by incubation with phenoxybenzamine at a concentration reported to produce a selective alkylation of neurokinin-2 receptors, while the response to substance P or KCl was unaffected. These findings indicate that multiple neurokinins co-exist in those bladder sensory nerves which are capsaicin-sensitive in adult rats. Both substance P- and tachykinin-like immunoreactivities in the rat bladder appear to be good functional markers of the sensory and "efferent" functions mediated by capsaicin-sensitive nerves, consistent with the hypothesis of a transmitter role for the corresponding peptides.

Animals↗
PubMed1988

Regional differences in the motor response to capsaicin in the guinea-pig urinary bladder: relative role of pre- and postjunctional factors related to neuropeptide-containing sensory nerves.

Capsaicin induced a contraction of isolated strips from the guinea-pig urinary bladder which was more evident in the dome than in the neck and inhibited contractions induced by field stimulation, particularly in the neck. Both responses exhibited prompt desensitization and were tetrodotoxin-resistant, suggesting a specific action on transmitter release from sensory nerve terminals. Indeed, the contractile response in the dome was prevented by a substance P antagonist while the inhibitory response in the neck was prevented by immunoblockade with anticalcitonin gene-related peptide (CGRP) serum. Substance P produced a contraction of the guinea-pig bladder, being about 5 times more potent in the dome than in the neck, while CGRP inhibited the evoked contractions, being about 8 times more potent in the neck than in the dome. Further, the maximal effect of CGRP in the neck was almost double that in the dome. Substance P- and CGRP-like immunoreactivity were detected in both the dome and the neck with no regional differences for each peptide. CGRP-like immunoreactivity was 6.3 and 7.9 times higher than substance P-like immunoreactivity in the dome and the neck, respectively. Exposure to capsaicin evoked release of both substance P- and CGRP-like immunoreactivity from the dome and the neck. Peak CGRP-like immunoreactivity released by capsaicin was 12.3 and 8 times greater than substance P-like immunoreactivity in the dome and the neck, respectively. For each peptide, no difference was found in peak release in the dome vs neck. Total substance P-like immunoreactivity released from the neck was 25% lower than that released from the dome. The ability of CGRP to stimulate accumulation of 3',5' cyclic adenosine monophosphate in membranes prepared from the bladder muscle was greater in preparations from the neck than from the dome. These findings indicate that postjunctional mechanisms (type and number of receptors for sensory neuropeptides, coupling with second messengers) are a major determinant of the type of motor responses consequent of the release of sensory neuropeptides from capsaicin-sensitive nerves.

Animals↗
PubMed1988

Cough and bronchoconstriction mediated by capsaicin-sensitive sensory neurons in the guinea-pig.

Neural pathways involved in cough and reflex bronchoconstriction and the effects of drugs on these airway reflexes have been studied in unanaesthetised guinea-pigs exposed to aerosols of citric acid (0.13-0.78 M), capsaicin (30 microM), nicotine (9.2 mM) and histamine (0.9 mM). The number of coughs was counted during the first 3 min of exposure and the time to onset of signs of dyspnea, as an indication of bronchoconstriction, was measured. Citric acid produced bronchoconstriction and dose-dependently increased the number of coughs. Capsaicin produced both cough and bronchoconstriction. Nicotine mainly produced cough and histamine bronchoconstriction. Pretreatment of adult guinea-pigs with capsaicin (50 mg kg-1 s.c.) produced a long-lasting (greater than or equal to 10 weeks) depletion of substance P- and calcitonin gene related peptide-like immunoreactivities in the sensory nerves of the larynx, tracheobronchial tree and lung. In capsaicin-treated animals, citric acid (0.39 M) and capsaicin (30 microM) caused neither cough nor bronchoconstriction. Nicotine (9.2 mM) and mechanical stimulation still produced cough, and histamine (0.9 mM) bronchoconstriction. It is concluded that in guinea-pigs both capsaicin-sensitive (probably C-fibre endings) and capsaicin-resistant (probably rapidly adapting stretch receptors) afferent neurons may be involved in cough and reflex bronchoconstriction.

Animals↗
PubMed1988

Cardiac function and cardiovascular hormone balance during hemodialysis with special reference to atrial natriuretic peptide.

Echocardiographically determined left ventricular function and cardiovascular hormone balance were assessed before and after hemodialysis in 10 patients who had been on hemodialysis for 4 months to 15 years. Plasma levels of atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), renin activity and aldosterone were determined. All patients had vector- and echocardiographic evidences of slight to moderate left ventricular hypertrophy. The body weight decreased 2.0 kg (3.3 +/- 0.5%) with dialysis. Nine out of ten patients showed a slightly reduced ejection fraction that normalized after dialysis (p less than 0.05). Left atrial and ventricular systolic dimensions were around the upper reference limit before dialysis with a decrease after dialysis (p less than 0.05 and p less than 0.02, respectively). The levels of ANP decreased with dialysis from 2-17 times to 1 to 15 times the upper reference value in nine out of the ten patients. In the whole group the decrease was 117 +/- 35% (p less than 0.005). A significant regression was obtained between percentage decrease of body weight and percentage change of ANP (r = 0.67; p less than 0.05). The plasma concentration of ADH did not change following dialysis but the mean value was significantly higher than the mean value of the reference group of the laboratory (p less than 0.05 before and p less than 0.005 after dialysis). Renin activity and aldosterone levels were low and did not change during dialysis. In conclusion, the slight left ventricular hypertrophy may partly be a response to volume overload with hyperdynamic circulation and partly to metabolically depressed myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗