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Biomedical subjects

E Theodorsson

Publications and source records attributed to E Theodorsson.

At least 181 records · Page 10Linked to original sources

A new assay for beta-thromboglobulin in urine.

Measurements of beta-thromboglobulin (beta TG) excretion in urine may be of value for "field" studies and due to problems with sampling artifacts for beta TG in plasma. Previous studies have used a radioimmunoassay designed for plasma without characterizing the "beta TG" immunoreactivity in urine. We describe modifications of the assay which increase its sensitivity and a sample work-up procedure using Sephadex G-25M columns separating high molecular weight (HMW) components (presumably intact beta TG) from low molecular weight (LMW) immunoreactivity (i.e. beta TG fragments and/or non-specific interferences). The sensitivity of the assay (with 2.5 ml sample) is less than 12 pg/ml HMW beta TG. Inter- and intraassay coefficients of variation were 7-10%. Only 33 (range 5-75)% of beta TG immunoreactivity in urine represented HMW beta TG. LMW immunoreactivity may be related to salt and other non-specific influences in the sample. Recoveries of beta TG were quite variable (9-100%) in unextracted urines, but high and reproducible (80 +/- 2%) in the HMW fraction. Thus, nonspecific interferences with beta TG measurements in certain urines are overcome by the separation step. Using Sephadex fractionation beta TG immunoreactivities in night urines (n = 15) were: 20 +/- 3 pg/ml in the HMW fraction, 70 +/- 8 pg/ml in the LMW fraction, and 85 +/- 10 pg/ml by direct assay. HMW beta TG increased in daytime samples (to 30 +/- 5 pg/ml; p less than 0.01), but no diurnal variation was seen in the LMW fraction or with the direct assay. Thus, selective analysis of HMW beta TG in urine circumvents problems with nonspecific immunoreactivity and apparent interferences with measurements of intact beta TG. The present more selective assay for HMW immunoreactivity increases the possibility of detecting physiological changes in beta TG release in vivo by urinary measurements.

Chromatography, Gel↗

Plasma concentrations of calcitonin gene-related peptide in fluid overload.

To investigate the hypothesis that calcitonin gene-related peptide (CGRP), a potent vasodilator, is an important physiological defence against fluid overload, plasma CGRP concentrations were measured in various degrees of fluid overload in 26 haemodialysis patients, for whom diuresis, mediated by atrial natriuretic peptide (ANP), is not a possible defence mechanism. Plasma CGRP concentrations were positively correlated with the degree of fluid excess (r = 0.815, p = 0.0001) and were significantly higher in 5 patients with severe fluid overload than in those less severely affected (143 [SE 14] vs 52 [11] pmol/l; p less than 0.001). CGRP may be an effective defence against complications of fluid overload since it can increase capitance by vasodilatation.

Atrial Natriuretic Factor↗

Neuroimmunomodulatory effects of acupuncture in mice.

The purpose of this study was to assess the effect of acupuncture on the immunological response. The induction of anti-sheep red blood cells (SRBC) plaque-forming cells (PFC) was used as a measurement of the immune response to treatment. In normal non-immunized mice, enhancement of PFC was seen after a single acupuncture treatment when spleen cells from stimulated mice were cultured with SRBC in vitro. After 3 acupuncture treatments, spleen cells from mice did not show PFC enhancement after treatment with anti-Thy-1.2 antibody and complement, nor after the removal of non-adherent cells. Serum obtained from mice 1 h after acupuncture stimulation enhanced the PFC of normal spleen cells in vitro, but the enhancement was abolished by the addition of propranolol. These results suggest that acupuncture, by activation of the autonomic nervous system, modulates the immune response.

Acupuncture Therapy↗

Aspects on the role of tachykinins and vasoactive intestinal polypeptide in control of secretion, motility and blood flow in the gut.

Both intrinsic and extrinsic neurons of the gut respond to mechanical and chemical stimuli by the release of neurotransmitters. We summarize here some of our recent work on the role of vasoactive intestinal polypeptide (VIP), substance P (SP) and neurokinin A (NKA) in the secretory, motor and vascular effects of hydrochloric acid stimulation in the isolated rat duodenal loop and electrical nerve stimulation and mechanical stimulation of the cat colon. Isolated duodenal loops of conscious rats were perfused with isotonic saline, and challenged at hourly intervals with brief exposures to increasing concentrations of HCL. The concentrations of bicarbonate and prostaglandin E2 (PGE2) released from the duodenal mucosa were significantly augmented already by pH 5.0 whereas VIP was significantly augmented at pH 3.0 and the tachykinins SP and NKA at pH 2.0. Continuous electric stimulation of the pelvic nerve in cats at 4 Hz during 1 s with 10 s rest produced a marked release of NKA-LI and SP-LI from the colon to blood. Reflex activation of the pelvic nervae by mechanical stimulation of the anus or rectal distension produced a less pronounced release of NKA-LI and SP-LI from the colon to blood. There was a simultaneous colonic contraction and vasodilation during each nerve stimulation. Close intraarterial infusions of NKA, neurokinin B, SP, neuropeptide K (NPK), eledoisin and physalemin at doses of 0.1-100 pmol/min induced dose-dependent proximal and distal colonic contractions and vasodilation, NKA being the most potent. The effects of the tachykinins were reduced after tetrodotoxin and atropine, but unchanged after treatment with hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Further studies on galanin-, substance P-, and CGRP-like immunoreactivities in primary sensory neurons and spinal cord: effects of dorsal rhizotomies and sciatic nerve lesions.

The peptides galanin (GAL), substance P (SP), and calcitonin gene-related peptide (CGRP) were analyzed with immunohistochemistry and radioimmunoassay in the spinal cord, dorsal root ganglia, dorsal roots, and sciatic nerve of normal rats and rats subjected to several experimental procedures, including ligation, crush, and/or sectioning of nerves. The results show that peripheral nerve transection induces a dramatic increase in GAL content both in dorsal roots and sciatic nerve, demonstrating that this lesion causes an increased out-transport of the newly synthesized peptide both into the central and peripheral branches of the primary sensory neurons. In contrast evidence was obtained for decreased out-transport of SP and CGRP. The functional significance of these findings remains to be analyzed.

Animals↗

Occurrence, release, and effects of multiple tachykinins in cat colonic tissues and nerves.

Neurokinin A (NKA)-immunoreactivities and substance P (SP)-immunoreactivities were found in picomolar amounts in colonic tissues and almost an order of magnitude higher amounts in vagal, pelvic, splanchnic, and lumbar colonic nerves of the cat. Continuous electric stimulation of the pelvic nerve at 4 Hz or intermittent electric burst stimulation of the pelvic nerve at 40 Hz during 1 second with 10-second rest periods produced a marked release of NKA-like immunoreactivity (NKA-LI) and SP-LI from the colon to blood (P less than 0.001). Reflex activation of the pelvic nerve by mechanical stimulation of the anus or rectal distension produced a less pronounced release of NKA-LI and SP-LI from the colon to blood (P less than 0.01). There was a simultaneous colonic contraction and vasodilation during each nerve stimulation. Reverse-phase high performance liquid chromatography showed presence of NKA, NKA oxide, NKA (3-10)/NKA (4-10), and neuropeptide K (NPK) in colonic tissues and release of all these molecular forms except NPK on nerve stimulation. Substance P and SP oxide were present both in colonic tissue extracts and in released material. Close intraarterial infusions of NKA, neurokinin B, SP, NPK, eledoisin, and physalaemin at doses of 0.1-100 pmol/min induced dose-dependent contractions of the proximal and distal colon (P less than 0.001) and vasodilatation (P less than 0.001), NKA being the most potent. The effects of the tachykinins were reduced after tetrodotoxin (P less than 0.05) and atropine (P less than 0.05) but unchanged after treatment with hexamethonium. Our findings indicate that tachykinins are released from the pelvic nerve to induce a nonadrenergic noncholinergic contraction and vasodilatation of the colon in the cat.

Animals↗

Concentrations of neuropeptides substance P, neurokinin A, calcitonin gene-related peptide, neuropeptide Y and vasoactive intestinal polypeptide in synovial fluid of the human temporomandibular joint. A correlation with symptoms, signs and arthroscopic findings.

Arthroscopy was performed on 18 patients (19 joints) with temporomandibular joint arthropathy. Arthroscopic investigation revealed that 12 patients had disk derangement, including 3 patients with rheumatoid arthritis. Six patients had osteoarthrosis, including one patient with rheumatoid arthritis. Synovial fluid content of substance P-like immunoreactivity (SP-LI), neurokinin A (NKA-LI), calcitonin gene-related peptide (CGRP-LI), neuropeptide Y (NPY-LI) and vasoactive intestinal polypeptide (VIP-LI) were analysed using radioimmunoassay technique. All peptides analysed were found, although in various concentrations, in the different joints. There were no significant differences in concentrations of the peptides in the synovial fluid between patients in the various groups. No significant correlation was found between clinical symptoms and signs, arthroscopic findings, or use of analgesic/anti-inflammatory medication versus concentrations of peptides in the synovial fluid. In comparison with earlier findings in the knee joint significantly higher concentrations of SP-LI, CGRP-LI and NPY-LI were found in the TMJ.

Adult↗

The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells.

The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT from tumour cells. The DNA contents of cultures were not affected by SMS (10(-8) M or 10(-10) M) treatment for 4 or 14 days. When tumour cell cultures were challenged with isoprenaline (IP) (10(-6) M) no reduction of the IP induced release of 5-HT could be detected after pretreatment of tumour cell cultures with SMS (10(-8) M) for 1 h, 4 h or 4 days. These studies provide evidence for a direct action of the somatostatin analogue on midgut carcinoid tumour cells, reducing both synthesis and secretion of hormones from tumour cells. This effect appears not to be related to inhibition of tumour cell growth. The inhibition of 5-HT secretion from tumour cells by SMS seems to operate via a second messenger system different from the one mediating the beta-adrenoceptor stimulated release of 5-HT.

Aged↗

Plasma chromogranin A + B, neuropeptide Y and catecholamines in pheochromocytoma patients.

Plasma levels of chromogranin A + B, neuropeptide Y and catecholamines were analysed before, during and after surgery in seven patients with pheochromocytoma. The aim of the study was to determine the diagnostic sensitivity of these plasma amines and peptides, and to investigate their peroperative fluctuations. Chromogranin A + B in plasma was increased preoperatively in all patients, showed no significant increase during surgery, and normalized postoperatively. Neuropeptide Y, which alone can induce hypertension, was present in high levels in plasma from three patients preoperatively, increased further in four patients during surgery, and was postoperatively low in all patients. Fractionated plasma catecholamines were increased in five patients before surgery, increased in all patients during tumour dissection, and normalized postoperatively. It may be concluded that plasma chromogranin A + B exhibited as high a sensitivity for pheochromocytoma as fractionated urinary catecholamines in the patients studied.

Adrenal Gland Neoplasms↗

Enzyme immunoassay for tachykinin-like immunoreactivity in the guinea pig spinal cord.

A solid-phase enzyme immunoassay for quantitation of tachykinin-like immunoreactivity (TK-LI) is presented. Because the antiserum K-12 recognizes various tachykinins, such as neurokinin A (100%), kassinin (103%), eledoisin (51%), neurokinin B (18%), physalaemin (0.7%), and substance P (0.7%), the immunoreactivity detected in this enzyme immunoassay has been termed TK-LI. The assay was performed on 96-well microtiter plates coated with a mouse monoclonal second antibody. After preincubation of soluble neurokinin A or samples and K-12 antiserum for 3 h at room temperature, acetylcholinesterase-labelled neurokinin A was allowed to react overnight at 4 degrees C. Samples were finally incubated with Ellman's reagent for 2 h and the absorbance was measured at 414 nm. The threshold for detection of TK-LI was 2 fmol/well. TK-LI release from guinea pig dorsal spinal cord slices was evoked by capsaicin or high K+ medium. The capsaicin-evoked TK-LI release was increased in the presence of thiorphan, but not in that of captopril.

Acetylcholinesterase↗

Plasma levels of atrial natriuretic peptide at rest and during exercise in heart failure--influence of cardiac rhythm and haemodynamics.

The relationship between plasma levels of immunoreactive atrial natriuretic peptide (ir-ANP), arginine vasopressin (AVP), cardiac rhythm and different haemodynamic variables were studied at rest and during exercise in 16 patients with heart failure undergoing heart catheterization for clinically indicated reasons. Even though there was no significant relationship between pulmonary capillary wedge pressure (PCW) and ir-ANP at rest (r = 0.39; P = 0.14) changes in these variables with exercise correlated well (r = 0.71; P = 0.002). Change in right atrial mean pressure, heart rate, mean arterial blood pressure or cardiac index did not significantly influence change in plasma levels of ir-ANP. The correlation between PCW and AVP at rest (r = 0.92; P less than 0.001) disappeared during exercise. Calculated ir-ANP/PCW ratios decreased slightly during exercise, but were not influenced by initial atrial pressures or atrial fibrillation. These observations provide evidence for a similar responsiveness of ANP in patients with sinus rhythm and atrial fibrillation. The ability of rapid change in ANP plasma levels during exercise was preserved and proportional to changes in PCW over a wide pressure range in the studied patient group. This finding indicates that left atrium distension rather than right atrium distension is the major determinant for the release of ANP in patients with congestive heart failure. The observed rapid responsiveness of ANP to change in left atrial pressure may allow the hormone to modulate haemodynamic response during short periods of exercise.

Adult↗

Renal and systemic plasma immunoreactive neuropeptide Y and calcitonin gene-related peptide responses to mental stress and adrenaline in humans.

Arterial plasma levels and renal venous overflows of immunoreactive neuropeptide Y (NPY-LI) and calcitonin gene-related peptide (CGRP-LI) were studied during mental stress (a modified version of Stroop's colour word conflict test--CWT) and during i.v. infusions of step-wisely increasing doses of adrenaline (ADR) in 12 healthy male volunteers. At rest, mean arterial plasma levels of NPY-LI and CGRP-LI were 27 +/- 2 pmol l-1 and 61 +/- 9 pmol l-1, respectively. No renal venoarterial concentration difference could be demonstrated for either peptide at rest. Although CWT caused a three-fold increase in the simultaneously measured renal venous overflow of noradrenaline, indicating markedly increased renal sympathetic nerve activity, the arterial levels of NPY-LI were unchanged and the net renal overflow of NPY-LI was only slightly (not significant) and transiently increased. CWT also failed to influence CGRP-LI levels in arterial plasma or CGRP overflow from the kidney. During ADR infusions, which increased arterial plasma ADR from 0.25 +/- 0.06 to 6.43 +/- 0.27 nmol l-1, NPY-LI levels were unaffected but CGRP-LI levels in arterial plasma were elevated (P less than 0.001 by ANOVA). No net renal overflow of CGRP-LI could, however, be demonstrated. These findings suggest that CWT is not powerful enough a stimulus to significantly enhance systemic or renal overflows of NPY-LI even though marked renal sympathetic activation occurs. During ADR infusions plasma CGRP-LI levels increased but renal veno-arterial differences of CGRP-LI were unaltered, indicating that CGRP-LI may be released from sites other than the kidney by ADR.

Adult↗

Neuropeptides in temporomandibular joints with rheumatoid arthritis: a clinical study.

There is evidence that neuropeptides play a role in the development of arthritis. Synovial fluid from arthritic temporomandibular joints in patients with rheumatoid arthritis was therefore investigated for presence of the neuropeptides calcitonin gene-related peptide, substance P, neurokinin A and neuropeptide Y. All four peptides were found in the synovial fluid above plasma level, but calcitonin gene-related peptide showed the highest concentration and substance P the lowest.

Adult↗

Comparison of 30 microgram and 120 microgram gentamicin disks for the prediction of gentamicin resistance in Enterococcus faecalis.

Single strain regression analysis was performed on PDM II medium for E. faecalis with 10, 30 and 120 micrograms gentamicin disks using E. faecalis, strain ATCC 29212 as the reference. This method permits the calculation of zone diameters corresponding to different MIC values for different disk contents. The lack of discrimination between normal low-level resistant strains and high-level resistance using the 10 micrograms disk was confirmed. However, both the 30 micrograms and 120 micrograms disks seemed to provide a separation of the normal low-level gentamicin-resistant population from strains with increased resistance. Since the 30 micrograms disk is used routinely in some countries, there should be no need for an extra high content disk in these laboratories. This was confirmed when 96 clinical isolates of E. faecalis were analysed and the results of routine disk diffusion tests were compared with the MIC values. Two of the strains showed high-level gentamicin resistance (greater than 2000 mg/l) and produced no zone of inhibition. The other 94 isolates showed gentamicin MIC values between 4-16 mg/l, and 72 of the MIC results were 8 mg/l. The zone diameters for these strains ranged between 15 and 25 mm with a mean of 18.2 and a median value of 18 mm. In order to include statistical considerations of the zone size populations for setting of breakpoints, a study of gentamicin zone size distributions was performed for several bacterial species. Inhibition zone diameter values around the 30 micrograms gentamicin disk for 2079 clinical isolates of E. faecalis, 2268 S. aureus, 3201 E. coli and 547 strains of P. mirabilis from different years were plotted as histograms. Tests for agreement with a Gaussian distribution showed that the histograms were slightly peaked and skewed towards higher zone values. Parametric and non-parametric statistical tests were compared and the results showed that means and medians were very similar and that parametric fractile estimations at the lower end of the histogram populations were conservative and could be used in view of a slightly lower rate of false resistance. The 1% parametric fractile of 12 mm was selected as a suitable breakpoint for the identification of normal, low-level resistant isolates of E. faecalis using the standardized disk test of the Swedish Reference Group for Antibiotics.

Drug Resistance, Microbial↗

Dual effects of vasoactive intestinal peptide (VIP) on leucocyte migration.

Vasoactive intestinal peptide, at different concentrations, was tested on the migration of leucocytes by using the sealed capillary migration test. Vasoactive intestinal peptide, at 10(-7)-10(-9)M, inhibited, while at 10(-12)-10(-14)M, stimulated mononuclear leucocyte migration. The migration of polymorphonuclear leucocytes was inhibited by vasoactive intestinal peptide at 10(-6)-10(-9)M, a stimulation was found at 10(-13)-10(-14)M. The inhibiting effect of vasoactive intestinal peptide on leucocyte migration was abolished when vasoactive intestinal peptide was split into C- and N-terminal fragments, while a stimulating effect was retained in the N-terminal fragment, at 10(-14)M, for mononuclear cells. Helodermin and peptide T, as well as two other members of the secretin-glucagon family, secretin and gastric inhibitory peptide, had no effect on the migration. When VIP antiserum was tested, it had an inhibiting effect, which was not seen with control serum, supporting a physiological effect of the lower vasoactive intestinal peptide concentrations. Vasoactive intestinal peptide seems to have dual effects on mononuclear and polymorphonuclear leucocyte migration and, generally, intact vasoactive intestinal peptide seems to be needed for these effects.

Cell Migration Inhibition↗

Renal neurohormonal and vascular responses to dynamic exercise in humans.

Effects of graded supine dynamic exercise (30, 60, and 80-90% of maximal physical capacity, i.e., work loads of 69, 132, and 188 W) on renal vascular resistance (RVR); renal sympathetic nerve activity [assessed by the renal venous overflow of norepinephrine (NE)]; renal overflows of dopamine (DA), immunoreactive neuropeptide Y (NPY-LI), and renin; as well as plasma concentrations of angiotensin-(1-8)-octapeptide (ANG II) were evaluated in eight healthy male volunteers. Exercise evoked stimulus-dependent and marked elevations of RVR, arterial NE, epinephrine (Epi), and DA. RVR increased by 140% and the renal overflows of NE and DA increased by 1,331 and 179%, respectively, at 188 W. A net removal of NPY-LI at rest turned into a small net renal overflow, which correlated with increases in RVR at 188 W. Increases in renin release (+1,200% at 188 W) correlated with increases in renal NE and DA overflows and with arterial Epi levels. Arterial ANG II levels increased stimulus dependently (by 264% at 188 W) and correlated more closely with increases in RVR than did other variables. Thus dynamic exercise is a potent stimulus for renal nerve activation in humans, and renal sympathetic nerve activity may contribute to increased RVR both directly (NE and, at exhaustive work loads, possibly NPY) and indirectly (via renin-mediated ANG II formation).

Adult↗