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C J Dalsgaard

Publications and source records attributed to C J Dalsgaard.

At least 19 recordsLinked to original sources
PubMed1997

Effects of ropivacaine on eicosanoid release from human granulocytes and endothelial cells in vitro.

OBJECTIVE: To examine the effects of ropivacaine, currently being investigated for treatment of ulcerative colitis, on the release of arachidonic acid metabolites. MATERIAL: Human granulocytes and endothelial cells. TREATMENT: Ropivacaine, lidocaine, hydrocortisone, 5-aminosalicylic acid or acetylsalicylic acid (10-1000 microM). METHODS: Leukotriene B4, 5-hydroxyeicosatetraenoic acid, 6-keto PGF1 alpha and 15-hydroxyeicosatetraenoic acid were measured using immuno assays. Wilcoxon signed rank test was used for statistical calculations. RESULTS: Ropivacaine dose-dependently inhibited zymosan-induced release of leukotriene B4 and 5-hydroxyeicosatetraenoic acid whereas the release after ionophore stimulation was not affected. Ropivacaine was more potent than 5-aminosalicylic acid but less potent compared to hydrocortisone. Ropivacaine had only a weak inhibitory effect on the release of 15-hydroxyeicosatetraenoic acid from zymosan- or ionophore-stimulated cells. In contrast to hydrocortisone and 5-aminosalicylic acid, ropivacaine only weakly affected the release of 6-keto PGF1 alpha after stimulation with thrombin. CONCLUSIONS: The inhibited release of 5-lipoxygenase products may account for some of the anti-inflammatory effects of ropivacaine seen in the treatment of ulcerative colitis.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Ropivacaine inhibits leukocyte rolling, adhesion and CD11b/CD18 expression.

Ropivacaine, a new local anesthetic, is currently being investigated for the treatment of ulcerative colitis, with promising results so far. The aim of this study was to examine anti-inflammatory properties of ropivacaine with regard to its effects on vascular permeability and inflammatory leukocyte behavior in vivo. The effects on leukocyte rolling, firm adhesion and vascular permeability were examined in the hamster cheek pouch microvasculature via intravital microscopy, and the effects on leukocyte adhesion molecules were examined in vitro by means of flow cytometry. In large venules, leukocyte adhesion induced by topical leukotriene B4 (LTB4) was almost completely inhibited during the combined application of ropivacaine and LTB4. The spontaneous rolling leukocyte flux was reduced by 72%, the rolling leukocyte fraction by 47% and the total leukocyte flux, which reflects blood flow, by 47%. In postcapillary venules, ropivacaine abolished rolling and LTB4-induced firm adhesion of leukocytes. LTB4 challenge also resulted in increased plasma exudation that was almost completely inhibited by ropivacaine. Moreover, ropivacaine inhibited the tumor necrosis factor alpha-induced up-regulation of CD11b/CD18 and L-selectin shedding by human leukocytes in vitro. Our results suggest that ropivacaine exerts anti-inflammatory activity, and this appears to be mediated to a significant extent by inhibition of both leukocyte rolling and adhesion.

Amides↗
PubMed1994

Substance P-, calcitonin gene-related peptide, growth-associated protein-43, and neurotrophin receptor-like immunoreactivity associated with unmyelinated axons in feline ventral roots and pia mater.

The spinal pia mater receives a rich innervation of small sensory axons via the ventral roots. Other sensory axons enter the ventral roots but end blindly or turn abruptly in hairpin loop-like formations and continue in a distal direction. In the present study, the content of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, growth-associated protein (GAP-43)-, and low-affinity neurotrophin receptor protein (p75NGFr)-like immunoreactivity (-LI) associated with these different types of sensory axons was assessed with light and electron microscopic immunohistochemical techniques. In addition, the binding of antibodies against synthetic peptides representing unique sequences of residues in the products of the trk and trkB protooncogenes was analyzed. These genes encode membrane spanning proteins, which have been shown to constitute specific high affinity binding sites for several members of the nerve growth factor family of neurotrophic factors. The results of the present study imply that the ventral root afferents comprise several different types of sensory axons, which all contain SP-, CGRP-, GAP-43-, and p75NGFr-like immunoreactivities. In addition, at least some of the presumed sensory fiber bundles in ventral roots and the pia mater were immunoreactive for the trkB gene product. Moreover, leptomeningeal cells and nonneuronal cells of the ventral roots were shown to bind antibodies to both the trk and trkB gene products. The ventral root afferents seem to share their immunohistochemical pattern with pain-transducing axons at some other locations, such as the tooth pulp. The contents of SP- and CGRP-LI in sensory axons that reach the central nervous system (CNS) through the ventral root indicate that ventral root afferents may be involved in sensory mechanisms, such as the ventral root pain reaction, as well as in the control of the pial blood vessels. The demonstration of GAP-43 and neurotrophin receptor-immunoreactivities associated with unmyelinated fibers in ventral roots and the pia mater is discussed in relation to previous reports on postnatal plasticity in these axonal populations.

Animals↗
PubMed1994

Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves.

OBJECTIVES: Cell-specific antibodies were used to identify immunocompetent cells in a comparison of valves from patients who had symptomatic tricuspid aortic stenosis with subjects who had no evidence of valvular heart disease. BACKGROUND: Nonrheumatic valvular aortic stenosis is the most common valvular heart disease among adults. The biologic processes involved in the development of this disease are poorly understood. METHODS: Tricuspid stenotic aortic valves were obtained from 19 patients undergoing surgery for nonrheumatic valvular aortic stenosis, and 10 control valves were collected at autopsy. The valves were fixed in formaldehyde, cryosectioned and stained with antibodies against fibroblasts, endothelial cells, macrophages, T lymphocytes and interleukin-2 receptors. A subset of valves were also analyzed with antibodies against T-helper cells and cytotoxic T cells. RESULTS: Stenotic valves were characterized by a basal accumulation of calcium deposits and a cell-rich subendothelial thickening. The immunohistologic analysis indicated that the cells in the subendothelial connective tissue were fibroblasts. T lymphocytes appeared to be the most common cell type in the vicinity of the calcium deposits and were also found close to the endothelial lining of the valves. T-helper cells were more frequent than cytotoxic T cells. Expression of interleukin-2 receptors occurred at the same location as T lymphocytes. Control valves lacked subendothelial thickening and contained only few cells reacting with antibodies against lymphocytes and macrophages. CONCLUSIONS: The presence of activated T lymphocytes in tricuspid stenotic valves suggests that immunologic mechanisms may be involved in the etiology of nonrheumatic aortic stenosis.

Aged↗
PubMed1994

Weight bearing as an objective measure of arthritic pain in the rat.

This study compares two methods for evaluating pain-related behavior in an animal model with carrageenan-induced monoarthritis. Rats injected with lambda-carrageenan into the right tibio-tarsal joint were videofilmed at various times after injection and later scored regarding their stance. Immediately after each videorecording session the animals were tested in a box constructed to register the weight load exerted by the hindpaws by means of force plates inserted in the floor. Following carrageenan injection (300 micrograms in 50 microL) the load on the injected paw fell from a control value of 39.3% +/- 0.4% of the body weight (mean +/- SEM, n = 6) to a minimum of 5.1% +/- 1.8% at 6 hr and then slowly increased to approach control levels at 72 hr. The weight load on the contralateral paw increased from a control value of 38.9% +/- 0.6% to 52.4% +/- 1.4% at 6 hr, whereafter it gradually decreased. The video-based stance scores also showed a maximal impairment at 4-6 hr, with a gradual return towards control values at 72 hr. However, the results based on the force plate measurements were less variable and more graded. Morphine inhibited the carrageenan-induced effect in a dose-dependent manner in both paradigms. In conclusion, the present results indicate that measurement of weight bearing as described in the present paper is a practical, useful, and objective method to assess the degree of arthritic pain in the rat.

Animals↗
PubMed1993

Ropivacaine and lidocaine inhibit proliferation of non-transformed cultured adult human fibroblasts, endothelial cells and keratinocytes.

Local anaesthetics are known to affect a variety of cell functions, many of which are involved in the inflammatory response. Local anaesthetics have also been shown to influence cell proliferation. The aim of this study was to examine the effect of two local anaesthetics (ropivacaine and lidocaine) on cell proliferation of cultured human fibroblasts, vascular endothelial cells and epithelial cells, i.e. keratinocytes, as earlier studies have not included primary human cell types. Significant inhibition of fibroblast proliferation was observed with concentrations of 50 microM ropivacaine or 100 microM lidocaine in 1% newborn calf serum and 500 microM ropivacaine or lidocaine in 10% newborn calf serum. The proliferation of endothelial cells was significantly inhibited by 1 mM ropivacaine in 5% human serum and 500 microM ropivacaine or 100 microM lidocaine in 40% human serum. Significant inhibition was not obtained with lidocaine when these cells were cultured in 5% HS. Significant inhibition of keratinocytes was obtained with 100 microM ropivacaine and 500 microM lidocaine. The effective concentrations are within the range of therapeutical concentrations in vivo and there seems to be a general correlation between the local anaesthetic potency and the inhibiting effect on cell proliferation. This suggest a mechanism by which local anaesthetics may exhibit anti-hyperproliferative effects in clinical situations.

Amides↗
PubMed1993

Mitotic activity in expanded human skin.

In 20 patients subjected to breast reconstruction by means of tissue expansion, a skin biopsy was obtained at the vertex of the breast before and the day after expansion. Samples were incubated in [3H]thymidine, and the number of labeled cells were counted. A statistically significant rise in the number of labeled basal and suprabasal keratinocytes was seen after expansion. The findings suggest a net gain of tissue not only by stretching but also by formation of new tissue generated by tissue expansion.

Biopsy↗
PubMed1993

Calcitonin gene-related peptide treatment of flaps with compromised circulation in humans.

Nineteen patients with surgical or traumatic flaps and one patient with a congenital vein vault deficiency were treated with the vasodilatory compound calcitonin gene-related peptide (CGRP) intravenously. The patients showed compromised circulation due to ischemia and/or venous stasis. In all but three patients, the treatment resulted in an improved tissue circulation, as measured by laser Doppler flowmetry. Thirteen of the flaps survived completely, and in three flaps a partial necrosis was encountered (< or = 25 percent). The three flaps that did not respond at all to calcitonin gene-related peptide treatment did not survive. Calcitonin gene-related peptide was shown to be much more effective than transcutaneous electrical nerve stimulation (TENS). Thus calcitonin gene-related peptide provides a pharmacologic tool to improve blood flow in surgical and traumatic flaps with compromised circulation in humans.

Adult↗
PubMed1992

Intrathecal CP-96,345 blocks reflex facilitation induced in rats by substance P and C-fiber-conditioning stimulation.

We have examined the effects of intrathecally (i.t.) administered CP-96,345, a non-peptide NK1 receptor ligand, on the spinal nociceptive flexor reflex and on the facilitation of this reflex evoked by i.t. substance P (SP), neurokinin A (NKA) and electrical conditioning stimulation of cutaneous C-afferents. CP-96,345 i.t. at 24 pmol-2.4 nmol had no significant effect on flexor reflex excitability. At the highest dose tested (24 nmol), CP-96,345 caused a brief facilitation of the flexor reflex, which was similar to the effect of the vehicle used at this drug concentration. CP-96,345 did not depress the flexor reflex at any dose. In rats with chronically implanted i.t. catheters, CP-96,345 at 24 nmol caused neither motor impairment nor morphological damage to the spinal cord. Pretreatment with CP-96,345 dose dependently and similarly antagonized facilitation of the flexor reflex induced by 7 pmol i.t. SP or by a 20-s, 1-Hz conditioning stimulus train applied to cutaneous C-fibers in the sural nerve innervation area. The vehicle had no effect. The antagonistic effect of CP-96,345 on the SP- and C-fiber reflex facilitation induced by conditioning stimulation became maximal only 20-30 min after the i.t. injection and lasted 3-4 h at the highest dose. CP-96,345 did not significantly block the facilitatory effect of 7 pmol i.t. NKA on the flexor reflex. These results demonstrate that CP-96,345 is a potent, long-lasting and selective antagonist of SP in rat spinal cord. Furthermore, facilitation of the flexor reflex (central sensitization) induced by conditioning stimulation of cutaneous C-afferents is mediated by NK1 tachykinin receptors, but the NK1 receptor may not be involved in the transmission of the flexor reflex. CP-96,345 is thus useful in experimental studies of the role of SP in the central nervous system.

Analysis of Variance↗
PubMed1992

NK-1, but not NK-2, tachykinin receptors mediate plasma extravasation induced by antidromic C-fiber stimulation in rat hindpaw: demonstrated with the NK-1 antagonist CP-96,345 and the NK-2 antagonist Men 10207.

The effects of intradermal injection of CP-96,345 and Men 10207, selective antagonists for NK-1 and NK-2 tachykinin receptors, respectively, on the extravasation of plasma protein induced by antidromic stimulation of unmyelinated sensory fibers in the sciatic nerve was studied in rat hindpaw. Activation of unmyelinated fibers by antidromic sciatic nerve stimulation (1 Hz, 5 min) consistently evoked a localized plasma extravasation of Evans blue on the skin area of the hindpaw innervated by the sciatic nerve, which was not inhibited by intradermal injection of saline or Men 10207 (9 and 35 nmol). In contrast, CP-96,345 (3 and 9 nmol, but not 1 nmol), injected intradermally 15 min prior to nerve stimulation dose-dependently inhibited this response. Plasma extravasation induced by intravenously injected substance P was also inhibited by CP-96,345. Since CP-96,345 is a highly selective antagonist for NK-1 tachykinin receptors, it is suggested that the plasma extravasation induced by antidromic C-fiber stimulation and by systemically applied tachykinins is mediated by NK-1 tachykinin receptors.

Animals↗
PubMed1992

Nicotine- and capsaicin-, but not potassium-evoked CGP-release from cultured guinea-pig spinal ganglia is inhibited by Ruthenium red.

In the present study we have investigated the effects of nicotine, capsaicin, potassium, glutamate and aspartate on release of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from guinea-pig dorsal root ganglion (DRG) cultures. In addition the possible influence of Ruthenium red (RR), neuropeptide Y (NPY) and noradrenaline (NA) on the CGRP-LI outflow has been evaluated. Nicotine, capsaicin and potassium, but not glutamate or aspartate, evoked a Ca(2+)-dependent increase in the culture medium, suggesting release of CGRP-LI. RR inhibited the effect of both capsaicin and nicotine but did not influence potassium-induced CGRP-LI release. Furthermore, the nicotine- but not capsaicin-evoked CGRP-LI release was inhibited by NPY. It is concluded that DRG cultures represent an experimental model where regulation of CGRP-LI release can be studied. The ability of RR to inhibit not only capsaicin but also nicotine effects indicate that the proposed selectivity of RR may depend on the agent used to evoke peptide release and/or concentrations used.

Animals↗
PubMed1992

Spinal substance P and N-methyl-D-aspartate receptors are coactivated in the induction of central sensitization of the nociceptive flexor reflex.

We have studied the effects and interactions of the neurokinin-1 receptor antagonist CP-96,345 and the N-methyl-D-aspartate receptor/channel blocker MK-801, both applied intravenously, on the flexor reflex and on the facilitation of the flexor reflex by conditioning stimulation of cutaneous C-afferents in decerebrate, spinalized, unanesthetized rats. The flexor reflex was evoked by subcutaneous electrical stimuli applied to the sural nerve innervation area 1/min at an intensity that activated C-fibers and was recorded as electromyogram from the ipsilateral hamstring muscles. The magnitude of the baseline flexor reflex was usually highly stable in the course of the experiments without experimental manipulations. The same stimulus was used as a conditioning train (0.9 Hz, 20 shocks) and caused a brief facilitation of the flexor reflex, which was maximal 0.5 and 1 min after stimulation (255.1 +/- 23.6% over baseline). During the course of the conditioning stimulus train, the reflex magnitude was gradually increased (wind-up). MK-801 (0.1 and 0.5 mg/kg) consistently depressed the polysynaptic flexor reflex. At a dose of 0.5 mg/kg, but not 0.1 mg/kg, MK-801 reduced the wind-up and blocked the facilitation of the flexor reflex induced by the conditioning stimulus by 90%. The facilitatory effect of 7 pmol intrathecal substance P was also partially reduced by MK-801. CP 96,345 (1 and 3 mg/kg) did not depress the flexor reflex, but dose-dependently antagonized reflex facilitation by the conditioning stimulus train, similarly to its antagonism of intrathecally applied 7 pmol substance P-induced facilitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Endothelin as a putative sensory neuropeptide in the guinea-pig: different properties in comparison with calcitonin gene-related peptide.

Both endothelin-(ET) and calcitonin gene-related peptide- (CGRP) like immunoreactivity (-LI) were present in a variety of organs and neuronal tissue of the guinea-pig as determined by radioimmunoassay (RIA). Neuronal tissues like dorsal root ganglia (DRG) contained by far the highest levels of both ET- (65 +/- 11 pmol/g) and CGRP-LI (34 +/- 5 pmol/g). The tissue levels of ET-LI remained unchanged after 6-hydroxydopamine and capsaicin-pretreatment, while CGRP-LI was markedly reduced after capsaicin. Chromatographic characterization revealed that the main portion of ET-LI in the DRG, right atrium and lung corresponded to synthetic ET-1. Immunohistochemical studies showed the presence of ET-LI in a few neurons of intact DRG and many neurons in DRG cell-cultures, partly co-existing with CGRP-LI. In the neuronal cells of DRG cultures the ratio between the ET- and CGRP-LI was 1:27 compared to 2:1 in intact DRG. 24 h after ligation of the sciatic or vagal nerves no accumulation of ET-LI was observed above the ligation, while CGRP-LI was increased 4-5-fold. Transection (10 days) of the sciatic nerve caused a 85-95% depletion of CGRP-LI in the distal skin, gastrocnemius muscle and trunk below the transection site, while in the proximal portion of the nerve CGRP-LI increased. No effects on ET-LI in these tissues were observed after sciatic nerve transfection. In release experiments on DRG cell cultures. Langendorff heart preparations or perfused guinea-pig lungs, potassium (60 mM), capsaicin or antidromic nerve stimulation evoked a clear-cut increase in the supernatant levels of CGRP-LI, suggesting release, while no effect on the ET-LI concentration was observed in the effluent. Furthermore, anoxia failed to influence the outflow of ET-LI from the heart and lung. It is concluded that ET-1-LI is present in high levels in spinal ganglia and ET-LI occurs in afferent cell-bodies, but in comparison with CGRP, ET shows remarkable inertness upon various experimental conditions including no evidence for axonal transport, loss after denervation or release. The neuronal ET-LI seems to increase under culture conditions, however. The possible function for the high content of ET-LI in the intact guinea-pig peripheral nervous system remains to be elucidated and may mainly be related to a non-neuronal pool considering the relatively low content of ET-LI compared to CGRP in cultured DRG cells.

Animals↗
PubMed1991

Ectatic blood vessels in port-wine stains lack innervation: possible role in pathogenesis.

The innervation pattern of port-wine stains was investigated using indirect immunohistochemistry with antibodies to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), calcitonin gene-related peptide (CGRP), and neurofilament (NF). The pathologically dilated vessels in the middle and deep dermis were found to have defective innervation with only single or no nerve fibers in their vicinity, while other structures in the skin showed a normal density of fibers. NSE- and PGP-like immunoreactive (-LI) nerve fibers were observed innervating vessels with a normal morphology and other structures in the skin, such as sweat glands and hair follicles, as free nerve endings and in nerve bundles. The nerve bundles were often seen to pass the ectatic vessels without giving off any branches. CGRP-LI nerve fibers were detected running toward epidermis, whereas no fibers were found around the ectatic vessels. NF-LI fibers were seen innervating normal vessels in dermis, while in relation to the dilated vessels, no or only occasional fibers were observed. The lack of innervation may be of importance for the development of the disease as a result of decreased tonus of the vessels and/or a loss of neuronal trophic factors.

Adult↗
PubMed1991

Conditioned medium from cultured human keratinocytes has growth stimulatory properties on different human cell types.

Evidence for growth-stimulatory properties of keratinocyte-conditioned medium (KCM) on human fibroblasts, endothelial cells, keratinocytes, smooth muscle cells, and a mouse fibroblast cell line (3T3 cells) is presented. On human fibroblasts KCM caused an increase of over 400% in DNA synthesis as revealed by 3H-thymidine incorporation and autoradiography. The proliferative effect was comparable to that of platelet-derived growth factor (PDGF), but was not inhibited by PDGF antibodies and exceeded that of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and basic fibroblast growth factor (bFGF). Furthermore, KCM was found to stimulate smooth muscle cells, keratinocytes, and endothelial cells more potently than PDGF, EGF/TGF-alpha, and bFGF, respectively. KCM was also potent in stimulating thymidine incorporation in 3T3 cells, whereas EGF showed a twenty-fold weaker stimulatory effect. Because keratinocytes have been shown to secrete TGF-alpha, which binds to the EGF receptor, binding of factors in KCM to the EGF receptor was assayed. The displacement of radiolabeled EGF by KCM corresponded to a low concentration of EGF (0.5 ng/ml), implying that the growth-stimulatory effect of KCM was not mediated via activation of EGF receptors. Taken together, these results suggest the presence of hitherto unidentified growth-stimulatory factor(s), expressed and secreted by cultured human keratinocytes.

3T3 Cells↗
PubMed1991

Transplantation of cultured autologous epithelium after meningococcal septicaemia in a 4-year-old with 35% skin loss.

A 4-year-old girl with scattered full-thickness skin and soft tissue wounds mainly on the extremities and corresponding to roughly 35% of the total body surface area was treated with early excision and transplantation of cultured autologous epidermal grafts. The transplantation was accomplished in one stage, three weeks after admission. The epidermal cells were cultured in Stockholm, Sweden and the time of transportation of the grafts to Reykjavik, Iceland (seven hours) did not seem to affect the quality, as 85% had taken one week after transplantation. The patient healed completely without further transplantation, but a few local skin flaps were needed to cover exposed articular surfaces. The patient was discharged from hospital with stable grafts five weeks after transplantation.

Cells, Cultured↗
PubMed1991

Early excision and skin grafting of selected burns of the face and neck.

Since 1979, 16 patients with facial and neck burns have been treated with excision and skin grafting within the first 4 days of injury. The injuries were tangentially excised and immediately covered with split-thickness skin grafts. Detailed consecutive results are presented. The patients can be divided into three groups. Group 1 consisted of small subdermal or circumscribed deep dermal burns of the face (n = 8). Healing was quick. Some patients developed signs of overgrafting. As a late result, unevenness and discoloration were seen. Group 2 consisted of mixed deep dermal and subdermal burns of the face and neck (n = 5). Usually, minor areas had to be regrafted. Some patients developed hypertrophic scars at border areas. In the completely excised and grafted area, the skin was smooth, pliable, and discolored. Group 3 consisted mostly of subdermal burns of the face and neck (n = 3). The surgical trauma was significant. Small areas had to be regrafted. Ectropion and microstomia developed. It is concluded that in selected cases of deep dermal and subdermal burns, early excision and skin grafting will result in faster healing and less scarring than expectant treatment.

Adolescent↗