Biomedical subjects

P Thomsen

Publications and source records attributed to P Thomsen.

At least 19 recordsLinked to original sources

PubMed1995

Antiarrhythmic effect of the selective I1-imidazoline receptor modulator moxonidine on ouabain-induced cardiac arrhythmia in guinea pigs.

Moxonidine is a centrally acting antihypertensive agent with potent action on I1-imidazoline receptors. Moxonidine as an SIR modulator elicits a persistent reduction in circulating levels of epinephrine, demonstrating a reduction in sympathetic tone. In the first experiment the threshold dose of ouabain needed to induce ventricular arrhythmia and asystole was determined in guinea pigs, and the influence of moxonidine was tested. In a dose range of 0.1-0.4 mg/kg body weight i.v., moxonidine increased the threshold dose needed to induce ventricular tachycardia, premature ventricular beats, ventricular flutter, ventricular fibrillation, and asystole. The effect was dose-dependent and statistically significant. Clonidine, in a dose range of 0.2-0.8 mg/kg body weight i.v., also increased the threshold dose of ouabain necessary to induce different cardiac rhythm disturbances. Moxonidine was more effective than clonidine. Pretreatment with the alpha 2-receptor and I1-receptor-influencing substances efaroxan, idazoxan, and SKF 86466 attenuated the effect of moxonidine and clonidine. Efaroxan, idazoxan, or SKF 86466 alone reduced the threshold dose of ouabain necessary to induce cardiac arrhythmia as a sign for arrhythmogenic effects. The alpha 1-receptor antagonist prazosin had no influence on ouabain-induced arrhythmia. Pretreatment with prazosin reduced the moxonidine but not the clonidine effect. In the second experiment the influence of moxonidine on aconitine-induced extrasystoles (ES) in the spontaneously beating guinea pig auricle was investigated. Moxonidine in a dose of 10(-7)-10(-8) M reduced the number of ES. A 10-fold higher dose had no influence on ES number. The beta-blocking agent propranolol showed antiarrhythmic effects in both methods. The ouabain-induced cardiac arrhythmia is associated with increased sympathetic tone on central stimulation. The reduced sympathetic tone by centrally acting moxonidine via imidazoline receptors seems responsible for the antiarrhythmic effect of this drug. Clonidine also reduced the sympathetic tone via imidazoline receptor. The selectivity of clonidine to imidazoline receptors is less pronounced than is that of moxonidine. The interaction of moxonidine with imidazoline receptors is not clear. The possible interaction between imidazoline and alpha-adrenoceptors in relation to the antiarrhythmic effect of moxonidine or clonidine is also unknown. Modulation of imidazoline receptors by moxonidine could be an agonistic effect or an antagonism to an endogenous agonistic or antagonistic substance and vice versa.

Aconitine↗

PubMed1995

Inflammatogenic properties of nucleus pulposus.

STUDY DESIGN: The inflammatogenic properties of nucleus pulposus were assessed in two experimental models previously used for screening of inflammatogenic properties of other substances. This study was performed to assess the inflammatogenic properties of nucleus pulposus in models previously screened for other substances. SUMMARY OF BACKGROUND DATA: Previous experimental studies, as well as clinical observations, have indicated that inflammatory mechanisms may constitute an important pathogenetic component in sciatica due to herniation of the nucleus pulposus. METHODS: In the first experimental series, autologous nucleus pulposus and retroperitoneal fat were placed in perforated titanium chambers, which were placed subcutaneously in pigs, together with an empty chamber as sham. After 7 days, the number of leukocytes in the chambers was determined. In the second experimental series, the microvascular reactions were studied by vital microscopy of the hamster cheek-pouch after local injections of suspensions of homologous nucleus pulposus and homologous subcutaneous fat. Macromolecular extravascular leakage was studied by fluorescence microscopy using FITC-dextran as a tracer. RESULTS: The leukocyte ratio between fat control and sham was 0.9 +/- 0.6 and between nucleus pulposus and sham 2.4 +/- 0.7. The nucleus pulposus thus attracted significantly more leukocytes than fat. Injection of nucleus pulposus suspension induced thrombosis formation and pronounced leakages of macromolecules in a majority of the injection sites. However, injection of vehicle and fat suspension in the cheek-pouch only resulted in minor vital microscopic changes. CONCLUSIONS: Nucleus pulposus demonstrated inflammatogenic properties as indicated by leukotaxis and an increase of vascular permeability. It was not clear, however, it these reactions were induced by substances from the nucleus pulposus per se or from substances being liberated from other tissues as a response to an interaction with components of the nucleus pulposus.

Animals↗

PubMed1995

Immunohistochemical study of the soft tissue around long-term skin-penetrating titanium implants.

Bone-anchored percutaneous titanium implants have become a well-established clinical procedure with a low incidence of adverse reactions. However, passage through the skin leads to a breach in the barrier to exogenous pathogens. In the present study, monoclonal antibodies were used to investigate the distribution of lymphocyte subpopulations in the soft tissue around such implants. Eight biopsies from patients with clinically irritated skin, five from non-irritated and eight from skin without skin-penetrating implants were analysed. The number of immune cells was increased in the group of patients with skin penetration compared with patients without skin penetration. In the group with clinical irritation there was an increased level of B-lymphocytes compared with those without irritation. The data suggest that there is an immunological compensation for the mechanical loss in barrier function at these implants and that an antibody-mediated response is present at clinical signs of irritation.

Adolescent↗

PubMed1995

Electron microscopic observations on the soft tissue around clinical long-term percutaneous titanium implants.

Percutaneous implants of titanium ad modum Brånemark have been in clinical use in the head and neck since 1977. The incidence of adverse reactions is low. In a previous study we have demonstrated the presence of inflammatory cells in the subcutaneous connective tissue surrounding the implants and this increased exposure to exogenous antigens was suggested to be compensated by a barrier of inflammatory cells in the soft tissue. To get further information on the nature of the tissue-implant contact, in the present study we have examined the structure of the tissue close to the percutaneous implant using transmission electron microscopy. We could not see evidence for an attachment of the epithelium to the implant, nor between the connective tissue and the implant. Retrieved implants were also analysed and we did not find any organized tissue remaining on the implants.

Adult↗

PubMed1995

Leucocyte accumulation and leukotriene B4 release in response to polyglactin 910 and expanded polytetrafluoroethylene in hollow chambers in the rat.

The acute inflammatory reaction elicited after implantation of polymer membranes used clinically to promote bone healing and augmentation was studied in a soft tissue titanium chamber model. The two materials compared were non-degradable expanded polytetrafluoroethylene (ePTFE) and degradable polyglactin 910, a copolymer of 90% polyglycolic acid and 10% polylactic acid. The membranes were implanted in the titanium chamber for 24 h and 6 d. The number of leucocytes increased for both materials, whereas the leukotriene B4 (LTB4) content decreased over time. In both groups polymorphonuclear granulocytes predominated. The number of leucocytes was significantly higher in chambers with polyglactin 910 than ePTFE. In contrast, the LTB4 content was higher in chambers with ePTFE than polyglactin 910. No differences in cell viability were observed between the materials tested. This study shows that both degradable and non-degradable polymers elicit a marked influx and activation of inflammatory cells during early healing in soft tissues.

Animals↗

PubMed1995

Rabbit polymorphonuclear granulocyte function during ethanol administration--migration and oxidative responses in a joint with immune complex synovitis.

Functional impairments of polymorphonuclear granulocytes (PMN) are believed to contribute to hampered inflammation and host defence in alcoholics. We studied effects of i.v. ethanol administration on PMN responses in rabbits during induction of a knee-joint synovitis. The synovitis conferred systemic effects, since chemiluminescent responses of peripheral blood PMN to opsonized zymosan and phorpbol myristate acetate (PMA) increased 6.4- and 17.9-fold, respectively. Chemiluminescent responses of synovial PMN were further amplified. This up-regulation was reduced to 33% in rabbits treated with ethanol when opsonized zymosan was used as the PMN stimulus; in contrast, PMA responses were unaffected. The appearance and migration of PMN to the synovitis joint were normal despite a blood ethanol concentration of 0.5%. Thus, ethanol impaired release of oxygen metabolites from PMN, but not the delivery of cells at an inflammatory site.

Animals↗

PubMed1994

Bone response to surface modified titanium implants: studies on electropolished implants with different oxide thicknesses and morphology.

In a series of experimental studies, bone formation was analysed around systematically modified titanium implants. In the present study, machined, electropolished and anodically oxidized implants were prepared, surface characterized and inserted in the cortical bone of rabbits (7 wks and 12 wks). SEM, scanning Auger electron spectroscopy and atomic force microscopy revealed no differences in surface composition but marked differences in oxide thickness, surface topography and roughness. Light microscopic morphology and morphometry showed that all implants were in contact with bone, and had a large proportion of bone within the threads. The smooth, electropolished implants were surrounded by less bone than the machined implants with similar oxide thickness, (4-5 nm) and the anodically oxidized implants with thicker oxides (21 nm and 180 nm, respectively) after 7 wks. These studies show that a high degree of bone contact and bone formation can be achieved with titanium implants which are modified with respect to oxide thickness and surface topography. However, it appears that a reduction of surface roughness may influence the rate of bone formation in rabbit cortical bone.

Animals↗

PubMed1994

Method for immunolocalization of extracellular proteins in association with the implant-soft tissue interface.

A method allowing immunolocalization of macromolecules surrounding biomaterial implants has been developed. Plugs of pure titanium were inserted into the abdominal wall of rats. One week after implantation plugs with adjacent tissue were gently fixed and cryoprotected before being rapidly frozen in LN2-cooled propane, followed by cryosubstitution, using methanol, and low temperature infiltration and UV curing of the methacrylate LR-Gold. Before sectioning, bulk metal was removed electrochemically, leaving the surface oxide intact, appearing in sections as a dense line in contact with the tissue. Postembedding immunolocalization for rat albumin, IgG, C3c, fibrinogen and fibronectin was performed at the light and electron microscopic levels. Our observations indicate that 1 wk after implant insertion, a network of fibrin and fibronectin decorates the tissue surface that faces the implant, but without any obvious concentration to the implant surface.

Abdominal Muscles↗

PubMed1994

Persistent irritation of the soft tissue around an osseointegrated titanium implant. Case report.

Percutaneous implants for hearing aids which are anchored in the bone have a low incidence of skin irritation. We report here the case of a man born in 1958 who had a long period of skin irritation, which was on two occasions associated with bacterial infection with Staphylococcus aureus. Despite local treatment with steroid/antibiotic ointment and skin grafts, episodes of skin irritation recurred, often in association with a relapse of ear drainage. Tests of delayed hypersensitivity to the implant and standard allergens were negative. Morphological and immunohistochemical analysis of the skin after removal of the abutment revealed an intense inflammatory reaction, with polymorphonuclear leucocytes, macrophages, lymphocytes, and HLA-DR expressing cells. In contrast to the inflammatory reaction in the soft tissue, there was a large amount of bone and the degree of bone-implant contact was good.

Adult↗

PubMed1993

Inflammatory cells and mediators in the silicone chamber model for nerve regeneration.

In the present study the inflammatory response was quantitatively evaluated during peripheral nerve regeneration. The fluid from silicone nerve regeneration chambers, inserted in rats, was collected during the early period of regeneration of transected sciatic nerves (6 h-7 d) and analysed with respect to inflammatory cells and mediators (leukotriene B4, LTB4, and interleukin-1 alpha, IL-1 alpha). Leucocytes were detected during the entire period (up to 7 d after implantation). The highest concentration was detected after 24 h. PMNG (polymorphonuclear granulocyte) was the predominant cell type in the chamber fluid during the initial 5d of regeneration. Analysis of the concentration of LTB4 demonstrated two peaks (at 24 h and 5 d). The IL-1 alpha concentration displayed an early and relatively smaller peak after 24 h and a second and much larger peak after 7 d, concomitant with an increase of the number of mononuclear cells.

Animals↗

PubMed1992

Influence of lidocaine on leukocyte function in the surgical wound.

The inflammatory response of the wound is mediated to a large extent by leukocytes, which play an important role in the wound healing process. Local anesthetics, which are routinely administered before minor skin surgery and for postoperative pain relief, have been shown to have diverse effects on wound healing. Local anesthetics have also been reported to induce potent inhibition of leukocytes in vitro, although their effects on leukocyte activity in the surgical wound have not been elucidated. The present study investigated the in vivo effects of lidocaine on leukocyte function in the surgical wound of rats by sampling leukocytes from hollow titanium implants. The surgical wound was treated with lidocaine or placebo after implantation of the titanium chamber and before skin closure. Leukocyte metabolic activity was measured by chemiluminescence. Cell count was analyzed in a Bürker chamber. Results showed progressive increase in leukocyte counts in the wounds of control animals and significantly lower cell counts in the wounds of lidocaine-treated animals 48 h (P less than 0.05) and 72 h (P less than 0.05) after surgery. A pronounced inhibition of the metabolic response to serum-opsonized zymosan was seen after 8 h in the lidocaine-treated animals versus controls (P less than 0.05). After 24 h, leukocyte metabolic activity decreased dramatically in the control group and remained at a low level until 72 h after surgery. In the lidocaine-treated group, the leukocyte response to zymosan remained constantly low throughout the study. The effects of lidocaine were not a result of impaired leukocyte viability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

A morphometric and biomechanic comparison of titanium implants inserted in rabbit cortical and cancellous bone.

The removal torques for screw-shaped pure titanium implants inserted in rabbit tibia and the femoral part of the knee joint and the tissue response to these implants, as quantitated with light microscopic morphometry on ground sections, were compared after 6 weeks, 3 months, and 6 months. The bone surrounding the femoral intra-articular implants was mostly cancellous, while cortical bone was formed around the tibial implants. The torque needed to remove the intra-articular implants increased with time, but there was no such increase for the tibial implants. At 6 weeks, significantly less torque was needed to remove the intra-articular implants in spite of the fact that significantly more bone was found in the threads of these implants as compared with the tibial implants. When calculating the amount of bone in threads situated in the cortical and subchondral passage, more was found in the threads of the tibial implants, which corresponded to the higher removal torque. Additional light microscopic observations on implants unscrewed after 12 months in rabbit tibia indicated that rupture occurred between the implant surface and calcified bone. Findings indicate that the resistance to unscrewing is dependent on the amount of compact bone surrounding a titanium implant.

Animals↗

PubMed1992

Rederivation of rat colonies seropositive for Bacillus piliformis and the subsequent screening for antibodies.

Latent infection of rats in a breeding colony with Bacillus piliformis detectable by antibodies to the agent in an immunofluorescence assay was eliminated by a combination of traditional rederivation techniques, using animal units not previously used for rat breeding, and the use of specific disinfection procedures. The success rate was apparently correlated with the use of peracetic acid instead of aldehyde products to decontaminate the animal unit.

Animal Husbandry↗

PubMed1991

Leukotriene B4, interleukin 1 and leucocyte accumulation in titanium and PTFE chambers after implantation in the rat abdominal wall.

The inflammatory reaction elicited after implantation of non-biologic materials was studied by analysis of the exudate in pure titanium or polytetrafluorethylene chambers 1-9 d after insertion in the abdominal wall of the rat. In chambers made of pure titanium, the number of leucocytes increased about twofold from 1.8 x 10(6)/ml to 4.1 x 10(6)/ml between 24 h and 6 d, whereas a larger increase from 2.1 x 10(6)/ml to 8.3 x 10(6)/ml was observed in the polytetrafluorethylene chambers. Irrespective of implant material, polymorphonuclear granulocytes constituted the vast majority of leucocytes (greater than 81%). After 24 h the leukotriene B4 content was slightly higher in polytetrafluorethylene chambers than in titanium chambers. In contrast to the titanium chambers, a marked increase in leukotriene B4 levels was detected in polytetrafluorethylene chambers 6 d after insertion, whereas the greatest amount of leukotriene B4 in titanium chambers was measured at 9 d. Interleukin 1 was only detected in both types of chambers after 6 d. The present study, together with previous findings, shows that the materials used in this study elicit different degrees of inflammatory reactions in the chamber exudate. Since the number of leucocytes in the exudate retrieved from the chambers correlated well with the leukotriene B4 levels, it is suggested that leukotriene B4, but not interleukin 1, may be an important mediator for polymorphonuclear granulocyte migration into the implant-tissue interface.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗

PubMed1991

Porcine SINEs: characterization and use in species-specific amplification.

A porcine repetitive DNA sequence has been isolated from an intron of the glucose phosphate isomerase gene. The copy number of this and related sequences was estimated to be approximately 10(5) copies per genome. The sequence possesses all the characteristics of short interspersed elements (SINEs) described in other mammals: The repeat is 300 bp in length, has an poly(A)stretch, and contains insertion duplication sites. Homology to seven other porcine sequences, which also have the characteristics of SINEs, has been demonstrated. Primer oligonucleotides, based on conserved regions in the SINE sequences, have been synthesized. Using these primers, PCR-mediated specific amplification of porcine sequences was demonstrated from pig x mouse and pig x hamster hybrid cell lines. Cloning and sequencing of some amplified porcine sequences verify that the sites of priming are SINE sequences.

Animals↗

PubMed1991

Leukocyte supplementation increases the luteinizing hormone-induced ovulation rate in the in vitro-perfused rat ovary.

Ovaries from eCG-primed (20 IU s.c. on Day 28) rats were perfused from the morning of Day 30 of age in a recirculating system initially containing a buffered blood cell-free medium (M199 + 4% BSA) for periods of up to 21 h. The addition of ovine LH (0.1 micrograms/ml) at 0 h of perfusion resulted in ovulations in all 6 ovaries perfused (3.2 +/- 0.7 ovulations per treated ovary; mean +/- SEM), whereas none of the 6 control ovaries ovulated. Rat leukocytes (50 x 10(6)), added at 7 h of perfusion significantly increased the number of LH-induced ovulations (7.8 +/- 0.5; p less than 0.05). All ovulated oocytes showed resumption of meiosis as judged from the presence of germinal vesicle breakdown. Ovaries perfused with leukocytes but without LH did not ovulate. Histological examination of ovaries 14 h after leukocyte administration showed a considerable number of perifollicular extravasated white blood cells. These findings indicate that leukocytes participate in the normal ovulatory process as part of an inflammation-like reaction.

Animals↗

PubMed1990

Difference in tissue response to nitrogen-ion-implanted titanium and c.p. titanium in the abdominal wall of the rat.

Ion implantation modifies the surface properties of different materials. We have compared the biological properties of titanium implanted with nitrogen with those of pure titanium. Implants were inserted in the abdominal wall of rats. The implants with surrounding tissue were excised after 1 and 6 weeks, and embedded in epoxy resin. The bulk metal was removed electrochemically and the tissue cut for light and electron microscopy. Using this technique the implant surface, formed by a thin oxide layer, remains and appears in sections as a dense line. After 1 week both types of implants were surrounded by a fluid space containing proteins and scattered macrophages but few polymorphonuclear granulocytes. The fluid space was wider around ion-implanted titanium (52 +/- 22 microns) than around pure titanium implants (15 +/- 3 microns). After 6 weeks the fluid space had largely disappeared around both type of implants. Around pure titanium implants macrophages and fibroblasts, quantified in 1-micron-thick sections in the light microscope, were present in about the same concentration in the inner tissue zone (within 25 microns from the implant surface). Around ion-implanted titanium macrophages predominated in the inner zone and multinuclear giant cells were present in almost all sections. Around both type of implants fibroblasts increased and macrophages decreased with increasing distance from the surface. In the electron microscope macrophages close to the surface of pure titanium were of small size and had an ultrastructure indicating a low activity. Macrophages close to ion-implanted titanium were large and had an active appearance as indicated by the presence of large amounts of endoplasmic reticulum and large Golgi areas in the cytoplasm. Our observations indicate that modification of the surface properties of titanium implants by ion implantation changes the biological properties.

Abdominal Muscles↗

PubMed1990

Method for ultrastructural studies of the intact tissue-metal interface.

Samples were prepared for ultrastructural studies of the intact interface between metallic implants and tissue by transmission electron microscopy. The method is based on plastic embedding of implant and tissue and subsequent removal of the bulk metal by electrochemical dissolution (electropolishing), to facilitate preparation of ultrathin sections for transmission electron microscopy. Surface sensitive spectroscopy (Auger electron microscopy and X-ray photoemission spectroscopy) and transmission electron microscopy EDX results show that the method produces samples with an intact interface, containing the implant surface oxide and the adjacent tissue. Examples of application of the method on titanium, zirconium and aluminium implants in soft tissue are given.

Aluminum↗