Biomedical subjects

K J Heyeraas

Publications and source records attributed to K J Heyeraas.

At least 19 recordsLinked to original sources

PubMed2006

Edema in oral mucosa after LPS or cytokine exposure.

Lowering of interstitial fluid pressure (P(if)) is an important factor that explains the rapid edema formation in acute inflammation in loose connective tissues. Lipopolysaccharide (LPS) and the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are pathogenetic in gingivitis. To test if these substances induce lowering of P(if) in rat oral mucosa, we measured P(if) with a micropuncture technique. IL-1beta and TNF-alpha caused lowering of P(if), whereas LPS induced an immediate increase in P(if), followed by lowering after 40 min. Measurements of fluid volume distribution showed a significant change in interstitial fluid volume (V(i)) 1.5 hr after LPS exposure as V(i) changed from 0.41 +/- 0.02 to 0.51 +/- 0.03 mL/g wet weight (p < 0.05), confirming edema. These findings show that LPS, IL-1beta, and TNF-alpha induce lowering of P(if) in the rat oral mucosa and contribute to edema formation in LPS-induced gingivitis.

Animals↗

PubMed2006

Modulation of dental inflammation by the sympathetic nervous system.

Recent findings have indicated that immune responses are subjected to modulation by the sympathetic nervous system (SNS). Moreover, the findings show that the SNS inhibits the production of pro-inflammatory cytokines, while stimulating the production of anti-inflammatory cytokines. The present review is an attempt to summarize the current results on how the SNS affects inflammation in dental tissues. In dental tissues, it has been found that the SNS is significant for recruitment of inflammatory cells such as CD 43+ granulocytes. Sympathetic nerves appear to have an inhibitory effect on osteoclasts, odontoclasts, and on IL-1alpha production. The SNS stimulates reparative dentin production, since reparative dentin formation was reduced after sympathectomy. Sprouting of sympathetic nerve fibers occurs in chronically inflamed dental pulp, and neural imbalance caused by unilateral sympathectomy recruits immunoglobulin-producing cells to the dental pulp. In conclusion, this article presents evidence in support of interactions between the sympathetic nervous system and dental inflammation.

Animals↗

PubMed2005

Immunoglobulin producing cells in the rat dental pulp after unilateral sympathectomy.

Recent studies show that sympathetic nerves participate in immunomodulation. We investigated the effects of unilateral sympathectomy on recruitment of cells expressing kappa and lambda (kappa and lambda) light chains in the rat dental pulp. Superior cervical ganglion was removed in experimental rats (n=10) while control rats (n=8) received sham surgery. Following perfusion 18 days later, mandibular jaws were processed for immunohistochemistry and electron microscopy. Sympathectomy results in recruitment of cells expressing kappa and lambda light chains into the dental pulp (P=0.005). Electron microscopy revealed these cells to be mainly plasma cells and Mott cells. We conclude that neural imbalance caused by unilateral sympathectomy recruits immunoglobulin producing cells in the dental pulp. Our results are in agreement with a model of immune regulation in which the sympathetic nervous system exerts a tonic regulatory effect over lymphocyte proliferation and migration.

Animals↗

PubMed2003

Effects of sympathectomy on experimentally induced pulpal inflammation and periapical lesions in rats.

The role of sympathetic nerves in bone physiology is largely unknown. Recent studies have shown a correlation between sympathectomy and bone remodeling. The present experiments were aimed to study the effects of unilateral sympathectomy on bilateral experimentally induced pulpitis and periapical lesions in the rat maxilla and mandible. Adult male Sprague-Dawley rats were used. Experimental rats (n=11) had the right superior cervical ganglion surgically removed (SCGx) and control rats (n=5) had sham surgery. Pulpal inflammation and periapical bone lesions in the maxilla and mandible were created 14 days later in both experimental and control rats by exposing the dental pulp in the first and second molars and leaving them open to the oral microflora. The rats were perfused 20 days thereafter and the jaws processed for immunohistochemistry with neuropeptide Y (NPY) and ED1 as primary antibodies. Sympathectomy resulted in an almost complete loss of NPY-immunoreactive (IR) fibers in the right SCGx jaws. In the non-sympathectomized (non-SCGx) left side and in the control rats, sprouting of NPY-IR fiber was observed in the inflamed pulp tissue adjacent to reparative dentin formation and in the apical periodontal ligament of the partially necrotic first molars. Significantly more ED1-IR osteoclasts were found in the resorptive lacunae lining the periphery of the periapical lesions on the SCGx side compared with the non-SCGx side (P<0.04) and the controls (P<0.03). The size of the periapical lesions were larger on the SCGx side compared with the non-SCGx side (P<0.03) in the mandible, but not in the maxilla. We conclude that inflammation causes sprouting of NPY-IR nerve fibers and that unilateral removal of the SCG increases both the area of the periapical lesions and the number of osteoclasts in the inflamed region.

Animals↗

PubMed2003

Role of K+ATP channels, endothelin A receptors, and effect of angiotensin II on blood flow in oral tissues.

K+(ATP) channels are involved in CGRP-mediated vasodilation and in the vasoconstriction induced by endothelin or angiotensin II. In this study, we examined the effects of a K+(ATP) channel antagonist and an ET(A) receptor antagonist on resting blood flow in the pulp and gingiva, and observed their role in the vasodilation induced by tooth stimulation. We also investigated whether receptors for angiotensin II exist in the pulp and gingiva. Blood flow was measured with laser-Doppler flowmetry. Under control conditions, the K+(ATP) channel antagonist and angiotensin II caused a significant drop in blood flow in both target tissues. Blocking of ET(A) receptor did not change basal blood flow. The vasodilation observed after tooth stimulation remained unchanged following blockade of K+(ATP) channels and ET(A) receptors. Analysis of the data shows that open K+(ATP) channels exist during resting conditions in the pulp and gingiva, but that CGRP seems to induce vasodilation mainly via mechanisms other than K+(ATP) channels. ET(A) and AT(1) receptors are found in the pulp and gingiva, but ET(A) receptors are not involved in modulation of a basal vascular tone in these tissues or in the vasodilation observed after tooth stimulation.

Adenosine Triphosphate↗

PubMed2003

Blood flow and interstitial fluid pressure in the rat submandibular gland during changes in perfusion.

The submandibular gland is a cell-rich encapsulated organ with high transport of fluid through the interstitial space during salivation. We hypothesized that the gland is a low-compliant tissue, i.e., that a modest increase in fluid volume will produce a rise in interstitial fluid pressure (IFP) counteracting fluid filtration into the interstitium. To test this hypothesis, we measured IFP with micropipettes and glandular blood flow (GBF) with a laser-Doppler flowmeter during changes in perfusion. Clamping of the carotid artery or the jugular vein, or electrical stimulation of the sympathetic or parasympathetic nerve to the gland, induced changes in perfusion. Baseline IFP averaged 3.5 +/- 0.5 mm Hg. Clamping of the artery reduced IFP and GBF (-56.5 +/- 8.4% and -53.1 +/- 6.4%, respectively), whereas clamping of the vein decreased GBF (-21.6 +/- 14.3%) and increased IFP (141.2 +/- 27.4%). Sympathetic nerve stimulation reduced both parameters (-86.9 +/- 16.5% and -74.4 +/- 7.0%, respectively). In contrast, stimulation of the parasympathetic nerve elicited an increase in GBF (133.2 +/- 5.9%) and in IFP (173.3 +/- 41.4%). Thus, changes in vascular volume led to concomitant changes in IFP consistent with low tissue compliance, a phenomenon of importance for fluid volume regulation.

Animals↗

PubMed2002

Merkel-like cells in Malassez epithelium in the periodontal ligament of cats: an immunohistochemical, confocal-laser scanning and immuno electron-microscopic investigation.

The cellular heterogeneity of Malassez epithelium (ME) residing in the periodontal ligament has recently been reported, and the presence and coexistence of the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal peptide (VIP) in single cells in ME has been shown (1). However, the identity of these neuroendocrine cells has so far not been verified. This study was undertaken in order to elucidate the identity of the neuroendocrine cells in ME by means of transmission electron microscopy, confocal scanning microscopy and immunohistochemistry using antibodies to protein gene product (PGP) 9.5 and cytokeratin 20 (CK). Gingival tissue was included in the study as a positive control for identification of Merkel-like cells in oral epithelium. CK 20 immunopositive cells were present in both Malassez epithelium and in basal cell layers of gingival epithelium showing a distribution consistent with PGP 9.5 labelled cells in both epithelia. The results from PGP 9.5 immuno electron microscopy clearly evidenced the presence of single, intensely labelled cells and some nerve fibres invested between the Malassez epithelial cells. The conformity of the immunopositive cells in Malassez and gingival epithelium verified by double immunolabelling with PGP 9.5 and CK 20, indicates that the labelled neuroendocrine cells are identical in ME and in gingival epithelium. This demonstrates that Malassez epithelium not only exhibits neuroendocrine cells, but additionally that the neuroendocrine cells represent Merkel-like cells.

Animals↗

PubMed2001

Drainage of plasma proteins from the renal medullary interstitium in rats.

1. Lymph vessels are scarce or lacking in the renal inner medulla, raising the question of whether plasma proteins entering the medullary interstitium are removed by diffusion through the interstitium to lymphatics in the outer medulla or cortex, or by convection into the vasa recta. 2. Using micropipettes, we infused 125I-albumin into the papilla of anaesthetized rats and watched its disappearance from the injection site as well as the uptake in the thoracic duct and plasma. 3. Tracer infused into the renal cortex appeared almost immediately in the thoracic duct lymph, and rose to a sevenfold higher concentration than in plasma, whereas tracer infused into the papilla appeared first and increased more sharply in plasma than in the lymph. No spread from the papillary injection site was observed. Tracer injected in renal hilar lymphatics was quantitatively recovered in the thoracic duct. 4. The plasma concentration pattern following papillary infusion was similar to that obtained by intravenous injection, indicating uptake in blood and subsequent distribution to extracellular fluid and lymph from all organs. 5. We conclude that plasma proteins normally diffusing out from the vasa recta are brought back through water flux (1) from the collecting ducts due to the high sodium chloride concentration in the papillary interstitium and (2) from the interstitium into the vasa recta driven by plasma protein osmotic pressure. Accordingly, there is no need for lymph vessels in the inner medulla.

Albumins↗

PubMed2001

The effect of unilateral sympathectomy and cavity preparation on peptidergic nerves and immune cells in rat dental pulp.

Recent evidence suggests interactions between primary afferent nociceptors and postganglionic sympathetic efferents in the pathogenesis of inflammation. The effect of unilateral removal of the superior cervical ganglion on the innervation pattern of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY), as well as the occurrence of immune cells in the injured and uninjured rat molar pulp, was investigated. Light microscopic immunocytochemistry demonstrated that the molar pulps contralateral to the sympathectomy contained a NPY-IR nerve fiber network more dense and heavily stained than unoperated control rats. The NPY-IR fibers showed, however, no sprouting after deep cavity preparation. There was no compensatory increase in CGRP- and SP-IR nerve fibers in the dental pulp after unilateral sympathectomy, although a significant increase in cells IR to CGRP and SP was found in the ipsilateral trigeminal ganglion. Unilateral sympathectomy induced a significant increase in immune cell density both in the inflamed and in the uninflamed dental pulp bilaterally. Our results demonstrate, for the first time, a trophic effect of the sympathetic nerves on immune cells in the dental pulp, indicating that an imbalance of sympathetic nerves may induce inflammation and pain in teeth.

Animals↗

PubMed2001

Effect of denervation on healing after tooth replantation in the ferret.

Studies have shown that the sensory nerves participate in inflammation and immune responses and possess trophic-facilitating wound healing in general. Tooth avulsion represents a pulpal and periodontal injury, and the mechanisms involved in the healing responses subsequent to replantation of teeth are still unclear. The objective of this study was to investigate the healing responses after denervation and replantation of teeth. Unilateral denervation was performed in 15 ferrets by axotomy of the inferior alveolar nerve, 5 days before extraction of the first lower premolars. Six weeks later the mandibles were excised and processed for histological evaluation. Immunohistochemistry was performed using antibodies against the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and measurements of root resorption and ankylosis were performed in four sections from each replanted tooth. After 6 weeks substantial reinnervation was observed in the jaws. Immunoreactivity in the pulp was observed in only two replanted teeth on the denervated side, compared with four on the innervated side. Total pulp necrosis appeared in 10 replanted teeth on the denervated side and in 5 on the innervated, indicating that sensory nerves promote survival of the pulp after replantation. SP-immunoreactive (IR) fibers were more frequently observed in the resorptive lacunae than CGRP-IR fibers. However, resorptive areas lacking IR fibers were frequently found along the root surface. Root resorption averaged 0.062 +/- 0.029 mm2 on the innervated side compared to 0.016 +/- 0.0043 mm2 on the denervated (P< 0.02). Ankylosis was observed in four of the replanted teeth on the innervated side (169.3 +/- 49.7 microm) and in six on the denervated side (332.56 +/- 193.2 microm) (P = 1). It is concluded that the sensory nerves promote root resorption after pulpoperiodontal injuries but have less influence on the osteoblastic activity expressed by ankylosis.

Animals↗

PubMed2001

Pulp-dentin biology in restorative dentistry. Part 1: normal structure and physiology.

Considerable knowledge has accumulated over the years on the structure and function of the dental pulp and dentin. Some of this knowledge has important clinical implications. This review, which is the first of seven articles, will be limited to those parts of the normal structure and physiology of the pulp and dentin that have been shown to result in, or are likely lead to, tissue reactions associated with the clinical treatment of these tissues. Although certain normal structures will be highlighted in some detail, a basic knowledge of pulpal and dentinal development and structure is a prerequisite for an understanding of this text.

Biology↗

PubMed2001

Pulp-dentin biology in restorative dentistry. Part 3: Pulpal inflammation and its sequelae.

Physiologic and histopathologic experimental studies over the last 30 to 40 years have demonstrated that the healing of the dental pulp is comparable to that of connective tissue elsewhere, despite its location in the low-compliance pulp chamber. The greatest difficulty from a clinical point of view is to assess cellular changes and vitality of the pulp. If it is vital, the potential for repair is present, especially in young individuals.

Animals↗

PubMed2000

Effect of the sensory neuropeptide antagonists h-CGRP((8-37)) and SR 140.33 on pulpal and gingival blood flow in ferrets.

In a previous study, it was concluded that the neuropeptides calcitonin gene-related peptide (CGRP) and substance P are released during resting conditions in the (exposed) ferret dental pulp, contributing to a basal vasodilator tone in the pulpal vessels. In order to exclude the possibility that the method used elicited axon reflexes, which might be responsible for neuropeptide release, the present study was designed without pulp exposure. Non-invasive laser-Doppler flowmetry was used to measure the effects of intra-arterial infusions of the antagonists h-CGRP((8-37)) and SR 140.33 (neurokinin 1-receptor antagonist) on pulpal and gingival blood flow before, during and after electrical tooth stimulation. Infusions of h-CGRP((8-37)) reduced the basal blood flow in the pulp by 31.4+/-5.2% (p<0.001) and in the gingiva by 22.6+/-4.8% (p<0.05). A further significant decrease in basal blood flow was measured in both pulp and gingiva following SR 140.33 administration. The reduction in blood flow was 16.9+/-1.9% (p<0.005) in the pulp and 19. 3+/-5.6% (p<0.05) in the gingiva. The systemic arterial pressure remained unchanged both during and after the periods of infusion. Tooth stimulation before the antagonist infusion significantly increased the pulpal blood flow by 71.9+/-15.3% (p<0.005). Infusion of h-CGRP((8-37)) greatly reduced this electrically induced vasodilatation, indicating that CGRP is the principal factor responsible for the vasodilatation observed after tooth stimulation. This study confirms the previous finding that a resting vasodilator tone due to the release of CGRP and SP exists in the ferret dental pulp. It is concluded that spontaneous, basal release of the neuropeptides CGRP and substance P exists both in dental pulp and gingiva in the ferret.

Animals↗

PubMed2000

Neuroendocrine cells in Malassez epithelium and gingiva of the cat.

Malassez epithelium has been designated as epithelial cell rests, the biological significance of which is still under debate. This study was designed to analyze Malassez epithelium for the presence of neuroendocrine cells. Gingival tissue was included as a positive control. Using immunohistochemistry, confocal and light microscopy, Malassez epithelium and gingival epithelium from mature cats (n = 5) were examined for cells containing the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Both Malassez epithelium and the basal epithelial cell layers in gingival rete pegs regularly displayed cells immunoreactive to CGRP, SP, and VIP. The immunopositive cells were most frequently present in the epithelial cell clusters and strands of Malassez located in the cervical half of thc periodontal ligament. Double immunolabeling revealed cellular co-expression of CGRP or SP with VIP, and the neuropeptides were co-localized in the cellular compartments. Labeled cells in both epithelia were occasionally supported by immunoreactive nerve fibers. This study shows that cells immunoreactive to CGRP, SP, and VIP arc located within the cat Malassez epithelium. The localization of neuroendocrine cells verifies the diversity of this epithelium and confirms that Malassez epithelium is composed of different cell types, in common with epithelia from other locations. The presence of neuroendocrine cells in Malassez epithelium strongly suggests biological functions of this tissue, and the neuropeptide content may thus indicate endocrine functions of the cells.

Animals↗

PubMed1999

The role of sensory neuropeptides and nitric oxide on pulpal blood flow and tissue pressure in the ferret.

A study was designed to investigate the effects of close intra-arterial infusion of antagonists to the sensory neuropeptides calcitonin gene-related peptide and substance P, as well as the effect of the nitric oxide synthesis inhibitor L-NAME on pulpal blood flow and interstitial fluid pressure during resting conditions and after electrical tooth stimulation. The micropuncture technique was used to measure tissue pressure and laser-Doppler flowmetry for blood flow recordings in ferret canine teeth. Close intra-arterial infusion of antagonists to calcitonin gene-related peptide and substance P significantly reduced resting blood flow (p < 0.05) and interstitial fluid pressure (p < 0.005) by unchanged systemic arterial pressure, while L-NAME administration caused a significant rise in interstitial fluid pressure (p < 0.05) and systemic arterial pressure (p < 0.005), with a concomitant fall in resting blood flow (p < 0.005). Tooth stimulation after calcitonin gene-related peptide antagonist infusion gave no significant change in blood flow or interstitial fluid pressure, whereas substance P antagonist infusion only partly eliminated the vasodilator response. L-NAME had no effect on the vasodilation induced by tooth stimulation. It is concluded that a resting vasodilator tone due to release of calcitonin gene-related peptide, substance P, and nitric oxide exists in the ferret dental pulp. The sensory neuropeptides exert their effect predominantly on pre-capillary vessels, and nitric oxide predominantly on post-capillary vessels. The sensory neuropeptide calcitonin gene-related peptide seems to be mainly responsible for the increase in blood flow and interstitial fluid pressure during tooth stimulation, whereas there was no evidence that nitric oxide participates in the vasodilation induced by tooth stimulation.

Analysis of Variance↗

PubMed1999

Interstitial fluid pressure in normal and inflamed pulp.

Tissue pressure is the hydrostatic pressure in the interstitial fluid which surrounds the pulpal cells. This pressure outside the vessels is normally considerably lower than the blood pressure inside the vessels. The dental pulp has a relatively low interstitial compliance due to its enclosure between rigid dentin walls. Accordingly, even a modest increase in pulpal fluid volume will raise the tissue pressure, which may compress blood vessels, leading to ischemia and necrosis. Inflammation may lead to an increase in both interstitial fluid volume and blood volume in the low-compliant pulp and thereby increase the tissue pressure. However, the increased tissue pressure may, in turn, initiate increased lymph flow and absorption of fluid into capillaries in nearby non-inflamed tissue. Both of these latter factors will transport fluid out of the affected area and subsequently out of the tooth and consequently lower the tissue pressure. Increased tissue pressure, whether caused by increased blood volume or increased capillary filtration, will promote outward flow of fluid through exposed dentin tubules and thereby help to protect the pulp against entry of harmful substances. It seems physiologically beneficial, therefore, for the pulp to have a high tissue pressure, which promptly increases when blood flow increases due to its low compliance.

Absorption↗

PubMed1998

Nerve fibers immunoreactive to calcitonin gene-related peptide, substance P, neuropeptide Y, and dopamine beta-hydroxylase in innervated and denervated oral tissues in ferrets.

The effect of sensory and sympathetic denervation on the localization and distribution of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and dopamine beta-hydroxylase (DBH) was studied in the dental pulp, periodontal ligament (PDL), and gingiva in ferrets. Unilateral axotomy was performed by resection of the inferior alveolar nerve (IAN) 10 days before the experiment (Group 1); sympathectomy, by unilateral removal of the cervical ganglion 5 days before the experiments (Group 2). Immunohistochemistry was performed on free-floating sections by the avidin-biotin-peroxidase technique. A considerably higher density of sensory fibers IR to CGRP and SP was found in the dental pulp than in PDL and gingiva. The majority of pulpal fibers were located in the walls of blood vessels. A subodontoblastic network of fibers IR to CGRP and SP was lacking in incisors and canines and was found only in the coronal pulp in premolars and molars. Sympathetic fibers were sparsely distributed in the pulp, and they were mainly confined to large vessels running centrally in the root pulp as well as the larger vessels in apical PDL and alveolar bone. Gingiva was well supplied with CGRP- and SP-IR nerves, and some NPY and DBH fibers were located in association with larger vessels. Round cell-like structures within the basal part of the epithelium were CGRP-IR. Axotomy induced a complete loss of CGRP- and SP-IR fibers in the anterior part of the jaws, whereas sympathectomy caused a reduction, but not a total loss, of NPY- and DBH-IR nerves. It is concluded that, except for some distributional differences, the oral tissues in the ferret have an abundant sensory innervation similar to that found in other species.

Alveolar Process↗

PubMed1998

Micropuncture measurements of interstitial fluid pressure in rat nasal mucosa during early inflammatory reactions.

Interstitial fluid pressure (Pif) has been studied in rat nasal mucosa during early inflammatory reactions induced by dextran anaphylaxis and local application of histamine. Pif was measured by using sharpened micropipettes connected to a servo-controlled counterpressure system. Access to the nasal mucosa was obtained from the facial side of the head through a small cavity drilled in the nasal bone. During dextran anaphylaxis, Pif increased significantly from control values of 2.2 +/- 0.4 to 3.8 +/- 0.21 mmHg (P < 0.05) within 1 h. Corresponding Pif values for histamine were 1.6 +/- 0.9 and 2.9 +/- 0.9 mmHg (P < 0.05), respectively. These measurements support the hypothesis that a major driving force for the rapid exudation across inflamed respiratory mucosa is a hydrostatic pressure gradient created by increased mucosa Pif. When the transvascular fluid shifts accompanying the inflammatory reactions are prevented by circulatory arrest, Pif decreased significantly to subatmospheric values, -0.8 +/- 0.8 and -3.3 +/- 1.2 mmHg in the dextran and histamine group, respectively (P < 0.05). The decrease in Pif in the nasal mucosa after inflammatory stimuli, during circulatory arrest, provides further evidence for "active" modulation of Pif through changes in mechanical properties of the interstitial matrix. The decrease in Pif seen under these circumstances reveals a possible mechanism participating in the rapid and initial edema formation after inflammatory provocations.

Animals↗