| 1. |
- Alfredson, Håkan, et al.
(författare)
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Glutamate NMDAR1 receptors localised to nerves in human Achilles tendons. Implications for treatment?
- 2001
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 9:2, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- In this investigation, we show the presence of both free glutamate (microdialysis) and glutamate NMDAR1 receptors (immunohistochemical analyses of tendon biopsies), in tendons from patients with chronic Achilles tendon pain (Achilles tendinosis) and in controls (pain-free tendons). The NMDAR1 immunoreaction was usually confined to acetylcholinesterase-positive structures, implying that the reaction is present in nerves. Glutamate is a potent pain mediator in the human central nervous system, and in animals it has been shown that peripherally administered glutamate NMDA receptor antagonists diminish the response to formalin-induced nociception. Our present finding of glutamate NMDA receptors in human Achilles tendons might have implications for pain treatment.
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| 2. |
- Alfredson, Håkan, et al.
(författare)
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In vivo microdialysis and immunohistochemical analyses of tendon tissue demonstrated high amounts of free glutamate and glutamate NMDAR1 receptors, but no signs of inflammation, in Jumper's knee.
- 2001
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 19:5, s. 881-886
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Tidskriftsartikel (refereegranskat)abstract
- This investigation describes, to our knowledge, the first experiment where the microdialysis technique was used to study certain metabolic events in human patellar tendons in combination with immunohistochemical analyses of tendon biopsies. In five patients (four men and one woman) with a long duration (range 12-36 months) of pain symptoms from Jumper's knee (localized tenderness in the patellar tendon verified as tendon changes with ultrasonography or MRI), and in five controls (four men and one woman) with normal patellar tendons, a standard microdialysis catheter was inserted into the patellar tendon under local anestesia. The local concentrations of glutamate (excitatory neurotransmitter) and prostaglandin E2 (PGE2) were registered under resting conditions. Samplings were done every 15 min during a 2 h period. In all individuals (patients and controls) biopsies were taken for immunohistochemical analyses. The results showed that it was possible to detect and measure the concentrations of glutamate and PGE2 in the patellar tendon with the use of microdialysis technique. There were significantly higher concentrations of free glutamate, but not PGE2, in tendons with tendinosis compared to normal tendons. In the biopsies, there were no inflammatory cell infiltrates, but, for the first time, it was shown that there was immunoreaction for the glutamate receptor NMDAR1 in association with nerve structures in human patellar tendons. These findings altogether indicate that glutamate might be involved in painful Jumper's knee, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in this chronic condition.
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| 3. |
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| 4. |
- Hagert, Elisabet, et al.
(författare)
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General innervation pattern and sensory corpuscles in the scapholunate interosseous ligament.
- 2004
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Ingår i: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 177:1, s. 47-54
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Tidskriftsartikel (refereegranskat)abstract
- The scapholunate interosseous ligament (SLIL) is biomechanically important in maintaining wrist motion and grip strength in the hand, but its possible sensory role in the dynamic muscular stability of the wrist joint has not been examined. The aim of this study was to use immunohistochemical methods to analyze the general innervation and the possible existence of sensory corpuscles in the SLIL. The ligament was excised in its entirety from 9 patients. Antibodies against the low-affinity p75 neurotrophic receptor (p75) were used to reveal sensory corpuscles as well as general innervation. Furthermore, antibodies against the general nerve marker protein gene product 9.5 (PGP 9.5) and the glial marker S-100 were used to additionally depict innervation and corpuscular structures. Blood vessels occurred in areas interspersed throughout the homogeneous collagenous structure. In these vascularized areas, the SLIL was found to be supplied with nerve fascicles and sensory corpuscles of both the Ruffini and lamellated type. p75 immunoreactivity (IR) was detected in association with the nerve fascicles and the corpuscles, particularly in their capsule. S-100 IR was found in the Schwann cells in the central regions of the corpuscle, and PGP 9.5 IR marked the axonal structures in the corpuscles. New information on neurotrophin receptor distribution in ligaments has been obtained here. The presence of nerve fascicles and particularly sensory corpuscles in the SLIL suggests that the ligament has a proprioceptive role in the stability of the wrist. The marked p75 IR further indicates that neurotrophins play a part in a proprioceptive system in the ligament, given the importance of neurotrophins in maintaining sensory function.
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| 5. |
- Hansson, Magnus, et al.
(författare)
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Expression of brain natriuretic peptide in the rat heart studies during heart growth and in relation to sympathectomy
- 2004
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Ingår i: Microscopy research and technique (Print). - : Wiley. - 1059-910X .- 1097-0029. ; 64:1, s. 30-42
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Tidskriftsartikel (refereegranskat)abstract
- Brain natriuretic peptide (BNP) might be of importance during heart development and is described to be increasingly expressed in congestive heart failure and to affect the progress of this condition. However, details in the normal expression of BNP are still unclear in various parts of the adult and growing heart, including the conduction system. In this study, we investigated the expression of BNP in relation to that of atrial natriuretic peptide (ANP) in the growing as well as in the adult rat heart. The effects of chemical sympathectomy in adult rats were also examined. Contrary to previous BNP immunohistochemical studies, the BNP antiserum was preabsorbed with an excess of ANP before staining to abolish the crossreactivity with ANP. There was a pronounced BNP immunoreaction in the auricles, the trabeculated ventricular walls, and the peripheral parts of the conduction system at 0-1 days postnatally. The degree of immunoreaction gradually decreased with increasing age. A similar developmental pattern was seen concerning ANP expression, but the magnitude of the latter clearly exceeded that for BNP. Immunoreaction for BNP was never detected in the atrioventricular (AV) node and AV bundle at any stage. In contrast to the situation for ANP previously observed, no obvious changes in BNP immunoreaction patterns were observed in response to sympathectomy. This is the first study to thoroughly demonstrate the expression of BNP in the various regions of the rat heart during growth and in the normal and sympathectomized adult stage. The observations are related to possible functions of natriuretic peptides in the growing and adult heart.
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| 6. |
- Höckerfelt, U, et al.
(författare)
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Early increase and later decrease in VIP and substance P nerve fiber densities following abdominal radiotherapy : a study on the human colon.
- 2002
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 78:11, s. 1045-53
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) mediate physiologic activities in the intestine, not least in relation to motility and inflammatory processes. Neuropeptides are up-regulated and play particular importance during tissue stress. This paper aims to quantify mucosal and smooth muscle SP, VIP and total innervation in human colon in short- and long-term perspectives after abdominal irradiation.MATERIALS AND METHODS: Colon specimens from 23 irradiated or non-irradiated patients were investigated with immunohistochemistry and computerized image analysis. Plasma levels of SP and VIP in 15 additional patients receiving radiotherapy were analyzed.RESULTS: At 4-7 days after irradiation (5 x 5 Gy), the overall innervation, and also VIP and SP nerve fiber densities, were increased in both mucosa and circular muscle layer. In contrast, 5-6 weeks as well as several years after irradiation, the VIP and SP nerve fiber densities were decreased. No peptide changes were revealed in plasma.CONCLUSIONS: The degree of VIP and SP intestinal innervation was increased after radiotherapy in the short-term perspective but it decreased in the long-term. In the short-term, SP may have pro-inflammatory and VIP anti-inflammatory effects and the peptides may have trophic effects and be related to the occurrence of motor changes. It cannot be excluded that the decrease in VIP and SP neuronal supply seen in the long-term may contribute to intestinal malfunction.
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| 7. |
- Ljung, Björn-Ove, et al.
(författare)
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Neurokinin 1-receptors and sensory neuropeptides in tendon insertions at the medial and lateral epicondyles of the humerus. Studies on tennis elbow and medial epicondylalgia.
- 2004
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Ingår i: Journal of Orthopaedic Research. - 0736-0266. ; 22:2, s. 321-7
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Tidskriftsartikel (refereegranskat)abstract
- There is no information on the sensory innervation at the flexor muscle origin at the medial epicondyle of the humerus and it is not known if substance P receptors (Neurokinin 1-receptors, NK1-R) are present in tendon insertions in general. In the present investigation, we have studied the muscle origin in patients suffering from medial epicondylalgia and tennis elbow. Immunohistochemistry and antibodies to substance P (SP) and CGRP as well as the general nerve marker PGP 9.5 were used. Specific immunoreactions were observed in nerve bundles and as free nerve fibers. The immunoreactive structures were partly seen in association with some of the blood vessels. The observations constitute a morphological correlate for the occurrence of nerve mediated effects in this region. By using immunohistochemistry and antibodies to NK1-R, the distribution of this receptor was studied at the insertion of the proximal tendon of the extensor carpi radialis brevis muscle at the lateral epicondyle. Specific immunoreactions were seen as varicose fibers occurring as single fibers or grouped into bundles, indicating that SP has effects in the nerves in this region. The results give further evidence for a possible neurogenic involvement in the pathophysiology of tennis elbow and in medial epicondylalgia.
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| 8. |
- Matsunaga, Noriko, et al.
(författare)
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Advanced glycation end products (AGE) and the receptor for AGE are present in gastrointestinal tract of familial amyloidotic polyneuropathy patients but do not induce NF-kappaB activation.
- 2002
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 104:5, s. 441-7
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Tidskriftsartikel (refereegranskat)abstract
- Familial amyloidotic polyneuropathy (FAP), Portuguese type, is a hereditary amyloidosis caused by mutated transthyretin (ATTR) in which an exchange of valine for methionine at position 30 has taken place (ATTR Val30Met). Gastrointestinal complications, such as nausea, diarrhoea and malabsorption, have a significant impact on survival since the cause of death in the majority of cases is a consequence of extreme malnutrition due to dysmotility of the gastrointestinal tract. Recently, a role of the receptor for advanced glycation end products (RAGE) has been implicated in amyloid toxicity. Transthyretin (TTR) amyloid fibrils have been shown to have affinity for RAGE and subsequently induce NF-kappaB activation and apoptosis. Since gastrointestinal dysfunction plays an important role in FAP, we wanted to investigate if amyloid toxicity in the gastrointestinal tract is related to RAGE, NF-kappaB activation and apoptosis. Gastrointestinal tract autopsy samples were studied for the distribution of amyloid, RAGE, advanced glycation end products (AGE) and NF-kappaB. Furthermore, we examined the immunoreactivity of an apoptotic marker to investigate if an apoptotic pathway contributes to amyloid toxicity. The distribution of RAGE and AGE strongly correlated to that of amyloid deposits. Sequential immunofluorescence staining revealed a clear relationship between TTR, AGE and RAGE. No correlation between NF-kappaB, apoptotic marker and amyloid deposits was found. We conclude that RAGE-AGE or RAGE-TTR interaction might play important roles for gastrointestinal dysfunction and amyloid toxicity, although not through NF-kappaB activation and apoptosis.
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| 9. |
- Westermark, T, et al.
(författare)
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Increased content of bombesin/GRP in human synovial fluid in early arthritis : different pattern compared with substance P
- 2001
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 19:6, s. 715-720
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Tidskriftsartikel (refereegranskat)abstract
- Objective Bombesin (BN) and the mammalian homologue gastrin-releasing peptide (GRP) are known trophic factors, neurotransmitters and paracrine hormones. BN/GRP has not previously been demonstrated in synovial fluid. In this study, the amounts of BN/GRP and substance P (SP) present in synovial fluid from the knee joints of patients with rheumatoid arthritis (RA) and of healthy, controls were measured. Methods Synovial fluid from the knee joint was collected from patients with either longstanding RA (n = 32) or early arthritis (symptoms for < 12 months; n = 9) and from control subjects, i.e., individuals without known joint disease (n = 10). These samples were analyzed using radioimmunoassays. Results Levels of BN/GRP-like peptide were below the assay detection limits in synovial fluid from controls. Detectable levels of immunoreactive BN/GRP were present in the majority of patients with either longstanding RA or early arthritis. The levels were significantly higher in the synovial fluid from patients classified as having early, arthritis compared with those with longstanding RA (p < 0.05). There was a strong correlation between BN/GRP levels and the number of leukocytes in the synovial fluid in the patients with early arthritis. The levels of SP-like peptide in the patients, whether with early arthritis or longstanding RA, were significantly elevated compared with controls. However there was no difference in the levels between these two patient groups. Conclusions These observations show that BN/GRP-like peptide is present in the synovial fluid of joints affected by arthritis and that the pattern of BN/GRP increase differs from that of SP It appears as if the presence of BN/GRP is particularly related to the early processes of joint involvement. These observations are of interest because BN/GRP has well-known trophic and paracrine effects and chondrocytes have recently been shown to produce neuropeptides such as BN/GRP.
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