Biomedical subjects

T Lundeberg

Publications and source records attributed to T Lundeberg.

At least 109 records · Page 6Linked to original sources

PubMed1997

Expression of corticotropin-releasing factor in the peripheral nervous system of the rat.

The occurrence and distribution of corticotropin-releasing factor (CRF) in the rat peripheral nervous system was studied by immunohistochemistry. CRF-positive nerve fibers were identified in the spleen, thymus, synovial membrane of the knee joint and adrenal gland. In general, CRF-positive fibers were seen predominantly in and around the blood vessels; however, many non-vascular thin varicose fibers were also observed. The neuronal character of the immunoreactive fibers was confirmed by staining consecutive tissue sections with a general neuronal marker, protein gene product 9.5. The finding of CRF-positive nerve fibers in the periphery demonstrates a strong anatomical link between the nervous, endocrine and immune systems, and may have pathophysiological implications in the inflammatory and stress-related disorders.

Animals↗

PubMed1997

Oxytocin decreases blood pressure in male but not in female spontaneously hypertensive rats.

The aim of the present study was to investigate the effects of repeated injections of oxytocin on blood pressure and heart rate in spontaneously hypertensive rats (SHR). For this purpose subcutaneous (s.c.) injections of oxytocin 1 mg/kg or saline were given for 5 days to male and female SHR. Blood pressure and heart rate were measured daily before, during and after the oxytocin treatment period. In male rats, a significant decrease in blood pressure (systolic; p < 0.01, diastolic; p < 0.05), but no effect on heart rate, was seen the day after the first injection of oxytocin, when compared to saline-treated controls. Blood pressure decreased further in response to each injection and a maximal difference of 21 mmHg (systolic) (p < 0.01), compared to controls, was reached after the last injection. The significant effect was gone 3 days after the last injection, although a tendency to a lower blood pressure in the oxytocin-treated rats persisted. On day 10, the oxytocin-treated SHR males again had a significantly lower systolic blood pressure (p < 0.05). In female SHR, the same treatment with oxytocin affected neither blood pressure nor heart rate. These results show that oxytocin may cause a sustained decrease in blood pressure, without affecting heart rate, in male but not in female SHR.

Animals↗

PubMed1997

Olfactory cues from an oxytocin-injected male rat can reduce energy loss in its cagemates.

Rats can recognize the odor of a stressed conspecific and react with stress themselves. Stress mobilizes energy, causing increased core temperatures and energy loss by radiation from the naked tail. Oxytocin administered in high doses (1 mg/kg, s.c.) reduces a rat's tail skin temperature and thereby the radiated energy loss. While administration of this high dose of oxytocin induces sedation low doses induce anxiolysis. This study demonstrates that the cagemates of an oxytocin-treated (1 mg/kg s.c.) rat, which themselves have not received any oxytocin-treatment, show energy conservation, apparent as reduced tail skin temperature. This effect was blocked by olfactory impairment. The temperature reduction in the cagemates probably reflects an oxytocin-mediated olfactorily activated stress inhibitory mechanism.

Animals↗

PubMed1997

Interleukin-1beta sensitizes the response of the gastric vagal afferent to cholecystokinin in rat.

Interleukin-1beta (IL-1beta) and cholecystokinin (CCK) are important mediators in the development of anorexic response during disease. The role of IL-1beta and CCK in the peripheral mechanisms of anorexia was studied by recording the mass afferent activity of the gastric vagal nerve in anesthetized rats. The i.v. administration of CCK (1 nmol) increased the activity of the vagal nerve, and this response was raised by 55-72% 2 h after i.v. injection of IL-1beta. It is proposed that IL-1beta-induced anorexia is mediated via the sensitization of type A CCK receptors in the periphery.

Animals↗

PubMed1997

Effects of histamine on neuropeptide release into the knee joint perfusate and cerebrospinal fluid in rats.

In the present study we examined the effect of histamine injection on neuropeptide release in vivo in rats. Rats were injected with histamine either into the left knee joint or intraperitoneally. Concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (-LI) were examined in the knee joint perfusates and cerebrospinal fluid at 2, 6 and 24 h following injection, by radioimmunoassay. Results show that intraarticular injection of histamine induced a bilateral release of SP-, NKA- and CGRP-LI in the knee joint perfusates while intraperitoneal injection of histamine induced a release of SP-, NKA- and CGRP-LI into the cerebrospinal fluid. No changes in concentrations of NPY-LI were observed following histamine injection. Results of the present study indicate that histamine selectively stimulates sensory neurons without affecting sympathetic. The increased concentrations of sensory neuropeptide-LI in the cerebrospinal fluid following intraperitoneal administration of histamine indicate a new mechanism by which histamine may exert systemic effects during inflammation and allergy.

Animals↗

PubMed1997

Interleukin-1 increases activity of the gastric vagal afferent nerve partly via stimulation of type A CCK receptor in anesthetized rats.

The response of mass activity of the gastric vagal afferent nerve to intravenous administration of interleukin-1 beta (IL-1 beta) and the involvement of cholecystokinin (CCK) in the response were investigated in pentobarbital-anesthetized rats. Intravenous administration of 2 micrograms.kg-1 of IL-1 beta caused an increase in the afferent activity, which reached 150% of control activity by 30 min after administration and persisted for more than 80 min. The increase in the nerve activity was significantly reduced in animals pretreated with a type A CCK receptor antagonist. IL-1 beta also significantly increased the CCK concentration in systemic blood. Furthermore, it was confirmed that intravenous administration of CCK produced an increase in the nerve activity via the type A CCK receptor. These findings suggest that systemically applied IL-1 beta increases CCK concentration in systemic blood secreted from mucosal endocrine cells of the small intestine, and that in turn CCK in the gastric blood flow augments or partly participates in the IL-1 beta-induced excitation of the gastric vagal afferent nerve via stimulation of the type A CCK receptor in the stomach. A possible involvement of IL-1-related excitation of the gastric vagal afferent nerve in IL-1-induced anorexia is discussed.

Animals↗

PubMed1997

Effects of environmental stress on tissue survival and neutrophil recruitment in surgical skin flaps in relation to plasma corticosterone levels in the rat.

OBJECTIVE: Because glucocorticoid treatment can improve the survival of surgical skin flaps, we examined the influence of environmental stress on skin flap survival in the rat. MATERIAL: Female Sprague-Dawley rats. TREATMENT: Dexamethasone (1 mg/kg i.p.). METHODS: A standardized dorsal skin flap was raised and sutured back into position, and six days latter the percentage of flap survival was assessed. Corticosterone in rat plasma was measured using radioimmuno assay, and skin flap myeloperoxidase accumulation (reflecting neutrophil recruitment) was determined spectrophotometrically. RESULTS: Skin flap survival decreased gradually during a 10 day acclimatization period after transportation of the animals from the supplier, and plasma corticosterone levels were increased during the first 5 days of acclimatization compared to day 7 and 10. Dexamethasone treatment of rats accustomed to their new environment for 10 days increased flap survival to a level close to that observed in animals operated at day 1 after arrival. Flap surgery induced pronounced neutrophil recruitment into flap tissue, and this cell accumulation was greatly reduced in both the dexamethasone treated rats and in rats with elevated corticosterone levels. CONCLUSIONS: Skin flap survival in rats exposed to environmental stress may be significantly increased as compared to animals accustomed to their new environment for one week, possibly as a consequence of anti-inflammatory actions exerted by stress-induced elevations in plasma corticosterone. These findings emphasize the importance of strictly controlling environmental stress factors in studies of inflammation and tissue damage after surgical skin trauma.

Animals↗

PubMed1997

Effects of capsaicin in temporomandibular joint arthritis in rats.

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P-(SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.

Animals↗

PubMed1997

Nitric oxide synthase activity and endothelial ultrastructure in ischaemic skin-flaps.

The aim of the present study was to detect and quantify nitric oxide synthase (NOS) activity and to investigate morphological changes in the endothelium in two different ischaemic dorsal flap models in the rat, one based cranially and one based caudally. Intact skin from the dorsum was used as control. In both groups flaps were removed at 1, 4, 12, 24 and 72 h after surgery respectively. NOS-activity was measured by the conversion of L-arginine to L-citrulline and endothelial morphology was investigated using transmission electron microscopy. Intact skin showed Ca(2+)-dependent but no Ca(2+)-independent NOS-activity. A time-dependent decrease in Ca(2+)-dependent NOS-activity was seen in the proximal and distal part of the flaps in both flap models and was most pronounced in the distal part. Ca(2+)-independent NOS-activity increased in the proximal and distal part of flaps based cranially and in the proximal part of flaps based caudally. Morphological analysis of the endothelium showed signs of endothelial damage including blebbed membranes, swelling and endothelial loss. These findings show that ischaemia caused by skin-flap surgery leads to endothelial damage and a decrease in Ca(2+)-dependent nitric oxide synthase activity. Furthermore, in the skin-flaps an induction of Ca(2+)-independent nitric oxide synthase (iNOS) activity was noted both in surviving flap tissue and in flap tissue destined to necrose.

Animals↗

PubMed1997

Neuropeptides in the saliva of healthy subjects.

Five neuropeptides: Substance P (SP), Neurokinin A (NKA), Calcitonin Gene-Related Peptide (CGRP), Neuropeptide Y (NPY) and Vasoactive Intestinal Polypeptide (VIP), were measured in the saliva of eight subjects. The saliva was collected using different stimulation techniques: whole resting saliva, whole paraffin stimulated saliva, whole citric acid stimulated saliva and parotid saliva of different secretion rates -0.25 mL/min, 0.50 mL/min and 1.00 mL/min, also stimulated by citric acid. The neuropeptides were analysed by radioimmunoassay. The results showed that the concentration of all neuropeptides decreased significantly, two- to four-fold (CGRP up to 16-fold) in whole saliva, when the salivary secretion rates increased six- to eight-fold due to stimulation. However, the amounts of all neuropeptides released over time into the whole saliva increased two- to five-fold (ten-fold for CGRP) as the volumes of saliva increased due to chewing-stimulation as compared to resting saliva or citric acid stimulated saliva. There was also more CGRP in the resting saliva than in the citric acid stimulated saliva. The concentration of CGRP in the parotid saliva decreased three- to ten-fold when the salivary flow increased, whereas the concentration of NKA increased three- to four-fold and that of NPY almost two-fold under the same conditions. The concentrations of SP and VIP did not change in the different flows of parotid saliva. The release of all neuropeptides in the parotid saliva over time showed significant increases (3-14-fold) when the secretion rates increased except CGRP, which showed no changes at all. We concluded that neuropeptides are continuously released into the saliva. Their amounts increase with stimulation, but they are diluted by the increased volume of saliva, and they are also affected by the mode of stimulation-muscular activity leads to a greater release than citric acid stimulation. As the neuropeptides play an important role in the control of salivary secretory mechanisms, their normal occurrence and release are of fundamental importance for the understanding of the function of the salivary glands.

Adult↗

PubMed1997

Intrathecal CGRP(8-37) results in a bilateral increase in hindpaw withdrawal latency in rats with a unilateral thermal injury.

The present study was performed to explore the effects of intrathecal administration of calcitonin gene-related peptide8-37 (CGRP(8-37)) on the hindpaw withdrawal latency (HWL) to pressure in rats with one thermally injured hindpaw. Furthermore, the interaction of CGRP(8-37)and naloxone was studied. Thermal injury was performed by dipping the left paw into 60 degrees C for 20 s. This induced a significant increase in the volume of the left hindpaw (P<0.001) and significant bilateral decreases of the latency of hindpaw withdrawal response to mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administration of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a significant bilateral increase in HWLs (P<0.001). The effect of CGRP(8-37) was partly reversed by intrathecal injection of naloxone at a dose of 32 and 64 microg respectively. Using radioimmunoassay, we found a significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws 24 h after unilateral thermal injury (left: P< 0.001; right: P< 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P< 0.001), but not in plasma. The results indicate that CGRP plays a role in the transmission of nociceptive information in the spinal cord of thermally injured rats. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.

Animals↗

PubMed1997

An experimental study of the neurogenic and the immunological contribution to "tennis elbow" in rats.

In the present study the content of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (-LI) was measured in rats cerebrospinal fluid (CSF), plasma and perfusates (PF) from both elbow enthesis during acute inflammation. Either substance P, SP, (10-5 M, 0.01 ml) or human recombinant interleukin-1 alpha (hrIl-1 alpha, 0.01 ml) were injected into the right enthesis of the extensor carpi radialis brevis (ECRB). The left ECRB and both ECRBs of control rats, were injected with 0.01 ml saline. Samples of CSF, plasma and PF from both ECRBs were obtained at 2, 6, and 24 h following injection and neuropeptide-LI was analysed by specific radioimmunoassays. Neuropeptide-LI was compared with control values and between the treated groups. In both treated groups NKA- and CGRP-LI was increased in CSF and NKA-LI decreased in plasma, while CGRP- and NPY-LI were raised to a similarly significant degree in the enthesis of the ECRB. SP-LI was increased in ECRB PF in comparison with controls and NKA-LI levels were higher in the hrIl-1 alpha group both in comparison with controls and between treated groups. In summary an unilateral injection of either SP or hrIl-1 alpha into the enthesis of the ECRB of the rat showed a similar influence at 2, 6, and 24 h following injection. The most pronounced changes in neuropeptide-LI occurred in the ECRB PF of both treated groups.

Animals↗

PubMed1997

Acute microcirculatory changes after scalding of the rat paw.

A scalding model in the anaesthetized rat was used to measure acute circulatory reactions after heat exposure. Local blood flow of both hindpaws was recorded simultaneously and continuously by laser Doppler flowmetry before, during and for 2 hours following scalding. The scalding injury was inflicted by dipping the right hindpaw into hot water at 60 degrees C for 20 s. Concomitantly, the mean arterial blood pressure (MAP) was displayed on a chart recorder. MAP was obtained by cannulation of the common carotid artery. Oedema formation was calculated by measuring the volume changes of the hindpaws in a plethysmometer before and 30, 60 and 120 min after scalding. Scalding was followed by a biphasic increase of cutaneous circulation. During the first minute after heat provocation, an immediate increase in blood perfusion of about 400% was recorded, followed by a slow decrease of circulation. At 30 min after scalding, there was a secondary phase of increased microcirculation of approximately 230%. A slow decline of cutaneous circulation then followed, and after about 60 min the value was stabilized at approximately 100% above pre-burn level throughout the observation time. Almost no change of perfusion was observed on the contralateral unscalded paw. The scalding injury was followed by a progressive oedema formation on the scalded paw, measured by a volume increase of approximately 72% during the observation period, whereas the non-scalded paw showed no change. MAP remained at a stable level throughout the experiment except for a short-lasting transient increase of approximately 10% at the same time as the first peak of blood perfusion. We could thus confirm that scalding in the present model is accompanied by an immediate and marked increase in the peripheral circulation of the scalded paw followed by a later propagation of oedema, and that these inflammatory changes do not appear to be related to central haemodynamic alterations.

Animals↗

PubMed1997

Intrathecal adenosine analog administration reduces substance P in cerebrospinal fluid along with behavioral effects that suggest antinociception in rats.

UNLABELLED: Adenosine and adenosine analogs induce analgesia in humans and presumed antinociception in animal models when administered both systemically and intrathecally. In the present investigation in rats, we studied the effects of intrathecally administered adenosine analogs, with or without systemic coadministration of an adenosine antagonist (theophylline), on substance P (SP) and calcitonin gene-related peptide (CGRP) concentrations in cerebrospinal fluid (CSF). In parallel, nociceptive reflex testing (tail immersion latency) and motor function were evaluated. The potent unselective adenosine receptor agonist N-ethylcarboxamide-adenosine (NECA) and the relatively adenosine A1 receptor selective agonist R-phenyl-isopropyl-adenosine (R-PIA) both reduced SP-like immunoreactivity (-LI) by 50%, whereas CGRP-LI remained unchanged. There was a dose-dependent increase in tail immersion latency. This effect was present without motor impairment when R-PIA was administered in doses up to 5 nmol. R-PIA (10-100 nmol), as well as 1-100 nmol of the unselective agonist NECA, produced dose-dependent motor impairment. The reduction of SP-LI as well as the behavioral effects were reversed by theophylline. We conclude that SP reduction in CSF, which possibly reflects reduced SP turnover after adenosine receptor stimulation, provides an additional possible mechanism of action for the analgesic effects of adenosine. IMPLICATIONS: We studied the interactions between the known pain mediator substance P and substances with effects similar to the endogenous pain modulator adenosine in rats. The results suggest that the pain-reducing effect of adenosine is, at least partly, due to a reduction of substance P in cerebrospinal fluid.

Adenosine↗

PubMed1997

Cell adhesion and short-term patency in human endothelium preseeded 1.5-mm polytetrafluoroethylene vascular grafts: an experimental study.

It has been shown that endothelialization improves short-term patency of 1.5-mm expanded polytetrafluoroethylene vascular grafts. A model for endothelialization of 1.5-mm expanded polytetrafluoroethylene vascular grafts with human endothelial cells is described. In this model, the adherence of endothelial cells was increased significantly in grafts coated with serum proteins and collagen. By means of this protocol, graft patency was tested after implantation in two animal models: the rat aorta and the rabbit common carotid artery. Anastomosis was performed with a 3M Precise Microvascular Anastomotic System. In both animal models, no significant loss of endothelial cells in the precoated grafts (rat, n = 8) were noted 1 hour after blood flow restoration. All uncoated grafts showed significant endothelial cell loss. In the rabbit model, all nonendothelialized grafts (n = 8) clotted 5 to 25 minutes after flow restoration. Seven (n = 8) endothelialized grafts showed no clotting during 1 hour's observation: one clotted immediately for a patency rate of 87.5 percent. These results indicate that endothelialization of 1.5-mm grafts is practical. Furthermore, adhesion of endothelial cells to the graft walls is not affected by short-term, pulsatile, high-pressure blood flow.

Animals↗

PubMed1997

Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery.

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.

Administration, Topical↗

PubMed1997

The influence of acupuncture on salivary flow rates in healthy subjects.

This study investigated the influence of acupuncture stimulation on the salivary secretion of eight healthy subjects. The salivary flow of each subject was measured before, during and after every acupuncture session. The unstimulated, chewing-stimulated and citric acid-stimulated flows were investigated, in combination with manual and electrically stimulated acupuncture. The results showed a significant increase of the unstimulated salivary flow both during and after the manual acupuncture stimulation as compared to baseline levels. There was no effect on the unstimulated salivary flow with electro-acupuncture. The stimulated salivary flow was not affected by manual acupuncture, while the electrically stimulated acupuncture led to a significant decrease of the chewing-stimulated salivary flow. The improvement of the unstimulated salivary secretion in healthy subjects was in accordance with our previous findings in xerostomic patients. It is possible that the salivary secretion is influenced by the augmented release of neuropeptides caused by acupuncture. Some neuropeptides have been shown to affect salivary secretion as well as capillary blood flow.

Acupuncture Therapy↗

PubMed1997

Effects of adjuvant on neuropeptide-like immunoreactivity in the temporomandibular joint and trigeminal ganglia.

To study the role of the nervous system in temporomandibular joint arthritis, substance P-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the trigeminal ganglia and temporomandibular joint of rats was examined. Arthritis was induced in female Lewis rats through bilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the temporomandibular joint. Control rats received paraffin oil via the same route. Tissues were collected for neuropeptide extraction 28 days after injection and analyzed by radioimmunoassay and reverse-phase high-performance liquid chromatography. Calcitonin gene-related peptide was significantly increased in the arthritic trigeminal ganglia. Substance P, calcitonin gene-related peptide, and neuropeptide Y in the arthritic temporomandibular joint were significantly increased as compared to controls. The results of this study show that sensory and sympathetic neuropeptides may possibly be associated with the development of arthritis in the temporomandibular joint of rats.

Animals↗