Serum concentrations of 17beta-estradiol in ovariectomized rats during two times six weeks crossover treatment by daily injections in comparison with slow-release pellets.

Estrogens exert widespread biological functions that reach far beyond their well-known role in reproduction. Exogenous administration of 17beta-estradiol to ovariectomized experimental animals is of the utmost importance in elucidating its mechanisms of action. In the present study, we compared two different modes of exogenous administration of 17beta-estradiol to ovariectomized rats in relation to the serum 17beta-estradiol concentrations over prolonged periods of time. 17beta-estradiol was administered either by slow-release pellets (Innovative Research of America, Sarasota, Fl. 34236, USA, 90-day release, NHH-115, 1.5 mg) or by daily subcutaneous injections of 15 microg 17beta-estradiol dissolved in sesame oil. After 6 weeks, the mode of administration of estradiol was changed to the opposite method and continued for a further 6 weeks. Blood samples for measurement of serum 17beta-estradiol were taken every second week. After 2 weeks, the serum concentrations of 17beta-estradiol in group A initially receiving the pellets were 73 % higher (p<0.001) compared to those of group B receiving daily injections. The difference was even more prominent, 580 % (p<0.001), after 4 weeks. Steady state was reached at week 6 in group A, but already by week 4 in group B. Once steady state was reached, the concentrations were the same in both groups for the remainder of the experiment (12 weeks in total). Our study indicates that steady-state concentrations of 17beta-estradiol occur 5-6 weeks later than the 48 h the manufacturer of the slow-release pellets claims.

Altered levels of neuropeptides characterize the brain of lupus prone mice.

It has been reported that more than 50% of lupus patients show various forms of neurological deficits including impaired cognitive functions and psychiatric disorders. Using an animal model of lupus we investigated the production of neuropeptides in the brain of NZB/W F1 female hybrid mice and its parental strain NZB and NZW. Our results indicate that the alteration in learning and memory described in lupus mice are paralleled by a decrease in calcitonin gene-related peptide, substance P and neuropeptide Y (NPY) levels in the hippocampus and a significant decrease of NPY in the cortex. These findings are interesting in the light of previously reported results suggesting that these neuropeptides can play an important role in cognitive functions. We also observed a decrease of NPY and vasoactive intestinal polypeptide levels in the hypothalamus of lupus prone mice and these changes may be related to the disregulation of the hypothalamus-pituitary-adrenal axis observed in lupus prone mice.

Synovial fluid sampling from the temporomandibular joint: sample quality criteria and levels of interleukin-1 beta and serotonin.

The aims of this study were to compare two sets of quality criteria (SQC A and B) with respect to synovial fluid (SF) sampling and to present temporomandibular joint (TMJ) SF levels of IL-1 beta and 5-HT. The study comprised 310 TMJ SF samples from 12 healthy individuals (HI) and 59 patients with TMJ inflammatory disorders. Ten HI and 37 patients were selected for investigation of TMJ SF levels and samples were obtained by a push-and-pull method with quantification by vitamin B12. The SQC comprised aspirate weight (AW), dilution factor (DF), blood contamination and hemolysis. IL-1 beta and 5-HT levels did not differ between the samples that satisfied SQC A or B. The proportion of samples that satisfied SQC A was higher than for SQC B. Patients with polyarthritides had significantly higher TMJ SF concentrations of 5-HT and IL-1 beta than HL. In conclusion, there is a recovery of TMJ SF of 0.1-0.2 g with the method used and the criteria set with the highest success rate do not differ from the other one with respect to SF levels of IL-1 beta and 5-HT. This set of sample quality criteria comprised no hemolysis, no or only minor blood contamination, AW > 0.5 g and DF < 0.98. The higher SF levels in the diseased TMJ (polyarthritides) compared to the healthy joint with respect to 5-HT and IL-1 beta is of clinical diagnostic relevance and the presence of 5-HT or IL-1 beta in TMJ SF seems to indicate a pathological joint condition probably of an inflammatory nature.

Sensory stimulation (acupuncture) increases the release of calcitonin gene-related peptide in the saliva of xerostomia sufferers.

Over the last decade, several patients afflicted with xerostomia have been treated with acupuncture. Their salivary flow rates increased significantly and the improvement lasted during a long observation period. We also found that the release of several neuropeptides in the saliva of healthy subjects can be increased by acupuncture stimulation. The concentration of vasoactive intestinal polypeptide increased significantly in the saliva of xerostomic patients after acupuncture treatment. The release of the neuropeptide calcitonin gene-related peptide (CGRP) was investigated in the saliva of xerostomic patients in order to elucidate further the mechanisms of the effect of sensory stimulation (acupuncture) on the salivary secretion. CGRP-like immunoreactivity was measured with radioimmunoassay (RIA) before and after a double series of acupuncture treatment, in stimulated saliva of 14 patients who suffered from xerostomia. The results showed that the concentration of CGRP increased significantly (P<0.001) in the saliva of these patients after the end of acupuncture treatment as compared to base-line levels. Taking into consideration the influence of CGRP on the salivary flow, as well as its trophic effect, we concluded that the increased release of CGRP could be one of the factors that affect positively the salivary flow rates of xerostomic patients who were treated with acupuncture.

Changes in dietary fatty acids alter phospholipid fatty acid composition in selected regions of rat brain.

1. Eighty rats were randomized into four groups receiving one of the following diets: rat chow containing (1) 6% soybean oil, (2) 6% primrose oil, (3) 6% fish oil, (4) a combination of 4.5% primrose and 1.5% fish oil. 2. Following two months of each regimen, the rats were sacrificed by microwave irradiation and the brain's fatty acid composition was analysed with gas chromatography for each of the following regions: frontal cortex, striatum, occipital cortex, hippocampus, hypothalamus, cerebellum and pituitary. 3. Linoleic acid was decreased by both primrose and fish oil supplementations. The fish oil substitution resulted in a significant elevation of 20:3n-6, a decrease of 22:4n-6 and a non-significant decrease of 20:4n-6, probably reflecting inhibition of delta-5-desaturation. At the same time the fish oil diet significantly elevated 22:5n-3 while 22:5n-6 was decreased. 4. The primrose oil diet lowered the n-3/n-6 ratio in all regions except in the cerebellum. In contrast, the fish oil diet elevated the n-3/n-6 ratio in all regions. 5. The results demonstrate that changes in dietary fat composition can alter the fatty acid composition of the adult rat brain and that these effects are region specific. 6. This is of interest since metabolites of essential fatty acids may be involved in physiological and pathological processes in the brain and it has been hypothesized that dietary intake of fats may influence the outcome of psychiatric disorders such as schizophrenia.

The influence of sensory stimulation (acupuncture) on the release of neuropeptides in the saliva of healthy subjects.

In recent studies we have shown that xerostomia (dry mouth) can be treated successfully with sensory stimulation (acupuncture). The increase of saliva secretion lasted often for at least one year. Some neuropeptides have been found to influence the secretion of saliva. The aim of this study was to investigate the mechanisms behind the effect of acupuncture on salivary secretion by measuring the release of neuropeptides in saliva under the influence of sensory stimulation. VIP-like immunoreactivity (VIP-LI), NPY-LI, SP-LI, CGRP-LI and NKA-LI were analysed in the saliva of eight healthy subjects. Manual acupuncture and acupuncture with low-frequency electrical stimulation (2 Hz) were used. The saliva was collected during 20 minutes before the start of acupuncture stimulation, then during 20 minutes while the needles were in situ and then for another 20 minutes after the needles were removed. Four different saliva sampling techniques were used: whole resting saliva, whole saliva stimulated by paraffin-chewing, whole saliva stimulated by citric acid (1%), and parotid saliva, also stimulated with citric acid (1%). The results showed significant increases in the release of CGRP, NPY and VIP both during and after acupuncture stimulation, especially in connection with electro-acupuncture. SP showed only few increases, mainly in connection with electro-acupuncture, whereas NKA generally was unaffected by the acupuncture stimulation. The sensory stimulation-induced increase in the release of CGRP, NPY and VIP in the saliva could be an indication of their role in the improvement of salivary flow rates in xerostomic patients who had been treated with acupuncture.

Substance P-associated increase of intra-articular temperature and pain threshold in the arthritic TMJ.

Neuropeptides are considered mediators and modulators of inflammatory joint disease. Substance P (SP) has been proposed as a mediator of pain, and its vasoactive properties are well documented. In this study, the presence of SP-like immunoreactivity in the synovial fluid was correlated to intra-articular temperature (IAT) and pain from the arthritic temporomandibular joint (TMJ) 3 to 5 weeks after one intra-articular injection of glucocorticosteroids. Eighteen TMJs were investigated for IAT and the presence of SP-like immunoreactivity in the synovial fluid in 12 patients with systemic inflammatory joint disease. After arthrocentesis, the aspirates were analyzed for SP-like immunoreactivity by means of competitive radio immunoassay. A visual analogue scale and an algometer determining the pressure pain threshold and tolerance level assessed arthritic pain and hyperalgesia in the TMJ. Our results indicate that SP-like immunoreactivity is associated with IAT and that increased concentrations of joint fluid SP-like immunoreactivity correspond to increased pain threshold and tolerance and a concomitantly decreased visual analogue scale. These findings suggest that SP is implicated in the vascular and nociceptive response of the arthritic joint and that SP, possibly assisted by the antinociceptive effect of local corticosteroids, has a modulatory role in arthritic pain and hyperalgesia.

Effects of physical activity and acupuncture on calcitonin gene-related peptide immunoreactivity in different parts of the rat brain and in cerebrospinal fluid, serum and urine.

Calcitonin gene-related peptide (CGRP) is a very potent vasodilator in the nervous system, and may be involved in hot flushes experienced by most women around menopause. Flushing post-menopausal women had higher urinary excretion of CGRP before than after successful treatment of their flushes with acupuncture. The prevalence of vasomotor symptoms is lower in physically active women. In a rat model we therefore intended to assess whether acupuncture and exercise affected CGRP concentrations in different parts of the brain and peripherally. The aim of the study was to elucidate the short- and long-term effects of exercise and acupuncture on CGRP concentrations in the nervous system of normal adult rats. In a rat model, we examined the effects of single interventions and long-term treatment with physical exercise and manual or electro-acupuncture on CGRP concentrations in urine, cerebrospinal fluid and serum and different parts of the brain. In all compartments studied, but significantly only in the cerebrospinal fluid, CGRP increased after a single session of physical exercise or electro-acupuncture. Manual acupuncture did not change CGRP concentrations in any compartment. Rats had the highest concentrations of CGRP in the pituitary and hypothalamus but the concentrations did not differ significantly between control rats and those subjected to long-term treatment with manual or electro-acupuncture or running rats. Rats treated with electro-acupuncture had twice the CGRP concentration in the frontal cortex compared to control rats, albeit the difference did not reach statistical significance. Evidently manual and electro-acupuncture have different effects, whereas electro-acupuncture and physical exercise have more similar effects on CGRP production and/or release. To elucidate the role of CGRP in vasomotor symptoms, further studies with older flushing rats should be performed.

Sensory stimulation (acupuncture) increases the release of vasoactive intestinal polypeptide in the saliva of xerostomia sufferers.

We have shown in earlier studies that xerostomia can be treated successfully with acupuncture. We also found that acupuncture stimulation can increase the concentration of neuropeptides in the saliva of healthy subjects. In this study, the concentration of the neuropeptide vasoactive intestinal polypeptide (VIP) was measured in the saliva of xerostomic patients in connection with acupuncture treatment (AP). Patients suffering from xerostomia caused by irradiation treatment, Sjögren's syndrome and other systemic disorders had been treated with acupuncture. Some of these patients showed an increase of their salivary flow rates after the AP was completed. Seventeen patients out of 65 were chosen due to their ability to produce enough saliva for the radio immunoassay (RIA) analyses to be conducted prior to the start of AP. VIP-like immunoreactivity (VIP-LI) was measured in the chewing stimulated saliva of these patients before and after the whole AP (24 sessions of 30 min each). The results showed that there was a significant increase of the concentration of VIP after the AP as compared to the measurements made before the start of the treatment (p<0.05). We concluded that the increase of neuropeptide VIP might be one of the mechanisms behind the positive effect of acupuncture on the salivary flow rates of the xerostomic patients.

Effects of electroconvulsive stimuli and MK-801 on neuropeptide Y, neurokinin A, and calcitonin gene-related peptide in rat brain.

Rats were pretreated with 0.9% NaCl, or 0.1 or 1.0 mg/kg MK-801, an anticonvulsant and a psychotomimetic drug, and 60 minutes later given ECS or sham ECS. After six sessions the animals were sacrificed and neuropeptide Y (NPY-), neurokinin A (NKA-), and calcitonin gene-related peptide (CGRP-) like immunoreactivity (-LI) measured with radioimmunoassays. ECS increased NPY-LI in frontal cortex, striatum, occipital cortex and hippocampus, and NKA-LI in occipital cortex and hippocampus. MK-801 increased CGRP in a dose-response manner in frontal cortex, and NKA-LI in occipital cortex. Although the higher MK-801 dose reduced seizure duration by 50%, the ECS induced NPY-LI increase in striatum, occipital cortex and hippocampus, and NKA-LI in occipital cortex was not diminished. In contrast, there was a parallel decrease in seizures and NPY-LI and NKA-LI changes in frontal cortex and hippocampus, respectively. Investigation of neuropeptides in brain may contribute to understanding of the mechanisms of action of antidepressive and antipsychotic treatments and of psychotomimetic drugs.

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.

Effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and concentrations of neuropeptides in the hippocampus in WKY and SHR rats.

The effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and on hippocampal concentrations of neuropeptide Y, neurokinin A, substance P, galanin and vasoactive intestinal peptide (VIP)-like immunoreactivities were studied in WKY (wistar-Kyoto) and SHR (spontaneously hypertensive) rats. Significantly higher concentrations of substance P-like immunoreactivity, neurokinin A-like immunoreactivity and neuropeptide Y-like immunoreactivity were found in the hippocampus immediately after 3 weeks of treatment (electro-acupuncture and running), but not 1 week after the last (tenth) changes in neuropeptide concentrations were similar in the two rat strains. Open-field behaviour was significantly reduced during the treatment period in both strains. There were significant negative correlations between behaviour and neuropeptide concentrations in SHR rats, suggesting interdependency with sympathetic activity. It is proposed that the effects of electro-acupuncture and physical exercise in rats are related to increases in neuropeptide Y, neurokinin A and substance P in the hippocampus.

A model for the study of experimentally induced temporomandibular arthritis in rats: the effect of human recombinant interleukin-1 alpha on neuropeptide-like immunoreactivity.

To study the interaction between human recombinant interleukin-1 alpha and the nervous system, substance P-, neurokinin A-, calcitonin gene-related peptide-, and neuropeptide Y-like immunoreactivity in the cerebrospinal fluid, plasma, and temporomandibular joint (TMJ) perfusates of rats during acute experimental monarthritis were examined. The right TMJs of the experimental rats were injected with 0.01 mL of human recombinant interleukin-1 alpha. The right TMJs of control rats were injected with 0.01 mL of saline. Cerebrospinal fluid, plasma, and perfusates from the right TMJs were obtained at 2, 6, and 24 hours following injection, and neuropeptide-like immunoreactivity was analyzed by specific radioimmunoassays. Values of neuropeptide-like immunoreactivity for the experimental rats were compared with those of the control rats. In the experimental group, substance P-, neurokinin A-, and calcitonin gene-related peptide-like immunoreactivities were increased in cerebrospinal fluid compared to those of the control group. In plasma, no changes in neuropeptide-like immunoreactivities rose significantly in the TMJ perfusates. Most pronounced changes in neuropeptide Y-like immunoreactivity occurred intra-articularly in the TMJ perfusates. The results indicate that the contribution of the nervous system to human recombinant interleukin-1 alpha-induced monarthritis is most pronounced in the affected joint.

Monosodium glutamate increases NGF and NPY concentrations in rat hypothalamus and pituitary.

The effects of MSG treatment on NGF and NPY levels were analysed in the hypothalamus, pituitary, adrenal, thyroid and testis of adult rats. Daily i.v. injections of MSG (1 g kg-1 for 1 week) induced an increase of NGF in the hypothalamus (control (C) = 378 +/- 54; saline (S) = 369 +/- 36; MSG = 479 +/- 35 pg g-1 tissue; p < 0.001) and pituitary (C = 310 +/- 34; S = 376 +/- 114; MSG = 576 +/- 98 pg g-1 tissue; p < 0.01). Hypothalamic and pituitary NPY concentrations were also altered in the MSG-treated rats. Compared with saline-treated rats, the NPY concentration increased by 43% in the hypothalamus and 37.5% in the pituitary of MSG-treated rats. No significant changes in NGF and NPY content were found in the adrenal or thyroid of treated animals. These results suggest that hypothalamic and pituitary NGF and NPY levels may be involved in the control of neuroendocrine functions that are affected by MSG treatment.

Determination of temporomandibular joint fluid concentrations using vitamin B12 as an internal standard.

The aim of the investigation was to test the reproducibility and accuracy of a new method to measure temporomandibular joint (TMJ) fluid concentrations of various substances by saline washing, using exogenous B12 as a marker. An in vitro test was first performed with glucose as a test substance. The difference between a B12-calculated and known standard concentration of glucose was very small. Saline washing of the TMJ was performed on 13 patients having signs of TMJ arthritis, and the aspirates obtained were analyzed for neuropeptide Y-like immunoreactivity (NPY-LI) and interleukin-1 beta (IL-1 beta). Vitamin B12 was mixed with the saline immediately before injection, and a sample of the aspirate was later compared photometrically with the injection solution. There were positive correlations between saline aspirate and joint fluid concentrations for NPY-LI and IL-1 beta, and the correlations were stronger for saline aspirates with high joint fluid content. This study shows that the method is reliable for measurement of joint fluid concentrations of various substances, such as NPY-LI and IL-1 beta.

Neuropeptide Y- and vasoactive intestinal polypeptide-like immunoreactivity in adjuvant arthritis: effects of capsaicin treatment.

The occurrence of the neuropeptides vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in ankle joints and dorsal root ganglia (L2-L6) was analyzed in normal and arthritic Lewis rats. In addition the effect of capsaicin pretreatment was investigated. The study included 92 rats consisting of 4 groups, 23 rats in each; normal rats, normal rats given capsaicin, arthritic rats and arthritic rats pretreated with capsaicin. The localization of the neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay (RIA). In the arthritic rats, there was a slight increase in NPY immunoreactive nerve fibres in the ankle joint synovium and bone marrow, as compared to normal rats. Notably, there was an intense fluorescence and significant increase (p < 0.01, 41%) in the number of NPY-positive megakaryocytes in the tibial bone marrow of arthritic rats. RIA showed that the concentration of NPY-like immunoreactivity (LI) was increased by 50% in the ankle joint. Pretreatment with capsaicin did not affect the increased level of NPY-LI in the ankle joint of arthritic rats. The concentration of NPY-LI in the dorsal root ganglia was not altered in arthritic rats, nor was it affected by the capsaicin treatment. No NPY immunoreactive cells could be detected in the dorsal root ganglia. The number of VIP immunoreactive nerve fibres observed in ankle joints of arthritic and normal rats did not differ. However, RIA measurements showed an 11% increase in the VIP concentration in arthritic rats, which was unaffected by capsaicin treatment. In dorsal root ganglia, RIA disclosed a 21% increase in VIP-LI, although no VIP-positive cells could be detected. Capsaicin treatment did not affect the increased concentration of VIP-LI in the dorsal root ganglia.

Co-variation of neuropeptide Y, calcitonin gene-related peptide, substance P and neurokinin A in joint fluid from patients with temporomandibular joint arthritis.

Forty-one patients (37 female and four male) with signs and symptoms of temporomandibular joint arthritis, were separated into two diagnostic groups (group I: inflammatory; group II: degenerative/non-specific joint disease). They were examined clinically, fluid was aspirated from the joint with saline and venous blood samples were collected at the same time. The joint fluid and plasma samples were analysed for neuropeptide-like immunoreactivity, i.e. neuropeptide Y (NPY-LI), calcitonin gene-related peptide (CGRP-LI), substance P (SP-LI) and neurokinin A (NKA-LI), using competitive radioimmunoassays. The aim was to investigate any co-variation of the peptides in the joint fluid and plasma. In group I, the median values of peptide concentrations in joint fluid were SP-LI = 129, CGRP-LI = 75, NKA-LI = 36 and NPY-LI = 676 pmol/l and in group II, SP-LI = 52, CGRP-LI = 64, NKA-LI = 45 and NPY-LI = 318 pmol/l. There were no significant differences between the groups for peptide concentrations. In group I, all the neuropeptides were strongly correlated. In group II, SP-LI and NKA-LI were strongly correlated while CGRP-LI was weakly correlated with NPY-LI and NKA-LI. Multiple step-wise regression analysis showed that most of the variation in NPY-LI, CGRP-LI and SP-LI in group I was explained by NKA-LI, but the regression did not reach statistical significance in group II.

Effects of electro-acupuncture and physical exercise on regional concentrations of neuropeptides in rat brain.

The effects of single or repeated treatments with manual acupuncture (ACU), electro-acupuncture (ELACU) or physical exercise on neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP), galanin (GAL) and vasoactive intestinal peptide (VIP)-like immunoreactivity (-LI) in different regions of the rat brain were studied. Initially the effect of microwave irradiation (MWI) was compared to decapitation on the recovery of neuropeptides, and significantly higher concentrations of SP-LI, NKA-LI and NPY-LI were found in the hippocampus, occipital cortex, pituitary and striatum following MWI. Repeated ELACU treatments significantly increased SP-LI, NKA-LI and NPY-LI in the hippocampus and NPY-LI in the occipital cortex. No changes were found in animals receiving ACU or performing physical exercise.

Glutamine supplementation does not prevent small bowel mucosal atrophy after total parenteral nutrition in the rat.

Glutamine supplementation to non-lipid parenteral nutrition has been demonstrated to attenuate villus atrophy and increase mucosal DNA content in the rat. This study was performed in order to determine the effects of glutamine supplementation to a balanced TPN mixture (including lipids) on epithelial cell kinetics using autoradiography. Male Sprague-Dawley rats were used. Group 1 (control) received food and an intravenous saline infusion. Group 2 received an intravenous TPN mixture including lipids but without glutamine. The same TPN mixture, glutamine replacing an isonitrogenous amount of non-essential amino acids, was given to Group 3. Animals were fed for 7 days, whereafter blood and intestinal samples were taken 1 h after injection of tritiated thymidine. Microscopy of specimens from proximal jejunum revealed a significant reduction in the number of cells in crypts and villi in both TPN groups (2 and 3) compared to orally fed animals (p < 0.001). Epithelial cell numbers were not significantly different in Group 2 and 3. Similarly, the labelling index (number of labelled cells/number of crypt cells) was not affected by glutamine administration. In plasma, glucagon concentrations in Group 2 (TPN without glutamine) seemed to decrease compared to Group 1 and 3 (p = 0.06). In this study, glutamine supplementation did not affect apithelial atrophy or cell proliferation. It is concluded, that the effects of glutamine on mucosal atrophy and renewal in jejunum may depend on the composition of the TPN mixture supplied during parenteral feeding.

Substance P-, neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity (-LI) in rat knee joint synovial fluid during acute monoarthritis is not correlated with concentrations of neuropeptide-LI in cerebrospinal fluid and plasma.

In a recent study we have shown a bilateral release of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (-LI) in rat synovial fluid during acute monoarthritis. In order to elucidate the mechanisms underlying these phenomena, we examined the correlation between neuropeptide-LI in rat cerebrospinal fluid (CSF) and synovial fluid and between plasma and synovial fluid following the intra-articular injection of equal volumes (0.05 ml) of either Freund's adjuvans, carrageenan 2%, substance P 10(-5) M or human recombinant interleukin-1 alpha. Control rats were given saline intra-articularly. CSF, plasma and synovial fluid from the knee joints were obtained at 2, 6 and 24 h after injection and were analysed by specific radioimmunoassays. The intra-articular injection of pro-inflammatory substances induced changes in neuropeptide-LI in synovial fluid, CSF and plasma. However, there was no correlation between neuropeptide-LI in synovial fluid and plasma or between synovial fluid and CSF. The results of the present study does not support the hypothesis that the bilateral changes in neuropeptide-LI in synovial fluid were due to a release of neuropeptides from the inflamed joint into the systemic circulation. However, in carrageenan induced inflammation there was a tendency towards a correlation in SP-LI between CSF and synovial fluid suggesting that central neurogenic mechanisms should be studied in order to explain the bilateral changes seen.