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Biomedical subjects

E Theodorsson

Publications and source records attributed to E Theodorsson.

At least 37 records · Page 2Linked to original sources

Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.

Islet amyloid polypeptide (IAPP or amylin) potently reduces food intake in rats at or near physiological concentrations. Although the mechanisms of action of IAPP are not understood, the brain is a suggested site. Changes in hypothalamic and striatal neurotransmission have been reported following acute systemic administration of a pharmacological concentration of IAPP. In the current study, we evaluated the effects of chronic administration of low doses of IAPP on satiety-related neurotransmitters and neuropeptides in the hypothalamus, hippocampus, striatum, left cortex, and right cortex of the rat. Doses of 0, 5 and 25 pmol IAPP/kg-min were administered subcutaneously for 2 or 5 days. Food intake was reduced by 27 and 44% (both P<0.001) for the 5 and 25 pmol/kg-min groups, respectively, in the 2-day experiment and was decreased by 14% (P<0.01) and 24% (P<0.001), respectively, in the 5-day experiment. Body weight was significantly decreased in a dose-dependent fashion. In the 2-day experiment, norepinephrine increased in the hypothalamus in the 5 pmol IAPP/kg-min group, and neurotensin increased in the hippocampus in the 25 pmol/kg-min rats (both P<0.05). In the 5-day, 5 pmol/kg-min rats, 5-hydroxyindoleacetic acid (5-HIAA) increased in the hypothalmus and cholecystokinin (CCK) increased in the striatum (both P<0.05). In the 5-day, 25 pmol/kg-min group, neuropeptide Y (NPY) increased in the hypothalamus (P<0.01) and CCK increased in the hypothalmus and striatum (both P<0.05). The present study confirms that IAPP is a potent anorectic peptide at low doses and suggests that IAPP not only affects classical neurotransmitters in the brain but also alters concentrations of neuropeptides known to be involved in food intake.

3,4-Dihydroxyphenylacetic Acid↗

Hypoglycaemic neuropathy: occurrence of axon terminals in plantar skin and plantar muscle of diabetic BB/Wor rats treated with insulin implants.

It is generally believed that diabetic neuropathy is due to chronic hyperglycaemia. However, experience from insulinoma patients and experimental studies show that hypoglycaemia may also cause neuropathy. Accordingly, the plantar nerves of diabetic eu-/hypoglycaemic BB/Wor rats treated with insulin implants exhibit a distinct neuropathy. To what extent hypoglycaemic neuropathy affects axon terminals in skin and muscle is unknown. In the present study we examine the occurrence of epidermal axon profiles and the neuropeptide calcitonin gene-related peptide (CGRP) in plantar skin, and of end plate axon terminals in a plantar muscle of diabetic BB/Wor rats subjected to long periods of hypoglycaemia. The number of protein gene product-immunoreactive axon profiles was found to be normal in heel skin biopsy specimens from eu-/hypoglycaemic rats, but many profiles were short and thin. The content of CGRP in the skin biopsy samples was significantly below normal. After staining with antibodies against the vesicular acetylcholine transporter protein, the occurrence of end plate axon terminals was significantly reduced in sections from the flexor hallucis brevis muscle of eu-/hypoglycaemic rats. Moreover, the end plate axon terminals tended to be abnormally small in these rats. We conclude that the hypoglycaemic neuropathy seen in plantar nerve trunks of diabetic BB/Wor rats treated with insulin implants is accompanied by mild alterations in the epidermal innervation of plantar skin and a more obviously abnormal nerve terminal pattern in plantar muscle.

Animals↗

Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours.

Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neuroblastomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less aggressive stage 1, 2 and 4S tumours (n = 12), (93%; 69-100%), (P= 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY processing (P = 0.025). In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue.

Child↗

Radioimmunoassay for rat galanin: immunochemical and chromatographic characterization of immunoreactivity in tissue extracts.

Galanin is a regulatory peptide with wide distribution in the central and peripheral nervous system and with numerous biological effects. Several radioimmunoassays based on antisera raised against porcine galanin have been used to measure immunoreactivity in rat tissues. However, considerable lack of parallelism has been observed between the porcine standard and rat tissue extracts, which may decrease the reliability of the quantitative data. The purpose of the present study was therefore to raise antibodies against rat galanin and establish a competitive radioimmunoassay for rat galanin. Two antisera, RatGal4 and RatGal5, were characterized in detail. The homogeneity of the immunoreactive material from several tissues was also investigated with column chromatography. At reverse-phase high-pressure liquid chromatography more than 95% of the immunoreactive material from rat CNS eluted as a single peak in the position of synthetic rat galanin, whereas almost half of the immunoreactive material from the intestine eluted in positions different from the synthetic peptide. Extracts of rat brains as well as jejunum diluted in parallel with the standard curve for both antisera. We conclude that measurements of rat galanin based on these antisera are therefore more reliable than those based on antisera raised against porcine galanin.

Animals↗

Altered influence of CCK-B/gastrin receptors on HDC expression in ECL cells after neoplastic transformation.

Gastrin is one of the main factors controlling enterochromaffin-like (ECL) cell endocrine function and growth. Long-standing hypergastrinemia may give rise to ECL cell carcinoids in the gastric corpus in man and in experimental models. We have analysed the expression and function of CCK-B/gastrin receptors in normal ECL cells and in ECL cell tumours (gastric carcinoids) of the African rodent Mastomys natalensis. Hypergastrinemia induced by short-term (5 days) histamine2-receptor blockade (loxtidine) resulted in increased histidine decarboxylase (HDC) mRNA expression in the gastric oxyntic mucosa. This increase was significantly and dose-dependently reversed by selective CCK-B/gastrin receptor blockade (YM022). Long-term (12 months) hypergastrinemia, induced by histamine2-receptor blockade, gave rise to ECL cell carcinoids in the gastric oxyntic mucosa. CCK-B/gastrin receptor mRNA was only slightly elevated while HDC mRNA expression was eight-fold elevated in ECL cell carcinoids and was not influenced by CCK-B/gastrin receptor blockade. Thus CCK-B/gastrin receptor blockade of hypergastrinemic animals reduces the HDC mRNA expression in normal mucosa but not in ECL cell carcinoids. These results demonstrate that HDC mRNA expression in neoplastic ECL cells is not controlled by CCK-B/gastrin receptors.

Animals↗

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.

Animals↗

Sex differences in neuropeptide distribution in the rat brain.

We have investigated possible sex differences in the regional concentrations of neuropeptides in the rat brain. Immunoreactive neurotensin (NT), neurokinin A (NKA), galanin (GAL), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) were measured by radioimmunoassay in frontal cortex, occipital cortex, hippocampus, striatum, hypothalamus and pituitary in male and female pre- and postpubertal rats. Sex differences were found for NPY (p < 0.001), NT (p < 0.01) and GAL (p < 0.05), in particular in hippocampus, striatum, hypothalamus and pituitary, but not for CGRP, SP and NKA. Results from analysis of neuropeptides in one sex may not be entirely applicable to the other.

Animals↗

Effects of estradiol, progesterone, and norethisterone on regional concentrations of galanin in the rat brain.

Concentrations of immunoreactive galanin were compared in eight gross brain regions of ovariectomized female rats treated with either estradiol, estradiol + progesterone, estradiol + norethisterone, or placebo. Higher concentrations with estradiol treatment compared with placebo were found in the pituitary (357%), frontal cortex (162%), occipital cortex (174%), hippocampus (170%), and median eminence (202%). A more profound difference with addition of progesterone or norethisterone was seen in the pituitary (529% and 467%, respectively). Sex steroids, particularly estradiol, modulate galanin concentrations not only in reproductive, but also in nonreproductive, brain regions.

Animals↗

Increased intestinal non-substance P tachykinin concentrations in malignant midgut carcinoid disease.

BACKGROUND: Diarrhoea is an important feature of the carcinoid syndrome, and various agents which may be released from carcinoid tumours have been considered to contribute pathophysiologically. The aim of the present study was to determine luminal concentrations of possible chemical mediators in an uninvolved small intestinal segment using a two-balloon six-channel tube in nine patients with malignant midgut carcinoid disease. METHODS: All patients were treated with interferon and/or octreotide to alleviate the most severe flush. Ion transport was measured during luminal perfusion and luminal perfusate concentrations of calcitonin gene-related peptide, neurotensin, prostaglandin E (PGE)2, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide, substance P and other tachykinins (neurokinin A, neurokinin B, neuropeptide K, eledoisin) were determined by separate assays. RESULTS: Carcinoid patients showed decreased absorption of Cl-, Na+, K+ and water and increased luminal content of non-substance P tachykinins to 424.5 fmol/cm per h, compared with 255.5 fmol/cm per h in control subjects. There were also increased luminal concentrations of PGE2, commonly claimed as a more general mediator of diarrhoea. CONCLUSIONS: The observed increase in intestinal tachykinins may involve extended activity from tachykinin-containing intrinsic neurones in the enteric nervous system, contributing to enhanced intestinal motility and secretory diarrhoea in patients with carcinoid syndrome.

Adult↗

Exercise and variations in neuropeptide concentrations in rheumatoid arthritis.

The aim of the present study was to investigate the influence of an exercise program on neuropeptide concentrations, disease activity, impairments and disabilities in rheumatoid arthritis (RA). Eleven females (median age 60 years, median disease duration 6.5 years, ARA functional classes I or II) exercised 30 min daily for 4 weeks. The urine concentrations of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) were analyzed 1 week prior to exercise start, at exercise start, after 2 and 4 weeks of exercise, and after a 4-week follow-up period. Measurements of disease activity, aerobic capacity, grip force, limb muscle function, and activities of daily living (ADL) were also undertaken. The results indicate a decrease (md 5.64 pM to md 3.48 pM, P</=0.05) of CGRP-LI concentrations after 4 weeks' exercise. NPY-LI concentrations remained unchanged, as did disease activity and aerobic capacity. Muscle function and ADL capacity improved significantly (P</=0.05) after the exercise period. Only the improved grip force remained after the follow-up period. In conclusion the results indicate that decreased CGRP-LI concentration, probably reflecting a decreased sympathetic tone, follows physical exercise and suggest that regular physical activity might be important among individuals with RA to maintain a decreased sympathetic tone and less symptoms from their disease.

Adult↗

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.

Acupuncture Therapy↗

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.

Adolescent↗

TMJ pain in relation to circulating neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis.

AIMS: The aim of this study was to test the hypothesis that temporomandibular joint (TMJ) pain is influenced by circulating levels of neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis. METHODS: Forty-three seropositive (RF+) or seronegative (RF-) rheumatoid arthritis patients and 24 healthy individuals were included in the study. RESULTS: High serum concentrations of serotonin were associated with low TMJ pressure pain thresholds and pain during mandibular movement in the RF+ patients. The results of this study do not support a relationship between circulating neuropeptide Y or interleukin-1 beta and TMJ pain. The RF+ patients had higher C-reactive protein levels and erythrocyte sedimentation rates than the RF- patients. There were also higher plasma levels of interleukin-1 beta in the RF+ patients than in the healthy individuals. Plasma levels of neuropeptide Y in the RF- patients were higher than in the healthy individuals. CONCLUSION: This study indicates that the serum concentration of serotonin is associated with TMJ allodynia in seropositive rheumatoid arthritis.

Adult↗

Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.

OBJECTIVES: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. MATERIAL AND METHODS: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. RESULTS: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. CONCLUSION: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

Calcitonin Gene-Related Peptide↗

[Many pitfalls in "simple" measuring of glucose in blood and plasma].

The measurement of plasma glucose concentrations is a cornerstone in the diagnosis and monitoring of diabetes mellitus. Kits for on-the-spot measurement of blood glucose are widely available both at healthcare facilities and in the patients' homes. Although measurement techniques have improved considerably in recent years, their optimal use is still dependent on the user's knowledge, skill and judgement. Fundamental pre-analytical, analytical, and post-analytical aspects of the measurement of blood glucose are presented in the article for the aid of healthcare personnel and patients alike. The new diagnostic criteria for diabetes mellitus are also presented, and their implications in different clinical situations are discussed.

Blood Chemical Analysis↗

Neuropeptide Y concentrations in experimental Leishmania major cutaneous leishmaniasis.

Neuropeptide Y (NPY) concentrations were investigated by radioimmunoassay and immunohistochemistry in a murine model of cutaneous leishmaniasis, using a susceptible (BALB/c) and a resistant (C57BL/6) mouse strain. The analyses were performed on the skin, secondary lymphoid organs and dorsal root ganglia (DRG) at 1, 3, 6 and 9 weeks postinfection. An overall reduction in the NPY concentrations in the studied organs was observed in both mouse strains; the reduction in the skin and draining lymph nodes was more evident and progressive in the susceptible strain. Using immunohistochemistry there seemed to be a reduction in NPY immunoreactivity in all inflamed tissues analysed compared to the controls. These observations might indicate a possible pathophysiological role for NPY in murine cutaneous leishmaniasis.

Animals↗