Biomedical subjects

S Forsgren

Publications and source records attributed to S Forsgren.

At least 19 recordsLinked to original sources

PubMed2002

Early increase and later decrease in VIP and substance P nerve fiber densities following abdominal radiotherapy: a study on the human colon.

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.

Abdomen↗

PubMed2002

Tyrosine hydroxylase in mouse pancreatic islet cells, in situ and after syngeneic transplantation to kidney.

Tyrosine hydroxylase (TH) is co-expressed with islet hormones in the fetal mouse pancreas. In the adult animal, the enzyme has been considered as a marker of ageing beta-cells. By immunohistochemical staining, we analyzed the expression of TH-like immunoreactivity (TH-LI), insulin-LI (INS-LI) and somatostatin-LI (SOM-LI) in adult mouse islets, in situ and after isolation and transplantation to kidney. In pancreas in situ, most TH-LI cells expressed INS-LI while less than 5% expressed SOM-LI. The total number of TH-LI cells/mm2 was significantly increased directly after isolation and in 0-day, 12-week and 52-week old grafts, but not in 3-day grafts. The proportion of TH-LI cells expressing SOM-LI increased after transplantation, amounting to about one-third by 52 weeks. As expressed per unit islet area, the frequencies of both TH/INS and TH/SOM cells increased significantly in the transplants. The results demonstrate that TH occurs in both beta-cells and D-cells of adult islets. In both cell types the enzyme appears to be responsive to the microenvironmental changes inherent in transplantation. This cellular phenotype plasticity might contribute to the altered insulin secretory dynamics in islet grafts.

Animals↗

PubMed2001

Substance P (NK1) receptor in relation to substance P innervation in rat duodenum after irradiation.

It has previously been shown that high dose of irradiation to the rat abdomen leads to an increased level of substance P (SP) in the duodenum. In the present study the pattern of distribution of NK1 receptors (NK1-R) in rat duodenum after irradiation (5-30 Gy), was examined at the same time-point (7 days) after irradiation, comparisons being made with the distribution of SP-innervation. Immunohistochemical methods were used. In controls, NK1-R-like immunoreactivity (-LI) was detected in epithelial cells, in cells in the region of the intestinal cells of Cajal within the deep muscular plexus (ICC-DMP), in neuronal cells in the myenteric plexus, and variably in granulocytes in the mucosa. Irradiation with 5-10 Gy did not lead to obvious changes in the pattern of NK1-R-LI. After irradiation with the highest doses (25-30 Gy), the mucosa was often gravely damaged, displaying granulation tissue. No epithelial NK1-R-LI was detected in this tissue, but was present in less affected mucosa after these doses. In the region of the ICC-DMP, in the myenteric plexus, and in granulocytes, NK1-R-LI was detected also after high dose irradiation. However, the degree of NK1-R-LI in the region of the ICC-DMP was somewhat lower than seen in controls and after low doses. SP-immunoreactive nerve fibers were present in the regions where NK1-R-LI was detected. These findings support a suggestion that an increased level of SP after irradiation may contribute to the dose-dependent gastrointestinal adverse effects that occur after radiotherapy.

Animals↗

PubMed2001

Glutamate NMDAR1 receptors localised to nerves in human Achilles tendons. Implications for treatment?

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.

Achilles Tendon↗

PubMed2001

Ingrowth of sympathetic innervation occurs concomitantly with a decrease of ANP in the growing rat cardiac ventricles.

The relationship between the immunohistochemical expression of atrial natriuretic peptide and the occurrence of sympathetic nerve fibres, as visualized by staining for tyrosine hydroxylase, in the growing rat heart was evaluated. Rats were investigated at four different stages from birth to 21 days postnatally. The effects of chemical destruction of sympathetic nerve terminals in neonatal rats on the cardiac atrial natriuretic peptide content were furthermore examined by use of radioimmunoassay. There was in principle a reciprocal pattern of immunoreaction for atrial natriuretic peptide and tyrosine hydroxylase positive innervation in the ventricular myocardium, atrial natriuretic peptide reaction becoming less and less pronounced with the ingrowth of innervation positive for tyrosine hydroxylase. Furthermore, in the peripheral Purkinje fibre network, there was a marked atrial natriuretic peptide immunoexpression and scarce or no nerve fibres throughout the examination period. The radioimmunoassay measurements showed that chemical sympathectomy lead to elevated cardiac levels of atrial natriuretic peptide. The study shows that sympathetic innervation grows into the ventricular parts concomitantly with the occurrence of a decline in atrial natriuretic peptide expression during development of the heart. Furthermore, it is shown that a reversion of the in growth of sympathetic innervation by destruction of cardiac sympathetic nerves at an early stage leads to increased levels of atrial natriuretic peptide in the heart. The results give new evidence to the phenomenon that the atrial natriuretic peptide levels in the ventricular myocardium and the peripheral parts of the conduction system are under influence of the presence of sympathetic innervation.

Animals↗

PubMed2001

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.

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.

Adult↗

PubMed2001

Nerve cells associated with the endocrine pancreas in young mice: an ultrastructural analysis of the neuroinsular complex type I.

The neuroinsular complex type 1 is composed of pancreatic endocrine islet cells and nerve cell bodies intrinsic to the islet. The details of the relation between nerve cells and between endocrine cells and nerve cells in the complex are unknown. Pancreata from newborn and 18-day-old mice were analysed by electron microscopy to establish the ultrastructural morphology of the neuroinsular complex. Immunohistochemical staining for protein gene-product 9.5 was also performed. The study showed that nerve cell bodies were closely associated to each other in the periphery of the islets with no connective tissue separating the cells. The nerve cells were closely associated to both beta-cells and alpha-cells. Direct intercellular contacts were observed between nerve cells and endocrine cells and between Schwann cells and endocrine cells. Varicose nerve endings were frequently observed in the neuroinsular complex. In the peripheral parts the varicosities were mostly being associated to the nerve cell bodies. The varicosities contained small clear or small clear and larger dense cored vesicles, suggesting cholinergic and peptidergic contents. The varicosities made specialized synaptic connections with adjacently located nerve cells. The study shows that the neuronal part of the neuroinsular complex is closely associated to the endocrine islet cells and that it is richly innervated, indicating an important regulatory function of the nerve cell component in the neuroinsular complex.

Animals↗

PubMed2001

Mouse islets cultured with vasoactive intestinal polypeptide: effects on insulin release and immunoreactivity for tyrosine hydroxylase.

Mouse islets cultured for 1 or 4 days with or without 10 nM vasoactive intestinal polypeptide (VIP) were stained for tyrosine hydroxylase (TH) and examined for insulin secretion during culture and in a postculture perifusion system. Exposure to exogenous VIP for 4 days increased the frequency of islet cells expressing TH-like immunoreactivity. Regardless of the culturing conditions, the islets exhibited significant insulin secretory responses to 16.7 mM glucose, the effect being potentiated by 10 nM VIP in the perifusion medium. The insulin-releasing action of glucose and the potentiating effect of VIP were less pronounced in islets cultured for 1 day with VIP than in islets cultured without this neuropeptide. The following conclusions are suggested: (a) VIP stimulates the expression of TH in mouse islet cells; (b) the latency of the VIP-induced TH is a postreceptor phenomenon; (c) islet cultures exposed to VIP represent a new instance of the association between increased functional demands on beta cells and enhanced expression of TH and a new instance of VIP having trophic effects.

Animals↗

PubMed2001

Effect of diabetic state on co-localization of substance P and serotonin in the gut in animal models.

Changes in the numbers of serotonin- and substance P-immunoreactive (IR) cells occur in several animal models of diabetes. It is not known, however, whether these changes are a result of actual cell loss or are caused by modified gene expression in cells showing co-localization of serotonin and substance P. The pattern of mono- and co-expression of serotonin, as well as of substance P, was therefore investigated in gastrointestinal endocrine cells from animal models of human type 1 and type 2 diabetes, namely non-obese diabetic (NOD) and obese diabetic (ob/ob) mice. Immunocytochemical staining by the avidin-biotin complex method was performed for computerized image analysis of each cell type, and by immunofluorescence double staining to study co-localization. Tissues from antrum, proximal duodenum and distal colon were investigated. Co-localization of serotonin- and substance P-IR was found in all investigated parts of the gut. In antrum, substance P immunoreactivity was found exclusively in serotonin-IR cells. In both NOD and ob/ob mice there was a reduced number of substance P-IR cells, but an unchanged serotonin-IR cell count, which thus tallies with a shut-off of substance P expression in antral enterochromaffin cells. In duodenum, both diabetes models showed a decreased number of serotonin-IR cells. Furthermore there was a decreased number of substance P-IR cells in the type 2 model. The proportion of serotonin-IR cells showing substance P-immuno-reactivity was decreased in both diabetic models, thus indicating a shut-off of substance P-gene expression. However, this does not fully explain the changes in duodenum, but the diabetic state probably affects the number of mono-expressed cells as well. In colon, no change was found in diabetic mice regarding co-localization of substance P and serotonin. However, pre-diabetic NOD mice showed a decreased proportion of substance P in serotonin-IR cells, which might be explained by the increased number of serotonin-IR cells, combined with an unchanged number of substance P-IR cells. In conclusion, diabetic animal models of both type 1 and type 2 appear to have a combination of decreased expression of substance P in serotonin-IR cells of both antrum and duodenum, as well as a change in the number of mono-expressed cells. The pattern in colon, on the other hand, seems to be unaffected.

Animals↗

PubMed2000

Pronounced substance P innervation in irradiation-induced enteropathy--a study on human colon.

The immunohistochemical expression of various neuropeptides, including substance P (SP), and the substance P receptor (SPR), was examined in irradiation-induced enteropathy in man. Samples from irradiated and non-irradiated patients operated on for rectal carcinoma were examined. The samples were from the sigmoid and corresponded macroscopically to non-cancerous sigmoid colon. There was a marked atrophy, ulcerations and inflammatory reactions in the irradiation-influenced mucosa. In this mucosa, there was a very pronounced innervation of varicose nerve fibers showing SP-like immunoreactivity (LI). The degree of SP-LI in the ganglionic cells of the submucous plexus was increased as compared to non-irradiated patients. There were only few or no nerve fibers showing immunoreaction for other neuropeptides examined (CGRP, enkephalin, NPY) in the irradiation-influenced mucosa. A marked SPR immunoreaction was detected in cells in the lamina propria which were interpreted as representing polymorphonuclear leukocytes. The marked expression of SP in the irradiation-damaged mucosa and the presence of SPR immunoreactive leukocytes suggest that SP is highly involved in the inflammatory reactions that occur in response to radiotherapy. The observations also suggest that SP, but not NPY, CGRP and enkephalin, has an important role in the reorganisation processes that take place in the mucosa in irradiation-induced enteropathy.

Calcitonin Gene-Related Peptide↗

PubMed2000

Peptides and other neuronal markers in transplanted pancreatic islets.

Functional alterations are developed in transplanted islets over time. Because islets in situ are densely innervated and isolation disconnects the endocrine organ from extrinsic nerves and from ganglia in the exocrine pancreas, it is important to examine the reinnervation of islet grafts. This review describes the patterns of appearances of intrinsic perikarya and reinnervating fibers demonstrating markers for parasympathetic, sympathetic or sensory nerve substances, most notably neuropeptides, in islet transplants. An altered innervation pattern, as compared to normal islets, develops. Presumably the expression of neuronal markers in the grafts is related to factors both in the islets and in the ectopic environment offered by the implantation organ.

Animals↗

PubMed2000

Parallel increase in substance P and VIP in rat duodenum in response to irradiation.

Irradiation was administered to the upper abdomen of rats, whereupon the duodenum was examined. Numerous vasoactive intestinal peptide (VIP)- and substance P (SP)-like immunoreactive nerve fibers were seen in the damaged mucosa, often in close association to each other. The intensity of the SP- and VIP-like immunoreaction was increased in several of the tissue compartments and, as measured with radioimmunoassay, the contents of SP- and VIP-like materials were increased after 30 Gray. The results show that SP and VIP levels increase after irradiation and suggest that SP and VIP are involved in interactive reactions in the reorganization and inflammatory processes in the gut after abdominal irradiation.

Animals↗

PubMed2000

Analysis of VIP and CGRP plasma levels after radiotherapy for treatment of metastasis from prostatic carcinoma.

It has previously been shown that radiotherapy leads to an increased level of neuropeptides in various organs. In the study we report here, we examined whether the plasma levels of two neuropeptides, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP), are influenced by radiotherapy. Blood was collected at four time intervals after radiotherapy; 1-12 days after treatment for skeletal metastasis from prostatic carcinoma. The VIP- and CGRP-plasma levels, as analyzed by radioimmunoassay, were not statistically different between the different time points analyzed.

Bone Neoplasms↗

PubMed2000

Does diabetic state affect co-localization of peptide YY and enteroglucagon in colonic endocrine cells?

BACKGROUND: Changes in the numbers of PYY- and enteroglucagon-immunoreactive cells in colon of animal models of human diabetes have been reported. As these peptides co-localize in the same cells it is possible that the observed changes are a result of changes in co-localization. METHODS: Animal models of human type 1 and type 2 diabetes, namely the non-obese diabetic (NOD) mouse and the obese (ob/ob) mouse, were studied. As controls for the NOD mice, BALB/cJ mice were used and for ob/ob mice, homozygous lean (+/+) mice were used. Tissue samples from colon were double-immunostained for PYY and enteroglucagon according to the indirect immunofluorescence method. RESULTS: Co-localization of enteroglucagon and PYY was found in colonic endocrine cells in all groups investigated. Compared with controls, pre-diabetic NOD mice showed a decreased proportion of enteroglucagon/PYY co-localization. There was no difference in diabetic NOD mice or diabetic ob/ob mice when compared with controls. CONCLUSIONS: Whereas the number of cells containing solely enteroglucagon and solely PYY increases in pre-diabetic NOD mice, production of enteroglucagon in PYY-immunoreactive cells decreases. Although the numbers of PYY and enteroglucagon cells have been reported to be changed in both diabetic NOD mice and in obese mice, the balance between co-expressing and mono-expressing cells seems to be preserved.

Animals↗

PubMed1999

Increase in bombesin-like peptides in the spinal cord after dexamethasone treatment of adrenalectomized rats.

The potential influence of corticosteroids on the bombesin (BN)-like peptide family is unknown. Therefore, the effects of adrenalectomy (ADX) on the nervous system of Sprague-Dawley rats, some of them being treated with high doses of the synthetic glucocorticoid dexamethasone (DEX), were investigated. After 8-10 days of treatment, the rats were sacrificed and tissues were prepared for radioimmunoassay (RIA) and immunohistochemical examination. We found an increase in BN-like immunoreactivity in the superficial layers of the dorsal horn of the lumbar spinal cord in the ADX + DEX animals. This increase was confirmed by RIA (P < 0.05). The observations show that the expression of BN-like peptides is influenced by glucocorticoids. The altered levels of BN-like peptides may be related to the trophic and antinociceptive effects previously reported for these peptides.

Adrenalectomy↗

PubMed1999

Substance P and calcitonin gene-related peptide expression at the extensor carpi radialis brevis muscle origin: implications for the etiology of tennis elbow.

With use of immunohistochemistry and antibodies to substance P and calcitonin gene-related peptide, nerve fibers showing substance P-like and calcitonin gene-related peptide-like immunoreactivity were demonstrated at the origin of the extensor carpi radialis brevis muscle in patients with tennis elbow (n = 6) and in healthy controls (n = 6). The nerve fibers were distributed in association with a subpopulation of small blood vessels and in nerve bundles but were not distributed in the tunica media-adventitia junction of the arterioles. There were no inflammatory-cell infiltrates and few solitary mast cells. The present study gives further evidence to previous suggestions that tennis elbow is not an inflammatory process in the sense of involving inflammatory cells. Frequent mechanical involvement affects sensory innervation, and substance P and calcitonin gene-related peptide may have various important efferent effects, including microvascular leakage and local edema formation; therefore, the observations from this study constitute a morphological substrate for possible effects of substance P and calcitonin gene-related peptide at the origin of the extensor carpi radialis brevis muscle.

Adult↗

PubMed1999

Colonic enteric nervous system in patients with familial amyloidotic neuropathy.

The colonic enteric nervous system was investigated in autopsy specimens from 12 patients with familial amyloidotic neuropathy (FAP) and 9 controls. The infiltration of amyloid deposits in the enteric nervous system was studied by double staining for amyloid and nerve elements. The myenteric plexus was immunostained for protein gene product (PGP) 9.5, vasoactive intestinal peptide (VIP), substance P and nitric oxide synthase (NOS). The immunostained nerve elements were quantified by computerised image analysis. Double staining revealed that there was no amyloid infiltration in the ganglia, or in the nerve fibres in the colonic enteric nervous system of FAP patients. The relative volume density of PGP 9.5-immunoreactive nerve fibres in both the circular and the longitudinal muscle layers in FAP patients did not differ significantly from that of controls. The relative volume density of VIP-immunoreactive nerve fibres in the circular muscle layer was significantly decreased in FAP patients compared with controls, but not in the longitudinal layer. The number of VIP-immunoreactive neurons/mm2 myenteric ganglia was significantly decreased in FAP patients. There were no statistical differences in the relative volume density for substance P- and NOS-immunoreactive nerve fibres between FAP patients and controls, nor was there any difference between FAP patients and controls regarding the number of NOS- and substance P-immunoreactive neurons/mm2 myenteric ganglia. It is concluded that the colonic enteric nervous system as a whole is intact and is not damaged by amyloid infiltration. The present observation of a reduction of VIP-immunoreactive nerve fibres and neurons in myenteric plexus of FAP patients might be one of the factors that contribute to the motility disorders seen in FAP patients.

Adult↗

PubMed1999

Irradiation induces marked immunohistochemical expression of vasoactive intestinal peptide in colonic mucosa of man.

Vasoactive intestinal peptide (VIP) is known to modulate inflammatory reactions, to have trophic effects, and to contribute to diarrhea and has been implicated as an important factor in several inflammatory conditions in the human gut. The aim of the present study was to investigate the effects of irradiation on the expression of VIP in the colon of patients operated on for adenocarcinoma. Some of the patients had received preoperative irradiation (25 Gy) within one week before the operation. Specimens of sigmoideum, 10 cm cranial to the margin of the cancer, were examined, by using antiserum against VIP and immunohistochemistry. There were numerous nerve fibers showing VIP-like immunoreactivity in the damaged mucosa, including the regions showing ulcerations. There was a higher degree of expression of VIP in the ganglion cells in the submucous plexuses in irradiated than nonirradiated patients. The study shows that there is a marked immunohistochemical expression of VIP concomitant with the occurrence of inflammatory and repair processes in the irradiation-damaged human colonic mucosa.

Adenocarcinoma↗