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Biomedical subjects

C J Dalsgaard

Publications and source records attributed to C J Dalsgaard.

At least 55 records · Page 3Linked to original sources

Substance P-, somatostatin- and calcitonin gene-related peptide-like immunoreactivity and fluoride resistant acid phosphatase-activity in relation to retrogradely labeled cutaneous, muscular and visceral primary sensory neurons in the rat.

The distribution of several peptides in cutaneous, muscular and visceral primary sensory neurons was investigated in the adult rat. The fluorescent dye Fast blue was applied to the proximal ends of transected saphenous (cutaneous), gastrocnemius (muscular) and greater splanchnic (visceral) nerves. Sections from corresponding dorsal root ganglia were incubated for simultaneous indirect immunocytochemical demonstration of calcitonin gene-related peptide (CGRP)-, substance P (SP)- or somatostatin (SOM)-like immunoreactivity (-LI) and Fast blue. In addition, the presence of fluoride resistant acid phosphatase (FRAP)-enzyme activity (-EA) in retrogradely Fast blue-labeled saphenous and gastrocnemius nerves was investigated by subsequent enzyme cytochemical analysis. The results revealed the presence of CGRP-LI, SP-LI, SOM-LI and FRAP-EA in cell bodies of primary sensory neurons which project to the saphenous and gastrocnemius nerves. CGRP-LI and SP-LI, but not SOM-LI, were found in splanchnic sensory neurons. The vast majority of the visceral sensory neurons were found to contain CGRP-LI.

Acid Phosphatase↗

Decreased survival of experimental critical flaps in rats after sensory denervation with capsaicin.

The role of capsaicin-sensitive primary sensory neurons on the survival of experimental critical flaps was studied in the rat. Pretreatment with capsaicin, which depletes neuropeptide transmitter content from primary sensory neurons, caused a dramatic decrease in flap survival area compared to normal animals. In contrast, pretreatment with reserpine, which depletes catecholamines from adrenergic neurons, including the sympathetic post-ganglionic fibers, resulted in a significant increase in the survival area. It was concluded that both capsaicin-sensitive primary sensory neurons and sympathetic postganglionic adrenergic neurons play a role in systemic vascular regulation and that intact primary sensory neurons are of importance for the survival of ischemic tissue.

Animals↗

Sensibility and cutaneous reinnervation in free flaps.

Sensibility and sensory reinnervation were investigated in 19 free flaps, predominantly located on the lower extremities, between 2 months and 3 years after flap transfer. All patients showed deep pressure sensibility. In 10 of the patients, primarily those examined late after surgery, a heat pain threshold was obtained at about 50 degrees C. None of the patients had superficial sensibility of any other modality. No neurofilament-positive sensory nerve fibers were observed in the dermis or epidermis. In one patient nerve fibers were detected in the subcutaneous tissue. It is concluded that patients will have deep pressure sensibility of the flap area even early after the operation and that most patients will develop a heat pain sensitivity, probably due to subcutaneous reinnervation.

Adolescent↗

Effects of capsaicin pretreatment on the inflammatory response to scalding injury in the rat.

The oedema formation after scalding injury to the rat paw was studied by means of the Evans blue exudation technique. An early and a delayed oedema formation were demonstrated after severe and light scalding, respectively. It was shown that the delayed, but not the early, form was reduced by capsaicin pretreatment, suggesting an involvement of chemosensitive primary sensory neurons in this reaction.

Animals↗

Sensory neuropeptides contribute to oedema formation in experimental burns.

The role of primary sensory neuropeptides in experimental burns was investigated. It was shown that after scalding, substance P-like immunoreactivity is released into the lymphatic fluid of dogs. Substance P, injected intravenously, was shown to cause dose-dependent oedema formation in rat skin, as measured with the Evans blue-technique. Furthermore, capsaicin pretreatment, which depletes the neuropeptide content of primary sensory neurons, was shown to inhibit late oedema formation in rats.

Animals↗

Sensory reinnervation and sensibility in skin transplants.

Reinnervation and sensibility were investigated in patients previously subjected to split thickness skin transplantation after excision of skin and subcutaneous fat for treatment of malignant melanoma. All patients except one showed poor sensibility and no neurofilament positive sensory nerve fibres were detected. Most patients had heat and pain sensibility but with a higher threshold than on the control side. It is suggested that this heat pain sensibility is mediated from nerve fibres in the underlying tissue. In one patient, however, sensibility was encountered and in this patient neurofilament positive sensory nerve fibres were observed in the dermis and epidermis.

Adult↗

DNA synthesis induced by the neuropeptide substance K correlates to the level of myc-gene transcripts.

Neuropeptides have recently been implicated in regulation of normal and neoplastic cell growth. Substance K is a neurotransmittor candidate that has been identified as a mitogen for smooth muscle cells and fibroblasts. However, the ability to respond to stimulation with substance K declines rapidly in cells serum-starved for more than 24 h and in parallel with a decrease in the intracellular level of myc-gene transcripts. Contrarily, myc-transformed cells, that inspite of a decrease demonstrated a high level of myc mRNA after 48 h in serum-free medium, maintained their ability to initiate DNA synthesis when stimulated with substance K. The results suggest that the intracellular signal of substance K-induced DNA synthesis interacts with the myc protein.

Animals↗

Distribution and origin of substance P- and neuropeptide Y-immunoreactive nerves in the guinea-pig heart.

The localization and origin of substance P (SP)-, neuropeptide Y (NPY)-, and noradrenaline/tyrosine hydroxylase (NA/TH)- immunoreactive (IR) nerves in the guinea-pig heart were investigated by means of immunohistochemistry; quantitative analysis was performed by radio-immunoassay (NPY) and high performance liquid chromatography (NA). Both untreated animals and animals subjected to stellatectomy, combined stellatectomy and local capsaicin pretreatment of the vagal nerves or systemic application of capsaicin were studied. A dense network of SP-IR nerves was observed in the right atrium in different locations: (1) around local cardiac ganglion cells, (2) close to blood vessels, (3) within the myocardium, and (4) close to and within peri- and endocardium. A moderately dense SP-innervation, mainly related to blood vessels, was found in the ventricles. Very dense networks of NPY- and TH-IR nerve fibers with an overlapping distributional pattern around blood vessels and in the myocardium were seen in both the atria and the ventricles. In addition, some cell bodies in local cardiac ganglia were NPY-IR. Bilateral stellatectomy resulted in a reduction of SP-IR in the right atrium (55% of control), which was more pronounced after additional capsaicin pretreatment of the vagal nerves (44% of control). In the left ventricle no significant depletion of SP-IR was seen by either stellatectomy or combined stellatectomy and capsaicin treatment of the vagal nerves. It was not possible to establish any defined target areas within the heart for vagal or spinal SP-IR afferents by use of immunohistochemical methods. Systemic capsaicin treatment caused a total loss of SP-IR nerves in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study.

Non-hairy and hairy human skin were investigated with the use of the indirect immunohistochemical technique employing antisera to different neuronal and non-neuronal structural proteins and neurotransmitter candidates. Fibers immunoreactive to antisera against neurofilaments, neuron-specific enolase, myelin basic protein, protein S-100, substance P, neurokinin A, neuropeptide Y, tyrosine hydroxylase and vasoactive intestinal polypeptide hydroxylase and vasoactive intestinal polypeptide (VIP) were detected in the skin with specific distributional patterns. Neurofilament-, neuron-specific enolase-, myelin basic protein-, protein S-100, neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities were found in or in association with sensory nerves; moreover, neuron-specific enolase-, myelin basic protein-, protein S-100, neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities occurred in or in association with autonomic nerves. It was concluded that antiserum against neurofilaments labels sensory nerve fibers exclusively, whereas neuron-specific enolase-, myelin basic protein- and protein S-100-like immunoreactivities are found in or in association with both sensory and autonomic nerves. Substance P- and neurokinin A-like immunoreactivities were observed only in sensory nerve fibers, and neuropeptide Y- and tyrosine hydroxylase-like immunoreactivities occurred only in autonomic nerve fibers, whereas vasoactive intestinal polypeptide (VIP)-like immunoreactivities was seen predominantly in autonomic nerves, but also in some sensory nerve fibers.

Autonomic Fibers, Postganglionic↗

Tachykinin multiplicity in rat central nervous system as studied using antisera raised against substance P and neurokinin A.

Antisera were raised in rabbits against the tachykinins neurokinin A (NKA) and substance P (SP). All NKA-antisera tested cross-reacted markedly with NKB, kassinin and eledoisin in radioimmunoassay (RIA), but virtually not with SP and physalaemin. Also when used for immunohistochemistry, one of the NKA-antisera was found to be virtually without cross-reactivity with SP. The most specific SP-antiserum did not cross-react with NKA but to some extent with NKB at the immunohistochemical level. Using these two antisera, the same distribution pattern of immunoreactivity was seen in both the rat substantia nigra and dorsal spinal cord. In neutral extracts of the substantia nigra, all NKA-antisera used for RIA detected a major component which eluted at the position of NKA in reverse phase high performance liquid chromatography, while no or only little immunoreactivity was detected at the position of NKB. A major component of substance P-like immunoreactivity (SPLI) co-eluting with SP and one or two minor SPLI-components were also detected in these extracts. An SP-antiserum, which cross-reacted markedly with physalaemin, detected an additional rather prominent component. In neutral water extracts of dorsal spinal cord the component detected with the NKA-antisera at the position of NKB, as well as one of the SPLI-components not eluting in the position of SP, were much more prominent than in the corresponding extracts of substantia nigra. In acetic acid extracts of both tissues, only one major SPLI-component co-eluting with SP could be detected, while only very small amounts of immunoreactivity eluting at the position of NKA and NKB (dorsal spinal cord only) could be detected using the NKA-antisera. The present results illustrate the importance of the extraction method used in immunochemical studies and demonstrate that the relative proportions of various tachykinins are markedly different in the rat substantia nigra and dorsal spinal cord.

Animals↗

Release of substance-P-like immunoreactivity in dog paw lymph after scalding injury.

The level of substance-P-like immunoreactivity (SPLI) in dog paw lymph was determined before and after scalding injury of the paw. At basal conditions, no SPLI could be detected in the paw lymph. Scalding induced an immediate increase of the SPLI-levels. Within 5-10 min after the scalding injury the levels increased up to 28 fmol ml-1 and then gradually decreased within 30-90 min after the injury. It is suggested that scalding injury results in release of substance P from sensory nerve endings, and that this release may contribute to the inflammatory response to scalding injury and, possibly, also wound healing.

Animals↗

Neuropeptide Y-like immunoreactivity in the lumbosacral pia mater in normal cats and after sciatic neuroma formation.

An indirect immunohistochemical technique was used to identify neuropeptide Y (NPY)-immunoreactive nerve fibers in the lumbosacral pia mater of normal cats and in kittens previously subjected to sciatic nerve resection. It was shown that NPY-positive fibers both associated with blood vessels and lacking vascular relation occur in the pia mater of normal cats. After nerve lesion some fibers which were not associated with blood vessels ramified extensively in the pia mater and formed thin beaded branches which ended blindly.

Amputation Stumps↗

Calcitonin gene-related peptide inhibits spontaneous contractions in human uterus and fallopian tube.

The localization and effects of calcitonin gene-related peptide (CGRP) in the human uterus and fallopian tube were investigated. CGRP-immunoreactive nerve fibers were found in the muscular layers, around blood vessels and close to the epithelium. The oviduct and uterine cervix were more densely innervated than the corpus of the uterus. Substance P (SP)-like immunoreactivity was found in nerves with an overlapping distribution to that of CGRP-positive fibers. CGRP (2 X 10(-10) to 10(-7) M) dose-dependently and reversibly inhibited spontaneous contractions of uterine and oviductal strips, as well as SP-induced contractions in the oviduct. A role for CGRP-containing nerve fibers in regulation of motor activity in human female reproductive organs is suggested.

Adult↗

Action and localization of neuropeptide Y in the human fallopian tube.

Using indirect immunohistochemistry, neuropeptide Y-like immunoreactivity was found in nerve fibers around blood vessels and in the muscle layers of the human fallopian tube. Apart from a network of immunoreactive nerve fibers in connection with the luminary epithelium of the isthmus, the distribution resembled that of adrenergic, tyroxine hydroxylase immunoreactive, nerve fibers. Neuropeptide Y was found to have a dose-dependent inhibitory action on the adrenergic contractile response to field stimulation in the external longitudinal muscle layer of the isthmus. Furthermore, neuropeptide Y inhibited [3H]noradrenaline release from isthmic preparations during field stimulation, suggesting a prejunctional inhibitory action on adrenergic neurotransmission.

Adult↗

Neurokinin A-like immunoreactivity in rat primary sensory neurons; coexistence with substance P.

Rat spinal cord, dorsal root ganglia and skin were investigated employing immunohistochemical technique with specific antisera to neurokinin A and substance P. Neurokinin A-like immunoreactivity was detected in the spinal dorsal horn and skin with a similar distribution pattern as that of substance P-like immunoreactivity. After dorsal root transection a parallel decrease of neurokinin A and substance P-like immunoreactivity was observed in the dorsal horn. Using colchicine pretreatment a population of neurokinin A positive cell bodies was seen in the dorsal root ganglia, and by comparison of consecutive sections of the same cells stained for substance P it was revealed that these neurons also display substance P-like immunoreactivity. However, substance P-, but not neurokinin A-, immunoreactive cells were also observed. It is concluded that neurokinin A- and substance P-like immunoreactivity coexist in a population of rat primary sensory neurons.

Animals↗

Evidence for substance P-immunoreactive spinal afferents that mediate bronchoconstriction.

The origin and functional role of capsaicin-sensitive substance P-(SP-) immunoreactive (IR) nerve fibres in the lower airways were studied in the guinea-pig. Stellatectomy caused a significant reduction of SP-IR in the lung and pulmonary artery. Immunohistochemical analysis, however, did not reveal any clear-cut change in the number and distribution of SP-IR fibres in the lung of these animals. After combined stellatectomy plus local capsaicin treatment of the vagal nerves, most SP-IR nerves disappeared in the lower airways. The bronchoconstriction induced by capsaicin was significantly reduced after stellatectomy and abolished after stellatectomy plus capsaicin pretreatment of the vagal nerves. Ether inhalation caused bronchoconstriction, which was not influenced by stellatectomy but markedly reduced by combined capsaicin treatment of vagal nerves and stellatectomy. Stellate ganglion stimulation in animals that had been chemically sympathectomized by 6-OH-dopamine caused bronchoconstriction, which was resistant to cholinergic or adrenergic receptor blockade. This response was absent after systemic capsaicin pretreatment, suggesting that it was due to antidromic stimulation of afferent fibres traversing the stellate ganglion. In conclusion, the present data suggest that the lower airways receive SP-IR capsaicin-sensitive C-fibre afferents of both vagal and spinal origin. These sensory fibres seem to have branches both within the bronchial smooth muscle and around blood vessels.

Afferent Pathways↗

Separate populations of primary sensory neurons project to the splanchnic nerve and thoracic spinal nerve rami of the rat. A fluorescent double labelling study.

Using fluorescent double labelling technique with one tracer applied to the greater splanchnic nerve and a second to the ventral or dorsal spinal nerve ramus at the T9 level, it was shown that two separate populations of sensory nerve cell bodies in the T9 dorsal root ganglion were projecting to the splanchnic nerve and spinal rami, respectively. Only two double labelled cells were detected. The results support the theory that spinal and/or supraspinal interactions and not dichotomizing sensory axons are responsible for referred pain.

Animals↗

Peripheral projections and neuropeptide coexistence in a subpopulation of fluoride-resistant acid phosphatase reactive spinal primary sensory neurons.

Combined retrograde axonal tracing with the fluorescent dye Fast Blue and fluoride-resistant acid phosphatase (FRAP) histochemistry revealed that the FRAP-containing sensory neurons project to both somatic and autonomic peripheral nerves. Furthermore, the combination of indirect immunohistochemistry after colchicine treatment and FRAP histochemistry showed that a population of FRAP-containing sensory neurons are also substance P, cholecystokinin or somatostatin positive.

Acid Phosphatase↗