Correction by erythropoietin of anaemia in autonomic failure.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Anand.
Explore the source record for details and available documents.
The expression of neuropeptides galanin, vasoactive intestinal polypeptide (VIP) and substance P was compared after injury to somatic (sciatic, pudendal) and visceral (pelvic) nerves. Studies in normal rats and the mutant rat 'mutilated foot' suggested that galanin increases in sensory but not sympathetic fibres after sciatic nerve injury, while VIP appears to increase in both sensory and sympathetic fibres, and substance P to decrease in sensory fibres. A direct comparison of neuropeptide changes after somatic and visceral nerve injury was made in the cat dorsal sacral spinal cord, where both pudenal (somatic) and pelvic (visceral) afferents terminate. Four weeks after pudendal nerve transection in the cat there was an increase of VIP and galanin but decrease of substance P in the dorsal sacral cord, similar to the changes in lumbar dorsal cord after sciatic nerve section in the rat. In contrast, 4 weeks after pelvic nerve transection in the cat, galanin was unchanged in the ipsilateral dorsal sacral spinal cord, whereas VIP is known to decrease markedly and substance P to remain unchanged. There is thus differential peptide expression before and after injury in somatic and visceral systems, which may be regulated in part by the target organ. We have proposed that the neuropeptide changes occur in neurons that regulate development, maintenance and repair after injury, processes that may differ in somatic and visceral systems.
A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF.
The neuropeptides vasoactive intestinal polypeptide (VIP), substance P and somatostatin were studied in skin biopsies from patients with eczema, psoriasis and axillary hyperhidrosis. VIP concentrations were elevated in skin affected by eczema and psoriasis, whereas substance P and somatostatin levels did not differ from controls. There was a higher concentration of VIP, but not of substance P or somatostatin, in normal axillary skin when compared to adjacent trunk skin, with abundant VIP-containing fibres surrounding eccrine sweat glands. The VIP concentration was unchanged in skin affected by axillary hyperhidrosis. VIP may increase local blood flow in eczema and psoriasis, but does not appear to play a role in axillary hyperhidrosis.
A dichotic listening task was used to investigate the affect-without-recognition phenomenon. Subjects performed a distractor task by responding to the information presented in one ear while ignoring the target information presented in the other ear. The subjects' recognition of and affect toward the target information as well as toward foils was measured. The results offer evidence for the affect-without-recognition phenomenon. Furthermore, the data suggest that the subjects' affect toward the stimuli depended primarily on the extent to which the stimuli were perceived as familiar (i.e., subjective familiarity), and this perception was influenced by the ear in which the distractor or the target information was presented. These data are interpreted in terms of current models of recognition memory and hemispheric lateralization.
The increased expression of vasoactive intestinal polypeptide (VIP) in injured peripheral neurons was studied. In contrast to substance P, there was a marked increase, and maintained fast axonal transport, of VIP in rat sciatic nerve after peripheral axotomy. Local capsaicin application to the nerve trunk failed to inhibit the injury-induced VIP increase, and capsaicin even increased VIP levels when applied locally to uninjured nerves. Pharmacological sympathectomy showed that some of the peripheral VIP increase may occur in post-ganglionic sympathetic fibres. The VIP increase after injury appeared unaffected in the mf mutant rat, in spite of its loss of lumbar dorsal root ganglion cells. VIP-staining fibres in the epi- and peri-neurium and perivascular plexuses of sciatic nerve showed an increase in number in parallel with the changes of the nerve VIP content. These findings suggest that sensory and sympathetic nerve fibres expressing VIP after injury play a role in the regulation of blood flow to nerves, and in the pathophysiological processes in nerve and dorsal spinal cord which follow peripheral nerve injury.
Explore the source record for details and available documents.
We have studied quantitatively the levels of substance P and calcitonin gene-related peptide in nerves innervating skin and muscle of rats, and examined the effects of cross-anastomosing these nerves so that they regenerate to an inappropriate target. We have also compared the ability of nerves to induce neurogenic extravasation with their peptide content. Peptide was measured by radioimmunoassay in the proximal section of ligated peripheral nerves, and neurogenic oedema was measured by determination of Evans Blue extravasation induced by either systemic capsaicin treatment or topical mustard oil application. The levels of these peptides are higher in cutaneous nerves than muscle nerves. This cannot be explained by differences in the number of fibres in the nerves studied. The levels of peptides fall when cutaneous afferents reinnervate muscle, and rise when muscle afferents reinnervate skin. We suggest that these changes occur because of some tissue-specific trophic influence arising from the tissue innervated. The ability to produce extravasation in skin is highly correlated with the substance P and calcitonin gene-related peptide levels of its innervation, even when this occurs in inappropriate nerves which do not normally produce extravasation.
Observations on streptozotocin-diabetic rats have confirmed overhydration of peripheral nerve. As in previous studies, the sorbitol and fructose content, when expressed in terms of wet weight of nerve was found to be increased and myo-inositol decreased. The reduction in myo-inositol content was less, although still significant, when expressed in terms of protein content. Nerve water content increased during Wallerian degeneration following a crush injury in both normal and diabetic animals, but was relatively less in the latter. Vasoactive intestinal polypeptide (VIP) concentrations were significantly increased in diabetic nerve, those for substance P being normal. Both became severely reduced during Wallerian degeneration following nerve crush and ligature. The significance of these findings is discussed. The accumulation of water in the endoneurial compartment may be related to impaired extraction by the perineurium, to which the increased VIP content may contribute. These changes are unlikely to be responsible for nerve fibre damage.
In view of the presence of neuropeptides in spinal cord autonomic pathways, their regional concentration was studied in post mortem thoracic cord from four cases of multiple system atrophy with progressive autonomic failure (MSA). A marked depletion was observed of substance P, its related peptide substance K, and of calcitonin gene-related peptide (CGRP), particularly in dorsal regions where peptide-containing sensory fibres terminate. As substance P and CGRP in primary sensory fibres are considered mediators of skin flares in Lewis' triple response, histamine-induced skin flares were measured in 12 MSA patients and were found to be preserved. These results provide a new key to the classification and aetiology of autonomic and multiple system degenerations, as well as a model to study the role of sensory neuropeptides in man.
That substance P may be a neurotrophic factor in urodele limb regeneration was investigated in the axolotl (Ambystoma mexicanum). Two weeks after section of the peripheral nerves to the forelimb, there was a marked increase in substance P-like immunoreactivity (IR) content of the nerves proximal to the lesion. A smaller increase occurred as early as 3 days after section of nerves innervating a regrowing limb bud (blastema), and substance P-IR fibres were observed by immunocytochemistry to innervate blastema tissue. As substance P-IR by applying capsaicin to peripheral nerve--capsaicin had no effect on substance P-IR in either intact or injured axolotl nerves. Substance P fulfills a number of criteria of a trophic substance in axolotl limb regrowth.
The peptides substance P, calcitonin gene-related peptide and somatostatin are present in nerve fibres in mammalian, including human, skin. There is evidence that in addition to having a putative neurotransmitter role, they may be trophic agents: a study was therefore undertaken of peptide changes during wound healing in rat skin. A significant depletion of the neuropeptides was found in the region of the wound within two days, and this persisted for two weeks. A smaller and delayed depletion also occurred in intact skin of the same dermatome, but not in an adjacent dermatome.
The regional distribution of a novel peptide (P7 of 1B236) in the human central nervous system (CNS) was examined. P7-like-immunoreactivity (p7-LI) was shown to be distributed throughout the CNS, with a chromatographic pattern closely similar to that previously described in rat. In the brain the concentrations of P7-LI were higher in the globus pallidus and substantia nigra than in any other regions. Considerable amounts of P7-L1 were also found in the cerebellum. In the spinal cord the concentration of P7-L1 was slightly higher in the ventral than in the dorsal cord, though no difference in concentration was found between cervical, thoracic, lumbar and sacral regions. The distribution pattern of this novel peptide reveals its predominance in sub-cortical motor areas. Studies of its pharmacological effects and possible role in movement disorders are awaited with interest.
Explore the source record for details and available documents.
Nerve fibres containing VIP and the co-produced PHI are found in the dorsal horn and autonomic centres of the sacral spinal cord and in pelvic organs. We have investigated the origin of these nerve fibres and a possible peptide-containing pathway linking pelvic viscera with the spinal cord of the cat and rat using neurochemical and neurosurgical procedures, retrograde tracing and immunocytochemistry. Cell bodies were located in the dorsal root ganglia (after colchicine injection), pelvic ganglia and bladder wall. Capsaicin treatment induced a loss of VIP/PHI from the dorsal horn. Retrograde tracing from the bladder revealed True Blue labelled cells in the dorsal root ganglia (L6, S1), parasympathetic nuclei and pelvic ganglia. Labelled cells were sequentially immunostained for VIP/PHI which were numerous in pelvic ganglia and scattered and weak in dorsal root ganglia. Pelvic nerve section induced a decrease of VIP/PHI immunoreactivity from the spinal cord and no change or a minimal increase in immunoreactive nerve fibers of the bladder. Thus pelvic visceral afferents with cell bodies in the dorsal root ganglia are a significant source of VIP/PHI-containing fibres in the sacral dorsal horn.
Explore the source record for details and available documents.
Radioimmunoassay and immunocytochemistry were used to study the distribution of galanin, a novel 29 amino acid porcine intestinal peptide, in the central nervous system of the rat and pig. The pattern of distribution was similar in the two species, with the highest concentrations of galanin-like immunoreactivity found in the neurohypophysis, hypothalamus and sacral spinal cord. Immunocytochemical studies of these regions localized galanin-like immunoreactivity to cell bodies in the paraventricular and supraoptic nuclei of the hypothalamus, to fibres in the pars nervosa and to numerous cell bodies and fibres in the dorsal horn of the spinal cord. On both gel and high pressure liquid chromatography, galanin-like immunoreactivity in rat and pig nervous tissue eluted as a single peak in a position similar to purified procine intestinal galanin standard. Surgical and pharmacological manipulations in the rat suggest the presence of galanin in afferent fibres. An increase of galanin-like immunoreactivity was observed in the sacral spinal cord of the rat following thoracic spinal cord transection. Thus galanin-like immunoreactivity in the brain is mainly localized in the hypothalamopituitary region. The decrease of galanin-like immunoreactivity in the dorsal horn of the spinal cord, following dorsal rhizotomy and pre-treatment of rats with capsaicin, indicates that many of the fibres, which are of small diameter, may well be derived from spinal sensory neurones.
Explore the source record for details and available documents.