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Biomedical subjects

S J Gibson

Publications and source records attributed to S J Gibson.

85 records · Page 5Linked to original sources

Cholestyramine-enhanced fecal elimination of carbon-14 in rats after administration of ammonium [14C]perfluorooctanoate or potassium [14C]perfluorooctanesulfonate.

After a single intravenous dose of ammonium [14C]perfluorooctanoate [( 14C]PFO, 13.3 mg/kg) or of potassium [14C]perfluorooctanesulfonate [( 14C]PFOS, 3.4 mg/kg) to rats, cholestyramine fed daily as a 4% mixture in feed was shown to increase the total carbon-14 eliminated via feces and to decrease liver concentration of carbon-14. Rats were fed cholestyramine in feed for 14 days after administration of [14C]PFO and for 21 days after administration of [14C]PFOS. Control rats were administered radiolabeled fluorochemical but were not treated with cholestyramine. Cholestyramine treatment increased mean cumulative carbon-14 elimination in feces by 9.8-fold for rats administered [14C]PFO and by 9.5-fold for rats administered [14C]PFOS. After [14C]PFO, a mean of 4% of the dose of carbon-14 was in liver of cholestyramine-treated rats at 14 days versus 7.6% in control rats; after [14C]PFOS, 11.3% of the dose was in liver at 21 days versus 40.3% in control rats. After administration of either radiolabeled compound, plasma and red blood cell carbon-14 concentrations, which were relatively lower than liver concentrations, were also significantly reduced by cholestyramine treatment.

Animals↗

Effect of peripheral nerve section and nerve crush on spinal cord neuropeptides in the rat; increased VIP and PHI in the dorsal horn.

An increase in vasoactive intestinal polypeptide (VIP) immunoreactivity in the dorsal lumbar hemisegment L4 of the spinal cord was observed by both radioimmunoassay and immunocytochemistry following sciatic nerve section or crush. Compared to the contralateral control hemisegment there was 125% and 35% more VIP immunoreactivity in the L4 hemisegment ipsilateral to the lesion 14 days following nerve section and crush respectively. The contralateral control hemisegment contained levels similar to L4 hemisegments from unoperated control rats. This increase appeared by immunocytochemistry to be confined to the substantia gelatinosa, in the region of termination of the majority of unmyelinated sciatic nerve afferents. Similar increases to VIP were observed for the peptide PHI, which is closely related to VIP. However, spinal cord substance P and somatostatin immunoreactivities were reduced following nerve section and unchanged following nerve crush whilst neurotensin and bombesin immunoreactivities were not affected following either lesion. Previous studies have shown that peripheral nerve injury produces a number of electrophysiological and biochemical changes in the dorsal horn of the spinal cord, including depletion of substance P in primary afferent neurones. The location of the cell bodies of fibres showing increased immunoreactivity remains to be established. Further studies are required to elucidate how these peptide changes are related to the adaptive processes which occur centrally following peripheral nerve injury.

Animals↗

Alterations in the structure, function, and chemistry of C fibers following local application of vinblastine to the sciatic nerve of the rat.

Vinblastine, a transport blocker, was applied locally to the sciatic nerve in rats. It was found to be a powerful neurotoxin with a dose-dependent action, destroying all afferents at doses of 5 X 10(-4)M, primarily C fibers at intermediate doses of 2.5 X 10(-4)M, and only at a critically low dose of 10(-4)M was a degeneration-free axon transport blockade, lasting for 4 to 5 days, produced. Such transport block failed to alter thermal responsiveness of the rats as measured behaviorally, by the flexor reflex, or by dorsal horn cell responses. It did, however, significantly reduce both the chemical sensitivity of the C afferents and their ability to produce neurogenic edema. This began 24 hr after treatment and lasted 4 to 5 days. Therefore, it is likely that these functions are dependent on the continuous transport of some compound to the axon terminals from the cell body. This low concentration of local vinblastine treatment also resulted in depletion of fluoride-resistant acid phosphatase from C fiber terminals in the dorsal horn of the spinal cord. Transmission from C fibers to second-order neurons in the spinal cord, however, was totally unaffected. Substance P levels in the spinal terminals was largely unaffected, although in 1 of 5 cases there was depletion. It appears, therefore, that some, but not all, retrograde changes in sensory neurons following peripheral nerve damage can be mimicked by blockade of axon transport. The effects following vinblastine treatment are compared to other peripheral nerve manipulations, such as cut, crush, and application of local capsaicin.

Afferent Pathways↗

Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species.

Calcitonin gene-related peptide (CGRP) immunoreactivity was found throughout the entire spinal cord of man, marmoset, horse, pig, cat, guinea pig, mouse, rat, and frog. CGRP-immunoreactive fibers were most concentrated in the dorsal horn. In the ventral horn of some species large immunoreactive cells, tentatively characterized as motoneurons, were present. Pretreatment of rats with colchicine enhanced staining of these large cells but did not reveal CGRP-immunoreactive cell bodies in the dorsal horn. In the dorsal root ganglia, CGRP immunoreactivity was observed in most of the small and some of the intermediate sized cells. Substance P immunoreactivity, where present, was co-localized with CGRP to a proportion of the small cells. In the cat the ratio of substance P-immunoreactive to CGRP-immunoreactive ganglion cells was 1:2.7 (p less than 0.001). The concentration of CGRP-immunoreactive material in tissue extracts was determined by radioimmunoassay. In the dorsal horn of the rat spinal cord the levels of peptide were found to range from 225.7 +/- 30.0 pmol/gm of wet weight in the cervical region to 340.6 +/- 74.6 pmol/gm in the sacral spinal cord. In the rat ventral spinal cord, levels of 15.7 +/- 2.7 to 35.1 +/- 10.6 pmol/gm were found. The concentration in dorsal root ganglia of the lumbar region was 225.4 +/- 46.9 pmol/gm. Gel permeation chromatography of this extractable CGRP-like immunoreactivity revealed three distinct immunoreactive peaks, one eluting at the position of synthetic CGRP and the others, of smaller size, eluting later. In cats and rats, rhizotomy induced a marked loss of CGRP-immunoreactive fibers from the dorsal horn of the spinal cord. In the cat, unilateral lumbosacral dorsal rhizotomy resulted in a significant (p less than 0.05) reduction of extractable CGRP from the ipsilateral lumbar dorsal horn (5.6 +/- 1.2 pmol/gm of wet weight) compared to the contralateral side (105.0 +/- 36.0 pmol/gm of wet weight). We conclude that the major origin of CGRP in the dorsal spinal cord is extrinsic, from afferent fibers which are probably derived from cells in the dorsal root ganglia. The selective distribution of CGRP throughout sensory, motor, and autonomic areas of the spinal cord suggests many putative roles for this novel peptide.

Animals↗

Improved section adhesion for immunocytochemistry using high molecular weight polymers of L-lysine as a slide coating.

Poly-L-lysine (PPL) has been used to coat glass slides in the preparation of tissue sections for immunocytochemical staining. The adhesive properties of different molecular weight (m.w.) polymers of L-lysine have been tested on pre-fixed cryostat sections which were subjected to a 3 day washing treatment. It has been found that the higher the molecular weight of the polymer, the greater the adhesive force it provides. PLL (m.w. 350,000) at concentrations in the range of 0.05-0.1% was found to be the most effective polymer.

Adhesiveness↗

Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat.

Rat sciatic nerves were treated with tetrodotoxin (TTX) for 4--10 days, by implanting a glass capillary tube filled with TTX into the nerve through the epineurium. Following this treatment the somatotopic organization of receptive fields in the L4 dorsal horn, an area of cord normally responding only to foot stimulation. The map was normal in animals treated with TTX. Dorsal horn levels of fluoride-resistant acid phosphatase, substance P, somatostatin, cholecystokinin-like peptide, neurotensin and neurophysin were also normal as assessed from density of staining. These results are discussed in the light of the positive changes that are seen following chronic sciatic nerve section.

Acid Phosphatase↗

Local application of capsaicin to one sciatic nerve of the adult rat induces a marked depletion in the peptide content of the lumbar dorsal horn.

In an earlier study we have shown that local application of capsaicin directly to one sciatic nerve induces a decrease of substance P and cholecystokinin octapeptide (CCK8)-like peptide from the dorsal spinal cord using immunocytochemical analysis. Here the effect of locally applied capsaicin on seven peptides known to be present in the L4 segment was assessed by radioimmunoassay and immunocytochemistry. The peptides investigated were substance P, somatostatin and CCK8-like peptide (which are present in small diameter primary afferent fibres), neurotensin, enkephalin (which are intrinsic to the spinal cord), neurophysin (of supraspinal origin) and bombesin (whose origin is unknown). Fourteen days after a single application of 49 mM solution of capsaicin a significant depletion of substance P and somatostatin was detected. These results were confirmed by parallel immunocytochemical analysis which localised the dramatic decreases of substance P and somatostatin to lamina 1 and lamina 2. In addition a depletion of CCK8-like immunoreactivity was observed by immunocytochemistry in this area, but quantitative radioimmunoassay of CCK8-like peptide did not detect this depletion. The capsaicin-induced changes were dose-dependent and reversible. Small decreases were noted with concentrations of capsaicin as low as 0.1 mM. The changes were apparent from day 9 onwards, maximal depletion seen by day 14. By 200 days post-operatively, a recovery to normal peptide levels in the ipsilateral dorsal horn was observed. In addition, a significant depletion of cutaneous substance P was noted in the area of the skin innervated by the capsaicin-treated nerve. These changes were accompanied by a significant increase in noxious thermal response (hind paw immersion test, T = 49 degrees C, ipsilateral leg 9.11 +/- 1.3 seconds, contralateral leg: 5.1 +/- 1.3 seconds, P = less than 0.005). The peptides neurotensin, enkephalin, neurophysin and bombesin were not affected by capsaicin treatment. These findings suggest that local application of capsaicin induces an indiscriminate depletion of peptide-containing primary sensory afferent fibres which is dose-dependent, long-lasting, but reversible.

Administration, Topical↗

The distribution of nine peptides in rat spinal cord with special emphasis on the substantia gelatinosa and on the area around the central canal (lamina X).

The comparative distribution of nine peptides was examined in the L4 segment of the rat cord using the peroxidase antiperoxidase technique. The peptides examined were substance P, neurotensin, cholecystokinin, methionine-enkephalin, oxytocin, neurophysin, adrenocorticotrophin, thyrotropin releasing hormone, and vasoactive intestinal polypeptide. No transport blocking agents were used and in spite of this cell bodies containing substance P, neurotensin, cholecystokinin, and methionine-enkephalin were observed. All peptides except for thyrotropin releasing hormone were observed in fibers in laminae I and II. All peptides were present in the area around the central canal, lamina X. Each peptide had its own characteristic distribution within fibers in the gray and white matter.

Adrenocorticotropic Hormone↗

An investigation into the validity of specifying 5 "O' levels in the General Certificate of Education as an entry requirement for the education and training of district nurses.

District nursing, like many other professionalizing occupations, has stipulated that possession of five ordinary level GCE passes might constitute one criterion of entry. This paper reports a longitudinal study over four intakes of district nurse students in one teaching centre and examines the relationship between selection criteria, in particular educational achievement prior to entry to the course, and the students' achievement during this. The research explored the relationship between educational achievement prior to commencing their course of study and the level of academic and practical performance during it. Additionally other factors, including the results of aptitude and personality tests, were examined to see if they would provide indication of the level of the students; grades during training. No factors were discovered that might provide an adequate basis for selection, which raises questions about trying to specify any pre-requisite for selection other than state registration and appropriate professional experience until further research has been undertaken.

Achievement↗

The distribution and origin of VIP in the spinal cord of six mammalian species.

The distribution of VIP-immunoreactivity was studied in the spinal cord and dorsal root ganglia of 6 mammalian species. Immunoreactive fibres and cell bodies were most apparent in the dorsal horn, dorsolateral funiculus, intermediolateral cell columns and the area around the central canal. The distribution of VIP immunoreactivity was similar in all species studied, mouse, rat, guinea pig, cat, horse and the marmoset monkey. There were fewer VIP fibres in the dorsal horn of cervical and thoracic segments than in lumbosacral segments. Using radioimmunoassay this gradient increase was quantitatively most marked in the sacral spinal cord of the cat. In dorsal root ganglia few nerve cell bodies but numerous fibres were present. A dual origin for VIP in the spinal cord is suggested: (A) Extrinsic, from dorsal root afferent fibres since immunoreactivity was decreased in dorsally rhizotomized animals (cats and rats) and in capsaicin pretreated rats (microinjection of dorsal root ganglia). (B) From local cell bodies intrinsic to the spinal cord which became visible after colchicine pretreatment of rats.

Animals↗

A VIP-containing system concentrated in the lumbosacral region of human spinal cord.

Neuropeptides were first localized in the human spinal cord by immunocytochemistry and substance P has been shown, by the same method, to be reduced ipsilaterally in the dorsal horn after limb amputation and bilaterally in the Riley-Day syndrome. Several neuropeptides increasingly fulfil the criteria to establish them as neurotransmitters or neuromodulators, and they may also have trophic actions in the spinal cord. Using radioimmunoassay and immunocytochemistry, we present here for the first time a quantitative regional distribution and localization of vasoactive intestinal polypeptide (VIP), substance P, somatostatin, bombesin and cholecystokinin (CCK-8) in normal postmortem human spinal cord. A comparison of the distribution of these peptides reveals an exceptional pattern for VIP, with relatively much higher levels in the lumbosacral region. Immunocytochemical analysis shows a distinctive distribution of VIP-containing fibres and terminals at the lumbosacral segments. This VIP-containing system may have an important role in the spinal control of urogenital function in man.

Bombesin↗

Pain in older persons.

Chronic pain is more prevalent in older persons than in young adults. In this review the physiological, pathological, and psychological reasons for altered pain sensibility in older persons are explored and strategies for the management of pain in older persons described. The evidence suggests that altered physiology of peripheral and central pain mechanisms combine with psychological attitudes, such as stoicism and reluctance to confirm the presence of pain, to raise pain threshold. However, once pain is experienced, older persons describe the same severity, quality, and psychological disturbance as younger persons. There is some evidence to suggest that the complaint of pain in the presence of pathology is reported less often in older persons. On the other hand, the presence of persistent or recurrent clinical pain may have a greater impact on the psychological, social, and physical function of older adults. It is also clear, however, that further empirical studies are required in order to delineate the age-related differences and similarities in the chronic pain experience. Management of chronic pain in the elderly requires meticulous diagnosis of the causal pain mechanisms as well as a holistic approach which gives due regard to psychological and social consequences of pain.

Affect↗