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Biomedical subjects

K Chung

Publications and source records attributed to K Chung.

At least 127 records · Page 7Linked to original sources

The effect of portal hypertension on indomethacin-induced small intestinal ulceration in the rat.

The purpose of this study was to determine whether portal hypertension potentiates intestinal ulceration induced by indomethacin. Portal hypertension was produced in male Sprague-Dawley rats by two-staged ligation of the portal vein. Sham-operated rats were used as controls. The rats were given 20 mg/kg of indomethacin intragastrically, 7 and 14 days, respectively, after complete portal vein ligation. Forty-eight and 72 h after indomethacin, portal pressures were measured and the whole small intestine removed for quantitative measurement of the percent of the mucosa ulcerated by computerized image analysis. There were no differences in the area of ulceration between the portal hypertensive and sham-operated rats at either 7 or 14 days, despite the presence of significant portal hypertension. Portal hypertension does not appear to potentiate small intestinal ulceration induced by indomethacin in rats.

Animals↗

Absence of neurogenesis of adult rat dorsal root ganglion cells.

Recently, an age-related increase in the number of dorsal root ganglion (DRG) cells was reported in adult rats. This suggests neurogenesis of adult primary afferent neurons, which would be an extremely important phenomenon if it occurred. Other evidence is not compatible with this idea, however, so the issue is not settled. The primary point of contention concerns the counts of DRG cells in relation to age. In our opinion, these disagreements arise, at least in part, because different counting methods give different results for the same material. Thus, any method for determining DRG cell numbers should be calibrated. We previously calibrated some of the common methods used to count DRG cells and found that an empirical method gave accurate cell counts. In the present study, we have used this method and asked whether an age-related increase in the number of lumbar DRG cells can be demonstrated in adult rats. Our data indicate that DRG cell numbers remain essentially constant from 3 to 22 months of age. Most ancillary evidence is consistent with the hypothesis that mammalian DRG cell numbers do not change during adult life. Thus, we feel that the evidence does not support the hypothesis that there is neurogenesis of adult rat primary afferent neurons.

Aging↗

Increased number of unmyelinated fibers in the ventral root after peripheral neurectomy in adult rat.

We examined the possibility that peripheral nerve injury in the adult rat triggers sprouting of unmyelinated ventral root afferent fibers. Three to 5 months after the sciatic nerve was sectioned on one side in the adult rat, myelinated and unmyelinated fibers were counted at 3 sites along the length of the ventral root. A sciatic nerve lesion resulted in about a 3-fold increase in the number of unmyelinated fibers in the L5 ventral root. Our data suggest that a peripheral nerve lesion in the adult rat triggers sprouting of unmyelinated afferent fibers in the ventral root. No evidence was found that dorsal rhizotomy triggers sprouting of afferent fibers.

Animals↗

The receptive part of the primary afferent axon is most vulnerable to systemic capsaicin in adult rats.

The present study shows that systemic capsaicin in adult rats results in a significant loss of axons in the subepidermal nerve plexus of the posterior leg but no loss of axons in the sural nerves of these same animals. These data are interpreted as indicating that the receptive part of the peripheral sensory axon is destroyed but that the cell body and most of the peripheral axon remains intact. Thus we suggest that the receptive part of the peripheral sensory axon is the most vulnerable part of the primary afferent neuron to capsaicin in these animals. These findings may explain the observation that adult rats treated with systemic capsaicin are deficient in their responses to certain painful stimuli but usually do not show obvious signs of primary afferent neuron death. We also suggest that as the dose of capsaicin is increased the whole neuron dies. It remains to be determined if the peripheral damage reported here is related to the striking loss of primary afferent markers in the dorsal horn that is also seen after this treatment.

Animals↗

Long ascending unmyelinated primary afferent axons in the rat dorsal column: immunohistochemical localizations.

The present study demonstrates a significant number of calcitonin gene-related peptide (CGRP) immunolabeled unmyelinated axons in the C3 fasciculus gracilis of the rat. Approximately 88% of these axons are lost following dorsal rhizotomies from midthoracic levels caudally. Assuming that CGRP labels primary afferent axons, these findings support the hypothesis that there are significant numbers of long ascending unmyelinated primary afferent axons in the dorsal columns of the rat. If these findings can be generalized, they may have clinical import.

Animals↗

Ascending unmyelinated primary afferent fibers in the dorsal funiculus.

The primary purpose of the present study is to obtain evidence as to the destination of the recently discovered unmyelinated primary afferent fibers in the mammalian dorsal funiculus. To do this rat dorsal roots were transected unilaterally from segments T8 or T9 caudally, and the numbers of axons were determined in the C3 fasciculus gracilis in normal animals and from both sides of the rhizotomied animals. In addition, C3 fasciculus gracilis counts were done in animals that had complete T6 or T10 spinal transections. The data indicate that there is an 80% loss of unmyelinated axons ipsilaterally and a 60% loss contralaterally in the fasciculus gracilis of the rhizotomied animals. These findings are interpreted as indicating that a significant fraction of the unmyelinated fibers in the fasciculus gracilis ascend, presumably to the nucleus gracilis in the brain stem, and also that a significant number of these fibers branch. We also provide evidence for contralateral myelinated primary afferent fiber projection in the fasciculus gracilis and show that the myelinated primary afferent fibers seem to be a more diverse population than the unmyelinated primary afferent fibers in the C3 fasciculus gracilis.

Animals↗

Changes in dorsal horn synaptic disc numbers following unilateral dorsal rhizotomy.

The present study estimates the numbers of synaptic discs and numbers of degenerating synaptic terminals in laminae I-IV of the rat S2 dorsal horn ipsi- and contralateral to unilateral dorsal rhizotomy. These data allow us to estimate the loss of synapses of primary afferents and to correlate this loss with the rate of axon disappearance in the proximal stump of a transected S2 dorsal root. Our first findings are that 47% of the ipsilateral synapses and 27% of the contralateral synapses disappear within a day following unilateral rhizotomy. Conclusions are that the predominant synaptic population in this part of the rat spinal cord is of primary afferent origin and that there is an extensive bilateral projection of the dorsal root fibers. The contralateral projection is confirmed by the appearance of numerous degenerating terminals on the contralateral side. We also find that synaptic loss and appearance of degenerating terminals occur relatively synchronously in laminae I-IV. Finally we find that the time course of the synaptic loss correlates primarily with the disappearance of unmyelinated fibers in the proximal stump of the transected dorsal root.

Animals↗

Immunohistochemical localization of seven different peptides in the human spinal cord.

It is necessary to study the normal chemical contents in the human spinal cord in order to understand neurochemical changes that might occur under pathological conditions. In the present study, the comparative distribution of seven peptides was examined immunohistochemically in four levels (cervical, C; thoracic, T; lumbar, L; sacral, S) of the human spinal cord by means of the peroxidase-antiperoxidase technique. The peptides examined included bombesin (BOM), substance P (SP), cholecystokinin (CCK), somatostatin (SOM), methionine-enkephalin (M-ENK), vasoactive intestinal polypeptide (VIP), and thyrotropin releasing hormone (TRH). Among the seven peptides examined, four (BOM, CCK, SOM, and TRH) have never been described in the human spinal cord and the present work clearly demonstrates their existence in specific patterns. The terminals that were immunostained for BOM and CCK were localized in high concentration in the superficial dorsal horn (laminae I-II), in moderate amounts in the lateral part of laminae V and VII, and lesser amounts in the intermediate gray (lamina VII) and the dorsal part of the central gray (lamina X). Whereas BOM showed a similar distribution pattern at all spinal levels, CCK was mainly found in thoracic and lumbar levels. The SOM terminals were localized in the superficial dorsal horn (the highest density in lamina II but very few in lamina I), the intermediolateral cell column, intermediate gray, and central gray. This peptide was more widely distributed in the sacral cord with its terminal field extending into the ventral horn. The TRH terminals were mainly located in the ventral horn. Frequently, TRH terminals were seen adjacent to large ventral horn neurons. Furthermore, many neurons in the ventral and intermediate gray and Clarke's column demonstrated TRH immunoreactivity. The other three peptides (SP, M-ENK, and VIP) have been previously demonstrated in the human spinal cord and the present study confirmed their general spinal distribution with minor differences.

Adult↗

Pharmacokinetics and disposition of pipecuronium bromide in dogs with and without ligated renal pedicles.

The pharmacokinetics of pipecuronium bromide have been studied in anesthetized beagle dogs with and without ligated renal pedicles. A gas chromatographic assay was used to measure the plasma, urine, bile concentrations, and liver content of pipecuronium, the later of which was obtained 8 h after injection. Following an iv bolus injection of 0.1 mg/kg, pipecuronium disappeared from the plasma exponentially with distribution half-lives of 3.9 +/- 1.1 min and 12.7 +/- 9.5 min (mean +/- SD), and elimination half-lives of 44.8 +/- 2.6 min and 196.7 +/- 102.0 min in animals with and without renal pedicle ligation, respectively. Except for the volume of central compartment, all other pharmacokinetic variables differed significantly between the two experimental groups. The elimination half-life was longer (196.7 +/- 102 (SD) vs. 44.8 +/- 2.6 min), plasma clearance slower (5.9 +/- 0.8 ml.kg-1.min-1 vs. 0.9 +/- 0.1 ml.kg-1.min-1) and mean residence time longer (221 +/- 73 vs. 51.1 +/- 1.8 min) in dogs with ligated renal pedicles. Eight hours after injection, the recovery of the parent form of pipecuronium approximated 77% of the administered dose in the urine, 4.5% in the bile, and 3.3% in the liver of normal animals. In animals with ligated renal pedicles 16% of the unchanged pipecuronium was excreted into the bile and 10% of the administered dose was recovered from the liver. Since the total recovery of unaltered pipecuronium approximated 85% of the administered dose in the intact animals, biotransformation seems to play an insignificant role in disposition of this new neuromuscular blocking drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstane-3,17-diol↗

Vasoactive intestinal polypeptide (VIP) immunoreactivity in the ependymal cells of the rat spinal cord.

Vasoactive intestinal polypeptide (VIP) was demonstrated immunohistochemically in the entire ependymal and subependymal cells in all levels (cervical: C, thoracic: T, lumbar: L and sacral: S) of normal adult rat spinal cord. The VIP-immunoreactive basal processes from the apical ependymal cells coursed dorsally or ventrally along the median plane and reached the pia mater of the dorsal and ventral median septa. Many VIP-immunoreactive basal processes terminated on the blood vessels in the neuropil around the central canal. A few microvilli of the ependymal cells that project into the central canal also demonstrated intense VIP immunoreactivity. These observations suggest that ependymal cells may be involved in the modulation of VIP levels in the cerebrospinal fluid and regulation of vascular tone of the blood vessels in the spinal cord.

Animals↗

Numbers of synapses in laminae I-IV of the rat dorsal horn.

The present study determines numerical densities (NVsyn) and total numbers of synaptic discs in laminae I-IV of the rat S2 dorsal horn. Previous methods for NVsyn have the advantage of being relatively simple, but these assume that the discs are round, flat, and of uniform size. In our material, serial reconstructions indicate that these assumptions are not met. Accordingly we use a stereological method that is not as dependent on these assumptions. This method is to divide the surface density of the discs by the mean surface area of a disc (NVsyn = SVsyn/Ssyn). We refer to this as a reconstruction method because synaptic discs are reconstructed from serial sections. We also calculate numerical densities by several previously used standard methods, and the findings are similar but not identical. We find that numerical density and total synaptic numbers are smallest in lamina I, and densities and total numbers are not significantly different when lamina II is compared to laminae III and IV. Thus the intense labeling of terminals with certain compounds that characterize lamina I and II does not imply an increase in total synaptic numbers or in synaptic density. In addition there is a general increase in synaptic densities and numbers as one proceeds from lamina I to lamina IV. Another point is that the numerical density of synapses in the dorsal horn is approximately that of the cerebral cortex. These data will serve as a basis from which to judge the effects of denervations and other manipulations that purportedly change synaptic numbers.

Animals↗

Organization of calcitonin gene-related peptide-immunoreactive terminals in the primate dorsal horn.

The present paper is concerned with the arrangement of axons and synaptic terminals immunostained for calcitonin gene-related peptide (CGRP), a primary afferent marker, in the primate (Macaca fascicularis) dorsal horn. The CGRP axons and terminals are uniformly distributed in laminae I and II outer (o) but they are concentrated laterally and distributed intermittently in the reticulated region of lamina V. A prominent bundle of labeled axons is seen in the sacral cord dorsal to the central canal. Emphasis is given to the relation of CGRP-immunoreactive terminals to other terminals, both labeled and unlabeled, in laminae I and IIo. In this regard, adjacent CGRP-immunoreactive terminals are often united by puncta adhaerentia. Of particular interest is the observation that CGRP-immunoreactive terminals can be found presynaptic to other terminals which sometimes resemble central primary afferent endings. In addition CGRP-immunoreactive terminals end on other CGRP terminals. Both findings suggest that primary afferent terminals interact synaptically with other primary afferent terminals.

Animals↗

The effects of dorsal rhizotomy and spinal cord isolation on calcitonin gene-related peptide-labeled terminals in the rat lumbar dorsal horn.

In the present study, the origin of calcitonin gene-related peptide (CGRP) to the dorsal horn in the rat lumbar spinal cord is investigated. CGRP immunoreactivity is examined following multiple unilateral and bilateral dorsal rhizotomies and isolated cord preparations (spinal cords are isolated by transecting the cord in two places and cutting all dorsal roots between the transections). Seven to 11 days after surgery, unilateral multiple dorsal rhizotomies result in a drastic decrease in CGRP-stained terminals on the operated side; following bilateral dorsal rhizotomies and isolated cord preparations, one or two CGRP varicosities remain in the dorsal horn in each section. The numbers of CGRP-immunostained varicosities observed in the latter two preparations are not significantly different, suggesting that few if any axons descending from the brain contribute to the CGRP terminal population in the spinal cord dorsal horn. Based on these data, we hypothesize that dorsal root ganglion cells are the only source of CGRP to the rat lumbar dorsal horn.

Animals↗

Calcitonin gene-related peptide immunostained axons provide evidence for fine primary afferent fibers in the dorsal and dorsolateral funiculi of the rat spinal cord.

The hypothesis being tested in the present paper is that there are large numbers of fine primary afferent axons in the dorsal and dorsolateral funiculi of the lumbar spinal cord of the rat. The data show numerous calcitonin gene-related peptide labeled fine myelinated and unmyelinated axons in these funiculi. Approximately 95% of the labeled axons disappear after dorsal rhizotomy. Accordingly, the hypothesis is confirmed. Thus it is becoming apparent that fine primary afferent fibers are more widely distributed in spinal white matter than had been previously recognized. Implications are that it is not possible to find areas in the spinal white matter that contain only large myelinated sensory axons and that significant numbers of fine primary afferent fibers will be lost even if lesions are restricted to the dorsal funiculus. The sizable population of fine myelinated primary afferent axons in the dorsal funiculus is emphasized. An obvious question, suggested by significant differences in average diameters of the axons in the different pathways, is whether there are differences in the types of information carried by the fine afferent fibers in their different locations in the white matter of the lumbar cord.

Afferent Pathways↗

Propriospinal fibers in the white matter of the cat sacral spinal cord.

The propriospinal system, which consists of those neurons completely contained within the spinal cord, is important because it underlies much spinal behavior. To provide quantitative data on this system, the present study determines numbers of axons in the isolated S2 cat spinal cord and compares these figures with the normal. The conclusion is that 60% of the fibers in the spinal cord at this location are propriospinal. Findings of particular interest are that the great majority of unmyelinated propriospinal axons are found in the dorsal part of the lateral funiculus, and that there are large numbers of descending myelinated fibers in the dorsal funiculi. These data will serve as a basis for evaluating axon numbers that follow various experimental regimens purporting to result in neural sprouting.

Animals↗

Calcitonin gene-related peptide (CGRP) in the human spinal cord: a light and electron microscopic analysis.

The distribution of CGRP immunoreactivity in the cervical, thoracic, lumbar, and sacral levels of the human spinal cord was mapped at the light microscopic level with the aid of a rabbit-generated antiserum against human calcitonin gene-related peptide (CGRP). CGRP-positive fibers formed a dense plexus in lamina I, II, the reticulated region of lamina V, and the tract of Lissauer at all spinal cord levels. The distribution of fibers showed some variations dependent on the cord level analyzed. At the light microscopic level, intervaricose fiber diameters consistently measured 1.0 micron or less, and two types of CGRP varicosities were observed: a small (1 to 2 microns in diameter), relatively round profile and a larger, (3 to 4 microns in diameter) oval or oblong profile. At the electron microscopic level, immunostained varicosities contained a mixture of round clear vesicles and vesicles that contained dense cores. The CGRP immunoreaction product was often associated with vesicles containing dense cores. The reaction product was also seen associated with clear round vesicles or in the cytoplasmic matrix. Postsynaptic elements included dendritic spines, small and large diameter dendritic shafts and vesicle containing profiles. The presence of CGRP in the superficial dorsal horn of human spinal cord is highly suggestive of a role in primary afferent transmission as postulated in lower vertebrates. This study establishes the distribution of CGRP at four different spinal levels in human cord and will serve as a basis for future studies related to the pathologic conditions affecting sensory systems.

Adult↗

Role of copper in the regulation and accumulation of superoxide dismutase and metallothionein in rat liver.

Weanling male Sprague-Dawley rats were fed one of four diets that varied in Cu, Zn or Cd content. To the control diet (I) Cu, Zn and Cd were added at 10, 100 and 0 mg/kg diet, respectively. Diets II and III also contained 10 mg/kg of dietary Cu, except that Zn was elevated to 1000 mg/kg for diet II, or Cd was added at 10 mg/kg for diet III. Diet IV was deficient in Cu (less than 1 mg/kg) with Zn at 100 mg/kg and no added Cd. At wk 6 postweaning, half of the rats fed diets I and IV were injected once with Cd acetate (5 mg Cd/kg body weight). The immediate response to Cd injection was an increase in metallothionein accumulation (three- to fourfold) and in Cu,Zn superoxide dismutase (SOD) accumulation (1.2- to 1.5-fold) in liver. SOD was estimated in an ELISA. These responses were not influenced by a change in Cu status (I vs. IV). However, in functional assays, SOD enzymatic activity was about half that of the control values. In this regard, SOD appears to be given high priority with respect to the utilization of cellular Cu, i.e., a 10-fold reduction in hepatic Cu only resulted in a twofold reduction in SOD activity and the amount of apoenzyme remained at normal levels.

Animals↗

Degree of conversion of seven visible light-cured posterior composites.

The infrared spectra of seven commercially available posterior composite resins were analysed by ratioing the C = C aliphatic peak to the C = C aromatic peak. The degree of conversion ranged from 43.5 to 73.8%. The result was similar to the range previously obtained from unfilled Bis-GMA based resins and commercial anterior composites.

Bisphenol A-Glycidyl Methacrylate↗