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Biomedical subjects

J S Han

Publications and source records attributed to J S Han.

At least 181 records · Page 10Linked to original sources
PubMed1994

Activation of rat brain phospholipase D by ADP-ribosylation factors 1,5, and 6: separation of ADP-ribosylation factor-dependent and oleate-dependent enzymes.

Two major forms of phospholipase D (PLD) activity, solubilized from rat brain membranes with Triton X-100, were separated by HPLC on a heparin-5PW column with buffer containing octyl glucoside. One form was completely dependent on sodium oleate for activity. The other, which was dramatically activated by the addition of ADP-ribosylation factor (ARF) 1 and guanine 5' [gamma-thio]triphosphate, required the presence of phosphatidylinositol 4,5-bisphosphate in the phosphatidylcholine substrate for demonstration of activity, as described by others. Oleate-dependent activity was unaffected by guanine 5' [gamma-thio]triphosphate, or phosphatidylinositol 4,5-bisphosphate. Both sodium oleate-and ARF-dependent activities catalyzed transphosphatidylation, thus identifying them as PLDs. ARF-dependent PLD was activated by recombinant ARF5 (class II) and ARF6 (class III), as well as ARF1 (class I). Myristoylated recombinant ARFs were more effective than their nonmyristoylated counterparts. ARFs were originally identified as activators of cholera toxin ADP-ribosyltransferase activity. The effects of recombinant ARF proteins from the three classes on cholera toxin activity (assayed under conditions identical to those used to assay PLD activity) did not, however, correlate with those on PLD, consistent with the notion that different aspects of ARF structure are involved in the two functions.

ADP-Ribosylation Factor 1↗
PubMed1994

Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor.

The analgesic effect of systemic morphine (4 mg/kg, s.c.) was antagonized in a dose-dependent manner by cholecystokinin octapeptide (CCK-8) (0.1-0.5 ng) administered bilaterally to the nucleus accumbens of the rat. This effect of CCK-8 could be reversed by devazepide, a CCK-A receptor antagonist, at 50 ng and 200 ng and by L-365,260, a CCK-B receptor antagonist, at 5 ng administered bilaterally to the nucleus accumbens. A marked potentiation of morphine analgesia was achieved by intra-nucleus accumbens injection of 200 ng devazepide or 5 ng L-365,260. Since the effect of L-365,260 in antagonizing the anti-opioid effect of CCK-8 in the nucleus accumbens is 40 times more potent than devazepide, it is suggested that the anti-opioid effect of CCK-8 is mediated by CCK-B receptors. In conclusion, nucleus accumbens is a strategic site where CCK-8 exerts an anti-opioid activity, most probably via the CCK-B receptors.

Animals↗
PubMed1994

A behavioral model for peripheral neuropathy produced in rat's tail by inferior caudal trunk injury.

We attempted to develop an experimental animal model using rat's tail for understanding the mechanisms involving peripheral neuropathic pain. Under sodium pentobarbital anesthesia, the left inferior caudal trunk of the rat was resected between the S3 and S4 spinal nerves. Latencies of tail-flick induced by the stimulus such as warm (40 degrees C) and cold (4 degrees C) water to the tail were measured for the following 30 weeks. In addition, sensitivity of the tail to mechanical stimulation was tested with von Frey hairs on these rats. Operated rats showed abnormal sensitivity of the tail to normally innocuous mechanical and thermal (warm and cold) stimuli. We interpreted these results as signs of neuropathic pain following nerve injury. The present model offers several advantages in performing behavioral tests; (1) it is easy to apply thermal stimulation to the rat's tail using a water bottle; (2) it is easy to apply the mechanical stimulation with von Frey hairs and to localize sensitive areas in the tail; and (3) blind behavioral studies are possible due to the lack of deformity in the tail after surgery.

Animals↗
PubMed1994

Regulation by lithium of the antagonistic effect of cholecystokinin octapeptide on ohmefentanyl-induced antinociception.

The antagonistic effect on opioid analgesia of central cholecystokinin octapeptide (CCK-8) has been amply demonstrated by behavioral and electrophysiological studies, although the mechanisms of action remain obscure. Since the phosphatidylinositol (PI) system is known to be involved in CCK effects in pancreatic tissue, and lithium has been shown to interfere with PI turnover, we sought to investigate whether LiCl would block the antiopioid effect of CCK-8 in the CNS. Nociceptive thresholds were assessed by the latency of the tail flick response (TFL). Intrathecal injection (ith) of LiCl at 4 cumulative doses (1.25-25 mumol) produced no significant change in the baseline TFL, nor was the antinociceptive effect induced by ohmefentanyl (OMF, the mu-selective opioid agonist, 20 ng, ith) reversed by LiCl. However, OMF-induced antinociception was dose-dependently reversed by CCK-8 (1-16 ng, ith), which alone at 5 cumulative doses (1-20 ng) had no influence on TFL, and the reversal effect of CCK-8 could be readily antagonized by LiCl (0.6-20 mumol, ith). The results are interpreted to mean that the PI signal system may play an important role in mediating the antiopioid effect of CCK-8.

Analgesics↗
PubMed1994

Effect of electroacupuncture tolerance by different frequencies on the opioid inhibition to cardiovascular activity in the spinal cord of rats.

Continuous 2-15 Hz or 2 Hz electroacupuncture (EA) of 6 h applied to rats resulted in electroacupuncture tolerance (ET). The effect of 2-15 Hz ET on the recovery of mean arterial blood pressure (MAP) and heart rate (HR) of rats after hemorrhagic shock, and the effect of intrathecal (i.t.) injection of [D-ala2, D-leu5]enkephalin (DADLE) on MAP and HR of 2 Hz ET rats were observed. The results were as follows: 1) there was no dramatic difference between the 2-15 Hz ET group and the control group in the recovery of MAP and HR from hemorrhagic shock; 2) DADLE (25 micrograms) caused almost the same depressor effect in the 2 Hz ET group as that in the control group. These data suggest that the spinal lateral horn cells (supposed to be involved in regulating blood pressure) are insensitive to EA and cannot be made tolerant to continuous EA, which is different from the dorsal horn cell (supposed to be involved in analgesia).

Animals↗
PubMed1994

Vasopressin-independent regulation of collecting duct water permeability.

Studies were conducted in microdissected rat terminal inner medullary collecting duct (IMCD) segments to determine whether agents that activate the phosphoinositide signaling pathway regulate osmotic water permeability independent of the action of vasopressin. Water was withheld from the rats for 24 h before the experiments, a procedure that yields a stably high osmotic water permeability in isolated perfused terminal IMCDs in the absence of vasopressin. In the present studies, the vasopressin-independent osmotic water permeability was sustained at approximately 300 microns/s for at least 90 min. We used the cholinergic agent carbachol (10-100 microM) to activate the phosphoinositide pathway. This agent has previously been reported to increase the hydrolysis of inositol phospholipids in IMCD cells without altering adenosine 3',5'-cyclic monophosphate production. In preliminary studies, we demonstrated (using fura 2) that carbachol transiently increases intracellular calcium and that this response was blocked by atropine, confirming that muscarinic receptors are coupled to activation of the phosphoinositide signaling pathway in these cells. In the absence of vasopressin, both carbachol (10 microM) and phorbol myristate acetate (1 nM) inhibited osmotic water permeability by 40-50% within 10 min. These effects were partially blocked by calphostin C, an inhibitor of protein kinase C. These results demonstrate that activation of phosphatidylinositol hydrolysis and/or activation of protein kinase C markedly inhibits osmotic water permeability in isolated perfused IMCD segments, even in the absence of prior stimulation by vasopressin.

Animals↗
PubMed1994

Protein c-fos induction in rat brain and spinal dorsal horn by sincalide and opioids in vitro.

Sincalide (CCK-8) is an antiopioid substance. In this study, we investigated the effects of sincalide and opioids on c-fos expression and their interaction in brain and spinal dorsal horn in vitro. Immunoprecipitation was used for detection of c-fos protein. The results indicated that 0.1 mumol.L-1 sincalide induced c-fos expression markedly in both brain (a 3.8-fold increase in c-fos protein level) and in spinal dorsal horn (a 3.6-fold increase). NDAP (a kappa receptor agonist) 0.1 mumol.L-1 showed some activating effects on c-fos expression, the c-fos protein level increased 2.7 and 2.6 times respectively in brain and spinal dorsal horn. Ohmefentanyl (Ohm, a mu receptor agonist) 0.1 mumol.L-1 also exhibited an inducing effect on c-fos protein production. Sincalide and NDAP exerted some additive effects on c-fos protein production in spinal cord. In contrast, the effect of sincalide on c-fos protein production is antagonistic to that of Ohm. The results suggested that there were changing patterns of interaction on c-fos expression between sincalide and opioids.

Animals↗
PubMed1994

66A-078:a kappa-opiate receptor agonist for amelioration of spinal spasticity.

The effect and mechanism of kappa opiate receptor agonist and high-frequency electrostimulation of acupoints in treating spinal spasticity were studied. The spinal spastic models were made by gradual mechanical compression on the cervical spinal cord of rabbits. 24 prepared rabbits were divided into 3 groups randomly, and each group with 8 rabbits was given intrathecally kappa-receptor agonist 66A-078, kappa-receptor antagonist +66A-078 and normal saline respectively. The degree of spasticity was quantified by both clinical score and electrophysiological examinations. The result showed that the spasticity was markedly inhibited by intrathecal injection of 66A-078 and that the kappa-receptor antagonist (naloxone) reversed this effect. We can infer that the antispastic effect of 66A-078 is mediated by kappa-receptors. This result is helpful in explaining the immediate antispastic mechanism of high-frequency electrostimulation of acupoints discussed in previous study.

Animals↗
PubMed1994

High frequency electroacupuncture induced changes of IP3 level in rat brain and spinal cord.

In the present study, the radioreceptor binding method was used to determine the changes of IP3 content in rat brain and dorsal spinal cord of high frequency (100 Hz) electroacupuncture (EA) analgesia and EA tolerance rat. The control levels of IP3 in rat brain (less cerebellum and cortex) and dorsal spinal cord were 6.3 +/- 0.78 pmol/mg protein and 3.4 +/- 0.60 pmol/mg protein, respectively. The results showed that IP3 in brain increased gradually within 45 min after stimulation in EA analgesia rat. Meanwhile, the dorsal spinal cord IP3 content decreased significantly 15 min, 30 min after EA stimulation and recovered to control level 45 min after EA stimulation. In EA tolerance rat, IP3 contents markedly increased in brain. And IP3 content in the spinal cord also increased dramatically within 30 min, but decreased rapidly to control level 45 min after EA stimulation. The IP3 level in EA tolerance rat brain and spinal cord was much higher than that in EA analgesia rat (P < 0.01). The studies first reported that high frequency (100 Hz) EA may be linked to PI system in its signal transduction pathways.

Acupuncture Analgesia↗
PubMed1994

[Cholecystokinin octapeptide antagonized the effect of NDAP on CaM in rat dorsal spinal synaptosome].

To elucidating the molecular mechanisms underlying CCK-8 anti-opioid effects, we have observed the effects and interactions of CCK-8 and kappa opiate agonist NDAP on CaM activity in rat dorsal spinal cord synaptosomes. The result indicated that 10 nmol/L-1 mumol/L NDAP produced dose-dependent decrease in CaM activity of rat spinal synaptosomes (P < 0.01). This suppressive effect was completely blocked by specific kappa receptor antagonist Nor-BNI at 1 mumol/L. In contrast, CCK-8 (10-100 nmol/L) induced a significant increase in CaM activity (P < 0.05-0.01), and was capable of antagonizing the suppressive effect induced by NDAP. Specific CCK-B receptor antagonist L365, 260 could partially block the effects of CCK-8 increased CaM activity at 1 mumol/L. The above results suggest that CCK-8 can antagonize the suppressive effect of NDAP on CaM activity in rat spinal synaptosomes via activation of CCK-B receptor, an effect that may constitute one of the mechanisms for the anti-opioid activity of CCK-8.

Animals↗
PubMed1994

Ultrastructure of spontaneous glomerular lesions in syrian hamsters of APA strain.

Electron microscopic observations were carried out on the spontaneous glomerular lesions in male APA hamsters from 3 to 12 months of age. Until 6 months of age, focal expansion of mesangial region due to an increase of matrix material and mesangial cells was characteristic, and segmental thickening of capillary basement membrane and partial effacement of foot processes of podocytes were also sometimes observed. At 12 months of age, although all of these changes became more severe, the most prominent alteration was found in podocytes, which showed various degenerative changes. No deposition of amyloid fibrils was detected in any portion of the glomerulus.

Age Factors↗
PubMed1994

Topical capsaicin treatment suppresses formalin-induced fos expression in rat spinal cord.

Capsaicin (Cap) is a pharmacological tool to inactivate nociceptive afferents. The present study was undertaken to investigate the effects of topical application of Cap to sciatic nerve on the formalin-induced expression of proto-oncogene proteins c-fos in the rat spinal cord using immunohistochemical display of fos-like protein. In rats subjected to formalin injection into the hind paw, numerous fos-like immunoreactivity (FLI) neurons were found in the spinal dorsal horn, with heavy labeling in laminae I-II and V-VI. Following pretreatment of Cap, formalin-induced FLI expression was significantly abolished. It was suggested that activation of Cap-sensitive unmyelinated nociceptive afferents following formalin injection was primarily responsible for the activation of c-fos gene. Our data also provided further evidence supporting that topical application was an effective way to block the transmission of noxious primary afferents.

Animals↗
PubMed1994

Serotonin receptor subtypes in spinal antinociception in the rat.

The aim of the present study was to clarify the subtypes of serotonin (5-HT) receptors involved in spinal antinociception in the rat. 1) Intrathecal (i.t.) injection of 5-HT (25-200 micrograms) produced a dose-dependent increase in tail-flick latency. 2) Intrathecal injection of fluoxetine, a 5-HT uptake blocker (25-40 micrograms), resulted in a bell-shaped dose-related antinociception with peak effects occurring at 10 micrograms. 3) A bell-shaped antinociceptive effect was obtained by i.t. injection of the 5-HT1A agonist (+)-hydroxy-2-(di-N-propylamino)tetralin (0.25-2 micrograms), with the maximal effect occurring at 0.5 micrograms, which can be prevented by the 5-HT1A antagonist spiperone (25 micrograms i.t.). 4) A similar dose-response curve was obtained following the i.t. injection of the 5-HT1B agonist 1-[3-(trifluoromethyl)phenyl]-piperazine maleate (1-125 micrograms) with the maximal effect observed at 25 micrograms. 5) Neither the 5-HT2 agonist (+/-)-alpha-methyl-5-HT-maleate nor the 5-HT3 agonist (+/-)-2-methyl-5-HT-maleate produced significant antinociceptive effects at doses up to 50 micrograms. Spontaneous tail-flicks emerged at doses higher than 50 micrograms. 6) The antinociceptive effect induced by 5-HT (200 micrograms i.t.) could be attenuated dose-dependently either by the 5-HT1A antagonist spiperone (5 and 25 micrograms i.t.) or by the 5-HT1C/2 antagonist mianserin (0.5-50 micrograms i.t.), but not by the 5-HT2 antagonist 1-(1-naphthyl)piperazine hydrochloride or the 5-HT3 antagonist 3-tropanyl-indole-3-carboxylate.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Transcutaneous electrical nerve stimulation for treatment of spinal spasticity.

Thirty-two patients with spinally originated muscle spasticity were treated with a transcutaneous electrical nerve stimulator, the Han's acupoint nerve stimulator (HANS) via skin electrodes placed over the acupoints on the hand and leg. High frequency (100 Hz), but not the low frequency (2 Hz), stimulation was effective in ameliorating muscle spasticity. While the therapeutic effect lasted for only 10 minutes in the first treatment, it became consolidated after consecutive daily treatment for 3 months. The anti-spastic effect induced by high frequency electrical stimulation can be partially reversed by a high dose of naloxone. The results suggest that the anti-spastic effect elicited by peripheral electrical stimulation is mediated, at least in part, by the endogenous opioid ligand interacting with the kappa opiate receptors, most probably dynorphin, in the central nervous system.

Acupuncture Points↗
PubMed1994

CCK receptor antagonist L-365,260 potentiated electroacupuncture analgesia in Wistar rats but not in audiogenic epileptic rats.

Cholecystokinin octapeptide (CCK-8) has been shown to be a neuropeptide with potent anti-opioid activity. Previous studies have shown that central administration of nanogram dose of CCK-8 totally abolished morphine analgesia in the rat, an effect mediated by CCK-B receptor in central nervous system. In the present study CCK-B antagonist L-365,260 was injected intracerebroventricularly (icv) to Wistar rats to see its effect on the analgesic effect induced by electroacupuncture (EA) stimulation. A marked potentiation of EA-induced analgesia was observed. The degree of potentiation depends on the frequency of EA used, with a rank order of 100 Hz > 15 Hz = 2/15 Hz > > 2 Hz. In a strain of rat with acoustically evoked epileptic seizure (P77PMC rats), an extra-ordinarily strong analgesic effect was produced in response to 100 Hz EA stimulation, which was similar to that in Wistar rats pre-treated with L-365,260. However, L-365,260 was not effective in potentiating EA analgesia in P77PMC rats. The results suggest that (1) high frequency EA is more likely to increase the release of CCK-8 in CNS as compared to low frequency EA, and (2) P77PMC rats may have a functional defect of the central CCK neurons in the nature of either a low CCK content or a reduced rate of release of CCK-8 in the CNS.

Acupuncture Analgesia↗
PubMed1993

A combined finite element and optimization investigation of lumbar spine mechanics with and without muscles.

A combined finite element and optimization approach to study the effects of muscles on the biomechanics of the lumbar spine was initiated. Briefly, a three-dimensional, nonlinear, finite element model of a ligamentous L3-4 motion segment was formulated (LIG model) for the predictions of stresses, etc., in the motion segment. A separate, biomechanical optimization-based force model with experimental input was developed to predict the forces in muscles and disc across the L3-4 segment in response to a person holding 90 N in his hands with spine flexed 30 degrees, and knees straight. The predicted muscle forces from the optimization model were then incorporated into the L3-4 finite element model as nodal forces to simulate the muscle action (MUS model). The predicted responses from the muscles active (MUS) finite element model were compared to the corresponding results from the ligamentous (LIG) finite element model subjected to an equivalent load. The biomechanical parameters compared were: translation and rotation of L3, disc bulge, intervertebral foramen gap, intradiscal pressure, facet loading, ligament tension, compressive disc load, and stresses in the vertebral body. The addition of muscular forces in the MUS model led to a decrease in the anteroposterior translation and flexion rotation (displacements in the sagittal plane) of the segment compared to the corresponding LIG model predictions. Thus, the muscles imparted stability to the ligamentous segment. The presence of muscles also led to a decrease in stresses in the vertebral body, the intradiscal pressure and other mechanical parameters of importance. However, the load bearing of the facets increased compared to the ligamentous model. Thus, facets play a significant role in transmitting loads in a normal intact spine. These results, for the first time, provide quantitative data on the stabilizing effects of muscles on the mechanics of a ligamentous spine. The results also provide a scientific explanation in support of the "degenerative cascade" concept proposed in the literature. The model predictions, in conjunction with the degenerative cascade concept, also support the observation that the osteoarthritis of facets may follow disc degeneration. Future research directions based on the current model are presented.

Biomechanical Phenomena↗