Anti-stress effects of ginseng via down-regulation of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) gene expression in immobilization-stressed rats and PC12 cells

Catecholamines are among the first molecules that displayed a kind of response to prolonged or repeated stress. It is well established that long-term stress leads to the induction of catecholamine biosynthetic enzymes such as tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) in adrenal medulla. The aim of the present study was to evaluate the effects of ginseng on TH and DBH mRNA expression. Repeated (2 h daily, 14 days) immobilization stress resulted in a significant increase of TH and DBH mRNA levels in rat adrenal medulla. However, ginseng treatment reversed the stress-induced increase of TH and DBH mRNA expression in the immobilization-stressed rats. Nicotine as a ligand of the nicotinic acetylcholine receptor (nAChR) in adrenal medulla stimulates catecholamine secretion and activates TH and DBH gene expression. Nicotine treatment increased mRNA levels of TH and DBH by 3.3- and 3.1-fold in PC12 cells. The ginseng total saponin exhibited a significant reversal in the nicotine-induced increase of TH and DBH mRNA expression, decreasing the mRNA levels of TH and DBH by 57.2% and 48.9%, respectively in PC12 cells. In conclusion, immobilization stress induced catecholamine biosynthetic enzymes gene expression, while ginseng appeared to restore homeostasis via suppression of TH and DBH gene expression. In part, the regulatory activity in the TH and DBH gene expression of ginseng may account for the anti-stress action produced by ginseng.

Recurrent Subarachnoid Hemorrhage after Complete Obliteration of Intracranial Aneurysm

The authors report a case of recurrent subarachnoid hemorrhage (SAH) after complete occlusion of an intracranial aneurysm. It is known that regrowth of an aneurysm after the complete clipping is a rare event. For detection of recurrence, however, it may be necessary to follow up with the patient regularly after the initial operation for intracranial aneurysms, because re-rupture of an aneurysm can cause a fatal result, and the cumulative risk of a recurrent SAH is thought to be not low over time.

Effects of Portulaca Oleracea L. Extract on Lipolysis and Hormone Sensitive Lipase (HSL) Gene Expression in 3T3-L1 Adipocytes

This study was performed to investigate the lipolytic effects of Portulaca oleracea L. extract in 3T3-L1 adipocytes. The Portulaca oleracea L. was extracted with extrusion method using twin-screw extruder under 58~60 rpm screw speed, 4~5 kg/hr feed rate, 140degrees C extrusion temperature. The lipolytic action of Portulaca oleracea L. extract was estimated by measuring the amount of glycerol and free fatty acids (FFA) released from 3T3-L1 adipocytes and by measuring the cellular lipid content in 3T3-L1 adipocytes. The hormone sensitive lipase (HSL) mRNA level was analyzed using quantitative real-time PCR. The Portulaca oleracea L. extract at 1 to 100 microgram/ml suppressed lipid accumulation. The release of glycerol and FFA into the medium, and the mRNA level of HSL were significantly increased by the addition of Portulaca oleracea L. extract at dose-dependent manner. In conclusion, the Portulaca oleracea L. extract was suggested to have the lipolytic effect through release of lipolytic products (FFA and glycerol) of triacylglyceride to the culture medium and suppression of lipid accumulation via up-regulation of HSL gene expression in 3T3-L1 adipocytes.

The Effect of Tyrosine Kinase Inhibitors on the L-type Calcium Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type Ca2+ channels play a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type Ca2+ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type Ca2+ channels currents in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. RESULTS: Patch clamp studies revealed a whole-cell current which resembles the L-type Ca2+ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein(n=5), tyrphostin A-23(n=3), A-25(n=6) 30micrometer reduced the amplitude of the L-type Ca2+ channel current in whole cell mode. In contrast, diadzein 30 micrometer (n=3), inactive analogue of genistein, did not decrease the amplitude of the L-type Ca2+ channels current. CONCLUSION: These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [Ca2+]i, by inhibition of L-type Ca2+ channel.

The Effect of Papaverine on the Calcium-dependent K+ Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Papaverine has been used in treating vasospasm following subarachnoid hemorrhage(SAH). However, its action mechanism for cerebral vascular relaxation is not clear. Potassium channels are closely related to the contraction and relaxation of cerebral smooth muscle. Therefore, to identify the role of potassium and calcium channels in papaverine-induced vascular relaxation, we examine the effect of papaverine on potassium channels in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. Papaverine was added to the bath solution. RESULTS: Papaverine of 100 microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by BKCa(large conductance calcium dependent potassium channels)blocker, IBX(iberiotoxin), and calcium chealator, BAPTA(1, 2-bis(o-aminophenoxy)ethane-N, N, N', N'-tetraacetic acid), in whole cell mode. CONCLUSION: These results strongly suggest that potassium channels may play roles in papaverine-induced vascular relaxation in rat basilar artery.

Effects of Tyrosine Kinase Inhibitors on the Calcium-Dependent K+ Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet reported whether potassium channel plays a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study is undertaken to clarify the role of potassium channel in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on outward potassium currents in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recoreded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. RESULTS: In present study, genistein(n=10), tyrphostin A-23(n=10), A-25(n=10) 30microM into bath solution increased the amplitude of the outward K+ current which was completely blocked by large conductance calcium-activated potassium channel(BK(Ca)) blocker, iberiotoxin(0.1microM), and calcium chelator, BAPTA, in whole cell mode. In contrast, diadzein 30microM(n=10), inactive analogue of genistein, did not increase the amplitude of the outward K+ current. CONCLUSION: Our results suggest tyrosine kinase inhibitors such as genistein, tyrphostin A-23 and A-25 increase the BK(Ca) channel activity in cerebral basilar smooth muscle cells, thereby contributing to the relaxation of cerebral artery.

Regulation of 3HNorepinephrine Release by Opioids in Human Cerebral Cortex

To investigate the receptors mediating the regulation of norepinephrine (NE) release in human cerebral cortex slices, we examined the effects of opioid agonists for mu-, delta-, and kappa -receptors on the high potassium (15 mM) -evoked release of [3H]NE. [3H]NE release induced by high potassium was calcium-dependent and tetrodotoxin-sensitive. [D-Pen2, D-Pen5]enkephalin (DPDPE) and deltorphin II (Delt II) inhibited the stimulated release of norepinephrine in a dose-dependent manner. However, Tyr-D-Ala-Gly- (Me) Phe-Gly-ol and U69, 593 did not influence the NE release. Inhibitory effect of DPDPE and Delt-II was antagonized by naloxone, naltrindole, 7-benzylidenaltrexone and naltriben. These results suggest that both delta 1 and delta 2 receptors are involved in regulation of NE release in human cerebral cortex.

The Effect of Papaverine on L-Type Ca2+ Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Papaverine has been used to manage vasospasm after subarachnoid hemorrhage. However, its mechanism for cerebrovascular smooth muscle are still not clear. This study was undertaken to investigate the effect of papaverine on L-type Ca2+ channels directly by using patch clamp techniques in freshly isolated single smooth muscle cells from rat basilar artery. METHODS: Whole-cell patch clamp technique was used for measuring the amplitude of L-type Ca2+ current. Papaverine was added to the bath solution. RESULTS: Patch clamp studies revealed a whole-cell current which resembles the L-type Ca2+ current reported by others. The amplitude of this current was decreased by nimodipidine and increased by Bay K 8644. Papaverine 100 micro M reduced the amplitude of the L-type Ca2+ channel current. CONCLUSION: We can conclude that papaverine may relax cerebral vessel through decreasing level of intracellular calcium, [Ca2+]i, by inhibition of L-type Ca2+ channel.

Results of Microsurgical Anterolateral Tunnel Approach for Cervical Disc Herniation

OBJECTIVE: The authors report the microsurgical anterolateral tunnel approach for the treatment of the cervical disc diseases and its postoperative surgical results. METHODS: All surgical procedures followed the method of classical microsurgical anterior discectomy. Small tunnel(7-8mm) was made on the disc space reaching to the posterior longitudinal ligament. The disc materials and bony spurs were removed through this tunnel. Thirty-one patients of cervical disc herniation(24 cases with pure disc herniation, 7 cases with combined cervical spondylosis) were evaluated on the symptoms, conformation in plain X-ray, C-T, and MRI. The follow up time was over 2 years . RESULTS: Postoperatively the result(following the out come scale) was excellent and good in Twenty-nine patients. One with fair result showed remnant disc particle and spur and another one is combined with cord contusion. One patient with lesion in C 3-4 space and two cervicothoracic junction showed excellent result. Two patients with osteoporosis also showed good results. Cervical spine curvature and disc space height were not changed on the plain X-ray and MRI in all patients. Twenty-nine patients were discharged within 3 days after surgery without any postoperative complications. CONCLUSIONS: The microsurgical anterolateral tunnel approach could be indicated for the treatment of patients with cervical disc diseases and with difficulty in achieving interbody fusion(the higher cervical level and cervicothoracic junction, osteoporosis etc.).

Isthmic Spondylolisthesis with Sciatica: Follow-up Results after Posterior Lumbar Interbody Fusion and Transpedicular Screw Fixation

The main symptoms of adult isthmic spondylolisthesis are frequently low back pain and radicular leg pain. Laminectomy and posterolateral fusion is somtimes unsuccessful because nerve roots are compressed by fibrocartilagenous tissue at pars defect, degenerated disc and slipped bony edge. The patients need complete neural decompression, reduction of slipping and stable fixation. We have operated 22 patients with PLIF using carbon cage and transpedicular screw fixation after posterior decompression by Gill's operation and complete removal of intervertebral disc. We studied the patients postoperatively to evaluate the symptomatic improvement, reduction rate of slipping and stability of lumbar spine. Twenty-two patients were operated from April, 1996 to June, 1997. Mean age was 46, ranging from 35 to 68. Mean follow-up duration was thirteen months. The levels of operarion were 9 at L4-5 and 9 at L5-S1, 4 at both levels. Mean preoprative slip was 17.2%, which was reduced to 11.3% postoperatively. Nineteen patients(86%) were satisfied with the result of operation. The fusion rate of PLIF was 86%. There was no breakage of instrumentation or postoperative instability. We consider that PLIF and transpedicular screw fixation for adult isthmic spondylolisthesis with radicular leg pain is a good methods to obtain complete neural decompression, reduction of slip and stable lumbar fixation.

The Effect of Activation of Protein Kinase C on the Calcium-dependent K; Current in Rat Basilar Smooth Muscle Cells

OBJECTIVE: Activation of protein kinase C(PKC) may play a certain role in the development of cerebral vasospasm. However, this mechanism still elusive. This study was undertaken to investigate the action of protein kinase C on calcium-dependent K+ channels(KCa) and internal calcium concentration [Ca2+]i in freshly isolated smooth muscle cells. METHODS: Whole-cell patch clamp and calcium microfluorimetry technique were used for measuring the K Ca and internal calcium concentration. RESULTS: In patch-clamp studies, depolarization evoked an outward KCa current which is sensitive to caffeine and A23187, and shown to be blocked by TEA(tetraethylammonium) but not by glibenclamide. Activation of protein kinase C by phorbol 12-myristate 13-acetate(PMA:1-100nmol/1) and phorbol 12, 13-dibutyrate(PDB:1-100nmol/1) dose-dependently enhanced KCa current. Subsequent application of TEA(10-30mmol/1) but not glibenclamide(3-6nmol/1), in the presence of phorbol esters, reduced the potassium current activated by phorbol esters. Preincubation with 1-(5-isoquinoline sulphonyl)-2-methylpiperazine(H-7:10nmol/1), a protein kinase C inhibitor, prevented the effect of phorbol esters on KCa. In calcium microfluorimetric studies, PMA(100nmol/1) increased intracellular calcium concentration and this effect of PMA was prevented by pre-incubation of cells with H-7(10nmol/1). CONCLUSION: These results indicate that activation of PKC increases intracellular calcium concentration and elevation of internal calcium concentration activates KCa in cerebral vascular smooth muscle cells.

Polymorphism of Angiotensin Converting Enzyme in Hypertensive Intracerebral Hemorrhage Patients

Polymorphism in the angiotensin-converting enzyme(ACE) gene may confer an increased risk of vascular disease. DD type of ACE polymorphism predispose a person to myocardial infarction and IgA nephropathy. The roles of the ACE insertion/deletion polymorphism are unknown in the patients with hypertensive intracerebral hemorrhage (HICH). Our objective is to test and to identify whether genotype distribution of the insertion/deletion polymorphism in ACE gene is different in HICH patients from control subjects. Fifty six HICH patients and sixty one control subjects were studied. Genotypes were determined by the polymerase chain reaction(PCR) with specific oligonucleotide primers flanking the polymorphic region in intron 16 of ACE gene to amplify genomic DNA isolated from patients blood PCR products were separated in 2% agarose gels and bands were visualized by ethidium bromide staining. The PCR reaction amplified a 490bp DNA fragment(II type) from genomic DNA if the subjects had an intact intron 16, and amplified a both 490bp and 190bp DNA fragments(ID type) if subjects had heterozygous polymorphism. While the distribution of ACE polymorphism in control subjects was 26.2%:57.4%:6.4%(II:ID:DD), and the distribution of it in patients with HICH was 37.5%:35.7%:26.8%. Thus, the pattern of distribution was no significant different between control subjects and patients with HICH. The factors of age and sex did not influence on the ratio of distribution in both control and HICH subjects. From these results, we conclude that there is no significant association between I/D polymorphism and HICH.

The Effect Erythrocyte lysate on Intracellular Calcium Concentration and the Potassium Channel in Cerebral Vasular Smooth Muscle Cells

Erythrocyte lysate increases intracellular Ca2+[Ca2+]i, causes contraction in cerebral arteries, and is thought to be the causative agent in cerebral vasospasm ; the mechanism of erythrocyte lysate-induced [Ca2+]i mobilization is not, however, clear. This study was undertaken to investigate the action of erythrocyte lysate on [Ca2+]i mobilization by monitoring [Ca2+]i and the Ca2+-dependent K+ channels(Kca) in freshly isolated rat basilar artery smooth muscle cells. In a [Ca2+]i imaging study, erythrocyte lysate produced a biphasic response, a transient peak and prolonged plateau [Ca2+]i elevation ; in the absence of external Ca2+, it induced only a transient peak [Ca2+]i response without a marked plateau phase, indicating that peak [Ca2+]i was due to Ca2+ released from internal stores. The erythrocyte lysate-induced plateau [Ca2+]i response was resistant to nicardipine, a voltage-dependent Ca2+ channel blocker, but was abolished by EGTA. The elevation [Ca2+]i induced by erythrocyte lysate caused contraction in smooth muscle cells. During the electrophysiological study, elevation of [Ca2+]i by erythrocyte lysate increased Kca currents in whole-cell patch-clamp configuration ; this effect was blocked by heparin, an antagonist of IP3 receptors. We conclude that erythrocyte lysate releases Ca2+ from IP3-sensitive intracellular stores and induces Ca2+ entry from voltage-independent Ca2+ pathways.

Surgical Treatment of Intractable Frontal Lobe Epilepsy

Recent advances of neuroimaging and electrophysiological monitoring technique have contributed in improving the surgical outcome of frontal lobe epilepsy. The authors have analysed 36 consecutive cases of intractable frontal lobe epilepsy that were treated at our institute between September, 1992 and December, 1995 to determine the clinical, electrophysiological, and neuroimaging characteristics as well as to delineate the efficacy of surgical treatment in improving the seizure outcome. The patients consisted of 19 males and 17 females. The mean age of the seizure onset and the mean duration of epilepsy were 14.9 and 11.6 years, respectively. Magnetic resonance imaging(MRI) showed no lesion in 9 patients and pathological lesions in 27 patients. The types of the lesions observed included primary brain tumor, mostly low-grade glioma in 10 patients, cortical dysplasia in 4, post-traumatic scar in 4, neocortical gliosis in 3, cyst in 3, and postencephalitic atrophy in 3. Intracranial recordings were performed in 23 cases to determine the epileptogenic zone. The surgical outcome was graded according to Engle's Classification as Class A in 20 patients, Class B in 2, Class C in 9, and Class D in 5. The surgical outcome was promising regardless of the presence or the absence of the lesion on MRI, invasive recording, age of seizure onset, and duration of epilepsy.

Clinical Results of Internal Fixation Using Several Instruments in Unstable Thoracolumbar Bursting Fracture

Fifty six patients with unstable thoracolumbar bursting fractures were treated using variable internal fixation devices such as the Kaneda Anterior Fixation System(Kaneda device), the Z-Plate-ATL(TM) Anterior Fixation System(Z-Plate ATL(TM) device), the Harrington device, Cotrel-Ducousset(CD) or Compact Contrel Dubousset(CCD) device or Steffee Transpedicular System with or without decompression. Such internal fixation devices were grouped into anterior and posterior internal fixation devices and compared with each other in the aspect of the degree of neurological improvement, the changes of the vertebral height and the kyphotic angle, the duration of admission, and postoperative complications. In conclusion, the anterior internal fixation device appears to be of more benefit in the management of patients with unstable thoracolumbar bursting fracture.

Results of Anterior Cervical Discectomy without Interbody Fusion

Anterior cervical discectomy with or without interbody fusion has been conventionally used to treat patients with cervical disc diseases. However, discectomy without bone fusion has been abandoned due to the feat of early collapse of interbody space and recurrency. The author has analysed twenty-two cases of microsurgical cervical discectomy without bone fusion between Jan. 1993 and Mar. 1994. All patients were followed up for more than 6 months or as long as 21 months with repeat interview, physical examination, and radiological evaluation. The analysis revealed that the results were highly satisfactory in 21 cases with radiculopathies in terms of early ambulation, no discomfort in the iliac bone, and shorter hospital stay, but unsatisfactory in one cases which needed reoperation due to postoperative scar. The above method which had demonstrated promising results is recommended for the patients suffering from radiculopathy.

Ring Clips for ICA Aneurysm Protruding Inferiorly: Report of Five Cases

The development of more appropriate shapes of aneurysm clips will hopefully enable excellent clipping of most types of difficult aneurysms. The clipping of internal carotid artery(ICA) aneurysms protruding inferiorly is relatively difficult and has the high risk of premature rupture during operation using conventional clips. We report five cases of ICA aneurysms protruding inferiorly in the operative field. All aneurysms were successfully clipped with ring clips without difficulty. Our results suggest that the ring clips rather than conventional clips were appropriate in the ICA aneurysm protruding inferiorly in the operative field.

Clinical Analysis of Outcome for Ruptured Intracerebral Aneurysm with Hematoma

This author analysed 34 cases of aneurysmal rupture which had a hematoma in ventricle, intracerebral and subdural space except subarachnoid space. All the patient had been treated in Chonbuk National University Hospital from Aug. 1. 1984 to Aug. 30. 1990. Among the 34 cases, 24 cases were treated with surgery and 10 cases conservatively. The result of operation showed favorable outcome(Good recovery, Moderately disabled);8 cases(33.3%) and unfavorable(severely disabled, vegetative state);5 cases(20.8%). Mortality rates were 70%(7/10) in nonoperative cases and 45.8%(11/24) in operative cases. The data for 34 cases were correlated with outcome by using Chi-square test and t-test. Mortality and morbidity were increased in patients with hypertension, poorer clinical grades at the time of admission or surgery, larger amounts of intracranial hematoma, and older age. From the overall results, the removal of hematoma and simultaneous clipping aneurysmal neck is necessary to obtain a good outcome.

Clinical Evaluation of Outcome of Hypertensive Cerebellar Hemorrhage

The authors analyzed 28 cases with hypertensive cerebellar hemorrhage, diagnosed by computerized tomography(CT), between 1987 and 1990, in Chonbuk National University Hospital. The authors assessed the relationship of outcome to the CT appearance of the quadrigeminal cistern, which in some cases was obliterated by rostral displacement of the vermis resulting from the cerebellar mass. Obliteration of the quadrigeminal cisterns was classified on the CT scans into three grades:Normal(Grade I), Compressed(Grade II), or Absent(Grade III). There were 7 cases with Grade I, 9 with Grade II, and 12 with Grade II cisterns. Of the 28 cases, 6(85%) of those with Grade I, 7(78%) of those with Grade II, and none of those with Grade III cisterns respectively returned to their previous activities at 6 months or more after onset. A Grade I cisterns predicted a good outcome whether the hematoma was evacuated or not, as long as obstructive hydrocephalus, if present, was relieved early. However, a Grade II cistern was not predictive of a good outcome unless the hematoma was evacuated within 48 hours after onset of the hemorrhage. A Grade III cisterns predicted an unfavorable outcome. Taken together, these results strongly suggest that the CT grade of quadrigeminal cistern obliteration may be an indicator of outcome and may be useful in selecting treatment for patients with cerebellar hemorrhage.

Clinical Analysis of Outcome for Ruptured Intracerebral Aneurysm with Hematoma

This author analysed 34 cases of aneurysmal rupture which had a hematoma in ventricle, intracerebral and subdural space except subarachnoid space. All the patient had been treated in Chonbuk National University Hospital from Aug. 1. 1984 to Aug. 30. 1990. Among the 34 cases, 24 cases were treated with surgery and 10 cases conservatively. The result of operation showed favorable outcome(Good recovery, Moderately disabled);8 cases(33.3%) and unfavorable(severely disabled, vegetative state);5 cases(20.8%). Mortality rates were 70%(7/10) in nonoperative cases and 45.8%(11/24) in operative cases. The data for 34 cases were correlated with outcome by using Chi-square test and t-test. Mortality and morbidity were increased in patients with hypertension, poorer clinical grades at the time of admission or surgery, larger amounts of intracranial hematoma, and older age. From the overall results, the removal of hematoma and simultaneous clipping aneurysmal neck is necessary to obtain a good outcome.