Association between heavy metal levels and acute ischemic stroke.

BACKGROUND: Few studies have examined the relationship between the amounts of heavy metal and stroke incidence. The aim of this study was to explore the relationship between levels of heavy metals, including Pb, Hg, As, and Cd, in patients with acute ischemic stroke (AIS). METHODS: We selected patients with first-ever AIS onset within 1 week as our study group. Healthy controls were participants without a history of stroke or chronic disease, except hypertension. The serum levels of Pb, Hg, As, and Cd in participants in the experimental and control groups were determined. All participants received a 1-g infusion of edetate calcium disodium (EDTA). Urine specimens were collected for 24 h after EDTA infusion and measured for heavy metal levels. RESULTS: In total, 33 patients with AIS and 39 healthy controls were enrolled in this study. The major findings were as follows: (1) The stroke group had a significantly lower level of serum Hg (6.4 ± 4.3 µg/L vs. 9.8 ± 7.0 µg/L, P = 0.032, OR = 0.90, 95% CI = 0.81-0.99) and a lower level of urine Hg (0.7 ± 0.7 µg/L vs. 1.2 ± 0.6 µg/L, P = 0.006, OR = 0.27, 95% CI = 0.11-0.68) than the control group. (2) No significant difference in serum Pb (S-Pb), As (S-As), and Cd (S-Cd) levels and urine Pb (U-Pb), As (U-As) and Cd (U-Cd) levels was observed in either group. CONCLUSIONS: Our study found low levels of serum and urine Hg in first-ever patients with AIS, providing new evidence of dysregulated heavy metals in patients with AIS.

Spontaneous spinal epidural hematoma: a case report and review of the literatures.

PURPOSE: To emphasize the importance of early recognition and emergent surgery for spontaneous spinal epidural hematoma (SSEH). CASE REPORT: A 61-year-old female presented with sudden onset of severe neck and back pain after finishing worshiping Buddha followed by quadriparesis, sensory deficits below C4 level and sphincter dysfunction. MR imaging demonstrated acute extensive epidural hematoma of cervico-thoracic spinal segments (C2-T7). Idiopathic SSEH was diagnosed and emergent decompressive laminectomy with hematoma evacuation was performed within 12 hours of symptoms onset. Good functional and neurological outcomes were obtained. CONCLUSION: SSEH is a rare but disabling or even fatal entity. Early diagnosis and prompt surgery improve the neurological and functional outcome but still remain a clinical challenge. Relevant physicians should pay attention to the typical symptoms of the rare entity and SSEH should be one of differential diagnoses.

Get With the Guidelines-Stroke performance indicators: surveillance of stroke care in the Taiwan Stroke Registry: Get With the Guidelines-Stroke in Taiwan.

BACKGROUND: Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. The Taiwan Stroke Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess the applicability of GWTG-Stroke in Taiwan, which spends ≈ 1/10 of what the United States does in medical costs per new or recurrent stroke. METHODS AND RESULTS: Taiwan Stroke Registry, sponsored by the Taiwan Department of Health, engages 39 academic and community hospitals and covers the entire country with 4 steps of quality control to ensure the reliability of entered data. Five GWTG-Stroke performance measures and 1 safety indicator are applicable to assess Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3 other indicators (intravenous tissue plasminogen activator, anticoagulation for atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall behind. Preliminary analysis shows that compliance with selected GWTG-Stroke guidelines is associated with better outcomes. CONCLUSIONS: Results suggest that GWTG-Stroke performance measures, with modification for ethnic factors, can become global standards across national and economic boundaries for assessing and improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated into ongoing stroke registries across nations.

Screening depression among institutionalized older Chinese men by minimum data set: we need a new instrument.

OBJECTIVE: To compare the effectiveness of the Minimum Data Set-based Depression Rating Scale (MDS-DRS) and Geriatric Depression Scale (GDS) in screening depression among older institutionalized Chinese men living in Taiwan. METHOD: MDS Nursing Home 2.1 Chinese version, Mini-Mental State Examination (MMSE), and short form Geriatric Depression Scale (GDS-15) were used among elderly residents in Banciao Veterans Home. Screening results of MDS-DRS and GDS-15, and relationship between 16 MDS Mood and Anxiety symptoms and depression were evaluated. RESULTS: The prevalence of depression defined by MDS-DRS and GDS were 0.2% and 8.7%, respectively. Multiple logistic regression disclosed that E1a (OR: 12.9, 95% CI: 2.8-58.8, p = 0.001), E1k (OR: 15.6, 95% CI: 5.6-43.5, p < 0.001), and E1l (OR: 22.2, 95% CI: 6.1-83.3, p < 0.001) were all independent associative factors for GDS-defined depression but only explained 51.9% of all depressive subjects. CONCLUSIONS: The effectiveness of MDS-DRS is limited, and a new MDS-based depression screening instrument is needed.

Urinary incontinence: an under-recognized risk factor for falls among elderly dementia patients.

AIMS: Elderly people with dementia are at increased risk of falls and intervention trials to prevent falls have failed to demonstrate clinical effectiveness in this population. This study evaluates the role of urinary incontinence as a fall risk factor in older patients with dementia, with the aim of developing relevant intervention strategies. METHODS: Elderly patients with dementia visiting our center were recruited. All subjects underwent a Comprehensive Geriatric Assessment (CGA), and patients were divided into two groups (fall and non-fall) according to their history of falls in the past year. Components of the CGA, including physical function, mental function, depressive symptoms, incontinence, and nutritional status, were evaluated according to fall history. RESULTS: Overall, 159 patients with dementia (mean age 77.3 ± 9.0 years, 59.1% male) participated. Fifty-four patients (34.0%) had experienced falls in the past year. Among all subjects, 50.3% were diagnosed with mild dementia, 37.7% with moderate dementia, and 12.0% with severe dementia according to an established Clinical Dementia Rating scale. Subjects in the fall group displayed poorer physical function, balance, depressive mood, nutritional status, urinary incontinence, and had an increased prevalence of polypharmacy. However, multivariate analysis revealed urinary incontinence as the only independent risk factor for falls (OR = 4.9 ± 2.2, 95% CI: 2.0-12.0, P < 0.001). CONCLUSIONS: Urinary incontinence is a previously unidentified risk factor for falls among elderly dementia patients. An interventional study with the focus of urinary incontinence could improve the effectiveness of fall prevention among these patients.

Efficacy and safety of levetiracetam as adjunctive therapy in adult patients with uncontrolled partial epilepsy: the Asia SKATE II Study.

This study evaluated the safety and efficacy of levetiracetam as adjunctive therapy for partial seizures in everyday clinical practice in Asian populations. Patients aged > or =16 years (N=251) with inadequately controlled partial epilepsy were recruited from 29 centers across Asia. Levetiracetam was added to existing antiepileptic medication for 16 weeks at a starting dose of 500 or 1000 mg/day and titrated to a maximum of 3000 mg/day according to clinical response. The study completion rate was 86.9%. Adverse events were reported by 73.3% of patients and were generally mild, leading to treatment withdrawal in only 7.2%. The most common adverse events were somnolence (30.3%) and dizziness (14.7%). Compared with pretreatment baseline, 44.0% of patients had a > or =50% reduction in seizure frequency, with a median reduction of 46.4%, and 17.7% became seizure free during the treatment period. Levetiracetam was well tolerated and efficacious as adjunctive therapy for partial epilepsy in clinical practice among Asian populations.

Baroreceptor Sensitivity Predicts Functional Outcome and Complications after Acute Ischemic Stroke.

Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS after AIS. All patients admitted to Kaohsiung Veterans General Hospital within 72 h after onset of first-ever AIS between April 2008 and December 2012 were enrolled. Autonomic evaluation with continuous 10-minute monitoring of beat-to-beat hemodynamic and intracranial parameters was performed within 1 week after stroke by using the Task Force Monitor and transcranial Doppler. The 176 enrolled AIS patients were divided into high-BRS and low-BRS groups. All but two enrolled patients (who died within 3 months after stroke) attended scheduled follow-ups. The high-BRS group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores at 1 and 2 weeks after stroke and at discharge; lower modified Rankin scale (mRS) scores 1, 3, 6, and 12 months after stroke; and lower rates of complications and stroke recurrence compared to the low-BRS group. This study provides novel evidence of the utility of BRS to independently predict outcomes after AIS. Furthermore, modifying BRS may hold potential in future applications as a novel therapeutic strategy for acute stroke.

A follow-up study in a Taiwanese family with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome.

BACKGROUND/PURPOSE: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome is often associated with A3243G point mutation of mitochondrial DNA (mtDNA). We previously described a MELAS family characterized by harboring an additional approximately 260 bp tandem duplication in the D-loop and a novel C3093G point mutation in the 16S rRNA gene of mtDNA in the proband. We studied the clinical progression and fluctuation of mtDNA mutations in this Taiwanese MELAS family. METHODS: We followed up the clinical course in all members of this family (1 proband, her mother and 3 sons) for 12 years. Mutations of mtDNA in serial muscle biopsies of the proband and blood samples and hair follicles taken at different time points from the members of this family were analyzed. RESULTS: The proband developed repeated stroke-like episodes, chronic intestinal pseudo-obstruction, polyneuropathy, progressive renal failure and dilated cardiomyopathy with heart failure. During the follow-up period, the mother and one of the siblings of the proband developed stroke-like episodes at age 62 and 12, respectively. There was no significant difference in the proportions of mtDNA with A3243G mutation among five serial muscle biopsies of the proband. In one carrier (I-2), the proportion of A3243G mutated mtDNA in blood cells was slightly increased with disease progression. CONCLUSION: This study underlines the importance of early detection of extraneuromuscular symptoms in the members of a family with MELAS syndrome by adequate follow-up. The age of onset of stroke-like episode in MELAS syndrome may be as late as 62 years. We suggest that the manifestations of MELAS syndrome in this family might be associated with the additional approximately 260 bp tandem duplication in the D-loop region and the coexistence of C3093G mutation in the 16S rRNA gene with the A3243G mutation of mtDNA.

Unusual subdural hematoma after SPA use.

We report a case of right tentorium subdural hematoma (SDH) in a 72-year-old man a few days after he visited a sanitas per aqua (SPA) facility. He had directed high-pressure water onto his head and neck. The patient was admitted to the emergency room during his 3rd day of severe throbbing and generalized headache. Cerebral computed tomography revealed a high-density SDH over the right tentorium. This is the first reported case of SPA-related SDH. Neurologists might consider the possibility that SPA use may be a factor in SDH or unexplained neurologic events in otherwise healthy persons.

Lithium intoxication-induced acute parkinsonism complicated with hyperparathyroidism and nephrogenic diabetes insipidus: report of a case.

OBJECTIVE: To describe a patient with lithium intoxication presenting as acute parkinsonism, adverse metabolic effects and nephrogenic diabetes insipidus (DI). CASE REPORT: We report a case of a 67-year-old woman with a bipolar affective disorder who was treated with lithium for 10 years. Under concomitant renal insufficiency and urinary tract infarction, she experienced progressive hand tremor, bradykinesia, and unsteady gait. Laboratory results revealed hypercalcemia and hypermagnesiemia. A high serum lithium level (3.6 mEq/L) was found; thus lithium was discontinued. She was found to have a high serum level of intact parathyroid hormone: 135.0 pg/ml and a suspicious parathyroid adenoma. Polyuria with hypernatremia was also noted. A water deprivation test confirmed nephrogenic diabetes insipitces. After correction of electrolyte imbalance and reduction of lithium level, her consciousness recovered. Her parkinsonian features were responsive to levodopa 400 mg/day in 2 divided doses. One month later, apart from the residual extrapyramidal symptoms and mania, her condition was otherwise stationary. CONCLUSIONS: Tremor is the most frequent movement disorder associated with lithium therapy, while severe parkinsonism has been rarely reported. It should be kept in mind in differential diagnosis of acute parkinsonism especially in elder patients who receive a chronic lithium carbonate therapy.

Familial hyperhomocysteinemia-related cerebral venous sinus thrombosis and pulmonary embolism: a case report.

Elevated plasma homocysteine levels are associated with an increased risk of deep vein thrombosis. Herein we report a case of familial hyperhomocysteinemia-related cerebral venous sinus thrombosis and pulmonary embolism in a 21-year-old man who presented with severe headache over bilateral frontal areas. Neurological examination revealed no evidence of focal neurological deficit. Chest CT showed pulmonary thromboembolism in bilateral basal lung fields and brain MRI disclosed right transverse and sigmoid venous sinus thrombosis. Routine immunological tests, coagulation factors and occult tumor screening were normal, as were vitamin B12 and folate levels. The DIC profile was negative, The only risk factor we were able to identify was an elevated serum homocysteine level, namely 46.23 microM/L. Hyperhomocysteinemia was also noted in the patient's asymptomatic elder brother (68.0 microM/L) and, to a lesser extent, in his parents (father 12.5 microM/L; mother 11.7 microM/L). In conclusion, the cause of cerebral venous thrombosis and pulmonary embolism in this young patient was most likely related to familial hyperhomocysteinemia, with the thromboembolic events precipitated by a preceding systemic infection. After anticoagulation therapy; the patient recovered completely without any residual neurological deficit.

Recurrent primary intracerebral hemorrhage: a hospital based study.

BACKGROUND: Primary intracerebral hemorrhage (ICH) occurs more commonly in Taiwan than in other western countries. Recurrence of primary ICH after a first episode is not rare. The purpose of this study is to investigate the incidence, risk factors, and prognosis of recurrent primary ICH. METHODS: From the stroke registration data of Kaohsiung Veterans General Hospital (KSVGH), all patients admitted between Jan. 1999 and Dec. 2003 with the discharge diagnosis of ICH were identified. The hospital records and images of each ICH patient were carefully reviewed and the diagnosis was confirmed by one of the investigators. For those patients admitted in this study period with the diagnosis of acute primary ICH who also had past medical history of ICH, the record and image of the past admission were also obtained for review, either from KSVGH or other hospitals. Patients with ICH due to secondary causes were excluded. RESULTS: 585 patients with primary ICH were reviewed. Among them, 34 (5.8%) patients were found to have recurrent primary ICH. The medical records of these 34 patients were obtained for further analysis. Cerebral amyloid angiopathy was diagnosed in 4 (11.7%) patients. Mean ages at the onset of the first and second hemorrhages were 64 +/- 13 and 66 +/- 13 years, respectively. The mean interval between first and second hemorrhages was 33 months (from 1 month to 10 years). The most common location of first-second bleeding was basal ganglion-basal ganglion. The mortality rate in this group was 23.5%. Fifteen (38.2%) patients became totally dependent or vegetative after the second ICH. CONCLUSIONS: Recurrent primary ICH is not uncommon. The main location of recurrent bleeding was basal ganglion. This may implicate hypertension as the main cause of ICH. Hypertension is an important risk factor of recurrent primary ICH. Amyloid angiopathy is another cause of recurrent primary ICH. The prognosis after the second hemorrhage is worse, while the mortality and morbidity after first ever primary ICH were 15.6% and 17.9%, respectively.

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients.

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Central vasomotor failure in a patient with medulla arteriovenous fistula.

We report on the case of a 60-year-old man who suffered from hiccup, dysphagia and unsteady gait for three months. He was diagnosed with intracranial dural arteriovenous fistula in medulla with retrograde perimedullary vein drainage. He developed quadriplegia, persistent shock status and symptomatic bradycardia immediately after a conventional cerebral angiography study. After excluding cardiogenic, hypovolemic, anaphylactic and septic shock, central vasomotor failure caused by venous thrombosis of the lesion was considered. The patient's central vasomotor failure recovered after continuous dopamine infusion treatment for 42 days. We concluded that venous hypertension with venous thrombosis in rostral ventrolateral medulla (RVLM), a major vasomotor center in the brainstem, was the lesion site. In our case, vasomotor dysfunction caused by an RVLM lesion related to venous thrombosis is considered as causative.

Carotid atherosclerosis: is it treatable?

The assessment of brachial-artery FMD is a reliable, reproducible and noninvasive tool for evaluating endothelial dysfunction, which, together with endothelial inflammation, causes carotid atherosclerosis. Atorvastatin therapy can reverse endothelial dysfunction after 4 months, and may have significant anti-inflammatory effects if continued for more than 4 months. Importantly, statin therapy can be used to treat carotid atherosclerosis.

Psychiatric morbidity in dementia patients in a neurology-based memory clinic.

The behavioral and psychological symptoms of dementia (BPSD) often present major problems for patients and their caregivers. In the past, neurologists paid less attention to such symptoms than to the cognitive symptoms of dementia. This prospective study investigated the prevalence of psychiatric morbidity in a neurology-based memory clinic and the stress of caregivers. Our patients with dementia were found to have a high prevalence of BPSD. The most frequent were anxiety, apathy, and delusion; the most distressing to caregivers were agitation, anxiety, delusion, and sleep disturbance. Using Clinical Dementia Rating (CDR), we compared BPSD between patients with mild dementia and those with moderate dementia. Only hallucinations and agitation were different significantly. Moderate dementia patients experienced these symptoms more frequently. The high prevalence of these symptoms might be explained by the fact that the cognitive symptoms were neglected or no enough information were received by many family members of patients with dementia until their own life quality was interfered and then they began to seek medical help. These symptoms and their effect of caregiver distress can be effectively reduced by pharmacologic and nonpharmacoloic managements, caregiver-focused training and education. They can be better approached by assessing neuropsychiatric symptoms regularly, educating the general population better, and treating these patients earlier.

Effect of arvanil (N-arachidonoyl-vanillyl-amine), a nonpungent anandamide-capsaicin hybrid, on ion currents in NG108-15 neuronal cells.

The effects of arvanil (N-arachidonoyl-vanillyl-amine), a structural hybrid between capsaicin and anandamide, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were examined with the aid of the whole-cell voltage-clamp technique. Arvanil (0.2-50 microM) caused an inhibition of voltage-dependent L-type Ca(2+) current (I(Ca,L)) in a concentration-dependent manner. Arvanil produced no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of arvanil-induced inhibition of I(Ca,L) was 2 microM. Arvanil (5 microM) could shift the steady-state inactivation curve of I(Ca,L) to a more negative potential by approximately -15mV. No effect of arvanil (20 microM) on delayed rectifier K(+) current (I(K(DR))) was observed; however, capsaicin (20 microM), glyceryl nonivamide (20 microM) and capsinolol (20 microM) suppressed it significantly. Arvanil (20 microM) caused a slight reduction in the amplitude of erg (ether-à-go-go-related)-mediated K(+) current (I(K(erg))) without modifying the activation curve of this current, while capsaicin and glyceryl nonivamide were more effective in suppressing I(K(erg)). Under current-clamp configuration, arvanil decreased the firing frequency of action potentials. Arvanil-mediated inhibition of I(Ca,L) appeared to be independent of its binding to either vanilloid or cannabinoid receptors. The channel-blocking properties of arvanil may, at least in part, contribute to the underlying mechanisms by which it affects neuronal or neuroendocrine function.

Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in C6 glioma cells.

The effect of nordihydroguaiaretic acid (NDGA) on Ca(2+) signaling in C6 glioma cells has been investigated. NDGA (5-100 microM) increased [Ca(2+)]i concentration-dependently. The [Ca(2+)]i increase comprised an initial rise and an elevated phase over a time period of 4 min. Removal of extracellular Ca(2+) reduced NDGA-induced [Ca(2+)]i signals by 52+/-2%. After incubation of cells with NDGA in Ca(2+)-free medium for 4 min, addition of 3 mM CaCl2 induced a concentration-dependent increase in [Ca(2+)]i. NDGA (100 microM)-induced [Ca(2+)]i increases in Ca(2+)-containing medium was not changed by pretreatment with 10 microM nifedipine or verapamil. In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (1 microM) abolished 100 microM NDGA-induced [Ca(2+)]i increases. Inhibition of phospholipase C with 2 microM U73122 had little effect on 100 microM NDGA-induced Ca(2+) release. Several other lipoxygenase inhibitors had no effect on basal [Ca(2+)]i. Collectively, the results suggest that NDGA increased [Ca(2+)]i in glioma cells in a lipoxygenase-independent manner, by releasing Ca(2+) from the endoplasmic reticulum in a manner independent of phospholipase C activity and by causing Ca(2+) influx.

Stimulatory effects of chlorzoxazone, a centrally acting muscle relaxant, on large conductance calcium-activated potassium channels in pituitary GH3 cells.

Chlorzoxazone, a centrally acting muscle relaxant, has been used as a marker for hepatic CYP2E1 activity. However, little is known about the mechanism of chlorzoxazone actions on ion currents in neurons or neuroendocrine cells. We thus investigated its effects on ion currents in GH(3) lactotrophs. Chlorzoxazone reversibly increased Ca(2+)-activated K(+) current (I(K(Ca))) in a concentration-dependent manner with an EC(50) value of 30 microM. The chlorzoxazone-stimulated I(K(Ca)) was inhibited by iberitoxin (200 nM) or clotrimazole (10 microM), but not by glibenclamide (10 microM) or apamin (200 nM). Chlorzoxazone (30 microM) suppressed voltage-dependent L-type Ca(2+) current. In the inside-out configuration, chlorzoxazone applied to the intracellular side of the patch did not modify single-channel conductance of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, but did increase channel activity by increasing mean open time and decreasing mean closed time. Chlorzoxazone also caused a left shift in the activation curve of BK(Ca) channels. However, Ca(2+)-sensitivity of these channels was unaffected by chlorzoxazone. 1-Ethyl-2-benzimidazolinone (30 microM), 2-amino-5-chlorobenzoxazole (30 microM) or chlormezanone (30 microM) enhanced BK(Ca) channel activity, while 6-hydroxychlorzoxazone (30 microM) slightly increased it; however, chlorphenesin carbamate (30 microM) had no effect on it. Under the current-clamp condition, chlorzoxazone (10 microM) reduced the firing rate of action potentials. In neuroblastoma IMR-32 cells, chlorzoxazone (30 microM) also stimulated BK(Ca) channel activity. The stimulatory effects of chlorzoxazone on these channels may be responsible for the underlying mechanism of chlorzoxazone actions on neurons and neuroendocrine cells.

Novel action of lignans isolated from Hernandia nymphaeifolia on Ca(2+) signaling in renal tubular cells.

The effect of five lignans, epi-aschantin, epi-magnolin, epi-yangambin, deoxypodophyllotoxin and yatein, isolated from Hernandia nymphaeifolia on Ca(2+) signaling in Madin-Darby canine kidney cells was examined using fura-2 as a Ca(2+) indicator. These lignans at concentrations between 10 and 100 microM increased [Ca(2+)](i) in a concentration-dependent manner. Removal of extracellular Ca(2+) abolished the Ca(2+) signals evoked by 50 microM of the lignans. La(3+)(50 microM) abolished the Ca(2+) signals induced by 100 microM of epi-aschantin, epi-magnolin and epi-yangambin, and 20 microM deoxypodophyllotoxin, but inhibited by 60% 50 microM yatein-induced responses. All five lignans (50-100 microM) inhibited by 42-65% thapsigargin-induced capacitative Ca(2+) entry, and inhibited by 23-61% thapsigargin-induced intracellular Ca(2+) release. Epi-yangambin (100 microM), epi-magnolin (100 microM), and epi-aschantin (100 microM) inhibited by 8-38% 10 microM ATP-induced Ca(2+) release. Trypan blue exclusion revealed that incubation with deoxypodophyllotoxin or yatein (but not the other lignans) decreased cell viability in a concentration-dependent manner. Together, the results suggest that, in renal tubular cells, these lignans exert multiple actions on Ca(2+) signaling. They caused Ca(2+) influx but reduced thapsigargin-induced capacitative Ca(2+) entry and also thapsigargin- and ATP-induced Ca(2+) release. Additionally, deoxypodophyllotoxin and yatein may be cytotoxic.