Horng-Huei Liou

Publications of Horng-Huei Liou

• Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization.

  Authors: Chin-Chuan Hung, Wei-Lun Chang, Jia-Ling Ho, John Jen Tai, Tsung-Jen Hsieh, Hsiao-Ching Huang, Yow-Wen Hsieh, Horng-Huei Liou

  Pharmacogenomics. 12/2011; 13(2):159-69.

  Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs. The aim of the present study is to investigate the impacts of polymorphisms in genes related to pharmacokinetic andCarbamazepine (CBZ) is one of the most widely used antiepileptic drugs. The aim of the present study is to investigate the impacts of polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of CBZ on the large interindividual variability in dosages and concentrations. Genetic polymorphisms in the candidate genes were detected in 234 epileptic patients under maintenance CBZ monotherapy by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant SCN1A IVS5-91G>A and EPHX1 c.337T>C allele tended to require higher CBZ dosages and lower ln(concentration-dose ratios) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher CBZ dosages and lower ln(concentration-dose ratios) (p < 0.0001). In addition, the multiple regression model of concentration-dose ratio of CBZ also revealed that genetic variants in SCN1A, EPHX1 and UGT2B7 genes interactively affect the concentration-dose ratio of CBZ (adjusted r(2) = 55%). The present study identified genetic factors associated with CBZ therapy optimization and provided useful information for individualized CBZ therapy in epileptic patients. Further studies in larger populations are needed to confirm our results.

• Protein kinase C mediated pH( i )-regulation of ROMK1 channels via a phosphatidylinositol-4,5-bisphosphate-dependent mechanism.

  Authors: Po-Tsang Huang, Chien-Hsing Lee, Horng-Huei Liou, Kuo-Long Lou

  Journal of molecular modeling. 12/2011;

  The protein kinase C (PKC) pathway is important for the regulation of K(+) transport. The renal outer medullar K(+) (ROMK1) channels show an exquisite sensitivity to intracellular protons (pH( i ))The protein kinase C (PKC) pathway is important for the regulation of K(+) transport. The renal outer medullar K(+) (ROMK1) channels show an exquisite sensitivity to intracellular protons (pH( i )) (effective pK ( a ) approximately 6.8) and play a key role in K(+) homeostasis during metabolic acidosis. Our molecular dynamic simulation results suggest that PKC-mediated phosphorylation on Thr-193 may disrupt the PIP(2)-channel interaction via a charge-charge interaction between Thr-193 and Arg-188. Therefore, we investigated the role of PKC and pH( i ) in regulation of ROMK1 channel activity using a giant patch clamp with Xenopus oocytes expressing wild-type and mutant ROMK1 channels. ROMK1 channels pre-incubated with the PKC activator phorbol-12-myristate-13-acetate exhibited increased sensitivity to pH( i ) (effective pK ( a ) shifted to pH approximately 7.0). In the presence of GF109203X-a PKC selective inhibitor-the effective pK ( a ) for inhibition of ROMK1 channels by pH( i ) decreased (effective pK ( a ) shifted to pH approximately 6.5). The pH( i ) sensitivity of ROMK1 channels mediated by PKC appeared to be dependent of PIP(2) depletion. The giant patch clamp together with site direct mutagenesis revealed that Thr-193 is the phosphorylation site on PKC that regulates the pH( i ) sensitivity of ROMK1 channels. Mutation of PKC-induced phosphorylation sites (T193A) decreases the pH( i ) sensitivity and increases the interaction of channel-PIP(2). Taken together, these results provide new insights into the molecular mechanisms underlying the pH( i ) gating of ROMK1 channel regulation by PKC.

• YC-1, a novel potential anticancer agent, inhibit multidrug-resistant protein via cGMP-dependent pathway.

  Authors: Chin-Chuan Hung, Horng-Huei Liou

  Investigational new drugs. 12/2011; 29(6):1337-46.

  The aim of the present study was to evaluate the effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on multidrug resistance. Expression of human P-glycoprotein was assessed by realtimeThe aim of the present study was to evaluate the effect of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on multidrug resistance. Expression of human P-glycoprotein was assessed by realtime quantitative RT-PCR and western blot. The efflux function of P-glycoprotein was evaluated by rhodamine 123 accumulation and calcein-AM uptake models. The mechanisms of action of YC-1 on different signaling pathways were studied using series of antagonists and the kinetics was also assessed. Cytotoxicity was evaluated by MTT assay. The results demonstrated that increased intracellular accumulation of rhodamine 123 and increased fluorescence of calcein were observed after YC-1 treatment. Furthermore, increased YC-1 concentration resulted in significant decrease in Vmax while K(M) remained unchanged suggested that YC-1 acted as a noncompetitive inhibitor of P-glycoprotein. Moreover, the inhibition of Pgp efflux function by YC-1 was significantly reversed by NO synthase inhibitor, (L)-NAME, the sGC inhibitor, ODQ, the PKG inhibitor, Rp-8-Br-PET-cGMPS, and the PKG inhibitor KT5823. In addition, ERK kinase inhibitor PD98059 also significantly restored YC-1 inhibited Pgp efflux function. These results indicated that YC-1 inhibited Pgp efflux via the NO-cGMP-PKG-ERK signaling pathway through noncompetitive inhibition. The present study revealed that YC-1 could be a good candidate for development as a MDR modulator.

• Neuropsychological performance and seizure-related risk factors in patients with temporal lobe epilepsy: a retrospective cross-sectional study.

  Authors: Wei-Han Wang, Horng-Huei Liou, Chih-Chuan Chen, Ming-Jang Chiu, Ta-Fu Chen, Ting-Wen Cheng, Mau-Sun Hua

  Epilepsy & behavior : E&B. 12/2011; 22(4):728-34.

  The aim of this study was to identify the neuropsychological features in patients with temporal lobe epilepsy (TLE) and their correlation with seizure-related variables. For this purpose, we carriedThe aim of this study was to identify the neuropsychological features in patients with temporal lobe epilepsy (TLE) and their correlation with seizure-related variables. For this purpose, we carried out a retrospective analysis of data from 65 patients with TLE who had undergone a comprehensive neuropsychological assessment. The results suggest that the majority of patients with TLE were impaired in more than one cognitive domain, and among these patients, the mean proportions with defective semantic memory, language, motor/psychomotor speed, verbal episodic memory, and executive function were >50% each. Moreover, age at seizure onset was the strongest predictor of general intellectual impairment, and number of antiepileptic drugs and seizure frequency could significantly predict deficits in verbal memory, language, and psychomotor speed. However, epilepsy duration was a less potent predictor of cognitive deficit than has been reported in cross-sectional studies.

• Geographic variation in the age- and gender-specific prevalence and incidence of epilepsy: analysis of Taiwanese National Health Insurance-based data.

  Authors: Chih-Chuan Chen, Li-Sheng Chen, Ming-Fang Yen, Hsiu-Hsi Chen, Horng-Huei Liou

  Epilepsia. 11/2011; 53(2):283-90.

  We studied geographic variation in age- and gender-specific prevalence and incidence of epilepsy in four different areas of Taiwan. By using large-scale, National Health Insurance (NHI)-based dataWe studied geographic variation in age- and gender-specific prevalence and incidence of epilepsy in four different areas of Taiwan. By using large-scale, National Health Insurance (NHI)-based data from 2000-2003 in Taiwan, we identified 131,287 patients diagnosed with epilepsy (ICD code 345) receiving at least of one of 11 antiepileptic drugs (AEDs). Information on age, gender, and location were also collected. The multivariable Poisson regression analysis was used to assess the heterogeneity of the morbidity of epilepsy in different regions. External data validation was also performed to assess the accuracy of capturing epilepsy cases through our NHI data set. The age-adjusted prevalence and incidence of epilepsy were 5.85 (per 1,000) between 2000 and 2003 and 97 (per 100,000 person-years) during the follow-up time from 2001 to 2003 in Taiwan. The sensitivity and specificity of ICD-9 coding for epilepsy in the NHI data set were 83.91% and 99.83%, respectively, resulting in a slight overestimation. Male patients had a higher probability of having epilepsy than did females. East Taiwan had significantly higher prevalence and incidence than did other areas. The age-specific incidence pattern in east Taiwan was atypical in that it revealed clustering in young and middle-aged groups. Our study demonstrated geographic variation in epidemiologic patterns of epilepsy within Taiwan. The findings are informative and provide insight into the clinical management of epilepsy based on consideration of different target groups in different areas.

• Association of genetic variants in six candidate genes with valproic acid therapy optimization.

  Authors: Chin-Chuan Hung, Jia-Ling Ho, Wei-Lun Chang, John Jen Tai, Tsung-Jen Hsieh, Yow-Wen Hsieh, Horng-Huei Liou

  Pharmacogenomics. 08/2011; 12(8):1107-17.

  Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The aim of the study was to investigate whether polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathwaysValproic acid (VPA) is one of the most widely used antiepileptic drugs. The aim of the study was to investigate whether polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of VPA were associated with the large interindividual variability in dosages and concentrations. Genetic polymorphisms in six candidate genes were detected in 162 epileptic patients under maintenance with VPA monotherapy and stable seizure control by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant UGT1A6 19T>G, 541A>G and 552A>C allele tended to require higher VPA dosages and lower ln(concentration-to-dose ratios [CDRs]) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher VPA dosages and lower lnCDRs (p < 0.0001). On the other hand, carriers of the variant GRIN2B -200T>G allele were more likely to require lower VPA dosages than noncarriers (p < 0.0001) and the homozygous carriers also tended to require lower dosages and higher lnCDRs (p < 0.0001). In addition, the regression model of CDR of VPA also revealed that genetic variants in UGT1A6, GRIN2B and UGT2B7 genes interactively affect CDRs of VPA (adjusted r² = 47%). Although there was a limited sample size, the study identified genetic factors associated with VPA therapy optimization that has not been revealed, and provided useful information for individualized VPA therapy in epileptic patients.

• Carisbamate (RWJ-333369) inhibits glutamate transmission in the granule cell of the dentate gyrus.

  Authors: Chun-Yao Lee, Meng-Larn Lee, Chien-Cheng Shih, Horng-Huei Liou

  Neuropharmacology. 07/2011; 61(8):1239-47.

  Carisbamate (CRS, RWJ-333369) is a novel antiepileptic drug awaiting approval for use in the treatment of partial and generalized seizures. Our aim was to determine whether CRS modulates synapticCarisbamate (CRS, RWJ-333369) is a novel antiepileptic drug awaiting approval for use in the treatment of partial and generalized seizures. Our aim was to determine whether CRS modulates synaptic transmission in the dentate gyrus (DG) and the underlying mechanism. The whole-cell patch-clamp method was used to record AMPA receptor- and NMDA receptor-mediated excitatory postsynaptic currents (EPSC(AMPA) and EPSC(NMDA)) and GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) in granule cells of the DG in brain slices prepared from 3- to 5-week-old male Wistar rats. CRS (30-300 μM) inhibited the evoked EPSC(AMPA) and EPSC(NMDA) by the same extent (20%) with significantly altered CV(-2), suggesting presynaptic modulation. It did not significantly change the inward currents induced by AMPA application. The inhibitory effect of CRS on the evoked EPSC(AMPA) was not occluded by selective voltage-gated Ca(2+) channel blockers, ruling out the involvement of presynaptic Ca(2+) channels. The frequency, but not the amplitude, of spontaneous EPSC(AMPA) was significantly reduced by CRS. However, CRS did not alter either the frequency or the amplitude of TTX-insensitive miniature EPSC(AMPA), indicating an action potential-dependent mechanism was involved. In addition, CRS (100 or 300 μM) did not significantly change the amplitude of the evoked IPSCs. To summarize, our results suggest that CRS reduces glutamatergic transmission by an action potential-dependent presynaptic mechanism and consequently inhibits excitatory synaptic strength in the DG without affecting GABAergic transmission. This effect may contribute to the antiepileptic action observed clinically at therapeutic concentrations of CRS.

• Painful neuropathy due to skin denervation after metronidazole-induced neurotoxicity.

  Authors: Chun-Hsiang Tan, Ya-Fang Chen, Chih-Chuan Chen, Chi-Chao Chao, Horng-Huei Liou, Sung-Tsang Hsieh

  Journal of neurology, neurosurgery, and psychiatry. 04/2011; 82(4):462-5.

  A 53-year-old male patient developed insidious onset of length-dependent painful neuropathy on a background of encephalopathy during prolonged treatment with metronidazole for a cumulative dose ofA 53-year-old male patient developed insidious onset of length-dependent painful neuropathy on a background of encephalopathy during prolonged treatment with metronidazole for a cumulative dose of 146 g in 88 days. The reversible encephalopathy was documented with gradual resolution of hyperintense lesions in bilateral cerebellum and brainstem on brain MRI together with the improvement in symptoms of ataxia and dysarthria. The concomitant impairment of small-diameter sensory nerves posed a diagnostic challenge. The authors took advantage of serial skin biopsies to demonstrate reversible metronidazole-induced small-fibre sensory neuropathy, that is, skin denervation after metronidazole and corresponding skin reinnervation with the disappearance of sensory symptoms.

• A novel postoperative seizure classification for long-term mortality of patients with intractable epilepsy: comparison with the Engel system.

  Authors: Yang-Hsin Shih, Amy Ming-Fang Yen, Der-Jen Yen, Ling-Pin Hung, Hsiu-Hsi Chen, Horng-Huei Liou

  Neurosurgery. 02/2011; 69(1):64-70; discussion 70-1.

  To explore the association of clinical seizure pattern with the long-term prognosis after epilepsy surgery is important for patient counseling and risk management. To study the long-term mortalityTo explore the association of clinical seizure pattern with the long-term prognosis after epilepsy surgery is important for patient counseling and risk management. To study the long-term mortality after surgery of intractable epilepsy patients with a novel classification of clinical patterns by long-term frequency and duration of seizure compared with the Engel classification. We conducted a longitudinal cohort study by enrolling 280 patients with epilepsy who underwent anterior temporal lobectomy between 1987 and 2002. In addition to the Engel classification, we proposed a novel classification of clinical patterns pertaining to at least 1 year of follow-up of the frequency and duration of seizures after surgery (inactive, delayed, intermittent, and intensive groups). We followed the vital status of these members until 2007 to obtain a 15-year survival rate for each classification. The standardized mortality ratio and hazard ratios with proportional hazards regression model by the extent of severity were estimated. The overall 15-year survival rate for patients who underwent anterior temporal lobectomy was 95.1%. The standardized mortality ratio estimates (95% confidence interval) for our classification showed a gradient relationship from 0.6 (0.1-2.3), 2.5 (0.7-6.3), 7.6 (0.8-27.3), and 8.9 (3.2-19.3) for inactive, delayed, intermittent, and intensive groups, respectively (Trend test, P = .04), whereas the corresponding estimates were 0.8 (0.2-2.2), 5.9 (1.2-17.2), 6.7 (2.5-14.7), and 7.2 (0.8-25.9) for Engel I to IV, respectively, which showed a less increasing trend (Trend test, P = .82). Similar findings were noted for hazard ratios for the 2 classifications. The proposed novel classification with long-term observed frequency and duration of seizures after surgery is more informative for predicting long-term mortality than the Engel classification.

• Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood-brain barrier and MPTP-induced dopaminergic toxicity in rodents.

  Authors: Chun-Jung Lin, Ying Tai, Miao-Tzu Huang, Yuan-Feen Tsai, Hao-Jui Hsu, Kai-Yuan Tzen, Horng-Huei Liou

  Journal of neurochemistry. 08/2010; 114(3):717-27.

  The cellular localization of organic cation transporter (OCT) 1 and OCT2 in isolated brain microvessel endothelial cells from humans, rats, and mice and in cultured adult rat brain endothelial cellsThe cellular localization of organic cation transporter (OCT) 1 and OCT2 in isolated brain microvessel endothelial cells from humans, rats, and mice and in cultured adult rat brain endothelial cells was examined by confocal microscopy and in isolated luminal and abluminal membrane fractions by Western blot analysis. Cellular uptake of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was measured with or without OCT1/OCT2 silencing. The interaction between MPTP and amantadine was studied by in vitro kinetic analysis and in vivo brain microdialysis. MPTP-induced dopaminergic toxicity was examined by measuring dopamine levels in the brain striatum and by positron emission tomography scanning. The results showed that both OCT1 and OCT2 were mainly expressed on the luminal side of brain microvessel endothelial cells and adult rat brain endothelial cells. Cellular uptake of MPTP was significantly (p < 0.05) decreased by about 53%, 60%, or 91% following silencing of OCT1, OCT2, or both, respectively. Amantadine competitively inhibited MPTP uptake in vitro and significantly (p < 0.05) reduced the area under the time-concentration curve for MPTP and MPP(+) in the brain extracellular fluid in rats and mice by 65-70% and 35-85%, respectively. MPTP-induced dopaminergic toxicity in mice was ameliorated by amantadine without stimulating dopamine turnover. In conclusion, OCT1 and OCT2 are important for MPTP transfer across the blood-brain barrier and amantadine reduces the blood-brain barrier transfer of MPTP and MPTP-induced dopaminergic toxicity in rodents.

• Impaired gist memory in patients with temporal lobe epilepsy and hippocampal sclerosis.

  Authors: Ming-Jang Chiu, Ching-Wei Lin, Chih-Chuan Chen, Ta-Fu Chen, Ya-Fang Chen, Hon-Man Liu, Chih-Pang Chu, Horng-Huei Liou, Mau-Sun Hua

  Epilepsia. 06/2010; 51(6):1036-42.

  Temporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memoryTemporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memory functions. We aimed to examine the effect of restricted hippocampal lesions on gist memory function in patients with TLE. Forty-five patients with TLE and HS (16 left, 15 right, and 14 bilateral lesions) and 22 control subjects were recruited. Patients with magnetic resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal lesions were excluded. All participants performed a gist-based recognition task following the Deese-Roediger-McDermott paradigm and were tested for verbal IQ and memory functions. We conducted hippocampal volumetry on MRI of all the participants. Patients showed multidomain memory impairments. Gist memory was impaired in patients with bilateral HS and probably in patients with right HS. Hippocampal volumetry supported such findings that total volume of hippocampi and volume of right hippocampus correlated positively with gist memory function. HS has a dose effect and a probable right dominance effect on gist memory; good item memory supports gist memory performance; and a disproportionate deficit was noted in tasks with high relational demand but not in tasks with simple association. We should develop memory skills for patients with TLE by enhancing performance of gist memory related to simple association task.

• Effect of acupressure and trigger points in treating headache: a randomized controlled trial.

  Authors: Lisa Li-Chen Hsieh, Horng-Huei Liou, Liang-Huei Lee, Tony Hsiu-Hsi Chen, Amy Ming-Fang Yen

  The American journal of Chinese medicine. 01/2010; 38(1):1-14.

  The efficacy of acupressure in relieving pain has been documented; however, its effectiveness for chronic headache compared to the muscle relaxant medication has not yet been elucidated. To addressThe efficacy of acupressure in relieving pain has been documented; however, its effectiveness for chronic headache compared to the muscle relaxant medication has not yet been elucidated. To address this, a randomized, controlled clinical trial was conducted in a medical center in Southern Taiwan in 2003. Twenty-eight patients suffering chronic headache were randomly assigned to the acupressure group (n = 14) or the muscle relaxant medication group (n = 14). Outcome measures regarding self-appraised pain scores (measured on a visual analogue scale; VAS) and ratings of how headaches affected life quality were recorded at baseline, 1 month after treatment, and at a 6-month follow-up. Pain areas were recorded in order to establish trigger points. Results showed that mean scores on the VAS at post-treatment assessment were significantly lower in the acupressure group (32.9+/-26.0) than in the muscle relaxant medication group (55.7+/-28.7) (p = 0.047). The superiority of acupressure over muscle relaxant medication remained at 6-month follow-up assessments (p = 0.002). The quality of life ratings related to headache showed similar differences between the two groups in the post treatment and at six-month assessments. Trigger points BL2, GV20, GB20, TH21, and GB5 were used most commonly for etiological assessment. In conclusion, our study suggests that 1 month of acupressure treatment is more effective in reducing chronic headache than 1 month of muscle relaxant treatment, and that the effect remains 6 months after treatment. Trigger points help demonstrate the treatment technique recommended if a larger-scale study is conducted in the future.

• Prevalence and Risk Factors of Somatic and Autonomic Neuropathy in Prediabetic and Diabetic Patients.

  Authors: Wei-Chih Hsu, Amy Ming-Fang Yen, Horng-Huei Liou, Han-Cheng Wang, Tony Hsiu-Hsi Chen

  Neuroepidemiology. 11/2009; 33(4):344-349.

  Aims/Hypothesis: To investigate the prevalence and correlates of somatic and autonomic neuropathies concurrently in prediabetic and diabetic subjects in the general population. Subjects and Methods:Aims/Hypothesis: To investigate the prevalence and correlates of somatic and autonomic neuropathies concurrently in prediabetic and diabetic subjects in the general population. Subjects and Methods: Nerve conduction and heart rate variability studies were used for detecting both types of diabetic neuropathy. Of 1,576 inhabitants, 143 persons were identified as prediabetic or having diabetic mellitus. One hundred and thirty-three persons completed a nerve conduction test and 118 persons a valid heart rate variability test. Significant correlates responsible for diabetic neuropathies were also collected. Results: The prevalence rates of definite, probable and no somatic neuropathy were 9.0% (12/133), 20.3% (27/133) and 70.7% (94/133), respectively. The corresponding figures for autonomic neuropathy were 14.4% (17/118), 54.2% (64/118) and 31.4% (37/118). The prevalence rate for the presence of both neuropathies was 16.9%. In a univariate analysis, age, renal insufficiency, HbA1c and fasting glucose level were significantly associated with somatic neuropathy whereas only systolic blood pressure was statistically significantly associated with autonomic neuropathy. In a multivariate analysis, systolic blood pressure and fasting glucose level were positively associated with somatic neuropathy and systolic blood pressure remained statistically significant for autonomic neuropathy. Conclusions: The prevalence of autonomic neuropathy is twofold compared with somatic neuropathy. Concurrence of the two kinds of neuropathy was approximately half of sole somatic neuropathy and a quarter of sole autonomic neuropathy. Systolic blood pressure and fasting glucose level were related to somatic neuropathy whereas only systolic blood pressure was correlated with autonomic neuropathy.

• Different Prevalence Rates of Parkinson's Disease in Urban and Rural Areas: A Population-Based Study in Taiwan.

  Authors: Chih-Chuan Chen, Ta-Fu Chen, Yuarn-Chung Hwang, Ying-Rong Wen, Yueh-Hsia Chiu, Chia-Yun Wu, Rong-Chi Chen, John Jen Tai, Tony Hsiu-Hsi Chen, Horng-Huei Liou

  Neuroepidemiology. 11/2009; 33(4):350-357.

  Background: Rural living has long been debated as a risk factor for idiopathic Parkinson's disease (IPD). But few community-based studies compared this difference between urban and rural areas.Background: Rural living has long been debated as a risk factor for idiopathic Parkinson's disease (IPD). But few community-based studies compared this difference between urban and rural areas. Methods: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. Results: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551-864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620-646) for people aged 40 and over and 230 (95% CI: 227-234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). Conclusions: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.

• Levetiracetam inhibits glutamate transmission through presynaptic P/Q-type calcium channels on the granule cells of the dentate gyrus.

  Authors: Chun-Yao Lee, Chih-Chuan Chen, Horng-Huei Liou

  British journal of pharmacology. 11/2009;

  Background and purpose: Levetiracetam is an effective anti-epileptic drug in the treatment of partial and generalized seizure. The purpose of the present study was to investigate whetherBackground and purpose: Levetiracetam is an effective anti-epileptic drug in the treatment of partial and generalized seizure. The purpose of the present study was to investigate whether levetiracetam regulates AMPA and NMDA receptor-mediated excitatory synaptic transmission and to determine its site of action in the dentate gyrus (DG), the area of the hippocampus that regulates seizure activities. Experimental approach: Whole-cell patch-clamp method was used to record the AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSC(AMPA) and EPSC(NMDA)) in the presence of specific antagonists, from the granule cells in the DG in brain slice preparations from young Wistar rats (60-120 g). Key results: Levetiracetam (100 microM) inhibited both evoked EPSC(AMPA) and EPSC(NMDA) to an equal extent (80%), altered the paired-pulse ratio (from 1.39 to 1.25), decreased the frequency of asynchronous EPSC and prolonged the inter-event interval of miniature EPSC(AMPA) (from 2.7 to 4.6 s) without changing the amplitude, suggesting a presynaptic action of levetiracetam. The inhibitory effect of levetiracetam on evoked EPSC(AMPA) was blocked by omega-agatoxin TK (100 nM), a selective P/Q-type voltage-dependent calcium channel blocker, but not by nimodipine (10 microM) or omega-conotoxin (400 nM). Conclusions and implications: These results suggest that levetiracetam modulated the presynaptic P/Q-type voltage-dependent calcium channel to reduce glutamate release and inhibited the amplitude of EPSC in DG. This effect is most likely to contribute to the anti-epileptic action of levetiracetam in patients.

• Clinical efficacy and cognitive and neuropsychological effects of levetiracetam in epilepsy: An open-label multicenter study.

  Authors: Tony Wu, Chih-Chuan Chen, Ta-Cheng Chen, Yuan-Fu Tseng, Chen-Bang Chiang, Chin-Chuan Hung, Horng-Huei Liou

  Epilepsy & behavior : E&B. 09/2009;

  The aim of this prospective, multicenter, open-label study was to investigate the efficacy of levetiracetam (LEV) and determine its effects on cognitive and neuropsychological function. Sixty-nineThe aim of this prospective, multicenter, open-label study was to investigate the efficacy of levetiracetam (LEV) and determine its effects on cognitive and neuropsychological function. Sixty-nine patients were evaluated for effects of LEV on seizure control, cognitive (Mini-Mental State Examination [MMSE]) and neuropsychological (Symptom Checklist-90 Revised [SCL-90-R]) functions, and quality of life (Quality of Life in Epilepsy-10 [QOLIE-10]) assessments at 3 and 12months of follow-up. Thirty-nine percent of patients achieved seizure freedom, and 68% had a 50% seizure frequency reduction after 1year of LEV (1235.5+/-392.7mg/day). There were also significant improvements in mean MMSE score and in the recall and language items of MMSE. There were modest improvements in interpersonal sensitivity and paranoid ideation scales of the SCL-90-R, and improvements in cognition and medication effect items of the QOLIE-10. The results demonstrate that LEV not only effectively reduces seizure frequency, but also possibly contributes to improvements in neuropsychological functions such as recall, language, interpersonal sensitivity, and paranoid ideation.

• Mortality of Parkinson's disease by Hoehn-Yahr stage from community-based and clinic series [Keelung Community-based Integrated Screening (KCIS) no. 17)].

  Authors: Horng-Huei Liou, Chia-Yun Wu, Yueh-Hsia Chiu, Amy Ming-Fang Yen, Rong-Chi Chen, Ta-Fu Chen, Chih-Chuan Chen, Yuarn-Chung Hwang, Ying-Rong Wen, Tony Hsiu-Hsi Chen

  Journal of evaluation in clinical practice. 09/2009; 15(4):587-91.

  PURPOSE: We aimed to quantify the mortality reduction by which the early detection of Parkinson's disease (PD) within a community-based study could reduce the number of advanced cases. METHODS: DataPURPOSE: We aimed to quantify the mortality reduction by which the early detection of Parkinson's disease (PD) within a community-based study could reduce the number of advanced cases. METHODS: Data used in this study were derived from two community-based surveys and from a clinical series of PD cases identified from a medical centre. The cumulative survival by Hoehn-Yahr (H-Y) scale was estimated and the mortality reduction derived from a community-based survey was predicted. RESULTS: A total of 117 PD patients were detected through two community-based approaches. By comparing the H-Y stage distribution of screen-detected cases with those from the clinical series, a 22.5% excess in the number of early PD (H-Y stage I and stage II) were identified with screening. The risk ratios of being H-Y stage III or severe for community-based detected cases versus clinical series were 0.49 (95% confidence interval: 0.30-0.78). The total death rate adjusted by H-Y stage distribution was 21% and 28% for cases from community and clinical series, respectively. CONCLUSIONS: The present study revealed that early detection of PD through a community-based survey may reduce 51% incidence of stage III or more severe PD at diagnosis, leading to a 25% reduction in mortality.

• Sibutramine-induced recurrent seizures.

  Authors: Bo-Cheng Huang, Horng-Huei Liou

  Epilepsy & behavior : E&B. 06/2009;

• Effects of Sodium Azide, Barium Ion, d-Amphetamine and Procaine on Inward Rectifying Potassium Channel 6.2 Expressed in Xenopus Oocytes.

  Authors: Fan-Lu Kung, Jung-Lung Tsai, Chien-Hsing Lee, Kuo-Long Lou, Chih-Yung Tang, Horng-Huei Liou, Kuan-Ling Lu, Yi-Hung Chen, Wun-Jheng Wang, Ming-Cheng Tsai

  Journal of the Formosan Medical Association = Taiwan yi zhi. 09/2008; 107(8):600-8.

  Background/Purpose: Inward rectifying potassium channel 6.2 (Kir6.2_C26 channel) is closely related to ATP-sensitive potassium channels. Whether sodium azide, barium ion, d-amphetamine or procaineBackground/Purpose: Inward rectifying potassium channel 6.2 (Kir6.2_C26 channel) is closely related to ATP-sensitive potassium channels. Whether sodium azide, barium ion, d-amphetamine or procaine acts directly on the Kir6.2_C26 channel remains unclear. We studied the effects of these compounds on Kir6.2_C26 channel expressed in Xenopus oocytes. Methods: The coding sequence of a truncated form of mouse Kir6.2 (GenBank accession number NP_034732.1), Kir6.2(1-364) (i.e. Kir6.2_C26), was subcloned into the pET20b(+) vector. Plasmid containing the correct T7 promoter-Kir6.2(1-364) cDNA fragment [Kir6.2/pET20b(+)] was then subject to NotI digestion to generate the templates for in vitro run-off transcriptions. The channel was expressed in Xenopus laevis oocytes. Two-electrode voltage clamping was used to measure the effects of sodium azide, barium ion, d-amphetamine and procaine on Kir6.2_C26 channel current. Results: Sodium azide activated and barium ion and d-amphetamine inhibited the Kir6.2_C26 channel. Procaine did not have any significant effect on the Kir6.2_C26 channel. Conclusion: Kir6.2_C26 channel expressed in Xenopus oocytes can be used as a pharmacological tool for the study of inward rectifying potassium channels.

• Paraquat inhibits postsynaptic AMPA receptors on dopaminergic neurons in the substantia nigra pars compacta.

  Authors: Chun-Yao Lee, Chien-Hsing Lee, Chien-Cheng Shih, Horng-Huei Liou

  Biochemical pharmacology. 09/2008;

  Parkinson's disease (PD) is a neurodegenerative disease that mainly affects dopaminergic (DA-ergic) neurons in the substantia nigra pars compacta (SNc). Glutamate modulates neuronal excitability, andParkinson's disease (PD) is a neurodegenerative disease that mainly affects dopaminergic (DA-ergic) neurons in the substantia nigra pars compacta (SNc). Glutamate modulates neuronal excitability, and a high concentration of glutamatergic receptors is found on DA-ergic neurons in the SNc. Paraquat (PQ) is a putative causative agent for PD. Its effects on synaptic glutamate transmission in SNc DA-ergic neurons were evaluated using whole-cell voltage-clamp recording in brain slices from 7- to 14-day-old Wistar rats. In the presence of bicuculline (BIC), strychnine, and dl-aminophosphonovaleric acid, PQ reversibly suppressed AMPA receptor-mediated evoked excitatory postsynaptic currents (eEPSCs) in a concentration-dependent manner (P<0.05). In the presence of tetrodotoxin (1muM), PQ (50muM) significantly reduced the amplitudes, but not the frequencies, of miniature EPSCs in the SNc, suggesting PQ inhibited eEPSCs through a postsynaptic mechanism. Exogenous application of AMPA to induce AMPA-mediated inward currents excluded involvement of a presynaptic response. The AMPA-induced currents in the SNc were significantly reduced by PQ (50muM) to 74% of control levels (P<0.05), supporting that PQ acts on postsynaptic AMPA receptors. No effect of PQ on eEPSCs was seen in the LD thalamic nucleus and hippocampus, showing PQ specifically inhibited DA-ergic neurons in the SNc. Our results demonstrate a novel mechanism of action of PQ on glutamate-gated postsynaptic AMPA receptors in SNc DA-ergic neurons. This effect may attenuate the excitability and function of DA-ergic neurons in the SNc, which may contribute to the pathogenesis of PD.