Motor symptoms of Parkinson's disease are affected by temperature: A controlled pilot study.

PURPOSE: The motor symptoms (MS) of Parkinson's disease (PD) have been affecting the quality of life in patients. In clinical practice, most patients with PD report that MS are more severe in winter than in summer, and hyperthermic baths (HTB) could temporarily improve MS. The study aimed to evaluate the effects of seasonal variation and aquatic thermal environment of HTB on the MS of PD. PATIENTS AND METHODS: A cross-sectional study of 203 Chinese Han patients was performed. Univariate and multivariate analyses were performed to analyze seasonal variation in MS relative to baseline data (sex, age at onset, duration, season of birth, Hoehn and Yahr stage, family history, levodopa equivalent dose, and the effect of HTB on MS). Ten subjects participated in the HTB study, and one patient dropped out. The paired Wilcoxon rank test was used to assess the differences in the Movement Disorder Society-United Parkinson's disease Rating Scale (MDS-UPDRS) part III motor examination total scores and the modified Webster Symptoms Score between non-HTB and before HTB and between non-HTB and after HTB. RESULTS: The improvement of MS after HTB was an independent risk factor for seasonal variation in MS (OR, 25.203; 95% CI, 10.951-58.006; p = .000). Patients with PD had significant improvements in the MDS-UPDRS part III motor examination total scores, especially in bradykinesia (p = .043), rigidity (p = .008), posture (p = .038), and rest tremor amplitude (p = .047). CONCLUSION: Seasonal variation in temperature and water temperature of HTB may affect MS in some patients with PD. Simple HTB could be recommended as physiotherapy for patients with PD who report temperature-sensitive MS.

Drooling disrupts the brain functional connectivity network in Parkinson's disease.

AIMS: This study aimed to investigate the causal interaction between significant sensorimotor network (SMN) regions and other brain regions in Parkinson's disease patients with drooling (droolers). METHODS: Twenty-one droolers, 22 PD patients without drooling (non-droolers), and 22 matched healthy controls underwent 3T-MRI resting-state scans. We performed independent component analysis and Granger causality analysis to determine whether significant SMN regions help predict other brain areas. Pearson's correlation was computed between imaging characteristics and clinical characteristics. ROC curves were plotted to assess the diagnostic performance of effective connectivity (EC). RESULTS: Compared with non-droolers and healthy controls, droolers showed abnormal EC of the right caudate nucleus (CAU.R) and right postcentral gyrus to extensive brain regions. In droolers, increased EC from the CAU.R to the right middle temporal gyrus was positively correlated with MDS-UPDRS, MDS-UPDRS II, NMSS, and HAMD scores; increased EC from the right inferior parietal lobe to CAU.R was positively correlated with MDS-UPDRS score. ROC curve analysis showed that these abnormal ECs are of great significance in diagnosing drooling in PD. CONCLUSION: This study identified that PD patients with drooling have abnormal EC in the cortico-limbic-striatal-cerebellar and cortio-cortical networks, which could be potential biomarkers for drooling in PD.

Dysregulation of Circulatory Levels of lncRNAs in Parkinson's Disease.

Emerging evidence suggested that long non-coding RNAs (lncRNAs) were involved in Parkinson's disease (PD) pathogenesis. Herein, we used gene expression profiles from GEO database to construct a PD-specific ceRNA network. Functional enrichment analysis suggested that ceRNA network might participate in the development of PD. PPI networks were constructed, and the ceRNA subnetwork based on five hub genes was set up. In a cohort of 32 PD patients and 31 healthy controls, the expression of 10 DElncRNAs (TTC3-AS1, LINC01259, ZMYND10-AS1, CHRM3-AS1, MYO16-AS1, AGBL5-IT1, HOTAIRM1, RABGAP1L-IT1, HLCS-IT1, and LINC00393) were further verified. Consistent with the microarray data, LINC01259 expression was significantly lower in PD patients compared with controls (P = 0.008). Intriguingly, such a difference was only observed among male patients and male controls when dividing study participants based on their gender (P = 0.016). However, the expression of other lncRNAs did not differ significantly between the two groups. Receiver operating characteristic (ROC) curve analysis revealed that the diagnostic power of LINC01259 was 0.694 for PD and 0.677 for early-stage PD. GSEA enrichment analysis revealed that LINC01259 was mainly enriched in biological processes associated with immune function and inflammatory response. Moreover, LINC01259 expression was not correlated with age of patients, disease duration, disease stage, MDS-UPDRS score, MDS-UPDRS III score, MMSE score, and MOCA score. The current study provides further evidence for the dysregulation of lncRNAs in circulating leukocytes of PD patients, revealing that LINC01259 has clinical potential as a novel immune and inflammatory biomarker for PD and early-stage PD diagnosis.

Angiotensin-(1-7) reduces α-synuclein aggregation by enhancing autophagic activity in Parkinson's disease.

Abnormal accumulation of α-synuclein contributes to the formation of Lewy bodies in the substantia nigra, which is considered the typical pathological hallmark of Parkinson's disease. Recent research indicates that angiotensin-(1-7) plays a crucial role in several neurodegenerative disorders, including Parkinson's disease, but the underlying mechanisms remain elusive. In this study, we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson's disease model. We investigated whether angiotensin-(1-7) is neuroprotective in this model by continuous administration of angiotensin-(1-7) into the right substantia nigra for 4 weeks. We found that angiotensin-(1-7) infusion relieved characteristic parkinsonian behaviors and reduced α-synuclein aggregation in the substantia nigra. Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone, angiotensin-(1-7), and/or the Mas receptor blocker A-779 for 24 hours. After binding to the Mas receptor, angiotensin-(1-7) attenuated apoptosis and α-synuclein aggregation in rotenone-treated cells. Primary dopaminergic neurons were also treated with angiotensin-(1-7) and/or the autophagy inhibitor 3-methyladenine for 24 hours. Angiotensin-(1-7) increased α-synuclein removal and increased the autophagy of rotenone-treated cells. We conclude that angiotensin-(1-7) reduces α-synuclein aggregation by alleviating autophagy dysfunction in Parkinson's disease. Therefore, the angiotensin-(1-7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson's disease and angiotensin-(1-7) has potential therapeutic value for Parkinson's disease. All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital (approval No. DWSY-2000932) in January 2020.

Contralateral Posterior Putaminal 18F-Fluorodopa Uptake in Mild Stage Parkinson's Disease: A PET/CT Study.

OBJECTIVE: Previous studies revealed that 18F-FDOPA uptake was significantly decreased in the subregions of striatum contralateral to the side with predominant symptoms and was helpful for improving the early diagnostic accuracy of PD. However, in these studies, more than half of the PD patients already have bilateral motor symptoms (mH&Y stage≥2). This study was aimed to extend previous findings to a milder disease stage. METHODS: Sixteen PD patients with only mild and unilateral motor symptoms (mH&Y stage=1 and disease duration≤2 years) and 22 healthy controls were involved. Striatal 18F-FDOPA uptake was analyzed using a ratio approach. RESULTS: The SORs in the subregions of the contralateral striatum, including caudate, anterior putamen and posterior putamen were significantly decreased in the mild stage PD patients. The SOR for the contralateral posterior putamen had the largest area under the receiver operating characteristic curve (0.963) and separated mild stage PD patients from healthy controls with a sensitivity of 93.75% and a specificity of 95.45% when the cut-off value of <2.160 was selected. CONCLUSION: These data indicate that contralateral posterior putaminal 18F-FDOPA uptake may represent a potential marker for early diagnosis of PD, especially in patients with only mild and unilateral motor symptoms.

Han Chinese family with early-onset Parkinson's disease carries novel compound heterozygous mutations in the PARK2 gene.

PURPOSE: To identify deletions, duplications, and point mutations in 55 previously reported genes associated with Parkinson's disease (PD) and certain genes associated with tremor, spinocerebellar ataxia, and dystonia in a Han Chinese pedigree with early-onset Parkinson's disease (EOPD). PATIENTS AND METHODS: Clinical examinations and genomic analyses were performed on six subjects belonging to three generations of a Han Chinese family. Target region capture and high-throughput sequencing were used to screen these genes associated with PD, tremor, spinocerebellar ataxia, and dystonia. The multiplex ligation-dependent probe amplification (MLPA) method was applied to detect rearrangements in PARK2 exons. Direct Sanger sequencing of samples from all subjects further verified the detected abnormal PRKRA, SPTBN2, and ATXN2 gene fragments. RESULTS: Two family members were diagnosed with PD based on the clinical manifestations, imaging analyses. PARK2 gene heterozygous deletion of exon 3 and heterozygous duplication of exon 6 were identified in them (II-3 and 4). A single heterozygous deletion of exon 3 in PARK2 was detected in II-5 and III-10. A single duplication of exon 6 in PARK2 was detected in I1. Both the heterozygous mutation c.2834G>A (p. R945H) in exon 16 and the heterozygous mutation c.1924 C>T (p. R642W) in exon 14 of the SPTBN2 gene were identified in II-3, II-4, and III-10. The heterozygous mutation c.2989 C>T (p. R997X) in exon 24 of the ATXN2 gene was detected in II-4 and II-5, and the heterozygous mutation c.170 C>A (p. S57Y) in exon 2 of the PRKRA gene was detected in II-3, II-4, and III-10. Other mutations in some genes associated with PD, tremor, spinocerebellar ataxia, and dystonia were not detected. CONCLUSIONS: Novel compound heterozygous mutations were identified in a Han Chinese pedigree and might represent a cause of EOPD.

Dihydroergotoxine mesylate for the treatment of sialorrhea in Parkinson's disease.

BACKGROUND: Many patients with Parkinson's disease (PD) suffer from sialorrhea. Sialorrhea is often treated with anticholinergics and botulinum toxin, but some adverse effects have limited the use of these treatments. Dihydroergotoxine mesylate is an α-adrenergic blocking agents as well as some affinities to the dopaminergic and serotonin (5-HT) receptors. In the current study, we examine the safety and efficacy of dihydroergotoxine mesylate in PD patients. METHODS: This study consisted of 2 phases. The intervention was 2.5-mg oral dihydroergotoxine mesylate twice daily in both phases. The first phase is a three-week open-label single-arm trial (n = 10). The second phase was a six-week randomized controlled trials with a crossover design (n = 20). Efficacy was assessed using the United Parkinson's Disease Rating Scale (UPDRS) sialorrhrea subscore and Sialorrhea Clinical Scale for PD (SCS-PD). RESULTS: In the first phase, the UPDRS sialorrhea score was 3.5 ±â€¯0.53 vs. 1.9 ±â€¯0.57 prior to and after the treatment (P = 0.004). The SCS-PD score decreased from 15.8 ±â€¯2.78 to 9.9 ±â€¯3.00 after the treatment (P = 0.005). The response rate (defined by at least 30% reduction in SCS-PD score) was 60%. In the second phase of crossover trial, the UPDRS sialorrhea score was 3.00 ±â€¯0.56 in placebo weeks vs. 2.00 ±â€¯0.65 on dihydroergotoxine in dihydroergotoxine weeks (P = 0.001). The SCS-PD was 12.50 ±â€¯2.84 and 9.25 ±â€¯2.86 versus, respectively (P < 0.001). The response rate was 10% and 55%, respectively (P = 0.003). There were no significant adverse effects. CONCLUSIONS: Dihydroergotoxine mesylate is safe and effective for sialorrhea in PD patients.

PM2.5 exposure aggravates oligomeric amyloid beta-induced neuronal injury and promotes NLRP3 inflammasome activation in an in vitro model of Alzheimer's disease.

BACKGROUND: Numerous studies suggested that PM2.5 exposure was associated with increased risk of Alzheimer's disease (AD). But the precise mechanisms by which PM2.5 contributed to AD pathogenesis have not been clarified. METHODS: In the presence or absence of neurons, oligomeric amyloid beta (oAß)-primed microglia were stimulated with PM2.5. Firstly, we determined the effects of PM2.5 exposure on neuronal injury and inflammation in neurons-microglia co-cultures. Then, we examined whether NLRP3 inflammasome activation was involved in PM2.5-induced inflammation. After that, we investigated whether PM2.5 exposure increased ROS level in oAß-stimulated microglia. At last, we examined whether ROS and NLRP3 inflammasome activation was required for PM2.5-induced neuronal injury in neurons-microglia co-cultures. RESULTS: In the present study, we showed that PM2.5 exposure aggravated oAß-induced neuronal injury and inflammation in neurons-microglia co-cultures via increasing IL-1ß production. Further, PM2.5-induced IL-1ß production in oAß-stimulated microglia was possibly dependent on NLRP3 inflammasome activation. Meanwhile, PM2.5 exposure increased ROS level in oAß-stimulated microglia. ROS was required for PM2.5-induced IL-1ß production and NLRP3 inflammasome activation in oAß-stimulated microglia. More importantly, ROS and NLRP3 inflammasome activation was required for PM2.5-induced neuronal injury in neurons-microglia co-cultures. CONCLUSIONS: For the first time, these results suggested that the effects of PM2.5 under AD context were possibly mediated by NLRP3 inflammasome activation, which was triggered by ROS. Taken together, these findings have deepened our understanding on the role of PM2.5 in AD pathogenesis.

Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson's disease.

Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased. Furthermore, we provided in vivo evidence that Ang II directly elicited apoptosis of dopaminergic neurons via activation of AT1R in the SN of rats. More importantly, we showed for the first time that oral administration of azilsartan, a newly developed AT1R blocker approved by the U.S. Food and Drug Administration for hypertension treatment, rescued the apoptosis of dopaminergic neurons and relieved the characteristic parkinsonian symptoms in PD rats. These results support the application of AT1R blockers in PD therapy, and strengthen the notion that many therapeutic agents may possess pleiotropic action in addition to their main applications.

Mitochondrial-dependent mechanisms are involved in angiotensin II-induced apoptosis in dopaminergic neurons.

INTRODUCTION: We recently demonstrated that angiotensin II (Ang II) was involved in the etiology of Parkinson's disease (PD) via induction of apoptosis of dopaminergic neurons, but the mechanisms are not completely elucidated. Here, we asked whether mitochondrial-dependent mechanisms contributed to the Ang II-induced dopaminergic neuronal apoptosis. MATERIALS AND METHODS: CATH.a cells were incubated with Ang II in combination with mitochondrial permeability transition pore (mPTP) inhibitors or angiotensin receptor antagonists, and apoptosis rate, caspase-3 activity, cytochrome c levels, and mPTP opening were assessed. RESULTS: We showed that Ang II triggered apoptosis via a mitochondrial-dependent pathway, as elevated cytochrome c levels were observed in the cytosol. By employing cyclosporin A and sanglifehrin A, two specific mPTP inhibitors, we revealed that cytochrome c release from mitochondria into cytoplasm was ascribed to mPTP opening. Meanwhile, the aforementioned effects could be abrogated by an AT1 receptor antagonist losartan rather than an AT2 receptor antagonist PD123319. CONCLUSION: This study demonstrates that Ang II triggers mitochondrial-dependent apoptosis via facilitating mPTP opening through an AT1 receptor-mediated fashion in dopaminergic neurons. These findings give insight into the effect of Ang II in the etiology of PD, and reinforce the application of AT1 receptor antagonists for PD treatment.

Independent Correlation of Serum Homocysteine with Cerebral Microbleeds in Patients with Acute Ischemic Stroke due to Large-Artery Atherosclerosis.

BACKGROUND AND AIM: The severity of cerebral microbleeds (CMBs) affected the prognosis of patients with acute cerebrovascular disease. Considering the impact of CMBs on clinical decision, it is necessary to assess the risk factors of CMBs. We aimed to evaluate the independent risk factors of CMBs in patients with acute ischemic stroke of large-artery atherosclerosis. MATERIALS AND METHODS: 112 patients were enrolled in the study. The baseline information, the results of laboratory examination and cranial MRI were collected. The independent risk factors of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis were evaluated. RESULTS: CMBs were found in 56 (50%) patients. Older age and higher homocysteine (Hcy) level were associated with an elevated chance of occurrence of CMBs. Further, there was a positive correlation between CMBs grade and serum Hcy level. CONCLUSIONS: Serum Hcy level is strongly associated with the presence of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis. Serum Hcy level may be a potential therapeutic target for alleviating adverse clinical outcomes of CMBs.

Angiotensin-(1-7) is Reduced and Inversely Correlates with Tau Hyperphosphorylation in Animal Models of Alzheimer's Disease.

As a recently identified bioactive peptide of brain renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)] along with its metabolic enzyme angiotensin-converting enzyme (ACE) 2 and its receptor Mas forms ACE2/Ang-(1-7)/Mas axis. Accumulating evidence suggests an essential role of ACE2/Ang-(1-7)/Mas axis in maintaining normal cognitive functions in both animals and human subjects, and dysregulation of this axis contributed to the pathogenesis of several neurodegenerative diseases such as hypertension-induced neurodegeneration and vascular dementia. To date, whether this axis was associated with the etiology and progression of Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, remains unclear. In the current study, by using senescence-accelerated mouse prone 8 (SAMP8) mice, an animal model of sporadic AD, we showed for the first time that the level of Ang-(1-7) in the brain was significantly reduced during disease progression. More importantly, an inverse correlation was found between Ang-(1-7) level and tau hyperphosphorylation, a pathological hallmark of AD, in cerebral cortex and hippocampus of SAMP8 mice. Meanwhile, this has been further confirmed in P301S mice, an animal model of pure tauopathy. All these findings suggested that Ang-(1-7), the main effector of brain ACE2/Ang-(1-7)/Mas axis, might be implicated in the etiology and progression of AD, possibly via modulation of tau hyperphosphorylation.

Activation of Autophagy Contributes to the Angiotensin II-Triggered Apoptosis in a Dopaminergic Neuronal Cell Line.

Our recent study indicated that angiotensin II (Ang II), the main component of renin-angiotensin system, participated in the pathogenesis of Parkinson's disease (PD) by triggering the apoptosis of dopaminergic neuronal cells. However, the underlying mechanisms are still not fully understood. In this study, by using CATH.a cells, a dopaminergic neuronal cell line stably expressing angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R), we tested the hypothesis that activation of autophagy contributed to the apoptosis triggered by Ang II. We showed that Ang II activated autophagy and triggered apoptosis in CATH.a cells in a dose-dependent manner. More importantly, inhibition of autophagy by 3-methyladenine markedly attenuated the apoptosis caused by Ang II in CATH.a cells. In addition, the Ang II-induced autophagy and subsequent cell apoptosis could be fully abolished by an AT1R antagonist losartan rather than PD1223319, an antagonist for AT2R. Taken together, our study provides the first evidence that Ang II triggers apoptosis via activation of autophagy in a dopaminergic neuronal cell line through an AT1R-mediated manner. These findings have deepened our understanding on the role of Ang II in the pathogenesis of PD and support the use of AT1R antagonists for the treatment of this devastating neurodegenerative disease.

Angiotensin II triggers apoptosis via enhancement of NADPH oxidase-dependent oxidative stress in a dopaminergic neuronal cell line.

Numerous studies reveal that Angiotensin II (Ang II), the main effector of renin-angiotensin system, contributes to the pathogenesis of Parkinson's disease (PD) via triggering dopaminergic cell loss. However, the underlying mechanisms remain largely unclear. In the current study, by using CATH.a cell, a dopaminergic neuronal cell line stably expressing Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R), we showed that Ang II treatment triggered cell apoptosis in a dose-dependent manner, providing the first evidence that apoptotic cell death contributed to the dopaminergic cell loss induced by Ang II. Ang II treatment also led to a significant increment in intracellular reactive oxygen species generation, which could be fully abolished by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors apocynin or diphenylene iodonium, indicating that Ang II enhanced oxidative stress via a NADPH oxidase-dependent manner. More importantly, inhibition of oxidative stress by NADPH oxidase inhibitors partially attenuated cell apoptosis caused by Ang II, implying that the enhancement of NADPH oxidase-dependent oxidative stress contributed to the cell apoptosis triggered by Ang II. Furthermore, the Ang II-induced oxidative stress and subsequent apoptosis could be completely abolished by AT1R blocker losartan rather than AT2R blocker PD1223319, suggesting that the aforementioned detrimental effects of Ang II are mediated by AT1R. In summary, these findings have deepened our understanding on the role of Ang II in PD pathogenesis, and support the use of AT1R blockers in the treatment of this devastating disease.

Salubrinal protects against rotenone-induced SH-SY5Y cell death via ATF4-parkin pathway.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, for which there are no effective disease-modifying therapies. Growing evidence from studies in human PD brain, in addition to genetic and toxicological models, indicates that endoplasmic reticulum (ER) stress is a common feature of the disease and contributes to neurodegeneration. We examine whether salubrinal, a ER stress inhibitor, can protect the rotenone-induced SH-SY5Y cell death and explore the mechanisms underlying this protection. Our results demonstrated that rotenone induced a significant ER stress response and caused cell apoptosis, which was inhibited by salubrinal. Activating transcription factor 4 (ATF4), a member of the ATF/CREB family of basic leucine zipper transcription factors, has been implicated in the pathogenesis of neurodegeneration. We showed that salubrinal increased the up-regulation of ATF4 expression. An ATF4 siRNA significantly increased the rotenone cytotoxicity and decreased the salubrinal's protection. Further, we showed that ATF4 siRNA inhibited the expression of parkin, and parkin knockdown similarly aggravated the rotenone cytotoxicity and reduced the salubrinal's protection. Additionally, the protein level of parkin was declined after treatment with rotenone, whereas this reduction was rescued by salubrinal. These findings indicate ATF4-parkin pathway plays an important role in the salubrinal-mediated neuroprotection of rotenone-induced dopaminergic cell death.

The association of ABCC3 promoter methylation with clopidogrel response in Chinese ischemic stroke patients.

Multidrug resistance protein 3 (MRP3), encoded by ABCC3, is an ATP-dependent efflux pump mediating the transport of many drugs, implicated in clopidogrel resistance. This study enrolled 87 ischemic stroke patients with CYP2C1 9*1/*1 genotype, who received clopidogrel (75 mg/day) for at least 5 days before discharge. The maximum platelet aggregation (MPA) was measured by light transmittance aggregometry (LTA) to assess platelet function. Whole blood samples were obtained to evaluate the ABCC3 promoter methylation and mRNA expression of ABCC3. Pyrosequencing was carried out to investigate ABCC3 methylation and ABCC3 mRNA expression was evaluated by qPCR. The ABCC3 methylation was neither significantly different among the four MPA quartile groups (P = 0.275) nor independently associated with MPA values (R = 0.100, P = 0.358). However, the ABCC3 promoter methylation status in 87 clinical samples from patients correlated inversely with the expression of ABCC3 (R = - 0.854, P < 0.001). In addition, the ABCC3 expression was neither significantly different among the four quartile groups (P = 0.499) nor independently associated with MPA values (R = 0.060, P = 0.582). ABCC3 promoter methylation does not seem to exhibit any impact on MPA and clopidogrel response at all.

Safety and efficacy of single-incision laparoscopic surgery for appendectomies: a meta-analysis.

AIM: To compare single incision laparoscopic surgery for an appendectomy (SILS-A) with conventional laparoscopic appendectomy (C-LA) when implemented by experienced surgeons. METHODS: Studies and relevant literature regarding the performance of single-incision laparoscopic surgery vs conventional laparoscopic surgery for appendectomy were searched for in the Cochrane Central Register of Controlled Clinical Trials, MEDLINE, EMBASE and World Health Organization international trial register. The operation time (OR time), complications, wound infection and postoperative day using SILS-A or C-LA were pooled and compared using a meta-analysis. The risk ratios and mean differences were calculated with 95%CIs to evaluate the effect of SILS-A. RESULTS: Sixteen recent studies including 1624 patients were included in this meta-analysis. These studies demonstrated that, compared with C-LA, SILS-A has a similar OR time in adults but needs a longer OR time in children. SILS-A has similar complications, wound infection and length of the postoperative day in adults and children, and required similar doses of narcotics in children, the pooled mean different of -0.14 [95%CI: -2.73-(-2.45), P > 0.05], the pooled mean different of 11.47 (95%CI: 10.84-12.09, P < 0.001), a pooled RR of 1.15 (95%CI: 0.72-1.83, P > 0.05), a pooled RR of 1.9 (95%CI: 0.92-3.91, P > 0.05), a pooled RR of 1.01 (95%CI: 0.51-2.0, P > 0.05) a pooled RR of 1.86 (95%CI: 0.77-4.48, P > 0.05), the pooled mean different of -0.25 (95%CI: -0.50-0, P = 0.05) the pooled mean different of -0.01 (95%CI: -0.05-0.04, P > 0.05) the pooled mean different of -0.13 (95%CI: -0.49-0.23, P > 0.05) respectively. CONCLUSION: SILS-A is a technically feasible and reliable approach with short-term results similar to those obtained with the C-LA procedure.

Antiepileptics topiramate and levetiracetam alleviate behavioral deficits and reduce neuropathology in APPswe/PS1dE9 transgenic mice.

BACKGROUND: The close relationship between epileptic seizure and Alzheimer's disease (AD) has been demonstrated in the past decade. Valproic acid, a traditional first-line antiepileptic drug, exerted protective effects in transgenic models of AD. It remains uncertain whether new antiepileptic drugs could reverse neuropathology and behavioral deficits in AD transgenic mice. AIMS: APPswe/PS1dE9 transgenic mice were used in this study, which over express the Swedish mutation of amyloid precursor protein together with presenilin 1 deleted in exon 9. 7-month-old APPswe/PS1dE9 transgenic mice were treated daily with 20 mg/kg topiramate (TPM) and 50 mg/kg levetiracetam (LEV) for 30 days by intraperitoneal injection to explore the effects of TPM and LEV on the neuropathology and behavioral deficits. RESULTS: The results indicated that TPM and LEV alleviated behavioral deficits and reduced amyloid plaques in APPswe/PS1dE9 transgenic mice. TPM and LEV increased Aß clearance and up-regulated Aß transport and autophagic degradation. TPM and LEV inhibited Aß generation and suppressed γ-secretase activity. TPM and LEV inhibited GSK-3ß activation and increased the activation of AMPK/Akt activation. Further, TPM and LEV inhibited histone deacetylase activity in vivo. CONCLUSIONS: Therefore, TPM and LEV might have the potential to treat AD effectively in patient care.

Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effects of candesartan cilexitil in the rotenone rat model of Parkinson's disease.

Recent studies indicated that angiotensin II (Ang II) receptor blockers could reduce neurotoxins-induced dopaminergic (DA) cell death, but the underlying mechanisms are still unclear. Given that endoplasmic reticulum (ER) stress plays a major role in rotenone-induced neuronal apoptosis, we investigated whether candesartan cilexetil, a selective and high-affinity Ang II receptor antagonist, could protect the DA neuron via reducing ER stress in a chronic rotenone rat model for Parkinson's disease (PD). Our data showed that candesartan cilexetil could ameliorate the descent latency in catalepsy tests, and decrease rotenone-induced DA neuron apoptosis. Moreover, candesartan cilexetil has been found to play a protective role via down-regulating the expression of activating transcription factor 4 (ATF4), the CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP), and p53 upregulated modulator of apoptosis (Puma). Thus, our experiments strongly suggest that administration of candesartan cilexetil protects DA neuron involving blocking ER stress, possibly via inhibiting activation of the ATF4-CHOP-Puma pathway, which could provide new insight into clinical therapeutics for PD.

Parkinson's disease in China.

Paralysis agitans was first documented in 1817 by James Parkinson, and therefore the syndrome was named Parkinson's disease (PD). In fact, as early as more than 2000 years ago, the clinical manifestations of this disease have been described in Chinese medicine classics, such as the "Huangdi Neijing (Yellow Emperor's Internal Classic)" and "Zhong Zang Jing (Hua's Zhong Zang Classic)." In recent years, especially in the past 30 years after reform and opening-up, PD has drawn a lot of attention by Chinese scholars. Although great progress in the studies of PD has been made in recent years, the gap between China and western countries still exists. In this review, we concentrate on the main progress made in epidemic characteristics, etiology, diagnosis and management of PD in China.