Objective To investigate the role of externally regulated kinase (ERK) in a rat model of levodopa-induced motor complications. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle(MFB). First, rats were intraperitoneally treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg, twice daily) for 22 days. On day 23, rats were treated with ERK inhibitor, PD98059 before levodopa administration. Rotational duration and peak rotation were estimated. After sacrificed, ERK1/2 phosphorylation was observed by Western blot. Results Our study showed that chronic treatment of lesioned rats with levodopa markedly upregulated the ERK1/2 phosphorylation of in lesioned striatum(155.6%±6.5%). PD98059 could reduce hyperphosphorylation of ERK1/2(85.4%±5.6%). Meanwhile, PD98059 reversed both the shortened rotational duration and increased peak rotation induced by chronic levodopa treatment. Moreover, PKC inhibitor could partly downregulated the ERK1/2 phosphorylation(101.2%±6.2%, compared with levodopa+vehide, t=3.2, P<0.05). Conclusions These results indicated that the development of motor complications could be associated with activation of ERK pathway. And more, activation of ERK was partly dependent on PKC. Pharmaceuticals which act to inhibit ERK pathway may be useful in the treatment of parkinsonism related motor complications.

ObjectiveTo investigate the role of N-methyl-D-aspartate receptor subunit 2B (NR2B) antagonist CP-101.606 in behaviour and expression of related signal proteins in a rat model of levodopa-induced motor complications.MethodsThe hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle.Then,rats were intraperitoneally treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days.On 23th day,rats received CP-101.606 before levodopa administration.Rotational duration was estimated.After sacrificed,phosphorylated NR2B and Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and glutamate receptor 1 ( GluR1S831 ) were observed by western blot.ResultsThe results showed that NR2B antagonist CP-101.606 reversed the levodopa-induced shortened rotational duration.Chronic levodopa treatment increased abundance of the phosphorylated NR2B and downstream related signal proteins CaMKⅡ and GluR1S831 to (145.3±6.5)％ and (132.5±5.7)％ and (105.6±6.3)％,respectively.Moreover,CP-101.606 could reduce hyperphosphorylation of NR2B and CaMKⅡ and GluR1 S831 to (102 ± 4.9 )％,(98.4±3.9)％ and (49.5 ± 4.2 )％,respectively.ConclusionsThese results indicate that the enhancement of N-methyl-D-aspartate (NMDA) receptor function mediated by NR2B phosphorylation contribute to development of motor complications,through a mechanism that involved the downstream signal mediators of NMDA receptor overactivation.Pharmaceuticals which act to inhibit NR2B may be useful in the treatment of the motor complications in parkinsonian patients.

Objective To explore the effects of chronic levodopa treatment on characteristics of N-methyl-D-aspartate(NMDA) receptor subunit 1(NR1) on the neurons of striatum in rat models of Parkinsonism related motor complications.Methods Rat models(n=25)of Parkinsonism related motor complications were established and were randomly divided into solvent treatment group(n=5,intraperitoneal injection with vitamin C),levodopa chronic treatment group(n=10,intraperitoneal injection with levodopa for 23 d) and MK-801 treatment group(n=10,intraperitoneal injection with MK-801 on d 23 after intraperitoneal injection with levodopa for 22 d).Another 5 rats were served as controls(sham-operation group,n=5).Locomotion changes of rats in MK-801 treatment group were recorded,and NR1 phosphorylation in the other three groups was detected by Western blotting. Results After chronic treatment with levodopa methylester for 1,8,15 and 22 d,rats in MK-801 treatment group displayed shortened rotational duration and increased peak rotation.Compared with d 22,MK-801 both prolonged rotational duration and reduced peak rotation(P0.05).The expression of NR1,phosphorylated NR1S890,NR1S896 and NR1S897 in striatal membranes in levodopa chronic treatment group was increased compared with that of solvent treatment group(P

Objective To investigate the alteration of phosphorylated GluR1Ser831 and behavioural effects in a rat model of levodopa-induced motor complications after Ca2 +/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibitor KN-93 treatment. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle. Then, rats were intraperitoneally treated with levodopa ( 50 mg/kg with benserazide 12.5 mg/kg,twice daily) for 22 days. On day 23 ,rats received KN-93 before levodopa administration. Rotational duration was estimated. After sacrificed, subcellualr distribution of GluR1 and phosphorylated GluR1Ser831 were observed by western blot. Results The study showed that CaMKⅡ inhibitor KN-93 prolonged rotational duration. Moreover, KN-93 could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser831, which was closely associated with levodopa-induced motor complications. The expression of membrane GluR1 and phosphorylated GluR1Ser831 was (83.4 ±4.2)% and (47.2 ±5.2)% ,respectively. Conclusions These results indicated that activation of CaMKⅡ contributed to development of motor complications, through a mechanism that involved an increase in phosphorylated GluR1 Ser831. Pharmaceuticals which act to inhibit CaMKⅡ may be useful in the treatment of the motor complications in parkinsonian patients.

Objective To examine the caregivers' burden and quality of life (QOL) of main caregivers of patients with Parkinson's disease by analyzing caregiver and patient-related factors. Methods A total of 53 cases with Parkinson's disease seen from October 2012 to December 2013 in Yantaishan hospital of Yantai City were selected. Assessments: (a) EuroQol-5 questionnaires, including: EQ-5 dimensions (EQ -5d) and visual analogue scale (VAS). (b) Unified Parkinson's Disease Rating Scale. (c) Hoehn-Yahr(H-Y) stage; (d) Parkinson's disease sleep scale (PDSS), 15 items; (e) Hamilton Anxiety Rating Scale (HAMD-14), Hamilton Depression Rating Scale (HAMA-24); (f) Chinese version of Zarit caregiver burden interview. Results Spearman correlation analysis showed that the EQ-5D index and EQ-VAS negatively correlated with HAMD-14 of caregivers of Parkinson diseasepatients (r=- 0.318, - 0.046) (P<0.05), and negatively correlated with H-Y staging (r=-0.592, -0.531), UPDRSI (r=-0.434, -0.316) , UPDRS Ⅱ (r=0.521, 0.513) , UPDRS Ⅲ (r=0.520, 0.534), UPDRS Ⅳ (r=0.564, 0.509), PDSS in patients with Parkinson's disease (r=0.547, 0.490), HAMD-14 (r=0.315, 0.350), HAMA-24 (r=0.413, 0.401) of Parkinson's disease patients (P<0.05). Caregiver burden was related with HAMD-14 (r=0.496), HAMA-24 (r=0.551),H-Y stage (r=0.697), PDSS (r=0.659), UPDRS Ⅰ-Ⅳ (r=0.538, 0.668, 0.696, 0.600), EQ-5D index of Parkinson disease patients (r=0.682), EQ-VAS of Parkinson disease patients (r=0.670) (P<0.05); and positively related with anxiety of caregivers (r=0.275) , and a negative correlation with the caregivers' quality of lives (r=0.665) (P<0.05). Bivariate analyses showed significant correlations between caregiver burden and patients' sleep, scores of Parkinson's motor symptoms, and caregivers' depression. Based on multiple regression analysis, Zarit score proved to be the main predictor of caregivers' QOL. Caregivers' age, total numbers of caregivers and H-Y stage also proved to be a relevant factor. Conclusion Improvement of patient's sleep, motor symptoms anddepression might alleviate caregivers' strain. There is a correlation between caregivers' burden and QOL. QOL of caregivers can be improved through reducing their care-burden.

Objective To explore the relationship between motor complications of Parkinson's disease(PD)with chronic L-dopa treatment and striatal phosphorylated GluR1Ser845.Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle(MFB).Then the hemi-parkinsonian rat was treated intraperitoneally with L-dopa methylester(25 mg?kg-1?d-1,twice one day)for 22 days and rotational duration and frequency of off period were respectively estimated.After they were sacrificed,their subcellualr distribution of GluR1 and GluR1Ser845 phosphorylation was observed with immunofluorescence and Western blot.Results After the chronic treatment with L-dopa methylester,PD rats displayed shortened rotational duration and increased frequency of off period,which was similar to fluctuations of the symptoms and on-off phenomenon in PD patients.In the lesioned striatum of PD rats,the amount of GluR1 and phosphorylated GluR1Ser845 in striatal membrane was reduced to 73.0%?4.8% and 42.0%?5.6%,respectively,compared with those non-lesioned.After chronic treatment of PD rats with L-dopa,the amount of GluR1 and phosphorylated GluR1Ser845 in striatal membranes were increased to 104.0%?5.5% and 112.0%?3.4%.These unique changes occurred only in parvalbumin-positive interneurons.Conclusions These findings suggest that subcellular distribution and phosphorylation state of GluR1Ser845 in parvalbumin-positive interneurons may play a significant role in the pathogenesis of motor complications of chronic L-dopa treatment for PD.

Malignant pleural effusion is a common complication of advanced cancer.The present study employed chest circulating hot infusion chemotherapy for 55 cases of malignant pleural effusion.The outcomes were complete remission (n =23,41.8％),partial remission (n =25,45.5％),stable disease (n=4,7.3 ％) and progressive disease (n =3,5.5％).And the effective rate was 87.3％.After treatment,the levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) were significantly lower than those before treatment (P ＜ 0.05).And the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) were significantly higher than those before treatment (P ＜ 0.05).Pleural circulation perfusion chemotherapy is both safe and effective in the treatment of malignant pleural effusion.And it helps to enhance immune functions and improve the quality-of-life of patients.

Niemann-Pick disease type C (NPC) is a fatal,neurovisceral lipid storage disease,neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons,progressive neuronal loss,neurofibrillary tangles (NFTs) formation,and axonal spheroids (AS).Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice).With a goal of elucidating the mechanisms underlying the lesion formation,we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2,cdk4,and cdk5 in lesion formation in young npc mice.Cytoskeletal lesions were detectable in npc mice at three weeks of age.Importantly,concomitant activation of cdc2/cyclin B 1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected.The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice,and this activation contributed to the lesion formation.We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2,cdk4,and cdk5 activation.Furthermore,cdc2/cyclin B1 may act as a key initial player one week earlier.Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.

Objective To explore the role ofpostsynaptic density 95 (PSD-95) in Parkinsonian rat models receiving chronic L-dopa treatment. Methods The hemi-parkinsonian rat models were established by stereotaxically injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of 60 rats. Thirty-two of them were successfully induced into models with PD and equally randomized into PD group, L-dopa plus physiological saline treatment group, L-dopa plus PSD-95antisense oligonucleotide treatment group and L-dopa plus TE treatment group (n=8). The rats in the PD group were treated intraperitoneally with 0.2% ascorbic acid physiological saline water. The rats in the for 22 d. On the following 3 days, the rats were performed intraperitoneal injection of physiological saline water, injection of PSD-95 antisense oligodeoxynucleotide and TE buffer in the striatum,respectively. Another 8 rats were chosen as normal control group, only given solvent. Rotational reaction time and the largest number of revolutions within 5 minutes of rotation were estimated on the 25th d of injection. After rats being sacrificed, Mrna and protein expressions of PSD-95 at the corpus striatum were observed by RT-PCR and Western blotting, repectively. Results After chronic treatment with L-dopa methylester, the rotational reaction time was prolonged and the the largest number of revolutions within 5 minutes of rotation of PD rats was decreased in the L-dopa plus PSD-95 antisense oligodeoxynucleotide group on the 25th d, as compared with those in the L-dopa plus physiological saline water group and L-dopa plus TE group (P＜0.05). In the lesioned striatum of PD rats, the abundance of PSD-95 Mrna and protein expressions were statistically and evidently reduced as compared with those in the control group (P＜0.05). After chronic treatment of PD rats with L-dopa, the abundance of PSD-95mRNA and protein expressions were statistically and evidently increased as compared with that in the PD group (P＜0.05). Pretreatment with PSD-95 antisense oligodeoxynucleotide statistically and obviously reduced the abundance of PSD-95 protein expression as compared with pretreatment with chronic L-dopa (P＜0.05). Conclusion PSD-95 may play a significant role in the pathogenesis of motor complications of rats with PD receiving chronic L-dopa treatment.