Preparation modification strategies for clinical treatment drugs of Parkinson's disease / 药学学报

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Experience with the Rehabilitation of Patients with Parkinson's Disease Using Levodopa-Carbidopa Intestinal Gel（LCIG）Treatment for Their Return to Work / The Japanese Journal of Rehabilitation Medicine

Patients with Parkinson's disease (PD) experience difficulties with activities of daily living (ADLs) at workplace and in their social life depending on the extent of disease progression. Because of their disabilities, patients with PD are forced into early retirement compared to other people of their age group. We present our experience with the rehabilitation of three patients with PD using levodopa-carbidopa intestinal gel (LCIG) treatment for their return to work. The rehabilitation program comprised the following three modules：1) evaluating the patients' ability to walk indoor for a short time；2) assessing their standing and sitting positions to enable them to more easily handle a device；and 3) improving their upper limb function, including skilled movements, for operating a device in emergency. Finally, all three patients exhibited improvements in the Timed Up and Go test results and device operation. Two of the patients returned to their former workplace within 10 months of LCIG treatment initiation and the remaining patient found new employment 1 year after treatment commencement.In conclusion, establishing a rational support system that involves rehabilitation programs and information sharing across multiple occupations is essential for the return to work of patients with PD receiving LCIG treatment.

Experience with the Rehabilitation of Patients with Parkinson's Disease Using Levodopa-Carbidopa Intestinal Gel（LCIG）Treatment for Their Return to Work / The Japanese Journal of Rehabilitation Medicine

Patients with Parkinson's disease (PD) experience difficulties with activities of daily living (ADLs) at workplace and in their social life depending on the extent of disease progression. Because of their disabilities, patients with PD are forced into early retirement compared to other people of their age group. We present our experience with the rehabilitation of three patients with PD using levodopa-carbidopa intestinal gel (LCIG) treatment for their return to work. The rehabilitation program comprised the following three modules：1) evaluating the patients' ability to walk indoor for a short time；2) assessing their standing and sitting positions to enable them to more easily handle a device；and 3) improving their upper limb function, including skilled movements, for operating a device in emergency. Finally, all three patients exhibited improvements in the Timed Up and Go test results and device operation. Two of the patients returned to their former workplace within 10 months of LCIG treatment initiation and the remaining patient found new employment 1 year after treatment commencement.In conclusion, establishing a rational support system that involves rehabilitation programs and information sharing across multiple occupations is essential for the return to work of patients with PD receiving LCIG treatment.

Effect of daidzein on Parkinson disease induced by reserpine in rats

Parkinson disease is a neurodegenerative disorder characterised by the cardinal symptoms of stiffness, resting tremor, slowness (bradykinesia) and reduction of movement (hypokinesia). Involvement of oxidative damage has been reported in the pathophysiology of Parkinson disease and its related complications. The purpose of this study was to examine the effect of daidzein to quench the free radicals produced as a result of the increased oxidative stress in Parkinson disease.Parkinson disease is induced by administration of reserpine (5 mg/kg/day, i.p) for 5 consecutive days. The symptoms of PD such as tremors, akinesia and rigidity were evaluated. The effect was evaluated by assessing various behavioral parameters (grip strength and locomotor activity), biochemical parameters (lipid peroxidation, and reduced glutathione), as well as histopathological parameters in brain tissue. Daidzein (an antioxidant) was administered at the dose of 50 and 100 mg/kg, p.o. once daily for 5 days. Reserpine significantly causes tremor, rigidity, akinesia and oxidative damage which were reversed by daily administration of daidzein when compared toreserpine group. There was a significant histological improvement in the neuronal degeneration in brain tissue with daidzein. So, the results indicated the protective effect of daidzein against PD.

8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Migration of a Percutaneous Endoscopic Gastrojejunostomy Tube into the Colon with Small Intestinal Telescoping

Continuous duodenal levodopa/carbidopa intestinal gel delivery by a gastrostomy infusion system improves control of Parkinson’s disease. The overall complication rates of percutaneous endoscopic gastrojejunostomy were reported to be 41% and 59% for immediate and delayed adverse events, respectively. A 72-year-old woman underwent percutaneous endoscopic gastrojejunostomy using the delivery system noted above. Abdominal pain and vomiting occurred 3 months later. Esophagogastroduodenoscopy showed a longitudinal ulcer extending from the lower gastric body to the ileum end, with small intestinal telescoping. Colonoscopy showed a large bezoar of food residue that was attached around the tip of the tube, reaching the ascending colon, which may have acted as an anchor. Thus, the gastric antrum and small intestine were shortened with telescoping. This complication was resolved by crushing the bezoar with forceps during colonoscopy and can be prevented by consuming a fiber-free diet and periodic exchanges of the tube using esophagogastroduodenoscopy.

Effect of Entacapone Plus Levodopa/Carbidopa on Anxiety, Depression, and Quality of Life in Patients with Parkinson Disease / 中国医科大学学报

Objective To investigate the effects of levodopa/carbidopa plus entacapone (LCE) and levodopa/carbidopa (LC) on anxiety, depression, and quality of life (QOL) between patients with Parkinson disease (PD). Methods In total, 120 patients with idiopathic PD were enrolled in this trial and randomized into the experimental (LCE) and control (LC) groups in a 1∶1 ratio to receive treatment for12 weeks. The Hamilton anxiety scale score (HAMA), Hamilton depression scale score (HAMD), 39-item PD QOL questionnaire score (PDQ-39), Unified PD rating scale score (UPDRS), "on" time (h/d), and "off" time (h/d) were measured at each visit (baseline 0, 4, 8, and 12 weeks). Results At the end point (12 weeks), the decrease in the HAMA score from baseline was higher in the LCE group compared with that in the LC group (3.6±1.3, 95％ CI:3.3-3.9 vs 1.3±0.7, 95％ CI:1.1-1.5, P＜0.001), as well as the HAMD score (5.2±1.9, 95％ CI:4.7-5.7 vs 1.2±0.7, 95％ CI:1.0-1.4, P ＜0.001). Similarly, the changes in the PDQ-39 score were evaluated, and the change was compared between the LCE group and the LC group (14.1±7.8, 95％ CI:12.1-16.1 vs 6.9±4.2, 95％ CI:5.8-8.0, P＜0.001). In addition, the LCE group presented better improvement in the UPDRS score (Ⅰ-Ⅳ), "on" time, and "off" time from the baseline than that in the LC group (P ＜ 0.05). Conclusion Entacapone combined with levodopa/carbidopa could significantly improve anxiety, depression, and QOL in patients with PD experiencing wearing-off.

Efficacy of Compound Carbidopa Tablets Combined with Bunao Xifeng Zhijing Soup in the Treatment of Parkinsonˊs Disease and Influence on the Levels of Serum Inflammatory Factors / 中国药师

Objective:To investigate the efficacy of compound carbidopa tablets combined with Bunao Xifeng Zhijing soup in the treatment of Parkinson’s disease(PD)and the influence on the levels of IL-6,IL-1β,MDA,SOD and serum cystatin C. Methods:Totally 68 patients with PD were divided into the observation group and the control group with 34 cases in each. The course of treatment was 3 months. The control group was treated with compound carbidopa tablets,and the observation group was treated with Bunao Xifeng Zhijing soup additionally. The Parkinson's disease quantitation table(UPDRS),quality of life,TCM symptoms,self-rating depression scale(SDS),self-rating anxiety scale(SAS)and changes of inflammatory factors before and after the treatment were compared between the two groups. Results:After the treatment,UPDRS-1,UPDRS-2,UPDRS-3, UPDRS-4,PDQ-39 SI,SDS,SAS and TCM symptom scores were all decreased in both groups(P < 0. 05),and the decrease was more notable in the observation group(P < 0. 05). Observation group UPDRS-4 score also significantly lower than the control group(P < 0. 05). After treatment,two groups of patients of interleukin(IL)6,IL-1 beta,malondialdehyde(MDA),serum(C level was a significant reduction in the inhibition(P < 0. 05),superoxide dismutase(SOD)levels,compared with the previous significantly increased(P < 0. 05). And the observation group of patients with IL-6,IL-1 beta,MDA,urinary inhibition C level significantly lower than the control group,serum SOD levels are significantly higher than control group(P < 0. 05). Observation group total effectiveness 91. 18% ,significantly higher than that of control group 64. 70%(P < 0. 05). Conclusion:compound carbidopa tablets combined with Bunao Xifeng Zhijing soup in the treatment of PD can significantly improve the movements and non-motor symptoms of the patients with high safety and good clinical efficacy.

Protein intake and the use of levodopa in patients with Parkinson's disease / Ingesta de proteínas y el uso de la levodopa en pacientes con enfermedad de Parkinson

Levodopa is the principal pharmacological treatment for Parkinson's disease (PD); however the protein content in diet may compromise its effectiveness. The aim of this study was to investigate the relationship of protein intake and the use of levodopa in ambulatory patients with PD. Thirty four PD patients were assessed for protein intake, evaluating the relation energy-protein intake by means of a register. An intake of 1762 kcal/day, 70.9 g of protein/day equivalent to 16.6% of the total energy intake as protein at a level of 1.1 g/kg bw/day. Of all patients, 47.1% took their medications with meals. We conclude that the studied patients consume more protein in their diet than those recommended for PD, with half the sample taking the medications with meals, which may affect the treatment.

La levodopa es el principal tratamiento farmacológico para la enfermedad de Parkinson, sin embargo, la proteína de la dieta puede comprometer su eficacia. El objetivo de este estudio fue investigar la ingesta de proteínas y el uso de la levodopa en pacientes con enfermedad de Parkinson tratados en régimen ambulatorio, 34 pacientes fueron evaluados. Evaluación de la ingesta de alimentos por los registros, tomas de 1762 kcal/día, 70.9 g/día, el 16,6% del total de energía y 1.1 g/kg/dia de energía y proteína, respectivamente, y que la ingesta de proteínas durante el día era 70,4% del total de proteínas diario. Todos los pacientes estaban tomando levodopa y 47,1% consumían sus medicamentos con las comidas. Se concluyó que, según las recomendaciones para la enfermedad de Parkinson, los pacientes estudiados consumían una dieta rica en proteínas y con una mayor concentración de este nutriente durante el día. Aproximadamente la mitad de la muestra ingiere los medicamentos con la comida, costumbre que puede afectar el tratamiento farmacológico de la enfermedad.

Theoretical studies on the pyridoxal-5'-phosphate dependent enzyme dopa decarboxylase: Effect of Thr 246 residue on the co-factor-enzyme binding and reaction mechanism.

Decarboxylation of amino acid is a key step for biosynthesis of several important cellular metabolites in the biological systems. This process is catalyzed by amino acid decarboxylases and most of them use pyridoxal-5'-phosphate (PLP) as a co-factor. PLP is bound to the active site of the enzyme by various interactions with the neighboring amino acid residues. In the present investigation, density functional theory (DFT) and real-time dynamics studies on both ligand-free and ligand-bound dopa decarboxylases (DDC) have been carried out in order to elucidate the factors responsible for facile decarboxylation and also for proper binding of PLP in the active site of the enzyme. It has been found that in the crystal structure Asp271 interacts with the pyridine nitrogen atom of PLP through H-bonding in both native and substrate-bound DDC. On the contrary, Thr246 is in close proximity to the oxygen of 3-OH of PLP pyridine ring only in the substrate-bound DDC. In the ligand-free enzyme, the distance between the oxygen atom of 3-OH group of PLP pyridine ring and oxygen atom of Thr246 hydroxyl group is not favorable for hydrogen bonding. Thus, present study reveals that hydrogen bonding with O3 of PLP with a hydrogen bond donor residue provided by the enzyme plays an important role in the decarboxylation process.