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Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation.Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression.Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD.Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.

Objective. To investigate the association between gender and gastrointestinal (GI) dysfunctions, as well as gender and other motor symptoms/nonmotor symptoms, in a sample of PD patients. Methods. 186 patients with PD were recruited into this study and divided into male PD group (M-PD) and female PD group (FM-PD). Demographic and PD-related clinical information of the participants were collected by the same neurologist. PD patients were objectively assessed by a spectrum of rating scales of motor symptoms and nonmotor symptoms (including GI dysfunctions). The data were analyzed by SPSS 20 statistical software. Results. Totally 95 cases (51.08%) were in the M-PD group and 91 cases (48.92%) in the FM-PD group. There were no significant differences in age, BMI, and lifestyles between the two groups (P > 0.05). Males had higher educational level (P = 0.002). Females were more likely to have early satiety and loss of appetite (P = 0.025, P = 0.001). There were no significant differences in LED disease duration, age of motor symptoms onset, types of motor symptoms onset, location of motor symptoms onset, and phenotype of motor symptoms between the two groups (P > 0.05). Females had significantly higher UPDRS-III and HAMD scores than males (P = 0.037, P = 0.034). There were no significant differences in PQSI, ESS, RLS, RBD, HAMA, HAMD, and MoCA scores between the two groups. Gender was associated with HAMD (OR = 0.682, P = 0.019). Conclusions. Gender is a risk factor for depression, but not for GI dysfunctions in patients with PD.

Objective: Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD), causing great disturbance to patients. The present study investigated the prevalence and the clinical features of constipation in patients with PD and explored the difference between prodromal and clinical constipation of PD.Methods: A total of 186 patients with PD were recruited into this study. Subjective constipation was defined by ROME III criteria. Demographic and PD-related clinical information of the participants were collected. The PD patients were objectively assessed by a spectrum of rating scales of motor symptoms, non-motor symptoms, and quality of life.Results: In total, 51.61% (96/186) of PD patients suffer from constipation. Compared with patients without constipation, the patients with constipation were prone to have restless leg syndrome, depression, and anxiety and have higher scores of the non-motor symptoms scale. Among patients with constipation, 21.88% (21/96) patients had constipation in prodromal stage. Compared with patients with constipation in clinical stage, patients with prodromal constipation had a lower age of constipation onset (56.48 ± 9.63 and 65.26 ± 8.42, χ2 = 4.091, P < 0.001), longer timespan from constipation onset to motor symptom onset (6.62 ± 3.91 and 3.18 ± 2.13, χ2 = −3.877, P = 0.001). Patients with prodromal constipation were predominantly tremor onset (χ2 = 4.405, P = 0.044) and usually had a better quality of life [28 (14.50–37.5) and 40 (25.0–55.0), χ2 = 2.011, P = 0.046]. Depression was the only risk factor of constipation in PD patients. Body mass index, depression, and anxiety were factors that affected the life quality in patients with constipation.Conclusions: Our results supported the high incidence of constipation in patients with PD and that, in some patients, constipation occurred before the onset of motor symptoms. The specific clinical characteristics of patients with constipation and with prodromal constipation help to make early diagnosis, to discover the relationship between constipation and PD, and to further explore the pathogenesis of this degenerative disease.

A new ice phase, ice XIX, was discovered in 2018, and is the second hydrogen-ordered polymorph of hydrogen-disordered ice VI. The first hydrogen-ordered polymorph of ice VI is ice XV, and ices XIX, VI, and XV comprise a unique triplet group in the ice family. However, the exact crystal structure of ice XIX has not been confirmed. We constructed four possible conformations of ice XIX using neutron diffraction data obtained by Gasser et al. We then optimized these structures and simulated their Raman scattering spectra using first-principles density functional theory. By comparing these simulated spectra with the experimental Raman scattering spectra, we were able to exclude the existence of a ferroelectric structure with the space group Cc. The other three candidate structures are in good agreement with the experimental Raman scattering data; two of them are ferroelectric structures with the space group P21; and the last one is a weak ferroelectric structure with the space group Cc. We proposed that the partially hydrogen-ordered structure of ice XIX maybe a mixing of several hydrogen-ordered structures. [ABSTRACT FROM AUTHOR]

A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for determining tacrolimus (FK506) in rat tissues to study the effect of Schisandra sphenanthera extract on FK506 tissue distribution. After a liquid-liquid extraction with ethyl acetate, FK506 and ascomycin (IS) were subjected to LC-MS/MS analysis using positive electrospray ionization under multiple reactions monitoring mode. Chromatographic separation of FK506 and ascomycin was achieved on a Hypersil BDS C18 column with a mobile phase consisting of methanol-water (containing 2 mM ammonium acetate, 95 : 5, v/v). The intra- and inter-batch precision of the method were less than 8.8 and 9.8%, respectively. The intra- and inter-batch accuracies ranged from 97.5 to 104.0%. The lowest limit of quantification for FK506 was 0.5 ng/mL. The method was applied to a FK506 tissue distribution study with or without a dose of Wuzhi (WZ) tablet. Most of the FK506 tissue concentrations were slightly increased after a concomitant WZ tablet dose, but the whole blood concentration of FK506 was dramatically increased 3-fold after a concomitant WZ tablet dose. These results indicated that the LC-MS/MS method was rapid and sensitive enough to quantify FK506 in different rat tissues, and strict drug monitoring is recommended when co-administering WZ tablet in clinical use. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect on postpartum pelvic girdle pain treated with the combined therapy of pelvic-sacral tendon-regulation needling technique of acupuncture and manipulative reduction and the simple manipulative therapy., Methods: A total of 80 patients with postpartum pelvic girdle pain were randomized into an observation group and a control group, 40 cases in each one. In the control group, the manipulative reduction was simply adopted. In the observation group, on the base of the treatment as the control group, the pelvic-sacral tendon-regulation needling technique of acupuncture was applied at Mingmen (GV 4), Dachangshu (BL 25), Yaoyangguan (GV 3), Ciliao (BL 32), Zhongliao (BL 33), Huantiao (GB 30) and Yanglingquan (GB 34). In either group, the treatment was given once every two days, three times a week and 3 treatments taken as one course. Totally, 3 courses of treatment were required. The clinical therapeutic effect was compared in the patients between the two groups. The changes in the scores of the pain visual analogue scale (VAS), Oswestry dysfunction index (ODI) and Japanese Orthopaedic Association (JOA), as well as the pelvic floor distress inventory - short form 20 (PFDI-20), the pelvic floor impact questionnaire (PFIQ-7) and the sex life index (the frequency of intercourse and orgasm) were recorded in the patients of the two groups before and after treatment., Results: The total effective rate was 95.0% (38/40) in the observation group, higher than 77.5% (31/40) in the control group ( P <0.01). After treatment, the scores of VAS, ODI, PFDI-20 and PFIQ-7 were lower than those before treatment respectively in the patients of the two groups ( P <0.01). JOA score and the sex life index were increased after treatment as compared with those before treatment in the two groups ( P <0.01). The difference value of each of the above indexes in the observation group was higher than the control group ( P <0.01)., Conclusion: The combined therapy of pelvic-sacral tendon-regulation needling technique of acupuncture and manipulative reduction effectively alleviates pain and improves the muscle strength of pelvic floor muscle fibers in the patients with postpartum pelvic girdle pain. Its therapeutic effect is better than that of the simple manipulative therapy.

This study was aimed to determine the hepatic and small intestinal distribution of active lignans in rats after treated with Wuzhi tablet (WZ, Schisandra sphenanthera extract) by LC-MS/MS method. Male Sprague-Dawley rats were sacrificed at 0.25, 1.5, 4, 6, 10, 24 h after an oral administration of WZ, and then hepatic and small intestinal samples were collected for analysis. The results showed that concentrations of lignans in liver and small intestine of rats were decreased with WZ pretreated time. The concentrations of all lignans in rat liver and small intestine at 0.25 h were the highest after a single oral administration. All lignans was undetectable in all tissues 24 h after oral dosing, suggesting lignans of WZ were eliminated rapidly in rats. The concentrations of schisandrin A, schisandrol B and schisantherin A in small intestine were much higher than those in the liver, suggesting the effect of WZ on the intestinal metabolism enzyme might be more potent than that on the liver. In short, the current results suggest that lignans of WZ were not accumulated in rat liver and small intestine. The concentrations of lignans of WZ in small intestine were much higher than those in liver.

The study aims to evaluate the effect of long-term pretreatment of the rat with Wuzhi tablet（WZ） on hepatic and intestinal CYP3A mRNA and protein expression and activity. Male Sprague-Dawley rats were orally administered of midazolam (2 mg·kg-1) with or without 14 days of pretreatment of WZ (0.25 g·kg-1) to determine CYP3A activity. Meanwhile, RNA and protein of rats liver and intestine samples were prepared 24 h after the last dose of 14 days of WZ treatment to determine CYP3A mRNA and protein expression. Long-term treatment of WZ increased the mRNA expression of hepatic Cyp3a1, Cyp3a9 and intestinal Cyp3a9 by 54.6%, 188.3%（P < 0.05） and 48.2%（P < 0.05）, respectively; and increased the protein expression of hepatic CYP3A by 43.2%. However, after long-term treatment of WZ, the AUC of orally administered of midazolam in the WZ group was increased 29.9%（WZ pretreatment group） and 154.2%（WZ coadministered group） compared to that of control group. In conclusion, long-term treatment of WZ increased the m RNA and protein expression of CYP3A, while could inhibit the activity of CYP3A.

The study was conducted to evaluate the pharmacokinetics of midazolam (MDZ) under different oral dosages in rats, and determine the optimum oral dosage of MDZ, a CYP3 A probe substrate in vivo. Male Sprague-Dawley rats were given a single oral dosages of MDZ at 1,2,5,10,15 or 20 mg·kg(-1). Plasma concentrations of MDZ and its major metabolite 1-hydroxyl midazolam (1-OH MDZ) were determined at different time points using a validated LC-MS/MS method. Pharmacokinetic parameters were calculated using non-compartmental model. The C(max), AUC(0-t) and AUC0(∞) of MDZ and 1-OH MDZ were linearly increased over the dose range of 1-5 mg·kg(-1) (r > 0.99), but not at the dose of 15 or 20 mg·kg(-1). The AUC/Dose at 1-10 mg·kg(-1) were not significant different, but that of 15 or 20 mg·kg(-1) were significantly higher. No significant sedative reaction was observed in all the rats at dosages of 1-5 mg·kg(-1), however loss of righting reflex was observed in rats receiving dosages of 10-20 mg·kg(-1). In conclusion, the optimized oral dose of MDZ was 1-5 mg·kg(-1) when MDZ is used as the CYP3 A probe substrate in rats.