Shear wave elastography characteristics of the gastrocnemius muscle in postural instability gait disorder vs tremor dominant Parkinson's disease patients.

OBJECTIVES: This study explored the characteristics of muscle stiffness of lower gastrocnemius in resting and exercise states in patients with postural instability gait difficulty (PIGD) and tremor dominant (TD) Parkinson's disease patients using shear wave elastography (SWE). DATA AND METHODS: 75 PD patients from the Department of Parkinson's Disease Center in the Hospital from September 2021 to December 2022 were prospectively included, including 44 patients with PIGD and 31 with TD. In the same period, 40 healthy subjects matching gender and age were included as the control group. SWE was used to detect Young's modulus of both sides (right and left, R- and L-) of the lateral head of the gastrocnemius in resting (YM1) and exerciser states (YM2) in all participants and the absolute difference Young's modulus between resting and exercise state (ΔYM) was calculated. RESULTS: R-YM2 and R-ΔYM were the highest in the normal controls, followed by the TD group, and lowest in the PIGD group. There were no differences in L-YM2 and L-ΔYM between the PIGD group and the TD group (all p > 0.05), but they were lower than those in the normal control group (all p < 0.05). In addition, R-YM2 and R-ΔYM were negatively correlated with disease duration and UPDRS III scores in the PIGD group (all p < 0.05). R-ΔYM has the highest value in the differential diagnosis of PIGD and TD patients. The area under the receiver operating characteristic curve (ROC) curve is 0.812 (95%CI, 0.730-0.893), and the diagnostic threshold is 120.5 Kpa with a sensitivity of 63.6%, a specificity of 90.1%, a positive predictive of 80%, and a negative predictive value of 80%. CONCLUSION: Shear wave elastography is a sensitive ultrasound method for evaluating muscle strength in patients with PIGD and TD. It also provides a new biological indicator to distinguish between different phenotypes of patients with PD.

NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice.

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1ß, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1ß, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.

NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1β, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1β, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.

Pharmacokinetics of orally disintegrating tablets of perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex in rabbits.

We investigated the pharmacokinetic behavior of orally disintegrating tablets (ODTs) containing perphenazine/hydroxypropyl-beta-cyclodextrin inclusion complex (PPZ/HP-beta-CD) in rabbits and evaluated their bioequivalence with conventional tablets. In this study, a simple, sensitive and accurate high performance liquid chromatography method was developed for the determination of perphenazine concentration in rabbit plasma. The pharmacokinetic parameters were calculated by non-compartmental methods and the bioequivalence between PPZ/HP-beta-CD ODTs with conventional tablets was determined by calculating 90% confidence interval (CI) for the ratio of logarithmic transformed C(max), AUC(0-t), AUC(0-infinity) values. The pharmacokinetic parameters of test ODTs and reference tablets were as follows: C(max), 82.86 and 62.71 ng/mL; AUC(0-24), 480 and 397.56 ng/mL/h; AUC(0-infinity), 505 and 400.12 ng/mL/h; T(max), 1.04 and 3.83h. The relative bioavailabilities of two formulations for AUC(0-t) and AUC(0-infinity) were 120.77% and 126.37%, respectively. The 90% CI statistical analysis demonstrated the two formulations were not bioequivalence. In conclusion, the ODTs showed faster absorption and higher peak concentration when compared with conventional tablets, which suggests ODTs could be promising oral formulations for PPZ.

Improved pharmacokinetics and reduced toxicity of brucine after encapsulation into stealth liposomes: role of phosphatidylcholine.

OBJECTIVE: Brucine was encapsulated into stealth liposomes using the ammonium sulfate gradient method to improve therapeutic index. MATERIALS AND METHODS: Four brucine stealth liposomal formulations were prepared, which were made from different phosphatidylcholines (PCs) with different phase transition temperatures (T(m)). The PCs used were soy phosphatidylcholine (SPC), dipalmitoyl phosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC), and distearoyl phosphatidylcholine (DSPC). The stabilities, pharmacokinetics, and toxicities of these liposomal formulations were evaluated and compared. RESULTS: Size, zeta potential, and entrapment efficiency of brucine-loaded stealth liposomes (BSL) were not influenced by PC composition. In vitro release studies revealed that drug release rate increased with decreased T(m) of PCs, especially with the presence of rat plasma. After intravenous administration, the area under the curve (AUC) values of BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC in plasma were 7.71, 9.24, 53.83, and 56.83-fold as large as that of free brucine, respectively. The LD(50) values of brucine solution, BSL-SPC, BSL-DPPC, BSL-HSPC, and BSL-DSPC following intravenous injection were 13.17, 37.30, 37.69, 51.18, and 52.86 mg/kg, respectively. It was found in calcein retention experiments that the order of calcein retention in rat plasma was SPC < DPPC << HSPC < DSPC stealth liposomes. CONCLUSION: PC composition could exert significant influence on the stabilities, pharmacokinetics, and toxicities of brucine-loaded stealth liposomes. DSPC or HSPC with T(m) above 50°C should be used to prepare the stealth liposomal formulation for the intravenous delivery of brucine. However, it was found in the present paper that the pharmacokinetics and toxicity of BSL were not influenced by the PC composition when the T(m) of the PC was in the range of -20°C to 41°C.

Capillary electrophoresis method for the determination of flavonoids.

Due to their biological and physiological importance, flavonoids received considerable attention in the literature. This review discusses the widely used analytical method i.e. capillary electrophoresis (CE) including the chiral flavonoids separation and the hyphenation of CE and MS. Techniques used for enhancement of sensitivity such as stacking, sweeping, isotachophoresis etc. were also discussed.