Preparation and in vivo evaluation of gel-based nasal delivery system for risperidone

The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax ) and the time to reach cmax (tmax) were 15.2 µg mL–1 and 5min for the nasal gel, 3.6 µg mL–1and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax, cmax and AUC between oral and nasal routes were significantly different (p ＜ 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0%. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible

Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats

Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several β-cyclodextrin （βCD） derivatives such as HPβCD, SBEβCD and DMβCD on simvastatin in aqueous solution were investigated using the phase solubility technique. The solubility diagram of simvastatin with each βCD derivative could be classified as AL-type, indicating soluble complex formation of 1:1 stoichiometry. Among the above βCD derivatives DMβCD was found to be the ideal complexing agent for improving drug solubility. The simvastatin complex with DMβCD was prepared using the co-evaporation method and was then characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and in vitro dissolution. Dissolution and pharmacokinetic studies indicated that the simvastatin/DMβCD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug. Maximum plasma concentration (cmax) and the time to reach it (tmax) were 21.86 µg mL–1 and 1.4 h for the drug complex, 8.25 µg mL–1 and 3.0 h for free drug, respectively. Main pharmacokinetic parameters such as tmax, cmax were significantly different (p < 0.01) between the simvastatin complex and free drug. Bioavailability of the simvastatin complex relative to free drug was up to 167.0 %

Botulinum toxin type A for hand tremor: a meta-analysis of randomised controlled trials

Background. Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain.Aims. To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor.Methods. We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger’s test.Results. Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias.Conclusions. Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions

Mechanism of Qihuang needle therapy in the management of tic disorders: a clinical trial protocol

BackgroundQihuang needle therapy is a newly developed acupuncture therapy to treat tic disorders in clinical practice. However, the mechanism to reduce tic severity remains unknown. Changes in intestinal flora and circulation metabolites are perhaps the potential pathogenesis of tic disorders. As a result, we present a protocol for a controlled clinical trial using multi-omics analysis to probe the mechanism of the Qihuang needle in managing tic disorders.MethodsThis is a matched-pairs design, controlled, clinical trial for patients with tic disorders. Participants will be allocated to either an experimental group or a healthy control group. The main acupoints are Baihui (GV20), Yintang (EX-HN3), and Jueyinshu (BL14). The experimental group will receive Qihuang needle therapy for a month, while the control group will receive no interventions.Expected outcomesThe change in the severity of the tic disorder is set as the main outcome. Secondary outcomes include gastrointestinal severity index and recurrence rate, which will be calculated after a 12-week follow-up. Gut microbiota, measured by 16S rRNA gene sequencing; serum metabolomics, assessed via LC/MS; and serum zonulin, assessed by enzyme-linked immunosorbent assay (ELISA), will be used as biological specimen analysis outcomes. The present study will investigate the possible interactions between intestinal flora and serum metabolites and the improvement of clinical profiles, which may elucidate the mechanism of Qihuang needle therapy for tic disorders.Trial registrationThis trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/). Registration number: ChiCTR2200057723, Date: 2022-04-14

A COMPARATIVE STUDY OF END USER COMPUTING PERFORMANCE FOR OBJECT-ORIENTED, EXTENDED ENTITY-RELATIONSHIP, AND RELATIONAL DATA MODELS AND QUERY LANGUAGES

Master'sMASTER OF SCIENC

A Method for Determining Intrinsic Mode Function Number in Variational Mode Decomposition and Its Application to Bearing Vibration Signal Processing

Variational mode decomposition (VMD) method has been widely used in the field of signal processing with significant advantages over other decomposition methods in eliminating modal aliasing and noise robustness. The number (usually denoted by K) of intrinsic mode function (IMF) has a great influence on decomposition results. When dealing with signals including complex components, it is usually impossible for the existing methods to obtain correct results and also effective methods for determining K value are lacking. A method called center frequency statistical analysis (CFSA) is proposed in this paper to determine K value. CFSA method can obtain K value accurately based on center frequency histogram. To shed further light on its performance, we analyze the behavior of CFSA method with simulation signal in the presence of variable components amplitude, components frequency, and components number as well as noise amplitude. The normal and fault vibration signals obtained from a bearing experimental setup are used to verify the method. Compared with maximum center frequency observation (MCFO), correlation coefficient (CC), and normalized mutual information (NMI) methods, CFSA is more robust and accurate, and the center frequencies results are consistent with the main frequencies in FFT spectrum

Image Encryption Algorithm Using 2-Order Bit Compass Coding and Chaotic Mapping

This paper proposes a novel image encryption algorithm based on an integer form of chaotic mapping and 2-order bit compass diffusion technique. Chaotic mapping has been widely used in image encryption. If the floating-point number generated by chaotic mapping is applied to image encryption algorithm, it will slow encryption and increase the difficulty of hardware implementation. An innovative pseudo-random integer sequence generator is proposed. In chaotic system, the result of one-iteration is used as the shift value of two binary sequences, the original symmetry relationship is changed, and then XOR operation is performed to generate a new binary sequence. Multiple iterations can generate pseudo-random integer sequences. Here integer sequences have been used in scrambling of pixel positions. Meanwhile, this paper demonstrates that there is an inverse operation in the XOR operation of two binary sequences. A new pixel diffusion technique based on bit compass coding is proposed. The key vector of the algorithm comes from the original image and is hidden by image encryption. The efficiency of our proposed method in encrypting a large number of images is evaluated using security analysis and time complexity. The performance evaluation of algorithm includes key space, histogram differential attacks, gray value distribution(GDV),correlation coefficient, PSNR, entropy, and sensitivity. The comparison between the results of coefficient, entropy, PSNR, GDV, and time complexity further proves the effectiveness of the algorithm

Insight into the Structural Determinants of Imidazole Scaffold-Based Derivatives as TNF-α Release Inhibitors by in Silico Explorations

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity relationships (3D-QSAR) of the compounds were explored. The proposed pharmacophore model, including two hydrophobic sites, two aromatic centers, two H-bond donor atoms, two H-bond acceptor atoms, and two H-bond donor sites characterizes the necessary structural features of TNF-α release inhibitors. Both the resultant CoMFA and CoMSIA models exhibited satisfactory predictability (with Q2 (cross-validated correlation coefficient) = 0.557, R2ncv (non-cross-validated correlation coefficient) = 0.740, R2pre (predicted correlation coefficient) = 0.749 and Q2 = 0.598, R2ncv = 0.767, R2pre = 0.860, respectively). Good consistency was observed between the 3D-QSAR models and the pharmacophore model that the hydrophobic interaction and hydrogen bonds play crucial roles in the mechanism of actions. The corresponding contour maps generated by these models provide more diverse information about the key intermolecular interactions of inhibitors with the surrounding environment. All these models have extended the understanding of imidazole-based compounds in the structure-activity relationship, and are useful for rational design and screening of novel 2-thioimidazole-based TNF-α release inhibitors

Image Encryption Algorithm Using 2-Order Bit Compass Coding and Chaotic Mapping

This paper proposes a novel image encryption algorithm based on an integer form of chaotic mapping and 2-order bit compass diffusion technique. Chaotic mapping has been widely used in image encryption. If the floating-point number generated by chaotic mapping is applied to image encryption algorithm, it will slow encryption and increase the difficulty of hardware implementation. An innovative pseudo-random integer sequence generator is proposed. In chaotic system, the result of one-iteration is used as the shift value of two binary sequences, the original symmetry relationship is changed, and then XOR operation is performed to generate a new binary sequence. Multiple iterations can generate pseudo-random integer sequences. Here integer sequences have been used in scrambling of pixel positions. Meanwhile, this paper demonstrates that there is an inverse operation in the XOR operation of two binary sequences. A new pixel diffusion technique based on bit compass coding is proposed. The key vector of the algorithm comes from the original image and is hidden by image encryption. The efficiency of our proposed method in encrypting a large number of images is evaluated using security analysis and time complexity. The performance evaluation of algorithm includes key space, histogram differential attacks, gray value distribution(GDV),correlation coefficient, PSNR, entropy, and sensitivity. The comparison between the results of coefficient, entropy, PSNR, GDV, and time complexity further proves the effectiveness of the algorithm