Degradation kinetic study of lysine in lysine hydrochloride solutions for injection by determining its main degradation product

AbstractA limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far. In the present work, the thermal degradation kinetics of lysine hydrochloride solutions for injection, the special solvent for ademetionine 1, 4-butanedisulfonate (SAM) for injection, was investigated at selected temperatures and pH values. The main degradation product of lysine was separated, purified, and confirmed as lysine lactam. A reversed-phase high performance liquid chromatographic (RP-HPLC) method without derivation was developed for the simultaneous determination of lysine and lysine lactam. The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics. The degradation and generation rate constants increased with increasing temperatures and decreasing pH values. The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol, respectively. Meanwhile, a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy. Considering there could be other side effects, we established an upper limit of lysine lactam (500 μg/ml), as the acceptable criteria for stability to estimate the shelf life together with lysine, which made the prediction more accurate and credible. Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature

Evaluation of medication treatment for Alzheimer's disease on clinical evidence

<p><strong>Objective</strong> To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. <strong>Methods</strong> Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI) databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT), controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. <strong>Results</strong> After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7), and 5 were low quality with score 3. It was summarized as follows: 1) Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and an N-methyl-D-aspartate (NMDA) receptor noncompetitive antagonist (memantine), are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2) Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. <strong>Conclusions</strong> Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment.</p><p> </p><p>doi: 10.3969/j.issn.1672-6731.2014.03.009</p

Hybrid AHS: A Hybrid of Kalman Filter and Deep Learning for Acoustic Howling Suppression

Deep learning has been recently introduced for efficient acoustic howling suppression (AHS). However, the recurrent nature of howling creates a mismatch between offline training and streaming inference, limiting the quality of enhanced speech. To address this limitation, we propose a hybrid method that combines a Kalman filter with a self-attentive recurrent neural network (SARNN) to leverage their respective advantages for robust AHS. During offline training, a pre-processed signal obtained from the Kalman filter and an ideal microphone signal generated via teacher-forced training strategy are used to train the deep neural network (DNN). During streaming inference, the DNN's parameters are fixed while its output serves as a reference signal for updating the Kalman filter. Evaluation in both offline and streaming inference scenarios using simulated and real-recorded data shows that the proposed method efficiently suppresses howling and consistently outperforms baselines.Comment: submitted to INTERSPEECH 2023. arXiv admin note: text overlap with arXiv:2302.0925

Bis[bis­(1-ethyl­benzimidazol-2-ylmeth­yl) ether]cobalt(II) dipicrate dimethyl­formamide disolvate

In the title complex, [Co(C20H22N4O)2](C6H2N3O7)2·2C3H7NO, the CoII ion is coordinated by two sets of two N atoms and an O atom from two independent tridendate ligands in a distorted octa­hedral coordination environment. There are significant differences between chemically equivalent coordination bond lengths. The crystal structure is stabilized by weak inter­molecular C—H⋯O hydrogen bonds and weak π–π stacking inter­actions [centroid–centroid distance 3.495 (1) Å]. In one of the anions one nitro group is rotationally disordered about the C—N bond with refined occupancies of 0.524 (8) and 0.476 (8)

An Effective Index for Truss-based Community Search on Large Directed Graphs

Community search is a derivative of community detection that enables online and personalized discovery of communities and has found extensive applications in massive real-world networks. Recently, there needs to be more focus on the community search issue within directed graphs, even though substantial research has been carried out on undirected graphs. The recently proposed D-truss model has achieved good results in the quality of retrieved communities. However, existing D-truss-based work cannot perform efficient community searches on large graphs because it consumes too many computing resources to retrieve the maximal D-truss. To overcome this issue, we introduce an innovative merge relation known as D-truss-connected to capture the inherent density and cohesiveness of edges within D-truss. This relation allows us to partition all the edges in the original graph into a series of D-truss-connected classes. Then, we construct a concise and compact index, ConDTruss, based on D-truss-connected. Using ConDTruss, the efficiency of maximum D-truss retrieval will be greatly improved, making it a theoretically optimal approach. Experimental evaluations conducted on large directed graph certificate the effectiveness of our proposed method.Comment: 8 pages, 8figure

Safety and efficacy of etomidate and propofol anesthesia in elderly patients undergoing gastroscopy: A double-blind randomized clinical study

The aim of the present study is to compare the safety, efficacy and cost effectiveness of anesthetic regimens by compound, using etomidate and propofol in elderly patients undergoing gastroscopy. A total of 200 volunteers (65–79 years of age) scheduled for gastroscopy under anesthesia were randomly divided into the following groups: P, propofol (1.5–2.0 mg/kg); E, etomidate (0.15-0.2 mg/kg); P+E, propofol (0.75–1 mg/kg) followed by etomidate (0.075-0.1 mg/kg); and E+P, etomidate (0.075-0.01 mg/kg) followed by propofol (0.75–1 mg/kg). Vital signs and bispectral index were monitored at different time points. Complications, induction and examination time, anesthesia duration, and recovery and discharge time were recorded. At the end of the procedure, the satisfaction of patients, endoscopists and the anesthetist were evaluated. The recovery (6.1±1.2 h) and discharge times (24.8±2.8 h) in group E were significantly longer compared with groups P, P+E and E+P (P<0.05). The occurrence of injection pain in group P+E was significantly higher compared with the other three groups (P<0.05). In addition, the incidence of myoclonus and post-operative nausea and vomiting were significantly higher in group P+E compared with the other three groups (P<0.05). There was no statistical difference among the four groups with regards to the patients' immediate, post-procedure satisfaction (P>0.05). Furthermore, there was no difference in the satisfaction of anesthesia, as evaluated by the anesthetist and endoscopist, among the four groups (P>0.05). The present study demonstrates that anesthesia for gastroscopy in elderly patients can be safely and effectively accomplished using a drug regimen that combines propofol with etomidate. The combined use of propofol and etomidate has unique characteristics which improve hemodynamic stability, cause minimal respiratory depression and less side effects, provide rapid return to full activity and result in high levels of satisfaction