Beagle: a near-edge X-ray absorption fine-structure spectroscopy data processing solution for beamline experiments at Pohang Accelerator Laboratory.

Near-edge X-ray absorption fine-structure (NEXAFS) spectroscopy is a powerful tool for identifying chemical bonding states at synchrotron radiation facilities. Advances in new materials require researchers in both academia and industry to measure tens to hundreds of samples during the available beam time on a synchrotron beamline, which is typically allocated to users. Automated measurement methods, along with analysis software, have been developed for beamlines. Automated measurements facilitate high-throughput experiments and accumulate vast amounts of measured spectral data. The analysis software supports various functions for analyzing the experimental data; however, these analysis methods are complicated, and learning them can be time-consuming. To process large amounts of spectral data, a new analysis software, dedicated to NEXAFS spectroscopy, that is easy to use and can provide results in a short time is desired. Herein, the development of Beagle is described, software calculating molecular orientation from NEXAFS spectroscopy data that can report results in a short time comparable with that required to measure one sample at the beamline. It was designed to progress in a single sequence from data loading to the printing of the results with a `click of a button'. The functions of the software include recognizing the dataset, correcting the background, normalizing the plot, calculating the electron yield and determining the molecular orientation. The analysis results can be saved as {\tt{.txt}} files (spectral data), {\tt{.pdf}} files (graphic images) and Origin files (spectral data and graphic images).

A Refined Thin-Film Model for Drug Dissolution Considering Radial Diffusion - Simulating Powder Dissolution.

PURPOSE: We aim to present a refined thin-film model describing the drug particle dissolution considering radial diffusion in spherical boundary layer, and to demonstrate the ability of the model to describe the dissolution behavior of bulk drug powders. METHODS: The dissolution model introduced in this study was refined from a radial diffusion-based model previously published by our laboratory (So et al. in Pharm Res. 39:907-17, 2022). The refined model was created to simulate the dissolution of bulk powders, and to account for the evolution of particle size and diffusion layer thickness during dissolution. In vitro dissolution testing, using fractionated hydrochlorothiazide powders, was employed to assess the performance of the model. RESULTS: Overall, there was a good agreement between the experimental dissolution data and the predicted dissolution profiles using the proposed model across all size fractions of hydrochlorothiazide. The model over-predicted the dissolution rate when the particles became smaller. Notably, the classic Nernst-Brunner formalism led to an under-estimation of the dissolution rate. Additionally, calculation based on the equivalent particle size derived from the specific surface area substantially over-predicted the dissolution rate. CONCLUSION: The study demonstrated the potential of the radial diffusion-based model to describe dissolution of drug powders. In contrast, the classic Nernst-Brunner equation could under-estimate drug dissolution rate, largely due to the underlying assumption of translational diffusion. Moreover, the study indicated that not all surfaces on a drug particle contribute to dissolution. Therefore, relying on the experimentally-determined specific surface area for predicting drug dissolution is not advisable.

Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile.

The solubility of glibenclamide was evaluated in DMSO, NMP, 1,4-dioxane, PEG 400, Transcutol® HP, water, and aqueous mixtures (T = 293.15~323.15 K). It was then recrystallized to solvate and compressed into tablets, of which 30-day stability and dissolution was studied. It had a higher solubility in 1,4-dioxane, DMSO, NMP (Xexp = 2.30 × 103, 3.08 × 104, 2.90 × 104) at 323.15 K, its mixture (Xexp = 1.93 × 103, 1.89 × 104, 1.58 × 104) at 298.15 K, and 1,4-dioxane (w) + water (1-w) mixture ratio of w = 0.8 (Xexp = 3.74 × 103) at 323.15 K. Modified Apelblat (RMSD ≤ 0.519) and CNIBS/R-K model (RMSD ≤ 0.358) suggested good comparability with the experimental solubility. The minimum value of ΔG° vs ΔH° at 0.70 < x2 < 0.80 suggested higher solubility at that molar concentration. Based on the solubility, it was recrystallized into the solvate, which was granulated and compressed into tablets. Among the studied solvates, the tablets of glibenclamide dioxane solvate had a higher initial (95.51%) and 30-day (93.74%) dissolution compared to glibenclamide reference (28.93%). There was no stability issue even after granulation, drying, or at pH 7.4. Thus, glibenclamide dioxane solvate could be an alternative form to improve the molecule's properties.

Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation.

The solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol® HP-water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelblat, van't Hoff, Buchowski-Ksiazaczak λh, Yalkowsky, and Jouyban-Acree van't Hoff models. The experimental results were correlated and utilized further to investigate the feasibility of nanosuspension formation using liquid anti-solvent precipitation. Thermodynamic solubility of ABN401 increased significantly with the increase in temperature and maximum solubility was obtained with Transcutol® HP while low solubility in was obtained water. An activity coefficient study indicated that high molecular interaction was observed in ABN401-Transcutol® HP (THP). The solubility increased proportionately as the mole fraction of Transcutol® HP increased in TWM, which was also supported by a solvent effect study. The result suggested endothermic and entropy-driven dissolution. Based on the solubility, nanosuspension was designed with Transcutol® HP as solvent, and water as anti-solvent. The mean particle size of nanosuspension decreased to 43.05 nm when the mole fraction of ABN401 in THP, and mole fraction of ABN401 in TWM mixture were decreased to 0.04 and 0.1. The ultrasonicated nanosuspension appeared to give comparatively higher dissolution than micronized nanosuspension and provide a candidate formulation for in vivo purposes.

pH-dependent nanodiamonds enhance the mechanical properties of 3D-printed hyaluronic acid nanocomposite hydrogels.

Nanocomposite hydrogels capable of undergoing manufacturing process have recently attracted attention in biomedical applications due to their desired mechanical properties and high functionality. 3D printing nanocomposite hydrogels of hyaluronic acid (HA)/nanodiamond (ND) revealed that the addition of ND with the low weight ratio of 0.02 wt% resulted in higher compressive force and gel breaking point, compared with HA only nanocomposites. These HA nanocomposite hydrogels loaded with surface functionalized ND allowed for the enforced compressive stress to be tuned in a pH-dependent manner. HA nanocomposite hydrogels with ND-OH at pH 8 showed an increase of 1.40-fold (0.02%: 236.18 kPa) and 1.37-fold (0.04%: 616.72 kPa) the compressive stress at the composition of 0.02 wt% and 0.04 wt, respectively, compared to those of ND-COOH (0.02%: 168.31 kPa, 0.04%: 449.59 kPa) at the same pH. Moreover, the compressive stress of HA/ND-OH (0.04 wt%) at pH 8 was mechanically enhanced 1.29-fold, compared to that of HA/ND-OH (0.04 wt%) at pH 7. These results indicate that the tunable buffering environment and interaction with the long chains of HA at the molecular level have a critical role in the dependency of the mechanical properties on pH. Due to the pH stability of the ND-OH nanophase, filament-based processing and layer-based deposition at microscale attained enforced mechanical properties of hydrogel. Fine surface tuning of the inorganic ND nanophase and controlled 3D printing leads to improved control over the pH-dependent mechanical properties of the nanocomposite hydrogels reported herein.

Formulation Optimization and in Vitro Characterization of Orally Disintegrating Films Using a Factorial Design and Mathematical Modeling for Drug Release.

Even though experimental designs are becoming popular especially for conventional dosage forms, limited studies have been performed to optimize formulations of orally disintegrating films (ODFs). This study aimed to evaluate sildenafil citrate-loaded ODFs for a controlled release with hydroxypropyl methylcellulose as a film-forming polymer. A factorial design was utilized for optimization with three control factors: ethanol ratio, plasticizer ratio, and the type of plasticizer. Tensile strength, disintegration time, water contact angle, and thickness were chosen as responses. For optimization, water contact angle, disintegration time, and thickness were minimized, while the tensile strength was maximized. Based on the conditions, optimal formulations were achieved for each type of plasticizer. Evaluation of desirability indicated that the response values were close to the target. When these optimal formulations were validated, the optimal solutions and target values were similar with small biases. The formulations were characterized using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, surface pH, in vitro dissolution, and drug release simulation with a mathematical modeling. After the drug was homogenously dispersed throughout the film, the crystalline form of the drug provided strong hydrogen bonds between the drug and the film components. Moreover, it showed a controlled drug release profiles that were well matched with simulated results. This study suggests that the optimized films may present a better alternative to conventional tablets for the treatment of male erectile dysfunction.

Protective microencapsulation of ß-lapachone using porous glass membrane technique based on experimental optimisation.

Even though ß-lapachone is a novel drug with pharmacological activity, it has limitations including instability under light conditions. The main purpose of the study was to enhance the stability of ß-lapachone using the microencapsulation method. The Shirasu porous glass membrane was used to achieve uniform-sized microcapsules. The prepared microcapsules were evaluated to investigate how process parameters affect the encapsulation efficiency, photostability and particle size distribution. The experimental design was conducted to obtain optimal formulations. In addition, an operating space was drawn to identify the safer range of control factors. All control factors showed significant effects on the encapsulation efficiency and photostability. For example, when a large amount of polymers was used, encapsulation efficiency and photostability were improved. However, as the amount of polymers increased, large and polydisperse microcapsules were produced. The robust design method provided information to characterise significant factors, thereby allowing effective control of photostability and size of microcapsules.

ß-Lapachone Regulates the Transforming Growth Factor-ß-Smad Signaling Pathway Associated with Collagen Biosynthesis in Human Dermal Fibroblasts.

The transforming growth factor (TGF)-ß-Smad signaling pathway regulates collagen biosynthesis in human dermal fibroblasts. We found that ß-lapachone stimulated type I collagen expression in human dermal fibroblasts. In this study, we evaluated whether the ß-lapachone-induced upregulation of collagen biosynthesis in human dermal fibroblasts is associated with the TGF-ß-Smad signaling pathway. In cultured human dermal fibroblasts, both Smad 2 and Smad 3 (Smad 2/3) were phosphorylated by ß-lapachone treatment in a concentration-dependent manner. SB431542, a specific inhibitor of TGF-ß receptor I kinase, inhibited the ß-lapachone-mediated Smad 2/3 phosphorylation and type I collagen expression, suggesting that ß-lapachone stimulates collagen production via the TGF-ß receptor I kinase-dependent pathway. ß-Lapachone did not increase TGF-ß1 synthesis in human dermal fibroblasts, suggesting that the molecular mechanism of ß-lapachone for the upregulation of collagen synthesis is due to the extracellular regulation of availability and activities of TGF-ß. This study provides new insights into the role of ß-lapachone in collagen synthesis in human dermal fibroblasts and suggests that ß-lapachone can be used as a pharmacological tool to study collagen homeostasis associated with TGF-ß-Smad signaling.

Stability of ß-Lapachone upon Exposure to Various Stress Conditions: Resultant Efficacy and Cytotoxicity.

Even though ß-lapachone is a promising compound with antitumor, antiinflammatory, antineoplastic, and wound-healing effects, there are still issues concerning its chemical stability and degradation mechanisms. The objective of this study was to obtain degradation profiles of ß-lapachone and evaluate its chemical stability under various stress conditions. Moreover, the correlation between stability and efficacy was evaluated. The degradation study of ß-lapachone was performed using heat, acid, base, oxidation, and light conditions. Kinetics and degradation profiles were investigated with HPLC and LC-MS. The stability indicated in the LC method was validated according to the International Conference on Harmonization guidelines. Human dermal fibroblast (HDF) cells were cultured with the standard and its degraded samples in the cellular activity and cytotoxicity test. ß-Lapachone was relatively unstable upon exposure to light, and its photodegradation was accelerated with high relative humidity. Three degradants were identified, and their degradation followed zero-order kinetics. It was shown to degrade to phthalic acid under oxidative conditions, and the degradation kinetics were dependent on the concentration of hydrogen peroxide. Two degradation products were identified upon exposure to basic conditions, which followed first-order kinetics. ß-Lapachone was relatively stable under acidic and thermal conditions. It increased the synthesis of collagen compared with the control. However, as the contents decreased, the synthesis of collagen also decreased in the photodegraded samples. ß-Lapachone did not exert cytotoxic effects at the effective concentration in the cytotoxicity test. Therefore, in order to ensure efficacy and safety, the chemical stability of ß-lapachone needs to be controlled carefully while considering instability mechanisms.

Strategic approaches for enhancement of in vivo transbuccal peptide drug delivery in rabbits using iontophoresis and chemical enhancers.

PURPOSE: To evaluate the feasibility of iontophoresis and the combination effects with chemical enhancers on in vivo hypocalcemic effect of transbuccally delivered salmon calcitonin (sCT). METHODS: N-acetyl-L-cysteine (NAC), sodium deoxyglycocholate (SDGC), and ethanol were used as chemical enhancers; and 0.5 mA/cm(2) fixed electric current was employed as a physical enhancer. sCT hydrogel was applied to rabbit buccal mucosa, and blood samples were obtained via the central auricular artery. Blood calcium level was measured by calcium kit and the conformational changes of buccal mucosa were investigated with FT-IR spectroscopy. Hematoxylin/eosin staining was used for the histological evaluation of buccal mucosa. RESULTS: Iontophoresis groups except iontophoresis-NAC group showed significant hypocalcemic effect compared to negative control, in particular iontophoresis-SDGC combination group showed fast onset of action as well as sustained hypocalcemic effect (p < 0.05). FT-IR result demonstrated the reduction of buccal barrier function, and the histological study showed a decrease in buccal thickness as well as minor damage to the dermal-epidermal junctions in the enhancing method groups; however, the damaged tissues virtually recovered within 24 h after the removal of electrodes. CONCLUSIONS: Iontophoresis and combination with SDGC were found to be safe and potential strategies for transbuccal peptide delivery in vivo.

Fundamental analysis of recombinant human epidermal growth factor in solution with biophysical methods.

Correlation of thermodynamic and secondary structural stability of proteins at various buffer pHs was investigated using differential scanning calorimetry (DSC), dynamic light scattering (DLS) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR FT-IR). Recombinant human epithelial growth factor (rhEGF) was selected as a model protein at various pHs and in different buffers, including phosphate, histidine, citrate, HEPES and Tris. Particle size and zeta potential of rhEGF at each selected pH of buffer were observed by DLS. Four factors were used to characterize the biophysical stability of rhEGF in solution: temperature at maximum heat flux (Tm), intermolecular ß-sheet contents, zeta size and zeta potential. It was possible to predict the apparent isoelectric point (pI) of rhEGF as 4.43 by plotting pH against zeta potential. When the pH of the rhEGF solution increased or decreased from pI, the absolute zeta potential increased indicating a reduced possibility of protein aggregation, since Tm increased and ß-sheet contents decreased. The contents of induced intermolecular ß-sheet in Tris and HEPES buffers were the lowest. Thermodynamic stability of rhEGF markedly increased when pH is higher than 6.2 in histidine buffer where Tm of first transition was all above 70 °C. Moreover, rhEGF in Tris buffer was more thermodynamically stable than in HEPES with higher zeta potential. Tris buffer at pH 7.2 was concluded to be the most favorable.

Human CLOCK gene-associated attention deficit hyperactivity disorder-related features in healthy adults: quantitative association study using Wender Utah Rating Scale.

Circadian rhythm disturbance is highly prevalent in attention deficit hyperactivity disorder (ADHD). Recently, the association between the CLOCK gene and ADHD has been demonstrated in clinical samples, and the CLOCK gene's role was thought to be mediated by rhythm dysregulation. Meanwhile, ADHD has been suggested as the extreme end of a continuously distributed trait that can be found in the general population. Therefore, we examined two possibilities: (1) an ADHD-related continuous trait may be associated with the CLOCK gene, and (2) this association may be mediated by the degree of individuals' evening preference. To explore these possibilities, we performed a quantitative trait locus association study with a sample of 1,289 healthy adults. The Wender Utah Rating Scale (WURS) and the Composite Scale of Morningness (CSM) were utilized to measure the quantitative traits. Quantitative association analysis was performed using PLINK software. We found that rs1801260 (=T3111C) was associated with WURS scores in both allele-wise (p = 0.018) and haplotype-wise analyses (range of p values: 0.0155-0.0171) in male participants only. After controlling for the CSM total score as a covariate, the strength of the association did not change at all, suggesting that the association was not mediated by evening preference. Despite the very weak association signal, our results provide evidence that the CLOCK gene's association with ADHD in clinical samples may be generalizable to traits measured in the normal population. However, as our results failed to show a mediating role of evening preference, ongoing efforts are needed to identify the mechanisms by which the CLOCK gene determines ADHD-related traits.

Effects of pH and buffer concentration on the thermal stability of etanercept using DSC and DLS.

The protein size, electrical interaction, and conformational stability of etanercept (marketed as Enbrel®) were examined by thermodynamic and light scattering methods with changing pH and buffer concentration. As pH of etanercept increased from pH 6.6 to 8.6, electrical repulsion in the solution increased, inducing a decrease in protein size. However, the size changed less in high buffer concentration and irreversible aggregation issues were not observed; in contrast, aggregates of about 1000 nm were observed in low buffer concentration at the pH range. Three significant unfolding transitions (Tm) were observed by differential scanning calorimetry (DSC). Unlikely to Tm1, Tm2 and Tm3 were increased as the pH increased. Higher Tm at high buffer concentration was observed, indicating increased conformational stability. The apparent activation energy of unfolding was further investigated since continuous increase of Tm2 and Tm3 was not sufficient to determine optimal conditions. A higher energy barrier was calculated at Tm2 than at Tm3. In addition, the energy barriers were the highest at pH from 7.4 to 7.8 where higher Tm1 was also observed. Therefore, the conformational stability of protein solution significantly changed with pH dependent steric repulsion of neighboring protein molecules. An optimized pH range was obtained that satisfied the stability of all three domains. Electrostatic circumstances and structural interactions resulted in irreversible aggregation at low buffer concentrations and were suppressed by increasing the concentration. Therefore, increased buffer concentration is recommended during protein formulation development, even in the earlier stages of investigation, to avoid protein instability issues.

Evaluation of taste-masking effects of pharmaceutical sweeteners with an electronic tongue system.

Electronic tongue systems have been developed for taste measurement of bitter drug substances in accurate taste comparison to development palatable oral formulations. This study was to evaluate the taste masking effect of conventional pharmaceutical sweeteners such as neohesperidin dihydrochalcone, sucrose, sucralose and aspartame. The model drugs were acetaminophen, ibuprofen, tramadol hydrochloride, and sildenafil citrate (all at 20 mM). The degree of bitterness was measured by a multichannel taste sensor system (an electronic tongue). The data was collected by seven sensors and analyzed by a statistical method of principal components analysis (PCA). The effect of taste masking excipient was dependent on the type of model drug. Changing the concentration of taste masking excipients affected the sensitivity of taste masking effect according to the type of drug. As the excipient concentration increased, the effect of taste masking increased. Moreover, most of the sensors showed a concentration-dependent pattern of the taste-masking agents as higher concentration provided higher selectivity. This might indicate that the sensors can detect small concentration changes of a chemical in solution. These results suggest that the taste masking could be evaluated based on the data of the electronic tongue system and that the formulation development process could be performed in a more efficient way.

Change in absolute neutrophil count after COVID-19 infection in patients using clozapine versus other antipsychotics.

It was reported that patients who contracted COVID-19 while taking clozapine exhibited a distinct hematological response. However, the absence of control groups made it difficult to attribute it to clozapine. The changes in absolute neutrophil counts (ANCs) during the 4 weeks after COVID-19 infection were compared between the two groups of patients with severe mental illnesses (SMIs) (49 patients using clozapine and 54 using other antipsychotics) using generalized additive modeling. Although the pattern of a transient drop in ANC followed by gradual recovery could be demonstrated in both groups, it was more pronounced in the clozapine group ( P  = 0.00025). Nevertheless, overall ANC remained at a higher level in the clozapine group. The results suggested potential interaction between clozapine and COVID-19 at the level of hematological dynamics. However, it did not necessarily indicate that such interaction is inevitably harmful or dangerous. It was more of a concern that some patients using other antipsychotics exhibited decreased ANC, which did not easily recover. Traditionally, clinicians have been concerned about the worsening of hematological side effects in clozapine patients after COVID-19 infection. However, the obtained result highlighted the necessity of hematological monitoring in patients using any type of antipsychotics for SMIs.

The Mediating Role of Anxiety/Depression Between Auditory Verbal Hallucinations and the Level of Insight in Schizophrenia.

OBJECTIVE: Auditory verbal hallucination (AVH) is a prominent symptom of schizophrenia causing profound distress. The influence of AVHs on insight appears to be intricate and contingent on other accompanying symptoms. This study investigated the relationship and possible mediators between AVHs and the degree of insight. METHODS: One hundred patients with schizophrenia participated in the study. Scales were used to evaluate the hallucinatory experience, the level of insight and other psychopathology. Complex relationships between variables were envisaged as a path model, whose initial structure was constructed via Gaussian Graphical Model. The validity of the final model was verified by Structural Equation Modeling. Separate analyses were performed for self-reported and clinician-rated data to enhance the model's robustness. RESULTS: The greater the severity of the physical aspects of AVHs, the lower the level of insight observed. Conversely, higher emotional distress was associated with increased insight. These relationships were only evident in the self-reported results and were not reflected in the clinician-rated results. The path model suggested that the Positive and Negative Syndrome Scale (PANSS) anxiety/depression factor was an important mediator that linked the found association. Notably, the PANSS negative symptom had the opposite effect on the PANSS anxiety/depression factor and insight, making it difficult to define its overall effect. CONCLUSION: The findings of this study provided one possible route for the positive influence of AVH experience in gaining insight. The mediating role of anxiety/depression modified by negative symptoms emerged as a valuable concept for clarifying this intricate relationship.

In-use stability of Rituximab and IVIG during intravenous infusion: Impact of peristaltic pump, IV bags, flow rate, and plastic syringes.

This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients' safety and treatment efficacy.

Combination therapy of acupuncture and herbal medicine for heart failure: A systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) is characterized by functional or structural dysfunction of the heart, resulting in impaired blood ejection or ventricular filling. Conventional Western Medicine (CWM) remains the mainstay of treatment for HF; however, the occurrence of adverse events (AEs) necessitates the exploration of alternative treatments. Herbal medicine and acupuncture are adjunctive therapies for HF and have shown potential for improving heart function. This systematic review and meta-analysis aimed to assess the effectiveness and safety of acupuncture and herbal medicine in treating HF. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by National Institute of Informatics, KoreaMed, Research Information Sharing Service, and DBpia were searched for randomized controlled trials (RCTs) evaluating the effects of acupuncture and herbal medicine along with CWM as adjunctive treatments for HF, published from inception to May 31, 2024. Treatment effectiveness was determined by evaluating the left ventricular ejection fraction as the primary metric, along with the measurement of the total effective rate, brain natriuretic peptide level, N-terminal prohormone of brain natriuretic peptide level, left ventricular end-diastolic volume, and left ventricular end-systolic volume; the administration of the Minnesota Living with Heart Failure Questionnaire; and the conduct of a 6-minute walk test. Treatment safety was evaluated based on the incidence of AEs. The methodological quality of all included RCTs was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager, version 5.4.1. RESULTS: Of the 133 publications identified, 8 RCTs met the inclusion criteria. The meta-analysis showed significant improvements in left ventricular ejection fraction, brain natriuretic peptide levels, N-terminal prohormone of brain natriuretic peptide levels, left ventricular end-systolic volume, left ventricular end-diastolic volume, and 6-minute walk test results. Additionally, significant differences were observed in the total effective rate and Minnesota Living with Heart Failure Questionnaire responses. No significant medication-related AEs occurred in the intervention group. Conversely, 7 control patients developed well-known AEs associated with CWM. CONCLUSION: Acupuncture combined with herbal medicine and CWM is more effective than CWM alone, indicating a safe treatment approach. Consequently, the proactive administration of acupuncture alongside herbal medicine to patients with HF can be undertaken without concerns regarding AEs.

Glycyrrhizin enhances therapeutic activity of a colon-specific methylprednisolone prodrug against experimental colitis.

BACKGROUND: Co-administration of a reduction inhibitor and a colon-specific prodrug of a glucocorticoid susceptible to colonic reductive metabolism is suggested as a strategy to circumvent the therapeutic loss of the glucocorticoid delivered to and acting locally at the large intestine. AIMS: We examined whether the strategy was feasible as a pharmacotherapy for treatment of inflammatory bowel disease. METHODS: Glycyrrhizin (GCZ), a reduction inhibitor, was tested for its inhibition of the colonic metabolism of methylprednisolone (MP). Therapeutic activity against TNBS-induced rat colitis and adrenal suppression were compared after oral administration of methylprednisolone 21-sulfate sodium (MPS), a colon-specific prodrug of MP, or MPS/GCZ to colitic rats. RESULTS: Upon incubation of MP with the cecal contents, MP disappeared, and this was delayed by addition of GCZ. In addition, more MP produced from MPS in the cecal contents accumulated in the presence of GCZ. Consistent with these results, upon oral administration of MPS/GCZ, MPS or MP, MP was detected at a greater level in the large intestine for MPS/GCZ. MPS/GCZ ameliorated TNBS-induced colitis of rats, and this therapeutic effect was superior to that of MPS and MP. Moreover, MPS/GCZ decreased the plasma levels of corticosterone and ACTH to a greater extent than MPS, but less than MP. CONCLUSIONS: Co-administration of GCZ, a reduction inhibitor, may be a plausible strategy to reduce the therapeutic loss of MP produced from MPS in the large intestine, thus improving the therapeutic property of the prodrug against inflammatory bowel disease.

A robust experimental design method to optimize formulations of retinol solid lipid nanoparticles.

A robust experimental design method was developed using a response surface methodology and models to facilitate the development process of retinol solid lipid nanoparticles (SLNs). The SLNs were evaluated to determine how different parameters including lipid and surfactant affect size and encapsulation efficiency. This was conducted using factorial analysis and a robust design (RD) method was used to achieve optimal formulations. Two models were developed based on the RD principle and both mean and variance of the response characteristics were estimated functionally using the least squares method. They proved useful in formulation studies aiming to develop optimum by allowing a systematic and reliable design method. A model for maximizing the overall desirability represented by the geometric mean of all objectives was found to provide a better solution. The newly designed method provides useful information to characterize significant factors and obtain optimum formulations, thereby allowing a systematic and reliable design method.