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In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new technique, various flow patterns and arterial phenomena—such as laminar, turbulent, antegrade, retrograde, and recirculating flow and potentially water hammer shock and vortex formation—are identified, recorded, and classified. These phenomena are then correlated with the presence of lesions at different locations within the coronary vasculature. The formation and growth of these lesions are explained from the perspective of fluid mechanics. As the pathophysiology of CAD and other cardiovascular conditions becomes clearer, new medical, surgical, and interventional treatments could be developed to reverse abnormal coronary flow dynamics and restore laminar flow, leading to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

The reconstruction of soft tissue defects in the foot and ankle remains a big challenge due to the anatomical characteristics of this area. This study evaluated the long-term effectiveness of covering by lateral supramalleolar flap in patients with soft tissue defects around the ankle and foot. We conducted a retrospective study from January 2017 to December 2020 at the Hospital for Traumatology and Orthopedics, Ho Chi Minh City, Vietnam. Data about patients' characteristics, detailed injuries, perioperative information, intraprocedural dossier, and complications of this method were recorded and analyzed. There were 31 male and 17 female patients, with an average age of 39.8 (ranging from 11 to 77) years. The skin defects ranged from 8 cm2 to 120 cm2. The blood supply for the flap included a mixed-flow pattern (n = 30) and retrograde flow (n = 18). The success rate was 94%. Forty-two patients had been successfully covered, five patients had partial flap necrosis (in which two cases needed skin graft afterwards and three cases got spontaneous healing), only one patient had total flap necrosis. In conclusion, the lateral supramalleolar flap can cover the soft tissue of ankle and foot defects in both mixed-blood supply pattern or retrograde pattern with high success rates. However, the risk of venous congestion should be considered, particularly when using the retrograde pattern flap. [ABSTRACT FROM AUTHOR]

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that can lead to terminal respiratory failure. Ultrafine carbonaceous particles, which are ubiquitous in ambient urban and indoor air, are increasingly considered as major contributors to the global health burden of air pollution. However, their effects on the expression of CFTR and associated genes in lung epithelial cells have not yet been investigated. We therefore evaluated the effects of carbon nanoparticles (CNP), generated by spark-ablation, on the human bronchial epithelial cell line 16HBE14o− at air–liquid interface (ALI) culture conditions. The ALI-cultured cells exhibited epithelial barrier integrity and increased CFTR expression. Following a 4-h exposure to CNP, the cells exhibited a decreased barrier integrity, as well as decreased expression of CFTR transcript and protein levels. Furthermore, transcriptomic analysis revealed that the CNP-exposed cells showed signs of oxidative stress, apoptosis and DNA damage. In conclusion, this study describes spark-ablated carbon nanoparticles in a realistic exposure of aerosols to decrease CFTR expression accompanied by transcriptomic signs of oxidative stress, apoptosis and DNA damage. [ABSTRACT FROM AUTHOR]

The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone K30 (PVP) as the most effective stabilizer for nanocrystals. The immediate-release layer containing the optimized nanocrystals (size of 279.5 ± 11.25 nm and polydispersity index of 0.204 ± 0.01) was then compressed on a zero-order sustained-release matrix core using different derivatives of hydroxypropyl methylcellulose (HPMC). Application of the Design of Experiment approach (DoE) was applied to optimize the formulation of tablet. Analysis of drug concentration in dog plasma by liquid chromatography-tandem mass spectrometry demonstrated an improvement in the release behavior of LNX from the optimal compression-coated tablet integrating a HPMC-based sustained release matrix core and a PVP-stabilized lornoxicam nanocrystals coating layer compared to the reference product. [ABSTRACT FROM AUTHOR]

The study aims to investigate the effect of formulation variables on the characteristics of azithromycin (AZI) nanoparticles using a quality by design approach. AZI nanoparticles were prepared by the emulsification solvent diffusion method. Two critical factors, the ratio of AZI: Eudragit EPO (X1) and volume of outer aqueous medium (X2), were chosen as independent variables for central composite design. The optimized formulation was further characterized by Fourier transform infrared spectroscopy, X-ray diffractometry, transmission electron microscopy, and dissolution test. The obtained results showed variability of mean particle size, entrapment efficacy, and zeta potential from 200 to 1232 nm, 10.78 to 75.9%, and 31 to 43 mV, respectively. The main coefficients indicated that the ratio of AZI: polymer (X1) possessed a synergistic effect on mean particle size (Y1), and volume of outer aqueous medium (X2) had an antagonistic effect on particle size. The interaction between the ratio of AZI: Eudragit EPO (X1) and volume of outer aqueous medium (X2) exhibited a significant antagonistic effect on entrapment efficacy (Y2) (p<0.05). AZI existed in an amorphous state in nanoparticles that were spherical and homogeneous in shape. The nanoparticles revealed the Korsmeyer-Peppas release model, from which AZI was released faster compared to raw material. [ABSTRACT FROM AUTHOR]

Background: Conformational transitions are implicated in the biological function of many proteins. Structural changes in proteins can be described approximately as the relative movement of rigid domains against each other. Despite previous efforts, there is a need to develop new domain segmentation algorithms that are capable of analysing the entire structure database efficiently and do not require the choice of protein-dependent tuning parameters such as the number of rigid domains. Results: We develop a graph-based method for detecting rigid domains in proteins. Structural information from multiple conformational states is represented by a graph whose nodes correspond to amino acids. Graph clustering algorithms allow us to reduce the graph and run the Viterbi algorithm on the associated line graph to obtain a segmentation of the input structures into rigid domains. In contrast to many alternative methods, our approach does not require knowledge about the number of rigid domains. Moreover, we identified default values for the algorithmic parameters that are suitable for a large number of conformational ensembles. We test our algorithm on examples from the DynDom database and illustrate our method on various challenging systems whose structural transitions have been studied extensively. Conclusions: The results strongly suggest that our graph-based algorithm forms a novel framework to characterize structural transitions in proteins via detecting their rigid domains. The web server is available at http://azifi.tz.agrar.uni-goettingen.de/webservice/. [ABSTRACT FROM AUTHOR]

• DoE-based approach is useful to optimize the formulation of microemulsion. • Carboxymethyl cellulose is chosen as optimal hydrogel-forming agent. • Anti-inflammatory effect of ME-hydrogel is higher than SLN-hydrogel, NLC-hydrogel. This study was performed to achieve two primary goals: First, a microemulsion containing betamethasone dipropionate was optimized using the quality by design approach. Second, a hydrogel-containing microemulsion was developed using cellulose derivatives, and its anti-inflammatory and skin irritation effects were evaluated. Face-centered central composite design was used to investigate the impacts of two independent variables (oleic acid and ratio of surfactant to cosolvent, S/CoS) on three dependent variables (skin deposition, flux of BMD, and microemulsion droplet size). The microemulsion including oleic acid at a low level (coded with -1) and S/CoS at a high level (coded with +1) was considered optimal since it was the most effective in terms of skin deposition and flux of BMD. Different cellulose derivatives (HPMC E6, HEC, NaCMC, and CMC) were screened to prepare a hydrogel-containing microemulsion based on four properties: flux and skin deposition of BMD, hydration of stratum corneum, and rheological properties of hydrogel-containing microemulsion (ME-hydrogel). The anti-inflammatory effect and flux of BMD from optimal ME-hydrogel with carboxymethyl cellulose as the hydrogel-forming agent were then compared to those of the hydrogel-containing solid lipid nanoparticles (SLN-hydrogel) and nanostructure lipid carriers (NLC-hydrogel). The percentage of edema inhibition declined proportionally with flux of BMD in the following order: ME-hydrogel (44.56 ± 8.08%) > NLC-hydrogel (35.93 ± 7.22%) > SLN-hydrogel (25.68 ± 9.05%). [ABSTRACT FROM AUTHOR]

Hoang Su Phi is a mountainous district in Ha Giang province, Vietnam. When the rainy season arrives in these parts, flash floods (besides landslides), frequently occur in many areas, seriously affecting the socio‐economic condition of the district. Therefore, in this paper, we have developed an early warning system for flash floods, established based on a geomorphological and hydrological approach. The basic principle underlying this system is the fact that flash floods will often occur where there is high potential risk with sufficient rainfall. In the model, eight parameters of the basin were used to build a potential flash flood map. Using the spatial processing module in an open source software, early predictions from automatic weather stations were interpolated and processed online to produce a potential risk map. Depending on the threshold of precipitation values, the results determined locations where flash flood may occur at various flash flood risk indices (FFRI). The system may be applied to support provision of early flash flood warning up to 1−6 days in advance in the district, allowing the local government ample time to make appropriate decisions on the prevention and/or mitigation of damages caused by flash flood hazards. [ABSTRACT FROM AUTHOR]

An operationally simple in situ protection/deprotection strategy that significantly expands the scope of kinetically controlled catalytic Z‐ and E‐selective olefin metathesis is introduced. Prior to the addition of a sensitive Mo‐ or Ru‐based complex, treatment of a hydroxy‐ or a carboxylic‐acid‐containing olefin with commercially available HB(pin) or readily accessible HB(trip)2 (pin=pinacolato, trip=2,4,6‐tri(isopropyl)phenyl) for 15 min is sufficient for efficient generation of a desired product. Routine workup leads to quantitative deprotection. A range of stereochemically defined Z‐ and E‐alkenyl chlorides, bromides, fluorides, and boronates or Z‐trifluoromethyl‐substituted alkenes with a hydroxy or carboxylic acid group were thus prepared in 51–97 % yield with 93 to >98 % stereoselectivity. We also show that, regardless of whether a polar functional unit is present or not, a small amount of HB(pin) may be used to remove residual water, significantly enhancing efficiency. Without a trace: Alkenes containing a hydroxy and/or a carboxylic acid group were converted into Z or E alkenes through one‐pot operations consisting of in situ protection, catalytic cross‐metathesis, and deprotection by mild workup/purification. Prior to the addition of a sensitive Mo or Ru complex, treatment of the olefin with HB(pin) or readily available HB(trip)2 for 15 min was sufficient for the efficient generation of a desired product (see scheme). [ABSTRACT FROM AUTHOR]

An operationally simple in situ protection/deprotection strategy that significantly expands the scope of kinetically controlled catalytic Z‐ and E‐selective olefin metathesis is introduced. Prior to the addition of a sensitive Mo‐ or Ru‐based complex, treatment of a hydroxy‐ or a carboxylic‐acid‐containing olefin with commercially available HB(pin) or readily accessible HB(trip)2 (pin=pinacolato, trip=2,4,6‐tri(isopropyl)phenyl) for 15 min is sufficient for efficient generation of a desired product. Routine workup leads to quantitative deprotection. A range of stereochemically defined Z‐ and E‐alkenyl chlorides, bromides, fluorides, and boronates or Z‐trifluoromethyl‐substituted alkenes with a hydroxy or carboxylic acid group were thus prepared in 51–97 % yield with 93 to >98 % stereoselectivity. We also show that, regardless of whether a polar functional unit is present or not, a small amount of HB(pin) may be used to remove residual water, significantly enhancing efficiency. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The first objective of this study was to optimize a supersaturatable self-nanoemulsifying drug delivery system (S-SNEDDS) containing silymarin through the investigation of the single and synergistic effect of either SNEDDS or a precipitation inhibitor on dissolution efficiency (DE) of silymarin. The bioavailability and hepatoprotective activity of S-SNEDDS were then compared to those of a branded product (Legalon®, Meda). SNEDDS containing silymarin was developed by titration technique, and Poloxamer 407 was selected as the optimal precipitation inhibitor by using casting film and solvent-shift method. The interaction of silybin (the major active constituent of silymarin) and the polymer was then determined by differential scanning calorimetry, powder X-ray diffractometry (PXRD), Fourier transforms infrared spectroscopy and 1H NMR analysis. The combination of two techniques including SNEDDS and addition of 10% of Poloxamer 407 remarkably increased DE 4h (88.28%) compared to the reference product (6.41%). The relative bioavailability of S-SNEDDS versus Legalon® was about 760%. The hepatoprotective activity of S-SNEDDS in CCl 4 -induced mice was also superior to the commercial product in declining both the levels of serum transaminases (ALT, AST) and lipid peroxidation as well as glutathione and superoxide dismutase (SOD) activities under tested doses calculated as silybin (10, 25 and 50 mg/kg). These biopharmaceutical and pharmacological advantages of S-SNEDDS indicated prospects in the development of a novel product that offers lower strength of silymarin while enhancing therapeutic outcomes. [ABSTRACT FROM AUTHOR]

A 22-year-old woman with myasthenia gravis (MG) presented with ptosis and mild muscle weakness symptoms for one year. Computed tomography (CT) presented a diffuse bilobulate enlargement gland with a high density of soft tissue. Magnetic resonance imaging (MRI) showed the gland with no suppression on the opposed-phase chemical shift. After the thymic tumor diagnosis, she underwent thoracoscopic surgery for tumor resection. The postoperative histopathological finding was thymic lymphoid hyperplasia. This case suggests chemical shift MRI is not enough in distinguishing, and supplementary examination is essential to avoid unnecessary thymic biopsy and surgery. [ABSTRACT FROM AUTHOR]

The objective of this study was to prepare and evaluate some physiochemical and biopharmaceutical properties of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets. In the first stage of the study, the bitter taste masking microparticles were prepared by solvent evaporation and spray drying method. When compared to the bitter threshold (32.43 µg/ml) of azithromycin (AZI), the microparticles using AZI:Eudragit L100 = 1:4 and having a size distribution of 45–212 µm did significantly mask the bitter taste of AZI. Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy ( 1 H NMR) proved that the taste masking of microparticles resulted from the intermolecular interaction of the amine group in AZI and the carbonyl group in Eudragit L100. Differential scanning calorimeter (DSC) analysis was used to display the amorphous state of AZI in microparticles. Images obtaining from optical microscopy and scanning electron microscopy (SEM) indicated the existence of microparticles in regular cube shape with many layers. In the second stage, dispersible tablets containing microparticles (DTs-MP) were prepared by direct compression technique. Stability study was conducted to screen pH modulators for DTs-MP, and a combination of alkali agents (CaCO 3 :NaH 2 PO 4 , 2:1) was added into DTs-MP to create microenvironment pH of 5.0–6.0 for the tablets. The disintegration time of optimum DTs-MP was 53 ± 5.29 s and strongly depended on the kinds of lubricant and diluent. The pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the mean relative bioavailability (AUC) and mean maximum concentration (C max ) of DTs-MP were improved by 2.19 and 2.02 times, respectively, compared to the reference product (Zithromax®, Pfizer). [ABSTRACT FROM AUTHOR]

Background: New onset of heart failure (HF) is an indication for the assessment of coronary artery disease. The aim of this study was to clarify the mechanistic causes of new onset HF associated with ischemic electrocardiograph (EKG) changes and chest pain in patients with patent or minimally diseased coronary arteries. Methods: Twenty consecutive patients (Group A) were retrospectively reviewed if they had an history of new onset of HF, chest pain, electrocardiographic changes indicating ischemia (ST depression or T wave inversion in at least two consecutive leads and a negative coronary angiogram [CA]) and did not require percutaneous coronary intervention or coronary artery bypass grafting. A 1:1 matched cohort (Group B) was adopted to validate the results. Results: All patients had a negative CA. The majority of subjects in Group A had a higher left ventricular end diastolic pressure (LVEDP) when compared to the control group (p<0.05). Similarly, the aortic diastolic (AOD) pressure was lower in Group A than in Group B (p<0.05). In patients with elevated LVEDP and low AOD, with a coronary perfusion pressure (CPP) <20 mmHg, deep T wave inversion in two consecutive leads were more frequently observed. When the CPP was between 20-30 mmHg, a mild ST depression were more frequently recorded (p<0.05). Conversely, when the CPP was >30 mmHg, only mild non-specific ST-T changes or normal EKG were observed. Conclusions: In patients with HF and EKG changes suggestive of ischemia in at least two consecutive leads, a lower AOD could aggravate ischemia in patients with elevated left ventricular end diastolic pressure. [ABSTRACT FROM AUTHOR]

The study first aimed to apply a design of experiment (DoE) approach to investigate the influences of excipients on the properties of liquid self-microemulsifying drug delivery system (SMEDDS) and SMEDDS loaded in the pellet (pellet-SMEDDS) containing l -tetrahydropalmatine (l-THP). Another aim of the study was to compare the bioavailability of l-THP suspension, liquid SMEDDS and pellet-SMEDDS in the rabbit model. By using Central Composite Face design (CCF), the optimum ratio of Capryol 90, and S mix `(Cremophor RH 40: Transcutol HP) in the formulation of SMEDDS was determined. This optimum SMEDDS was absorbed on the solid carrier (Avicel or Aerosil) for the preparation of pellet-SMEDDS by extrusion and spheronization method. The ANOVA table indicated that Avicel was more effective than Aerosil, the traditional solid carrier, in both terms of preservation of dissolution rate of l-THP from the original SMEDDS and pelletization yield. Results obtained from scanning electron microscopy (SEM) indicated that the existence of liquid SMEDDS droplets on the surface of pellet-SMEDDS was due to the absorption on Avicel. The powder X-ray diffractometry proved the amorphous state of l-THP in pellet-SMEDDS. Pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the SMEDDS improved the oral bioavailability of l-THP by 198.63% compared to l-THP suspension. Besides, pharmacokinetics study also proved that the mean relative bioavailability (AUC) and mean maximum concentration (C max ) of pellet-SMEDDS were not significantly different from the original liquid SMEDDS (p > 0.05). [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the miscibility of cellulose derivatives to improve the release rate and stability of microparticles containing the weakly basic drug itraconazole (ITZ). We also investigated the effect of some organic acids on the microenvironmental pH (pH m) and the release rate of ITZ from the cellulose-based microparticles. The synergistic effect of cellulose-based microparticles and pH m modulators on the bioavailability of ITZ compared with the reference product was investigated in a rabbit model. Differential scanning calorimetry and Fourier-transform infrared spectroscopy (FTIR) analysis showed that ITZ, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose phthalate were miscible at a ratio of 1.5:3:1 (w /w/w), and the stability of the microparticles was maintained for 6 months under accelerated conditions. In addition, X-ray diffraction, FTIR, and scanning electron microscopy were used to characterize the properties of the microparticles. Through the titration technique and determination of pH m , the combination of fumaric acid and maleic acid (1:2, w /w) was found to be the most effective pH m modulator for microparticles. The integration of cellulose-based microparticles and pH m modulators showed a synergistic effect on the flux and relative bioavailability of ITZ and its active metabolite OH-ITZ (182.60 % and 217.67 %, respectively) when compared with the reference product. [ABSTRACT FROM AUTHOR]

Motivation: Large-scale conformational changes in proteins are implicated in many important biological functions. These structural transitions can often be rationalized in terms of relative movements of rigid domains. There is a need for objective and automated methods that identify rigid domains in sets of protein structures showing alternative conformational states. Results: We present a probabilistic model for detecting rigid-body movements in protein structures. Our model aims to approximate alternative conformational states by a few structural parts that are rigidly transformed under the action of a rotation and a translation. By using Bayesian inference and Markov chain Monte Carlo sampling, we estimate all parameters of the model, including a segmentation of the protein into rigid domains, the structures of the domains themselves, and the rigid transformations that generate the observed structures. We find that our Gibbs sampling algorithm can also estimate the optimal number of rigid domains with high efficiency and accuracy. We assess the power of our method on several thousand entries of the DynDom database and discuss applications to various complex biomolecular systems. [ABSTRACT FROM AUTHOR]

A major shortcoming in olefin metathesis, a chemical process that is central to research in several branches of chemistry, is the lack of efficient methods that kinetically favor E isomers in the product distribution. Here we show that kinetically E-selective cross-metathesis reactions may be designed to generate thermodynamically disfavored alkenyl chlorides and fluorides in high yield and with exceptional stereoselectivity. With 1.0 to 5.0 mole % of a molybdenum-based catalyst, which may be delivered in the form of air- and moisture-stable paraffin pellets, reactions typically proceed to completion within 4 hours at ambient temperature. Many isomerically pure E-alkenyl chlorides, applicable to catalytic cross-coupling transformations and found in biologically active entities, thus become easily and directly accessible. Similarly, E-alkenyl fluorides can be synthesized from simpler compounds or more complex molecules. [ABSTRACT FROM AUTHOR]

There has been a great scientific interest in exploring the great potential of the piperazine-phosphonates in flame retardant (FR) application on cotton fabric by investigating the thermal decomposition of cotton fabric treated with them. This research tries to understand the mode of action of the two piperazine-phosphonates derivatives on cotton fabric. The investigation proceeds by preparing Tetraethyl piperazine-1,4-diyldiphosphonate ( TEPP) and Diethyl 4-methyl piperazin-1-ylphosphoramidate ( DEPP ), engrafting them on cotton fabric and studying their mechanism of thermal degradation on fabric. In studying the mechanism, we learned the chemical functional groups of the chemicals on the surface of the treated fabrics and of the evolved gases produced thermogravimetrically and pyrolytically by using different analytical techniques such as attenuated total reflection infrared (ATR-IR), thermogravimetric analysis–Fourier transform infrared (TGA–FTIR) spectroscopy and pyrolysis-gas chromatography–mass spectrometry (Py-GC/MS). The experiment's results showed some distinctive details in the thermal degradation of the fabric when applied with these additives. [ABSTRACT FROM AUTHOR]

Thepresent research is aimed at studying the structural effect of twophosphoramidate derivatives diethyl 3-hydroxypropylphosphoramidate EHPand dimethyl 3-hydroxypropylphosphoramidate MHPas flame retardants for cotton fabric. EHPand MHPwere obtained in very high yield and purity by one stepprocedures. Cotton twill fabrics treated with the two compounds atdifferent add-ons (5–20 wt %) were characterized. Verticalflammability, limiting oxygen index, thermogravimetric, and microscalecombustion calorimeter analyses were performed, and all resulted inbetter flame retardancy and thermal behavior for MHPcomparedto EHP. A study of the functional groups which appearedon the treated fabrics by attenuated total reflection infrared spectroscopyrevealed different binding mechanisms between each compound and cottoncellulose. Analysis of the released gas products by thermogravimetricanalysis-Fourier transform infrared spectroscopy showed some distinctivedetails in the degradation of the treated fabrics during the burningprocess. [ABSTRACT FROM AUTHOR]

There isa lack of evidence from randomized clinical trials (RCT) supporting percutaneous coronary intervention (PCI) in patients with high bleeding risk or active bleeding. The management decisions are based on extrapolation of subgroups data in RCTs or experts' opinions. Bleeding in the peri-PCI period also increases mortality. In general, PCI can be performed if bleeding can be stopped by mechanical means (compressing or ligating the artery) and the patient can tolerate 4 hours of anticoagulant without further bleeding. For patient with acquired or inherited high risk of bleeding, anecdotal reports showed that either unfractionated heparin or bivalirudin would be acceptable for PCI. For patients on chronic oral anticoagulants, PCI could be performed without new antithrombotic therapy if the international ratio (INR) is between 2 and 3. Antiplatelet therapy would be needed if new thrombi are detected at the index artery. Ultimately, the decision to perform PCI or treat the patient conservatively must be managed on a case-by-case basis. If the benefits outweigh the risk, then the patient can undergo PCI. (Anadolu Kardiyol Derg 2013; 13:165-70) [ABSTRACT FROM AUTHOR]

Objectives Rebamipide, a novel anti-ulcer agent, is listed in biopharmaceutics classification class IV because of its low aqueous solubility and permeability. Consequently, the bioavailability of rebamipide is under 10% in humans. The aim of this study was to increase the solubility and determine the effect of solubility enhancement on the bioavailability and efficacy of rebamipide (RBM). Methods After taking into account the physiochemical properties of RBM (solubility, melting point, dosage etc.), solid dispersion was chosen as the solubility enhancement method. A rebamipide solid dispersion system containing the drug, l-lysine, PVP-VA 64 and poloxamer 407 was obtained from a spray-drying method. Solubility enhancement of RBM from the solid dispersion was determined by a dissolution test in 900 ml at pH 1.2. The bioavailability and efficacy of RBM solid dispersion were evaluated in a rat model. Key findings The aqueous solubility of RBM was improved 62.17 times by solid dispersion. The oral bioavailability of the drug was also increased 1.74-fold from solid dispersion compared with the reference product in a rat model. With regard to the anti-ulcer effect, the percentage inhibition of the solid dispersion was 2.71 times higher than that of the reference product in the ulcer-induced rat model. Conclusions A solid dispersion of rebamipide was successfully formulated using the spray-drying method. Bioavailability and efficacy of rebamipide were increased significantly by solubility enhancement of the drug. [ABSTRACT FROM AUTHOR]

(J Interven Cardiol 2005;18:107–110) [ABSTRACT FROM AUTHOR]

(J Interven Cardiol 2004;17:339–346) [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of a surfactant on the liquid-liquid phase separation, dissolution, diffusion, and the oral bioavailability of a weakly basic drug (l-tetrahydropalmatine; l-THP) from an amorphous solid dispersion (ASD). The carrier used in the ASD was optimized by the application of casting film, solvent shift, and pH shift methods. The interaction between the optimized carrier (HPMCP) and l-THP was then evaluated by Fourier transform-infrared spectroscopy and powder X-ray diffraction. The impact of the surfactant on ASD prepared by the spray-drying method was evaluated by both in vitro and in vivo studies. The results of in vitro studies, including liquid-liquid phase separation, drug diffusion, and pH-shift dissolution, indicated that the addition of a surfactant at a certain concentration below critical micelle concentration to ASD caused the precipitation of and a reduction in the membrane diffusion of l-THP in pH 6.8. This observation was confirmed in an in vivo study in which the drug concentration of l-THP in rabbit plasma was determined by the LC-MS/MS analysis method. Then the absolute and relative bioavailability of l-THP was calculated from the obtained pharmacokinetic parameters. Specifically, the addition of 1.5% surfactant (Poloxamer 188) to the binary ASD decreased the relative bioavailability of l-THP by approximately 2.4 times compared with the original binary ASD. Besides, the study proved that l-THP had low absolute bioavailability (around 1.24%), and the application of binary ASD was meaningful in enhancing the oral bioavailability of l-THP by around 334.77% compared to the raw material. The study is expected to provide a better understanding of how different dosage forms influence the bioavailability of l-THP, thereby allowing the selection of the optimal approach for this weakly basic drug. [Display omitted] [ABSTRACT FROM AUTHOR]

Harnessing non-spatial properties of photons as if they represent an additional independent coordinate underpins the emerging synthetic dimension approach. It enables probing of higher-dimensional physical models within low-dimensional devices, such as on a planar chip where this method is relatively nascent. We demonstrate an integrated thin-film lithium niobate ring resonator that, under dynamic modulation, simulates a tight-binding model with its discrete frequency modes representing lattice sites. Inter-mode coupling, and the simulated lattice geometry, can be reconfigured by controlling the modulating signals. Up to a quasi-3D lattice connectivity with controllable gauge potentials has been achieved by simultaneous synchronized nearest-, second- and third-nearest-neighbor coupling, and verified by acquiring synthetic band structures. Development of synthetic frequency dimension devices in the thin-film lithium niobate photonic integration platform is a key step in increasing the complexity of topological models achievable on a chip, combining efficient electro-optic mode coupling with non-linear effects for long-range mode interactions. Lithium niobate on insulator (LNOI) is emerging as a powerful photonic integration platform for synthetic dimension approaches that enable probing of higher-dimensional physical models within low-dimensional devices. The authors present a LNOI ring device, whose frequency modes represent lattice sites for versatile simulation of tight-binding models with up to three-dimensional connectivity. [ABSTRACT FROM AUTHOR]

Photonic metamaterials interact with light at the micro–nano scale, enabling unprecedented optical manipulation capabilities, which play a key role in nonlinear optics, spin optics, negative index, and zero index materials. Recently, thin‐film lithium niobate on insulator (LNOI) has emerged as a promising platform for integrated photonics due to its unique material properties, including an excellent electro–optic effect, wide transparency window, and low waveguide losses. Metamaterial structures are promising for constructing novel integrated photonic circuit building blocks on LNOI as they can provide advantageous circuit functionality. In this work, as a proof of concept, high‐performance polarization manipulating devices including polarization splitter rotator (PSR), polarization rotator (PR), and polarizer are demonstrated using photonic metamaterials on the etchless LNOI platform by introducing a silicon nitride layer on the top of LNOI wafer as the loading material. In this way, full advantage of lithium niobate (LN) can be taken to achieve various high‐performance integrated photonic devices, while avoiding the etching of LN and simplifying the fabrication process greatly, which can bring bright prospects for achieving large‐scale lithium niobate integrated photonic circuits. [ABSTRACT FROM AUTHOR]

The theoretical analysis and experimental demonstration of a waveguide resonator are presented based on bound states in the continuum in an integrated photonic chip platform. The continuum has the form of a collimated beam of light which is confined vertically in a transverse electric (TE) mode of a silicon slab. The bound state is a discrete transverse‐magnetic (TM)‐like mode of a ridge on the silicon slab. The coupling between the slab and ridge modes results in a single sharp resonance at the wavelength where they phase match. This phenomenon is experimentally demonstrated on a silicon photonic chip using foundry‐compatible parameters and it is interfaced on‐chip to standard single‐mode silicon nanowire waveguides. The fabricated chip exhibits a single sharp resonance near 1550 nm with a line width of a few nanometers, an extinction ratio of 25 dB, and a thermal stability of 19.5 pm °C−1. It is believed that the demonstration of a resonance operating near a bound state in the continuum realized using guided wave components will form the basis of a new approach to on‐chip wavelength filtering and sensing applications. [ABSTRACT FROM AUTHOR]

The association of alcohol abuse, especially binge drinking, and atrial fibrillation, recently termed 'holiday heart,' has been recognized for some time. The effects of alcohol on atrial fibrillation, however, have not been studied. Accordingly, measurements of hemodynamics and duration of electrically induced atrial fibrillation were made in α-chloralose anesthetized dogs during the 30 min before and during a 30-min intravenous infusion of 1.7 g/kg of ethanol (25%, v/v), which produced an average infusion concentration of 254 ± 21 mg/dl. Average cardiac output, left ventricular (LV) peak dp/dt, and pulmonary artery mean pressure did not change, whereas LV systolic (116 ± 8 to 107 ± 9 mm Hg, p < 0.05) and aortic mean (95 ± 7 to 87 ± 9 mmHg, p < 0.05) pressures decreased. Heart rate and atrioventricular conduction in sinus rhythm, and atrial and ventricular activity in atrial fibrillation also did not change. Despite a decrease in arterial pH, duration of atrial fibrillation decreased (356 ± 143 to 93 ± 38 sec, p < 0.05). Moreover, at 15 min, when average ethanol concentration was 208 ± 20 mg/dl, and aortic mean pressure (95 ± 7 to 85 ± 8 mm Hg, p < 0.05), pulmonary artery mean pressure (16 ± 2 to 14 ± 2 mm Hg, p < 0.05), and LV peak dp/dt (1563 ± 143 to 1285 ± 167 mm Hg-sec−1, p < 0.05) were reduced, duration of atrial fibrillation was less than control (356 ± 143 to 114 ± 56 sec, p < 0.05). Thus, at blood levels of ethanol in which the vasodilatory and myocardial depressant effects of ethanol are evident, alcohol has an antiatrial fibrillatory effect. [ABSTRACT FROM AUTHOR]

Lithium niobate on insulator (LNOI) has emerged as a promising platform for photonic integrated circuits (PICs) due to the excellent electro‐optic (EO) properties of lithium niobate (LN). However, such a platform still lacks many critical passive components with superior performance for constructing PICs. The 3 dB power splitters are one of the important passive components in PICs for separating and combining optical energy to construct the other crucial photonic devices such as Mach–Zehnder modulators, optical switches, and optical phased arrays, et al. In this contribution, an ultra‐broadband and compact 3 dB power splitter is proposed and demonstrated using a tapered subwavelength grating (SWG)‐assisted Y‐branch on a silicon nitride (Si3N4) loaded LNOI platform. The SWG is used to alleviate fabrication challenges and reduce radiation loss while increasing the evanescent coupling. The simulation result shows an excellent operation bandwidth of 800 nm (from 1.2 to 2.0 µm) at the insertion loss (IL) of 0.12 dB. The proposed device with a compact footprint (9.6 × 3 µm2) is finally fabricated on a Si3N4 loaded LNOI platform, and the experimental result shows the IL of <0.2 dB in the wavelength ranges from 1.5 to 1.6 µm, which makes it suitable for broadband PICs required for future communication systems. [ABSTRACT FROM AUTHOR]