Solid phase extraction of palbociclib from palbociclib-loaded therapeutic micelles: Novel synthesis of hybrid reduced graphene oxide-modified magnetic iron oxide (rGO@SiO2@Fe3O4)nanosorbent-based plasma extraction and pharmacokinetics study in rats.

The magnetic properties of a synthetic bornite, Cu5FeS4, and of a Mn-bearing synthetic
\nbornite were investigated using Superconducting Quantum Interference Device (SQUID)
\nmagnetometry and room temperature X-band Electron Paramagnetic Resonance (EPR)
\nspectroscopy. Samples were synthesised from the elements using conventional dry methods.
\nChemical and phase compositions of the samples were confirmed by means of Electron Probe
\nMicro-Analysis (EPMA) and by powder X-Ray Diffraction (XRD).
\nExperimental results, interpreted using spectral simulations, highlight the superexchange
\nnature of ionic interactions between paramagnetic centres and the role played by partial
\nintervalence charge transfer between the Fe(III) and Cu(I) species in natural and synthetic
\nbornite. The cation distribution in synthetic samples was shown to be different from the natural
\nsample, in spite of the close similarity in chemical composition and structure.

Determination of isosinensetin in rat plasma by UHPLC-MS/MS: Application to oral and intravenous pharmacokinetic study in healthy rats

The authors assessed the ability of a Superconducting Quantum Interference Device (SQUID) magnetometer to noninvasively detect mesenteric ischemia in a rabbit model. Superconducting Quantum Interference Device magnetometers have been used to detect magnetic fields created by the basic electrical rhythm (BER) and to detect changes in BER of exteriorized bowel of anesthetized rabbits during mesenteric ischemia. The BER of rabbit ileum was noninvasively measured transabdominally using a SQUID magnetometer and compared with the electrical activity recorded with surgically implanted serosal electrodes before, during, and after snare occlusion of the superior mesenteric artery. Transabdominal SQUID recording of BER frequency was highly correlated to the measurements obtained with electrodes (R = 0.91). Basic electrical rhythm frequency decreased from 16.4 +/- 0.8 to 8.3 +/- 0.3 cpm (p < 0.001) after 25 minutes of ischemia. Reperfusion of ischemic bowel resulted in recovery of BER frequency to 14.3 +/- 0.4 cpm 10 minutes after blood flow was restored. A SQUID magnetometer is capable of noninvasively detecting mesenteric ischemia reliably and at an early stage by detecting a significant drop in BER frequency. These positive findings have encouraged the authors to continue development of clinically useful, noninvasive, detection of intestinal magnetic fields using SQUID magnetometers.

Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48h to 1month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.

FAF1 (FAS-associated factor 1) is involved in the activation of Fas cell surface death receptors and plays a role in apoptosis and necrosis. In patients with Parkinson’s disease, FAF1 is overexpressed in dopaminergic neurons in the substantia nigra. KM-819, an FAF1 inhibitor, has shown potential for preventing dopaminergic neuronal cell death, promoting the degradation of α-synuclein and preventing its accumulation. This study aimed to develop and validate a quantitative analytical method for determining KM-819 levels in rat plasma using liquid chromatography–tandem mass spectrometry. This method was then applied to pharmacokinetic (PK) studies in rats. The metabolic stability of KM-819 was assessed in rat, dog, and human hepatocytes. In vitro metabolite identification and metabolic pathways were investigated in rat, dog, and human hepatocytes. The structural analog of KM-819, namely N-[1-(4-bromobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-2-(phenylsulfanyl) acetamide, served as the internal standard (IS). Proteins were precipitated from plasma samples using acetonitrile. Analysis was carried out using a reverse-phase C18 column with a mobile phase consisting of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile. The analytical method developed for KM-819 exhibited linearity within the concentration range of 0.002–10 μg/mL in rat plasma. The precision and accuracy of the intra- and inter-day measurements were <15% for the lower limit of quantification (LLOQ) and all quality control samples. KM-819 demonstrated stability under various sample storage conditions (6 h at room temperature (25 °C), four weeks at −20 °C, three freeze-thaw cycles, and pretreated samples in the autosampler). The matrix effect and dilution integrity met the criteria set by the Food and Drug Administration and the European Medicines Agency. This sensitive, rapid, and reliable analytical method was successfully applied in pharmacokinetic studies in rats. Pharmacokinetic analysis revealed the dose-independent kinetics of KM-819 at 0.5–5 mg/kg, with a moderate oral bioavailability of ~20% in rats. The metabolic stability of KM-819 was also found to be moderate in rat, dog, and human hepatocytes. Metabolite identification in rat, dog, and human hepatocytes resulted in the discovery of six, six, and eight metabolites, respectively. Glucuronidation and mono-oxidation have been proposed as the major metabolic pathways. Overall, these findings contribute to a better understanding of the pharmacokinetic characteristics of KM-819, thereby aiding future clinical studies.

Superconducting quantum interference device (SQUID) magnetometers have been widely used to perform biomagnetic measurements. In biomagnetic measurements such as magnetocardiograms (MCGs) and magnetoencephalograms, a magnetically shielded room (MSR) is used for noise reduction. However, because the MSR is expensive and heavy, the environments in which it can be used are restricted. In addition, MCG measurements obtained outside the MSR have a poor signal-to-noise ratio. We developed a wide dynamic range SQUID magnetometer that uses the flux-quanta counting (FQC) method with direct-feedback noise cancellation for MCG measurements and does not require the MSR. The FQC method is used to expand the dynamic range of the SQUID magnetometers to enable MCG measurements outside the MSR in the presence of large magnetic noise. The noise cancellation system uses two SQUID sensors; one for sensing and another one for reference. Both the sensing and reference signals are fed back to the sensing SQUID. This makes it possible to reduce the magnetic noise. We demonstrated the dynamic range, noise spectrum of the developed SQUID system, and MCG waveforms measured outside the MSR when the noise cancellation was set to ON or OFF. The noise cancellation factor of the developed SQUID system ranged from 10 to 20 dB. In MCG waveforms with noise cancellation, the QRS complex and T wave were clearly observed. The results show that the developed SQUID system clearly measures MCG waveforms in a condition involving large environmental magnetic noise.

High-performance liquid chromatographic assays for a second-generation novel oral iron chelator (APCP363) and their application to pharmacokinetic studies in rats

We constructed a multichannel superconducting quantum interference device (SQUID) magnetometer system for magnetoencephalogram measurements. The SQUID is based on the double relaxation oscillation SQUID (DROS), which consists of a hysteretic signal SQUID and a reference junction, and shunted by a relaxation circuit of a resistor and an inductor. With the high flux-to-voltage transfers, usually larger than 1 mV//spl Phi//sub 0/, simple flux-locked loop circuits could be used for SQUID operation. The SQUID system consists of 37 integrated magnetometers, distributed on a hemispherical surface, and external feedback scheme was used to eliminate magnetic coupling with the adjacent channels. In addition to the 37 signal channels, 8 reference channels were installed to pickup background noise and to apply software gradiometer. The average noise level of the magnetometers is about 3 fT//spl radic/Hz at 100 Hz, operated inside a magnetically shielded room. The magnetometer system was applied to measure auditory-evoked fields.

Traditionally airborne time-domain electromagnetic (AEM) survey systems use induction coils as the sensor (receiver). We have replaced the induction coil in a transient electromagnetic (TEM) system with a liquid-nitrogen cooled superconducting quantum interference device (SQUID) magnetometer sensor. Using this prototype system, we aimed to improve performance in detecting conductive mineralization, particularly where the conductive mineralization of interest is covered by a conductive regolith.; We successfully demonstrated one- and three-component SQUID sensors in airborne TEM surveying, and achieved performance comparable to the induction-coil systems. Implementation of the SQUID system required development of devices capable of operating in magnetically unshielded environments with low noise, high slew rate, and wide bandwidth. Operation of the SQUID sensor in the highly dynamic environment of a towed bird was also necessary, and this implies a high dynamic range and high level of noise associated with the motion in Earth's magnetic field. The high dynamic range of the SQUID response was handled by a combination of resetting the SQUID flux locked loop, reducing the bandwidth, and providing high-gain feedback in parallel with the flux locked loop. A digital stacking filter was used to eliminate low-frequency noise associated with sensor motion. Isolation of the sensor from motion at the TEM signal frequencies required development of a sophisticated suspension system. The SQUID systems were tested over two known conductive targets, and their performance compared with the induction-coil TEM system. A comparative performance measure is developed to take the different sensitivities of the SQUID magnetometer and induction-coil receivers into account. This measure indicates that the SQUID system has superior performance for responses over earth structures with decay time constants greater than ∼6 ms when compared with the induction-coil signals. We also estimate the performance in comparison with integrated outputs of the induction-coil system and show that, at the demonstrated levels of SQUID performance, it is expected to have poorer performance by a factor of two or more. This disadvantage will be reduced for lower frequency, wider channel width TEM configurations or by improvements in the SQUID devices.

We attempt a comprehensive review of all published research in nondestructive evaluation (NDE) performed with the superconducting quantum interference device (SQUID) magnetometer since the first work was reported in the mid-1980s. The SQUID is the most sensitive detector of magnetic flux known. The energy sensitivity of the SQUID may make it the most sensitive detector of any kind. The research on SQUIDs for NDE is based on the promise of that sensitivity and on the various other desirable properties developed for SQUID instrumentation in biomagnetism and other fields. The sensitivity of SQUID instruments down to very low frequencies allows them to function as eddy-current sensors with unparalleled depth resolution, and to image the static magnetization of paramagnetic materials and the flow of near-dc corrosion currents. The wide dynamic range of the SQUID makes it possible to image defects in steel structures and to measure the magnetomechanical behaviour of ferromagnetic materials with high sensitivity. In the last decade SQUID instrumentation designed specifically for NDE has appeared and improved the spatial resolution of most work to roughly 1 mm, with promise of another order of magnitude improvement within the next five years. Algorithms for flaw detection and image deconvolution have begun to flourish. With many talented, industrious people in the field, the future of SQUID NDE looks bright, provided the crucial first niche can be found.

A description is given of an optical-fiber feedback superconducting quantum interference device (SQUID) magnetometer which was developed to improve electromagnetic interference characteristics. The SQUID consists of an RF SQUID control unit. Phase-locked pulse-width modulation (PWM) was used to construct a flux-locked-loop (FLL) circuit in the SQUID control unit. The operation of the optical fiber feedback SQUID is stable when a common mode voltage of AC 100 V/50 Hz is applied. It has an energy resolution of 1*10/sup -28/ J/Hz. The authors describe the measurement of an auditory evoked field from the human brain in a magnetically shielded room using the fiber feedback SQUID with a gradiometer-type pickup coil. >

Background and PurposeThe traditional Chinese medicine, diosgenin (Dio), has attracted increasing attention because it possesses various therapeutic effects, including anti-tumor, anti-infective and anti-allergic properties. However, the commercial application of Dio is limited by its extremely low aqueous solubility and inferior bioavailability in vivo. Soluplus, a novel excipient, has great solubilization and capacity of crystallization inhibition. The purpose of this study was to prepare Soluplus-mediated Dio amorphous solid dispersions (ASDs) to improve its solubility, bioavailability and stability.MethodsThe crystallization inhibition studies were firstly carried out to select excipients using a solvent shift method. According to solubility and dissolution results, the preparation methods and the ratios of drug to excipient were further optimized. The interaction between Dio and Soluplus was characterized by differential scanning calorimetry (DSC), fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and molecular docking. The pharmacokinetic study was conducted to explore the potential of Dio ASDs for oral administration. Furthermore, the long-term stability of Dio ASDs was also investigated.ResultsSoluplus was preliminarily selected from various excipients because of its potential to improve solubility and stability. The optimized ASDs significantly improved the aqueous solubility of Dio due to its amorphization and the molecular interactions between Dio and Soluplus, as evidenced by dissolution test in vitro, DSC, FT-IR spectroscopy, SEM, PXRD and molecular docking technique. Furthermore, pharmacokinetic studies in rats revealed that the bioavailability of Dio from ASDs was improved about 5 times. In addition, Dio ASDs were stable when stored at 40°C and 75% humidity for 6 months.ConclusionThese results indicated that Dio ASDs, with its high solubility, high bioavailability and high stability, would open a promising way in pharmaceutical applications.

This paper demonstrates a design of a planar multi-turn flux transformer integrated with a superconducting labyrinth resonator serving as the planar tank circuit for a radio frequency (rf) superconducting quantum interference device (SQUID) magnetometer. All structures were patterned from 200 nm-thick epitaxial YBa/sub 2/Cu/sub 3/O/sub 7/ (YBCO) films grown on 10/spl times/10 mm/sup 2/ LaAlO/sub 3/ substrates. A double-hole washer SQUID had one hole coupled to the input coil of the labyrinth resonator and the other hole coupled to the input coil of the multi-turn flux transformer using a flip-chip configuration to form a magnetometer. This resonator has a good high-frequency coupling to the double-hole rf SQUID, thus securing its optimum operation. For the voltage-to-flux (transfer function) coefficient, a value of 300-500 /spl mu/V//spl Phi//sub 0/ was obtained. A SQUID magnetometer with an inductance of 210 pH exhibited white flux noise of 11.5 /spl mu//spl Phi//sub 0///spl radic/Hz at 77 K. This corresponded to a white magnetic field noise of 11.5 fT//spl radic/Hz.

We propose a new configuration for direct-coupling-type high-Tc superconducting quantum interference device (SQUID) magnetometers consisting of two pickup coils per SQUID on a bicrystal substrate. The SQUID and pickup coils can be arranged symmetrically without covering the bicrystal line on the substrate. This configuration should produce a large coupling coefficient from the pickup coil to the SQUID, and thus a large effective pickup area. First, we optimized the structure and dimensions of the pickup coils using an analogous model made of normal metal. Second, we fabricated SQUIDs for this configuration, in which the slitlike holes were located parallel to the bicrystal line. We also fabricated magnetometers consisting of pickup coils and SQUIDs of this configuration from YBCO film on bicrystal 10 mm × 10 mm SrTiO3 substrates. An effective area of 0.42 mm2 has been achieved, which was measured by applying an external magnetic field.

Inductance is a key parameter when optimizing the performance of superconducting quantum interference device (SQUID) magnetometers made from the high temperature superconductor YBa2Cu3O7−x (YBCO) because lower SQUID inductance L leads to lower flux noise, but also weaker coupling to the pickup loop. In order to optimize the SQUID design, we combine inductance simulations and measurements to extract the different inductance contributions, and measure the dependence of the transfer function VΦ and flux noise on L. A comparison between two samples shows that the kinetic inductance contribution varies strongly with film quality, hence making inductance measurements a crucial part of the SQUID characterization. Thanks to the improved estimation of the kinetic inductance contribution, previously found discrepancies between theoretical estimates and measured values of VΦ and could to a large extent be avoided. We then use the measurements and improved theoretical estimations to optimize the SQUID geometry and reach a noise level of = 44 fT/ for the best SQUID magnetometer with a 8.6 mm × 9.2 mm directly coupled pickup loop. Lastly, we demonstrate a method for reliable one-time sensor calibration that is constant in a temperature range of several kelvin despite the presence of temperature dependent coupling contributions, such as the kinetic inductance. The found variability of the kinetic inductance contribution has implications not only for the design of YBCO SQUID magnetometers, but for all narrow linewidth SQUID-based devices operated close to their critical temperature.