Determination of rat plasma levels of sertraline enantiomers using direct injection with achiral–chiral column switching by LC–ESI/MS/MS

A highly sensitive and selective on-line two-dimensional reversed-phase liquid chromatography/electrospray ionization–tandem mass spectrometric (2D-LC–ESI/MS/MS) method to determine sertraline (SRT) enantiomers in rat plasma was developed and validated. The method was applied to separate and determine the diastereomers and enantiomers of SRT simultaneously. The 2D-LC–ESI/MS/MS system consisted of RAM column in first dimension for trapping proteineous part of plasma and a chiral Cyclobond column as second dimension for separation of enantiomers and diastereomers of SRT using 0.1% aqueous trifluoroacetic acid:acetonitrile (86:14, v/v) as mobile phase in an isocratic elution mode. The linear dynamic range was 0.5–200 ng/mL (r² > 0.999). Acceptable precision and accuracy were obtained over the calibration range. The assay was successfully used in the analysis of SRT enantiomers in rat plasma to support pharmacokinetic studies.     

Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from patients with Parkinson's disease: preliminary study

BACKGROUND: Evidence suggests that mitochondrial dysfunction stimulates the production of reactive oxygen species (ROS) that promote neural cell death in stroke and in Parkinson's disease. The sites of mitochondrial ROS production are not established but are generally believed to be located within the electron transport chain. AIMS: We studied the mitochondrial respiratory chain enzymes function from human circulating lymphocytes. SETTING AND DESIGN: Open study. MATERIALS AND METHODS: Forty patients with Parkinson's disease (PD) with 30 age-matched control subjects were selected in this study. The patients had received no treatment before the study was conducted. STATISTICAL ANALYSIS: The data from patients and controls were compared using two-tailed student's t-test and values were expressed as means +/- standard deviation (SD). RESULTS: Respiratory complex I + III and IV activities were significantly lower (P < 0.001) in patients than in control subjects. CONCLUSIONS: The use of lymphocytes for investigating the respiratory chain enzymes provides an easy, noninvasive method to assess mitochondrial function in patients with PD. Furthermore, our study supports the hypothesis that a biochemical defect in the respiratory chain may be involved in the pathogenesis of PD.     

The antithrombotic and anti-inflammatory effects of BCX-3607, a small molecule tissue factor/factor VIIa inhibitor

Tissue factor (TF) is a transmembrane glycoprotein that binds its zymogen cofactor, Factor VIIa (FVIIa) on the cell surface. Together (TF/FVIIa) they activate Factor X (FX) and Factor IX (FIX) and start the extrinsic pathway of blood coagulation. As such, the TF/FVIIa complex plays an important role in normal physiology as well as in thrombotic diseases such as unstable angina (UA), disseminated intravascular coagulation (DIC), and deep vein thrombosis (DVT). In addition to its function as an initiator of coagulation, TF/FVIIa plays an important role in inflammation. Expression of TF on the cell surface and its appearance as a soluble molecule are characteristic features of acute and chronic inflammation in conditions such as sepsis and atherosclerosis. Here we demonstrate that BCX-3607, a small molecule potent inhibitor of TF/FVIIa, reduces thrombus weight in an animal model of DVT. BCX-3607 also decreases the level of interleukin-6 (IL-6) in a LPS-stimulated mouse model of endotoxemia. Additionally, in vitro studies indicate that BCX-3607 blocks the generation of TF/FVIIa-induced IL-8 mRNA in human keratinocytes and reduces the TF/FVIIa-mediated generation of IL-6 and IL-8 in human umbilical vein endothelial cells (HUVEC). Therefore, BCX-3607 might block the TF/FVIIa-mediated coagulation and inflammation associated with pathological conditions.     

Evaluation of the pharmaceutical quality of docetaxel injection using new stability indicating chromatographic methods for assay and impurities

New stability indicating chromatographic methods have been developed for estimation of Assay and Impurities of Docetaxel in Docetaxel injection for evaluation of pharmaceutical quality. With this method, the process related impurities and degradants are well separated from the peaks due to placebo. The relative retention times and relative response factors of the known impurities have been established. The LOQ of the known impurities and docetaxel are found to be less than 0.2 μg /ml and the recovery falls in the range of 90–110%. Peak purities demonstrated the stability indicating nature of the methods. The methods developed in the present study overcome the lacunae of the existing published methodologies in evaluation of the quality of Docetaxel injection. In essence, the present study provides an improved methodology for evaluation of the pharmaceutical quality of Docetaxel injection.     

Candida Albicans Sub-Retinal Abscess following COVID-19

A 42-year-old male post-renal transplantation presented with sudden diminution of vision in the left eye. The right eye was lost following a failed vitreoretinal surgery 5 years ago. The patient had been hospitalized 4 months prior for coronavirus disease 2019 infection with a good recovery. The presenting visual acuity was 20/600 in the right eye and 20/250 in the left eye. Fundus examination revealed a sub-macular sub-retinal abscess in the left eye. Sub-retinal aspiration of the abscess revealed Candida albicans. The patient was managed with repeated intravitreal amphotericin B injections, following which the abscess resolved with scarring and vision improving to 20/60.     

Flexible and Polarization Independent Miniaturized Double-Band/Broadband Tunable Metamaterial Terahertz Filter

In this paper, the design of a double-band terahertz metamaterial filter with broadband characteristics using a single conducting layer is presented. The design uses a structured top metallic layer over a polyimide material. The proposed design has achieved broadband band-pass transmission characteristics at the resonances of 0.5 THz and 1.65 THz, respectively. The 3-dB bandwidths for these two resonances are 350 GHz and 700 GHz, respectively, which indicates that dual-band resonance with broadband transmission characteristics was obtained. The design has achieved the same transmission characteristics for two different orthogonal polarizations, which was confirmed using numerical simulation. The design was tested for a different angle of incidences and it was observed that this results in angle-independent transmission behavior. In addition, for obtaining tunable resonant behavior, the top conductor layer was replaced by graphene material and a silicon substrate was added below the polymer layer. By varying the Fermi level of graphene, modulation in amplitude and phase was observed in numerical simulation. The physical mechanism of double-band behavior was further confirmed by surface current distribution. The proposed design is simple to fabricate, compact, i.e., the size is λ₀/8, and obtained dual-band/broadband operation.