Kinetics and mechanism of oxidation of chloramphenicol by 1-chlorobenzotriazole in acidic medium

Chloramphenicol (CAP) is an antibiotic drug having a wide spectrum of activity. The kinetics of oxidation of chloramphenicol by 1-chlorobenzotriazole (CBT) in HClO4 medium over the temperature range 293–323 K has been investigated. The reaction exhibits first-order kinetics with respect to [CBT]o and zero-order with respect to [CAP]o. The fractional-order dependence of rate on [H+] suggests complex formation between CBT and H+. It fails to induce polymerization of acrylonitrile under the experimental conditions employed. Activation parameters are evaluated. The observed solvent isotope effect indicates the absence of hydride transfer during oxidation. Effects of dielectric constant and ionic strength of the medium on the reaction rate have been studied. Oxidation products are identified. A suitable reaction scheme is proposed and an appropriate rate law is deduced to account for the observed kinetic data

Hesperidin Ameliorates Immobilization-Stress-Induced Behavioral and Biochemical Alterations and Mitochondrial Dysfunction in Mice by Modulating Nitrergic Pathway

The present study was aimed to evaluate the protective effect of hesperidin against immobilization-stress-induced alterations in biochemical, behavioral, and mitochondrial functions in mice. In many instances neuroscientists have reported that acute immobilization stress for 6 h resulted in anxiety and impaired locomotor activity due to excess oxidative-nitrergic stress, depletion of antioxidant defense mechanisms, and mitochondrial dysfunction in animals. In the present study, 6 h of acute immobilization stress had significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in Swiss albino mice. Fourteen days of pretreatment with Hesperidin (50 and 100 mg/kg, p.o.) significantly and dose-dependently inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress. Furthermore, pre-treatment of l-arginine (50 mg/kg, i.p.), a nitric oxide precursor, reversed the protective effect of Hesperidin (50 and 100 mg/kg) (P < 0.05). In contrast, pretreatment of l-NAME (5 mg/kg, i.p.), a nitric oxide synthase inhibitor, potentiated the protective effect of Hesperidin (P < 0.05). These results suggest the possible involvement of nitrergic pathway in the protective effect Hesperidin against immobilization-stress-induced behavioral, biochemical, and mitochondrial dysfunction in mice

DEVELOPMENT AND VALIDATION OF SEVEN PHENYL HYDRAZINE CHLORO ESTER ISOMERS (PGIs) BY RP-HPLC-UV METHOD IN ANTICOAGULANT DRUG SUBSTANCE; APIXABAN

Objective: The objective of this work was to develop and validate a simple and sensitive reverse-phase high-pressure liquid chromatography method for the determination of seven potential genotoxic impurities in Apixaban drug substance. Methods: The optimized separation was achieved by using ACE 3 C18 PFP (150 mm×4.6 mm, 3 µm) HPLC column. The mobile phase-A was a degassed mixture of 0.01M Ammonium acetate buffer(PH adjusted 4.9±0.05 with diluted glacial acetic acid) and mobile phase-B was a degassed mixture of Acetonitrile, Isopropyl alcohol and Buffer PH 4.9 in the ratio of 60:20:20 v/v/v. The gradient program was operated at a flow rate of 1.0 ml/min and UV detection was at 330 nm. Results: The method was superior at linearity for seven impurities and correlation coefficient values were larger than 0.999, moreover, in the separation point of view, this method further achieved no matrix interference through chromatography by better resolution of the other impurities from the Apixaban drug substance and its related impurities for the accurate analysis of seven potential genotoxic impurities. The established limits of detection (LOD), limits of quantification (LOQ) values for the seven mutagenic impurities were each of 5 ppm (0.015µg/ml) and15 ppm (0.045µg/ml) respectively. The developed method was validated as per ICH guidelines and applied as a generic method to determine these seven potential genotoxic impurities for the pharmaceutical process control and drug material release. Conclusion: Validation of this analytical method was carried out including stability, selectivity, linearity, accuracy, system precision, method precision and intermediate precision thus proving that the described RP-HPLC method could be employed for fast and simple analysis of sevenphenyl hydrazine chloro ester isomers in Apixaban drug substance

Subthreshold dynamics of the neural membrane potential driven by stochastic synaptic input

In the cerebral cortex, neurons are subject to a continuous bombardment of synaptic inputs originating from the network's background activity. This leads to ongoing, mostly subthreshold membrane dynamics that depends on the statistics of the background activity and of the synapses made on a neuron. Subthreshold membrane polarization is, in turn, a potent modulator of neural responses. The present paper analyzes the subthreshold dynamics of the neural membrane potential driven by synaptic inputs of stationary statistics. Synaptic inputs are considered in linear interaction. The analysis identifies regimes of input statistics which give rise to stationary, fluctuating, oscillatory, and unstable dynamics. In particular, I show that (i) mere noise inputs can drive the membrane potential into sustained, quasiperiodic oscillations (noise-driven oscillations), in the absence of a stimulus-derived, intraneural, or network pacemaker; (ii) adding hyperpolarizing to depolarizing synaptic input can increase neural activity (hyperpolarization-induced activity), in the absence of hyperpolarization-activated currents

Preparation, Characterization and In Vitro Drug Release Studies of 6-mercaptopurine Thin Film

Oral thin films of 6-mercaptopurine were fabricated from mucoadhesive polymer, chitosan and polyvinylpyrrolidone for the purpose of prolonging drug release and improving its bioavailability. All fabricated film formulations prepared were smooth and translucent, with good flexibility. The weight and thickness of all the formulations were found to be uniform. These films were also evaluated for surface pH, folding endurance, swelling percentage (% S) and in vitro disintegration time. Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) were used to evaluate the physico-chemical nature of the films. In-vitro drug release have shown enhanced release profiles for thin films compared to pure drug and the release patterns have been found to be pH dependant. The results of the study reveals that fabrication of 6-MP oral thin film by using solvent cast technology is a simple and an efficient method for drug delivery to achieve desired therapeutic compliance.Keywords: 6-mercaptopurine; In Vitro Drug Release; SEM; FTI

Application of 57Fe Mössbauer spectroscopy as a tool for mining exploration of bornite (Cu5FeS4) copper ore

Nuclear resonance methods, including Mössbauer spectroscopy, are considered as unique techniques suitable for remote on-line mineralogical analysis. The employment of these methods provides potentially significant commercial benefits for mining industry. As applied to copper sulfide ores, Mössbauer spectroscopy method is suitable for the analysis noted. Bornite (formally Cu5FeS4) is a significant part of copper ore and identification of its properties is important for economic exploitation of commercial copper ore deposits. A series of natural bornite samples was studied by 57Fe Mössbauer spectroscopy. Two aspects were considered: reexamination of 57Fe Mössbauer properties of natural bornite samples and their stability irrespective of origin and potential use of miniaturized Mössbauer spectrometers MIMOS II for in-situ bornite identification. The results obtained show a number of potential benefits of introducing the available portative Mössbauer equipment into the mining industry for express mineralogical analysis. In addition, results of some preliminary 63,65Cu nuclear quadrupole resonance (NQR) studies of bornite are reported and their merits with Mössbauer techniques for bornite detection discussed

Assessment of the status of empowerment of fisherwomen in Coastal Karnataka

Assessment of the status of empowerment of fisherwomen in Coastal Karnatak