Synthesis,Characterization, and in Vitro Stability of Chitosan-Methotrexate Conjugates

Pharmaceutical Research -     

Anti-anxiety effect of a novel 5-HT3 receptor antagonist N-(benzo[d]thiazol-2-yl)-3-ethoxyquinoxalin-2-carboxamide (6k) using battery tests for anxiety in mice

Objective:

To investigate the anti-anxiety activity of “6k”, a novel 5-hydroxytryptamine type 3 (5-HT₃) receptor antagonist in in mice.

Materials and Methods:

Anti-anxiety activity of “6k” (1, 2, and 4 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by behavioral tests such as elevated plus maze (EPM), open field test (OFT), light-dark box (L&D), and hole board test (HBT). Diazepam (2 mg/kg, i.p.) served as reference standard.

Results:

“6k” significantly (P < 0.05) increased the time and entries in open arm in EPM as compared to vehicle control group. Further, “6k” significantly (P < 0.05) increased the central and peripheral ambulation along with rearings and time in central area; whereas, reduced the fecal pellets in OFT as compared to vehicle control group. There was significant (P < 0.05) reduction in the latency to enter dark chamber; whereas, increased number of crossings and time in light chamber in L&D aversion test by treatment with “6k” as compared to vehicle control group. In HBT, “6k” significantly (P < 0.05) increased the number of head dipping and squares crossed; whereas, reduced the latency for first head dip and number of fecal pellets as compared to vehicle control group.

Conclusion:

A novel 5-HT₃ receptor antagonist has anti-anxiety action.KEY WORDS: 5-HT₃ antagonist, anxiety, elevated plus maze, open field test, hole board test     

UFLC method development and validation of a novel triethylamine containing thiophene S006‐830 ‐ an antitubercular molecule and its application to pharmacokinetic and bioavailability studies in SD rats

A sensitive and selective ultra fast liquid chromatography (UFLC) method has been developed and validated for the determination of a potent and novel antitubercular compound S006‐830 in Sprague Dawley (SD) rat plasma. Samples were extracted and processed by protein precipitation method using acetonitrile. Chromatographic separation was achieved on a Phenomenex, Luna C‐18 column (3μm, 100mm x 2mm i.d.) under isocratic condition. Detection was performed on UFLC‐NEXERA system (LC‐30AD, Shimadzu, Kyoto, Japan) with a degasser (DGU‐20A), auto‐injector (SIL‐30AC), fixed with a 100‐μL loop. Method was found sensitive and reproducible over a linearity range of 15.6‐2000 ng/mL. Recovery of S006‐830 and internal standard was found >90% for spiked matrix control and standard quality control plasma samples. This validated method was successfully applied to generate pharmacokinetic profile of S006‐830 in SD rats. Oral dose proportionality studies were conducted at 100, 50, 25 mg/Kg dose levels, while an IV study was conducted at 25 mg/Kg dose. There was dose dependent increase in AUC and C_max indicating S006‐830 to exhibit linear pharmacokinetics. S006‐830 exhibited favorable bioavailability in the range of 45‐55%. Copyright © 2014 John Wiley & Sons, Ltd.     

Electrocochleography in cochlear implantation: Development,applications, and future directions

Electrocochleography (ECochG) is an electrophysiological technique that records electrical potentials generated by different components of the inner ear and peripheral cochlear nerve in response to acoustic stimulation. ECochG responses can be analyzed into (1) cochlear microphonics (CM), (2) auditory nerve neurophonics, (3) summating potential, and (4) compound action potential. Over the past few decades, there have been ongoing refinements in technique and updates in the understanding of recorded potentials. Historically, ECochG found its main application in the diagnostic evaluation of Meniere’s disease (MD). However, in the last decade, the focus has shifted towards cochlear implantation (CI). In patients with residual hearing after CI, combined electric and acoustic stimulation has resulted in improved hearing and speech outcomes. Despite efforts to mitigate trauma during electrode insertion, hearing preservation rates vary after surgery. During implantation, real-time ECochG offers an opportunity to measure frequency specific CMs elicited from a localized region in the cochlea as the surgeon inserts the electrode array. In extracochlear ECochG recordings, the recording electrode can be placed on the promontory, the stapes, or the tympanic membrane. Intracochlear ECochG can be performed by inserting a recording electrode into the cochlea or by using one of the CI electrodes as the recording electrode. The loss of intraoperative ECochG signal may indicate cochlear trauma from electrode insertion, but the association between intraoperative ECochG changes and cochlear trauma remains controversial. The ability to monitor cochlear trauma during CI electrode placement holds promise to improve hearing preservation outcomes, modify surgical techniques, and change electrode design. The goal of this review is to provide a comprehensive overview of the electrophysiology and history of ECochG, discuss its recent applications in CI, and explore the ongoing research in this expanding field.     

Hydatid cyst

A 3-year-old girl who presented with clinical features suggesting a choledochal cyst was found to have a retroperitoneal hydatid cyst. The correct diagnosis was made at operation. Details regarding the history, results of investigations, and operative findings are presented.     

Psoas abscess: drainage through Petit's triangle

Thirteen cases of psoas abscess were treated by surgical drainage through Petit's triangle. This underutilized anatomic space provides a simple and effective route for drainage of retroperitoneal abscesses. Correspondence to: K. L. N. Rao     

The absence of CD20 messenger RNA in recurrent cutaneous B-cell lymphoma following rituximab therapy

BACKGROUND: Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported. METHODS: Four patients with CD20-positive cutaneous B-cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available. RESULTS: Cutaneous relapses occurring within 1.5-3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction-based methodology. CONCLUSIONS: Rituximab may be associated with the emergence of CD20-negative B-cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re-expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.