Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone as Potential Therapeutics for Colorectal Cancers

There is a critical requirement for alternative strategies to provide the better treatment in colorectal cancer (CRC). Hence, our goal was to propose novel biomarkers as well as drug candidates for its treatment through differential interactome based drug repositioning. Differentially interacting proteins and their modules were identified, and their prognostic power were estimated through survival analyses. Drug repositioning was carried out for significant target proteins, and candidate drugs were analyzed via in silico molecular docking prior to in vitro cell viability assays in CRC cell lines. Six modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were highlighted considering their prognostic performance. Drug repositioning resulted in eight drugs (abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone). Moreover, significant in vitro inhibition profiles were obtained in abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline (positive control). Our findings may provide new and complementary strategies for the treatment of CRC.

Estimation of Nortriptyline hydrochloride in Bulk and Formulation by UV-Spectrophotometric Area Under Curve Method

The simple, precise and accurate UV-Spectrophotometric method has been developed and validated for the estimation of nortriptyline hydrochloride in bulk and dosage form. In that work was carried out for estimation of nortriptyline hydrochloride in bulk and pharmaceutical dosage form by utilizing area under curve (AUC) method. For this purpose the wavelength range 200-400nm was selected. DMSO was used as solvent throughout the work. Linearity was observed in concentration range 5-25µg/ml (R2 =0.996) for the method. The present method was found which can be used for routine quality control analysis for spectrophotometric estimation of Nortriptyline hydrochloride in bulk and dosage form. Keywords: Nortriptyline hydrochloride, Area under curve (AUC), DMSO, UV-Spectrophotometric.

Myofascial Pain: Diagnosis and Behavior in Patients with Orofacial Pain and TMD

The high prevalence, significant demand for treatment of patients with Chronic Pain, and the general difficulty of establishing an accurate diagnosis, together with psychosocial and behavioral conditions, lead many therapeutic approaches to failure or unexpected outcomes. The objective of the present report was to show the evolution of a clinical case of long-term and highintensity Myofascial Pain, in which the patient had been undergoing treatment with Tricyclic Antidepressants (Nortriptyline Hydrochloride) for two years, using minimally invasive conduct. In order to reach the Diagnostic Hypothesis of Myalgia, the DC/TMD (Diagnosis Criteria for Temporomandibular Disorders) protocol was employed, in which the subdivision of this form of TMD was attained. We found substantial myofascial impairment of chewing and cervical muscles, with referred pain and secondary cephalea. The temporomandibular joints (TMJ) did not exhibit any clinical changes in movement, noise or arthralgia. After locating the myofascial trigger points (TrPs), Dry Needling was incorporated, with manipulation of the oral and cervical musculature (with and without resistance), in addition to electrotherapy with TENS (Transcutaneous Electrical Nerve Stimulation) coupled with heat application. The patient was instructed to perform cervical and masseter stretching exercises twice daily and to carry out sleep and medication prophylaxis. The result was rewarding. After seven visits in six months, with an interval from the sixth to the seventh visit of sixty days (follow-up), the patient was discharged and scheduled to return after a six-month period. Pain episodes continue to occur occasionally, but with low intensity, score 3 on the visual analog scale (VAS), and short duration. The course of treatment was well administered by the patient, without the use of antidepressants and cephalea and myofascial pain, and without the use of interocclusal devices, as shown in this report.