Clinical pharmacology has a rich and storied history of many successful clinicians and scientists who have developed novel therapeutic and preventive agents, refined drug dosing regimens, and probed the depths of human physiology and molecular biology [1-5].

Abstract: Neurotensin (NT) contributes to pathophysiology of neurodegenerative and psychiatric diseases, and the signal of NT and neurotensin receptor 1 (NTR1) is closely associated with cancer, inflammation and immunomodulatory disease. So far, drug targeting NTR1 has not reached any primary endpoint in clinical trial or approval, and the number of reported active compounds against NTR1 is too small to provide any novel scaffold in facilitating NTR1-based lead identification. Thus, the search for new inhibitors is of great interest to current drug discovery. This work explored the use of support vector machine (SVM) combined with putative non-inhibitor generation method as a virtual screening (VS) tool. SVM developed by NTR1 inhibitors published before 2011 was verified by cross validation and by 20 independent test inhibitors published after 2011. By scanning large chemical libraries, low false-hit rates of 0.026% (3,452 out of 13.56M PubChem chemicals) and 0.065% (109 out of 168K MDDR chemicals) were identified. A further investigation of 115 compounds identified by this work found 17 novel scaffolds against NTR1, 29% of which have been reported to show CNS and cancer-related therapeutic effects. Therefore, SVM is effective in identifying novel NTR1 inhibitors, which can be a good starting point to facilitate CNS and anticancer drug discovery in the near future.

Abstract: Stress, both physical and psychological, is attracting increasing attention among neuro researchers. In the last 20 decades, there has been a surge of interest in the research of stress induced manifestations and this approach has resulted in the development of more appropriate animal models for stress associated pathologies and its therapeutic management. These stress models are an easy and convenient method for inducing both psychological and physical stress. To understand the behavioral changes underlying major depression, molecular and cellular studies are required. Dysregulation of the stress system may lead to disturbances in growth and development, and may this may further lead to the development of various other disorders. This article reviews the interrelation of Vitamin B12, androgens and cortisol in chronic stress model and their neurobiology, including the different neurotransmitters and heart function affected. There are various complications associated with stress and their management through various pharmacological and Non-Pharmacological techniques. The use of vitamin b12 in the treatment of stress related problems is in practice in both Indian and Western societies, Examination of the hyper-responsiveness of the Hypothalamic-Pituitary-Adrenal axis, consequent elevated serum cortisol, Androgens plus the effects of this upon brain structure and function, provides a model for understanding how chronic stress may be a causal vector in the development of major organ dysfunction like CVS dysfunction.

Abstract: It is important to prevent nausea and vomiting to maintain both the quality of life of patients with cancer and the efficacy of chemotherapy. The aim of this study was to examine the efficacy of aprepitant for treatment of chemotherapy-induced nausea and vomiting (CINV) in Japanese patients with gastrointestinal cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC) regimens. A single-center, retrospective study was performed in 37 consecutive patients scheduled for HEC (n=7) or MEC (n=30). The MASCC Antiemesis Tool (MAT) was used to assess CINV and safety and patient charts were assessed before and after use of the aprepitant regimen. During the first course of chemotherapy, patients received a standard antiemetic regimen. Aprepitant was added in the second chemotherapy cycle for patients who had insufficient relief of CINV with the standard antiemetic regimen. All patients in the HEC cohort were treated with S-1 and cisplatin and those in the MEC cohort received chemotherapy including FOLFOX, FOLFIRI and irinotecanmonotherapy. In patients receiving HEC, CINV symptoms tended to improve with use of aprepitant compared with antiemetic regimens without aprepitant; however, the differences were not significant. In patients receiving MEC, there were significant differences in acute and delayed nausea and vomiting with aprepitant treatment (p<0.05, Wilcoxon rank test). CINV symptoms improved in 70% and 78% of patients treated with HEC and MEC, respectively. These results suggest that aprepitant is effective for preventing CINV in patients with gastrointestinal cancer receiving HEC or MEC.

Abstract: We present for the first time treatment of patients with multiple sclerosis by minimally invasive therapeutic plasmapheresis using a nanomembrane (EC Certificate No CQ102011-ll). Plasmapheresis was carried out in accordance with the sixth revised edition of the “Guidelines on the use of Therapeutic Apheresis in Clinical Practice” [1], published in 2013, and the National consensus for intensive treatment of diseases by therapeutic apheresis in Bulgaria [2]. Four procedures of plasmapheresis were applied every other day with separation of plasma out of the circulation. The plasma separated from the patient was substituted with saline. This separated plasma contained immunoglobulins A, G and M, among others. Oxygen saturation was improved in the course of the plasmapheresis procedure. The observed reversal of the pathological process in the treated MS patients was not only based on subjective opinion of the patients, but also on objective research based on the scale of Kurtzke. During the plasmapheresis procedures we did not observe hemodynamic disturbances associated with the cardiovascular or the respiratory system.
The obtained results gave us ground to assume that the removal of pathogenic autoantibodies along with the application of a modern immunosuppressive therapy can change the prognosis, associated with invalidization of these patients.
We believe that this new, low-invasive plasmapheresis based on the use of nanomembrane, combined with modern immunosuppressive therapy would provide a good perspective for the quality of life and the prognosis of the treated patients.