DESIGN AND DEVELOPMENT OF FLOATING PULSATILE DRUG DELIVERY OF LOSARTAN POTASSIUM

Objective: The objective of the present investigation was to the development of floating pulsatile drug delivery system of Losartan potassium (LP) tablets for obtaining no drug release during floating followed by pulsed, rapid drug release to achieve chronotherapeutic release. In hypertension, the risk of getting heart attacks early in the morning is high and therefore, there was need to develop drug delivery, which will release drugs at morning hours and provide efficacious therapy. LP is a short biological half-life (1.5-2.5h) and readily absorbed from the stomach and upper gastrointestinal tract. Methods: Tablet formulation was prepared by press coating of rapid release core tablets and core tablets were further top coated with a buoyant layer of HPMC K4M and sodium bicarbonate. Various grades of HPMC polymer (E5/E15/E50) were used for the pulsatile coating layer. The developed formulations were characterized for physical characteristics, floating lag time, floating time, release lag time, drug content, swelling index, in vitro dissolution studies, DSC and XRD. Results: The FTIR and DSC studies predicted that there was no chemical interaction between drug and excipients. The core tablet coated with HPMC E50 showed a high swelling index and release the drug 97.60±1.2% at 6h. Buoyant layer with 80 mg HPMC K4M and 25 mg sodium bicarbonate gave satisfactory floating lag time. Conclusion: The system showed an excellent lag phase followed by burst release in the distal small intestine, which gives site and time-specific delivery of LP acting as per chronotherapy for treatment of hypertension

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Covidetect: A Tkinter Desktop Application to Detect Coronavirus Using Chest Ct-scan

We are currently facing the threat of the Coronavirus Pandemic. The daily lives of people have come to a standstill. Tests to find out whether a person has contracted the virus are being conducted on a large scale. Due to this, the results are taking a long time to be released to the general people. This report proposes a desktop application built using the tkinter library which will help to detect COVID by checking for abnormalities in CT-Scan. This system tries to give a somewhat accurate prediction of whether the user is infected by coronavirus or not. This system basically tries to help the user to make use of his/her CT-SCAN images to predict corona virus in minimum time as compared to traditional tests. This system can be used as a primary or an intermediary step in the detection of the virus

Role of Immunohistochemical Markers in Evaluating Malignant Transformation of Oral Submucous Fibrosis: A Systematic Review

Objective(s): We present a systematically to identify, evaluate and assess the role of Immunohistochemical markers in Malignant Transformation of Oral Submucous Fibrosis (OSF). Materials and Methods: Extensive literature search was done to identify eligible through “MEDLINE”/ “PubMed”, “Scopus” and “Cochrane library” were searched for relative studies until December 2021. The included studies were published in English language were mainly retrospective original research\.These studies mainly evaluated the role of Immunohistochemical markers in Malignant Transformation of Oral Submucous Fibrosis. Results: Thirteen studies were included in the present study which had total of 549 cases. Most of the studies suggested use of combined biomarker model or panel of antibodies to minimize the risk of bias. Almost all the studies used ANOVA and chi-square test while kappa test analysis for interobserver variability test. Conclusions: The significance of immunohistochemical markers has been shown in study which can significantly contribute in diagnosing early event in process of Malignant transformation of suspicious OSF cases so that better treatment plan could be formulated for better prognosis. More efforts should be emphasized on combination of \antibodies and its importance in target drug therapy