1. Nano chloroquine delivery against Plasmodium berghei NK65 induced programmed cell death in spleen
Satyajit TRIPATHY ; Sandeep K. DASH ; Somenath ROY ; Satyajit TRIPATHY ; Motlalepula G. MATSABISA ; Sourav CHATTOPADHYAY ; Sandeep K. DASH
Asian Pacific Journal of Tropical Medicine 2018;11(9):540-546
Objective: To compare the protective effects of chitosan-trypolyphosphate (CS-TPP) nanoparticle conjugated chloroquine(CQ) with effect of CQ alone on the reversal of splenic damages and induction of apoptosis. Methods: Different researches have been carried out to explore the potential role of chitosan based drug delivery system against parasitic diseases. After successive Plasmodium berghei NK65 parasiste infection by intraperitoneal injection in Swiss mice and subsequent parasite development, the ROS generation, anti-apoptotic and pro apoptotic protein levels in spleen were measured. To analyze caspases, flow cytometry study was performed with annexin V-FITC and with PI staining. Results: The results revealed that ROS mediated caspase 3 and 9 activation and the induction of apoptosis occurred during the parasitic infection. However, CS-TPP conjugated CQ was relatively better in reversing the splenic damage compared with similar effects of CQ alone. Conclusions: This study indicates that Plasmodium berghei NK65 induces apoptosis in the spleen. The study further shows that CS-TPP nanoparticles conjugation with CQ have positive influence on the recovery of damaged host's system towards maintenance of normal homeostasis, and this is shown to be selective to CS-TPP conjugated CQ treated animals only.
2.Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring
Peeyush KUMAR ; Sudheer K. VUYYURU ; Prasenjit DAS ; Bhaskar KANTE ; Mukesh Kumar RANJAN ; David Mathew THOMAS ; Sandeep MUNDHRA ; Pabitra SAHU ; Pratap Mouli VENIGALLA ; Saransh JAIN ; Sandeep GOYAL ; Rithvik GOLLA ; Shubi VIRMANI ; Mukesh K. SINGH ; Karan SACHDEVA ; Raju SHARMA ; Nihar Ranjan DASH ; Govind MAKHARIA ; Saurabh KEDIA ; Vineet AHUJA
Intestinal Research 2023;21(4):460-470
Background/Aims:
Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD).
Methods:
Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies.
Results:
One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively.
Conclusions
Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.