Pathogenic mechanisms of pancreatitis

Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.

Modeling the effect of time delay in implementation of mitigation policies on the control of atmospheric greenhouse gases

Mitigation of the enhanced greenhouse gas(GHG)concentrations in the Earth's atmosphere is imperative to meet the climate change mitigation objective.Governments of many countries are developing and implementing various mitigation strategies to reduce their GHG emissions.However,a time delay between the formulation and implementation of these mitigation policies can affect their effectiveness in controlling greenhouse gas levels in the atmosphere.This work presents a nonlinear mathematical model to investigate the effect of application of mitigation strategies and the delay involved in their implementation over the reduction of atmospheric greenhouse gases.In model formulation,it is assumed that the mitigation strategies work two-fold;first they reduce the GHG emission rate from the anthropogenic source and second they increase the removal rate of greenhouse gas from the atmosphere.A comprehensive stability analysis of the proposed model system is made to examine its long-term behavior.The model analysis shows that an increase in the implementation rate of mitigation strategies and their efficiencies to cut down the GHG emission rate from point sources and increase the GHG uptake rate lead to reduction in equilibrium GHG concentration.It is found that a long delay in the execution of mitigation policies can destabilize the system dynamics and leads to the generation of periodic oscillations.The expression for the threshold value of the delay parameter at which periodic oscillations arise via Hopf-bifurcation is determined.The stability and direction of bifurcating periodic solutions are discussed.A sensitivity analysis is performed to investigate the effect of changes in key parameters over system dynamics.