ABSTRACT
Acute pancreatitis is the most common iatrogenic dilemma of endoscopic retrograde cholangiopancreatography, and it is associated with significant morbidity and mortality. Several factors have been implicated in the pathogenesis of post-endoscopic retrograde cholangiopancreatography pancreatitis, and preventive measures were practiced accordingly. This study aims to refine the potential mechanisms that trigger post-endoscopic retrograde cholangiopancreatography pancreatitis and define the role of enteropeptidase in the pathogenesis of post-endoscopic retrograde cholangiopancreatography pancreatitis. Furthermore, address the role of a new novel medication known as SCO-792, a potent enteropeptidase inhibitor, in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Post-endoscopic retrograde cholangiopancreatography pancreatitis is caused by premature activation of the pancreatic enzymes within the pancreatic parenchyma. This activation is either an autoactivation due to direct provocation of intra-acinar enzymes as a result of the procedure or due to activation by enterpeptidase, a rate-limiting enzyme. Endoscopic retrograde cholangiopancreatography interjects duodenal juice that is rich in enterokinase into the pancreatic-biliary tract, which in turn leads to intra-ductal activation of trypsinogen and subsequent enzymes. Given the vital role of enterokinase in initiating the pathogenesis of pancreatitis, enteropeptidase inhibition may prevent and reduce the severity of post-endoscopic retrograde cholangiopancreatography pancreatitis. SCO-792, a novel enteropeptidase inhibitor, is developed by SCOHIA Pharma, and pre-clinical trials confirmed its efficacy in inhibiting enteropeptidase. Studies are needed to confirm the efficacy of enteropeptidase inhibitors in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis.
ABSTRACT
Polycystic ovary syndrome (PCOS) is a complex and common multisystemic disorder. Women with PCOS have up to eight times higher prevalence of depression than control groups. This paper aims to explore the underlying risk factors for developing depression in this high-risk group. Studies indicate an interplay of multiple mechanisms that place women with PCOS at an increased risk for depression. The pathophysiology thought to play a role includes disturbances in the endocrine axes and changes to the metabolic pathway. The risk of depression is independently linked to insulin resistance and obesity in this population. However, rates of depression were still higher than control groups when accounting for these variables, demonstrating that they are not the only mechanism causing depression. The clinical manifestations of hyperandrogenism and menstrual abnormalities may compound negative views and lower self-esteem and negatively impact mood. Many of these women also struggle with infertility, and due to the added external pressures like societal beliefs and culture, they may be further negatively impacted and worsen their depressive symptoms. The prevalence of depression in women with PCOS is high; thus, this paper highlights the essential understanding of the underlying mechanisms at play. This is to better aid in addressing the fundamental cause of depression in this high-risk group effectively.
