Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Hypoglycemia.

A relatively recent addition to the arsenal of antidiabetic drugs used for the treatment of type 2 diabetes mellitus (T2DM) has been the "incretin mimetics," a group of drugs that work on the glucagon-like peptide-1 (GLP-1) receptor and enhance insulin secretion from the pancreatic ß-cells in a glucose-dependent manner, more potently in hyperglycemic conditions, while suppressing glucagon secretion at the same time. Therefore, it was assumed that this class of drugs would have a lower risk of hypoglycemia than insulin secretagogues like sulphonylureas. However, GLP-1 receptor agonists have been proposed to cause hypoglycemia in healthy normoglycemic subjects implying that their action is not as glucose-dependent as once thought. Other studies concluded that they might not induce hypoglycemia and the risk is dependent on other individual factors. However, the FDA announced that the 12 GLP-1 receptor agonists currently available on the market had potential safety signs and evaluated the need for regulatory action. This review provides an overview of the studies that investigated the possible hypoglycemic effect of GLP-1 receptor agonists. In addition, the current review describes other adverse effects of GLP-1 receptor agonist treatment.

Coronaviruses in children: A review of potential mechanisms of childhood protection.

AIM: The 2019 coronavirus disease (COVID-19) has spread worldwide and the number of cases continues to rise exponentially. Epidemiologic reports indicate that severity of illness increases with age. However, the reasons behind the relative protection of children and infants are unclear. Whether the rationale is host-related or virus dependent is important to determine since the latter could change with viral mutations. We review factors that could affect the susceptibility of children to the novel coronavirus. METHODS: We search publications indexed on PUBMED. RESULTS: Descriptions of the pathophysiology of current and previous coronavirus infections suggest several viral targets and immunomodulatory pathways affecting the severity of illness. There is limited evidence to suggest age-variability of viral cell receptors and transmembrane co-factors required for coronavirus entry and replication. However, the ensuing cytokine storm and the effect of higher melatonin in children are age-dependent and could explain decreased disease variability in children. CONCLUSION: We believe that current evidence suggests host factors can play a role in disease severity in children and thus may remain protective despite potential virus mutation in the future. However, we recognise and discuss avenues of future research that can further illuminate the reasons children are protected from severe COVID-19 illness.

Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage.

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.

SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far.

In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes.

Successful transcatheter cryoablation in infants with drug-resistant supraventricular tachycardia: a case series.

PURPOSE: Drug-resistant supraventricular tachycardia can cause hemodynamic instability, especially in infants. There are no case-series reports of transcatheter cryoablation treatment for infants with drug-resistant supraventricular tachycardia. Our purpose is to report our experience with transcatheter cryoablation in three infants with drug-resistant supraventricular tachycardia. METHODS: We reviewed clinical and electrophysiologic data from infants who underwent cryothermal ablation for drug-resistant supraventricular tachycardia (SVT) at our institution. RESULTS: Three patients (age 10-42 days) underwent transcatheter cryothermal ablation over a 1-year period. None had arrhythmia suppression on medical management, and all had hemodynamic instability from persistent SVT episodes. Cryothermal mapping (-30 C) localized the suspected foci. All foci were adjacent to the AV node. Cryoablation lesions were delivered at and around mapped foci. In one patient, cryothermal energy application eliminated the SVT but resulted in transient right bundle branch block that resolved later. Two patients had hemodynamically insignificant episodes of SVT in the immediate post-ablation period that resolved with standard antiarrhythmic treatment. One died of sepsis but remained SVT free for 10 days after the procedure without antiarrhythmic medications. Neither of the two surviving patients had SVT recurrence at 6-month follow-up off medications. CONCLUSIONS: In our series, transcatheter cryoablation was an effective treatment for drug-resistant SVT in infants. We encountered some early nonsustained post-procedure SVT; however, such episodes did not predict procedural failure.