Epipericardial Fat Necrosis and Covid-19.

Background: Epipericardial fat necrosis (EFN) is a rare and self-limiting cause of acute chest pain. We describe a case of EFN in a patient with a recent coronavirus disease (COVID-19). Case Presentation: A 55-year-old male presented with a sudden onset of left-sided pleuritic chest pain for the past two days. The patient was diaphoretic, tachypneic, and tachycardic. Acute coronary syndrome was ruled out. A computed tomography (CT) pulmonary angiogram revealed an ovoid encapsulated fatty mass surrounded by dense appearing tissue. Patient symptoms improved remarkably with a short course of non-steroidal anti-inflammatory drugs (NSAIDs). Discussion: EFN typically presents with a sudden onset of excruciating chest pain. Misdiagnosis, under-diagnosis, and mismanagement are unavoidable. EFN is incidentally diagnosed on CT scan. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects visceral adipose tissue and appears to increase the risk of EFN by promoting inflammatory cytokine production and death of adipocytes. Conclusion: EFN is a rare cause of acute chest pain. SARS-CoV-2 is likely to induce EFN. This rare clinical entity should be considered in the differential of acute chest pain especially in patients with active or recent COVID-19. LEARNING POINTS: Epipericardial fat necrosis (EFN) is a rare cause of acute pleuritic chest pain that is often misdiagnosed and mismanaged.SARS-CoV-2 can possibly increase the risk of EFN and this entity should be considered in the differential of chest pain, especially in patients with active or recent coronavirus disease (COVID-19).Clinician awareness of EFN and its potential association with COVID-19, can reduce unnecessary testing and emotional distress.

Thiadiazine-thione derivatives ameliorate STZ-induced diabetic neuropathy by regulating insulin and neuroinflammatory signaling.

Diabetes Mellitus is accompanied by chronic hyperglycemia, inflammation, and related molecular processes, which leads to diabetic neuropathy. In this work, we tested Thiadiazine-thione (TDT) synthetic derivatives TDT1 and TDT2 against streptozotocin (STZ)-induced diabetic neuropathy. Sprague Dawley's rats, SH-SY5Y neuronal and BV2 microglial cells were employed in this work, followed by behavioral, biochemical, and morphological studies utilizing RT-qPCR, ELISA, Immunoblotting, immunohistochemistry, Immunofluorescence, and in silico analyses. TDT1 and TDT2 abolished STZ-induced allodynia and hyperalgesia. Next, we examined IRS1/PI3K/AKT signaling to assess TDT1 and TDT2's impact on diabetic neuropathy. STZ downregulated IRS1, PI3K, AKT mRNA and protein expression in rat spinal cord and SH-SY5Y neuronal cells. TDT1 and TDT2 improved IRS1, PI3k, and AKT mRNA and protein expression. STZ elevated GSK3ß mRNA and protein expression in vivo and in vitro, whereas TDT1 and TDT2 mitigated it. STZ increased the expression of inflammatory mediators such as p-NF-κB, TNF-α, and COX-2 in rat spinal cord lysates. TDT1 and TDT2 co-treatment with STZ decreased inflammatory cytokine expression by ameliorating astrocytosis (revealed by increased GFAP) and microgliosis (indicated by increased Iba1). TDT1 and TDT2 reduced STZ-induced JNK, Iba1, and COX-2 upregulation in BV2 microglial cells validating our in vivo findings. In silico molecular docking and MD simulations analyses suggested that TDT1 and TDT2 have IRS binding affinity, however, both compounds had an identical binding affinity, but distinct interaction pattern with IRS protein residues. Overall, these findings demonstrate that TDT derivatives mitigated STZ-induced neuropathy through modulating the insulin and inflammatory signaling pathways.

The effect of statins on RyR and RyR-associated disease.

We sought to review the effects of statins on the ryanodine receptor (RyR) and on RyR-associated diseases, with an emphasis on catecholaminergic polymorphic ventricular tachycardia (CPVT). Statins can affect skeletal muscle and produce statin-associated muscle symptoms (SAMS) but have no adverse effects on cardiac muscle. These contrasting effects may be due to differences in how statins affect the skeletal (RyR1) and cardiac (RyR2) RyR. We searched PubMed to identify English language articles reporting the pathophysiology of the RyR, the effect of statins on RyR function, and on RyR-associated genetic diseases. We selected 150 articles for abstract review, 96 of which provided sufficient information to be included and were reviewed in detail. Fifteen articles highlighted the interaction of statins with the RyR. Nine identified the interaction of statins with RyR1, six addressed the interaction of statins with RyR2, 13 suggested that statins reduce ventricular arrhythmias (VA), and seven suggested that statins increase the risk of malignant hyperthermia (MH). In general, statins increase RyR1 and decrease RyR2 activity. We identified no articles examining the effect of statins on CPVT, a condition often caused by defects in RyR2. Statins appear to increase the risk of MH and decrease the risk of ventricular arrhythmia. The effect of statins on CPVT has not been directly examined, but statins' reduction in RyR2 function and their apparent reduction in VA suggest that they may be beneficial in this condition.