Inhibiting Monoamine Oxidase in CNS and CVS would be a Promising Approach to Mitigating Cardiovascular Complications in Neurodegenerative Disorders.

The flavoenzyme monoamine oxidases (MAOs) are present in the mitochondrial outer membrane and are responsible for the metabolism of biogenic amines. MAO deamination of biological amines produces toxic byproducts such as amines, aldehydes, and hydrogen peroxide, which are significant in the pathophysiology of multiple neurodegenerative illnesses. In the cardiovascular system (CVS), these by-products target the mitochondria of cardiac cells leading to their dysfunction and producing redox imbalance in the endothelium of the blood vessels. This brings up the biological relationship between the susceptibility of getting cardiovascular disorders in neural patients. In the current scenario, MAO inhibitors are highly recommended by physicians worldwide for the therapy and management of various neurodegenerative disorders. Many interventional studies reveal the benefit of MAO inhibitors in CVS. Drug candidates who can target both the central and peripheral MAO could be a better to compensate for the cardiovascular comorbidities observed in neurodegenerative patients.

Translational Significance of GMF-ß Inhibition by Indazole-4-yl-methanol in Enteric Glial Cells for Treating Multiple Sclerosis.

In the emerging context of gut-brain control of multiple sclerosis (MS), developing therapeutics targeting proinflammatory proteins controlling the gut-brain immunomodulation is welcoming. One such immunomodulator is glia maturation factor-ß (GMF-ß). GMF-ß activation following GMF-ß-ser-83 phosphorylation upregulates proinflammatory responses and exacerbates experimental autoimmune encephalomyelitis (EAE). Notably, GMF-ß-/- mice exhibited no EAE symptoms. Thus, we identified 1H-indazole-4-yl-methanol (GMFBI.1) inhibitor which blocked GMF-ß-ser-83 phosphorylation critical in EAE suppression. To establish gut GMF-ß's role in EAE in the context of gut-brain involvement in neurodegenerative diseases, we altered gut GMFBI.1 bioavailability as an index of EAE suppression. At first, we identified Miglyol 812N as a suitable biocompatible GMFBI.1 carrier compared to other FDA-approved carriers using in silico molecular docking analysis. GMFBI.1 administration in Miglyol 812N enhanced its retention/brain permeability. Subsequently, we administered GMFBI.1-Miglyol 812N by subcutaneous/oral routes at different doses with differential GMFBI.1 bioavailability in gut and brain to assess the role of local GMFBI.1 bioavailability in EAE reversal by a pharmacokinetic approach. Deprival of gut GMFBI.1 bioavailability led to partial EAE suppression despite having sufficient GMFBI.1 in circulation to inhibit brain GMF-ß activity. Restoration of gut GMFBI.1 bioavailability led to complete EAE reversal. Molecular pathology behind partial/full EAE reversal was associated with differential GMF-ß-Ser-83 phosphorylation/GM-CSF expression levels in enteric glial cells owing to GMFBI.1 bioavailability. In addition, we observed leaky gut reversal, tight junction protein ZO-1 restoration, beneficial gut microbiome repopulation, recovery from gut dysbiosis, and upregulation of Treg cells. GMFBI.1's dual gut/brain targeting of GMF-ß has therapeutical/translational potential in controlling autoimmunity in MS.

Dietary foods containing nitric oxide donors can be early curators of SARS-CoV-2 infection: A possible role in the immune system.

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is a lethal virus that causes COVID-19 (Coronavirus disease 2019), the respiratory illness that has caused the COVID-19 pandemic. Even though multiple pharmacological trials are ongoing, there is no proof that any treatment will effectively cure or prevent COVID-19. Currently, COVID-19-infected patients are being managed with non-specific medications to suppress the symptoms and other associated co-morbidities. Nitric oxide is a bio-signaling molecule that has been shown to be effective for treating several viral infections in humans. Household Natural foods rich in nitrites and nitrates (NO donors) have been scientifically proven to have therapeutic benefits against immune-related respiratory tract infections. It was understood that NO could inhibit the early stage of SARS CoV-2 invasion into the human cell. Fruits and vegetables containing nitrites and nitrates have been revised and are now thought to be potential anti-CoV agents for effective control of other associated systemic disorders. The purpose of this review is to highlight some key facts about the treatment and prevention of COVID-19 infection with foods rich in nitric oxide and its donors. PRACTICAL APPLICATIONS: Improving the body's immune system is the early step to be considered as a preventive measure to stop the spreading of COVID-19 infection. Emerging research continues to mount that dietary nitrates/nitrites from plant foods are being healthy as well as keep us away from infectious diseases. They are now incorporated into low-risk adjuvant therapy for various infections and systemic disorders. This concept portrays the regular consuming foods such as fruits and vegetables that are rich in nitric oxide which have the potential to promote health, improve general well-being, and reduce the risk associated with the highly contagious diseases. Hence, we recommend adding nitrates and nitrites-containing food to the regular diet to improve the self-immunity as well as to fight against COVID-19 disease.

Anaesthesia for fixation of repeated pathological fractures in a patient with multiple myeloma.

The introduction of new chemotherapeutic agents for the treatment of multiple myeloma (MM) has improved the life expectancy and quality of life for these patients in the last decade. Therefore, more patients with MM are being treated for repeated pathological fractures. The anaesthesiologist should continue the optimum supportive care received by these patients in the perioperative period also, by understanding the pathophysiology of the disease, the adverse effects of the chemotherapeutic agents and the guidelines for their supportive care. We report the perioperative management of a patient with MM and discuss the perioperative anaesthetic considerations.