The outcomes of growth hormone therapy in the obstructive sleep apnea parameters of Prader-Willi syndrome patients: a systematic review.

PURPOSE: Prader-Willi syndrome is a serious genetic condition, capable of causing endocrinological imbalance, which has as one of its main treatments the growth hormone therapy. However, this therapy still causes some uncertainty concerning its effects on the respiratory parameters of those patients, especially in cases of obstructive sleep apnea, therefore, presenting a need for the analysis of the relationship between the therapy and the otolaryngologic condition. METHODS: A systematic review following the PRISMA model was developed, with searches for keywords made in the databases PubMed (MEDLINE), Scopus, and Web of Science and registration in the PROSPERO platform (CRD42023404250). RESULTS: Three randomized controlled trials were considered eligible for inclusion in the review. None of the studies demonstrated statistically significant modifications in the obstructive sleep apnea parameters of Prader-Willi patients related to the growth hormone administration. CONCLUSIONS: Growth hormone therapy is safe for Prader-Willi syndrome patients when analyzing their obstructive sleep apnea parameters.

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.

Anti-inflammatory Therapy by Cholinergic and Purinergic Modulation in Multiple Sclerosis Associated with SARS-CoV-2 Infection.

The virus "acute respiratory syndrome coronavirus 2" (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19), initially responsible for an outbreak of pneumonia in Wuhan, China, which, due to the high level of contagion and dissemination, has become a pandemic. The clinical picture varies from mild to critical cases; however, all of these signs already show neurological problems, from sensory loss to neurological diseases. Thus, patients with multiple sclerosis (MS) infected with the new coronavirus are more likely to develop severe conditions; in addition to worsening the disease, this is due to the high level of pro-inflammatory cytokines, which is closely associated with increased mortality both in COVID-19 and MS. This increase is uncontrolled and exaggerated, characterizing the cytokine storm, so a possible therapy for this neuronal inflammation is the modulation of the cholinergic anti-inflammatory pathway, since acetylcholine (ACh) acts to reduce pro-inflammatory cytokines and acts directly on the brain for being released by cholinergic neurons, as well as acting on other cells such as immune and blood cells. In addition, due to tissue damage, there is an exacerbated release of adenosine triphosphate (ATP), potentiating the inflammatory process and activating purinergic receptors which act directly on neuroinflammation and positively modulate the inflammatory cycle. Associated with this, in neurological pathologies, there is greater expression of P2X7 in the cells of the microglia, which positively activates the immune inflammatory response. Thus, the administration of blockers of this receptor can act in conjunction with the action of ACh in the anticholinergic inflammatory pathway. Finally, there will be a reduction in the cytokine storm and triggered hyperinflammation, as well as the level of mortality in patients with multiple sclerosis infected with SARS-CoV-2 and the development of possible neurological damage.

Purinergic Signaling of ATP in COVID-19 Associated Guillain-Barré Syndrome.

Declared as a global public health emergency, coronavirus disease 2019 (COVID-19) is presented as a disease of the respiratory tract, although severe cases can affect the entire organism. Several studies have shown neurological symptoms, ranging from dizziness and loss of consciousness to cerebrovascular and neurodegenerative diseases. In this context, Guillain-Barré syndrome, an immune-mediated inflammatory neuropathy, has been closely associated with critical cases of infection with "severe acute respiratory syndrome of coronavirus 2" (SARS-CoV-2), the etiological agent of COVID-19. Its pathophysiology is related to a generalized inflammation that affects the nervous system, but neurotropism was also revealed by the new coronavirus, which may increase the risk of neurological sequel, as well as the mortality of the disease. Thus, considering the comorbidities that SARS-CoV-2 infection can promote, the modulation of purinergic signaling can be applied as a potential therapy. In this perspective, given the role of adenosine triphosphate (ATP) in neural intercommunication, the P2X7 receptor (P2X7R) acts on microglia cells and its inhibition may be able to reduce the inflammatory condition of neurodegenerative diseases. Finally, alternative measures to circumvent the reality of the COVID-19 pandemic need to be considered, given the severity of critical cases and the viral involvement of multiple organs.

Increased oxidative stress and inflammatory markers contrasting with the activation of the cholinergic anti-inflammatory pathway in patients with metabolic syndrome.

INTRODUCTION: Metabolic syndrome (MetS) is a disorder that is closely associated with risk factors that increase the chance of atherosclerosis and cardiovascular diseases. We demonstrate the presence of inflammation and oxidative stress in patients with MetS through levels of antioxidants and oxidative and inflammatory markers, in order to determine influential variables in therapy. METHODS: In this study, lipid peroxidation, carbonylated protein content and enzymatic and non-enzymatic antioxidants were evaluated in samples obtained from 30 patients with MetS and 30 control patients. In addition, acetylcholinesterase (AChE) activity, C-reactive protein (CRP) and uric acid (UA) levels were determined to investigate the inflammatory process in patients with MetS. RESULTS: Our results demonstrated an increase in the levels of oxidative markers, such as substances reactive to thiobarbituric acid (TBARS) and carbonyl protein. In addition, a decrease in the defense of non-enzymatic antioxidants, such as levels of vitamin C and glutathione (GSH) in patients with MetS. As for inflammatory markers, CRP and UA were increased in patients with MetS. Finally, activation of the cholinergic anti-inflammatory pathway was observed due to decreased AchE activity in patients with MetS. CONCLUSION: The analyzes indicated oxidative stress, together with a reduction in the levels of antioxidant enzymes, corroborating the high consumption of these proteins. In addition, inflammation and activation of the cholinergic anti-inflammatory pathway was observed by the AChE analysis. Thus, the activation of this pathway can be studied as a possible route to a potential therapy. In addition, the markers AChE, CRP and UA may be used as a focus for the treatment of MetS.

Potential Therapeutic Role of Purinergic Receptors in Cardiovascular Disease Mediated by SARS-CoV-2.

Novel coronavirus disease 2019 (COVID-19) causes pulmonary and cardiovascular disorders and has become a worldwide emergency. Myocardial injury can be caused by direct or indirect damage, particularly mediated by a cytokine storm, a disordered immune response that can cause myocarditis, abnormal coagulation, arrhythmia, acute coronary syndrome, and myocardial infarction. The present review focuses on the mechanisms of this viral infection, cardiac biomarkers, consequences, and the possible therapeutic role of purinergic and adenosinergic signalling systems. In particular, we focus on the interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2 and of adenosine (Ado) with A2A and A3 receptors, as well as their roles in host immune responses. We suggest that receptors of purinergic signalling could be ideal candidates for pharmacological targeting to protect against myocardial injury caused by a cytokine storm in COVID-19, in order to reduce systemic inflammatory damage to cells and tissues, preventing the progression of the disease by modulating the immune response and improving patient quality of life.