Cytokine storm in human monkeypox: A possible involvement of purinergic signaling.

Some evidence has indicated that monkeypox can induce a cytokine storm. Purinergic signaling is a cell pathway related to the cytokine storm. However, the precise mechanisms that lead to cytokine storms in monkeypox infections and the possible involvement of purinergic signaling in the immune response to this virus remain unknown. In this review article, we aimed to highlight a body of scientific evidence that consolidates the role of the cytokine storm in monkeypox infection and proposes a new hypothesis regarding the roles of purinergic signaling in this immune-mediated mechanism. We further suggested some purinergic signaling modulators to mitigate the deleterious and aggravating effects of immune dysregulation in human monkeypox virus infection by inhibiting P2X3, P2X7, P2Y2, and P2Y12, reducing inflammation, and activating A1 and A2A receptors to promote an anti-inflammatory response.

Implications of COVID-19 in Parkinson's disease: the purinergic system in a therapeutic-target perspective to diminish neurodegeneration.

The pathophysiology of Parkinson's disease (PD) is marked by degeneration of dopaminergic neurons in the substantia nigra. With advent of COVID-19, which is closely associated with generalized inflammation and multiple organ dysfunctions, the PD patients may develop severe conditions of disease leading to exacerbated degeneration. This condition is caused by the excessive release of pro-inflammatory markers, called cytokine storm, that is capable of triggering neurodegenerative conditions by affecting the blood-brain barrier (BBB). A possible SARS-CoV-2 infection, in serious cases, may compromise the immune system by triggering a hyperstimulation of the neuroimmune response, similar to the pathological processes found in PD. From this perspective, the inflammatory scenario triggers oxidative stress and, consequently, cellular dysfunction in the nervous tissue. The P2X7R seems to be the key mediator of the neuroinflammatory process, as it acts by increasing the concentration of ATP, allowing the influx of Ca2+ and the occurrence of mutations in the α-synuclein protein, causing activation of this receptor. Thus, modulation of the purinergic system may have therapeutic potential on the effects of PD, as well as on the damage caused by inflammation of the BBB, which may be able to mitigate the neurodegeneration caused by diseases. Considering all the processes of neuroinflammation, oxidative stress, and mitochondrial dysfunction that PD propose, we can conclude that the P2X7 antagonist acts in the prevention of viral diseases, and it also controls purinergic receptors formed by multi-target compounds directed to self-amplification circuits and, therefore, may be a viable strategy to obtain the desired disease-modifying effect. Thus, purinergic system receptor modulations have a high therapeutic potential for neurodegenerative diseases such as PD.

Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.

Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.

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.

Current Pharmacology and Modulation of the Purinergic System in Takotsubo Syndrome Triggered by Cytokine Storm.

Studies show that with the COVID-19 pandemic, the world's population went through multiple stress and anxiety factors, generating serious psychological problems, in addition, the virus also caused damage and physical stress to those contaminated. In this way, the intense emotional experiences and stressful effects on the body caused by SARS-CoV-2 are capable of triggering the excessive release of catecholamines in the body. Thus, the framework of Takotsubo Syndrome is characterized by myocardial dysfunction as a response of cardiac receptors to the spillage of such hormones in an unregulated way in the human body. The purinergic system plays a central role in this process, as it actively participates in actions responsible for the syndromic cascade, such as the stress generated by the cytokine storm triggered by the virus and the stimulation of deregulated catecholamine release. Therefore, further pharmacological studies on the role of purines in this pathology should be developed in order to avoid the evolution of the syndrome and to modulate its P1 and P2 receptors aiming at developing means of reversing or treating the Takotsubo Syndrome.

Calcineurin inhibitors in the management of recurrent miscarriage and recurrent implantation failure: Systematic review and meta-analysis.

Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications.

Total Mercury Content in the Tissues of Freshwater Chelonium (Podocnemis expansa) and a Human Health Risk Assessment for the Amazon Population in Brazil.

Researchers recognize the silent, negative and deleterious effects caused by mercury pollution in gold mining areas. Freshwater turtles are culturally part of the diet of riverside populations in the Amazon region and this area presents mercury (Hg) pollution issues mainly due to gold mining activities. Thus, this research aimed to evaluate the total mercury (THg) content in the different organs of Amazonian giant river turtle (Podocnemis expansa) and carry out a human health risk assessment associated with the consumption of these animals. This study was conducted in the Vila Balbina, municipality of Presidente Figueiredo, state of Amazonas, Brazil. Skin (n = 28), muscle (n = 19) and brain (n = 2) samples were analyzed by Atomic Absorption Spectrometry (TDA-AAS) and a DMA-80™ mercury analyzer was used for the total mercury determinations. The average values found for THg in the skin, muscle and brain samples were, respectively, 0.1045 mg·kg-1, 0.1092 mg·kg-1 and 0.0601 mg·kg-1. Thus, THg was observed even though the P. expansa were kept in captivity, possibly due to previous contamination by air, water and food. The Hazard Quotient (HQ) was calculated considering a 9.07 g·day-1 intake dose of P. expansa and the consumption of turtles once a week showed an HQ = 2.45, which may cause long-term injuries to human health. Although the muscle concentrations were below the maximum limit established by the World Health Organization (WHO) and Brazilian regulatory agencies, it is important to evaluate consumption factors such as amount ingested, frequency and animal gender, which may cause a potential risk to regular consumers due to mercury bioaccumulation. The WHO may consider various aspects in order to warn the Amazon population about the severity and silent hazard of this metal, especially due to the importance of this matrix in the region. This region urgently needs government actions to inhibit clandestine mining and to prevent future serious, chronic health problems of the entire population.

Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19.

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.

Action of the Purinergic and Cholinergic Anti-inflammatory Pathways on Oxidative Stress in Patients with Alzheimer's Disease in the Context of the COVID-19 Pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the 2019 coronavirus disease (COVID-19), has affected more than 20 million people in Brazil and caused a global health emergency. This virus has the potential to affect various parts of the body and compromise metabolic functions. The virus-mediated neural inflammation of the nervous system is due to a storm of cytokines and oxidative stress, which are the clinical features of Alzheimer's disease (AD). This neurodegenerative disease is aggravated in cases involving SARS-CoV-2 and its inflammatory biomarkers, accelerating accumulation of ß-amyloid peptide, hyperphosphorylation of tau protein, and production of reactive oxygen species, which lead to homeostasis imbalance. The cholinergic system, through neurons and the neurotransmitter acetylcholine (ACh), modulates various physiological pathways, such as the response to stress, sleep and wakefulness, sensory information, and the cognitive system. Patients with AD have low concentrations of ACh; hence, therapeutic methods are aimed at adjusting the ACh titers available to the body for maintaining functionality. Herein, we focused on acetylcholinesterase inhibitors, responsible for the degradation of ACh in the synaptic cleft, and muscarinic and nicotinic receptor agonists of the cholinergic system owing to the therapeutic potential of the cholinergic anti-inflammatory pathway in AD associated with SARS-CoV-2 infection.

Qualidade de vida em pacientes com espondiloartrites: análise comparativa entre as formas axial, periférica pura e mista / Quality of life in spondyloarthritis: a comparison among axial, peripheric and mixed forms

Introdução: As espondiloartrites são doenças musculoesqueléticas crônicas que podem ter envolvimento axial, periférico ou misto. Devido ao grande comprometimento físico esta doença causa importante redução da qualidade de vida, mas não se sabe se isto acontece de igual maneira nas 3 formas. Objetivo: Estudar a associação entre qualidade de vida e formas de espondiloartrites. Método: Coletaram-se dados acerca de epidemiologia, perfil clínico, comorbidades e de qualidade de vida (através do SF-12 ou Short Form Health Survey­12 questions). Resultados: Incluíram-se 120 indivíduos: 60 EpA e 60 controles. O SF-12 físico tinha mediana de 38,05 para espondiloartrites e 55,1 para controle (p<0,0001). No quesito mental as medianas foram de 42,1 e 50,1 com p=0,04. Não foi possível demonstrar diferenças nos subgrupos de espondiloartrites, tanto no aspecto físico como mental (p=0,33 e 0,30 respectivamente). Conclusão: Existem diferenças significativas na qualidade de vida entre espondiloartrites e controles, mas não entre os subgrupos das espondiloartrites.

Introduction: Spondyloarthritis are chronic musculoskeletal diseases divided as axial, peripherical and mixed diseases. Due to a great physical involvement, it reduces patients' quality of life, but it is unknown how the 3 forms of the disease behave in such context. Objective: To study the quality of life association with spondyloarthritis forms. Methods: Data collection included: epidemiologic data, clinical profile, and quality of life data evaluated through the SF-12 (Short Form Health Survey­12 questions). Results: About 120 individuals were included: 60 spondyloarthritis and 60 controls. The physical SF-12 showed median of 38.05 for spondyloarthritis and 55.1 for controls (p<0.0001). The medians in mental SF-12 were 42.1 and 50.1 with p= 0.04. No differences in quality of life in the spondyloarthritis subgroups could be detected (with p=0.33 and 0.30 for physical and mental aspects). Conclusion: There was a significant difference in quality of life between spondyloarthritis sample and controls but not among the spondyloarthritis subgroups.

Therapeutic Potential of P2X7 Purinergic Receptor Modulation in the Main Organs Affected by the COVID-19 Cytokine Storm.

Defined by the World Health Organization as a global public health pandemic, coronavirus 2019 (COVID-19) has a global impact and has caused the death of thousands of people. The "severe acute respiratory syndrome coronavirus 2" virus (SARS-CoV-2) is the etiologic agent of this disease, which uses the angiotensinconverting enzyme receptor 2 (ACE2) to infect the body, so any organ that expresses the gene ACE2 is a possible target for the new coronavirus. In addition, in severe cases of COVID-19, a cytokine storm occurs, which triggers widespread systemic inflammation due to the uncontrolled release of proinflammatory cytokines. In this perspective, the modulation of purinergic receptors is highlighted in the literature as a possible therapy, considering its application in other viral infections and systemic inflammation. Therefore, this review aims to gather information on the modulation of the P2X7 receptor in the main organs directly affected by the virus and by the cytokine storm: the heart, brain, lung, liver and kidneys. Thus, demonstrating possible therapies for reducing inflammation and the level of morbidity and mortality of COVID-19. In severe cases of COVID-19, SARS-CoV-2 infection is capable of triggering an exacerbated release of cytokines, called a cytokine storm. With this inflammation, or less the direct infection of the virus, the whole organism can be affected. In this way, major and important organs such as the heart, lung, brain, and liver are affected, triggering different pathologies. In this perspective, purinergic signaling is highlighted in the literature for its anti-inflammatory role and has been listed in the pandemic scenario as a potential therapy. Therefore, knowing the expression of the purinergic receptor P2X7 in these tissues, the modulation of its inflammatory activity may be favorable in this severe and systemic condition.

COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route.

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.

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.

Study of inorganic elements in different organs and tissues of Amazonian manatee (Trichechus inunguis) from Brazil.

Multielement concentrations (P, S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Rb, and Rh) and total mercury (T-Hg) were analyzed in different organs and tissues of Amazonian manatee (Trichechus inunguis). Samples of 27 T. inunguis specimens, maintained in the collection of the Amazonian Center for the Research and Preservation of Aquatic Mammals, were used, situated in an area highly impacted by gold mining in the northern region of the Brazilian Amazon. Samples of aquatic plants used as food by the animals were also analyzed. The elements S, Cl, K, Cr, and Mn accumulated mainly in the musculature, while Fe and Cu were more concentrated in the liver. Trace elements, such as rubidium (Rb) and rhodium (Rh), not previously reported in the organs of animals of the family Trichechidae, were also identified. The averages for T-Hg in the skin, muscle, encephalon, liver, kidney, and lung samples were, respectively, 0.1540 ± 0.1332, 0.0593 ± 0.1044, 0.0517 ± 0.0467, 0.0486 ± 0.0543, 0.0237 ± 0.0336, and 0.0013 ± 0.0032 µg.g-1. The values obtained for the vibrissae samples were below the limit of quantification, which allows for the conclusion that this tissue cannot be used as a contamination marker. It was observed that even when kept in a conservation breeding site, these animals were exposed to non-essential trace elements. Differences in the accumulation of elements were observed between the different organs and tissues analyzed. The presence of contaminants in animals that live in a preservation center, even at low levels, deserves attention.

Assessment of total mercury content in tissues of Mullus argentinae in Rio de Janeiro, Brazil / Assessment of total mercury content in tissues of Mullus argentinae in Rio de Janeiro, Brazil

This study has as objective to determine total mercury (Total Hg) levels by atomic absorption spectrophotometry in 134 individuals edible part of Mullus argentinae, in two different fishing areas and two seasons in Rio de Janeiro State. Also, proximate composition was performed. Total Hg results in wet weight basis ranged from 0.0867 to 0.7476 µg.g-1 in muscle; 0.0023 to 0,1034 µg.g-1 in flippers; and 0.0177 to 0.1849 µg.g-1 in skin. Mean evaluated moisture was 73.39%; protein was 18.76%; lipid concentration of 5.36%; carbohydrates of 2.35%; and ashes were 0.85%. Results showed that Total Hg contents was lower than accepted limits established by regulatory organization. Higher averages were observed in muscle (0.2441 µg.g-1) when compared with skin (0.2386 µg.g-1) and flippers (0.0195 µg.g-1). In general, samples collected on summer showed higher values of total Hg when comparing to winter. Regarding beach areas there was no significant difference (p>0.05). We can conclude that this specie should be cautious consumed because of total Hg bioaccumulation characteristics, although neither levels were above limits established.

This study has as objective to determine total mercury (Total Hg) levels by atomic absorption spectrophotometry in 134 individuals edible part of Mullus argentinae, in two different fishing areas and two seasons in Rio de Janeiro State. Also, proximate composition was performed. Total Hg results in wet weight basis ranged from 0.0867 to 0.7476 µg.g-1 in muscle; 0.0023 to 0,1034 µg.g-1 in flippers; and 0.0177 to 0.1849 µg.g-1 in skin. Mean evaluated moisture was 73.39%; protein was 18.76%; lipid concentration of 5.36%; carbohydrates of 2.35%; and ashes were 0.85%. Results showed that Total Hg contents was lower than accepted limits established by regulatory organization. Higher averages were observed in muscle (0.2441 µg.g-1) when compared with skin (0.2386 µg.g-1) and flippers (0.0195 µg.g-1). In general, samples collected on summer showed higher values of total Hg when comparing to winter. Regarding beach areas there was no significant difference (p>0.05). We can conclude that this specie should be cautious consumed because of total Hg bioaccumulation characteristics, although neither levels were above limits established.

Assessment of total mercury content in tissues of Mullus argentinae in Rio de Janeiro, Brazil / Avaliação de mercúrio total em tecido comestível de Mullus argetinae coletados no Rio de Janeiro, Brasil

This study has as objective to determine total mercury (Total Hg) levels by atomic absorption spectrophotometry in 134 individuals edible part of Mullus argentinae, in two different fishing areas and two seasons in Rio de Janeiro State. Also, proximate composition was performed. Total Hg results in wet weight basis ranged from 0.0867 to 0.7476 µg.g-1 in muscle; 0.0023 to 0,1034 µg.g-1 in flippers; and 0.0177 to 0.1849 µg.g-1 in skin. Mean evaluated moisture was 73.39%; protein was 18.76%; lipid concentration of 5.36%; carbohydrates of 2.35%; and ashes were 0.85%.Results showed that Total Hg contents was lower than accepted limits established by regulatory organization. Higher averages were observed in muscle (0.2441 µg.g-1) when compared with skin (0.2386 µg.g-1) and flippers (0.0195 µg.g-1). In general, samples collected on summer showed higher values of total Hg when comparing to winter. Regarding beach areas there was no significant difference (p>0.05). We can conclude that this specie should be cautious consumed because of total Hg bioaccumulation characteristics, although neither levels were above limits established.

O objetivo deste estudo foi determinar o teor de mercúrio no tecido comestível de Mullus argentinae, conhecido como peixe trilha, espécie amplamente consumida no Rio de Janeiro, Brasil. Foi determinado o teor de mercúrio total (Hg total) por espectrofotometria de absorção atômica em 134 amostras, coletados em duas áreas e estações climáticas diferentes. Além disso, foi avaliada a composição centesimal das amostras. Os resultados de Hg total em peso úmido variaram de 0,0867 a 0,7476 µg.g-1 no músculo; 0,0023 a 0,1034 µg.g-1 nas nadadeiras; e 0,0177 a 0,1849 µg.g-1 na pele. Os valores médios da composição centesimal foram de 73,30% de umidade, 18,76% de proteína, 5,36% de lipídios, 2,35% de carboidratos e 0,85% de matéria mineral. Os resultados das 134 amostras analisadas demostraram que os teores de Hg Total apresentam concentração inferior aos limites aceitos pelos órgãos reguladores. As maiores médias foram observadas no músculo (0,2441 µg.g-1) quando comparadas à pele (0,2386 µg.g-1) e nadadeiras (0,0195 µg.g-1). Em geral, as amostras coletadas no verão apresentaram maiores valores de Hg total em relação ao inverno. Em relação aos locais de coleta não houve diferença significativa (p> 0,05). Podemos concluir que esta espécie deve ser consumida com cautela devido às características de bioacumulação do Hg total, apesar das médias apresentadas estarem abaixo dos limites estabelecidos pela legislação.

Targeting purinergic receptors to suppress the cytokine storm induced by SARS-CoV-2 infection in pulmonary tissue.

The etiological agent of coronavirus disease (COVID-19) is the new member of the Coronaviridae family, a severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), responsible for the pandemic that is plaguing the world. The single-stranded RNA virus is capable of infecting the respiratory tract, by binding the spike (S) protein on its viral surface to receptors for the angiotensin II-converting enzyme (ACE2), highly expressed in the pulmonary tissue, enabling the interaction of the virus with alveolar epithelial cells promoting endocytosis and replication of viral material. The infection triggers the activation of the immune system, increased purinergic signaling, and the release of cytokines as a defense mechanism, but the response can become exaggerated and prompt the so-called "cytokine storm", developing cases such as severe acute respiratory syndrome (SARS). This is characterized by fever, cough, and difficulty breathing, which can progress to pneumonia, failure of different organs and death. Thus, the present review aims to compile and correlate the mechanisms involved between the immune and purinergic systems with COVID-19, since the modulation of purinergic receptors, such as A2A, A2B, and P2X7 expressed by immune cells, seems to be effective as a promising therapy, to reduce the severity of the disease, as well as aid in the treatment of acute lung diseases and other cases of generalized inflammation.

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.