Global Human Threat: The Potential Synergism between Mercury Intoxication and COVID-19.

The COVID-19 pandemic affected billions of people worldwide, and exposure to toxic metals has emerged as an important risk factor for COVID-19 severity. Mercury is currently ranked as the third toxic substance of global concern for human health, and its emissions to the atmosphere have increased globally. Both COVID-19 and mercury exposure present a high prevalence in similar regions: East and Southeast Asia, South America and Sub-Saharan Africa. Since both factors represent a multiorgan threat, a possible synergism could be exacerbating health injuries. Here, we discuss key aspects in mercury intoxication and SARS-CoV-2 infection, describing the similarities shared in clinical manifestations (especially neurological and cardiovascular outcomes), molecular mechanisms (with a hypothesis in the renin-angiotensin system) and genetic susceptibility (mainly by apolipoprotein E, paraoxonase 1 and glutathione family genes). Literature gaps on epidemiological data are also highlighted, considering the coincident prevalence. Furthermore, based on the most recent evidence, we justify and propose a case study of the vulnerable populations of the Brazilian Amazon. An understanding of the possible adverse synergism between these two factors is crucial and urgent for developing future strategies for reducing disparities between developed and underdeveloped/developing countries and the proper management of their vulnerable populations, particularly considering the long-term sequelae of COVID-19.

Inhibition of Melanization by Kojic Acid Promotes Cell Wall Disruption of the Human Pathogenic Fungus Fonsecaea sp.

Chromoblastomycosis (CBM) is a chronic human subcutaneous mycosis caused by various aetiologic agents. CBM does not have an established treatment but may be managed using antifungal agents, surgical removal of the lesions, or cryotherapy. Kojic acid (KA), a known tyrosinase inhibitor with a variety of biological actions, including fungistatic action against the fungus Cryptococcus neoformans, mediated by inhibiting melanin production, seems to be an alternative to improve the treatment of CBM. The aim of the present study was to analyze the action of KA against the pathogenic fungus Fonsecaea sp., an aetiological agent of CBM. The fungal culture was incubated with KA, and the amount of melanin was assessed, followed by cytochemical detection. Subsequently, the samples were analyzed by light microscopy, transmission and scanning electron microscopy. Culture analysis revealed that 100 g/mL KA significantly decreased the melanization of the fungus and the exocytosis of melanin into the culture supernatant. Additionally, KA induced less growth of biofilm formation and intense disruption of the cell wall, and decreased the number of melanin-containing vesicles in the culture supernatant. Finally, KA inhibited fungal filamentation in culture and the subsequent phagocytosis process. Thus, KA may be a promising substance to help in the treatment of CBM.

GABA and glutamate transporters: new events and function in the vertebrate retina

The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na+-dependent transporter and one Na+-independent transporter. The Na+-dependent uptake system presented characteristics related to the high-affinity xAG- system (EAAT1), and the Na+-independent uptake system presented characteristics related to the xCG- system, which highly contributes to glutamate transport in the retina. Glutamate shares the xCG- system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Müller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA, GATs may also release GABA through a reverse transport mechanism. In the chicken retina, a GAT-1 blocker, but not GAT2/3 blocker, was shown to inhibit GABA uptake, suggesting that GABA release from retina cells is mainly mediated by a GAT-1-like transporter.

GABA and glutamate transporters: new events and function in the vertebrate retina

The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na+-dependent transporter and one Na+-independent transporter. The Na+-dependent uptake system presented characteristics related to the high-affinity xAG- system (EAAT1), and the Na+-independent uptake system presented characteristics related to the xCG- system, which highly contributes to glutamate transport in the retina. Glutamate shares the xCG- system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Müller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA, GATs may also release GABA through a reverse transport mechanism. In the chicken retina, a GAT-1 blocker, but not GAT2/3 blocker, was shown to inhibit GABA uptake, suggesting that GABA release from retina cells is mainly mediated by a GAT-1-like transporter.(AU)

Estudo comparativo da veiculação do diclofenaco sódico pela fonoforese de alta e baixa frequência em ratos / Comparative study of sodic diclofenaco veiculation by fonoforesis using high and low frequency in rats

Objetivo: estudar a aplicação do ultrassom terapêutico com alta frequência-3MH em estudo comparativo com aplicação do ultrassom terapêutico de baixa frequência-1MHz, na indução do aumento na absorção transcutânea do diclofenaco de sódio pela pele de ratos. Método: estudo experimental utilizando 15 ratos machos, adultos, da linhagem Wistar, com peso entre 250 a 350 gramas, distribuídos em três grupos: Alta, Baixa Frequência e Controle de 5 ratos cada. Foram coletadas 4 amostras de sangue de cada animal, nos tempos de 0? antes da aplicação do ultrassom, 30?, 60? e 90? minutos após a realização da técnica específica para cada grupo. Na leitura das amostras, foi utilizado o equipamento de Cromatografia Líquida de Alta Eficiência-CLAE. Resultado: a análise foi obtida através do método não paramétrico, ANOVA de Kruskal-Wallis, não comprovando diferença estatisticamente significante entre os grupos analisados no que diz respeito a maior absorção do fármaco. Conclusão: os resultados obtidos sugerem novos estudos, que busquem aperfeiçoar o método aplicado e possa agregar maiores conhecimentos ao assunto pesquisado o que possibilitará resultados cada vez mais precisos.

Objective: to study the application of therapeutic ultrasound with high frequency-3MH in a comparative study with application of therapeutic ultrasound, low-frequency 1MHz-induced increase in transcutaneous absorption of diclofenac sodium by the skin of mice. Method: an experimental study using 15 male rats, adult male rats, weighing 250 to 350 grams were divided into three groups: High, Low Frequency Control and 5 mice each. We collected 4 blood samples from each animal at 0 'prior to the application of ultrasound, 30', 60 'and 90' minutes after the completion of specific techniques for each group. In reading the samples, we used the equipment Chromatography High Performance Liquid-HPLC. Result: the analysis was performed using the method nonparametricANOVA Kruskal-Wallis test does not confirm a statistically significant difference between the groups with regard to the greater absorption of the drug. Conclusion: the results suggest further studies that seek to improve the methodology used, and may add more knowledge to the subject researched the results will enable more precise.

Atividade anti-inflamatória do óleo-resina da Copaífera reticulata em modelo inflamatório de edema de pata / Anti-inflammatory activity of the oil-resin Copaífera reticulata of model inflamatory paw edema

Objetivo: avaliar a ação do óleo-resina de copaíba da espécie copaifera reticulata como anti-inflamatório em modelos experimentais de reação inflamatória aguda. Método: o estudo experimental foi realizado no Laboratório de Imunofarmacologia da Fundação Instituto Oswaldo Cruz ? FIOCRUZ/RJ, foram utilizados 30 (trinta) camundongos da linhagem Swiss Webster (SW). O óleo-resina de copaíba utilizada foi extraído de árvore da espécie Copaífera reticulata. O modelo de inflamação aguda induzida por carragenina foi utilizado para avaliar o efeito anti-inflamatório das concentrações, foi utilizado o teste estatístico de Kruskal-Wallis para comparar os valores medianos conforme os grupos com nível de significância alfa = 0,05. Resultados: no grupo C500 ocorreu significativa redução do volume no instante T3; somente os grupos Indo e C10 apresentaram significativa redução do volume em T6. Não houve diferença estatisticamente significante no Índice de Inibição do Edema nos grupos (Indo, C10, C100 e C500) nos intantes T1, T3 e T6. Conclusão: a atividade anti-inflamatória do óleo-resina foi confirmada pelo modelo do edema de pata induzido por carragenina através da redução do volume deslocado.

Objective: To evaluate the action of the oil-resin of Copaiba Copaifera reticulata as anti-inflammatory effect in experimental models of acute inflammatory reaction. Method: A total of 30 (thirty) mice of Swiss strain Webster (SW). The oil-resin of Copaiba used was extracted from tree species Copaifera reticulata. The model of acute inflammation induced by carrageenan was used to evaluate the anti-inflammatory effect of the extracts, we used the statistical test of Kruskal-Wallis test to compare the median values for the different groups with a significance level alpha = 0.05. Results: The group C500 was a significant reduction in the volume at time T3, only the Indus and C10 groups showed significant reduction in volume at T6. There was no statistically significant difference in the Index of Inhibition of edema in groups (Indo, C10, C100 and C500), in the instant, T1, T3 and T6. Conclusion: The anti-inflammatory activity of oil-resin was confirmed by the model of paw edema induced by carrageenan by reducing the volume displaced.

Exposição humana ao mercúrio na região oeste do Estado o Pará / Human Exposure to mercury in the west region of state of Pará

Objetivo: realizar um levantamento da literatura existente sobre os níveis de exposição mercurial das populações da região oeste do Estado do Pará. Método: revisão bibliográfica pertinente ao objetivo. Conclusão: os níveis do mercúrio detectados por diferentes trabalhos em populações expostas da bacia do Rio Tapajós foram elevados em certas comunidades (São Luís do Tapajós, Barreiras e Rainha), no entanto, apresentando uma diminuição gradual com o passar dos anos. Esses mesmos dados revelam uma exposição ambiental ao mercúrio de comunidades vizinhas com valores significativos. A exposição mercurial pode ser perigosa, por gerar níveis de intoxicação que estão acima do limite determinado pela Organização Mundial de Saúde, podendo desencadear neurotoxicidade, perda do controle motor entre outros problemas de saúde

Viabilidade celular da mucosa do intestino delgado de ratos, após correçäo de choque hipovolêmico com soluçäo de NaCl 7,5 por cento / Celular viability of rat small bowel mucosa, after hypovolemic shock correction with NaCl 7,5 percent solution

OBJETIVO: Estudar o efeito da correçäo volêmica com diferentes tipos de soluçäo, na mucosa do intestino delgado de ratos. MÉTODOS: Foram utilizados 120 ratos Wistar (Rattus norvegicus albinus), machos, adultos, com peso individual entre 310 e 410g, oriundos do Instituto Evandro Chagas de Belém do Pará, submetidos a período de adaptaçäo por 15 dias, recebendo água e raçäo ad libitum, durante todo o experimento. Os animais foram distribuídos em: Grupo Padräo (P), Grupo Choque (C), Grupo Soluçäo Fisiológica (SF) e Grupo Soluçäo Hipertônica (SH), com 30 animais cada. Estes foram divididos em subgrupos com 10 animais cada, de acordo com o dia de pós-operatório (DPO) previsto para a eutanásia dos animais, (1º, 3º ou 7º DPO), sendo após esta, colhido material para realizaçäo de teste de absorvância pelo MTT em todos os animais. RESULTADOS: O grupo SF apresentou menores índices de viabilidade celular comparado aos grupos SH e C (p<0.05). CONCLUSÄO: A correçäo volêmica com soluçäo de cloreto de sódio a 7.5 por cento levou a manutençäo de maior quantidade de células viáveis, no intestino delgado em ratos no 7º dia do experimento.