Caracterización epidemiológica de las exposiciones a dióxido de cloro/clorito de sodio en el contexto de la pandemia COVID-19: Reporte de los centros toxicológicos de América Latina / Epidemiological characterization of exposures to chlorine dioxide/ sodium chlorite in the context of the COVID-19 pandemic: Report of Poison Control Centers in Latin America

Resumen Los centros de información y asesoramiento toxicológico CIATs de América Latina, en el contexto de la pandemia de COVID-19, recibieron una serie de llamadas para consultas y asesoramientos relacionados con el uso de dióxido de cloro/clorito de sodio, que se estaban empleando en el tratamiento o prevención de dicha enfermedad. Dentro de la legislación vigente en los países de América Latina, no se contemplan productos farmacéuticos registrados para uso en humanos, ni se tiene evidencia de registros sanitarios en Europa, Canadá o Estados Unidos para tal fin, que contengan dióxido de cloro o clorito de sodio. Esta publicación, compila la información registrada como parte de la estadística del trabajo de ocho CIATs correspondientes a igual número de países de América Latina. Se identificó sexo, edad, sintomatología, circunstancia y grado de severidad de los 56 casos de pacientes intoxicados con dióxido de cloro/clorito de sodio registrados en el período del 15 de marzo al 30 de septiembre de 2020 en estos ocho países. Los resultados obtenidos confirman que la causa más común fue por mal uso, y el lugar de ocurrencia fue el hogar o sus alrededores, siendo el mayor porcentaje adultos jóvenes comprendidos entre 30 y 49 años. Los síntomas de intoxicación más frecuentemente encontrados fueron gastrointestinales, seguidos de cardiovasculares y respiratorios. La vía de ingreso al organismo en la mayoría de los casos fue por vía oral, reportándose algunos casos por vía inhalatoria, y en el 50% de los casos se constituyeron casos de severidad moderada, severa o fatal (3 fallecimientos). Este estudio contribuye a generar información relevante para las diferentes autoridades sanitarias, los ministerios de salud, las entidades encargadas de inspección, vigilancia y control de los países en los que se comercializan estos productos de manera ilegal por medio de redes sociales y promoviéndolos para uso en humanos para prevenir o curar COVID-19.

Abstract The Poison Control Centers in Latin America, in the context of COVID-19 pandemic, received a series of calls for consultations and recommendations related to the use of chlorine dioxide/sodium chlorite, in the treatment or prevention of CO-VID-19. Under current legislation in Latin America, no pharmaceutical products are registered for use in humans that contain chlorine dioxide or sodium chlorite, nor is there evidence of sanitary registries in Europe, Canada, or the United States for this purpose. This publication compiles the information registered by eight Poison Control Centers that correspond to the same number of Latin American countries. Sex, age, symptoms, circumstance, and degree of severity of the 56 cases of patients poisoned with chlorine dioxide/ sodium chlorite registered in the period from March 15th to September 30th, 2020 were identified. The results obtained confirm that the most common cause of poisoning was unintentional misuse, all of which occurred at home or its surroundings, with the highest percentage of registered cases being young adults between 30 and 49 years old. The most frequent symptoms of intoxication were gastrointestinal, followed by cardiovascular and respiratory. The route of exposure in most cases was oral, with some cases reported by inhalation; 48.2% of the cases were of moderate, severe, or fatal (3 deaths). This study contributes to the generation of relevant information for different health authorities, ministries of health, entities in charge of inspection, surveillance, and control in countries where these products are illegally marketed through social networks and promoted for use in humans to prevent or cure COVID-19.

Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival.

OBJECTIVE: We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes. DESIGN: We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads. SETTING: University Medical Center. PATIENTS: Patients admitted to ICUs from 2000 to 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year. CONCLUSIONS: Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

Zinc causes acute impairment of glutathione metabolism followed by coordinated antioxidant defenses amplification in gills of brown mussels Perna perna.

Zinc demonstrates protective and antioxidant properties at physiological levels, although these characteristics are not attributed at moderate or high concentrations. Zinc toxicity has been related to a number of factors, including interference with antioxidant defenses. In particular, the inhibition of glutathione reductase (GR) has been suggested as a possible mechanism for acute zinc toxicity in bivalves. The present work investigates the biochemical effects of a non-lethal zinc concentration on antioxidant-related parameters in gills of brown mussels Perna perna exposed for 21 days to 2.6 µM zinc chloride. After 2 days of exposure, zinc caused impairment of the antioxidant system, decreasing GR activity and glutathione levels. An increase in antioxidant defenses became evident at 7 and 21 days of exposure, as an increase in superoxide dismutase and glutathione peroxidase activity along with restoration of glutathione levels and GR activity. After 7 and 21 days, an increase in cellular peroxides and lipid peroxidation end products were also detected, which are indicative of oxidative damage. Changes in GR activity contrasts with protein immunoblotting data, suggesting that zinc produces a long lasting inhibition of GR. Contrary to the general trend in antioxidants, levels of peroxiredoxin 6 decreased after 21 days of exposure. The data presented here support the hypothesis that zinc can impair thiol homeostasis, causes an increase in lipid peroxidation and inhibits GR, imposing a pro-oxidant status, which seems to trigger homeostatic mechanisms leading to a subsequent increase on antioxidant-related defenses.

Preliminary assessment of cardiac short term safety and efficacy of manganese chloride for cardiovascular magnetic resonance in humans.

BACKGROUND: Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl2 allows for rapid Mn2+ uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl2) for cardiovascular magnetic resonance (CMR) in humans. METHODS: Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T1 calculations. MnCl2 was infused over three minutes at a total dose of 5 µMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated. RESULTS: There was a significant decrease in T1 values compared to baseline, sustained up to 30 minutes after the MnCl2 infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl2 with no major adverse events, despite all reporting transient facial flush. CONCLUSIONS: In the short term, MnCl2 appears safe for human use. It effectively decreases myocardium T1, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.

A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity.

Manganese (Mn) is a metal required by biological systems. However, environmental or occupational exposure to high levels of Mn can produce a neurological disorder called manganism, which has similarities to Parkinson's disease. Diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is an organotellurium compound with a high antioxidant activity, especially in the brain. The present study was designed to investigate the effects of long-term low-dose exposure to Mn in drinking water on behavioral and biochemical parameters in rats and to determine the effectiveness of vinylic telluride in attenuating the effects of Mn. After 4 months of treatment with MnCl(2) (13.7 mg/kg), rats exhibited clear signs of neurobehavioral toxicity, including a decrease in the number of rearings in the open field and altered motor performance in rotarod. The administration of DPTVP (0.150 micromol/kg, ip, 2 weeks) improved the motor performance of Mn-treated rats, indicating that the compound could be reverting Mn neurotoxicity. Ex vivo, we observed that Mn concentrations in the Mn-treated group were highest in the striatum, consistent with a statistically significant decrease in mitochondrial viability and [(3)H]glutamate uptake, and increased lipid peroxidation. Mn levels in the hippocampus and cortex were indistinguishable from controls, and no significant differences were noted in the ex vivo assays in these areas. Treatment with DPTVP fully reversed the biochemical parameters altered by Mn. Furthermore, DPTVP treatment was also associated with a reduction in striatal Mn levels. Our results demonstrate that DPTVP has neuroprotective activity against Mn-induced neurotoxicity, which may be attributed to its antioxidant activity and/or its effect on striatal Mn transport.

Impacto da lixiviação de nitrato e cloreto no lençol freático sob condições de cultivo irrigado / Nitrogen and chloride impact on water table under irrigated condition

Os impactos ambientais provocados pelos fertilizantes nitrogenados, pesticidas e sais presentes nas áreas irrigadas vêm se tornando uma preocupação crescente, uma vez que estes podem se mover no solo desde a zona radicular até atingirem águas subterrâneas. Esta pesquisa teve como objetivo identificar a influência do manejo da irrigação e das chuvas sobre a dinâmica dos íons cloreto e nitrato ao longo dos perfis dos solos, bem como o seu impacto nas águas do lençol freático do Distrito Irrigado do Baixo Acaraú - DIBAU, Ceará. As amostras de solo foram coletadas a cada 50cm de profundidade, da superfície até a zona de saturação do lençol freático (7m) em duas áreas distintas, sendo uma irrigada com a cultura do coco (S1) e a outra uma mata nativa (S2). As amostras dos solos foram realizadas em período de plena atividade da irrigação (nov/06) e ao final da estação chuvosa (mai/07). As medições dos níveis e as coletas de água do lençol freático foram efetuadas, mensalmente, em quatro poços rasos, sendo dois inseridos na área irrigada e dois na área de mata nativa, no período de dez/2003 a nov/2005, nos meses de nov/2006, março e abril/2007. As maiores concentrações de cloreto nos perfis dos solos foram registradas durante a estação chuvosa, sugerindo a influência das chuvas no aporte de cloreto oriundo de aerossóis de sais marinhos. Já as maiores concentrações de nitrato ocorreram durante o período da irrigação. Os resultados também mostraram um aumento preocupante dos teores de nitrato nas águas dos poços influenciados diretamente pela agricultura irrigada, variando de 1,52 a 19,3mg L-1, excedendo significativamente os limites máximos aceitáveis pela Portaria n° 518/2004 para consumo humano e pela Resolução 357/05.(AU)

Environmental impacts of nitrogenous fertilizers, pesticides and salts contained in irrigation are becoming an increasing concern, because they may move with soil water from root zone to groundwater. The aim of this research was to identify the irrigation management and the rainfall depth influence over nitrate and chloride concentration in the soil profiles, as well as the risk of water table pollution in the Irrigated District of Baixo Acaraú (DIBAU), Ceará, Brazil. Soil samples were taken each 50cm deep soil profiles until to saturated zone (7m) in two different types of land use: irrigated area (S1) and native area (S2). Samples occurred during irrigation activities (Nov/06) and rainfall season (May/07). The water table was measured, monthly, from Dec/2003 to Nov/2005, Nov/2006, Mar and April/2007 in four shallow wells, two located in irrigated fields and the others in native. The greatest chloride concentration in the soil profiles was registered during rainfall season, suggesting the effect of sea-salt aerosols influence on chloride soil content. The greatest nitrate concentration occurred under irrigation period. Also, the results show that irrigation caused the groundwater concentration of NO3-N to increase from 1.52 to 19.3mgL-1, thereby, exceeding the standards on Regulation MS number 518/2004 and 357/2005 Resolution.(AU)

Hypersensitivity to metals in orthodontics.

To study the incidence of hypersensitivity to orthodontic metals, patch tests were carried out before and 2 months after the placement of orthodontic appliances in 38 patients (17 male, 21 female). The tested substances were cobalt chloride, copper sulfate, potassium dichromate, iron sulfate, manganese chloride, molybdenum salt, nickel sulfate, and titanium oxide. Eight strips containing the test substances were positioned on the patients' backs. They were removed after 48 hours and assessed by a dermatologist at 48 and 72 hours after antigen application. The obtained data were analyzed by the chi-square test and McNemar's chi-square test. Statistically significant positive reactions were observed for nickel sulfate (21.1%), potassium dichromate (21.1%), and manganese chloride (7.9%); reactions to nickel sulfate had the greatest intensity. No differences were observed between the reactions before and after placement of the orthodontic appliances; this indicates that they did not sensitize the patients or affect their tolerance to these metals during the study period. No statistical difference was observed regarding sex for any evaluated substance, although a greater tendency to positivity to nickel sulfate was observed among female patients and to potassium dichromate in male patients.

Influence of nickel chloride on iron deficiency in rats

The present study was designed to investigate the effects of nickel chloride on dietary iron deficiency in rats. The gree of iron deficiency was relatively moderate, but a more generalized anemia occurred in iron deficiency, in absence of nickel chloride. Moderate iron deficiency anemia induced increased lactate-dehydrogenase activity of serum and bone marrow, perhaps related to the decreased production of energy by oxidative means, Nickel chloride, perhaps for its ability to change iron absorption, for the maintenance of bone marrow metabolism and for to increase ceruloplasmin activity, inhibited the alteration on hemoglobin synthesis. Furthermore, nickel chloride possibly for its action on copper content and Cu-Zn superoxide-dismutase activity, inhibits the shortening of the red cell life span, caused by superoxide radicals

Identificaçäo da célula de Langerhans no epitélio da gengiva humana após gengivectomia / Identification of Langerhans cell in the human gengival epithelium after gengivectomy

Os autores estudaram nove biopsias da gengiva humana, depois de prévio tratamento para gengivectomia, a fim de verificar a localizaçäo e morfologia das células de Langerhans, usando o método de impregnaçäo pelo cloreto de ouro. Também correlacionaram as suas observaçöes com as de outros autores, que obtiveram semelhantes achados em gengivas normais e na epiderme humana