Acidosis metabólica neonatal por síndrome de enterocolitis inducido por proteína de alimentos: reporte de caso / Neonatal metabolic acidosis caused by food proteininduced enterocolitis syndrome: a case report

El síndrome de enterocolitis inducido por proteínas de los alimentos (FPIES, por su sigla en inglés) es una reacción alérgica no mediada por inmunoglobulina E (IgE) con síntomas gastrointestinales, como vómitos y diarrea. El diagnóstico se basa en criterios clínicos y en una prueba de provocación para confirmarlo. Es una enfermedad desconocida en las unidades neonatales, debido a la inespecificidad de los síntomas en los recién nacidos. La cifra de metahemoglobina elevada es una opción sencilla de aproximación diagnóstica. Se describe el caso clínico de un recién nacido que ingresa al servicio de urgencias por deshidratación, letargia, vómitos, diarrea y acidosis metabólica grave con elevación de metahemoglobina, con mejora clínica y recuperación total tras el inicio del aporte de fórmula elemental. La sospecha diagnóstica se confirmó tras la prueba de provocación positiva.

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated allergic reaction with gastrointestinal symptoms, such as vomiting and diarrhea. FPIES diagnosis is based on clinical criteria and on a food challenge test. It is an unknown disease in neonatal units due to its nonspecific symptoms in newborn infants. An elevated methemoglobin level is a simple way to approach diagnosis. Here we describe a clinical case of a newborn admitted to the emergency department because of dehydration, lethargy, vomiting, diarrhea, severe metabolic acidosis, and a high methemoglobin level. Clinical improvement and complete recovery was achieved after initiation of elemental formula. The diagnostic suspicion was confirmed after a positive challenge test.

Profilage phytochimique par chromatographie sur couche mince haute performance d'extraits de flavonoïdes totaux du Drepanoalpha® et évaluation de leur activité anti-drépanocytaire in vitro / In vitro evaluation of anti-sickling activity of crude flavonoid extracted from Drepanoalpha® and their phytochemical profiling by high performance thin layer chromatography

Contexte et objectif. Le défi le plus important dans la drépanocytose consiste à améliorer l'état de santé des patients dans les pays en développement. L'une des meilleures solutions est donc le développement de la phytomédecine basée sur la connaissance de la pharmacopée traditionnelle. L'objectif de la présente étude était d'évaluer les activités anti-drépanocytaires des flavonoïdes totaux extraits du phytomédicament Drépanoalpha® d'une part et déterminer leur profilage chimique par chromatographie sur couche mince haute performance d'autre part. Méthodes. Les flavonoïdes totaux ont été obtenus par fractionnement de l'extrait méthanolique par chromatographie flash (PURIFLASH COLUMN 30 SILICA HP - 12,0 g) et purifies à l'aide d'une cartouche (Polymeric Reversed Phase) puis caractérisés et dosés par chromatographie sur couche mince haute performance (CCMHP). L'activité anti-drépanocytaire a été mise en évidence grâce aux tests d'Emmel, de polymérisation, de rapport Fe2+/Fe3+, d'hémolyse et de la fragilité osmotique membranaire. Résultats. La poudre du Drépanoalpha® contenait une quantité de flavonoïdes totaux de 8,14 mg équivalent de quercétine/g d'extrait. Les flavonoïdes totaux extraits du Drépanoalpha® possèdent une activité antifalcémiante (avec le taux maximal de normalisation d'environ 90 % et une concentration minimale de normalisations de 11,4 µg/mL), un taux d'augmentation du rapport Fe2+/Fe3+ de 97,0 %, une activité anti-hémolytique avec une fragilité corpusculaire membranaire des érythrocytes (FCM) de 0,73 et un taux d'inhibition de la polymérisation de 77,5%. Conclusion. La pertinence des résultats de cette étude permet de confirmer les flavonoids comme phytomarqueur pour le contrôle de qualité et de standardisation de cet alicament.

Therapeutic effect of ascorbic acid on dapsone-induced methemoglobinemia in rats

OBJECTIVE: Dapsone (diaminodiphenyl sulfone, DDS) is currently used to treat leprosy, malaria, dermatitis herpetiformis, and other diseases. It is also used to treat pneumocystis pneumonia and Toxoplasma gondii infection in HIV-positive patients. The most common adverse effect of DDS is methemoglobinemia from oxidative stress. Ascorbic acid is an antioxidant and reducing agent that scavenges the free radicals produced by oxidative stress. The present study aimed to investigate the effect of ascorbic acid in the treatment of DDS induced methemoglobinemia. METHODS: Male Sprague-Dawley rats were divided into three groups: an ascorbic acid group, a methylene blue (MB) group, and a control group. After DDS (40 mg/kg) treatment via oral gavage, ascorbic acid (15 mg/kg), MB (1 mg/kg), or normal saline were administered via tail vein injection. Depending on the duration of the DDS treatment, blood methemoglobin levels, as well as the nitric oxide levels and catalase activity, were measured at 60, 120, or 180 minutes after DDS administration. RESULTS: Methemoglobin concentrations in the ascorbic acid and MB groups were significantly lower compared to those in the control group across multiple time points. The plasma nitric oxide levels and catalase activity were not different among the groups or time points. CONCLUSION: Intravenous ascorbic acid administration is effective in treating DDS-induced methemoglobinemia in a murine model.

A Case of a Herbicide Poisoning Induced Methemoglobinemia Patient Treated with High-dose Vitamin C

Methemoglobinemia is a condition in which the iron portion of hemoglobin, which binds to oxygen, is oxidized to produce methemoglobin, which increases blood concentration. There are many causes of methemoglobinemia, the most common being food, drugs, and chemicals. A 75-year-old male patient who had taken an herbicide did not notice any nonspecific symptoms. However, after 4 hours, his methemoglobin levels increased to 17.1%, while after 7 hours it increased to 26.5%, at which time intravenous administration of methylene blue 1 mg/kg (an antidote) was started. After a total of five doses of methylene blue at 1 mg/kg due to reactive methemoglobinemia for about 36 hours, the methemoglobin levels increased to 23.7%. Because no more methylene blue could be administered, 10 g of ascorbic acid (vitamin C) was administered intravenously. After 82 hours, ascorbic acid 10 g was administered six times for repeated reactive methemoglobinemia. No additional reactive methemoglobinemia was observed. The ventilator and endotracheal tube were successfully removed on day 5 after admission.

A Case of Methemoglobinemia Caused by Primaquine / 대한내과학회지

Primaquine is often administered for the hypnozoite stage of Plasmodium vivax and Plasmodium ovale. Primaquine (with clindamycin) is also an alternative drug for treatment of pneumocystis pneumonia when trimethoprim/sulfamethoxazole cannot be used. Primaquine may cause methemoglobinemia, an altered state of hemoglobin in which the ferrous state of heme is oxidized to the ferric state. We report a case of methemoglobinemia caused by a standard dose of primaquine plus clindamycin in a 27-year-old female recipient of a kidney transplant who was diagnosed with pneumocystis pneumonia.

Rattlesnake Crotalus molossus nigrescens venom induces oxidative stress on human erythrocytes

Background Globally, snake envenomation is a well-known cause of death and morbidity. In many cases of snakebite, myonecrosis, dermonecrosis, hemorrhage and neurotoxicity are present. Some of these symptoms may be provoked by the envenomation itself, but others are secondary effects of the produced oxidative stress that enhances the damage produced by the venom toxins. The only oxidative stress effect known in blood is the change in oxidation number of Fe (from ferrous to ferric) in hemoglobin, generating methemoglobin but not in other macromolecules. Currently, the effects of the overproduction of methemoglobin derived from snake venom are not extensively recorded. Therefore, the present study aims to describe the oxidative stress induced by Crotalus molossus nigrescens venom using erythrocytes. Methods Human erythrocytes were washed and incubated with different Crotalus molossus nigrescens venom concentrations (0-640 μg/mL). After 24 h, the hemolytic activity was measured followed by attenuated total reflectance-Fourier transform infrared spectroscopy, non-denaturing PAGE, conjugated diene and thiobarbituric acid reactive substances determination. Results Low concentrations of venom (<10 μg/mL) generates oxyhemoglobin release by hemolysis, whereas higher concentrations produced a hemoglobin shift of valence, producing methemoglobin (>40 μg/mL). This substance is not degraded by proteases present in the venom. By infrared spectroscopy, starting in 80 μg/mL, we observed changes in bands that are associated with protein damage (1660 and 1540 cm−1) and lipid peroxidation (2960, 2920 and 1740 cm−1). Lipid peroxidation was confirmed by conjugated diene and thiobarbituric acid reactive substance determination, in which differences were observed between the control and erythrocytes treated with venom. Conclusions Crotalus molossus nigrescens venom provokes hemolysis and oxidative stress, which induces methemoglobin formation, loss of protein structure and lipid peroxidation.(AU)

Metahemoglobinemia durante a utilização de óxido nítrico em criança submetida a transplante cardíaco: relato de caso / Acquired methemoglobinemia during nitric oxide utilization in a pediatric heart transplantation: case report

Paciente de 7 anos, sexo masculino, portador de miocardiopatia restritiva relacionada ao gene BAG3 e histórico de hipertensão pulmonar com insuficiência tricúspede importante, admitido para avalição de transplante cardíaco. Após a cirurgia deu entrada na UTI estável mas evoluiu no 1º PO com acidose metabólica, choque refratário ao volume e hipoxemia refratária a manobras de fisioterapia. Os níveis de metahemoglobina foram dosados e o óxido nítrico foi imediatamente suspenso. Iniciou-se administração endovenosa de azul de metileno na dose 3mg/kg com melhora progressiva do quadro clínico. Os níveis de metahemoglobina eram 29,05 e 5,2 ao início e final da administração da droga, respectivamente. Conclusão: Metahemoglobinemia deve ser suspeitada em pacientes que utilizam NO. Níveis elevados de metahemoglobina no sangue podem ser incompatíveis com a vida. O tratamento deve ser instituído de forma rápida e eficaz.

A 7-year-old boy was admitted for evaluation to heart transplantation with a restrictive cardiopathy congenital associated to BAG3 gene. During childhood, he developed high pulmonary hipertension with a significant tricuspid insufficiency. At first post-operative, patient has evoluted with metabolic acidosis, shock refractory to volume and refractory hypoxemia presented at maneuvers physiotherapy. The levels of methemoglobin were checked on laboratory and the nitric oxide was immediately suspended. It started the administration of methylene blue in 3 mg/kg with progressive improvement of clinical situation. Levels of metheboglobin were 29,05 before the treatment and 5,2 after methylene blue administration. Conclusion: Metahemoglobinemia must be suspected in patients using NO. Elevated levels of metahemoglobin may be incompatible with life. Treatment should be instituted quickly and effectively.

Erythrocyte oxidative stress markers in children with sickle cell disease / Marcadores de estresse oxidativo em eritrócitos de crianças com doença falciforme

Abstract Objective To determine eight parameters of oxidative stress markers in erythrocytes from children with sickle cell disease and compare with the same parameters in erythrocytes from healthy children, since oxidative stress plays an important role in the pathophysiology of sickle cell disease and because this disease is a serious public health problem in many countries. Methods Blood samples were obtained from 45 children with sickle cell disease (21 males and 24 females with a mean age of 9 years; range: 3–13 years) and 280 blood samples were obtained from children without hemoglobinopathies (137 males and 143 females with a mean age of 10 years; range: 8–11 years), as a control group. All blood samples were analyzed for methemoglobin, reduced glutathione, thiobarbituric acid reactive substances, percentage of hemolysis, reactive oxygen species, and activity of the enzymes glucose 6-phosphate dehydrogenase, superoxide dismutase, and catalase. Data were analyzed using Student's t-test and were expressed as the mean ± standard deviation. A p-value of <0.05 was considered significant. Results Significant differences were observed between children with sickle cell disease and the control group for the parameters methemoglobin, thiobarbituric acid reactive substances, hemolysis, glucose 6-phosphate dehydrogenase activity, and reactive oxygen species, with higher levels in the patients than in the controls. Conclusions Oxidative stress parameters in children's erythrocytes were determined using simple laboratory methods with small volumes of blood; these biomarkers can be useful to evaluate disease progression and outcomes in patients.

Resumo Objetivo Determinar parâmetros de estresse oxidativo em eritrócitos de crianças com doença falciforme e compará-los com os mesmos parâmetros em eritrócitos de crianças saudáveis, pois o estresse oxidativo desempenha um importante papel na fisiopatologia da doença falciforme, considerada um sério problema de saúde pública em muitos países. Métodos Foram obtidas amostras de sangue de 45 crianças com doença falciforme (21 meninos e 24 meninas com média de 9 anos, variação de 3 a 13) e 280 amostras de sangue de crianças sem hemoglobinopatias (137 meninos e 143 meninas com média de 10 anos, variação de 8 a 11), como grupo controle. Em todas as amostras foram determinados meta-hemoglobina, glutationa reduzida, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade das enzimas glucose6-fosfato desidrogenase, superóxido dismutase e catalase. Os dados foram analisados com o teste t de Student e foram expressos como média ± desvio padrão. Um valor de p < 0,05 foi considerado significativo. Resultados Foram observadas diferenças significativas entre as crianças com doença falciforme e o grupo controle para os parâmetros meta-hemoglobina, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade da enzima glucose6-fosfato desidrogenase, com níveis aumentados nos pacientes. Conclusões Foi possível determinar parâmetros de estresse oxidativo em eritrócitos de crianças, com técnicas laboratoriais simples e pequenos volumes de sangue. Esses biomarcadores podem ser úteis na avaliação da progressão e dos resultados de tratamentos da doença.

Determinação da metemoglobina em voluntários fumantes e não fumantes / Determination of methemoglobin in smokers and non smokers volunteers

Objetivo ­ Determinar a concentração de metemoglobina (MetHb) em voluntários fumantes e não fumantes, e comparar com as possíveis alterações bioquímicas. Métodos ­ Os sujeitos do estudo foram voluntários do município de Sorocaba/SP (n=30), sendo metade para o grupo de fumantes (n=15) e outra metade para o grupo de não fumantes (n=15). Foi realizada a extração de saponina utilizando a droga vegetal Quilaia sp., para a realização de hemólise nas amostras de sangue e, então, dosar a metemoglobina dos voluntários. Amostras de sangue foram coletadas diretamente em tubos comerciais à vácuo e a metemoglobina foi determinada através da técnica que dispensa o uso do cianeto, evitando risco tóxico. Resultados ­ Os resultados estão apresentados em Média ± Desvio Padrão da porcentagem de MetHb: Grupo Fumantes foi de 3,4 ± 0,82% e o Grupo Não Fumantes foi de 8,3 ± 4,9% (valor normal: 1,9 a 3,8%), sendo diferentes significativamente. Os valores para a dosagem de glicemia e colesterol total não apresentaram diferença significativa, quando comparado o grupo de Fumantes com o Não Fumantes. Conclusões ­ Conclui-se que os valores de MetHb se apresentaram alterados em indivíduos fumantes, porém serão necessários maiores estudos acerca da comparação da alteração de MetHb com glicemia e/ou colesterol total.

Objective ­ To determine the concentration of methemoglobin (MetHb) in smoker and non-smoker volunteers comparing with possible biochemical alteration. Methods ­ The study were performed with volunteers of city Sorocaba/SP (n=30), separated in two groups: smokers group (n=15) and non-smokers group (n=15). The extraction of saponin was performed using the plant Quilaia sp., for hemolysis in the blood samples and, so, measure mehtemoglobin levels in the volunteers. Blood samples were collected directly in commercial tubes of vacuum and the methemoglobin was determined through of method described that dispenses the use of cyanide, avoiding the toxic risk. Results ­ The results are express in mean ± standard deviation of percentage MetHb: Non-smokers Group 3.4 ± 0.82%; Smokers Group 8.3 ± 4.9% (normal values 1.9%-3.8%), being different significantly. The glycemic and total cholesterol results, do not present significant difference when compared the smokers group with non-smokers group. Conclusions ­ The MetHb results presented are altered in smoker volunteers, however larger studies are needed on the comparison of the change of MetHb with glycaemia and/or total cholesterol.

Study on the anemia status of Chinese urban residents in 2010-2012 / 中华预防医学杂志

<p><b>OBJECTIVE</b>The level of blood hemoglobin and the anemia status of Chinese urban residents in 2010-2012 was analyzed.</p><p><b>METHODS</b>All the data in this study came from the China Nutrition and Health Survey in 2010-2012. By using multi-stage stratified sampling and population proportional stratified random sampling method, 74 276 residents aged above 6 from 34 metropolis and 41 middle-sized and small cities were included in this study. The concentration of blood hemoglobin was determined by cyanmethemoglobin method. Anemia was judged by the anemia standard recommended by WHO, combined with elevation correction standard. The level of blood hemoglobin, the prevalence of anemia and the 95%CI value were analyzed by using the complex sampling weighted processing, combined with the population figures released by the National Bureau of Statistics in 2009.</p><p><b>RESULTS</b>In 2010-2012, the level of blood hemoglobin of Chinese city population was(144.16 ± 0.78)g/L, (152.88 ± 0.94)g/L for male and(135.01 ± 0.71)g/L for female, while (145.65 ± 1.22)g/L for metropolis and (143.90 ± 0.89)g/L for small and medium-sized. The anemia prevalence of Chinese city population (pregnant women were not included) was 9.7%(95%CI: 9.4%-10.1%), 6.8%(95%CI: 6.4%-7.3%) for male and 12.8%(95%CI: 12.2%-13.4%) for female, while 8.5%(95% CI: 8.0%-9.0%) for metropolis and 10.0%(95%CI: 9.5%-10.4%) for small and medium-sized. The anemia prevalence of 18-44 women (15.4%, 95%CI: 14.3%-16.6%) was the highest among all the age-groups, and the average anemia prevalence of people more than 60 years-old (including) (12.5%, 95%CI: 11.8%-13.2%) was higher than the other age-groups.</p><p><b>CONCLUSION</b>The anemia prevalence of Chinese city population in 2010-2012 was obviously decreased in comparison of 10 years ago, while, more attention and improvement measures should be take upon women at reproductive age and the elder people.</p>

Dosagem de metemoglobina em pacientes adultos com anemia falciforme: influência do tratamento com hidroxiureia / Methemoglobin measure in adult patients with sickle-cell anemia: influence of hydroxyurea therapy

Introduction: Hemoglobin S (HbS) is unstable hemoglobin that easily oxidizes, causing methemoglobin (MetHb) increased production in patients with sickle-cell anemia (SCA). Objectives: To determine MetHb levels and the influence of hydroxyurea (HU) therapy on this marker in patients with SCA. Materials and methods: Blood samples from 53 patients with SCA at the steady-state, with and without HU therapy, and 30 healthy individuals were collected to evaluate MetHb levels. The MetHb measurement was performed by spectrophotometry. Complete blood count, HU measurements, and fetal hemoglobin (HbF) and HbS concentrations were taken from medical records. Results: MetHb levels were statically higher in patients with SCA when compared to control group (p < 0.001). There was no statistical difference in MetHb level between SCA patients, either using or not HU. We obtained a positive correlation between MetHb measurements and HbS concentration (r = 0.2557; p = 0.0323). Conclusion: HbS presence favored hemoglobin breaking down, and consequently increased MetHb production. Treatment with HU, however, did not influence the levels of this marker...

Introdução: A hemoglobina S (HbS) é uma hemoglobina instável que facilmente se oxida, causando aumento da produção de metemoglobina (MetHb) em pacientes com anemia falciforme (AF). Objetivos: Determinar os níveis de MetHb e verificar a influência do tratamento com a hidroxiureia (HU) sobre as dosagens desse marcador em pacientes com AF. Materiais e métodos: Amostras de sangue de 53 pacientes adultos com AF em estado basal, em uso ou não de HU, e 30 indivíduos saudáveis foram coletadas para avaliar os níveis de MetHb. A dosagem de MetHb foi realizada pelo método espectrofotométrico. Os parâmetros hematológicos, a dosagem de HU e a concentração de hemoglobina F (HbF) e HbS foram retirados dos prontuários médicos. Resultados: Níveis de MetHb apresentaram-se mais elevados estatisticamente em pacientes com AF em relação ao grupo-controle (p < 0,0001). Não foi verificada diferença estatística nos níveis de MetHb entre pacientes em uso ou não de HU. Observou-se correlação positiva entre as dosagens de MetHb e a concentração de HbS (r = 0,2557; p = 0,0323). Conclusão: A presença da HbS favoreceu a degradação da hemoglobina, causando elevação da produção de MetHb. Tratamento com HU, entretanto, não influenciou nos níveis desse marcador...

Methemoglobinemia Caused by an Inert Ingredient after Intentional Ingestion of Pesticide / 대한중환자의학회지

We report two cases of toxic methemoglobinemia caused by an inert ingredient in pesticide product after intentional ingestion of pesticide. First, 51-year-old male visited to the emergency department (ED) after the ingestion of pesticide in a suicide attempt. Initial methemoglobin (MetHb) level was 25.6%. We did not know the cause of methemoglobinemia at that time. Second, 56-year-old female visited to the ED after the ingestion of the same pesticide in a suicide attempt. MetHb level after 30 minutes was 16.1%. The patients were treated with methylene blue. We contacted to the Korean Rural Development Administration and estimated that magnesium nitrate was more likely to cause methemoglobinemia. This report highlights the importance of considering the possibility of methemoglobinemia caused by inert ingredient in pesticide and early antidotal therapy.

Methemoglobinemia Caused by an Inert Ingredient after Intentional Ingestion of Pesticide / 대한구급학회지

We report two cases of toxic methemoglobinemia caused by an inert ingredient in pesticide product after intentional ingestion of pesticide. First, 51-year-old male visited to the emergency department (ED) after the ingestion of pesticide in a suicide attempt. Initial methemoglobin (MetHb) level was 25.6%. We did not know the cause of methemoglobinemia at that time. Second, 56-year-old female visited to the ED after the ingestion of the same pesticide in a suicide attempt. MetHb level after 30 minutes was 16.1%. The patients were treated with methylene blue. We contacted to the Korean Rural Development Administration and estimated that magnesium nitrate was more likely to cause methemoglobinemia. This report highlights the importance of considering the possibility of methemoglobinemia caused by inert ingredient in pesticide and early antidotal therapy.

Two Cases of Methemoglobinemia Induced by the Exposure to Nitrobenzene and Aniline

OBJECTIVE: To report two cases of methemoglobinemia induced by inhaled nitrobenzene and dermally absorbed aniline. METHODS: We have evaluated a 37-year-old male worker exposed to nitrobenzene by inhalation while conducting maintenance job of mononitrobenzene pump and a 25-year-old male worker exposed dermally to aniline while unloading. RESULTS: The first case is a 37-year-old male exposed to nitrobenzene. His blood methemoglobin concentration level was initially 19.8%, and chest X-ray was normal. After oxygen therapy, the blood methemoglobin concentration level decreased to 2.1%, and the symptoms were alleviated. The second case is a 25-year-old male exposed dermally to aniline. His chest X-ray was normal, but blood methemoglobin concentration level reached maximally 46.8%. He was treated with methylene blue due to relatively high blood methemoglobin level. Gradually after the treatment, his methemoglobin concentration level was normalized to 0.8% and simultaneously symptoms were resolved. CONCLUSIONS: After the thorough exposure investigations and medical evaluations, we have concluded that these cases were methemoglobinemia induced by occupational exposure to nitrobenzene and aniline. We suggest that businesses which handle methemoglobinemia-causing substances control the engineering process strictly, implement periodic screening, and establish emergency patient management system.

A Patient with "Rebound Methemoglobinemia" during Treatment of Methemoglobinemia Caused by Propanil Intoxication

Methemoglobinemia results from the oxidation of ferrous iron (Fe++) to ferric iron (Fe+++) within hemoglobin. It is caused by various etiologies, including the herbicide Propanil. Patients with low levels of methemoglobin (metHb) are asymptomatic but symptomatic patients and patients with high levels of metHb require treatment. Methylene blue is the first choice for the treatment of methemoblobinemia, but has some complications such as hemolytic anemia and rebound methemoglobinemia. We report the case of a 91-year-old woman who died of aniline herbicides poisoning. The level of metHb in her blood was initially 20.7% and her mental status was drowsy. She was intravenously treated with methylene blue within a therapeutic range for methemoglobinemia. After treatment with methylene blue, the level of metHb decreased but later increased above 20%. Methylene blue treatment was repeatedly attempted, but the patient suffered from hemolytic anemia and rebound methemoglobinemia. The patient finally died from renal failure and cardiopulmonary collapse. We must be careful because methemoglobinemia can occur even when treated pesticides such as propranil.

Clinical Characteristics of Patients with Indoxacarb Insecticide Poisoning

PURPOSE: Indoxacarb insecticide poisoning causes methemoglobinemia, which is occasionally life-threatening. However, there is limited data on indoxacarb effects after human ingestion. The purpose of this study was to examine the clinical features, complications, management, and medical outcome of patients with indoxacarb insecticide poisoning. METHODS: We retrospectively reviewed the medical records of 10 patients with indoxacarb insecticide poisoning who had visited our emergency centers from January 2008 to December 2011. We collected data on the general characteristics of the patients, their clinical symptoms and signs, laboratory data, management of their condition, and clinical results. RESULTS: Among the 10 patients, 8 were diagnosed with methemoglobinemia. The clinical manifestations of indoxacarb insecticide poisoning were hypotension (3 patients), altered mentality (5 patients), cyanosis (5 patients), dyspnea (2 patients), seizure (3 patients), and cardiac arrest (2 patients). Four patients had a poisoning severity score of 3 and 2 patients had a poisoning severity score of 2. Four patients were treated with methylene blue for methemoglobinemia and one patient was treated with a high dose (150 mg/kg) of ascorbic acid. The serum methemoglobin saturation of five patients who were treated with methylene blue or a high dose of ascorbic acid was nearly normalized. Four patients experienced rhabdomyolysis, pneumonia, hemolytic anemia, acute pancreatitis, and heart failure as a complication of indoxacarb insecticide poisoning. CONCLUSION: We observed a variety of clinical features, complications, management, medical outcome, and clinical course of patients with indoxacarb insecticide poisoning. We could also ascertain the efficacy of methylene blue and high dose ascorbic acid for indoxacarb-induced metheglobinemia.

Methemglobinemia from Antifreeze Containing Sodium Nitrite

Sodium nitrite is commercially used as a coloring agent, food preservative, and corrosion inhibitor. Accidental poisoning with sodium nitrite from contaminated food and water causes gastrointestinal irritation, vasodilatation, and methemoglobinemia with subsequent tissue hypoxia. We describe an outbreak case of sodium nitrite-induced methemoglobinemia following the ingestion of noodles contaminated with industrial antifreeze. The eEight patients involved initially complained that their noodles tasted 'unpleasant' and soon afterwards experienced nausea, vomiting, dizziness, and fatigue. Some of them noted cyanosis on their lips and fingers. Subsequent investigations demonstrated a high methemoglobin concentration which was corrected by the intravenous administration of methylene blue three hours after the onset of symptoms. The patients made a prompt, uncomplicated recovery and were discharged home 4 four days later. Industrial antifreeze contains sodium nitrite and calcium nitrite. Because an accidental poisoning of industrial antifreeze causes fatal methemoglobinemia, emergency physicians should promptly identify its symptoms and institute treatment with methylene blue promptly. In addition, industrial agencies must caution construction businesses against such contamination events.

Antidotes of cyanide intoxication

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.

Antidote for acquired methemoglobinemia: methylene blue

Methylene blue (MB) is an effective antidote for methemoglobinemia. MB is a basic dye, yielding a blue solution. In the human body, hemoglobin is the oxygen-carrying protein including a ferrous atom. Hemoglobin is oxidized to methemoglobin (MetHb) with the ferric atom, which cannot bind to or carry oxygen. Equilibrium between hemoglobin and MetHb is approximately 99:1. Thus a healthy man can have about 1% of methemoglobinemia. The cytochrome b5 MetHb reductase pathway plays a major role in reducing MetHb to hemoglobin. The nicotin amide adenine dinucleotide phosphate (NADPH) MetHb reductase pathway is a minor reducing system of MetHb, and it needs NADPH as a cofactor. However, to the exceeding exogenous oxidative stress, the cytochrome b5 MetHb reductase pathway is soon exhausted, and the NADPH MetHb reductase pathway can be activated 4 to 5 times by the exogenous cofactor, MB. The decision to initiate MB therapy for methemoglobinemia depends on the MetHb level and the symptoms. The indication for MB therapy in a symptomatic patient is a MetHb level >20% and in an asymptomatic patient, a MetHb level >30%. Patients with comorbidities such as anemia, heart disease, pneumonia, chronic obstructive pulmonary disease, or liver cirrhosis can be candidates for MB therapy with an even lower MetHb level. The recommended initial dose of MB is 1 to 2 mg/kg. It can be repeated every 30 minutes to 1 hour. However, the dose should not exceed 7 mg/kg. A high dose of MB may induce methemoglobinemia paradoxically and also cause hemolytic anemia. Like other antidotes, MB has its own adverse effects.

Effects of freeze-drying process on polymerized human placenta hemoglobin / 生物医学工程学杂志

The present study was aimed to investigate the influence of freeze-drying on the quality of polymerized human placenta hemoglobin (PolyPHb). The PolyPHb solution was freeze-drying under suitable conditions. Hemoglobin concentration, methemoglobin (MetHb) content, UV spectrum, Fe3 content, oxygen-carrying capacity, pH, the average molecular weight and its distribution, circular dichroism, oxygen equilibrium curve and other indicators were measured before and after freeze-drying. The appearance, residual water content, rehydration time of the lyophilized product were also evaluated. The results showed that there was no significant difference on all the indicators measured above, which indicated that freeze-drying process had no effect on the physical and chemical properties of PolyPHb, as well as on its biological activity. Therefore, the properties of PolyPHb were stable during this freeze-drying process and could be preserved after such freeze-drying process.