Combination Therapy for the Cardiovascular Effects of Perinatal Lead Exposure in Young and Adult Rats / Alterações cardiovasculares da exposição perinatal ao chumbo em ratos jovens e adultos: papel da terapia combinada

Background: Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes. Objective: To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated). Results: Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05). Conclusions: All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These ...

Introdução: A terapia combinada parece desempenhar papel significativo em reduzir os efeitos cardiovasculares deletérios da exposição ao chumbo (Pb). Objetivo: Para investigar esta possibilidade, ratas Wistar receberam Pb (500 ppm na água de beber) ou água durante a prenhez e a lactação. Ratos com 22 e 70 dias, expostos perinatalmente ao Pb ou não, receberam DMSA, L- arginina, enalapril e a combinação destes por 30 dias adicionais. Métodos: Curvas concentração-efeito à noradrenalina foram obtidas em aortas intactas e desnudas, de ratos com 23, 52, 70 e 100 dias expostos ou não ao Pb, tratados ou não. Resultados: A pressão arterial sistólica caudal (mmHg) foi avaliada e mostrou-se aumentada em ratos expostos ao Pb [23, 52, 70 e 100 dias, respectivamente: controle 107,1±1,8, 118,8±2,1, 126,1±1,1, 120,5±2,2; Pb 117,8±3,9*, 135,2±1,3*, 139,6±1,6* e 131,7± 2,8*]. Observou-se aumento de reatividade à noradrenalina em aorta intacta, mas não desnudada, de ratos com 52, 70 e 100 dias expostos ao Pb [resposta máxima (g de tensão) 52 dias: Pb 3,43±0,16*, controle 2,38±0,33; 70 dias: Pb 4,32±0,18*, controle 3,37±0,13; 100 dias: Pb 4,21±0,23*, controle 3,22±0,21]. (*) p < 0,05 em relação ao respectivo controle. Conclusões: Todos os tratamentos restauraram as alterações de reatividade à noradrenalina em aortas de ratos expostos perinatalmente ao Pb. Exceto pelo enalapril em ratos jovens, a terapia combinada restaurou mais precocemente a pressão arterial de ratos expostos ao Pb em relação aos tratamentos isolados. Estes resultados representam uma nova abordagem no desenvolvimento de protocolos terapêuticos no tratamento da hipertensão induzida pela exposição ao Pb. .

Lead poisoning due to gunshot bullet in contact with cerebrospinal fluid: case report / Intoxicação por chumbo devida a projétil de arma de fogo em contato com o líquido cefalorraquidiano: relato de caso

CONTEXT: Lead poisoning due to retained gunshot bullets is a well-known clinical problem that is fairly frequently described in the literature. The risk factors for this occurrence relate mainly to whether the lead bullet is in contact with the joint fluid or cerebrospinal fluid (CSF). The treatment for these cases entails chelation therapy while symptoms are shown and definitive surgical removal of the bullet as a potential source of lead. The aim of this paper is to describe a clinical case of lead poisoning due to a retained gunshot bullet in contact with CSF. CASE REPORT: A 42-year-old male was hit by gunshot bullets during a holdup, and one of them was retained in the spinal cord. Six years later, he developed intense low back pain and underwent laminectomy. Nine years later, he then underwent arthrodesis on L5-S1, but he developed intense abdominal pain after the surgical procedure. For five years, he was treated with calcium versenate in five-day cycles, with a good response. The chelation therapy cycles showed great efficacy during symptomatic periods, thus reducing the symptoms and signs of poisoning and promoting great amounts of lead excretion, thereby reducing the total lead burden responsible for the symptoms. Fortunately, over the last four years, the symptoms have improved and the urine levels of aminolevulinic acid (ALA) have declined, to reach complete normalization. This shows that a healing process is probably taking place on the spinal wound, thereby isolating the bullet fragments from CSF contact.

CONTEXTO: A intoxicação por chumbo devida a projétil retido em ferimento por arma de fogo é uma complicação já conhecida e descrita na literatura. O risco de intoxicação endógena por chumbo está associado ao contato do projétil com o líquido sinovial ou líquido o cefalorraquidiano. O tratamento requer terapia de quelação e retirada cirúrgica do projétil como tratamento definitivo. Este artigo descreve caso clínico de paciente que desenvolveu intoxicação por chumbo devida a projétil retido em contato com líquido cefalorraquidiano. RELATO DE CASO: Paciente masculino, 42 anos, foi baleado durante assalto e teve projéteis que se alojaram no abdômen, perna direita e coluna lombo-sacra. Seis anos depois, desenvolveu intensa lombociatalgia e foi submetido a laminectomia. Nove anos após o acidente, foi submetido a artrodese de L5-S1, quando foi tentada a retirada do projétil, sem sucesso, desenvolvendo no pós-operatório intensa dor abdominal. Foi então feito diagnóstico de intoxicação por chumbo, que foi tratada com gluconato de cálcio, com boa resposta. Durante os cinco anos seguintes, fez ciclos de quelação com ácido etilenodiaminotetracético (EDTA) cálcico, com boa evolução. Os ciclos de quelação mostraram grande eficácia na redução dos sinais e sintomas da intoxicação, promovendo um grande aumento da excreção de chumbo e reduzindo a carga corpórea total de chumbo responsável pelos sintomas. Nos últimos quatro anos, apresentou melhora dos sintomas de intoxicação, com diminuição dos níveis de ALA urinário até a normalização, mostrando que provavelmente houve um processo de cicatrização da lesão, isolando os fragmentos de chumbo do contato com o líquor.

[Protective effect of thiamine on the induced lesions by experimental lead poisoning in gold fish [carassius auratus]]

Lead is one of the heavy metal that is very toxic for environment and organisms. Lead can inhibits many physiological processes and it is so dangerous for body tissues. In this study, four groups of fish [carassius auratus] 35 in each, were used for experiment. Group 1 was as control, in group 2 fishes were exposed to lead acetate at concentration of 8.5 mg/l, fishes in group 3 and 4 were also exposed to lead acetate in the same concentration of group 2 supplemented with vitamin B1[thiamine] at doses 30mg/l and 60mg/l, for 21 days respectively. Tissue specimens including gill, brain, kidney and liver were fixed in 10% buffered formalin, and stained with H and E. Results of histopathological findings evaluated with two non parametric Kruskal - Wallis Test and Mann - Whitney Test. Histopathology of brains of fishes in group two, showed hyperemia, privascular edema, prineuronal edema and ischemic cell changes. According to Mann - Whitney Test, hyperemia and edema lesions, the difference between group 2 and 4 was significant. This result showed some efficacy of thiamine at concentration of 60mg/l in prevention of brain lesions caused by lead poisoning. Histopathology of kidneys revealed hyperemia, degenerative and necrotic changes, swelling of epithelial cells, hyperplasia of melanomacrophage centers, intranuclear inclusion bodies in epithelial cells. In kidney, goup 2 and 3 showed significant difference in swelling of epithelial cells, intranuclear inclusion bodies and degenerative necrotic changes according to Mann - Whitney test. In liver, hyperemia, hyperplasia of melanomacrophage centers, hepatocellular vacular degeneration and intranuclear inclusion bodies were observed. In liver, the difference of hyperemia were significant in group 2 and 4. Considering the histopathological findings and based on Mann-Whitney test, non of lesions revealed significant difference in gill. According to the result of this experiment, it seems that thiamine has some degrees of protective effects on lead poisoning lesions in brain, kidney and liver of Goldfish, and it seems that the thiamine has a dose depended role dose on lead poisoning in fish

Effect of Lead Intoxication and D-Penicillamine Treatment on Hematological Indices in Rats / Efectos de Intoxicación con Plomo y Tratamiento de D-Penicilamina en índices Hematológicos en Ratas

Lead is one of the most important environmental pollution which is toxic to many organ systems. D-penicillamine (D-P) is a chelator drug which is used for treatment of lead toxicity for several years. This study was conducted in order to evaluate the efficacy of D-P in reducing the effects of lead on hematological indices. This study was done on 36 male adult, 6-8 weeks albino Wistar rats in Gorgan University of Medical Sciences. At first male adult rats were exposed to lead acetate in their drinking water. After 8 weeks, 6 rats were selected and blood samples were prepared to assess the effects of lead toxicity. The remained lead exposed rats were divided into recovery and treatment groups where distilled water and D-P was administered for them, respectively. After lead exposure, red blood cell count increased slightly, but hemoglobin and hematocrite were decreased. Also MCV and MCH were significantly decreased (P<0.05). RDW, PDW and MPV were significantly higher in lead exposed rats (P<0.05). After recovery period, most of parameters were close to normal while there were no significant differences between recovery and treatment groups. This study showed that hematologic effects of lead are reversible and D-P administration do not play an important role in subchronic lead intoxication.

El plomo es uno de los más importantes contaminantes ambientales, tóxico para la mayoría de los sistemas orgánicos. La D-penicillamina (D-P) es una droga quelante, la cual se ha usado para el tratamiento de la toxicidad por plomo durante varios años. Este estudio fue dirigido para evaluar la eficacia de la D-P en la reducción de los efectos del plomo en los índices hematológicos. Este estudio se realizó en 36 machos adultos de ratas Wistar albinas de 6-8 semanas, en la Universidad de Ciencias Médicas de Gorgan, Irán. Al inicio, las ratas machos adultas fueron expuestas al acetato de plomo en el agua de beber. Después de 8 semanas, 6 ratas se seleccionaron para evaluar los efectos de la toxicidad del plomo en muestras sanguíneas. Las restantes ratas expuestas fueron divididas para su recuperación, a las cuales se les administró agua destilada y un grupo con tratamiento al que se le suministró D-P. Después de la exposición al plomo, el conteo de glóbulos rojos se incrementó ligeramente, pero la hemoglobina y el hematocrito disminuyeron. También el MCV y el valor de MCH disminuyeron significativamente (P< 0,05). Los valores de RDW, PDW y MPV fueron significativamente altos en las ratas expuestas al plomo (p< 0,05). Luego del periodo de recuperación, la mayoría de los parámetros se acercaron al valor normal y no hubo diferencias significativas entre el grupo recuperado y con tratamiento. Este estudio mostró que los efectos hematológicos del plomo son reversibles y la administración de D-P no juega un rol importante en la intoxicación subcrónica.

Acute lead poisoning associated with backyard lead smelting in Jamaica / Envenenamiento agudo con plomo asociado con la fundición casera de plomo en Jamaica

Long-term backyard smelting of lead in a district known as Mona Commons, Kingston, Jamaica, has produced lead burdens as high as 30 000 mg/kg in soils near to the smelter, and indoor dust loadings of 373 microg/f2 in the residents' home. The blood lead levels (BPb) of 107 children from the district were in the range 2.2-202 microg/dL. Fifty-nine per cent of these had BPb levels above 10 microg/dL and the population mean was an unacceptably high 25.1 microg/dL. The highest levels were observed for five siblings, two of whom presented with lead encephalopathy. This severe chronic exposure to lead was exacerbated by a significant history of pica, and chronic nutritional anaemia. Chelation therapy significantly reduced the BPb levels but due to lead storage in other organs, the values after several months were still higher than desirable. This study emphasizes the importance of reducing the exposure of children to lead.

Protection of adrenal and male gonadal functions by androgen in lead-treated rats.

The potential health hazard of the large amounts of Lead that occurs in canned baby food, domestic water from lead-lined tanks and, in printing and petroleum industries. Lead acetate administration at a does of 8 mg/kg body weight for 21 days resulted a significant increase in adrenal steroidogenic enzyme (Delta5-3beta- HSD) and serum levels of corticosterone, while serum levels of testosterone, FSH, LH and testicular spermatogenesis were decreased in albino rats. But lead-treated rats received exogenous testosterone for the last 14 days of lead treatment, showed prevention of adrenocortical hyperactivity by decreasing adrenal Delta5-3beta-HSD activity and serum level of corticosterone. Testosterone administration also increased serum level of testosterone, FSH and LH along with spermatogenesis. The results suggest that testosterone supplementation in lead-treated rats protects adrenocortical activity and testicular spermatogenesis.

case of recurrent abdominal pain

The paper decribes the case of a forty-year-old male patient who was admitted with recurrent abdominal pain. Investigations revealed high levels of blood lead; symptoms responded promptly to treatment. The paper also reviews lead poisoning and its treatment

Lead poisoning after gunshot wound

CONTEXT: Despite the absence of symptoms in the majority of patients carrying lead bullet fragments in their bodies, there needs to be an awareness of the possible signs and symptoms of lead intoxication when bullets are lodged in large joints like knees, hips and shoulders. Such patients merit closer follow-up, and even surgical procedure for removing the fragments. OBJECTIVE: To describe a patient who developed clinical lead intoxication several years after a gunshot wound. DESIGN: Case report. CASE REPORT: A single white 23-year-old male, regular job as a bricklayer, with a history of chronic alcohol abuse, showed up at the emergency department complaining of abdominal pain with colic, weakness, vomiting and diarrhea with black feces. All the symptoms had a duration of two to three weeks, and had been recurrent for the last two years, with calming during interval periods of two to three weeks. Abdominal radiograms showed a bullet lodged in the left hip, with a neat bursogram of the whole synovial capsule. A course of chelating treatment using calcium versenate (EDTACaNa2) intravenously was started. After the chelation therapy the patient had recurrence of his symptoms and a radical solution for the chronic mobilization of lead was considered. A hip arthroplasty procedure was performed, leading to complete substitution of the left hip.

¿Ha pensado usted en el plomo como agente causante de diversos síndromes? / Had you think in lead as caused agent of diverse syndromes?

La intoxicación con plomo sigue siendo una causa de importancia no despreciable de una serie de síndromes que principalmente afectan a los niños, y que pocas veces se sugiere como agente etiológico. A continuación descutiremos los aspectos más importante de este tipo de intoxicación, elementos para poder sospecharla y esquemas de tratamiento sugeridos por el Centro de Información Toxicológica UC (CITUC)

Intoxicación plúmbica: saturnismo / Lead poisoning: saturnism

Se presenta el caso clínico de un paciente de 35 años obrero en una industria de fundición de celdas de batería que ingresa al Servicio de Urgencia que un cuadro caracterizado por intenso dolor abdominal, distensión, vómitos, constipación, signos de irritación peritoneal y fiebre. Se practica laparotomía exploradora que solo revela dilatación de asas intestinales y de colon. El estudio de laboratorio confirma la existencia de niveles sanguíneo de plomo elevados (70 µg por ciento) de niveles urinarios de ácido delta-aminolevulínicvo y de coproporfirinas también elevados. No se encontró ningún cuadro séptico que explicara la fiebre del ingreso. Se detectó una anemia normocrómica y normocítica no regenerativa (sideroblástica) que regresó con la administración con la administración de piridoxina. No se emplearon quelantes ni antídotos

Effect of homeopathic drugs plumbum and opium on experimentally induced lead toxicity in rats.

Homeopathic drugs plumbum 1M and Opium 30 were partially effective in the recovery of delta ALAD activity of the lead (150 mg% lead acetate) intoxicated rats. Plumbum 1M did not exhibit protective effect when dietary lead at high concentrations (> 25 mg% lead acetate) were given concurrently as assessed by blood delta ALAD activity and hemoglobin concentration. However it was partially effective in the recovery of delta ALAD activity and relieving anemia caused by chronic exposure of low doses of lead (below 15 mg% lead acetate).

Intoxicaçäo crônica por chumbo / Chronic lead poisoning

Os autores relatam o caso de paciente de 30 anos, do sexo masculino, proveniente de Apucarana-PR, que desenvolveu alteraçöes gastrintestinais neurológicas graves devido à exposiçäo ao chumbo durante 10 anos. Trabalhava em fábrica de baterias automotivas, mantendo durante este período contato cutâneo e inalatório com o produto.

Intoxicaçäo pelo chumbo: aspectos gerais e descriçäo de caso inusitado / Lead poisoning: brief review and report of unusual case

Os autores relatam caso de saturnismo cuja fonte de contaminaçäo foi um projétil de arma de fogo alojado ao nível da articulaçäo coxofemural direita. Inclui-se abordagem geral do tema, sobretudo no que diz respeito a exposiçäo, absorçäo, diagnóstico e tratamento das intoxicaçöes pelo chumbo.

Hematina en el tratamiento de la crisis aguda de la intoxicación plúmbica / Hematin in the treatment acute crisis the lead intoxication

Se trató exitosamente con hematina la crisis aguda en un paciente en estado de impregnación crónica por plomo. El paciente no había respondido previamente al tratamiento convencional de analgésicos y B-bloqueadores. Ocho horas después de la infusión intravenosa de 300 mg de hematina desaparecieron totalmente los síntomas abdominales y musculares. Este novedoso tratamiento de las crisis agudas de las intoxicaciones plúmbicas, está basado en el concepto de que la alteración de la biosíntesis del hemo es la más importante alteración metabólica en la intoxicación por plomo, y que, al igual que en las crisis agudas porfíricas, existiría una severa depleción del hemo, afectando la actividad de numerosas hemoproteínas, que podría explicar la sintomatología de esta intoxicación. Paralelamente a la mejoría clínica y dentro de las 30h posteriores a la infusión de hematina, se observó una importante normalización de la excreación de porfirinas y precursores. Sin embargo, la excreación urinaria de ácido 8 aminolevulínico y de porfobilinógeno volvió a elevarse a los niveles similares a los del comienzo de la crisis, pero sin observar manifestaciones clínicas.

Intoxicación plúmbica (saturnismo) / Lead Poisoning (plumbism)

Se presenta un caso de intoxicación plúmbica, en una niña de 3 años, quien presentaba una historia típica, de 3 meses de evolución, antecedentes epidemiológicos clarísimos, inclusiones basófilas en los eritrocitos y depósitos de plomo en los huesos, sin compromiso del sistema nervioso central. Se tomó muestra sanguínea para plubemia, y el resultado de ésta no se esperó para iniciar el tratamiento. Se usó sólo EDTA, ya que no había disponibilidad de otro medicamento en la farmacia. No se pidieron otros exámenes específicos (plomo en orina, coproporfirinas,etc.) por no contar con laboratorio adecuado. El nivel de plumbemia, que confirmó el diagnóstico cuando ya se había iniciado el tratamiento, bajó en forma franca al cabo de éste, no llegando a niveles normales. El control neurológico a los 2 meses de tratamiento fue muy satisfactorio. Se pidió en forma estricta a la familia, que cumplieran las normas de seguridad instauradas para los talleres de baterías, dado el gran riesgo que corren todos en ese ambiente, normas que actualmente las acatan. Se citó a la familia control dentro de 3 meses para nuevo estudio y ver posibilidad de repetir la plumbemia