Metales pesados en el ambiente: síndrome de Guillain-Barré / likeHeavy metals in the enviroment: Guillain-Barré like syndrome

El síndrome de Guillain-Barré constituye una entidad de etiología diversa, que se caracteriza por debilidad muscular aguda, simétrica, ascendente y progresiva, y es una de las polineuropatías adquiridas más frecuentes en la infancia. Entre los diagnósticos diferenciales, deben considerarse las neuropatías producidas por metales pesados, mercurio y plomo, y metaloides, como el arsénico, plaguicidas organofosforados y el tetracloruro de carbono.Se presenta a un paciente de 14 años con diagnóstico de síndrome de Guillain-Barré sin respuesta al tratamiento convencional con gammaglobulina. Considerando otras etiologías, se sospechó neuropatía producida por metales pesados, y se confirmó intoxicación por mercurio.El objetivo de esta presentación es concientizar a los pediatras acerca del impacto de los tóxicos ambientales en la salud infantil para realizar un diagnóstico precoz pesquisando datos clave a través de la historia clínica ambiental

Guillain-Barré syndrome is an entity of diverse etiology, characterized by acute, symmetric, ascending and progressive muscle weakness, being one of the most frequent acquired polyneuropathies in childhood. Neuropathies produced by heavy metals, mercury and lead, and metalloids, such as arsenic, organophosphorus pesticides and carbon tetrachloride, should be considered among the differential diagnoses.We present a 14-year-old patient with a presumptive diagnosis of Guillain-Barré syndrome without response to conventional treatment with gamma globulin. Considering other etiologies, heavy metal neuropathy was suspected, and mercury poisoning was confirmed.The aim of this presentation is to make pediatricians aware about the impact of environmental toxic agents on children's health in order to make an early diagnosis by researching key data through the environmental clinical history.

Evaluation of mercury exposure level, clinical diagnosis and treatment for mercury intoxication

Mercury occurs in various chemical forms, and it is different to health effects according to chemical forms. In consideration of the point, the evaluation of the mercury exposure to human distinguished from occupational and environmental exposure. With strict to manage occupational exposure in factory, it is declined mercury intoxication cases by metallic and inorganic mercury inhalation to occupational exposure. It is increasing to importance in environmental exposure and public health. The focus on the health impact of exposure to mercury is more on chronic, low or moderate grade exposure—albeit a topic of great controversy—, not high concentration exposure by methylmercury, which caused Minamata disease. Recently, the issue of mercury toxicity according to the mercury exposure level, health effects as well as the determination of what mercury levels affect health are in the spotlight and under active discussion. Evaluating the health effects and Biomarker of mercury exposure and establishing diagnosis and treatment standards are very difficult. It can implement that evaluating mercury exposure level for diagnosis by a provocation test uses chelating agent and conducting to appropriate therapy according to the result. but, indications for the therapy of chelating agents with mercury exposure have not yet been fully established. The therapy to symptomatic patients with mercury poisoning is chelating agents, combination therapy with chelating agents, plasma exchange, hemodialysis, plasmapheresis. But the further evaluations are necessary for the effects and side effects with each therapy.

Niigata Minamata Disease: A Revisit

Minamata disease is a well-known mercury contamination that happened in Japan in 1953. Due to demand during world war, second mercury disaster occurred in Niigata Prefecture in 1965. This is a review on the Niigata Minamata disease based on available documents and local expert opinions on the disaster. The aims of this paper are to record exposure history like the source of mercury in Agano River and specific fish that was associated with the disease. It is for an appraisal of the basic mercury exposure control, particularly to protect Japanese and world population during that time. There was indication that initial exposure limit for mercury was calculated incorrectly, and higher safe dose was applied. This epidemiological study is very useful and significant in comprehend the correct estimation of the human exposure to any hazardous substances.

Manifestações neurológicas em ribeirinhos de áreas expostas ao mercúrio na Amazônia brasileira / Neurological manifestations in riverine populations from areas exposed to mercury in the Brazilian Amazon / Manifestaciones neurológicas en las comunidades ribereñas expuestas al mercurio de la Amazonia brasileña

This study evaluated current levels of mercury exposure and sensory symptoms in adults from three riverine communities in Pará State, Brazil, two of which located in the Tapajós River basin and one in the Tocantins basin. Participants in this study included 78 residents in Barreiras (Tapajós), 30 in São Luiz do Tapajós (Tapajós), and 49 in Furo do Maracujá (Tocantins). Total hair mercury concentrations were quantified by atomic absorption spectrophotometry, and neurological evaluation was conducted by routine examination. Mercury concentrations in the Tapajós communities were higher than those in the Tocantins (p < 0.01). Evaluation of neurological changes showed no significant difference between the communities in exposed areas and control areas for the changes observed by conventional neurological examination, except for gait deviation (p < 0.05). The study concludes that despite the mercury exposure levels, there was a low frequency of sensory alterations according to conventional neurological testing.

No presente estudo, foram avaliados comparativamente os níveis atuais de exposição ao mercúrio e as manifestações neurológicas em ribeirinhos residentes em comunidades situadas no Estado do Pará, Brasil. Participaram do estudo 78 ribeirinhos de Barreiras (bacia do rio Tapajós), 30 de São Luiz do Tapajós (bacia do rio Tapajós) e 49 do Furo do Maracujá (bacia do rio Tocantins). As concentrações de mercúrio total foram quantificadas, em cabelo, pela espectrofotometria de absorção atômica, e a avaliação neurológica foi realizada por meio de testes de rotina. As concentrações de mercúrio nas comunidades do Tapajós foram maiores que as do Tocantins (p < 0,01). A avaliação das alterações neurológicas não mostrou diferença significativa entre as comunidades das áreas expostas e controle para os resultados observados pelo exame neurológico convencional, exceto para desvio da marcha (p < 0,05). Concluiu-se que, apesar dos níveis de exposição ao mercúrio, houve uma baixa frequência de alterações somatossensoriais encontradas por meio de exames neurológicos convencionais.

En el presente estudio se evaluó comparativamente los niveles actuales de exposición al mercurio y sus manifestaciones neurológicas en los residentes de las comunidades ribereñas en el Estado de Pará, Brasil. Los participantes fueron 78 de las riberas limítrofes (cuenca del Tapajós), 30 en São Luís do Tapajós (cuenca del Tapajós) y 49 en Pasiflora (cuenca del río Tocantins). Las concentraciones de mercurio total en el pelo se cuantificaron por espectrofotometría de absorción atómica y la evaluación neurológica se realizó mediante el análisis de rutina. Las concentraciones de mercurio en las comunidades Tapajós fueron más altas que en Tocantins (p < 0,01). La evaluación de los trastornos neurológicos no mostró diferencias significativas entre las comunidades de las zonas expuestas, ni en el control de los resultados observados durante el examen neurológico convencional, excepto por desviaciones de la marcha (p < 0,05). Se concluyó que, si bien existen niveles de exposición al mercurio, hubo una baja frecuencia de cambios, cuyo examen neurológico fue de tipo estándar somatosensorial.

Methylmercury Exposure and Health Effects / 예방의학회지

Methylmercury is a hazardous substance that is of interest with regard to environmental health, as inorganic mercury circulating in the general environment is dissolved into freshwater and seawater, condensed through the food chain, ingested by humans, and consequently affects human health. Recently, there has been much interest and discussion regarding the toxicity of methylmercury, the correlation with fish and shellfish intake, and methods of long-term management of the human health effects of methylmercury. What effects chronic exposure to a low concentration of methylmercury has on human health remains controversial. Although the possibility of methylmercury poisoning the heart and blood vessel system, the reproductive system, and the immune system is continuously raised and discussed, and the carcinogenicity of methylmercury is also under discussion, a clear conclusion regarding the human health effects according to exposure level has not yet been drawn. The Joint FAO/WHO Expert Committee on Food Additives proposed to prepare additional fish and shellfish intake recommendations for consumers based on the quantified evaluation of the hazardousness of methylmercury contained in fish and shellfish, methylmercury management in the Korea has not yet caught up with this international trend. Currently, the methylmercury exposure level of Koreans is known to be very high. The starting point of methylmercury exposure management is inorganic mercury in the general environment, but food intake through methylation is the main exposure source. Along with efforts to reduce mercury in the general environment, food intake management should be undertaken to reduce the human exposure to methylmercury in Korea.

Protective effects of organoselenium compounds against methylmercury-induced oxidative stress in mouse brain mitochondrial-enriched fractions

We evaluated the potential neuroprotective effect of 1-100 µM of four organoselenium compounds: diphenyl diselenide, 3’3-ditri-fluoromethyldiphenyl diselenide, p-methoxy-diphenyl diselenide, and p-chloro-diphenyl diselenide, against methylmercury-induced mitochondrial dysfunction and oxidative stress in mitochondrial-enriched fractions from adult Swiss mouse brain. Methylmercury (10-100 µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, which occurred in parallel with increased glutathione oxidation, hydroperoxide formation (xylenol orange assay) and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with diphenyl diselenide (100 µM) completely prevented the disruption of mitochondrial activity as well as the increase in TBARS levels caused by methylmercury. The compound 3’3-ditrifluoromethyldiphenyl diselenide provided a partial but significant protection against methylmercury-induced mitochondrial dysfunction (45.4 ± 5.8 percent inhibition of the methylmercury effect). Diphenyl diselenide showed a higher thiol peroxidase activity compared to the other three compounds. Catalase blocked methylmercury-induced TBARS, pointing to hydrogen peroxide as a vector during methylmercury toxicity in this model. This result also suggests that thiol peroxidase activity of organoselenium compounds accounts for their protective actions against methylmercury-induced oxidative stress. Our results show that diphenyl diselenide and potentially other organoselenium compounds may represent important molecules in the search for an improved therapy against the deleterious effects of methylmercury as well as other mercury compounds.

Inventario de mercurio metálico presente en hospitales públicos y privados con capacidad mayor de 50 camas, ubicados en la Ciudad de Guatemala / Inventory of metallic mercury present in public and private hospitals with over 50 beds capcidad, located in Guatemala City

El mercurio (Hg) es un metal a temperatura ordinaria, además de ser el ünico metal conocido que se mantiene líquido a 0 C centigrados. Todas sus formas (fundamental, orgánica e inorgánica) son tóxicas, con una especial afinidad por el riñon y el sistema nervioso (9;719;21). Aún siendo tóxico tiene bastantes aplicaciones en el sector salud, de ahí la importancia de realizar un inventario de este metal en los hospitales públicos y privados con capacidad mayor de 50 camas, ubicados en la Ciudad de Guatemala, por tratarse de los centros del cuidado de la salud más grandes. El estudio fue de tipo descriptivo y la información fue recolectada a través de una encuesta al personal de cada uno de los servicios de los hospitales participantes, a través de la cual se identificaron las fuentes de mercurio metálico presentes en cada uno de los servicios y se cuantificó el número de cada una de ellas...

Metallic embolism from intravenous injection of elemental mercury in a 27-year-old male for excision of multiple subcutaneous foreign body granuloma under general anesthesia

This is a case of 27-year-old male who sustained multiple metallic embolism from non-accidental self-injection of elemental mercury through the intravenous route. The patient allegedly self-injected at least twenty thermometers' worth of elemental mercury in a span of one year. The patient presented with generalized body fatigue, difficulty in position sense, distal hand weakness, tremors, labile mood, insomnia, and emotional instability. Physical examination showed multiple subcutaneous granulomas in the extremities at the sites of elemental mercury injection. Radiographic studies in the lungs, abdomen and extremities showed multiple dense spherules and pinpoint opacities indicative of metallic mercury embolism. Serum mercury levels were elevated. The patient underwent multiple hemodialysis sessions due to acute renal failure and tubular nephropathy secondary to mercury poisoning. The patient was eventually referred to the anesthesia department for excision of foreign body granulomas. Fentanyl, Propofol, Atracurium and Sevoflurane were used to induce and maintain anesthesia. Intra-operative course was unremarkable. Chelation therapy with DMSA (2,3-dimercaptosuccinic acid) was done postoperatively. Serum mercury was undetectable 20 days after surgery and chelation therapy. There were no postoperative complications. The patient was discharged well after 43 days of admission.

Efectos neurotóxicos del timerosal, a dosis de vacuna, sobre el encéfalo y el desarrollo en hámsteres de 7 días de nacidos / Neurotoxic effects of thimerosal at vaccines doses on the encephalon and development in 7 day-old hamters

Objetivos: Determinar si la administración de timerosal, en cantidades equivalentes al contenido en las vacunas, produce efectos neurotóxicos a nivel encefálico en hámsteres de 7 días de nacidos y evaluar las influencias sobre el desarrollo de los animales de experimentación. Diseño: Estudio experimental, prospectivo y bietápico. Lugar: Bioterio de la Facultad de Medicina de San Fernando, Universidad Nacional Mayor de San Marcos. Material biológico: Hámsteres de 7 días de nacidos. Métodos: Se estudió 45 hámsteres divididos en tres grupos: grupo A (n = 15), grupo B (n = 15) y grupo C (n = 15). Se administró a los grupos B y C, por vía intramuscular, 3 dosis equivalentes de sucrosa y timerosal, respectivamente, los días 7 (0,227 μg), 9 (0,216 μg) y 11 (0,220 μg) de nacimiento, en un volumen de 20 μL de suero fisiológico. El grupo A solo recibió igual cantidad de suero fisiológico en los mismos días. Principales medidas de resultados: Peso corporal, peso encefálico, talla de los hámsteres y alteraciones histopatólógicas encefálicas. Resultados: Las pruebas Anova y t de student fueron significativas en favor al menor peso corporal, menor peso encefálico y menor talla del grupo C con respecto a los grupos A y B (p menor que 0,000). Mediante χ2, se obtuvo significancia en relación a la presencia de alteraciones histopatológicas en el grupo C (p menor que 0,000). El RR de presentar alteraciones fue muy elevado en este grupo. Conclusiones: La exposición a timerosal...

Objectives: To determine if thimerosal administration in amounts equivalent to vaccines content produces neurotoxic effects on the encephalon in postnatal hamsters and on experimentation animals' development. Design: Experimental, prospective, bietapic study. Setting: San Fernando Faculty of Medicine, Universidad Nacional Mayor de San Marcos. Biologic material: Seven-day old hamsters. Material: We divided 45 postnatal hamsters in three groups: group A (n = 15), group B (n = 15) and group C (n = 15). We administered three intramuscular equivalent doses of sucrose and thimerosal in 20 μL of physiological serum respectively to groups B and C on birth-days 7 (0,227 μg), 9 (0,216 μg) and 11 (0,220 μg). Group A received only 20 μL of saline solution. Main outcome measures: Body weight, encephalon weight, hamster's stature and encephalon histopathological alterations. Results: Anova and student t tests showed statistical significance in favor of low body weight, low encephalon weight and smaller stature in group C with respect to groups A and B hamsters (p minor 0,000). χ2 statistical significance in relation to the presence of histopathological alterations in group C was also obtained (p minor 0,000). We observed greater relative risk of encephalic alterations in group C. Conclusions: The administration of thimerosal à...

Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity

This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage.

Hypertensive encephalopathy induced by mercury poisoning; A report of 3 cases [in one iranian family]

Mercury poisoning is one of the important recent causes of mortality and mortality in children worldwide, particularly in industrial environments; mercury is a poisonous metal, especially harmful to the nervous and immune systems and the kidneys and can even be fatal. Elemental mercury is present in thermometers, barometer batteries, sphygmomanometers and latex paints. Inorganic mercury salts are found in antiseptics, pesticides, pigments and explosives and are used as preservatives in medicine. Mercury was once used to stop fever, and this worked because the immune system was so weakened that it could no longer sustain the attack for which the fever was created. Some medical drugs still contain mercury chloride and mercurous chloride and certain forms of mercury are still used in some laxatives. Mercury toxicity of the nervous system causes anorexia, ataxia, lack of ability to coordinate voluntary muscle movements, dementia, depression, dizziness, emotional instability, erethism. [abnormal irritability in response to stimulation], incoordination, insomnia, irritability, loss of ability to speak, memory impairment, numbness, saresthesias [sensation of prickling, tingling or creeping on the skin], psychosis, tremors, drowsiness, fatigue and weakness. Other organ damages include kidney failure, headaches, hearing impairment, visual impairment, hypertension, dermatitis, digestive tract problems, colitis, diarrhea, stomatitis and excessive salivation, loss of teeth, metallic taste, chromosomal damage, birth defects and ensuing organ failure. Chronic mercury poisoning can cause Acrodynia [Pink disease]. Mercury poisoning is a rare cause of hypertension in children. Herein we report 3 cases, the first a child with hypertensive encephalopathy due to severe mercury poisoning and his two siblings with moderate symptoms

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

Avaliaçäo da exposiçäo ao metil-mercúrio na população ribeirinha da baixada cuiabana, no Pantanal Mato-Grossense - Brasil / Evaluation of methylmercury exposure in riverine population from Baixada Cuiabana, Pantanal Region of Brazil

A população ribeirinha na região do Pantanal, Brasil, é dependente do peixe, como principal fonte de alimentos e proteínas. Naquela região, o resultado de décadas de mineração de ouro, em pequena escala, foi a contaminação de muitos sistemas aquáticos com mercúrio. Conseqüentemente, muitas espécies de peixes possuem níveis de MeHg relativamente altos. O objetivo deste trabalho foi avaliar o nível de exposição ao MeHg entre a população ribeirinha do Pantanal. No primeiro artigo, apresentam-se os resultados de validação do método recordatório de 24 horas auto-referido, utilizando-se como padrão ouro, o método da pesagem, tendo-se verificado que há aproximadamente um erro de 30 por cento ao estimar a quantidade de peixe consumido por aquela população. Um erro de 30 por cento na estimativa do consumo de peixe pode nao ter muita influencia na avaliaçao da ingestão de mercúrio, se se considerarem os peixes das espécies herbívoras. Porém, este erro pode ser importante em se tratando do consumo de peixes carnívoros, os quais apresentam altos teores de mercúrio. No segundo artigo, ao analisar a associação entre o status neurocognitivo e a concentração de mercúrio no cabelo da população acima, os resultados indicaram que adultos expostos ao metil-mercúrio, através do consumo de peixe, podem ter déficits importantes nas medidas do desempenho neurocomportamental, sem alterações detectáveis no humor ou afetividade. Os efeitos mais importantes do mercúrio, entre os indivíduos analisados, foram detectados nos testes de velocidade e destreza da coordenação motora fina, na inibição da resposta na busca visual, e em tarefas de atenção. Estes resultados são consistentes com outros estudos, que sugeriram que o mercúrio causa alterações no cerebelo. A possibilidade de efeitos adversos, em adultos expostos a níveis mais baixos de mercúrio, foi também levantada por outros estudos no Brasil, que abordaram o consumo de peixe pelas populações ribeirinhas. No terceiro artigo ... calculou-se a dose marcadora (BMD) e o limite inferior do intervalo de confiança do BMD (BMDL)...

Avaliaçäo da contaminaçäo mercurial mediante análise do teor de Hg total em amostras de cabelo em comunidades ribeirinhas do Tapajós, Pará, Brasil / Total mercury in hair samples of inhabitants of Tapajós river, Pará State, Brazil

Este estudo avalia a contaminaçäo mercurial em comunidades de pescadores em quatro localidades nas margens do rio Tapajós: Rainha, Barreiras, Säo Luís do Tapajós e Paraná-Mirim. Análises toxocológicas das amostras de cabelo foram realizadas por espectofotometria de absorçäo atômica. Os níveis de mercúrio total em amostras de cabelo variaram entre 2,9µg/g e 71,5µg/g. Os valores mais baixos foram encontrados na comunidade de Paraná-Mirim. Os mais elevados, em Säo Luís do Tapajós e Barreiras, cerca de seis a sete vezes superiores ao valor estabelecido. As diferenças entre as concentraçöes médias de mercúrio total nas amostras, coletadas em populaçöes ribeirinhas, a montante e a jusante do rio Tapajós em Itaituba, näo apresentaram significância estatística (p > 0, 05). Conclui-se que a exposiçäo humana ao mercúrio por ingestäo de peixes contaminados constitui risco potencial para o aparecimento de sintomas e sinais da doença de Minamata, o que recomenda a manutençäo de um programa de vigilância epidemiológica

role of calcium channel blockers in methyl mercury-induced neurotoxicity and nephrotoxicity in adult Albino rats

This study was carried out on 135 adult albino rats of both sexes to investigate the effect of repeated administration of methyl mercury on brain and kidney and to evaluate the possible protective role of calcium channel blockers. The rats were divided into nine equal groups. The brain and the kidneys were dissected and prepared for a light microscopical examination. The administration of methyl mercury [group VI] resulted in an affection of certain areas of the brain. The cerebellar cortex was mostly affected. The purkinje cells were shrunken with irregular outlines, while many granule cells showed pyknotic nuclei. Certain areas of the cerebral cortex were affected, especially the occipital cortex. The kidney function tests were significantly affected and histologically, both proximal and distal convoluted tubules were severely affected. In group VII and group VIII, there was a slight biochemical and histological improvement. A marked improvement was also observed in group IX. It was concluded that the use of multiple calcium channel blockers could improve neurotoxicity and nephrotoxicity induced by methyl mercury

Effect of Methylmercury in Cultured Rat Myocardial Cells

BACKGROUND: It is known that methylmercury poisoning, Minamata disease is very toxic to human body. But, cardiotoxic mechanism of methylmercury is left unknown, Recent study has been reported that the cleavage of methylmercury produce oxygen radicals as well as methyl radicals, and also these radicals induce the release of excitotoxic amino acids(EAAs). So, oxygen radicals and EAA are regarded as a causative factors in the various diseases such as heart disease induced by toxicity of methylmercury. We studied to know the cardiotoxic effect of methylmercury on cultured myocardial cells derived from neonatal rat in order to evaluate the toxic mechanism of methylmercury. METHODS: Myocardial cells of neonatal rat were incubated with various concentrations of methylmercuric chloride for 1-96 hours. MTT90 and MTT50 values were measured and cell viability was determined by MTT assay. In addition, morphological study was performed by light microscope after cultured myocardial cells that were exposed to methymercuric chloride. RESULTS: MTT90 and MTT50 values were 1microM and 15microM of methylmercuric chloride in cultured myocardial cells of neonatal rat respectively. Exposure of cultured rat myocardial cells to methylmercuric chloride resulted in a significant cell death in a time-dependent manner. In the observation of morphological changes, cultured cells treated with methlymercuric chloride showed decrease of cell number and disconnection between cultured myocardial cells. CONCLUSION: These observation suggest that methylmercury has a severe myocardiotoxicity on cultured myocardial cells derived from neonatal rat by the decrease of cell viability and morphological changes.