Ocular manifestations of microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) syndrome associated with mutations in KIF11

Purpose Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is an autosomal dominant condition. Mutations in KIF11 have been found to be causative in approximately 75% of cases. This study describes the ocular phenotype in patients with confirmed KIF11 mutations. Methods Standard ophthalmic examination and investigation including visual acuity, refraction and fundus examination was carried out in all patients. Fundus autofluorescence imaging (FAF) was performed in three patients, and four patients underwent spectral domain optical coherence tomography (OCT). Flash electroretinography (ERG) was performed in seven patients, and five underwent additional pattern electroretinography (PERG). Results The patients ranged in age from 2 to 10 years. Most presented with visual acuity loss. Fundus examination revealed lacunae of chorioretinal atrophy. Pigmentary macular changes and optic disc pallor were present in three of seven patients. Fundus autofluorescence demonstrated hypoautofluorescence at the macula in two of three patients. The lacunae of chorioretinal atrophy were hypoautofluorescent. The OCT showed atrophic maculae in three of four patients. Follow-up in one patient showed no deterioration of the vision over a 9-year period. The lesions appear not to be progressive on the follow-up imaging. Electrophysiology showed generalized rod and cone dysfunction and severe macular dysfunction. Inner retinal dysfunction was evident in three of seven patients. Conclusions Patients with KIF11 mutations show a specific ocular phenotype with variable expressivity and intrafamilial variability. Macular atrophy and dysfunction have not been consistently documented before. The fundus lesions appear non-progressive. The findings assist in providing an accurate diagnosis and thus improving the management and follow-up of patients with this syndrome.

Neuroreceptor availability and cerebral morphology in human obesity

Obesity is a major challenge to human health worldwide. Little is known about the brain mechanisms that are associated with overeating and obesity in humans. In this project, multimodal neuroimaging techniques were utilized to study brain neurotransmission and anatomy in obesity. Bariatric surgery was used as an experimental method for assessing whether the possible differences between obese and non-obese individuals change following the weight loss. This could indicate whether obesity-related altered neurotransmission and cerebral atrophy are recoverable or whether they represent stable individual characteristics. Morbidly obese subjects (BMI ≥ 35 kg/m2) and non-obese control subjects (mean BMI 23 kg/m2) were studied with positron emission tomography (PET) and magnetic resonance imaging (MRI). In the PET studies, focus was put on dopaminergic and opioidergic systems, both of which are crucial in the reward processing. Brain dopamine D2 receptor (D2R) availability was measured using [11C]raclopride and µ-opioid receptor (MOR) availability using [11C]carfentanil. In the MRI studies, voxel-based morphometry (VBM) of T1-weighted MRI images was used, coupled with diffusion tensor imaging (DTI). Obese subjects underwent bariatric surgery as their standard clinical treatment during the study. Preoperatively, morbidly obese subjects had significantly lower MOR availability but unaltered D2R availability in several brain regions involved in reward processing, including striatum, insula, and thalamus. Moreover, obesity disrupted the interaction between the MOR and D2R systems in ventral striatum. Bariatric surgery and concomitant weight loss normalized MOR availability in the obese, but did not influence D2R availability in any brain region. Morbidly obese subjects had also significantly lower grey and white matter densities globally in the brain, but more focal changes were located in the areas associated with inhibitory control, reward processing, and appetite. DTI revealed also signs of axonal damage in the obese in corticospinal tracts and occipito-frontal fascicles. Surgery-induced weight loss resulted in global recovery of white matter density as well as more focal recovery of grey matter density among obese subjects. Altogether these results show that the endogenous opioid system is fundamentally linked to obesity. Lowered MOR availability is likely a consequence of obesity and may mediate maintenance of excessive energy uptake. In addition, obesity has adverse effects on brain structure. Bariatric surgery however reverses MOR dysfunction and recovers cerebral atrophy. Understanding the opioidergic contribution to overeating and obesity is critical for developing new psychological or pharmacological treatments for obesity. The actual molecular mechanisms behind the positive change in structure and neurotransmitter function still remain unclear and should be addressed in the future research.

Processos degenerativos do tecido cutâneo

Os processos degenerativos do tecido cutâneo estão amplamente associados ao seu envelhecimento natural, onde se verifica perda de tecido fibroso, renovação celular mais lenta e redução da rede vascular e glandular da pele. Alguns fatores externos ao organismo podem contudo acelerar estes processos, como por exemplo a exposição solar, consumo excessivo de álcool e tabaco, poluição ambiental e aumento de peso. De entre estes processos destacam-se o processo descamativo, um fenómeno natural do mecanismo de diferenciação dos queratinócitos. É um processo complexo que envolve essencialmente a degradação da coesão entre células da pele. A lipodistrofia ginóide é outro destes processos, comummente denominado de celulite, e que se caracteriza como uma distrofia celular complexa, com alterações do metabolismo hídrico que conferem uma aparência de "casca de laranja" à pele. A flacidez é um processo resultante da atrofia tecidular, onde se verifica a perda progressiva de massa muscular que é substituída por tecido adiposo. Está diretamente relacionada com a redução da produção de fibras de colagénio e fibras elásticas no tecido subcutâneo. Por fim, insuficiência venosa é um termo utilizado para caracterizar um processo que afeta o sistema venoso dos membros inferiores, que se desenvolve por aumento da pressão venosa em combinação com um retorno venoso ineficiente. Embora ainda não exista compreensão total destes mecanismos, já é possível encontrar uma série de tratamentos que visam minimizar ou mesmo tratá-los, de modo a que não se agravem e representem um risco sério para a saúde.

Altération de la régénération musculaire dans la maladie pulmonaire obstructive chronique

Altération de la régénération musculaire dans la maladie pulmonaire obstructive chronique. La maladie pulmonaire obstructive chronique (MPOC) est caractérisée par une obstruction bronchique irréversible et progressive. L’atrophie musculaire périphérique y est fréquente et a un impact négatif sur la capacité fonctionnelle et la survie des sujets atteints. Toutefois, on ignore si une altération du processus de régénération musculaire est un processus ayant cours dans l’atrophie musculaire périphérique. Le but de la présente thèse était donc d’étudier les cellules satellites, principales cellules responsables de la régénération musculaire dans les muscles périphériques de patients ayant une MPOC. Dans un premier temps, nous avons évalué l’historique de réplication du tissu musculaire et la sénescence des cellules satellites. Les changements morphologiques ayant lieu dans le muscle au cours de la progression de la maladie rendent le muscle plus susceptible aux dommages, induisant un raccourcissement prématuré des télomères. Un raccourcissement des télomères chez les sujets ayant une MPOC avec atrophie est concomitant avec une augmentation du nombre de cellules satellites sénescentes et de l’épuisement du potentiel de régénération compromettant le maintien de la masse musculaire chez ces sujets. Dans un deuxième et troisième temps, nous avons étudié les étapes amenant une cellule satellite vers une cellule musculaire dans les muscles périphériques et respiratoires de patients ayant une MPOC comparativement à des sujets contrôles. Les cellules satellites sont impliquées dans la réparation du tissu musculaire. Dans les cellules satellites provenant des sujets ayant une MPOC, une altération de la prolifération et de la différentiation a été observée. Ces résultats sont compatibles avec une altération de la régénération musculaire pouvant conduire à l’atrophie musculaire dans la MPOC. Le quatrième volet de ce projet s’intéressait à l’impact d’un entraînement en résistance sur l’activité des cellules satellites et le rôle joué par la myostatine dans ce contexte. La littérature montre que l’exercice en résistance est bien toléré et aide les patients ayant une MPOC à retrouver une meilleure qualité de vie. Cependant, il semble qu’ils n’y répondent pas tous aussi bien que les sujets contrôles. La capacité de réponse des cellules satellites à un entraînement en résistance semble inadéquate, suggérant ainsi un défaut de leur activation. Dans la dernière étude de cette thèse, nous avons voulu évaluer l’impact de l’inflammation systémique en étudiant SAA1, une protéine de phase aiguë et p21, une protéine du cycle cellulaire dans la dégradation des protéines des cellules musculaires. Les liens de causalité entre l’affection primaire et les différentes comorbidités demeurent nébuleux dans la MPOC. SAA1 et p21 sont augmentés dans les muscles squelettiques des patients ayant une MPOC et par ailleurs, SAA1 est capable d’induire la dégradation des protéines musculaires. Cette thèse expose les premiers éléments impliquant l’altération de la régénération musculaire avec la dysfonction musculaire observée chez les patients ayant une MPOC. Ces résultats vont certainement contribuer au développement de nouvelles thérapies et stratégies d’intervention dans le but d’améliorer la qualité de vie des personnes atteintes d’une MPOC. En somme, les travaux effectués dans le cadre de la présente thèse montrent que plusieurs mécanismes agissent de concert avec l’inactivité physique afin d’induire le phénotype dysfonctionnel dans les muscles des patients ayant une MPOC.

Prevenção da reabsorção óssea alveolar após extração dentária

Introdução: O processo alveolar é o conjunto de osso que se encontra em redor da raiz do dente. Este osso é sensível a uma variedade de fatores ambientais e fisiológicos que influenciam a sua integridade e o seu funcionamento. Como tal, a sua formação assim como a sua preservação é dependente da presença contínua do dente. A reabsorção do processo alveolar após extração dentária é uma consequência natural e fisiológica indesejável, que pode dificultar a colocação de um implante dentário na posição desejada. Com o aumento cada vez mais das demandas estéticas em medicina dentária, torna-se, portanto, necessário prevenir que a reabsorção óssea provoque este defeito na arcada dentária. Objetivos: Realizar uma revisão bibliográfica sobre as várias técnicas e materiais para preservação do rebordo alveolar, a fim de prevenir ou minimizar a reabsorção alveolar após extração dentária. Material e Métodos: A pesquisa foi realizada nas bases de dados Pubmed, B-on e Scielo, não foi aplicado nenhum limite temporal, e os critérios de inclusão foram artigos em língua inglesa e portuguesa. Num total de 164 artigos, selecionaram-se 82 estritamente relacionados com o tema. Os artigos excluídos desviavam-se do objetivo do trabalho ou eram inconclusivos. Selecionaram-se, também, capítulos do livro Clinical Periodontology and Implant Dentistry Volume 1 e 2, dos autores Niklaus P.Lang e Jan Lindhe. Desenvolvimento: De modo a compreender como o processo alveolar reabsorve, deve-se ter em conta as várias técnicas que se podem realizar para permitir uma boa quantidade de osso remanescente na arcada adequada a cada caso para uma possível reabilitação. As técnicas de preservação do osso alveolar após extração passam pela realização de técnicas cirúrgicas minimamente invasivas, estabilização do coágulo pelo princípio da cicatrização por primeira intenção usando membranas ou retalhos, preenchimento do alvéolo dentário com materiais de enxerto ou substitutos ósseos, terapias combinadas com a colocação de implantes imediatos e o recurso a células e fatores de crescimento. Conclusão: A preservação alveolar tem grande importância para uma posterior reabilitação oral com implantes com maior quantidade de osso disponível do que quando não é feita qualquer tipo de preservação. A extração das peças dentárias deve ser feita com cuidado para preservar ao máximo ou não danificar as superfícies ósseas remanescentes. É aconselhado que o encerramento da ferida seja por primeira intenção e que proporcione estabilidade ao coágulo, podendo ser usado retalhos ou mesmo membranas. O uso de enxertos ósseos tem uma importante função de proporcionar uma matriz para o coágulo se formar e promover o processo de cicatrização. O método de implante imediato, para além de ser bastante usado, tem como finalidade o conforto para o paciente de não ser submetido a uma posterior cirurgia para colocação do mesmo e, simultaneamente, mantem a estabilidade dos tecidos moles. Ainda uma técnica menos usada é com células e fatores de crescimento que proporciona uma cicatrização mais rápida e um aumento do potencial regenerativo dos tecidos.

Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

Efeitos de um programa de reabilitação instituído a pessoas submetidas a artroplastia total da anca

Introdução: O aumento da esperança média de vida torna as pessoas mais vulneráveis e dependentes, especialmente no que se refere às atividades quotidianas. A coxartrose é uma das osteoartroses mais comuns, manifestada por dor, limitação progressiva da mobilidade articular e atrofia muscular. A artroplastia total da anca tem-se afirmado como alternativa eficaz e com sucesso ao longo do tempo. Hoje em dia, a necessidade de recuperação funcional após a cirurgia é irrefutável. Neste contexto, a reabilitação assume um papel primordial, quer na maximização das capacidades e minimização dos défices pós-cirúrgicos da pessoa, quer no restabelecimento da sua autonomia e consequente retorno à vida social e profissional. Objetivo: Avaliar os efeitos de um programa de reabilitação instituído a pessoas submetidas a artroplastia total da anca. Metodologia: Foi realizado um programa de reabilitação às pessoas submetidas a artroplastia total da anca, com início no primeiro dia de pós-operatório até à consulta pós-operatória, baseado em exercícios resistidos, a 28 pessoas. Avaliaram-se a força muscular (Lafayette manual muscle tester), a amplitude articular (goniometria), a escala de Tinetti e o questionário WOMAC. A colheita de dados foi realizada em três momentos (admissão – T0, alta – T1 e primeira consulta pós-cirurgia – T2). Resultados: Após o programa verificou-se uma melhoria substancial da qualidade de marcha e dos domínios do questionário WOMAC, até ao dia da consulta de ortopedia, que em média foi de 41 dias. A força muscular, quer força máxima quer força média, diminuiu ligeiramente em T1 e em T2 aumentou, exceto nos isquiotibiais em que existe um incremento em todas as avaliações. Verificou-se ainda que os resultados obtidos são independentes da idade, sexo e existência de cirurgia ortopédica anterior. Conclusão: Comprova-se que um programa de reabilitação que forneça as competências necessárias às pessoas, em que se conjugue reabilitação em ambiente hospitalar e domiciliário, é crucial para uma recuperação rápida e eficaz.

The pathophysiology of CADASIL: studies in a Scottish cohort

Since identification that mutations in NOTCH3 are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the early 1990s, there has been extensive characterisation of the clinical and radiological features of the disease. However therapeutic interventions remain elusive, partly due to a limited understanding of the vascular pathophysiology and how it leads to the development of strokes, cognitive decline and disability. The apparent rarity and heterogenous natural history of CADASIL potentially make conducting any longitudinal or therapeutic trials difficult. The role of disease biomarkers is therefore of some interest. This thesis focuses on vascular function in CADASIL and how it may relate to clinical and radiological markers of disease. Establishing the prevalence of CADASIL in the West of Scotland was important to assess the impact of the disease, and how feasible a trial would be. A mutation prevalence of 10.7 per 100,000 was demonstrated, suggesting significant under diagnosis of the disease across much of Scotland. Cerebral hypoperfusion is thought to be important in CADASIL, and it has been shown that vascular abnormalities precede the development of brain pathology in mouse models. Investigation of vascular function in patients, both in the brain and systemically, requires less invasive measures. Arterial spin labelling magnetic resonance imaging (MRI) and transcranial Doppler ultrasound (TCD) can both be used to obtain non-invasive and quantifiable indices of vascular function. Monitoring patients with MRI whilst they receive different concentrations of inspired oxygen and carbon dioxide can provide information on brain function, and I reviewed the practicalities of this technique in order to guide the design of the studies in this thesis. 22 CADASIL patients were recruited to a longitudinal study. Testing included peripheral vascular assessment, assessment of disability, neurological dysfunction, mood and cognition. A CO2 reactivity challenge during both TCD and arterial spin labelling MRI, and detailed MRI sequences were obtained. I was able to demonstrate that vasoreactivity was associated with the number of lacunes and brain atrophy, as were carotid intima-media thickness, vessel stiffness, and age. Patients with greater disability, higher depressive symptoms and poorer processing speed showed a tendency to worse cerebral vasoreactivity but numbers were small. This observation suggests vasoreactivity may have potential as a therapeutic target, or a biomarker. I then wished to establish if arterial spin labelling MRI was useful for assessing change in cerebral blood flow in CADASIL patients. Cortical grey matter showed the highest blood flow, mean (SD), 55 (10) ml/100g/min and blood flow was significantly lower within hyperintensities (19 (4) ml/100g/min; p <0.001). Over one year, blood flow in both grey matter (mean -7 (10) %; p = 0.028) and deep white matter (-8 (13) %; p = 0.036) declined significantly. Cerebrovascular reactivity did not change over one year. I then investigated whether baseline vascular markers were able to predict change in radiological or neuropsychological measures of disease. Changes in brain volume, lacunes, microbleeds and normalised subcortical hyperintensity volume (increase of 0.8%) were shown over one year. Baseline vascular parameters were not able to predict these changes, or those in neuropsychological testing. NOTCH3 is found throughout the body and a systemic vasculopathy has been seen particularly affecting resistance vessels. Gluteal biopsies were obtained from 20 CADASIL patients, and ex vivo myography investigated the response to vasoactive agents. Evidence of impairment in both vasodilation and vasoconstriction was shown. The addition of antioxidants improved endothelium-dependent relaxation, indicating a role for oxidative stress in CADASIL pathology. Myography measures were not related to in vivo measures in the sub-group of patients who had taken part in both studies. The small vessels affected in CADASIL are unable to be imaged by conventional MR imaging so I aimed to establish which vessels might be responsible for lacunes with use of a microangiographic template overlaid onto brain images registered to a standard brain template. This showed most lacunes are small and associated with tertiary arterioles. On the basis of this thesis, it is concluded that vascular dysfunction plays an important role in the pathophysiology of CADASIL, and further assessment of vascular measures in longitudinal studies is needed. Arterial spin labelling MRI should be used as it is a reliable, non-invasive modality that can measure change over one year. Furthermore conventional cardiovascular risk factor prevention should be undertaken in CADASIL patients to delay the deleterious effects of the disease.

Huge Tracheal Diverticulum in a Patient with Mounier-Kuhn Syndrome

Tracheal diverticulum is a rare benign entity. Tracheobronchomegaly (TBM), also known as Mounier-Kuhn syndrome, is a rare disorder characterized by marked dilation of the trachea and main bronchi, associated with thinning or atrophy of the elastic tissue. Because of the weakened trachea and increased intraluminal pressure related to chronic cough, some patients may develop mucosal herniation leading to tracheal diverticulosis. We report the case of a patient with TBM with a huge tracheal diverticulum, diagnosed by bronchoscopy and computed tomography with three-dimensional reconstruction. To our knowledge this is the largest tracheal diameter described in a patient affected by this syndrome.

Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis

International audience

OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology

International audience

Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction

International audience

Friedreich Ataxia

Friedreich ataxia (FRDA) is an autosomal recessive disease characterized by progressive neurological and cardiac abnormalities. It has a prevalence of around 2×10⁵ in whites, accounting for more than one-third of the cases of recessively inherited ataxia in this ethnic group. FRDA may not exist in nonwhite populations.The first symptoms usually appear in childhood, but age of onset may vary from infancy to adulthood. Atrophy of sensory and cerebellar pathways causes ataxia, dysarthria, fixation instability, deep sensory loss, and loss of tendon reflexes. Corticospinal degeneration leads to muscular weakness and extensor plantar responses. A hypertrophic cardiomyopathy may contribute to disability and cause premature death. Other common problems include kyphoscoliosis, pes cavus, and, in 10% of patients, diabetes mellitus.The FRDA gene (FXN) encodes a small mitochondrial protein, frataxin, which is produced in insufficient amounts in the disease, as a consequence of the epigenetic silencing of the gene triggered by a GAA triplet repeat expansion in the first intron of the gene. Frataxin deficiency results in impaired iron-sulfur cluster biogenesis in mitochondria, in turn leading to widespread dysfunction of iron-sulfur center containing enzymes (in particular respiratory complexes I, II and III, and aconitase), impaired iron metabolism, oxidative stress, and mitochondrial dysfunction. Therapy aims to restore frataxin levels or to correct the consequences of its deficiency.

Growth, feed intake, survival, and histological response of white shrimp Litopenaeus vannamei fed diets containing grains naturally contaminated with aflatoxin = Crecimiento, consumo de alimento, supervivencia y respuesta histológica del camarón blanco Litopenaeus vannamei alimentado con dietas de granos contaminados naturalmente con aflatoxinas

Two feeding trials were carried out to evaluate the effect of diets containing corn or peanut grains naturally contaminated with aflatoxins on the growth, feed intake, survival, and histological response of the white shrimp Litopenaeus vannamei. In trial 1, four experimental diets were formulated to contain 0, 500, 1000, and 2000 g kg–1 of total aflatoxins (TA) and fed to L. vannamei juveniles for 28 days. In trial 2, six experimental diets were formulated to contain 0, 10, 20, 40, 60, and 120 g kg–1 TA and fed to L. vannamei juveniles for 64 days. Feed intake and weight gain were significantly affected by the presence of aflatoxins from naturally contaminated grains. Feed conversion rate increased significantly from a level of inclusion of 60 g kg–1. Survival was significantly reduced only for shrimp fed diets supplemented with 1000 and 2000 g kg–1 TA. Shrimp exposed to higher aflatoxin inclusion levels presented significantly lower lipid vacuole levels in R-cells (12–28%), lower B-cell activity, and lower mitotic E-cell activity. Tubular epithelial atrophy increased from the inclusion level of 20 g kg–1. Hepatopancreatocyte sloughing was significantly higher in shrimp fed diets supplemented with 1000 and 2000 g kg–1 TA. It is worth noting that shrimp fed 40 g kg–1 TA presented a high hepatopancreatocyte sloughing coefficient. Based on these results we conclude that the presence of aflatoxins, even at low levels, reduces feed intake and weight gain, and alters the cells of the hepatopancreas. RESUMEN. Se llevaron a cabo dos bioensayos para evaluar el efecto de granos de maíz y maní contaminados naturalmente con aflatoxinas sobre el crecimiento, consumo de alimento, supervivencia y daños histológicos de juveniles del camarón blanco Litopenaeus vannamei. Para el bioensayo 1, se formularon cuatro dietas con 0, 500, 1000 y 2000 g kg–1 de aflatoxinas totales (AT) y se proporcionaron a juveniles de L. vannamei durante 28 días. Para el bioensayo 2, se formularon seis dietas con 0, 10, 20, 40, 60 y 120 g kg–1 AT y se proporcionaron a juveniles de L. vannamei durante 64 días. El consumo de alimento fue significativamente afectado por la presencia de aflatoxinas. La tasa de conversión alimenticia incrementó significativamente a partir de un nivel de inclusión de 60 g kg–1. La supervivencia fue significativamente reducida solamente en los camarones que fueron alimentados con las dietas suplementadas con 1000 y 2000 g kg–1 AT. Los camarones expuestos a los niveles de inclusión altos presentaron un menor nivel de vacuolas lipídicas en las células R (12–28%), y una menor actividad de las células B y de la actividad mitótica de las células E. La atrofia de los túbulos del epitelio se incrementó a partir de un nivel de inclusión de 20 g kg–1. La descamación de las células del hepatopáncreas fue significativamente mayor en camarones alimentados con las dietas suplementadas con 1000 y 2000 g kg–1 AT, mientras que para las dosis bajas no se observaron diferencias significativas, aunque en camarones alimentados a partir de 40 g kg–1 AT se observa un coeficiente de descamación alto. Con base en los resultados, se concluye que la presencia de aflatoxinas, incluso a niveles bajos, reduce el consumo de alimento y el aumento de peso y altera las células del hepatopáncreas.