Trastornos del espectro autista: observaciones en el patrón evolutivo. Lo que los padres nos cuentan en la consulta / Autism spectrum disorders: observations in the evolutionary pattern. What parents tell us in the consultation

La necesidad de mejorar la detección temprana del trastorno del espectro autista (TEA) implica mejorar las herramientas en la primera línea de atención al niño. La dimensionalidad del TEA, recogida en las clasificaciones internaciones (APA y CIE), reconoce el carácter heterogéneo del trastorno y la afectación de múltiples áreas en diferentes niveles de gravedad. Con el fin de evitar la demora en el proceso de diagnóstico se propone que, en la entrevista general de anamnesis, el pediatra incluya la exploración de manifestaciones conductuales que suelen concurrir en el patrón evolutivo de estos niños para agilizar la evaluación por el especialista correspondiente, quien determinará finalmente el diagnóstico, si fuera el caso. Estas observaciones se encuentran diferenciadas en 11 áreas, recogiendo además cómo expresan estos problemas los padres en la consulta. Se espera que esta aportación sirva de orientación práctica para la detección precoz de los TEA entre los profesionales que atienden en primer lugar al niño (AU)

The need to improve early detection of Autism Spectrum Disorder (ASD) implies improving tools in the first line of care for the child. The dimensionality of ASD, according to the international classifications (APA and ICD), recognizes the heterogeneous nature of the disorder and the involvement of multiple areas at different levels of severity. In order to avoid delay in the diagnosis process, it is proposed that the paediatrician could include in the general anamnesis the exploration of behavioural manifestations that usually concur in the evolutionary pattern of these children to expedite the evaluation by the corresponding specialist who finally determines the diagnosis, if applicable. These observations are differentiated in 11 areas, also reflecting how parents express these problems in the consultation. This contribution is expected to serve as a practical guide for the early detection of ASD among the professionals who care for the child first. (AU)

Perfil de desarrollo en una cohorte de muy bajo peso al nacimiento / Developmental profile of a cohort of very low birth weight

Introducción: Los estudios longitudinales realizados en niños que presentaron un peso al nacimiento inferior a 1.500 g (muy bajo peso al nacimiento [MBPN]) han demostrado la presencia de dificultades en la edad adulta que no son explicables por las variables clásicamente analizadas (inteligencia, sexo, etc.). Objetivos: Conocer las condiciones evolutivas de estos niños en diferentes momentos cronológicos y la capacidad predictiva de los controles iniciales en edades tempranas respecto a la edad escolar. Sujetos y método: Se realizó un estudio descriptivo en una cohorte de 317 niños con MBPN, nacidos entre 2001 y 2010 en la Unidad de Neonatología del Hospital General Universitario de Alicante, y se obtuvieron datos del perfil psicomotor e intelectual y de las alteraciones conductuales. Las evaluaciones se realizaron a los 20 y 28 meses de edad corregida, y a los 6,5 años. Resultados: Observamos una mayor presencia de niveles de desarrollo psicomotor en el límite inferior del promedio adecuado a la edad cronológica, cocientes intelectuales en el rango medio-bajo, mayor frecuencia de síntomas y signos de trastorno por déficit de atención e hiperactividad (TDAH), y la presencia de alteraciones cualitativas como posibles indicadores de trastornos del espectro autista (TEA). Los controles iniciales a la edad de 20 y 28 meses han resultado ser predictivos de la capacidad intelectual y los síntomas de probable TEA obtenidos a los 6 años. Conclusión: Cabe afirmar que la evolución posterior de estos niños está condicionada no tanto por los aspectos relacionados con la capacidad intelectual, como por la posibilidad de que presenten TDAH y/o TEA (AU)

Introduction: Longitudinal studies done in children who presented at birth a weight lower than 1,500 g (very low birth weight [VLBW]), have evidenced difficulties in their adulthood which cannot be explained by the classical analyzed variables (intelligence, gender, etc.). Objectives: To research the developmental conditions of these children in different chronological moments and find out the predictive capacity of the initial trials done at early ages regarding to the results at school age. Subjects and method: A descriptive study was carried out in a cohort of 317children with VLBW, born between 2001 and 2010, on the Neonatology Unit at the Hospital General Universitario de Alicante obtaining data of the psychomotor and intellectual profiles, and behavior disturbances. Evaluations had been done at the corrected age of 20 and 28 months, and 6.5 years. Results: We observed higher presence of: psychomotor quotients in the low border of the appropriate average for the chronological age, intelligent quotients in the medium-low range, higher frequency of symptoms and signs of attention deficit and hyperactive disorder (ADHD), and presence of qualitative disturbances which might indicate an autism spectrum disorder (ASD). Initial controls at the age of 20 and 28 months had shown they are predictors of the intellectual capacity and the possible symptoms of ADS obtained at the age of 6. Conclusion: It is likely to affirm that the later development of these children is compromised not as much by their intellectual capacity, as by for the possibility of being presenting ASD or ADHD (AU)

Autoimmunity as a prognostic factor in sporadic adult onset cerebellar ataxia.

Cerebellar adult onset ataxia is a heterogeneous condition. The aim of this study was to ascertain if there is a heightened autoimmune background in patients with sporadic cerebellar ataxia of unknown origin, and if autoimmunity correlates with a more rapid evolution of the ataxia. We selected patients with sporadic progressive adult onset cerebellar ataxia with a follow-up of >5 years. As controls we included 43 patients with genetically demonstrated hereditary ataxia. All patients were tested for a panel of neuronal (onconeuronal, glutamate-decarboxylase [GAD], IgG/IgA transglutaminase 6 antibodies) and systemic non-neuronal antibodies (including IgG/IgA gliadin and transglutaminase 2, thyroperoxidase, thyroglobulin, antinuclear, striational, smooth muscle, mitochondrial, liver kidney microsomal, and parietal gastric cells antibodies). Correlation between the antibodies and disease progression was studied with Cox regression models and Kaplan-Meier plots. Forty-four patients were included. All patients were negative for onconeuronal or GAD antibodies. There were no significant differences between patients and controls in the prevalence of transglutaminase 6, 2, gliadin, or thyroid antibodies. However, when we studied the panel of systemic non-neuronal autoantibodies as a group, antibodies were more frequent in patients with sporadic ataxia (p = 0.018). The presence of one or more systemic non-neuronal antibodies correlated with a faster evolution to stage 2 (loss of independent gait) (p = 0.03) and shorter survival (p = 0.03) in patients with sporadic ataxia. We conclude that there is probably a heightened autoimmune background in some patients with sporadic cerebellar ataxia of unknown origin. The presence of systemic non-neuronal autoantibodies is a prognostic marker.

Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients.

Laing myopathy is a distal myopathy caused by mutations in the tail of the slow beta-myosin heavy chain gene MYH7. A large cluster of patients belonging to different families, with Laing myopathy due to p.K1729del mutation, was found in the Safor region, Spain. The same mutation was previously reported in an American family with Italian ancestry. The possibility that p.K1729del in MYH7 might be a founder mutation in the Safor patients and the chance of a common origin with the Italian-American family mutation was investigated by haplotype analyses, mutation data origin estimation and historical inquiry. Our results show that the p.K1729del in MYH7 harboured by patients from the Safor indeed is a founder mutation. A common ancestral origin of this mutation in the Spanish and Italian families is also suggested because they all share a core SNP haplotype at locus MYH7. Data estimation yields the origin of the mutation in the Safor at the beginning of the XVII century, when the Moorish were spelt and the region was resettled with Italian families.

Microdeleción 15q11.2 (BP1-BP2). Un nuevo síndrome con expresividad variable / 15Q11.2 (BP1-BP2) microdeletion, a new syndrome with variable expressivity

Presentamos el caso de un niño con retraso psicomotor y rasgos dismórficos afectado de una microdeleción 15q11.2 de 1.5 Mb de origen paterno diagnosticada mediante array-based comparative genomic hybridization. La deleción está comprendida entre los puntos de rotura BP1-BP2 de la región crítica descrita para los síndromes Prader-Willi/Angelman. Comparamos las características clínicas de nuestro paciente con las halladas en los 10 casos de deleción puraBP1-BP2 descritos hasta la fecha (AU)

The case of a boy with psychomotor retardation and dysmorphic features is presented. He has a 1.5 Mb 15q11.2 microdeletion of paternal origin diagnosed by a CGH. The deletionis located between breakpoints BP1 and BP2 of the Prader-Willi/Angelman syndromes critical region. Clinical features in our patient fit well with those described in ten cases of pure BP1-BP2deletion published to date (AU)

[15Q11.2 (BP1-BP2) microdeletion, a new syndrome with variable expressivity]. / Microdeleción 15q11.2 (BP1-BP2). Un nuevo síndrome con expresividad variable.

The case of a boy with psychomotor retardation and dysmorphic features is presented. He has a 1.5 Mb 15q11.2 microdeletion of paternal origin diagnosed by aCGH. The deletion is located between breakpoints BP1 and BP2 of the Prader-Willi/Angelman syndromes critical region. Clinical features in our patient fit well with those described in ten cases of pure BP1-BP2 deletion published to date.

Peripheral nerve hyperexcitability: a clinical and immunologic study of 38 patients.

OBJECTIVE: We studied a case series of peripheral nerve hyperexcitability (PNH) aiming to describe clinical characteristics, immunologic and cancer associations, antibodies against neuronal antigens (voltage-gated potassium channel antibodies [VGKC-Abs] and other), and muscle biopsy findings. METHODS: Patients presenting with clinical and electrophysiologic signs of PNH were selected. We studied clinical and electrophysiologic features; a panel of non-neuronal organ-specific antibodies, immunofluorescence on rat nervous tissues, and radioimmunoprecipitation for VGKC-Abs; and muscle biopsies. RESULTS: Thirty-eight patients were included. After the exclusion of 6 cases with axonopathy of known origin, patients were subdivided according to the presence of electrophysiologic findings of motor axonopathy and association with cancer: axonopathic-PNH (group A: 12 patients), isolated nonparaneoplastic PNH (group B: 16 patients), and isolated paraneoplastic PNH (3 with thymoma and myasthenia gravis, 1 with thyroid carcinoma). PNH clinical features were similar in groups A and B. We found an overall high prevalence of clinical autoimmunity (33% of group A and 63% of group B) and systemic non-neuronal autoantibodies (42% of group A and 75% of group B). However, VGKC-Abs were only positive in 2 patients of group B. Ten patients underwent muscle biopsy, which showed inflammatory changes in 2 cases and nonspecific myopathic features in 8. CONCLUSIONS: PNH is a heterogeneous disorder involving the peripheral nerves in patients with a high propensity for developing autoimmunity. Associated muscle diseases are frequent in the form of myositis, myasthenia gravis, or nonspecific myopathic pathologic findings. VGKC-Abs were uncommon in this series.

MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.

OBJECTIVE: To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy. METHODS: A study conducted in the Safor region (Spain), setting of a large cluster of patients. Clinical, neurophysiologic, muscle imaging, and muscle biopsy studies and MYH7 gene sequencing were investigated in 32 patients from 4 kindreds. Data from 36 deceased or nonexamined patients were collected from hospital records or relatives. RESULTS: Onset ranged from congenital to the 6th decade. All patients presented weakness of great toe/ankle dorsiflexors and many had associated neck flexor, finger extensor, and mild facial weakness. In most cases, involvement of proximal and axial muscles was observed either clinically or by muscle imaging, sometimes giving rise to scapuloperoneal and limb-girdle syndromes. Disabling myalgias, skeletal deformities, and dilated cardiomyopathy in one patient were associated features. Life expectancy was not reduced but the spectrum of disability ranged from asymptomatic to wheelchair confined. Electromyographic neurogenic features were frequently recorded. Muscle fiber type disproportion, core/minicore lesions, and mitochondrial abnormalities were the most relevant pathologic alterations. All patients carried the p.K1729del mutation in MYH7. CONCLUSIONS: The p.K1729del mutation in the MYH7 gene expresses notable clinical variability and electromyographic and pathologic features that can lead to the misdiagnosis of neurogenic atrophies, congenital myopathies, or mitochondrial myopathies. Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection.

The role of the nuclear lamins in the pathogenesis of heart failure in patients undergoing cardiac transplantation.

The nuclear lamins A/C play a critical role in maintaining the structure of the nuclear lamina and the organization of various proteins, such as emerin. These protein levels may play roles in the pathogenesis and clinical evolution of both ischemic (ICM) and dilated (DCM) cardiomyopathy. We evaluated the nuclear morphology of cardiomyocytes and determine lamins A/C and emerin levels among DCM and ICM heart failure patients compared with control human hearts. We determined protein levels by Western blots using mouse monoclonal antibodies in 23 explanted human hearts. Lamin A was increased in failing hearts but significantly different only among the DCM compared with the control group: mean, 236 +/- 51 vs 100 +/- 34; (P < .05). However, lamin C in the DCM group was near control values and significantly decreased in the ICM cohort compared to controls 75 +/- 7 versus 100 +/- 3 (P < .05). No alterations in emerin levels were observed in ICM or DCM, compared with controls. In conclusion, hearts with ICM or DCM showed different alterations in the nuclear morphology of cardiomyocytes; ICM patients had decreased lamin C, whereas DCM patients had increased lamin A. These changes affecting nuclear structure and function may have prognostic implications, for cardiomyopathy etiology.

Endocytosis and transcytosis in growing astrocytes in primary culture. Possible implications in neural development.

Endocytosis constitutes an essential process in the regulation of the expression of cell surface molecules and receptors and, therefore, could participate in the neural-glial interactions occurring during brain development. However, the relationship between endocytic pathways in astroglial cells under physiological and pathological conditions remains poorly understood. We analyzed the endocytosis and transcytosis processes in growing astrocytes and the possible effect of ethanol on these processes. Evidence demonstrates that ethanol affects endocytosis in the liver and we showed that ethanol exposure during brain development alters astroglial development changing plasma membrane receptors and surface glycoprotein composition. To study these processes we use several markers for receptor-mediated endocytosis, fluid phase endocytosis and non-specific endocytosis. These markers were labeled for fluorescence microscopy and electron microscopy. 125I-BSA was used to study the effect of ethanol on the internalization and recycling of this macromolecule. The distribution of several proteins involved in endocytosis (caveolin, clathrin, rab5 and beta-COP) was analyzed using immunofluorescence, immunoelectron microscopy and immunoblotting. Our results indicate that growing astrocytes have a developed endocytic system mainly composed of caveolae, clathrin coated pits and vesicles, tubulo-vesicular and spheric endosomes, multivesicular bodies and lysosomes. Ethanol exposure induces a fragmentation of tubular endosomes, decreases the internalization of 125I-BSA, alters the processing of internalized BSA, and decreases the levels of caveolin, clathrin, rab5 and beta-COP. These results indicate that ethanol alters the endocytosis and transcytosis processes and impairs protein trafficking in astrocytes, which could perturb astrocyte surface expression of molecules involved in neuronal migration and maturation during brain development.

Colocalization of aldehyde dehydrogenases and Fe/NADPH-induced lipid peroxidation in tissue sections of rat retina.

Epidemiological and experimental studies suggest the involvement of lipid peroxidation (LPO) in retinal diseases. Clinicians usually prescribe antioxidants to help in the treatment of proliferative diabetic vitreoretinopathy and age-related macular degeneration. In spite of this, these processes inexorably induce visual impairment and may progress towards blindness. In addition to other pathogenic mechanisms not fully understood, it may be that peroxidic aldehydes from LPO occurring in the eyes, acting as cytotoxic chemicals, mediate in these chronic disorders. To test the mechanisms of removing peroxidic aldehydes from retinal cells and in an attempt to understand long-lasting changes induced by LPO, the distribution and activity of aldehyde dehydrogenases (ALDH) in the rat retina were studied and compared with the LPO sites induced by iron/nicotine adenine dinucleotide phosphate. Histochemical and immunocytochemical assays revealed the colocalization of LPO and ALDH, mainly in the photoreceptors and inner retinal layers. This suggests the involvement of ALDH in detoxifying peroxidic aldehydes from the retina. Any change in ALDH retinal expression and distribution might be of crucial importance in assessing the paths of LPO-mediated vitreoretinopathies. Further research is needed to evaluate these findings and their application to new ophthalmic therapy.

The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein.

By immunoelectron microscopy with a polyclonal antibody against the cytosolic glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Candida albicans (anti-GAPDH PAb), the protein was clearly detected at the outer surface of the cell wall, particularly on blastoconidia, as well as in the cytoplasm. Intact blastoconidia were able to adhere to fibronectin and laminin immobilized on microtiter plates, and this adhesion was markedly reduced by both the anti-GAPDH PAb and soluble GAPDH from Saccharomyces cerevisiae. In addition, semiquantitative flow cytometry analysis with the anti-GAPDH PAb showed a decrease in antibody binding to cells in the presence of soluble fibronectin and laminin. Purified cytosolic C. albicans GAPDH was found to bind to fibronectin and laminin in a ligand Western blot assay. These observations suggest that the cell wall-associated form of the GAPDH in C. albicans could be involved in mediating adhesion of fungal cells to fibronectin and laminin, thus contributing to the attachment of the microorganism to host tissues and to the dissemination of Candida infection.

The c-erbA alpha protooncogene induces apoptosis in glial cells via a protein kinase C- and bcl-2-suppressible mechanism.

The c-erbA protooncogene encodes the thyroid hormone (3,5,3'-triiodothyronine; T3) receptor alpha1 (TR alpha1). c-erbA/TR alpha1 is expressed in many cell types including glial cells, particularly in the immature state. We show here by morphological and biochemical criteria that c-erbA induces apoptosis of glial B3.1 cells in serum-deprived conditions. This effect is mostly T3 independent. Growth factors such as platelet-derived growth factor, basic fibroblast growth factor, or transforming growth factor-alpha prevent B3.1 + TR alpha1 cell death. Protein kinase C (PKC) activators also prevent the apoptosis phenomenon, an effect that was blocked by the PKC-specific inhibitor GF109203X. Expression of an exogenous bcl-2 gene led also to B3.1 + TR alpha1 cell survival. Neither a series of inhibitors including GF109203X nor T3 inhibits bcl-2 action, indicating that bcl-2 blocks a downstream step in the death-promoting process. B3.1 + TR alpha1 cell apoptosis is not blocked by caspase-1 or poly-ADP-ribosyltransferase inhibitors, suggesting that the activation of these classic pathways is not involved in the apoptotic mechanism. In addition, direct interaction with specific neuronal cells but not incubation with their conditioned medium inhibits also apoptosis of B3.1 + TR alpha1 cells. Our results show that c-erbA promotes an apoptotic process in glial B3.1 cells that is suppressible by PKC activation and bcl-2, probably by distinct mechanisms.

Prenatal alcohol exposure affects galactosyltransferase activity and glycoconjugates in the Golgi apparatus of fetal rat hepatocytes.

Prenatal exposure to alcohol affects the morphological, structural, and functional features of the Golgi apparatus (GA), thus altering the glycosylation process in fetal hepatocytes. To elucidate the cellular mechanisms underlying these alterations, we have studied the effect of alcohol exposure in utero on the activity of liver galactosyltransferase, an enzyme involved in the glycosylation process, and on the hepatic glycoprotein sugar composition. For this, livers from 21-day-old fetuses obtained from control and ethanol-fed rats were used. Galactosyltransferase (GT) activity was determined in isolated GA cis and trans fractions. Colloidal gold-labeled lectin cytochemistry was used to analyze sugar residues in hepatocytes at the subcellular level. Finally, the integrity of the GA after alcohol treatment was assessed by electron microscopy and by evaluating the distribution of the Golgi beta-COP, a protein involved in vesicular trafficking. Prenatal alcohol exposure induces a significant increase in both liver weight and total protein content in the trans Golgi. Moreover, this treatment decreases the activity of galactosyltransferase, increases alpha-L-Fuc residues, and reduces the number of alpha-Man, GlcNAc(beta1,4,GlcNAc)1,2, GalNAc alpha1,3GalNAc, alpha-GalNAc, and a-Gal residues. Alcohol exposure also causes the Golgi cisternae to disappear in about 30% of the hepatocytes, and reduces 75% the number of anti-Golgi beta-COP protein binding sites. Our results suggest that the decrease in galactosyltransferase activity, the alterations in the oligosaccharide chain composition, and the reduction in the amount of Golgi beta-COP protein could be involved in the alterations in the glycosylation process, as well as in the accumulation of hepatic proteins observed after prenatal alcohol exposure. These alterations could contribute, therefore, to the alcohol-induced injury in the developing liver.

[Clinical course and prognostic factors in newborns with very low birth weight]. / Evolución y factores pronósticos en recién nacidos de muy bajo peso.

OBJECTIVE: We report the results of survival and incidence of neurodevelopmental sequelae in a group of 249 infants treated in our hospital between 1986-91, whose birth weight was under 1,500 grams. METHOD: We perform a follow-up at corrected ages of 3, 6, 10, 18, 36 months and 5 years thought results only included children followed until 18. Sequelae were classified in three groups, according to the disability degree. RESULTS: Survival resulted to be 69.87% (174), 38.7% for the group under 1,000 grams and 84.7% for those over 1,000 grams. Sequelae were present in 22.6% (11.6% moderate and 10.9% severe). The incidence of severe sequelae was very different on basis of the birth weight, 25.8% for children under 1,000 grams, 13.9% for 1,000-1,249 grams and 1.6% for 1,250-1,500 grams. CONCLUSIONS: Intracranial haemorrhage, hyperbilirubinemia, assisted ventilation and persistence of ductus arteriosus were significantly associated sequelae. We didn't find differences with respect to multiple pregnancy, seizures, sepsis or neonatal hypoxia.

Ethanol increases cytochrome P4502E1 and induces oxidative stress in astrocytes.

We demonstrate the presence of cytochrome P4502E1 (CYP2E1) in astrocytes in primary culture, its induction by ethanol, and the concomitant generation of free radical species. Double immunofluorescence using anti-CYP2E1 and anti-glial fibrillary acidic protein showed that CYP2E1 was distributed over the cytoplasm and processes, although labeling was more pronounced over the nuclear membrane. Immunogold labeling confirmed this pattern of distribution. Addition of 25 mM ethanol to the astrocyte culture medium for 14 days resulted in an increase in the CYP2E1 content, as determined by confocal microscopy and dot blot. In addition, ethanol induced a dose-dependent increase in the formation of reactive oxygen species that was partially prevented by incubating the astrocytes with anti-CYP2E1. Alcohol also induced a dose-dependent increase in malonaldehyde and hydroxynonenal formation and a depletion of the glutathione (GSH) content. These results suggest that ethanol induces oxidative damage in astrocytes, which could explain some of the toxic effects of ethanol on these cells, such as cytoskeletal alterations. This assumption is supported here by the fact that an increase in GSH content prevents the deleterious effects of alcohol on the cytoskeleton of astrocytes. These results suggest the importance of oxidative stress as a mechanism involved in alcohol-induced neural and brain damage.

Effect of tert-butyl hydroperoxide addition on spontaneous chemiluminescence in brain.

It is well known that light emission is related to lipid peroxidation in biological material, and that this process occurs spontaneously in the brain. tert-Butyl hydroperoxide (tBHP) is an organic peroxide widely used as initiator of free radical production in several biological systems. However, the prooxidant capacity of this compound remins unclear. To clarify its role in brain spontaneous autooxidation, rat brain homogenates were incubated with and without tBHP. Light emission and lipid peroxidation were measured by luminometry and the TBARs test, respectively. Several inhibitors of free radical-induced lipid peroxidation were also used. These inhibitors included ascorbate, EDTA, and desferrioxamine. Our results indicate that the pattern of light emission spontaneously produced in brain was different from that observed after the addition of tBHP to the homogenates, and that these differences depended on the tBHP concentration. The main difference was that tBHP caused a rapid light emission that reached its maximum more quickly than in the case of spontaneous emission. Addition of ascorbate resulted in an increase in chemiluminescence in presence of tBHP. In contrast, EDTA and desferrioxamine inhibited light emission in homogenates both with and without tBHP. The results of MDA determination were similar to those described, including the effect of inhibitors. A common feature in MDA and luminometric determinations was the dispersion of data. In conclusion, these results suggest that tBHP, under specific conditions, modify the kinetic pattern of brain spontaneous autooxidation.

Variations in peroxisomal catalase of neonatal rat hepatocyte subpopulations. Effect of pre- and postnatal exposure to alcohol.

Alcohol consumption during pregnancy is teratogenic and induces severe alterations in hepatocytes. In the hepatocyte peroxisomal system, ethanol is converted in the presence of H2O2 to acetaldehyde and water. Therefore, peroxisomal catalase also acts as an antioxidant defence mechanism by removing H2O2 and preventing the formation of hydroxyl radicals in the cell. Alterations in peroxisomal catalase after pre- and pre+postnatal alcohol exposure were investigated in the rat. The effect of pre- and postnatal exposure to ethanol on hepatocyte subpopulations was analysed in isolated hepatocytes originating from periportal, intermediate and perivenous zones. Analysis of catalase revealed that the total activity and content of this enzyme were higher in 12-day-old cells than in cells from newborns and that this increment was more pronounced in treated cells. In controls, the amount of peroxisomal catalase increased mainly in periportal cells, whereas alcohol exposure induced a significant increase in the catalase of perivenous hepatocytes. We conclude that pre- and postnatal alcohol exposure mainly affects the perivenous hepatocyte peroxisomes and that the increase in peroxisomal catalase could constitute a defence mechanism against free radical generation induced by alcohol exposure during the perinatal period.