RESUMEN
Despite the reported absence of the 25-kDa heat shock protein Hsp25 in the rodent cerebellum, we have determined that Hsp25 is constitutively expressed in a subset of Purkinje cells in the adult cerebellum of the mouse. No other cerebellar neurons are Hsp25 immunoreactive, but there is weak staining associated with blood vessels. In the vermis, Hsp25-immunoreactive Purkinje cells are confined to two regions: one in lobules VI/VII, the other in lobules IX/X. In each region, only a subset of the Purkinje cells is immunoreactive. These cells are grouped in five parasagittal bands arranged symmetrically about the midline. The boundaries of these expression domains correspond to transverse zones previously inferred from other expression patterns. A third Hsp25-immunopositive domain is seen in the paraflocculus and flocculus. Again, only a subset of Purkinje cells within the paraflocculus and flocculus express Hsp25, revealing three distinct bands. Previous descriptions of compartmentation antigens have not differentiated between adult populations of Purkinje cells in these regions, suggesting that Hsp25 is a novel compartmentation antigen in the adult cerebellum.
Asunto(s)
Ceguera/metabolismo , Cerebelo/citología , Cerebelo/metabolismo , Proteínas de Choque Térmico , Proteínas de Neoplasias/análisis , Células de Purkinje/citología , Células de Purkinje/metabolismo , Animales , Proteínas de Choque Térmico HSP27 , Ratones , Ratones Endogámicos , Chaperonas Moleculares , Ratas , Ratas Sprague-DawleyRESUMEN
The small heat shock protein Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal stripes of Purkinje cells confined to the caudal central zone ( approximately lobules VI and VII), the nodular zone ( approximately ventral lobule IX and lobule X), and the paraflocculi/flocculi. During development several distinct phases in Hsp25 expression can be distinguished. Hsp25-immunopositive Purkinje cells are first seen at birth, when four clusters are visible in the vermis of lobules IV/V, and scattered Hsp25-immunoreactive Purkinje cells are seen in lobule VIII. By postnatal day 2/3, six narrow parasagittal stripes of Hsp25-immunopositive Purkinje cells are seen in the vermis of the anterior lobe. In the posterior lobules, most Purkinje cells in the vermis of lobules VIII and IX express Hsp25. This initial limited expression is followed by a phase of widespread expression (postnatal days 6-9) in which Hsp25 immunoreactivity is detected in virtually all Purkinje cells. This global cerebellar expression of Hsp25 then gradually disappears, first in the anterior zone and the hemispheres and subsequently in the posterior zone, to leave the restricted adult expression pattern. Western blotting analysis and immunoprecipitation with anti-Hsp25 suggest that all immunocytochemistry can be attributed the expression of Hsp25. Furthermore, visual deprivation had no effect on the development of Hsp25 expression in Purkinje cells, suggesting that visuomotor input is not responsible for the establishment of constitutive Hsp25 expression in the cerebellar cortex.
Asunto(s)
Animales Recién Nacidos/metabolismo , Tipificación del Cuerpo/fisiología , Corteza Cerebelosa/crecimiento & desarrollo , Corteza Cerebelosa/metabolismo , Proteínas de Choque Térmico , Proteínas de Neoplasias/metabolismo , Células de Purkinje/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos/anatomía & histología , Animales Recién Nacidos/crecimiento & desarrollo , Ceguera/complicaciones , Corteza Cerebelosa/citología , Enucleación del Ojo/efectos adversos , Ratones , Ratones Endogámicos , Chaperonas Moleculares , Proteínas del Tejido Nervioso/metabolismo , Células de Purkinje/citologíaRESUMEN
Immunohistochemistry and in situ hybridization have been used to survey constitutive heat shock protein (HSP)25 expression in the brain and spinal cord of the developing and adult mouse. The data reveal both transient and sustained patterns of expression and demonstrate robust differences between mice and rats. During development, HSP25 is transiently expressed in neurons of the inferior colliculus, various thalamic subnuclei, and the majority of Purkinje cells in the cerebellum. Sustained expression into adulthood is seen in neurons of the cranial nerve nuclei, spinal cord motoneurons, median preoptic nucleus, and a subset of Purkinje cells. Differences in HSP25 expression between adult rats and mice include the somatic motor nuclei innervating the extraocular muscles, which are HSP25 immunoreactive only in the rat. Similar differences in HSP25 expression are seen during the development of the inferior colliculus, thalamus, and cerebellum, where expression is restricted to mice.
Asunto(s)
Química Encefálica/fisiología , Proteínas de Choque Térmico , Ratones Endogámicos/fisiología , Proteínas de Neoplasias/genética , Animales , Nervios Craneales/crecimiento & desarrollo , Nervios Craneales/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica , Proteínas de Choque Térmico HSP27 , Hibridación in Situ , Colículos Inferiores/crecimiento & desarrollo , Colículos Inferiores/fisiología , Masculino , Ratones , Chaperonas Moleculares , Proteínas de Neoplasias/análisis , Embarazo , Área Preóptica/crecimiento & desarrollo , Área Preóptica/fisiología , Células de Purkinje/fisiología , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie , Médula Espinal/crecimiento & desarrollo , Médula Espinal/fisiología , Núcleos Talámicos/crecimiento & desarrollo , Núcleos Talámicos/fisiologíaRESUMEN
BACKGROUND: Assumptions about the damaging effects of radiotherapy (XRT) are based on studies in which total dose, dose fraction, treatment volume, degree of malignancy, chemotherapy, tumor recurrence, and neurologic comorbidity interact with XRT effects. This is a prospective, long-term study of XRT effects in adults, in which total dose and dose fraction were constrained and data related to tumor recurrence and neurologic comorbidity (e.g., hypertension) were excluded. METHODS: The effects of XRT on the cognitive and radiographic outcomes of 26 patients with low-grade, supratentorial, brain tumors yearly from baseline (6 weeks after surgery and immediately before XRT) and yearly to 6 years were examined. Radiographic findings were examined regionally. RESULTS: Selective cognitive declines (in visual memory) emerged only at 5 years, whereas ratings of clinical MRI (T2 images) showed mild accumulation of hyperintensities with post-treatment onset from 6 months to 3 years, with no further progression. White matter atrophy and total hyperintensities demonstrated this effect, with subcortical and deep white matter, corpus callosum, cerebellar structures, and pons accounting for these changes over time. About half of the patients demonstrated cognitive decline and treatment-related hyperintensities. CONCLUSIONS: There was no evidence of a general cognitive decline or progression of white matter changes after 3 years. Results argue for limited damage from XRT at this frequently used dose and volume in the absence of other clinical risk factors.
Asunto(s)
Trastornos del Conocimiento/etiología , Radioterapia/efectos adversos , Neoplasias Supratentoriales/radioterapia , Adulto , Corteza Cerebral/patología , Trastornos del Conocimiento/patología , Depresión/diagnóstico , Fatiga/diagnóstico , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Estudios Prospectivos , Dosificación Radioterapéutica , Neoplasias Supratentoriales/mortalidad , Neoplasias Supratentoriales/patologíaRESUMEN
The critical neurocognitive components of Attention-Deficit/Hyperactivity Disorder (ADHD) remain controversial, despite extensive research to disclose the essential cognitive components of this disorder. We propose to organize this research into three types of cognitive mechanisms while demonstrating the consistencies and inconsistencies in each: studies of response inhibition, of executive function, and of attentional inhibition. We also present the results of cluster analyses of a group (n = 25) of narrowly selected adult patients with childhood onset of ADHD, reveal three subtypes of ADHD, and argue that the only evidence of a general cognitive deficit is found in tests of selective attention. Finally, we provide the results of exploratory studies of selective attention for perception and for semantic memories. The data suggest that the cognitive disinhibition of ADHD is found in semantic recognition, but not in visuoperceptual recognition.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Atención/fisiología , Trastornos del Conocimiento/complicaciones , Inhibición Neural/fisiología , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Encéfalo/fisiopatología , Trastornos del Conocimiento/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
cis-Nonachlor and trans-nonachlor are bioaccumulating components of the pesticide chlordane, which can be detected in various environmental biota and in humans. Existing studies have focused on the potential adverse health effects of the parent chlordane mixture. Comparable toxicity data are nonexistent for individual chlordane constituents such as trans-nonachlor, cis-nonachlor, or oxychlordane, which are among the most common chlordane-related environmental contaminants and tissue residues. In this study, rats were administered cis-nonachlor, trans-nonachlor, or technical chlordane by gavage for 28 days at doses of 0.25 to 25 mg/kg body weight. Residue analyses indicated that trans-nonachlor accumulation in adipose was greater than cis-nonachlor when rats were administered each chemical under identical conditions of dose and exposure. For all test chemicals, the major metabolite oxychlordane accumulated in adipose tissue. Adipose tissue residue levels of all test chemicals and the major metabolite were higher in female rats. The liver was a target organ in male and female rats, indicated by increased liver weight and histopathological changes consistent with microsomal enzyme induction. Hepatic changes were most pronounced in rats treated with trans-nonachlor. Elevated kidney weights and depressed organic ion transport were observed in males treated with trans-nonachlor and chlordane. Although in general, changes in target organs and clinical chemistry endpoints were similar for all 3 test chemicals, the approximate toxicity ranking from most to least toxic was trans-nonachlor > technical chlordane > cis-nonachlor.
Asunto(s)
Clordano/toxicidad , Hidrocarburos Clorados/toxicidad , Insecticidas/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Estereoisomerismo , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patologíaRESUMEN
The paratrigeminal nucleus, located in the spinal trigeminal tract rostral to the obex, is important in the integration of visceral and somatosensory afferent information and may modulate autonomic function through its projections to the dorsal vagal complex. Anterograde and retrograde neuroanatomical tracers were used in conjunction with immunohistochemistry to determine the neurochemical organization of the efferent pathway from the paratrigeminal nucleus to the dorsal vagal complex in the rat. Double-labelling studies demonstrated that leu-enkephalin, 28-kDa calbindin, and neuronal nitric oxide synthase were present in neurons in the paratrigeminal nucleus that project to the dorsal vagal complex. The results of this study are consistent with the hypothesis that neurochemically distinct pathways from the paratrigeminal nucleus are involved in the sensory modulation of autonomic function.
Asunto(s)
Vías Eferentes/anatomía & histología , Vías Eferentes/fisiología , Neuronas/citología , Neuronas/fisiología , Estilbamidinas , Núcleos del Trigémino/anatomía & histología , Núcleos del Trigémino/fisiología , Animales , Transporte Axonal , Axones/fisiología , Axones/ultraestructura , Calbindinas , Colchicina , Vías Eferentes/citología , Encefalina Leucina/análisis , Colorantes Fluorescentes , Inmunohistoquímica , Masculino , Terminaciones Nerviosas/fisiología , Terminaciones Nerviosas/ultraestructura , Proteínas del Tejido Nervioso/análisis , Óxido Nítrico Sintasa/análisis , Ratas , Ratas Wistar , Proteína G de Unión al Calcio S100/análisis , Núcleos del Trigémino/citologíaRESUMEN
The mental rotation required in the Road Map Test of Direction Sense (the "Road Map Test"; J. Money, 1976; J. Money, D. Alexander, & H. T. Walker, 1965) has been thought to be impaired as a function of age, but not dementia. However, spatial rotation in dementia has not been investigated in reference to spatial coordinate systems. Patients with dementia (Alzheimer's and ischemic vascular dementias) and elderly control participants were administered the Road Map Test. The authors analyzed whether the geocentric or egocentric coordinate system determined rotation of Road Map Test turns and predicted impairment in dementia patients. They found equivalent impairment in both types of dementia, greater angulation effect in the geocentric system in patients relative to normal controls, and no egocentric effect. Results also suggest early emergence of spatial rotation deficit in dementia. Spatial rotation is most often associated with working memory, which predicts the correlations found.
Asunto(s)
Envejecimiento/fisiología , Demencia/fisiopatología , Imaginación/fisiología , Orientación/fisiología , Trastornos de la Percepción/fisiopatología , Percepción Espacial/fisiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Mapas como Asunto , Trastornos de la Memoria/fisiopatología , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Análisis de RegresiónRESUMEN
Cultured post-fused human skeletal muscle monolayers exposed to WSN influenza A virus were analyzed by scanning and transmission electron microscopy. At 12-14h post-inoculation (p.i.), affected mononuclear cells retracted from the cell surface, but remained anchored to the substrate by taut filar processes. Retraction was accompanied by shortening of microvilli, appearance of hemispherical cytoplasmic protrusions and corrugation of the surface proper. These changes were more pronounced at 24 and 48h p.i. The rounded, moribund mononuclear cells eventually detached from the substratum. Surface alterations were accompanied by the intracellular appearance of electron-dense nuclear inclusions (often associated with the nucleolus) and paracrystalline ribosomestudded cytoplasmic bodies, which increased in size and number with time. In myotubes, distinct surface alterations appeared later (24h p.i.). Early myotube retraction was accompanied by accentuation of the longitudinally oriented surface pleats and appearance of "blebs" followed by cell-rounding. At 48-72 h, many myotubes detached from the substratum. The surfaces of those still adhering appeared corrugated. Intranuclear and cytoplasmic inclusions accumulated, and budding virions, often filamentous, could be demonstrated at the plasmalemma of mononuclear cells and myotubes. Late (end-stage) cytopathic effects included clumping of chromatin, breakdown of the nuclear envelope, disappearance of cortical and endoplasmic cytofilaments, mitochondrial swelling, and vesiculation of surface membranes. The lesions leading to cell injury and cell death appeared to be due to massive accumulation of virus-induced products that altered cellular metabolism, with physical and functional abnormalities of surface membranes.
Asunto(s)
Virus de la Influenza A/patogenicidad , Músculos/microbiología , Autorradiografía , Fusión Celular , ADN/biosíntesis , Replicación del ADN , Humanos , Cuerpos de Inclusión/ultraestructura , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Músculos/ultraestructura , Factores de TiempoRESUMEN
We found that fused human muscle in culture supports neurotropic influenza A viral infection, as demonstrated by viral growth experiments, hemadsorption, observation of cytopathic changes and detection of intracellular viral antigen. The time of peak virion production and the appearance of cytopathic effects in these experiments were similar to previously described characteristics in influenza A-susceptible organotypic cultures of other tissues. Cytopathological changes occurred earlier in mononucleated cells than in myotubes and included cell-rounding; cytoplasmic retraction, granularity and vacuolization; ribonucleic acid-containing cytoplasmic inclusions; nucleolar enlargement; and clumping of chromatin. Immunofluorescent staining demonstrated early nuclear fluorescence, followed by spread of viral antigen into the cytoplasm. A subpopulation of mononucleated cells, shown by cloning studies to be myoblasts, showed no cytopathic effects or evidence of intracellular viral antigen and was presumably resistant to neurotropic influenza A infection. The adverse effects of influenza A on fused human muscle cells in tissue culture contrast with the inability of the virus to replicate in skeletal muscle after animal inoculation in acute experiments. Therefore, host factors may affect attempts to produce an animal model of human muscle disease with this virus.
Asunto(s)
Virus de la Influenza A/crecimiento & desarrollo , Músculos/microbiología , Núcleo Celular/patología , Células Cultivadas , Humanos , Músculos/inmunología , Músculos/patología , Factores de Tiempo , Replicación ViralRESUMEN
A reversibility study was initiated to determine if the length of feeding with 2% butylated hydroxyanisole (BHA) altered the incidence of forestomach lesions observed after a 24-month observation period. Groups of male Fischer 344 rats were fed 2% BHA for 0, 3, 6, 12, and 24 months and then the basal diet for the completion of the 24-month experimental period. Subgroups were serially sacrificed for histopathological examination and [methyl-3H]thymidine radioautography at the time when each group of animals was transferred to the basal diet and also at 15 months. The results showed that except for carcinomas and some epithelial downgrowths, cellular proliferation, measured by radioautography in the epithelium lining the greater and the lesser curvature of the forestomach, remained dependent on the continuous presence of 2% BHA for, at least, 12 months. Superficial hyperplasias, inflammatory lesions and many of the papillomas regressed after cessation of treatment at 12 months. The epithelial downgrowths did not appear to enlarge after the BHA was withdrawn. The squamous cell carcinomas occurred in almost identical yields whether the rats were fed 2% BHA for 12 months and then returned to the basal diet for 12 months or received 2% BHA continuously for 24 months. It is shown here that at several times, 2% BHA stimulated the [methyl-3H]thymidine labelling index of the transitional epithelium of the urinary bladder and that at 3 months the no observed effect level was greater than 0.5% BHA. The significance of the studies on the forestomach and bladder epithelia are discussed. It is concluded that the lesions induced by BHA are most unlikely to be relevant to humans exposed to much lower levels of BHA.
Asunto(s)
Hidroxianisol Butilado/efectos adversos , Carcinógenos , Neoplasias Gástricas/inducido químicamente , Neoplasias de la Vejiga Urinaria/inducido químicamente , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas F344 , Estómago/efectos de los fármacos , Neoplasias Gástricas/patología , Timidina/análogos & derivados , Tritio , Vejiga Urinaria/efectos de los fármacosRESUMEN
The sensitivity of elevated serum ornithine carbamyltransferase (OCT) as an index of hepatotoxicity in rats was assessed in different studies conducted over a number of years and originally designed to examine the toxicity or carcinogenicity of a variety of test chemicals and diets. Changes in serum OCT activities were compared with the more widely used clinical endpoints, alanine aminotranserase (ALT) and aspartate aminotransferase (AST). In the first study, rats received a single oral dose of the hepatotoxic and hepatocarcinogenic fungal toxin aflatoxin B(1) (AFB(1)). The increase in enzyme levels between control and AFB(1)-treated rats was greater for serum OCT than for ALT or AST. This response was similar to the changes in serum enzyme levels in studies where rats ingested a hepatotoxic and hepatocarcinogenic choline deficient (CD) diet. When rats were exposed to the hepatotoxic and nephrotoxic fungal toxin fumonisin B(1) (FB(1)) by intraperitoneal injection for 6 days, serum AST and ALT were significantly elevated above control levels while OCT was unaffected. The peroxisome proliferator ciprofibrate caused elevated ALT and AST but not OCT at week 52 of dietary exposure, after the development of liver nodules and tumours. Of the two liver-specific enzymes examined in all of the studies, ALT was more consistently predictive of hepatotoxicity than OCT.
Asunto(s)
Aflatoxina B1/toxicidad , Azaserina/toxicidad , Ácidos Carboxílicos/toxicidad , Ácido Clofíbrico/análogos & derivados , Fumonisinas , Hígado/enzimología , Ornitina Carbamoiltransferasa/efectos de los fármacos , Administración Oral , Aflatoxina B1/administración & dosificación , Alanina Transaminasa/sangre , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/toxicidad , Aspartato Aminotransferasas/sangre , Azaserina/administración & dosificación , Ácidos Carboxílicos/administración & dosificación , Deficiencia de Colina/enzimología , Ácido Clofíbrico/administración & dosificación , Ácido Clofíbrico/toxicidad , Relación Dosis-Respuesta a Droga , Ácidos Fíbricos , Inyecciones Intraperitoneales , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Masculino , Micotoxinas/administración & dosificación , Micotoxinas/toxicidad , Ornitina Carbamoiltransferasa/metabolismo , Proliferadores de Peroxisomas/administración & dosificación , Proliferadores de Peroxisomas/toxicidad , Valor Predictivo de las Pruebas , Ratas , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Estudios RetrospectivosRESUMEN
Anthraquinones and structurally related compounds were cytotoxic to mammalian cell lines using cloning efficiency and MTT reduction as endpoints. In V79 cells, the concentration of chemical causing 50% inhibition ranged from 0.21 to 21.6 mug/ml for cloning efficiency and from 0.86 to 14.6 mug/ml for MTT reduction. The anthrones anthralin and chrysarobin were 4.1 and 3.2 times more toxic, respectively, in the cloning efficiency assay than in the MTT assay. In contrast, the anthraquinones danthron and emodin were 2.8 and 2.1 times more toxic, respectively, in the MTT assay than in the cloning efficiency assay. Among the four mammalian cell lines tested using the MTT assay, the human leukaemia cell line (K562) was the most sensitive to the test chemicals. In contast, anthraquinone toxicity was reduced in rat hepatoma (H4IIE) cultures. In general, structures with carbonyl groups in positions 9 and 10 on the anthracene skeleton (anthraquinones) were less toxic than structures with carbonyl groups in position 9 only (anthrones). Toxicity was also influenced by the position of hydroxy substituents on the tricyclic skeleton. The results suggested that in vitro cytotoxicity assays are useful in elucidating the relationships between structure and biological activity for anthraquinones and related compounds.
RESUMEN
Despite advances in obstetrical management, the problems that women with diabetes experience most frequently during their pregnancies and postpartum have not been clearly defined. The purpose of this study was to provide morbidity data on this patient population to assist in determining appropriate interventions.
Asunto(s)
Diabetes Gestacional/complicaciones , Embarazo en Diabéticas/complicaciones , Adolescente , Adulto , Diabetes Gestacional/prevención & control , Femenino , Humanos , Morbilidad , Readmisión del Paciente/estadística & datos numéricos , Embarazo , Resultado del Embarazo , Embarazo en Diabéticas/prevención & control , Atención Prenatal/estadística & datos numéricos , MuestreoRESUMEN
Each year 90,000 women in the United States are diagnosed with gestational diabetes. The transition from diagnosis to home management is a time of high stress for these women. Anxiety may lead to difficulty with self-care in general and the diabetic diet in particular. Follow-up education by a diabetes educator can help clients plan meals that comply with the nutritional meal plan without disrupting the family's eating habits. The client should be taught to measure portions, to recognize sugar as an ingredient in foods and medicines, and to deal with special occasions such as holiday meals, travel, and illness. If extended home care is not feasible, the creative diabetes educator will devise other educational opportunities, such as home videos, telephone support networks, special childbirth classes for women with gestational diabetes, and luncheon meetings at which nutritionally correct meals are served.
Asunto(s)
Diabetes Gestacional/dietoterapia , Ciencias de la Nutrición/educación , Educación del Paciente como Asunto/métodos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/psicología , Femenino , Humanos , Alta del Paciente , Embarazo , AutocuidadoRESUMEN
Fumonisins B1 and B2 (FB1 and FB2) are fungal secondary metabolites produced by members of the genus Fusarium. Although FB1 is usually detected in greater quantities, FB2 frequently co-occurs in contaminated feeds and foods and contributes to the total toxin load. In the present study, the comparative toxicity of FB1 and FB2 was examined in male Sprague-Dawley rats administered toxin (0.75 mg/kg body weight) or vehicle control intraperitoneally (ip) for 2, 4 or 6 consecutive days. Clinical changes, including elevated serum cholesterol, alanine aminotransferase (ALT), creatinine and protein, were slightly more pronounced in FB1-treated rats. The most consistent hematological change was an increase in vacuolated bone marrow cells, which was more pronounced in FB1-treated rats. Histopathological changes were similar in FB1- and FB2-treated rats and included single cell necrosis in kidneys and liver, cytoplasmic vacuolation in adrenal cortex and lymphocytolysis in thymus. In the liver mRNA expression for the cyclin kinase inhibitor p21 gene was significantly increased in FB1- and FB2-treated rats, compared to controls. Expression of mRNA for the cyclin D1 gene was significantly depressed in FB2-treated rats. Hepatic cyclin E mRNA was elevated in response to FB1 and FB2 compared to controls. In FB2-treated animals this corresponded with decreased liver p27 mRNA expression. Hepatic proliferating cell nuclear antigen (PCNA) transcription was elevated in FB1- but not FB2- treated rats. Changes in liver microsomal protein levels of p27, cyclin E and PCNA were similar to changes in gene expression. In contrast, cyclin D1 protein levels were elevated in rats treated with FB1 and, to a lesser extent, FB2. The data indicate that FB1 and FB2 can alter the expression of genes associated with the cell cycle, and indicate a need for a further understanding of the mechanistic basis of FB1 and FB2 toxicity.
Asunto(s)
Ácidos Carboxílicos/toxicidad , Ciclo Celular/efectos de los fármacos , Fumonisinas , Micotoxinas/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Ácidos Carboxílicos/administración & dosificación , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/fisiología , Ingestión de Alimentos/efectos de los fármacos , Inyecciones Intraperitoneales , Riñón/patología , Hígado/metabolismo , Hígado/patología , Masculino , Micotoxinas/administración & dosificación , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-DawleyRESUMEN
Fumonisin B1 (FB1) is a fungal toxin produced by members of the genus Fusarium. Ingestion of FB1 causes species-specific neurotoxic, nephrotoxic, hepatotoxic and pulmonary effects. The clinical, haematological and pathological responses of adult male and female B6C3F1 mice to FB1 were assessed following 14 daily gavage doses ranging from 1 to 75 mg FB1/kg body weight/day. There were no consistent sex-related changes. Although all responses were modest, the most notable effects of FB1 were on the liver, bone marrow, adrenals and kidneys. In the liver, hepatocellular single cell necrosis, mitosis and anisokaryosis were observed, accompanied by elevated serum ALT. In the kidneys, minor histopathological changes were confined to female mice, while mild decreases in ion transport and increases in blood urea nitrogen were seen only in males. Small changes in glutathione levels were observed in the kidneys and livers of male mice. Adrenal cortical cell vacuolation was observed at 15 mg FB1/kg and higher in females and from 35 mg FB1/kg in males. Serum cholesterol was elevated in both male and female mice, possibly due to FB1-induced changes in lipid metabolism in the liver and adrenals. Although bone marrow cell numbers were unchanged, increases in vacuolated myeloid cells and lymphocytes were observed in female mice. In general, the degree of changes observed indicate that mice are not as sensitive a model of FB1 toxicity as rats.
Asunto(s)
Ácidos Carboxílicos/toxicidad , Carcinógenos Ambientales/toxicidad , Fumonisinas , Micotoxinas/toxicidad , Administración Oral , Animales , Transporte Biológico/efectos de los fármacos , Recuento de Células Sanguíneas/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Células de la Médula Ósea/efectos de los fármacos , Femenino , Glutatión/análisis , Inmunoglobulinas/sangre , Inmunoglobulinas/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Factores Sexuales , Tetraetilamonio/metabolismoRESUMEN
The fungal toxin fumonisin B1 (FB1) is a contaminant of corn-based foods and feeds produced by members of the genus Fusarium. Fumonisin B1 toxicity was examined using gavage administration of purified toxin to female Sprague-Dawley rats. For 11 consecutive days each rat received a single dose of FB1 at the following concentrations: control (saline), 1, 5, 15, 35, or 75 mg FB1/kg body weight/d. Significantly depressed body weight and food consumption occurred at 35 and 75 mg FB1/kg/d. By the end of the dosing period there were no significant changes in food consumption. Kidneys and bone marrow were most sensitive to FB1 exposure. Changes in renal morphology were observed from 5 to 75 mg FB1/kg/d, accompanied by transient changes in urine osmolality and urine enzyme levels. Increased cellular vacuolation was the primary change associated with bone-marrow toxicity, starting at doses of 5 mg FB1/kg/d. Hepatotoxicity was indicated by reduced liver weight, elevated serum alanine amonitransferase (ALT), and mild histopathological changes occurring at doses of 15 mg FB1/kg/d and higher. Increased cytoplasmic vacuolation of adrenal cortex cells occurred in rats treated with 15 mg FB1/kg/d and higher, indicating that the adrenals are also potential targets of FB1. Elevated serum cholesterol, which is a consistent response to FB1 was observed at 5 mg FB1/kg/d and higher. Based on responses in this study, gavage is an appropriate substitute for longer feeding studies. Compared to previous work with male rats, gender-related difference in FB1 responses lacked consistency but indicated that males may be marginally more sensitive than female Sprague-Dawley rats.
Asunto(s)
Ácidos Carboxílicos/toxicidad , Carcinógenos Ambientales/toxicidad , Fumonisinas , Administración Oral , Glándulas Suprarrenales/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Femenino , Intubación Gastrointestinal , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Caracteres Sexuales , Timo/efectos de los fármacos , UrinálisisRESUMEN
The objectives of this study were to evaluate visual and chemical attributes of beefsteaks from various USDA quality grades and muscles packaged in high-oxygen (80% O2/20% CO2) modified-atmosphere packaging (MAP). A total of nine carcasses were selected to represent Select (n = 3), low Choice (n = 3), and high Choice (n = 3) USDA quality grades. The semimembranosus (SM), semitendinosus (ST), and biceps femoris (BF) muscles were removed from each carcass and allotted to two packaging types (MAP or polyvinyl chloride over-wrap) and were displayed for up to 10 d, with evaluation on d 1, 3, 5, 7, and 10. Fifty-four steaks were evaluated on each day by a five-member trained panel for visual color (lean color and discoloration) and were also analyzed with a Minolta Chroma Meter CR-310 for L* and a* values (lightness and redness, respectively). Chemical properties measured included percentage of metmyoglobin formation and fat content. Visual color scores did not differ (P > 0.05) at d 1 and 3 with respect to all quality grades, but decreased after d 3, with a greater reduction (P < 0.05) in high Choice steaks for both lean color and discoloration. The low Choice steaks packaged in MAP displayedhigher (P < 0.05) lean color scores and less (P < 0.05) discoloration at d 7 and 10 than did Select and high Choice steaks. Redness (a*) values also decreased (P < 0.05) after d 3, whereas (lightness) L* values declined (P < 0.05) from d 1 to 5. The high Choice steaks had higher (P < 0.05) metmyoglobin content than low Choice and Select steaks, but packaging had no effect (P > 0.05) on metmyoglobin content. Muscle type did affect metmyoglobin content; however, the metmyoglobin content of the SM was greatest (P < 0.05), followed by the BF, with the ST having the lowest (P < 0.05) metmyoglobin formation. Results indicate that low Choice steaks react the best in MAP, and the ST maintained greater storage characteristics regardless of quality grade or packaging.
Asunto(s)
Embalaje de Alimentos/métodos , Carne/normas , Músculo Esquelético/metabolismo , Oxígeno/farmacología , Animales , Bovinos , Carne/clasificación , Metamioglobina/análisis , Oxidación-Reducción , Pigmentación , Control de Calidad , Factores de Tiempo , Estados Unidos , United States Department of AgricultureRESUMEN
Dehulled soybean meal prepared from genetically modified, herbicide (glyphosate)-tolerant Roundup Ready soybeans containing the CP4 EPSPS protein and near-isogenic conventional soybeans were assessed in an experiment with growing-finishing pigs. The soybeans were grown in the yr 2000 under similar agronomic conditions except that the Roundup Ready soybeans were sprayed with Roundup herbicide. Both were processed at the same plant. The composition of the two types of soybeans and the processed soybean meal were similar. Corn-soybean meal diets containing conventional or Roundup Ready soybean meal and fortified with minerals and vitamins were fed to 100 cross-bred pigs from 24 to 111 kg BW. Diets contained approximately 0.95% lysine initially and were reduced to 0.80 and 0.65% lysine when pigs reached 55 and 87 kg BW, respectively. There were 10 pens (five pens of barrows and five pens of gilts) per treatment with five pigs per pen. All pigs were scanned at 107 kg mean BW and all barrows were killed at the end of the test for carcass measurements and tissue collection. Rate and efficiency of weight gain, scanned backfat and longissimus area, and calculated carcass lean percentage were not different (P > 0.05) for pigs fed diets containing conventional or Roundup Ready soybean meal. Gilts gained slower, but they were more efficient and leaner (P < 0.05) than barrows. Responses to the type of soybean meal were similar for the two sexes with no evidence of a diet x sex interaction for any of the traits. In most instances, carcass traits of barrows were similar for the two types of soybean meal. Longissimus muscle samples from barrows fed conventional soybean meal tended (P = 0.06) to have less fat than those fed Roundup Ready soybean meal, but water, protein, and ash were similar. Sensory scores of cooked longissimus muscles were not influenced (P > 0.05) by diet. The results indicate that Roundup Ready soybean meal is essentially equivalent in composition and nutritional value to conventional soybean meal for growing-finishing pigs.