RESUMO
Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1). The livers of SAMP8 mice show fatty degeneration, hepatocyte death, fibrosis, cirrhotic changes, inflammatory mononuclear cell infiltration and sporadic neoplastic changes. SAMP8 mice also show abnormal liver function tests: significantly increased levels of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Furthermore, titers of murine leukemia virus are higher in livers of SAMP8 than in those of SAMR1 mice. Our observations suggest that SAMP8 mouse strain is a valuable animal model for the study of liver diseases. The possible mechanisms of liver damage in SAMP8 mice are also discussed.
Assuntos
Hepatopatias/patologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Vírus da Leucemia Murina/isolamento & purificação , Fígado/ultraestrutura , Hepatopatias/enzimologia , Hepatopatias/etiologia , Camundongos , Camundongos Endogâmicos , Microscopia Eletrônica , Especificidade da EspécieRESUMO
Ultrastructural reconstruction of 27 fibrillar plaques in different stages of formation and maturation was undertaken to characterize the development of fibrillar plaques in the brains of human APP(SW) transgenic mice (Tg2576). The study suggests that microglial cells are not engaged in Abeta removal and plaque degradation, but in contrast, are a driving force in plaque formation and development. Fibrillar Abeta deposition at the amyloid pole of microglial cells appears to initiate three types of neuropil response: degeneration of neurons, protective activation of astrocytes, and attraction and activation of microglial cells sustaining plaque growth. Enlargement of neuronal processes and synapses with accumulation of degenerated mitochondria, dense bodies, and Hirano-type bodies is the marker of toxic injury of neurons by fibrillar Abeta. Separation of amyloid cores from neurons and degradation of amyloid cores by cytoplasmic processes of hypertrophic astrocytes suggest the protective and defensive character of astrocytic response to fibrillar Abeta. The growth of cored plaque from a small plaque with one microglial cell with an amyloid star and a few dystrophic neurites to a large plaque formed by several dozen microglial cells seen in old mice is the effect of attraction and activation of microglial cells residing outside of the plaque perimeter. This mechanism of growth of plaques appears to be characteristic of cored plaques in transgenic mice. Other features in mouse microglial cells that are absent in human brain are clusters of vacuoles, probably of lysosomal origin. They evolve into circular cisternae and finally into large vacuoles filled with osmiophilic, amorphous material and bundles of fibrils that are poorly labeled with antibody to Abeta. Microglial cells appear to release large amounts of fibrillar Abeta and accumulate traces of fibrillar Abeta in a lysosomal pathway.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Amiloidose/patologia , Astrócitos/patologia , Microglia/patologia , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/patologia , Sinapses/patologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Amiloidose/metabolismo , Animais , Astrócitos/metabolismo , Humanos , Hipertrofia/metabolismo , Hipertrofia/patologia , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Microscopia Eletrônica , Placa Amiloide/metabolismo , Sinapses/metabolismoRESUMO
The effects of supplemental feeding by tourists on wild Japanese monkey's home range size and location, and troop size and composition were studied for two monkey troops, Troop A and Troop B, living along the Irohazaka loop road, Nikko National Park, central Japan. Changes were documented based on data gathered from 1982 to 1996 by the use of radio telemetry. Troop A's home range size shrank and changed from separate winter and summer ranges to a single, year-round home range, with its core located in a high elevation area where supplemental feeding by tourists was heavy. Troop B's home range also shrank and shifted to a lower elevation where supplemental feeding by tourists was heavy. Troop A's population size increased between the winters of 1983-1984 and 1990-1991 in conjunction with an increase in human encounter rates, and then decreased. Troop B's size increased until the winter of 1993-1994, and then decreased. The instability of troop size between 1993 and 1996 may be explained by documented factors such as a decrease in the adult sex ratio, an increase in the infant-female ratio, and an increase in juvenile mortality and/or emigration, all of which may have been influenced by supplemental feeding by tourists.
RESUMO
To clarify the molecular mechanism and significance of homologous desensitization of platelet-activating factor (PAF) signaling, we examined the effect of PAF on PAF receptor mRNA expression in rat mesangial cells by Northern blot analysis. Treatment of the cells with PAF (10(-7)-10(-8) M) reduced the expression of PAF receptor mRNA in 1 h, and this reduction was recovered by pretreatment of mesangial cells with a specific PAF receptor antagonist, WEB-2086 (10(-6) M), or a cyclooxygenase inhibitor, indomethacin (10(-6) M), for 10 min. PAF-stimulated prostaglandin E2 (PGE2) and adenosine 3',5'-cyclic monophosphate (cAMP) formation was measured by radioimmunoassays specific for each substance. Reduction of PAF receptor mRNA expression was mimicked by treatment of the cells with PGE2 (10(-6) M) or dibutyryl-cAMP (10(-3) M), a cell-permeable analog of cAMP. These results, taken together, suggest that PAF receptor mRNA expression is downregulated by exposure to PAF in cultured mesangial cells. This homologous downregulation is mediated by cAMP production through PGE2 synthesis.
Assuntos
AMP Cíclico/metabolismo , Regulação para Baixo/fisiologia , Mesângio Glomerular/fisiologia , Fator de Ativação de Plaquetas/farmacologia , Glicoproteínas da Membrana de Plaquetas/biossíntese , Receptores de Superfície Celular , Receptores Acoplados a Proteínas G , Animais , Azepinas/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Regulação para Baixo/efeitos dos fármacos , Feminino , Mesângio Glomerular/efeitos dos fármacos , Indometacina/farmacologia , Cinética , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/fisiologia , Triazóis/farmacologia , Fatores de Virulência de Bordetella/farmacologiaRESUMO
Puromycin aminonucleoside (PAN) toxicity was totally inhibited in the rat in vivo and in cultured glomerular epithelial cells (GECs) in vitro using the adenosine deaminase (ADA) inhibitor, 2'-deoxycoformycin (DCF). DCF completely inhibited ADA activity in glomeruli and protected against the development of PAN nephrosis; the 24-h urinary protein excretion of treated rats compared with controls (PAN rats) 9 days after PAN injection was 16 +/- 2 mg and 524 +/- 55 mg, respectively (p < .01). Morphological examination also demonstrated that the glomerular epithelial cells were protected against PAN-induced damage. Furthermore, when DCF was added to the first passage of GECs simultaneously with PAN, the adenosine triphosphate contents of remnant GECs on culture substrata increased in a dose-dependent manner, and PA toxicity was completely inhibited by 10(-4) M DCF. The order of ADA activity in glomeruli from various species was as follows: rat > monkey > guinea pig > dog > rabbit > mouse. High activity of ADA in the glomerulus was limited to species in which PAN induced nephrosis. Additionally, DCF increased glomerular cyclic AMP contents, resulting from enhanced adenosine accumulation in the pericellular space. These results indicate that the pathogenesis of PAN toxicity is closely related to adenosine metabolism and that ADA plays a key role in this model. Furthermore, we speculate that DCF contributes to the inhibition of reactive oxygen metabolites by decreasing the substrate of xanthine oxidase and/or increasing pericellular adenosine accumulation.
Assuntos
Inibidores de Adenosina Desaminase , Inibidores Enzimáticos/farmacologia , Rim/efeitos dos fármacos , Puromicina Aminonucleosídeo/antagonistas & inibidores , Puromicina Aminonucleosídeo/toxicidade , Adenosina/farmacologia , Animais , AMP Cíclico/metabolismo , Cães , Radicais Livres/metabolismo , Cobaias , Haplorrinos , Rim/metabolismo , Rim/patologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Masculino , Camundongos , Microscopia Eletrônica , Pentostatina/farmacologia , Coelhos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Especificidade da EspécieAssuntos
Nervo Óptico/metabolismo , Retina/metabolismo , Taurina/deficiência , Taurina/metabolismo , beta-Alanina/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Gatos , Dieta , Alimentos Fortificados , Imuno-Histoquímica , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/ultraestrutura , Especificidade de Órgãos , Retina/efeitos dos fármacos , Retina/ultraestrutura , Taurina/administração & dosagem , beta-Alanina/administração & dosagemAssuntos
Alimentos Infantis , Retina/ultraestrutura , Taurina/deficiência , Animais , Humanos , Lactente , Macaca mulatta , Especificidade de Órgãos , Células Fotorreceptoras/efeitos dos fármacos , Células Fotorreceptoras/ultraestrutura , Retina/efeitos dos fármacos , Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Células Fotorreceptoras Retinianas Cones/ultraestrutura , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/ultraestrutura , Taurina/metabolismoAssuntos
Taurina/deficiência , Taurina/fisiologia , Córtex Visual/ultraestrutura , Animais , Animais Recém-Nascidos , Astrócitos , Gatos , Contagem de Células , Feminino , Proteína Glial Fibrilar Ácida/análise , Imuno-Histoquímica , Troca Materno-Fetal , Microscopia Eletrônica , Gravidez , Taurina/análise , Córtex Visual/química , Ácido gama-Aminobutírico/análiseAssuntos
Macaca mulatta , Doenças dos Macacos/fisiopatologia , Taurina/deficiência , Córtex Visual/crescimento & desenvolvimento , Envelhecimento , Animais , Astrócitos/patologia , Contagem de Células , Dieta , Doenças dos Macacos/patologia , Neuroglia/patologia , Neurônios/patologia , Oligodendroglia/patologia , Taurina/administração & dosagem , Córtex Visual/patologiaRESUMO
Rhesus monkey infants were raised from birth until 6 or 12 months of age on a taurine-free soy protein-based human infant formula or on the same formula supplemented with taurine. An additional group received taurine-free formula until 6 months and then the supplemented diet from 6 until 12 months. The densities of rod and cone visual pigments were measured by fundus reflectometry at 6 and 12 months, and retinal morphology was then examined by light and electron microscopy. The densities of rhodopsin, measured in the near periphery after a white bleach, and of cone pigment, measured in the macula after a red bleach, were significantly reduced in the taurine-deprived monkeys at 6 months but not at 12 months. The retinas of 6-month-old taurine-deprived infants showed degenerative morphological changes in photoreceptors, particularly in cones in the foveal region, which were somewhat less severe than those seen in a previous study at 3 months of age. The prevalence and degree of these abnormalities continued to decrease with age in taurine-deprived animals, but changes persisted in some animals at 12 months. Recovery was more complete in monkeys reversed to the supplemented diet from 6 to 12 months. Thus, monkey infants are dependent on dietary taurine to maintain normal retinal structure until at least 6 months of age; the effects of taurine deprivation regress spontaneously but incompletely by 12 months.
Assuntos
Animais Recém-Nascidos , Alimentos Infantis , Retina/crescimento & desenvolvimento , Pigmentos da Retina/metabolismo , Taurina/deficiência , Envelhecimento , Animais , Núcleo Celular/ultraestrutura , Citoplasma/ultraestrutura , Humanos , Lactente , Macaca mulatta , Microscopia Eletrônica , Oftalmoscopia , Retina/metabolismo , Retina/ultraestrutura , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/ultraestrutura , Rodopsina/metabolismo , Taurina/administração & dosagemRESUMO
The localization of taurine, GABA and glutamate in developing feline cerebellum was performed using antibodies raised against the amino acids conjugated to bovine serum albumin with glutaraldehyde. Distinct patterns of immunostaining were observed for each of the amino acids. Taurine-like immunoreactivity reached a peak at 4 weeks after birth, as did GABA-like immunoreactivity, whereas glutamate-like immunoreactivity was greatest in the mature cerebellum. Purkinje cells are all taurine-positive in cerebellum from neonatal animals, whereas in the mature cerebellum they appear to contain only GABA and glutamate, with virtually no taurine, in contrast to observations reported with rodent cerebellum. Ultrastructural studies and immunogold labelling visualized by electron microscopy show that the band of taurine-like immunoreactivity observed in newborn feline cerebellum is localized within dendrites, axons and glial processes. Granule cells migrating through this region also show prominent taurine-like immunoreactivity.
Assuntos
Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Glutamatos/metabolismo , Taurina/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Animais Recém-Nascidos , Axônios/ultraestrutura , Gatos , Cerebelo/ultraestrutura , Dendritos/ultraestrutura , Feminino , Glutamatos/imunologia , Ácido Glutâmico , Imuno-Histoquímica , Microscopia Eletrônica , Neuroglia/ultraestrutura , Células de Purkinje/metabolismo , Taurina/imunologia , Ácido gama-Aminobutírico/imunologiaRESUMO
The concentrations of taurine in blood and brain regions of the toad Bufo boreas have been measured. Most of these values are considerably lower than those found in mammals. Using an antibody prepared against conjugated taurine, the distribution of taurine in three brain regions of the toad has been visualized. The possible osmoregulatory functions of taurine have been investigated by making toads hyper- or hypo-osmotic in vivo. Induction of hypoosmolality is accompanied by a massive taurine tide in blood plasma, but has no immediate effects upon the taurine concentrations in the brain areas studied. However, histochemical visualization indicates a marked redistribution of taurine between cellular components and extracellular space of brain tissues. This may indicate that taurine has an osmoregulatory function in brain tissue under hypo-osmotic conditions. Hyperosmolality results in no elevation of the taurine concentration in blood plasma of toads, but rather in a very gradual decline of total plasma taurine content over a prolonged time period. Histochemical studies reveal little change in frontal cortex after 1 hour but deeper staining of many neurons in optic lobe accompanied by greater staining in the extracellular fluid. By 3 hours there is a depletion of taurine from all compartments of cerebral cortex tissues. No evidence of any prolonged direct osmoregulatory role for taurine is indicated under hyperosmotic conditions. A possible indirect osmoregulatory function of taurine is discussed.
Assuntos
Encéfalo/metabolismo , Bufonidae/metabolismo , Taurina/metabolismo , Animais , Imuno-Histoquímica , Microscopia Eletrônica , Concentração Osmolar , Volume Plasmático , Taurina/sangue , Distribuição Tecidual , Equilíbrio HidroeletrolíticoAssuntos
Glomérulos Renais/citologia , Animais , Antígenos de Superfície , Células Cultivadas , Colágeno , Técnicas Citológicas , Células Epiteliais , Epitélio/imunologia , Estudos de Avaliação como Assunto , Mesângio Glomerular/citologia , Mesângio Glomerular/imunologia , Glomérulos Renais/imunologia , Membranas Artificiais , Permeabilidade , RatosAssuntos
Encéfalo/crescimento & desenvolvimento , Dieta/efeitos adversos , Retina/crescimento & desenvolvimento , Taurina/deficiência , Animais , Animais Recém-Nascidos/metabolismo , Encéfalo/metabolismo , Carboxiliases/metabolismo , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Macaca mulatta , Degeneração Neural/fisiologia , Retina/metabolismo , Taurina/administração & dosagem , Taurina/farmacocinética , Fatores de Tempo , Distribuição Tecidual/fisiologiaRESUMO
Glomerular function and tubuloglomerular feedback (TGF) responses were studied in rats treated with antithymocyte rabbit serum (ATS). Microscopic findings revealed extensive mesangial cell loss and injury, enlarged capillary lumen, and decreased tortuosity of glomerular capillaries. Whole kidney GFR and SNGFR were lower in ATS-treated rats than in control rats (1.04 +/- 0.04 vs 0.94 +/- 0.03 ml/min/g kidney weight, 32 +/- 2 vs 27 +/- 1 nl/min, respectively) due to a decrease in Kf (0.017 +/- 0.001 vs 0.021 +/- 0.001 nl/s/mmHg). The magnitude of the TGF responses of SNGFR was less in ATS rats than in control rats (17% +/- 4% vs 34% +/- 5%), but that of SFP was not significantly different (18% +/- 2% vs 23% +/- 1%). These results indicate that the mesangial cells are necessary for full expression of the TGF mechanism and suggest the involvement of changes in Kf in the TGF mechanism.
Assuntos
Glomérulos Renais/fisiopatologia , Túbulos Renais/fisiopatologia , Animais , Soro Antilinfocitário/administração & dosagem , Retroalimentação , Taxa de Filtração Glomerular/fisiologia , Mesângio Glomerular/imunologia , Mesângio Glomerular/patologia , Masculino , Néfrons/fisiopatologia , Ratos , Ratos EndogâmicosRESUMO
In an attempt to increase taurine biosynthesis in cats fed a taurine-free diet we supplied an excess of the precursor, cystine, in the diet. All nine cats exhibited extreme signs of neurotoxicity including lethargy, inability to stand, rigidity of the neck and lower limbs, absence and epileptic seizures, severe retinal damage and death. In a similar group of cats fed 0.05% taurine in addition to an excess of cystine, four cats died after showing minimal symptoms of lethargy and unsteadiness and the remainder showed no adverse effects. Biochemical measurements, tissue concentrations of cystine, cysteine, bound cysteine, glutamate and taurine and activities of enzymes involved in taurine biosynthesis, revealed significant differences only in taurine concentrations.
Assuntos
Cistina/toxicidade , Sistema Nervoso/efeitos dos fármacos , Taurina/deficiência , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Gatos , Cistina/análise , Dieta , Feminino , Glutamatos/análise , Ácido Glutâmico , L-Lactato Desidrogenase/sangue , Células Fotorreceptoras/citologia , Retina/ultraestrutura , Taurina/análise , Distribuição TecidualRESUMO
Rhesus monkey infants were raised from birth on a taurine-free soy protein-based human infant formula or on the same formula supplemented with taurine. The monkeys were killed 3 months after birth and the retinas examined by light and electron microscopy. All of the monkeys raised on formula alone showed degenerative ultrastructural changes in photoreceptor outer segments that ranged from swelling and disorientation to fragmentation and disorganization. Cones were more severely affected than rods, and changes were most pronounced in the foveal region. Changes were also noted in the fine structure of the retinal pigment epithelium. These changes were prevented in all but one monkey fed the same formula supplemented with taurine. These results provide further support for the addition of taurine to commercial human infant formulas.