RESUMO
Auditory categorization requires listeners to integrate acoustic information from multiple dimensions. Attentional theories suggest that acoustic dimensions that are informative attract attention and therefore receive greater perceptual weight during categorization. However, the acoustic environment is often noisy, with multiple sound sources competing for listeners' attention. Amid these adverse conditions, attentional theories predict that listeners will distribute attention more evenly across multiple dimensions. Here we test this prediction using an informational masking paradigm. In two experiments, listeners completed suprasegmental (focus) and segmental (voicing) speech categorization tasks in quiet or in the presence of competing speech. In both experiments, the target speech consisted of short words or phrases that varied in the extent to which fundamental frequency (F0) and durational information signalled category identity. To isolate effects of informational masking, target and competing speech were presented in opposite ears. Across both experiments, there was substantial individual variability in the relative weighting of the two dimensions. These individual differences were consistent across listening conditions, suggesting that they reflect stable perceptual strategies. Consistent with attentional theories of auditory categorization, listeners who relied on a single primary dimension in quiet shifted towards integrating across multiple dimensions in the presence of competing speech. These findings demonstrate that listeners make greater use of the redundancy present in speech when attentional resources are limited.
RESUMO
NF-kappa B1 p105 forms a high-affinity, stoichiometric interaction with TPL-2, a MEK kinase essential for TLR4 activation of the ERK mitogen-activated protein kinase cascade in lipopolysaccharide (LPS)-stimulated macrophages. Interaction with p105 is required to maintain TPL-2 metabolic stability and also negatively regulates TPL-2 MEK kinase activity. Here, affinity purification identified A20-binding inhibitor of NF-kappa B 2 (ABIN-2) as a novel p105-associated protein. Cotransfection experiments demonstrated that ABIN-2 could interact with TPL-2 in addition to p105 but preferentially formed a ternary complex with both proteins. Consistently, in unstimulated bone marrow-derived macrophages (BMDMs), a substantial fraction of endogenous ABIN-2 was associated with both p105 and TPL-2. Although the majority of TPL-2 in these cells was complexed with ABIN-2, the pool of TPL-2 which could activate MEK after LPS stimulation was not, and LPS activation of TPL-2 was found to correlate with its release from ABIN-2. Depletion of ABIN-2 by RNA interference dramatically reduced steady-state levels of TPL-2 protein without affecting levels of TPL-2 mRNA or p105 protein. In addition, ABIN-2 increased the half-life of cotransfected TPL-2. Thus, optimal TPL-2 stability in vivo requires interaction with ABIN-2 as well as p105. Together, these data raise the possibility that ABIN-2 functions in the TLR4 signaling pathway which regulates TPL-2 activation.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/química , Proteínas de Transporte/genética , Linhagem Celular , DNA Complementar/genética , Ativação Enzimática , Células HeLa , Humanos , Técnicas In Vitro , MAP Quinase Quinase Quinases/química , MAP Quinase Quinase Quinases/genética , Substâncias Macromoleculares , Macrófagos/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Dados de Sequência Molecular , Subunidade p50 de NF-kappa B , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Solubilidade , Receptor 4 Toll-Like , Receptores Toll-Like , Fatores de Transcrição/química , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , TransfecçãoRESUMO
The aims of this study were to determine how Prostaglandin E2 (PGE2) locally applied affected the immunodistribution of latent transforming growth factor-beta 1 (TGF-beta1), and how the eicosanoid modified TGF-beta1 release and TGF-beta receptors gene expression in cultured osteoblasts. PGE2 locally delivered on the rat mandible at doses of 0.1 and 0.05 mg/day, but not 0.025 mg/day, over 20 days significantly increased latent TGF-beta1 immunodistribution (P<0.001), comparing with a placebo-treated group. Cultured osteoblasts stimulated with 10(-5) or 10(-7)M PGE2 significantly varied the level of activated TGF-beta1 released into supernatants at different experimental periods compared with negative and positive controls. TGF-beta receptor type I gene expression was significantly increased in osteoblasts (P<0.01) after 10 days of treatment with 10(-5) and 10(-7)M PGE2, whereas 10(-3) M PGE2 produced the opposite effect. It is concluded that PGE2 may stimulate bone deposition by affecting TGF-beta pathway. This effect on the pathway appears to be dose-dependent.
Assuntos
Dinoprostona/farmacologia , Expressão Gênica/efeitos dos fármacos , Receptores de Fatores de Crescimento Transformadores beta/genética , Fator de Crescimento Transformador beta/metabolismo , Receptores de Ativinas Tipo I/genética , Fosfatase Alcalina/análise , Animais , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Meios de Cultivo Condicionados/química , Preparações de Ação Retardada/administração & dosagem , Dinoprostona/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Implantes Experimentais , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Proteínas Serina-Treonina Quinases , Ratos , Ratos Endogâmicos Lew , Ratos Wistar , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta1RESUMO
It has been shown that prostaglandin E2 (PGE2) locally released adjacent to the mandible over a 20-day period increases alveolar bone area, in part, due to a reduction in the percentage of eroded surface. To determine the effect of PGE2 on alveolar bone resorption, left mandibles from 24 Lewis rats were treated over a 20-day period with a local application of PGE2 (0.1, 0.05 or 0.025 mg/day) or placebo. The right side served as the non-treated matched control. Tissue sections were stained for tartrate resistant acid phosphatase (TRAP) calcitonin receptor (CTR) and metalloproteinase-2 (MMP-2). Matched samples were analysed by Wilcoxon matched pairs test and, a non-parametric one-way analysis of variance compared groups of treatment. Those tissues treated with PGE2 at doses of 0.1 and 0.05 mg/day showed significantly reduced numbers of TRAP and CTR-positive multinucleated cells compared with matched controls (p<0.005), as well as significantly reduced numbers of TRAP- and CTR-positive multinucleated cells when compared with the placebo-treated group (p<0.001). The number of periodontal ligament cells expressing MMP-2 was also significantly reduced in tissues treated with the two higher doses of PGE2 (p<0.001) comparing with both matched controls and the placebo-treated group. Following a 20-day period, locally released PGE2 at doses of 0.1 and 0.05 mg/day appears to affect alveolar bone resorption in the periodontium of rats, as the number of multinucleated cells expressing TRAP and CTR are significantly reduced. Furthermore, the same doses of PGE2 also significantly reduced the expression of MMP-2 by the periodontal cells.
Assuntos
Fosfatase Ácida/metabolismo , Dinoprostona/farmacologia , Isoenzimas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Periodonto/efeitos dos fármacos , Receptores da Calcitonina/metabolismo , Fosfatase Ácida/análise , Perda do Osso Alveolar/metabolismo , Perda do Osso Alveolar/patologia , Animais , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Contagem de Células , Feminino , Imuno-Histoquímica/métodos , Isoenzimas/análise , Doenças Mandibulares/metabolismo , Doenças Mandibulares/patologia , Metaloproteinase 2 da Matriz/análise , Periodonto/química , Periodonto/metabolismo , Ratos , Ratos Endogâmicos Lew , Receptores da Calcitonina/análise , Fosfatase Ácida Resistente a TartaratoRESUMO
Prostaglandin E2 (PGE2) induces bone formation in stress-bearing bones. The mandible, a stress-bearing bone, is loaded daily during mastication. The aim of this study was to determine if PGE2 delivered locally to the mandible over 20 days enhances alveolar bone deposition. In 18 Lewis rats, controlled-release pellets containing PGE2 were implanted on the buccal aspect on the left-hand side of the mandible, mesial to the root of the first molar. Controlled-release pellets locally delivered 0.1, 0.05, or 0.025 mg/day of PGE2. The right side of the mandible was used as a matched control for each animal. Six sham-treated animals were implanted with a placebo pellet. On days 7 and 19, animals were injected with the bone markers tetracycline and calcein, respectively. On day 21, animals were sacrificed and undecalcified tissues obtained for morphometrical analysis. Morphometrical measurements were analyzed by paired t test to determine differences between the matched samples and one-way ANOVA to compare the different treatment groups. A significant increase in alveolar bone area was observed in mandibles treated with 0.1 and 0.05 mg/day when compared with matched controls and the placebo group. This was accompanied by a significant increase in alveolar bone height and width. The proportions of double-labeled surface (dLS), the mineral apposition rate (MAR), and bone formation rate (BFR) were significantly increased in mandibles treated with the two higher doses of PGE2. The proportion of resorptive surface (RS) was significantly reduced in these two groups. It is concluded that PGE2 induces alveolar bone formation in the mandible when locally delivered at a dose of 0.1 or 0.05 mg/day for 20 days.
Assuntos
Regeneração Óssea/efeitos dos fármacos , Dinoprostona/administração & dosagem , Mandíbula/efeitos dos fármacos , Mandíbula/fisiologia , Animais , Regeneração Óssea/fisiologia , Relação Dose-Resposta a Droga , Feminino , Mandíbula/citologia , Ratos , Ratos Endogâmicos LewRESUMO
1 Low doses (50 and 80 mg/kg) of benserazide (Ro4-4602), an aromatic amino acid decarboxylase inhibitor, markedly reduced 5-hydroxytryptamine and melatonin in the rat pineal gland without affecting hypothalamic 5-hydroxytryptamine. 2 This differential effect shows that inhibition of the pineal gland decarboxylase activity is possible, and confirms that the rat pineal gland is accessible to peripherally acting agents.
Assuntos
Benserazida/farmacologia , Hidrazinas/farmacologia , Hipotálamo/metabolismo , Melatonina/metabolismo , Glândula Pineal/metabolismo , Serotonina/metabolismo , Animais , Hipotálamo/efeitos dos fármacos , Masculino , Glândula Pineal/efeitos dos fármacos , RatosRESUMO
The effect of melatonin on the stimulated release of LH from prepubertal female rat pituitary cells in vitro was investigated. Significant inhibition of LH-releasing hormone and calcium ionophore-induced LH release was seen but not of potassium-induced release. These results suggest a specific interaction between melatonin and the endogenous events leading to LH release, and may implicate melatonin as an important neuroendocrine component of pubertal development in this species.
Assuntos
Hormônio Luteinizante/metabolismo , Melatonina/farmacologia , Hipófise/efeitos dos fármacos , Maturidade Sexual , Animais , Calcimicina/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Técnicas In Vitro , Hipófise/citologia , Hipófise/metabolismo , Potássio/farmacologia , Radioimunoensaio , Ratos , Ratos EndogâmicosRESUMO
Three groups of Suffolk-cross ewes were kept in (A) summer photoperiod plus melatonin feeding in such a way as to mimic the plasma levels found in winter photoperiod, (B) winter photoperiod or (C) natural light/dark from mid-June onwards. Prolactin levels remained high in group C throughout July and August but were dramatically reduced in both groups A and B. The rise in prolactin levels associated with dusk, however, was still apparent in all three groups. Appropriate administration of melatonin can thus influence prolactin secretion in the same way as an extension of the dark phase. This effect is associated with an early onset of the breeding season in the ewe.
Assuntos
Melatonina/metabolismo , Prolactina/sangue , Estações do Ano , Ovinos/sangue , Ração Animal , Animais , Feminino , Luz , Melatonina/administração & dosagemRESUMO
Breeding activity was similarly advanced in ewes given continuous (s.c. implant) or timed (oral dose at 15.30 h) melatonin treatments or subjected to a short (8 h light: 16 h darkness) artificial photoperiod. Treatments commenced in mid-June and were terminated in mid-November. Weekly and serial blood samples were collected before and after treatments commenced, to ascertain the effects on plasma prolactin, LH and FSH concentrations. In addition, serial blood samples were collected for 24 h plasma prolactin and melatonin estimations before and after cessation of the treatments. Plasma prolactin levels were significantly reduced immediately following the start of the melatonin (implant and oral) and short-photoperiod treatments but 'rebounded' to levels greater than control values. The normal seasonal (spring) rise in plasma prolactin was noted in the following year. Before the onset of breeding activity, mean plasma LH and FSH concentrations and LH pulse frequency did not change following any of the treatments. The 24-h plasma melatonin profile accurately reflected the various applied treatments but had re-entrained to the prevailing (natural) photoperiod 1 week after termination of the treatments. There were no significant group differences in 24-h plasma prolactin levels 1 week before or 1 and 11 weeks after the treatments had ceased. Such treatments, although successfully advancing the onset of breeding activity and modifying the seasonal plasma prolactin rhythm, were not manifested through any apparent change in peripheral LH or FSH.
Assuntos
Cruzamento , Hormônio Foliculoestimulante/sangue , Luz , Hormônio Luteinizante/sangue , Melatonina/farmacologia , Prolactina/sangue , Animais , Feminino , Periodicidade , Ovinos/sangueRESUMO
Patterns of plasma melatonin, similar in the duration of high levels to those found in winter, were induced in Suffolk-cross ewes kept in summer light (16 h light: 8 h darkness) by daily oral administration of melatonin (3 mg/13 mumol). The onset of oestrous cycles in these sheep occurred in August, 2-8 weeks before the onset of oestrous cycles in untreated ewes kept in natural light. The onset of oestrous cycles in a further group of ewes kept in winter light (8 h light: 16 h darkness) from mid-June was indistinguishable from that of the melatonin-treated ewes. Rams were excluded from the premises. These data indicate that melatonin alone in physiological quantities is sufficient to induce early onset of the breeding season in the ewe, and provide strong evidence for a hormonal role of melatonin in a short-day breeder.
Assuntos
Estro/efeitos dos fármacos , Luz , Melatonina/farmacologia , Periodicidade , Ovinos/fisiologia , Animais , Feminino , Melatonina/sangue , Melatonina/fisiologia , GravidezRESUMO
Ewes were treated with s.c. implants of melatonin in mid-April, mid-May and mid-June. From mid-June, other animals were given oral doses of melatonin daily at 16.30 h and another group was maintained under a short (8 h light:16 h darkness) artificial photoperiod (lights out 16.30 h). Serial blood samples were taken from all animals in June and July. Plasma prolactin concentrations were significantly reduced in ewes treated in May and June (implant, oral and photoperiod treatments) but not in those treated in April. After treatment in June, prolactin levels were significantly suppressed after 7 days of oral and implant melatonin therapy, and after 28 days of a short artificial photoperiod. Melatonin treatment appeared more efficient than an artificial photoperiod in reducing plasma prolactin concentrations.
Assuntos
Melatonina/farmacologia , Prolactina/sangue , Animais , Ritmo Circadiano , Implantes de Medicamento , Feminino , Luz , Melatonina/administração & dosagem , Melatonina/sangue , Ovinos , Fatores de TempoRESUMO
PIP: The continued circulation of free steroids depends on their resorption from the gut following the hydrolysis of biliary conjugates. In this study, the bile duct of female Wistar albino rats was cannulated. Animals receiving labeled steroids or labeled bile intraductally also had the duodenum fitted with a cannula connected with a dosing syringe. In neomycin-treated rats, recirculation was impaired up to 50%. The deconjugation of mestranol and estradiol biliary conjugates was shown in vitro uponiincubation with rat caecal microorganisms, and the inhibition of such hydrolysis by neomycin was observed in vitro. Neomycin pretreatment reduced the biliary excretion of mestranol and estradiol after intraductal administration. It was thought that suppression of the gut microflora by neomycin was a major factor in the impairment of the intrahepatic circulation of mestranol and estradiol metabolites. This effect may be important regarding the half-life of estrogenic compounds of the contraceptive pill.^ieng
Assuntos
Bile/metabolismo , Circulação Êntero-Hepática/efeitos dos fármacos , Estradiol/metabolismo , Mestranol/metabolismo , Neomicina/farmacologia , Animais , Bactérias/metabolismo , Bile/efeitos dos fármacos , Ceco/microbiologia , Feminino , Meia-Vida , Hidrólise , Ratos , Fatores de TempoRESUMO
Fed and fasted, male, Wistar albino rats exposed to light ether anaesthesia and killed immediately or after 30 or 120 min recovery were compared with non-anaesthetized rats for changes in liver and kidney cytochrome P450 (CYP) activities. In fed rats, liver total CYP (nmol/mg protein) decreased by 30% immediately after ether, but was restored to normal levels after 30 min recovery; in fasted rats, liver total CYP increased by 20% by fasting alone, then decreased by 65% immediately after ether, and recovered to only 70% of control at 2 hr after ether. Rat liver cytochrome P4501A (CYP1A; 7-ethoxyresorufin O-deethylase or EROD activity) and cytochrome P4502B (CYP2B; 7-pentoxyresorufin O-dealkylase or PROD activity) were decreased after ether anaesthesia, similar to those for total CYP. In contrast, rat liver cytochrome P4502E1 (CYP2E1), determined by p-nitrophenol hydroxylation, increased by 40% by ether anaesthesia alone, 70% by fasting alone and 140% by ether plus fasting; these increases were confirmed by the CYP2E1-mediated activation of nitrosopyrrolidine and by immunoblot analysis using antibody to CYP2E1. In rat kidney, losses of total CYP, CYP1A and CYP2B, and increases of CYP2E1, induced by ether anaesthesia, were much more marked in fasted (90% loss in total CYP, 30% increase in CYP2E1) than in fed rats (slight loss in total cytochrome P450, 30% increase in CYP2E1). As maximum losses of total CYP in liver of fasted rats exposed to ether occurred at the time of maximum increase of CYP2E1 and maximum rate of generation of reactive oxygen species (ROS), it is suggested that the increase of CYP2E1, resulting from its stabilization by fasting and ether, leads to generation of ROS, increase in lipid peroxidation and consequent loss of total CYP, associated with the hepatic and renal necrosis seen in ether intoxication and surgical trauma.
Assuntos
Anestesia Geral , Sistema Enzimático do Citocromo P-450/análise , Éter , Jejum/metabolismo , Isoenzimas/análise , Rim/enzimologia , Fígado/enzimologia , Animais , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/análise , Fatores de TempoRESUMO
Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells show exaggerated growth and increased expression of platelet-derived growth factor (PDGF) A-chain mRNA. We examined the effect of methylene methylimino linkage of antisense oligodeoxynucleotide, a novel modification of antisense oligodeoxynucleotide designed to increase nuclease resistance, to PDGF A-chain on the exaggerated growth of vascular smooth muscle cells from SHR. Methylene methylimino-linked oligodeoxynucleotide provided complete resistance against S1 nuclease. Methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain resulted in a rapid inhibition of basal DNA synthesis of vascular smooth muscle cells from SHR. This inhibition was much greater than that produced by phosphorothioate linkage of antisense oligodeoxynucleotide to PDGF A-chain. The methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain may prove useful in the treatment of arterial proliferative diseases including hypertension.
Assuntos
Divisão Celular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Oligonucleotídeos Antissenso/farmacologia , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Alcenos/química , Animais , Células Cultivadas , DNA/biossíntese , DNA/efeitos dos fármacos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/metabolismo , Fator de Crescimento Derivado de Plaquetas/genética , Ratos , Ratos Endogâmicos SHR , Endonucleases Específicas para DNA e RNA de Cadeia Simples/metabolismo , Tionucleotídeos/química , Tionucleotídeos/metabolismo , Tionucleotídeos/farmacologiaRESUMO
Transforming growth factor-beta 1 (TGF-beta1) has been reported to be expressed within several tissue compartments of developing molar crowns and therefore is implicated in tooth development. Additionally, TGF-beta1 may also play a crucial role in tissue repair and regeneration. The aim of this study was to determine the distribution of TGF-beta1 in the developing periodontal attachment apparatus (cementum, periodontal ligament, and alveolar bone) in Lewis rats. Animals aged 3, 6, and 12 wks were killed, their mandibles removed, fixed, demineralized, and processed in paraffin. The localization of TGF-beta1 in tissues was detected by polyclonal goat antibodies against human TGF-beta1 by means of immunoperoxidase techniques. TGF-beta1 messenger RNA was detected by in situ hybridization with a cocktail oligonucleotide probe. Cell counts were determined for analysis of the percentage of cells stained positive for TGF-beta1. Results revealed that TGF-beta1 was expressed in the developing alveolar bone, periodontal ligament, and cementum at all stages of tissue development studied. Staining was stronger at sites of cementum and alveolar bone compared with the periodontal ligament. Intensity of the positive staining, based on 3 grades, indicated a similarity between the tissues obtained from different ages, but varied between several cell types. Cementoblasts and osteoblasts stained more strongly than fibroblasts. Large numbers (approximately 90%) of the osteocytes in developing bone expressed TGF-beta1; however, in mature bone, fewer osteocytes stained for TGF-beta1. The percentages of positively stained cementoblasts, osteoblasts, and fibroblasts in the periodontal space were greater at the apical portion than at the cervical portion of the root. TGF-beta1 mRNA was expressed in osteoblasts, some bone marrow cells, cementoblasts, and fibroblasts. This study indicates that TGF-beta1 may play an important role in the modulation of tissue formation and development of the periodontium.
Assuntos
Periodonto/crescimento & desenvolvimento , Periodonto/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Envelhecimento/metabolismo , Animais , Contagem de Células , Imuno-Histoquímica , Hibridização In Situ/métodos , Dente Molar , Periodonto/citologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Erupção Dentária/fisiologiaRESUMO
Rats, with and without overnight fasting, were anaesthetised for 5, 15 and 30 min with diethyl ether, killed immediately and total glutathione (total GS), thiobarbituric acid-reacting substances (TBAR), radical-trapping activity (RTA), total cytochrome P450 (CYP), and 7-ethoxyresorufin O-deethylase (CYP1), 7-pentoxyresorufin O-dealkylase (CYP2B) and 4-nitrophenol hydroxylase (CYP2E1) activities of liver and kidney determined. Liver, after ether anaesthesia, but no fasting, showed 30-60% losses of total GS, RTA, and total CYP, after 5, 15 and 30 min of anaesthesia, while TBAR increased 10-, 20- and 35-fold for the same periods. Liver after ether anaesthesia and overnight fasting showed 50-85% losses of total GS, RTA and total CYP, for 0, 5, 15 and 30 min of anaesthesia, while TBAR increased 4-, 30-, 40- and 60-fold for the same periods of anaesthesia. Kidney changes were similar to those in liver. Liver CYP1 and CYP2B were decreased by 45% and 35%, respectively for 30 min of anaesthesia in fed rats, and by 80% and 30% respectively for 30 min of anaesthesia in fasted rats; in contrast, liver CYP2E1 was increased 30% by fasting alone and 70% by fasting plus 5 min of ether anaesthesia. Kidney CYP1 and CYP2B were similarly decreased by ether anaesthesia (70% and 50% respectively) in both fed and fasted rats, and CYP2E1 was similarly increased (by 40-90% in fed and 30-110% in fasted rats). The decrease in tissue total GS, RTA, total CYP, CYP1 and CYP2B, and the increase in lipid peroxidation products (TBAR), are all considered to be due to generation of reactive oxygen species and oxidative stress, associated with the increase in CYP2E1 activity that results from both fasting and exposure to diethyl ether.
Assuntos
Éter/farmacologia , Rim/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Anestesia por Inalação , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Jejum , Rim/metabolismo , Masculino , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Oxigênio/metabolismo , Ratos , Ratos WistarRESUMO
Anoestrous Suffolk-Cross ewes can be induced into early seasonal ovarian activity by administration of melatonin at the appropriate time of day or by melatonin implants. This treatment is successful if commenced in June, but not earlier in April or May and suggests that a critical period of long days may be necessary before artificial short-day melatonin profiles act as winter time-cues. We have investigated whether the lack of sensitivity to melatonin in April could be overcome in ewes in which breeding activity had been artificially moved forward the previous season. The results indicate that this was indeed the case and that the breeding season in untreated ewes which also previously experienced an early induced breeding season reverted to the normal timing for the Suffolk-Cross breed.
Assuntos
Estro/efeitos dos fármacos , Melatonina/farmacologia , Periodicidade , Animais , Implantes de Medicamento , Feminino , Ovário/efeitos dos fármacos , Ovário/fisiologia , Progesterona/sangue , Valores de Referência , Estações do Ano , OvinosRESUMO
BACKGROUND: A well-characterized cell culture model for cementoblasts is essential to understand the mechanisms of periodontal ligament (PDL) reattachment and regeneration. Whether cementoblasts express alkaline phosphatase (ALP) activity in vivo and in vitro remains to be determined. METHODS: Using a 2-step method of enzyme digestion/explant culture, osteoblasts, gingival/PDL fibroblasts, and cementoblasts were obtained from alveolar bone, gingiva, and the root surface of rat first molars and cultured. Initially, bone sialoprotein (BSP) was immunolocalized on tissue sections of periodontium and on cultured cells to distinguish mineral-forming cells from fibroblasts. Proteins were extracted from these cells to assess ALP activity by using an enzyme assay. RNA was extracted from the same cell source to detect ALP mRNA by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Cultured PDL/gingival fibroblasts were spindle shaped. Osteoblasts were irregularly shaped, and cell clusters/nodules were observed as they approached confluence. The cementoblasts manifested a polygonal shape and had two morphotypes: osteoblast-like and cuboidal or stratified. BSP was localized within the mineralized tissues and in osteoblasts and cementoblasts in culture and in tissue sections. The highest level of ALP activity was found in osteoblasts, a moderate level in PDL fibroblasts, and the lowest level in gingival fibroblasts. The cementoblasts lacked ALP activity, and this was reflected by a very weak signal (or no signal at all) for ALP mRNA in the cementoblasts. CONCLUSIONS: These studies indicate that cells consistent with a cementoblast-like phenotype may be successfully cultured, and that they lack ALP activity.
Assuntos
Fosfatase Alcalina/genética , Cemento Dentário/enzimologia , Fosfatase Alcalina/análise , Processo Alveolar/citologia , Processo Alveolar/enzimologia , Animais , Agregação Celular , Tamanho Celular , Células Cultivadas , Modelos Animais de Doenças , Fibroblastos/enzimologia , Regulação Enzimológica da Expressão Gênica , Gengiva/citologia , Gengiva/enzimologia , Sialoproteína de Ligação à Integrina , Osteoblastos/enzimologia , Ligamento Periodontal/citologia , Ligamento Periodontal/enzimologia , Ligamento Periodontal/fisiologia , Fenótipo , Reação em Cadeia da Polimerase , RNA/análise , RNA/genética , Ratos , Ratos Endogâmicos Lew , Regeneração/fisiologia , Sialoglicoproteínas/análise , Sialoglicoproteínas/genética , Raiz Dentária/citologia , Raiz Dentária/enzimologiaRESUMO
The effect of growth hormone (GH) on the dentition has been described in children with pituitary dwarfism where teeth fail to form; those that do form tend to be reduced in size and the eruption potential is diminished. The aim here was to examine the effect of GH on odontogenesis via molar development in Lewis (control), dwarf (Dw) and Dw GH-treated (Dw+GH) rats aged 3, 6, 9, 12 and 15 days. Dw+GH animals received a twice-daily dose (65 microg/kg) of GH which commenced at 2 days of age. Animals were killed, mandibles removed, processed to embedding in paraffin, sectioned and stained for histological examination of molar morphology during development. Variations in enamel mineralization and root development were observed. In 6-day-old animals, enamel mineralization was delayed in Dw and Dw+GH animals. Root initiation was evident at 6 days of age in controls but was not observed until 9 days of age in Dw and Dw+GH animals. At 12 days of age, maturation of enamel in Dw and Dw+GH animals remained delayed. By 15 days of age no variation in tooth development was evident. These data indicate that enamel mineralization is affected by the level of circulating GH in the rat. A specific deficiency of GH did not appear to delay bone resorption prior to tooth emergence.
Assuntos
Nanismo/fisiopatologia , Hormônio do Crescimento/uso terapêutico , Odontogênese/efeitos dos fármacos , Dente/efeitos dos fármacos , Animais , Reabsorção Óssea/fisiopatologia , Corantes , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/patologia , Modelos Animais de Doenças , Nanismo/tratamento farmacológico , Nanismo/patologia , Hormônio do Crescimento/administração & dosagem , Masculino , Dente Molar , Inclusão em Parafina , Ratos , Ratos Endogâmicos Lew , Dente/anatomia & histologia , Calcificação de Dente/efeitos dos fármacos , Coroa do Dente/efeitos dos fármacos , Coroa do Dente/patologia , Erupção Dentária/efeitos dos fármacos , Germe de Dente/efeitos dos fármacos , Germe de Dente/patologia , Raiz Dentária/efeitos dos fármacos , Raiz Dentária/patologiaRESUMO
Changes in the surrounding alveolar bone occur during tooth eruption. The microphthalmic (mi/mi) mouse suffers from osteopetrosis and lack of bone resorption; tooth form and eruption were examined in both affected mi/mi mice and unaffected litter-mates to determine the effect of osteopetrosis on tooth development and eruption. Paraffin sections of mandibles from 3, 7, 10, 13, 15 and 20-day-old mice were examined by light microscopy after staining with haematoxylin and eosin and for stable acid phosphatase activity. Mandibles from 15- and 20-day-old mice were examined by scanning electron microscopy. The ultrastructure of odontoblasts was observed in 15-day-old mice. Tooth eruption was significantly reduced in the mi/mi mice; the bone of affected mice increased in area with increasing age and marrow spaces narrowed. There was little bony remodeling in the mi/mi mouse, as indicated by layers of reversal lines. This lack of bone resorption affected tooth eruption and root formation. No abnormalities were detected in odontoblasts, suggesting functional normality, but the wide predentine layer in the mi/mi mouse may indicate an alteration in dentine mineralization.