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1.
Nature ; 452(7185): 332-5, 2008 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-18354478

RESUMO

Equal amounts of matter and antimatter are predicted to have been produced in the Big Bang, but our observable Universe is clearly matter-dominated. One of the prerequisites for understanding this elimination of antimatter is the nonconservation of charge-parity (CP) symmetry. So far, two types of CP violation have been observed in the neutral K meson (K(0)) and B meson (B(0)) systems: CP violation involving the mixing between K(0) and its antiparticle (and likewise for B(0) and ), and direct CP violation in the decay of each meson. The observed effects for both types of CP violation are substantially larger for the B(0) meson system. However, they are still consistent with the standard model of particle physics, which has a unique source of CP violation that is known to be too small to account for the matter-dominated Universe. Here we report that the direct CP violation in charged B(+/-)-->K(+/-)pi(0) decay is different from that in the neutral B(0) counterpart. The direct CP-violating decay rate asymmetry, (that is, the difference between the number of observed B(-)-->K(-)pi(0) event versus B(+)-->K(+) pi(0) events, normalized to the sum of these events) is measured to be about +7%, with an uncertainty that is reduced by a factor of 1.7 from a previous measurement. However, the asymmetry for versus B(0)-->K(+)pi(-) is at the -10% level. Although it is susceptible to strong interaction effects that need further clarification, this large deviation in direct CP violation between charged and neutral B meson decays could be an indication of new sources of CP violation-which would help to explain the dominance of matter in the Universe.

2.
Br J Anaesth ; 101(5): 666-72, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18791187

RESUMO

BACKGROUND: Hyperventilation, with the resulting hypocapnia, reduces cerebral blood flow and causes slowing of the EEG activity. However, neuronal oscillating properties including the thalamocortical network during hyperventilation have not been elucidated. To assess these features provoked by hyperventilation, the present study examined quadratic phase coupling features by means of bicoherence analysis. METHODS: Twenty-two patients were anaesthetized using sevoflurane 1.5% combined with remifentanil or epidural anaesthesia. After a stable normocapnic period, hypocapnia was induced by hyperventilation, and the raw EEG signals were collected. Bispectral analysis (bicoherence) and power spectrum analysis were performed before and after hypocapnia. RESULTS: Mean (sd) peak bicoherence in the delta- area increased from 35.6 (10.9)% during normocapnia to 43.8 (10.9)% during hypocapnia (P<0.05), whereas mean (sd) peak bicoherence in the alpha area decreased from 42.8 (14.4)% during normocapnia to 37.5 (12.3)% during hypocapnia (P<0.05). Normalized power in the delta- frequencies on the power spectrum increased from 60.2 (13.1)% to 72.5 (12.7)% (P<0.05). Bispectral index and spectral edge frequency changed from 45.9 (7.0) to 40.1 (5.6) (P<0.05) and from 15.0 (2.3) to 14.0 (2.5) Hz (P<0.05), respectively. No significant differences in these values were observed between the two types of anaesthesia. CONCLUSIONS: Hypocapnia enlarged bicoherence growth in the delta- frequency range, suggesting the contribution of subcortical oscillating mechanisms in regulating EEG during hyperventilation.


Assuntos
Anestésicos Inalatórios/farmacologia , Eletroencefalografia/efeitos dos fármacos , Hiperventilação/fisiopatologia , Hipocapnia/fisiopatologia , Éteres Metílicos/farmacologia , Adolescente , Adulto , Idoso , Dióxido de Carbono/sangue , Humanos , Hipocapnia/sangue , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Pressão Parcial , Sevoflurano , Processamento de Sinais Assistido por Computador
3.
Biochim Biophys Acta ; 1123(1): 18-26, 1992 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-1346092

RESUMO

The delta 6-desaturase reaction is regarded to be the rate-limiting step in the conversion of linoleic acid (18:2(n - 6)) to arachidonic acid (20:4(n - 6)). The same is probably also the case with the conversion of alpha-linolenic acid (18:3(n - 3)) to eicosapentaenoic acid (20:5(n - 3)). However, there are very few in vivo studies that directly compared the conversion rate between 18:3(n - 3) and stearidonic acid (18:4(n - 3)), which is the delta 6-desaturated product of 18:3(n - 3). We compared this rate by feeding rats on a lipid-free diet supplemented with lard (9%, w/w) and 18:3(n - 3) ethyl ester (1%) diet or on a diet containing lard (9%) and 18:4(n - 3) ethyl ester (1%). A lard (10%)-supplemented diet was used as the control diet. The fatty acid compositions of total phospholipids, triglycerides and free fatty acids of both liver and plasma were measured after 1 or 3 weeks on different diets. The molar ratio of 20:5(n - 3) of most lipid fractions was about 2-fold higher in rats fed the 18:4(n - 3)-supplemented diet than in rats fed the 18:3(n - 3)-supplemented diet. 18:4(n - 3) was found in the liver lipid fraction in only a very small amount, even in the 18:4(n - 3)-supplemented groups. Thus, desaturation at C-6 is suggested to be the rate-limiting step in the conversion of 18:3(n - 3) to 20:5(n - 3).


Assuntos
Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Linolênicos/metabolismo , Animais , Peso Corporal , Dieta , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos Insaturados/sangue , Cinética , Masculino , Fosfolipídeos/sangue , Ratos , Ratos Endogâmicos , Ácido alfa-Linolênico
4.
J Cereb Blood Flow Metab ; 17(6): 680-5, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9236724

RESUMO

This study was designed to determine age related changes in autoregulatory responses of the brain stem circulation in vivo. In anesthetized adult (4 to 6 months, n = 8) and aged (24 to 26 months, n = 7) Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. In aged rats, the lower limit of CBF autoregulation shifted upward to 60 to 75 mm Hg from 30 to 45 mm Hg in adult rats. Dilator responses of the basilar artery (baseline diameter: 254 +/- 15 microns), large branch (109 +/- 23 microns), and small branch (44 +/- 10 microns) to hypotension were much smaller in aged rats than in adult rats. The maximum change in diameter of the basilar artery during profound hypotension was significantly smaller in aged rats (11 +/- 8%) than that in adult ones (23 +/- 12%, P < 0.05); that of the large branch was 12 +/- 8% versus 33 +/- 17% (P < 0.005); and that of the small branch was 17 +/- 7% versus 40 +/- 13% (P < 0.0005), suggesting greater attenuation of the responses in the smaller vessels. Thus, this study provides direct evidence that aging diminishes the compensatory dilatation of brain stem arterioles and arteries during hypotension and modifies the autoregulatory plateau of CBF, which seems to increase the risk of the brain stem ischemia during hypotensive conditions.


Assuntos
Envelhecimento/fisiologia , Tronco Encefálico/irrigação sanguínea , Hipotensão/fisiopatologia , Acetilcolina/farmacologia , Análise de Variância , Animais , Artéria Basilar/efeitos dos fármacos , Artéria Basilar/fisiologia , Circulação Cerebrovascular/fisiologia , Fluxometria por Laser-Doppler , Masculino , Ratos , Ratos Sprague-Dawley , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
5.
Eur J Endocrinol ; 138(5): 557-61, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9625369

RESUMO

We describe three siblings with hyperparathyroidism due to multiple parathyroid adenomas without evidence of other endocrinological abnormalities. A 22-year-old woman had two parathyroid adenomas complicated by multiple ossifying jaw fibromas. Her sister, aged 29, also suffered from primary hyperparathyroidism associated with two parathyroid adenomas one of which was also suspected to be a carcinoma. These two female patients had unusual multiple small uterine polyps, which were diagnosed as adenomyomatous polyps. Their brother, aged 17, had two parathyroid adenomas complicated by urolithiasis. These three patients are characterized by young adult-onset familial isolated hyperparathyroidism due to multiple adenomas with various complications including ossifying jaw fibroma and uterine adenomyomatous polyps. These clinical features are different from those of familial hyperparathyroidism associated with multiple endocrine neoplasia.


Assuntos
Pólipos Adenomatosos/genética , Fibroma Ossificante/genética , Hiperparatireoidismo/genética , Neoplasias Maxilomandibulares/genética , Neoplasia Endócrina Múltipla/genética , Neoplasias Uterinas/genética , Adenoma/genética , Adulto , Feminino , Humanos , Neoplasias das Paratireoides/genética , Linhagem , Tomografia Computadorizada por Raios X
6.
Phys Rev Lett ; 84(6): 1078-81, 2000 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-11017448

RESUMO

The energy spectrum of cosmic-ray antiprotons ( &pmacr;'s) has been measured in the range 0.18-3.56 GeV, based on 458 &pmacr;'s collected by BESS in a recent solar-minimum period. We have detected for the first time a characteristic peak at 2 GeV of &pmacr;'s originating from cosmic-ray interactions with the interstellar gas. The peak spectrum is reproduced by theoretical calculations, implying that the propagation models are basically correct and that different cosmic-ray species undergo a universal propagation. Future BESS data with still higher statistics will allow us to study the solar modulation and the propagation in detail and to search for primary &pmacr; components.

7.
J Control Release ; 62(1-2): 161-70, 1999 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-10518647

RESUMO

The promoting effect of O-ethylmenthol (MET) on the percutaneous absorption of ketoprofen from alcoholic hydrogels was evaluated in rats in vitro and in vivo. Furthermore, a novel simultaneous optimization technique incorporating an artificial neural network (ANN) was applied to a design of a ketoprofen hydrogel containing MET. When a small quantity of MET (0.25-0.5%) was added to the hydrogels, the permeation of ketoprofen increased remarkably, compared with the control. On the other hand, little change in permeation was observed when small amounts of menthol were used (<1%), and at least 2% menthol was required to obtain a promoting efficiency comparable with 0.25% MET. The partitioning of ketoprofen from the hydrogel to the skin was improved by the addition of a small amount of MET, whereas the diffusivity of the drug was enhanced at higher concentration of MET (0.5-1%). For the optimization study, the amount of ethanol and MET were selected as causal factors. A rate of penetration (R(p)) and lag time (t(L)) and total irritation score (TIS) were selected as response variables. A set of causal factors and response variables was used as tutorial data for ANN and fed into a computer. Nonlinear relationships between the causal factors and the response variables were represented well with the response surface predicted by ANN. The optimization of the ketoprofen hydrogel was performed according to the generalized distance function method. The observed results of R(p) and TIS, which had a lot of influence on the effectiveness and safety, coincided well the predictions.


Assuntos
Sistemas de Liberação de Medicamentos , Cetoprofeno/farmacocinética , Mentol/análogos & derivados , Redes Neurais de Computação , Absorção Cutânea , Animais , Química Farmacêutica , Sinergismo Farmacológico , Hidrogéis , Masculino , Mentol/farmacologia , Ratos , Ratos Wistar , Software
8.
J Control Release ; 68(2): 175-86, 2000 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-10925126

RESUMO

Formulation of the controlled-release tablet containing theophylline was optimized based on the simultaneous optimization technique in which an artificial neural network (ANN) was incorporated. As model formulations, 16 kinds of theophylline tablets were prepared. The amounts of Controse, the mixture of hydroxypropylmethyl cellulose with lactose, cornstarch and compression pressure were selected as causal factors. The release profiles of theophylline were characterized as the sum of the fast and slow release fractions. The initial weight, the rate constant in the fast release fraction and the rate constant in the slow release fraction were estimated as release parameters. A set of release parameters and causal factors were used as tutorial data for ANN and analyzed using a computer. Based on the plasma concentration profiles of theophylline predicted by the pharmacokinetic analysis in humans, a desirable set of release parameters was provided. The simultaneous optimization was performed by minimizing the generalized distance between the predicted values of each response and the desirable one that was optimized individually. The optimization technique incorporating ANN showed a fairly good agreement between the observed values of release parameters and the predicted results.


Assuntos
Redes Neurais de Computação , Teofilina/administração & dosagem , Química Farmacêutica , Comprimidos , Teofilina/química
9.
Clin Chim Acta ; 185(3): 265-70, 1989 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-2620458

RESUMO

The mechanisms of leakage of intracellular enzymes, and especially the cytosolic and mitochondrial isozymes of aspartate aminotransferase (AST), in ischemic rat liver were studied. On recirculation of ischemic liver, cytosolic AST (cAST) promptly appeared in the blood. Release of cytosolic enzymes, including cAST and lactic dehydrogenase, resulted from disruption of blebs that protruded from parenchymal cells into the sinusoidal space. When these blebs were formed in ischemic liver, mitochondria still remained in core regions of the injured cells and were not found in the blebs. Consistent with this fact, mitochondrial AST (mAST) did not leak into the circulation from ischemic liver until most of the cAST had leaked out. This delayed leakage of mitochondrial enzymes was also consistent with the fact that the mitochondrial membranes maintained a diffusion barrier against matrix enzymes even after anoxia for 2 h, when their oxidative phosphorylation capacity had been lost. These results indicate that mitochondrial enzymes are liberated into the blood only after appreciable disintegration of the cells, probably necrosis, and that the cumulative activity of mAST in the blood should reflect the extent of necrosis in ischemic organs better than that of cAST.


Assuntos
Aspartato Aminotransferases/sangue , Citosol/enzimologia , Isquemia/enzimologia , Isoenzimas/sangue , Fígado/patologia , Mitocôndrias Hepáticas/enzimologia , Animais , Membrana Celular/patologia , Feminino , Membranas Intracelulares/patologia , Fígado/irrigação sanguínea , Fígado/enzimologia , Masculino , Mitocôndrias Hepáticas/ultraestrutura , Necrose , Ratos , Ratos Endogâmicos
10.
Thyroid ; 6(6): 619-25, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9001198

RESUMO

A 33-year-old woman with inappropriate secretion of TSH and a 2-mm pituitary microadenoma is described. She had a high serum free T4 concentration (31 pmol/L) with an inappropriately nonsuppressible serum TSH concentration (0.93 mU/L). The alpha/TSH molar ratio was 2.3 and magnetic resonance imaging with gadolinium enhancement identified an area of low signal intensity in the left lateral pituitary gland. However, TSH secretion was not completely autonomous. There was a significant response to exogenous TRH stimulation and suppression by T3 administration. Therefore, it was difficult to rule out a nonfunctioning pituitary adenoma with concomitant pituitary selective thyroid hormone resistance syndrome. A 2-mm microadenoma was excised via transsphenoidal surgery. The tumor cells were immunoreactive to antisera to alpha-subunit and minimally immunoreactive to antisera to TSHbeta. The patient's thyroid function normalized after surgery without medication. Because the adenoma could become large and intractable if the patient was treated inadequately, early diagnosis and treatment are important in patients with TSH secreting adenomas.


Assuntos
Adenoma/metabolismo , Neoplasias Hipofisárias/metabolismo , Síndrome da Resistência aos Hormônios Tireóideos/diagnóstico , Tireotropina/metabolismo , Adenoma/complicações , Adenoma/diagnóstico , Adulto , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Síndrome da Resistência aos Hormônios Tireóideos/complicações , Tireotropina/sangue , Hormônio Liberador de Tireotropina , Tiroxina/sangue , Tri-Iodotironina
11.
Thyroid ; 8(1): 53-8, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9492154

RESUMO

We describe a 75-year-old man who had had a lump in his neck for about 15 years. At his first visit to our hospital, poorly differentiated papillary carcinoma of the thyroid was diagnosed by means of aspiration cytology; x-rays revealed the presence of lung metastases. He was thyrotoxic with positive thyroid stimulating antibody (TSAb). He was reluctant to undergo surgery. In an early stage of the treatment for Graves' disease, he became hypothyroid with decreased TSAb activity and strongly positive thyroid stimulation blocking antibody (TSBAb), and rapid growth of the thyroid carcinoma with anaplastic transformation was observed. The increase in the size of the transformed thyroid carcinoma was shown to be exponential by ultrasonography. This is a rare case in which anaplastic transformation of the thyroid papillary carcinoma became apparent during treatment of Graves' disease with varied activity of thyrotropin receptor antibodies.


Assuntos
Anticorpos/imunologia , Carcinoma Papilar/patologia , Carcinoma/patologia , Doença de Graves/complicações , Doença de Graves/imunologia , Receptores da Tireotropina/imunologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Carcinoma/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Doença de Graves/tratamento farmacológico , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/imunologia , Imunoglobulinas Estimuladoras da Glândula Tireoide/análise , Masculino , Metimazol/efeitos adversos , Metimazol/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
12.
J Pharm Sci ; 90(8): 1004-14, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11536204

RESUMO

The influence of the amounts of additives including 1-O-ethyl-3-n-butylcyclohexanol (OEBC), diisopropyl adipate (DIA), and isopropanol (IPA) on the penetration rate (R(p)) of ketoprofen from hydrogels through rat skin in vivo was investigated. Skin irritation evoked by the application of hydrogels was evaluated based on a microscopic observation of skin cross-sections. Both optimization techniques incorporating an artificial neural network (ANN) and a second-order polynomial regression analysis were applied to the optimization of ketoprofen hydrogel formulations. Findings indicated that the R(p) and total irritation score (TIS) of the skin were predicted quantitatively as a function of quantities of OEBC, DIA, and IPA, employing ANN. In contrast, the prediction ability of the polynomial regression equation was somewhat poorer compared with that of ANN. The observed results of R(p) and TIS in the optimal formulation coincided well with the predictions in the simultaneous optimization technique incorporating ANN.


Assuntos
Anti-Inflamatórios não Esteroides/química , Cicloexanóis/farmacologia , Cetoprofeno/química , Redes Neurais de Computação , Absorção Cutânea/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Hidrogéis , Cetoprofeno/farmacocinética , Masculino , Ratos , Ratos Wistar
13.
Pharmacol Biochem Behav ; 50(3): 339-43, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7617671

RESUMO

The present study was undertaken to investigate whether beta-adrenoceptors are involved in regulation of yawning responses to oxytocin and alpha-melanocyte-stimulating hormone (alpha-MSH) in rats. Oxytocin administered intracerebroventricularly (ICV) at doses of 50 and 100 ng/rat elicited yawning. alpha-MSH (20 micrograms/rat, ICV) elicited not only yawning but also stretching and body shaking. RS-86 (2-ethyl-8-methyl-2,8-diazaspiro-(4,5)-decan-1,3-dion hydrobromide), a putative muscarinic M1 receptor agonist, administered ICV at a lower dose of 100 micrograms/rat and subcutaneously (SC) at doses of 0.25-2.5 mg/kg also elicited yawning. The yawning responses produced by these agents were markedly increased by intraperitoneal (IP) pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg), which per se did not elicit yawning. The yawning induced by oxytocin (50 ng/rat, ICV) plus pindolol, but not that by alpha-MSH (20 micrograms/rat, ICV) or RS-86 (0.5 mg/kg, SC) plus pindolol, was inhibited by [d(CH2)5,Tyr(Me)2,Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. The yawning induced by oxytocin, alpha-MSH, or RS-86 administered in combination with pindolol was inhibited by scopolamine (0.5 mg/kg, SC), a mucarinic receptor antagonist, without being affected by spiperone (0.5 mg/kg, SC), a dopamine D2 receptor antagonist. The results suggest that the yawning produced by the neuropeptides oxytocin and alpha-MSH is modulated by beta-adrenoceptor activity in an inhibitory manner as that produced by muscarinic M1 receptor agonists, and that it involves cholinergic, but not dopaminergic, activation.


Assuntos
Ocitocina/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacos , Bocejo/efeitos dos fármacos , alfa-MSH/farmacologia , Animais , Injeções Intraventriculares , Masculino , Agonistas Muscarínicos , Ocitocina/antagonistas & inibidores , Pindolol/farmacologia , Ratos , Ratos Wistar , Succinimidas/antagonistas & inibidores , Succinimidas/farmacologia , alfa-MSH/antagonistas & inibidores
14.
Pharmacol Biochem Behav ; 55(1): 55-60, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8870038

RESUMO

The present experiments were performed to examine the effects of a new muscarinic M1-receptor agonist, (-)-YM796 ((-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane L-tartrate monohydrate), on yawning and oxytocin secretion from the posterior pituitary gland in rats YM796, at doses of 2.5-50 mg/kg (SC), elicited yawning. The yawning response was markedly increased by pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg, IP), which per se did not elicit yawning. The yawning induced by YM796 (10 mg/kg, SC) in combination with pindolol (20 mg/kg, IP) was inhibited by scopolamine (0.5 mg/kg, SC), a muscarinic receptor antagonist, and pirenzcpine (300 micrograms/ rat, ICV) and EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) (5 mg/kg, IP), muscarinic M1-receptor antagonists, but not by spiperone (0.5 mg/kg, SC), a dopamine D2-receptor antagonist, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) (100 micrograms/rat, ICV), a muscarinic M3-receptor antagonist, and [d(CH2)5, Tyr(Mc)2, Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. YM796 at 2.5-50 mg/kg (SC) did not exert an action on prolactin levels but increased oxytocin secretion from the posterior pituitary gland in rats. This augmentation of oxytocin secretion by YM796 was inhibited by scopolamine (0.5 mg/kg, SC) and pirenzepine (3 mg/kg, SC), but not by mecamylamine (1 mg/kg, IP), a nicotinic receptor antagonist. The present findings obtained with YM796 suggest that the muscarinic M2-receptor stimulation participates in causing yawning behavior and oxytocin secretion in rats.


Assuntos
Ocitocina/metabolismo , Parassimpatomiméticos/farmacologia , Neuro-Hipófise/metabolismo , Compostos de Espiro/farmacologia , Bocejo/efeitos dos fármacos , Antagonistas Adrenérgicos beta/farmacologia , Animais , Antagonistas de Dopamina/farmacologia , Técnicas In Vitro , Injeções Intraventriculares , Masculino , Antagonistas Muscarínicos/farmacologia , Parassimpatomiméticos/administração & dosagem , Pindolol/farmacologia , Neuro-Hipófise/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de Ocitocina/antagonistas & inibidores , Compostos de Espiro/administração & dosagem , Compostos de Espiro/antagonistas & inibidores
15.
Pharmacol Biochem Behav ; 53(4): 903-9, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8801596

RESUMO

The present experiments were performed to examine the behavioral effects of OPC-14597, which acts on dopamine receptors in rats. OPC-14597 administered subcutaneously (SC) at doses of 0.1-5 mg/kg elicited yawning, as did OPC-4392 (0.5-2 mg/kg, SC) and (-)-3-PPP (2.5-10 mg/kg, SC). These yawning responses were blocked by intraperitoneal (IP) pretreatment with haloperidol (0.5 mg/kg) but were increased by pindolol (20 mg/kg, IP) or reserpine (5 mg/kg, IP), which per se did not elicit yawning. The yawning induced by talipexole, a selective dopamine D2 receptor agonist, was inhibited by OPC-14597 (0.5-5 mg/kg, SC) and (-)-3-PPP (10 mg/kg, SC). Apomorphine (0.5 mg/kg, SC), a dopamine D1/D2 receptor agonist, elicited stereotypy such as sniffing and licking but OPC-14597 (5-20 mg/kg, SC) did not induce this behavior. The stereotypy induced by apomorphine was inhibited not only by haloperidol (0.5 mg/kg, IP) and (-)-3-PPP (10 mg/kg, SC) but also by OPC-14597 (5-20 mg/kg, SC), without being affected by OPC-4392 (2 mg/kg, SC). In 6-hydroxydopamine (6-OHDA)-treated rats, apomorphine (0.5 mg/kg, SC) elicited rotation behavior whereas OPC-14597, OPC-4392 and (-)-3-PPP did not produce this behavior. These findings suggest that OPC-14597 provokes yawning without causing stereotypy and rotation but markedly antagonizes the talipexole-induced yawning and apomorphine-induced stereotypy, and that OPC-14597 thus exerts partial agonistic effects on yawning behavior but antagonistic effects on stereotypy in rats.


Assuntos
Antipsicóticos/farmacologia , Piperazinas/farmacologia , Quinolonas/farmacologia , Bocejo/efeitos dos fármacos , Animais , Antipsicóticos/antagonistas & inibidores , Aripiprazol , Azepinas/antagonistas & inibidores , Azepinas/farmacologia , Agonistas de Dopamina/farmacologia , Sinergismo Farmacológico , Masculino , Oxidopamina , Piperazinas/antagonistas & inibidores , Piperidinas/antagonistas & inibidores , Piperidinas/farmacologia , Quinolonas/antagonistas & inibidores , Ratos , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Comportamento Estereotipado/efeitos dos fármacos , Simpatectomia Química
16.
Brain Dev ; 21(7): 474-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10522525

RESUMO

The present study was performed to examine the effects of regular (1 Hz) and modified rapid random stimulation (RRS) (6 and 12 Hz) on visual evoked potentials (VEPs), by simultaneously recording negative waves around 100 ms, wave IV-latency, positive waves around 60 ms, wave III-latency, and amplitudes calculated from peak to peak, without causing impairment of visual acuity, in 44 patients aged 5-17 years. The wave IV-latencies of VEPs obtained by 6 and 12 Hz RRS were easily determined, and the latencies were not significantly changed compared to those obtained by previous 1 Hz regular stimulation. On the other hand, the amplitudes decreased in a frequency-dependent manner (1 < 6 < 12 Hz). These results were found to be similar in both preschool and school children. The examination time of VEPs determined by RRS is one-tenth shorter than that of 1 Hz regular stimulation. Thus, this method has the benefit of shortening the examination time, which decreases fatigue and inattention of the subjects, suggesting that modified RRS is a practically useful method for children.


Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Potenciais Evocados Visuais/fisiologia , Córtex Visual/fisiologia , Adolescente , Análise de Variância , Criança , Pré-Escolar , Eletroencefalografia , Humanos , Estimulação Luminosa , Tempo de Reação/fisiologia , Córtex Visual/fisiopatologia , Vias Visuais/fisiologia , Vias Visuais/fisiopatologia
17.
Int J Pharm ; 212(2): 223-31, 2001 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-11165080

RESUMO

The effect of 35 newly synthesized O-ethylmenthol (MET) derivatives on percutaneous absorption of ketoprofen was investigated in rats. In order to understand the relationship between the structure of compounds and promoting activity (structure-activity relationship), an artificial neural network (ANN) was employed. In the in vivo percutaneous absorption study, male Wistar rats, weighing 160-180 g, were used. The apparent penetration rate (Rp) was estimated based on a pharmacokinetic model with a constant rate of penetration through the skin after a lag time. As an index of the promoting activity of each compound, an enhancement factor (Ef), defined as follows, was used: Ef=Rp(with enhancer)/Rp(without enhancer). An irritation evoked on rat skin was microscopically judged at the end of the in vivo percutaneous absorption experiment and evaluated as a total irritation score (TIS). Ef and TIS were selected as output variables to determine the ANN structure. Calculated logP, molecular weight, steric energy (SE), van der Waals area, van der Waals volume, dipole moment, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were used as factors to determine the structural nature of cyclohexanol derivatives. Among these parameters, logP, SE and LUMO significantly affected the prediction of Ef and TIS. The predicted values of Ef and TIS coincided well with in vivo percutaneous absorption experimental values. However, results observed with a linear regression method were poor compared with the ANN approach. The contribution index of logP was approximately 50% in the prediction of Ef, suggesting that lipophilicity among physicochemical properties contributes most of the promoting activity of these compounds.


Assuntos
Cetoprofeno/farmacocinética , Mentol/farmacologia , Redes Neurais de Computação , Absorção Cutânea/efeitos dos fármacos , Animais , Masculino , Mentol/análogos & derivados , Ratos , Ratos Wistar , Análise de Regressão , Relação Estrutura-Atividade
18.
Lipids ; 24(9): 765-8, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2555648

RESUMO

Streptozotocin (45 mg/kg) was intravenously administered to 7-week-old Wistar rats through their tail veins. After 11 days, the rats were divided into two groups. One group was fed a lipid-free diet (90%, w/w) plus lard (8%) and safflower oil (2%) for four weeks (Diet 1 group, n = 12). The other group was fed in the same way, except that safflower oil was replaced by 90% pure eicosapentaenoic acid (EPA) ethyl ester (Diet 2 group, n = 13). Twenty-four-hour urine was collected just before the diets started and during the experiment at 7-day intervals. In the second and third week, the levels of proteinuria were significantly lower in the Diet 2 group than they were in the Diet 1 group. There was no significant difference in the levels of creatinine, urea nitrogen, or lipids in plasma or in body weights between the two groups after four weeks on the diets. Because Diet 2 reduced proteinuria of diabetic rats compared to Diet 1, an EPA-rich diet may retard the development of diabetic nephropathy.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Proteinúria/metabolismo , Animais , Glicemia , Peso Corporal , Gorduras na Dieta/análise , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/análise , Glicosúria , Rim/metabolismo , Lipídeos/sangue , Masculino , Ratos , Ratos Endogâmicos , Estreptozocina
19.
Clin Plast Surg ; 17(2): 273-85, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2189643

RESUMO

Two features of greatest importance in achieving a normal appearance in the reconstruction of an ear with microtia are that a conchal component with sufficient size, shape, and depth is present; and that auricular projection, sufficient in degree to show contours that appear normal from a posterior view, is present. The authors describe the construction of a staged, laminated framework that helps achieve these goals.


Assuntos
Cartilagem da Orelha/cirurgia , Orelha Externa/cirurgia , Cirurgia Plástica/métodos , Orelha Externa/anormalidades , Humanos , Costelas , Transplante de Pele/métodos , Retalhos Cirúrgicos
20.
Artigo em Inglês | MEDLINE | ID: mdl-10225626

RESUMO

OBJECTIVE: The prevalence of hepatitis G virus infection was evaluated in dental patients whose clinical laboratory test results were positive for hepatitis C virus antibody, hepatitis B virus surface antigen, or elevated serum alanine transaminase concentrations. STUDY DESIGN: Frozen serum samples from patients with hepatitis C virus antibody (n = 63), hepatitis B virus surface antigen (n = 20), or alanine transaminase concentrations greater than 100 IU (n = 14) were assessed for GB virus C (GBV-C)/hepatitis G virus RNA by a reverse transcriptase-polymerase chain reaction. RESULTS: Six of 63 patients with hepatitis C virus antibodies had serum hepatitis G virus RNA (9.5%), and 2 of 20 subjects with hepatitis B virus surface antigen had hepatitis G virus RNA (10.0%). None of 14 patients whose alanine transaminase concentration was greater than 100 IU/L had hepatitis G virus RNA. Of 4 subjects with both hepatitis C virus antibody and hepatitis B virus surface antigen, 2 had hepatitis G virus RNA (50%). In the total study population (N = 92), 6 subjects (6.5%) had hepatitis G virus RNA. All hepatitis G virus-infected patients also had hepatitis C virus antibody. Neither serum alanine transaminase nor aspartate transaminase concentrations were different between subjects with and subjects without hepatitis G virus RNA. The lack of a relationship between hepatitis G virus infection and elevation of alanine transaminase and aspartate transaminase might suggest that this virus is not truly a hepatitis virus. CONCLUSIONS: Hospitalized dental patients are infected with hepatitis G virus at a prevalence similar to or slightly higher than that seen in the general population. Dentists should pay close attention to infection control with respect to the potential new hepatitis virus known as hepatitis G virus.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Assistência Odontológica para Doentes Crônicos , Flaviviridae , Hepatite Viral Humana/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Feminino , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Hepatite Viral Humana/enzimologia , Hepatite Viral Humana/virologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Probabilidade , RNA Viral/sangue , Fatores de Risco
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