RESUMO
In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}Nâ_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.
RESUMO
We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}â1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}â1/2^{+}), E1(1/2^{-}â1/2^{+}), and E1(1/2^{-}â3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.
RESUMO
The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}â0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.
RESUMO
We investigated the therapeutic effect of tauroursodeoxycholate on phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration of phalloidin (500 microg/kg, i.p.) for 7 days. From the day of the last phalloidin injection, tauroursodeoxycholate (60-360 micromol/kg) was given intravenously twice a day for 4 days. On the next day after the last tauroursodeoxycholate administration, bile flow, serum biochemical parameters and biliary lipid excretion rates were determined. Tauroursodeoxycholate significantly suppressed the decrease in bile flow and increases in serum alkaline phosphatase, leucine aminopeptidase and glutamic pyruvic transaminase activities, cholesterol, phospholipid and bile acid concentrations observed in phalloidin-induced cholestasis in rats. Furthermore, tauroursodeoxycholate significantly improved the biliary cholesterol and phospholipid excretion rates in phalloidin-induced cholestasis in rats. These results demonstrate the usefulness of tauroursodeoxycholate as a therapeutic agent in intrahepatic cholestasis.
Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Faloidina/farmacologia , Ácido Tauroquenodesoxicólico/farmacologia , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Fosfatase Alcalina/sangue , Fosfatase Alcalina/efeitos dos fármacos , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/efeitos dos fármacos , Bile/efeitos dos fármacos , Bile/metabolismo , Ácidos e Sais Biliares/sangue , Sistema Biliar/efeitos dos fármacos , Sistema Biliar/metabolismo , Bilirrubina/sangue , Colestase Intra-Hepática/induzido quimicamente , Colesterol/sangue , Relação Dose-Resposta a Droga , Leucil Aminopeptidase/sangue , Leucil Aminopeptidase/efeitos dos fármacos , Masculino , Fosfolipídeos/sangue , Ratos , Ratos WistarRESUMO
BACKGROUND: Estradiol-17 beta-D-glucuronide (E-17G), a metabolite of natural estrogen, is well known to cause intrahepatic cholestasis in humans. We therefore investigated the effect of sodium tauroursodeoxycholate (T-UDCA), on E-17G-induced cholestasis in female rats. METHODS: For the evaluation of the drug, animals given E-17G (10 mumol/kg) were divided into three groups, and T-UDCA was administered intravenously at various doses after E-17G treatment. RESULTS: T-UDCA significantly prevented a marked reduction of bile flow in E-17G-treated rats in all experimental schedules. Furthermore, T-UDCA significantly increased in the biliary E-17G excretion rate at an early stage after E-17G treatment in rats. However, this drug caused no significant change in the biliary excretion rate of estradiol-3-sulfate-17 beta-D-glucuronide (E-3S-17G), which is identified as the major biliary metabolite with E-17G throughout the recovery periods. CONCLUSION: These results suggest that T-UDCA can improve E-17G induced acute cholestasis by rapidly increasing the biliary E-17G excretion rate. Thus our finding may provide a useful approach for attempts to prevent drug-induced acute cholestasis in humans.
Assuntos
Colestase/tratamento farmacológico , Ácido Tauroquenodesoxicólico/uso terapêutico , Animais , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Colestase/induzido quimicamente , Estradiol/análogos & derivados , Estradiol/metabolismo , Feminino , Ratos , Ratos Sprague-Dawley , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the effect of dehydrocholic acid. UR-906 (30-180 mumol/kg) and dehydrocholic acid (180 mumol/kg) were intravenously given once daily for consecutive 20 days in rats and the common bile duct was ligated for the last 10 days. On the next day after the last test drug administration, serum biochemical and plasma hemostatic variables were determined. UR-906 significantly ameliorated the elevation of serum cholesterol, phospholipid, bilirubin and bile acid concentrations in bile duct-ligated rats. UR-906 significantly suppressed the prolongation of plasma prothrombin time and activated partial thromboplastin time. Furthermore, UR-906 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause significant changes in any of the variables examined in this model. These results suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders.
Assuntos
Colagogos e Coleréticos/farmacologia , Colestase/tratamento farmacológico , Ácido Desidrocólico/farmacologia , Ácido Tauroquenodesoxicólico/farmacologia , Animais , Ácidos e Sais Biliares/sangue , Ductos Biliares/fisiopatologia , Ductos Biliares/cirurgia , Bilirrubina/sangue , Colestase/fisiopatologia , Colesterol/sangue , Modelos Animais de Doenças , Fator X/análise , Hemostasia/efeitos dos fármacos , Ligadura , Masculino , Tempo de Tromboplastina Parcial , Fosfolipídeos/sangue , Protrombina/análise , Tempo de Protrombina , Ratos , Ratos WistarRESUMO
We investigated sequential changes in bile flow, serum and biliary biochemical parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration with phalloidin (500 microg/kg) for 7 days, and then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the last treatment. In phalloidin-treated rats, bile flow significantly decreased up to 4 days of recovery, compared with the control animals. In contrast, serum ALP activity, LAP activity, cholesterol concentration and phospholipid concentration exhibited a marked elevation throughout the recovery periods. For biliary parameters, bilirubin excretion rate was unchanged but, cholesterol excretion rate showed a marked decrease throughout the recovery periods. These results demonstrate that some parameters, particularly important indexes of cholestasis (serum ALP, cholesterol, bile flow and so on), continued significant changes at least 4 days after the last administration of phalloidin. These results demonstrate that successive treatment with phalloidin can cause damage in most of serum and biliary parameters at a chronic stage of cholestasis. Thus, our findings may provide useful information for diagnosis of drug-induced cholestasis and help to further elucidate the biochemical mechanisms of drug-induced cholestasis in humans.
Assuntos
Colestase/induzido quimicamente , Colestase/fisiopatologia , Faloidina/toxicidade , Animais , Bile/química , Bile/metabolismo , Biomarcadores , Análise Química do Sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Ratos , Ratos WistarRESUMO
We investigated the effects of tauroursodeoxycholate (UR-906) and ursodeoxycholic acid (UDCA) on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis in mice. UR-906 and UDCA were given intravenously 2 hr prior to and 2 hr after ANIT (80 mg/kg, p.o.) treatment. The animals were sacrificed 48 hr after ANIT administration, and serum markers of liver injury were examined. UR-906 prevented significant elevations in total bilirubin, bile acids and LDH. Furthermore, this drug reduced significant elevations in ALP and LAP. UDCA also prevented significant elevations in total bilirubin and LAP. These results indicate that UR-906 as well as UDCA has a beneficial effect against ANIT-induced cholestasis in mice.