Cardioprotective effect of edaravone against ischaemia-reperfusion injury in the rabbit heart before, during and after reperfusion treatment.

The free radical scavenger edaravone is able to stimulate prostacyclin release and inhibit the lipoxygenase pathway in the arachidonic acid cascade. The effect of edaravone administration on myocardial damage in rabbit hearts subjected to ischaemia-reperfusion was examined at different times relative to reperfusion. All rabbits underwent sustained coronary artery occlusion for 30 min followed by 3 h of reperfusion. Rabbits were divided into the following groups: control; early (3 mg/kg edaravone IV 10 min before reperfusion); immediate (3 mg/kg edaravone IV immediately after the start of reperfusion); and late (3, 6 or 10 mg/kg edaravone IV 5 min after the start of reperfusion). Single bolus administration of edaravone 10 min before reperfusion or immediately upon initiation of reperfusion appears to be associated with reductions in infarction size and the percentage of apoptotic cells, but treatment with edaravone 5 min after initiation of reperfusion does not appear to have this protective effect.

An inhibitor of aldose reductase and sorbitol accumulation from Anthocepharus chinensis.

A flavonoid glycoside was isolated from Anthocepharus chinensis. Its structure was elucidated by spectral data and determined to be myricetin 3-O-(4"-acetyl)-alpha-fucoside. This flavonoid glycoside and its aglycone showed potent inhibition against rat and porcine lens aldose reductase. The flavonoid aglycone also inhibited sorbitol accumulation in human red blood cells.

Antiperoxidative activity of neolignans from Magnolia obovata.

Honokiol and magnolol, neolignans in Magnolia obovata, have been evaluated as antioxidants. Microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH and mitochondrial lipid peroxidation induced by Fe(III)-ADP/NADH were inhibited by these compounds. These neolignans protected mitochondrial respiratory chain enzyme activity against NADPH-induced peroxidative stress and protected red cells against oxidative haemolysis. The anti-oxidative activity of honokiol was more potent than that of magnolol. Neolignans in M. obovata were shown to be effective in protecting biological systems and functions against oxidative stress.

Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes.

The sulfated flavonoids in Polygonum hydropiper showed potent inhibiton against lens aldose reductase. Among these flavonoids isorhamnetin 3,7-disulfate (5) was most potent. Kinetic analysis showed that 5 exhibited noncompetitive inhibition against both dl-glyceraldehyde and NADPH.

Ceruloplasmin concentration in human colostrum and mature milk.

The concentration of ceruloplasmin (CP) in human milk was obtained by measuring the increased absorbance of a solution containing apotransferrin and Fe2+ at 460 nm after adding the milk. The CP concentrations in colostrum and mature milk at less than 1 month after parturition were 4.45 +/- 1.23 mg and 4.09 mg +/- 1.47 mg/100 ml, respectively. In mature milk after more than one month, the CP concentration had decreased to 1.72 +/- 0.91 mg/100 ml.

Hypothalamic neurons are resistant to the intoxication with 3-nitropropionic acid that induces lesions in the striatum and hippocampus via the damage in the blood-brain barrier.

Modulation of the function of the blood-brain barrier (BBB) in the hypothalamus was investigated after the intoxication with 3-nitropropionic acid (3-NPA) that inhibits the succinate dehydrogenase. 3-NPA was administered to rats for three days. Following transcardial perfusion, brain sections were studied by immunohistochemistry. On the 2nd or 3rd day after 3-NPA, strong immunoreactions for blood-borne macromolecules, IgG, appeared in the striatum and hippocampus. Glial fibrillary acidic protein (GFAP) positive astroglias distributed heterogeneously, and induced nitric oxide synthase (iNOS) positive cells appeared around the vessels. A week later, bilateral lesions were detected in these areas. In the hypothalamus, there appeared a moderate immunoreaction for IgG, but no expression of iNOS. GFAP positive astroglias were rich especially around the vessels, and no loss in microtubule-associated protein 2 (MAP2) immunoreaction was detected, suggesting an intact BBB structure and no neuronal loss following 3-NPA intoxication. Data indicate that hypothalamic neurons are resistant to 3-NPA that induces specific lesions in the striatum and hippocampus via the damage in the BBB.

Reactivation of phototoxicity test for psoralens plus ultraviolet A by low-dose methotrexate.

Reactivation of a solar burn has been reported after administration of methotrexate for cancer and psoriasis patients. We report a case of psoriasis with a similar but delayed elicitation of phototoxic reaction by administration of low-dose methotrexate one month after psoralen and long-wave ultraviolet light (PUVA) treatment. The reactivation was seen in an already receding phototoxicity test area but not in a less phototoxic, noninterval PUVA treated area, suggesting that the reactivation by methotrexate is related with the severity of light-induced skin inflammation.

17 beta-estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP.

The process by which 17 beta-estradiol rapidly modulates the excitability of neurons in the ventromedial hypothalamus, a facilitation center of female sexual behavior and satiety center of feeding behavior, through mediation by cyclic nucleotides, was investigated by intracellular recording from the guinea pig brain slice preparations. Two types of short-term responses were produced by depolarization with decreased K+ conductance and hyperpolarization with increased K+ conductance. These two responses were enhanced by the phosphodiesterase inhibitor, isobutylmethylxanthine. However, the specific adenylate cyclase activator, forskolin, enhanced only the depolarization. The analogue of cyclic adenosine 3',5'-monophosphate (cAMP), 8-bromo-cAMP, induced only depolarization, the ionic mechanism of which was similar to that of 17 beta-estradiol. In addition, the possibility of non-specific effects of cyclic nucleotides was precluded by an experiment using an analogue of cyclic guanosine 3',5'-monophosphate (cGMP), 8-bromo-cGMP, which hyperpolarized neurons. Thus, the present study strongly suggests that the production of depolarizing responses of neurons in the hypothalamus produced by estradiol is specifically mediated through cAMP.

Long-term effects of hyperthermia combined with chemotherapy and irradiation for the treatment of patients with carcinoma of the esophagus.

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable or unresectable squamous cell carcinoma of the esophagus. The long term results were compared between two groups of patients; one group was treated with chemotherapy, radiotherapy and hyperthermia (HCR), and the other was treated with chemotherapy and radiotherapy, but not hyperthermia (CR). The five year survival rates of patients with resectable carcinoma, given preoperative HCR or CR, were 43.2 and 14.7 per cent, respectively; the difference was statistically significant (p less than 0.05). The two year survival rates of those with unresectable carcinoma and receiving HCR or CR were 15.5 and 1.2 per cent, respectively. In particular, for the patients classified as TNM Stages I and II, a significantly longer survival period was obtained with HCR. As severe side effects in patients given hyperthermia were nil, this treatment deserves serious consideration when treating patients with a malignant lesion of the esophagus.