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A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.
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A double targets of high throughput screening model for xanthine oxidase inhibitors and superoxide anion scavengers was established. In the reaction system of xanthine oxidase, WST-1 works as the probe for the ultra oxygen anion generation, and product uric acid works as xanthine oxidase activity indicator. By using SpectraMax M5 continuous spectrum enzyme sign reflectoscope reflector, the changes of these indicators' concentration were observed and the influence factors of this reaction system to establish the high throughput screening model were studied. And the model is confirmed by positive drugs. In the reaction system, the final volume of reaction system is 50 μL and the concentrations of xanthine oxidase is 4 mU x mL(-1), xanthine 250 μmol x L(-1) and WST-1 100 μmol x L(-1), separately. The Z'-factor of model for xanthine oxidase inhibitors is 0.537 4, S/N is 47.519 9; the Z'-factor of model for superoxide anion scavengers is 0.507 4, S/N is 5.388 9. This model for xanthine oxidase inhibitors and superoxide anion scavengers has more common characteristics of the good stability, the fewer reagent types and quantity, the good repeatability, and so on. And it can be widely applied in high-throughput screening research.
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Objective To explore the relationship between the size and location of the aneurysm after subarachnoid hemorrhage (aSAH) and its clinical classification. Methods A retrospective study was performed in patients with aSAH from January 1, 2008 to December 31, 2014. The relevant clinical data were collected including age, gender, aneurysm size, location, and Hunt-Hess (H-H) classification. The aneurysms were classified by size (A group d<5.00 mm, B group 5.00 mm≤d<10.00 mm, C group d≥10.00 mm), location and H-H classification according to the results of CT, digital subtrac?tion angiography (DSA), and magnetic resonance angiography (MRA). The relationship between size, position of aneurysm and H-H classification was observed and analyzed. Results There were 750 cases included in this study, with average age (56.14 ± 11.88), male 292 and female 458. The total number of aneurysms was 903, and the number of multiple aneurysms was 91 (12.13%). There was one case with multiple aneurysms that can be included in A, B and C groups. There were two cases with multiple aneurysms that can be included in A and B groups, two cases can be included in A and C groups, and three cases can be included in B and C groups. The number of aneurysms and the ratios of groups A, B and C were 20(3.9%), 12 (3.8%), 5 (7.5%), 70 (13.6%), 39 (12.2%), 10(14.9%), 2 (0.4%), 4 (1.3%), 2 (3.0%), 165 (32.0%), 94 (29.4%), 6 (9.0%), 130 (25.2%), 90 (28.1%), 6 (9.0%), 17 (3.3%), 11 (3.4%) and 2 (3.0%) for the location in the anterior cerebral artery, the middle cerebral artery, the posterior cerebral artery, the internal carotid artery, the anterior communicating artery, the posterior communicating artery, and the vertebral basilar artery, respectively. The number of aneurysms and the ratios of H-H classificationⅠ,Ⅱ,Ⅲ,ⅣandⅤin groups A, B and C were 48 (9.3%), 45 (14.1%), 12 (17.9%), 228 (44.2%), 150 (46.9%), 14 (20.9%), 68 (13.2%), 54 (16.9%), 30 (44.8%), 142 (27.5%), 43 (13.4%), 9 (13.4%), 30 (5.8%), 28 (8.8%) and 2 (3.0%). There was a negative correlation between the size of aneurysm and the H-H grade (rs=-0.075, P=0.024). Conclusion The anterior communicating artery and posterior communicating artery are high-risk areas for smaller aneurysms. The internal ca?rotid artery is high-risk areas for larger aneurysms. The size of aneurysm is negatively correlated with H-H classification.
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ObjectiveTo analyze and compare the difference and prognosis between vascular embolization and craniotomy occlusion in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) with Hunt-Hess levelⅢ-Ⅳ, and acute postoperative hydrocephalus.Methods A retrospective study was conducted on 767 patients who had undergone vascular embolization (vascular embolization group,n = 403) or craniotomy occlusion operation (craniotomy occlusion operation group,n = 364), and the patients with postoperative acute hydrocephalus were screened. The clinical data of patients of both groups was analyzed. By judging short-term prognosis in patients with hydrocephalus with Glasgow outcome scale (GOS) score estimated at discharge, the advantages and disadvantages of two surgical procedures were compared.Results The number of cases with postoperative hydrocephalus in vascular embolization group was 56 (13.90%), while that in craniotomy occlusion group was 33 (9.07%). The difference between the two groups of incidence of hydrocephalus was statistically significant (χ2= 4.350,P = 0.037 ). In 767 patients with aSAH, the incidence of hydrocephalus among the patients after the hematoma removal operation was significantly lower than that of patients without hematoma removal [3.07% (11/358) vs. 19.07% (78/409),χ2 = 47.635,P = 0.000]. The incidence of hydrocephalus among the patients after ventricular drainage was significantly lower than that of patients without the drainage [2.77% (19/685) vs. 85.37% (70/82),χ2 = 487.032,P = 0.000]. In 403 cases of vascular embolization group, the incidence of hydrocephalus in the patients after the hematoma removal operation was lower than that of patients without it [8.06% (5/62) vs. 14.96% (51/341),χ2 = 2.082,P = 0.168]. The incidence of hydrocephalus in the patients after the ventricular drainage was lower than that of patients without drainage [2.59% (9/347) vs. 83.93% (47/56),χ2 = 266.599,P = 0.000]. In 364 cases of craniotomy occlusion operation group, the incidence of hydrocephalus in the patients after hematoma removal operation was significantly lower than that of patients did not receive [2.03% (6/296) vs. 39.71% (27/68),χ2 = 95.226,P = 0.000]. The incidence of hydrocephalus among the patients after the ventricular drainage was significantly lower than that of patients without drainage [2.96% (10/338) vs. 88.46% (23/26),χ2 = 203.852,P = 0.000]. The difference in incidence of hydrocephalus between the patients who had hematoma removal surgery between vascular embolization group and craniotomy occlusion operation group was statistically significant [8.06% (5/62) vs. 2.03% (6/296),χ2 = 4.411,P = 0.027], while no statistically difference was present in ventricular drainage patients [2.59% (9/347) vs. 2.96% (10/338),χ2 = 0.085,P = 0.819]. There were 23 patients (41.07%) with good outcome (GOS score 4-5), while 33 (58.93%) with poor outcome (GOS score 1-3) in 56 patients undergone vascular embolization operation. Good result (GOS score 4-5) was shown in 21 (63.64%) and 12 (36.36%) with poor outcome (GOS score 1-3) among 33 patients with hydrocephalus after craniotomy occlusion operation, and the difference was statistically significant (χ2 = 4.230,P = 0.039).Conclusions Hematoma is one of the main factor contributing to the differences in the incidence of postoperative hydrocephalus of Hunt-Hess gradeⅢ-Ⅳ patients either receiving vascular embolization or craniotomy occlusion operation. Lateral ventricle drainage may not be the factor that contributes to the difference in incidence of hydrocephalus formation between the vascular embolization and craniotomy occlusion operation groups in Hunt-Hess levelⅢ-Ⅳ patients. The short term prognosis in the craniotomy occlusion operation group is superior to that of endovascular intervention embolization group.
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To enhance the quality and efficiency of ozagrel by investigating the differences between the ozagrel polymorphs in bioavailability. Solid ozagrel in different polymorph forms were orally administered to SD rats. An HPLC method was established to determinate plasma level of ozagrel. The bioavailabilities of two polymorph forms were calculated and compared. The pharmacokinetic parameters of ozagrel, were as follows: Cmax was 32.72 ± 17.04 and 34.01 ± 19.13 mg · L(-1), respectively; AUC0-t was 61.14 ± 14.76 and 85.56 ± 18.08 mg · L(-1) · h, respectively; t½ was 1.53 ± 0.51 and 4.73 ± 3.00 h, respectively. There was no significant difference in pharmacokinetic parameters between form I and II polymorphs of ozagrel while the t½ of form II is longer, which indicates that the use of form II polymorph as pharmaceutical product may prolong the effective action time in clinics. This would help the polymorph quality control in drug production.