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Objective To analyze the risk factors and correlation between clinical indicators and the four main pathological lesions of IgA ne?phropathy in the Oxford classification:mesangial hypercellularity(M0/1),endocapillary proliferation(E0/1),segmental sclerosis or adhesion(S0/1), and tubular atrophy/interstitial fibrosis(T0/1/2). Methods Clinical and pathological data were collected from 514 patients with biopsy?proven IgA nephropathy admitted in our hospital from February 17,2006 to October 11,2011. These patients were all above 18 years old. Cases with sec?ondary causes of mesangial IgA deposition were excluded,such as Henoch?chonlein purpura,ankylosing spondylitis and psoriasis et al. The inde?pendent risk factors affecting the pathological classification were analyzed by Spearman rank correlation analysis and two?category and multi?classi?fication logistic regression using SPSS 17.0 statistical software. Results In 514 IgAN patients,the ratio of males to females was 1.06:1. The aver?age age was 35.70±11.99 years,and the average disease duration was 18.31±30.42 months. M0E0S0T0 was the major pathologic classification of isolated hematuria. Chronic kidney disease(CKD)stage,24 hours proteinuria,albuminuria,urine transferrin and IgG levels were positively corre? lated with M lesion;serum albumin,C3 and PLT showed a negative correlation with M lesion. Twenty four hours proteinuria and blood platelet count were the independent risk factors for M lesion. As shown by stratified analysis ,the proportion of M1 in cases with 24 hours proteinuria≥3.5 g/d is much higher than that in cases with non?nephrotic range proteinuria. Age,systolic blood pressure,uRBC,24 hours proteinuria,albuminuria urine transferrin and IgG levels were positively correlated with E lesion,Duration,serum albumin showed a negative correlation with E lesion. Age and duration of nephritis were independent risk factors for E lesion. 73.3%of patients that above 60 years old showed endothelial proliferation. CKD stage,24 hours proteinuria were positively correlated with S lesion. Age,CKD stage,systolic blood pressure,diastolic blood pressure,C4,TC, LDL?C,CRP,Fib,UA,Cys?C and 24 hours proteinuria,urineβ2?microglobulin,albumin,transferrin and IgG levels were positively associated with T lesion;hemoglobin,serum albumin,serum IgG showed a negative correlation with T lesion. Infection history,high CRP levels,DBP more than 90 mmHg,hypoalbuminemia,high low density lipoproteinemia,and anemia were independent risk factors for T lesion. Conclusion Twenty four hours proteinuria,blood platelet count,age,duration of nephritis,hypoalbuminemia,anemia,hyperlipidemia,DBP≥90 mmHg and high CRP lev?els were risk factors for the Oxford classification of IgA nephropathy. Renal biopsy should be carried out in time to make clear the pathological clas?sification and individual treatment,so as to improve the prognosis.
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To establish HPLC-MS/MS method for simultaneous determination of daphnetin, daphnoretin, and daphneticin in rat plasma after oral and intravenous administration of Daphne giraldii extract, and then use them in the calculation of pharmacokinetic parameters. Six sprague-dawley rats received intragastric administration of D. giraldii extract (daphnetin, daphnoretin and daphneticin were 88.40, 3.24 and 4.28 mg•kg⁻¹, respectively). Their drug plasma concentration was determined by LC-MS/MS with schisandrin as an internal standard to draw plasma concentration-time curve. The pharmacokinetic parameters were calculated by Kinetica 4.4. The results showed that the linear range was 5-1 000 μg•L⁻¹ for daphnetin, daphnoretin and daphneticin, and the method ological test showed conformance to the requirements.The intraday and inter-day variable coefficients (RSD) were both less than 15.0%, indicating that both of legitimate precise and accuracy were consistent with the analysis requirements of biological samples. For daphnetin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 4 h, 858.96 μg•L⁻¹, 10 566.4 μg•L⁻¹•h, 5.19 h and 9.43 h, respectively. For daphnoretin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2.92 h, 178.00 μg•L⁻¹, 905.89 μg•L⁻¹•h, 3.50 h and 6.95 h, respectively. For daphneticin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2 h, 36.67 μg•L⁻¹, 355.11 μg•L⁻¹•h, 4.95 h and 8.27 h, respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of daphnetin, daphnoretin and daphneticin.
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Ischemic brain injury is a major disease which threatens human health and safety. (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone (PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1:5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.
Subject(s)
Benzoates , Chemistry , Brain Ischemia , Drug Therapy , Chemistry, Pharmaceutical , Methods , Drug Delivery Systems , Povidone , Chemistry , SolubilityABSTRACT
To establish an appropriate experimental and data processing method on the basis of the general kinetic model for extraction of traditional Chinese medicines, in order to study the effect of total flavonoids in water extracts from Puerariae Radix on the adaptability of the model, with total flavonoids of Puerariae Radix as the determination indicator. The results showed that the natural logarithm of mass concentration of total flavonoids showed a good linearity with the changes in extraction time and solvent volume. Through calculating and fitting, we successfully established the kinetic model for water extraction of total flavonoids from Puerariae Radix, and verified its accuracy. Its good fitting degree and controllable deviation within the range of industrial production requirements indicated a good adaptability of the model. However, its equation correction factors require further studies.
Subject(s)
Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Chemistry , Flavonoids , Chemistry , Kinetics , Plant Roots , Chemistry , Pueraria , ChemistryABSTRACT
Objective The effects of candesartan,an angiotensin Ⅱ type 1 receptor blocker (ARB) were investigated on advanced glycation end-products accumulation and the receptor for AGE (RAGE) expression in type 2 diabetic KK/Ta mouse kidneys.MethodsKK/Ta mice(n=72)were random divided into three groups(n=24) and it was treated with candesartan [4 mg/(kg·d)] or vehicle from 6 or 12 to 28 weeks of age.BALB/c mice(n=24) treated with vehicle were used as controls.Body weight,blood pressure,blood glucose,urinary microalbumin,urinary creatinine and serum creatinine were measured every four weeks.At 28 weeks,renal expressions of carboxymethyllysine and RAGE were evaluated by immunohistochemistry and/or competitive RT-PCR.Results KK/Ta mice developed high body weight,high blood glucose,and high urinary microalbumin/creatinine ratio in KK/Ta mice at 28 weeks of age,and it was significantly higher than that of BALB/c mice [(427.49±89.37)mg/g vs (9.54±3.25)mg/g,P＜0.01 ].Protein and mRNA expressions of RAGE were upregulated in KK/Ta kidneys with increased immunostaining intensities of carboxymethyllysine.Candesartan treatment has markedly reduced urinary microalbumin/creatinine ratio [Early treatment group (32.18±9.41)mg/g,Late treatment group (53.20±7.26)mg/g,P＜0.01 ].Treatment with candesartan down-regulated the protein and mRNA expressions of RAGE and reduced the accumulation of carboxymethyllysine.There were no significant differences between the two treatment groups (from 6 or 12 weeks).ConclusionsThe results suggest that candesartan,an ARB,reduces advanced glycation end-products accumulation and subsequent albuminuria by down-regulating RAGE expression in type 2 diabetic KK/Ta mouse kidneys.