Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.
Algorithms ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Humans ; Intestinal Absorption ; Intestines ; chemistry ; metabolism ; Models, Theoretical ; Solubility

Objective To evaluate the using of either 225 or 150 microgrammes of mifepristone combined with misoprostol for termination of second-trimester gestation(16～24 weeks).Methods 180 women requesting voluntary induced abortion during gestation 16～24 weeks were randomised to three groups,group 1:oral mifepris- tone 225rag,group 2:oral mifepristone 150mg,and group 3:injected 100rag rivanot by amniocentestis.The total suc- cess rate,once success rate,the interval of having-medicine to uterine-constraction,the volume of bleeding within 2 hours after labour and cervical laceration rate were observed.Results The once success rate of induced labour in group 1 was higher than that in group 2 and group 3(P

Objective To observe the expression of the polysialic acid neural cell adhesion molecule ( PSA-NCAM) in the hippocampus of rats after exposure to low intensity ( 16 Hz,90 dB) infrasound for different periods.Methods One hundred and twenty male Sprague-Dawley rats were randomly divided into infrasound exposure and normal groups.The exposure group was tjem further divided into 1 day,7 days,14 days and 21 days exposure groups.After exposure,the rats' brains were removed and an immunohistochemical technique was used to observe the expression of PSA-NCAM in the hippocampus after 1,7,14 or 21 days of exposure. Methods The expression of PSA-NCAM had increased significantly after exposure for 7 days. It peaked at 14 days,then had decreased by 21 days,but always remaining higher than in the normal group.After the infrasound exposure had ended,the expression of PSA-NCAM demonstrated a tendency of decrease over time,and the least was on the 21st day.The largest decrease was observed in the 14 days exposure groups. Conclusion 16 Hz,90 dB infrasound can increase the expression of PSA-NCAM in the hippocampus,at least in rats.This suggests that low intensity infrasound might initiate recovery of an injured central nervous system.Migration of neural stem cells may aid in the repair of neural injuries resulted from infrasound exposure.

Objective To investigate the effect of 8 Hz infrasound on the expression of brain derived neurotrophic factor(BDNF)in the rat hippocampus.Methods Forty-eight Sprague-Dawley rats were randomly divided into groups to be exposed to 90,100 and 130 dB infrasound,and a control group(n=12).All the animals in the infrasound exposure groups were exposed to 8 Hz infrasound at the planned intensity for 2 hours daily for 4 weeks.The rats of the control group were treated identically except that the infrasound amplitude was 0 dB.The animals were sacrificed and their brains were examined at the end of the 4-week infrasound exposure.Western blotting was used to detect the expression of BDNF protein,and in situ hybridization(ISH)was used to observe the distribution of BDNF mBNA in the hippocampus.Results Eight Hz infrasound induced down-regulation of BDNF protein in the hippocampus,with volume-dependent characteristics.ISH showed that BDNF mRNA was distributed widely in the hippocampus.After exposed to infrasound,BDNF mRNA in the hippocampus decreased,especially in the dental gyrus.Conclusion Eight Hz infrasound can down-regulate the expression of BDNF in the hippocampus,especially in the dental gyrus.

Objective To improve the level of early detection and treatment of pyonephrosis. Methods This study included 41 cases(17 men and 24 women;mean age,49 years)of pyonephrosis.A variety of examinations,including urinary analysis,blood analysis,kidney nuclear medicine scan,ultrasonog- raphy,intravenous urography(IVU),and CT were used for the early diagnosis of pyonephrosis.Pereutaneous nephrostomy(PCN)drainage was done for the interim management of pyonephrosis,then phase 2 operation was performed in 28 cases.The double-J tube was placed in ureter by ureteroscope for drainage,and then phase 2 operation was done in 2 cases.Emergency operation was done in 10 cases.The remaining 1 case un- derwent ESWL after anti-infective therapy.Results Definite diagnosis of pyonephrosis before operation was made by invasive examinations in 31 cases(75.6%),and by percutaneous drainage in 4 cases;the other 6 cases were detected during operation.Only 6 cases(14.6%)underwent nephrectomy;the other 35 cases (85.4%)underwent kidney-sparing operation.Follow-up of 3 months to 9 years was available in 37 cases. No nephrectomy was needed in 33 cases with spared kidney.Serum creatinine was normal in the 4 cases un- dergoing nephrectomy.Conclusions The key to the treatment of pyonephrosis by kidney-sparing surgery is early diagnosis,timely drainage and relief of obstruction.Ultrasonography plays an important role in the early diagnosis of pyonephrosis,and CT has a high sensibility in the diagnosis.Pereutaneons nephrolithotomy (PCNL)secondary to drainage through pereutaneous nephrostomy was beneficial to the patients with kidney stones or upper ureter stones.

Objective To determine a suitable standard of hirsutism for Chinese polycystic ovary syndrome(PCOS)patients living in Shandong region.Methods A total of 623 unbiased women from the general population in Jinan city,131 PCOS patients and 84 controls from outpatients in Shandong region were studied with questionnaires,physical and pelvic ultrasound examination,body hair on 11 sites were evaluated,and 9(lip,chin,arm,thigh,chest,upperbelly,lowerbelly,upperback,lowback)of them which were called hormone Ferriman-Gallwey(F-G)score and 2(forearm,leg)sites of indifferent hormone score were calculated according to the score system described by Ferriman and Gallwey.Results(1)Both body hair F-G score and indifferent hormone score distribution mode in the≤40 years old population were un-normal and both the 95th percentages of score were 2.(2)The hirsutism was significantly higher in PCOS patients[48.1%(63/131)]than in controls[4.8%(4/84)]by F-G score≥2(X~2=47.68,P

AIMTo investigate antimalarial mechanism of Qinghaosu ( QHS) and its derivatives.

METHODSThe electronic structure of QHS and its derivatives were completely optimized and calculated at B3LYP/6-31G * level, while the route was at HF/STO-3G level.

RESULTSThe peroxide bridge is the active center of QHS and induced by ferrous iron to produce cyclic product.

CONCLUSIONHeme can link with QHS derivatives.

Antimalarials ; chemistry ; isolation & purification ; Artemisia ; chemistry ; Artemisinins ; chemistry ; isolation & purification ; Electron Transport ; Free Radicals ; chemistry ; Heme ; chemistry ; Models, Chemical ; Peroxides ; chemistry ; Plants, Medicinal ; chemistry ; Quantum Theory

OBJECTIVETo investigate the values of combination of urinary liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery in children.

METHODSA total of 97 children with congenital heart disease undergoing cardiopulmonary bypass surgery were enrolled. Serum and urine samples were collected before and after surgery. Levels of serum creatinine (Scr), urinary L-FABP, and urinary NGAL from AKI group (n=18) and non-AKI group (n=79) were measured, and the postoperative dynamic changes in these markers were compared between the two groups. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to assess the values of these markers alone or in combination in the prediction of postoperative AKI.

RESULTSThe levels of urinary L-FABP and NGAL in the AKI group were significantly higher than those in the non-AKI group at 2 and 6 hours after surgery, and the changes in their concentrations were earlier than Scr. The AUCs of urinary L-FABP alone in predicting AKI at 2 and 6 hours after surgery were 0.921 and 0.896 respectively, and those of urinary NGAL alone were 0.908 and 0.928 respectively. Those of their combination were 0.942 and 0.929 respectively.

CONCLUSIONSUrinary L-FABP and NGAL significantly increase in the early stage of AKI after cardiac surgery in children, which are significantly earlier than the changes in Scr. They can be used to predict the occurrence of AKI in the early stage. A combination of the two biomarkers can further improve the accuracy of diagnosis.

Acute Kidney Injury ; diagnosis ; urine ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; Child ; Child, Preschool ; Creatinine ; blood ; Fatty Acid-Binding Proteins ; urine ; Female ; Humans ; Infant ; Lipocalin-2 ; urine ; Male

OBJECTIVE: To determine the mechanism of Toll-like receptor 4(TLR4) in hypertensive renal injury and the protective effect of fosinopril(Fos) and losartan(Los). METHODS: NRK-52E was incubated into 5 groups: NRK-52E (normal control), NRK-52E+AngII, NRK-52E+AngII+Fos(10(-5) mmol/L),and NRK-52E+AngII+Los(10(-5) mmol/L), NRK-52E +AngII+Fos(10(-5) mmol/L)+Los(10(-5) mmol/L). TLR4-specific RNAi plasmids were stably transfected into NRK-52E. After 24 h, TLR4, IL-6, and TNF-alpha mRNAs were examined by reverse transcription-polymerase chain reaction(RT-PCR). TLR4 proteins were detected by Western blot, NF-kappaB nuclear translocations were tested by immunocytochemistry,and IL-6 and TNF-alpha supernatant levels were tested by enzyme linked immuno-sorbent assay(ELISA). RESULTS: TLR4, NF-kappaB, IL-6,and TNF-alpha were highly expressed in AngII induced NRK-52E(P<0.01). In NRK-52E that was stably transfected TLR4-special RNAi plamids, TLR4 protein and mRNA expression were obviously inhibited(P<0.05). After stimulation by AngII, the TLR4, IL-6, TNF-alpha levels in the stabe transfection group were increased compared with the normal group(P<0.05). Fos or/and Los down-regulated TLR4, IL-6, and TNF-alpha expressions(P<0.05), but no cooperation was observed. CONCLUSION TLR4 may lead to inflammatory reaction in hypertensive renal injury. Fos or/and Los can decrease the expressions of TLR4 and correlate inflammatory factors, which may be part of the renal protective mechanism.
Animals ; Cell Line ; Epithelial Cells ; immunology ; metabolism ; Fosinopril ; pharmacology ; Hypertension ; complications ; Kidney Diseases ; prevention & control ; Kidney Tubules ; cytology ; metabolism ; Losartan ; pharmacology ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Toll-Like Receptor 4 ; biosynthesis ; genetics

BACKGROUNDOur previous research has suggested that platelet activating factor receptor was related to atherosclerosis. The present study investigated the effect of a platelet activating factor receptor antagonist-WEB2086 on angiogenesis in aortal plaque and ischemic hindlimb of apolipoprotein E-deficient mice.

METHODSEight-week-old apolipoprotein E-deficient mice were fed with a 0.15% cholesterol diet to develop advanced lesions. At age 32 weeks unilateral hindlimb ischemia was surgically induced and the mice were divided into two groups: with or without WEB2086 mixed with their drinking water (4.3 mg in 100 ml). At age 40 weeks blood was collected from the orbit for measurement of serum lipids and an enzyme linked immunosorbent assay was used to determine platelet activating factor and oxidized low density lipoprotein in the gastrocnemius and aorta. Whole-Mount CD31 stain and plaque-associated sprouting have been used to estimate angiogenesis in plaque from the aorta and laser Doppler perfusion imaging and immunohistochemical expression of von Willebrand factor have been used to estimate angiogenesis in ischemic hindlimb.

RESULTSThe lipid composition of serum was not different between the groups. However, the amount of platelet activating factor and oxidized low density lipoprotein detected in the aorta was significantly higher than that in the gastrocnemius of ischemic hindlimb. The ratio of lesion to aorta levels was significantly reduced by administration of WEB2086, (31.52 +/- 6.18)% vs (55.58 +/- 8.34)%, P < 0.01. The mean density of intimal capillaries in atherosclerotic plaque, (31.13 +/- 9.20)% vs (57.74 +/- 11.28)%, P < 0.01, and the mean number of sprouts per aorta were significantly reduced, 183.92 +/- 34.17 vs 392.54 +/- 76.79, P < 0.01, in the WEB2086 group. Blood flow (0.85 +/- 0.12 vs 0.45 +/- 0.06, P < 0.01) and capillary density of ischemic hindlimb (1.18 +/- 0.17 vs 0.53 +/- 0.09, P < 0.01) were markedly increased in apolipoprotein E-deficient mice treated with WEB2086 versus controls.

CONCLUSIONThe study provides evidence that WEB2086 can inhibit angiogenesis in atherosclerotic plaque but promote it in ischemic hindlimb.

Animals ; Apolipoproteins E ; deficiency ; Atherosclerosis ; physiopathology ; Azepines ; pharmacology ; Capillaries ; Cholesterol ; blood ; Hindlimb ; blood supply ; Ischemia ; physiopathology ; Lipoproteins, LDL ; blood ; physiology ; Male ; Mice ; Neovascularization, Physiologic ; drug effects ; Platelet Activating Factor ; analysis ; Platelet Membrane Glycoproteins ; antagonists & inhibitors ; Receptors, G-Protein-Coupled ; antagonists & inhibitors ; Triazoles ; pharmacology