Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

Objective Prospective comparison was done on concurrent chemo-radiotherapy and se- quential chemo-radiotherapy for unresectable stageⅢnon-small cell lung cancer(NSCLC) and to evaluate three different regimens of concurrent chemo-radiotherapy.Methods Ninety-six such patients were ran- domized into four groups:1.sequential chemo-radiotherapy group received two cycles of induction chemother- apy with 40 mg/m~2 of cisplatin on D 1-3,29-31 and 100 mg/m~2 of etoposide on D 1-3,29-31 before conven- tional radiotherapy,2.concurrent chemo-radiotherapy group 1 received 100 mg/m~2 etoposide on D 1-3 and DDP 40 mg/m~2 on D 1-3,D 29-31,iv.drip,3.concurrent chemo-radiotherapy group 2 received concurrent chemotherapy with 40 mg/m~2 of paclitaxel every Monday during conventional radiotherapy,4.concurrent chemo-radiotherapy group 3 received concurrent chemotherapy with 40 mg/m~2 of paclitaxel every Monday during three-dimensional conformal radiotherapy.All patients were irradiated with 2.0 Gy/fraction,5 frac- tions/week,to a total dose of 60-64 Gy.They all received two cycles of consolidation themotherapy with 40 mg/m~2 of cisplatin on D 1-3 and 100 mg/m~2 of etoposide on D 1-3.Results The overa/1 response rate was 67%,71%,71% and 79% for sequential ehemo-radiotherapy group,concurrent chemo-radiotherapy group 1,2 and 3,respectively.There was a significant difference between the concurrent chemo-radiotherapy and sequential chemo-radiotherapy(P＜0.05).The 1-,3-and 5-year overall survival rate(OS) was 54%,8% and 4%;71%,17% and 8%;79%,17% and 8%;83%,46% and 13%,respectively for the four groups. The difference among all these groups(P=0.017) was significant.It was also significant between the con- current chemo-radiotherapy group 1 and 3 (P=0.046).The difference of distant metastasis rate among all the groups was statistically insignificant (P＞0.05) also was the difference of toxicity (P＞0.05),but the severe toxicity of concurrent chemo-radiotherapy groups 1 and 2 were higher than the sequential chemo-radio- therapy group and concurrent chemo-radiotherapy group 3.Conclusions Better locoregional progression- free survival and overall survival of unresectable stageⅢnon-small cell lung cancer could be achieved by concurrent chemo-radiotherapy as compared with sequential chemo-radiotherapy though at the expense of in- crease in toxicity.With the combination of concurrent chemo-radiotherapy and conforrnal radiotherapy,the o- verall survival rate could be much improved with miider toxicity.

Objective To observe the distribution and metabolism of arsenic speciation in urine of rats exposed to different concentrations of dimethylaraenic acid (DMA) through drinking water.Methods Thrity six weaning Wistar rats were randomly divided into normal control,low-dose group and high-dose group,12 rats in each group(6 female and 6 male); average body weight of female rats was (60 ± 5)g,and male rats was (50 ± 5)g.All rats of the 3 groups were given DMA at concentrations of 0,100,200 mg/L,respectively,corresponding to their specific groups through drinking water for 10 weeks.Inorganic arsenic(iAs),monomethylarsenic acid(MMA),DMA and trimethylarsenic compound (TMA) in urine were measured by hydride generation trapping and ultrahypothermia coupled with atomic absorption spectrometry.Results After feeding for 10 weeks,the differences of rat urinary concentrations of iAs,MMA,DMA and TMA between normal control,low-dose group and high-dose group were statistically significant(x2 =25.441,25.942,25.751,17.767,all P＜ 0.01).Urinary concentrations of iAs,MMA and DMA(2.541,4.383,24.447 mg/L) of low-dose group were significant higher than those of normal control (0.784,0.000,0.743 mg/L,all P ＜ 0.05) ; iAs,MMA,DMA and TMA(3.978,7.186,35.112,4.518 mg/L) of high-dose group were significantly higher than those of normal control(0.784,0.000,0.743,0.000 mg/L,all P ＜ 0.05).The concentrations increased along with increasing doses of DMA concentrations in drinking water(all P ＜ 0.05).Conclusions After rats are exposed to DMA,most of the DMA are excreted in unchanged form in urine and a small portion of DMA is metabolized into TMA.

OBJECTIVETo analyze the complications of percutaneous kyphoplasty except bone leakge for the treatment of osteoporotic thoracolumbar vertebral compression fractures.

METHODSFrom October 2008 to October 2012,178 patients with 224 osteoporotic vertebral compression fractures were treated with percutaneous kyphoplasty under local anethsia. There were 72 males and 106 females,ranging in age from 58 to 92 years old,with an average of 75.3 years,including 93 thoracic vertebrae and 131 lumbar vertebrae. The complications except bone cement leakage were analyzed during operation and after operation.

RESULTSAll operations were successful and all patients were followed up from 12 to 60 months with an average of 26.2 months. No death was found. Bone cement leakage occurred in 27 cases, about 15.1% in 178 cases; and complications except bone cement leakage occurred in 15 cases. There was 1 case with cardiac arrest,was completely recovery by cardiopulmonary resuscitation (CPR) immediately; and 1 case with temporary absence of breathing,was recovery after treatment. There were 3 cases with fall of blood pressure and slower of heart rate; 1 case with intestinal obstruction; 2 cases with local hematoma and 1 case with intercostal neuralgia. Vertebral body fractures of 2 cases were split by bone cement and the fractures of adjacent body occurred in 4 cases.

CONCLUSIONIt's uncommon complication except bone cement leakge in treatment of osteoporotic thoracolumbar vertebral compression fractures with percutaneous kyphoplasty. The complication of cardiopulmonary system is a high risk in surgery; and cytotoxicity of bone cement,nervous reflex,fat embolism and alteration of intravertebral pressure may be main reasons.

Aged ; Aged, 80 and over ; Female ; Fractures, Compression ; surgery ; Humans ; Kyphoplasty ; adverse effects ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Postoperative Complications ; etiology ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; surgery

Arsenites ; toxicity ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Keratinocytes ; cytology ; Skin ; cytology ; Sodium Compounds ; toxicity

AIM: To investigate the protective effect of huoxuehuayu decoction on macula after phacoemulsification. Into A, B groups. The 80 eyes of A group were treated by conventional phacoemulsification; the patients (60 eyes) of B group were given huoxuehuayu decoction orally for two courses after phacoemulsification. Best-corrected visual acuity(BCVA), corneal and aqueous conditions ,thickness of macular central fovea and changes of macular retinal tissue in A, B groups were observed before surgery, 1 day; 1 week,2,4,6,8 weeks and 3 months after surgery. Was significantly higher than that of group A. One week after surgery the ratio of mild aqueous flare in group B was significantly lower than that of group A. The thickness of central fixation was significantly increased in both groups 1 week, 2, 4, 6, 8 weeks and 3 months after phacoemulsification; the difference between 2 to 8 weeks after surgery and pre-operation showed statistical significance in both groups. 11 eyes in A group had macular edema during 2 to 6 weeks after surgery, including 9 eyes with fovea thickened and 2 eyes with cystoid macular edema, and seven eyes' edema disappeared in 3 months. 2 eyes in B group had macular edema, including 1 eye fovea thickened and 1 eye cystoid macular edema, during 4 to 6 weeks after surgery, and the two eyes' edema disappeared 3 months after surgery. The fovea thickness in group B during 2 to 8 weeks after surgery was statistically lower than group A. Phacoemulsification.

Background Macular edema following phacoemulsification with intraocular lens (IOL) implantation is a main factor to influent visual function.The administration of traditional medicine can relieve tissue edema,but its preventive and treatment efficacy on macular edema after phacoemulsification with IOL implantation remaines unclear.Objective This study was to investigate the protective effect of huoxuehuayu decoction on macula after phacoemulsification with IOL implantation.Methods A case-controlled observational study was designed.One hundred and eighty eyes of 150 patients with age-related cataract were randomized into operation group and operation + medicine group.Phacoemulsification with IOL implantation was performed in both groups,but huoxuehuayu decoction was orally administered for 14 days in operation+medicine group.The best corrected visual acuity,inflammatory reaction of the ocular anterior segment,and macular edema were recorded before operation and 1 week,2,4,6,8 and 12 weeks,and the central macular thickness was measured using optical coherence tomography.Results Twelve weeks after surgery,the ratio of visual acuity ≥ 1.0 was in significantly higher in operation+medition group than that of in operation group (x2 =1.066,P＞0.05).One week after surgery,the eyes of the aqueous flare were much nore in the operation group than that of operation+medicine group(x2 =9.341,P＜0.05).The thickness of the central fovea was significantly increased in both groups at 1 week,2,4,6,8 and 12 weeks after surgery,showing significant differences in comparison with preoperation (operation group:P ＜ 0.01 ; operation + medicine group:P ＜0.05).Macular edema occurred in 13 eyes in operation group during the following-up duration,including 11 eyes with thickened fovea and 2 eyes with cystoid macular edema.Maeular edema disappeared in 10 eyes 12 weeks later.In the operation+medition group,3 eyes happened macular edema,including thickened fovea in 2 eye and cystoid macular edema in 1 eye.Four to six weeks after surgery,macular edema disappeared in 3 eyes 12 weeks later.The fovea thickness in the operation+medicine group was statistically significantly lower from 2 through 8 weeks after surgery than that in the operation group(t=2.315,2.323,3.104,2.470,P＜0.05).Conclusions Oral administration of huoxuehuayu decoction is helpful for the restoration of the anterior ocular segment.Huoxuehuayu decoction can protect macula from the edema induced by phacoemulsification.

BACKGROUND: Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke. METHODS: Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with right-hemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed. RESULTS: The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (P < 0.001). In response to either valid or invalid cues in the left side, the accuracy in the VSN group was lower than that in the non-VSN group (P < 0.001), and the accuracy in the non-VSN group was lower than that in controls (P < 0.05). The P1 latency in the VSN group was significantly longer than that in the control group (F[2, 30] = 5.494, P = 0.009), and the N1 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.343, P = 0.022). When responding to right targets, the left-hemisphere P300 amplitude in the VSN group was significantly lower than that in the control group (F[2, 30] = 4.255, P = 0.025). With either left or right stimuli, the bilateral-hemisphere P300 latencies in the VSN and non-VSN groups were both significantly prolonged (all P < 0.05), while the P300 latency did not differ significantly between the VSN and non-VSN groups (all P > 0.05). CONCLUSIONS Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.
Adult ; Aged ; Cerebral Infarction ; physiopathology ; Electrophysiology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Nitric Oxide Synthase Type III ; genetics ; PPAR gamma ; genetics ; Perceptual Disorders ; genetics ; metabolism ; physiopathology ; Polymorphism, Genetic ; genetics ; Reaction Time ; genetics ; physiology ; Reactive Oxygen Species ; metabolism ; Stroke ; genetics ; metabolism ; physiopathology ; Superoxide Dismutase ; genetics

Objective To investigate the effect of seafood intake on the urinary iodine level in women for exploring an alternative to iodine supplementation.Methods Healthy pregnant women and non-pregnant women, aged 20～40 years,were selected during their health examination in local women'S health care in 2006.The types of seafood and its intake frequency were recorded from these women.and urine and kitchen salt samples were collected for iodine determination.Results A total of 198 women including 148 pregnant and 50 non-pregnant women were recmitod for this study;they had a median level of urine iodine of 87.51 mg/L.The median levels of urine iodine of83.49,91.52,166.45μg/L in three group women classified as hardly,seldom and often intake of see food showed significant difference(X2=6.202,P<0.05).Urine iodine level in non-pregnant women taking seafood (90.94μg/L)was higher than that in pregnant women(84.79μg/L),the difference being statistically significant (U=3318.00,P<0.05).The urine iodine in pregnant women with seldom intake of seafood(94.46 μg/L)was significantly higher than that in the hardly intake women(83.28 μg/L),the difference being statistically significant (U=1257.5,P<0.05).During late period of gestation,the urinary iodine in the women ofthree statUS of hardly. Seldom and often intake of seafood were 81.93,97.97 and 140.18 μg/L,respective,with significant differences among them.Conclusions A certain amount of seafood taken every week Can increase urine iodine levels,and a direct relationship Was observed.Therefore,we suggest that it is necessary to advocate taking seafood to pregnant women for prevention of cretinism,particularly in the air.as where iodized salt was difficult to implement.

OBJECTIVETo investigate the analgesic effect of interleukin-2 (IL-2) in mice with spared nerve injury (SNI).

METHODIL-2 was intraperitoneally injected in mice with induced SNI, and von Frey Filaments test and cold plate test were carried out to accesses the analgesic effects of IL-2 and the effect of naloxone in antagonizing the effects of IL-2.

RESULTSIL-2 produced analgesic effects against hyperalgesia and allodynia in mouse models of SNI, and the effect of IL-2 lasted for more than 24 h, showing a double-peak pattern in its action with the two peaks occurring at 30 and 105 min, respectively. The effect of IL-2 could be significantly antagonized by naloxone.

CONCLUSIONSIL-2 has long-lasting analgesic effects in mouse models of SNI model, showing a double-peak pattern of its action. The analgesic effect of IL-2 is probably mediated by opiate receptor.

Analgesics ; administration & dosage ; antagonists & inhibitors ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Humans ; Hyperalgesia ; complications ; drug therapy ; Interleukin-2 ; administration & dosage ; antagonists & inhibitors ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred BALB C ; Naloxone ; pharmacology ; Trauma, Nervous System ; complications ; drug therapy