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Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistance-associated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3-/-)rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99%of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 μM and 382.2 μM for OAT1 and OAT3,respectively)and renal clearance half-life(ti/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0-t)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.
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Objective To explore the clinical pharmacist’s role in drug therapy and monitoring for the patient with postoperative MRSA infection. Methods Clinical pharmacists participated in planning anti-infective treatment, antimicrobial medication selection, identification of high-risk factors for MRSA infection, evaluation of vancomycin efficacy, dosage adjustment using TDM technology, monitoring and management of vancomycin adverse reactions. Results With the pharmaceutical care provided by clinical pharmacists, the patient received effective treatment with minimal vancomycin-related adverse reactions. Conclusion Clinical pharmacists played an important role in accelerating patient recovery by rational and safe medication use.
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OBJECTIVE@#To study the expressions of the members of HSP110 family in the testis and epididymis of mice at different stages of development and whether they are regulated by hormones.@*METHODS@#The testicular and epididymis tissues of mice at different ages (14, 21, 28, 35, 42, 49, 70, and 90 days after birth, 3 mice at each age) were collected for RT-PCR detection of the expression levels of HSP110 family members. Forty-eight mice were randomized into 3 groups for sham operation, castration, or castration with testosterone injections every other day (starting at 7 days after castration), and at 1, 3, 5, and 7 days after first testosterone injection, the expressions of HSP110 family in the epididymis were detected using RT-PCR.@*RESULTS@#The mRNA expression levels of HSP110 family members underwent obvious variations with the development of the mice: , and expressions in the testicles of the mice first increased and then decreased, and gradually became stable; they also exhibited similar temporal patterns of changes in the epididymis. In the castrated mice, the mRNA expressions of and in the epididymis decreased significantly with the reduction of serum hormone levels ( < 0.05), and became normal after the supplementation of exogenous hormone.@*CONCLUSIONS@#The expression levels of HSP110 family are affected by developmental regulation, and the expressions of and are under the regulation by hormones.
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Animales , Masculino , Ratones , Epidídimo , Regulación del Desarrollo de la Expresión Génica , Proteínas del Choque Térmico HSP110 , Genética , Metabolismo , Orquiectomía , Testículo , Testosterona , FarmacologíaRESUMEN
OBJECTIVE: To evaluate the exposure status of hand-transmitted vibration(HTV)in golf ball head grinding workers.METHODS: The golf ball head grinding positions in a sports equipment factory were selected as the research subjects by the judgement sampling method.The HTV exposure level of the workers in 66 grinding positions was measured,the key control points for HTV hazards were identified,and the damage of HTV was classified.RESULTS: The median(M)of 4 hours energy equivalent frequency-weighted acceleration to vibration[a_(hw(4))]of grinding positions in this sports equipment factory was 4.21 m/s~2,and the a_(hw(4)) over standard rate was 50.0%(33/66).The a_(hw(4)) of rough grinding positions was higher than that of fine grinding positions(M:5.50 v.s 3.94 m/s~2,P<0.05).In both rough grinding positions and fine grinding positions,the a_(hw(4)) of different ball head grinding types from high to low were hollow titanium alloy ball heads, hollow stainless steel ball heads,and solid stainless steel ball heads(rough grinding positions M:7.41 vs4.43 vs 3.11 m/s~2,P<0.01; fine grinding p ositions M:5.24 vs 4.21 vs 2.93 m/s~2,P<0.01).For the hollow titanium alloy ball head grinding positions,the a_(hw(4)) of rough grinding was higher than that of fine grinding(M:7.47 vs 5.24 m/s~2,P<0.01).Rough grinding positions,especially hollow stainless steel ball heads and hollow titanium alloy ball head grinding positions were key control points for HTV hazards.In the 66 grinding positions,the HTV hazards were classified as grade 0,Ⅰ,Ⅱ,and Ⅲ in the grinding positions accounted for 3.0%,47.0%,40.9%,and 9.1%,respectively,and those with grade Ⅱ and above were 50.0%(33/66). CONCLUSION: The exposure level of HTV in golf ball head grinding workers is high,with a trend of exceeding the standard.The golf ball head grinding workers have a high occupational health risk.
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OBJECTIVE: To investigate the effect of hyperthermia on the expression of PANDAR, LncRNA-p21 and ST8SIA genes in the human lung adenocarcinoma A549 cells. METHODS: A549 cells were randomly divided into 4 groups. The A549 cells in control group were cultured at 37 ℃; the cells at experimental groups were cultured at 40, 42 or 44 ℃ respectively. The cells in these 4 groups were incubated for 1 hour, and the levels of PANDAR, LncRNA-p21 and ST8SIA genes were analyzed by real-time fluorescence quantitative polymerase chain reaction. RESULTS: In cells cultured at 40, 42 or 44 ℃ experimental groups, the relative expression of PANDAR gene was lower than that of control group(P<0.05). In cells cultured at 44 ℃ experimental group, the relative expression of PANDAR gene was lower than that of the 40 and 42 ℃ experimental groups(P<0.05). There was no significant change in the relative expression of LncRNA-p21 and ST8SIA genes among the four groups(P>0.05). CONCLUSION: Hyperthermia decrease the expression of PANDAR gene in A549 cells.
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Hippocampus,as an important organization of the nervous system,has a close relationship with the biology function of learning,memory and spatial cognition.It is very important to clarify the specific influence of non-ionizing radiation on the hippocampus.This paper summarized briefly the effects of nonionzing radiation on hippocampus and relevant research method.
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This study aims to investigate the change of plasma concentration of digoxin (DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group (n = 6). All rats plasma was collected after a single dose of 2 mg x kg(-1) DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, C(max) of ovariectomized group decreased significantly (P < 0.01). There was no significant difference of AUC(0-t), and the level of P-gp was elevated in ovariectomized group. It was found that C(max) of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp.
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The study aims to establish a method for simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-MS/MS and to study its pharmacokinetic interactions. Eighteen male SD rats were divided into repaglinide group, pravastatin sodium group and co-administration group. Blood samples were collected at different times after oral administration. Repaglinide and pravastatin sodium in rat plasma were separated by Agilent HC-C18 with the mobile phase consisting of methanol-0.1% formic acid (80 : 20). Detection and quantification were performed by using ESI-MS. The detector was operated in selected Reaction-monitoring mode at m/z 453.3-->230.1 for repaglinide, m/z 447.2-->327.4 for pravastatin sodium and m/z 285.1-->192.9 for diazepam as the internal standard. The calibration curve obtained was linear (R2>0.99) over the concentration range of 9.77-10,000 ng.mL-1 for repaglinide and 4.88-625 ng.mL-1 for pravastatin sodium. Compared with the single administration group, Cmax and AUC0-6h of repaglinide increased significantly (P<0.05) and tmax of pravastatin sodium prolonged (P<0.05) in co-administration group. The method is found to be simple, sensitive and accurate for determining the concentration of repaglinide and pravastatin sodium in rat plasma. There exists pharmacokinetic interactions in the co-administration of repaglinide and pravastatin sodium.
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OBJECTIVE:To provide a method for a scientific and rational formation of hospital drug purchase plan.METHODS:Based on the major factors influencing the drug purchase plans,a moving-average method(mathematical principle)was used to establish computational formula for hospital drug purchase plan model,which was then put into practice.RESULTS:The predicted amount calculated using the computation model could be used to track the actual consumption quantity rapidly;this model could auto-adjust the inventory and dynamically forecast the drug purchase amount.CONCLUSION:The computation model contributes to the scientific and reasonable formation of hospital drug purchase plan thus meeting the needs of majority clinical drugs.
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OBJECTIVE: To establish the quality standard of l of Zengshi oral liquid. METHODS: Thin-layer chromatography(TLC) was employed for the qualitative determination of the Lycium barbarum,Cassia obtusifolia and schisandra chinensis. High performance liquid chromatography (HPLC) was applied for the determination of chrysophanol in Zengshi Oral Liquid. RESULTS: The quality standard of Zengshi oral liquid could be established through qualitative determination of the Lycium barbarum,Cassia obtusifolia and Schisandra chinensis.The linear range of Chrysophanol was 0.083~0.416?g (r=0.999 9). The average recovery was 98.38% and the RSD was 1.72%. CONCLUSION: The established standard can be used for the quality control of Zengshi oral liquid.
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OBJECTIVE:To investigate the epidemiological characteristics of adverse reaction(ADR) caused by Shenmai injection.METHODS:By retrieving from Chinese medical periodicals issued in 1990 to 2010,145 cases of ADR induced by Shenmai injection were collected to establish database using ACCESS.Based on established database,the epidemiological information was analyzed statistically.RESULTS:The incidence of ADR was the highest in the middle-aged and old sufferers(87.6%),and was 37.9% in the male(n=55) and 62.1% in the female(n=90).Of primary diseases cases,cardiovascular disease took up 62.1%.The incidence of allergic reaction took up 38.0% in ADR cases and ADRs usually occurred within 30 min after first injection(64.8%).CONCLUSION:The establishment of ADR database is beneficial to the storage and analysis of ADR information and provided reference for the prevention and therapy of ADR caused by Shenmai injection.
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Objective To investigate the genetic effect of low power microwave radiation on the anomaly of sperm and micronucleus(MN) formation in the marrow polychromatic erythrocyte (PCE) in rat. Methods Rats were randomly divided into three groups, namely control, experimental group Ⅰ and experimental group Ⅱ. Abnormal sperms and MN formation in marrow PCE were observed and detected after exposure to 1 800 MHz (Continuous wave, CW) microwave radiation for 21 days (12 h/d) with the average power density of 0 mW/cm 2 (control), 0 5 mW/cm 2 (group Ⅰ) and 1 0 mW/cm 2 (group Ⅱ). Results No significant difference in the rate of sperm abnormality and MN formation in marrow PCE was found between the experimental groups and the control. Conclusion No obvious genetic damage caused by low power microwave radiation to the sperm anomaly and MN formation in marrow PCE of rats is found.
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OBJECTIVE:To study the correlation between the rate of inpatients using antibacterials and the cross-sectional rate of inpatients using antibacterials.METHODS:A cross sectional study was conducted on the use of antibacterials in 1040 inpatients between May 22 and May 23 in 2007.Besides,the discharge case histories of 100 cases were collected randomly for an analysis.RESULTS:Of the total 1 040 inpatients,510(49.04%)used antimicrobials.The rate of inpatients using antibacterials in comprehensive ICU took the lead at 100%,followed by pediatric department(86.05%)and the department of nephrology(84.62 %).The average rate of inpatients using antibacterials in surgery department was significantly higher than in the department of internal medicine(63.52% vs.33.94%).81% of the discharged cases used antibacterials.The irrational use of antibacterials manifested as improper timing of medication,prolonged use of antibacterials for prophylactic purpose etc.CONCLUSION:The proportion of the patients using antibacterials in descending order were inpatients,cross-sectional inpatients and outpatients.It is necessary to tighten control on the rational use of antimicrobials.
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OBJECTIVE:To prepare nicotine-?-CD inclusion compound and evaluate its quality.METHODS:The inclusion complex was prepared by saturated water solution method,and the preparation conditions were optimized by orthogonal test with the ratio of nicotine to?-CD(A),the inclusion temperature(B),the inclusion time(C)as factors and with the inclusion rate and the yield as indexes for evaluation.The formation of the inclusion complexes were verified by inclusion equilibrium constant analysis and its dissolution characteristics in vitro were investigated.The stability of nicotine-?-CD inclusion compound and the mixture of nicotine and?-CD were studied by conducting high-temperature,high humidity and high light tests.RESULTS:The optimum preparation conditions for the inclusion compound were established as:A was 1:3, B was 60℃and C was 2 hours.The inclusion rate of nicotine reached 65.28%;the yield was 79.55%,and the slow-release rate at 150 min was 92.26%.Under different temperature,humidity and high light conditions,the content of nicotine was always significantly higher in the inclusion complex than in the mixture.CONCLUSIONS:The inclusion technology is simple and the conditions were easily controllable,and the prepared nicotine-?-CD inclusion compound enjoys good stability and sustained-release property.
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OBJECTIVE:To prepare a rapid-disintegrated lozenge METHODS:The formula and technology were decided by taking the disintegrating time and dissolubility as standard RESULTS:The lozenge could completely disintegrate in 20s and the accumnlated dissolubility of the model drug was 99% after 5 minutes in phosphate buffer(pH=6 80) CONCLUSION:Using now available equipment,suitable excipients and workmanship can prepare a rapid-disintegrated lozenge
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0.05).But the female offspring in exposure group showed weaker capability of spatial location compared with that of male offspring in exposure group(P
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AIM: To establish the method of determining five anthraquinone components in Shaotangshang Gel(Rhizoma Coptidis,Cortex Phellodendri Chinensis,Radix et Rhizoma Rhei,etc.). METHODS:HPLC was used to determine emodin,chrysophanol,rhein,physcion,alone-emodin in Shaotangshang Gel.The separation was performed on Yilited-C_(18) Column with MeOH-phosphate acid(0.1%)(80∶20) as the modile phase,the flow rate was 1.0 mL/min and detection wavelength was set at 430 nm. RESULTS: The resolution and the linearity of the method were good with the average recoveries and RSD values of emoldin,chrysophanol,rhein,physcion,aloe-(emodin) of(98.0%),1.3%;97.1%,1.8%;97.8%,1.5%;97.4%,1.7%;96.7%,1.2% respectively.CONCLUSION: This method is sensitive,accurate and can be used for the quality control of Shaotangshang Gel.
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Objective To establish the computer controlled operant behavior test system for rats,and to explore the effects of prenatal exposure to low level methylmercury on the ability of learning and memory in rats Methods The Wistar rats were perorally perfused by 0,0.01,0.05,2.00 mg/(kg?d) methylmercury chloride(MMC) during the period from the 6th day to the 9th day after conception respectively.In every dose group,8 offspring aged 10 weeks were randomly selected to be tested by operant behavior test system.The operant performance was measured in automated nocturnal 15 hour session(16∶00~7∶00).The trial pragram Differential Reinforcement of High (DRH) rate and of low (DRL) rate was carried out by a double blind method.The DRH tests required observed animals to press levers frequently,while the DRL test required the subjects to respect a blocking interval after a reinforcement for pressing lever again. Results The performances scores of 3 exposure groups at doses of 0.01,0.05 and 2.00 mg/(kg?d) methylmercury were significantly lower than that of the control group( P
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OBJECTIVE:To establish the quality criteria of Kesuting oral liquid. METHODS: Qualitative identification of Herba Ephedrae,Folium Mori and Radix Et Rhizoma Glycyrrhizae was conducted using TLC method. The content of Baicalin was determined by HPLC in which the chromatographic separation was performed on Spherigel ODS C18(250mm?4.6mm,5?m) column with mobile phase consisted of methanol-0.4%phosphate solvent(52∶48) at a flow rate of 1.0 mL?min-1. The UV wavelength was set at 280 nm. RESULTS: The TLC spots of Herba Ephedrae,Folium Mori and Radix Et Rhizoma Glycyrrhizae were characteristic and obvious, and which can be used for qualitative identification. The linear range of Baicalin was 0.24~1.20 ?g (r=0.999 8) with a mean recovery rate of 98.72%(RSD=1.02%,n=6). CONCLUSION:The establish criteria are suitable for the quality control of Kesuting oral liquid.
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Objective To explore the maternal toxicity and offspring's neurobehavioral effects in Wistar rats induced by exposure to methylmercury during pregnancy. Methods Methylmercury were continuously orally perfued with different doses of 0.00, 0.01, 0.05 and 2.00 mg/(kg?d) to 52 pregnant Wistar rats during the 6th~9th day after conception. The toxicity to maternal rats was observed and general teratology test were carried out. The parameters of physical and neurobehavioral develpment at early stage of 205 offspring were measured and the operant behavior test of 32 offspring was carried out at the age of 10 weeks. The brain's morphology and the levels of monamine neurotransmitter were tested in 24 maternal rats after 5 weeks of the delivery and 24 offspring in 10 weeks old. Double blind randomized design was used in whole experiment. Results No maternal toxicity and offspring teratogenicity were observed. The increase of body weight and tail development of embryos in 3 exposure groups were slower than those of control group (P