1.Intestinal absorption and renal excretion mediated by transporters and the relationship with drug-drug interaction.
Acta Pharmaceutica Sinica 2010;45(9):1089-94
Drug-drug interaction (DDI) is referred as the changes of physical and chemical properties, as well as the pharmacokinetics or pharmacodynamics of drugs administered simultaneously or consecutively. The clinical results for drug-drug interaction could be divided into good clinical efficacy and adverse interaction. With the kinds of drugs increasing every year, new drug resistances spring up frequently. This phenomenon makes drug combination increased so that the drug interaction, especially the adverse interaction emerged. The mechanisms of in vivo drug-drug interaction are relevant to a number of factors, including drug-metabolizing enzyme systems and membrane transporters. Recent studies have revealed the important role played by transporters in drug absorption, distribution, metabolism and elimination. In order to avoid severe side effects mediated by transporters and to promote rational combination in clinics, the mechanisms of intestinal absorption and renal excretion mediated by transporters are reviewed.
2.Interactions of intestinal H~+/oligopeptide cotransporter PEPT1 with drugs and regulation by affecting factors
Chinese Journal of Clinical Pharmacology and Therapeutics 2000;0(03):-
H+/oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell. transports dipeptide/tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as ?-lactam antibiotics,angiotensin-converting enzyme inhibitor (ACEI) and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1. PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract. With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPT1 expression in membrane, their functional activities and substrate affinities. Some associated mechanism of regulation have been studied. As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery. Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.
3.Experimental study of treasure pill pretreatment on Fas and Fas L of neonatal rats hypoxic brain injury
Yan ZHANG ; Kexin HUANG ; Hongxi MA
Chinese Journal of Immunology 2014;(8):1051-1054
To investigate the effect of treasure pill pretreatment on hypoxic brain injury Fas and Fas L protein expression.Methods:Newborn 7d Wistar rats 200,male or female,were randomly divided into 5 groups(n=40):normal control group, model group 1h hypoxia(Ⅰm-12h,Ⅰm-24h,Ⅰm-48h,Ⅰm-72h),model group 4h hypoxia(Ⅳm-12h,Ⅳm-24h,Ⅳm-48h,Ⅳm-72h), hypoxic 1h treasure pill treatment group(ⅠT-14h,ⅠT-24h,ⅠT-48h,ⅠT-72h),hypoxic 4h treasure pill treatment group(ⅣT-14h,ⅣT-24 h ,ⅣT-48 h ,ⅣT-72 h ).The newborn Wistar rats were placed in hypoxia chamber of 8%O2+92%N2 ( V/V) for establishment the model of neonatal rats with hypoxia.Before modeling continuous 7 d once-daily oral administration of saline and treasure pill , during hypoxia also dose ,after hypoxia 12 h,24 h,48 h,72 h animals were sacrificed blood and brain tissues tested.By ELISA to detect the protein levels of Fas and Fas L in serum and brain tissue;by immunohistochemistry method to detect the expression of Fas and Fas L in rat brain tissue.Results:Compared with normal control group ,other four groups the protein content and protein expression of Fas and Fas L are in the 12h time points after hypoxic significantly increased ,and 24 h time point that pealed at statistically significant ( P<0.01 ) ,model group was significantly higher than the treatment group at each time point ;model groups in 48 h,72 h time point the protein expression and protein content of Fas and Fas L was less than 12 h time point but still significantly higher than the control group ( P<0.01 );treasure pill groups in 48 h,72 h time point the protein expression and protein content of Fas and Fas L was less than 12 h time point ,and slightly higher than the normal control group ( P<0.05 ).Conclusion: Treasures pill can cut hypoxic brain damage in rats,the positive expression of Fas and Fas L protein content and protein ,and thus the hypoxic brain injury has a protective effect.
4.A prospective randomized study of TOT and TVT procedure for female intrinsic sphincter deficiency(ISD)
Weiyu ZHANG ; Qi WANG ; Xiaopeng ZHANG ; Hao HU ; Kexin XU
Chinese Journal of Urology 2016;37(10):777-780
Objective To compare the outcomes of TOT and TVT procedure treating female intrinsic sphincter deficiency (ISD).Methods From May 2010 to September 2015,42 stress urinary incontinence (SUI) patients whose abdominal leak point pressure was less than 60 cmH2O were enrolled in this study.Thirty-five patients were followed up.The mean age was (56.8 ±10.5) years,with a range of 30-80 years.The mean history was(10.5 ± 9.1)years,with a range of 4 months to 30 years,with 26 (74.3%) of them being postmenopausal,5 (14.3%) having a history of pelvic surgery,and no pelvic organ prolapsed or hormone replacement.All of them were randomly divided into 2 groups to undergo either TVT operation (13 cases) or TOT operation (22 cases).The baseline characteristics of the two groups including age,length of history,urodynamic parameters and scale scores showed no significant difference.The scales including urinary incontinence severity score (UISS),detrusor instability score (DIS),Quality of Life Scale Evaluation (I-QOL),lower urinary tract symptoms affect score (UDI-6) were used.The outcomes between TVT group and TOT group were compared.Result After procedure,patients in TVT group got a lower UISS score than TOT group(17.2 ± 2.2 vs.17.7 ± 3.1),and their severity of urinary incontinence improved significantly (P < 0.05).Patients from TVT group got a lower DIS score than TOT group (12.6 ± 4.2 vs.14.2 ± 3.5),and their detrusor instability symptoms improved more significantly (P < 0.05).Patients from TVT group got a higher I-QOL score than TOT group(17.5 ± 14.5 vs.16.1 ± 13.0),and their quality of life improved more significantly (P < 0.05).Patients from TVT group got a lower UDI-6 score than TOT group (10.1 ± 3.0 vs.11.2 ± 3.4),and their lower urinary tract symptoms improved more significantly (P < 0.05).Conclusion Urinary incontinence of female ISD patients were improved greater by TVT than TOT procedure.
5.Surgical treatment for epididymal obstructive azoospermia
Guoxi ZHANG ; Xiaofeng WANG ; Wenjun BAI ; Kexin XU
Chinese Journal of Urology 2010;31(11):782-785
Objective To discuss the clinical outcomes of surgical treatment on epididymal obstructive azoospermia (EOA) and the factors affecting clinical results. Methods The clinical data of 51 EOA patients who underwent single layer longitudinal 2-suture intussusception vasoepididymostomy (LIVE) were retrospectively analyzed. The months of follow up, mean level of sperm count per ejaculate and percentage of grade A sperm were collected. Patency and pregnancy rates were recorded during followups. Results A total of 51 men were taken scrotal exploration. Sperms were bilaterally or unilaterally present in epididymal fluid in 49 cases, including 1 case had sperm in one side of the epididymal fluid and the contralateral vasal fluid. No sperm was found in epididymis in 2 cases. Bilateral and unilateral LIVE were performed in 48 cases. 44 were followed for more than 6 months and 39 for more than 1 year. Sperm was present in ejaculate in 32 of cases, the overall patency rates were 72.7%. The mean sperm count was (24±23) × 106 per ejaculate. Grade A sperm was present in the ejaculate in 28 cases with a mean levels of (12± 11.2)%. A total of 10 cases achieved pregnancy.Pregnancy was achieved only when the site of anastomosis was at cauda epididymis. Conclusions Loupe-assisted LIVE, with lower cost and simplified surgical procedure, could achieve optimistic patency outcomes and pregnancy results. Data of this paper also suggested that it should be taken into account that pregnant outcome was related to the site of anastomosis.
7.Effect of xiongbitong capsule on releasing of vasoactive substances of rats with myocardial ischemia
Taiguo ZHANG ; Kexin TANG ; Shumei ZHAO ; Keqing TANG ; Li TIAN
Chinese Journal of Tissue Engineering Research 2005;9(31):206-207
BACKGROUND: By detecting vasoactive substances of experimental rats with myocardial ischemia, pharmacological mechanism of xiongbitong was studied in this research.OBJECTIVE: To observe the effect of xiongbitong capsule on release of vasoactive substances of rats with myocardial ischemia.DESIGN: A completely randomized controlled study.SETTING: Department of Health, Weifang Medical College; Department of Physiology, Department of Immunity and Pathogenic Biology, Department of Internal Medicine, Weifang College of Traditional Chinese Medicine.MATERIALS: The experiment had been carried out in the Laboratory of Physiology of Weifang Medical College from January 2003 to June 2003.The cleansing grade 30 Wistar rats, 6-8 months, of either sex, were randomly divided into three groups:namely, normal control group, model control group and model group of treatment with xiongbitong capsule.METHODS: [1] At 12 hours before making model, rats of model treatment group were irrigated with xiongbitong capsule 2.5 g/kg (a capsule contents dried medicinal herbs 1 g), which consists of tuckahoe, rhizoma, immature bitter orange, exocarpium citri grandis, rhizoma acori tatarinowi, moxibustion, dalbergia wood, mongolian snakegourd, curcuma root, red sage root,root of donopsis pilosula, ilyturf root, ophiopogon, polygala root, date kernel etc., and dissolved in 4 mL physiological saline. AT ten hours after making model, they were irrigated with same dose once more. The rats of normal control group and model control group were irrigated with the same dose physiological saline at the same time. One hour after the first irrigation, the animal models of myocardial ischemia of rats of model control group and model treatment group were established by injecting vitriol isoprenaline according to 10 mg/kg subcutaneously. [2] Endothelin (ET), calcitonin generelates peptide (CGRP), 6-keto-prostaglandin Fl alpha (6-keto-PGF1α) and thromboxane B2 (TXB2) in the plasma of rats were detected according to the explanation of Institute of Beijing East Asia Immune Technique. [3] The analysis of variance and q test were used for comparing between groups.MAIN OUTCOME MEASURES: Contents of vasoactive substances in the plasma of rats in each experimental group.RESULTS: The date of all thirty rats was entered the final analysis. [1]The contents of (TXB2) and ET, TXB2/6-Keto-PGF1α, ET/CGRP: Compared with the model group, the normal control group and model treatment group reduced obviously (q=2.99-9.87, P < 0.05-0.01). [2] The contents of 6-Ke-to-PGF1α and CGRP: Compared with the model group, the normal control group and model treatment group increased obviously [(603.3 ±90.6),(190.0±64.2) ng/L; (560.7±111.1), (174.9±41.4) ng/L; (380.4±705),(114.9±36.4) ng/L, q=3.88-7.64, P < 0.05-0.01].CONCLUSION: Xiongbitong capsule may suppress unusual release of vasoactive material at myocardial ischemia area obviously, increase the content of expanding the blood vessel material, and correct out-of-balance of content of important TXB2, 6-keto-PGF1α, XTB and CGRP in the body.
8.Significance of preoperative urodynamics for clinical diagnosis of female patients with stress urinary incontinence
Weiyu ZHANG ; Hao HU ; Qi WANG ; Jingwen CHEN ; Kexin XU
Journal of Peking University(Health Sciences) 2016;48(4):655-658
Objective:To investigate the impact of preoperative urodynamic study on the diagnosis and treatment for female patients with clinical diagnosis of stress urinary incontinence by studying their diag-nosis and treatment database,and to assess its clinical significance of urodynamic study.Methods:From April 2011 to December 2015,196 female patients diagnosed clinically with stress urinary incontinence underwent preoperative urodynamics study,after excluding pelvic organ prolapse.The preoperative uro-dynamic data of these 196 cases were analyzed and the clinical significance of urodynamics on differential diagnosis and treatment for the female patients with stress urinary incontinence was evaluated.Results:In this study,23 cases (11.73%)changed or amended their diagnoses by the urodynamic study,which were inconsistent with the previous clinical diagnoses concluded by the symptoms,physical examinations, and lab tests.A total of 10 cases underwent a different surgery or conservative treatment instead of the original treatment according to urodynamic study.Of them,3 were diagnosed as detrusor overactive and undertook conservative treatment;3 were diagnosed as bladder outlet obstruction plus stress urinary in-continence and were undertaken the transurethral resection of the bladder neck (TURBN)plus tension free vaginal tape (TVT);2 were diagnosed as bladder outlet obstruction plus stress urinary incontinence and were undertaken TURBN alone;1 was diagnosed as bladder outlet obstruction plus stress urinary in-continence and was undertaken TURBN plus tension free vaginal tape obturator (TOT);1 was found no abnormal bladder function turned out to be interstitial cystitis and went for a bladder instillation of drug. The changed treatments avoided the risk of dysuria or residual urine increased after operation due to inap-propriate surgical methods.Conclusion:In order to make a correct diagnosis and suitable treatment for female patients with stress urinary incontinences,the preoperative urodynamic study is necessary besides detailed medical history,physical examination,and laboratory tests.With the help of the urodynamic study,the concomitant diseases of patients with stress urinary incontinence may be detected,the individualized treatment regimen can be developed,and more importantly,the inappropriate surgical de-cision can be avoided.
9.Design principle and development tendency of artificial lumbar disc prosthesis
Kexin DONG ; Dechun MA ; Qiuju LI ; Li ZHANG ; Lei LI
Chinese Journal of Tissue Engineering Research 2014;(26):4254-4259
BACKGROUND:Artificial lumbar disc replacement is a new choice for the treatment of degenerative disc disease, and preserves lumbar vertebra’s biomechanical characteristics during pain elimination. The design of the prosthesis structure and material needs further study and validation. OBJECTIVE:To review the structure and material types of presently designed artificial lumbar discs, then to discuss the trends in the optimization design of prosthesis. METHODS:The PubMed database, China National Knowledge Infrastructure database and Chinese BioMedical Literature Database were searched for related articles concerning artificial lumbar disc and type and biomechanics of nucleus pulposus prosthesis material published from January 2005 to February 2013 by the first author. Key words were“artificial lumbar disc, principle of prosthesis design, structure, material, clinical trials”in Chinese and“artificial lumbar disc, total disc replacement, structure, material, clinical trial”in English. Repetitive and old studies were excluded. 135 articles were found, but 36 articles were included for review. RESULTS AND CONCLUSION:At present, the materials for intervertebral discs include cobalt-chromium al oy, ceramics, stainless steel, titanium al oy and ultrahigh molecular weight polyethylene. Artificial lumbar disc is commonly made by different materials. Bryan prosthesis is most commonly used in the clinic. Three-dimensional finite element analysis, in vitro trial and clinical studies verified its good biomechanical property. The successful rate of replacement was high. Nucleus prosthesis contains prefabricated type and situ polymerization type, and obtains smal injury, so it is a hot focus in present study, but it cannot achieve biomechanical function of human nucleus pulposus. To dig novel material is a future direction for designing individual prosthesis. The prosthetic structure and biomaterial design experience constant improvement and development. This study combines latest study trend and prospects the development of biomimetic design, material improvement, the optimization design of prosthesis and assisted devices.
10.Relation of personality to life satisfaction and depression in visual artists
Yanqing LIU ; Kexin WANG ; Guannan ZHANG ; Yixin ZHOU ; Mingjie ZHOU
Chinese Mental Health Journal 2015;(10):785-789
Objective:To explore the linear and nonlinear relation of personality to life satisfaction and de-pression in visual artists.Methods:Totally 132 visual artists were recruited,most of them focused on painting, sculpture and photography.The Mini International Personality Item Pool-Five-Factor Model Measure (Mini-IPIP), the Satisfaction with Life Scale (SWLS)and the Center for Epidemiological Studies Depression Scale (CES-D) were adopted to all subjects.Results:The Mini-IPIP neuroticismscores had positive predictability to CES-D scores (β=0.41),while the scores of agreeableness,conscientiousnessand extraversionhad negative pre-dictability to CES-D scores(β=-0.27,-0.23,-0.19).Only conscientiousnessscores had positive predictabil-ity (β = 0.25 ) to SWLS scores in terms of linear relationship between personality traits and life satisfaction.Meanwhile,both'neuroticism'and conscientiousnessscores had U curve relationship with SWLS scores (β=0.32,0.22)after linear effects were controlled.Conclusion:It suggests that personality traits in visual artists could explain depression symptoms and life satisfaction.However,pattern between personality and life satis-faction may be more complex.