With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.
Enzymes ; chemistry ; Humans ; Inactivation, Metabolic ; Mass Spectrometry ; Membrane Transport Proteins ; chemistry ; Pharmacokinetics ; Proteomics

Objective To observe Meissner's corpuscles in prepuces of different shapes and ages. Methods The Meissner's corpuscles were detected with immunohistochemical stain in 204 prepuce sam- ples of different shapes and ages (3-59 years),and the density of Meissner's corpuscles in every sample was obtained as well.The difference of Meissner's corpuscle densities between phimosis and redundant pre- puce,and correlation between Meissner's corpuscle densities and ages were analyzed with Chi-square test and linear regression,respectively.Results The density of Meissner's corpuscles in redundant prepuce has begun to increase since infancy and reached the peak at the age about 15 years.No significant difference in densities of Meissner's corpuscles between phimosis and redundant prepuce was observed till the age of 20 years,and then there was a trend of disappearance of Meissner's corpuscles in redundant prepuce.A signifi- cantly negative correlation between the densities of Meissner's corpuscles and ages was revealed in redundant prepuce (r=-0.236,P=0.009),whereas an insignificantly positive correlation between the densities of Meissner's corpuscles and ages was shown in phimosis (r=0.193,P=0.084).Conclusions The den- sities of Meissner's corpuscles in redundant prepuce develop synchronically with genital differentiation and accord with the status of sexual function in adult males.The persistent high level of Meissner's corpuscles in adult phimosis might be a mechanism of physiological compensation.

Objective To study the effect of injured podocytes on glomerular maturation and its underlying mechanism in neonatal mice.Methods Single i.p.injection with puromycin aminonucleoside (PA,0.1 mg/g BW) was given to ICR neonatal mice at day 1 after birth (1 dpp). Littermates injected with normal saline (NS) were used as control.Animals were examined for urine protein,blood pressure,kidney weight/body weight (KW/BW),renal histology at 2,4,8,12, 30,60 and 90 dpp (n=6～9 for each group).Immunohistochemistry and quantitative RT-PCR were performed to examine the expression of WT-1,CD31,VEGF,Flk-1,Ang-1,Ang-2,Tie-1 and Tie-2.Results Mice with PA injection had lower kidney weight and body weight at all time points as well as lower KW/BW at 4,8,12 dpp when compared with NS controls.Electron microscopy revealed nearly complete foot process effacement and segmental microvillous transformation as early as 1 day after PA injection.PA-injected kidneys showed fewer capillary loops and decreased maturation index as well as less CD31-positive endothelium in cortical glomeruli at 12 dpp. Glomerular mesangial injury and developing glomerulosclerosis along with proteinuria were noted in PA-injected kidneys starting from 30 dpp.Significantly increased systolic blood pressure was detected at 60 dpp in PA mice.Compared with NS injection,PA injection significantly induced decreased mRNA expression of Flk-1 and Tie-2 as well as increased expression of Ang-1,without obvious changes of VEGF at 2 dpp.Conclusions Podocytes in neonatal kidney of ICR mice are susceptible to PA. Such podocyte injury can alter the expression of VEGF and angiopoietin system in glomeruli,leading to abnormal development of glomerular capillaries,and subsequent proteinuria,hypertension and glomerulosclerosis.

OBJECTIVETo compare therapeutic effects between suspine rotation and flexion manipulation for treating lumbar disc herniation.

METHODSFrom December 2008 to January 2011, 134 patients with lumbar disc herniation were treated, including 74 males and 60 females,ranging in age from 17 to 67 years,33 patients with age over 50 years old. According to diagnosis the ladder of the 9 cases bulging type, 74 hernia type, 51 cases free type. The patients were randomly divided into treatment group ( 69 cases) and control group (65 cases). All the patients were treated with the three-dimensional computer-controlled traction therapeutic apparatus,with continued traction for 20 minutes. After traction, flexion manipulation and rotat-ing manipulation were respectively adopted in treatment group and control group (on alternate days one time, 3 times as a course of treatment). The symptoms and signs (including back pain and discomfort, lower limb pain and numbness, powerless urination and defecation,numbness in perineum, straight-leg raising degree,ability of lower extremity walking,work and live) of patients were observed after treatment.

RESULTSAll patients were followed up for 0.5 to 6 months with an average of 1.1 months. After treatment, the symptoms and signs of patients have significantly improved (P < 0.01), but the symptomes of powerless urination and defecation,numbness in perineum was not improved obviously (P>0.05). Forty-two of 69 patients in treatment group got excellent result, moderate in 20, poor in 7; Twenty of 65 patients in control group got excellent result, moderate in 25,poor in 20.

CONCLUSIONThe whole effect of lumbar backwards rotation manipulation is more satisfactory than flexsion manipulation for treating lumbar intervertebral disc herniation. But spinning force and times should be noticed.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Intervertebral Disc Displacement ; physiopathology ; therapy ; Lumbar Vertebrae ; physiopathology ; Male ; Manipulation, Orthopedic ; methods ; Middle Aged ; Recovery of Function ; Rotation ; Young Adult

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

OBJECTIVETo observe the relation of androgen levels and atherosclerosis (AS) in elderly males.

METHODSBoth carotid arteries and arteries of lower extremity were examined with Doppler ultrasonography. Those with arteriosclerosis and much atheromatous plaque were designated as case group, and those with normal results formed control group. Total testosterone (TT), free testosterone (FT) and estradiol (E2) were measure by radioimmunoassay, HDL-C, LDL-C, TC and TG were assayed by colorimetry, vascular endothelium growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1) were determined by ELISA.

RESULTFT was significantly lower in case group than in control group (P<0.01), no differences were found in TT, E2. HDL-C in control group was higher than that in case group (P<0.01), TC and TG were higher in case group than those in control group (P<0.05). HDL-C was correlated positively and LDL-C was negatively with FT level, while both TC and TG in case group had negative relation with FT. VEGF was higher in case group (P<0.05), and it had negative relation with FT in both groups. TNF-alpha and IL-6 were significantly higher in case group (P<0.05), and they had negative relation with FT. sICAM-1 was significantly lower in control group than it in case group (P<0.01).

CONCLUSIONThe normal androgen levels, especially FT, have beneficial effect in AS development in elderly males. Low FT level may be an independent risk factor in AS development.

Aged ; Androgens ; blood ; Atherosclerosis ; blood ; diagnostic imaging ; Carotid Arteries ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Risk Factors ; Testosterone ; blood ; Ultrasonography, Doppler

OBJECTIVETo explore the clinical and physical factors that might give rise to radiation-induced esophagitis in three-dimensional conformal radiotherapy for non-small cell lung cancer.

METHODSTo collect the clinical and physical records and follow-up information of 106 NSCLC patients without undergoing surgery in our hospital. χ(2) test, linear tendency test and analysis of variance were employed to analyze the relationship between occurrence of radiation-induced esophagitis and clinical and physical treatment. Logistic analysis was also used for multivariate analysis.

RESULTSAmong the 47 cases of radiation-induced esophagitis, 31 cases were of grade I, 11 of grade II, 5 of grade III, and with a total occurrence rate of 44.3% (47/106). Radiation-induced esophagitis was correlated with Karnofsky scores, radiation sensitization and tumor location (χ(2) = 11.30, 8.45, 7.67, P < 0.05). Radiation-induced esophagitis was correlated with the length of irradiated esophagus and average dose of irradiated esophagus (F = 20.82, 83.08, P < 0.001). With the increase of the irradiated volume percentage from V20, V30, V40 up to V50, the occurrence rate of radiation-induced esophagitis was also increased, almost with a linear trend (P < 0.05). Application of all the above factors to logistic model indicated that radiation sensitization,length of irradiated esophagus, average dose and V50 were all statistically significant foactors in the occurrence of radiation-induced esophagitis (OR = 0.321, 2.850, 7.307 and 8.558, P < 0.05).

CONCLUSIONSRadiation sensitization,length of irradiated esophagus, average dose of irradiated esophagus and V50 are independent factors in the occurrence of radiation-induced esophagitis. V50 is of greater importance in the judgement of occurrence of radiation-induced esophagitis.

Aged ; Carcinoma, Non-Small-Cell Lung ; radiotherapy ; Esophagitis ; etiology ; Esophagus ; pathology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; radiotherapy ; Male ; Middle Aged ; Multivariate Analysis ; Radiation Injuries ; etiology ; Radiation Tolerance ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; methods ; Retrospective Studies

AIMTo study the relationship of neurotoxicity of 6-hydroxydopamine (6-OHDA) and the function of glutamate transporter.

METHODSUsing in vivo microdialysis together with high performance liquid chromatography (HPLC) to detect the alteration of glutamate in the striatum and extracellular fluid of the PC12 cell. The rate of apoptosis and the activity of PC12 cells are read in a flow cytometer and a photometer for enzyme-labeled assays. The function of glutamate transporter is decided by detecting the ability of L-[3H]-glutamate uptake.

RESULTS6-OHDA was shown to induce apoptosis and decrease the activity of PC12 cells. Increased release of glutamate was also found in PC12 cells and the injured striatum of the PD rats. But glutamate uptake in PC12 cells and rat striatum synaptosomes are inhibited obviously.

CONCLUSIONThe neurotoxicity of 6-hydroxydopamine is associated with declined function of glutamate transporters, which may be one important pathogenesis mechanisms of Parkinson's disease.

Amino Acid Transport System X-AG ; drug effects ; Animals ; Apoptosis ; drug effects ; Corpus Striatum ; metabolism ; Glutamic Acid ; metabolism ; Male ; Oxidopamine ; toxicity ; PC12 Cells ; Parkinson Disease ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUNDLeft ventricular aneurysm (LVA) is one of the serious complications after acute myocardial infarction. We attempted to evaluate the preliminary efficacy of LVA repair combined with epicardial radiofrequency ablation for ventricular arrhythmia during off-pump coronary artery bypass grafting (OPCAB).

METHODSFrom June 2009 to April 2011, 31 patients with LVA had angina symptoms and ventricular arrhythmia. In all patients, circular and cross-shaped radiofrequency epicardial ablations were performed using unipolar ablation pen along the border between the aneurysm wall and normal cardiac tissue and in the central zone of the aneurysms, followed by a linear placation of ventricular aneurysms on beating heart.

RESULTSAll the patients showed complete recovery. The average number of grafted vessels was 2.7 ± 1.3. Intraoperative examinations revealed that the ventricular arrhythmia was effectively controlled by radiofrequency ablation. All cases had been followed up for one year. Holter monitoring revealed a significant reduction in ventricular arrhythmias (P < 0.05). Echocardiography showed significant increase in left ventricular ejection fraction (P < 0.05) and decrease in left ventricular end-diastolic diameter (P < 0.05).

CONCLUSIONSFor patients with ventricular aneurysm and preoperative malignant arrhythmia, aneurysm repair plus epicardial radiofrequency ablation in OPCAB was found to be an effective and feasible therapeutic technique. However, medium- to long-term therapeutic efficacy of this method remains to be determined by future studies and observations.

Aged ; Arrhythmias, Cardiac ; surgery ; Catheter Ablation ; Coronary Artery Bypass, Off-Pump ; Female ; Heart Aneurysm ; complications ; Heart Ventricles ; surgery ; Humans ; Male ; Middle Aged ; Pericardium ; surgery