To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Humans ; Isoenzymes ; genetics ; metabolism ; Liver Cirrhosis ; drug therapy ; enzymology ; genetics ; Male ; Mass Spectrometry ; Rats ; Rats, Wistar

Animals ; COS Cells ; Female ; Hepatitis B Core Antigens ; genetics ; Hepatitis B Surface Antigens ; genetics ; Hepatitis B Vaccines ; immunology ; Interleukin-12 ; genetics ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA ; immunology

OBJECTIVETo investigate the effect of the RNAi and the chemotherapy drugs nolatrxed on the expression of thymidylate synthase(TS) and the growth of the colorectal carcinoma LOVO cells.

METHODSThe siRNA was constructed targeting the human TS gene, and then transfected into the human colorectal cancer LOVO cells. RT-PCR and Western blot technique were used to observe the TS gene and protein expression levels, and MTT was used to detect cell proliferation after silencing the TS gene. In addition, siRNA and nolatrxed were applied to the LOVO cells to observe the TS protein expression and cell growth.

RESULTSTS siRNA significantly reduced the expression of TS gene and protein in LOVO cells, and inhibited cell growth. The IC50 value of LOVO cells was (1.46±0.25) μmol/L in TS siRNA combined with nolatrexed group, (6.81±0.31) μmol/L in the negative control group, and (6.47±0.43) μmol/L in the single nolatrexed group. After treatment of TS siRNA combined with nolatrexed on LOVO cells for 36 hours, the apoptosis index was higher than that in single TS siRNA and nolatrexed[(62.12±0.89)% vs.(21.56±0.67)% and(40.51±0.83)%, both P<0.05].

CONCLUSIONTS siRNA can partly suppress the expression of TS gene in LOVO cells, inhibit cell proliferation, promote cell apoptosis and enhance cell sensitivity to apoptosis induced by nolatrexd.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Quinazolines ; pharmacology ; RNA Interference ; Thymidylate Synthase ; genetics ; metabolism

No abstract available.

OBJECTIVETo investigate the predictive value of the ambulatory blood pressure monitoring parameters on left ventricular hypertrophy (LVH) and carotid artery intima-media thickness (IMT) in the hypertensives.

METHODSWe evaluated 147 hypertensive patients who were never treated regularly before. All patients underwent ultrasound examinations of the heart and the IMT of carotid arteries. We classified them as LVH group (n = 45) or no LVH group (n = 102), and as IMT increased group (n = 52) or no IMT increased group (n = 95). The record of medical history, physical examination and 24 h ambulatory blood pressure monitoring (ABPM) were performed in all the patients. The biochemical parameters such as blood lipids, glucose and so on were tested. Then the data comparison was made.

RESULTS(1) There were no significant differences in clinical manifestations and biochemical parameters between the LVH and no LVH groups (P > 0.05). Age (68.3 +/- 6.2) year vs (65.6 +/- 5.8) year, male 75.6% vs 66.7%, body mass index (24.1 +/- 4.1) vs (23.8 +/- 4.7) (kg/m(2)), diabetes mellitus and(or) impaired glucose tolerance 40.0% vs 38.2%, angina pectoris 42.3% vs 38.9%, cerebral vascular diseases 19.2% vs 15.7%, total cholesterol (5.40 +/- 1.42) vs (5.28 +/- 1.46) mmol/L, triglycerides (1.80 +/- 1.02) vs (1.74 +/- 1.08) mmol/L, low-density lipoprotein cholesterol (4.03 +/- 1.43) vs (4.06 +/- 1.48) mmol/L, high-density lipoprotein cholesterol (1.00 +/- 0.30) vs (0.99 +/- 0.26) mmol/L. (2) The parameters of ABPM in LVH group were higher than those in no LVH group. There were significant differences (P < 0.05) in 24 h mean systolic blood pressure (140.7 +/- 14.1) vs (128.3 +/- 12.3) mm Hg, 24 h mean diastolic blood pressure (86.4 +/- 8.9) vs (81.6 +/- 9.3) mm Hg, daytime mean systolic blood pressure (142.8 +/- 13.9) vs (130.9 +/- 11.1) mm Hg, daytime mean diastolic blood pressure (86.9 +/- 8.8) vs (83.4 +/- 9.0) mm Hg, nighttime mean systolic blood pressure (129.0 +/- 13.2) vs (114.6 +/- 11.4) mm Hg, nighttime mean diastolic blood pressure (77.2 +/- 9.4) vs (67.5 +/- 8.1) mm Hg, 24 h pulse pressure (54.2 +/- 10.2) vs (46.9 +/- 9.6) mm Hg, daytime pulse pressure (55.9 +/- 10.5) vs (47.5 +/- 9.1) mm Hg, nighttime pulse pressure (51.8 +/- 10.7) vs (47.1 +/- 8.7) mm Hg, 24 h systolic blood pressure variance (8.4 +/- 2.0) vs (7.2 +/- 1.9), 24 h diastolic blood pressure variance (9.5 +/- 2.2) vs (8.0 +/- 2.1), the non-dipper rhythm of ambulatory blood pressure 55.6% vs 25.5%. (3) There were also no significant differences in clinical manifestations between the IMT increased and no IMT increased group (P > 0.05). While there were significant differences between the IMT increased and no IMT increased group in those parameters of ABPM (P < 0.05).

CONCLUSIONThere were more LVH or IMT increased persons in the hypertensives whose ABPM parameters were abnormal.

Aged ; Aged, 80 and over ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Carotid Arteries ; diagnostic imaging ; pathology ; Female ; Humans ; Hypertension ; diagnostic imaging ; pathology ; physiopathology ; Hypertrophy, Left Ventricular ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Predictive Value of Tests ; Ultrasonography

Acute Disease ; Animals ; Ginkgo biloba ; Glutathione ; analysis ; Lung ; drug effects ; metabolism ; pathology ; Malondialdehyde ; analysis ; Paraquat ; toxicity ; Phytotherapy ; Plant Extracts ; therapeutic use ; Poisoning ; drug therapy ; Rats ; Superoxide Dismutase ; analysis ; Treatment Outcome

OBJECTIVE: To compare the iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) method with a fat-saturated T2-weighted (T2W) fast recovery fast spin-echo (FRFSE) imaging of the spine. MATERIALS AND METHODS: Images acquired at 3.0 Tesla (T) in 35 patients with different spine lesions using fat-saturated T2W FRFSE imaging were compared with T2W IDEAL FRFSE images. Signal-to-noise ratio (SNR)-efficiencies measurements were made in the vertebral bodies and spinal cord in the mid-sagittal plane or nearest to the mid-sagittal plane. Images were scored with the consensus of two experienced radiologists on a four-point grading scale for fat suppression and overall image quality. Statistical analysis of SNR-efficiency, fat suppression and image quality scores was performed with a paired Student's t test and Wilcoxon's signed rank test. RESULTS: Signal-to-noise ratio-efficiency for both vertebral body and spinal cord was higher with T2W IDEAL FRFSE imaging (p < 0.05) than with T2W FRFSE imaging. T2W IDEAL FRFSE demonstrated superior fat suppression (p < 0.01) and image quality (p < 0.01) compared to fat-saturated T2W FRFSE. CONCLUSION: As compared with fat-saturated T2W FRFSE, IDEAL can provide a higher image quality, higher SNR-efficiency, and consistent, robust and uniform fat suppression. T2W IDEAL FRFSE is a promising technique for MR imaging of the spine at 3.0T.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Signal-To-Noise Ratio ; Spinal Diseases/*diagnosis/pathology ; Statistics, Nonparametric

OBJECTIVETo investigate the expression changes of metabotropic glutamate receptor 5 (mGluR5) in neuropathic pain.

METHODSEighty-four adult male Sprague Dawley rats weighing 180-220 g were randomly divided into 7 groups (n = 12) : control group; S3, S7, and S14 groups: rats received the sham operation, the mechanical pain threshold was measured, and then the rats were decapitated and the ipsilateral lumbar spinal cord dorsal horn and dorsal root ganglion (DRG) samples were obtained on the 3rd, 7th, 14th postoperative day, respectively; C3, C7, and C14 groups: the chronic sciatic nerve constriction (CCI) model was established, the mechanical pain threshold was measured and the samples were obtained on the 3rd, 7th, 14th postoperative day, respectively. The expression level of mGluR5 mRNA and protein in the spinal cord and DRG were measured using the reverse transcriptase polymerase chain reaction and Western blot.

RESULTSIn the CCI group, the mechanical pain threshold in each observation day was significantly lower than in the sham operation group (P < 0.05). In the spinal cord, the expressions of mGluR5 mRNA and protein were significantly elevated in the C3 group than in the S3 and the control group (P < 0.05). On the 7th and the 14th postoperative day, no significant difference was found in the expression of mGluR5 mRNA and protein between CCI groups and the sham operation groups or the control group. No change was detected in DRG mRNA or protein.

CONCLUSIONmGluR5 is differentially expressed in spinal cord in response to neuropathic pain, which suggests that mGluR5 may be involved in the mechanism of neuropathic pain.

Animals ; Disease Models, Animal ; Ganglia, Spinal ; metabolism ; Male ; Neuralgia ; metabolism ; Pain Threshold ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; genetics ; metabolism ; Sciatic Neuropathy ; metabolism ; Spinal Cord ; metabolism

OBJECTIVETo evaluate bi-directional modulation effect of Chinese herbal medicine on immunol cells.

METHODTwo different active portions were isolated from Kudzuvine Root(Radix puerariae), one being the ethanol extraction and another the water extraction. Different concentration of these two different portions was studied by using PMA stimulated lymphocyte or eosinophil initiated chemiluminescence system.

RESULTWater extraction of Kudzuvine Root could enhance chemiluminescence concentration dependently whereas enthanol extraction of Kudzuvine Root inhibited the chemiluminescence significantly.

CONCLUSIONThe bi-directional regulation effect of Chinese herbal medicine can be found in the same herb, because of its efficacy of different active compounds.

Cell Separation ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Eosinophils ; drug effects ; Ethanol ; Humans ; Luminescent Measurements ; Lymphocytes ; drug effects ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Water

OBJECTIVETo compare the effect of the extracts from Decoction for resuscitation (DRE) and its component herbs on prostacyclin (PGI2), thromboxane A2 (TXA2) and nitric oxide (NO) release from rat vascular endothelial cells under hypoxia.

METHODAfter treatment with the extracts from DRE and its component herbs, the contents of 6-keto-prostaglandin F1alpha(6-keto-PGF1alpha), thromboxane B2 (TXB2) as well as nitrite (NO), which were degradation products of PGI2, TXA2 and NO respectively, in culture medium of rat vascular endothelial cells under hypoxia were measured with radioimmunoassay and Griess Reaction.

RESULTCompared with the control group, the results indicated that DRE, prepared licorice root extract (LE), dried ginger extract (GE), aconite root extract (AE), extracts of aconite root and prepared licorice root (ALE), extracts of aconite root and dried ginger (AGE) increased significantly the content of 6-keto-PGF1alpha and the ratio of 6-keto-PGF1alpha/TXB2, but had no effect on the content of TXB2 in culture medium of rat vascular endothelial cells under hypoxia. The content of 6-keto-PGF1alpha in the DRE group was higher than that in the groups of LE, GE, AE, ALE, AGE. The ratio of 6-keto-PGF1alpha/TXB2 in the DRE group was higher than that of the groups of GE, AE, ALE. Compared with the control group, DRE, LE, GE, AE, ALE, AGE increased significantly the content of NO2- in culture medium of rat vascular endothelial cells under hypoxia. Moreover, the content of NO2- in the DRE group was higher than that of the groups of GE, AE, ALE.

CONCLUSIONThe results suggested that DRE increased significantly the content of PGI2 and the ratio of PGI2/TXA2 as well as the content of NO. The effect of DRE on the parameters in culture medium of rat vascular endothelial cells under hypoxia was better than that of the extracts from its component herbs.

6-Ketoprostaglandin F1 alpha ; metabolism ; Aconitum ; chemistry ; Animals ; Aorta, Abdominal ; cytology ; Cell Hypoxia ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Endothelial Cells ; metabolism ; Ginger ; chemistry ; Glycyrrhiza uralensis ; chemistry ; Nitric Oxide ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Thromboxane B2 ; metabolism