In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.
Animals ; Brain Ischemia ; drug therapy ; Chemical and Drug Induced Liver Injury ; drug therapy ; Humans ; Inflammation ; drug therapy ; Medicine, Chinese Traditional ; Nervous System Diseases ; drug therapy

Objective To observe tigecycline (TGC),minocycline (MH)and polymyxin B (PB)in vitro antibacterial activity of pan-resistant Acinetobacter baumannii (PDR-Ab)for clinical treatment,provide the basis for infection control.Methods Collected 76 patients’clinical specimens used for no repeat count of isolation and identification with pan-resistant Acineto-bacter baumannii in Shaanxi Provincial People’s Hospital from October 2013 to March 2013.Used tigecycline,minocycline and polymyxin B to do susceptibility testing with disk diffusion method (KB).Results 76 pan-resistant Acinetobacter bau-mannii ,sensitive to the rate for tigecycline and polymyxin B were 100% sensitivity rate of minocycline and intermediary rates were 67.11%,27.63%.Conclusion Tigecycline,minocycline and polymyxin B for the Pan-resistant Acinetobacter bau-mannii had good in vitro antibacterial activity.It provide a reference for clinical pan-resistant Acinetobacter baumannii infec-tions caused by diseases treatment.

Objective To establish cell strain expressing the genes of HIV vpr and mutant HIV vpr-FS, and to explore cell apoptosis ability by HIV Vpr and Vpr-FS. Methods The recombinant plasmids were constructed by cloning HIV vpr and HIV vpr-FS genes into the eukaryotic expression vector pcDNA3.1respectively. To determine the primary structures of HIV vpr and HIV vpr-FS, plasmids were cleaved by restriction enzymes. After the plasmids were transfected into HeLa cells by liposome, the HeLa cells were selected with G418 selective medium, mRNA expression of HIV vpr or HIV vpr-FS of transfected cells was detected by RT-PCR, and Vpr and Vpr-FS protein expression were detected by Western blot assay respectively. The DNA content and the percentage of apoptosis in HeLa HIV vpr cell, HeLa HIV vpr-FS cell and HeLa pcDNA3.1 cell were monitored by flow cytometry and the DNA fragmentation was analyzed by agarose gel electrophoresis. Results BamH Ⅰ and Hind Ⅲ cleavaged products of pcDNA3.1-vpr and pcDNA3.1-vpr-Fincluded 342 bp length fragments suggesting that the length of DNA sequence containing HIV vpr (HIV vpr-FS) within pcDNA3.1 was the same as theoretical length. The HeLa cells transfected by pcDNA3.1-vpr or pcDNA3, l-vpr-FS and selected with G418 could express HIV vpr or HIV vpr-FS by RT-PCR, and express HIV Vpr or HIV Vpr-FS protein by Western blot. The results of flow cytometry and DNA fragmentation showed that there was significant different in the number of apoptotic cells between HeLa HIV vpr cell and HeLa HIV vpr-FS cell, but the difference between HeLa HIV vpr-FS cell and control group was not obvious. Conclusion Recombinant plasmids pcDNA3.1-vpr and pcDNA3. 1-vpr-FS were constructed successfully, and the cell strain expressing HIV Vpr and HIV Vpr-FS proteins was established. The HIV Vpr could induce host cell apoptosis, while the mutant of Vpr did not or weakened this ability. This study provides foundation for further study on HIV vpr gene.

A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.
Administration, Oral ; Animals ; Biological Availability ; Biomedical Research ; methods ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Liver ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Temperature

OBJECTIVETo observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction.

METHODMale Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed.

RESULTSpleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01).

CONCLUSIONThe formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.

Animals ; Brain ; drug effects ; enzymology ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Calmodulin ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Intestines ; drug effects ; enzymology ; metabolism ; Male ; Qi ; Rats ; Rats, Wistar ; Spleen ; drug effects ; Splenic Diseases ; drug therapy ; enzymology ; genetics ; metabolism

OBJECTIVETo study the effects of high-density lipoprotein (HDL) and oxidized high-density lipoprotein (ox-HDL) on the expression of ATP-binding cassette transporter A1 (ABCAl) and cholesterol efflux in human umbilical vein endothelial cells (HUVECs).

METHODSIn vitro cultured HUVECs were incubated in the presence of 100 microg/ml HDL or 100 microg/ml ox-HDL for 24 h, using PBS as the negative control. ABCA1 mRNA level and cholesterol efflux rate were determined using RT-PCR and a liquid scintillator, respectively.

RESULTSHDL and ox-HDL significantly elevated the level of ABCA1 mRNA by 58% and 23% relative to the control level, respectively (P<0.05). The cholesterol efflux rate in ox-HDL group was significantly lower than that in HDL group (P<0.01).

CONCLUSIONHDL increases ABCAl expression and cholesterol efflux in HUVECs. Oxidative modification of HDL decrease cholesterol efflux by inhibiting the expression of ABCAl, suggesting a possible mechanism of ox-HDL in the pathogenesis of atherosclerosis.

ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; genetics ; metabolism ; Cells, Cultured ; Cholesterol ; metabolism ; Endothelial Cells ; metabolism ; Humans ; Lipoproteins, HDL ; metabolism ; physiology ; Umbilical Veins ; cytology

AIMTo study the effect of antiparallel phosphorothioate triplex-forming oligonucleotide (apsTFO) matching with the shear stress response element (SSRE) of tissue factor (TF) gene promoter region on the expression of TF in endothelial cells (ECs) of rat common carotid artery stenosis.

METHODSThe model of common carotid artery middle segment stenosis was established by silica gel pipe loop ligation in SD rats. The mRNA expression and protein synthesis of TF, early growth response-1 (Egr-1) and specificity protein 1 (Sp1) were measured by in situ hybridization (ISH) and immunohistochemistry (IHC) technique. GT21-apsTFO, GT20-apsTFO, GT20-psTFO and FITC-labeled apsTFO, matching with the SSRE of TF gene promoter region, were designed, and intravenously injected into rats at 0.5 h before operation. TFO was detected 4 h after the operation, and the mRNA expression and protein synthesis of TF, Egr-1 and Sp1 were detected 6 h after the operation.

RESULTSThere were much fluorescence in vascular tissue, especially in the nuclear of ECs 4.5 h after the injection of apsTFO. The mRNA expression and protein synthesis of TF reduced by 22% - 23% with injection of GT20-apsTFO 6.5 h after stenosis (P < 0.01) and by 10% - 11% with GT21-apsTFO at the same time (P < 0.05). The inhibition by GT20-apsTFO was stronger than that of the GT21-apsTFO (P < 0.05). The expression of TF was not inhibited by the GT20-psTFO (P > 0.05). The mRNA expression and protein synthesis of Egr-1 and Sp1 did not change in the rat treated with GT20-apsTFO, GT20-psTFO and GT21-apsTFO (P > 0.05).

CONCLUSIONapsTFO could mero-inhibit the expression of TF gene but could not change the expression of Egr-1 and Sp1 protein.

Animals ; Carotid Stenosis ; genetics ; metabolism ; pathology ; Early Growth Response Protein 1 ; genetics ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; pathology ; Gene Expression ; drug effects ; Immunohistochemistry ; In Situ Hybridization ; Male ; Oligonucleotides ; chemical synthesis ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shear Strength ; Sp1 Transcription Factor ; genetics ; metabolism ; Stress, Mechanical ; Thromboplastin ; genetics ; metabolism

High-density lipoprotein (HDL), an abundant plasma lipoprotein, has been thought to be anti-inflammatory in both health and infectious diseases. It binds lipopolysaccharide (LPS) and neutralizes its bioactivity. The present study aimed to investigate the potential role of HDL, which was separated from human plasma, in LPS-induced acute lung injury in mice. Kunming mice (18-22 g) were treated with either HDL (70 mg/kg body weight, via tail vein) or saline 30 min after LPS administration (10 mg/kg body weight, intraperitoneally) and were decapitated 6 h after LPS challenge. The arterial blood was collected and analyzed for blood gas variables (PaO(2), pH, and PaCO(2)). The bronchoalveolar lavage fluid (BALF) samples were analyzed for total protein concentration, lactate dehydrogenase (LDH) activity, and white blood cell (WBC) count. The lung samples were taken for histopathological evaluation and for determination of lung wet-to-dry weight ratio (W/D), malondialdehyde (MDA) content, myeloperoxidase (MPO) activity and tumor necrosis factor α (TNF-α) content. Arterial blood gas analysis showed that after LPS challenge, HDL-treated mice exhibited a higher PaO(2), and pH, but a lower PaCO(2) than HDL-untreated ones (P<0.01). LPS-induced increases in total protein concentration, WBC number and LDH activity in BALF were significantly attenuated in HDL-treated mice (P<0.01). HDL treatment also resulted in a significant protection of lung tissues against LPS-induced acute lung injury via decreasing W/D ratio, MPO activity, MDA content, and the content of the pro-inflammatory cytokine TNF-α (P<0.05, P<0.01). Histological examination revealed that HDL treatment resulted in significantly lower scores of acute lung injury induced by LPS, with reduced hemorrhage, intra-alveolar edema and neutrophilic infiltration (P<0.01). It is suggested that HDL plays a protective role in attenuating LPS-induced acute lung injury in mice.
Acute Lung Injury ; chemically induced ; therapy ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Inflammation ; metabolism ; Leukocyte Count ; Lipopolysaccharides ; adverse effects ; Lipoproteins, HDL ; pharmacology ; Lung ; pathology ; Malondialdehyde ; metabolism ; Mice ; Peroxidase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVELong term glucocorticoid (prednisolone) treatment on human growth hormone (hGH) secretion in children and adolescents and to investigate the effectiveness and safety of the recombinant human growth hormone (rhGH) treatment.

METHODSTwelve patients (age: 10.4∓1.2 years) who were treated in Peking Union Medical College Hospital from September 1999 to November 2009 were enrolled in this study. All of them had taken prednisolone with a dose of 0.5∓2.0 mg/(kg.d) for 6~18 months. Two different hGH stimulating tests was done and their growth and development was evaluated at regular intervals. Seven patients were given rhGH with a dose of 0.1 U/(kg.d) for 6~12 months to improve their growth and development after half a year of prednisolone withdrawal when their disease conditions were improved.

RESULTSThe growth speed of these 12 children decreased significantly during prednisolone treatment compared with before prednisolone treatment (1.2∓0.3cm/year vs.3.7∓1.2 cm/year,P12 months than those with a 6~12 months course (P0.05). The growth speed of seven children who received rhGH therapy for half a year were increased from 2.2∓0.1cm/year to 7.8∓0.5cm/year (P<0.05), and then to 6.9∓0.4cm/year one year later.

CONCLUSIONSThe long-term glucocorticoid treatment can decrease the hGH secretion, and thus leads to short stature and agenesis. However, the rhGH replacement can safely and effectively improve growth and development in these children after their primary diseases are improved and glucocorticoids are withdrawn.

Adolescent ; Child ; Female ; Follow-Up Studies ; Glucocorticoids ; adverse effects ; therapeutic use ; Human Growth Hormone ; secretion ; therapeutic use ; Humans ; Male ; Recombinant Proteins ; therapeutic use ; Treatment Outcome