The usage of Chinese materia medica (CMM) is a key scientific problem on its safety and efficacy in clinical application. The daily administration time is one of the main issues and contents of CMM usage, which is directly related to the clinical efficacy. But, it is hardly to find the research aiming at the rationality of daily administration times of CMM. To achieve new breakthrough in research on daily administration times of CMM, one research presumption is put forward for the first time and it is the evaluation pattern for the rationality of daily administration times of CMM based on pharmacodynamics-pharmacokinetics. The further purpose is to supply innovative and practical research thought and method for scientifically confirming the daily administration times of CMM and enhancing its clinical efficacy.

OBJECTIVEEndothelial apoptosis plays an important role in the initiation of atherosclerosis. It would be useful to clarify whether activation of non-neuronal muscarinic receptor (NNMR) could prevent endothelial apoptosis and atherosclerosis. We investigated the effects of NNMR activation on regulating rat aortic endothelial cells (RAECs) apoptosis induced by homocysteine, an independent risk factor of atherosclerosis, and further studied its molecular mechanism.

METHODSRAECs were incubated using homocysteine at the concentration of 2.7 mmol/L for 36 h. RAECs were also pre-treated with carbachol or arecoline to examine their effects. RT-PCR was used to assess changes in the gene expression related to cell apoptosis.

RESULTSIncubation of RAECs with homocysteine at the concentration of 2.7 mmol/L resulted in morphologic changes, such as cellular shrinkage, membrane blebbing, chromatin condensation and margination. These could be attenuated by pretreatment with carbachol and arecoline at the concentration of 10 micromol/L for 12 h. Homocysteine induced apoptosis in RAECs and the molecular mechanisms were associated with the regulation of fas, fas-L and caspase-8 in the death receptor pathway, bcl-2, bcl-xL and bax in the mitochondrial pathway, caspase-12 in the endoplasmic reticulum pathway and caspase-3, caspase-6 and p53 as downstream effectors. Carbachol and arecoline attenuated the effects of homocysteine on genes in the death receptor pathway, in the mitochondrial pathway and in the downstream pathway. Atropine could reverse all of the effects of arecoline.

CONCLUSIONActivation of NNMR by carbacol and arecoline inhibits homocysteine-induced endothelial cell apoptosis mainly through regulation of death receptor pathway, mitochondrial pathway and downstream effectors.

Animals ; Aorta ; cytology ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Arecoline ; Carbachol ; Cell Cycle ; Endoplasmic Reticulum ; metabolism ; Endothelial Cells ; cytology ; drug effects ; Homocysteine ; adverse effects ; Mitochondria ; metabolism ; Rats ; Receptors, Muscarinic ; metabolism

Based on the structure and function of acupoint and in association of the definition and principle of sensor, the acupoint is the sensitive element, being sensitive to the physical stimulation with acupuncture and moxibustion and sensitively responded to the disorders; the acupoint is the sensing element, transforming the changes of the acupoint information via the complicated internet conduction, integration and regulation, so as to generate the effects on organic body; the acupoint is the conversion element, transforming every irritation into the bioelectric signal or optical signal so that the organic body could recognize it. Therefore, the acupoint is regarded as the sensor of information in the organic body.
Acupuncture Points ; Electrophysiological Phenomena ; Humans ; Meridians

Objective:To summarize our experience in perioperative anesthetic management for fulminant hepatic failure (FHF)patients receiving liver transplantation.Methods:The clinical anesthetic data of 48 FHF patients receiving orthotopic liver transplantations(OLT)from January 2006 to January 2007 were retrospectively analyzed,and the anesthetic management expe- rience was summarized.General anesthesia was applied;the hemodynamics was monitored during the operation and doses of adrenaline and phenylephrine were adjusted according to the monitoring results.Blood samples were obtained before operation, before anheptic,30 min after anhepatic phase,5 min before neohepatic phase,and 5 min,30 min and 60 min after neohepatic phase for blood gas and electrolyte analysis and for determination of coagulation function;the drugs were subsequently adjusted according to analysis results.Results:All the 48 patient underwent successful anesthetic management and there was no death dur- ing opearation.The average blood loss during operation was(5 219?478)ml.Mild alkalosis,hypokalemia,hyponatrium,and hy- pocalcemia were present before operations,pH,BE and HCO_3~- were obviously reduced 30 min after anhepatic phase and in- creased 60 min after neohepatic phase.Kalemia was obviously increased 30 min following anhepatic phase and began to increase 60 min following neohepatic phase.Calium concentration was decreased at the end of preanhepatic phase(P

Objective To investigate the correlation between asymmetric dimethylarginine (AD-MA) and endothelial dysfunction in patients with uremia.Methods Uremic patients who did not receive hemodialysis were defined as A group (n =40) ; uremic patients who had received hemodialysis were divided into B group (n =45) ;healthy people were defined as C group (n =20) ;and chronic kidney disease (stage 2 ～ 4) patients were defined as D group (n =20).The diameter of intima-media thickness,and endothelium-dependent or independent dilation (EDD or EID) of radial artery in right forearm were detected with diasonography.The levels of ADMA were determined by high-performance liquid chromatography.Results Compared to C group,the levels of ADMA in A,B and D groups were significantly increased [C:(0.78 ±0.19) μmol/L,A:(1.51 ±0.16) μ mol/L,B:(1.13 ±0.14) μmol/L,D:(0.92 ±0.11) μmol/L; P ＜0.05].Compared to A group,the levels of ADMA were significantly decreased in B group (P ＜0.05).EDD and EID were decreased significantly in A,B and D groups compared to C group [EDD:C:(13.52±1.73)％ vs A:(7.32 ±0.54)％,B:(9.02 ±0.86)％,D:(10.13 ±1.25)％,P ＜0.05;EID:C:(14.45±1.85)％ vsA:(10.37 ±1.51)％,B:(9.54±1.39)％,D:(11.17±1.56)％,P ＜0.05].EDD in B group was significantly lower than A group (P ＜0.05).In group A,a negative correlation was found between EDD and the level of ADMA (r =-0.81,P =0.020).Conclusions ADMA level was significantly increased in uremic patients.A close correlation existed between ADMA and endothelial dysfunction of radial artery.

Objective To compare the effects of biphasic square waveform (BSW) with low or high energy on external defibrillation.Method Adult swine model of closed chest ventricular fibrillation induced by electricity was established.Eighteen swine,weighing (30?3.3) kg were randomly divided into three groups:50-50-50 J group (n=6),30-50-75 J group (n=6),120-150-200 J (n=6).After three minutes of ventricular fibrillation without treatment,the pigs in the three groups were defibrillated accordance to the above sequences. Results 30 J BSW didn't succed to external defibrillate.The first defibrillation successful rate of 50 J and 120 J BSW was 5/6.The total defibrillation successful rate of every group was 100%.All pigs quickly had spontaneous circulation after defibrillation and survived more than 24 hours.ST-T change of low-energy was less than that of high-energy.After resuscitation,myocardial function decreased,but there had not significant differences between groups.Conclusions In the study,30J BSW could not reach successful defibrillation,and 50 J and 120 J BSW had similar defibrillation efficacy.The ideal energy of BSW external defibrillation was 50 J.

Objective To investigate the changes of vital signs and the damage of important organs in dog progressive circulatory failures induced by soman.Method Seven male dogs,weighing(12～15)kg,were injected intramuscularly 1/3 LD sornan(1 LD=10μg/kg)per ten minutes.The moan blood pressure decreased to (40～45)mmHg was defined as circulatory failure.The changes of heart rate,blood pressure.and hemodynamic parameters were evaluated by an eight-channel direct-witing oscillograph,blood gas,pH value,electrolyte,and the damage of important organs were observed before and after sornan injection.Statistical analysis of the data was performed using the self control t test with the SAS 6.12 Software Program.Results In anesthetized dogs intoxicated with sornan,the circulatory failure was characterized by the significant decreases in blood pressure,heart rate and hemodymrnic parameters(P<0.05).Partial pressure of oxygen was less than 60 mmHg,saturation of oxygen Was less than 90% and partial pressure of carbon dioxide was greater than 50 mmHg in arterial blood of the dog model.These results showed mix respiratory failure occurred during intermittent positive pressure.Significant metabolic acidosis was induced by soman[pH(7.345±0.064)vs.(6.956±0.022),P<0.01].The concentralion of sodium ion and chloride ion in blood were changed gently.The concentrations of GTP,GOT,Cr,BUN,CK-MB and LDH were increased significantly(P<0.05),which showed multiple important organs including liver,kidney and heart were damaged by sornan.Conclusions The severe progressive circulatory failure induced by cholinesterase inhibitor sornan leads to the darnage of vital signs and important organs significantly.

A novel drug delivery system combining oral fast dissolving film with sodium deoxycholate/phospholipid mixed micelles was prepared to increase the absorption of cucurbitacin B that is a poor aqueous solubility substance. Encapsulation efficiency, particle size, zeta potential, polydispersity coefficient, investigated the morphology, disintegration time of oral fast dissolving film and the pharmacodynamic properties of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles before and after solidified in mice were evaluated and compared. The oral fast dissolving film prepared in this study showed a homogeneous pale yellow and could completely disintegrated in the 30 s. It could meet the requirements of rapidly disintegrating fully. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles loaded in oral fast dissolving film were (43.36 +/- 2.12)%, (108.82 +/- 5.2) nm, (-34.18 +/- 1.07) mV, 0.088 +/- 0.012, respectively. The encapsulation efficiency, particle size, zeta potential, polydispersity coefficient of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles in solution were (41.26 +/- 2.22)%, (181.82 +/- 4.48) nm, (-30.67 +/- 0.81) mV, 0.092 +/- 0.012, respectively. The difference of pharmacodynamics among film of cucurbitacin B-loaded micelles, cucurbitacin B-loaded micelles and free cucurbitacin B in vivo was compared. Solubility of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles has also been greatly improved. The tumor inhibition rate of cucurbitacin B loaded in sodium deoxycholate/phospholipid-mixed micelles was significantly improved and did not change significantly before and after solidified. These showed that the sodium deoxycholate/phospholipid-mixed micelles could enhance the antitumor activities of cucurbitacin B and the stability of cucurbitacin B sodium deoxycholate/phospholipid-mixed micelles was improved significantly after solidified by oral fast dissolving film technology without pharmacodynamic properties changed significantly.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; Cell Line, Tumor ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Humans ; Male ; Mice ; Neoplasms ; drug therapy ; Phospholipids ; chemistry ; Solubility ; Triterpenes ; administration & dosage ; chemistry

OBJECTIVETo observe the antiviral efficacy of Ganneng Dripping Pill (GDP) in treating patients with chronic hepatitis B.

METHODSEighty-four patients of chronic hepatitis B with positive HBV-DNA, HBsAg, and HBeAg were randomly assigned to 2 groups, the treated group (56 patients) treated with GDP and the control group (28 patients) treated with lamivudine. The therapeutic course for both groups was 6 months. The negative conversion rate of HBeAg and HBV-DNA, changes of liver function, symptoms and physical signs in patients were observed before and after treatment.

RESULTSIn the treated group, the negative conversion rate of HBV-DNA and HBeAg was 54.0% (27/50) and 30.0% (15/50) respectively, and the ALT normalizing rate was 80.0% (40/50), while those were 67.86% (19/28), 21.8% (6/28) and 75.0% (21/28) respectively in the control group, showing no significant difference between the two groups (all P > 0.05). However, the AST normalizing rate was 97.96% (48/49) in the treated group, higher than that in the control group (48.0%, 12/25, P < 0.01); and the clinical symptoms, especially the poor appetite, lassitude, gastric distention and yellow urine, were improved more significantly in the treated group than those in the control group (P <0.05 or P < 0.01).

CONCLUSIONGDP has a favorable short-term effect on chronic hepatitis B, it could effectively inhibit HBV replication and improve the liver function, symptoms and signs in patients.

Adult ; DNA, Viral ; biosynthesis ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Male ; Middle Aged ; Phytotherapy ; Treatment Outcome ; Virus Replication ; drug effects

OBJECTIVEHigh altitude pulmonary edema (HAPE), a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers.

METHODSA complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay (ELISA).

RESULTSEight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin(alpha1-AT), Haptoglobin(Hp), apolipoprotein A-1 (apoA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV (apoA-IV) decreased significantly. The variation of alpha1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis.

CONCLUSIONSIt is well known that Hp, alpha1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, alpha1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.

Altitude ; Biomarkers ; blood ; Blood Proteins ; metabolism ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Humans ; Peptide Mapping ; Proteome ; Pulmonary Edema ; blood ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization