Calcineurin ; metabolism ; Cardiovascular System ; growth & development ; metabolism ; Humans ; NFATC Transcription Factors ; metabolism ; Signal Transduction

This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.
Aconitine ; analogs & derivatives ; chemistry ; pharmacokinetics ; Animals ; Biological Availability ; Dogs ; Drug Stability ; Female ; Male

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

Adult ; Carcinogens ; Epoxy Compounds ; poisoning ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Multivariate Analysis ; Mutation ; drug effects ; Occupational Exposure ; analysis ; Regression Analysis ; Sister Chromatid Exchange ; drug effects

Objective To explore CT manifestion of multiple primary lung cancer (MPLC)and to improve the recognization of MPLC.Methods The CT manifestions of 12 cases with MPLC proved by pathology were retrospectively reviewed.Results All the 12 cases were double primary lung cancer.There were 24 lesions with 21 peripheral and 3 central,the average diameter was (2.2 ± 0.6)cm.Lesions located in contralateral lobes were in 2 patients,and located in ipsilateral lobes were in 10 patients,with 3 located in the same lobe and 7 in the different lobes.There were 7 cases of adenocarcinoma-adenocarcinoma,3 cases of squamous cell carci-noma-adenocarcinoma,1 case of squamous cell carcinoma-squamous cell carcinoma and 1 case of squamous cell carcinoma-carcinoid. 1 1 cases were metachronous and 1 case was synchronous.3 lesions were lump located at hilus of the lung,21 lesions were intrapul-monary nodules,showing masses with lobulated shape,spicules of margin,vascular convergence,vacuole and pleural indentation sign.Most foci displayed moderate intensity enhancement and homogeneous density in triphase enhanced scans,the CT value of le-sions on enhanced images ranged from 20-60 HU.Conclusion MPLC are synchronous and peripheral adenocarcinoma type,all of the lesions have typical CT features of primary lung cancer.

Obesity is an established risk factor for endometrial cancer. Leptin, a secreted protein of the ob gene by white adipose tissue, plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic cancer cells. However, a direct role for leptin in endometrial cancer has not been demonstrated. In the present study, the effect of leptin on the proliferation of Ishikawa endometrial cancer cells was investigated as well as the possible mechanism(s) underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors. The expression of leptin receptor (ObRb) in Ishikawa cells was detected by RT-PCR and Western blotting. The cells after serum starvation, were treated by leptin with various concentrations (0, 10, 50, 100, 150 ng/mL) for different durations (6, 12, 24 h). The effect of leptin treatment on cell proliferation was examined by MTT assay. Meanwhile, inhibitory effect of Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) inhibitor AG490 or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on the proliferation of Ishikawa cells induced by leptin was also studied. Ishikawa cells were treated with 100 ng/mL leptin for various periods (0, 20, 40, 60 min), and the levels of STAT3 phosphorylation and ERK1/2 phosphorylation were examined by Western blotting. The results showed that leptin induced the phosphorylation of STAT3 and the activation of ERK1/2 in a time- and dose-dependent manner in the Ishikawa endometrial cancer cells. Blocking STAT3 phosphorylation with the inhibitor AG490, or blocking ERK1/2 activation by the specific ERK1/2 kinase inhibitor, PD98059, abolished leptin-induced proliferation of Ishikawa cells. In addition, leptin was found to potently induce the invasion of endometrial cancer cells in a Matrigel invasion assay. Leptin-stimulated invasion was effectively blocked by pharmacological inhibitors of STAT3 (AG490) and ERK1/2 kinase (PD98059). These results suggested that leptin promotes endometrial cancer growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways and therefore blocking its action at the receptor level can be a rational therapeutic strategy.

Objective:To evaluate the clinical application of 64-slice spiral computer tomography pulmonary angiography (CTPA)in diagnosis of pulmonary embolism(PE).Methods:Sixty-two patients suspected of PE were examined by 64-slice spiral CTPA.The image findings combined with their clinical data were retrospectively analyzed.Results:Twenty-four of the 62 patients were confirmed to have PE by clinical data,laboratory examination and follow-up examination.64-slice spiral CTPA discovered 152 involved branches in the 24 PE patients,including 4 branches in left and right pulmonary trunk,52 in lobar pulmonary arteries,82 in segmental pulmonary arteries,and 14 in subsegmental arteries.Four types of PE were detected in our group,including eccentric filling defect in 58 branches,central filling defect in 49 branches,total occlusion of the pulmonary arteries in 21 branches,and mural embolism of host artery in 24 branches.The diagnosis accuracy of 64-slice spiral CTPA in the present group of patients was 100%,with no missed diagnosis and misdiagnosis.Besides,64-slice spiral CTPA could reflect the location,morphology,involvement and degrees of PE.Conclusion:64-slice spiral CTPA is a rapid,accurate and non-invasive diagnostic approach for PE.It is the first choice in clinical screening of PE and may serve as a gold standard for diagnosis of pulmonary embolism.

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 evaluate the screening for consecutive patient population with suspected Coronary atherosclerotic heart disease (CAD) by noninvasive 64-slice computed tomographic coronary angiography.

METHODS2082 consecutive symptomatic subjects (1218 males, 868 female, with, mean age of 58.2 years old) with suspected CAD underwent MSCT studies. And 218 patients underwent coronary angiography within 7 days. Invasive coronary angiography was taken as golden standard for calculations of diagnostic accuracy.

RESULTSOf 2082 subjects, 2063 (99.1%) were assessable, the mean examination duration was 4 minutes. Compared with CAG, the sensitivity of CTA to diagnose significant stenosis was 97.4%, specificity 90.1%, positive predictive value (PPV) 91.8% and negative predictive value (NPV) 96.8%.

CONCLUSIONSixty-four-MSCT is accurate, convenient, noninvasive, safe means to coronary angiography with economic benefit. Thus, it can be considered as a valuable noninvasive screening technique.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Tomography, Spiral Computed ; methods

OBJECTIVETo discuss the indication and outcome of volar Barton fracture treated by nonoperative method.

METHODSTwenty-three cases of volar Barton fracture treated by closed method included 8 male and 15 female with an average age of 52.2 years,ranging 16 to 84 years. Among them, 16 cases showed subluxation of the carpus (15 cases were Mehara type I ,1 case was Mehara type III) by radiographs except the other 7 cases. By the experimentation in 32 cadavers, the injury of dorsal radiocarpal ligament was supposed to be a very important cause of the subluxation of the radiocarpal joint. The criteria of Pattee and Thompson was used to evaluate the outcome of the treatment.

RESULTSTwenty-three patients were followed up for 7 to 70 months, 11 cases gained satisfactory outcome (1 case as excellent, 10 cases as good), 12 cases gained unsatisfactory outcome (5 cases as fair, 7 cases as poor). Five of 7 cases without the subluxation of the carpus by the radiographs gained satisfactory outcome. Six of 16 cases with the subluxation of the carpus gained satisfactory outcome.

CONCLUSION(1) The result of reduction will influence the outcome of the treatment, the step on articular surface shoud be less than 2 mm after reduction. (2) Nonoperative method is recommended if volar Barton fractures are not associated with subluxation of the carpus. (3) Nonoperative method can be tried first if the fractures associated with the subluxation of the carpus, however operation is recommended when the articular step is more than 2 mm.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Casts, Surgical ; Female ; Follow-Up Studies ; Fractures, Bone ; therapy ; Hand Bones ; injuries ; Humans ; Male ; Middle Aged ; Musculoskeletal Manipulations ; Treatment Outcome