A sensitive, rapid and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) method with pre-column derivatization was developed for the simultaneous determination of erdosteine and its thiol-containing active metabolite in human plasma. Paracetamol and captopril were chosen as the internal standard of erdosteine and its active metabolite, respectively. Aliquots of 100 microL plasma sample were derivatized by 2-bromine-3'-methoxy acetophenone, then separated on an Agilent XDB-C18 (50 mm x 4.6 mm ID, 1.8 microm) column using 0.1% formic acid methanol--0.1% formic acid 5 mmol x L(-1) ammonium acetate as mobile phase, in a gradient mode. Detection of erdosteine and its active metabolite were achieved by ESI MS/MS in the positive ion mode. The linear calibration curves for erdosteine and its active metabolite were obtained in the concentration ranges of 5-3 000 ng x mL(-1) and 5-10 000 ng x mL(-1), respectively. The lower limit of quantification of erdosteine and its active metabolite were both 5.00 ng x mL(-1). The pharmacokinetic results of erdosteine and its thiol-containing active metabolite showed that the area under curve (AUC) of the thiol-containing active metabolite was 6.2 times of that of erdosteine after a single oral dose of 600 mg erdosteine tables in 32 healthy volunteers, The mean residence time (MRT) of the thiol-containing active metabolite was (7.51 +/- 0.788) h, which provided a pharmacokinetic basis for the rational dosage regimen.
Administration, Oral ; Area Under Curve ; Chromatography, Liquid ; Female ; Humans ; Male ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; Thioglycolates ; administration & dosage ; blood ; metabolism ; pharmacokinetics ; Thiophenes ; administration & dosage ; blood ; metabolism ; pharmacokinetics

OBJECTIVETo observe the clinical effect and safety of circumcision stapler in the treatment of phimosis and redundant prepuce.

METHODSWe treated 120 patients with redundant prepuce or phimosis using circumcision stapler and another 60 by conventional dorsal-incision circumcision. We observed intraoperative blood loss, operation time, postoperative pain, wound healing time, cosmetic appearance of the penis, and postoperative complications and compared them between the two groups of patients.

RESULTSStapler circumcision showed obvious advantages over the conventional method in intraoperative blood loss ([2. 3 ± 1. 3] vs [15.6 ± 2.9] ml), operation time ([7.1 ± 1.4] vs [22.6 ± 4.6] min), wound healing time ([12.0 ± 2.9] as [16.3 ± 3. 1] d), postoperative pain score (1. 9 ± 1. 3 vs 5. 2 ± 1. 7), incision edema, and cosmetic appearance of the penis (all P <0. 05). Besides, stapler circumcision exempted the patients from stitch-removal pain. However, the incidence rate of postoperative local ecchymosis was significantly higher in the circumcision stapler group than in the conventional circumcision group (20. 8% vs 8. 3% , P <0. 05).

CONCLUSIONCircumcision stapler, with its advantages of easier manipulation, shorter operation time, better cosmetic penile appearance, less pain, and fewer complications, is superior to conventional circumcision in the treatment of phimosis and redundant prepuce.

Blood Loss, Surgical ; Circumcision, Male ; instrumentation ; methods ; Ecchymosis ; etiology ; Humans ; Male ; Pain, Postoperative ; Penis ; abnormalities ; Phimosis ; therapy ; Postoperative Complications ; Postoperative Period ; Surgical Staplers ; adverse effects ; Wound Healing

This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm x 4.6 mm, 5 μm) column using a mobile phase of methanol and 5 mmol x L(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3] + on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng x mL(-1) for ivabradine, and 0.050 0 to 20.0 ng x mL(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.
Benzazepines ; blood ; Chromatography, High Pressure Liquid ; Delayed-Action Preparations ; Humans ; Isotope Labeling ; standards ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry

A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.7 mL · min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng · mL(-1) for sivelestat, and 2.50-1000 ng · mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng · mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers.
Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Glycine ; analogs & derivatives ; blood ; Humans ; Inosine Monophosphate ; blood ; Reproducibility of Results ; Sulfonamides ; blood ; Tandem Mass Spectrometry

With the significant and continuous growth of the research and application of complementary and alternative medicine (CAM) all over the world, the demand for medical information services has been increasing correspondingly. However, the barriers of accessing and utilizing non-English literature, and the barrier of language have blocked English speaking clinicians and researchers of CAM from obtaining high quality and authoritative medical evidence from the non-English medical resources. This article, with introducing the UCLA Information Center for East-West Integrative Medicine, will demonstrate a new collaborative mode of integrative medicine information service between China and the US, and discuss the perceived challenges.
China ; Complementary Therapies ; Information Services ; Information Storage and Retrieval ; Integrative Medicine ; Language ; United States

Objective To determine the expression of membrane-bound B lymphocyte stimulator (BLyS) protein and its mRNA in vitro of peripheral blood mononuclear cells (PBMCs) from individuals with systemic lupus erythematosus (SLE),and to investigate the role of interferon-?(IFN-?) on the expression of BLyS.Methods PBMCs were obtained from 25 SLE patients (mean age of 31+14) and 20 healthy volunteers (mean age of 28?10).They were randomized into IFN-?(5 ng/ml) group and control group.PBMCs were col- lected at 0,6,12 and 24 h for BLyS mRNA assessment using semi-quantitative reverse transcription-PCR (RT-PCR).PBMCs were also collected at 72 h for membrane-bound BLyS protein detection using flow cy- tometry (FACS) and direct immunofluorescence.Results①The expression of BLyS mRNA and membrane- bound protein in PBMCs was significantly higher in individuals with SLE compared with healthy controls (P＜0.05);②IFN-?enhanced BLyS mRNA expression in PBMCs in both healthy controls and SLE patients,with the greatest effect at 6 h (stimulated vs unstimulated,0.42?0.19 vs 0.25?0.14,P＜0.01;0.59?0.28 vs 0.44?0.21,P＜0.01 );③IFN-?also increased the expression of membrane-bound BLyS protein in both healthy con- trols and individuals with SLE (FACs,mean fluorescence intensity,4.5+3.0 vs 3.7~2.6,P

BACKGROUND: Adipose-derived stem cells (ADSCs) represent one of the promising cell sources for myocardial regeneration due to their easy accessibility and efficacy in the improvement of cardiac function following myocardial infarction. However, previously reported studies on the underlying mechanism of ADSCs-mediated cardioprotective effect mainly focused on the ADSCs cultured at room air. OBJECTIVE: To test the paracrine actions and anti-apoptotic effect of ADSCs under hypoxic conditions. METHODS: After isolation and culture, neonatal rat myocardial cells were injured by hydrogen peroxide and co-cultured with rat ADSCs under normoxia and hypoxia (10% O2) conditions. Ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in the cell pellet and levels of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and basic fibroblast growth factor (bFGF) were tested by ELISA. Expression of apoptotic proteins Bax and Bcl-2 were determined by western blot. RESULTS AND CONCLUSION: GSH/GSSG, VEGF, IGF-1, and bFGF were decreased in neonatal rat myocardial cells injured by hydrogen peroxide. ADSCs significantly attenuated hydrogen peroxide-induced myocardial apoptosis by increasing the ratio of GSH/GSSG and the secretion of VEGF, IGF-1 and bFGF. ADSCs also down-regulated Bax expression and up-regulated Bcl-2 expression. To conclude, hypoxic conditions can enhance the anti-apoptosis and cardioprotective effects of ADSCs through the paracrine mechanism.

Objective To evaluate the advantages and short term clinical results of arthroscopic release with radiofrequeney vaporization for knee joint stiffness.Methods Arthroscopic release with ra- diofrequency vaporization was done in 32 cases with knee joint stiffness resulted from various causes be- tween January 2002 and June 2005.According to degree of stiffness,32 cases were divided into three groups,ie,Group A(18 cases with suprapatellar bursa adhesions)treated with confectioning at suprapa- tellar bursa and lateral grooves;Group B(eight cases with joint compartment adhesions)managed with debridement at suprapatellar bursa and lateral groove and intereondyloid fossa,bending the knee with pressure and abscising the adhesion part in the joint compartment with radiofrequency vaporization;and Group C(six cases with most part of the joint adhered)treated by making small incision at the lateral or medial upper pole of the patellar as well as a space at the suprapatellar bursa by blunt dissection when it was difficult to insert arthroscope.After that,release combined with massage manipulation and thorough hemostasis by radiofrequency vaporization were carried out.There was no drainage after operation.Pas- sive and active flexion and extension exercises with pressure began two days after operation.Results Pre-operative limitation of flexion was 35?-75?that was increased to 115?-125?three weeks after opera- tion,with mean improvement of 78?in Group A.Pre-operative limitation of flexion was 40?-60?that was increased to 95?-120?three weeks after operation,with mean improvement of 72?in Group B.Pre-opera- tive limitation of flexion was 25?-45?that was increased to 90?-110?three weeks after operation,with mean improvement of 64?in Group C.No haematocele occurred postoperatively,with only slight swelling of the knee.Conclusion Arthroscopic release with radiofrequency vaporization for knee joint stiffness is characterized by less bleeding,minor trauma and reliable release and can be applicable especially for the eases with only adhesion at suprapatellar bursa,lateral groove or joint compartment.

BACKGROUNDRhabdomyosarcoma (RMS) is an uncommon malignancy of the breast. The aim of this study was to summarize its clinicopathologic features and biological behavior.

METHODSFive primary or secondary breast RMSs were collected. Their clinicopathological characteristics and all published literature about breast RMS were reviewed. Immunohistochemical study of desmin, myogenic differentiation 1 (MyoD1), myogenin, leukocyte common antigen (LCA), vimentin, cytokeratin (AE1/AE3), E-cadherin, neuron specific enolase (NSE), CD99, chorioallantoic membrane 5.2 (CAM5.2) and epithelial membrane antigen (EMA) expression were performed.

RESULTSThe five patients were all female with ages ranging from 16 to 46 years old (mean, 30 years). Three were metastatic breast RMSs, two embryonal and one solid variant alveolar, with the primary tumor sites the right labium majus, left nasal meatus and nasopharynx, respectively. The other two, one embryonal and one alveolar, were primaries. Grossly, the surgical specimens revealed round or oval, well-demarcated but nonencapsulated masses. Their cut surfaces consisted of homogeneous grayish yellow or white tissue. Microscopically, most tumor cells were poorly differentiated small round, oval or small polygons with eosinophilic cytoplasm. All cases were positive for vimentin, desmin, MyoD1 and myogenin. One embryonal RMS also had a few cells with perinuclear staining of AE1/AE3. The other markers were negative.

CONCLUSIONSAlthough primary or metastatic RMS in breast was almost confined to young adolescent females, our cases suggested that it can also happen to the middle-aged women. Embryonal RMS has a certain metastatic potential. MyoD1 and myogenin are two useful markers when making differential diagnosis. Axillary lymph node status and age may play a role in the prognosis of primary breast RMS patients.

Adolescent ; Adult ; Breast Neoplasms ; diagnosis ; metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Rhabdomyosarcoma ; diagnosis ; metabolism ; Young Adult