Ghrelin improves endothelial function and reduces blood pressure in Ang II-induced hypertensive mice: Role of AMPK.

BACKGROUND: Endothelial dysfunction is a major pathophysiology observed in hypertension. Ghrelin, a key regulator of metabolism, has been shown to play protective roles in cardiovascular system. However, whether it has the effect of improving endothelial function and lowering blood pressure in Ang II-induced hypertensive mice remains unclear. METHODS: In this study, hypertension was induced by continuous infusion of Ang II with a subcutaneous osmotic pumps and ghrelin (30 µg/kg/day) was intraperitoneal injection for 4 weeks. Acetylcholine-induced endothelium-dependent relaxation in aortae was measured on wire myograph and superoxide production in mouse aortae was assessed by fluorescence imaging. RESULTS: We found that ghrelin had protective effects on Ang II-induced hypertension by inhibiting oxidative stress, increasing NO production, improving endothelial function, and lowering blood pressure. Furthermore, ghrelin activated AMPK signaling in Ang II-induced hypertension, leading to inhibition of oxidative stress. Compound C, a specific inhibitor of AMPK, reversed the protective effects of ghrelin on the reduction of oxidative stress, the improvement of endothelial function and the reduction of blood pressure. CONCLUSIONS: our findings indicated that ghrelin protected against Ang II-induced hypertension by improving endothelial function and lowering blood pressure partly through activating AMPK signaling. Thus, ghrelin may be a valuable therapeutic strategy for hypertension.

Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel.

BACKGROUND: Curcumin (Cur) is a bioactive dietary polyphenol of turmeric with various biological activities against several cancers. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Intestinal cholesterol homeostasis is associated with CRC. Chemotherapy for CRC is related to varied adverse effects. Therefore, natural products with anti-cancer properties represent a potential strategy for primary prevention of CRC. METHODS: The present study used Cur as a therapeutic approach against CRC using the Caco-2 cell line. The cells were treated with different concentrations of Cur for different duration of time and then the proliferation ability of cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2'-deoxyuridine assays. Oil red O staining and cholesterol assay kit were used to evaluate cellular lipid content and cholesterol outward transportation. Finally, the protein expressions of cholesterol transport-related protein and signal transduction molecules were assessed using Western blot assay. RESULTS: Cur inhibited cell proliferation in Caco-2 cells in a dose- and time-dependent manner by activating the transient receptor potential cation channel subfamily A member 1 (TRPA1) channel. Activation of the TRPA1 channel led to increased intracellular calcium, peroxisome proliferator-activated receptor gamma (PPARγ) upregulation, and the subsequent downregulation of the specificity protein-1 (SP-1)/sterol regulatory element-binding protein-2 (SREBP-2)/Niemann-Pick C1-like 1 (NPC1L1) signaling pathway-related proteins, and finally reduced cholesterol absorption in Caco-2 cells. CONCLUSIONS: Cur inhibits cell proliferation and reduces cholesterol absorption in Caco-2 cells through the Ca2+/PPARγ/SP-1/SREBP-2/NPC1L1 signaling by activating the TRPA1 channel, suggesting that Cur can be used as a dietary supplement for the primary prevention of CRC. In Caco-2 cells, Cur first stimulates calcium influx by activating the TRPA1 channel, further upregulates PPARγ and downregulates SP-1/SREBP-2/NPC1L1 signaling pathway, and finally inhibits the absorption of cholesterol. TRPA1, transient receptor potential cation channel subfamily A member 1; NPC1L1, Niemann-Pick C1-like 1; PPARγ, peroxisome proliferator-activated receptor gamma; SP-1, specificity protein-1; SREBP-2, sterol regulatory element-binding protein-2; Cur, curcumin.

A Novel Heterozygous NF1 Variant in a Neurofibromatosis-Noonan Syndrome Patient with Growth Hormone Deficiency: A Case Report

Neurofibromatosis-Noonan syndrome (NFNS), a rare autosomal-dominant hereditary disease, is characterized by clinical manifestations of both neurofibromatosis type 1 (NF1) and NS. We present a case of NFNS with short stature caused by a heterozygous nonsense variant of the NF1 gene. A 12-year-old boy was admitted because of short stature, numerous café-au-lait spots, low-set and posteriorly rotated ears, sparse eyebrows, broad forehead, and inverted triangular face. Cranial and spinal magnetic resonance imaging showed abnormal nodular lesions. Molecular analysis revealed a novel heterozygous c.6189 C > G (p.(Tyr2063*)) variant in the NF1 gene. The patient was not prescribed recombinant growth hormone (GH) therapy because exogenous GH may have enlarged the abnormal skeletal lesions. During follow-up, Lisch nodules were found in the ophthalmologic examination. NFNS, a variant form of NF1, is caused by heterozygous mutations in the NF1 gene. The mechanism of GH deficiency caused by NF1 is still unclear. Whether NFNS patients should be treated with exogenous GH remains controversial.

Highly Efficient I2 Sorption, CO2 Capture, and Catalytic Conversion by Introducing Nitrogen Donor Sites in a Microporous Co(II)-Based Metal-Organic Framework.

Recently, the development of porous absorbents for efficient CO2 and I2 capture has attracted considerable attention because of severe global climate change and environmental issues with the nuclear energy. Hence, a unique porous metal-organic framework (MOF), {[Co(L)]·DMF·2H2O}n (1, DMF = N,N-dimethylformamide) with uncoordinated N atoms was rationally constructed via using a heterofunctional 4,6-bis(4'-carboxyphenyl)pyrimidine (H2L) linker. Interestingly, 1 exhibits exceptional properties for I2 sorption, CO2 capture, and catalytic conversion. Particularly, I2 can be efficiently removed in both vapor and solution forms, and the adsorption amount can reach 676.25 and 345.28 mg g-1, respectively. Furthermore, complex 1 displays high adsorption capacity for CO2 (53.78 cm3 g-1, 273 K). Consequently, 1 is expected to be a promising and practical material for environmental purification due to its excellent adsorption properties.

Highly efficient simultaneous removal of HCHO and elemental mercury over Mn-Co oxides promoted Zr-AC samples.

MnxCoy/Zrz-AC prepared by impregnation method was investigated on the simultaneous removal of HCHO and Hg0. The samples were characterized by BET, SEM, XRD, H2 pulse chemisorption, H2-TPR, XPS, Hg-TPD and in-situ DRIFTS. Thereinto, the optimal Mn2/3Co8/Zr10-AC achieved 99.87% HCHO removal efficiency and 82.41% Hg0 removal efficiency at 240 °C, respectively. With increased surface area and pore volume, Zr-AC support facilitated higher dispersion of MnOx-CoOx. Moreover, the co-doping of MnOx-CoOx endowed the sample with more active oxygen species and higher reducibility, which further facilitated the removal of HCHO and Hg0. Chemisorption was proved to predominate in Hg0 removal, and oxidation also worked as Hg2+ was detected in outlet gas. Besides, HCHO predominated in the competition of active oxygen species, especially for lattice oxygen, thus suppressed the Hg0 removal. According to in-situ DRIFTS, HCHO removal proceeded as HCHOads → DOM → formate species → CO2 + H2O, and was boosted by active oxygen species. Furthermore, Mn2/3Co8/Zr10-AC was proved with excellent regeneration performance, indicating its potential in practical application.

Insight into the effect of SO2 on the Hg0 removal performance over a 1V-8Ce/AC sorbent at low temperatures.

The influences of SO2 on Hg° removal over the 1V-8Ce/AC sorbent were systematically investigated at low temperatures. The experimental results showed that SO2 has a dual effect on Hg° removal, that is, SO2 has both a promoting effect and an inhibiting effect on Hg° removal. The SO2 transient response experiment indicated that SO2 could not only react with Hg° to promote the removal of Hg° but also react with the active components and poison the sorbent. O2 is indispensable for the removal of Hg°, which can offset the adverse effects caused by SO2 and H2O. HCl exhibited an obvious promoting effect on Hg° removal in the presence of SO2. The 1V-8Ce/AC sorbent exhibited good sulfur resistance and excellent stability (EHg = 90.04 %) after a 24 h reaction performed under the 1000 ppm SO2 condition at 150 °C. In addition, the Hg-TPD and XPS methods were used to assist in studying the effect of SO2 on Hg° removal over the 1V-8Ce/AC sorbent. Finally, the mechanism of Hg° removal in an SO2 atmosphere was also explored, which showed that Hg° was removed by two possible pathways over the 1V-8Ce/AC sorbent.

Correlation between the subchondral bone marrow lesions and cartilage repair tissue after matrix-associated autologous chondrocyte implantation in the knee: a cross-sectional study.

BACKGROUND: The contribution of the subchondral bone in the development and progression of osteoarthritis (OA) has long been recognized, but its role in cartilage repair procedures has only recently attracted more attention. PURPOSE: To explore the correlation between the cartilage repair tissue (RT) and the subchondral bone marrow lesions (BMLs) after matrix-associated autologous chondrocyte implantation (MACI) in the knee joint. MATERIAL AND METHODS: A total of 30 patients who underwent MACI in the knee from January 2015 to June 2018 and follow-up magnetic resonance imaging (MRI) scan were recruited in this study. The MRI results of cartilage RT were evaluated using T2* relaxation time. Subchondral BMLs were also qualitatively evaluated by use of the two-dimensional proton density-weighted fat-suppressed (2D-PD-FS) and three-dimensional dual-echo steady-state (3D-DESS) sequences. RESULTS: The univariate analysis displayed a significant negative correlation between subchondral BMLs and cartilage RT (P < 0.01). In the minimally adjusted model (only age, sex, and body mass index [BMI] adjusted), the results did not show obvious changes (ß = -6.54, 95% confidence interval [CI] = -10.99 to -2.09; P = 0.008). After adjustment for the full models (age, sex, BMI, defect size, combined injury, and preoperative duration of symptoms adjusted), the connection was also detected (ß = -6.66, 95% CI -11.82 to -1.50; P = 0.019). CONCLUSION: After MACI, the subchondral BMLs are significantly correlated with cartilage RT-T2* relaxation time. The role of subchondral bone in cartilage repair procedures should not be underestimated.

Promotional removal of gas-phase Hg0 over activated coke modified by CuCl2.

Impregnating CuCl2 on AC (activated coke) support to synthesize xCuCl2/AC showed superior activity with higher 90% Hg0 removal efficiency at 80-140 °C, as well as a lower oxygen demand of 2% O2 for Hg0 removal. The acceleration on Hg0 removal was observed for NO and SO2. The BET, SEM, XRD, XPS, TPD, and FT-IR characterizations revealed that the larger surface area, sufficient active oxygen species and co-existence of Cu+ and Cu2+ may account for the efficient Hg0 removal. In addition, the low demand of gaseous O2 was contributed to higher content of active oxygen and formed active Cl. After adsorbing on Cu sites, Cl sites, and surface functional groups, the Hg0(ads) removal on xCuCl2/AC was proceeded through two ways. Part of Hg0(ads) was oxidized by active O and formed Hg0, and the other part of Hg0 combined with the active Cl, which was formed by the activation of lattice Cl with the aid of active O, and formed HgCl2. Besides, the Hg2+ detected in outlet gas through mercury speciation conversion and desorption peak of HgCl2 and Hg0 further proved it. As displayed in stability test and simulated industrial application test, CuCl2/AC has a promising industrial application prospect.

Catalytic removal of toluene over manganese oxide-based catalysts: a review.

It is necessary to control the emissions of toluene, which is hazardous to both human health and the atmosphere environment and has been classified as a priority pollutant. Manganese oxide-based (Mn-based) catalysts have received increased attention due to their high catalytic performance, good physicochemical characteristic, availability in various crystal structures and morphologies, and being environmentally friendly and low cost. These catalysts can be classified into five categories, namely single manganese oxide, Mn-based composite oxides, Mn-based special oxides, supported Mn-based oxides, and Mn-based monoliths. This review focused on the recent progress on the five types of Mn-based catalysts for catalytic removal of toluene at low temperature and further systematically summarized the strategies improving catalysts, including improving synthetic methods, incorporating MnOx with other metal oxides, depositing Mn-based oxides on proper supports, and tuning the supports. Moreover, the effect of coexisting components, the reaction kinetics, and the oxidation mechanisms toward the removal of toluene were also discussed. Finally, the future research direction of this field was presented.

Organic Emitters with a Rigid 9-Phenyl-9-phosphafluorene Oxide Moiety as the Acceptor and Their Thermally Activated Delayed Fluorescence Behavior.

With the 9-phenyl-9-phosphafluorene oxide (PhFlOP) moiety as the acceptor (A) and various donors (D), a series of new organic emitters have been synthesized with a D-A-D configuration. Their photophysical and electrochemical behaviors and electroluminescent (EL) performances have been characterized in detail. The photophysical results have indicated that the PhFlOP-based emitters with acridyl, phenoxazyl, and phenothiazyl as donors show efficient, thermally activated delayed fluorescence (TADF) behavior, especially for the TADF emitter with the phenoxazyl donor possessing an exceptionally high rate constant of reverse intersystem crossing (kRISC) of 6.2 × 105 s-1. It has also been found that their TADF behavior can be greatly affected by the substitution position of the donors. Different from the reported aryl phosphine oxide (APO) acceptors in TADF emitters, the PhFlOP moiety adopts a highly rigid configuration to guarantee a photoluminescent quantum yield as high as 0.80 in the 4,4'-N,N'-dicarbazolebiphenyl film, representing the top-ranking emission ability for the TADF emitters with APO-type acceptors. Benefitting from their advanced TADF performances, the doped organic light-emitting diodes/devices based on these PhFlOP-based TADF emitters can achieve exceptional EL performances with the maximum external quantum efficiency (ηext) of 23.3%, current efficiency (ηL) of 83.7 cd A-1, and power efficiency (ηP) of 59.1 lm W-1. These encouraging EL data show the great potential of the PhFlOP moiety in developing highly efficient TADF emitters.

Association of Overt and Subclinical Hyperthyroidism During Weeks 4-8 with Adverse Pregnancy Outcomes.

Background: Although increasing data suggest that hyperthyroidism is associated with adverse pregnancy outcomes, there are only a few reports with different conclusions on whether the mild transient reduction in thyrotropin (TSH) with or without free thyroxine (FT4) elevation during the early stage of pregnancy also causes adverse pregnancy outcomes. Subjects and Methods: We analyzed data from 3,783 women in this study from August 2011 to December 2013. Participants completed a questionnaire survey. Samples of blood were obtained in the 4th-8th week of pregnancy and their TSH, FT4, thyroid peroxidase antibody, and thyroglobulin antibody were measured. We divided the participants into overt hyperthyroidism group (OHG), subclinical hyperthyroidism group (SHG), and control group based on their blood results and followed up on their pregnancy outcomes. Results: (1) The serum level of FT4 in the SHG was much higher than the control group (p < 0.05). No difference was found in the TSH between the OHG and SHG. The positive rate of autoimmune thyroid antibodies in the OHG (25.6%) was significantly higher than that in the SHG (14.2%) and control group (13.9%) (p < 0.05), whereas there was no difference between the SHG and control group. (2) The SHG had a lower incidence of miscarriage (1.7% vs. 7.2%; OR = 0.218, p = 0.016) than the control group, and the OHG had a higher incidence of placenta previa (3.3% vs. 0.8%; OR = 4.366, p = 0.039) than the control group. (3). We used a binary logistic regression to take other factors into consideration and found that subclinical hyperthyroidism was associated with a lower risk of abortion (OR = 0.206; 95% CI = 0.050-0.840; p = 0.028) but higher risk of preeclampsia (OR = 5.143; 95% CI = 1.463-18.076; p = 0.011) and placental abruption (OR = 4.676; 95% CI = 1.017-21.509; p = 0.048), and overt hyperthyroidism may increase the incidence of placenta previa (OR = 4.193; 95% CI = 1.222-14.382; p = 0.023). Conclusions: Subclinical hyperthyroidism during weeks 4-8 of pregnancy may be associated with the decreased incidence of abortion but might be a risk factor for preeclampsia and placental abruption. Meanwhile, pregnancy with overt hyperthyroidism may be an independent risk factor for placenta previa.

[Study on drop-out from antiretroviral therapy among adult HIV-infected individuals in Dehong prefecture, Yunnan province].

OBJECTIVE: To examine the proportion and reasons of drop-out from antiretroviral therapy (ART) among 8 367 adult HIV-infected individuals in Dehong prefecture, Yunnan province. METHODS: All adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART. RESULTS: The proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4% (1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART was significantly correlated with factors as: living area, gender, age, marital status, HIV transmission route, baseline CD4⁺ T cell counts and initial treatment regimen of the patients. After adjusted for potential confounding variables by multiple logistic regression model, drop-out from ART was significantly correlated with residential area, marital status, HIV transmission route, baseline CD4⁺ T cell count and initial treatment regimen of the patients. HIV-infected patients who were living in Mangshi city, Lianghe county or Yingjiang County, being married or living with partner, HIV infection through sexual contact, with baseline CD4⁺ T cell counts ≤ 200 cells/mm³, and ART included in the initial treatment regimen etc., were less likely to drop out from ART. The proportion of drop out from ART was significantly decreasing along with the increasing time of ART. Data from specific investigation revealed that among the 1 202 patients who dropped out from ART, 704 (58.6%) were lost to follow-up, 303 (25.2%) did not adhere to treatment, 74 (6.2%) moved out the region, 64 (5.3%) were Burmese that had returned to Burma, 29 (2.4%) stopped the treatment according to doctors' advice, 18 (1.5%) were incarcerated and 10 (0.8%) were under other reasons. Reasons for the drop-out varied, according to the situation of patients. CONCLUSION: The proportion of drop-out from ART varied significantly according to the characteristics of HIV-infected patients in Dehong prefecture that underscoring the needs for tailored responses to reduce drop-out of ART. Focus should be targeted on reducing the loss to follow-up and improving the treatment adherence.

[Study on HIV viral load in plasma and drug resistance among AIDS patients receiving antiretroviral treatment in Dehong prefecture,Yunnan province].

OBJECTIVE: To understand HIV rival suppression and drug resistance (HIVDR) among AIDS patients who were receiving antiretroviral treatment (ART) in Dehong prefecture, Yunnan province. METHODS: All AIDS patients who were aged over 15 years and with experience more than six months on ART by the end of 2012 in Dehong prefecture, were enrolled to receive testing for HIV viral load in plasma and genetic mutations associated with HIVDR. RESULTS: A total of 4 390 AIDS patients were qualified for the study according to the selection criteria, of whom 3 964 (90.3%) finally participated in the study. Among them, 2 307(58.2%) had CD4(+) cell counts more than 350 cells/mm³. 3 169 (79.9%) patients showed undetectable plasma HIV viral load which was lower than the detection threshold. Those who had the following factors as:resided in Ruili city, being female, older than 45 years of age, married, heterosexually infected with HIV, having received ART more than 5 years, and CD4(+) cell counts >500 cells/mm³, were more likely to have undetectable plasma virus load, with the differences statistically significant. 402 (10.1%) patients had plasma viral load ≥ 1 000 copies/ml, of whom 353 (87.8%) were successfully amplified and examined for HIVDR. Among them, 198 (56.1% ) were identified to bear genetic mutations associated with HIVDR. Most mutations were related to the resistance to nucleotide reverse transcriptase inhibitors (NNRTIs) or non-nucleotide reverse transcriptase inhibitors (NNRTIs), with M184V and K103N most frequently seen. 12 patients (3.4%) were found to have mutations resistant to protease inhibitors (PI). Data from multiple logistic regression analysis indicated that the period of receiving ART and the initial ART regimen could both significantly predict the occurrence of HIV resistance. CONCLUSION: Viral suppression was highly achieved among ART-prescribed AIDS patients in Dehong prefecture,Yunnan province. However, among those who did not show effective viral suppression, the proportion of HIVDR was high, underscoring the needs for health education so as to improve the adherence to drugs as well as for improving testing for viral load and HIVDR among AIDS patients.

Acoustic reconstruction of the velocity field in a furnace using a characteristic flow model.

An acoustic method can provide a noninvasive, efficient and full-field reconstruction of aerodynamic fields in a furnace. A simple yet reasonable model is devised for reconstruction of a velocity field in a cross section of a tangential furnace from acoustic measurements based on typical physical characteristics of the field. The solenoidal component of the velocity field is modeled by a curved surface, derived by rotating a curve of Gaussian distribution, determined by six characteristic parameters, while the nonrotational component is governed by a priori knowledge. Thus the inverse problem is translated into determination of the characteristic parameters using a set of acoustic projection data. First numerical experiments were undertaken to simulate the acoustic measurement, so as to preliminarily validate the effectiveness of the model. Based on this, physical experiments under different operating conditions were performed in a pilot-scale setup to provide a further test. Hot-wire anemometry and strip floating were applied to compare with acoustic measurements. The acoustic measurements provided satisfactory consistency with both of these approaches. Nevertheless, for a field with a relatively large magnitude of air velocities, the acoustic measurement can give more reliable reconstructions. Extension of the model to measurements of hot tangential furnaces is also discussed.

[Survival analysis on 3103 HIV/AIDS patients receiving antiretroviral treatment in Dehong prefecture, Yunnan province].

OBJECTIVE: To determine the survival rate of HIV/AIDS patients after receiving free antiretroviral treatment in Dehong prefecture, Yunnan province. METHODS: A retrospective cohort analysis was conducted on all the HIV/AIDS patients aged over 16 years who had started antiretroviral treatment during January 2007 throughout December 2009 in Dehong prefecture. RESULTS: A total of 3103 HIV/AIDS patients had received antiretroviral treatment during the study period. Among them, the mean age was (36.0 ± 9.9) years and 62.4% were males. 66.2% of them were infected with HIV through heterosexual transmission, and the mean treatment follow-up time was 21.7 months. Most patients well complied with the treatment, i.e., the average times of not taking the medicine were less than 5 per month. The cumulative survival rate of antiretroviral treatment after 1, 2, 3, 4, and 5 years were 0.95, 0.94, 0.93, 0.92, and 0.92, respectively. Data from the Cox proportional hazard regression model analysis indicated that, after adjustment for age, gender, and marital status, the baseline CD4(+)T cell counts and transmission route could significantly predicate the rates of survival. Those who were with baseline CD4(+)T cell counts as 200 - 350/mm(3)were less likely to die of AIDS than those with CD4(+) T cell counts < 200/mm(3) (Hazard Ratio or HR = 0.16, 95%CI: 0.09 - 0.28), and HIV-infected through mother-to-child transmission or routes other than heterosexual transmission were less likely to die of AIDS than through injecting drug use (HR = 0.35, 95%CI: 0.13 - 1.00). CONCLUSION: Free antiretroviral treatment had significantly improved the survival of HIV/AIDS patients. Earlier initiation of antiretroviral treatment was likely to have achieved better survival effects.

Synthesis and biological evaluations of novel bendazac lysine analogues as potent anticataract agents.

Novel bendazac analogues and their salts have been designed and prepared. The resulting compounds (13c-d, 15c, 17c) showed very good aqueous solubility (>100 mg/mL). An in vitro assay showed that most of the resulting compounds had potent protective activity against the oxidative damage. Particularly, compound 13d was also able to enhance the WSP and T-AOC level in the H(2)O(2)/FeCl(3)-induced oxidative damage model, indicating the resulting compound may protect the lens through an antioxidant pathway.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of xanthinol in human plasma and its application in a bioequivalence study of xanthinol nicotinate tablets.

A sensitive, rapid liquid chromatographic-electrospray ionization mass spectrometric method for the determination of xanthinol in human plasma was developed and validated. Xanthinol nicotinate in plasma (0.5 mL) was pretreated with 20% trichloroacetic acid for protein precipitation. The samples were separated using a Lichrospher silica (5 microm, 250 mm x 4.6 mm i.d.). A mobile phase of methanol-water containing 0.1% formic acid (50: 50, v/v) was used isocratically eluting at a flow rate of 1 mL/min. Xanthinol and its internal standard (IS), acyclovir, were measured by electrospray ion source in positive selected reaction monitoring mode. The method demonstrated that good linearity ranged from 10.27 to 1642.8 ng/mL with r=0.9956. The limit of quantification for xanthinol in plasma was 10.27 ng/mL with good accuracy and precision. The mean plasma extraction recovery of xanthinol was in the range of 90.9-100.2%. The intra- and inter-batch variability values were less than 4.8% and 7.9% (relative standard deviation, R.S.D.), respectively. The established method has been successfully applied to a bioequivalence study of two xanthinol nicotinate tablets for 20 healthy volunteers.

Sensitive HPLC-ESI-MS method for the determination of tiotropium in human plasma.

A sensitive high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) assay is established for the determination of tiotropium in human plasma using benzyltriethylammonium chloride as the internal standard (IS). After being treated with C(18) cartridges, plasma samples are separated by HPLC on a reversed-phase C(18) column with a mobile phase of 40mM ammonium acetate buffer-methanol (56:44, v/v). Tiotropium is determined in a single-quadrupole MS. HPLC-ESI-MS is performed in the selected ion monitoring mode using target ions at m/z 392.0 for tiotropium and m/z 192.3 for the IS. The calibration curve is linear over the range 1.5-30 pg/mL. The intra- and inter-assay variability values are less than 10.1% and 13.6%, respectively. The mean plasma extraction recovery of tiotropium is 92.3 +/- 5.0%. The method has been successfully applied to studying the pharmacokinetics of tiotropium in healthy Chinese volunteers.

HPLC-APCI-MS for the determination of teprenone in human plasma: method and clinical application.

A sensitive high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS) method for the determination of teprenone (GGA) in human plasma using menatetrenone as the internal standard (I.S.) was established. After protein precipitation with ethanol, the plasma sample was extracted by cyclohexane and separated by high performance liquid chromatography on a reversed phase C8 HPLC column with a mobile phase of water-methanol (4:96, v/v). GGA was determined with atmospheric pressure chemical ionisation-mass spectrometry (APCI-MS). HPLC-APCI-MS was performed in the selected ion monitoring (SIM) mode using target ions at [M+H]+m/z 331.3 for GGA and [M+H]+m/z 445.4 for the I.S. Calibration curve was linear over the range of 0.3-1000 ng/ml. The lower limit of quantification was 0.3 ng/ml. The intra- and inter-batch variability values were less than 7.8% and 8.7%, respectively. The method was successfully applied in the pharmacokinetic study in which plasma concentrations of GGA in 20 healthy Chinese volunteers were determined up to 24 h after administration of capsule containing 50 mg GGA. The maximum GGA plasma concentration (Cmax) was 246.9+/-85.4 ng/ml, the elimination half-life (t1/2) was 3.38+/-1.20 h, and the time to the Cmax was 5.35+/-1.39 h.

Simultaneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC-MS/MS.

BACKGROUND: Although roxithromycin and ambroxol HCl were often administered concomitantly for the treatment of respiratory infections, the pharmacokinetic interactions between them have not been reported. We investigated the interactions between these drugs in health male Chinese volunteers by LC-MS/MS in human plasma. METHODS: The pharmacokinetics were studied in 12 healthy male Chinese volunteers after an overnight fast by a single oral dose, 4-way crossover design with a period of 7-day washout. Each subjects was randomized to receive a single oral dose of 1 compound roxithromycin (150 mg) and ambroxol HCl (30 mg) dispersible tablet (test formulation, treatment A), one 150 mg roxithromycin dispersible tablet together with one 30 mg ambroxol HCl tablet (combined reference formulations, treatment B), one 150 mg roxithromycin dispersible tablet (reference formulation I, treatment C), or one 30 mg ambroxol HCl tablet (reference formulation II, treatment D) with 250 ml of water. Venous blood was collected at pre-dose (0 h) and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72 h after dosing. The plasma concentrations of roxithromycin and ambroxol HCl were simultaneously determined by using a validated internal standard LC-MS/MS method. RESULTS: No significant differences were observed for the major pharmacokinetic parameters such as C(max), T(max), t(1/2) and AUC of both roxithromycin and ambroxol HCl between different treatments. CONCLUSION: The pharmacokinetics of both roxithromycin and ambroxol HCl are not affected by their concomitant oral administration. Therefore, there are no obvious pharmacokinetic interactions between roxithromycin and ambroxol HCl after oral administration. Roxithromycin and ambroxol HCl dispersible tablets were bioequivalent with reference to the roxithromycin dispersible tablets and ambroxol HCl tablets in combination usage.