Publications by authors named "Hemei Wang"

15 Publications

  • Page 1 of 1

Effects of perchlorate and exogenous T4 exposures on development, metamorphosis and endochondral ossification in Bufo gargarizans larvae.

Aquat Toxicol 2021 Nov 17;242:106036. Epub 2021 Nov 17.

College of Life Science, Shaanxi Normal University, Xi'an 710119, China. Electronic address:

Several endocrine-disrupting chemicals (EDCs) have been proven to interfere with the physiological function of thyroid hormone (TH), which affected growth and development. However, few studies have investigated the effects of EDCs on TH axis with consequence for skeletal development in amphibians. This study thus examined the potential role of perchlorate and T4 in growth, development and endochondral ossification during metamorphosis of Bufo gargarizans. Our studies showed that NaClO₄ treatment caused weight gain and delayed the developmental stage in B. gargarizans tadpoles, while T4 decreased body size and survival rate, accelerated metamorphic duration and increased the risk of early death. Histological sections suggested that NaClO₄ and T4 treatments caused damages to thyroid tissue, such as decreased thyroid gland size, follicle size, colloid area, the height of follicular epithelial cells and the number of follicles. In addition, the double skeletal staining and RT-qPCR showed that NaClO₄ and T4 treatments inhibited the endochondral ossification by regulating TH synthesis (TRs, Dios) and endochondral ossification-related genes (MMPs, Runxs, VEGFs and VEGFRs) expression levels, which might affect terrestrial locomotion and terrestrial life. Altogether, these thyroid injury and gene expression changes as caused by NaClO₄ and T4 may have an influence on development and endochondral ossification during the metamorphosis of amphibians.
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http://dx.doi.org/10.1016/j.aquatox.2021.106036DOI Listing
November 2021

Development of a CAUTI risk factor evaluation index system for postoperative patients with gynecological malignant tumors.

J BUON 2021 Jul-Aug;26(4):1292-1297

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Purpose: In this study, we developed a CAUTI risk factor evaluation index system for postoperative patients with gynecologic malignant tumors and provided scientific evidence for the prevention of catheter-related urinary tract infection (CAUTI).

Methods: A comprehensive method, including literature review, group discussion and Delphi method, was adopted to establish a CAUTI risk factor evaluation index system for postoperative patients with gynecologic malignant tumors.

Results: Two rounds of expert consultations resulted in effective response rates of 100%, with authority coefficients of 0.94, and coordination coefficients of 0.473 and 0.388 respectively (p<0.01). The risk factor indicator system consisted of 4 first-level indicators, 13 second-level indicators, and 56 third-level indicators.

Conclusion: The experts showed high enthusiasm, good authority, and coordination. The CAUTI risk factor evaluation index system for postoperative patients with gynecologic malignant tumors is comprehensive and scientific, and could serve as an important guide for assessment and prevention of CAUTI in patients with gynecologic malignant tumor postoperatively.
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September 2021

Sevoflurane represses the migration and invasion of gastric cancer cells by regulating forkhead box protein 3.

J Int Med Res 2021 Apr;49(4):3000605211005936

Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.

Objective: Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells.

Methods: GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively.

Results: FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells.

Conclusions: Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion .
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http://dx.doi.org/10.1177/03000605211005936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108091PMC
April 2021

Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma.

J Control Release 2016 Mar 16;226:193-204. Epub 2016 Feb 16.

School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, Tianjin 300070, PR China. Electronic address:

Stepwise pH-responsive nanoparticle system containing charge reversible pullulan-based (CAPL) shell and poly(β-amino ester) (PBAE)/poly(lactic-co-glycolic acid) (PLAG) core is designed to be used as carriers of paclitaxel (PTX) and combretastatin A4 (CA4) for combining antiangiogenesis and chemotherapy to treat hepatocellular carcinoma (HCC). CAPL-coated PBAE/PLGA (CAPL/PBAE/PLGA) nanoparticles displayed step-by-step responses to weakly acidic tumor microenvironment (pH ≈6.5) and endo/lysosome (pH ≈5.5) respectively through the cleavage of β-carboxylic amide bond in CAPL and the "proton-sponge" effect of PBAE, thus realized the efficient and orderly releases of CA4 and PTX. In human HCC HepG2 cells and human umbilical vein endothelial cells, CAPL/PBAE/PLGA nanoparticles significantly enhanced synergistic effects of PTX and CA4 on cell proliferation and cell migration. In HepG2 tumor-bearing mice, CAPL/PBAE/PLGA nanoparticles showed excellent tumor-targeting capability and remarkably increased inhibitory effects of PTX and CA4 on tumor growth and angiogenesis. In conclusion, this novel nanoparticle system is a promising candidate as carrier for drugs against HCC.
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http://dx.doi.org/10.1016/j.jconrel.2016.02.030DOI Listing
March 2016

Effect of neoadjuvant chemotherapy on sevoflurane MAC-BAR value of patients undergoing radical stomach carcinoma surgery.

Int J Clin Exp Med 2015 15;8(4):5649-57. Epub 2015 Apr 15.

Department of Anesthesiology, Section II, The Fourth Hospital of Hebei Medical University No. 12, Jiankang Road, Shijiazhuang 050011, Hebei Province, China.

Objective: To determine the minimum alveolar concentration (MAC) of sevoflurane required for 50% blockade of the adrenergic response (BAR) to surgical incision in patients treated with neoadjuvant chemotherapy prior to radical gastrectomy.

Patients And Design: Forty-four patients were selected for this study. Patients with preoperative neoadjuvant chemotherapy comprised the NC group (n = 22) and patients without preoperative neoadjuvant chemotherapy were included as the C group (n = 22). Patients in the NC group were treated with two cycles of 14-day neoadjuvant chemotherapy with combination of oxaliplatin and Gio, and underwent surgery 3 weeks later. Patients in the C group received no chemotherapy prior to surgery. A sequential allocation method was employed to determine the MAC-BAR for each group. The initial end-tidal concentration of sevoflurane was set as 3% for both the NC and C groups. Sympathetic responses to surgical incision were evaluated 6 times by measuring the heart rate (HR) and mean arterial blood pressure (MAP) at 1 min intervals before (T1, T2, T3) and after (T4, T5, T6) skin incision, and used to adjust the end-tidal sevoflurane concentrations for each patient. More than a 15% increase in MAP or HR after incision was scored as a positive response.

Main Results: The HR and MAP levels measured pre- (T1) and post-incision (T6) were significantly lower than base line values at admission in both groups, but without statistical difference between the groups. The MAC-BAR value of sevoflurane was 2.2% in the NC group and 3.0% in the C group (P < 0.05).

Conclusions: Neoadjuvant chemotherapy reduced the MAC-BAR value of sevoflurane in gastric cancer patients by enhancing the inhibitory effect of sevoflurane on the stress response.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483812PMC
July 2015

A polymeric prodrug of cisplatin based on pullulan for the targeted therapy against hepatocellular carcinoma.

Int J Pharm 2015 Apr 11;483(1-2):89-100. Epub 2015 Feb 11.

School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Research Center of Basic Medical Science, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address:

A polymeric prodrug of cisplatin (CP) with simple chemical structure was synthesized based on pullulan and its therapeutic effects on human hepatocellular carcinoma (HCC) were studied in vitro and in vivo. Briefly, CP was linked to pullulan monosuccinate (SUPA) via coordination bond to form prodrug of CP-SUPA with the CP weight content of 18.7%. CP-SUPA exhibited in vitro sustained releases and strong interactions with genomic DNA. CP-SUPA could effectively inhibit the proliferation of HCC HepG2 cells by promoting the cell apoptosis and arresting the cell cycle, and showed a significantly higher cytotoxicity on HepG2 cells than that on human lung epithelial A549 cells. Compared to free CP, CP-SUPA obviously prolonged the survival times of Balb/c mice after intravenous injection at CP doses of 15 and 30 μmol/kg, and no signs of toxic effects in main tissues were detected by histologic examination. In MHCC-97H tumor-bearing nude mice, CP-SUPA was mainly distributed in the liver and the tumor after 24h post administration and evidently inhibited the tumor growth at CP doses of 3.5 and 7.0 μmol/kg. In conclusion, CP-SUPA was an ideal candidate of polymeric prodrug for the targeted therapy against HCC.
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http://dx.doi.org/10.1016/j.ijpharm.2015.02.027DOI Listing
April 2015

Hints for cyclical recruitment of atelectasis during ongoing mechanical ventilation in lavage and oleic acid lung injury detected by SpO₂ oscillations and electrical impedance tomography.

Exp Lung Res 2014 Nov 25;40(9):427-38. Epub 2014 Aug 25.

1Department of Anaesthesiology, University Medical Center Mainz, Mainz, Germany.

Purpose Of The Study: Detection of cyclical recruitment of atelectasis after induction of lavage (LAV) or oleic acid injury (OAI) in mechanically ventilated pigs. Primary hypothesis is that oxygen oscillations within the respiratory cycle can be detected by SpO₂ recordings (direct hint). SpO₂ oscillations reflect shunt oscillations that can only be explained by cyclical recruitment of atelectasis. Secondary hypothesis is that electrical impedance tomography (EIT) depicts specific regional changes of lung aeration and of pulmonary mechanical properties (indirect hint).

Materials And Methods: Three groups (each n = 7) of mechanically ventilated pigs were investigated applying above mentioned methods before and repeatedly after induction of lung injury: (1) sham treated animals (SHAM), (2) LAV, and (3) OAI.

Results: Early oxygen oscillations occurred in the LAV group (mean calculated amplitude: 73.8 mmHg reflecting shunt oscillation of 11.2% in mean). In the OAI group oxygen oscillations occurred hours after induction of lung injury (mean calculated amplitude: 57.1 mmHg reflecting shunt oscillations of 8.4% in mean). The SHAM group had no relevant oxygen oscillations (<30 mmHg, shunt oscillations < 1.5%). Synchronously to oxygen oscillations, EIT depicted (1) a decrease of ventilation in dorsal areas, (2) an increase in ventral areas, (3) a decrease of especially dependent expiratory impedance, 3) an increase in late inspiratory flow especially in the dependant areas, (4) an increase in the speed of peak expiratory flow (PEF), and (5) a decrease of dorsal late expiratory flow.

Conclusions: SpO2 and EIT recordings detect events that are interpreted as cyclical recruitment of atelectasis.
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http://dx.doi.org/10.3109/01902148.2014.944719DOI Listing
November 2014

Fatigue self-management: a survey of Chinese cancer patients undergoing chemotherapy.

J Clin Nurs 2013 Apr;22(7-8):1053-65

School of Nursing, Hangzhou Normal University, Hangzhou, China.

Aims And Objectives: To examine Chinese cancer patients' fatigue self-management, including the types of self-management behaviours used, their confidence in using these behaviours, the degree of relief obtained and the factors associated with patients' use of fatigue self-management behaviours.

Background: Fatigue places significant burden on patients with cancer undergoing chemotherapy. While some studies have explored fatigue self-management in Western settings, very few studies have explored self-management behaviours in China.

Design: Cross-sectional self- and/or interviewer-administered survey.

Methods: A total of 271 participants with self-reported fatigue in the past week were recruited from a specialist cancer hospital in south-east China. Participants completed measures assessing the use of fatigue self-management behaviours, corresponding self-efficacy, perceived relief levels plus items assessing demographic characteristics, fatigue experiences, distress and social support.

Results: A mean of 4.94 (± 2.07; range 1-10) fatigue self-management behaviours was reported. Most behaviours were rated as providing moderate relief and were implemented with moderate self-efficacy. Regression analyses identified that having more support from one's neighbourhood and better functional status predicted the use of a greater number of self-management behaviours. Separate regression analyses identified that greater neighbourhood support predicted greater relief from 'activity enhancement behaviours' and that better functional status predicted greater relief from 'rest and sleep behaviours'. Higher self-efficacy scores predicted greater relief from corresponding behaviours.

Conclusions: A range of fatigue self-management behaviours were initiated by Chinese patients with cancer. Individual, condition and environmental factors were found to influence engagement in and relief from fatigue self-management behaviours.

Relevance To Clinical Practice: Findings highlight the need for nurses to explore patients' use of fatigue self-management behaviours and the effectiveness of these behaviours in reducing fatigue. Interventions that improve patients' self-efficacy and neighbourhood supports have the potential to improve outcomes from fatigue self-management behaviours.
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http://dx.doi.org/10.1111/jocn.12174DOI Listing
April 2013

Influence of fluid and volume state on PaO2 oscillations in mechanically ventilated pigs.

Exp Lung Res 2013 Mar 15;39(2):80-90. Epub 2013 Jan 15.

Department of Anaesthesiology, University Medical Center, Mainz, Germany.

Varying pulmonary shunt fractions during the respiratory cycle cause oxygen oscillations during mechanical ventilation. In artificially damaged lungs, cyclical recruitment of atelectasis is responsible for varying shunt according to published evidence. We introduce a complimentary hypothesis that cyclically varying shunt in healthy lungs is caused by cyclical redistribution of pulmonary perfusion. Administration of crystalloid or colloid infusions would decrease oxygen oscillations if our hypothesis was right. Therefore, n=14 mechanically ventilated healthy pigs were investigated in 2 groups: crystalloid (fluid) versus no-fluid administration. Additional volume interventions (colloid infusion, blood withdrawal) were carried out in each pig. Intra-aortal PaO2 oscillations were recorded using fluorescence quenching technique. Phase shift of oxygen oscillations during altered inspiratory to expiratory (I:E) ventilation ratio and electrical impedance tomography (EIT) served as control methods to exclude that recruitment of atelectasis is responsible for oxygen oscillations. In hypovolemia relevant oxygen oscillations could be recorded. Fluid and volume state changed PaO2 oscillations according to our hypothesis. Fluid administration led to a mean decline of 105.3 mmHg of the PaO2 oscillations amplitude (P<0.001). The difference of the amplitudes between colloid administration and blood withdrawal was 62.4 mmHg in pigs not having received fluids (P=0.0059). Fluid and volume state also changed the oscillation phase during altered I:E ratio. EIT excluded changes of regional ventilation (i.e., recruitment of atelectasis) to be responsible for these oscillations. In healthy pigs, cyclical redistribution of pulmonary perfusion can explain the size of respiratory-dependent PaO2 oscillations.
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http://dx.doi.org/10.3109/01902148.2012.758192DOI Listing
March 2013

Influence of crystalloid and colloid fluid infusion and blood withdrawal on pulmonary bioimpedance in an animal model of mechanical ventilation.

Physiol Meas 2012 Jul 27;33(7):1225-36. Epub 2012 Jun 27.

Department of Anaesthesiology, University Medical Centre, 55101 Mainz, Germany.

Electrical impedance tomography (EIT) is considered useful for monitoring regional ventilation and aeration in intensive-care patients during mechanical ventilation. Changes in their body fluid state modify the electrical properties of lung tissue and may interfere with the EIT measurements of lung aeration. The aim of our study was to assess the effects of crystalloid and colloid infusion and blood withdrawal on bioimpedance determined by EIT in a chest cross-section. Fourteen anaesthetized mechanically ventilated pigs were subjected to interventions affecting the volume state (crystalloid and colloid infusion, blood withdrawal). Six animals received additional crystalloid fluids (fluid group) whereas eight did not (no-fluid group). Global and regional relative impedance changes (RIC, dimensionless unit) were determined by backprojection at end-expiration. Regional ventilation distribution was analyzed by calculating the tidal RIC in the same regions. Colloid infusion led to a significant fall in the global end-expiratory RIC (mean differences: fluid: -91.2, p < 0.001, no-fluid: -38.9, p < 0.001), which was partially reversed after blood withdrawal (mean differences, fluid: +45.1, p = 0.047 and no-fluid: +26.2, p = 0.009). The RIC was significantly lower in the animals with additional crystalloids (mean group difference: 45.5, p < 0.001). Global and regional tidal volumes were not significantly affected by the fluid and volume states.
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http://dx.doi.org/10.1088/0967-3334/33/7/1225DOI Listing
July 2012

Isolation of nine Phytophthora capsici pectin methylesterase genes which are differentially expressed in various plant species.

J Basic Microbiol 2011 Feb 24;51(1):61-70. Epub 2011 Jan 24.

Department of Plant Pathology, Shandong Agricultural University, Tai'an, PR China.

Phytophthora capsici causes damage on many plants species, and secretes various pectin methylesterases during all stages of infection. We identified nine Pme genes (Pcpme 1-9) from a genomic library of highly virulent P. capsici strain SD33 and further analyzed the expression pattern of nine genes on three hosts: pepper, tomato, and cucumber using qRT-PCR during all stages of infection. All nine genes were found to be differentially expressed in three host species in the course of P. capsici interaction. The expression levels of the respective genes increased from 1 to 7 dpi in pepper, while most genes presented a decreasing trend of expression from 1 to 5 dpi in tomato fruits. However, in both fruits peaks were reached at 7 dpi. In cucumber fruits, each gene showed minor expression levels from 1 to 3 dpi, exhibited definite peaks at 5 dpi, and then decreased from 5 to 7 dpi. Thus, evidence from our studies of Pcpme gene expression in different plants at a rang of time points suggests that the late stages of infection may represent the most critical time for P. capsici to successfully express or/and secret PMEs.
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http://dx.doi.org/10.1002/jobm.201000317DOI Listing
February 2011

Observation of ventilation-induced Spo(2) oscillations in pigs: first step to noninvasive detection of cyclic recruitment of atelectasis?

Exp Lung Res 2010 Jun;36(5):270-6

Department of Anaesthesiology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.

High arterial partial oxygen pressure (Pao(2)) oscillations within the respiratory cycle were described recently in experimental acute lung injury. This phenomenon has been related to cyclic recruitment of atelectasis and varying pulmonary shunt fractions. Noninvasive detection of Spo(2) (oxygen saturation measured by pulse oximetry) as an indicator of cyclic collapse of atelectasis, instead of recording Pao(2) oscillations, could be of clinical interest in critical care. Spo(2) oscillations were recorded continuously in three different cases of lung damage to demonstrate the technical feasibility of this approach. To deduce Pao(2) from Spo(2), a mathematical model of the hemoglobin dissociation curve including left and right shifts was derived from the literature and adapted to the dynamic changes of oxygenation. Calculated Pao(2) amplitudes (derived from Spo(2) measurements) were compared to simultaneously measured fast changes of Pao(2), using a current standard method (fluorescence quenching of ruthenium). Peripheral hemoglobin saturation was capable to capture changes of Spo(2) within each respiratory cycle. For the first time, Spo(2) oscillations due to cyclic recruitment of atelectasis within a respiratory cycle were determined by photoplethysmography, a technology that can be readily applied noninvasively in clinical routine. A mathematic model to calculate the respective Pao(2) changes was developed and its applicability tested.
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http://dx.doi.org/10.3109/01902140903575971DOI Listing
June 2010

Functional analysis of pcpme6 from oomycete plant pathogen Phytophthora capsici.

Microb Pathog 2010 Jul-Aug;49(1-2):23-31. Epub 2010 Mar 20.

Department of Plant Pathology, Shandong Agricultural University, No. 61 Daizong street, Tai'an 271018, PR China.

The Phytophthora capsici inflicts damage on numerous crop plants by secreting a series of pectinase including pectin methylesterase (PME). We identified a PME gene (pcpme6) from a genomic library of a highly virulent P. capsici strain SD33 which had an encoded a polypeptide of 348 amino acid residues with a predicted molecular mass of 38.18 kDa. We also confirmed that pcpme6 was increasingly expressed during symptom development following P. capsici infection of pepper leaves. The wild-type protein (PCPME6) ca. 50 kDa was obtained from pcpme6 expression, and PME activity trend in PCPME6-treated pepper leaves increased with symptom development. PCPME6 degraded leaf cell walls, resulting in the production of necrotic lesions. Mutation of Asp residues in active sites within pcpme6 affected PCPME6 activity and its virulence on pepper leaves. Results show that pcpme6 is a gene within the pme gene family that is important for pathogenesis of P. capsici on pepper.
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http://dx.doi.org/10.1016/j.micpath.2010.03.004DOI Listing
October 2010

A comparison of micropore membrane inlet mass spectrometry-derived pulmonary shunt measurement with Riley shunt in a porcine model.

Anesth Analg 2009 Dec;109(6):1831-5

Department of Anesthesiology, Johannes Gutenberg- University, Mainz, Germany.

Background: The multiple inert gas elimination technique was developed to measure shunt and the ratio of alveolar ventilation to simultaneous alveolar capillary blood flow in any part of the lung (V(A)'/Q') distributions. Micropore membrane inlet mass spectrometry (MMIMS), instead of gas chromatography, has been introduced for inert gas measurement and shunt determination in a rabbit lung model. However, agreement with a frequently used and accepted method for quantifying deficits in arterial oxygenation has not been established. We compared MMIMS-derived shunt (M-S) as a fraction of total cardiac output (CO) with Riley shunt (R-S) derived from the R-S formula in a porcine lung injury model.

Methods: To allow a broad variance of atelectasis and therefore shunt fraction, 8 sham animals did not receive lavage, and 8 animals were treated by lung lavages with 30 mL/kg warmed lactated Ringer's solution as follows: 2 animals were lavaged once, 5 animals twice, and 1 animal 3 times. Variables were recorded at baseline and twice after induction of lung injury (T1 and T2). Retention data of sulfur hexafluoride, krypton, desflurane, enflurane, diethyl ether, and acetone were analyzed by MMIMS, and M-S was derived using a known algorithm for the multiple inert gas elimination technique. Standard formulas were used for the calculation of R-S.

Results: Forty-four pairs of M-S and R-S were recorded. M-S ranged from 0.1% to 35.4% and R-S from 3.7% to 62.1%. M-S showed a correlation with R-S described by linear regression: M-S = -4.26 + 0.59 x R-S (r(2) = 0.83). M-S was on average lower than R-S (mean = -15.0% CO, sd = 6.5% CO, and median = -15.1), with lower and upper limits of agreement of -28.0% and -2.0%, respectively. The lower and upper limits of the 95% confidence intervals were -17.0 and -13.1 (P < 0.001, Student's t-test).

Conclusions: Shunt derived from MMIMS inert gas retention data correlated well with R-S during breathing of oxygen. Shunt as derived by MMIMS was generally less than R-S.
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http://dx.doi.org/10.1213/ANE.0b013e3181bbc401DOI Listing
December 2009

Suppression of perfluoroisobutylene induced acute lung injury by pretreatment with pyrrolidine dithiocarbamate.

J Occup Health 2007 Mar;49(2):95-103

Beijing Institute of Pharmacology and Toxicology, the China PLA, PR, China.

Perfluoroisobutylene (PFIB) is produced as a main by-product in large quantities by the fluoropolymer industry. As a highly toxic compound, even the case of brief inhalation of PFIB can result in acute lung injury (ALI), pulmonary edema and even death. To test for any preventive or therapeutic effects of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB activation inhibitor, against PFIB inhalation-induced ALI, mice were exposed in a flow-past exposure system to PFIB and the prophylactic and therapeutic effects of PDTC were studied. The inhibitory effects of PDTC on ALI, the activation of NF-kappaB, as well as the expression of cytokines (IL-1beta and IL-8) after PFIB exposure were evaluated. The results demonstrated that pretreatment with PDTC (120 mg/kg, 30 min before PFIB exposure) could significantly lower the lung coefficient (wet lung-to-body weight ratio, dry lung-to-body weight ratio, water content in the lung, and lung wet-to-dry weight ratio) and protein content in bronchoalveolar lavage fluid (BALF), but no effects of PDTC were found when PDTC was treated after PFIB inhalation, suggesting a preventative effect rather than a therapeutic effect of PDTC. Furthermore, the above preventative effects of PDTC (when given at 30 min before PFIB exposure) on PFIB-induced lung injury were achieved in a dose-dependent manner. In support of these preventive effects of PDTC, our toxicological studies demonstrated that PFIB-inhalation induced a quick activation of NF-kappaB (0.5 h post PFIB exposure) and expression of IL-1beta and IL-8 (0.5 h and 1 h post PFIB exposure, respectively). Pretreatment with PDTC (120 mg/kg, 30 min before PFIB exposure) resulted in a significant inhibitive effect on the activation of NF-kappaB (0.5 h post PFIB exposure) and expression of IL-1beta and IL-8 (1 h post PFIB exposure). The mortality, the extent of lung injury of the mice indexed by lung coefficients, the content of total protein and albumin in BALF, as well as the lung histopathologic changes, were dramatically alleviated in PFIB exposure after pretreatment with PDTC, clearly suggesting that PDTC has a prophylactic role against PFIB inhalation-induced ALI, and that NF-kappaB activation might play a central role in initiating an acute inflammatory response and in causing injury to the lungs after PFIB inhalation.
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http://dx.doi.org/10.1539/joh.49.95DOI Listing
March 2007
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