scholarly journals Ketamine Inhibits Lung Fluid Clearance through Reducing Alveolar Sodium Transport

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Yong Cui ◽  
Hongguang Nie ◽  
Hong Ma ◽  
Lei Chen ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Clinical Evidence ◽  
Ex Vivo ◽  
A549 Cells ◽  
Intratracheal Instillation ◽  
Lung Fluid ◽  
Whole Cell Patch Clamp ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Lung Lobes

Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobesex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker), fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+currents (ENaC activity) in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.

scholarly journals Evaluation of the anti-cancer potential of Cedrus deodara total lignans by inducing apoptosis of A549 cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaofeng Shi ◽  
Ruiqin Du ◽  
Junmin Zhang ◽  
Yanping Lei ◽  
Hongyun Guo
Keyword(s):  
Cell Cycle ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
A549 Cells ◽  
Cedrus Deodara ◽  
Anti Cancer ◽  
M Phase ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Lung Adenocarcinoma Cancer

Abstract Background Cedrus deodara (Roxb.) Loud (normally called as deodar), one out of four species in the genus Cedrus, exhibits widely biological activities. The Cedrus deodara total lignans from the pine needles (CTL) were extracted. The aim of the study was to investigate the anticancer potential of the CTL on A549 cell line. Methods We extracted the CTL by ethanol and assessed the cytotoxicity by CCK-8 method. Cell cycle and apoptosis were detected by a FACS Verse Calibur flow cytometry. Results The CTL were extracted by means of ethanol hot refluxing and the content of total lignans in CTL was about 55.77%. By the CCK-8 assays, CTL inhibited the growth of A549 cells in a dose-dependent fashion, with the IC50 values of 39.82 ± 1.74 μg/mL. CTL also inhibited the growth to a less extent in HeLa, HepG2, MKN28 and HT-29 cells. Conclusion At low doses, the CTL effectively inhibited the growth of A549 cells. By comparison of IC50 values, we found that A549 cells might be more sensitive to the treatment with CTL. In addition, CTL were also able to increase the population of A549 cells in G2/M phase and the percentage of apoptotic A549 cells. CTL may have therapeutic potential in lung adenocarcinoma cancer by regulating cell cycle and apoptosis.

Alveolar type II-like cells release G-CSF as neutrophil chemotactic activity

1998 ◽  
Vol 275 (4) ◽  
pp. L687-L693 ◽  
Author(s):  
Sekiya Koyama ◽  
Etsuro Sato ◽  
Takeshi Masubuchi ◽  
Akemi Takamizawa ◽  
Keishi Kubo ◽  
...  
Keyword(s):  
A549 Cells ◽  
Chemotactic Activity ◽  
Alveolar Epithelial Cells ◽  
Epithelial Cell Line ◽  
Alveolar Type ◽  
Type Ii ◽  
Tnf Α ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Neutrophil Chemotactic Activity

We evaluated the potential of A549 cells, an alveolar type II epithelial cell line, to release granulocyte colony-stimulating factor (G-CSF), in addition to interleukin (IL)-8 and leukotriene B4, as neutrophil chemotactic activity (NCA). Human recombinant IL-1β stimulated A549 cells to release NCA in a time- and dose-dependent fashion. The released NCA was blocked by mouse anti-human G-CSF polyclonal antibody. Molecular-sieve column chromatography revealed that IL-1β induced the release of a 19- to 20-kDa chemotactic mass that was inhibited by anti-human G-CSF antibody. IL-1β stimulated the release of G-CSF in a dose-dependent fashion, but the time-dependent profile of G-CSF showed that the concentration of G-CSF declined after 48 h. Tumor necrosis factor (TNF)-α, Escherichia coli lipopolysaccharide (LPS), and bradykinin (BK) stimulated A549 cells to release NCA that was inhibited by anti-G-CSF antibody. The release of G-CSF in response to TNF-α, LPS, and BK was significantly increased. The similar concentrations of human recombinant G-CSF (10–1,000 pg/ml) as in the supernatant fluid induced neutrophil chemotaxis. G-CSF mRNA was expressed time and dose dependently at 4 h and declined after 4 h in response to IL-1β as evaluated by RT-PCR. The expression of G-CSF mRNA was also observed by TNF-α, LPS, and BK stimulation. These data suggest that type II alveolar epithelial cells may produce G-CSF as NCA and may participate in the regulation of leukocyte extravasation.

scholarly journals Restoring HSP70 deficiencies improves glucose tolerance in diabetic monkeys

2011 ◽  
Vol 300 (5) ◽  
pp. E894-E901 ◽  
Author(s):  
Kylie Kavanagh ◽  
David M. Flynn ◽  
Kurt A. Jenkins ◽  
Li Zhang ◽  
Janice D. Wagner
Keyword(s):  
Heat Shock ◽  
Glucose Tolerance ◽  
Ex Vivo ◽  
Heat Shock Factor 1 ◽  
Vervet Monkeys ◽  
Primate Model ◽  
Chronic Hyperglycemia ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Improve Glucose Tolerance

We evaluated heat shock protein 70 (HSP70) changes in diabetes mellitus (DM) in a nonhuman primate model. To this end, two studies were conducted in DM vervet monkeys. 1) Normal control and streptozotocin-induced DM monkeys (Stz-DM) that were differentiated into moderately or poorly controlled DM by judicious insulin administration were evaluated. Liver was collected at 4, 8, 12, 16, and 20 wk after streptozotocin, exposed to ex vivo heat shock at 42°C, and immunoblotted for heat shock factor 1 (HSF1), HSP70, and phosphorylated HSF1. 2) Spontaneous DM monkeys that were not pharmacologically induced were included in a crossover study of the HSP70-inducing drug geranylgeranylacetone (GGA). GGA at 20 mg/kg was given for 14 days with a 6-wk washout period. Glucose tolerance testing and plasma and muscle HSP70 were the primary outcome measurements. In Stz-DM, hyperglycemia reduced hepatic HSP70 in a dose-dependent fashion. HSF1 was increased in livers of monkeys with Stz-DM, but responses to ex vivo heat shock were impaired vs. normal monkeys. Activation of HSF1 appears to be important, because the phosphorylation change with heat stress was nearly perfectly correlated with HSP70 increases. Impaired HSF1 activation was also seen in Stz-DM after chronic hyperglycemia (>12 wk). In naturally occurring DM, increased circulating HSP70 resulted in significantly improved glucose tolerance and significant, positive trends in other measurements of insulin resistance. No change in muscle HSP70 content was observed. We conclude that increasing HSP70, potentially through targeting hyperglycemia-related deficits in HSF1 induction and activation in the liver, is a potent and viable strategy to improve glucose tolerance.

Synthetic smoke with acrolein but not HCl produces pulmonary edema

1988 ◽  
Vol 64 (3) ◽  
pp. 1121-1133 ◽  
Author(s):  
C. A. Hales ◽  
P. W. Barkin ◽  
W. Jung ◽  
E. Trautman ◽  
D. Lamborghini ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Low Dose ◽  
Smoke Inhalation ◽  
High Dose ◽  
Lung Water ◽  
Thermodilution Technique ◽  
Carbon Particles ◽  
Delayed Onset ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The chemical toxins in smoke and not the heat are responsible for the pulmonary edema of smoke inhalation. We developed a synthetic smoke composed of carbon particles (mean diameter of 4.3 microns) to which toxins known to be in smoke, such as HCl or acrolein, could be added one at a time. We delivered synthetic smoke to dogs for 10 min and monitored extravascular lung water (EVLW) accumulation thereafter with a double-indicator thermodilution technique. Final EVLW correlated highly with gravimetric values (r = 0.93, P less than 0.01). HCl in concentrations of 0.1-6 N when added to heated carbon (120 degrees C) and cooled to 39 degrees C produced airway damage but no pulmonary edema. Acrolein, in contrast, produced airway damage but also pulmonary edema, whereas capillary wedge pressures remained stable. Low-dose acrolein smoke (less than 200 ppm) produced edema in two of five animals with a 2- to 4-h delay. Intermediate-dose acrolein smoke (200-300 ppm) always produced edema at an average of 147 ± 57 min after smoke, whereas high-dose acrolein (greater than 300 ppm) produced edema at 65 ± 16 min after smoke. Thus acrolein but not HCl, when presented as a synthetic smoke, produced a delayed-onset, noncardiogenic, and peribronchiolar edema in a roughly dose-dependent fashion.

Plasminogen Interactions with Immobilized Fibrinogen

1989 ◽  
Vol 62 (04) ◽  
pp. 1078-1082 ◽  
Author(s):  
Burt Adelman ◽  
Patricia Ouynn
Keyword(s):  
Immunosorbent Assay ◽  
Aminocaproic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Binding Regions ◽  
Dose Dependent Fashion ◽  
Epsilon Aminocaproic Acid ◽  
Dose Dependent

SummaryThis report describes the binding of plasminogen to fibrinogen adsorbed onto polystyrene wells. Binding was determined by enzyme linked immunosorbent assay. Both glu- and lys-plasminogen bound to immobilized fibrinogen in a dose-dependent fashion. However, more lys- than glu-plasminogen bound when equal concentrations of either were added to immobilized fibrinogen. Plasminogen binding was inhibited by epsilon aminocaproic acid indicating that binding was mediated via lysine-binding regions of plasminogen. Soluble fibrinogen added in excess of immobilized fibrinogen did not compete for plasminogen binding but fibrinogen fragments produced by plasmin digestion of fibrinogen did. Treatment of immobilized fibrinogen with thrombin caused a small but significant (p <0.01) increase in plasminogen binding. These studies demonstrate that immobilized fibrinogen binds both glu- and lys-plasminogen and that binding is mediated via lysine-binding regions. These interactions may facilitate plasminogen binding to fibrinogen adsorbed on to surfaces and to cells such as platelets which bind fibrinogen.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

1986 ◽  
Vol 56 (02) ◽  
pp. 147-150 ◽  
Author(s):  
V Pengo ◽  
M Boschello ◽  
A Marzari ◽  
M Baca ◽  
L Schivazappa ◽  
...  
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Ex Vivo ◽  
Early Stage ◽  
Shape Change ◽  
Adenosine Diphosphate ◽  
Dose Dependent ◽  
Plateletderived Growth Factor ◽  
Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

2020 ◽  
Vol 21 ◽  
Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Species ◽  
A549 Cells ◽  
Bactericidal Effect ◽  
Minimal Bactericidal Concentration ◽  
Viability Assay ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

Cancer Immunology and CAR-T Cells: A Turning Point Therapeutic Approach in Colorectal Carcinoma with clinical insight

2020 ◽  
Vol 20 ◽  
Author(s):  
Suman K Ray ◽  
Yamini Meshram ◽  
Sukhes Mukherjee
Keyword(s):  
T Cells ◽  
Colorectal Carcinoma ◽  
Cancer Immunotherapy ◽  
Clinical Evidence ◽  
Ex Vivo ◽  
Clinical Success ◽  
Recent Decade ◽  
Molecular Immunology ◽  
Car T ◽  
Engineered T Cells

: Cancer immunotherapy endeavours in harnessing delicate strength and specificity of immune system for therapy of different malignancies including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies including colorectal carcinoma in a recent decade. Despite considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.

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