Hyperoxia prevents hypoxia-induced bronchial hyperreactivity via a cyclooxygenase-independent mechanism

1991 ◽  
Vol 70 (2) ◽  
pp. 740-747 ◽  
Author(s):  
J. D'Brot ◽  
T. Ahmed
Keyword(s):  
Airway Responsiveness ◽  
Prior Exposure ◽  
Gas Mixture ◽  
Protective Effects ◽  
Bronchial Reactivity ◽  
Independent Mechanism ◽  
Before And After ◽  
Sham Exposure ◽  
Hypoxic Gas Mixture ◽  
Dependent Mechanism

We tested the hypothesis that prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity, possibly via a cyclooxygenase-dependent mechanism. In 15 sheep, specific lung resistance (sRL) was measured before and after 30 min of exposure to either air or a hypoxic gas mixture (13% O2). The sheep then inhaled 50 breaths of aerosolized 5% histamine solution (n = 9) or 10 breaths of 2.5% carbachol solution (n = 9), and measurements of sRL were repeated. On subsequent days the above protocols were repeated after a 30-min exposure to hyperoxia (O2 greater than or equal to 95%), without or after pretreatment with indomethacin (2 mg/kg). After air-sham exposure, carbachol and histamine increased mean sRL to 370 +/- 40 (SE) and 309 +/- 65% of baseline, respectively. Exposure to the hypoxic gas mixture had no effect on baseline sRL but enhanced the airway responsiveness to carbachol and histamine; mean sRL increased to 740 +/- 104 and 544 +/- 76% of baseline, respectively (P less than 0.05). Prior 30-min exposure to hyperoxia prevented the hypoxia-induced enhancement of bronchial reactivity to carbachol (sRL = 416 +/- 66% of baseline) and histamine (sRL = 292 +/- 41% of baseline) without affecting the airway responsiveness to these agents after air. Pretreatment with indomethacin did not reverse the protective effects of hyperoxia or the hypoxia-induced enhancement of bronchial reactivity. We conclude that 1) prior exposure to alveolar hyperoxia prevents the hypoxia-induced enhancement of bronchial reactivity and 2) neither the protective effects of hyperoxia nor the hypoxia-induced enhancement of bronchial reactivity is mediated via a cyclooxygenase-dependent mechanism.

Hypoxia-induced enhancement of nonspecific bronchial reactivity: role of leukotrienes

1988 ◽  
Vol 65 (1) ◽  
pp. 194-199 ◽  
Author(s):  
J. D'Brot ◽  
T. Ahmed
Keyword(s):  
Lavage Fluid ◽  
Lung Lavage ◽  
Gas Mixture ◽  
Base Line ◽  
Bronchial Reactivity ◽  
Air Exposure ◽  
Before And After ◽  
Alveolar Hypoxia ◽  
Conscious Sheep ◽  
Hypoxic Gas Mixture

Because alveolar hypoxia has been shown to cause an increase of leukotrienes in lung lavage fluid, we tested the hypothesis that enhancement of nonspecific bronchial reactivity during alveolar hypoxia may be mediated by leukotrienes. In nine conscious sheep we determined specific lung resistance (sRL) before and after exposure to either air or a hypoxic gas mixture (13% O2) for 30 min. The sheep then inhaled 50 breaths of aerosolized 5% histamine solution (n = 6) or 10 breaths of 2.5% carbachol solution (n = 6) on different days, and the measurements of sRL were repeated. On subsequent days the above protocols were repeated after pretreatment with aerosolized FPL 57231 (3 ml, 1% solution), a leukotriene receptor antagonist. Inhalation of histamine and carbachol after exposure to air caused an increase in mean sRL to 337 and 342% of base line, respectively (P less than 0.05). Exposure to the hypoxic gas mixture had no effect on sRL but enhanced the histamine- and carbachol-induced increases in mean sRL to 621 and 646% of base line, respectively (P less than 0.05); these increases were significantly higher than those observed after air exposure (P less than 0.05). FPL 57231 prevented the hypoxia-induced enhancement of bronchial reactivity to histamine and carbachol without affecting the airway responsiveness to these agents after air. In another group of eight sheep, aerosolized leukotriene C4, at a dose (50 micrograms) that per se had no affect on sRL, enhanced the bronchial reactivity to carbachol. These data suggest that in sheep during alveolar hypoxia airway hyperresponsiveness may be due to the priming of airway smooth muscle by leukotrienes.

scholarly journals Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs

2000 ◽  
Vol 279 (5) ◽  
pp. H2077-H2084 ◽  
Author(s):  
David B. Pearse ◽  
Patrice M. Becker
Keyword(s):  
Nitric Oxide ◽  
High Pressure ◽  
Reflection Coefficient ◽  
Cyclic Nucleotides ◽  
Fluid Flux ◽  
No Donor ◽  
Independent Mechanism ◽  
Dependent Mechanism ◽  
Intravascular Pressure

We previously found that increased intravascular pressure decreased ischemic lung injury by a nitric oxide (NO)-dependent mechanism (Becker PM, Buchanan W, and Sylvester JT. J Appl Physiol 84: 803–808, 1998). To determine the role of cyclic nucleotides in this response, we measured the reflection coefficient for albumin (ςalb), fluid flux ( J˙), cGMP, and cAMP in ferret lungs subjected to either 45 min (“short”; n = 7) or 180 min (“long”) of ventilated ischemia. Long ischemic lungs had “low” (1–2 mmHg, n = 8) or “high” (7–8 mmHg, n = 6) vascular pressure. Other long low lungs were treated with the NO donor ( Z)-1-[ N-(3-ammoniopropyl)- N-( n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate; 5 × 10−4 M, n = 6) or 8-bromo-cGMP (5 × 10−4 M, n = 6). Compared with short ischemia, long low ischemia decreased ςalb (0.23 ± 0.04 vs. 0.73 ± 0.08; P < 0.05) and increased J˙ (1.93 ± 0.26 vs. 0.58 ± 0.22 ml · min−1 · 100 g−1; P < 0.05). High pressure prevented these changes. Lung cGMP decreased by 66% in long compared with short ischemia. Lung cAMP did not change. PAPA-NONOate and 8-bromo-cGMP increased lung cGMP, but only 8-bromo-cGMP decreased permeability. These results suggest that ischemic vascular injury was, in part, mediated by a decrease in cGMP. Increased vascular pressure prevented injury by a cGMP-independent mechanism that could not be mimicked by administration of exogenous NO.

scholarly journals Clinical and Radiologic Disease Activity in Pregnancy and Postpartum in MS

2021 ◽  
Vol 8 (2) ◽  
pp. e959
Author(s):  
Annika Anderson ◽  
Kristen M. Krysko ◽  
Alice Rutatangwa ◽  
Tanya Krishnakumar ◽  
Chelsea Chen ◽  
...  
Keyword(s):  
San Francisco ◽  
Relapse Rate ◽  
Treatment Decision ◽  
Clinical Activity ◽  
Protective Effects ◽  
Treatment Decision Making ◽  
Early Postpartum ◽  
Pregnancy And Postpartum ◽  
Before And After ◽  
The University

ObjectiveTo evaluate radiologic and clinical inflammatory activity in women with MS during pregnancy and postpartum.MethodsWe performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the University of California, San Francisco MS Center between 2005 and 2018. Proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions (primary outcome) and annualized relapse rate (ARR; secondary) were compared before and after pregnancy.ResultsWe identified 155 pregnancies in 119 women (median Expanded Disability Status Scale [EDSS] 2.0). For the 146 live birth pregnancies, prepregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p = 0.017) and increased in the 3 months postpartum (ARR 0.61, p = 0.012); and 16% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 53% had new T2 and/or Gd+ lesions postpartum compared with 32% prepregnancy (p < 0.001). Postpartum clinical relapses were associated with Gd+ lesions (p < 0.001). However, even for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 31%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio = 0.3, 95% confidence interval 0.1–0.9) were observed for relapses.ConclusionsBuilding on previous reports of increased relapse rate in the first 3 months postpartum, we report a significant association between inflammation on MRI and this clinical activity. We also detected postpartum radiologic activity in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.

Analysis of the cell adhesion mechanism using somatic cell hybrids. I. Aggregation of hybrid cells between adhesive V79 and non-adhesive Ehrlich's ascites tumour cells

1980 ◽  
Vol 43 (1) ◽  
pp. 391-406
Author(s):  
H. Aoyama ◽  
T.S. Okada ◽  
M. Takeichi
Keyword(s):  
Cell Adhesion ◽  
Chinese Hamster ◽  
Hybrid Cells ◽  
Adhesive Properties ◽  
V79 Cells ◽  
Ascites Tumour ◽  
Independent Mechanism ◽  
Eat Cells ◽  
Hybrid Clones ◽  
Dependent Mechanism

V79 Chinese hamster cells dissociated with 1 nm EDTA retain 2 kinds of cell adhesion mechanisms, one dependent on Ca2+ and the other independent of Ca2+. Ehrlich's ascites tumour (EAT) cells are provided with neither Ca2+-dependent nor CA2+-independent mechanisms. Studies on the aggregation of cells of 25 different hybrid clones obtained by fusing these 2 lined cells revealed the following points with regard to adhesive properties of hybrid cells. (1) The activity of the Ca2+-independent mechanism was lower in most hybrid clones than in parental V79 cells. (2) There were a few hybrid clones whose Ca2+-dependent mechanism activity was lower than in V79 cells. In these clones, the Ca2+-independent mechanism was also less active than the parental cells. (3) A hybrid clone with reduced Ca2+-dependent mechanism activity only was not found. (4) All the hybrid clones have at least one set of chromosomes derived from V79. (5) The number of chromosomes derived from EAT cells tended to be less in hybrid clones with lower aggregative ability. These results can be explained by assuming that the activity of the Ca2+-independent and Ca2+-dependent mechanisms of V79 cells may be differently inhibited by genes contained in EAT cells.

Different mechanisms in the attachment of cells to native and denatured collagen

1979 ◽  
Vol 38 (1) ◽  
pp. 267-281
Author(s):  
S.L. Schor ◽  
J. Court
Keyword(s):  
Cell Attachment ◽  
Experimental Conditions ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Independent Mechanism ◽  
Cell Matrix Interactions ◽  
Serum Dependent ◽  
Kinetics Of ◽  
Dependent Mechanism

The attachment of cells to collagen has been reported previously to require the presence of serum and the particular serum protein involved in this process, variously known as CIG, CAP or fibronectin, has been isolated. This conclusion that cell attachment to collagen requires serum (or more precisely, fibronectin) is based on experiments measuring the kinetics of cell attachment to films of collagen. We have measured the kinetics of attachment of HeLa and attachment to films of collagen-containing substrata under a variety of experimental conditions and present evidence that the serum-dependent mechanism of cell attachment described by others is actually only the case for films of denatured collagen, while cell attachment to native collagen fibres occurs by a different, serum-independent, mechanism. The possible relevance of these findings to cell-matrix interactions in vivo is discussed.

Elevation Of Antithrombin III By Sulfinpyrazone Therapy In Chronic Renal Failure

1981 ◽  
Author(s):  
M Bern ◽  
J Green
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Antithrombin Iii ◽  
Chronic Hemodialysis ◽  
Protective Effects ◽  
Platelet Factor ◽  
At Iii ◽  
Before And After ◽  
Artery Disease ◽  
And Function

Sulfinpyrazone can reduce the incidence of thrombosis of A-V shunts in chronic renal failure. The drug is also reported to prevent acute deaths from coronary artery disease. This study was to determine mechanisms for these protective effects.Patients on chronic hemodialysis served as the study models. Six patients on dialysis three times per week for 6 or more months received sulfinpyrazone 200 mgm t.i.d. p.o. for 14 days. Blood samples were obtained before dialysis was begun before and after the 14 days of drug therapy.Results are shown as mean ± standard error of mean.AT III levels rose significantly by functional and immune assays. Functional levels (by von Kaulla technique) rose 24.5 ± 3.1 sec. to 47.3 + 5.5 sec. (P>.005) Plasma protein AT III (by radial immunodiffusion) rose 31.2 ± 2.17 mg/dl to 37.9 ± 2.1 mgm/dl. (P>.01) Platelet factor 4 (by Abbot radioimmunology assay) fell from 46.4 + 13.6 ngm/ml to 9.5 ± 1.1 ngm/ml.(P>.005) The concentration of thrombin-anti-thrombin complex (by R. Rosenberg, Harvard Medical School, Boston) rose from 4.2 ± .09 to 8.4 ± 1.0 (P>.005)Thus it appears that sulfinpyrazone elevates antithrombin concentration and function while simultaneously suppressing platelet release. These two effects may or may not be mutually dependent. The clinical efficacy of sulfinpyrazone may relate in part to the elevation of antithrombin III, probably by inhibiting its consumption, while also inhibiting platelet function.

Priming-Induced Shift in Synaptic Plasticity in the Rat Hippocampus

1999 ◽  
Vol 82 (4) ◽  
pp. 2024-2028 ◽  
Author(s):  
Hongyan Wang ◽  
John J. Wagner
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Crossover Point ◽  
Term Potentiation ◽  
Before And After ◽  
History Of ◽  
The Brain ◽  
Dependent Mechanism

The activity history of a given neuron has been suggested to influence its future responses to synaptic input in one prominent model of experience-dependent synaptic plasticity proposed by Bienenstock, Cooper, and Munro (BCM theory). Because plasticity of synaptic plasticity (i.e., metaplasticity) is similar in concept to aspects of the BCM proposal, we have tested the possibility that a form of metaplasticity induced by a priming stimulation protocol might exhibit BCM-like characteristics. CA1 field excitatory postsynaptic potentials (EPSPs) obtained from rat hippocampal slices were used to monitor synaptic responses before and after conditioning stimuli (3–100 Hz) of the Schaffer collateral inputs. A substantial rightward shift (>5-fold) in the frequency threshold between long-term depression (LTD) and long-term potentiation (LTP) was observed <1 h after priming. This change in the LTD/P crossover point occurred at both primed and unprimed synaptic pathways. These results provide new support for the existence of a rapid, heterosynaptic, experience-dependent mechanism that is capable of modifying the synaptic plasticity phenomena that are commonly proposed to be important for developmental and learning/memory processes in the brain.

scholarly journals Protective Effects of ALDH1A Enzyme Inhibition on Helicobacter-Induced Colitis in Smad3−/− Mice are Associated with Altered α4ß7 Integrin Expression on Activated T Cells

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2927
Author(s):  
Audrey Seamons ◽  
Michael Haenisch ◽  
Stacey Meeker ◽  
Olesya Pershutkina ◽  
Thea Brabb ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Enzyme Inhibition ◽  
Treatment Options ◽  
T Cell Subsets ◽  
Protective Effects ◽  
Activated T Cells ◽  
Before And After ◽  
Inflammatory Bowel ◽  
Draining Lymph Nodes

Many inflammatory bowel disease (IBD) patients require surgical intervention due to limited pharmacological treatment options. Antibodies targeting α4ß7, a gut-homing integrin, are one of the most promising IBD treatments. As retinoic acid (RA) regulates expression of gut-homing proteins including α4ß7 integrin, we tested if ALDH1A enzymes in the RA synthesis pathway could be targeted for IBD treatment using a potent inhibitor, WIN 18,446. Age- and sex-matched Smad3−/− mice were fed a diet with and without WIN 18,446 for 3 weeks before triggering inflammation with Helicobacter bilis infection. Colitis was evaluated by histopathology one week following the IBD trigger, and T cell subsets were evaluated before and after the IBD trigger. WIN 18,446 treatment significantly reduced IBD severity in Smad3−/− mice and reduced expression of α4ß7 integrin on multiple activated CD4+ T cell subsets. This change was associated with increased ratios of induced regulatory T cells to Th17 cells during the inflammatory response in the draining lymph nodes. These studies indicate that RA reduction via ALDH1A enzyme inhibition is a potential new target for IBD treatment. Further studies are needed to examine its effects on other types of immune cells, to evaluate the efficacy window for this target, and to determine its efficacy in other animal models of IBD.

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