scholarly journals Effect of Bronchial Thermoplasty on Airway Closure

2007 ◽  
Vol 1 ◽  
pp. CCRPM.S365
Author(s):  
Robert Brown ◽  
William Wizeman ◽  
Christopher Danek ◽  
Wayne Mitzner
Keyword(s):  
Experimental Studies ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Bronchial Thermoplasty ◽  
Basket Catheter ◽  
Significant Impairment ◽  
High Concentrations ◽  
High Doses ◽  
Higher Doses ◽  
Very High

Background Bronchial Thermoplasty, a procedure that applies thermal energy to the airway wall has been shown to impair the ability of airway to contract in response to methacholine chloride (Mch). The technique has been advocated as an alternative treatment for asthma that may permanently limit airway narrowing. In previous experimental studies in dogs and humans, it was shown that those airways treated with bronchial thermoplasty had significant impairment of Mch responsiveness. Methods In the present study, we investigated the ability of canine airways to close completely with very high concentrations of Mch after bronchial thermoplasty. Bronchial thermoplasty was performed on dogs using the Alair System, comprising a low power RF controller and a basket catheter with four electrodes. A local atomization of Mch agonist was delivered directly to the epithelium of the same airway locations with repeated challenges. Airway size was measured with computed tomography, and closure was considered to occur in any airway where the lumen fell below the resolution of the scanner (< 1 mm). Results Our results show that, while treated airways still have the capacity to close at very high doses of Mch, this ability is seriously impaired after treatment, requiring much higher doses. Conclusions Bronchial thermoplasty as currently applied seems to simply shift the entire dose response curve toward increasing airway size. Thus, this procedure simply serves to minimize the ability of airways to narrow under any level of stimulation.

scholarly journals Vitamin B12 transport in blood. I. Congenital deficiency of transcobalamin II

Blood ◽  
1975 ◽  
Vol 45 (1) ◽  
pp. 71-82 ◽  
Author(s):  
E Gimpert ◽  
M Jakob ◽  
WH Hitzig
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Congenital Deficiency ◽  
Complete Clinical Remission ◽  
High Concentrations ◽  
High Doses ◽  
Vitamin B12 Binder ◽  
Very High ◽  
Transcobalamin Ii

Abstract Some characteristics of vitamin B12 binding and transport in the serum of an infant with congenital hereditary transcobalamin II (TC II) deficiency were studied using the following parameters and methods: vitamin B12 level and binding capacity; electrophoretic mobility in polyacrylamide gel electrophoresis; various immunodiffusion and absorption experiments, using a specific anti-TC II antiserum and the patient's serum as antigen. The results of these studies point to a deficient synthesis of TC II. Parenteral administration of high doses of vitamin B12 was followed by rapid and complete clinical remission and the appearance of vitamin B12 binder in the alpha 2 region which is similar to “fetal binder.” Thus, very high concentrations of vitamin B12, either carrier free or bound to this alpha 2 binder, were able to correct the disturbed physiology of TC II deficiency, presumably by normalization of DNA-thymine synthesis.

scholarly journals Administration of erythropoietin to newborn rats results in diminished neutrophil production

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1241-1246
Author(s):  
RD Christensen ◽  
KW Liechty ◽  
JM Koenig ◽  
KR Schibler ◽  
RK Ohls
Keyword(s):  
Tritiated Thymidine ◽  
Neonatal Rat ◽  
Newborn Rats ◽  
Suicide Rates ◽  
Colony Forming Units ◽  
High Concentrations ◽  
Macrophage Colony ◽  
High Doses ◽  
Very High

Very high concentrations of erythropoietin (epo), in clonogenic cultures, result in reduced production of neutrophils, and fetal progenitors are more sensitive to this effect of epo than are those of adults. However, the significance of this observation is unclear because no evidence of reduced neutrophil production has been presented following administration of recombinant epo to human or animal subjects. In the present study we injected newborn rats, beginning on the first day of life, with 20, 200, or 2,000 U epo/kg body weight, and measured serum epo concentrations after 2, 8, 24, or 48 hours. After selecting a dose that resulted in serum concentrations greater than 1,000 mU/mL (a concentration that resulted in down-modulation of neutrophil production from neonatal rat progenitors in vitro) other newborn rats were treated for 3 days with that dose (1,000 U epo/kg) or a vehicle control. Administration of epo resulted in increased hematocrits (P less than .001), reticulocyte counts (P less than .001), normoblasts/femur (P less than .05), and normoblasts/spleen (P less than .001). Recipients of epo also had more erythroid colony-forming units (CFU-E) (P less than .001) and higher CFU-E tritiated thymidine suicide rates (P less than .01) than did controls. However, femurs and spleens of epo recipients contained fewer postmitotic neutrophils (femur, P less than .01; spleen, P less than .01), proliferative neutrophils (femur, P less than .01; spleen, P less than .02), granulocyte-macrophage colony-forming units (CFU-GM) (P less than .005), and lower CFU-GM tritiated thymidine suicide rates (P less than .01). Seven and nine days after twice-daily administration of 2,000 U epo/kg, blood neutrophil concentrations had diminished (P less than .05). Thus, administration of high doses of recombinant epo to newborn rats resulted in diminished neutrophil production accompanying accelerated erythropoiesis.

scholarly journals Uremic Toxins and Ciprofloxacin Affect Human Tenocytes In Vitro

2020 ◽  
Vol 21 (12) ◽  
pp. 4241
Author(s):  
Erman Popowski ◽  
Benjamin Kohl ◽  
Tobias Schneider ◽  
Joachim Jankowski ◽  
Gundula Schulze-Tanzil
Keyword(s):  
Type I Collagen ◽  
Uremic Toxins ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Cell Matrix ◽  
High Concentrations ◽  
High Doses ◽  
Very High

Tendinopathy is a rare but serious complication of quinolone therapy. Risk factors associated with quinolone-induced tendon disorders include chronic kidney disease accompanied by the accumulation of uremic toxins. Hence, the present study explored the effects of the representative uremic toxins phenylacetic acid (PAA) and quinolinic acid (QA), both alone and in combination with ciprofloxacin (CPX), on human tenocytes in vitro. Tenocytes incubated with uremic toxins +/- CPX were investigated for metabolic activity, vitality, expression of the dominant extracellular tendon matrix (ECM) protein type I collagen, cell-matrix receptor β1-integrin, proinflammatory interleukin (IL)-1β, and the ECM-degrading enzyme matrix metalloproteinase (MMP)-1. CPX, when administered at high concentrations (100 mM), suppressed tenocyte metabolism after 8 h exposure and at therapeutic concentrations after 72 h exposure. PAA reduced tenocyte metabolism only after 72 h exposure to very high doses and when combined with CPX. QA, when administered alone, led to scarcely any cytotoxic effect. Combinations of CPX with PAA or QA did not cause greater cytotoxicity than incubation with CPX alone. Gene expression of the pro-inflammatory cytokine IL-1β was reduced by CPX but up-regulated by PAA and QA. Protein levels of type I collagen decreased in response to high CPX doses, whereas PAA and QA did not affect its synthesis significantly. MMP-1 mRNA levels were increased by CPX. This effect became more pronounced in the form of a synergism following exposure to a combination of CPX and PAA. CPX was more tenotoxic than the uremic toxins PAA and QA, which showed only distinct suppressive effects.

scholarly journals Vitamin B12 transport in blood. I. Congenital deficiency of transcobalamin II

Blood ◽  
1975 ◽  
Vol 45 (1) ◽  
pp. 71-82 ◽  
Author(s):  
E Gimpert ◽  
M Jakob ◽  
WH Hitzig
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Congenital Deficiency ◽  
Complete Clinical Remission ◽  
High Concentrations ◽  
High Doses ◽  
Vitamin B12 Binder ◽  
Very High ◽  
Transcobalamin Ii

Some characteristics of vitamin B12 binding and transport in the serum of an infant with congenital hereditary transcobalamin II (TC II) deficiency were studied using the following parameters and methods: vitamin B12 level and binding capacity; electrophoretic mobility in polyacrylamide gel electrophoresis; various immunodiffusion and absorption experiments, using a specific anti-TC II antiserum and the patient's serum as antigen. The results of these studies point to a deficient synthesis of TC II. Parenteral administration of high doses of vitamin B12 was followed by rapid and complete clinical remission and the appearance of vitamin B12 binder in the alpha 2 region which is similar to “fetal binder.” Thus, very high concentrations of vitamin B12, either carrier free or bound to this alpha 2 binder, were able to correct the disturbed physiology of TC II deficiency, presumably by normalization of DNA-thymine synthesis.

Efficacy of AT in pre-eclampsia: a case-control prospective trial

2004 ◽  
Vol 91 (02) ◽  
pp. 283-289 ◽  
Author(s):  
Sara Fantinato ◽  
Francesca Manganelli ◽  
Massimo Milani ◽  
Umberto Nicolini ◽  
Antonio Girolami ◽  
...  
Keyword(s):  
Prospective Trial ◽  
Experimental Studies ◽  
High Dose ◽  
Granulocyte Elastase ◽  
Markers Of Inflammation ◽  
Significant Prolongation ◽  
Inflammatory State ◽  
High Doses ◽  
Higher Doses ◽  
D Dimer

SummaryPre-eclampsia is an extremely severe condition. It is associated with vasospasm, activation of the coagulation system and abnormal haemostasis. In pre-eclamptic patients increased plasmatic concentrations of fibronectin, laminin, von Willebrand factor (VWF) and endothelin are observed. Experimental studies on rats have also shown that the doses of antithrombin III (AT) needed to mediate anti-inflammatory processes are much higher than those required to obtain the anti-coagulant effect. The study aimed to evaluate the clinical efficacy of treatment with high AT doses (HD) in comparison with standard doses (SD). The primary endpoint was the prolongation of pregnancy defined as time (in days) from enrollment to delivery and to assess the maternal bleeding at and after delivery. The secondary endpoint was to demonstrate a role for AT in controlling haemostasis at conventional doses, and the inflammatory state at higher doses. The biochemical parameters assessed were: AT activity (%), Fibronectin (Fn), Fibrinogen, D-dimer, Uricemia, Proteinuria 24h, Protein C Reactive (PCR), Granulocyte Elastase and Endothelin. This study included 23 pre-eclamptic women. Patients were randomly subdivided into two groups: 10 patients (“cases”) were treated with high doses of AT (6 vials: 3000 units) once daily for 5 days, or until delivery, while 13 women (“controls”) were treated with doses of AT sufficient to maintain at least 80% of the activity. High-dose therapy was associated with prolongation of pregnancy by 2.5 days more when compared with controls (p = 0.03; Mann-Whitney test). The incidence of clinical significant bleeding was lower in cases than in controls (mean 550 mL vs. 650 mL, respectively). Preventiveand conservative-type treatment of moderatesevere pre-eclampsia, based on the administration high doses of AT, allows a significant prolongation of pregnancy, and thus a better neonatal outcome, as well as less maternal intra-and post-operative bleeding. Fn, PCR and elastase levels (markers of inflammation) decrease in the HD group in comparison with SD group. In the HD group, the AT plasma levels were obviously higher both at the end of the treatment (p < 0.0001) and after delivery (p = 0.03), in comparison with SD group. The fibrinogen and D-dimer levels were above the reference interval in both groups. TPA and PAI 1 were found to be significantly raised in the course of pre-eclampsia. In conclusion, the biochemical findings support a role for AT in controlling the haemostasis at conventional doses, and the inflammatory state at higher doses.

Effect of Gamma Irradiation on the Microstructure and Morphology of Polyethylene Oxide and Polyvinyl Alcohol Blends

2009 ◽  
Vol 83-86 ◽  
pp. 524-529
Author(s):  
Mariam Al-Ma'adeed ◽  
N.J. Al-Thani
Keyword(s):  
Thin Films ◽  
Thermal Stability ◽  
Hydrogen Bonding ◽  
Free Radicals ◽  
Polyvinyl Alcohol ◽  
Polyethylene Oxide ◽  
Diffusion Controlled ◽  
High Doses ◽  
Higher Doses ◽  
Very High

Thin films of a blend of 90, 75, 50 (wt/wt%) percentage of polyethylene oxide and polyvinyl alcohol were synthesized and irradiated with 5, 25, 50, 100 and 200 kGy. The presence of PVA leads to diffusion controlled mechanism where it decreases the crystallinity of PEO as restricted crystallization occurs.Low doses of 5 kGy cause crosslinking of the blends and increase the thermal stability. Higher doses up to 100 kGy cause the PEO crystallite boundaries to be erased and to blur spherulites structure; it also leads to an increase in the crystallinity. Higher doses of 200 kGy cause an increase in the hydrogen bonding where the material is more crystalline in structure and broken down which made more segments available for the hydrogen bonding. Degradation and oxidation of the blends due to the presence of free radicals in the polymer irradiated in air is noticed for blends with very high doses. Never the less, PVA in these blends protects the PEO composite from the effect of radiation.

scholarly journals CD14 Mediates Binding of High Doses of LPS but Is Dispensable for TNF-αProduction

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Kinga Borzęcka ◽  
Agnieszka Płóciennikowska ◽  
Hanna Björkelund ◽  
Andrzej Sobota ◽  
Katarzyna Kwiatkowska
Keyword(s):  
Dextran Sulfate ◽  
Inhibitory Effect ◽  
Scavenger Receptors ◽  
Signaling Complex ◽  
Lower Extent ◽  
High Concentrations ◽  
High Doses ◽  
Higher Doses ◽  
Competitive Ligand ◽  
Lps Binding

Activation of macrophages with lipopolysaccharide (LPS) involves a sequential engagement of serum LPS-binding protein (LBP), plasma membrane CD14, and TLR4/MD-2 signaling complex. We analyzed participation of CD14 in TNF-αproduction stimulated with 1–1000 ng/mL of smooth or rough LPS (sLPS or rLPS) and in sLPS binding to RAW264 and J744 cells. CD14 was indispensable for TNF-αgeneration induced by a low concentration, 1 ng/mL, of sLPS and rLPS. At higher doses of both LPS forms (100–1000 ng/mL), TNF-αrelease required CD14 to much lower extent. Among the two forms of LPS, rLPS-induced TNF-αproduction was less CD14-dependent and could proceed in the absence of serum as an LBP source. On the other hand, the involvement of CD14 was crucial for the binding of 1000 ng/mL of sLPS judging from an inhibitory effect of the anti-CD14 antibody. The binding of sLPS was also strongly inhibited by dextran sulfate, a competitive ligand of scavenger receptors (SR). In the presence of dextran sulfate, sLPS-induced production of TNF-αwas upregulated about 1.6-fold. The data indicate that CD14 together with SR participates in the binding of high doses of sLPS. However, CD14 contribution to TNF-αproduction induced by high concentrations of sLPS and rLPS can be limited.

Comparative effects of arginine vasopressin and oxytocin in cell culture systems

1992 ◽  
Vol 263 (2) ◽  
pp. F222-F227
Author(s):  
V. A. Briner ◽  
P. Tsai ◽  
H. L. Choong ◽  
R. W. Schrier
Keyword(s):  
Arginine Vasopressin ◽  
Mesangial Cells ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Cell Culture Systems ◽  
Antagonist Binding ◽  
High Concentrations ◽  
High Doses ◽  
Dose Dependent ◽  
Very High

Arginine vasopressin (AVP) and oxytocin (OXT) induced contraction in cultured vascular smooth muscle cells (VSMC) and glomerular mesangial cells (GMC). The contractile response of AVP and OXT was paralleled by Ca2+ mobilization as assessed by 45Ca2+ efflux in a dose-dependent manner. The effects of AVP were blocked by pretreating VSMC and GMC with a V1 antagonist. OXT-stimulated effects, however, were not affected by preexposure of VSMC and GMC to an OXT antagonist but were inhibited by the V1 antagonist. Competition studies demonstrated displacement of [3H]AVP from its receptors by unlabeled AVP, the V1 antagonist, and high doses of OXT. The OXT antagonist was the least effective in displacing [3H]AVP. Thus occupancy of the V1 receptor by OXT may initiate signal transduction and contraction in VSMC and GMC in a manner qualitatively similar to that of the AVP agonist. Cultured myometrium cells (MMC) also contracted in response to AVP and OXT. Moreover, 45Ca2+ efflux increased in response to both hormones in a dose-dependent manner. AVP-stimulated contraction and 45Ca2+ efflux were blocked in MMC by pretreatment with V1 antagonist. OXT-induced effects were inhibited by the OXT antagonist but not by the V1 antagonist. Binding experiments showed that [3H]AVP was displaced equally by unlabeled AVP and V1 antagonist. Very high concentrations of OXT antagonist also demonstrated displacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-6 is a centrally acting endogenous pyrogen in the rat

1991 ◽  
Vol 69 (10) ◽  
pp. 1465-1469 ◽  
Author(s):  
N. J. Rothwell ◽  
N. J. Busbridge ◽  
R. A. Lefeuvre ◽  
A. J. Hardwick ◽  
J. Gauldie ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Cyclooxygenase Inhibitor ◽  
Endogenous Pyrogen ◽  
Conscious Rats ◽  
Corticotrophin Releasing Factor ◽  
High Doses ◽  
Colonic Temperature ◽  
Higher Doses ◽  
Very High ◽  
Factor Antagonist

Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20–100 ng) caused significant increases in colonic temperature and resting oxygen consumption [Formula: see text] in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (α-helical CRF 9–41, 25 μg, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in [Formula: see text] and temperature, and very high doses given intravenously (i.v.) (4 μg/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1β (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and [Formula: see text] in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.Key words: interleukin 6, fever, thermogenesis, brain, pyrogen.

scholarly journals Administration of erythropoietin to newborn rats results in diminished neutrophil production

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1241-1246 ◽  
Author(s):  
RD Christensen ◽  
KW Liechty ◽  
JM Koenig ◽  
KR Schibler ◽  
RK Ohls
Keyword(s):  
Tritiated Thymidine ◽  
Neonatal Rat ◽  
Newborn Rats ◽  
Suicide Rates ◽  
Colony Forming Units ◽  
High Concentrations ◽  
Macrophage Colony ◽  
High Doses ◽  
Very High

Abstract Very high concentrations of erythropoietin (epo), in clonogenic cultures, result in reduced production of neutrophils, and fetal progenitors are more sensitive to this effect of epo than are those of adults. However, the significance of this observation is unclear because no evidence of reduced neutrophil production has been presented following administration of recombinant epo to human or animal subjects. In the present study we injected newborn rats, beginning on the first day of life, with 20, 200, or 2,000 U epo/kg body weight, and measured serum epo concentrations after 2, 8, 24, or 48 hours. After selecting a dose that resulted in serum concentrations greater than 1,000 mU/mL (a concentration that resulted in down-modulation of neutrophil production from neonatal rat progenitors in vitro) other newborn rats were treated for 3 days with that dose (1,000 U epo/kg) or a vehicle control. Administration of epo resulted in increased hematocrits (P less than .001), reticulocyte counts (P less than .001), normoblasts/femur (P less than .05), and normoblasts/spleen (P less than .001). Recipients of epo also had more erythroid colony-forming units (CFU-E) (P less than .001) and higher CFU-E tritiated thymidine suicide rates (P less than .01) than did controls. However, femurs and spleens of epo recipients contained fewer postmitotic neutrophils (femur, P less than .01; spleen, P less than .01), proliferative neutrophils (femur, P less than .01; spleen, P less than .02), granulocyte-macrophage colony-forming units (CFU-GM) (P less than .005), and lower CFU-GM tritiated thymidine suicide rates (P less than .01). Seven and nine days after twice-daily administration of 2,000 U epo/kg, blood neutrophil concentrations had diminished (P less than .05). Thus, administration of high doses of recombinant epo to newborn rats resulted in diminished neutrophil production accompanying accelerated erythropoiesis.

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