scholarly journals Dynamic airway constriction in rats: heterogeneity and response to deep inspiration

2019 ◽  
Vol 317 (1) ◽  
pp. L39-L48
Author(s):  
Thien-Khoi N. Phung ◽  
Scott E. Sinclair ◽  
Patrudu Makena ◽  
Robert C. Molthen ◽  
Christopher M. Waters
Keyword(s):  
Computational Models ◽  
Small Airways ◽  
Respiratory Resistance ◽  
Dynamic Changes ◽  
Airway Narrowing ◽  
Airway Constriction ◽  
X Ray Imaging ◽  
Model Predictions ◽  
Dose Dependent Increase ◽  
Dose Dependent

Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous. To directly investigate regional variations in airway narrowing and the response to deep inspirations (DIs), we utilized tantalum dust and microfocal X-ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. Airway resistance was simultaneously measured using the flexiVent system. Custom-developed software was used to track changes in airway diameters up to generation 19 (~0.3–3 mm). Changes in diameter during bronchoconstriction were then measured in response to methacholine (MCh) challenge. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to MCh challenge. Although there was a dose-dependent increase in total respiratory resistance with MCh, the percent change in airway diameters was similar for increasing doses. A single DI following MCh caused a significant reduction in resistance but did not cause a significant increase in airway diameters. Multiple DIs did, however, cause significant increases in airway diameters. These measurements allowed us to directly quantify dynamic changes in airways during bronchoconstriction and demonstrated greater constriction in larger airways.

scholarly journals Probing airway conditions governing ventilation defects in asthma via hyperpolarized MRI image functional modeling

2009 ◽  
Vol 106 (4) ◽  
pp. 1293-1300 ◽  
Author(s):  
Lisa Campana ◽  
Jennifer Kenyon ◽  
Sanaz Zhalehdoust-Sani ◽  
Yang-Sheng Tzeng ◽  
Yanping Sun ◽  
...  
Keyword(s):  
Computational Models ◽  
Maximum Size ◽  
Measured Data ◽  
Lung Imaging ◽  
Small Airways ◽  
Functional Modeling ◽  
Airway Constriction ◽  
The Mean ◽  
Hyperpolarized Mri ◽  
Central Airway

Image functional modeling (IFM) has been introduced as a method to simultaneously synthesize imaging and mechanical data with computational models to determine the degree and location of airway constriction in asthma. Using lung imaging provided by hyperpolarized 3He MRI, we advanced our IFM method to require matching not only to ventilation defect location but to specific ventilation throughout the lung. Imaging and mechanical data were acquired for four healthy and four asthmatic subjects pre- and postbronchial challenge. After provocation, we first identified maximum-size airways leading exclusively to ventilation defects and highly constricted them. Constriction patterns were then found for the remaining airways to match mechanical data. Ventilation images were predicted for each pattern, and visual and statistical comparisons were done with measured data. Results showed that matching of ventilation defects requires severe constriction of small airways. The mean constriction of such airways leading to the ventilation defects needed to be 70–80% rather than fully closed. Also, central airway constriction alone could not account for dysfunction seen in asthma, so small airways must be involved.

Increased Expression of u-PA and u-PAR on Monocytes by LDL and Lp(a) Lipoproteins – Consequences for Plasmin Generation and Monocyte Adhesion

1999 ◽  
Vol 81 (04) ◽  
pp. 594-560 ◽  
Author(s):  
Florence Ganné ◽  
Marc Vasse ◽  
Jean-Louis Beaudeu ◽  
Jacqueline Peynet ◽  
Arnaud François ◽  
...  
Keyword(s):  
Fold Increase ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Atheromatous Plaque ◽  
Monocyte Adhesion ◽  
Blood Monocytes ◽  
Proteolytic Cascade ◽  
Ecm Degradation ◽  
Dose Dependent Increase ◽  
Dose Dependent

SummaryMonocyte-derived foam cells figure prominently in rupture-prone regions of atherosclerotic plaque. As urokinase/urokinase-receptor (u-PA/u-PAR) is the trigger of a proteolytic cascade responsible for ECM degradation, we have examined the effect of atherogenic lipoproteins on monocyte surface expression of u-PAR and u-PA. Peripheral blood monocytes, isolated from 10 healthy volunteers, were incubated with 10 to 200 µg/ml of native or oxidised (ox-) atherogenous lipoproteins for 18 h and cell surface expression of u-PA and u-PAR was analysed by flow cytometry. Both LDL and Lp(a) induced a dose-dependent increase in u-PA (1.6-fold increase with 200 μg/ml of ox-LDL) and u-PAR [1.7-fold increase with 200 μg/ml of ox-Lp(a)]. There is a great variability of the response among the donors, some of them remaining non-responders (absence of increase of u-PA or u-PAR) even at 200 μg/ml of lipoproteins. In positive responders, enhanced u-PA/u-PAR is associated with a significant increase of plasmin generation (1.9-fold increase with 200 μg/ml of ox-LDL), as determined by an amidolytic assay. Furthermore, monocyte adhesion to vitronectin and fibrinogen was significantly enhanced by the lipoproteins [respectively 2-fold and 1.7-fold increase with 200 μg/ml of ox-Lp(a)], due to the increase of u-PAR and ICAM-1, which are receptors for vitronectin and fibrinogen. These data suggest that atherogenous lipoproteins could contribute to the development of atheromatous plaque by increasing monocyte adhesion and trigger plaque weakening by inducing ECM degradation.

LH-RH TEST IN 100 PATIENTS WITH OVARIAN INSUFFICIENCY

1974 ◽  
Vol 75 (3) ◽  
pp. 428-434 ◽  
Author(s):  
P.-J. Czygan ◽  
M. Breckwoldt ◽  
F. Lehmann ◽  
R. Langefeld ◽  
G. Bettendorf
Keyword(s):  
Intravenous Injection ◽  
Functional State ◽  
Clear Correlation ◽  
Normal Range ◽  
Ovarian Insufficiency ◽  
Lh Rh ◽  
Dose Dependent Increase ◽  
Dose Dependent

ABSTRACT The effect of synthetic LH-RH was studied in 100 patients with various types of ovarian insufficiency by following up the FSH- and LH-levels in plasma. LH-RH was administered in doses of 12.5, 25 and 100 μg as a rapid intravenous injection. The patients were classified according to the endocrine state of the pituitary as evidenced by the urinary gonadotrophin levels. A clear correlation between the functional state of the pituitary and its responsiveness to exogenous LH-RH was demonstrated. Most of the patients with undetectable low urinary gonadotrophin levels failed to respond. The majority of patients with gonadotrophin excretion in the normal range and those with elevated levels reacted with a dose dependent increase in circulating LH. The amount of liberated FSH however was related to the injected dose only in patients with high gonadotrophic excretion. The present study indicates that synthetic LH-RH provides a useful tool in the evaluation of the pitutiary function particularly in patients with low and with undetectable gonadotrophin excretion. The data presented in this paper also demonstrate that the functional state of the pituitary is clearly reflected by the urinary gonadotrophin levels.

Lung Computational Models and the Role of the Small Airways in Asthma

PEDIATRICS ◽  
2020 ◽  
Vol 146 (Supplement 4) ◽  
pp. S359.2-S360
Author(s):  
Jennilee Eppley ◽  
Todd Mahr
Keyword(s):  
Computational Models ◽  
Small Airways

Evaluation of the Laxative activity of Saponin Enriched Hydroethanolic Pericarp extract of Sapindus emarginatus in Animal models

2020 ◽  
Vol 16 ◽  
Author(s):  
Lalitha Vivekanandan ◽  
Roxanne Gekonge Mandere ◽  
Sivakumar Thangavel
Keyword(s):  
Animal Models ◽  
Gravimetric Analysis ◽  
Triterpene Saponins ◽  
Laxative Effect ◽  
Saponin Content ◽  
The Family ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Efficacious Drug

Background: Constipation is a common, predominant, chronic gastrointestinal functional disorder. The drugs available to treat constipation are limited because of their side effects in long term use. So we need of efficacious drug to treat constipation. Sapindus emarginatus Vahl belongs to the family Sapindaceae, commonly known as soapnut. Traditionally used for the antipruritic, antifertility, constipation, and anti-inflammatory agents. Objective: The present study was undertaken to evaluate the laxative activity of hydroethanolic pericarp extract of Sapindus emarginatus (HESE) in animal models. Methods: The saponin content in extract was measured by gravimetric analysis. The laxative activity of hydroethanolic pericarp extract of Sapindus emarginatus is evaluated by the weight of feces matter, charcoal meal hyperperistalsis test, and loperamide induced constipation model. Results: The saponin content of the soapnut pericarp was 13.48 % and the extract was found to be 11.92 %. The results obtained from these models showed a significant dose-dependent increase in fecal weight, peristalsis index, and moisture content compared to control animals. Conclusion: The present study concluded that the oral administration of HESE showed a significant laxative activity by using different animal models. The presence of triterpene saponins is responsible for this activity. Further studies are needed to confirm their mechanism behind the laxative effect. The administration of extract was found to be a valid candidate in constipation therapy.

scholarly journals Morphological and Behavioral Effects in Zebrafish Embryos after Exposure to Smoke Dyes

Toxics ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 9
Author(s):  
Kimberly T. To ◽  
Lindsey St. Mary ◽  
Allyson H. Wooley ◽  
Mitchell S. Wilbanks ◽  
Anthony J. Bednar ◽  
...  
Keyword(s):  
Dose Dependence ◽  
Behavioral Effects ◽  
Zebrafish Embryos ◽  
Comprehensive Understanding ◽  
Anthraquinone Dyes ◽  
Locomotor Movement ◽  
Different Types ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Significant Mortality

Solvent Violet 47 (SV47) and Disperse Blue 14 (DB14) are two anthraquinone dyes that were previously used in different formulations for the production of violet-colored smoke. Both dyes have shown potential for toxicity; however, there is no comprehensive understanding of their effects. Zebrafish embryos were exposed to SV47 or DB14 from 6 to 120 h post fertilization (hpf) to assess the dyes’ potential adverse effects on developing embryos. The potential ability of both dyes to cross the blood–brain barrier was also assessed. At concentrations between 0.55 and 5.23 mg/L, SV47 showed a dose-dependent increase in mortality, jaw malformation, axis curvature, and edemas. At concentrations between 0.15 and 7.54 mg/L, DB14 did not have this same dose-dependence but had similar morphological outcomes at the highest doses. Nevertheless, while SV47 showed significant mortality from 4.20 mg/L, there was no significant mortality on embryos exposed to DB14. Regardless, decreased locomotor movement was observed at all concentrations of DB14, suggesting an adverse neurodevelopmental effect. Overall, our results showed that at similar concentrations, SV47 and DB14 caused different types of phenotypic effects in zebrafish embryos.

Increased Urinary Excretion of Carnitine and Acylcarnitine by Mercuric Chloride Is Reversed by 2,3-Dimercapto-1-Propanesulfonic Acid in Rats

2010 ◽  
Vol 29 (3) ◽  
pp. 313-317
Author(s):  
Waleed A. Al-Madani ◽  
Nikhat J. Siddiqi ◽  
Abdullah S. Alhomida ◽  
Haseeb A. Khan ◽  
Ibrahim A. Arif ◽  
...  
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Mercuric Chloride ◽  
Free Carnitine ◽  
Male Rats ◽  
Significant Protection ◽  
Total Carnitine ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Wistar Male Rats

This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl2)-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC), and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl2 at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl2 injection. A separate batch of animals received HgCl2 (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl2 resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl2. Pretreatment with DMPS offered statistically significant protection against HgCl2-induced alterations in various urinary carnitine fractions in rats.

Regulation of food intake by neuropeptide Y in goldfish

2000 ◽  
Vol 279 (3) ◽  
pp. R1025-R1034 ◽  
Author(s):  
Yuwaraj K. Narnaware ◽  
Pierre P. Peyon ◽  
Xinwei Lin ◽  
Richard E. Peter
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Mrna Levels ◽  
Food Ration ◽  
Y1 Receptor ◽  
Daily Food ◽  
Daily Food Ration ◽  
Brain Ventricle ◽  
Dose Dependent Increase ◽  
Dose Dependent

In mammals, neuropeptide Y (NPY) is a potent orexigenic factor. In the present study, third brain ventricle (intracerebroventricular) injection of goldfish NPY (gNPY) caused a dose-dependent increase in food intake in goldfish, and intracerebroventricular administration of NPY Y1-receptor antagonist BIBP-3226 decreased food intake; the actions of gNPY were blocked by simultaneous injection of BIBP-3226. Goldfish maintained on a daily scheduled feeding regimen display an increase in NPY mRNA levels in the telencephalon-preoptic area and hypothalamus shortly before feeding; however, a decrease occured in optic tectum-thalamus. In both fed and unfed fish, brain NPY mRNA levels decreased after scheduled feeding. Restriction in daily food ration intake for 1 wk or food deprivation for 72 h resulted in increased brain NPY mRNA levels. Results from these studies demonstrate that NPY is a physiological brain signal involved in feeding behavior in goldfish, mediating its effects, at least in part, through Y1-like receptors in the brain.

POTENTIAL DIURETIC EFFECT OF CURCUMA AMADA ROXB. RHIZOME EXTRACTS

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (04) ◽  
pp. 34-38
Author(s):  
P Bommannavar ◽  
◽  
K. Patil
Keyword(s):  
Aqueous Extract ◽  
Urine Volume ◽  
Control Group ◽  
Aqueous Extracts ◽  
Diuretic Activity ◽  
Curcuma Amada ◽  
Male Wistar Rats ◽  
Total Urine ◽  
Dose Dependent Increase ◽  
Dose Dependent

The present study was undertaken to establish the diuretic activity of alcoholic and aqueous extract of dried rhizomes of Curcuma amada Roxb in rats. Alcoholic and aqueous extracts of rhizomes were administered to experimental male Wistar rats orally at doses of 250 and 500 mg/kg and compared with furosemide (10 mg/kg) as the reference standard. The parameters measured for diuretic activity were total urine volume, urine electrolyte concentration such as sodium, potassium and chloride have been evaluated. The rats treated with alcoholic and aqueous extract of Curcuma amada in a dose of 250 and 500 mg/kg showed higher urine output when compared to the respective control. Both alcoholic and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group. The result indicates that alcoholic and aqueous extract is an effective natriuretic and kaliuretic diuretic, which supports the traditional claim about the Curcuma amada Roxb being used as diuretics.

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