Effects of pH and osmolarity on aerosol-induced cough in normal volunteers

1988 ◽  
Vol 74 (4) ◽  
pp. 373-376 ◽  
Author(s):  
R. H. Lowry ◽  
A. M. Wood ◽  
T. W. Higenbottam
Keyword(s):  
Citric Acid ◽  
Sodium Citrate ◽  
Isotonic Saline ◽  
Chloride Concentration ◽  
Hypertonic Solution ◽  
Ionic Content ◽  
Normal Volunteers ◽  
Cough Frequency ◽  
Saline Solutions

1. The chemosensitivity of cough receptors stimulated by inhalation of aqueous aerosols was evaluated in 21 normal volunteers in three experiments. 2. The pH of isotonic saline was altered using small amounts of phosphate or glycine buffers to produce solutions with a pH range of 2.6–10.0. These solutions were nebulized ultrasonically and breathed for 1 min periods by seven subjects in random order and on separate days. Cough frequency during each 1 min inhalation was recorded. Only the two solutions of extreme pH (2.6 and 10.0) caused cough. 3. The effect of altering the osmolarity of the inhaled aerosol on cough was assessed using d-glucose over a range of 77–1232 mosmol/l. Saline solutions over the same range of osmolarity were also tested. The pH of d-glucose was raised to match that of saline by adding small amounts of sodium hydroxide. All solutions were nebulized and inhaled by seven subjects as described above for 1 min periods during which cough frequency was recorded. Forced expired volume in 1 s was recorded after each inhalation and did not alter in any subject by more than 10%. Subjects coughed when inhaling all the d-glucose solutions over the whole range of osmolarity. Cough occurred with saline solutions only at low chloride concentration and at the highest concentration. 4. In order to clarify whether the response to hypertonic saline was due to the high ionic content of the solutions or to its hypertonicity, two other solutions were tested. These were an isotonic and a hypertonic mixture of d-glucose and saline, containing ‘normal’ (150 mmol/l) ionic content. Cough occurred with the hypertonic solution but not with the isotonic solution, suggesting that hypertonicity does stimulate cough. 5. The mechanism of cough induction by citric acid was studied. An aerosol of 0.68% citric acid in saline was compared with sodium citrate, both with and without chloride, with d-glucose and with water in seven subjects. Cough occurred in response to all aerosols except sodium citrate in saline solvent. Additive effects of low pH and lack of chloride, and not the citrate ion, are responsible for the irritant properties of citric acid. 6. The chemosensitivity of the cough reflex induced by inhaled aerosols mirrors that already described in vivo for laryngeal rapidly adapting receptors.

Hyperosmolarity alters micturition: a comparison of urinary bladder motor activity in hyperosmolar and cyclophosphamide-induced models of overactive bladder

2010 ◽  
Vol 88 (9) ◽  
pp. 899-906 ◽  
Author(s):  
Kajetan Juszczak ◽  
Agata Ziomber ◽  
Marek Wyczółkowski ◽  
Piotr J. Thor
Keyword(s):  
Motor Activity ◽  
Isotonic Saline ◽  
Bladder Capacity ◽  
Physiological Model ◽  
Female Rats ◽  
Hypertonic Solution ◽  
Motility Index ◽  
Pressure Threshold ◽  
Experimental Tool ◽  
Saline Solutions

Hyperosmolar factors induce the neurogenic inflammatory response, leading to bladder overactivity (OAB). The aim of the study was to compare the bladder motor activity in a hyperosmolar and acute cyclophosphamide (CYP)-induced model of OAB. Furthermore, we set our sights on defining the most physiological model of OAB in experimental practice. Forty-two female rats were divided randomly into 5 groups. All animals underwent cystometry with the usage of isotonic saline or saline of increasing concentration. Acute chemical cystitis was induced by CYP to elicit OAB. The following cystometric parameters were analyzed: basal pressure, threshold pressure, micturition voiding pressure, intercontraction interval, compliance, functional bladder capacity, motility index, and detrusor overactivity index. CYP and hypertonic saline solutions induced OAB. Having been compared with CYP OAB, none of the rats infused with hypertonic solution exhibited macroscopic signs of bladder inflammation. The comparison of CYP and hyperosmolar models of OAB revealed that the greatest similarity existed between the 2080 mOsm/L OAB model and the acute CYP-induced model. We postulate that the 2080 mOsm/L model of OAB can be established as being a less invasive and more physiological model when compared with the CYP-induced OAB model. Additionally, it may also be a more reliable experimental tool for evaluating novel therapeutics for OAB as compared with CYP-induced models.

Pulmonary fluid extraction and osmotic conductance, ςK, measured in vivo

1998 ◽  
Vol 84 (3) ◽  
pp. 769-781 ◽  
Author(s):  
Joseph M. Karch ◽  
Jen-Shih Lee
Keyword(s):  
Osmotic Pressure ◽  
Lung Tissue ◽  
Isotonic Saline ◽  
Fluid Volume ◽  
Density Change ◽  
Hypertonic Solution ◽  
Tissue Fluid ◽  
Fluid Extraction ◽  
Fluid Filtration

The change in aortic blood density in an in vivo rabbit preparation was measured to assess fluid movement at the pulmonary capillaries caused by infusion of hypertonic solution (NaCl, urea, glucose, sucrose, or raffinose in isotonic saline) into the vena cava over 20 s. The hypertonic disturbance increased the plasma osmotic pressure by ≤30 mosmol/l. The density change indicates that the fluid extraction from the lung tissue was completed within 10 s. It was followed by a fluid filtration into the lung tissue and then an extraction and filtration from peripheral organs. An exchange model with flow dispersion yields two equations to estimate the osmotic conductance (ς K; where ς is the reflection coefficient of the test solute and K is the filtration coefficient including the total capillary surface area), and the tissue fluid volume from the area and first moment of the measured density change over the extraction phase. The values of ς K are 1.40 ± 0.11, 1.00 ± 0.10, 1.71 ± 0.10, 2.60 ± 0.23, and 3.73 ± 0.34 (SE) ml ⋅ h−1 ⋅ mosmol−1 ⋅ l ⋅ g−1for NaCl, urea, glucose, sucrose, and raffinose, respectively. Consistent with the model prediction, the tissue fluid volume (0.28 ± 0.04 ml/g wet lung tissue) was independent of the solute used. This value suggests that all fluid spaces in the alveolar septa participate in the process of fluid extraction due to an increase in plasma osmotic pressure.

Activation of KCI Cotransport by Urea Induces Dehydration in Both Sickle and Normal Reticulocytes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3591-3591 ◽  
Author(s):  
Clinton H. Joiner ◽  
R. Kirk Rettig ◽  
Maorong Jiang ◽  
Robert S. Franco
Keyword(s):  
Regulatory Volume Decrease ◽  
Isotonic Saline ◽  
Renal Medulla ◽  
Cell Swelling ◽  
Maximal Volume ◽  
Abnormal Response ◽  
Saline Solutions ◽  
Volume Decrease ◽  
Stimulation Of

Abstract KCl Cotransport (KCC) is highly expressed in sickle red blood cells (SS RBC) and recent data have demonstrated its abnormal response to cell swelling and acid pH. We showed that the final MCHC achieved by SS reticulocytes upon activation of KCC by these stimuli was higher than that of normal (AA) reticulocytes (Joiner et al, Blood, in Press). Here we report studies examining the sensitivity of KCC to activation by urea at concentrations present in the kidney and the effect of urea stimulation of KCC on reticulocyte MCHC. KCC fluxes were assayed as Rb uptake over 20 min in isotonic saline solutions buffered with HEPES to pH 7.4 (37°C) containing 0.1 mM ouabain, and 0.01 mM bumetanide, with 27 mM RbCl replacing equimolar NaCl. Under these conditions > 95 % of Rb uptake was Cl-dependent (assessed by sulfamate replacement of Cl). The maximal volume-stimulated KCC flux (VSmax KCC) was measured for each sample in cells swollen isotonically to MCHC < 27 gm/dl (nystatin method). Urea (100 to 1000 mM) increased osmolality of buffers, but did not alter initial MCHC. MCHC of reticulocytes (detected by flow cytometry) was tracked by measuring density changes on calibrated OPTIprep® gradients. Cl-dependent, ouabain- and bumetanide-insensitive Rb influx in both AA and SS RBC was increased by urea, reaching a plateau at 1000 mM urea that was similar to VSmax KCC. SS RBC were more sensitive to urea stimulation than AA RBC: 50% VSSmax KCC was achieved at 330 mM urea in SS RBC vs 550 mM in AA RBC. This effect was sulfhydryl dependent: exposure to the reducing agent dithiothreitol (preincubation for 30 min at 37°C with 10 mM DTT, then 1 mM in flux media) normalized the response to urea in SS RBC, with no effect in AA RBC. When swollen to MCHC 30 gm/dl, SS and AA retics exhibited Regulatory Volume Decrease (RVD) which increased MCHC. RVD in both AA and SS retics was abolished by incubation in sulfamate media, indicating mediation by KCC. As previously reported, final MCHC achieved after two hours incubation by SS retics was greater than AA retics (see Table, Control). Final Reticulocyte MCHC, gm/dl [mean (SD), n = 3] AA SS p (AA vs SS) Control 31.9 (0.7) 34.7 (1.2 0.03 Urea 35.3 (0.5) 37.8 (0.3) 0.002 p (Control vs Urea) 0.005 0.03 Urea (600 mM) enhanced RVD in both AA retics and SS retics. Sulfhydryl reduction with DTT had no effect on urea-stimulated RVD in SS reticulocytes. RVD stimulated by urea was complete within 60 minutes, and was irreversible: additional incubation without urea did not lower MCHC. The partially dehydrating effect of brief (10 min) exposure to urea was also irreversible, and was cumulative: cells exposed to two 10 min exposures to high urea (600 mM), separated by 10 min at a low, non-stimulating concentration of urea (100 mM), yielded the same MCHC as a continuous 20 min exposure. These data demonstrate that urea, at concentrations found in the renal medulla, is a powerful stimulant of KCC and intiates a striking RVD in reticulocytes. To the extent that intermittent stimulation of KCC by urea in the kidney occurs in vivo, this could contribute an exaggerated RVD resulting in dehydration of SS reticulocytes.

scholarly journals Pathology of Infestation of the Rat With Nippostrongylus Muris (Yokogawa) III. Jejunal Fluxes in Vivo of Water, Sodium, and Chloride

1960 ◽  
Vol 13 (2) ◽  
pp. 171 ◽  
Author(s):  
LEA Symons
Keyword(s):  
Small Intestine ◽  
Hypertonic Saline ◽  
Isotonic Saline ◽  
Mucosal Tissue ◽  
Unidirectional Fluxes ◽  
Saline Solutions ◽  
Net Fluxes ◽  
Infested Animal

The net fluxes of water, sodium, and chloride were measured in vivo by perfusion of the jejunum. There was a net absorption of these three substances from isotonic saline solutions in normal rats, but a net influx to the lumen in each instance in rats infested with the nematode Nippo8trongylu8 muri8. The unidirectional fluxes of sodium and the net fluxes during perfusion with hypo- and hypertonic saline solutions indicated that this was fundamentally due to a derangement of efflux while influx was unaffected. The gross effect, however, was also due to an increase of influx because of the greater weight of mucosal tissue per centimetre of jejunum in the infested animal. The unidirectional fluxes of water did not support these conclusions unequivocally. The fluid which accumulates in the infested� small intestine can be explained by these results.

scholarly journals Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 260 ◽  
Author(s):  
Dongwei Wan ◽  
Min Zhao ◽  
Jingjing Zhang ◽  
Libiao Luan
Keyword(s):  
Citric Acid ◽  
Drug Release ◽  
Sustained Release ◽  
Release Rate ◽  
Diffusion Rate ◽  
Immediate Release ◽  
Pharmacokinetic Studies ◽  
Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

scholarly journals Crude Citric Acid of Trichoderma asperellum: Tomato Growth Promotor and Suppressor of Fusarium oxysporum f. sp. lycopersici

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 222
Author(s):  
Abdulaziz A. Al-Askar ◽  
WesamEldin I. A. Saber ◽  
Khalid M. Ghoneem ◽  
Elsayed E. Hafez ◽  
Amira A. Ibrahim
Keyword(s):  
Citric Acid ◽  
Plant Growth ◽  
Organic Acid ◽  
Wilt Disease ◽  
Growth And Yield ◽  
Total Phenolic ◽  
Growth Promoters ◽  
Chlorophyll Pigments

Presently, the bioprocessing of agricultural residues to various bioactive compounds is of great concern, with the potential to be used as plant growth promoters and as a reductive of various diseases. Lycopersiconesculentum, one of the most consumed crops in the human diet, is attacked by Fusarium wilt disease, so the main aim is to biocontrol the pathogen. Several fungal species were isolated from decayed maize stover (MS). Trichodermaasperellum was chosen based on its organic acid productivity and was molecularly identified (GenBank accession number is MW195019). Citric acid (CA) was the major detected organic acid by HPLC. In vitro, CA of T.asperellum at 75% completely repressed the growth of Fusariumoxysporum f. sp. lycopersici (FOL). In vivo, soaking tomato seeds in CA enhanced the seed germination and vigor index. T. asperellum and/or its CA suppressed the wilt disease caused by FOL compared to control. There was a proportional increment of plant growth and yield, as well as improvements in the biochemical parameters (chlorophyll pigments, total phenolic contents and peroxidase, and polyphenol oxidase activities), suggesting targeting both the bioconversion of MS into CA and biological control of FOL.

scholarly journals Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

2012 ◽  
Vol 20 (3) ◽  
pp. 376-383 ◽  
Author(s):  
Rodrigo Cavassim ◽  
Fábio Renato Manzolli Leite ◽  
Daniela Leal Zandim ◽  
Andrea Abi Rached Dantas ◽  
Ricardo Samih Georges Abi Rached ◽  
...  
Keyword(s):  
Citric Acid ◽  
Sodium Citrate ◽  
Concentration Time

scholarly journals Compositional Changes during the Fruit Development of Two Peach Cultivars Differing in Juice Acidity

1998 ◽  
Vol 123 (5) ◽  
pp. 770-775 ◽  
Author(s):  
Annick Moing ◽  
Laurence Svanella ◽  
Dominique Rolin ◽  
Monique Gaudillère ◽  
Jean-Pierre Gaudillère ◽  
...  
Keyword(s):  
Citric Acid ◽  
Fruit Development ◽  
Prunus Persica ◽  
Sucrose Concentration ◽  
Titratable Acidity ◽  
The Difference ◽  
Normal Acidity ◽  
Vacuolar Ph ◽  
C Nmr

Changes in metabolites were studied during the fruit development of two greenhouse grown peach [Prunus persica (L.) Batsch] cultivars with low acidity (`Jalousia') or normal acidity (`Fantasia'). Both cultivars had the same sucrose concentration in fruit mesocarp at maturity. In the fruit juice, pH was higher and titratable acidity was lower for `Jalousia' than for `Fantasia' from 80 days after bloom to maturity. At four different times during fruit development, in vivo 13C NMR spectroscopy was used to measure the vacuolar pH of fruit mesocarp. At 55 days after bloom, the vacuolar pH of fruit mesocarp was not significantly different between `Jalousia' and `Fantasia', whereas the juice pH was different between cultivars. The three major organic acids in fruit mesocarp were malic, citric, and quinic acids for both cultivars. Citric acid concentrations were similar in both cultivars until ≈85 days after bloom and then became significantly higher in `Fantasia'. A significantly higher concentration in malic acid in `Fantasia' than in `Jalousia' was observed from the end of the first growth phase to maturity. At maturity, `Fantasia' fruit had two and five times more malic and citric acid, respectively, than `Jalousia' fruit. The differences observed between `Jalousia' and `Fantasia' fruit for malic and citric acid concentrations accounted for the difference in titratable acidity. The differences in acid concentration appeared during the plateau between the two rapid growth phases of the fruit, i.e., far before the onset of maturation. The three major amino acids were asparagine, glutamic acid, and proline for both cultivars. Their concentration followed similar patterns in acid and low-acid fruit.

scholarly journals The Use of Citric Acid and Sodium Citrate in Buttermaking

1935 ◽  
Vol 18 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Hugh L. Templeton ◽  
H.H. Sommer
Keyword(s):  
Citric Acid ◽  
Sodium Citrate
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