Increased intracellular calcium and decreased activities of leucocyte Na+,K+-ATPase and Ca2+-ATPase in asthma

1999 ◽  
Vol 97 (5) ◽  
pp. 595-601 ◽  
Author(s):  
Sunil Kumar CHHABRA ◽  
Anita KHANDUJA ◽  
Deepika JAIN

The present study was carried out to determine the intracellular free calcium concentration ([Ca2+]i) and the activity of its regulatory enzymes (Na+,K+-ATPase and Ca2+-ATPase) in leucocytes. Levels of plasma lysophosphatidylcholine (LPC) were also measured. Then the relationship between these parameters and the clinical severity of asthma and bronchial reactivity was studied. Patients with asthma were divided into three groups: acute asthma (subjects in acute exacerbation), uncontrolled asthma (subjects currently symptomatic) and stable asthma (subjects currently asymptomatic). A group of normal subjects was also studied. Spirometry, specific airway conductance and bronchial reactivity measurements were carried out. The following biochemical parameters were studied in venous blood: leucocyte [Ca2+]i, Na+,K+-ATPase and Ca2+-ATPase activities, and plasma LPC. Leucocyte [Ca2+]i was increased and the activities of Na+,K+-ATPase and Ca2+-ATPase were decreased in patients with asthma. Plasma levels of LPC were also increased. These changes were observed to be greatest among asthmatics in acute exacerbation of asthma, and lesser in magnitude in patients with less severe asthma. The activities of both ATPases were found to have a significant positive correlation, and [Ca2+]i and the levels of plasma LPC a significant negative correlation, with predicted forced expiratory volume in 1 s (FEV1). No significant correlation was observed between the biochemical parameters and bronchial reactivity. It is concluded that intracellular calcium homoeostasis is abnormal in asthma; specifically, the activities of Na+,K+-ATPase and Ca2+-ATPase are decreased. These abnormalities may modulate the clinical severity of asthma.

1989 ◽  
Vol 77 (5) ◽  
pp. 467-471
Author(s):  
Alan J. Knox ◽  
John R. Britton ◽  
Anne E. Tattersfield

1. Recent evidence suggests that a high salt diet increases bronchial reactivity, but the underlying mechanism is unclear. 2. To determine whether alterations in circulating vasopressin might be responsible, we have studied the effect of an infusion of vasopressin on the airways of six normal and eight asthmatic subjects measuring the response as expiratory flow at 30% of vital capacity (V̇30P) in the normal subjects and as forced expiratory volume in 1s (FEV1) in the asthmatic subjects, in a double-blind, placebo-controlled, cross-over study. 3. Vasopressin, given as an infusion at a rate of 2 i.u./h for 1 h, followed by 4 i.u./h for a further hour, produced plasma concentrations of 12.8 and 17 ng/l, respectively, compared with 2.0 and 2.0 ng/l on placebo. 4. Airway reactivity to histamine was measured after 1 and 2 h as the provocative doses of histamine causing a 40% reduction in V̇30P (PD40V̇30P) in the normal subjects and a 20% reduction in FEV1 (PD20FEV1) in the asthmatic subjects. 5. There was a small increase in PD40V̇30P after both vasopressin and placebo in normal subjects (refractoriness) but no change in PD20FEV1 in the asthmatic subjects. 6. There was no significant difference between vasopressin and placebo in V̇30P or PD40 V̇30P over the 2 h after the drug in the normal subjects or in FEV1 or PD20FEV1 over the 2 h after the drug in the asthmatic subjects. 7. We conclude that alterations in circulating vasopressin are unlikely to be responsible for the increase in bronchial reactivity when dietary salt intake is increased.


1989 ◽  
Vol 66 (3) ◽  
pp. 1059-1064 ◽  
Author(s):  
O. Michel ◽  
J. Duchateau ◽  
R. Sergysels

Endotoxins are released from the membrane of Gram-negative bacteria present in the environment and in oral and nasal cavities. They are proinflammatory substances that could participate in bronchial obstruction and hyperreactivity in asthmatic patients. This hypothesis was tested by using bronchial challenge tests with inhaled lipopolysaccharides (LPS) from Escherichia coli 026:B6 (22.2-micrograms total dose) followed by a histamine nonspecific challenge test and compared with a placebo procedure, in which the diluent was substituted for the LPS solution. In doing so we showed that LPS induces a slight but significant (P less than 0.01) bronchial obstruction (measured as forced expiratory volume in 1 s) in asthmatics (n = 8) but not in normal subjects (n = 6). The histamine hyperresponsiveness, expressed as the dosage of histamine necessary to decrease the bronchial specific conductance by 50%, was increased 5 h after LPS inhalation in asthmatics (P less than 0.05) but not in normal subjects. This effect of LPS on bronchial obstruction and hyperresponsiveness was observed in extrinsic (n = 6) as well as in intrinsic (n = 2) asthma.


1987 ◽  
Vol 58 (02) ◽  
pp. 737-743 ◽  
Author(s):  
Frarnçois Lanza ◽  
Alain Beretz ◽  
Martial Kubina ◽  
Jean-Pierre Cazenave

SummaryIncorporation into human platelets of the calcium fluorescent indicators quin2 or fura-2 at low concentrations used to measure intracellular free calcium leads to the potentiation of the effects of agonists on platelets. This was shown by increased aggregatory and secretory responses of quin2 or fura-2 loaded platelets after stimulation with ADP, PAP and with low concentrations of thrombin, collagen, the endoperoxide analog U-46619 and the calcium ionophore A 23187. Quin2 and fura-2 mediated platelet sensitisation could be due to altered arachidonic acid metabolism since it was inhibited by prior treatment with the cydooxygenase inhibitor acetylsalicylate. In contrast, platelets loaded with higher concentrations of calcium chelators exhibited diminished aggregation responses to all aggregating agents. This latter effect was accompanied by increased fluidity of the platelet plasma membrane bilayer and by the exposure of a new pool of membranes to the outer surface of platelets, as monitored with trimethylammonium- diphenylhexatriene (TMA-DPH) in platelets loaded with the non-fluorescent calcium probe analog MAPT. In contrast, low concentrations of quin2 did not potentiate shape change of platelets activated with ADP. Thus, shape change and aggregation can be influenced separately by intracellular Ca2+ chelators. We conclude that platelet responses are altered by the incorporation of intracellular calcium chelators at concentrations used to monitor intracellular calcium changes.


1969 ◽  
Vol 21 (01) ◽  
pp. 134-143 ◽  
Author(s):  
W. D Walls ◽  
M. S Losowsky

SummaryA kinetic method for the quantitative estimation of plasma F.S.F. activity is described and discussed.This method was applied to normal subjects and to patients with chronic liver disease. The plasma F.S.F. activity was uninfluenced by either sex or age, and the normal range has been defined.A significant decrease in plasma F.S.F. activity was observed in patients with chronic liver disease. Subnormal levels of activity were found in 25% of such patients but were unrelated to episodes of abnormal haemorrhage. Plasma F.S.F. activity tended to be lower in patients with disease of greater clinical severity. In 2 patients showing clinical improvement there was an increase in plasma F. S. F. activity.It was confirmed that plasma fibrinogen levels increase with age.


2021 ◽  
pp. 1-8
Author(s):  
Foad Alzoughool ◽  
Huda Al Hourani ◽  
Manar Atoum ◽  
Sajedah Bateineh ◽  
Hanan Alsheikh ◽  
...  

BACKGROUND/AIM: The newly described proteins adropin and irisin are a highly conserved polypeptide that plays essential roles in metabolic and energy homeostasis, insulin resistance, and fat browning. The aim of this study is to evaluate the circulating levels of serum adropin and irisin in type 2 diabetes mellitus (T2DM) patients and also to elucidate possible relationships between serum adropin and irisin levels with anthropometric obesity indices and biochemical parameters. SUBJECTS AND METHODS: Single-center prospective observational study included 90 T2DM patients referred to the diabetes outpatient clinic. Height, weight, and waist circumference (WC) were measured. Body mass index (BMI) and waist to height ratio (WHtR) were calculated. Fasting blood glucose, glycosylated hemoglobin, serum lipids, creatinine, urea, and blood urea nitrogen were evaluated. Estimated glomerular filtration rate (GFR) was calculated, serum adropin and irisin were evaluated. RESULTS: The results showed a significant positive correlation between adropin and irisin in females but not in males (r = 0.311; P = 0.042). In males’ group, serum adropin levels showed significant negative correlation with serum glucose (–0.423, P = <  0.05), HbA1C (–0.364, P = <  0.05), and GFR (–0.355, P = <  0.05). In contrast, creatinine was showed a significant positive correlation with adropin in males (0.381, P = <  0.05). In females’ group, adropin showed a significant negative correlation with weight (–0.371, P = <  0.05), BMI (–0.349, P = <  0.05), WC (–0.402, P = <  0.01), and WHtR (–0.398, P = <  0.01). Contrary, in males’ group, serum irisin levels showed significant positive correlation with weight (0.338, P = <  0.05), BMI (0.332, P = <  0.05), WC (0.409, P = <  0.01), and WHtR (0.432, P = <  0.01). CONCLUSION: This study demonstrated that, in T2DM patients, circulating serum adrpoin correlated negatively with anthropometric obesity indices of obesity in females, while serum irisin was positively correlated with anthropometric obesity indices of obesity in males.


1984 ◽  
Vol 67 (6) ◽  
pp. 613-618 ◽  
Author(s):  
B. F. Robinson ◽  
R. J. W. Phillips

1. The effect of a small increase in local plasma calcium concentration on the responsiveness of the forearm resistance vessels to verapamil has been examined in normal subjects, by using a plethysmographic method with infusion of calcium and other agents into the brachial artery. 2. Infusion of calcium at a rate which increased the concentration in forearm venous blood by about 0.5 mmol/l caused basal blood flow to fall by 19% and the dilator response to verapamil to fall by 35% (n = 8; P<0.02). 3. When, after 46 min, the infusion of calcium was discontinued, the dilator response to verapamil increased to reach a level 53% higher than the initial control (n = 8; P<0.02). 4. Infusion of calcium had no effect on the dilator response to sodium nitroprusside. 5. Infusion of noradrenaline at a rate which caused a greater reduction in basal flow than that induced by calcium had no effect on the response to verapamil. 6. It is concluded that the dilator response to verapamil, which is thought to reflect activity of the potential operated system for calcium entry, is selectively depressed by a small elevation of plasma calcium concentration, but subsequently becomes elevated. These findings point to an important role for calcium in the regulation of membrane function in the resistance vessels and support the view that altered calcium handling may contribute to the development of primary hypertension.


1972 ◽  
Vol 70 (2) ◽  
pp. 331-341 ◽  
Author(s):  
Roland R. Tremblay ◽  
Thomas P. Foley ◽  
Pierre Corvol ◽  
In-Joo Park ◽  
Avinoam Kowarski ◽  
...  

ABSTRACT Twenty patients with the syndrome of testicular feminization have been studied along with a group of normal subjects of both sexes and of comparable ages. Peripheral and gonadal venous blood were analysed for their content in testosterone (T), androstenedione (Δ), dihydrotestosterone (DHT), testosterone-oestradiol binding globulin (TeBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Normal or even higher than normal male concentrations of T, Δ, and DHT were observed. An actual secretion of the three androgens by the testis was demonstrated. Elevated levels of serum LH were found despite normal male or higher levels of T, Δ, and DHT. High concentrations of TeBG presumably could alter the dynamics of plasma androgens. The gonadal production of DHT and the normal levels of DHT in peripheral plasma shows that 5α-reductase activity is definitely present in the patients.


2012 ◽  
Vol 140 (7-8) ◽  
pp. 436-440 ◽  
Author(s):  
Milos Novovic ◽  
Vesna Topic

Introduction. Arterial blood gas (ABG) analyses have an important role in the assessment and monitoring of the metabolic and oxygen status of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Arterial puncture could have a lot of adverse effects, while sampling of venous blood is simpler and is not so invasive. Objective. The aim of this study was to evaluate whether venous blood gas (VBG) values of pH, partial pressure of carbon dioxide (PCO2), partial oxygen pressure (PO2), bicarbonate (HCO3), and venous and arterial blood oxygen saturation (SO2) can reliably predict ABG levels in patients with acute exacerbation of COPD. Methods. Forty-seven patients with a prior diagnosis of COPD were included in this prospective study. The patients with acute exacerbation of this disease were examined at the General Hospital EMS Department in Prijepolje. ABG samples were taken immediately after venous sampling, and both were analyzed. Results. The Pearson correlation coefficients between arterial and venous parameters were 0.828, 0.877, 0.599, 0.896 and 0.312 for pH, PCO2, PO2, HCO3 and SO2, respectively. The statistically significant correlation between arterial and venous pH, PCO2 and HCO3, values was found in patients with acute exacerbation of COPD (p<0.001). Conclusion. When we cannot provide arterial blood for analysis, venous values of the pH, Pv,CO2 and HCO3 parameters can be an alternative to their arterial equivalents in the interpretation of the metabolic status in patients with acute exacerbation of COPD, while the values of venous Pv,O2 and Sv,O2 cannot be used as predictors in the assessment of oxygen status of such patients.


2002 ◽  
pp. 299-303 ◽  
Author(s):  
R Goswami ◽  
R Guleria ◽  
AK Gupta ◽  
N Gupta ◽  
RK Marwaha ◽  
...  

OBJECTIVES: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. METHODS: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffP(oeso)), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5+/-2 months. RESULTS: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59+/-26 to 23+/-13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57+/-0.62 to 2.94+/-0.60 l), forced expiratory volume in the first second (2.21+/-0.49 to 2.45+/-0.47 l), total lung capacity (3.57+/-1.19 to 4.1+/-1.12 l), diaphragmatic movement during deep respiration (5.5+/-1.0 to 6.6+/-1.1 cm) and SniffP(oeso) (68.7+/-23 to 93.1+/-25.2 cmH(2)O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffP(oeso). CONCLUSIONS: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis.


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