Responsiveness of superficial hand veins to adrenergic stimuli in patients with cystic fibrosis

1989 ◽  
Vol 76 (3) ◽  
pp. 283-287 ◽  
Author(s):  
Hans-Georg Eichler ◽  
Irmgard Eichler ◽  
Norman Lewiston ◽  
Terrence F. Blaschke ◽  
Brian B. Hoffman
Keyword(s):  
Cystic Fibrosis ◽  
Cyclic Amp ◽  
Geometric Mean ◽  
Clinical Score ◽  
Secretory Cells ◽  
Adrenergic Stimulation ◽  
Dorsal Hand Vein ◽  
Severity Of The Disease ◽  
And Control

1. The basic biochemical defect of cystic fibrosis (CF) remains undetermined, but impaired function of the β-adrenoceptor-mediated adenosine 3′:5′-cyclic monophosphate (cyclic AMP)-dependent regulatory pathway in secretory cells is likely to be involved in the pathophysiology of the disease. 2. We have compared responsiveness to β-adrenergic stimulation in vivo by infusing isoprenaline locally into peripheral veins of CF patients and control subjects; the dorsal hand vein technique was used to measure the vascular response to isoprenaline. 3. CF patients required significantly higher doses of isoprenaline for half-maximal dilatation of the preconstricted veins (ED50) than controls (geometric mean: 44.5 ng/min in CF patients compared with 14.8 ng/min in controls; P < 0.05). Maximal venodilatation was 74 ± 30% of baseline in CF patients compared with 94 ± 50% in controls (NS between groups). 4. The clinical score of CF patients was uncorrelated with the ED50 of isoprenaline. Thus the decreased β-adrenergic responsiveness does not seem to be related to the severity of the disease. 5. Our results indicate a defect in the cyclic-AMP-dependent pathway in vascular smooth muscle cells of CF patients. Whether this is associated with the CF gene defect itself requires further study.

scholarly journals Mechanism and control of hyperosmotic NaCl-rich secretion by the rectal gland of Squalus acanthias

1983 ◽  
Vol 106 (1) ◽  
pp. 25-41 ◽  
Author(s):  
F. H. Epstein ◽  
J. S. Stoff ◽  
P. Silva
Keyword(s):  
Cyclic Amp ◽  
Chloride Secretion ◽  
Squalus Acanthias ◽  
Rectal Gland ◽  
Energetic Efficiency ◽  
Secondary Active Transport ◽  
Transport Pathway ◽  
Rectal Glands ◽  
And Control

Secretion of chloride from blood to lumen is accomplished in the rectal gland of elasmobranchs by a process of secondary active transport involving the co-transport of Cl- with Na+ across the basolateral membranes of rectal gland cells. Energy is provided by ATP via membrane Na-K-ATPase, which establishes an electrochemical gradient favouring Na+ influx into the cell. The involvement of K+ in the co-transport mechanism, so as to provide a ratio of 1 Na+:1 K+:2 Cl- entering the cell, would increase the energetic efficiency of the process, and is consistent with the Cl/O2 ration of 27–30 observed in secreting rectal glands. Secretion is stimulated by cyclic AMP (cAMP) and by vasoactive intestinal peptide (VIP) and adenosine, which activate adenylate cyclase. Activation of the gland in vivo probably occurs via VIP-secreting nerves as well as circulating agents; it is inhibited by somatostatin. Cyclic AMP probably stimulates chloride secretion by at least three mechanisms: (1) increasing chloride conductance across the luminal cell membrane, (2) enhancing the co-transport pathway for transmembrane movements of Na+, K+ and Cl- and (3) activating Na-K-ATPase.

Effect in vivo of β-adrenergic stimulation, angiotensin II, dibutyryl cyclic AMP, and theophylline on tonin concentration in rat saliva and submaxillary gland

1977 ◽  
Vol 55 (5) ◽  
pp. 983-989 ◽  
Author(s):  
R. Garcia ◽  
K. Kondo ◽  
B. Scholkens ◽  
R. Boucher ◽  
J. Genest
Keyword(s):  
Angiotensin Ii ◽  
Cyclic Amp ◽  
Submaxillary Gland ◽  
Dibutyryl Cyclic Amp ◽  
Adrenergic Stimulation ◽  
Adrenergic Drug ◽  
Β Blocker ◽  
Derivatives Of ◽  
Prior Administration

Tonin (an enzyme present in rat submaxillary gland and saliva) has previously been shown to be able, unlike renin and reninlike substances, to release angiontensin II either directly by acting on an appropriate substrate or from angiotensin I. The administration of a β-adrenergic drug, isoproterenol, produces a rise of tonin concentration in saliva without affecting its concentration in the submaxillary gland. Prior administration of a β blocker, propranolol, partially prevents this effect. The administration of theophylline increases the tonin concentration in both saliva and the submaxillary gland, whereas dibutyryl cyclic AMP increases tonin concentration in the former. These results suggest that β-adrenergic stimulation enhances both tonin release into the saliva and tonin synthesis in the submaxillary gland, and that these effects might be mediated by cyclic AMP. Infusion of angiotensin II blocked the stimulatory effect of isoproterenol on salivary tonin. 1Sar-8Ile-angiotensin II is both a weak antagonist of angiotensin II in this respect and a strong agonist in terms of blocking the effect of isoproterenol, another role mirrored in other physiological mechanisms of derivatives of angiotensin II.

scholarly journals Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein

1999 ◽  
Vol 277 (4) ◽  
pp. C833-C839 ◽  
Author(s):  
Beate Illek ◽  
Lei Zhang ◽  
Nancy C. Lewis ◽  
Richard B. Moss ◽  
Jian-Yun Dong ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Wild Type ◽  
Adrenergic Stimulation ◽  
Transmembrane Conductance ◽  
Patch Clamp Technique ◽  
Open Probability ◽  
Nasal Potential Difference ◽  
Cystic Fibrosis Transmembrane

The patch-clamp technique was used to investigate the effects of the isoflavone genistein on disease-causing mutations (G551D and ΔF508) of the cystic fibrosis transmembrane conductance regulator (CFTR). In HeLa cells recombinantly expressing the trafficking-competent G551D-CFTR, the forskolin-stimulated Cl currents were small, and average open probability of G551D-CFTR was P o = 0.047 ± 0.019. Addition of genistein activated Cl currents ∼10-fold, and the P o of G551D-CFTR increased to 0.49 ± 0.12, which is a P o similar to wild-type CFTR. In cystic fibrosis (CF) epithelial cells homozygous for the trafficking-impaired ΔF508 mutation, forskolin and genistein activated Cl currents only after 4-phenylbutyrate treatment. These data suggested that genistein activated CFTR mutants that were present in the cell membrane. Therefore, we tested the effects of genistein in CF patients with the G551D mutation in nasal potential difference (PD) measurements in vivo. The perfusion of the nasal mucosa of G551D CF patients with isoproterenol had no effect; however, genistein stimulated Cl-dependent nasal PD by, on average, −2.4 ± 0.6 mV, which corresponds to 16.9% of the responses (to β-adrenergic stimulation) found in healthy subjects.

scholarly journals Bidimensional and Contrast-Enhanced Ultrasonography of the Spleen in Dogs Affected by Leishmaniosis

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1437
Author(s):  
Massimo De Majo ◽  
Giulia Donato ◽  
Marisa Masucci ◽  
Cyndi Mangano ◽  
Maria Flaminia Persichetti ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Controlled Study ◽  
Canine Leishmaniosis ◽  
Heterogeneous Distribution ◽  
Contrast Enhanced ◽  
Contrast Enhanced Ultrasonography ◽  
Severity Of The Disease ◽  
And Control ◽  
First Time

Canine leishmaniosis (CanL) is responsible for splenic pathological changes. The main features detectable from ultrasound examination are splenomegaly and diffuse alterations of the echostructure. The study aimed to highlight whether these ultrasound changes are related to the severity of the disease or to a modification of splenic microvascularization that can be detected in vivo through contrast-enhanced ultrasonography (CEUS). Twenty-five adult dogs tested for CanL were enrolled in this prospective, controlled study and staged according to LeishVet guidelines. Bidimensional ultrasonography revealed that splenomegaly was seen in 50% of the affected dogs, and diffuse parenchymal changes were seen in more than 60% of dogs with splenomegaly, showing a positive correlation with severity of the disease; therefore, splenomegaly could be of prognostic significance. CEUS showed that a persistent heterogeneous distribution pattern appeared only in spleens with diffuse echostructure alterations. The evaluation of quantitative CEUS parameters regarding the volume and velocity of flow in three regions of interest did not show differences between affected and control dogs. Diffuse spleen microvascular modifications evidenced by CEUS were reported for the first time in dogs with CanL. In endemic areas, CanL could be included in the differential diagnoses list when detecting splenic alterations in dogs.

scholarly journals Corticotropin regulation of the synthesis of a specific rat adrenal cytosolic protein. Effects of hypophysectomy and actinomycin D

1979 ◽  
Vol 182 (3) ◽  
pp. 717-725 ◽  
Author(s):  
Alice Dazord ◽  
Dominique Gallet ◽  
Helene Cohen ◽  
Jose M. Saez
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Total Protein ◽  
Actinomycin D ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cytosolic Protein ◽  
And Control ◽  
Corticotropin Stimulation ◽  
Stimulation Of

The mechanism of corticotropin stimulation of the synthesis of a specific rat adrenal cytosolic protein was investigated. This protein (protein E) has a mol.wt. of approx. 30000. It is detected by polyacrylamide-gel electrophoresis of cytosol prepared from adrenal slices from rats treated with corticotropin in vivo and control rats, the slices being incubated with [3H]- and [14C]-leucine respectively. In rats 1–15 days after hypophysectomy, corticotropin, like dibutyryl cyclic AMP, induces an increase in protein E similar to that induced in control rats, even though both compounds no longer stimulate total protein synthesis. Corticotropin stimulation of protein E synthesis is mediated by cyclic AMP but not by corticosterone, since aminoglutethimide, a steroidogenic inhibitor, does not affect corticotropin stimulation, and dexamethasone alone has no effect. Actinomycin D, when injected in vivo 1h before or after corticotropin injection, prevents the effect of corticotropin on protein E synthesis, which is interpreted as evidence that mRNA synthesis is necessary for the stimulation of protein E synthesis. When injected more than 2h after corticotropin, actinomycin D does not prevent corticotropin stimulation of protein E synthesis, but completely blocks corticotropin stimulation of total protein synthesis. This is interpreted as meaning that, after stimulation of mRNA coding for protein E, corticotropin has no effect on the synthesis of protein E. On the other hand, corticotropin stimulation of protein E synthesis persists after hypophysectomy even though it no longer stimulates total protein synthesis. These data suggest that the factor(s) involved in the synthesis of protein E are more stable than those involved in total protein synthesis.

scholarly journals Haemodynamic effects of secretory agents on the isolated elasmobranch rectal gland

1983 ◽  
Vol 103 (1) ◽  
pp. 193-204 ◽  
Author(s):  
T. J. Shuttleworth
Keyword(s):  
Cyclic Amp ◽  
Adrenergic Receptors ◽  
Rectal Gland ◽  
Secretory Cells ◽  
Vascular Effects ◽  
Alpha Adrenergic Receptors ◽  
Perfusion Flow ◽  
Flow Through ◽  
Ribose Moiety

Perfusion flow rate in the isolated elasmobranch rectal gland, perfused at in vivo pressures, was measured in Scyliorhinus canicula L. and Squalus acanthias L. Flow through the secretory parenchyma of the gland was reduced in the presence of concentrations of catecholamines in the physiological range, an effect mediated via alpha-adrenergic receptors within the gland vasculature. Flow through the non-secretory vascular shunts of the rectal gland was unaffected. The vasoconstriction induced by noradrenaline was blocked by the addition of cyclic AMP + theophylline or adenosine at concentrations known to stimulate secretion by the gland. In Squalus, a similar effect was seen with the secretagogue vasoactive intestinal peptide, but this agent had no effect in the glands of Scyliorhinus. Experiments indicate that the blockage of the noradrenaline effect by the secretory agents does not involve any stimulation of vasodilatory beta-adrenergic receptors and, furthermore, that the vasomotor effects of these agents appear to be entirely independent of their actions on the secretory cells. Evidence is presented indicating that the vasomotor action of adenosine may be mediated via receptors specific for the ribose moiety of the nucleoside (Ra receptors) activating adenylate cyclase, and that this may, in turn, explain the observed effects of the addition of exogenous cyclic AMP. The significance of the observed vascular effects in the overall control of secretion rate by the gland in vivo is discussed.

THE EFFECT OF ADRENERGIC STIMULATION UPON SWEATING IN NORMAL CHILDREN AND CYSTIC FIBROSIS PATIENTS

PEDIATRICS ◽  
1968 ◽  
Vol 42 (3) ◽  
pp. 458-464
Author(s):  
Lewis E. Gibson
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Concentration ◽  
Adrenergic Stimulation ◽  
Water Reabsorption ◽  
Normal Children ◽  
Significant Drop ◽  
Control Subjects ◽  
And Control ◽  
Intracutaneous Injection ◽  
Excessive Water

An abnormality of the autonomic nervous system has frequently been postulated as having a role in the pathogenesis of cystic fibrosis. The author investigated the effects of adrenergic stimulation upon sweating in cystic fibrosis patients and in control subjects. It was found that the iontophoresis of isoproterenol, prior to the iontophoresis of pilocarpine, produces, in all subjects, more sweat than that produced by the iontophoresis of pilocarpine alone. In the cystic fibrosis patients, but not in the control subjects, the iontophoresis of isoproterenol led to a small (8.9%) but significant drop in the chloride concentration of the sweat. Sweating produced by the intracutaneous injection of isoproterenol, but not that produced by intracutaneous norepinephrine, could be blocked by the iontophoresis of atropine. This occurred in both cystic fibrosis patients and control subjects. These experimental results can be explained by hypothesizing that excessive water reabsorption occurs in the sweat duct of cystic fibrosis patients and that isoproterenol inhibits ductal water reabsorption in both the cystic fibrosis patients and the unaffected controls.

scholarly journals “Switching Partners”: Piperacillin-Avibactam Is a Highly Potent Combination against Multidrug-Resistant Burkholderia cepacia Complex and Burkholderia gladioli Cystic Fibrosis Isolates

2019 ◽  
Vol 57 (8) ◽  
Author(s):  
Elise T. Zeiser ◽  
Scott A. Becka ◽  
Brigid M. Wilson ◽  
Melissa D. Barnes ◽  
John J. LiPuma ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Multidrug Resistant ◽  
Burkholderia Cepacia Complex ◽  
Content Type ◽  
Burkholderia Gladioli ◽  
Alternative Antibiotic ◽  
And Control

ABSTRACT In persons with cystic fibrosis (CF), airway infection with Burkholderia cepacia complex (Bcc) species or Burkholderia gladioli presents a significant challenge due to inherent resistance to multiple antibiotics. Two chromosomally encoded inducible β-lactamases, a Pen-like class A and AmpC are produced in Bcc and B. gladioli. Previously, ceftazidime-avibactam demonstrated significant potency against Bcc and B. gladioli isolated from the sputum of individuals with CF; however, 10% of the isolates tested resistant to ceftazidime-avibactam. Here, we describe an alternative antibiotic combination to overcome ceftazidime-avibactam resistance. Antimicrobial susceptibility testing was performed on Bcc and B. gladioli clinical and control isolates. Biochemical analysis was conducted on purified PenA1 and AmpC1 β-lactamases from Burkholderia multivorans ATCC 17616. Analytic isoelectric focusing and immunoblotting were conducted on cellular extracts of B. multivorans induced by various β-lactams or β-lactam-β-lactamase inhibitor combinations. Combinations of piperacillin-avibactam, as well as piperacillin-tazobactam plus ceftazidime-avibactam (the clinically available counterpart), were tested against a panel of ceftazidime-avibactam nonsusceptible Bcc and B. gladioli. The piperacillin-avibactam and piperacillin-tazobactam-ceftazidime-avibactam combinations restored susceptibility to 99% of the isolates tested. Avibactam is a potent inhibitor of PenA1 (apparent inhibitory constant [Ki app] = 0.5 μM), while piperacillin was found to inhibit AmpC1 (Ki app = 2.6 μM). Moreover, piperacillin, tazobactam, ceftazidime, and avibactam, as well as combinations thereof, did not induce expression of blapenA1 and blaampC1 in the B. multivorans ATCC 17616 background. When ceftazidime-avibactam is combined with piperacillin-tazobactam, the susceptibility of Bcc and B. gladioli to ceftazidime and piperacillin is restored in vitro. Both the lack of blapenA1 induction and potent inactivation of PenA1 by avibactam likely provide the major contributions toward susceptibility. With in vivo validation, piperacillin-tazobactam-ceftazidime-avibactam may represent salvage therapy for individuals with CF and highly drug-resistant Bcc and B. gladioli infections.

Differing luminal potential difference of cystic fibrosis and control sweat secretory coils in vitro

1984 ◽  
Vol 247 (4) ◽  
pp. R646-R649 ◽  
Author(s):  
K. Sato
Keyword(s):  
Cystic Fibrosis ◽  
Driving Force ◽  
Potential Difference ◽  
Sweat Glands ◽  
Adrenergic Stimulation ◽  
Human Control ◽  
Secretory Coil ◽  
And Control ◽  
Eccrine Sweat Glands

Transepithelial potential difference (PD) of isolated segments of the secretory coil of both human control and cystic fibrosis (CF) eccrine sweat glands was measured during stimulation with methacholine (MCh) and isoproterenol (ISO) in vitro. Negative luminal PD of about 10 and 16 mV developed across the secretory coil epithelium in control and CF secretory coil, respectively, during maximal MCh stimulation. ISO (10(-5) M) stimulation generated a mean of 1.9-mV negative luminal PD in control glands; however, ISO failed to enhance the luminal PD beyond the resting level of 0.9 mV in the CF secretory coil. The inhibition of ISO-induced (10(-5) M) luminal PD in control secretory coil by propranolol (5 X 10(-5) M) but not by atropine (10(-5) M) indicated its pharmacologic specificity. The possibility is discussed that this lack of electrical driving force during ISO stimulation could be one of the mechanisms for the absence of sweating response to beta-adrenergic stimulation in CF sweat glands reported recently (8). The mechanism for the higher MCh-induced luminal PD in the CF secretory coil remains to be studied.

Changes in Na+/K+-ATPase expression during adaptive cell differentiation in avian nasal salt gland

1997 ◽  
Vol 200 (13) ◽  
pp. 1895-1904 ◽  
Author(s):  
JP Hildebrandt
Keyword(s):  
Salt Stress ◽  
Cyclic Amp ◽  
Atpase Activity ◽  
Time Course ◽  
Atp Hydrolysis ◽  
Salt Gland ◽  
Secretory Cells ◽  
Salt Glands ◽  
Atpase Subunit

Chronic salt stress in ducklings (Anas platyrhynchos) resulted in a sustained accumulation of cyclic AMP in the secretory cells of the nasal salt glands. Adaptive increases in the activity of the Na+/K+-ATPase, measured as ATP hydrolysis rates in freshly isolated tissue, were observed after 12 h of salt stress. This change in enzyme activity was associated with increases in protein abundance in the - as well as in the ss-subunit of Na+/K+-ATPase and an increase in ss-subunit glycosylation. We investigated whether the increase in the cytosolic cyclic AMP concentration and the adaptive changes in Na+/K+-ATPase activity were causally related. Using an organotypic tissue culture system for salt gland slices from unstressed (naive) ducklings, we produced similar changes in Na+/K+-ATPase activity and subunit abundance by treating cultured tissue with drugs that elevate cytosolic cyclic AMP levels (forskolin, 8-CPT-cAMP) during a 15 h culture period. Protein synthesis assays using cultured tissue revealed that elevations in cytosolic cyclic AMP level mediate increases in Na+/K+-ATPase subunit abundance by slowing down the degradation of ATPase subunits. This increase in the amount of enzyme protein was associated with a significant increase in Na+/K+-ATPase activity in tissue homogenates. The time course of these changes in cyclic-AMP-treated cultured tissue resembled that observed in salt-stressed intact animals, indicating that the elevation in cyclic AMP level in salt gland tissue may constitute a portion of the signalling events ultimately leading to the adaptive increase in Na+/K+-ATPase activity in vivo.

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