New strategies in ion channel screening for drug discovery: are there ways to improve its productivity?

Farre, Cecilia; Fertig, Niels

doi:10.1517/17460441.2014.942217

Cited by 16 publications

(17 citation statements)

References 13 publications

(5 reference statements)

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“…1,2 It is also a rare cause of acquired valvular heart disease, although cardiac involvement has been described in up to 60% of patients with carcinoid syndrome. 3 Therefore, screening for heart involvement with transthoracic echocardiography is essential in patients with a newly diagnosed carcinoid tumour. 3 Therefore, screening for heart involvement with transthoracic echocardiography is essential in patients with a newly diagnosed carcinoid tumour.…”

Section: Introductionmentioning

confidence: 99%

“…3 Therefore, screening for heart involvement with transthoracic echocardiography is essential in patients with a newly diagnosed carcinoid tumour. 3 Transthoracic echocardiography is indicated in all patients diagnosed with carcinoid syndrome, and it should be performed on a routine basis every 3-6 months depending on the clinical presentation of the patient and the severity of the disease. 3 Transthoracic echocardiography is indicated in all patients diagnosed with carcinoid syndrome, and it should be performed on a routine basis every 3-6 months depending on the clinical presentation of the patient and the severity of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…1 Without treatment, carcinoid heart disease has a poor prognosis with a 3 year survival rate as low as 31% (compared with 68% in patients without concomitant heart disease). 3 Therefore, screening for heart involvement with transthoracic echocardiography is essential in patients with a newly diagnosed carcinoid tumour. 4 NETs of the small bowel, followed by the lung, large bowel, pancreas, appendix, and ovaries, have the highest incidence of heart disease.…”

Section: Introductionmentioning

confidence: 99%

“…4 NETs of the small bowel, followed by the lung, large bowel, pancreas, appendix, and ovaries, have the highest incidence of heart disease. 3 Transthoracic echocardiography is indicated in all patients diagnosed with carcinoid syndrome, and it should be performed on a routine basis every 3-6 months depending on the clinical presentation of the patient and the severity of the disease. 4 Cardiac involvement can vary widely in patients.…”

Section: Introductionmentioning

confidence: 99%

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Carcinoid heart disease involving the left heart: a case report and biomarker analysis

et al. 2019

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Herein, we report the case of a 67‐year‐old woman who was admitted to our hospital because of dyspnoea and oedema of the lower extremities. Transthoracic echocardiography revealed severe tricuspid and mitral regurgitation, and the leaflets of the tricuspid valve were found to be rigid and almost immobile. The plasma concentrations of serotonin and chromogranin A were elevated, and hence, suspicion for carcinoid heart disease was raised. In addition to the diagnostic workup and medical and surgical treatment, we analysed levels of novel cardiovascular biomarkers throughout the entire follow‐up by means of enzyme‐linked immunosorbent assay. A dopa positron emission tomography (DOPA‐PET) was conducted and showed a neoplasm in the terminal ileum. Tricuspid valve replacement, mitral valve repair, and a closure of the patent foramen ovale (PFO) were conducted. Two months later, hemicolectomy and liver segment resection were performed. The tumour was resected, and the diagnosis of a neuroendocrine tumour (NET) was confirmed. Throughout the follow‐up, we observed a decrease in the plasma levels of novel biomarkers [e.g. interleukin‐8 (IL‐8), soluble suppression of tumorigenicity‐2 (sST2), and heart‐type fatty acid‐binding protein (H‐FABP)] over the follow‐up period. In our case, carcinoid heart disease resulted in a severe tricuspid regurgitation as commonly seen in these patients. Moreover, a pre‐existent mitral regurgitation was likely aggravated by fibrotic remodelling, because a PFO has led to a right‐to‐left shunt and might have caused left heart involvement. As IL‐8 was associated with adverse outcomes in patients with NETs, and sST2 and H‐FABP were associated with adverse outcomes in patients with heart failure previously, these biomarkers could aid in the risk stratification of patients with NET.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carcinoid heart disease involving the left heart: a case report and biomarker analysis

et al. 2019

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“…From a drug discovery point of view, ion channels are important targets: they regulate a large number of physiological processes and they are involved in many pathologies [ 15 – 17 ]. Ion channels had been much more difficult to screen than soluble proteins; the gold standard assay for assessing their activity, the patch clamp technique, requires a highly skilled operator.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of T-Junction Solution Switching Aimed at Patch Clamp Experiments

2015

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Solutions exchange systems are responsible for the timing of drug application on patch clamp experiments. There are two basic strategies for generating a solution exchange. When slow exchanges are bearable, it is easier to perform the exchange inside the tubing system upstream of the exit port. On the other hand, fast, reproducible, exchanges are usually performed downstream of the exit port. As both strategies are combinable, increasing the performance of upstream exchanges is desirable. We designed a simple method for manufacturing T-junctions (300 μm I.D.) and we measured the time profile of exchange of two saline solutions using a patch pipette with an open tip. Three factors were found to determine the timing of the solution switching: pressure, travelled distance and off-center distance. A linear relationship between the time delay and the travelled distance was found for each tested pressure, showing its dependence to the fluid velocity, which increased with pressure. The exchange time was found to increase quadratically with the delay, although a sizeable variability remains unexplained by this relationship. The delay and exchange times increased as the recording pipette moved away from the center of the stream. Those increases became dramatic as the pipette was moved close to the stream borders. Mass transport along the travelled distance between the slow fluid at the border and the fast fluid at the center seems to contribute to the time course of the solution exchange. This effect would be present in all tubing based devices. Present results might be of fundamental importance for the adequate design of serial compound exchangers which would be instrumental in the discovery of drugs that modulate the action of the physiological agonists of ion channels with the purpose of fine tuning their physiology.

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