NEWS HIGHLIGHTS
Published Studies Related to Miochol-E (Acetylcholine)
Quantification of eccrine sweat glands with acetylcholine sweat-spot test and anatomical redistribution of sweating after T2-T3 thoracoscopic sympathicolysis. [2009.02]
BACKGROUND: In this study, patients treated by thoracoscopic sympathicolysis for palmar hyperhidrosis were evaluated to determine the number and response of sweat glands to intradermal acetylcholine stimulus... CONCLUSION: It is well-known that Cannon's law of denervation (1939) is not applicable to the sweat glands, that is, there is no hyperactivation following intradermal acetylcholine stimulation. However, some response, which increased over the first 6 months following surgery, was observed in our study. Nevertheless, this activation is subsequently self-limiting, resulting in no gland atrophy, and reinnervation occurs without patient awareness.
Nicotinic acetylcholine receptor beta2 subunit gene implicated in a systems-based candidate gene study of smoking cessation. [2008.09.15]
Although the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated, there is substantial variability among individuals in treatment response. We performed a systems-based candidate gene study of 1295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled randomized clinical trial.
Contribution of the M3 muscarinic receptors to the vasodilator response to acetylcholine in the human forearm vascular bed. [2008.08]
AIMS: Acetylcholine (ACh) is a muscarinic agonist that causes receptor-mediated, endothelium-dependent vasodilatation in the forearm vasculature. Previous indirect evidence suggests this effect may be mediated by muscarinic M(3) receptors. Darifenacin is a recently developed antimuscarinic drug with greater M(3) selectivity, and our main objective was to investigate whether darifenacin affects dose-dependent vasodilatation to ACh in the forearm circulation... CONCLUSIONS: These results suggest that, in the forearm vasculature, muscarinic M(3) receptors play a major role in ACh-induced endothelium-mediated vasodilatation.
Nicotinic acetylcholine receptor {beta}2 subunit gene implicated in a systems-based candidate gene study of smoking cessation. [2008.07.01]
While the efficacy of pharmacotherapy for tobacco dependence has been previously demonstrated, there is substantial variability among individuals in treatment response. We performed a systems-based candidate gene study of 1,295 single nucleotide polymorphisms (SNPs) in 58 genes within the neuronal nicotinic receptor and dopamine systems to investigate their role in smoking cessation in a bupropion placebo-controlled randomized clinical trial.
M2 and M3-muscarinic acetylcholine receptors remodelling in patients with a dilated atrium. [2008.04]
BACKGROUND: Studies have shown that autonomic tone plays an important role in the pathogenesis of atrial fibrillation (AF) and remodelling of I(K, ACh) in chronic AF serves as a compensatory mechanism for the AF. The relation between atrial size and AF has been established. We investigated the remodelling of muscarinic receptors in patients with dilated atrium and assessed the relationship between the muscarinic receptor remodelling and the dilated atrium... CONCLUSION: Remodelling of M2 and M3 receptors is not associated with AF, but with the dilated left atrium.
Clinical Trials Related to Miochol-E (Acetylcholine)
Clonidine-Induced Spinal Acetylcholine Release: Normal Volunteers vs. Neuropathic Pain [Recruiting]
The purpose of this study is to compare the amount of acetylcholine release after a single
injection of clonidine in normal volunteers and individuals with neuropathic pain.
Adenosine Receptors Influence Ischemia-Reperfusion Injury [Suspended]
Ischemic preconditioning is defined as the development of tolerance to ischemia-reperfusion
injury by a previous short bout of ischemia resulting in a marked reduction in infarct size.
This mechanism can be mimicked by several pharmacological substances such as acetylcholine
and adenosine.
To detect ischemia-reperfusion injury in humans in vivo Kharbanda et al. developed a method
in which endothelial dysfunction represents the effects of ischemic preconditioning. This
method, however, uses acetylcholine to measure endothelial function before and after forearm
ischemia. We, the investigators at Radboud University, hypothesize that the use of
acetylcholine in this model reduces ischemia-reperfusion injury. Therefore, we will compare
this protocol with a protocol in which endothelial function is only measured after ischemia.
We expect an increase in ischemia-reperfusion injury when endothelial function is only
measured after the forearm ischemia.
After determining the optimal method to measure ischemia-reperfusion injury of the vascular
endothelium we will determine the effect of acute and chronic caffeine, an adenosine receptor
antagonist, on ischemic preconditioning. With this study we expect to find that adenosine
mimics ischemic preconditioning of the vascular endothelium. Moreover, we expect to find that
acute caffeine intake reduces ischemia-reperfusion injury whereas chronic caffeine intake
does not. This study will increase our knowledge about the mechanism of ischemic
preconditioning and may also provide leads to exploit this endogenous protective mechanism in
a clinical setting.
Microvascular Reactivity. [Completed]
This study attempts to test capillary responses to various challenges without the need for
iontophoresis (electrical current).
Imaging of Brain Receptors in Healthy Volunteers and in Patients With Schizophrenia [Completed]
This study will use single photon emission computed tomography (SPECT) to study brain nicotine receptors (proteins on the surface of brain cells) in healthy subjects and in patients with schizophrenia. Autopsy findings in patients with schizophrenia show changes in their nicotine receptors. This study will use SPECT to look at these receptors in living schizophrenia patients and compare them with those in healthy subjects.
The following individuals between 21 and 50 years of age (or between 21 and 80 years of age for Group 1 only) are eligible for this study: healthy non-smokers (Group 1); schizophrenia patients who smoke (Group 2); schizophrenia patients who do not smoke (Group 3); healthy smokers (Group 4); healthy non-smokers (Group 5). Patients with schizophrenia must be taking olanzapine (Zyprexa) or risperidone (Risperdal) for at least 6 months. All candidates will be screened at the first visit. Group 1 participants will have three more visits; Groups 2 through 5 will have two more visits.
Visit 1
All participants will be screened with physical and neurological examinations; blood and urine tests; and neuropsychological tests to assess their ability to learn and remember words and numbers, to pay attention, and to quickly perform motor tasks, such as putting pegs into a piece of wood. In addition, they will have an eye movement test and event-related potential testing. For the eye test, the subject sits in a chair and leans forward with the chin on a chin rest. A band is tied around the head and very small amounts of invisible (infrared) light are shined into the eyes. The light is reflected back and measured. Wire electrodes are placed around the area of the eye and cheek to monitor eye blinks and eye movements. Subjects are asked to follow a light with their eyes and to look away from a light. For event- related potential testing, electrodes are placed on the scalp, forehead and cheeks, and brain activity is recorded while the subject identifies particular pictures and sounds.
Visit 2 (and Visit 3 for Group 1)
Participants will have a SPECT scan. On the night before the scan, the day of the scan, and for 4 days after the scan, subject take an oral dose of potassium iodide to protect the thyroid gland from the radioactive tracer used in the SPECT procedure. (Individuals allergic to potassium iodide will take potassium perchlorate instead.) For the SPECT scan, small radioactive markers containing 99mTc are glued to the subject's head. Two catheters (thin, flexible tubes) are placed in veins in the arms to inject the radioactive tracer [123I]5-I-A-85380 and to draw blood samples. During the scan, the subject lies on a bed with his or her head held still with a headholder. The scans are taken over a 9-hour period after injection of the tracer injection. An electrocardiogram, respiration, and blood pressure measures are taken before injection of [123I]5-I-A-85380, then 5 minutes after the injection, and again 30 to 60 minutes after the injection. Breath samples are collected every 60 minutes. Blood and urine samples are collected 5 to 6 hours after starting the scan. Group 1 subjects will have a second SPECT scan within 4 weeks of the first.
Visit 3 (Visit 4 for Group 1)
Participants will have a magnetic resonance imaging (MRI) scan. For this procedure, the subject lies on a table that slides into a narrow metal cylinder with a strong magnetic field for the scan. The scanner uses a magnetic field and radio waves to produce images that show structural and chemical changes in tissues. The test lasts up to 1 hour.
Imaging of Vesicular Acetylcholine and Dopamine Transporters in Dementia With Lewy Bodies [Recruiting]
The general aim of this research project is to determine the relationships between
alterations of central cholinergic (ACh) and dopaminergic (DA) systems and neurobehavioral
features of dementias with Lewy bodies (DLB).
Both clinical and neurochemical data support the view that DLB is not a homogeneous entity
and it can be hypothesized that differential alterations of central ACh systems (i. e.
anterior vs posterior vs striatal interneurons) in association or not with a DA
nigrostriatal dysfunction could partly support the clinical heterogeneity observed in this
disease. ACh in vivo imaging has been relatively underutilized to date and to our knowledge
only on the postsynaptic side. Furthermore, ACh/DA interactions and their relationships with
the symptomatology of DLB and related pathologies (PDD) had never been investigated.
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