Cohen A

References (4)

Title : Acute response to cholinergic challenge predicts long-term response to galantamine treatment in patients with Alzheimer's Disease - Baakman_2021_Br.J.Clin.Pharmacol__
Author(s) : Baakman AC , Gavan C , van Doeselaar L , de Kam M , Broekhuizen K , Bajenaru O , Camps L , Swart EL , Kalisvaart K , Schoonenboom N , Lemstra E , Scheltens P , Cohen A , van Gerven J , Groeneveld GJ
Ref : British Journal of Clinical Pharmacology , : , 2021
Abstract : BACKGROUND: Cholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's Disease (AD) patients, but are associated with multiple side effects and only 20-40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of a single dose administration of galantamine on CNS functioning in mild to moderate AD patients and its potential to predict long-term treatment response. METHODS: This study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double-blind, placebo-controlled cross-over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open-label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non-responder based on their MMSE, NPI and DAD scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non-responders. RESULTS: A single dose of galantamine significantly reduced saccadic reaction time (-0.0099; 95%CI=-0.0195,-0.0003; p=.0430), absolute frontal EEG parameters in alpha (-14.9; 95%CI=-21.0,-8.3; p=.0002), beta (-12.6; 95%CI=-19.4,-5.3; p=.0019) and theta (-17.9; 95%CI=-25.0,-10.0; p=.0001) frequencies. Relative frontal (-1.669; 95%CI=-2.999,-0.339; p=.0156) and occipital (-1.856; 95%CI=-3.339,-0.372; p=.0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95%CI=0.158,2.475; p=.0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (-20.4; 95%CI=-31.6,-7.47; p=.0046), beta (-15.7; 95% CI=-28.3,-0.93; p=.0390) and theta (-25.9; 95%CI=-38.4,-10.9; p=.0024) EEG parameters and of relative frontal theta power (-3.27%; 95%CI=-5.96,-0.58; p=.0187) on EEG significantly distinguished responders (n=11) from non-responders (n=32) after 6 months. CONCLUSIONS: This study demonstrates that acute PD effects after single dose of galantamine are correlated with long-term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.
ESTHER : Baakman_2021_Br.J.Clin.Pharmacol__
PubMedSearch : Baakman_2021_Br.J.Clin.Pharmacol__
PubMedID: 34964149

Title : Hyaluronan control of the primary vascular barrier during early mouse pregnancy is mediated by uterine NK cells - Hadas_2020_JCI.Insight_5_
Author(s) : Hadas R , Gershon E , Cohen A , Atrakchi O , Lazar S , Golani O , Dassa B , Elbaz M , Cohen G , Eilam R , Dekel N , Neeman M
Ref : JCI Insight , 5 : , 2020
Abstract : Successful implantation is associated with a unique spatial pattern of vascular remodeling, characterized by profound peripheral neovascularization surrounding a periembryo avascular niche. We hypothesized that hyaluronan controls the formation of this distinctive vascular pattern encompassing the embryo. This hypothesis was evaluated by genetic modification of hyaluronan metabolism, specifically targeted to embryonic trophoblast cells. The outcome of altered hyaluronan deposition on uterine vascular remodeling and postimplantation development were analyzed by MRI, detailed histological examinations, and RNA sequencing of uterine NK cells. Our experiments revealed that disruption of hyaluronan synthesis, as well as its increased cleavage at the embryonic niche, impaired implantation by induction of decidual vascular permeability, defective vascular sinus folds formation, breach of the maternal-embryo barrier, elevated MMP-9 expression, and interrupted uterine NK cell recruitment and function. Conversely, enhanced deposition of hyaluronan resulted in the expansion of the maternal-embryo barrier and increased diffusion distance, leading to compromised implantation. The deposition of hyaluronan at the embryonic niche is regulated by progesterone-progesterone receptor signaling. These results demonstrate a pivotal role for hyaluronan in successful pregnancy by fine-tuning the periembryo avascular niche and maternal vascular morphogenesis.
ESTHER : Hadas_2020_JCI.Insight_5_
PubMedSearch : Hadas_2020_JCI.Insight_5_
PubMedID: 33208556

Title : Acetylcholinesterase-ISFET based system for the detection of acetylcholine and acetylcholinesterase inhibitors - Hai_2006_Biosens.Bioelectron_22_605
Author(s) : Hai A , Ben-Haim D , Korbakov N , Cohen A , Shappir J , Oren R , Spira ME , Yitzchaik S
Ref : Biosensors & Bioelectronics , 22 :605 , 2006
Abstract : A bioelectronic hybrid system for the detection of acetylcholine esterase (AChE) catalytic activity was assembled by way of immobilizing the enzyme to the gate surface of an ion-sensitive field-effect transistor (ISFET). Photometric methods used to characterize bonded enzyme and linker layers on silicon substrates confirm the existence of a stable amino-cyanurate containing AChE monolayer. The transduction of the enzyme-functionalized ISFET, in ionic solutions, is detected in response to application of acetylcholine (ACh). Recorded sensitivity of the modified ISFET to ACh has reached levels of up to 10(-5)M. The Michaelis-Menten constant of the immobilized AChE is only moderately altered. Nevertheless, the maximum reaction velocity is reduced by over an order of magnitude. The ISFET response time to bath or ionophoretic application of ACh from a micropipette was in the range of a second. The catalytic activity of the immobilized AChE is inhibited in a reversible manner by eserine, a competitive inhibitor of AChE. We conclude that the immobilized enzyme maintains its pharmacological properties, and thus the described bioelectronic hybrid can serve as a detector for reagents that inhibit AChE activity.
ESTHER : Hai_2006_Biosens.Bioelectron_22_605
PubMedSearch : Hai_2006_Biosens.Bioelectron_22_605
PubMedID: 16529923

Title : Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities - Bryk_2005_J.Neurochem_92_1216
Author(s) : Bryk B , Benmoyal-Segal L , Podoly E , Livnah O , Eisenkraft A , Luria S , Cohen A , Yehezkelli Y , Hourvitz A , Soreq H
Ref : Journal of Neurochemistry , 92 :1216 , 2005
Abstract : The 5.5 Mb chromosome 7q21-22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)-inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP-hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE-PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE-homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4-, 6.5-, 7.2- and 15.5-fold variability, respectively, with genotype-specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the - 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome-environment interactions.
ESTHER : Bryk_2005_J.Neurochem_92_1216
PubMedSearch : Bryk_2005_J.Neurochem_92_1216
PubMedID: 15715671