17β-estradiol (E2) in membranes: Orientation and dynamic properties.

Non-genomic membrane effects of estrogens are of great interest because of the diverse biological activities they may elicit. To further our understanding of the molecular features of the interaction between estrogenic hormones and membrane bilayers, we have determined the preferred orientation, location, and dynamic properties of 17β-estradiol (E2) in two different phospholipid membrane environments using (2)H-NMR and 2D (1)H-(13)C HSQC in conjunction with molecular dynamics simulations. Unequivocal spectral assignments to specific (2)H labels were made possible by synthesizing six selectively deuterated E2 molecules.

Hydrogen-bonded His93 as a sensitive probe for identifying inhibitors of the endocannabinoid transport protein FABP7.

The human brain FABP (FABP7) has been shown to be an intracellular carrier protein that can significantly potentiate the uptake of the endocannabinoid anandamide. For this reason, there is a great interest in the discovery and development of FABP7 inhibitors for treating stress, pain, inflammation, and drug abuse. We found that in the (1) H-NMR spectrum of the protein, a well-separated downfield resonance arising from the hydrogen-bonded His93 side chain is very sensitive to ligand binding.

Targeting the Endocannabinoid System for Neuroprotection: A F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.

Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection. We have developed a brain permeable FAAH inhibitor, AM5206, which has served as a valuable pharmacological tool to explore neuroprotective effects of this class of compounds. In the present work, we characterized the interactions of AM5206 with a representative AEA carrier protein, human serum albumin (HSA), using F nuclear magnetic resonance (NMR) spectroscopy.

The interaction of fatty acid amide hydrolase (FAAH) inhibitors with an anandamide carrier protein using (19)F-NMR.

It has been reported that the endocannabinoid anandamide (AEA) binds to a class of fatty acid-binding proteins and serum albumin which can serve as carrier proteins and potentiate the cellular uptake of AEA and its intracellular translocation. Here, we employed (19)F nuclear magnetic resonance spectroscopy to study the interactions of serum albumin with two inhibitors of fatty acid amide hydrolase (FAAH), the enzyme involved in the deactivation of anandamide. We found that, for both inhibitors AM5206 and AM5207, the primary binding site on serum albumin is drug site 1 located at subdomain IIA.

[Gastroscopic and pathological characteristics of patients with or without schistosomiasis in Poyang Lake area].

Objectives: To understand the gastroscopic and pathological characteristics of patients with miasis in Poyang Lake area, and to explore the relationship between schistosomiasis and pathological changes of gastric mucosa.

Methods: Volunteers with or without schistosomiasis were recruited and divided into a case group and a control group. All the objects were examined by electronic gastroscopy and pathological examinations.

The interaction of cannabinoid receptor agonists, CP55940 and WIN55212-2 with membranes using solid state 2H NMR.

Two key commonly used cannabinergic agonists, CP55940 and WIN55212-2, are investigated for their effects on the lipid membrane bilayer using (2)H solid state NMR, and the results are compared with our earlier work with delta-9-tetrahydrocannabinol (Δ(9)-THC). To study the effects of these ligands we used hydrated bilayers of dipalmitoylphosphatidylcholine (DPPC) deuterated at the 2' and 16' positions of both acyl chains with deuterium atoms serving as probes for the dynamic and phase changes at the membrane interface and at the bilayer center respectively. All three cannabinergic ligands lower the phospholipid membrane phase transition temperature, increase the lipid sn-2 chain order parameter at the membrane interface and decrease the order at the center of the bilayer.

Magnetically aligned bicelles to study the orientation of lipophilic ligands in membrane bilayers.

Magnetically aligned bicelles were used as a model membrane to study the orientation and dynamic properties of two cannabinoids (Delta (8)-THC and Me-Delta (8)-THC) using (31)P and (2)H NMR. The uniform alignment of the bicelles allowed us to obtain well resolved deuterium spectra from a solution NMR spectrometer. The preferred orientations of Delta (8)-THC and Me-Delta (8)-THC were calculated on the basis of the measurements of individual quadrupolar splittings.

[A study of environmental changes on new snail habitat though multi-temporal relative radiometric normalized TM images].

Objective: To study the environmental changes of new snail habitual by using multi-temporal relative radiometric normalized TM images taken in Wuzhoutou of Nanchang, Jiangxi province.

Methods: TM images of Poyang Lake were collected on 3rd April 1998, 16th April 2000 and 5th May 2004. Taking images in 2004 as a reference, the TM images in 1998 and 2000 were radiometric normalized.

[Application of global positioning system and geographic information system in surveillance of schistosomiasis].

Objective: To use the snail survey data of Yugan, Jiangxi Province as an example to evaluate the effects and advantages of global positioning system integrated with digital maps and remote sensing data in order to manage and analyze the whole country's surveillance data of schistosomiasis by using geographic information system.

Methods: The data of geographic information and snail information of 20 marshlands in Yugan, Jiangxi Province were collected, and by the correction of remote sensing images based on the digital maps and index extraction, the snail current situation and trend were analyzed and expressed.

Results: A series of specific procedure images of these 20 marshlands was established and the effects of Yugan surveillance platform based on geographic information system were validated.

The conformation, location, and dynamic properties of the endocannabinoid ligand anandamide in a membrane bilayer.

The endogenous cannabinoid ligand anandamide is biosynthesized from membrane phospholipid precursors and is believed to reach its sites of action on the CB1 and CB2 receptors through fast lateral diffusion within the cell membrane. To gain a better insight on the stereochemical features of its association with the cell membrane and its interaction with the cannabinoid receptors, we have studied its conformation, location, and dynamic properties in a dipalmitoylphosphatidylcholine multilamellar model membrane bilayer system. By exploiting the bilayer lattice as an internal three-dimensional reference grid, the conformation and location of anandamide were determined by measuring selected inter- and intramolecular distances between strategically introduced isotopic labels using the rotational echo double resonance (REDOR) NMR method.

Conformational study of lipophilic ligands in phospholipid model membrane systems by solution NMR.

Phospholipid bicelles were employed as a membrane bilayer model in the conformational studies of two lipophilic cannabinoids, delta(8)-THC and its O-methyl ether analogue, Me-Delta(8)-THC using conventional high-resolution NMR. A preparation of 8% (w/v) phospholipid concentration and a high DMPC/DHPC ratio (q = 2.0) was found to be optimal for not only effectively incorporating our ligands, but also providing a more bilayerlike environment suitable for conformational studies.