I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

http://www.phytecs.com/wp-content/uploads/2015/02/Pharmacol-Rev-2006-Pacher-389-462.pdf

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

The potent analgesic effects of cannabis-like drugs and the presence of CB1-type cannabinoid receptors in pain-processing areas of the brain and spinal cord, indicate that endogenous cannabinoids such as anandamide may contribute to the control of pain transmission within the central nervous system (CNS). Here we show that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS. Palmitylethanolamide (PEA), which is released together with anandamide from a common phospholipid precursor, exerts a similar effect by activating peripheral CB2-like receptors. When administered together, the two compounds act synergistically, reducing pain responses 100-fold more potently than does each compound alone. Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors. In agreement with this possibility, the CB1 antagonist SR141716A and the CB2 antagonist SR144528 prolong and enhance the pain behaviour produced by tissue damage. These results indicate that peripheral CB1-like and CB2-like receptors participate in the intrinsic control of pain initiation and that locally generated anandamide and PEA may mediate this effect.

Control of pain initiation by endogenous cannabinoids

Statins and the risk of dementia

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system — known as the endocannabinoidome — that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma. In this Review, Cristino, Bisogno and Di Marzo outline the biology of cannabinoids, the endocannabinoid system and the expanded endocannabinoid system and discuss the involvement of these systems and the therapeutic potential of cannabinoids across the spectrum of neurological disease.

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Background: Fixed-loop and adjustable-loop are two types of cortical suspension devices that are used for graft fixation in anterior cruciate ligament reconstruction (ACLR). In this study, the authors compared clinical and functional outcomes of these devices in ACLR surgery. Methods: In a retrospective study, 60 patients who underwent ACLR using either fixed-loop (30 patients) or adjustable-loop were included. Clinical measures were Lachman test, pivot shift test, KT-1000, lack of extension, and flexion. Functional measures were 12-item Short-Form Health Survey, including the Physical Component Summary and the Mental Component Summary, International Knee Documentation Committee score, and Lysholm-Tegner activity scale. Results: The mean age of the patients was 31±7.5 yr. The mean follow-up of the patients was 18.5±6.4 mo. The grading of the Lachman test, pivot shift test, and KT-1000 were not significantly different between the study groups (P=0.47, P=1, and P=0.6, respectively). Lack of extension and flexion were not significantly different between the study groups (P=0.79 and P=0.28, respectively). The Physical Component Summary, Mental Component Summary, International Knee Documentation Committee, and Lysholm-Tegner activity scale were statistically comparable between the two study groups (P=0.46, P=0.68, P=0.55, P=0.77, respectively). Graft failure (KT>5 mm) was seen in seven patients (23.3%) of the fixed-loop group and four patients (13.3%) of the adjustable-loop group (P=0.31). Conclusions: Clinical and functional outcomes of fixed and adjustable-loop devices are comparable when used for femoral fixation in patients undergoing ACLR. Level of Evidence: Level IV.

Comparison of fixed versus adjustable-loop device for femoral graft fixation in anterior cruciate ligament reconstruction: a retrospective cohort study

We report on the growth of highly pure and single crystalline gallium nitride (GaN) nanostructures on different silicon (Si) substrates by thermal vapor deposition via the direct reaction of gallium with volatile ammonia solution. The structural and optical characteristics of the as-grown GaN/Si nanostructured heterojunctions are investigated. The morphology of the formed GaN nanostructures is strongly dependent on the crystal orientation of the Si substrate. The X-ray diffraction and Raman analysis reveal that the fabricated GaN nanostructures have a hexagonal wurtzite structure. The photoluminescence spectra of all GaN nanostructures exhibit a strong near-band-edge ultraviolet (UV) emission peak (365–372 nm), which illustrates their potential in optoelectronic applications. The current–voltage measurements under dark, visible, and UV illumination conditions are performed to study the light sensing ability of the fabricated heterojunctions. Under reverse bias (5 V), the photocurrent of the GaN/n-Si (111) photodetector was comparably much higher than that of the GaN/n-Si (100) photodetector, probably due to the better quality of the GaN formed on Si (111) compared with those formed on Si (100), resulting in a higher photoresponse. The calculated rectification ratio revealed that the sensitivity of the GaN/n-Si (111) photodiode is higher than that of the GaN/n-Si (100), indicating the importance of the interface architecture. The fabricated photodiodes showed photoresponse toward UV and visible wavelengths, demonstrating shorter rise and decay times compared with other materials used to fabricate UV and visible light photodetectors. The prototype device shows a simple method for GaN synthesis and demonstrates the possibility of constructing nanoscale photodetectors for nano-optics applications. V C 2013 AIP Publishing LLC.

Enhanced light sensing characteristics of nanostructured

Zinc oxide microspheres synthesized by the assembly of nanoplatelets have been deposited on seeded polycarbonate substrates using the electrochemical deposition technique with the assistance of glycerol. An electrochemical cell with platinum mesh as anode and the seeded substrates as cathode was employed to deposit ZnO microspheres. A computer-controlled potentiostat was used to supply sufficient current for the growth of ZnO nanoplatelets. Zinc chloride was used as a Zn source, and glycerol was applied to assist in the formation of microspheres. The average diameter of formed microspheres was 4 µ m, and the average size of nanoplatelets that formed the microspheres was a few nanometers. The morphology of the nanostructures indicated the formation of ZnO nanoplatelets with various orientations, which can significantly increase the entrapment of incident photons. X-ray diffraction analysis showed a dominant peak related to (002) as a reflection corresponding to the hexagonal ZnO structure. The enhanced photoluminescence (PL) intensity revealed improvement in the light-capturing ability due to the multiple scattering of light in the nanostructures. The quantum confinement phenomenon in the ZnO crystallites was evident from the blue shift of the PL peak position. A flexible photodetector was fabricated using the metallization of ZnO nanostructures to investigate the capability of ZnO microspheres in light sensing. The optoelectrical properties of fabricated devices were tested under ultraviolet radiation. The devices based on ZnO microspheres exhibited high sensitivity to the incident photons and showed stable photoelectric behavior under various bending conditions. • Zinc oxide microspheres were synthesized by the assembly of nanoplatelets • The role of glycerol in the aggregation of ZnO nanoplatelets was investigated • The improved PL properties of microspheres revealed enhanced light-capturing ability • Flexible photodetectors were fabricated based on ZnO microspheres and nanoplatelets • The ZnO spheres showed stable photoelectric behavior under various bending conditions 

Ultrasensitive Flexible Ultraviolet Detectors Based on Electrochemically Deposited ZnO Microspheres Synthesized by the Assembly of Nanoplatelets

Cyclooxygenase (COX), which plays a role in converting arachidonic acid to inflammatory mediators, could be inhibited by non-steroidal anti-inflammatory drugs (NSAIDs). Although potent NSAIDs are available for the treatment of pain, fever, and inflammation, some side effects, such as gastrointestinal ulcers, limit the use of these medications. In recent years, selective COX-2 inhibitors with a lower incidence of adverse effects attained an important position in medicinal chemistry. In order to introduce some new potent COX-2 inhibitors, a new series of 2-(4-(methylsulfonyl)phenyl)-N-phenylimidazo[1,2-a]pyridin-3-amines was designed, synthesized, and evaluated. The docking studies performed by AutoDock Vina demonstrated that docked molecules were positioned as well as a crystallographic ligand in the COX-2 active site, and SO2Me pharmacophore was inserted into the secondary pocket of COX-2 and formed hydrogen bonds with the active site. The designed compounds were synthesized through two-step reactions. In the first step, different 1-(4-(methylsulfonyl)phenyl)-2-(phenylamino)ethan-1-one derivatives were obtained by the reaction of aniline derivatives and α-bromo-4-(methylsulfonyl)acetophenone. Then, condensation of intermediates with different 2-aminopyridines gave final compounds. Enzyme inhibition assay and formalin test were performed to evaluate the activity of these compounds. Among these compounds, 8-methyl-2-(4-(methylsulfonyl)phenyl)-N-(p-tolyl)imidazo[1,2-a]pyridin-3-amine (5n) exhibited the highest potency (IC50 = 0.07 µM) and selectivity (selectivity index = 508.6) against COX-2 enzyme (selectivity index: COX-1 IC50/COX-2 IC50). The antinociceptive activity assessment via the formalin test showed that nine derivatives (5a, 5d, 5h, 5i, 5k, 5q, 5r, 5s, and 5t) possessed significant activity compared with the control group with a p value less than 0.05. 

/pdf/design-synthesis-and-biological-evaluation-of-new-2-4-14d9qcwu.pdf

Nima Naderi

Papers

Comparison of fixed versus adjustable-loop device for femoral graft fixation in anterior cruciate ligament reconstruction: a retrospective cohort study

Enhanced light sensing characteristics of nanostructured

Ultrasensitive Flexible Ultraviolet Detectors Based on Electrochemically Deposited ZnO Microspheres Synthesized by the Assembly of Nanoplatelets

Design, synthesis, and biological evaluation of new 2-(4-(methylsulfonyl)phenyl)-N-phenylimidazo[1,2-a]pyridin-3-amine as selective COX-2 inhibitors

The Role of the Possible Receptors and Intracellular Pathways in Protective Effect of Exogenous Anandamide in Kindling Model of Epilepsy