Am 6545

Laser-metal additive manufacturing capabilities have advanced from single-material printing to multimaterial/multifunctional design and manufacturing. Material-structure-performance integrated additive manufacturing (MSPI-AM) represents a path toward the integral manufacturing of end-use components with innovative structures and multimaterial layouts to meet the increasing demand from industries such as aviation, aerospace, automobile manufacturing, and energy production. We highlight two methodological ideas for MSPI-AM-"the right materials printed in the right positions" and "unique structures printed for unique functions"-to realize major improvements in performance and function...

The endocannabinoid system (ECS) is known to modulate not only food intake but also pain, especially via the cannabinoid type 1 receptor (CB1R) expressed throughout the central nervous system and the peripheral tissues. Our previous study demonstrated that fasting produces an analgesic effect in adult male mice, which is reversed by intraperitoneal (i.p.) administration of CB1R antagonist (SR 141716). In the present study, we further examined the effect of CB1R expressed in the peripheral tissues. In the formalin-induced inflammatory pain model, i...

Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of antiobesity drugs has often been riddled with problems in the past...

RATIONALE: Cannabinoid CB1 inverse agonists hold therapeutic promise as appetite suppressants but have produced suicidal behaviors among a small subpopulation in clinical trials. Anatomical and pharmacological evidence implicate the 5HT1A serotonin receptor in suicide in humans and impulsivity in humans and animals. OBJECTIVE: The objective of the study is to assess whether 5HT1A blockade is necessary for CB1 ligands to produce impulsivity. METHODS: Sprague Dawley rats were administered the CB1 inverse agonist AM 251, the CB1 antagonist AM 6527, or the peripherally restricted antagonist AM 6545, with or without pretreatment with the 5HT1A antagonist WAY 100,635 (WAY) on the paced fixed consecutive number (FCN) task, which measures choice to terminate a chain of responses prematurely...