Springer protocols feed by Pharmacology/Toxicology 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Synthesis and Evaluation of 18F-Labeled Fluoroalkyl Triphenylphosphonium Salts as Mitochondrial Voltage Sensors in PET Myocardial Imaging
We present an optimized procedure for synthesis of three 18F-labeled fluoroalkyl triphenylphosphonium salts ([18F]FATPs) via two-step simple nucleophilic substitution reactions to develop new myocardial imaging agents for positron emission tomography (PET). The total reaction time of [18F]FATPs was within 60 min, and the overall decay-corrected radiochemical yield was approximately 15–30 % (decay corrected). Radiochemical purity was >98 % according to analytical high-performance liquid chromatography (HPLC). The specific activity of [18F]FATPs was >6.1 TBq/μmol. The micro-PET imaging studies in rats showed a...
Source: Springer protocols feed by Pharmacology/Toxicology - February 5, 2015 Category: Drugs & Pharmacology Source Type: news
Bridging the Gap Between Nature and Antioxidant Setbacks: Delivering Caffeic Acid to Mitochondria
As mitochondria have an important role as ATP supplier, cellular ROS producer and apoptosis regulator, these organelles are a promising target for pharmacological intervention in the treatment and management of several diseases. Consequently, research on mitochondria-targeted drugs, which exclude other intracellular structures or extracellular processes, is becoming a hot topic. One approach to address the specific targeting is to conjugate bioactive molecules to a lipophilic cation such as the triphenylphosphonium (TPP+). In this chapter, the development of a new antioxidant based on the dietary cinnamic acid—caffei...
Source: Springer protocols feed by Pharmacology/Toxicology - February 5, 2015 Category: Drugs & Pharmacology Source Type: news
Mitochondriotropic Nanoemulsified Genistein-Loaded Vehicles for Cancer Therapy
Genistein (Gen), a major soy isoflavone, produces extensive pro-apoptotic anticancer effects, mediated predominantly via induction of mitochondrial damage. Based on several biophysical model criteria, our rational assumptions for the native mitochondrial selectivity of Gen allowed its design as a cationic lipid-based nanocarrier (NC) system. Proof-of-concept nano-formulations, lipidic micelles (Mic), and nanoemulsions (NEs) incorporated Gen, which serves as therapeutic and targeting moieties, specific for mitochondria. Our in vitro experimental data demonstrated superior physicochemical properties and significant cytotoxic...
Source: Springer protocols feed by Pharmacology/Toxicology - February 5, 2015 Category: Drugs & Pharmacology Source Type: news
Formulation and Optimization of Mitochondria-Targeted Polymeric Nanoparticles
Targeted delivery of therapeutics to the mitochondria of cells without alteration of drug properties can be a vital technique in the treatment of a variety of mitochondrial-dysfunction-related diseases. Herein, we describe a detailed protocol for synthesis and characterization of a functionalized polymer to build mitochondria-targeted nanoparticles (NPs). The block polymer was decorated with a lipophilic triphenylphosphonium (TPP) cation for mitochondrial trafficking of payload-loaded polymeric NPs. TPP-based lipophilic cations have the ability to cross the mitochondrial membrane. A mitochondria-targeted block copolymer po...
Source: Springer protocols feed by Pharmacology/Toxicology - February 5, 2015 Category: Drugs & Pharmacology Source Type: news
Ex Vivo Generation of Functional Immune Cells by Mitochondria-Targeted Photosensitization of Cancer Cells
Stimulating the immune system for potent immune therapy against cancer is potentially a revolutionary method to eradicate cancer. Tumors stimulated with photosensitizers (PSs) not only kill cancer cells but also help to boost the immune system. We recently reported that tumor-associated antigens (TAAs) generated by delivery of a mitochondria-acting PS zinc phthalocyanine (ZnPc) to MCF-7 breast cancer cells followed by laser irradiation can lead to ex vivo stimulation of mouse bone marrow-derived dendritic cells (BMDCs). The antigens generated from the breast cancer cells were also found to cause significant DC maturation a...
Source: Springer protocols feed by Pharmacology/Toxicology - February 5, 2015 Category: Drugs & Pharmacology Source Type: news
Analysis of Opioid-Seeking Reinstatement in the Rat
The inability to maintain drug abstinence is often referred to as relapse and consists of a process by which an abstaining individual slips back into old behavioral patterns and substance use. Animal models of relapse have been developed and validated over the last decades, and significantly contributed to shed light on the neurobiological mechanisms underlying vulnerability to relapse. The most common procedure to study drug-seeking and relapse-like behavior in animals is the “reinstatement model.” Originally elaborated by Pavlov and Skinner, the concepts of reinforced operant responding and conditioned behavi...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Role of Opioid Receptors in the Reinstatement of Opioid-Seeking Behavior: An Overview
Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
The Role of Opioid Receptors in Migration and Wound Recovery In Vitro in Cultured Human Keratinocytes and Fibroblasts
We have previously described significant changes in skin differentiation and the delay in wound healing from delta-opioid receptor knockout mice. In addition, we have shown that opioid receptor ligands and their receptor systems affect wound healing in vitro and the migration pattern of human skin cells, such as keratinocytes and fibroblasts (Bigliardi-Qi et al., Differentiation 74:174–185, 2006; Bigliardi et al., Exp Dermatol 18:424–430, 2009; Bigliardi et al., J Recept Signal Transduct Res 22:191–199, 2002). This observation is true for both primary keratinocytes and fibroblasts derived from foreskin or...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Measurement of Macrophage Toll-Like Receptor 4 Expression After Morphine Treatment
The immune system is a complex and finely orchestrated system, and many soluble molecules and receptors contribute to its regulation. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Evaluation of Murine Macrophage Cytokine Production After In Vivo Morphine Treatment
The discovery of opioid receptors expression on immune cells has originated a large research activity on the possible modulation by opioid drugs of immune system responses. In the present chapter we describe an easy methodology useful to obtain information about the potential immunomodulatory activity of opioid drugs. An in vivo treatment schedule is used, and macrophages are studied for their ability to release different cytokines. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Opioid Receptors: Methods for Detection and Their Modes of Actions in the Eye
This study provides evidence for the presence of opioid-receptors in the retina, optic nerve, and optic nerve head astrocytes. These receptors were measured by more than one technique including Western blotting, immunohistochemistry, and functional assays such as scotopic electroretinogram (ERG) and Pattern ERG. I also have provided evidence in recently published work from my laboratory that opioid receptors, more specifically δ-opioid receptors, play crucial roles in retina neuroprotection against ischemic and glaucomatous injuries. This chapter provides detailed procedures to measure opioid receptor activation and ...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Detecting Zinc Release Induced by Mu-Opioid Receptor Agonists in Brain Slices
After iron, zinc is the second most abundant transition metal in living organisms and it is known to be a contributory factor in a series of neurological disorders. In biological systems zinc exists as either bound Zn2+, representing the majority of the total zinc in tissues, or free (chelatable) Zn2+. Several fluorescents dyes have been developed to detect free zinc when it is released from zinc-binding proteins, which occurs via redox mechanisms in response to the stimulation of a number of neurotransmitter receptors, including the μ opioid receptor. Here we describe a detailed protocol to detect drug stimulated intra...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Mechanical Nociception Measurement in Mice and Rats with Automated Von Frey Equipment
Von Frey hairs are important tools for the study of mechanisms of cutaneous stimulation-induced sensory input. Mechanical force is exerted via application of a particular hair to the cutaneous receptive field until buckling of the hair occurs. The most commonly used Von Frey filaments are productive in evaluating behavioral responses of neuropathic pain in preclinical and clinical research. To reduce the potential experimenter bias, automated instruments are being developed for behavioral assessment. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Skin–Nerve Preparation to Assay the Function of Opioid Receptors in Peripheral Endings of Sensory Neurons
This chapter describes the methodology of the in vitro skin–saphenous nerve preparation and its application to test for the modulatory effects of opioids on the function of cutaneous sensory neurons in experimental models of pain. We detail the skin–nerve setup requirements and the technique to record action potentials from single sensory fibers. We address how to test for inhibitory effects of opioid receptor activation on mechanical and thermal sensitivity of nociceptors and mechanoreceptors in the complete Freund’s adjuvant-induced inflammation and the chronic constriction injury model of neuropathic p...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
Electrophysiological Patch Clamp Assay to Monitor the Action of Opioid Receptors
The patch clamp is a valuable electrophysiological technique, which allows the study of single or multiple ion channels in cells, and it is particularly useful in testing the excitable cells such as neurons. Activation of neuronal opioid receptors results in the modulation of various ion channels, which enables to examine the receptors’ action with the patch clamp. In this chapter, we analyze the activation of the G-protein-coupled inwardly rectifying potassium channel 2 by opioids, and the capsaicin-induced transient receptor potential vanilloid 1 channel currents during opioid withdrawal, using the whole cell patch...
Source: Springer protocols feed by Pharmacology/Toxicology - October 9, 2014 Category: Drugs & Pharmacology Source Type: news
