ABSTRACT
The endogenous neuropeptide nociceptin (N/OFQ), which mediates its actions via the nociceptin receptor (NOP), is implicated in multiple behavioural and physiological functions. This study examined the effects of the NOP agonists N/OFQ and the synthetic agonist Ro 64-6198, the antagonists NNN and NalBzoH, as well as deletion of the Pronociceptin gene on emotional memory in mice. The animals were tested in the passive avoidance (PA) task, dependent on hippocampal and amygdala functions. N/OFQ injected intraventricularly (i.c.v.) prior to training produced a biphasic effect on PA retention; facilitation at a low dose and impairment at higher doses. Ro 64-6198 also displayed a biphasic effect with memory facilitation at lower doses and impairment at a high dose. None of the agonists influenced PA training latencies. NNN did not significantly modulate retention in the PA task but antagonized the inhibitory effects of N/OFQ. NalBzoH facilitated memory retention in a dose-dependent manner and blocked the impairing effects of N/OFQ. However, neither NNN nor NalBzoH blocked the memory-impairing effects of Ro 64-6198. Finally, the Pnoc knockout mice exhibited enhanced PA retention latencies compared to the wild type mice. The biphasic effect of the natural ligand and Ro 64-6198 and the failure of the antagonists to block the action of Ro 64-6198 indicate complexity in ligand-receptor interaction. These results indicate that brain nociceptin and its NOP has a subtle role in regulation of mechanisms of relevance for treatment of disorders with processing disturbances of aversive events e.g. Alzheimer's disease, anxiety, depression and PTSD.
Subject(s)
Avoidance Learning/physiology , Opioid Peptides/metabolism , Receptors, Opioid/deficiency , Animals , Association Learning/drug effects , Avoidance Learning/drug effects , Dose-Response Relationship, Drug , Imidazoles/pharmacology , Injections, Intraventricular , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Naloxone/analogs & derivatives , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Opioid Peptides/genetics , Opioid Peptides/pharmacology , Peptide Fragments/pharmacology , Receptors, Opioid/agonists , Receptors, Opioid/genetics , Retention, Psychology/drug effects , Spiro Compounds/pharmacology , Nociceptin Receptor , NociceptinABSTRACT
OBJECTIVES: To describe media strategies for the Nordic countries outlined in internal Philip Morris documents and to evaluate their implementation and outcomes. METHODS: Systematic search of internal tobacco industry documents from the databases available on the Internet and retrieval of newspaper and magazine articles from Sweden and Finland. RESULTS: The Philip Morris Nordic journalist program contained a broad range of strategies to communicate company views and to counteract negative publicity, including trips for journalists, media briefings and special events. While several of these strategies were implemented, the efforts were largely unsuccessful in that the media in Sweden and Finland carried few tobacco industry friendly articles. Articles defending the tobacco industry appeared mainly in business papers. However, support of smokers' rights' groups and sponsoring of cultural events generated positive publicity for Philip Morris. CONCLUSIONS: Despite minor transient victories The Philip Morris Nordic journalist program was largely unsuccessful in providing the anticipated media coverage to question the health hazards of environmental tobacco smoke (ETS) and in preventing ETS regulation in the Nordic countries. The study further supports the notion that the internal corporate documents may expose the intents of the industry, but do not include enough information to evaluate implementation of industry's strategies or their outcomes.
Subject(s)
Interinstitutional Relations , Journalism , Tobacco Industry , Bibliometrics , Finland , Marketing/methods , Program Evaluation , Public Opinion , Smoking/adverse effects , SwedenABSTRACT
It is now 50 years since the double helical structure of DNA was discovered. Even if the knowledge about the DNA structure has had great implications for many disciplines in medical and genetic research, the big breakthrough is still to come in clinical practice. Much research is now focusing on elucidating the regulatory mechanisms controlling the activity and behaviour of the genes of our genome. Many researchers and clinicians are hoping that the tangle of nucleic acids and proteins that fills the cellular nucleus harbours interesting and potential drug targets.
Subject(s)
DNA/history , DNA/chemistry , Europe , Genetic Research/history , Genome, Human , History, 19th Century , History, 20th Century , Humans , Nobel Prize , United StatesSubject(s)
Hippocampus/physiology , Learning/physiology , Memory/physiology , Brain Mapping , Humans , Magnetic Resonance ImagingABSTRACT
Every year, malaria kills between 1 and 2 million people. Another half billion get infected but survive. Most cases of malaria are found in sub-Saharan Africa. Because of drug and insecticide resistance and social and environmental changes the problems are still increasing. There is therefore a desperate need for vaccines and new drugs and insecticides. Several recently published research discoveries may help to speed up the development of new tools to fight malaria. Two years ago the draft human genome sequence was released. Now the sequencing of the genomes for the most common malaria parasite, Plasmodium falciparum, and the vector mosquito, Anopheles gambiae, have been completed. For the first time researchers have the genomic maps of all three organisms in an infectious disease available.
