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CT-3 (ajulemic acid) is a synthetic analogue of a metabolite of Delta9-tetrahydrocannabinol that has reported analgesic efficacy in neuropathic pain states in man. Here we show that CT-3 binds to human cannabinoid receptors in vitro, with high affinity at hCB1 (Ki 6 nM) and hCB2 (Ki 56 nM) receptors. In a functional GTP-gamma-S assay CT-3 was an agonist at(More)
OBJECTIVE To postulate reasons as to why the benefits seen with novel therapies in animal models of sepsis fail to translate to the clinical setting. DATA SOURCE MEDLINE searches and relevant book chapters. DATA SUMMARY Thousands of preclinical trials performed over more than five decades have failed to find more than a handful of drugs and techniques(More)
Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of(More)
BACKGROUND Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. METHODS AND FINDINGS In a long-term rat model of faecal peritonitis, biotransformation and(More)
OBJECTIVE To explore the hypothesis that beta-1 adrenoreceptor blockade may be protective through the attenuation of sympathetic hyperactivity and catecholaminergic inflammatory effects on cardiac and hepatic function. DESIGN Prospective, randomized, controlled study. SETTING Animal laboratory in a university medical center. SUBJECTS Male adult Wistar(More)
Sepsis affects both macro- and micro-circulatory transport of oxygen to tissues, causing regional hypoxia. However, this relationship is poorly characterized with respect to inter-organ variability, disease severity and the evolution to organ dysfunction. We hypothesized that an early circulatory insult precedes the development of organ dysfunction, and is(More)
INTRODUCTION Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality. Septic patients with delirium may differ from a general critically ill population. The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and(More)
Myocardial function is depressed in sepsis and is an important prognosticator in the human condition. Using echocardiography in a long-term fluid-resuscitated Wistar rat model of faecal peritonitis we investigated whether depressed myocardial function could be detected at an early stage of sepsis and, if so, whether the degree of depression could predict(More)
Tissue Po(2) (tPo(2)) reflects the balance between local O(2) supply and demand and, thus, could be a useful monitoring modality. However, the consistency and amplitude of the tPo(2) response in different organs during different cardiorespiratory insults is unknown. Therefore, we investigated the effects of endotoxemia, hemorrhage, and hypoxemia on tPo(2)(More)
PURPOSE OF REVIEW The term 'multiorgan failure' (MOF) carries the negative connotation of major homeostatic breakdown and severe malfunction. However, this traditional paradigm may not be necessarily accurate. This review will investigate the rationale for no longer considering MOF to be simply a 'failed' pathophysiological state. RECENT FINDINGS(More)