Frontiers in pharmacology
-
Malaria and iron have a complex but important relationship. Plasmodium proliferation requires iron, both during the clinically silent liver stage of growth and in the disease-associated phase of erythrocyte infection. Precisely how the protozoan acquires its iron from its mammalian host remains unclear, but iron chelators can inhibit pathogen growth in vitro and in animal models. ⋯ Key to understanding the pathophysiology of iron metabolism in malaria is the activity of the iron regulatory hormone hepcidin. Hepcidin is upregulated during blood-stage parasitemia and likely mediates much of the iron redistribution that accompanies disease. Understanding the regulation and role of hepcidin may offer new opportunities to combat malaria and formulate better approaches to treat anemia in the developing world.
-
Frontiers in pharmacology · Jan 2014
ReviewOpioid receptor desensitization: mechanisms and its link to tolerance.
Opioid receptors (OR) are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. ⋯ This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of the receptor.
-
Frontiers in pharmacology · Jan 2014
Deleterious effects of maternal ingestion of cocoa upon fetal ductus arteriosus in late pregnancy.
Cocoa powder has twice more antioxidants than red wine and three times more than green tea. Ten percent of its weight is made up of flavonoids. Cocoa has antioxidant and anti-inflammatory effects by downregulating cyclooxigenase-2 receptors expression in the endothelium and enhancing nitric oxide bioavailability. ⋯ Polyphenols present in many foods and their anti-inflammatory and antinociceptive activities have been shown to be as or more powerful than those of indomethacin. These effects are dependent on the inhibition of modulation of the arachidonic acid and the synthesis of prostaglandins, especially E-2, which is responsible for fetal DA patency. So, we hypothesized that this same mechanism is responsible for the harmful effect of polyphenol-rich foods, such as cocoa, upon the fetal DA after maternal intake of such substances in the third trimester of pregnancy, thereby rising the perspective of a note of caution for pregnant women diet.
-
Frontiers in pharmacology · Jan 2014
ReviewDoes the kappa opioid receptor system contribute to pain aversion?
The kappa opioid receptor (KOR) and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. ⋯ While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.