Polyamines in inflammation and their modulation by conventional anti-inflammatory drugs

Significant increase in polyamines levels in inflamed tissue was observed in the experimental animal models of inflammation. Treatment with dexamethasone positively modulated the levels of polyamines whereas non-steroidal drugs, diclofenac and valdecoxib negatively modulated their levels.     

BMP antagonists: their roles in development and involvement in pathophysiology

Bone morphogenetic proteins (BMPs) are phylogenetically conserved signaling molecules that belong to the transforming growth factor (TGF)-beta superfamily, and are involved in the cascades of body patterning and morphogenesis. The activities of BMPs are precisely regulated by certain classes of molecules that are recently recognized as BMP antagonists. BMP antagonists function through direct association with BMPs, thus prohibiting BMPs from binding their cognate receptors. In this review, the classification and functions of BMP antagonists will be discussed, especially focusing on the new family of tissue-specific BMP antagonists composed of uterine sensitization-associated gene 1 (USAG-1) and sclerostin.     

Sphingolipids in inflammation: roles and implications

Sphingolipids, historically described as potential reservoirs for bioactive lipids, presently define a new family of cellular mediators, joining the well-established glycerolipid-derived mediators of signal transduction such as diacylglycerol, phosphatidylinositides, and eicosanoids. Sphingolipid metabolism is clearly involved in the regulation of cell growth, differentiation, and programmed cell death. Indeed, a majority of the greater than four thousand studies conducted on sphingolipids during the past five years were investigations of the role of sphingolipids as cellular bioregulators. Studies spanning more than a decade have shown multiple interactions and intersections of the sphingolipid-mediated pathways and the eicosanoid pathway. This review will discuss the emerging mechanisms by which sphingolipids induce inflammatory responses via the eicosanoid pathway in addition to linking previous literature on sphingolipids and inflammation with newer findings of distinct roles for sphingosine-1-phosphate in regulating cyclooygenase-2 and ceramide-1-phosphate in the regulation of cytosolic phospholipase A2alpha. Finally, the relationship between bioactive sphingolipids and inflammation is discussed.     

Viruses and the immune system: their roles in seizure cascade development

Viral encephalitis affects approximately 7.5 people/100 000 and carries a high rate of morbidity and mortality. Most patients with viral encephalitis will develop some form of seizure during the infectious process, and of those who survive encephalitic disease, approximately 4–20% will develop epilepsy. Arthropod-borne (arbo)viruses are the leading cause of viral encephalitis in the world today, with between 10% and 35% of patients infected with these viruses displaying some form of seizure. Several neurotropic DNA viruses, including Herpes and cytomegalovirus also commonly cause seizures in infected patients. In the clinical setting, the cause of seizures seen during viral encephalitis is usually attributed to acute febrile responses. However, it has become apparent that the mechanisms behind seizure generation during viral encephalitis are likely to be much more complicated. For example, CD4⁺ and CD8⁺ T cells possibly through their secretion of interferon-γ, appear to play an important role in determining neuronal responses when challenged with kainic acid. In addition, the ability of the human immunodeficiency virus, transactivating protein to modulate NMDA signaling possibly triggering seizures, highlights the fact that elements of the antiviral response and even virally derived proteins are capable of directly manipulating neuronal function. Understanding the complex relationships between the CNS, the immune system, and invading pathogens is a critical step in understanding the pathogenesis of seizures seen during viral infections and informing the development of novel therapies.     

Endothelin-1: physiological and pathological roles in myometrium

Endothelin-1 (ET-1), a member of endothelin peptide family is released by many different tissues including uterine smooth muscle. ET-1 acts through ETA and ETB receptors and is implicated in a wide range of biological and pathological functions that explain the great attention of the pharmacological industry for ET-1 receptors as potential therapeutic targets in vascular pathologies and cancers. It is now well established that ET-1 is also able to regulate myometrial functions. In the present review, we focused on ET axis and related signaling pathways involved in the regulation of myometrial contraction, as well as cell proliferation and survival. Such ET-1-mediated cellular functions play a critical role in normal pregnancy, preterm birth and uterine leiomyoma.