Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response?

American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation.     

Cognitive performance among cohorts of children exposed to a waste disposal site containing heavy metals in Chile

Between 1984 and 1998, people living in Arica were involuntarily exposed to metal-containing waste stored in the urban area. The study aims to determine whether children who lived near the waste disposal site during early childhood experienced negative effects on their cognitive development. The cognitive performance was assessed using the Wechsler Intelligence Scale for Children. The exposure variable was defined by the year of birth in three categories: (1) Pre-remediation (born before 1999); (2) During-remediation (born between 1999 and 2003); and (3) Post-remediation (born after 2003). In the crude analysis, a difference of 10 points in the IQ average was observed between the group born in the pre- (81.9 points) and post-remediation period (91.1 points). The difference between both groups was five times higher as compared to children of similar age and socioeconomic status in other cities of Chile. This result could be related with a period of high potential for exposure to this contaminated site.     

A patent update on cannabinoid receptor 1 antagonists (2015-2018)

Introduction: The endocannabinoid system is an important regulator of various physiological processes. Preclinical and clinical studies indicate that attenuation of the endocannabinoid system via antagonism of the type 1 cannabinoid receptor (CB1) is an excellent strategy to treat obesity, metabolic syndrome and associated disorders. However, centrally acting antagonists of CB1 also produce adverse effects like depression and anxiety. Current efforts are geared towards discovery and optimization of antagonists and modulators of CB1 that have limited brain penetration.

Areas covered: Several recent publications and patent applications support the development of peripherally acting CB1 receptor antagonists and modulators. In this review, recent patents and applications (2015–2018) are summarized and discussed.

Expert opinion: Approximately 30 new inventions have been reported since 2015, along with 3 recent commercial deals, highlighting the importance of this class of therapeutics. Taken together, peripherally acting CB1 receptor antagonists and modulators are an emerging class of drugs for metabolic syndrome, non-alcoholic steatohepatitis (NASH) and other important disorders where this receptor has been implicated.