Emerging therapeutic options in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.     

Novel cystamine-core dendrimer-formulation rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection by augmenting autophagy

Background: Cystic fibrosis (CF) is challenged with pathophysiological barriers for effective airway drug-delivery. Hence, we standardized the therapeutic efficacy of the novel dendrimer-based autophagy-inducing anti-oxidant drug, cysteamine.

Research design and methods: Human primary-CF epithelial-cells, CFBE41o-cells were used to standardize the efficacy of the dendrimer-cystamine in correcting impaired-autophagy, rescuing ΔF508-CFTR and Pseudomonas-aeruginosa (Pa) infection.

Results: We first designed a novel cystamine-core dendrimer formulation (G4-CYS) that significantly increases membrane-ΔF508CFTR expression in CFBE41o-cells (p < 0.05) by forming its reduced-form cysteamine, in vivo. Additionally, G4-CYS treatment corrects ΔF508-CFTR-mediated impaired-autophagy as observed by a significant decrease (p < 0.05) in Ub-LC3-positive aggresome-bodies. Next, we verified that in non-permeabilized CFBE41o-cells, G4-CYS significantly (p < 0.05) induces ΔF508-CFTR’s forward-trafficking to the plasma membrane. Furthermore, cysteamine’s known antibacterial and anti-biofilm properties against Pa were enhanced as our findings demonstrate that both G4-CYS and its control DAB-core dendrimer, G4-DAB, exhibited significant (p < 0.05) bactericidal-activity against Pa. We also found that both G4-CYS and G4-DAB exhibit marked mucolytic-activity against porcine-mucus (p < 0.05). Finally, we demonstrate that G4-CYS not only corrects the autophagy-impairment by rescuing ΔF508-CFTR in CFBE41o-cells but also corrects the intrinsic phagocytosis defect (p < 0.05).

Conclusions: Overall, our data demonstrates the efficacy of novel cystamine-dendrimer formulation in rescuing ΔF508-CFTR to the plasma membrane and inhibiting Pa bacterial-infection by augmenting autophagy.     

Synthetic Cannabinoid Intoxication Presenting as Malignant Catatonia: a Case Report

International Journal of Mental Health and Addiction - The use of synthetic cannabinoids (SCs) has been steadily increasing in recent years and represents a new class of substances of abuse....     

Our Next Pandemic Ethics Challenge? Allocating “Normal” Health Care Services

The pandemic creates unprecedented challenges to society and to health care systems around the world. Like all crises, these provide a unique opportunity to rethink the fundamental limiting assumptions and institutional inertia of our established systems. These inertial assumptions have obscured deeply rooted problems in health care and deflected attempts to address them. As hospitals begin to welcome all patients back, they should resist the temptation to go back to business as usual. Instead, they should retain the more deliberative, explicit, and transparent ways of thinking that have informed the development of crisis standards of care. The key lesson to be learned from those exercises in rational deliberation is that justice must be the ethical foundation of all standards of care. Justice demands that hospitals take a safety-net approach to providing services that prioritizes the most vulnerable segments of society, continue to expand telemedicine in ways that improve access without exacerbating disparities, invest in community-based care, and fully staff hospitals and clinics on nights and weekends.     

First paleoparasitological record of acanthocephalan eggs from Northwestern Patagonia (Late Holocene,Argentina)

Eggs representative of an acanthocephalan were found in an ancient fragment of raptor pellet, probably belonged to the barn owl, Tyto alba, from the archeological site named “Epullán Chica cave.” This site is a cave located at the southern of Neuquén Province, Patagonia, Argentina. The fragment of pellet was found in a layer with charcoals dated at 1980 ± 80 years B.P. A total of 56 eggs were found. Eggs were brown colored and thick-shelled, and presented four membranes, the outer lightly sculpted. The embryos presented hooks in one extremity. Measurements ranged from 87.5 to 107.5 μm long and 50 to 57.5 μm wide. Eggs were very well-preserved, and were identified as belonged to Class Archiacanthocephala, Order Oligacanthorhynchida, Family Oligacanthorhynchidae, probably Macracanthorhynchus Travassos, 1917, or an unidentified species. This is the first report of small mammal acanthocephalans from ancient material worldwide.     

Melasma: How hormones can modulate skin pigmentation

We described—along with a genetic predisposition and exposure to sunlight, as the main factors for melasma development—pregnancy, hormonal therapies, and oral contraceptive pills. Whilst hormonal alteration or therapies are frequently reported in literature in association with melasma, studies analyzing the laboratoristic correlation are limited. We review data published on hormones variations both in women and males with melasma and report some peculiar clinical cases that further demonstrate how the relationship between hormone secretion and melasma development is difficult to be defined.