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Objectives: Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD)., Methods: Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards., Results: There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms., Conclusion: There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion., Competing Interests: Acioly L. T. Lacerda reports grants and personal fees from Janssen Pharmaceutical; personal fees from DaiichiSankyo, Cristália, Libbs, Pfizer, Myralis-Farma, Aché Laboratórios, Hypera-Pharma, and Sanofi-Aventis; grants from Eli-Lilly, Lundbeck, Servier-Laboratories, Hoffman-La-Roche, and Forum-Pharmaceuticals. Lucas C. Quarantini reports consulting fees from Allergan, Abbot, Janssen-Pharmaceutical and Lundbeck, and research fees from Janssen-Pharmaceutical. No other conflicts of interest declared concerning the publication of this article.

Psoriasis is a chronic, inflammatory disease affecting the skin and joints. The pathogenesis of this disease is associated with genetic, environmental and immunological factors, especially unbalanced T cell activation and improper keratinocyte differentiation. Psoriatic lesion infiltrate is composed of monocytes and T cells, and most studies have focused on the participation of T cells in the pathogenesis of this disease. Here we investigated the contribution of mononuclear phagocytes in the immunopathology observed in psoriatic patients. Significant increases in the levels of TNF, IL-1β, CXCL9, as well as the soluble forms of CD14 and CD163, were observed within the lesions of psoriatic patients compared to skin biopsies obtained from healthy individuals. Moreover, we found an association between the levels of CCL2, a monocyte attractant chemokine, and disease severity. In conclusion, our findings suggest a potential role for mononuclear phagocytes in the pathogenesis of psoriasis., (Copyright © 2020 Costa, Paixão, Viana, Rocha, Saldanha, da Mota, Machado, Pagliari, de Oliveira, Arruda, Carvalho and Carvalho.)

Introduction: The use of ketamine as an option in the treatment of depressive disorder is growing rapidly, supported by numerous clinical trials attesting its efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most widely used form in the anesthetic environment in some countries, and new studies have shown that it may also be effective in depression and with better tolerability. However, no study so far has directly compared esketamine with racemic ketamine. Here we propose a protocol of a clinical trial to evaluate esketamine as a noninferior medication when compared to ketamine in the treatment of patients with treatment-resistant depression., Methods/design: This study protocol is for a randomized, controlled, double-blind noninferiority clinical trial. Subjects will be 18 years or older, with major depression characterized as treatment-resistant. Participants will receive a single infusion of either esketamine (0.25 mg/kg) or ketamine (0.5 mg/kg) over 40 minutes. The primary outcome will be the difference in remission rates between the 2 treatment arms at 24 and 72 hours after drug infusion. Secondary outcomes will include other timepoints, measurements of cognition, dissociation, and blood biomarkers., Discussion: A head-to-head study is the best way to evaluate whether the esketamine is in fact comparable to the racemic ketamine in terms of both efficacy and safety, and, if positive, it would be an initial step to increase the access to that type of treatment worldwide., Ethics and Dissemination: The study was approved by the local Institutional Review Board (University Hospital Professor Edgard Santos-Federal University of Bahia-Number: 46657415.0.0000.0049). Subjects will only participate after voluntarily agreeing and signing the Informed Consent Form. The study findings will be published in peer-reviewed journals and presented at national and international conferences., Trial Registration: This trial has been registered in the Japan Primary Registries Network (JPRN): UMIN000032355, which is affiliated with the World Health Organization.

Background: Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure., Methods: A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects., Results: A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL., Conclusions: The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease, mainly manifested by skin and / or joints lesions, presenting with a wide degree of clinical severity, but generally with great impact on patients' quality of life. Despite advances in the understanding of its pathogenesis, especially regarding the participation of T-lymphocytes and the key role of TNF, the triggering factor of the disease at the molecular level remains unknown, as well as the function of other cell populations. By presenting antigens to T-lymphocytes, monocytes assume an important role in both innate and adaptive immune response. In the last two decades, by using flow cytometry with antibodies against CD14 (receptor for lipopolysaccharide) and CD16 (low affinity receptor for IgG), human blood monocytes were classified into three subpopulations: classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++). Under normal conditions the population of classical monocytes corresponds to about 85%, while intermediate to 5.4%, and nonclassical to 9.2%. However, intermediate and nonclassical subsets are increased in various inflammatory situations, such as moderate to severe asthma, colorectal cancer, and rheumatoid arthritis. Despite psoriasis being considered a disease of inflammatory nature, scarce studies evaluating the frequency of subpopulations of monocytes in psoriatic patients are found on current medical literature, and they are restricted to peripheral blood analysis. This study aims to identify the frequency of monocyte subpopulations in blood levels as well as lesional skin of plaque psoriasis patients, and to evaluate their association to cytokines, and clinical disease severity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)