Inflammation in Bipolar Disorder (BD): Identification of new therapeutic targets.

Bipolar disorder (BD) is a chronic and cyclic mental disorder, characterized by unusual mood swings between mania/hypomania and depression, raising concern in both scientific and medical communities due to its deleterious social and economic impact. Polypharmacy is the rule due to the partial effectiveness of available drugs. Disease course is often unremitting, resulting in frequent cognitive deficits over time. Despite all research efforts in identifying BD-associated molecular mechanisms, current knowledge remains limited. However, the involvement of inflammation in BD pathophysiology is increasingly consensual, with the immune system and neuroinflammation playing a key role in disease course. Evidence includes altered levels of cytokines and acute-phase proteins, pathological microglial activation, deregulation of Nrf2-Keap1 system and changes in biogenic amines neurotransmitters, whose expression is regulated by TNF-α, a pro-inflammatory cytokine highly involved in BD, pointing out inflammation as a novel and attractive therapeutic target for BD. As result, new therapeutic agents including non-steroidal anti-inflammatory drugs, N-acetylcysteine and GSK3 inhibitors have been incorporated in BD treatment. Taking into consideration the latest pre-clinical and clinical trials, in this review we discuss recent data regarding inflammation in BD, unveiling potential therapeutic approaches through direct or indirect modulation of inflammatory response.

Identification of new targets of S-nitrosylation in neural stem cells by thiol redox proteomics.

Nitric oxide (NO) is well established as a regulator of neurogenesis. NO increases the proliferation of neural stem cells (NSC), and is essential for hippocampal injury-induced neurogenesis following an excitotoxic lesion. One of the mechanisms underlying non-classical NO cell signaling is protein S-nitrosylation. This post-translational modification consists in the formation of a nitrosothiol group (R-SNO) in cysteine residues, which can promote formation of other oxidative modifications in those cysteine residues. S-nitrosylation can regulate many physiological processes, including neuronal plasticity and neurogenesis. In this work, we aimed to identify S-nitrosylation targets of NO that could participate in neurogenesis. In NSC, we identified a group of proteins oxidatively modified using complementary techniques of thiol redox proteomics. S-nitrosylation of some of these proteins was confirmed and validated in a seizure mouse model of hippocampal injury and in cultured hippocampal stem cells. The identified S-nitrosylated proteins are involved in the ERK/MAPK pathway and may be important targets of NO to enhance the proliferation of NSC.

Complications of coracoid transfer procedures for the treatment of recurrent shoulder dislocation.

HIGHLIGHTS: Coracoid transfer procedures are known to be successful when it comes to prevention of recurrence. However, all of them are invariably associated with high complication rates, especially limited range of motion.Arthroscopic technique was found to have an overall lower rate of complications when compared to the open procedures.Despite being scarce, the CHSJ data roughly overlap the literature. BACKGROUND: Different surgical procedures have been described for the treatment of the recurrent anterior dislocation of the shoulder. Despite the documented success of the open procedures, some studies suggest that the arthroscopic technique leads to more favorable results. However, there still seems to be some disagreement concerning the incidence of complications, when comparing open and arthroscopic techniques. OBJECTIVE AND METHODS: As an attempt to clarify these doubts about the incidence of complications associated with the different techniques, this study contains a free literature review along with a retrospective case series of the patients who underwent these procedures in an University hospital in the past 10 years. DISCUSSION AND CONCLUSION: There are various techniques for the treatment of the recurrent dislocation of the shoulder, all of them with known success when it comes to prevention of recurrence. However, all of them are invariably associated with high complication rates.Despite being associated with a slightly higher re-operation rate, in the literature, the arthroscopic technique was found to have an overall lower rate of complications when compared to the open procedures. Centro Hospitalar São João (CHSJ) presented a higher rate of screw related complications and revision surgery than the literature. However, concerning other complications and when assessing the procedures individually, no tendency was verified. One can therefore conclude that, despite being scarce, the Centro Hospitalar São João CHSJ data roughly overlap the literature.

Macrophage response to chitosan/poly-(γ-glutamic acid) nanoparticles carrying an anti-inflammatory drug.

The inflammatory response to biomaterials, traditionally viewed as detrimental, is nowadays considered essential for tissue repair/regeneration, being macrophages recognized as the key players in resolving inflammation. Here, the preparation of chitosan (Ch)/poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) as vehicle for a non-steroid anti-inflammatory drug, diclofenac (Df), is described and the response of primary human macrophages to this system is evaluated. Df was incorporated in Ch/γ-PGA NPs at controlled pH (5.0) (maximum 0.05 mg/ml). The components molar ratio and order of addition revealed to be critical to obtain NPs (315 ± 50 nm with 0.36 ± 0.06 polydispersion index). Df was released at physiological pH and this drug-delivery system was proved to be non toxic to macrophages, being rapidly internalized (95 %). Importantly, efficacy of Df-NPs was confirmed by their ability of inhibit/revert PGE2 production of activated macrophages. Therefore, Df-NPs could contribute to stifle local inflammatory reactions, namely those associated with biomaterials.