Potential Therapeutic Effects of Physical Exercise for Bipolar Disorder

Cognitive deficits are observed in a variety of domains in patients with bipolar disorder (BD). These deficits are attributed to neurobiological, functional and structural brain factors, particularly in prefrontal cortex. Furthermore, cortical alterations in each phase (mania/hypomania, euthymia and depression) are also present. A growing basis of evidence supports aerobic exercise as an alternative treatment method for BD symptoms. Its benefits for physical health in healthy subjects and some psychiatric disorders are fairly established; however evidence directly addressed to BD is scant. Lack of methodological consistency, mainly related to exercise, makes it difficult accuracy and extrapolation of the results. Nevertheless, mechanisms related to BD physiopathology, such as hormonal and neurotransmitters alterations and mainly related to brain-derived neurotrophic factors (BDNF) can be explored. BDNF, specially, have a large influence on brain ability and its gene expression is highly responsive to aerobic exercise. Moreover, aerobic exercise trough BDNF may induce chronic stress suppression, commonly observed in patients with BD, and reduce deleterious effects caused by allostatic loads. Therefore, it is prudent to propose that aerobic exercise plays an important role in BD physiopathological mechanisms and it is a new way for the treatment for this and others psychiatric disorders.

Macrophages as biomarkers in BCG treatment response in bladder cancer

Bladder cancer is a common urologic cancer and the majority has origin in the urothelium. Patients with intermediate and high risk of recurrence/progression bladder cancer are treated with intravesical instillation with Bacillus Calmette-Guérin, however, approximately 30% of patients do not respond to treatment. At the moment, there are no accepted biomarkers do predict treatment outcome and an early identification of patients better served by alternative therapeutics. The treatment initiates a cascade of cytokines responsible by recruiting macrophages to the tumor site that have been shown to influence treatment outcome. Effective BCG therapy needs precise activation of the Th1 immune pathway associated with M1 polarized macrophages. However, tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype, either immunosuppressive or angiogenic, that interfere in different ways with the BCG induced antitumor immune response. The M2 macrophage is influenced by different microenvironments in the stroma and the tumor. In particular, the degree of hypoxia in the tumors is responsible by the recruitment and differentiation of macrophages into the M2 angiogenic phenotype, suggested to be associated with the response to treatment. Nevertheless, neither the macrophage phenotypes present nor the influence of localization and hypoxia have been addressed in previous studies. Therefore, this work devoted to study the influence of TAMs, in particular of the M2 phenotype taking into account their localization (stroma or tumor) and the degree of hypoxia in the tumor (low or high) in BCG treatment outcome. The study included 99 bladder cancer patients treated with BCG. Tumors resected prior to treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. Tumor hypoxia was evaluated based on HIF-1α expression. As a main finding it was observed that a high predominance of CD163+ macrophage counts in the stroma of tumors under low hypoxia was associated with BCG immunotherapy failure, possibly due to its immunosuppressive phenotype. This study further reinforces the importance the tumor microenvironment in the modulation of BCG responses.

Alternative chelating agents: Evaluation of the ready biodegradability and complexation properties

The ready biodegradability of four chelating agents, N,N -(S,S)-bis[1-carboxy-2-(imidazol-4-yl)ethyl]ethylenediamine (BCIEE), N - ethylenedi-L-cysteine (EC), N,N -bis (4-imidazolymethyl)ethylenediamine (EMI) and 2,6-pyridine dicarboxylic acid (PDA), was tested according to the OECD guideline for testing of chemicals. PDA proved to be a readily biodegradable substance. However, none of the other three compounds were degraded during the 28 days of the test. Chemical simulations were performed for the four compounds in order to understand their ability to complex with some metal ions (Ca, Cd, Co, Cu, Fe, Mg, Mn, Ni, Pb, Zn) and discuss possible applications of these chelating agents. Two different conditions were simulated: (i) in the presence of the chelating agent and one metal ion, and (ii) in the simultaneous presence of the chelating agent and all metal ions with an excess of Ca. For those compounds that were revealed not to be readily biodegradable (BCIEE, EC and EMI), applications were evaluated where this property was not fundamental or even not required. Chemical simulations pointed out that possible applications for these chelating agents are: food fortification, food process, fertilizers, biocides, soil remediation and treatment of metal poisoning. Additionally, chemical simulations also predicted that PDA is an efficient chelating agent for Ca incrustations removal, detergents and for pulp metal ions removal process.