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Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among adults worldwide. It is characterised by the death of dopaminergic neurons in the substantia nigra pars compacta and, in some cases, presence of intracytoplasmic inclusions of α-synuclein, called Lewy bodies, a pathognomonic sign of the disease. Clinical diagnosis of PD is based on the presence of motor alterations. The treatments currently available have no neuroprotective effect. The exact causes of PD are poorly understood. Therefore, more precise preclinical models have been developed in recent years that use induced pluripotent stem cells (iPSC). In vitro studies can provide new information on PD pathogenesis and may help to identify new therapeutic targets or to develop new drugs.

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AIMS: Endotracheal intubation in rats is challenging due to the difficult anatomical characteristics of the airway. The success rate at first attempt is low and airway damage is a common complication. We aimed to compare and evaluate the conventional intubation method with a modified procedure using an inclined plate, headlamp (700-Lumen), and 3D mouth-piece designed with a 20° curvature. Both techniques were conducted by laboratory personnel with and without previous experience in airway management of laboratory rats. MATERIAL AND METHODS: In this study, we used 36 Wistar rats of both genders. Three groups of laboratory personnel (anesthesiologists, medical students, and laboratory technicians) performed both endotracheal intubation techniques, i.e., blind intubation at supine position and endotracheal intubation at 70° supine position with a 3D mouth-piece and direct illumination of the glottis. RESULTS: The modified technique had a significantly higher success rate and shorter procedure duration. Moreover, there was no significant difference in the procedure duration between personnel with and without previous training in airway management. CONCLUSION: Previous knowledge and experience in airway management are required when performing conventional endotracheal intubation; moreover, its success rate is low. Contrastingly, using proper instruments and the 3D mouth-piece facilitated easier and quicker airway management regardless of previous experience.

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The purpose of calculating the capillary filtration coefficient is to experimentally evaluate edema formation in models of pulmonary ischemia-reperfusion injury. For many years, the obtaining of this coefficient implies a series of manual maneuvers during ex-vivo reperfusion of pulmonary arterial pressure, venous pressure and weight, as well as the calculation of the Kfc formula. Through automation, the calculation of capillary filtration coefficient could be easier and more efficient. To describe an automatic method designed in our laboratory to calculating the capillary filtration coefficient and compare with traditional determination of capillary filtration coefficient as gold standard method. An automatic three valve perfusion system was constructed, commanded by a mastery module connected to a graphical user interface. To test its accuracy, cardiopulmonary blocks of Wistar rats were harvested and distributed in manual (n=8) and automated (n=8) capillary filtration coefficient determination groups. Physiological parameters as pulmonary arterial pressure, pulmonary venous pressure, weight and capillary filtration coefficient were obtained. Results: Capillary filtration coefficient, pulmonary arterial pressure, venous arterial pressure shown no statistical significance difference between the groups. The automated perfusion system for obtaining Kfc was standardized and validated, giving reliable results without biases and making the process more efficient in terms of time and personal staff.

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In the present work, C-F bond cleavage mediated by the super-reduced form of cobalamin (i.e., CoICbl) was theoretically studied at the ONIOM(BP86/6-311++G(d,p):PM6) + SMD level of theory. Dispersion effects were introduced by employing Grimme's empirical dispersion at the ONIOM(BP86-D/6-311++G(d,p):PM6) + SMD level. In the first stage of the study, cobalamin was characterized in terms of the coordination number of the central cobalt atom. The ONIOM(BP86/6-311++G(d,p):PM6) results showed that the base-off form of the system is slightly more stable than its base-on counterpart (ΔE = E base-off - E base-on ~ -2 kcal/mol). The inclusion of dispersive forces in the description of the system stabilizes the base-on form, which becomes as stable as its base-off counterpart. Moreover, in the latter case, the energy barrier separating both structures was found to be negligible, with a computed value of 1.02 kcal/mol. In the second stage of the work, the reaction CoICbl + CH3F → MeCbl + F- was studied considering the base-off and the base-on forms of CoICbl. The reaction that occurs in the presence of the base-on form of CoICbl was found to be kinetically more favorable (ΔE ≠ = 13.7 kcal/mol) than that occurring in the presence of the base-off form (ΔE ≠ = 41.2 kcal/mol). Further reaction-force analyses of the processes showed that the energy barrier to C-F bond cleavage arises largely due to structural rearrangements when the reaction occurs on the base-on form of the CoICbl complex, but is mainly due to electronic rearrangements when the reaction takes place on the base-off form of the complex. The latter behavior emerges from differences in the synchronicity of the bond strengthening/weakening processes along the reaction path; the base-on mode of CoICbl is able to decrease the synchronicity of the chemical events. This work gives new molecular-level insights into the role of Cbl-based systems in the cleavage of C-F bonds. These insights have potential implications for research into processes for degrading fluorine-containing pollutants.

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BACKGROUND: Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury. METHODS: Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured. RESULTS: Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group. CONCLUSIONS: Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model.

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Background Primary spinal epidural lymphoma (PSEL) is one of the rarest categories of tumors. Spinal cord compression is an uncommon primary manifestation and requires to be treated with surgery for the purpose of diagnosis and decompression. Case Presentation A 45-year-old man presented with a new onset thoracic pain and progress to an anterior spinal syndrome with hypoesthesia and loss of thermalgesia. Magnetic resonance image showed a paravertebral mass that produces medullary compression at T3. The patient was taken up to surgery, where the pathology examination showed a diffuse large B-cell lymphoma. Conclusions PSEL is a pathological entity, which must be considered on a middle-aged man who began with radicular compression, and the treatment of choice is decompression and biopsy. The specific management has not been established yet, but the literature suggests chemotherapy and radiotherapy; however, the outcome is unclear.

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The mode of action of cyclosporine (CsA) has been ascribed to its capacity to inhibit IL-2 and IFNgamma production by T cells, two cytokines implicated in allograft rejection. Recently, it has been reported that upon activation, dendritic cells (DCs) exhibit transient production of IL-2, a property that appears to be related to their capacity to initiate immune responses. On the other hand, DCs can generate signals determining Th1/Th2 polarizing effects, an effect that can drastically influence the outcome of organ transplant. The purpose of the present study was to investigate the effect of CsA on cytokine production by immature and mature DCs. DC precursors from mouse bone marrow were induced to differentiate by incubation with GM-CSF for 5 days followed by activation with LPS for 4 hours. CsA was added at different times during this process. Our results show that when CsA is added during the differentiation period following activation with LPS, IL-2 and IL-12 secretion are significantly reduced without affecting the evolution of the DC. Conversely, CsA had no effect when added during the LPS activation period. These results show that CsA affects DCs before they receive the final activation stimulus, preconditioning them to antigen stimulation. This preconditioning of DCs by calcineurin-inhibiting drugs conceptually integrates the mode of action of CsA with the tolerogenic and T-cell polarization function ascribed to DCs. These results may be especially meaningful for the future design of immunosuppressive protocols.

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