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BACKGROUND: Ischemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors (HIF), which are downregulated by the EGLN family of prolyl-4-hydroxylases, a potential biological target for the development of strategies based on pharmacological preconditioning. For that reason, this study aims to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] on liver IR injury in Wistar rats. METHODS: Twenty-eight female Wistar rats were divided into the following groups: sham (SH, n = 7), non-toxicity (HGTox, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days), IR (n = 7, total liver ischemia: 20 minutes, reperfusion: 60 minutes), and (S)-2HG+IR (HGIR, n = 7, 25 mg/kg of (S)-2HG, twice per day for two days, total liver ischemia as the IR group). Serum ALT, AST, LDH, ALP, glucose, and total bilirubin were assessed. The concentrations of IL-1ß, IL-6, TNF, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured in liver tissue, as well as the expression of Hmox1, Vegfa, and Pdk1, determined by RT-qPCR. Sections of liver tissue were evaluated histologically, assessing the severity of necrosis, sinusoidal congestion, and cytoplasmatic vacuolization. RESULTS: The administration of (S)-2HG did not cause any alteration in the assessed biochemical markers compared to SH. Preconditioning with (S)-2HG significantly ameliorated IR injury in the HGIR group, decreasing the serum activities of ALT, AST, and LDH, and the tissue concentrations of IL-1ß and IL-6 compared to the IR group. IR injury decreased serum glucose compared to SH. There were no differences in the other biomarkers assessed. The treatment with (S)-2HG tended to decrease the severity of hepatocyte necrosis and sinusoidal congestion compared to the IR group. The administration of (S)-2HG did not affect the expression of Hmox1 but decreased the expression of both Vegfa and Pdk1 compared to the SH group, suggesting that the HIF-1 pathway is not involved in its mechanism of hepatoprotection. In conclusion, (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers, without evidence of the involvement of the HIF-1 pathway. No hepatotoxic effect was observed at the tested dose.

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INTRODUCTION: A complication underserved in diabetic patients is the cognitive deficits that can reach dementia. Studying the association between electrophysiological, neuropsychological, and biochemical measures could provide a breakthrough in the understanding of this phenomenon. OBJECTIVES: To compare P200 parameters between subjects with and without diabetes mellitus type 2 and to determine their relationship with biochemical and neuropsychological indicators. METHODS: This is an observational, prospective, transversal and analytical study. Seventy-four participants were divided into two groups: 37 with diabetes mellitus type 2, and 37 subjects as controls. P200 latency, amplitude, and rate of rise to somatosensory stimuli were measured and related to the Mini Mental State Examination (MMSE) test and blood glucose and glycosylated hemoglobin. RESULTS: Diabetics showed longer latency (p < 0.042, 1-tail) and lower MMSE score (p < 0.0001) than controls. Negative associations of amplitude and rising rate with glycosylated hemoglobin were observed in patients (p < 0.025); also, between amplitude and blood glucose (p < 0.038, 1-tail) and between MMSE score and time with diabetes mellitus type 2 (p < 0.007). CONCLUSIONS: The P200 parameters of the somatosensory system are sensitive to metabolic deterioration of diabetic patients, so its use in monitoring the cognitive state of patients is recommended.

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This is a second part of a research aimed to study the effects of alcohol on the electrophysiological processes in student volunteers. The first part showed that alcohol slowed the Omitted Stimulus Potential (OSP). This work studied the ethanol effects on the parameters (i.e. rate of rise, amplitude and peak latency) of the P2 component of the evoked potentials (EPs) yielded by trains of auditory stimuli. It is hypothesized here that if P2 and OSP waves share some common neural processes then alcohol should also affect these specific parameters. A dose of 0.8 g/kg of alcohol or a placebo (0 g/kg) was administered to two groups of 15 young men who were tested before and again after treatment. The pre-post treatment change in each of the measurements was used to assess the treatment effects. The results showed that compared to placebo, alcohol slowed the P2 rise rate and reduced its amplitude, with no effects on peak latency. The rise rate is more sensitive to alcohol but more resistant to the adaptation process. Alcohol resembles the response inhibition model acting against the adaptation. The rise rate of the P2 and the OSP waves are affected by alcohol in a similar fashion, suggesting similar neural generative mechanisms.

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INTRODUCTION: Diabetic retinopathy remains the leading visual complication of diabetes mellitus type 2 (DM2) in productive patients. It evolves from a non-proliferative stage, occasionally asymptomatic, until a proliferative phase with neovascularization, retinal detachment and blindness. There are many reports that compare visual, biochemical or electrophysiological parameters among diabetic patients and healthy controls. However, much less information has been published comparing parameters between diabetics with and without non-proliferative retinopathy. Thus, it is essential to know what changes take place in the retina and the visual post retinal pathway as the disease progresses, but before the establishment of a proliferative process involving blindness. Therefore, the purpose of this study was to compare and correlate electrophysiological and visual parameters of diabetics with and without non-proliferative retinopathy, using modern, non invasive techniques. These data will allow us to a better understanding of the process and to determine the use of these parameters in the monitoring of diabetes and its complications. MATERIAL AND METHODS: This is an observational, prospective, transversal and analytical study. Twenty-two patients with DM2 were divided into two groups (50% on each group): group with non-proliferative retinopathy and group without retinopathy. We measured the central fovea thickness (CFT) by optical coherence tomography, the P100 wave of the Visual Evoked Potentials (VEP) and other visual and biochemical parameters. RESULTS: Retinopathy patients had lower visual acuity (p < 0.047), lower P100 amplitude (p < 0.043) and lower rate of rise (p < 0.026, 1-tailed). They also showed a more biochemical disturbance with higher glycemia (p < 0.015) and HbA1c (p < 0.033), and longer disease duration (p < 0.011), compared with those without retinopathy. Visual acuity showed a negative correlation with disease duration (r = -0.65; p < 0.017) and severity of ocular damage (r = -0.76; p < 0.007) in patients with retinopathy. CONCLUSIONS: Patients with retinopathy have lower visual acuity, decreased central visual fibers and a tendency to increase the ECF. Although the data favor the use of these non-invasive techniques to monitor the disease and prevent progression of visual complications, additional studies are needed with larger sample size to confirm the results obtained here.

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This within-subjects experiment tested the relationship between the premotor (cognitive) component of reaction time (RT) to a missing stimulus and parameters of the omitted stimulus potential (OSP) brain wave. Healthy young men (N=28) completed trials with an auditory stimulus that recurred at 2s intervals and ceased unpredictably. Premotor RT and Motor RT were measured on active trials that required an immediate response to a missing stimulus. Passive trials required no response in order to measure the complete set of OSP parameters (i.e., onset, rate of rise, amplitude and peak latency). The results showed that faster Premotor RT was strongly associated with a faster rate of rise in the OSP wave. Motor RT was unrelated the OSP parameters. This new evidence is consistent with the occurrence of some common cognitive processes generating behavioral and brain reactions to a missing stimulus.

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RATIONALE: The possibility that moderate blood alcohol concentrations (BACs) may impair cognitive processes before disturbing motor functions has raised concern about the safety of BACs

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Two experiments tested the adequacy of behavioral criteria to fractionate reaction time (RT) into independent premotor (cognitive) and motor components. Healthy participants performed an omitted stimulus reaction time task in which they responded to the termination of a train of lateralized visual, auditory or tactile stimuli. Exp. 1 with 48 participants (24 men) showed premotor RT was independent of motor RT in each sensory modality and did not differ as a function of side of presentation or sex. Repeated tests administered in Exp. 2 (N= 12) also showed no significant association between the behaviorally fractionated measures. These results are comparable to those obtained using muscle potential to fractionate RT and suggest behaviorally fractionated premotor and motor RT could be a reliable, useful tool in the assessment of cognitive and motor processing in different sensory modalities of healthy people or those with brain injury, disease, or drug-induced disturbances.

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