Introduction NLRP3 inflammasome is a molecular platform of innate immune system that regulates the inflammatory response through the activation of caspase‐1 and IL‐1β. It can be activated by several ligands, for example, mitochondrial DNA (mDNA). Some studies have shown that circulating mDNA is increased in patients with diabetes and play a role in the development of the disease; however, its role in vascular changes is still unknown. In this sense, we tested the hypothesis that mDNA contributes to vascular inflammatory/oxidative processes associated to type 1 diabetes (T1D) via NLRP3 inflammasome activation. Methods Wild‐type and NLRP3‐deficient (NLRP3−/−) mice were treated with vehicle (Veh) or streptozotocin (40 mg/kg) (T1D) for 5 days. Vascular reactivity was determined in mesenteric arteries. Caspase‐1 and IL‐1β expression were evaluated by western blot. Pancreatic mDNA was extracted from control (cmDNA) and diabetic animals (dmDNA) for endothelial cells stimulation. ROS generation was determined by chemiluminescence. Hydrogen peroxide (H2O2) production and calcium influx were determined by fluorescence. Data are presented as mean ± standard error of the mean. Results Diabetes increased vascular caspase‐1 and IL‐1β activation [arbitrary units (a.u.), 1.2±0.1 vs. 0.8±0.1; 4.8±1.1 vs. 0.8±0.5 vs. the Veh, respectively, p <0.05]. However, this activation was attenuated in T1D NLRP3−/−. Mesenteric arteries from T1D exhibited decreased ACh‐induced vasodilatation vs. Veh [(Emax), 46.6±4.0 vs. 91.5±2.8, n=4–5, p<0.05], which was not observed in T1D NLRP3−/−. The NLRP3 inhibitor MCC950 acutely improved endothelium‐dependent vasodilation in T1D [(Emax), 62.5±3.8 vs. 85.6±3.7, n=4–5, p<0.05]. ROS generation [(Relative luminescence unit, RLU), 1.5×107±2.3 vs. 48.9×103±1.1, n=4–5, p<0.05] as well as H2O2 production [(Relative fluorescence unit, RFU), 1082±242.6 vs. 232.0±42.8, n=4–5, p<0.05] were lower in mesenteric bed from T1D NLRP3−/− than T1D. Only incubation with dmDNA reduced ACh‐induced vasodilation [(Emax), 48.4 ± 4.1 vs. 90.7 ± 3.4, n=4–5, p<0.05], which was attenuated by the presence of an antioxidant [(Emax), 48.4 ± 4.1 vs. 71.5 ± 3.1, n=4–5, p<0.05]. Similarly, only LPS‐primed cells incubated with dmDNA had significant NLRP3 activation (caspase‐1 and IL‐1β activation, respectively) [(u.a.), 1.6 ± 0.2 vs. 0.9 ± 0.1; and 1.6 ± 0.2 vs. 1.0 ± 0.1, n=4–5, p<0.05]. The dmDNA induced in a time‐dependent way both calcium influx and ROS generation in endothelial cells, being the last reversed by the presence of an antioxidant. Likewise, T1D patients had increased circulating mDNA vs. healthy volunteers and also higher NLRP3 serum expression, and caspase‐1/IL‐1β activation. Conclusion The T1D increases mDNA release which in turn stimulates increased calcium influx, induces ROS generation, and triggers vascular NLRP3 inflammasome activation contributing to inflammatory response and endothelial dysfunction in diabetes. Support or Funding Information Financial Support: FAPESP and CAPES. Ethics Committee number (026/2015)...
Little is known about the ability of blind people to cross obstacles after they have explored haptically their size and position. Long-term absence of vision may affect spatial cognition in the blind while their extensive experience with the use of haptic information for guidance may lead to compensation strategies. Seven blind and 7 sighted participants (with vision available and blindfolded) walked along a flat pathway and crossed an obstacle after a haptic exploration. Blind and blindfolded subjects used different strategies to cross the obstacle. After the first 20 trials the blindfolded subjects reduced the distance between the foot and the obstacle at the toe-off instant, while the blind behaved as the subjects with full vision. Blind and blindfolded participants showed larger foot clearance than participants with vision. At foot landing the hip was more behind the foot in the blindfolded condition, while there were no differences between the blind and the vision conditions. For several parameters of the obstacle crossing task, blind people were more similar to subjects with full vision indicating that the blind subjects were able to compensate for the lack of vision.
Resumo GARCIA, V. D. Visão de cores, sensibilidade ao contraste e mfERG em indivíduos com Diabetes Mellitus tipo 1.
Abstract-Human motion seems to be guided by some optimal principles. In general, it is assumed that human walking is generated with minimal energy consumption. However, in the presence of disturbances during gait, there is a trade-off between stability (avoiding a fall) and energyconsumption. This work analyses the obstacle-crossing with the leading foot. It was hypothesized that energy-saving mechanisms during obstacle-crossing are modulated by the requirement to avoid a fall using the available sensory information, particularly, by vision. A total of fourteen subjects, seven with no visual impairment and seven blind, walked along a 5 meter flat pathway with an obstacle of 0.26 m height located at 3 m from the starting point. The seven subjects with normal vision crossed the obstacle successfully 30 times in two conditions: blindfolded and with normal vision. The seven blind subjects did the same 30 times. The motion of the leading limb was recorded by video at 60 Hz. There were markers placed on the subject's hip, knee, ankle, rear foot, and forefoot. The motion data were filtered with a fourth order Butterworth filter with a cut-off frequency of 4 Hz. The following variables were calculated: horizontal distance between the leading foot and the obstacle at toe-off prior to (DHPO) and after (DHOP) crossing, minimal vertical height from the foot to the obstacle (DVPO), average step velocity (VELOm). The segmental energies were also calculated and the work consumed by the leading limb during the crossing obstacle was computed for each trial. A statistical analysis repeated-measures ANOVA was conducted on these dependent variables revealing significant differences between the vision and non-vision conditions in healthy subjects. In addition, there were no significant differences between the blind and people with vision blindfolded. These results indicate that vision is crucial to determine the optimal trade-off between energy consumption and avoiding a trip during obstacle crossing.
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