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This work was designed to determine in vivo the influence of the metabolic control of streptozotocin-induced diabetic rats, measured by the levels of haemoglobin glycosylation in blood (HbA1c), on developing vascular endothelial dysfunction. For this, the vasoactive responses to basal and stimulated endothelial nitric oxide (NO) were studied using the technique of the anaesthetized autoperfused rat, analyzing the responses to acetylcholine (ACh) and N(G)-nitro-L-arginine methyl ester (L-NAME) in non-diabetic and diabetic rats with different degrees of metabolic control (four groups with HbA1c levels of 5.5-7.4%, 7.5-9.4%, 9.5-12%, and >12%, respectively). When administered over a noradrenaline-induced vasopressor tone, ACh (0.25, 0.75, 2.5, 7.5 and 25 microg kg(-1)) induced dose-dependent vasodilatatory responses in all rat groups, reducing both mean arterial pressure and perfusion pressure of the left hindlimb. These responses were similar in non-diabetic and in diabetic rats with good metabolic control (HbA1c 5.5-7.4%), while diabetic rats with levels of HbA1c higher than 7.5% showed significantly lower vasodilatatory responses to ACh. In untreated diabetic rats, the relaxant responses evoked by the NO donor sodium nitroprusside were also impaired. On the other hand, increasing doses of L-NAME (0.1 to 10 mg kg(-1)) enhanced both mean arterial pressure and left hindlimb perfusion pressure in diabetic and non-diabetic rats. As with ACh, the responses to L-NAME were significantly reduced in diabetic rats with HbA1c levels higher than 7.5%. To determine the mechanism underlying the NO-mediated endothelial dysfunction, the responses to ACh in untreated diabetic rats (HbA1c >12%) were studied in the presence of the NO substrate L-arginine, in the presence of the oxygen-derived free radical scavenger superoxide dismutase (SOD), or in the presence of both compounds. Both L-arginine and SOD produced a partial improvement of the ACh-induced vasodilatatory responses, but the effects of these agents were not additive. In this group of animals, SOD also induced a partial recovery of the L-NAME-evoked vasoconstrictions. In non-diabetic and untreated diabetic rats, the plasma levels of NO derivatives and arginine were measured. No significant differences were obtained in the amount of nitrites plus nitrates, while plasma levels of arginine were markedly reduced in the untreated diabetic animals. The results indicate that the endothelial dysfunction associated to diabetes is closely related to the level of metabolic control of the disease. Therefore, it is possible to establish a threshold for developing endothelium impairment from percentages of HbA1c higher than 7.5%. As the responses to the NO synthase blocker L-NAME were analogously impaired, it is reasonable to suggest that diabetic endothelial dysfunction is related to the interference with mechanisms linked both to stimulated and basal production of NO. We suggest that this interference is partially due to a deficit in the substrate availability for NO and to an increas...

Genetics of resistance to Tetranychus urticae Koch and of glandular trichomes of Lycopersicon pimpinellifolium accession TO-937 in a cross between susceptible L. esculentum Mill. `Moneymaker' and resistant TO-937 was studied in a greenhouse experiment. Parents, F1, F2, and two BC1 generations, interspersed with susceptible tomato plants to avoid negative interplot interference, were artificially infested. Mite susceptibility was evaluated by a rating based on plant capacity to support mite reproduction. TO-937, BC1 to TO-937, and F1 were resistant, `Moneymaker' susceptible, and the F2 and the BC1 to `Moneymaker' segregated. Resistance was controlled by a single dominant major locus, but modulated by unknown minor loci. TO-937 presented type IV glandular trichomes, their presence governed by two dominant unlinked loci. Type IV trichome density correlated to resistance; however, a causal relationship between type IV trichomes and mite resistance could not be definitively established. The relatively simple inheritance mode will favor successful introgression of resistance into commercial tomatoes from the close relative L. pimpinellifolium.

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The high prevalence of falls and the enormous impact they have on the elderly population is a cause for concern. We aimed to develop a walking-monitor gait pattern (G-STRIDE) for older adults based on a 6-axis inertial measurement (IMU) with the application of pedestrian dead reckoning algorithms and tested its structural and clinical validity. A cross-sectional case–control study was conducted with 21 participants (11 fallers and 10 non-fallers). We measured gait using an IMU attached to the foot while participants walked around different grounds (indoor flooring, outdoor floor, asphalt, etc.). The G-STRIDE consisted of a portable inertial device that monitored the gait pattern and a mobile app for telematic clinical analysis. G-STRIDE made it possible to measure gait parameters under normal living conditions when walking without assessing the patient in the outpatient clinic. Moreover, we verified concurrent validity with convectional outcome measures using intraclass correlation coefficients (ICCs) and analyzed the differences between participants. G-STRIDE showed high estimation accuracy for the walking speed of the elderly and good concurrent validity compared to conventional measures (ICC = 0.69; p < 0.000). In conclusion, the developed inertial-based G-STRIDE can accurately classify older people with risk to fall with a significance as high as using traditional but more subjective clinical methods (gait speed, Timed Up and Go Test).

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In patients with diabetes type 1, glycaemic control determines the functioning of the NO system by a reversible mechanism involving superoxide anions. This finding provides an explanation of the relationship between glycaemic control and vascular complications in diabetes.

Objectives to determine the safety and effect of intravenous iron sucrose on functional outcomes, delirium, nosocomial infections and transfusion requirements in older patients with hip fracture. Design single-centre randomised, double-blind, placebo-controlled clinical trial. Setting and participants orthogeriatric share care service at an academic tertiary care hospital. A total of 253 patients were recruited: 126 patients were assigned to intravenous iron and 127 to placebo. Methods on days 1, 3 and 5 after admission, the iron group received 200 mg Venofer® (iron sucrose) in 100 ml saline and the placebo group 100 ml saline. The primary outcome was absolute functional gain, considered as Barthel index (BI) at discharge minus BI on admission. Secondary outcomes included incidence of postoperative delirium according to the confusion assessment method, proportion of patients recovering prior functional status at 3 months, postoperative transfusion requirements, haemoglobin at 3 months, incidence of nosocomial infections and safety. Results the median participant age was 87 (interquartile range, 82.5–91.5) years. Most patients were female (72.7%), and the median previous BI was 81(59–95). No significant effect of intravenous iron was observed for the primary outcome: the median AFG score was 17.1 points (4.8–23.3) in the intravenous iron group and 16 points (6–26) in the placebo group (P = 0.369). No significant treatment effects were observed for other functional outcomes or secondary end points. Conclusion while we found no impact of intravenous iron sucrose on functional recovery, incidence of postoperative delirium, transfusion requirements, haemoglobin at 3 months, mortality and nosocomial infections rates in older patients with hip fracture, we did find that the intervention was safe.