Plasma H(2)S levels are reduced in overweight participants and patients with type 2 diabetes. Increasing adiposity is a major determinant of plasma H(2)S levels.

Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwanncell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application.

Aims/hypothesis Adults with type 2 diabetes mellitus have impaired microvascular function. It has been hypothesised that microvascular function may be restored through regular exercise. The aim of this study was to investigate whether 6 months of regular aerobic exercise would improve microvascular function in adults with type 2 diabetes. Materials and methods Fifty-nine patients with type 2 diabetes (32 males, age 62.9±7.6 years, HbA 1c 6.8±0.9%) were randomised to either a 6-month aerobic exercise programme (30 min, three times a week, 70-80% of maximal heart rate) or a 'standard care' control group. Before and after the intervention period, microvascular function was assessed as the maximum skin hyperaemia to local heating and endothelial and non-endothelial responsiveness following the iontophoretic application of acetylcholine and sodium nitroprusside. Maximal oxygen uptake, as an index of aerobic fitness, was assessed using a maximal exercise test.

There are reports of abnormal pulmonary oxygen uptake (Vo(2)) and deoxygenated hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr of age with disease durations of <5 yr. We examined the Vo(2) and muscle [HHb] kinetics in 12 older T2D patients with extended disease durations (age: 65 ± 5 years; disease duration 9.3 ± 3.8 years) and 12 healthy age-matched control participants (CON; age: 62 ± 6 years). Maximal oxygen uptake (Vo(2max)) was determined via a ramp incremental cycle test and Vo(2) and [HHb] kinetics were determined during subsequent submaximal step exercise. The Vo(2max) was significantly reduced (P < 0.05) in individuals with T2D compared with CON (1.98 ± 0.43 vs. 2.72 ± 0.40 l/min, respectively) but, surprisingly, Vo(2) kinetics was not different in T2D compared with CON (phase II time constant: 43 ± 17 vs. 41 ± 12 s, respectively). The Δ[HHb]/ΔVo(2) was significantly higher in T2D compared with CON (235 ± 99 vs. 135 ± 33 AU·l(-1)·min(-1); P < 0.05). Despite a lower Vo(2max), Vo(2) kinetics is not different in older T2D compared with healthy age-matched control participants. The elevated Δ[HHb]/ΔVo(2) in T2D individuals possibly indicates a compromised muscle blood flow that mandates a greater O(2) extraction during exercise. Longer disease duration may result in adaptations in the O(2) extraction capabilities of individuals with T2D, thereby mitigating the expected age-related slowing of Vo(2) kinetics.

In conclusion, we were unable to demonstrate any improvement in microvascular endothelial function in non-hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid-lowering therapy.

CapiFlow (CF), a new fully computerized system for the measurement of capillary blood velocity (CBV) was compared to manual frame by frame analysis (a) in a model system, and (b) in finger nailfold capillaries recorded on video tape. In the model the overall agreement between the two methods was very good (figure 1), with no significant differences being noted between the two sets of results and the calculated velocities. However, when comparing frame by frame and CapiFlow directly, CapiFlow read on average 4.50 +/- 5.21% higher than frame by frame analysis (figure 2). The in vivo results obtained by the two methods showed similar dynamic changes although some differences between the overall mean CBVs were noted (capillary 1, manual 0.13 +/- 0.59 mm s-1 versus CF 0.12 +/- 0.02 mm s-1, (mean +/- SD), p = 0.354; capillary 2, manual 0.66 +/- 0.23 mm s-1 versus CF 0.47 +/- 0.09 mm s-1, p < 0.001; capillary 3, manual 2.53 +/- 0.73 mm s-1 versus CF 2.35 +/- 0.34 mm s-1, p = 0.062). Further analyses established the optimum settings of delta limit and cross correlation. Investigations into the effects of changes in window size, window distance or video settings on CBV results obtained by CapiFlow, indicated that only settings radically different from the optimum had a significant effect on the results obtained.

Aims/hypothesis: Insulin resistance is associated with abnormal microvascular function. Treatment with insulin sensitisers may provoke oedema, suggesting microvascular effects. The mechanisms underlying the peripheral oedema observed during glucose-lowering treatment with thiazolidinediones are unclear. Therefore we examined the effect of pioglitazone on microvascular variables involved in oedema formation. Methods:: Subjects (40-80 years) with type 2 diabetes and on insulin were randomised to 9 weeks of pioglitazone therapy (30 mg/day; n=14) or placebo (n=15). The following assessments were performed at baseline and 9 weeks: microvascular filtration capacity; isovolumetric venous pressure; capillary pressure; capillary recruitment following venous or arterial occlusion; postural vasoconstriction; and maximum blood flow. A number of haematological variables were also measured including vascular endothelium growth factor (VEGF), IL-6 and C-reactive protein (CRP). Results: Pioglitazone did not significantly influence any microcirculatory variable as compared with placebo (analysis of covariance [ANCOVA] for microvascular filtration capacity for the two groups, p=0.26). Mean VEGF increased with pioglitazone (61.1 pg/ml), but not significantly more than placebo (9.76 pg/ml, p=0.94).HbA 1c levels and the inflammatory markers IL-6 and CRP decreased with pioglitazone compared with placebo (ANCOVA: p=0.009, p=0.001 and p=0.004, respectively). Conclusions/interpretation: Pioglitazone improved glycaemic control and inflammatory markers over 9 weeks but had no effect on microcirculatory variables associated with oedema or insulin resistance in type 2 diabetic patients treated with insulin.

The parameters derived from reservoir-excess pressure analysis have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM and whether they would predict cardiovascular events in individuals with T2DM. We studied 306 people with T2DM with cardiovascular disease (CVD; DMCVD, 70.4±7.8 years), 348 people with T2DM but without CVD (diabetes mellitus, 67.7±8.4 years), and 178 people without T2DM or CVD (control group [CTRL], 67.2±8.9 years). Reservoir-excess pressure analysis–derived parameters, including reservoir pressure integral, peak reservoir pressure, excess pressure integral, systolic rate constant, and diastolic rate constant, were obtained by radial artery tonometry. Reservoir pressure integral was lower in DMCVD diabetes mellitus and than CTRL. Peak reservoir pressure was lower, and excess pressure integral was greater in DMCVD diabetes mellitus than and CTRL. Systolic rate constant was lower in a stepwise manner among groups (DMCVD< diabetes mellitus <CTRL). Diastolic rate constant was greater in DMCVD than CTRL. In the subgroup of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9 noncardiovascular causes), and 108 cardiovascular events occurred during a 3-year follow-up period. Logistic regression analysis revealed that reservoir pressure integral (odds ratio, 0.59 [95% CI, 0.45–0.79]) and diastolic rate constant (odds ratio, 1.60 [95% CI, 1.25–2.06]) were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors (both P <0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered reservoir-excess pressure analysis–derived parameters are associated with T2DM. Furthermore, baseline values of reservoir pressure integral and diastolic rate constant independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM.