PCSK9 and inflammatory biomarkers in the early post kidney transplantation period.

OBJECTIVE:   Various biomarkers have been studied in the early post-kidney transplantation (post-KTx) period in order to identify potential therapeutic targets for improving long-term graft survival. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a biomarker that has recently gained interest in cardiovascular disease but its role still remains to be defined post-KTx. PATIENTS AND METHODS: We prospectively evaluated the levels of PCSK9, interleukin (IL)-6, WBC and C-reactive protein in seventy-three hemodialysis patients undergoing KTx, at 3 time-points; pre-transplantation (day 0) and at 1 and 6-months post-KTx. All data were also analyzed according to donor-type (living or deceased) and compared with hemodialysis patients on transplant waiting list. RESULTS: At Day 0 there was no difference in WBC, CRP, IL-6 and PCSK9 levels between patients scheduled for transplantation and those who remained on hemodialysis. In transplanted patients WBC, CRP and IL-6 levels were significantly reduced early post-KTx [logIL-6 Day 0: 0.68 (0.33, 0.85) vs. 1-month: 0.57 (0.37, 0.75) vs. 6-months: 0.50 (0.32, 0.69) pg/ml, p=0.01], while PCSK9 levels were significantly increased (Day 0: 199.8±63.0 vs. 1-month: 276.2±79.4 vs. 6-months: 245.9±62.5 ng/ml, p<0.001). In contrast, no change of WBC, CRP, IL-6 and PCSK9 levels was observed in hemodialysis patients on follow-up (p=NS for all). Between living-donor and deceased-donor recipients, analysis showed reduced CRP and increased PCSK9 levels in both groups (p<0.05 for all), while IL-6 levels were reduced in living-donor and increased in deceased-donor recipients 1-month post-KTx. PCSK9 levels were not correlated with renal function, delayed graft function, rejection episodes or inflammatory biomarkers. CONCLUSIONS: PCSK9 levels were increased post-KTx independently from renal function and inflammatory biomarkers, in both living and deceased-donor recipients.

Ultra-compact III‒V-on-Si photonic crystal memory for flip-flop operation at 5 Gb/s.

We report on a photonic crystal (PhC) nanolaser based on the heterogeneous integration of a III-V PhC nanocavity on SOI, configured to operate as a Set-Reset Flip-Flop (SR-FF). The active layer is a nanobeam cavity made of a 650 nm × 285 nm InP-based wire waveguide evanescently coupled to 500 nm × 220 nm SOI wire waveguides, demonstrating a record-low footprint of only 6.2 µm2. Injection locking enables optical bistability allowing for memory operation with only 6.4 fJ/bit switching energies and <50 ps response times. Bit-level SR-FF memory operation was evaluated at 5 Gb/s with PRBS-resembling data patterns, revealing error free operation with a negative power penalty.

Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension.

BACKGROUND AND AIMS: Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension. METHODS AND RESULTS: In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p < 0.0001), exhibited higher ACR (36.3 ± 51.6 vs. 17.2 ± 1.2 mg g(-1), p < 0.0001) and c-f PWV (8.3 ± 1.5 vs. 7.8 ± 1.1 m s(-1), p = 0.003), independently of confounding factors. Multiple regression analyses revealed that age, male sex, 24-h systolic BP and sRAGE were the 'independent correlates' of ACR (R(2) = 0.493, p < 0.0001), while age, 24-h systolic BP and sRAGE were the 'independent correlates' of c-f PWV (R(2) = 0.428, p < 0.0001). CONCLUSION: In hypertensives, decreased sRAGE levels are accompanied by pronounced albuminuria and arterial stiffening. The association of sRAGE with ACR and c-f PWV suggests involvement of sRAGE in the progression of hypertensive vascular damage.

Acute systemic inflammation induced by influenza A (H1N1) vaccination causes a deterioration in endothelial function in HIV-infected patients.

OBJECTIVES: Vaccination of HIV-infected patients against the influenza A/H1N1 subtype was proposed as a mandatory precautionary measure during the 2009 pandemic. The immediate cardiovascular effects of the novel vaccine have been largely unexplored. We investigated the impact of vaccination on indices of endothelial function in a cohort of HIV-infected patients. METHODS: We included 24 HIV-infected patients in a study with a randomized, sham procedure-controlled design. A monovalent, adjuvanted vaccine against influenza A/H1N1 was used in the vaccine arm (n=16); patients in the control group (n=8) were subjected to a sham procedure. Endothelial function, as assessed by flow-mediated dilatation (FMD), and inflammatory markers were assessed prior to and 8 and 48 h post vaccination. RESULTS: FMD deteriorated following vaccination (baseline, 6.5 ± 1.1%; 8 h, 1.1 ± 1.5%; 48 h, 2.0 ± 1.4%; P=0.04). The white blood cell count increased at 8 h and remained elevated at 48 h. Soluble intercellular adhesion molecule-1 levels decreased after vaccination; the maximum decrease was noted at 48 h. Conversely, the sham procedure did not induce changes in endothelial function or inflammatory markers, apart from a reduction in the white blood cell count at 48 h. CONCLUSIONS: Acute systemic inflammation induced by vaccination against the influenza A/H1N1 virus resulted in a deterioration in endothelial function in HIV-infected patients, and this effect was sustained for at least 48 h. Our findings may have important implications in view of the high cardiovascular risk that HIV infection carries. The effect of the novel vaccine on endothelial function should be weighed against the immunological protection that it confers.

Exercise duration as a determinant of vascular function and antioxidant balance in patients with coronary artery disease.

BACKGROUND: Exercise improves the clinical outcome of patients with coronary artery disease (CAD); however, the ideal exercise duration for each patient remains unclear. OBJECTIVE: To investigate the effects of exercise duration on arterial elastic properties and antioxidant/pro-oxidant mechanisms in patients with CAD. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Sixty male patients with CAD were randomised into two groups, and underwent exercise for 30 min or 60 min in a crossover design with 2 weeks' wash-out period. In all participants aortic and radial blood pressures (BP) and arterial elastic properties (augmentation index (AIx)/pulse wave velocity (PWV)) were determined at baseline and 24 h after exercise. Plasma malonyldialdehyde (MDA) and superoxide dismutase (SOD)1 and SOD2 levels were also measured. RESULTS: Exercise had no effect on aortic and radial BP (p=NS for all). Walking for 30 min improved AIx (from 33.79 ± 0.91% to 31.73 ± 0.86%, p<0.001) and PWV (from 9.26 ± 0.95 m/s to 9.06 ± 0.21 m/s, p<0.001), while exercise for 60 min had adverse effects on vascular stiffness (for AIx: from 33.37 ± 0.93% to 33.73 ± 1.05%, p=NS and for PWV: from 9.25 ± 0.19 m/s to 9.37 ± 0.21 m/s, p < 0.05 mainly in older patients). Exercise for 60 min was associated with a significant 20% increase in MDA levels (p<0.05). Exercise had no effects on SOD1 levels, however it significantly increased SOD2 levels after 30 min (from 2.26 ± 0.22 ng/mL to 2.36 ± 0.18 ng/mL, p < 0.05) but not after 60 min (p=NS). Conclusion Shorter exercise duration was associated with favourable antioxidant and vascular effects, while longer exercise blunted these beneficial effects and was accompanied by adverse effects on vascular function, mainly in older coronary patients. Further studies are required to explore the hypothesis that a more individualised approach to the selection of the appropriate exercise programme should be considered for patients with CAD.

Divergent anti-inflammatory effects of different oil acute consumption on healthy individuals.

BACKGROUND/OBJECTIVES: Inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and tumor necrosis factor-α (TNF-α), are implicated in atherogenesis. In addition, several types of oil as part of different types of diet are associated with the initiation of atherosclerosis and consequently with the risk of cardiovascular disease. However, the exact role of oil consumption on vascular inflammation remains unknown. In this parallel study, we assessed the acute effects of extra virgin olive oil, soy oil, corn oil and cod liver oil on circulating soluble(s) forms of adhesion molecules and TNF-α. SUBJECTS/METHODS: In all, 67 healthy volunteers were randomized to receive 50 ml of oil. Soluble forms of VCAM-1, ICAM-1 and TNF-α were measured by enzyme-linked immunosorbent assay at baseline and at 3 h post oil consumption. RESULTS: All types of oil had no significant effect on soluble VCAM-1 levels (P=nonsignificant (NS) for all). On the contrary, all oil types decreased ICAM-1 levels (P<0.01). Olive oil (P<0.05), soy oil and cod liver oil (P<0.01 for both) reduced TNF-α levels significantly, in contrast to corn oil, which induced a nonsignificant decrease (P=NS). Moreover, there was a significant correlation between the absolute change in ICAM-1 and TNF-α levels (ρ=0.379, P<0.05), but not between the absolute changes in VCAM-1 and TNF-α levels (ρ=0.019, P=NS). CONCLUSIONS: Acute consumption of all types of oil decreased significantly ICAM-1 levels. In addition, olive oil, soy oil and cod liver oil decreased significantly TNF-α levels. Moreover, the absolute change in TNF-α levels was correlated with the absolute change in ICAM-1 levels. These findings indicate that acute consumption of specific types of oil is associated with specific significant anti-inflammatory effects.

Independent association of circulating resistin with glomerular filtration rate in the early stages of essential hypertension.

Resistin, a newly discovered protein, promotes endothelial dysfunction and proinflammatory activation, contributing to subclinical atherosclerosis in different clinical settings. In this study we sought to investigate the relationship of increased resistin levels with estimated glomerular filtration rate (eGFR), the most established marker of kidney impairment, in hypertensive subjects. Our population consisted of 132 untreated non-diabetic subjects with stage I-II essential hypertension (49 males, mean age=54 years, office blood pressure (BP)=159/100 mm Hg). In all patients eGFR was assessed by the Modification in Renal Disease equation and venous blood sampling was performed for estimation of resistin concentrations. The distribution of resistin was split by the median (4.63 ng ml(-1)) and accordingly subjects were stratified into those with high and low values. Hypertensive patients with high (n=66) compared to those with low resistin (n=66) exhibited lower eGFR values (77.1+/-9.4 vs 89.1+/-12.2 ml min(-1) per 1.73m(2), P<0.0001), even after adjustment for established confounders. In the total population, resistin was associated with 24-h systolic BP (r=0.244, P<0.05), serum creatinine (r=0.311, P=0.007) and eGFR (r=-0.519, P<0.0001). Multiple regression analysis revealed that age (b=0.379, P=0.01), body mass index (b=0.158, P=0.022), 24-h systolic BP (b=0.284, P=0.006) and resistin (b=0.429, P<0.0001) were independent predictors of eGFR (R(2)=0.436, P<0.0001). In essential hypertensive subjects, higher resistin levels are associated with renal function impairment, as reflected by decreased eGFR. Moreover, the independent association of resistin with eGFR suggests involvement of resistin in the progression of kidney damage in the early stages of hypertension.

Locus control region function and heterochromatin-induced position effect variegation.

Human CD2 locus control region (LCR) sequences are shown here to be essential for establishing an open chromatin configuration. Transgenic mice carrying an hCD2 mini-gene attached only to the 3' CD2 transcriptional enhancer exhibited variegated expression when the transgene integrated in the centromere. In contrast, mice carrying a transgene with additional 3' sequences showed no variegation even when the latter integrated in centromeric positions. This result suggests that LCRs operate by ensuring an open chromatin configuration and that a short region, with no enhancer activity, functions in the establishment, maintenance, or both of an open chromatin domain.

Modeling of the index change in K(+)-Na(+) ion-exchanged glass.

We have measured the surface index change and birefringence in K(+)-Na(+) ion-exchanged waveguides and compared the results with theory. The contribution to the index change caused by the polarizability/volume changes (Deltan(p)) is calculated using two theoretical models which use empirical relations based on the glass composition. In both cases, we encounter large discrepancies between the predicted and measured values which are attributed to the inherent deficiency in the models, which assume free expansion of the glass in calculating the volume changes. Recognizing that the net volume change is much smaller, we accurately measure its value and show that both models can be used to predict Deltan(p) with the same accuracy, provided that the correct volume change is used. We show that the limitation in accuracy is dictated by measurement errors and uncertainties in the values of the ionic radii and polarizabilities. We also present a unique and systematic method for determining the compressive stress generated in the glass resulting from ion exchange.