Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.

BACKGROUND: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation. METHODS: We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. RESULTS: The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03). CONCLUSIONS: Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.     

The effect of combined Angiotensin-converting enzyme inhibition and calcium antagonism on allograft coronary vasculopathy validated by intravascular ultrasound.

BACKGROUND: Hypertension is a potential risk factor for allograft coronary vasculopathy. We evaluated the efficacy of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists, and their combined use, on the development of coronary vasculopathy in hypertensive heart transplant recipients. METHODS: Eighty-two heart transplant recipients underwent serial intravascular ultrasound (IVUS) analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for the development of coronary vasculopathy. Patients were divided into 4 groups. Nineteen normotensive recipients received no treatment, control (Group A). Hypertensive patients were treated with either ACE inhibitors (Group B, n = 37), calcium antagonists (Group C, n = 16), or both (Group D, n = 10). RESULTS: We found a significant reduction in IVUS indices of coronary vasculopathy in heart transplant recipients who used a combination of an ACE inhibitor and a calcium antagonist compared with recipients who used either drug alone (p < 0.05). This synergistic efficacy was independent of the baseline indices evaluated in a multivariate regression analysis model and was noted despite comparable mean arterial pressure among the 3 hypertensive groups at 1 year, thus suggesting the presence of a synergistic anti-proliferative effect beyond the anti-hypertensive efficacy. CONCLUSIONS: The combined use of an ACE inhibitor and a calcium antagonist is more effective than the individual use of either drug alone on the development of coronary vasculopathy in cardiac transplant recipients. Large randomized clinical trials are warranted to evaluate such a synergistic efficacy.     

Resection of clinically localized segments of painful retinaculum in the treatment of selected patients with anterior knee pain

We reviewed the long-term results of 25 patients who had localized soft tissue resections for refractory anterior retinacular knee pain. Patients completed visual analog scales to determine their activity and pain level changes, subjective assessment of their results, and whether they would have the surgery again under the same circumstances. Five of the 25 patients (20%) had had no knee surgery before the soft tissue excision, with the rest having had an average of two prior operations (range, 1 to 6). Subjectively, 22 patients (88%) noted moderate-to-substantial improvement after surgery; 3 patients (12%) declared no long-term benefit. All 25 patients stated that they would repeat the surgery under the same circumstances. Five patients (20%) noted a decrease in their results over time, but only two patients (8%) decreased their job level after surgery because of their knee pain. The average activity level dropped 60% after knee symptoms developed and increased 40% after surgery. Pain levels decreased 50% after surgery. The patients with the best overall results had lesions that were in the medial, inferomedial, or inferolateral retinaculum. The histologic results of the specimens included fibrosis, vascular proliferation, and small nerves with decreased myelin (neuromata). Our results show that specific soft tissue excision of painful tissue can often lead to successful clinical outcomes.     

Compensatory enlargement of human coronary arteries during progression of atherosclerosis is unrelated to atheroma burden: serial intravascular ultrasound observations from the REVERSAL trial.

AIMS: On the basis of the evidence from autopsy studies, it is accepted that compensatory enlargement (remodelling) of coronary arteries during progression of atherosclerosis diminishes once atheroma burden (cross-sectional area stenosis) reaches approximately 40%. Our aim was to evaluate whether atheroma burden is a limiting factor for coronary arterial remodelling using in vivo serial intravascular ultrasound (IVUS). METHODS AND RESULTS: From the cohort of the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we identified 210 focal coronary lesions at baseline IVUS. Of these, 128 lesions that had an increase in atheroma area at the 18-month follow-up IVUS were included in the analysis. Lesions were matched at baseline and follow-up. The increase in external elastic membrane (EEM) area for each mm(2) increase in atheroma area was not significantly different in lesions with <40 and >or=40% atheroma burden at baseline (1.62 vs. 1.28 mm(2), P=0.30). There were no correlations between atheroma burden at baseline and change in EEM (r=0.02, P=0.86) or change in lumen (r=0.04, P=0.64) areas. CONCLUSION: Assessment of coronary arterial remodelling by serial IVUS revealed that compensatory remodelling is not limited by atheroma burden. Atheroma burden is not a determinant of arterial enlargement during the progression of atherosclerosis.     

Characteristics of atherosclerotic plaque distribution in coronary artery bifurcations: an intravascular ultrasound analysis

OBJECTIVE: Vessel bifurcations are prone to atherosclerotic plaque accumulation. Using volumetric intravascular ultrasound analysis, we investigated atheroma distribution at human coronary bifurcations in vivo. METHODS: We analyzed plaque distribution in 49 left anterior descending coronary artery-diagonal and 20 left circumflex coronary artery-obtuse marginal bifurcations with <50% angiographic stenosis. Cross-sections were analyzed at 1 mm intervals in segments 5 mm proximal and distal from the bifurcation. Planimetry of the lumen and external elastic membrane (EEM) was performed and plaque thickness measured at four different points relative to the branch: 0 degrees, 90 degrees, 180 degrees and 270 degrees. EEM, lumen and plaque volume and percentage plaque burden (plaque volume/EEM volume) were calculated in the proximal and distal segments. The side-branch take-off angle was analyzed in the cross-sectional images. RESULTS: Volumetric analysis showed that EEM, lumen and plaque were larger (P<0.001) in proximal segments than distal segments, whereas percent plaque burden was similar in these segments. Plaque accumulated on the opposite wall to the flow divider. Plaque distribution tended to be more eccentric in distal segments (P=0.05) compared to proximal segments. In 26 of 69 lesions, an asymmetric side-branch take-off was found and was associated with asymmetric plaque distribution compared to those lesions that had a symmetric side-branch take-off (P<0.01). CONCLUSION: We found characteristic patterns of plaque distribution at coronary bifurcations. Proximal segments demonstrated larger plaque volume than distal segments, despite similar percentages of plaque burden. Plaque volume accumulated opposite to the flow divider, especially in distal segments. The side-branch take-off angle in the cross-sectional plane influenced the plaque distribution in bifurcation lesions.     

Isoflavone Genistein Induces Fluid Secretion and Morphological Changes in the Uteri of Post-Pubertal Rats

A reported increase in the incidence of infertility following high genistein intake could be related to alteration in the normal fluid volume and morphology of the uterus in adult female. In view of this, we investigated the effect of this compound on fluid secretion, fluid volume and morphology of the uterus in post-pubertal rats. Methods: Ovariectomised SD rats were treated with 17-β oestradiol (E) (0.8 X 10^-4 mg/kg/day) and genistein (0.5, 5, 10, 25, 50 and 100 mg/kg/day) for three days. Following drug treatment, in-vivo uterine perfusion was performed and the rate of fluid secretion and the volume of fluid in the uterus were determined via changes in weight (μl/min) and F-dextran concentration of the perfusate respectively. The animals were then sacrificed and the uteri were removed for weight determination, morphological analyses and proliferative cell nuclear antigen (PCNA) expression analyses by Western blotting. Results: Subcutaneous genistein treatment resulted in a dose-dependent increase in fluid secretion rate, fluid volume and uterine wet weight. Treatment with 100 mg/kg/day genistein resulted in a remarkable increase in the rate of uterine fluid secretion, the volume of the uterine luminal fluid as well as the circumference of the uterine and uterine glandular lumen suggesting an excessive fluid accumulation. Meanwhile, there were evidence of glandular hyperplasia and an increase in the expression of PCNA following treatment with 50 and 100 mg/kg/day genistein. Conclusion: High genistein intake could potentially cause adverse effects on the uterus by inducing excessive fluid secretion and accumulation as well as hyperplasia.     

Effects of Al-dopant at Ni or Co sites in LiNi0.6Co0.3Ti0.1O2 on interlayer slabs (Li–O) and intralayer slabs (TM–O) and their influence on the electrochemical performance of cathode materials

In order to satisfy the energy demands of the electromobility market, further improvements in cathode materials are receiving much attention, especially high energy density cathode materials for Li-ion batteries (LIBs). In this work, the self-propagating combustion (SPC) method is use to synthesise undoped LiNi_0.6Co_0.3Ti_0.1O₂ (LNCT), novel nano-sized Al-doped LiNi_0.6Co_0.3−xAl_xTi_0.1O₂ (LCA) and LiNi_0.6−xCo_0.3Al_xTi_0.1O₂ (LNA) (x = 0.01) cathode materials. LNCT, LCA and LNA were annealed at 700 °C for 24 h. Following the synthesis, the phase, chemical structure and purity of the materials were analysed using X-ray diffraction (XRD). Based on the XRD results, all materials exhibit a single-phase structure with rhombohedral layered structure. Based on the HRTEM and EDX results, all samples exhibit polyhedral-like shapes, while the Al-doped samples display smaller crystallite sizes compared to the undoped sample. As for the electrochemical performances, the initially discharged capacity of LCA (238.6 mA h g⁻¹) is higher than that of LNA (214.7 mA h g⁻¹) and LNCT (150.5 mA h g⁻¹). However, LNA has a lower loss of capacity after the 50^th cycle compared to the LCA sample, which makes it a more excellent candidate for electrochemical applications. The main reason for the excellent electrochemical behaviour of LNA is due to lower cation mixing. Furthermore, Rietveld refinements reveal that the LNA sample has a longer atomic distance of Li–O and shorter TM–O in the cathode structure, which makes Li⁺ ion diffusion more efficient, leading to excellent electrochemical performance. These findings further proved the potential of the novel nano cathode material of LiNi_0.6−xCo_0.3Al_xTi_0.1O₂ (LNA) to replace the existing commercialized cathode materials for rechargeable Li-ion batteries.

Al substitute into Ni site increase Li–O and reduce M–O atomic distance lead to excellent cycleability with high energy density.