Altered levels of blood proteins in Alzheimer\u27s disease longitudinal study: Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort

Introduction A blood-based biomarker panel to identify individuals with preclinical Alzheimer\u27s disease (AD) would be an inexpensive and accessible first step for routine testing. Methods We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort. Results Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P =.0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P =.0008). Discussion These data suggest that apoJ may have potential in the context of use (COU) of AD diagnostics, I-309 may be specifically useful in the COU of identifying individuals at greatest risk for progressing toward AD. This work takes an initial step toward identifying blood biomarkers with potential use in the diagnosis and prognosis of AD and should be validated across other prospective cohorts. © 2017 The Author

Correlation between lipid abnormalities and immunosuppressive therapy in renal transplant recipients with stable renal function

Background: Hyperlipidemia following successful renal transplantation is a frequent and persistent complication. Several immunosuppressive agents including cyclosporine A (CyA), corticosteroids, and tacrolimus appear to have a significant pathogenetic role. The aim of this study is to investigate the differential effects of different immunosuppressive agents on lipids in renal transplant patients. Methods: Two groups of renal transplant recipients, each treated with a different combination of immunosuppressive agents, were studied: Group A (n = 13), cyclosporine A, mycophenolate mofetil (MMF), steroids, and basiliximab; Group B (n = 13), tacrolimus, MMF, steroids, and daclizumab). Plasma lipids [cholesterol (CHOL), low-density lipoprotein (LDL)-CHOL, high-density lipoprotein (HDL)- CHOL, and triglycerides (TG)] were examined before transplantation and 1 and 6 months posttransplantation. Results: The patients treated with cyclosporine A-MMF showed a significant increase in mean cholesterol and mean LDL-cholesterol values at the 1-month posttransplantation follow-up compared with pretransplant levels (CHOL: 208.9 ± 47.4 vs. 268.7 ± 42.2 mg/dl, P = 0.004; LDL: 118.4 ± 49.9 vs. 198.7 ± 40.7 mg/dl, P = 0.002; pretransplant vs. 1 month, respectively). At 6 months, LDL-cholesterol levels were significantly elevated compared with pretransplant levels (LDL: 118.4 ± 49.9 vs. 148.3 ± 48.5 mg/dl, P = 0.034), whereas there was no significant change in the cholesterol level during the same period. In cyclosporine A-MMF-treated patients, plasma triglyceride levels were reduced at the 1- and 6-month follow-up (TG: 293.9 ± 59.2 vs. 182.9 ± 48.7 mg/dl, P = 0.03; 293.9 ± 59.2 vs. 178.6 ± 74.2 mg/dl, P = 0.023; pretransplant vs. 1 and 6 months, respectively). Patients receiving combined therapy with tacrolimus-MMF showed no significant changes in LDL-CHOL levels during the trial. Cholesterol levels at 6 months posttransplantation were significantly lower than the pretransplant measurements (CHOL: 182.9 ± 44.4 vs. 162.3 ± 37.2 mg/dl, P = 0.024; pretransplant vs. 6 months ). A significant reduction in triglyceride level was documented at the 1-month follow-up followed by a subsequent decrease within 6 months (TG: 228.5 ± 61.6 vs. 147.6 ± 51.5 mg/dl, P = 0.005; TG: 228.5 ± 61.6 vs. 130.4 ± 54.7 mg/dl, P = 0.011; pretransplant vs. 1 and 6 months, respectively). Conclusions: In posttransplant patients with stable renal function cyclosporine therapy is associated with increased cholesterol and LDL-cholesterol levels. Hyperlipidemia is less pronounced in patients given tacrolimus. Tacrolimus appears to an immunosuppressant agent with fewer and less severe adverse effects on lipid metabolism. © Springer Science+Business Media B.V. 2008

Mechanical behavior of colonic anastomosis in experimental settings as a measure of wound repair and tissue integrity

Aim: To determine the mechanical properties of anastomotic colonic tissue in experimental settings and therefore give a measure of wound healing. Methods: Thirty-six male Wistar rats were used as experimental models of anastomotic tissue integrity. On the 5th post-operative day, the tensile strength was measured by application of an axial force, providing a quantitative measure of anastornotic dehiscence and leakage. Results: Diagrams of the load as a function of the time [P = P (t)] and of the displacement also as a function of time [Δs = Δs (t)] were recorded for each test, permitting the design of the load versus the displacement diagram and thus providing significant data about the critical values of anastornotic failure. Quantitative data were obtained concerning the anastornotic strength of both control specimens (healthy rats), as well as specimens from non-healthy rats for comparison. Conclusion: This experimental model provides an excellent method of measuring anastomotic strength. Despite the relative small number of specimens used, this method provides an accurate way of measuring wound repair. More experimental measurements need to be performed to correlate emerging tensile strength values to anastomotic failure. © 2006 The WJG Press. All rights reserved

The effects of hypothyroidism on the mechanical properties and histomorphological structure of the thoracic aorta

This experimental study investigates the effects of hypothyroidism on the descending thoracic aorta. Hypothyroidism was induced in 20 male Wistar rats by administering 0.05% of 6-n propyl 2-thiouracil (PTU) in their drinking water for 8 weeks. Euthyroid rats were used as controls. Animals were sacrificed and longitudinal strips of the descending aorta were subjected to various preselected levels of stress in a uniaxial tensile-testing device. Analysis of stress-strain, elastic modulus-strain curves disclosed significant differences between groups, indicative of stiffer aortas in hypothyroid animals at the upper physiologic and higher levels of pressure. Remodeling of the aortic wall of hypothyroid animals revealed significant histological changes. The thoracic aorta of hypothyroid rats compared with that of euthyroid ones became stiffer at high strains, including the upper physiologic range, loosing part of its distensibility. Hypothyroidism was also associated with diameter enlargement and substantial lengthening of the aorta

Effect of statins on serum apolipoprotein J and paraoxonase-1 levels in patients with ischemic heart disease undergoing coronary angiography

It has been proposed that apolipoprotein J (apo J) and paraoxonase-1 (PON1) correlate with the extent and severity of ischemic heart disease (IHD). This article compares apo J and PON1 serum concentrations, PON1 activity, and the apo J/PON1 ratio in 138 IHD patients (64 statins users and 74 statin nonusers) referred for angiography and possible percutaneous coronary intervention. The effect of statin treatment on apo J and PON1 concentrations, PON1 activity, and the degree of coronary artery stenosis were evaluated. In both groups, apo J levels were increased, whereas PON1 concentration and activity decreased. IHD patients on statins had significantly lower apo J concentration and higher PON1 concentration and activity. Patients on statins had less coronary artery stenosis. High apo J levels, low PON1 levels, low PON1 activity, and a high apo J/PON1 ratio were associated with IHD. Statin treatment reverses these changes, probably by multiple beneficial actions. © 2008 Sage Publications

Association between plasma levels and immunolocalization of cytokines in heart valve lesions: A possible target for treatment?

Objective: To compare the distribution of pro-inflammatory cytokines in heart valve lesions with their plasma levels. Methods: Plasma leveLs of TNF-α and IL-10 were determined in 70 patients with heart valve lesions. TNF-(α and IL-6 levels were also quantified in tissue specimens obtained from these patients after valve replacement. Results: Plasma concentrations of TNF-α and the extent of calcium deposits were significantly higher in patients with aortic valve stenosis compared with individuals with mitral valve stenosis. A direct relationship was demonstrated between TNF-α blood and tissue levels. There was an increase in TNF-α and IL-6 tissue immunoreactivity with the progression of heart valve disease from mild to advanced inflammation. The increased accumulation of calcium deposits in damaged heart valves correlated with plasma TNF-α and IL-10 levels. Conclusions: The association between plasma and tissue sample cytokine concentrations suggests that plasma cytokine levels reflect the extent and severity of valvular lesions. Statins may attenuate progressive calcific valve stenosis. Statins also affect TNF-α and IL-10 plasma levels. These associations may help not only predict the progression but also attenuate the deterioration of valvular lesions. Verification of these results in larger scale studies is required before definite conclusions can be drawn. © 2008 Informa UK Ltd