Estimation of Selected Minerals in Aortic Aneurysms-Impaired Ratio of Zinc to Lead May Predispose?

The objective of this study was to estimate the content of copper, zinc, selenium, cadmium, and lead in the tissue of patients with aortic aneurysms. Molar ratio of Cu/Zn and antioxidant micronutrients to toxic elements was also calculated. A total of 108 patients: 47 with abdominal aortic aneurysm (AAA), 61 patients with thoracic aortic aneurysm (TAA), and a control group of 20 abdominal aortic (AA) and 20 thoracic aortic (TA) wall samples from the deceased were studied. The concentrations of mineral components in the tissue samples were determined by the AAS method. The average concentration of Cu in the aortic wall of patients with TAA was significantly lower than in the aortic wall samples of healthy people. The mean concentration of Zn in the aortic wall of patients with AAA and TAA was significantly lower than in the control group samples. Cu/Zn ratio was significantly higher in AAA patients than in control group which indicates a greater role of oxidative stress and inflammatory process in this type of aneurysm. The concentration of Se was significantly decreased in TAA patients compared with the control group; in turn, the concentration of Pb was increased in this group of patients. We observed significantly lower Cu/Pb ratio in TAA patients than in control group, whereas Zn/Pb ratio was significantly lower comparing with control samples in both types of aneurysms. In the examined aneurysms, we have shown the differences in concentrations of mineral components compared with the control tissues. The Zn concentration was decreased in both AAA and TAA samples. Impaired ratio of Zn to Pb may predispose to aortic aneurysms.

The Relationship between the Concentration of Cathepsin A, D, and E and the Concentration of Copper and Zinc, and the Size of the Aneurysmal Enlargement in the Wall of the Abdominal Aortic Aneurysm.

BACKGROUND: Despite advances in diagnostics and treatment, aortic aneurysms are an important clinical problem, mainly due to the accompanying complications that may lead to direct loss of life, also the number of diagnosed and operated aneurysms is constantly increasing. The aim of this study is to determine the relationship between the concentration of lysosomal peptidases cathepsin A, D, and E in the wall of the abdominal aortic aneurysm and the concentration of copper and zinc, and the size of the aneurysm widening in the wall of the abdominal aortic aneurysm. METHODS: The study included 27 patients with abdominal aortic aneurysm from the Department of Vascular Surgery and Transplantation of the University Clinical Hospital in Bialystok. The research material was the wall of the abdominal aortic aneurysm collected intraoperatively. The control material consisted of fragments of the abdominal aorta obtained from organ donors for transplantation. The concentration of cathepsin A, D, and E was determined using enzyme-linked immunosorbent assays. Concentrations of copper and zinc were determined by flame atomic absorption spectrometry after prior mineralization of the samples. All patients were interviewed and asked about basic demographic data, comorbidities, and risk factors for cardiovascular disease to which they were exposed in the past. The statistical analysis was performed using Statistica 10 statistical package. Mann-Whitney U-tests were used and also Spearman's r correlation assuming a significance level of P < 0.05. RESULTS: The concentration of cathepsin A, D, and E was higher in the aortic wall altered by the aneurysm than in the wall of the control aorta (P < 0.05). The analysis of the data showed that there was a positive correlation between the concentration of cathepsin A and D and the width of the aneurysmal widening (r = 0.699 and 0.750, respectively). There was no correlation between cathepsin E concentration and aneurysm width. CONCLUSIONS: The higher contents of cathepsin A, D, and E in the wall of the aortic aneurysm than in the normal aortic wall, as well as a positive correlation between the concentration of cathepsin A and D and the width of the aneurysmal widening, allow to assume the participation of these enzymes in the pathogenesis of the aneurysm.

Desorption electrospray ionization-based imaging of interaction between vascular graft and human body.

The desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) is known as a fast and convenient MS-based method for lipid imaging in various biological materials. Here, we applied this technique to visualize lipid distribution in a vascular graft removed from a patient's body. This is a good example of the DESI system capabilities toward imaging of interaction between artificial material and living tissues. Detailed analysis allowed for visualization of the spatial distribution of selected lipids in this implanted, artificial material. Not only DESI-MSI allowed visualization of lipid distribution in the investigated material but also enabled identification of the detected molecular species using MS/MS. Here, this technique was successfully used to evaluate the saturation and spatial distribution of endogenous lipids in the artificial vascular graft. Unambiguous identification of the lipids was done with the aid of fragmentation procedure. We also showed that various lipids localize preferably in graft material or internal plaque existing inside the graft.

Basilic vein transposition in the forearm for secondary arteriovenous fistula.

Radiocephalic (RC) fistulae remain the first choice access for hemodialysis. The antecubital fossa is recommended as the next site. However, for some patients a basilic vein can be used to create an arteriovenous (av) fistula. We report a series of patients where the forearm basilic vein served as an alternative conduit for secondary procedures. Over an 8-year period, 30 patients who had a failed RC fistula underwent a basilic vein transposition. The immediate results were satisfactory. All fistulas were successfully cannulated. Cumulative patency was 93% after 1 year, 78% after 2 years, and 55% after 3 years. No ischemic or infectious complications were noted during the study period. The use of the forearm basilic vein to create a native av fistula appears to be a good alternative to procedures in the antecubital fossa or upper arm, thus preserving more proximal veins for future use.

Assessment of effectiveness of endovascular treatment of common and external iliac artery stenosis/occlusion using self-expanding Jaguar SM stents.

The goal of this work was to assess the effectiveness of endovascular treatment of common and external iliac artery stenosis/occlusion classified according to TASC using a self-expanding stent Jaguar SM. The study group included 95 patients (61 men and 34 women) who underwent treatment for stenosis or occlusion of lower limb arteries at the Department of Radiology of the University Hospital in Bialystok and the Diagnostic Radiology Department of the Central Clinical Hospital of the Ministry of Interior (MSWiA) in Warsaw between 2005 and 2007. All arterial lesions were of atherosclerotic etiology. The shortest stenotic fragment was 10 mm long and the longest occluded arterial fragment did not exceed 90 mm. Morphological classification of iliac artery lesions in treated patients was performed according to TASC II classification and included 10 patients with type A, 39 cases of type B, 36 with type C and 10 patients with type D lesions. Endovascular procedure failed to restore flow in five patients with TASC type D lesions, who were later referred for surgery. One patient suffered a complication - vessel perforation during predilatation, and had a stentgraft implanted. In 95% of patients stents were expanded using a balloon after implantation. Good results were achieved in practically all patients who underwent stent implantation. Patients were subjected to follow-up clinical and imaging evaluation during next 1-24 months. Success rate of the performed procedures as well as in a 30-day observation period was 100% in case of stenosis and 80% in case of vessel occlusion. A follow-up after 12 and 24 months showed patency of treated vessels in 84% and 76% of patients, respectively.

Effect of heavy metal cations on the activity of cathepsin D (in vitro study).

We studied the effect of heavy metal cations: Fe²âº, Cu²âº, Zn²âº, Cd²âº, Hg²âº, Pb²âº on the activity of cathepsin D in human aorta homogenate and blood serum. The concentration of cations was 1 mmol/l. Hemoglobin was the cathepsin D substrate. The activity of cathepsin D was determined at pH 3.5. Only Hg²âº cations inhibit the activity of cathepsin D. Cations Hg²âº damage lysosomes and release cathepsin D from these organelles.

Role of cathepsin A and cathepsin C in the regulation of glycosidase activity.

Increased tissue activity of cathepsin A and cathepsin C can be observed in many pathological conditions. It is associated with an enhanced degradation of glycosaminoglycans, proteoglycans, and glycoproteins, and results in their decreased tissue content. Cathepsin C releases the glycosidases from complexes formed with cathepsin A, and reinstates their activity. In this review a current state of knowledge is presented concerning the regulation of selected glycosidases activity by cathepsin A (EC 3.4.16.1) and C (EC 3.4.14.1).

Decreased serum level of IL-12 in the course of ischemia and reperfusion during abdominal aortic surgery.

Ischemic-reperfusion injury (IRI) is defined as tissue damage, organ dysfunction or failure developed in the course of inflammatory response following ischemia and reperfusion (IR). Abdominal aortic aneurysm (AAA) repair required IR of distal parts of the body carries a risk of organ injury and postoperative mortality of between 4% and 12%. The aim of this study was the evaluation of IL-12 serum level during AAA repair in relation to IR. Blood samples were taken before surgery (Preop), before aortic unclamping (Pre-X(off)), 90 min after unclamping (90 min-X(off)) and 24 h after surgery (Postop) from 37 AAA patients; and before surgery (Preop), at 90 min of surgery (90 min-surg), at 180 min of surgery (180 min-surg) and 24 h after operation (stop) from ten patients scheduled for elective surgery of lumbar discopathy (SC); and once from ten healthy controls. IL-12 was measured using the ELISA technique. Preoperative IL-12 was higher in AAA (0.21 pg/ml) and SC (0.31 pg/ml) patients than in controls (0.05 pg/ml). A significant decrease in IL-12 (0.09 pg/ml) was observed at 90 min-X(off) in comparison to the preoperative value in AAA but not in the SC group. 24 h after surgery, IL-12 levels were still low in the AAA group (0.13 pg/ml), and nonsignificantly surpassed the preoperative value in the SC group (0.36 pg/ml). We conclude that operative injury was associated with increased IL-12 levels, and IR with decreased IL-12 levels. Diminished IL-12 during AAA repair might be associated with a higher risk of postoperative complications, but this needs further evaluation.

Cathepsin A activity of a parietal thrombus of an abdominal aortic aneurysm.

We evaluated the cathepsin A activity of a parietal thrombus of an abdominal aortic aneurysm. We compared this activity to that of a retracted blood clot homogenate. Cathepsin A of aneurysm parietal thrombus homogenate and blood clot homogenate showed the highest activity on Z-Phe-Ala. It was lower on Z-Phe-Phe, Z-Glu-Tyr, Z-Glu-Phe, Z-Gly-Phe, and the lowest activity was on Z-Gly-Ala. We conclude that cathepsin A's activity on a parietal thrombus of an aneurysm is much higher than blood clot cathepsin A activity.

Cathepsin E (EC 3.4.23.34)--a review.

Cathepsin E belongs to the third class of enzymes - hydrolases, a subclass of peptide bond hydrolases and a sub-subclass of endopeptidases with aspartic catalytic sites. Cathepsin E is an endopeptidase with substrate specificity similar to that of cathepsin D. In a human organism, cathepsin E occurs in: erythrocytes, thymus, dendritic cells, epithelial M cells, microglia cells, Langerhans cells, lymphocytes, epithelium of gastrointestinal tract, urinary bladder, lungs, osteoclasts, spleen and lymphatic nodes. In human cells, loci of the gene of pre-procathepsin E are located on chromosome 1 in the region 1231-32. The catalytic site of cathepsin E is two residues of aspartic acid - Asp96 and Asn281, occurring in amino acid triads with sequences DTG96-98 and DTG281-283. To date, no particular role of cathepsin E in the metabolism of proteins in normal tissues has been found. However, it is known that there are many documented pathological conditions in which overexpression of cathepsin E occurs.

Evaluation of transforming growth factor-beta signaling pathway in the wall of normal and varicose veins.

OBJECTIVE(S): Extracellular matrix remodeling in the vein wall is involved in varicose vein pathogenesis, with transforming growth factor beta(1) (TGF-beta(1)) playing a potential role. The aim of the study was to assess the TGF-beta signaling pathway including its receptor (TGF-beta RII) and phosphorylated receptor-regulated Smads (p-Smad2/3) in varicose veins. METHODS: Varicose veins from patients undergoing varicose vein surgery were the studied material, whereas normal greater saphenous veins from patients undergoing infrainguinal arterial bypass surgery were the control material. Expression of TGF-beta RII mRNA was assessed with RT-PCR, whereas expression of TGF-beta RII and p-Smad2/3 proteins was assessed with Western blot. RESULTS: A significantly increased TGF-beta RII mRNA level was found in varicose veins (287 +/- 24%), when compared with normal veins (100 +/- 26%). The receptor protein expression reflected a changed mRNA level with significantly increased TGF-beta RII protein in varicose veins (290 +/- 21%), when compared with controls (100 +/- 16%). Enhanced TGF-beta RII expression was accompanied by increased p-Smad2/3 protein expression in varicose veins (257 +/- 19%) in comparison with normal veins (100 +/- 9%). CONCLUSION(S): Increased TGF-beta RII expression and activation in the wall of varicose veins may be involved in extracellular matrix remodeling related to TGF-beta(1) and supports its role in the disease pathogenesis.

Influence of thrombophlebitis on TGF-ß1 and its signaling pathway in the vein wall.

Extensive extracellular matrix remodeling of the vein wall is involved in varicose veins pathogenesis. This process is controlled by numerous factors, including peptide growth factors. The aim of the study was to evaluate influence of thrombophlebitis on TGF-ß1 and its signaling pathway in the vein wall. TGF-ß1 mRNAlevels, growth factor content and its expression were evaluated by RT-PCR, ELISA, and western blot methods, respectively, in the walls of normal veins, varicose veins and varicose veins complicated by thrombophlebitis. Western blot analysis was used to assess TGF-ß receptor type II (TGF-ß RII) and p-Smad2/3 protein expression in the investigated material. Unchanged mRNA levels of TGF-ß1, decreased TGF-ß1 content, as well as decreased expression of latent and active forms of TGF-ß1 were found in varicose veins. Increased expression of TGF-ß RII and p-Smad2/3 were found in varicose veins. Thrombophlebitis led to increased protein expression of the TGF-ß1 active form and p-Smad2/3 in the vein wall compared to varicose veins. TGF-ß1 may play a role in the disease pathogenesis because of increased expression and activation of its receptor in the wall of varicose veins. Thrombophlebitis accelerates activation of TGF-ß1 and activity of its receptor in the varicose vein wall.

Quantitative determination and localization of cathepsin D and its inhibitors.

A literature survey was performed of the methods of quantitative assessment of the activity and concentration of cathepsin D and its inhibitors. Usefulness of non-modified and modified proteins and synthetic peptides as measurement substrates was evaluated. The survey includes also chemical and immunochemical methods used to determine the distribution of cathepsin D and its inhibitors in cells and tissues.

Serum chemokine growth-related oncogene alpha profile during abdominal aortic aneurysm repair: preliminary report.

INTRODUCTION: High postoperative mortality in patients undergoing aortic abdominal aneurysm (AAA) repair is predominantly associated with ischemia and reperfusion organ injury followed by multiple organ dysfunction syndrome (MODS). Experimental studies have shown a role of growth-related oncogene a (GROa) chemokine in mediating organ damage during ischemia-reperfusion injury. OBJECTIVES: The study evaluated serum GROalpha levels during elective AAA repair in humans and the relationship between their changes and ischemia-reperfusion and the postoperative course. PATIENTS AND METHODS: Peripheral blood samples were taken from 17 patients before surgery (Preop), before aorta unclamping, 90 minutes after unclamping (90 min-Xoff) and 24 hours after surgery, and from 11 controls. The GROalpha was measured with an enzyme-linked immunosorbent assay. RESULTS: During AAA repair the GROalpha level showed an insignificant decrease from 79 pg/ml at Preop to 61 pg/ml at 90 min-Xoff followed by an increase to 100 pg/ml 24 hours after surgery. In complicated cases the GROalpha level showed a tendency to intraoperative higher values and increased to 133 pg/ml 24 h after surgery. Significant positive correlations were found between GROalpha and duration of surgery (r = 0.317), duration of aorta clamping (r = 0.322) and MOD score (r = 0.417). CONCLUSION: AAA repair is associated with insignificant alterations in the serum GROalpha level. A decrease in chemokine levels after ischemia and reperfusion may suggest uncomplicated postoperative courses. The tendency to high chemokine levels may be associated with high risk of postoperative organ dysfunction in patients undergoing AAA repair.

Evaluation of aFGF/bFGF and FGF signaling pathway in the wall of varicose veins.

BACKGROUND: Extensive extracellular matrix remodeling of the vein wall is involved in varicose veins pathogenesis. The process is controlled by numerous factors, including peptide growth factors. The aim of the study was to evaluate acidic (aFGF) and basic (bFGF) fibroblast growth factors, their receptor (FGFR) and the MAP kinase pathway (ERK 1/2) in the wall of varicose and varicose veins complicated by thrombophlebitis, when compared to normal ones. METHODS: Segments of normal, varicose, and varicose veins complicated by thrombophlebitis were collected during varicose veins surgery in 17 patients. Expression and content of aFGF and bFGF were evaluated with Western blot and enzyme-linked immunosorbent assay (ELISA) methods, respectively, whereas RT-PCR was employed to assess mRNA level of growth factors. Expression of FGFR and ERK 1/2 was examined with Western blot method. RESULTS: Increased aFGF expression and content were accompanied by increased aFGF mRNA level in the wall of varicose veins. Furthermore, alternatively spliced aFGF mRNA was shown in varicose veins complicated by thrombophlebitis. Expression, content, and mRNA level of bFGF were comparable in the investigated material. FGFR and ERK 1/2 expression was demonstrated in the wall of diseased veins, however, without any significant differences in comparison with the wall of normal veins. CONCLUSIONS: Overexpressed aFGF in the wall of varicose veins via FGFR and the MAP kinase pathway may influence expression of enzymes involved in extracellular matrix metabolism and play a role in vein wall remodeling, as well as in the disease pathogenesis.

The activity of class I, II, III and IV of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in the wall of abdominal aortic aneurysms.

OBJECTIVE: Human blood vessels contain a huge amount of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which play a significant role in the metabolism of many biological substances and participate in various metabolic pathways. The aim of this study was the investigation of the differences between the activities of ADH and ALDH in the wall of aortic aneurysm and wall of healthy aorta, that can explain the pathological background of aneurysm development. METHODS: For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity the fluorometric methods was employed. The total ADH activity and activity of class III and IV isoenzymes was measured by the photometric method. The study material consisted of vessels wall samples obtained from 45 abdominal aortic aneurysm. RESULTS: The activity of the class I ADH isoenzyme was significantly lower in the wall of aortic aneurysm than in healthy aorta. The other tested classes of ADH showed the tendency to lower level of the activity in aneurysm tissue than that in wall of unchanged aorta. The activities of total ADH and ALDH were also not significantly lower in the aneurysms. CONCLUSION: The decrease of the activity of class I ADH isoenzymes in the wall of aortic aneurysm may be a factor of some disorders in metabolic pathways with participation of these isoenzymes.

Thiocyanate concentration in saliva of cystic fibrosis patients.

Thiocyanates (SCN-) are ubiquitous in nature. There are indispensable part of host defense system that act as a substrate for lactoperoxidase (LPO). In our study we present initial data on SCN- concentration in saliva of CF patients in comparison to healthy non-smokers and healthy smokers. 5 ml of saliva was collected from each subject to a sterile tube and thiocyanate concentration was measured in each sample. The results of the measurements are presented on Fig. 1. Mean concentration of SCN- in saliva of CF patients was 0.031 +/- 0.0052 g/l, in healthy non-smokers 0.039 +/- 0.0048 g/l and in healthy smokers 0.048 +/- 0.0161 g/l. The differences between each group were statistically significant. Studies on larger group of patients and probably on different material (BALF or induced sputum) should present interesting data complementing the in vitro studies.

Human cathepsin D.

A literature survey was performed of human cathepsin D gene, cathepsin D biosynthesis, posttranslatory modifications, transport within the cell, substrate specificity and catalytic effect. Methods used to determine the activity and level of this proteinase as well as its role in the biochemistry and pathobiochemistry of cells, tissues and organs were considered.

[Arterio-venous fistula and cardiovascular system disturbances]. / Przetoka tqtniczo-zylna a zmiany w ukladzie kraienia.

There is an increasing number of patients with end-stage renal disease all over the world, mainly in the population of patients with diabetic nephropathy and in the elderly. One of the most important issues in nephrology care is the vascular access. The closest to the ideal vascular access is the native arterio-venous fistula. On the other hand, patients with end-stage renal failure are prone to cardiovascular complications, including left ventricular hypertrophy, cardiomyopathy, accelerated arterio- and atherosclerosis, vascular remodeling. Congestive heart failure is 20-fold more common than in the general population, and is found in about 30% of dialyzed patients, whereas left ventricular hypertrophy in 75%. Creating vascular access in patients with already established cardiovascular complications, may enhance the risk of exacerbation of cardiovascular complications with a negative effect on the patients' survival. The novel cardiovascular problems following vascular access creation may include: decompensation of congestive heart failure, pulmonary hypertension, inadequately low blood flow in the fistula with subsequent inadequate dialysis and fistula thrombosis, fistula infection (with local and systemic symptoms), and micro-inflammation (particularly in the politetrafluoroethylene grafts). The data concerning mutual relationship between vascular access and cardiovascular system in hemodialyzed patients are very scarce, mainly casual. In the review the updated status concerning the effects of vascular access creation on the cardiovascular system is presented.

Regulatory role of cathepsin D in apoptosis.

Cathepsin D (CTSD, EC 3.4.23.5) is well known aspartyl protease. Among different role in cell physiology, a new function of this enzyme is examined. Cathepsin D is an important regulator of apoptotic pathways in cells. It acts at different stage of intrinsic and extrinsic pathway of apoptosis. Cathepsin D can either induce apoptosis in presence of cytotoxic factors, but in certain studies an inhibitory role in apoptosis was also reviewed. Detailed review of involvement of cathepsin D in cell apoptosis is a purpose of this paper.