Effect of some newly synthesized xanthone and piperazine derivatives with cardiovascular activity on rheology of human erythrocytes in vitro.

This in vitro study was designed to examine the effect of some newly synthesized aminoalcanolic derivatives of xanthone (I, II) and aroxyalkyl derivatives of 2-methoxyphenylpiperazine (III, IV) having cardiovascular activity on the haemorheological parameters of RBCs from healthy individuals and patients with chronic venous disease. Additionally, the influence of compounds I-IV on some RBCs associated enzymes such as acetylcholinesterase (Ache), glucose-6-phosphate dehydrogenase (G6PD) and glutathione reductase (GR) as well as glutathione (GSH) content were determined in vitro in RBCs from healthy subjects. The study showed that compounds I, III and IV significantly increased RBCs deformability. Moreover, both xanthone derivatives reduced RBCs aggregation and diminished RBCs aggregates strength in all RBCs groups. Compounds II and III significantly improved Ache activity, whereas compounds I and II increased G6PD and GR activity and GSH level. In conclusion, compounds I, III and IV, which significantly improved RBCs deformability in vitro, may facilitate the passage of blood in the vascular system. Additionally, compounds I and II which inhibit RBCs aggregates formation in vitro may contribute to more rapid degradation of red blood cell aggregates in circulating blood.

Effect of Micronized Purified Flavonoid Fraction Therapy on Endothelin-1 and TNF-α Levels in Relation to Antioxidant Enzyme Balance in the Peripheral Blood of Women with Varicose Veins.

OBJECTIVE: The aetiology of varicose veins involves various factors and pathomechanisms including endothelial cell activation or dysfunction, venous hypertension, vein wall hypoxia, shear stress disturbances, inflammatory reaction activation or free radical production. To improve our understanding of the mechanisms of potential pharmacological interventions for chronic venous disease, we evaluated the influence of micronized purified flavonoid fraction (MPFF) on the relationship between antioxidant enzyme balance, endothelin-1 (ET-1) and tumour necrosis factor-α (TNF-α) levels. MATERIAL AND METHODS: Blood samples were obtained from 89 women with primary varicose veins; 34 were treated with MPFF and 55 did not receive any phlebotropic drug treatment. For the evaluation of the blood antioxidant enzyme balance, catalase (CAT) and superoxide dismutase (SOD) activity was assessed and the CAT/SOD ratio was calculated. RESULTS: Patients taking MPFF had significantly lower ET-1 levels than those not taking MPFF [median (25-75th quartile): 24.2 (22.30-27.87) vs 37.62 (24.9-44.58) pg.ml-1; p <0.05]. In those taking MPFF, a higher CAT/SOD ratio [39.8 (24.7-72.6) vs 28.8 (16.3-57.7); p<0.05] and a lower TNF-α concentration [6.82 (4.42-13.39) vs 12.94 (6.01-27.33) pg.ml-1; p<0.05] was also observed. In women not taking MPFF, ET-1 levels increased with the CAT/SOD ratio. In those taking MPFF, the ET-1 level was stable at approximately 25.0 pg.ml-1¬ up to a CAT/SOD ratio of 100. TNF-α level increased continuously with an increasing CAT/SOD ratio; however, the highest levels of TNF-α were observed in women not taking MPFF. CONCLUSION: We demonstrate the ability of MPFF to effectively lower the levels of ET-1 and TNF-α in patients with chronic venous disease. Further investigations are needed to define the therapeutic potential of MPFF including the potential effect on chronic subclinical inflammation, antioxidant imbalance and vascular dysfunction during the development of chronic venous disease.

Rheological properties of young and aged erythrocytes in chronic venous disease patients with varicose veins.

We hypothesize that heterogeneity in RBC rheology can be attributed not only to the aging process but also to various disease states. The present study aims at investigating the rheological properties of young and old RBC in chronic venous disease (CVD) patients. RBC were separated on the basis of their density. RBC rheology was assessed with Laser Optical Rotational Cell Analyzer. For medium and high shear stress elongation index (EI) of young RBC from CVD patients was significantly higher than of young cells from controls. The same was observed for the old cells. Threshold shear rate (THR) of young RBC from CVD patients was significantly higher than of young cells from controls indicating a decreased tendency towards the formation of aggregates and of their stability in CVD patients. The same situation was observed for the old cells. To sum up, the present study demonstrated that heterogeneity in RBC rheology is both affected by age and CVD. Additionally, CVD-induced changes in RBC rheology occur to different degrees among the subpopulations of young and old RBC. CVD patients subpopulations of RBC had higher deformability and increased tendency towards aggregates formation and of their stability when compared to appropriate subpopulations of controls.

Red blood cell deformability and aggregation in chronic venous disease patients with varicose veins.

INTRODUCTION: Red blood cells' (RBC) rheological properties are disturbed in chronic venous disease (CVD). The aim of the study was to compare deformability and aggregation of erythrocytes taken from the varicose vein and the antecubital vein of patients with chronic venous disease. MATERIALS AND METHODS: Blood samples were taken from twelve CVD patients presenting clinical, aetiological, anatomical and pathological elements (CEAP) stages II and III. Blood was sampled from varicose veins and antecubital veins of patients (as control). Deformability and aggregation of RBC were analysed with a Laser-assisted Optical Rotational Cell Analyser (LORCA). RESULTS: A significant increase in deformability was found in varicose vein RBC for shear stress values 4.24, 8.23 and 15.96 Pa as compared to RBC from the antecubital vein. The aggregation index was significantly lower and aggregation halftime was significantly increased for RBC taken from antecubital veins than for RBC from varicose veins. DISCUSSION: In conclusion, RBC taken from varicose and antecubital veins of CVD patients are not entirely rheologically comparable and show different deformability and aggregation. Varicose vein RBC are more deformable and show a higher tendency for aggregation than antecubital vein RBC. Perhaps the deformability of varicose vein RBC has been increased as a compensation mechanism in subjects with CVD, due to increased resistance in their microcirculation.

In vitro effect of pentoxifylline and lisofylline on deformability and aggregation of red blood cells from healthy subjects and patients with chronic venous disease.

Purpose. The aim of the study was to assess the in vitro potency of pentoxifylline (PTX) and one of its most active metabolites lisofylline (LSF) to improve rheological properties of red blood cells (RBC) from healthy individuals and patients with chronic venous disease (CVD). Additionally, the study aimed to compare the effects of PTX and LSF on RBC deformability and aggregation. Methods. Blood samples were collected from healthy volunteers (antecubital vein) and from CVD patients (varicose and antecubital vein). Deformability and aggregation of RBC were assessed using Laser-assisted Optical Rotational Cell Analyser (LORCA). Results. PTX and LSF increased RBC elongation significantly. Additionally, RBC incubation with PTX resulted in a marked decrease in RBC aggregation. PTX reduced the tendency towards the formation of RBC aggregates and of their stability. The beneficial effect of PTX on RBC aggregation was most apparent for those cells whose aggregation tendency and aggregate stability was the greatest. Conclusions. In vitro addition of PTX or LSF effectively increased deformability of RBC from healthy donors and patients with CVD. Thus, LSF may contribute to the in vivo hemorheological effects of pentoxifylline. On the other hand, there was no significant effect of LSF on aggregation of RBC in vitro. Hence, LSF has no contribution to this particular effect of PTX. Additionally, the present study demonstrated the use of RBC with impaired deformability and aggregation for the evaluation of in vitro rheological activity of xenobiotics.

Iron content (PIXE) in competent and incompetent veins is related to the vein wall morphology and tissue antioxidant enzymes.

Impaired venous drainage of the lower extremities determines a cascade of pathologic events leading to chronic venous disease (CVD). It is believed that the one cause of CVD is red blood cell extravasation and local iron overload that could generate free radicals and iron-dependent inflammation. The aim of this study was to investigate the relationship between: the intracellular iron deposits in varicose veins and tissue oxidative state measured by: the Proton Induced X-ray Emission Spectroscopy (Fe(PIXE)), (tSOD), (tGPx), (tTBARs) and (boxDNA). Patients with diagnosed CVD were qualified for surgical procedure. Entire trunk of the great saphenous vein (GSV) was extracted. Part located near medial ankle was considered competent (C) in duplex ultrasonography (USG) examination. The incompetent (I) part was extracted from GSV where USG showed incompetent valves and massive venous reflux. The difference between local tFe(PIXE), tTBARS, boxDNA, tGPx, tSOD in incompetent and competent part of vein tissue was statistically significant. Intima/media ratio directly correlated with Fe(PIXE) C/I concentration. Iron deposition in competent vs incompetent part of vein was also related to the oxidative stress parameters (boxDNA). The findings from this pilot study suggest that Fe(PIXE) measurement may be useful for explaining the progression of chronic venous disease.

Oxidative DNA Damage in Blood of CVD Patients Taking Detralex.

The main goal of the work reported here was to determine the degree of oxidative/alkali-labile DNA damages in peripheral blood as well as in the blood stasis from varicose vein of (chronic venous disorder) CVD patients. Moreover, determination of the impact of Detralex usage on the level of (oxidative) DNA damages in CVD patients was evaluated as well.The degree of oxidative DNA damages was studied in a group consisted of thirty patients with diagnosed chronic venous insufficiency (CVI) in the 2nd and 3rd degree, according to clinical state, etiology, anatomy and pathophysiology (CEAP), and qualified to surgical procedure. The control group consisted of normal volunteers (blood donors) qualified during standard examinations at Regional Centers of Blood Donation and Blood Therapy.The comet assay was used for determination of DNA damages.Analyses of the obtained results showed increase in the level of oxidative/alkali-labile DNA damages in lymphocytes originating from antebrachial blood of CVD patients as compared to the control group (Control) (p < 0.002; ANOVA). In addition, it was demonstrated that the usage of Detralex® resulted in decrease of the level of oxidative/alkali-labile DNA damages in CVD patients as compared to patients without Detralex® treatment (p < 0.001; ANOVA).Based on findings from the study, it may be hypothesized about occurrence of significant oxidative DNA damages as the consequence of strong oxidative stress in CVD. In addition, antioxidative effectiveness of Detralexu® was observed at the recommended dose, one tablet twice daily.

Generation of reactive oxygen species by a sufficient, insufficient and varicose vein wall.

Despite numerous theories, the etiology and pathogenesis of primary varicose veins remain unclear. The etiology of chronic venous diseases (CVDs) known as chronic venous insufficiency (CVI) is related to leukocyte trapping. Leukocyte trapping involves trapping of white cells in vessel walls followed by their activation and translocation outside the vessel. Release of reactive oxygen species (ROS) from trapped white cells has been documented. Superoxide dismutase (SOD) directly inhibits the generation of free radicals and compounds that are produced during oxidation by ROS, such as malonyldialdehyde (MDA). The aim of this study was to determine the involvement of free radicals in the etiology of venous changes. The following material was used for the study: fragments of sufficient or insufficient venous system and varices from 31 patients diagnosed with chronic venous disease in the 2nd or 3rd degree, according to clinical state, etiology, anatomy and pathophysiology (CEAP), which were qualified for surgical procedure. The levels of oxidative stress markers strongly correlated with lesions observed by USG in insufficient and varicose veins. In both a higher concentration of MDA was observed, which is a sign of lipid peroxidation. Antioxidative mechanisms, SOD activity and total antioxidative power expressed as FRAP were inversely proportional to MDA concentration. In insufficient and varicose veins both FRAP and SOD activities were significantly lower than in normal veins. The severity of clinical changes was inversely dependent on the efficiency of scavenging of ROS, which additionally proves the participation of free radicals in pathogenesis of CVDs.

[Role of Zn, Cu--trace elements and superoxide dismutase (SOD) in oxidative stress progression in chronic venous insufficiency (CVI)]. / Rola Zn i Cu--pierwiastków sladowych oraz dysmutazy ponadtlenkowej (SOD) w rozwoju stresu oksydacyjnego w przewleklej chorobie zylnej (PChZ).

INTRODUCTION: Ions of trace elements, zinc and copper, play a key role in a number of vital signs and metabolic processes occurring in human organism. In venous vessels, Cu and Zn ions contribute to formation of free oxygen radicals (catalysts for Habera-Weisa reaction) and may result in development of changes leading to chronic venous disease (CVD), also known as chronic venous insufficiency (CVI). These elements lead to changes occurring in cells by contributing to lipid peroxidation process. As enzyme activators, Zn and Cu ions maintain proper cell membranes functioning. In addition, these ions create the catalytic center of one of the most important enzymes of the antioxidant defence system, superoxide dismutase (SOD). THE AIM OF THE PRESENT STUDY: The aim of the present study was determination of copper and zinc ions in sufficient and insufficient vessels lyophilized and varicose veins lyophilized from patients with CVD. Further, a comparison of SOD activity in homogenates of above-mentioned tissues was done. MATERIALS AND METHODS: Study material consisted of tissues lyophilized and homogenates. This material contained: - Insufficient vessels originating from area of saphenous vein ostium (VSM, vena saphe magna), where venous insufficiency with massive venous reflux was observed during ultrasonography (USG); - Sufficient vessels which fulfilled criteria of sufficient vessels during USG examination; - Varicose veins. The study group consisted of 31 patients (23 females and 8 males) and the average age was 49.9 +/- 12.5. These patients were diagnosed with the 2nd and 3rd degree of CVD according to CEAP and they underwent surgery at II Department of General Surgery UJ CM, Poland (November, 2007-March 2008). Concentration of trace elements was determined by Proton Induced X-ray Emission (PIXE) method. Activity of superoxide dismutase was determined according to method reported by Spitz and Oberley. RESULTS: Concentration of Zn and Cu ions was significantly higher in varicose veins in the area of insufficient valves compared to sufficient vessels. Activity of superoxide dismutase both in homogenates of varicose veins and insufficient veins was significantly higher than in homogenates of sufficient veins. CONCLUSIONS: Clinical changes occurring during CVD were linearly dependant on SOD activity and concentration of Zn and Cu ions, which suggested the participation of free radicals in CVD

[Obesity and its' influence on reactive oxygen species (ROS) in the blood of patients with varicose veins of the lower limbs]. / Wplyw otylosci na poziom reaktywnych form tlenu (RTF) we krwi chorych z zylakami konczyn dolnych.

INTRODUCTION: Oxidative stress is considered as a probable mechanism in the pathogenesis and development of many diseases, including chronic venous disease (CVD). Local increased production of reactive oxygen species is taken into account as a mediator in vessel wall changes leading to damage of the endothelium and may be the mechanism leading to its' decreased blood flow and venous stasis. Obesity is a known clinical factor influencing venous blood flow from the lower limbs. AIM: Research aim was to evaluate the local production of ROS on the basis of malonylodialdehyde (MDA) production--a product of lipid peroxidation in blood samples taken from varicose veins of the lower limbs; as well as from blood taken from the forearms of patients that undertook surgery for lower limb varicose veins. The correlation between MDA level and body mass index (BMI) was also examined. MATERIALS AND METHODS: The examined group consisted of 31 patients with diagnosed CVD of the 2nd and 3rd degree according to CEAP qualified for surgical procedure. The analyzed group consisted of 23 females and 8 males between the ages of 26-68 years (mean age 49.9 +/- 12.5). The control group included 31 patients (20 females and 11 males) between the ages of 51-72 years (mean age 60 +/- 12); volunteers were without signs and symptoms of CVD whom had MDA levels measured from forearm veins during routine exam. Lipid peroxidation products were identified by measuring reactive species reaction with thiobarbital, measured by the spectro-fluorometrical method given by Austa. MDA concentration were expressed as nmol of MDA per ml of plasma and measured using the fluorometric method at fluorescence emission at 553 nm and ebullition at 532 nm. RESULTS: Significant increase in the MDA level in blood with various veins was noted in comparison to peripheral blood in patients with signs and symptoms of CVD (p < or = 0.0001). Overall MDA concentrations was higher in venous blood plasma in patients with CVD than in healthy volunteers (p < or = 0.0005). BMI substantially correlated with increased MDA concentration in blood plasma. MDA concentration was higher in obese patients than in patients with normal BMI. These results were substantially significant (p < or = 0.001). CONCLUSIONS: CVD is associated with increased oxidative stress measured by the level of MDA in blood plasma. Measurement of MDA may be a useful marker in evaluation of vessel changes in patients with CVD. 3. Obesity increases risk of lipid peroxidation and influences increment of oxidative stress in the group of patients with CVD.

[Risk and prophylaxis of venous thromboembolism in the material of 2nd Chair of Surgery JUMC]. / Ryzyko i profilaktyka zylnej choroby zakrzepowo-zatorowej w materiale II Katedry Chirurgii UJCM.

INTRODUCTION: Venous thromboembolism (VTE) is one of the most dangerous complication that could occur in patiens treated in surgical ward. Threat is increased due to presence of additional, apart from surgical procedures, risk factors. It is assesed, that approximately 50 000 patients are at risk of VTE yearly in Poland, 20 000 of them develop pulmonary thromboembolism during hospitalisation, which is fatal in 10% of cases. AIM: Aim of the study was to asses presence of VTE risk factors in the group of patients treated in the 2nd Chair of Surgery Jagiellonian University Medical College and to analyse applied prophylaxis. MATERIAL AND METHODS: The study enrolled 170 patients, 89 (52%) females and 81 (48%) males. Average age of the studied group was 57.9. Medical history of all patients was taken with an emphasis on presence of VTE risk factors. It had a form of questionnaire and enclosed questions. Apart from the anamnesis, physical examination was performed. Type of applied prophylaxis was assesed on the basis of medical records. RESULTS: Each patient was charged with 4 risk factors on average. The most common risk factors were: age, surgical procedure lasting longer than 45 minutes, ischaemic heart disease and hipertension. Clinical probability of deep venous thrombosis was assesed according to Wells scale; low: 59% of studied group, intermediate: 41%, high: 0%. Applied prophylaxis included pharmacotherapy, physiotherapy, and mechanical methods (compression). CONCLUSIONS: The most common risk factor that could be changed was duration of the surgery lasting longer than 45 minutes. Pharmacological prophylaxis should be more often complemented by mechanical methods and physiotherapy, especially in group burdened with high risk of VTE.

[Surgical treatment of the lower extremities varicose veins throughout the ages]. / Zabiegowe leczenie zylaków konczyn dolnych na przestrzeni wieków.

The authors describe a historical review of surgical treatment of varicose veins from antiques to modern methods. Diseases of the veins have been recognized and attempts of their surgical resection have been described since antiquity. Hippocrates wrote about surgical treatment of varicose veins, Celsus and also Galien himself described varicose veins ligatures. The end of 19th century with Trendelenburg and Madelung was a start of modern period of varicose vein surgery. Parallel to surgical the less invasive methods of varicose veins treatment developed and gave a base for modern sclerotherapy.

[Surgical treatment of chronic venous insufficiency in own material]. / Chirurgiczne leczenie przewleklej niewydolnosci zylnej w materiale wlasnym.

Nowadays most issues regarding venous disorders are described as chronic venous insufficiency (CVI)-which is defined as all symptoms that manifestate as impaired blood outflow from the lower limbs or in general the result of blood stasis in the deep and superficial venous system. Due to the fact that the symptomatology of venous diseases is wide, the treatment should be multioriented and often as well multi-specialized. The treatment of CVI needs a good understanding of the etiology of the primary insufficiency of the superficial and the deep venous systems. The main purpose of the surgical therapy is to remove the reflux in the great saphenous vein and the perforating veins. Additionally, during the surgical treatment the various veins should be removed in a way that gives the best cosmetic effect. In this article we presented the analysis of different surgical treatments in patients diagnosed with CVI 2-4 grade according to CEAP scale. The patients were hospitalized in our Clinic between april 1998 and april 2003. This group consisted of 311 patients, among them were 257 patients with primary varices, 25 patients with recurrent varices and 29 with postthrombotic syndrome. The choice of surgery was based on clinical examination and the result of venous USG. The most frequent (62%) surgical therapy was removal of the great saphenous vein with miniphlebectomy. To make the treatment more efficient we used the endoscopic method of obliteration of the insufficient perforating veins in lower limbs, called subfascial endoscopic perforating surgery (SEPS).

[Petit's triangle hernia clinically mimicking gluteal abscess]. / Przepuklina ledzwiowa trójkata Petita pod kliniczna postacia ropnia posladka.

Lumbar hernias are a very uncommon variety of abdominal wall defects. Diagnosis similar as obturatory hernia is often delayed until laparotomy. We describe a case of a 58 year old woman with parietal incarceration of the descending colon within a hernia in the inferior lumbar triangle (Petit's), under clinical form of a giant gluteal abscess.