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1.
Metastatic renal carcinoma: evaluation of antiangiogenic therapy with dynamic contrast-enhanced CT.
Fournier, LS, Oudard, S, Thiam, R, Trinquart, L, Banu, E, Medioni, J, Balvay, D, Chatellier, G, Frija, G, Cuenod, CA
Radiology. 2010;(2):511-8
Abstract
PURPOSE To determine whether tumor perfusion parameters assessed by using dynamic contrast material-enhanced computed tomography (CT) could help predict and detect response in patients receiving antiangiogenic therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS Institutional ethics committee approval and informed consent were obtained. In two phase-III trials involving 51 patients with metastatic renal cell carcinoma (38 men, 13 women; age range, 30-80 years) receiving antiangiogenic drugs (sorafenib [n = 10], sunitinib [n = 22]), a placebo (n = 12), or interferon alfa (n = 7), serial dynamic contrast-enhanced CT was performed, during 90 seconds before and after injection of 80 mL of iobitridol. Perfusion parameters of a target metastatic tumor (tumor blood flow [TBF], tumor blood volume [TBV], mean transit time, and vascular permeability-surface area product) were calculated. Values before and after treatment were compared by using a Wilcoxon signed rank test, and relative changes in groups were compared by using the Wilcoxon rank sum test. Results were compared with Response Evaluation Criteria in Solid Tumors response and with progression-free and overall survival by using Kaplan-Meier curves. RESULTS Among patients receiving antiangiogenic drugs, baseline perfusion parameters were higher in responders than in stable patients (TBF = 245.3 vs 119.5 mL/min/100 mL, P = .04; TBV = 15.5 vs 8.2 mL/100 mL, P = .02) but were not significantly predictive of survival. After the first cycle of treatment, there was a significant decrease in TBF (162.5 vs 76.7 mL/min/100 mL, P = .0002) and TBV (9.1 vs 3.9 mL/100 mL, P < .0001) in patients receiving antiangiogenic treatment. CONCLUSION Renal carcinoma perfusion parameters determined with dynamic contrast-enhanced CT can help predict biologic response to antiangiogenic drugs before beginning therapy and help detect an effect after a single cycle of treatment.
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2.
[Effect of fluvastatin extended release on the protein-lipid structure of erythrocyte membrane and C-reactive protein in patients with hyperlipidemia].
Broncel, M, Balcerak, M, Cieślak, D, Duchnowicz, P, Koter-Michalak, M, Sikora, J, Chojnowska-Jezierska, J
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2007;(128):107-11
Abstract
UNLABELLED The aim of the study was to estimate the effects of 4-weeks therapy of fluvastatin extended release (XL) on lipids serum, C-reactive protein (CRP), erythrocyte structure membrane (thiobarbituric acid reactive substances--TBARS concentrations, membrane cholesterol and the activity of Na+K(+)-ATPase in erythrocytes) in patients with hyperlipidemia without any clinical signs of atherosclerosis. MATERIAL AND METHODS The study comprised 37 persons, including 15 healthy volunteers and 22 patients with hyperlipidemia (TC > 200 mg/dl, LDL-C > 130 mg/dl, TG < 400 mg/dl) treated with fluvastatin XL 80 mg/d. Before and after 4 weeks of active treatment the following parameters were determined: lipids (by enzymatic method using BioMerieux tests), CRP (by immunoturbidimetric method), TBARS concentrations (by method of Stock and Dormandy), membrane cholesterol (method of Ilcy), Na+K(+)-ATPase activity (method of Bartosz et al.). RESULTS It was noticed significantly higher concentrations of CRP, TBARS, membrane cholesterol and lower activity of Na+K(+)-ATPase in erythrocytes of patients with hyperlipidemia than in the control group. Fluvastatin XL caused a significant decrease in serum TC (by 18%), LDL-C (by 24%), TG (by 16%), CRP (by 23%) and TBARS (by 31%), membrane cholesterol (by 30%) in comparison to the initial values before active therapy. The activity of Na+K(+)-ATPase didn't significantly change. The mean values of CRP, TBARS, membrane cholesterol level after active treatment are still higher than in the control group. CONCLUSION The short-term treatment of fluvastatin extended release wasn't enough efficient to compensate disorders in erythrocyte membrane structure of patients with hyperlipidemia.
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3.
Angiotensin II-induced oxidative burst is fluvastatin sensitive in neutrophils of patients with hypercholesterolemia.
Seres, I, Fóris, G, Páll, D, Kosztáczky, B, Paragh, G, Varga, Z, Paragh, G
Metabolism: clinical and experimental. 2005;(9):1147-54
Abstract
The aim of this study was to investigate the effect of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor fluvastatin (Flu) on angiotensin II (AII)-stimulated neutrophils of patients with hypercholesterolemia. Results suggest that a 6-week-long Flu administration completely counteracted the AII-induced increase in superoxide anion and leukotriene C4 production of the neutrophils of patients with hypercholesterolemia. However, the failure of signal processing through pertussis toxin-sensitive G protein, the increase in [Ca2+]i in membrane-bound protein kinase C activity, and the increase in neutrophil-bound cholesterol content were only partially restored by Flu. In addition, Flu had no effect on the increased membrane rigidity of the neutrophils of patients with hypercholesterolemia. To sum it up, Flu administration had a beneficial effect on AII-triggered reactive oxygen species generation; it resulted in partial restoration of signaling processes and of membrane composition, but membrane fluidity remained unchanged.
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4.
[Estimation of antioxidative effect of atorvastatin and fluvastatin used in primary prevention of coronary heart disease--effect on lipid peroxidation].
Kowalski, J, Pawlicki, L, Grycewicz, J, Błaszczyk, J, Irzmański, R, Cegliński, T, Kowalczyk, E, Liban-Gałka, B
Wiadomosci lekarskie (Warsaw, Poland : 1960). 2005;(7-8):386-90
Abstract
The study comprised 35 patients with mixed hyperlipidaemia and coronary heart disease (CHD) risk factors (overweight or obesity, low physical activity, family history). Seventeen patients were administered atorvastatin in a dose of 10 mg and 18 -fluvastatin in a dose of 40 mg once daily at bed time for 6 weeks. The control group consisted of 12 clinically healthy subjects with no CHD risk factors. Blood samples for testing were collected from cubital vein of patients after hypolipaemic diet prior to and 6 weeks after drugs application and once in control group. Malondialdehyde (MDA) concentrations in erythrocytes and plasma were determined by the method of Placer et al. MDA concentrations in erythrocytes and plasma were significantly higher (p < 0.05) in patients than in healthy subjects. After 6-week atorvastatin therapy MDA concentrations in erythrocytes and plasma decreased to the values observed in healthy subjects. In fluvastatin group erythrocyte and plasma MDA concentrations were unchanged and still significantly higher in comparison to the healthy subjects. Atorvastatin, contrary to fluvastatin, decreases lipid peroxidation in CHD risk patients.
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5.
Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in renal transplant recipients.
Barlage, S, Hauser, IA, Elbracht, R, Abletshauser, C, Schmieder, RE, Weidinger, G, Lackner, KJ, Rothe, G, Schmitz, G
Journal of biological regulators and homeostatic agents. 2005;(3-4):159-68
Abstract
Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients. At baseline, the population size of activated (HLA-DR+) T-cells was negatively correlated to serum HDL cholesterol suggesting an increased T-cell activation at low HDL levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two months significantly decreased the LDL cholesterol. A longitudinal analysis revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+ or CD56+) over time which was significantly attenuated in fluvastatin treated patients but not in normocholesterolemic controls. Moreover, a relative decrease of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon fluvastatin treatment. NK-cell number and activity did not differ between groups. In summary, fluvastatin treatment of hypercholesterolemic renal transplant recipients is associated with a specific modulation of T-cells exerting cytotoxic effector functions.
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6.
Effects of fluvastatin in type 2 diabetic patients with hyperlipidemia: reduction in cholesterol oxidation products and VCAM-1.
Guan, JZ, Murakami, H, Yamato, K, Tanabe, J, Matsui, J, Tamasawa, N, Suda, T
Journal of atherosclerosis and thrombosis. 2004;(2):56-61
Abstract
The purpose of this study was to investigate the lipid-lowering and anti-oxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in type 2 diabetic patients. Six patients (3 men and 3 women, mean age = 56.2) took 20 mg of fluvastatin once daily (at night) for 12 weeks. Several markers of oxidative stress were then measured in these patients including plasma cholesterol oxidation products, i.e. oxysterols, and the levels of circulating adhesion molecules. Plasma total cholesterol levels were reduced by 12.3% in these individuals after 4 weeks of treatment, with levels remaining below 220 mg/dl for the entire treatment period. LDL levels were significantly reduced at 4 (18.1%) and 12 weeks (16.1%), and triglyceride levels were significantly reduced after 8 (22.5%) and 12 (37.7%) weeks of treatment. HDL-C levels increased from 50.7 +/- 15.4 prior to treatment to 63.8 +/- 24.3 mg/dl after 12 weeks of treatment, though this increase was not statistically significant. Lipid hydroperoxide, thiobarbituric acid-reactive substance (TBARS), and oxysterol levels were also reduced, suggesting that fluvastatin also had anti-oxidative effects. Finally, VCAM-1 levels were similarly reduced by fluvastatin treatment. We conclude that fluvastatin safely improves the plasma lipid profile in type 2 diabetic patients with hyperlipidemia. We speculate that this drug might be doubly effective in reducing atherosclerosis and cardiac events in these patients as a result of its demonstrated anti-oxidative effects and its ability to reduce VCAM-1 levels.
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7.
Fluvastin therapy affects TAFI concentration in kidney transplant recipients.
Malyszko, J, Malyszko, JS, Mysliwiec, M
Transplant international : official journal of the European Society for Organ Transplantation. 2003;(1):53-7
Abstract
Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. Recently, attention has been drawn to the beneficial effects of statins on haemostasis in kidney patients prone to dyslipidaemia and with a high risk of cardiovascular death. The purpose of this study was to assess whether fluvastatin affects TAFI concentration in renal transplant recipients. We evaluated thrombin-antithrombin (TAT) complexes, prothrombin fragments 1+2, thrombomodulin, plasmin-antiplasmin (PAP) complexes, TAFI, P-selectin, and lipoprotein (a), 1, 2, and 3 months before and after fluvastatin treatment and in normolipaemic kidney transplant recipients and healthy volunteers. Cholesterol and LDL fell significantly as soon as 1 month after treatment had begun and remained lowered during the therapy. TAFI and prothrombin fragments 1+2 decreased significantly after 3 months of fluvastatin administration, whereas P-selectin decreased significantly after 2 months and remained significantly lower after 3 months of this therapy. We can conclude that fluvastatin is an effective hypolipaemic agent that favourably affects haemostasis.
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8.
Fluvastatin prevents development of arterial stiffness in haemodialysis patients with type 2 diabetes mellitus.
Ichihara, A, Hayashi, M, Ryuzaki, M, Handa, M, Furukawa, T, Saruta, T
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2002;(8):1513-7
Abstract
BACKGROUND Arterial stiffness assessed by pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality in diabetic patients with end-stage renal disease. We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on arterial PWV values in this population. METHODS Twenty-two patients with normal serum lipid levels received fluvastatin (20 mg/day p.o.) or a placebo for 6 months. Their serum lipid levels, serum levels of C-reactive protein (CRP), arterial PWV, and ankle brachial indexes (ABI) were determined before, and 3 and 6 months after taking the medication to evaluate arterial stiffness. RESULTS At the beginning of the follow-up, there were no differences in age, blood pressure, body mass index, serum haemoglobin A1c level, serum CRP level, serum lipid levels, PWV or ABI between the placebo- (n=10) and the fluvastatin-treated patients (n=12). After 6 months, the PWV and the serum oxidized low-density lipoprotein cholesterol (LDL-C) level increased significantly (from 1969+/-140 to 2326+/-190 cm/s and 70.4+/-13.8 to 91.8+/-15.5 U/l, respectively) in the placebo-treated patients. However, the fluvastatin group had a significantly reduced PWV (from 1991+/-162 to 1709+/-134 cm/s), oxidized LDL-C serum levels (from 89.0+/-9.6 to 73.0+/-5.8 U/l) and CRP serum levels (from 0.97+/-0.32 to 0.26+/-0.16 mg/dl) compared with those in the placebo group. CONCLUSIONS Long-term administration of fluvastatin prevents further worsening of arterial biomechanics in haemodialysis patients with type 2 diabetes mellitus, even in the presence of serum lipid levels in the normal range.
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9.
[Experience of biologically active supplements to food containing indoles and isothiocyanates in patients with chronic viral hepatitis].
Gichev, IuP, Gichev, IuIu, Grek, OR, Tolokonskaia, NP, Chernousova, NIa, Tomilenko, TG, Makkosland, K
Voprosy pitaniia. 2002;(4):27-31
Abstract
We have studied the effect of dietary supplement "ExPress" on clinical and biochemical parameters and on the activity of detoxification enzymes of liver in patients with chronic viral hepatitis B and C. 24 patients (19 females and 5 males aged 16-39 years) were enrolled in the study. Patients in case group received dietary supplement "ExPress" in addition to basic treatment. Average indices of total bilirubin in cases after treatment were 26.98 +/- 2.85 mmol/l, while in controls--34.31 +/- 5.72 mmol/l (p > 0.05). Average indices of alanin-aminotransferase and aspartate-aminotransferase were 78.75 +/- 11.25 and 160.75 +/- 23.67 units while in controls--208.5 +/- 56.4 and 330.25 +/- 65.14 units respectively (p < 0.05). In case group we observed full normalization of thymol test--from 9.99 +/- 1.51 to 4.03 +/- 0.73 units (p = 0.001), while in controls--from 7.9 +/- 1.56 only to 5.2 +/- 1.15 units (p = 0.194). Contents of non-metabolized antipyrine in cases decreased from 9.76 +/- 1.2% (p = 0.0002) whilst in controls--from 9.38 +/- 1.28% only to 3.93 +/- 1.18% (p = 0.01). Results of the study show that dietary supplement "ExPress" induces the activity of detoxification enzymes of liver and increases the efficiency of basic treatment.
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10.
The effect of fluvastatin of hyperlipidemia in renal transplant recipients: a prospective, placebo-controlled study.
Türk, S, Yildiz, A, Tükek, T, Akkaya, V, Aras, U, Türkmen, A, Uras, AR, Sever, MS
International urology and nephrology. 2001;(4):713-6
Abstract
Posttransplant hyperlipidemia is a common complication which may affect long term cardiovascular mortality. In this prospective, placebo-controlled study, 19 renal transplant recipients (11 male 8 female, mean age 31.2 +/- 8.4 years) with good allograft function (serum creatinine <2 mg/dl) more than 6 months after transplantation were included. All the patients had hyperlipidemia (serum cholesterol >230 mg/dl and/or LDL-cholesterol >130 mg/dl) despite dietary interventions. The patients were treated with a triple immunosuppressive regimen. After a 8-week period of placebo plus diet regimen, the patients were put on fluvastatin plus diet for another 8 weeks. The patients were followed for its effect on lipid parameters and side effects. After convertion to fluvastatin, serum cholesterol (263.0 +/- 31.6 vs 223.2 +/- 31.6 mg/dl, p = 0.001), LDL-cholesterol (174.4 +/- 28.3 vs 136.4 +/- 28.5 mg/dl, p = 0.002), Apolipoprotein (Apo) A1 (131.1 +/- 16.9 vs 114.7 +/- 18.4 mg/dl, p = 0.001) and Apo B (109.0 +/- 29.8 vs 97.3 +/- 31.5 mg/dl, p = 0.02) levels decreased significantly. Serum levels of triglycerides, VLDL-cholesterol and HDL-cholesterol levels did not vary under fluvastatin. Serum lipoprotein (a) levels were also unchanged during the whole study period (24.9 +/- 19.4 vs 23.1 +/- 19.8 mg/dl, p > 0.05). We concluded that fluvastatin effectively decreased atherogenic lipoproteins such as serum cholesterol, LDL-cholesterol, Apo B in posttransplant hyperlipidemia, however fluvastatin had no effect on another independent risk factor of atherogenesis, serum lipoprotein (a) levels.