Life-style activities in systemic lupus erythematosus.

OBJECTIVE: We evaluated the life-style activities of outpatients with SLE and factors that reduce their social activities. SUBJECTS: SLE group = 60 patients, Control 1 = 30 healthy subjects and Control 2 = 30 patients with other autoimmune diseases. The Frenchay Activity Index (FAI), Zung's self-rating depression scale (SDS), and the Japanese version of the Philadelphia Geriatric Center morale scale-revised (MS) were compared between groups. Relation between FAI and age, disease duration, steroid dose, SDS, and MS were examined in the SLE group, Control 1, and Control 2. RESULTS: Total scores by FAI was 28.1 +/-8.0 points in Control 1, whereas it was 26.5 +/- 5.8 points in Control 2 and 24.5 +/- 7.7 points in the SLE group. While there was no statistical difference between the SLE group and Control 2, the scores were significantly lower in the SLE group than in Control 1 (P < 0.05). In SLE patients, age, the duration of the disease, and the steroid dose had no correlation, but MS had a positive correlation (P < 0.05) and SDS had a negative correlation (P < 0.05). In Control 2, age, the duration of the disease, the steroid dose, MS and SDS had no correlation whereas there was significant negative relation between FAI and SDS in Control 1 (r= -0.516, P<0.005). CONCLUSION: The significant relation between life-style activities and subjective well-being, and depression in SLE suggests that detection and treatment of mental status is important in improving the life-style activities of SLE patients.

Beneficial effect of low-density lipoprotein apheresis (LDL-A) on refractory nephrotic syndrome (NS) due to focal glomerulosclerosis (FGS).

AIMS: Hypercholesterolemia is one of the factors which deteriorate renal function in NS especially due to FGS. LDL-A is a potential option for treating NS due to FGS accompanied by hypercholesterolemia and resistant to conventional drug therapy with steroids and/or cyclosporine A (CsA). As reported by Muso et al. [2001], LDL-A combined with drug therapy yields more rapid relief from NS and better prognosis than drug therapy alone. However, very limited data are available on outcome at several years after treatment. The aim of this study was to clarify long-term outcome of NS patients treated with LDL-A and to evaluate the effectiveness of this treatment. PATIENTS AND METHODS: To clarify the long-term outcome of LDL-A, we conducted a retrospective survey on outcome up to 5 years. From 36 hospitals in Japan, 41 patients with NS whose short-term outcomes with LDL-A were reported from 1999-2004 were collected and analyzed. RESULTS: In all, 29 and 15 patients with outcomes determined at 2 and 5 years after treatment, respectively, were obtained. At 2 and 5 years after treatment, 62 and 87% of patients, respectively, were classified into complete or Type 1 incomplete remission. The strength of correlations between outcome and several factors including parameters of renal function measured before and after treatment and treatment condition revealed that early administration of LDL-A after the onset of NS provided a good long-term outcome. The data also suggest that more drastic decrease of LDL favored a better prognosis. CONCLUSIONS: In NS due to FGS treated with LDL-A, long-term outcome was as good as short-term outcome. Early administration of LDL-A after the onset of NS provided a good long-term outcome. To obtain more precise findings regarding the effects of this treatment, a large-scale prospective study will be needed.

Human immunodeficiency virus and other sexually transmitted diseases in Cuban women.

A cross-sectional study was performed in 60 Cuban women of child-bearing age who were seropositive for human immunodeficiency virus (HIV) and 60 controls. Human papillomavirus (HPV) was identified most frequently, with oncogenic HPV serotypes 16, 33 and 58 detected in HIV-positive patients, and serotypes 11, 33 and 51 in the controls (relative risk 4.41; 95% CI 2.21-8.29). Syphilis and hepatitis B and C viruses were detected exclusively in HIV-seropositive women (p<0.05). Sexually transmitted diseases (STDs) appeared to pose a substantial health problem, especially for HIV-positive women. Clinics should consider screening and treatment for STDs as part of their HIV prevention programmes.

Selective urinary excretion of phosphatidyl ethanolamine in patients with chronic glomerular diseases.

Urinary phospholipids and lipoproteins in chronic glomerular diseases were analyzed. The subjects used were 26 patients consisting of 14 with chronic glomerulonephritis and 12 with nephrotic syndrome. Nine healthy normals served as controls. Phospholipids were isolated by one-dimensional thin-layer chromatography (TLC) using an internal standard for quantification and partially by two-dimensional TLC and, furthermore, quantified by two different methods to ascertain the kinds of phospholipids. Urinary lipoproteins were isolated by density gradient ultracentrifugation and analyzed by electrophoresis. The urinary excretion of phosphatidyl ethanolamine (PE) was recognized exclusively in the patient group and that of phosphatidyl serine (PS) in most cases with nephrotic syndrome. The daily urinary PE excretion rate was closely correlated to the urinary albumin excretion rate. However, phosphatidyl choline (PC) and sphingomyelin (SPH), which are main phospholipids in serum and red blood cell membranes, in most cases were hardly detected in urine. These observations were confirmed by two-dimensional TLC using valuable spot tests for identification of phospholipids and also by the two different quantification methods. In density gradient ultracentrifugation, urinary lipoproteins did not form such peaks as seen in the profiles of serum lipoproteins. The presence of urinary lipoproteins in two nephrotic patients has been shown, but although the method used was not very sensitive, it was suggested that lipoproteins were hardly excreted into urine as the lipoprotein deficient fraction (LPDF) (d greater than 1.21 g/ml), in which albumin is predominant. PE was found mainly in LPDF of urine, although the amount of PE in urinary lipoproteins was very limited.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of MCP-1 and M-CSF in glomerular foam cell formation in ExHC rats.

BACKGROUND: An increase in glomerular macrophages (MO) is considered a potential effector mechanism by which hypercholesterolemia exacerbates glomerular injury. To investigate the mechanism underlying recruitment of MO into glomeruli, the expression of glomerular monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF) mRNA were examined using a lipid-induced glomerular injury rat model. METHODS: Eight-week-old male ExHC rats, a strain susceptible to hyperlipidemia, were divided into the following 4 groups: a control group (C), a high cholesterol diet group (HH), a high cholesterol diet/standard diet group (HN), which were fed a high cholesterol diet for the first 4 weeks and a standard diet for the following 4 weeks, and a probucol-treatment group (PT). Both MCP-1 and M-CSF mRNA expression in glomeruli were analyzed using the RT-PCR method. An additional experimental group (M) fed a high cholesterol diet was administered M-CSF daily for 4 weeks. RESULTS: The expression of MCP-1 mRNA in glomeruli increased accompanied by an increased total serum cholesterol level in HH and HN. However, M-CSF mRNA expression was significantly suppressed at 1 or 2 weeks and gradually increased to almost basal levels. In the PT group, MCP-1 mRNA expression was suppressed. The early suppression of M-CSF mRNA expression was inhibited in PT. Renal histology showed a significant increase in foam cells in glomeruli in HH and HN rats at 4 weeks. HH rats showed increased and expanded foam cells at 8 weeks. In HN rats, however, foam cells decreased significantly after the transfer to a standard diet from a high cholesterol diet. The MCP-1 mRNA expression was suppressed after the transfer. In the PT group, foam cell formation was also suppressed. Foam cells were identified as MO. M-CSF-treatment significantly suppressed foam cell formation in glomeruli when compared with the untreated group levels. CONCLUSION: These findings suggest that hypercholesterolemia stimulated the expression of MCP-1 in glomeruli and attracted the MO into glomeruli. They also suggest that the reduction of hypercholesterolemia after the change in diet or treatment with probucol suppressed glomerular injury by suppressing the glomerular MCP-1 expression. M-CSF may suppress the recruitment of MO into glomeruli and foam cell formation at an early stage of hypercholesterolemia-induced glomerular injury.

Erythropoietin supplement increases plasma lipoprotein lipase and hepatic triglyceride lipase levels in hemodialysis patients.

BACKGROUND: We reported in previous studies that plasma triglyceride levels, as well as remnant-like particles-cholesterol (RLP-C) and -triglyceride (RLP-TG) levels, were significantly lower in maintenance hemodialysis (HD) patients treated with erythropoietin (EPO) than in HD patients treated without EPO. However, little is known about the mechanisms underlying the improvements in abnormal RLP metabolism in HD patients. This study investigates whether EPO supplement therapy in cases of uremic anemia increases the plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) levels in HD patients. METHODS: Twenty HD patients who had not previously received EPO were divided into two groups according to the stage of HD: 12 at the initial stage, defined as a mean HD duration of 0.35 +/- 0.68 months (range of 0 to 2.47 months), and 8 at the maintenance stage, defined as a mean HD duration of 114.1 +/- 91.9 months (range of 13.0 to 253.9 months). Fasting plasma was collected from the HD patients prior to the start of the EPO supplement therapy and at one month after the therapy. RLP-C levels were determined using a RLP-C JIMRO II kit. Fasting plasma was also collected from the HD patients 10 minutes after an intravenous injection of heparin (30 U/kg body wt). Plasma LPL levels were determined using an enzyme immunoassay, and HTGL levels were determined using a modified version of the Hernell et al method. RESULTS: Plasma RLP-C levels showed a tendency to decrease after the start of the EPO supplement therapy in HD patients at the maintenance stage. Plasma LPL levels were significantly higher in the two groups of HD patients one month after the start of the EPO supplement therapy than in the same patients prior to the start of the EPO supplement therapy. Plasma HTGL levels were significantly higher in HD patients at the maintenance stage one month after the start of the EPO supplement therapy than in HD patients at the maintenance stage prior to the start of the EPO supplement therapy. CONCLUSIONS: The results of this study suggest that the EPO supplement therapy may reduce plasma RLP-C levels by increasing the plasma LPL and HTGL levels in maintenance-stage HD patients.

Factors associated with calcification of the abdominal aorta in hemodialysis patients.

BACKGROUND: Cardiovascular and cerebrovascular injury caused by arteriosclerosis has been the major cause of the death in hemodialysis (HD) patients. We quantitatively analyzed and evaluated the severity of abdominal aortic calcification in HD patients in comparison to risk factors for arteriosclerosis. METHODS: One hundred thirty-seven HD patients were examined. Using image analysis software, areas of the calcified abdominal aorta were quantitatively analyzed on plain computerized tomography images. Other factors such as blood pressure (BP), lipid levels, and calcium (Ca) x phosphorus (Pi) value were also analyzed. RESULTS: Patients with a higher one-year average of systolic BP showed a higher severity of abdominal aortic calcification. That is, the severity of abdominal aortic calcification in patients with a one-year systolic BP average above 160 mm Hg was 31.5 +/- 13.6%, and this severity was significantly higher than that in patients with a one-year systolic BP average of less than 120 mm Hg (8.0 +/- 7.7%, P < 0.01). The severity of abdominal aortic calcification in patients demonstrating risk values of ectopic calcification, that is serum Ca x Pi > or = 60 (mg/dl), on more than 4 of 24 measurements within one year (25.8 +/- 13.6%) was significantly higher than the severity of aortic calcification in patients demonstrating this value less than four times in one year (P < 0.05). There was no correlation between levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, lipoprotein(a), and severity of abdominal aortic calcification. CONCLUSIONS: Systolic BP levels and the product of serum Ca and Pi were related to the severity of abdominal aortic calcification in HD patients. These observations suggested that BP control, as well as control of serum Ca and Pi levels, was important in preventing the progression of abdominal aortic arteriosclerosis.

Phosphotyrosine of macrophage by low-density lipoproteins from hemodialysis patients.

BACKGROUND: Because of the possible importance of tyrosine phosphorylation in the signal transduction process, we investigated whether an interaction of low-density lipoprotein (LDL) from hemodialysis patients (HD-LDL) and human macrophages induces tyrosine-phosphorylated proteins in the macrophages. METHODS: Human monocyte-derived macrophages were incubated with HD-LDL (100 micrograms/ml) or native LDL (100 micrograms/ml) for 15 minutes at 37 degrees C. Whole cells were lyzed with Tris-HCl buffer containing vanadate and Triton X-100. After centrifugation, lyzed proteins were divided into Triton-soluble and -insoluble fractions. Both fractions (soluble and insoluble) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were electroblotted onto a polyvinylidene difluoride (PVDF) membrane. Immunoblotting was performed using an antibody against phosphotyrosine or c-Src. RESULTS: Several proteins in the range 40 to 100 kDa were found to be phosphorylated constitutively in the macrophages and not affected by the addition of HD-LDL. HD-LDL did not induce any tyrosine-phosphorylated proteins either in the soluble or insoluble fractions. Macrophages pretreated with tyrosine kinase inhibitor genestein drastically inhibited tyrosine phosphorylation of these proteins. The nonreceptor tyrosine kinase, c-Src p60, was also strongly tyrosine phosphorylated in the macrophages, and this was not enhanced by the stimulation of HD-LDL. CONCLUSION: These data suggest that tyrosine autophosphorylated proteins may play a role in the early step of signal transduction in the macrophages.

Vitamin E treatment of experimental glomerular disease in rats.

BACKGROUND: Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease. METHODS: A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS). RESULTS: In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction. CONCLUSIONS: Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.

Ongoing clinical trials of lipid reduction therapy in patients with renal disease.

BACKGROUND: Lipid abnormalities in renal disease are associated with both a progressive decline in renal function and cardiovascular complications. Whether or not lipid anomalies are causal is not yet clear. Experimental studies have demonstrated that potentially atherogenic lipoproteins, such as low density lipoproteins (LDL), are associated with renal pathophysiological changes that result in progressive glomerular and interstitial damage and an ultimate reduction in renal function. These findings indicate that hyperlipidemia accelerates glomerular and interstitial damage in renal disease. Clinical studies also show that renal function declines more rapidly among patients with primary renal disease or diabetic nephropathy who have hyperlipidemia. However, few reports have demonstrated the effect of hypolipidemic agents on the progression of renal function among patients with renal disease, and those renal patients who were treated with lipid-lowering agents have not been clinically studied under large-scale controlled conditions. In addition, although cardiovascular complications are the most important factors associated with mortality in dialysis patients, randomized, large-scale trials studying the relationship between therapeutic intervention by lipid-lowering agents and prevention of cardiovascular complications have not been implemented. METHODS: We reviewed controlled and uncontrolled reported studies that examined the effects of lipid-lowering therapy in patients with renal disease. RESULTS: Most studies showed that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce cholesterol-rich apolipoprotein (apo)B-containing lipoproteins with no effects on renal function or proteinuria among patients with progressive renal disease. Small uncontrolled studies show that simvastatin and probucol moderately reduce proteinuria among patients with membranous nephropathy. One small retrospective study showed that long-term vitamin E therapy reduces aortic calcification in dialysis patients. CONCLUSIONS: Prospective, randomized large-scale trials including ongoing clinical trials of lipid reduction therapy and therapeutic interventions such as the use of the combination therapy with hypolipidemic agents and angiotensin converting enzyme (ACE) inhibitors, vitamins, or LDL apheresis are urgently required. Such trials will clarify the effect of treating dyslipidemia on the progression of renal insufficiency and dialysis-related cardiovascular complications.

Evaluation of serum lipid abnormalities in chronic nephritis.

BACKGROUND: In glomerular disease, disorders of lipid metabolism are suspected as factors exacerbating glomerular dysfunction. Although many reports have been published regarding metabolic disorders of lipids in renal disease, including nephrotic syndrome and chronic renal failure, there have been few published reports describing metabolic disorders of lipids in chronic nephritis. Therefore, in patients with IgA nephritis, we evaluated correlations between serum lipid levels and renal function and proteinuria. METHODS: In 191 patients with IgA nephritis, we evaluated the correlations between serum lipid levels and renal function [creatinine clearance (CCr)] and proteinuria (UP). Serum lipids examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteins, phospholipids (PL), lipoprotein(a) [Lp(a)], and malondialdehyde (MDA). RESULTS: Significant correlations were observed between serum lipid levels and CCr, UP, and age. There were no abnormalities in the mean values of respective serum lipids examined. Although TC levels increased with age, HDL-C levels were not correlated with age. Hyperlipidemia was observed in 39.8% of subjects. Significant correlations were observed between levels of TC, TG, PL, LDL-C, apoB, apoC-II, and apoC-III and Ccr, UP, and age. Significant correlations were also observed between levels of MDA, apoB/apoA-I, apoE/apoC-III, and Ccr and age, as well as between apoE levels and UP and age. The levels of apoA-I and apoA-I/apoA-II ratio were significantly correlated with UP alone, whereas the apoC-II/apoC-III ratio was significantly correlated with Ccr alone. There were no significant correlations between levels of HDL-C, apoA-II, and Lp(a) and Ccr, UP, and age. CONCLUSIONS: Age, proteinuria, and renal function were related with changes in serum lipid levels in IgA nephritis. There were correlations between proteinuria and levels of apoA, as well as between renal function and apoC levels.

Lysophosphatidylcholine up-regulates IL-1 beta-induced iNOS expression in rat mesangial cells.

BACKGROUND: Nitric oxide (NO), a simple molecule synthesized from L-arginine by NO synthases (NOS), has been identified to play an important role in cell communication, cell defense and cell injury. Several studies have shown that glomeruli from rats with immune-mediated glomerular inflammation have increased production of NO. Recently, it was also reported that inducible NOS (iNOS) is localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased human glomeruli. On the other hand, while oxidized low density lipoprotein (ox-LDL) has been suggested to be related to progression of glomerular disease, the mechanism remains unknown. We investigated the effect of lysophosphatidylcholine (LPC), a modified phospholipid produced during LDL oxidation, on iNOS expression in rat mesangial cells. METHODS AND RESULTS: Treatment of mesangial cells with interleukin-1 beta (IL-1 beta) induced iNOS activity measured as nitrite levels in cell culture supernatants. Treatment with LPC had no effect. In contrast, coincubation with LPC and IL-1 beta resulted in a markedly higher nitrite content compared to that after incubation with IL-1 beta alone. Western blot analysis revealed that LPC caused a significant increase in the formation of iNOS protein in the presence of IL-1 beta. CONCLUSION: These findings suggest that LPC may contribute to progression of glomerular inflammation by augmenting IL-1 beta-induced iNOS expression.

Phospholipase A2 activity in ox-LDL-stimulated mesangial cells and modulation by alpha-tocopherol.

BACKGROUND: Oxidized LDL increases the production of both prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in rat mesangial cells. These increases were suppressed by antioxidants such as alpha-tocopherol (alpha-Toc) or probucol. METHODS: We investigated the mechanism by which oxidized LDL leads to an increase in PGE2 production using rat mesangial cells in culture. We also examined how alpha-Toc supresses this augmentation, by measuring intracellular Ca2- and phospholipase A2 (PLA2) activity. RESULTS: In rat mesangial cells, oxidized LDL increased PLA2 activity by increasing the intracellular calcium ion content, which resulted in the induction of PGE2 production. On the other hand, pretreatment of cells with alpha-Toc, which resulted in a large uptake of alpha-Toc in cell membranes, markedly suppressed the augmentation of PGE2 production and PLA2 activity by oxidized LDL in a dose dependent manner. However, cytosolic PLA2 partially purified from mesangial cells was not inhibited by alpha-Toc despite an increase of alpha-Toc. CONCLUSION: These results suggest that the augmentation of PLA2 activity in mesangial cells by oxidized LDL in a result of oxidative stresses, and that the antioxidant action of alpha-Toc is responsible for the suppression of augmentation of PLA2 activity observed in mesangial cells exposed to oxidized LDL.

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Effect of vitamin E on lipid metabolism and atherosclerosis in ESRD patients.

BACKGROUND: Oxidative stress is enhanced in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Bioincompatibility represents an important source of reactive oxygen species. HD patients exhibit altered anti-oxidative defences and anti-oxidative vitamins such as vitamin E and C are altered in uremia. Frequently, HD patients also suffer from atherosclerotic cardiac disease. We have previously reported that low density lipoprotein (LDL) of HD patients is rich in malondialdehyde (MDA), an end product of lipid peroxidation. MDA rich LDL is thought to be an atherogenic lipoprotein due to its enhancement of macrophage foam cell formation. METHODS: We conducted a controlled study for two years comparing the effects of a vitamin E coated cellulose membrane dialyzer and an ordinary cellulose membrane dialyzer on lipid metabolism and the progress of atherosclerosis. LDL-MDA and oxidized LDL (ox-LDL) were measured in HD patients using these two types of dialyzers. Plasma vitamin E and lipid concentrations were also evaluated. The aortic calcification index (ACI) was evaluated by CT scan to assess the progress of atherosclerosis before and for every year after treatment. RESULTS: Use of a vitamin E coated cellulose membrane dialyzer for six months, one year and two years resulted in a significant reduction in LDL-MDA and ox-LDL compared to the ordinary cellulose membrane dialyzer. Treatment with a vitamin E-coated dialyzer significantly reduced the percentage increase in ACI after 24 months compared to the control. There were no significant changes in plasma vitamin E and lipid concentrations between the two groups. CONCLUSIONS: These results suggest that the oxidative stress could be one of the stimulating factors of abnormal lipid metabolism and atherosclerosis in ESRD patients.

Effect of simvastatin on the lipid profile of hemodialysis patients.

BACKGROUND: Simvastatin, a 3-hydroxy 3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor, is used widely for treatment of hypercholesterolemia. Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis (HD) patients. However, investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited. In this study, we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD. METHODS: Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein cholesterol (HDL-C) levels (35 mg/dl). Every four weeks, serum lipids, apolipoprotein, lipoprotein (a) [Lp(a)] and malondialdehyde (MDA) levels were measured. In addition, lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation. RESULTS: After 24 weeks of simvastatin administration, TC significantly decreased by 25.7%, and low-density lipoprotein cholesterol (LDL-C) was significantly decreased by 33.6%. Triglyceride (TG) and HDL-C showed no significant changes. Apolipoprotein (apo) B significantly decreased by 24.5% and apo E by 30.0%. No significant changes were observed in the other apolipoproteins. MDA was also significantly decreased, whereas Lp(a) was not significantly altered. In the lipoprotein fractions, very LDL cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL1 cholesterol (LDL1-C), and LDL2 cholesterol (LDL2-C) showed significant decreases. No particular side-effects were observed during the 12 months of simvastatin administration. CONCLUSIONS: These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia.

Effect of dietary fish oil, vitamin E, and probucol on renal injury in the rat.

Dietary fish oil, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomized cholesterol-fed rats as a model for progressive kidney disease, we examined the effect of 5% dietary fish oil, or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-month-old Sprague Dawley rats were fed a control diet (C group) or a cholesterol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FO+E group) or fish oil plus probucol (FO+P group). After 4 weeks of dietary treatment, the right kidney was electrocoagulated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was collected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that proteinuria was highest in FO+P group. Rats receiving the cholesterol diets had higher serum low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol (P < 0.05). In contrast, rats in the FO+P group had the lowest serum total cholesterol and LDL+VLDL cholesterol among all groups. The FO group had 26% lower kidney alpha-tocopherol concentrations than the C group. However, inclusion of vitamin E in the diet (FO+E group) increased the kidney alpha-tocopherol status to a level comparable to that in the C group, whereas inclusion of probucol in fish oil diet (FO+P group) did not improve the kidney alpha-tocopherol status. Rats fed the cholesterol diet had a 2.5-fold higher glomerular segmental sclerosis (GSS) score and 1.5-fold higher glomerular macrophage (GM) subpopulation than the C group. These effects of the cholesterol diet were ameliorated by a fish oil diet (FO group: GSS by 30%, GM by 24%). The inclusion of vitamin E in the fish oil diet (FO+E group) did not further improve the GSS score or GM subpopulation. However, inclusion of probucol in fish oil diet (FO+P group) lowered the GSS score by 73% and reduced GM subpopulation by 83% compared with the Ch group. These remarkable changes can be attributed to the powerful hypocholesterolemic activity of probucol. Our findings indicate that progression of glomerular sclerosis in the rat remnant kidney model of progressive kidney disease can be significantly modulated with fish oil treatment.

Long-term local hyperthermia in the treatment of advanced breast cancer (case report).

BACKGROUND: It is difficult to control non-resectable locally advanced primary and recurrent breast cancer by conventional modalities. Recently, hyperthermia (HT) has been recognized as an effective adjuvant to radiotherapy (RT) and chemotherapy (CT) in treatment of various malignancies, including breast cancer. PATIENT AND METHODS: The patient was a 58-year-old female Japanese, with breast cancer, T4N2M0, stage IIIb (papillo-tubular carcinoma). Previous treatment included RT and neoadjuvant CT Local HT was performed with a total number of 87 sessions given over 12 months. The mean time of each session was 40 minutes. Elevation of temperature to a tumoricidal level of 43 degrees C was confirmed. The patient received cyclophosphamide (50 mg p.o./day) and tamoxifen (20 mg p.o./day) during the whole period of HT. Due to the decreased amount of WBC, further CT was not possible, except for one course of CMF performed 3 months after the start of HT. RESULTS: The patient had a decrease in the intensity of pain even after the first 3 sessions. In one month, movement in the right shoulder became possible in an anterio-posterior direction. By 5 months, the healing of ulceration became evident. At present, the patient is in continuous CR for 15 months after HT. The movement in the shoulder joint is markedly improved in all directions. In addition, HT did not cause any notable complications. CONCLUSION: Long-term HT may be useful in the management of locally advanced breast cancer and these results should encourage further clinical study.

Effect of platelet-activating factor on lipoprotein lipase and blood lipids.

We investigated the effect of platelet-activating factor (PAF) and of the PAF specific antagonist CV-6209 on plasma lipid metabolism, and particularly on post-heparin plasma lipolytic activity in male Wistar rats. Lipoprotein lipase (LPL) activity was enhanced by intravenous injection of PAF before intravenous injection of heparin when the PAF dose was low (0.2 micrograms/kg). PAF activated hepatic triacylglycerol lipase (HTGL) activity dose-dependently. Plasma triacylglycerols (TG) significantly decreased with the activation of LPL and/or HTGL. Plasma total cholesterol (TC) and phospholipid (PL) levels decreased at a low dose of PAF (0.2 micrograms/kg), but increased when higher doses were used. The PAF antagonist CV-6209 partially reversed the PAF induced effects on HTGL, TC and PL.

Viral isolation from cases of epidemic neuropathy in Cuba.

OBJECTIVE: To investigate the possibility of a viral agent in the central nervous system of patients with epidemic neuropathy. DESIGN: Virus isolation attempts, in cell cultures and suckling mice, from cerebrospinal fluid (CSF) of neuropathy patients and controls undergoing lumbar puncture for unrelated reasons. Serologic studies in patients, contacts, and controls. SETTING: An epidemic of optic and peripheral neuropathy affected more than 50,000 people in Cuba in 1991 through 1993. Illness was associated with dietary limitations and increased physical demands accompanying the shortages of food and fuel experienced in Cuba since 1989. Most patients responded to parenteral vitamin therapy, and the epidemic began to subside when oral vitamin supplementation was begun for the entire Cuban population. RESULTS: Coxsackievirus A9 (five isolates) and a similar, less cytopathic virus (100 isolates) were recovered from 105 (84%) of 125 CSF specimens from neuropathy patients. The strains with light cytopathic effect were antigenically related to Coxsackieviruses A9 and B4 by cross-neutralization and immunoblotting assays. Virus persisted in CSF of some patients for 1 to 12 months. Cerebrospinal fluid from patients and both types of virus from cell culture produced illness, including complete posterior flaccid paralysis, in newborn mice, and virus was reisolated from the mice. Mouse tissues and sural nerve biopsy specimens from patients were stained by immunoperoxidase and colloidal gold techniques using hyperimmune rabbit antisera against the virus with light cytopathic effect. CONCLUSIONS: Coxsackievirus A9 or an antigenically related agent with a light cytopathic effect was present in CSF of 84% of 125 patients with epidemic neuropathy. The role of these agents, probably in combination with nutritional factors, in the pathophysiology of the disease requires further investigation.