Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to investigate the mechanisms by which marine lipids rich in long chain omega-3 fatty acids inhibit autoimmune disease and prolong the survival rate in female (NZB/NZW) F1 (B/W) mice, an animal model for human SLE. Nutritionally adequate semipurified diets containing at 10% either corn oil (CO) or fish oil (FO) were fed from 1 mo of age and were monitored for proteinuria and survival. Proteinuria was detected earlier and became progressively severe in CO-fed mice. The average life span was significantly shortened by the CO diet (266.7 days +/- 12.5), whereas FO extended the survival significantly (402.1 days +/- 26.1; p < 0.001). A cross-sectional study at 6.5 mo of age revealed an increased proliferative response to T cell mitogens including bacterial superantigens and decreased serum anti-dsDNA Ab titers in the FO group compared with the CO group. Furthermore, splenocytes from the FO group when stimulated with Con A had higher IL-2 and lower IL-4 production similar to that of young (3.5 mo) mice. Flow cytometric analyses of splenocytes revealed lower Ig+, higher lymphocyte endothelial cell adhesion molecule-1, and lower Pgp-1+ cells within CD4+ and CD8+ subsets in FO-fed mice. Also, elevated IL-2 and IL-4 and significantly higher TGF-beta 1 and lower c-myc and c-ras mRNA expression and higher TGF-beta 1 and significantly lower c-Myc and c-Ha-Ras proteins were detected in spleens of FO-fed mice. Fatty acid analysis revealed significantly higher linoleic (18:2 omega-6) and arachidonic (20:4 omega-6) acid levels in splenocytes of the CO-fed group and higher eicosapentaenoic (20:5 omega-3) and docosahexanoic (22:6 omega-3) acid levels in the FO-fed group, indicating that changes in membrane fatty acid composition may contribute to the altered immune function and gene expression during the development of murine SLE.
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PMID:Increased TGF-beta and decreased oncogene expression by omega-3 fatty acids in the spleen delays onset of autoimmune disease in B/W mice. 820 22

To evaluate the results, the long-term prognosis and the rates of complication of an immunosuppressive regimen with corticosteroids and cyclophosphamide in the treatment of the nephritis of systemic lupus erythematosus, 21 patients with lupus glomerulonephritis were studied. Renal biopsies were performed in 17/21 of them and indicated diffuse proliferative (6 patients), diffuse mesangial (4) and membranous (7) glomerulonephritis. Treatment was structured in 4 phases: 1) induction with methylprednisolone 250 mg i.v. for 7-14 days, and cyclophosphamide 100-200 mg p.o., q.d., or 20 mg/kg i.v. every 28 days; 2) maintenance with prednisone p.o., 2 mg/kg q.o.d. for 45 days, and cyclophosphamide as before; 3) tapering, with reduction of prednisone by 15% each month for 4 months; 4) indefinite maintenance with prednisone slowly tapered to the least effective q.o.d. dose and cyclophosphamide discontinued after six months of treatment. This cycle was repeated in the event of a relapse. After a first immunosuppressive cycle, 20/21 patients achieved remission of glomerulonephritis. Plasma creatinine fell from 97 +/- 6 to 80 +/- 3 microMol/l (p < 0.01). Proteinuria fell from 2.1 +/- 0.4 to 0.2 +/- 0.4 g/d (p < 0.0001) and the nephrotic syndrome, present in 8 patients, disappeared. After an average of 20 +/- 7 months, 8 patients relapsed: all remitted again after a repeat cycle, but 1 later progressed to end-stage renal failure during pregnancy. After an average of 56 months 4 out of these 8 patients relapsed again: 1 progressed to end-stage renal disease following an abortion and 3 remitted completely after a third cycle. Thus, 18 out of 21 patients are presently in remission with an average dose of prednisone of 13.7 mg/day after an average follow-up of 52 +/- 38 months (range 2 to 156). Three patients are presently off treatment. In 16 patients with extended follow-up of 2 to 13 years, anti-nuclear antibodies, anti-DNA antibodies, albuminuria and cylindruria fell below post-cycle levels (p < 0.001 for all). We conclude that intensive immunosuppression with steroids and cyclophosphamide can achieve excellent long-term results in the treatment of systemic lupus with glomerulonephritis.
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PMID:Immunosuppressive treatment of the glomerulonephritis of systemic lupus. 871 48

Systemic lupus erythematosus is an uncommon disease in men. The clinical and pathological features and prognosis in 50 male patients with lupus nephritis (LN) and 50 age-matched female patients with LN were analysed. The age at which the disease began and the diagnosis was made was generally older in the male. The incidence of LN was higher in the male than in female (P < 0.01). The incidence of types IV and V LN was more common in the male than in female. Type II LN was not found in male patients. Proteinuria over 3.5g/24h and renal failure were more common in the male than in female (P < 0.05). The three most common clinical manifestations in male patients were irregular fever, skin rashes and painful joints. Rashes, hepatomegaly and neuropsychiatric dysfunction were more common in the male than in female. The patients were followed up one to twelve years. The rate of recovery and improvement was lower, but that of relapse and mortality higher in the male than in female.
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PMID:[Lupus nephritis in male adults, an analysis of the clinical and pathological features]. 873 62

The effects of recombinant mouse DNase on a well established murine model of spontaneous SLE have been evaluated. Daily intraperitoneal injections of DNase were given to female NZB/NZW F1 mice during the period of disease development from 4 to 7 months of age or at the height of disease activity from the age of 7 months for 3 weeks. This treatment was compared with the injections of diluent and with an immunosuppressive dose of dexamethasone. The effects of treatment were evaluated using the immunological parameters of disease activity (antinucleoprotein antibody, immune complexes, serum immunoglobulins, anti-cardiolipin antibodies), protein-uria, serum creatinine and renal histopathology (light microscopy, immunofluorescence and electron microscopy). The dose of dexamethasone used (1 mg/kg per day from the age of 4 months) was sufficient to suppress the development of lupus entirely. Treatment with DNase starting at the age of 4 months postponed the development of the disease by about 1 months and extended the period from the onset of disease to death by about 30%. Mice treated for 3 weeks during the most active phase of the disease at 7 months of age showed more dramatic effects. Proteinuria and serum creatinine were significantly reduced and renal histopathology was strikingly less severe than in the control group. Immune complexes involving DNA-containing antigens are believed to play a crucial role in the pathogenesis of SLE. DNA-nucleoprotein, even in immune complexes, can be destroyed by DNase. This enzyme therefore provides a rational way to interfere with the disease process. The results reported here encourage a trial of recombinant human DNase in human SLE and lupus nephritis.
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PMID:The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone. 891 61

Dexamethasone palmitate (D-PAL) incorporated into lipid microspheres (D-PAL emulsion) is taken up by the reticuloendothelial system and by some inflammatory cells. Therefore, it has a stronger anti-inflammatory activity than free corticosteroids in vivo. To study the effect of D-PAL emulsion on systemic lupus erythematosus (SLE), we administered D-PAL emulsion to MRLlpr/lpr mice, an animal model for human SLE. The effect of D-PAL emulsion was compared with that of methylprednisolone (m-PSL), a water-soluble steroid. Percent survival was higher in the group treated with 0.25 mg of D-PAL emulsion intravenously once every 4 weeks than in those groups treated similarly with m-PSL or PBS control. Swelling of lymph nodes was frequent in the group treated with m-PSL or with PBS, while rarely observed in the group treated with D-PAL emulsion. Proteinuria was more frequent in the groups treated with m-PSL or PBS than in the group treated with D-PAL emulsion. Although the frequency of skin lesions was not different between these three groups, the control and m-PSL treated mice had severe skin lesions, such as hair loss of erythematous skin with scales and crusts at the nape, while D-PAL emulsion treated animals showed only facial alopecia without inflammatory skin changes. These data demonstrate that D-PAL emulsion was more effective than a corresponding dose of m-PSL on autoimmune prone mice. This suggests that intermittent administration of D-PAL emulsion may be effective in the treatment of human SLE.
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PMID:Effects of liposteroid on skin lesions in autoimmune MRLlpr/lpr mice. 943 7

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.
Lupus 1998
PMID:Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study. 949 46

Non-immune mechanisms appear to be important in the majority of patients with lupus nephritis and progressive renal injury. Proteinuria, hypertension and dyslipidemia are associated non-immune risk factors often implicated in the deterioration of kidney function. There is ample animal experimental evidence that they are independent risk factors for progressive renal injury and their treatment results in amelioration of renal function. Proteinuria and hypertension, unlike dyslipidemia, have been shown to be independent risk factors for progressive renal injury in patients with lupus nephritis. Treatment of hypertension and proteinuria in the diabetic and non-diabetic progressive renal disease population results in stabilization of kidney function. Response to treatment should target both blood pressure of 120/80 and significant reductions in protein excretion. If protein excretion rate is unaltered by use of an angiotensin-converting enzyme inhibitor and salt restriction, one might resort to the use of an angiotensin II antagonist. Treatment of the dyslipidemia following good control of proteinuria, blood pressure and dietary change may not alter renal progression but should provide similar protection from accelerated vascular disease to the non-renal dyslipidemia population.
Lupus 1998
PMID:Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease. 988 5

Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens. This study reports on the clinical experiences at two institutions with mycophenolate mofetil (MMF) for severe lupus nephritis. Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included. During combined MMF/prednisone therapy, serum creatinine values remained normal or declined from elevated values: mean change in serum creatinine was -0.26+/-0.46 microM/L, P = 0.039. Proteinuria significantly decreased: mean change in urine protein-to-creatinine ratios was -2.53+/-3.76, P = 0.039. Decreased serum complement component C3 and elevated anti-double-stranded DNA antibody levels at baseline improved in some, but not all, patients. The mean initial dose of MMF was 0.92 g/d (range, 0.5 to 2 g/d). The mean duration of therapy was 12.9 mo (range, 3 to 24 mo). Adverse events included herpes simplex stomatitis associated with severe leukopenia (n = 1), asymptomatic leukopenia (n = 2), nausea/ diarrhea (n = 2), thinning of scalp hair (n = 1), pancreatitis (n = 1), and pneumonia without leukopenia (n = 1). Recurrence of the pancreatitis led to discontinuation of MMF in this patient; all other adverse events resolved with dose reduction. It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus. Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis.
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PMID:Mycophenolate mofetil therapy in lupus nephritis: clinical observations. 1020 68

We report a patient with systemic lupus erythematosus (SLE) complicated with nocardiosis. This case is very important that the complication of nocardiosis in SLE is very rare and the treatment to both SLE and nocardiosis is very difficult. A twenty-one-year old female was admitted to our hospital because of thoracic empyema and active lupus nephritis. Her medical history revealed that the diagnose of SLE was made when she was 18 with lymphocytopenia, proteinuria, positive antinuclear antibodies, and high titer of antibodies to native DNA. She was treated with prednisolne 60 mg daily and became better. Proteinuria appeared again in September 1995 and she was admitted to the former hospital. Renal biopsy proved diffuse proliferative glomeluronephritis (WHO IVb). She was treated with 1 g per day of methylprednisolone for 3 days and succeeded with 60 mg day of prednisolone. In early November she developed left chest pain and fever and chest X-ray demonstrated left pleural effusion. Antibiotics, antituberculosis, and antifungal therapy failed to subside her pleuritis and it turned to empyema. Then she was transferred to our hospital for further treatment. Nocardia farcinica was detected from the aspirated pleural fluid obtained at the former hospital. Drainage and intrathoracic impenem injection were effective. While long usage of minocycline was continued for the nocardiosis, 500 mg of cyclophosphamide pulse therapy to lupus nephritis was administrated. Two weeks later a new pulmonary lesion with left chest pain and liver abscess developed. Administration of trimethoprim-sulfamethoxazole subsided the nocardiosis. She was discharged with 1 g per day of proteinuria the prescribed 13 mg per day of prednisolone and continuous TMP-SMZ intake for nocardial infection. When immunosuppressive therapy must be given to the immunocompromised host, a more potent therapy must be added to avoid infection.
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PMID:[A case of systemic lupus erythematosus complicated by Nocardia farcinica]. 1038 29

Proteinuria is defined as urinary protein excretion exceeding 150 mg/day. It may result from nonpathological (posture, fever, exercise) or pathological (glomerular or tubular) processes. Glomerular proteinuria is an early sign of kidney disease and may also play a role in the progression of glomerular damage. Asymptomatic proteinuria is common; it may be transient or persistent. Transient proteinuria is a benign condition and requires no evaluation. Persistent proteinuria can be the first sign of kidney disease. Persistent proteinuria commonly results from disorders associated with increased glomerular permeability such as nephrotic syndrome, glomerulonephritis (e.g., post-infectious, membranous, membranoproliferative, lupus, IgA), and genetic defects (Alport syndrome, mesangial sclerosis). Tubular disorders should also be considered. Evaluation for the underlying cause is traditional. Whether the early detection and evaluation of proteinuria prevents progressive disease is unknown.
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PMID:A practical approach to proteinuria. 1050 30


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