Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of difluoromethylornithine (DFMO), an experimental drug that inhibits the biosynthesis of natural polyamines, on anti-DNA antibody production, immunoglobulin synthesis, proteinuria, and blood urea nitrogen (BUN) in lupus-prone female NZB/W mice. Administration of 1% of the drug in drinking water reduced anti-DNA antibody levels by about 80% of that of untreated mice of the same strain. There was a reduction of IgG and IgA levels in older DFMO treated mice, whereas IgM level was not affected. Proteinuria and BUN were also significantly reduced in treated mice. Moreover, DFMO treatment reduced the concentration of putrescine and spermidine in spleen cells. Our results suggest that polyamine biosynthesis inhibition by DFMO may provide a new approach to the treatment of lupus.
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PMID:Difluoromethylornithine therapy of female NZB/W mice. 202 14

The renal glomeruli are vulnerable to injury by a number of drugs and other toxic agents. These agents may lead to damage by one of two basic mechanisms: direct, dose-related toxic injury; indirect, immunologically mediated injury, largely dose-independent. Proteinuria is the simplest and most important functional indicator of glomerular injury. It occurs almost immediately in direct toxic injury, but there is a latent period of weeks to months with immunologically mediated processes. Of the two mechanisms, the second is by far the more common in clinical settings. The best studied experimental agent causing direct toxic injury is the aminonucleoside of puromycin. Clinically, perhaps the most important agent is Cyclosporine A. Although this agent is usually thought of primarily as a tubular toxin, it is capable of giving rise to a microangiopathic glomerular lesion similar to that in the hemolytic uremic syndrome. The classic model for immunologic glomerular lesion is Heymann nephritis, which produces a membranous glomerulopathy. Clinically, most drug mediated glomerulopathies also take the form of a membranous nephropathy, usually with a frank nephrotic syndrome. Among the more common offenders are penicillamine, gold salts used in rheumatoid arthritis, and captopril used in hypertension. The other common type of drug-related glomerulopathy occurs as part of a lupus-like syndrome induced by a variety of drugs, including hydralazine, procainamide, and penicillamine. All of these give rise to a variety of antibodies, most prominently antinuclear antibodies, and in the more severe cases there may be lupus-like glomerular lesions as well.
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PMID:Drug-associated glomerulopathies. 294 Jun 67

Respiratory stridor and hoarseness were the predominant presenting symptoms in a 63-year-old woman with an hydralazine induced lupus syndrome. Laryngeal tomograms and direct laryngoscopy were consistent with cricoarytenoid arthritis. Proteinuria, anemia, arthritis, and leukocytoclastic vasculitis, as well as the laryngeal findings, all resolved after withdrawal of hydralazine. Laryngeal manifestations of systemic lupus erythematosus are reviewed.
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PMID:Laryngeal manifestations of drug induced lupus. 359 9

Early reports on SLE were too small in number to determine that pregnancy was contraindicated in patients with renal involvement. Later reports show that patients with lupus nephropathy can have successful pregnancies provided certain preconditions are established. Optimal preconditions include prepregnancy remission of at least 6 months, renal function with serum creatinine 1.5 mg/dl or less or creatinine clearance of 60 ml/min or more or proteinuria of 3 g/24 hr or less. Successful pregnancies have been recorded in some patients with more severe renal impairment. Renal function will remain unchanged in approximately 60% of pregnancies; and although deterioration may occur, it is only severe or permanent in less than 10%. In 26% of patients, mild to severe renal impairment was transient, with recovery to prepregnancy levels of renal function. Proteinuria with good creatinine clearance may not be dangerous. Hypertension or superimposed preeclampsia jeopardizes the outcome. Fetal outcome averaged approximately 70% (range, 41-77%) live births, 17.8% (range, 5.1-40%) spontaneous abortions, 19.7% (range, 3.0-38.5%) prematurity, and 8.2% SGA. Therapeutic abortion is not a modality of treatment of lupus nephropathy. Management of patients with lupus nephropathy is twofold and includes suppression of underlying lupus activity as well as the serial evaluation of chronic renal disease. In chronic lupus nephropathy with inactive SLE maternal and fetal outcome is the same as for pregnant patients with chronic renal disease of other causes. Strict fetal surveillance must be performed to decrease the stillbirth rate. The concomitant increase in prematurity demands the services of a tertiary care neonatal unit. Management necessitates the team approach of the obstetrician, nephrologist, rheumatologist, and neonatologist working in collaboration. The reports which contain large numbers of patients now allow better counseling of these patients who are contemplating pregnancy.
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PMID:Lupus nephropathy and pregnancy. 389 19

A 58 year-old woman had atypical chronic urticaria, arthralgias and abdominal pain. Attacks of angioneurotic edema occurred. Proteinuria was discovered. She had clinical and biological signs of inflammation, leukoneutropenia , antileukocyte antibodies and low CH 50, C1q and C4 levels without functional C1 esterase deficiency. C1q precipitins were not detectable. Skin biopsy disclosed angiitis and by immunofluorescence a lupus band test was positive. Serologic investigations in search of SLE were negative. Renal biopsy showed mesangial deposits, capillary loop thickening and mesangial fixation of anti-IgG, C3 C1q and C4 antisera. In the interstitium, voluminous perivenular inflammatory infiltrates were visible. With corticosteroid treatment clinical manifestations subsided and proteinuria disappeared. This observation of McDuffie 's angiitis with renal venulitis leads to a review of the literature with discussion of the mechanisms of hypocomplementemia.
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PMID:[Hypocomplementemic urticarial vasculitis with glomerulopathy and renal venulitis]. 672 99

Flaxseed is rich in alpha-linolenic acid (alpha-LA) which has anti-atherogenic properties, and lignans which are platelet activating factor (PAF)-receptor antagonists. These constituents of flaxseed, and its beneficial effects in the MRL/lpr lupus mouse prompted us to perform this dosing study in lupus nephritis patients. Nine patients were enrolled, eight of whom completed the study. After the baseline studies, patients were given 15, 30, and 45 g of flaxseed/day sequentially at four week intervals, followed by a five-week washout period. Compliance, disease activity, blood pressure, plasma lipids, rheology, PAF-induced platelet aggregation, renal function, and serum immunology were assessed. Flaxseed-sachet count and a significant increase of serum alpha-LA indicated good compliance for 15 and 30 g doses. Total and LDL cholesterol, and blood viscosity were significantly reduced with 30 g and to a lesser extent 45 g doses. PAF-induced platelet aggregation was inhibited by all doses. There was a significant decline in serum creatinine with 30 and 45 g, and a concomitant increase in creatinine clearance with increasing flaxseed dose. Proteinuria was reduced with 30 g and to a lesser extent with 45 g of flaxseed. Complement C3 was significantly elevated by all three doses. CD11b expression on neutrophils, a measure of C3bi receptors, was significantly reduced with the 30 g dose. In conclusion, 30 g flaxseed/day was well tolerated and conferred benefit in terms of renal function as well as inflammatory and atherogenic mechanisms important in the pathogenesis of lupus nephritis.
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PMID:Flaxseed: a potential treatment for lupus nephritis. 756 15

Proteinuria was characterized by SDS-PAGE and by immunoblotting with anti-human albumin sera for the detection of urinary polymers of albumin (PA) in 40 patients with biopsy proven lupus glomerulonephritis (LN) (6 pts class III WHO, 24 pts class IV, 10 pts class V) with various clinical presentations (nephrotic syndrome with normal or impaired renal function, 14 pts; urinary abnormalities with normal or impaired renal function, 21 pts; clinical remission, 5 pts); in 25 pts, for whom the characterization of proteinuria and the renal biopsy were performed at the same time, the activity and chronicity index scores were calculated. The mixed SDS-PAGE patterns, characterized by the presence of low molecular weight proteins, were the more frequently found; the mixed patterns were significantly associated with interstitial leukocyte infiltration (p = 0.05) and glomerular sclerosis (p = 0.046) and nonsignificantly associated with higher values of serum creatinine; no SDS-PAGE pattern had predictive value on functional outcome at 36 months. Albumin polymers were present in 67% of pts; in active disease they were present in 33% of class III, in 100% of class IV and in 45% of class V WHO (p = 0.026); PA were not present in 5 pts with clinical remission (4 class IV and 1 class V WHO). The presence of PA was significantly associated with high values (> 10) of activity index (p = 0.009) and with extracapillary proliferation (p = 0.041). Serum creatinine was lower in patients without PA (Scr 1.0 +/- 0.4 mg/dl) than in those with PA (Scr 1.5 +/- 1.0 mg/dl), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SDS-PAGE patterns and polymeric albumin in proteinuria of lupus glomerulonephritis. 773 85

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

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

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


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